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Archive for the ‘Curation methodology’ Category


Analysis of Utilizing LPBI Group’s Scientific Curation Platform as an Educational Tool: New Paradigm for Student Engagement

Author: Stephen J. Williams, Ph.D.

 

 

Use of LBPI Platform for Educational Purposes

Goal:  to offer supplemental information for student lessons in an upper level Biology course on Cell Signaling and Cell Motility with emphasis on disease etiology including cancer, neurological disease, and cardiovascular disease.

Course:  Temple University Department of Biology course Cell Signaling and Motility Spring semester 2019. Forty five students enrolled.

Methodology:  Each weekly lesson was presented to students as a PowerPoint presentation.  After each lesson the powerpoint presentation was originally meant to be disseminated to each class-registered student on the students Canvas account.  Canvas is a cloud based Learning Management Software developed by educational technology company Salt Lake City, Utah company Infrastructure, Inc.  According to rough figures, Canvas® charges a setup fee and at least $30 per user (for a university the size of Temple University: 55,000 students at $30 each = 1.6 million a semester for user fees only).

As a result of a technical issue with uploading the first week lesson on this system, I had informed the class that, as an alternative means, class presentation notes and lectures will be posted on the site www.pharmaceuticalintelligence.com as a separate post and searchable on all search engines including Google, Twitter, Yahoo, Bing, Facebook etc. In addition, I had informed the students that supplemental information, from curated posts and articles from our site, would be added to the class lecture post as supplemental information they could use for further reading on the material as well as helpful information and reference for class projects.

The posted material was tagged with #TUBiol3373 (university abbreviation, department, course number) and disseminated to various social media platforms using our system.  This allowed the students to enter #TUBiol3373 in any search engine to easily find their lecture notes and supplemental information.

This gave students access to lectures on a mobile platform which was easily discoverable due to our ability to do search engine optimization. (#TUBiol3373 was among the first search results on most popular search engines).

From a technical standpoint,  the ease at which posts of this nature can be made as well as the ease of including links to full articles as references as well as media has been noted.  Although students seem to navigate the Canvas software with ease, they had noticed many professors have issues or problems with using this software, especially with navigating the software for their needs.   LBPI’s platform is an easily updated, accessible, and extensive knowledge system which can alleviate many of these technical issues and provide the added value of incorporating media based instructional material as well as downloadable file and allow the instructor ability to expound on the presented material with commentary.  In addition due to the social nature of the platform, feedback can be attained by use of curated site statistics and commentary sections as well as online surveys.

 

Results

After the first week, all 45 students used LBPI platform to access these lecture notes with 17 out of 45 continuing to refer to the site during every week (week 1-4) to the class notes.  This was evident from our site statistics as well as number of downloads of the material.  The students had used the #TUBIol3373 and were directed to the site mainly from search engines Google and Yahoo.  In addition, students had also clicked on the links corresponding to supplemental information which I had included, from articles on our site.  In addition, because of the ability to incorporate media on our site, additional information including instructional videos and interviews were included in lecture posts, and this material was easily updated on the instructor’s side.

Adoption of the additional material from our site was outstanding, as many students had verbally said that the additional material was very useful in their studies.  This was also evidenced by site statistics owing to the secondary clicks made from the class lecture post going to additional articles, some not even included as links on the original post.

In addition, and  more important, students had incorporated many of the information from the additional site articles posted and referenced in their class group projects.  At end of semester a survey was emailed to each student  to assess the usefulness of such a teaching strategy. Results of the polling are shown below.

Results from polling of students of #TUBiol3373 “Cell Signaling & Motility” Class

Do you find using a web based platform such as a site like this an easier communication platform for posting lecture notes/added information than a platform like Canvas®? (5 votes)

Answer Votes Percent  
Yes 2 40%  
Somewhat but could use some improvement 2 40%  
No 1 20%  
Did not use web site 0 0%  

 

Do you find using an open access, curated information platform like this site more useful than using multiple sources to find useful extra study/presentation materials? (6 votes)

Answer Votes Percent  
Yes 5 83%  
No 1 17%  

 

Did you use the search engine on the site (located on the top right of the home page) to find extra information on topics for your presentations/study material? (5 votes)

Answer Votes Percent  
Yes 4 67%  
No 1 17%  
Did not use web site 1 17%  

 

Were you able to easily find the supplemental information for each lecture on search engines like Google/Yahoo/Bing/Twitter using the hashtag #TUBiol3373? (6 votes)

Answer Votes Percent  
Yes I was able to find the site easily 4 67%  
No 1 17%  
Did not use a search engine to find site, went directly to site 1 17%  
Encountered some difficulty 0 0%  
Did not use the site for supplemental or class information 0 0%  

 

How did you find the supplemental material included on this site above the Powerpoint presented material for each of the lectures? (7 votes)

Answer Votes Percent  
Very Useful 4 57%  
Did not use supplemental information 2 29%  
Somewhat Useful 1 14%  
Not Useful 0 0%  

How many times did you use the information on this site (https://www.pharmaceuticalintelligence.com) for class/test/project preparation? (7 votes)

Answer Votes Percent  
Frequently 3 43%  
Sparingly 2 29%  
Occasionally 1 14%  
Never 1 14%  

 

 

 

 

 

 

 

Views of #TUBiol3373 lessons/posts on www.pharmaceuticalintelligence.com                    

 

Lesson/Title Total # views # views 1st day # views 2nd day % views day 1 and 2 % views  after 1st 2 days
Lesson 1 AND 2 Cell Signaling & Motility: Lessons, Curations and Articles of reference as supplemental information: #TUBiol3373 60 27 15 93% 45%
Lesson 3 Cell Signaling And Motility: G Proteins, Signal Transduction: Curations and Articles of reference as supplemental information: #TUBiol3373 56 12 11 51% 93%
Lesson 4 Cell Signaling And Motility: G Proteins, Signal Transduction: Curations and Articles of reference as supplemental information: #TUBiol3373 37 17 6 48% 31%
Lesson 5 Cell Signaling And Motility: Cytoskeleton & Actin: Curations and Articles of reference as supplemental information: #TUBiol3373 13 6 2 17% 15%
Lesson 8 Cell Signaling and Motility: Lesson and Supplemental Information on Cell Junctions and ECM: #TUBiol3373 16 8 2 22% 13%
Lesson 9 Cell Signaling: Curations and Articles of reference as supplemental information for lecture section on WNTs: #TUBioll3373 20 10 3 28% 15%
Curation of selected topics and articles on Role of G-Protein Coupled Receptors in Chronic Disease as supplemental information for #TUBiol3373 19 11 2 28% 13%
Lesson 10 on Cancer, Oncogenes, and Aberrant Cell Signal Termination in Disease for #TUBiol3373 21 10 2 26% 20%
Totals 247 69 46 31% 62%
           

 

Note: for calculation of %views on days 1 and 2 of posting lesson and supplemental material on the journal; %views day1 and 2 = (#views day 1 + #views day 2)*100/45 {45 students in class}

For calculation of %views past day 1 and 2 = (total # views – day1 views – day2 views) * 100/45

For calculation in total column last two columns were divided by # of students (45) and # of posts (8)

 

Overall class engagement was positive with 31% of students interacting with the site during the course on the first two days after posting lessons while 61% of students interacted with the site during the rest of the duration of the course.  The higher number of students interacting with the site after the first two days after lecture and posting may be due to a higher number of students using the posted material for study for the test and using material for presentation purposes.

Engagement with the site for the first two days post lecture ranged from 93% engagement to 22% engagement.  As the class neared the first exam engagement with the site was high however engagement was lower near the end of the class period potentially due to the last exam was a group project and not a written exam.  Students appeared to engage highly with the site to get material for study for the written exam however there still was significant engagement by students for purposes of preparation for oral group projects.  Possibly engagement with the site post 2 days for the later lectures could be higher if a written exam was also given towards the end of the class as well.  This type of analysis allows the professor to understand the level of class engagement week by week.

The results of post-class polling confirm some of the conclusions on engagement.  After the final grades were given out all 45 students received an email with a link to the poll.  Of the 45 students emailed, there were 20 views of the poll with 5-7 answers per question.  Interestingly, most answers were positive on the site and the use of curated material for learning and a source of research project material.   It was very easy finding the posts using the #classname and most students used Google to find the material, which was at the top of Google search results.  Not many students used Twitter or other search engines.  Some went directly to the site.  A majority (71%) found the material useful or somewhat useful for their class presentations and researching topics.

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eScientific Publishing a Case in Point: Evolution of Platform Architecture Methodologies and of Intellectual Property Development (Content Creation by Curation) Business Model

Author: Aviva Lev- Ari, PhD, RN

 

Six demonstrations that justify the claims made in our 2019 VISION:

https://pharmaceuticalintelligence.com/vision/

  • Point #1: Top Author, Chief Scientific Officer, MD, FCAP – share in the Journal’s archive computed
  • Point #2: Top authors by e-Readers per article – A Team at work
  • Point #3: Team members Led by Key Opinion Leader [https://lnkd.in/eEyn69r] generated Intellectual Property (IP) of Three Asset Classes
  • Point #4: Functions and Forms by Asset Class
  • Point #5: SYNERGY among the Three Asset Classes stimulates Value Creation
  • Point #6: Plan for Team membership augmentation and Training under existing Leadership and New Ownership

 

POINT #1: Top Author, Chief Scientific Officer, a retired Chief of Pathology, LHB, MD, FCAP – share in the Journal’s archive computed

Journal archive has 5,486 articles published

LHB has published 1,390 articles = 25.33% – he joined our team with a publication list of +200 articles in referred academic journals. LHB is co-curator of many articles with many of the team members

  • The Young Surgeon and The Retired Pathologist: On Science, Medicine and HealthCare Policy– The Best Writers Among the WRITERS

https://pharmaceuticalintelligence.com/2013/12/10/the-young-surgeon-and-the-retired-pathologist-on-science-medicine-and-healthcare-policy-best-writers-among-the-writers/

 

POINT #2: Top authors by e-Readers per article – A Team at work

Click on this link to review the contributions of Team members who’s articles achieved >1,000 Views.

  • Article Title, Author/Curator’s Name and Article Views >1,000, 4/2012 – 1/2019 @pharmaceuticalintelligence.com

https://pharmaceuticalintelligence.com/2019/01/30/article-title-author-curators-name-and-article-views-1000-4-2012-1-2018-pharmaceuticalintelligence-com/

 

POINT #3: Team members led by Key Opinion Leader (KOL) [https://lnkd.in/eEyn69r] generated Intellectual Property (IP) of Three Asset Classes

 

List of LPBI IP Assets by Asset Class representing a Team Effort

 

  • IP Asset Class I: Launched Open Access Online Scientific Journal @com, 4/2012

https://lnkd.in/erfbayJ

  •  IP Asset Class II: Launched BioMed eSeries, 16-Volumes in Life Sciences and Medicine, 10/2012

BioMed e-Series: 16 Volumes – electronic Table of Contents (eTOCs) of each Volume

https://pharmaceuticalintelligence.com/2017/12/12/biomed-e-series-16-volumes-electronic-table-of-contents-of-each-volume/


Launched 6 Volumes Cardiovascular Diseases e-Series, Bundled on Amazon for $515

https://lnkd.in/e6WkMgF

Launched 10 Volumes in Medicine: Genomics 1,2  Cancer 1,2 Immunology 1,2,3  Precision Medicine 1,2,3,4

https://lnkd.in/ekWGNqA

 

  • IP Asset Class III: Launched Real Time Press Coverage of Biotech Conferences, 3/2013

https://pharmaceuticalintelligence.com/press-coverage/

Part One: The Process of Real Time Coverage using Social Media

Part Two: List of BioTech Conferences 2013 to Present

Part Three: Conference eProceedings DELIVERABLES & Social Media Analytics

 

POINT #4: FUNCTIONS and FORMS by ASSET CLASS

 

LPBI Group’s IP:VENTURE’s Future Potential
IP Asset Class I
https://lnkd.in/erfbayJ
IP Asset Class II
https://lnkd.in/ekWGNqA
IP Asset Class III
https://pharmaceuticalintelligence.com/press-coverage/
Open Access Journal– M1.5 e-Readers,- 5.5K articles- 670 categories,- 7.3K comments- 10K Tags
BioMed E-Series– 16 Volumes- 5 Specialties in Medicine- 6 Volumes Cardiovascular Diseases e-Series, Bundled on Amazon for $515https://lnkd.in/e6WkMgF
Real Time Coverage BioTech/Medicine Conferences– eProceedings- Real Time Tweets on- Two Twitter Handles- Conference Hash Tags@pharma_BI@AVIVA1950- Part Two: List of BioTech Conferences 2013 to Present
Editor-in-Chief’sLeadership:- Senior Editors- Our Team
Our Team’s Product
https://pharmaceuticalintelligence.com/contributors-biographies/
Senior Editors’ Product with Our Team
https://pharmaceuticalintelligence.com/contributors-biographies/senior-editors/https://pharmaceuticalintelligence.com/contributors-biographies/
Editor-in-Chief’s Initiative
https://lnkd.in/eEyn69r
Architecture   Methodologies for ourPlatforms
·       Multi-Authoring Platform – wordpress.com·       Authoring Privilege levels·       Categories of research forming the Journal’s Ontology, a Dynamic Relational and Hierarchical database Multi-Authoring architecture·       Generation of new categories by authors developing the categories they are Owners of·       Article update policy
·       eTOCs design by Editors·       e-Book Style uniformity across all eSeries·       Structure of eBook Parts·       Structure of Chapters·       Structure of Articles·       Commission of Articles Specifically for given e-Books by Editor-in-Chief·       Overarching guidance for e-Books within each eSeries and across eSeries
·       Part One: The Process of Real Time Coverage using Social Media·       Methodology for Conference Coverage using Social Media: 2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA·       Template Development Process·       Channels of Social Media Development
Business ModelDevelopment: Content Creation by Curation of Scientific Findings
·       Author/Curator initiated article·       Article Commissions by Editor-in-Chief·       Co-Curations·       Research Category Ownership·       e-Books Editors role defined (Job description)
·       e-Books in Kindle Store·       30,000 Oncologists in the US·       40,000 Cardiologists in the US·       All Primary Care Physicians·       All Medical Schools for Curriculum development·       Global market for Medical EducationALL BioMed 16 Volumes [$515+$190+$175+$190+$274 = $1,344]@Amazon BUNDLED 6 Volumes Cardiovascular Diseases for $515https://lnkd.in/e6WkMgF@Amazon UNBUNDLED 10 Volumeshttps://lnkd.in/ekWGNqA·       Genomics 1,2 ($190)·       Cancer 1,2 ($175)·       Metabolomics, Immunology, Infectious Diseases 1,2,3 (#190)·       Precision Medicine 1,2,3,4 ($274)
·       The market is defined as “All Biotech Conferences Organizers around the Globe” in need to own eProceedings for their Conferences for electronic dissemination to conference attendees.·       Digital Archive of Conferences eProceedingsPart Three: Conference eProceedings DELIVERABLES & Social Media Analytics
 
IP Asset Class III
https://pharmaceuticalintelligence.com/press-coverage/
Real Time Coverage BioTech/Medicine Conferences
– eProceedings
– Real Time Tweets on
– Two Twitter Handles
– Conference Hash Tags
@pharma_BI
@AVIVA1950
Part Two: List of BioTech Conferences 2013 to Present
Editor-in-Chief’s Initiative
https://lnkd.in/eEyn69r
·       Part One: The Process of Real Time Coverage using Social Media
·       Methodology for Conference Coverage using Social Media: 2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA
·       Template Development Process
·       Channels of Social Media Development
·       The market is defined as “All Biotech Conferences Organizers around the Globe” in need to own eProceedings for their Conferences for electronic dissemination to conference attendees.
·       Digital Archive of Conferences eProceedings
Part Three: Conference eProceedings DELIVERABLES & Social Media Analytics

POINT #4 (IN DETAIL): Functions and Forms by Asset Class

 

IP Asset Class I: The Journal

 

The Methodology of Curation for Scientific Research Findings

https://pharmaceuticalintelligence.com/2014/07/30/the-methodology-of-curation-for-scientific-research-findings/

 

>> Evolution of Platform Architecture Methodologies: 

  • Multi-Authoring Platform – wordpress.com
  • Authoring Privilege levels
  • Categories of research forming the Journal’s Ontology, a Dynamic Relational and Hierarchical database Multi-Authoring architecture
  • Generation of new categories by authors developing the categories they are Owners of
  • Article update policy

 

>> Intellectual Property Development (Content Creation by Curation) Business Model 

  • Author/Curator initiated article
  • Article Commissions by Editor-in-Chief
  • Co-Curations
  • Research Category Ownership
  • e-Books Editors role defined (Job description)

 

IP Asset Class II: BioMed e-Series

 

> Evolution of Platform Architecture Methodologies

Cardiovascular Original Research: Cases in Methodology Design for Content Curation and Co-Curation

https://pharmaceuticalintelligence.com/2013/07/29/cardiovascular-original-research-cases-in-methodology-design-for-content-curation-and-co-curation/

  • eTOCs design by Editors
  • e-Book Style uniformity across all eSeries
  • Structure of eBook Parts
  • Structure of Chapters
  • Structure of Articles
  • Commission of Articles Specifically for given e-Books by Editor-in-Chief
  • Overarching guidance for e-Books within each eSeries and across eSeries

 

> Intellectual Property Development (Content Creation by Curation) Business Model 

 

  • e-Books in Kindle Store
  • 30,000 Oncologists in the US
  • 40,000 Cardiologists in the US
  • US & Global markets for Cardiology, Genomics, Cancer, Immunology, Infectious Diseases, Precision Medicine
  • All Primary Care Physicians
  • All Medical Schools for Curriculum development
  • Global market for Medical Education

 

ALL BioMed 16 Volumes [$515+$190+$175+$190+$274 = $1,344]

@Amazon BUNDLED 6 Volumes Cardiovascular Diseases for $515 https://lnkd.in/e6WkMgF

@Amazon UNBUNDLED 10 Volumes in #Medicine https://lnkd.in/ekWGNqA

  • Genomics 1,2 ($190)
  • Cancer 1,2 ($175)
  • Metabolomics, Immunology, Infectious Diseases 1,2,3 (#190)
  • Precision Medicine 1,2,3,4 ($274)

 

Series A – Cardiovascular Diseases – 6 volumes $515

 

Series B – Genomics 1,2  – 2 volumes $190

  • VOLUME 1: Genomics Orientations for Personalized Medicine. On comsince 11/23/2015

http://www.amazon.com/dp/B018DHBUO6

  • VOLUME 2: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

https://pharmaceuticalintelligence.com/biomed-e-books/genomics-orientations-for-personalized-medicine/volume-two-genomics-methodologies-ngs-bioinformatics-simulations-and-the-genome-ontology/

Volume 2 is Work-in-Progress To Be Published in 6/2019 at $115

 

Series C – Cancer & Oncology $175 

  • VOLUME 1 Cancer Biology Genomics

http://www.amazon.com/dp/B013RVYR2K

  • VOLUME 2 Therapies Genomics Interventional Immunotherapy Nanotechnology in Drug Delivery

http://www.amazon.com/dp/B071VQ6YYK

 

Series D – Metabolomics, Immunology, Infectious Diseases $190

  • VOLUME 1 Metabolomics

http://www.amazon.com/dp/B012BB0ZF0

  • VOLUME 2 Infectious Diseases & VOLUME 3 Immunology

https://www.amazon.com/dp/B075CXHY1B

 

Series E Precision Medicine – Four Volumes, Volumes 1,2,3,4 at $274

  • Patients Voices

https://www.amazon.com/dp/B076HGB6MZ

  • Physiology and Therapeutics

https://www.amazon.com/dp/B078313281

  • Medical Discoveries: Genomics Therapeutics

http://www.amazon.com/dp/B019VH97LU

  • 3D #BioPrinting in Medicine for Precision Medicine

https://www.amazon.com/dp/B078QVDV2W

 

IP Asset Class III: Real Time Coverage of BioTech Conferences

 

>> Evolution of Platform Architecture Methodologies

https://pharmaceuticalintelligence.com/2014/04/07/methodology-for-conference-coverage-using-social-media-2014-massbio-annual-meeting-43-44-2014-royal-sonesta-hotel-cambridge-ma/

  • Template Development Process
  • Channels of Social Media Development

 

>> Intellectual Property Development (Content Creation by Curation) Business Model 

  • The market is defined as “All Biotech Conferences Organizers around the Globe” in need to own eProceedings for their Conferences for electronic dissemination to conference attendees.
  • Digital Archive of Conferences eProceedings

 

POINT #5: SYNERGY among the Three Asset Classes stimulates Value Creation

 

  • Concepts from +60 Conferences I covered yielded ~300 new articles, five new per conference, at least
  • Electronic Table of Contents [eTOCs] for each e-Book of the [1,2,3..,16] is derived from the Research categories of the Journal
  • Journal Ontology has 700 Research Categories – knowledge architecture designed by experts
  • Every article in the Journal is connected with Social Media Icons on wordpress.com as an engine for
  1. Pingbacks
  2. New eReaders
  3. Scientists applying to author for the Journal
  4. +7,300 Scientific comments on 5,486 articles published – AGORA  

Electronic Scientific AGORA: Comment Exchanges by Global Scientists on Articles published in the Open Access Journal @pharmaceuticalintelligence.com – Four Case Studies

https://pharmaceuticalintelligence.com/2018/04/10/electronic-scientific-agora-comment-exchanges-by-global-scientists-on-articles-published-in-the-open-access-journal-pharmaceuticalintelligence-com-four-case-studies/

 

POINT #6: Plan for Team membership augmentation and Training under existing Leadership and New Ownership

Work-in-Progress

 

 

Other related articles published in this Open Access Online Scientific Journal include the following: 

 

Innovations in electronic Scientific Publishing (eSP): Case Studies in Marketing eContent, Curation Methodology, Categories of Research Functions, Interdisciplinary conceptual innovations by Cross Section of Categories, Exposure to Frontiers of Science by Real Time Press coverage of Scientific Conferences

https://pharmaceuticalintelligence.com/2017/05/06/case-studies-of-innovations-in-electronic-scientific-publishing-esp-marketing-econtent-curation-methodology-categories-of-research-functions-interdisciplinary-conceptual-innovations-by-cross-sec/

 

e-Scientific Publishing: The Competitive Advantage of a Powerhouse for Curation of Scientific Findings and Methodology Development for e-Scientific Publishing – LPBI Group, A Case in Point

https://pharmaceuticalintelligence.com/2017/06/20/e-scientific-publishing-the-competitive-advantage-of-a-powerhouse-for-curation-of-scientific-findings-and-methodology-development-for-e-scientific-publishing-lpbi-group-a-case-in-point/

 

The Methodology of Curation for Scientific Research Findings

https://pharmaceuticalintelligence.com/2014/07/30/the-methodology-of-curation-for-scientific-research-findings/

 

@PharmaceuticalIntelligence.com – A Case Study on the LEADER in Curation of Scientific Findings

https://pharmaceuticalintelligence.com/2017/06/29/pharmaceuticalintelligence-com-a-case-study-on-the-leader-in-curation-of-scientific-findings/

 

Curation of Scientific Content @Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

https://pharmaceuticalintelligence.com/2016/08/15/curation-of-scientific-content-leaders-in-pharmaceutical-business-intelligence-lpbi-group-boston/

 

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson

https://pharmaceuticalintelligence.com/2014/07/17/scientific-curation-fostering-expert-networks-and-open-innovation-lessons-from-clive-thompson-and-others/

 

Cardiovascular Diseases and Pharmacological Therapy: Curations by Aviva Lev-Ari, PhD, RN, 2006 – 4/2018

https://pharmaceuticalintelligence.com/2014/04/17/cardiovascular-diseases-and-pharmacological-therapy-curations-by-aviva-lev-ari-phd-rn/

 

Methodology for Conference Coverage using Social Media: 2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA

https://pharmaceuticalintelligence.com/2014/04/07/methodology-for-conference-coverage-using-social-media-2014-massbio-annual-meeting-43-44-2014-royal-sonesta-hotel-cambridge-ma/

 

Cardiovascular Original Research: Cases in Methodology Design for Content Curation and Co-Curation

https://pharmaceuticalintelligence.com/2013/07/29/cardiovascular-original-research-cases-in-methodology-design-for-content-curation-and-co-curation/

 

 

 

 

Read Full Post »


Article Title, Author/Curator’s Name and Article Views >1,000, 4/2012 – 1/2019 @pharmaceuticalintelligence.com

 

Reporter: Aviva Lev-Ari, PhD, RN

 

Expert, Author, Writer’s Initials

Name & Bio

Roles

@LPBI Group

LHB Larry Bernstein, MD, FACP,

 

Member of the Board

Expert, Author, Writer – All Specialties of Medicine & Pathology

Content Consultant to Series B,C,D,E

Editor, Series D, Vol. 1, Series E, Vols 2,3,

Co-Editor – BioMed E-Series 13 of the 16 Vols

JDP Justin D. Pearlman, AB, MD, ME, PhD, MA, FACC,

 

Expert, Author, Writer, All Specialties of Medicine, Cardiology and Cardiac Imaging

Content Consultant for SERIES A, Cardiovascular Diseases Co-Editor: Vols 2,3,4,5,6

ALA Aviva Lev-Ari, PhD, RN,

-Ex – SRI, Int’l

-Ex – MITRE

-Ex – McGraw-Hill

Director and Founder

Editor-in-Chief, @pharmaceuticalintelligence.com

Methodologies Developer:

  • Journal Platform Architect,
  • CURATION of Scientific Findings Modules,
  • REALTIME eProceedings Digital 1-Click Publishing

Expert, Author, Writer:

  • Analytics
  • Molecular Cardiology
  • Vascular Biology
TB Tilda Barliya, PhD,

@BIU

Expert, Author, Writer: Nanotechnology for Drug Delivery

Co-Editor, Series C, Vols. 1,2

DN Dror Nir, PhD,

 

Expert, Author, Writer: Cancer & Medical Imaging Algorithms
ZR       
Ziv Raviv, PhD,
@Technion
Expert, Author, Writer: Biological Sciences, Cancer
ZS Zohi Sternberg, PhD, Expert, GUEST Author, Writer

 

Expert, GUEST Author, Writer

Neurological Sciences

SJW Stephen J. Williams, PhD Pharmacology, BSc Toxicology

Ex-Fox Chase

EAW – Cancer Biology

Co-Editor, Series A, Vol.1

Co-Editor, Series B, Genomics: Vols. 1,2

Co-Editor, Series C, Cancer, Vols. 1,2

DS Demet Sag, PhD, CRA, GCP,

 

Expert, Author, Writer: Genome Biology, Immunology, Biological Sciences: Cancer
SS Sudipta Saha, PhD,

 

Expert, Author, Writer: Reproductive Biology, Endocrinology, Bio-Instrumentation

Co-Editor, Series D, Volume 2, Infectious Diseases

AV Aviral Vatsa, PhD, MBBS

 

Expert, Author, Writer: Medical Sciences, Bone Disease, Human Sensation and Cellular Transduction: Physiology and Therapeutics

 

RS Ritu Saxena, PhD,

 

Expert, Author, Writer: Biological Sciences, Bone Disease, Cancer (Lung, Liver)
GST Gail S. Thornton, PhD(c),

Ex-MERCK

Contributing Editor, Author and Medical Writer

Co-Editor, Series E, Vol.1 Voices of Patients

RN Raphael Nir, PhD, MSM, MSc

Ex-ScheringPlough

– Expert, Author, Writer – Member of the Cancer Research Team: Brain Cancer, Liver Cancer, Cytokines

– CSO, SBH Sciences, Inc.

MB Michael R. Briggs, Ph.D.

Ex-Pfizer

– Expert, Author, Writer – Member of the Cancer Research Team: NASH

– CSO, Woodland Biosciences

AK Alan F. Kaul, R.Ph., Pharm.D, M.Sc., M.B.A., FCCP, Expert, Author, Writer

Ex-Director BWH Pharmacy

Expert, Author, Writer: Pharmacology – all aspects of Drug development and dispensation, Policy analyst
AS Anamika Sarkar, PhD,

 

Expert, Author, Writer: Computation Biology & Bioinformatics
MWF Marcus Feldman, PhD,

Stanford University, Biological Sciences, Center for Genomics

751
Research items
51,402
Reads
39,126
Citations
Member of the Board,

Scientific Counsel: Life Sciences,

Content Consultant Series B, Genomics, Vols. 1,2

Co-Editor, Vol. 2, NGS

 

Article Title and Views >1,000,

4/2012 – -1/2018

 

 

 

 

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600,145

Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View? LHB 16,720
Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) and PRADAXA (dabigatran)

JDP

ALA

13,225
Paclitaxel vs Abraxane (albumin-bound paclitaxel) TB 11,872
Recent comprehensive review on the role of ultrasound in breast cancer management DN 11,715
Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care ALA 7,045
Apixaban (Eliquis): Mechanism of Action, Drug Comparison and Additional Indications ALA 6,435
Mesothelin: An early detection biomarker for cancer (By Jack Andraka) TB 6,309
Our TEAM ALA 6,213
Akt inhibition for cancer treatment, where do we stand today? ZR 4,744
Biochemistry of the Coagulation Cascade and Platelet Aggregation: Nitric Oxide: Platelets, Circulatory Disorders, and Coagulation Effects LHB 4,508
Newer Treatments for Depression: Monoamine, Neurotrophic Factor & Pharmacokinetic Hypotheses ZS 4,188
AstraZeneca’s WEE1 protein inhibitor AZD1775 Shows Success Against Tumors with a SETD2 mutation SJW 4,128
Confined Indolamine 2, 3 dioxygenase (IDO) Controls the Hemeostasis of Immune Responses for Good and Bad DS 3,678
The Centrality of Ca(2+) Signaling and Cytoskeleton Involving Calmodulin Kinases and Ryanodine Receptors in Cardiac Failure, Arterial Smooth Muscle, Post-ischemic Arrhythmia, Similarities and Differences, and Pharmaceutical Targets LHB 3,652
FDA Guidelines For Developmental and Reproductive Toxicology (DART) Studies for Small Molecules SJW 3,625
Cardiovascular Diseases, Volume One: Perspectives on Nitric Oxide in Disease Mechanisms Multiple

Authors

3,575
Interaction of enzymes and hormones SS 3,546
AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo SJW 3,403
Causes and imaging features of false positives and false negatives on 18F-PET/CT in oncologic imaging DN 3,399
Introduction to Transdermal Drug Delivery (TDD) system and nanotechnology TB 3,371
Founder ALA 3,363
BioMed e-Series ALA 3,246
Signaling and Signaling Pathways LHB 3,178
Sexed Semen and Embryo Selection in Human Reproduction and Fertility Treatment SS 3,044
Alternative Designs for the Human Artificial Heart: Patients in Heart Failure – Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community

JDP

LHB

ALA

3,034
The mechanism of action of the drug ‘Acthar’ for Systemic Lupus Erythematosus (SLE) Dr. Karra 3,016
VISION ALA 2,988
Targeting the Wnt Pathway [7.11] LHB 2,961
Bone regeneration and nanotechnology AV 2,922
Pacemakers, Implantable Cardioverter Defibrillators (ICD) and Cardiac Resynchronization Therapy (CRT) ALA 2,892
The History and Creators of Total Parenteral Nutrition LHB 2,846
Funding, Deals & Partnerships ALA 2,708
Paclitaxel: Pharmacokinetic (PK), Pharmacodynamic (PD) and Pharmacogenpmics (PG) TB 2,700
LIK 066, Novartis, for the treatment of type 2 diabetes LHB 2,693
FDA Adds Cardiac Drugs to Watch List – TOPROL-XL® ALA 2,606
Mitochondria: Origin from oxygen free environment, role in aerobic glycolysis, metabolic adaptation LHB 2,579
Nitric Oxide and Platelet Aggregation Dr. Karra 2,550
Treatment Options for Left Ventricular Failure – Temporary Circulatory Support: Intra-aortic balloon pump (IABP) – Impella Recover LD/LP 5.0 and 2.5, Pump Catheters (Non-surgical) vs Bridge Therapy: Percutaneous Left Ventricular Assist Devices (pLVADs) and LVADs (Surgical) LHB 2,549
Isoenzymes in cell metabolic pathways LHB 2,535
“The Molecular pathology of Breast Cancer Progression” TB 2,491
In focus: Circulating Tumor Cells RS 2,465
Nitric Oxide Function in Coagulation – Part II LHB 2,444
Monoclonal Antibody Therapy and Market DS 2,443
Update on FDA Policy Regarding 3D Bioprinted Material SJW 2,410
Journal PharmaceuticalIntelligence.com ALA 2,340
A Primer on DNA and DNA Replication LHB 2,323
Pyrroloquinoline quinone (PQQ) – an unproved supplement LHB 2,294
Integrins, Cadherins, Signaling and the Cytoskeleton LHB 2,265
Evolution of Myoglobin and Hemoglobin LHB 2,251
DNA Structure and Oligonucleotides LHB 2,187
Lipid Metabolism LHB 2,176
Non-small Cell Lung Cancer drugs – where does the Future lie? RS 2,143
Biosimilars: CMC Issues and Regulatory Requirements ALA 2,101
The SCID Pig: How Pigs are becoming a Great Alternate Model for Cancer Research SJW 2,092
About ALA 2,076
Sex Hormones LHB 2,066
CD47: Target Therapy for Cancer TB 2,041
Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes ALA 2,017
Swiss Paraplegic Centre, Nottwil, Switzerland – A World-Class Clinic for Spinal Cord Injuries GST 1,989
Introduction to Tissue Engineering; Nanotechnology applications TB 1,964
Problems of vegetarianism SS 1,940
The History of Infectious Diseases and Epidemiology in the late 19th and 20th Century LHB 1,817
The top 15 best-selling cancer drugs in 2022 & Projected Sales in 2020 of World’s Top Ten Oncology Drugs ALA 1,816
Nanotechnology: Detecting and Treating metastatic cancer in the lymph node TB 1,812
Unique Selling Proposition (USP) — Building Pharmaceuticals Brands ALA 1,809
Wnt/β-catenin Signaling [7.10] LHB 1,777
The role of biomarkers in the diagnosis of sepsis and patient management LHB 1,766
Neonatal Pathophysiology LHB 1,718
Nanotechnology and MRI imaging TB 1,672
Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions JDP

ALA

1,659
Ultrasound-based Screening for Ovarian Cancer DN 1,655
Justin D. Pearlman, AB, MD, ME, PhD, MA, FACC, Expert, Author, Writer, Editor & Content Consultant for e-SERIES A: Cardiovascular Diseases JDP 1,653
Scientific and Medical Affairs Chronological CV ALA 1,619
Competition in the Ecosystem of Medical Devices in Cardiac and Vascular Repair: Heart Valves, Stents, Catheterization Tools and Kits for Open Heart and Minimally Invasive Surgery (MIS) ALA 1,609
Stenting for Proximal LAD Lesions ALA 1,603
Mitral Valve Repair: Who is a Patient Candidate for a Non-Ablative Fully Non-Invasive Procedure? JDP

ALA

1,602
Nitric Oxide, Platelets, Endothelium and Hemostasis (Coagulation Part II) LHB 1,597
Outcomes in High Cardiovascular Risk Patients: Prasugrel (Effient) vs. Clopidogrel (Plavix); Aliskiren (Tekturna) added to ACE or added to ARB LHB 1,588
Diet and Diabetes LHB 1,572
Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination? ALA 1,546
Dealing with the Use of the High Sensitivity Troponin (hs cTn) Assays LHB 1,540
Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers ALA 1,534
Altitude Adaptation LHB 1,527
Baby’s microbiome changing due to caesarean birth and formula feeding SS 1,498
Interview with the co-discoverer of the structure of DNA: Watson on The Double Helix and his changing view of Rosalind Franklin ALA 1,488
Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes ALA 1,476
IDO for Commitment of a Life Time: The Origins and Mechanisms of IDO, indolamine 2, 3-dioxygenase DS 1,469
CRISPR/Cas9: Contributions on Endoribonuclease Structure and Function, Role in Immunity and Applications in Genome Engineering LHB 1,468
Cancer Signaling Pathways and Tumor Progression: Images of Biological Processes in the Voice of a Pathologist Cancer Expert LHB 1,452
Signaling transduction tutorial LHB 1,443
Diagnostic Evaluation of SIRS by Immature Granulocytes LHB 1,440
UPDATED: PLATO Trial on ACS: BRILINTA (ticagrelor) better than Plavix® (clopidogrel bisulfate): Lowering chances of having another heart attack ALA 1,426
Cardio-oncology and Onco-Cardiology Programs: Treatments for Cancer Patients with a History of Cardiovascular Disease ALA 1,424
Nanotechnology and Heart Disease TB 1,419
Aviva Lev-Ari, PhD, RN, Director and Founder ALA 1,416
Cardiotoxicity and Cardiomyopathy Related to Drugs Adverse Effects LHB 1,415
Nitric Oxide and it’s impact on Cardiothoracic Surgery TB 1,405
A New Standard in Health Care – Farrer Park Hospital, Singapore’s First Fully Integrated Healthcare/Hospitality Complex GST 1,402
Mitochondrial Damage and Repair under Oxidative Stress LHB 1,398
Ovarian Cancer and fluorescence-guided surgery: A report TB 1,395
Sex determination vs. Sex differentiation SS 1,393
LPBI Group ALA 1,372
Closing the Mammography gap DN 1,368
Cytoskeleton and Cell Membrane Physiology LHB 1,367
Crucial role of Nitric Oxide in Cancer RS 1,364
Medical 3D Printing ALA 1,332
Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty LHB 1,325
The Final Considerations of the Role of Platelets and Platelet Endothelial Reactions in Atherosclerosis and Novel Treatments LHB 1,310
Disruption of Calcium Homeostasis: Cardiomyocytes and Vascular Smooth Muscle Cells: The Cardiac and Cardiovascular Calcium Signaling Mechanism

LHB

JDP

ALA

1,301
Mitochondrial Dynamics and Cardiovascular Diseases RS 1,284
Nitric Oxide and Immune Responses: Part 2 AV 1,282
Liver Toxicity halts Clinical Trial of IAP Antagonist for Advanced Solid Tumors SJW 1,269
Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells using a bacterial CRISPR/Cas ALA 1,261
Autophagy LHB 1,255
Mitochondrial fission and fusion: potential therapeutic targets? RS 1,246
Summary of Lipid Metabolism LHB 1,239
Nitric Oxide has a Ubiquitous Role in the Regulation of Glycolysis – with a Concomitant Influence on Mitochondrial Function LHB 1,233
Future of Calcitonin…? Dr. Karra 1,211
Transcatheter Aortic Valve Implantation (TAVI): FDA approves expanded indication for two transcatheter heart valves for patients at intermediate risk for death or complications associated with open-heart surgery ALA 1,197
Gamma Linolenic Acid (GLA) as a Therapeutic tool in the Management of Glioblastoma

RN

MB

1,193
Nanotechnology and HIV/AIDS Treatment TB 1,181
Patiromer – New drug for Hyperkalemia ALA 1,179
‘Gamifying’ Drug R&D: Boehringer Ingelheim, Sanofi, Eli Lilly ALA 1,177
A Patient’s Perspective: On Open Heart Surgery from Diagnosis and Intervention to Recovery Guest Author: Ferez S. Nallaseth, Ph.D. 1,173
Assessing Cardiovascular Disease with Biomarkers LHB 1,167
Development Of Super-Resolved Fluorescence Microscopy LHB 1,166
Ubiquitin-Proteosome pathway, Autophagy, the Mitochondrion, Proteolysis and Cell Apoptosis: Part III LHB 1,162
Atrial Fibrillation contributing factor to Death, Autopsy suggests CEO Dave Goldberg had heart arrhythmia before death ALA 1,159
Linus Pauling: On Lipoprotein(a) Patents and On Vitamin C ALA 1,156
Bystolic’s generic Nebivolol – Positive Effect on circulating Endothelial Progenitor Cells Endogenous Augmentation ALA 1,154
The History of Hematology and Related Sciences LHB 1,151
Heroes in Medical Research: Barnett Rosenberg and the Discovery of Cisplatin SJW 1,146
Overview of New Strategy for Treatment of T2DM: SGLT2 Inhibiting Oral Antidiabetic Agents AV 1,143
Imatinib (Gleevec) May Help Treat Aggressive Lymphoma: Chronic Lymphocytic Leukemia (CLL) ALA 1,140
Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing SJW 1,137
New England Compounding Center: A Family Business AK 1,120
EpCAM [7.4] LHB 1,113
Amyloidosis with Cardiomyopathy LHB 1,110
Can Mobile Health Apps Improve Oral-Chemotherapy Adherence? The Benefit of Gamification. SJW 1,095
Acoustic Neuroma, Neurinoma or Vestibular Schwannoma: Treatment Options ALA 1,089
Treatment of Refractory Hypertension via Percutaneous Renal Denervation ALA 1,088
Proteomics – The Pathway to Understanding and Decision-making in Medicine LHB 1,085
Low Bioavailability of Nitric Oxide due to Misbalance in Cell Free Hemoglobin in Sickle Cell Disease – A Computational Model AS 1,085
Pancreatic Cancer: Genetics, Genomics and Immunotherapy TB 1,083
A NEW ERA OF GENETIC MANIPULATION   DS 1,075
Targeting Mitochondrial-bound Hexokinase for Cancer Therapy ZR 1,074
Normal and Anomalous Coronary Arteries: Dual Source CT in Cardiothoracic Imaging JDP

ALA

1,062
Transdermal drug delivery (TDD) system and nanotechnology: Part II TB 1,057
Lung Cancer (NSCLC), drug administration and nanotechnology TB 1,046
Pharma World: The Pharmaceutical Industry in Southeast Asia – Pharma CPhI 20-22 March, 2013, Jakarta International Expo, Jakarta, Indonesia ALA 1,045
Nitric Oxide and Sepsis, Hemodynamic Collapse, and the Search for Therapeutic Options LHB 1,044
Targeted delivery of therapeutics to bone and connective tissues: current status and challenges- Part I AV 1,044
Press Coverage ALA 1,036
Carbohydrate Metabolism LHB 1,036
Open Abdominal Aortic Aneurysm (AAA) repair (OAR) vs. Endovascular AAA Repair (EVAR) in Chronic Kidney Disease Patients – Comparison of Surgery Outcomes LHB

ALA

1,032
In focus: Melanoma Genetics RS 1,018
Cholesteryl Ester Transfer Protein (CETP) Inhibitor: Potential of Anacetrapib to treat Atherosclerosis and CAD ALA 1,015
Medical Devices Start Ups in Israel: Venture Capital Sourced Locally – Rainbow Medical (GlenRock) & AccelMed (Arkin Holdings) ALA 1,007
The Development of siRNA-Based Therapies for Cancer ZR 1,003

Other related articles published in this Open Access Online Scientific Journal include the following:

FIVE years of e-Scientific Publishing @pharmaceuticalintellicence.com, Top Articles by Author and by e-Views >1,000, 4/27/2012 to 1/29/2018

https://pharmaceuticalintelligence.com/2017/04/28/five-years-of-e-scientific-publishing-pharmaceuticalintellicence-com-top-articles-by-author-and-by-e-views-1000-4272012-to-4272017/

Read Full Post »


Electronic Scientific AGORA: Comment Exchanges by Global Scientists on Articles published in the Open Access Journal @pharmaceuticalintelligence.com – Four Case Studies

Curator and Editor-in-Chief: Journal and BioMed e-Series, Aviva Lev-Ari, PhD, RN

 

Introduction

Case Study #1: 40 Responses

  • Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

Author: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2012/10/17/is-the-warburg-effect-the-cause-or-the-effect-of-cancer-a-21st-century-view/

Case Study #2: 26 Responses

·      Knowing the tumor’s size and location, could we target treatment to THE ROI by applying…..

Author: Dror Nir, PhD

https://pharmaceuticalintelligence.com/2012/10/16/knowing-the-tumors-size-and-location-could-we-target-treatment-to-the-roi-by-applying-imaging-guided-intervention/

Case Study #3: 24 Responses

  • Personalized Medicine: Cancer Cell Biology and Minimally Invasive Surgery (MIS)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/01/personalized-medicine-cancer-cell-biology-and-minimally-invasive-surgery-mis/

Case Study #4: 13 Responses

  • Judging the ‘Tumor response’-there is more food for thought

https://pharmaceuticalintelligence.com/2012/12/04/judging-the-tumor-response-there-is-more-food-for-thought/

Conclusions

 

Introduction

Members of our Team published 5,295 articles, in the period between 4/2012 to 4/10/2018, and engaged in Comment Exchanges with Global Scientists Online. 1,412,106 eReaders had viewed our articles and 7,283 scientific comments are included in the Journal Archive.

Team Members’ Profile

Team Profile: DrugDiscovery @LPBI Group – A BioTech Start Up submitted for Funding Competition to MassChallenge Boston 2016 Accelerator

In our Scientific Agora: Multi Scientific Comment exchanges between Global e-Readers Scientists and LPBI’s Scientists/Experts/Authors/Writers take place. In this curation I am presenting four articles that generated dozens of scientific comments and multifaceted exchanges.

The Voice of Aviva Lev-Ari, PhD, RN:

It is my strongest conviction on the merit of the following features of Global SHARING the Scientific product, aka “An Article written by a Scientist” in the Digital Scientific Publishing Age:

  • Every new article published in Open Access Journals contributes to mitigate the most acute challenge of the e-Scientific Publishing industry today: Information Obsolescence – the newness of findings
  • Every new article published in Open Access Journals contributes AND in the Subscription-based Journals contributes to the second most acute challenge of of the e-Scientific Publishing industry today: Information Explosion – the volume of findings
  • The Scientific Agora as presented, below, in four Case Studies is an optimal means for Global SHARING in Real Time scientific knowledge deriving from clinical expertise and lab experience of all the participants in the Agora. REAL TIME means minimization of the negative impact of the most acute challenge of of the e-Scientific Publishing industry today: Information Obsolescence 
  • Knowledge SHARING of our Scientists articles occurs among two FORUMS:

Forum One, is the Scientists that joined the comment exchanges between the Article Author and other members of our Team on a given Scientific product, aka “An Article written by a Scientist”

Forum Two, is the Global Universe of Scientists that (a) are e-mail Followers opting to our Open Access Journal free subscription and (b) eReaders of our Journal that did not yet opt to follow the Journal by e-mail, a robust crowd of +1.4 Million Scientists

  • We mitigate the negative impact of the second most acute challenge of the e-Scientific Publishing industry today: Information Explosion by our own developed and advanced achievements reached in the practice of
  1. Development of the Methodology for Curation of Scientific Findings, Curation of Scientific Content @Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston
  2. Application of the Methodology for Curation of Scientific Findings in a BioMed e-Series of 16-Volumes in Medicine and Life Sciences on Amazon.com

electronic Table of Contents (eTOCs) of each Volume in the SIXTEEN Volume BioMed e-Series

WE ARE ON AMAZON.COM

https://www.amazon.com/s/ref=nb_sb_noss?url=search-alias%3Ddigital-text&field-keywords=Aviva+Lev-Ari&rh=n%3A133140011%2Ck%3AAviva+Lev-Ari

Commentaries on each Volume’s Contribution to Medical Education by L.H. Bernstein, MD, FCAP and by Aviva Lev-Ari, PhD, RN – BioMedical e-Books e-Series: Multiple Volumes in Five e-Series

https://pharmaceuticalintelligence.com/biomed-e-books/commentaries-on-each-volumes-contribution-to-medical-education-by-l-h-bernstein-md-fcap-and-aviva-lev-ari-phd-rn-biomedical-e-books-e-series-multiple-volumes-in-five-e-series/

In 2016, LPBI’s BioMed e-Series was Submitted for Nomination for 2016 COMMUNICATION AWARD FOR EXCELLENCE IN REPORTING SCIENCE, MEDICINE AND ENGINEERING – Reference #: 9076095, on 1/27/2016

https://pharmaceuticalintelligence.com/biomed-e-books/

  • Lastly, It is my strong belief that the Methodology of Curation will become a major tool used in Content creation for Curriculum Development in Medical Schools, in the Life Sciences and Healthcare Allied professions.
  • We have pioneered and showed the way BY EXAMPLE, +5,200 Scientific products, aka “An Article written by a Scientist” constitute our Journal Archive created by content curation
  • More New e-Book Titles are coming in 2018-2019 in LPBI’s BioMed e-Series.
  • More e-Scientific Publishers will use the Methodology of Creation of electronic Table of Contents of e-Books by combing Archives by very experienced subject matter Editors.
  • Global SHARING of Information became best practice for Academic Course Contents in the last ten years
  • On-Line Degrees are spreading in many disciplines and are offered by very many colleges, including the Ivy League
  • Open Access Scientific Journals is the FUTURE of the e-Scientific Publishing Industry.

 

Case Study #1:

  • Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

Author: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2012/10/17/is-the-warburg-effect-the-cause-or-the-effect-of-cancer-a-21st-century-view/

40 Responses

  1. This is OUTSTANDING.

    Now we need a “shortcliff” post to follow one chart that traces the dynamic process, no reader shall get lost inside any of the process boxes.

  2. Really nice overview and very interesting metabolic changes.
    However, related to the title, the cancerous changes- event always comes first before lactate preferred metabolism comes into place. Right?

  3. This is what has been inferred. So if that is the premise, then the mutation would be the first event. That position has been successfully challenged and also poses a challenge to the proper view of genomic discovery. The real event may very well be the ongoing oxidative stress with aging, and decreased physiochemical reserve.

    I haven’t developed the whole picture. Nitric oxide and nitrosylation contribute to both vascular relaxation and vasoconstriction, which is also different in major organs. The major carriers of H+ are NADH and FADH2. Electron transport is in the ETC in mitochondria. I called attention to the “escape” of energy in aerobic glycolysis. As disease ensues, it appears that lactate generation is preferential as the mitochondrion takes up substrate from gluconeogenesis. Whether it is an endotoxic shock or a highly malignant fast growing tumor, the body becomes trapped in “autocatabolism”. So the tumor progresses, apoptosis is suppressed, and there is a loss of lean body mass.
    All of this is tied to genetic instability.

    We see the genetic instability as first because of the model DNA–RNA–protein. We don’t have a map.

  4. It is a very nice report. I did work for a short time to develop compounds to block the glucose uptake especially using glucose-mimics. I wonder is there any research on this area going on now?

  5. Thanks. I have been researching this exhaustively. There are even many patents trying to damp this down. You were on the right track. The biggest problem has been multidrug resistance and tumor progression.

  6. […] Is the Warburg Effect the cause or the effect of cancer: A 21st Century View? (pharmaceuticalintelligence.com) […]

  7. […] Is the Warburg Effect the cause or the effect of cancer: A 21st Century View? (pharmaceuticalintelligence.com) […]

  8. Martin Canizales • Warburg effect (http://www.cellsignal.com/reference/pathway/warburg_effect.html), is responsible of overactivation of the PI3K… the produced peroxide via free radicals over activate the cyclooxigenase and consequently the PI3K pathway activating there, the most important protein-kinase ever described in the last mmmh, 60-70 years? maybe… to broke the Warburg effect, will stop the PI3K activation (http://www.cellsignal.com/reference/pathway/Akt_PKB.html) then all the cancer protein related with the generation of tumor (pAKT,pP70S6K, Cyclin D1, HIF1, VEGF, EGFrc, GSK, Myc, etc, etc, etc), will get down regulation. That is what happen, when I knock down the new protein-kinase in pancreatic cancer cell lines… stable KD of pancreatic cancer cell lines divide very-very-veeeery slow (by Western blotting, cyclin D1 disapear, VEGF, HIF1a, MyC, pAKT, pP70S6K, GSK, and more and more also has, very-very few consume of glucose [diabetes and cancer]. Stable cells can be without change the media for 3 weeks and the color doesn’t change, cells divide but VERY slow and are alive [longevity]) are not able to generate xenograft tumors related, to scramble shRNA stable cell lines. When, we broke the warburg effect, the protein kinase get’s down as well all the others. Is the same, with bacteria infections…. bacteria infections, has many things to teach us about cancer and cell proliferation (http://www.ncbi.nlm.nih.gov/pubmed/22750098)

  9. edit this on November 12, 2012 at 5:41 PM | Replyhijoprodigoendistancia

    research paper, should be ready (writing) very soon and must be submmited before end this year. Hee hee! you know… end of the world is in December 21 2012

    • The emphasis on p13 and the work on pancreatic cancer is very interesting. I’ll check the references you give. The Warburg effect is still metabolic, and it looks like you are able to suppress the growth of either cancer cells or bacteria. The outstanding question is whether you can get a head start on the SIR transition to sepsis to severe sepsis to MODS, to shock.

      It looks like an article will be necessary after your work is accepted for publication. Thanks a lot for the response.

  10. edit this on November 12, 2012 at 8:52 PM | Replyhijoprodigoendistancia

    Also, when this protein-kinase is over expressed… UCP1 get down..then, less mitochondria, consequently less aerobic cell functions…in adipose tissue, less mitochondria promote the differentiation of BAT (Brown Adipose Tissue) to, WAT (White Agipose Tissue). Has relation with AS160 phosphorylation, Glut4 membrane translocation, promote the GABA phosphorylation (schizophrenia-autism), neuronal differentiation (NPCs:Neural Progenitor Cells), dopaminergic cell differentiation….

  11. edit this on November 12, 2012 at 8:55 PM | Replyhijoprodigoendistancia

    Larry, all comments are part of the second paper.

  12. […] Is the Warburg Effect the cause or the effect of cancer: A 21st Century View? […]

  13. […] Is the Warburg Effect the cause or the effect of cancer: A 21st Century View? […]

  14. Larry please take a look at Gonzalez et al. The Bioenergetic theory of Carcinogenesis. Med Hypotheses 2012; 79: 433-439 and let me know your thoughts.

  15. […] The Initiation and Growth of Molecular Biology and Genomics, Part I […]

  16. […] Is the Warburg Effect the cause or the effect of cancer: A 21st Century View? […]

  17. edit this on May 22, 2013 at 11:36 PM | ReplyAashir Awan, Phd

    Informative article especially concerning activation of HIF under normoxic conditions. Recently, a paper has come out showing patients showing symptoms of mood disorder having increased expression of Hif1a. Also, there are reports that Hif1a is important in development of certain tissue types.

  18. COLOURS AND LIFE. The basic idea of this theory is that the oxidation of hydrogen and carbon atoms, arising from the degradation of carbohydrates, is by two distinct processes based on oxidation-reduction electron transfer and photochemical process of energy release on the basis of color complementary, predominance of one or another depending on intracellular acid-base balance. I can not understand why nobody wants to do this experiment. I’m sure this assumption hides a truth. Before considering it a fiction to be checked experimentally. I would like to present a research project that concerns me for a long time that I can not experience myself.
    Involuntarily, after many years of searching, I have concluded that in the final biological oxidation, in addition to the oxidation-reduction electron transfer occurs photo-chemical process, accordance to the principle of color complementary energy transfer. I imagine an experiment that might be relevant (sure it can be improved). In my opinion, if this hypothesis proves true, one can control the energy metabolism of the cell by chromotherapy, as the structures involved are photosensitive and colorful. I would be very happy if this experiment were done under your leadership. Sincerely yours Dr. Viorel Bungau

    INNER LIGHT – LIGHT OF LIFE.
    CHROMOTHERAPY AND THE IMPLICATIONS IN THE METABOLISM OF THE NORMAL AND NEOPLASTIC CELL. “Chlorophyll and hemoglobin pigments of life porphyrin structure differs only in that chlorophyll is green because of magnesium atoms in the structure, and hemoglobin in red because of iron atoms in the structure. This is evidence of the common origin of life.” (Heilmeyer) We propose an experiment to prove that the final biological oxidation, in addition to its oxidation-reduction, with formation of H2O and CO2, there is a photochemical effect, by which energy is transferred from the H atom, or C, process is done selct, the colors, complementary colors on the basis of the structures involved are colored (red hemoglobin Fe, Mg chlorophyll green, blue ceruloplasmin Cu, Fe cytochrome oxidase red, green cytochrome oxidase with Cu etc.). The basic idea is that if life pigments (chlorophyll, hemoglobin, cytochromes), which provides energy metabolism of the cell, are colored, we can control their activities through chromotherapy, on the basis of complementary color and energy rebalance the body, with a figured X- body-colored-ray.
    In my opinion, at the basis of malign transformation is a disturbance of energetical metabolism, which reached a level that cell can not correct (after having succeeded before, many times), disturbance that affects the whole body in different degrees and requires corection from outside starting from the ideea that the final biological oxidizing takes place through photochemical process with releasing and receieving energy. “Duality of cytochrome oxidase. Proliferation (growth) and Differentiation (maturation) cell.” Cytochrome oxidase is present in two forms, depending on the context of acid-base internal environment : 1.- Form acidic (acidosis), which contains two Iron atoms, will be red, will absorb the additional green energy of the hydrogen atom, derived from carbohydrates, with formation of H2O, metabolic context that will promote cell proliferation. 2.-Form alkaline (alkalosis), containing two copper atoms, will be green, will absorb the additional red energy of the carbon atom, derived from carbohydrates, with formation of CO2, metabolic context that will promote cell differentiation. Cytochrome oxidase structure has two atoms of copper. It is known that in conditions of acidosis (oxidative potential), the principle electronegativity metals, copper is removed from combinations of the Iron. So cytochrome oxidase will contain two atoms of iron instead of copper atoms, which changes its oxidation-reduction potential, but (most important), and color. If the copper was green, the iron is red, which radically change its absorption spectrum, based on the principle of complementary colors.
    “Inner Light- Light of Life. Endogenous monochromatic irradiation. Red ferment of Warburg – Green ferment of Warburg.”
    In my opinion, at the basis of malign transformation is a disturbance of energetical metabolism, which reached a level that cell can not correct (after having succeeded before, many times), disturbance that affects the whole body in different degrees and requires corection from outside starting from the ideea that the final biological oxidizing takes place through photochemical process with releasing and receieving energy. If the structures involved in biological oxidation finals are colored, then their energy absorption is made based on the principle of complementary colors. If we can determine the absorption spectrum at different levels, we can control energy metabolism by chromotherapy – EXOGENOUS MONOCHROMATIC IRRADIATION . Energy absorption in biological oxidation process itself, based on complementary colors, the structures involved (cytochromes), is the nature of porphyrins, in combination with a metal becomes colored, will absorb the complementary color, corresponding to a specific absorption spectrum, it will be in – ENDOGENOUS MONOCHROMATIC IRRADIATION.
    This entitles us to believe that: In photosynthesis, light absorption and its storage form of carbohydrates, are selected, the colors, as in cellular energy metabolism, absorption of energy by the degradation of carbohydrates, is also done selectively, based on complementary colors. In the final biological oxidation, in addition to an oxidation-reduction process takes place and a photo-chemical process,based on complementary colors, the first in the electron transfer, the second in the energy transfer. So, in the mitochondria is a process of oxidation of atoms C and H, derived from carbohydrates, with energy release and absorption of its selection (the color), by the structures involved, which is the nature of porphyrins, are photosensitive and colorful, if we accept as coenzymes involved, containing a metal atom gives them a certain color, depending on the state of oxidation or reduction (red ferment of Warburg with iron, all copper cerloplasmin blue, green chlorophyll magnesium, red iron hemoglobin, green cytochrome oxidase with copper, etc.)
    According to the principle electronegativity metals, under certain conditions the acid-base imbalance (acidosis), iron will replace copper in combination , cytocromoxidase became inactive, leading to changing oxidation-reduction potential, BUT THE COLOR FROM GREEN, TO REED, to block the final biological oxidation and the appearance of aerobic glycolysis. In connection with my research proposal, to prove that the final biological oxidation, in addition to an oxidation-reduction process takes place and a photo-chemical process, the first in the electron transfer, the second in the energy transfer.
    I SUGGEST TO YOU AN EXPERIMENT:

    TWO PLANTS, A RED (CORAILLE) LIGHT ONLY, IN BASIC MEDIUM, WITH ADDED COPPER, WILL GROW, FLOWER AND FRUIT WILL SHORT TIME, AND THE OTHER ONLY GREEN LIGHT (TOURQUOISE), IN AN ACID MEDIUM, WITH ADDED COPPER CHELATOR , WHICH GROWS THROUGHOUT WILL NOT GROW FLOWERS AND FRUIT WILL DO.

    CULTURE OF NEOPLASTIC TISSUE, IRRADIATED WITH MONOCHROMATIC GREEN ( TOURQUOISE) LIGHT, IN AN ALKALINE MEDIUM, WITH ADDED COPPER, WILL IN REGRESSION OF THE TISSUE CULTURE.

    CULTURE OF NEOPLASTIC TISSUE, IRRADIATED WITH RED ( CORAILLE) LIGHT, IN AN ACID MEDIUM, WITH ADDED COPPER CHELATOR, WILL LEAD TO EXAGERATED AND ANARCHICAL MULTIPLICATION.
    If in photosynthesis is the direct effect of monochromatic irradiation, in the final biological oxidation effect is reversed. Exogenous irradiation with green, induces endogenous irradiation with red, and vice versa. A body with cancer disease will become chemically color “red”- Acid -(pH, Rh, pCO2, alkaline reserve), and in terms of energy, green (X-body-colored-ray). A healthy body will become chemically color “green”-Alkaline – (as evidenced by laboratory), and in terms of energy, red (visible by X-body-colored-ray). Sincerely, Dr. Viorel Bungau

    -In addition-
    “Life balance: Darkness and Light – Water and Fire – Inn and Yang.”

    Cytochrome oxidase structure has two atoms of copper. It is known that in conditions of acidosis (oxidative potential), the principle electronegativity metals, copper is removed from combinations of the Iron. So cytochrome oxidase will contain two atoms of iron instead of copper atoms, which changes its oxidation-reduction potential, but (most important), and color. If the copper was green, the iron is red, which radically change its absorption spectrum, based on the principle of complementary colors. If neoplastic cells, because acidosis is overactive acid form of cytochrome oxidase (red with iron atoms), which will absorb the additional green energy hydrogen atom (exclusively), the production of H20 , so water will prevail, in Schizophrenia , neuronal intracellular alkaline environment, will promote the basic form of cytochrome oxidase (green with copper atoms), which will oxidize only carbon atoms, the energy absorption of red (complementary) and production of CO2, so the fire will prevail. Drawn from this theory interdependent relationship between water and fire, of hydrogen(H2O) and carbon(CO2) ,in a controlled relationship with oxygen (O2). If photosynthesis is a process of reducing carbon oxide(CO2) and hydrogen oxide(H2O), by increasing electronegativity of C and H atoms, with the electrons back to oxygen, which will be released in the mitochondria is a process of oxidation of atoms C and H, derived from carbohydrates, with energy release and absorption of its selection (the color), by the structures involved, which is the nature of porphyrins, are photosensitive and colorful. It means that matter and energy in the universe are found in a relationship based on complementary colors, each color of energy, corresponding with a certain chemical structure. In my opinion, at the basis of malign transformation is a disturbance of energetical metabolism, which reached a level that cell can not correct (after having succeeded before, many times), disturbance that affects the whole body in different degrees and requires corection from outside starting from the ideea that the final biological oxidizing takes place through photochemical process with releasing and receieving energy. The final biological oxidation is achieved through a process of oxidation-reduction, while a photochemical process, based on the principle of complementary colors, if we accept as coenzymes involved, containing a metal atom gives them a certain color, depending on the state of oxidation or reduction (red ferment of Warburg with copper, all copper cerloplasmin blue, green chlorophyll magnesium, red iron hemoglobin,etc. If satisfied, the final biological oxidation is achieved by a photochemical mechanism (besides the oxidation-reduction), that energy is released based on complementary colors, means that we can control the final biological oxidation mechanism, irreversibly disrupted in cancer, by chromotherapy and correction of acid-base imbalance that underlies this disorder.We reached this conclusions studying the final biological oxidation, for understanding the biochemical mechanism of aerobic glycolysis in cancer. We found that cancer cell, energy metabolism is almost exclusively on hydrogen by oxidative dehydrogenation, due to excessive acidosis , coenzymes which makes carbon oxidation, as dormant (these coenzymes have become inactive). If we accept the nature of these coenzymes chloride (see Warburg ferment red), could be rectivate, by correcting acidosis (because that became leucoderivat), and by chromoterapie, on the basis of complementary colors. According to the principle electronegativity metals, under certain conditions the acid-base imbalance (acidosis), iron will replace copper in combination , cytocromoxidase became inactive (it contains two copper atoms) leading to changing oxidation-reduction potential, BUT THE COLOR FROM GREEN, TO REED, to block the final biological oxidation and the appearance of aerobic glycolysis.

    Malignant transformation occurs by energy metabolism imbalance in power generation purposes in the predominantly (exclusively) of the hydrogen atom of carbon oxidation is impossible. Thus at the cellular level will produce a multiplication (growth) exaggerated (exclusive), energy from hydrogen favoring growth, multiplication, at the expense of differentiation (maturation). Differentiation is achieved by energy obtained by oxidation of the carbon atom can not take, leading to carcinogenesis . The energy metabolism of the cell, an energy source is carbohydrate degradation, which is done by OXIDATIVE DEHYDROGENATION AND OXIDATIVE DECARBOXYLATION , to obtain energy and CO2 and H2O. In normal cells there is a balance between the two energy sources. If cancer cells, oxidation of the carbon atom is not possible, the cell being forced to summarize the only energy source available, of hydrogen. This disorder underlying malignant transformation of cells and affect the whole body, in various degrees, often managing to rebalance process, until at some point it becomes irreversible. The exclusive production of hydrogen energy will cause excessive multiplication, of immature cells, without functional differentiation. Exclusive carbon energy production will lead to hyperdifferentiation, hyperfunctional, multiplication is impossible. Normal cell is between two extremes, between some limits depending on the adjustment factors of homeostasis. Energy from energy metabolism is vital for cell (body). If the energy comes predominantly (or exclusively) by oxidation of the hydrogen atom, green energy, will occur at the structural level (biochemical), acidification of the cellular structures that will turn red, so WE HAVE MORPHOLOGICAL AND CHEMICAL STRUCTURES “RED”, WITH “GREEN” ENERGY. This background predisposes to accelerated growth, without differentiation, reaching up uncontrolled, anarchical. ENERGY STRUCTURE OF THE CELL BODY WOULD BE INN. If necessary energy cell derived mainly by oxidation of the carbon atom, red energy,cell structures will be colored green, will be alkaline(basic), so WE HAVE MORPHOLOGICAL AND CHEMICAL STRUCTURES “GREEN”, WITH “RED” ENERGY, on the same principle of complementarity. This context will lead hyperdifferentiation, hyperfunctional ,maturation, and grouth stops. ENERGY STRUCTURE OF THE CELL BODY WOULD BE YANG. If in photosynthesis, porphyrins chemicals group, whic be photosensitivity (their first feature), shows and a great affinity for metals with chelate forming and becoming colored (pigments of life), can absorb monochromatic light complementary, so if these pigments, which constitutes the group of chromoprotheine, in photosynthesis will achieve CO2 and H2O reduction the recovery of C, H respectively, and the issuance of and release of O, atoms as H and C that reduced the energy load, representing carbohydrates, is in the form of solar energy storage, in cellular energy metabolism, processes necessary life, energy will come from the degradation of substances produced in photosynthesis, the carbohydrates, by oxidative dehydrogenation and oxidative decarboxylation, through like substances, which form chelates with the metals, are colored, metals contained in the form of oxides of various colors(green Mg, red Fe, blue Cu,etc.),suffering from complementary color absorption process of reduction with H in case,if the oxidative dehydrogenation, when chelated metal pigment is red, becoming leucoderivat (colorless) by absorbing complementary color (green) of hydrogen, formation of H2O, or C, if the oxidative decarboxylation when chelated metallic pigment is green, energy absorbing additional, red energy of atom C, CO2 production, the process is identical. The process that lies at base cellular energy metabolism, takes place in the final biological oxidation, reducing the O atom in the form of metal oxide, in combination with photosensitive substance, porohyrin, colorful,absorbing complementary color, will reduce the O atom, with H and C, with the production of H2O and CO2. Green energy release of H atom in the oxidative dehydrogenation process, it is a process of”IRRADIATION MONOCHROMATIC ENDOGENOUS WITH GREEN”, and red energy release of C atom in the oxidative decarboxylation process, consists in an “IRRADIATION MONOCHROMATIC ENDOGENOUS WITH RED”. Porphyrin-metal combination in photosynthesis, the chelated form, by absorbing light in the visible spectrum, will be able to reduce to low and turn, C and H respectively, the state of oxide (CO2 and H2O),release of O. The final biological oxidation, the combination of metal-porphyrins in aerobically in the absence of light, will find in the oxidized state, so in the form of porphyrins and metal-oxide, will oxidize to C and H atom of hydrocarbonates, with formation of CO2 and H2O, or rather, will be reduced by C and H atom of hydrocarbonates,formation of CO2 and H2O, by absorbing energy produced by photosynthesis. If we can control the final biological oxidation, we can control cellular growth, thus multiplying, and on the other hand, maturation, so differentiation. Green energy will prevail if the cell (body) which multiplies (during growth), will in case of adult cell (functional) will prevail red energy . The two types of energy, that obtained by oxidative dehydrogenation , which will cause cell multiplication without differentiation , and that obtained by oxidative decarboxylation , which will be to stop proliferation, and will determine the differentiation (maturity, functionality). This process is carried out based on complementary colors, which are coenzymes oxidative dehydrogenation and oxidative decarboxylation is colored . It reveals the importance of acid-base balance, the predominance of the acidic or basic, as an acid structure (red), not only can gain energy from the carbon atom red (the principle of complementarity), but can not assimilate ( under the same principle). It must therefore acid-base balance of internal environment, and alkalinization his intake of organic substances by the electron donor. By alkalinization (addition of electrons) will occur neutralize acid structures, the red, they become leucoderivat, colorless, and inactive, while the basic, which because of acidosis became neutral, colorless and inactive, will be alkaline in electron contribution, will be in green, and will absorb red energy from the carbon atom. So, on two kinds of vital energy, it is clear correlation between the chemical structure of the cell(body),and type of energy that can produce and use. Thus a cell with acidic chemical structure, can produce only energy by oxidative dehydrogenation (green energy), because the acid can only be active coenzymes with acid chemical structure, red, will absorb the complementarity only green energy of hydrogen. Basic structures which should absorb red energy from carbon , are inactive due to acid environment, which in turn chemically in leucoderivat, so colorless structures, inactive. Conversion of these structures to normal, operation by alkalinization could be a long lasting process, therefore, we use parallel chromotherapy, based on the fact that these COENZYMES INVOLVED IN BIOLOGICAL OXIDATION FINALS ARE COLORED AND PHOTOSENSITIVE. Thus, exogenous irradiation with monochromatic green will neutralize, by complementarity, coenzymes red, acidic. In will reactivate alkaline coenzymes, which have become due acidosis leucoderivat, so colorless and inactive. Without producing CO2, carbonic anhydrase can not form H2CO3, severable and thus transferred through mitochondrial membrane. Will accumulate in the respiratory Flavin, OH groups, leading to excessive hydroxylation, followed by consecutive inclusion of amino (NH2). It is thus an imbalance between the hydrogenation-carboxylation and hydroxylation-amination, in favor of the latter. This will predominate AMINATION and HYDROXYLATION at the expense CARBOXYLATION and HYDROGENATION, leading to CONVERSION OF STRUCTURAL PROTEINS IN NUCLEIC ACIDS. Meanwhile, after chemical criteria not genetic, it synthesizes the remaining unoxidized carbon atoms, nucleic bases “de novo” by the same process of hydroxylation-amination, leading to THE SYNTHESIS OF NUCLEIC ACIDS “DE NOVO”. Sincerely yours, Dr. Viorel Bungau viorelbungau20@yahoo.com

    • Dr. Viorel Bungau,

      Your comment is beautiful, clorful, insightful, magestic.

      This article has drawn 3007 views

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  19. Dear Mr. Professor, Please join me in this research proposal, as leader, because I can not go alone.
    The basic idea of this theory is that the oxidation of hydrogen and carbon atoms, arising from the degradation of carbohydrates, is by two distinct processes based on oxidation-reduction electron transfer and photochemical process of energy release on the basis of color complementary, predominance of one or another depending on intracellular acid-base balance. I can not understand why nobody wants to do this experiment. I’m sure this assumption hides a truth. Before considering it a fiction to be checked experimentally. I would like to present a research project that concerns me for a long time that I can not experience myself.
    Involuntarily, after many years of searching, I have concluded that in the final biological oxidation, in addition to the oxidation-reduction electron transfer occurs photo-chemical process, accordance to the principle of color complementary energy transfer. I imagine an experiment that might be relevant (sure it can be improved). In my opinion, if this hypothesis proves true, one can control the energy metabolism of the cell by chromotherapy, as the structures involved are photosensitive and colorful. I would be very happy if this experiment were done under your leadership. Sincerely yours, Dr. Viorel Bungau

    INNER LIGHT – LIGHT OF LIFE.
    CHROMOTHERAPY AND THE IMPLICATIONS IN THE METABOLISM OF THE NORMAL AND NEOPLASTIC CELL. “Chlorophyll and hemoglobin pigments of life porphyrin structure differs only in that chlorophyll is green because of magnesium atoms in the structure, and hemoglobin in red because of iron atoms in the structure. This is evidence of the common origin of life.” (Heilmeyer) We propose an experiment to prove that the final biological oxidation, in addition to its oxidation-reduction, with formation of H2O and CO2, there is a photochemical effect, by which energy is transferred from the H atom, or C, process is done selct, the colors, complementary colors on the basis of the structures involved are colored (red hemoglobin Fe, Mg chlorophyll green, blue ceruloplasmin Cu, Fe cytochrome oxidase red, green cytochrome oxidase with Cu etc.). The basic idea is that if life pigments (chlorophyll, hemoglobin, cytochromes), which provides energy metabolism of the cell, are colored, we can control their activities through chromotherapy, on the basis of complementary color and energy rebalance the body, with a figured X- body-colored-ray.
    In my opinion, at the basis of malign transformation is a disturbance of energetical metabolism, which reached a level that cell can not correct (after having succeeded before, many times), disturbance that affects the whole body in different degrees and requires corection from outside starting from the ideea that the final biological oxidizing takes place through photochemical process with releasing and receieving energy. “Duality of cytochrome oxidase. Proliferation (growth) and Differentiation (maturation) cell.” Cytochrome oxidase is present in two forms, depending on the context of acid-base internal environment : 1.- Form acidic (acidosis), which contains two Iron atoms, will be red, will absorb the additional green energy of the hydrogen atom, derived from carbohydrates, with formation of H2O, metabolic context that will promote cell proliferation. 2.-Form alkaline (alkalosis), containing two copper atoms, will be green, will absorb the additional red energy of the carbon atom, derived from carbohydrates, with formation of CO2, metabolic context that will promote cell differentiation. Cytochrome oxidase structure has two atoms of copper. It is known that in conditions of acidosis (oxidative potential), the principle electronegativity metals, copper is removed from combinations of the Iron. So cytochrome oxidase will contain two atoms of iron instead of copper atoms, which changes its oxidation-reduction potential, but (most important), and color. If the copper was green, the iron is red, which radically change its absorption spectrum, based on the principle of complementary colors.
    “Inner Light- Light of Life. Endogenous monochromatic irradiation. Red ferment of Warburg – Green ferment of Warburg.”
    In my opinion, at the basis of malign transformation is a disturbance of energetical metabolism, which reached a level that cell can not correct (after having succeeded before, many times), disturbance that affects the whole body in different degrees and requires corection from outside starting from the ideea that the final biological oxidizing takes place through photochemical process with releasing and receieving energy. If the structures involved in biological oxidation finals are colored, then their energy absorption is made based on the principle of complementary colors. If we can determine the absorption spectrum at different levels, we can control energy metabolism by chromotherapy – EXOGENOUS MONOCHROMATIC IRRADIATION . Energy absorption in biological oxidation process itself, based on complementary colors, the structures involved (cytochromes), is the nature of porphyrins, in combination with a metal becomes colored, will absorb the complementary color, corresponding to a specific absorption spectrum, it will be in – ENDOGENOUS MONOCHROMATIC IRRADIATION.
    This entitles us to believe that: In photosynthesis, light absorption and its storage form of carbohydrates, are selected, the colors, as in cellular energy metabolism, absorption of energy by the degradation of carbohydrates, is also done selectively, based on complementary colors. In the final biological oxidation, in addition to an oxidation-reduction process takes place and a photo-chemical process,based on complementary colors, the first in the electron transfer, the second in the energy transfer. So, in the mitochondria is a process of oxidation of atoms C and H, derived from carbohydrates, with energy release and absorption of its selection (the color), by the structures involved, which is the nature of porphyrins, are photosensitive and colorful, if we accept as coenzymes involved, containing a metal atom gives them a certain color, depending on the state of oxidation or reduction (red ferment of Warburg with iron, all copper cerloplasmin blue, green chlorophyll magnesium, red iron hemoglobin, green cytochrome oxidase with copper, etc.)
    According to the principle electronegativity metals, under certain conditions the acid-base imbalance (acidosis), iron will replace copper in combination , cytocromoxidase became inactive, leading to changing oxidation-reduction potential, BUT THE COLOR FROM GREEN, TO REED, to block the final biological oxidation and the appearance of aerobic glycolysis. In connection with my research proposal, to prove that the final biological oxidation, in addition to an oxidation-reduction process takes place and a photo-chemical process, the first in the electron transfer, the second in the energy transfer.
    I SUGGEST TO YOU AN EXPERIMENT:

    TWO PLANTS, A RED (CORAILLE) LIGHT ONLY, IN BASIC MEDIUM, WITH ADDED COPPER, WILL GROW, FLOWER AND FRUIT WILL SHORT TIME, AND THE OTHER ONLY GREEN LIGHT (TOURQUOISE), IN AN ACID MEDIUM, WITH ADDED COPPER CHELATOR , WHICH GROWS THROUGHOUT WILL NOT GROW FLOWERS AND FRUIT WILL DO.

    CULTURE OF NEOPLASTIC TISSUE, IRRADIATED WITH MONOCHROMATIC GREEN ( TOURQUOISE) LIGHT, IN AN ALKALINE MEDIUM, WITH ADDED COPPER, WILL IN REGRESSION OF THE TISSUE CULTURE.

    CULTURE OF NEOPLASTIC TISSUE, IRRADIATED WITH RED ( CORAILLE) LIGHT, IN AN ACID MEDIUM, WITH ADDED COPPER CHELATOR, WILL LEAD TO EXAGERATED AND ANARCHICAL MULTIPLICATION.
    If in photosynthesis is the direct effect of monochromatic irradiation, in the final biological oxidation effect is reversed. Exogenous irradiation with green, induces endogenous irradiation with red, and vice versa. A body with cancer disease will become chemically color “red”- Acid -(pH, Rh, pCO2, alkaline reserve), and in terms of energy, green (X-body-colored-ray). A healthy body will become chemically color “green”-Alkaline – (as evidenced by laboratory), and in terms of energy, red (visible by X-body-colored-ray). Sincerely yours, Dr. Viorel Bungau

    -In addition-
    Life balance: Darkness and Light – Water and Fire – Inn and Yang.

    Cytochrome oxidase structure has two atoms of copper. It is known that in conditions of acidosis (oxidative potential), the principle electronegativity metals, copper is removed from combinations of the Iron. So cytochrome oxidase will contain two atoms of iron instead of copper atoms, which changes its oxidation-reduction potential, but (most important), and color. If the copper was green, the iron is red, which radically change its absorption spectrum, based on the principle of complementary colors. If neoplastic cells, because acidosis is overactive acid form of cytochrome oxidase (red with iron atoms), which will absorb the additional green energy hydrogen atom (exclusively), the production of H20 , so water will prevail, in Schizophrenia , neuronal intracellular alkaline environment, will promote the basic form of cytochrome oxidase (green with copper atoms), which will oxidize only carbon atoms, the energy absorption of red (complementary) and production of CO2, so the fire will prevail. Drawn from this theory interdependent relationship between water and fire, of hydrogen(H2O) and carbon(CO2) ,in a controlled relationship with oxygen (O2). If photosynthesis is a process of reducing carbon oxide(CO2) and hydrogen oxide(H2O), by increasing electronegativity of C and H atoms, with the electrons back to oxygen, which will be released in the mitochondria is a process of oxidation of atoms C and H, derived from carbohydrates, with energy release and absorption of its selection (the color), by the structures involved, which is the nature of porphyrins, are photosensitive and colorful. It means that matter and energy in the universe are found in a relationship based on complementary colors, each color of energy, corresponding with a certain chemical structure. In my opinion, at the basis of malign transformation is a disturbance of energetical metabolism, which reached a level that cell can not correct (after having succeeded before, many times), disturbance that affects the whole body in different degrees and requires corection from outside starting from the ideea that the final biological oxidizing takes place through photochemical process with releasing and receieving energy. The final biological oxidation is achieved through a process of oxidation-reduction, while a photochemical process, based on the principle of complementary colors, if we accept as coenzymes involved, containing a metal atom gives them a certain color, depending on the state of oxidation or reduction (red ferment of Warburg with copper, all copper cerloplasmin blue, green chlorophyll magnesium, red iron hemoglobin,etc. If satisfied, the final biological oxidation is achieved by a photochemical mechanism (besides the oxidation-reduction), that energy is released based on complementary colors, means that we can control the final biological oxidation mechanism, irreversibly disrupted in cancer, by chromotherapy and correction of acid-base imbalance that underlies this disorder.We reached this conclusions studying the final biological oxidation, for understanding the biochemical mechanism of aerobic glycolysis in cancer. We found that cancer cell, energy metabolism is almost exclusively on hydrogen by oxidative dehydrogenation, due to excessive acidosis , coenzymes which makes carbon oxidation, as dormant (these coenzymes have become inactive). If we accept the nature of these coenzymes chloride (see Warburg ferment red), could be rectivate, by correcting acidosis (because that became leucoderivat), and by chromoterapie, on the basis of complementary colors. According to the principle electronegativity metals, under certain conditions the acid-base imbalance (acidosis), iron will replace copper in combination , cytocromoxidase became inactive (it contains two copper atoms) leading to changing oxidation-reduction potential, BUT THE COLOR FROM GREEN, TO REED, to block the final biological oxidation and the appearance of aerobic glycolysis.

    Malignant transformation occurs by energy metabolism imbalance in power generation purposes in the predominantly (exclusively) of the hydrogen atom of carbon oxidation is impossible. Thus at the cellular level will produce a multiplication (growth) exaggerated (exclusive), energy from hydrogen favoring growth, multiplication, at the expense of differentiation (maturation). Differentiation is achieved by energy obtained by oxidation of the carbon atom can not take, leading to carcinogenesis . The energy metabolism of the cell, an energy source is carbohydrate degradation, which is done by OXIDATIVE DEHYDROGENATION AND OXIDATIVE DECARBOXYLATION , to obtain energy and CO2 and H2O. In normal cells there is a balance between the two energy sources. If cancer cells, oxidation of the carbon atom is not possible, the cell being forced to summarize the only energy source available, of hydrogen. This disorder underlying malignant transformation of cells and affect the whole body, in various degrees, often managing to rebalance process, until at some point it becomes irreversible. The exclusive production of hydrogen energy will cause excessive multiplication, of immature cells, without functional differentiation. Exclusive carbon energy production will lead to hyperdifferentiation, hyperfunctional, multiplication is impossible. Normal cell is between two extremes, between some limits depending on the adjustment factors of homeostasis. Energy from energy metabolism is vital for cell (body). If the energy comes predominantly (or exclusively) by oxidation of the hydrogen atom, green energy, will occur at the structural level (biochemical), acidification of the cellular structures that will turn red, so WE HAVE MORPHOLOGICAL AND CHEMICAL STRUCTURES “RED”, WITH “GREEN” ENERGY. This background predisposes to accelerated growth, without differentiation, reaching up uncontrolled, anarchical. ENERGY STRUCTURE OF THE CELL BODY WOULD BE INN. If necessary energy cell derived mainly by oxidation of the carbon atom, red energy,cell structures will be colored green, will be alkaline(basic), so WE HAVE MORPHOLOGICAL AND CHEMICAL STRUCTURES “GREEN”, WITH “RED” ENERGY, on the same principle of complementarity. This context will lead hyperdifferentiation, hyperfunctional ,maturation, and grouth stops. ENERGY STRUCTURE OF THE CELL BODY WOULD BE YANG. If in photosynthesis, porphyrins chemicals group, whic be photosensitivity (their first feature), shows and a great affinity for metals with chelate forming and becoming colored (pigments of life), can absorb monochromatic light complementary, so if these pigments, which constitutes the group of chromoprotheine, in photosynthesis will achieve CO2 and H2O reduction the recovery of C, H respectively, and the issuance of and release of O, atoms as H and C that reduced the energy load, representing carbohydrates, is in the form of solar energy storage, in cellular energy metabolism, processes necessary life, energy will come from the degradation of substances produced in photosynthesis, the carbohydrates, by oxidative dehydrogenation and oxidative decarboxylation, through like substances, which form chelates with the metals, are colored, metals contained in the form of oxides of various colors(green Mg, red Fe, blue Cu,etc.),suffering from complementary color absorption process of reduction with H in case,if the oxidative dehydrogenation, when chelated metal pigment is red, becoming leucoderivat (colorless) by absorbing complementary color (green) of hydrogen, formation of H2O, or C, if the oxidative decarboxylation when chelated metallic pigment is green, energy absorbing additional, red energy of atom C, CO2 production, the process is identical. The process that lies at base cellular energy metabolism, takes place in the final biological oxidation, reducing the O atom in the form of metal oxide, in combination with photosensitive substance, porohyrin, colorful,absorbing complementary color, will reduce the O atom, with H and C, with the production of H2O and CO2. Green energy release of H atom in the oxidative dehydrogenation process, it is a process of”IRRADIATION MONOCHROMATIC ENDOGENOUS WITH GREEN”, and red energy release of C atom in the oxidative decarboxylation process, consists in an “IRRADIATION MONOCHROMATIC ENDOGENOUS WITH RED”. Porphyrin-metal combination in photosynthesis, the chelated form, by absorbing light in the visible spectrum, will be able to reduce to low and turn, C and H respectively, the state of oxide (CO2 and H2O),release of O. The final biological oxidation, the combination of metal-porphyrins in aerobically in the absence of light, will find in the oxidized state, so in the form of porphyrins and metal-oxide, will oxidize to C and H atom of hydrocarbonates, with formation of CO2 and H2O, or rather, will be reduced by C and H atom of hydrocarbonates,formation of CO2 and H2O, by absorbing energy produced by photosynthesis. If we can control the final biological oxidation, we can control cellular growth, thus multiplying, and on the other hand, maturation, so differentiation. Green energy will prevail if the cell (body) which multiplies (during growth), will in case of adult cell (functional) will prevail red energy . The two types of energy, that obtained by oxidative dehydrogenation , which will cause cell multiplication without differentiation , and that obtained by oxidative decarboxylation , which will be to stop proliferation, and will determine the differentiation (maturity, functionality). This process is carried out based on complementary colors, which are coenzymes oxidative dehydrogenation and oxidative decarboxylation is colored . It reveals the importance of acid-base balance, the predominance of the acidic or basic, as an acid structure (red), not only can gain energy from the carbon atom red (the principle of complementarity), but can not assimilate ( under the same principle). It must therefore acid-base balance of internal environment, and alkalinization his intake of organic substances by the electron donor. By alkalinization (addition of electrons) will occur neutralize acid structures, the red, they become leucoderivat, colorless, and inactive, while the basic, which because of acidosis became neutral, colorless and inactive, will be alkaline in electron contribution, will be in green, and will absorb red energy from the carbon atom. So, on two kinds of vital energy, it is clear correlation between the chemical structure of the cell(body),and type of energy that can produce and use. Thus a cell with acidic chemical structure, can produce only energy by oxidative dehydrogenation (green energy), because the acid can only be active coenzymes with acid chemical structure, red, will absorb the complementarity only green energy of hydrogen. Basic structures which should absorb red energy from carbon , are inactive due to acid environment, which in turn chemically in leucoderivat, so colorless structures, inactive. Conversion of these structures to normal, operation by alkalinization could be a long lasting process, therefore, we use parallel chromotherapy, based on the fact that these COENZYMES INVOLVED IN BIOLOGICAL OXIDATION FINALS ARE COLORED AND PHOTOSENSITIVE. Thus, exogenous irradiation with monochromatic green will neutralize, by complementarity, coenzymes red, acidic. In will reactivate alkaline coenzymes, which have become due acidosis leucoderivat, so colorless and inactive. Without producing CO2, carbonic anhydrase can not form H2CO3, severable and thus transferred through mitochondrial membrane. Will accumulate in the respiratory Flavin, OH groups, leading to excessive hydroxylation, followed by consecutive inclusion of amino (NH2). It is thus an imbalance between the hydrogenation-carboxylation and hydroxylation-amination, in favor of the latter. This will predominate AMINATION and HYDROXYLATION at the expense CARBOXYLATION and HYDROGENATION, leading to CONVERSION OF STRUCTURAL PROTEINS IN NUCLEIC ACIDS. Meanwhile, after chemical criteria not genetic, it synthesizes the remaining unoxidized carbon atoms, nucleic bases “de novo” by the same process of hydroxylation-amination, leading to THE SYNTHESIS OF NUCLEIC ACIDS “DE NOVO”. Sincerely yours, Dr. Viorel Bungau viorelbungau20@yahoo.com

  20. […] Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View? Author: Larry H. Bernstein, MD, FCAP https://pharmaceuticalintelligence.com/2012/10/17/is-the-warburg-effect-the-cause-or-the-effect-of-ca… […]

Case Study #2:

·      Knowing the tumor’s size and location, could we target treatment to THE ROI by applying…..

Author: Dror Nir, PhD

https://pharmaceuticalintelligence.com/2012/10/16/knowing-the-tumors-size-and-location-could-we-target-treatment-to-the-roi-by-applying-imaging-guided-intervention/

26 Responses

  1. GREAT work.

    I’ll read and comment later on

  2. Highlights of The 2012 Johns Hopkins Prostate Disorders White Paper include:

    A promising new treatment for men with frequent nighttime urination.
    Answers to 8 common questions about sacral nerve stimulation for lower urinary tract symptoms.
    Surprising research on the link between smoking and prostate cancer recurrence.
    How men who drink 6 cups of coffee a day or more may reduce their risk of aggressive prostate cancer.
    Should you have a PSA screening test? Answers to important questions on the controversial USPSTF recommendation.
    Watchful waiting or radical prostatectomy for men with early-stage prostate cancer? What the research suggests.
    A look at state-of-the-art surveillance strategies for men on active surveillance for prostate cancer.
    Locally advanced prostate cancer: Will you benefit from radiation and hormones?
    New drug offers hope for men with metastatic castrate-resistant prostate cancer.
    Behavioral therapy for incontinence: Why it might be worth a try.

    You’ll also get the latest news on benign prostatic enlargement (BPE), also known as benign prostatic hyperplasia (BPH) and prostatitis:
    What’s your Prostate Symptom Score? Here’s a quick quiz you can take right now to determine if you should seek treatment for your enlarged prostate.
    Your surgical choices: a close look at simple prostatectomy, transurethral prostatectomy and open prostatectomy.
    New warnings about 5-alpha-reductase inhibitors and aggressive prostate cancer.

  3. Promising technique.

    INCORE pointed out in detail about the general problem judging response and the stil missing quality in standardization:

    http://www.futuremedicine.com/doi/abs/10.2217/fon.12.78?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov

    I did research in response evaluation and prediction for about 15y now and being honest: neither the clinical, nor the molecular biological data proved significant benefit in changing a strategy in patient diagnosis and / or treatment. I would state: this brings us back on the ground and not upon the sky. Additionally it means: we have to ´work harder on that and the WHO has to take responsibility: clinicians use a reponse classification without knowing, that this is just related to “ONE” experiment from the 70’s and that this experiment never had been rescrutinized (please read the Editorial I provided – we use a clinical response classification since more than 30 years worldwide (Miller et al. Cancer 1981) but it is useless !

  4. Dr. BB

    Thank you for your comment.
    Dr. Nir will reply to your comment.
    Regarding the Response Classification in use, it seems that the College of Oncology should champion a task force to revisit the Best Practice in use in this domain and issue a revised version or a new effort for a a new classification system for Clinical Response to treatment in Cancer.

  5. I’m sorry that I was looking for this paper again earlier and didn’t find it. I answered my view on your article earlier.

    This is a method demonstration, but not a proof of concept by any means. It adds to the cacophany of approaches, and in a much larger study would prove to be beneficial in treatment, but not a cure for serious prostate cancer because it is unlikely that it can get beyond the margin, and also because there is overtreatment at the cutoff of PSA at 4.0. There is now a proved prediction model that went to press some 4 months ago. I think that the pathologist has to see the tissue, and the standard in pathology now is for any result that is cancer, two pathologist or a group sitting together should see it. It’s not an easy diagnosis.

    Björn LDM Brücher, Anton Bilchik, Aviram Nissan, Itzhak Avital, & Alexander Stojadinovic. Tumor response criteria: are they appropriate? Future Oncol. (2012) 8(8), 903–906. 10.2217/FON.12.78. ISSN 1479-6694.

    ..Tumor heterogeneity is a ubiquitous phemomenon. In particular, there are important differences among the various types of gastrointestinal (GI) cancers in terms of tumor biology, treatment response and prognosis.

    ..This forms the principal basis for targeted therapy directed by tumor-specific testing at either the gene or protein level. Despite rapid advances in our understanding of targeted therapy for GI cancers, the impact on cancer survival has been marginal.

    ..Can tumor response to therapy be predicted, thereby improving the selection of patients for cancer treatment?

    ..In 2000 theNCI with the European Association for Research and Treatment of Cancer, proposed a replacement of 2D measurement with a decrease in the largest tumor diameter by 30% in one dimension. Tumor response as defined would translate into a 50% decrease for a spherical lesion

    ..We must rethink how we may better determine treatment response in a reliable, reproducible way that is aimed at individualizing the therapy of cancer patients.

    ..we must change the tools we use to assess tumor response. The new modality should be based on empirical evidence that translates into relevant and meaningful clinical outcome data.

    ..This becomes a conundrum of sorts in an era of ‘minimally invasive treatment’.

    ..integrated multidisciplinary panel of international experts – not sure that that will do it

    Several years ago i heard Stamey present the totality of his work at Stanford, with great disappointment over hsPSA that they pioneered in. The outcomes were disappointing.

    I had published a review of all of our cases reviewed for 1 year with Marguerite Pinto.
    There’s a reason that the physicians line up outside of her office for her opinion.
    The review showed that a PSA over 24 ng/ml is predictive of bone metastasis. Any result over 10 was as likely to be prostatitis, BPH or cancer.

    I did an ordinal regression in the next study with Gustave Davis using a bivariate ordinal regression to predict lymph node metastasis using the PSA and the Gleason score. It was better than any univariate model, but there was no followup.

    I reviewed a paper for Clin Biochemistry (Elsevier) on a new method for PSA, very different than what we are familiar with. It was the most elegant paper I have seen in the treatment of the data. The model could predict post procedural time to recurrence to 8 years.

    • I hope we are in agreement on the fact that imaging guided interventions are needed for better treatment outcome. The point I’m trying to make in this post is that people are investing in developing imaging guided intervention and it is making progress.

      Over diagnosis and over treatment is another issue altogether. I think that many of my other posts are dealing with that.

  6. Tumor response criteria: are they appropriate?
    Future Oncology 2012; 8(8): 903-906 , DOI 10.2217/fon.12.78 (doi:10.2217/fon.12.78)
    Björn LDM Brücher, Anton Bilchik, Aviram Nissan, Itzhak Avital & Alexander Stojadinovic
    Tumor heterogeneity is a problematic because of differences among the metabolic variety among types of gastrointestinal (GI) cancers, confounding treatment response and prognosis.
    This is in response to … a group of investigators from Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada who evaluate the feasibility and safety of magnetic resonance (MR) imaging–controlled transurethral ultrasound therapy for prostate cancer in humans. Their study’s objective was to prove that using real-time MRI guidance of HIFU treatment is possible and it guarantees that the location of ablated tissue indeed corresponds to the locations planned for treatment.
    1. There is a difference between expected response to esophageal or gastric neoplasms both biologically and in expected response, even given variability within a class. The expected time to recurrence is usually longer in the latter case, but the confounders are – age at time of discovery, biological time of detection, presence of lymph node and/or distant metastasis, microscopic vascular invasion.
    2. There is a long latent period in abdominal cancers before discovery, unless a lesion is found incidentally in surgery for another reason.
    3. The undeniable reality is that it is not difficult to identify the main lesion, but it is difficult to identify adjacent epithelium that is at risk (transitional or pretransitional). Pathologists have a very good idea about precancerous cervical neoplasia.

    The heterogeneity rests within each tumor and between the primary and metastatic sites, which is expected to be improved by targeted therapy directed by tumor-specific testing. Despite rapid advances in our understanding of targeted therapy for GI cancers, the impact on cancer survival has been marginal.

    The heterogeneity is a problem that will take at least another decade to unravel because of the number of signaling pathways and the crosstalk that is specifically at issue.

    I must refer back to the work of Frank Dixon, Herschel Sidransky, and others, who did much to develop a concept of neoplasia occurring in several stages – minimal deviation and fast growing. These have differences in growth rates, anaplasia, and biochemical. This resembles the multiple “hit” theory that is described in “systemic inflammatory” disease leading to a final stage, as in sepsis and septic shock.
    In 1920, Otto Warburg received the Nobel Prize for his work on respiration. He postulated that cancer cells become anaerobic compared with their normal counterpart that uses aerobic respiration to meet most energy needs. He attributed this to “mitochondrial dysfunction. In fact, we now think that in response to oxidative stress, the mitochondrion relies on the Lynen Cycle to make more cells and the major source of energy becomes glycolytic, which is at the expense of the lean body mass (muscle), which produces gluconeogenic precursors from muscle proteolysis (cancer cachexia). There is a loss of about 26 ATP ~Ps in the transition.
    The mitochondrial gene expression system includes the mitochondrial genome, mitochondrial ribosomes, and the transcription and translation machinery needed to regulate and conduct gene expression as well as mtDNA replication and repair. Machinery involved in energetics includes the enzymes of the Kreb’s citric acid or TCA (tricarboxylic acid) cycle, some of the enzymes involved in fatty acid catabolism (β-oxidation), and the proteins needed to help regulate these systems. The inner membrane is central to mitochondrial physiology and, as such, contains multiple protein systems of interest. These include the protein complexes involved in the electron transport component of oxidative phosphorylation and proteins involved in substrate and ion transport.
    Mitochondrial roles in, and effects on, cellular homeostasis extend far beyond the production of ATP, but the transformation of energy is central to most mitochondrial functions. Reducing equivalents are also used for anabolic reactions. The energy produced by mitochondria is most commonly thought of to come from the pyruvate that results from glycolysis, but it is important to keep in mind that the chemical energy contained in both fats and amino acids can also be converted into NADH and FADH2 through mitochondrial pathways. The major mechanism for harvesting energy from fats is β-oxidation; the major mechanism for harvesting energy from amino acids and pyruvate is the TCA cycle. Once the chemical energy has been transformed into NADH and FADH2 (also discovered by Warburg and the basis for a second Nobel nomination in 1934), these compounds are fed into the mitochondrial respiratory chain.
    The hydroxyl free radical is extremely reactive. It will react with most, if not all, compounds found in the living cell (including DNA, proteins, lipids and a host of small molecules). The hydroxyl free radical is so aggressive that it will react within 5 (or so) molecular diameters from its site of production. The damage caused by it, therefore, is very site specific. The reactions of the hydroxyl free radical can be classified as hydrogen abstraction, electron transfer, and addition.
    The formation of the hydroxyl free radical can be disastrous for living organisms. Unlike superoxide and hydrogen peroxide, which are mainly controlled enzymatically, the hydroxyl free radical is far too reactive to be restricted in such a way – it will even attack antioxidant enzymes. Instead, biological defenses have evolved that reduce the chance that the hydroxyl free radical will be produced and, as nothing is perfect, to repair damage.
    Currently, some endogenous markers are being proposed as useful measures of total “oxidative stress” e.g., 8-hydroxy-2’deoxyguanosine in urine. The ideal scavenger must be non-toxic, have limited or no biological activity, readily reach the site of hydroxyl free radical production (i.e., pass through barriers such as the blood-brain barrier), react rapidly with the free radical, be specific for this radical, and neither the scavenger nor its product(s) should undergo further metabolism.
    Nitric oxide has a single unpaired electron in its π*2p antibonding orbital and is therefore paramagnetic. This unpaired electron also weakens the overall bonding seen in diatomic nitrogen molecules so that the nitrogen and oxygen atoms are joined by only 2.5 bonds. The structure of nitric oxide is a resonance hybrid of two forms.
    In living organisms nitric oxide is produced enzymatically. Microbes can generate nitric oxide by the reduction of nitrite or oxidation of ammonia. In mammals nitric oxide is produced by stepwise oxidation of L-arginine catalyzed by nitric oxide synthase (NOS). Nitric oxide is formed from the guanidino nitrogen of the L-arginine in a reaction that consumes five electrons and requires flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) tetrahydrobiopterin (BH4), and iron protoporphyrin IX as cofactors. The primary product of NOS activity may be the nitroxyl anion that is then converted to nitric oxide by electron acceptors.
    The thiol-disulfide redox couple is very important to oxidative metabolism. GSH is a reducing cofactor for glutathione peroxidase, an antioxidant enzyme responsible for the destruction of hydrogen peroxide. Thiols and disulfides can readily undergo exchange reactions, forming mixed disulfides. Thiol-disulfide exchange is biologically very important. For example, GSH can react with protein cystine groups and influence the correct folding of proteins, and it GSH may play a direct role in cellular signaling through thiol-disulfide exchange reactions with membrane bound receptor proteins (e.g., the insulin receptor complex), transcription factors (e.g., nuclear factor κB), and regulatory proteins in cells. Conditions that alter the redox status of the cell can have important consequences on cellular function.
    So the complexity of life is not yet unraveled.

    Can tumor response to therapy be predicted, thereby improving the selection of patients for cancer treatment?
    The goal is not just complete response. Histopathological response seems to be related post-treatment histopathological assessment but it is not free from the challenge of accurately determining treatment response, as this method cannot delineate whether or not there are residual cancer cells. Functional imaging to assess metabolic response by 18-fluorodeoxyglucose PET also has its limits, as the results are impacted significantly by several variables:

    • tumor type
    • sizing
    • doubling time
    • anaplasia?
    • extent of tumor necrosis
    • type of antitumor therapy and the time when response was determined.
    The new modality should be based on individualized histopathology as well as tumor molecular, genetic and functional characteristics, and individual patients’ characteristics, a greater challenge in an era of ‘minimally invasive treatment’.
    This listing suggests that for every cancer the following data has to be collected (except doubling time). If there are five variables, the classification based on these alone would calculate to be very sizable based on Eugene Rypka’s feature extraction and classification. But looking forward, time to remission and disease free survival are additionally important. Treatment for cure is not the endpoint, but the best that can be done is to extend the time of survival to a realistic long term goal and retain a quality of life.

    Brücher BLDM, Piso P, Verwaal V et al. Peritoneal carcinomatosis: overview and basics. Cancer Invest.30(3),209–224 (2012).
    Brücher BLDM, Swisher S, Königsrainer A et al. Response to preoperative therapy in upper gastrointestinal cancers. Ann. Surg. Oncol.16(4),878–886 (2009).
    Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer47(1),207–214 (1981).
    Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl Cancer Inst.92(3),205–216 (2000).
    Brücher BLDM, Becker K, Lordick F et al. The clinical impact of histopathological response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas. Cancer106(10),2119–2127 (2006).

    • Dr. Larry,

      Thank you for this comment.

      Please carry it as a stand alone post, Dr. Ritu will refer to it and reference it in her FORTHCOMING pst on Tumor Response which will integrate multiple sources.

      Please execute my instruction

      Thank you

    • Thank you Larry for this educating comment. It explains very well why the Canadian investigators did not try to measure therapy response!

      What they have demonstrated is the technological feasibility of coupling a treatment device to an imaging device and use that in order to guide the treatment to the right place.

      the issue of “choice of treatment” to which you are referring is not in the scope of this publication.
      The point is: if one treatment modality can be guided, other can as well! This should encourage others, to try and develop imaging-based treatment guidance systems.

  7. The crux of the matter in terms of capability is that the cancer tissue, adjacent tissue, and the fibrous matrix are all in transition to the cancerous state. It is taught to resect leaving “free margin”, which is better aesthetically, and has had success in breast surgery. The dilemma is that the patient may return, but how soon?

    • Correct. The philosophy behind lumpectomy is preserving quality of life. It was Prof. Veronesi (IEO) who introduced this method 30 years ago noticing that in the majority of cases, the patient will die from something else before presenting recurrence of breast cancer..

      It is well established that when the resection margins are declared by a pathologist (as good as he/she could be) as “free of cancer”, the probability of recurrence is much lower than otherwise.

  8. Dr. Larry,

    To assist Dr. Ritu, PLEASE carry ALL your comments above into a stand alone post and ADD to it your comment on my post on MIS

    Thank you

  9. Great post! Dr. Nir, can the ultrasound be used in conjunction with PET scanning as well to determine a spatial and functional map of the tumor. With a disease like serous ovarian cancer we typically see an intraperitoneal carcimatosis and it appears that clinicians are wanting to use fluorogenic probes and fiberoptics to visualize the numerous nodules located within the cavity Also is the technique being used mainy for surgery or image guided radiotherapy or can you use this for detecting response to various chemotherapeutics including immunotherapy.

    • Ultrasound can and is actually used in conjunction with PET scanning in many cases. The choice of using ultrasound is always left to the practitioner! Being a non-invasive, low cost procedure makes the use of ultrasound a non-issue. The down-side is that because it is so easy to access and operate, nobody bothers to develop rigorous guidelines about using it and the benefits remains the property of individuals.

      In regards to the possibility of screening for ovarian cancer and characterising pelvic masses using ultrasound I can refer you to scientific work in which I was involved:

      1. VAES (E.), MANCHANDA (R), AUTIER, NIR (R), NIR (D.), BLEIBERG (H.), ROBERT (A.), MENON (U.). Differential diagnosis of adnexal masses: Sequential use of the Risk of Malignancy Index and a novel computer aided diagnostic tool. Published in Ultrasound in Obstetrics & Gynecology. Issue 1 (January). Vol. 39. Page(s): 91-98.

      2. VAES (E.), MANCHANDA (R), NIR (R), NIR (D.), BLEIBERG (H.), AUTIER (P.), MENON (U.), ROBERT (A.). Mathematical models to discriminate between benign and malignant adnexal masses: potential diagnostic improvement using Ovarian HistoScanning. Published in International Journal of Gynecologic Cancer (IJGC). Issue 1. Vol. 21. Page(s): 35-43.

      3. LUCIDARME (0.), AKAKPO (J.-P.), GRANBERG (S.), SIDERI (M.), LEVAVI (H.), SCHNEIDER (A.), AUTIER (P.), NIR (D.), BLEIBERG (H.). A new computer aided diagnostic tool for non-invasive characterisation of malignant ovarian masses: Results of a multicentre validation study. Published in European Radiology. Issue 8. Vol. 20. Page(s): 1822-1830.

      Dror Nir, PhD
      Managing partner

      BE: +32 (0) 473 981896
      UK: +44 (0) 2032392424

      web: http://www.radbee.com/
      blogs: http://radbee.wordpress.com/ ; http://www.MedDevOnIce.com

       

  10. totally true and i am very thankfull for these briliant comments.

    Remember: 10years ago: every cancer researcher stated: “look at the tumor cells only – forget the stroma”. The era of laser-captured tumor-cell dissection started. Now , everyone knows: it is a system we are looking at and viewing and analyzing tumor cells only is really not enough.

    So if we would be honest, we would have to declare, that all data, which had been produced 13-8years ago, dealing with laser capture microdissection, that al these data would need a re-scrutinization, cause the influence of the stroma was “forgotten”. I ‘d better not try thinking about the waisted millions of dollars.

    If we keep on being honest: the surgeon looks at the “free margin” in a kind of reductionable model, the pathologist is more the control instance. I personally see the pathologist as “the control instance” of surgical quality. Therefore, not the wish of the surgeon is important, the objective way of looking into problems or challenges. Can a pathologist always state, if a R0-resection had been performed ?

    The use of the Resectability Classification:
    There had been many many surrogate marker analysis – nothing new. BUT never a real substantial well tought through structured analysis had been done: mm by mm by mm by mm and afterwards analyzing that by a ROC analysis. BUt against which goldstandard ? If you perform statistically a ROC analysis – you need a golstandard to compare to. Therefore what is the real R0-resectiòn? It had been not proven. It just had been stated in this or that tumor entity that this or that margin with this margin free mm distance or that mm distance is enough and it had been declared as “the real R0-classification”. In some organs it is very very difficult and we all (surgeons, pathologists, clinicians) that we always get to the limit, if we try interpretating the R-classification within the 3rd dimension. Often it is just declared and stated.

    Otherwise: if lymph nodes are negative it does not mean, lymph nodes are really negative, cause up to 38% for example in upper GI cancers have histological negative lymph nodes, but immunohistochemical positive lymph nodes. And this had been also shown by Stojadinovic at el analyzing the ultrastaging in colorectal cancer. So the 4th dimension of cancer – the lymph nodes / the lymphatic vessel invasion are much more important than just a TNM classification, which unfortunately does often not reflect real tumor biology.

    AS we see: cancer has multifactorial reasons and it is necessary taking the challenge performing high sophisticated research by a multifactorial and multidisciplinary manner.

    Again my deep and heartly thanks for that productive and excellent discussion !

    • Dr. BB,

      Thank you for your comment.

      Multidisciplinary perspectives have illuminated the discussion on the pages of this Journal.

      Eager to review Dr. Ritu’s forthcoming paper – the topic has a life of its own and is embodied in your statement:

      “the 4th dimension of cancer – the lymph nodes / the lymphatic vessel invasion are much more important than just a TNM classification, which unfortunately does often not reflect real tumor biology.”

    • Thank you BB for your comment. You have touched the core limitation of healthcare professionals: how do we know that we know!

      Do we have a reference to each of the test we perform?

      Do we have objective and standardise quality measures?

      Do we see what is out-there or are we imagining?

      The good news: Everyday we can “think” that we learned something new. We should be happy with that, even if it is means that we learned that yesterday’s truth is not true any-more and even if we are likely to be wrong again…:)

      But still, in the last decades, lots of progress was made….

  11. Dr. Nir,
    I thoroughly enjoyed reading your post as well as the comments that your post has attracted. There were different points of view and each one has been supported with relevant examples in the literature. Here are my two cents on the discussion:
    The paper that you have discussed had the objective of finding out whether real-time MRI guidance of treatment was even possible and if yes, and also if the treatment could be performed in accurate location of the ROI? The data reveals they were pretty successful in accomplishing their objective and of course that gives hope to the imaging-based targeted therapies.
    Whether the ROI is defined properly and if it accounts for the real tumor cure, is a different question. Role of pathologists and the histological analysis they bring about to the table cannot be ruled out, and the absence of a defined line between the tumor and the stromal region in the vicinity is well documented. However, that cannot rule out the value and scope of imaging-based detection and targeted therapy. After all, it is seminal in guiding minimally invasive surgery. As another arm of personalized medicine-based cure for cancer, molecular biologists at MD Anderson have suggested molecular and genetic profiling of the tumor to determine genetic aberrations on the basis of which matched-therapy could be recommended to patients. When phase I trial was conducted, the results were obtained were encouraging and the survival rate was better in matched-therapy patients compared to unmatched patients. Therefore, everytime there is more to consider when treating a cancer patient and who knows a combination of views of oncologists, pathologists, molecular biologists, geneticists, surgeons would device improvised protocols for diagnosis and treatment. It is always going to be complicated and generalizations would never give an answer. Smart interpretations of therapies – imaging-based or others would always be required!

    Ritu

    • Dr. Nir,
      One of your earlier comments, mentioned the non invasiveness of ultrasound, thus, it’s prevalence in use for diagnosis.

      This may be true for other or all areas with the exception of Mammography screening. In this field, an ultrasound is performed only if a suspected area of calcification or a lump has been detected in the routine or patient-initiated request for ad hoc mammography secondery to patient complain of pain or patient report of suspected lump.

      Ultrasound in this field repserents ascalation and two radiologists review.

      It in routine use for Breast biopsy.

    • Thanks Ritu for this supporting comment. The worst enemy of finding solutions is doing nothing while using the excuse of looking for the “ultimate solution” . Personally, I believe in combining methods and improving clinical assessment based on information fusion. Being able to predict, and then timely track the response to treatment is a major issue that affects survival and costs!

  12. […] Dror Nir authored a post on October 16th titled “Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-gu…” The article attracted a lot of comments from readers including researchers and oncologists and […]

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  14. […] ted in this area; New clinical results supports Imaging-guidance for targeted prostate biopsy and Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-gu… Today I report on recent publication presenting the advantage of using targeted trans-perineal […]

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Case Study #3:

  • Personalized Medicine: Cancer Cell Biology and Minimally Invasive Surgery (MIS)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/01/personalized-medicine-cancer-cell-biology-and-minimally-invasive-surgery-mis

 

This article generated a Scientific Exchange of 24 Comments, some scholarly comments are quite lengthy

24 Responses

  1. GREAT work.

    I’ll read and comment later on

  2. Highlights of The 2012 Johns Hopkins Prostate Disorders White Paper include:

    A promising new treatment for men with frequent nighttime urination.
    Answers to 8 common questions about sacral nerve stimulation for lower urinary tract symptoms.
    Surprising research on the link between smoking and prostate cancer recurrence.
    How men who drink 6 cups of coffee a day or more may reduce their risk of aggressive prostate cancer.
    Should you have a PSA screening test? Answers to important questions on the controversial USPSTF recommendation.
    Watchful waiting or radical prostatectomy for men with early-stage prostate cancer? What the research suggests.
    A look at state-of-the-art surveillance strategies for men on active surveillance for prostate cancer.
    Locally advanced prostate cancer: Will you benefit from radiation and hormones?
    New drug offers hope for men with metastatic castrate-resistant prostate cancer.
    Behavioral therapy for incontinence: Why it might be worth a try.

    You’ll also get the latest news on benign prostatic enlargement (BPE), also known as benign prostatic hyperplasia (BPH) and prostatitis:
    What’s your Prostate Symptom Score? Here’s a quick quiz you can take right now to determine if you should seek treatment for your enlarged prostate.
    Your surgical choices: a close look at simple prostatectomy, transurethral prostatectomy and open prostatectomy.
    New warnings about 5-alpha-reductase inhibitors and aggressive prostate cancer.

  3. Promising technique.

    INCORE pointed out in detail about the general problem judging response and the stil missing quality in standardization:

    http://www.futuremedicine.com/doi/abs/10.2217/fon.12.78?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov

    I did research in response evaluation and prediction for about 15y now and being honest: neither the clinical, nor the molecular biological data proved significant benefit in changing a strategy in patient diagnosis and / or treatment. I would state: this brings us back on the ground and not upon the sky. Additionally it means: we have to ´work harder on that and the WHO has to take responsibility: clinicians use a reponse classification without knowing, that this is just related to “ONE” experiment from the 70′s and that this experiment never had been rescrutinized (please read the Editorial I provided – we use a clinical response classification since more than 30 years worldwide (Miller et al. Cancer 1981) but it is useless !

  4. Dr. BB

    Thank you for your comment.
    Dr. Nir will reply to your comment.
    Regarding the Response Classification in use, it seems that the College of Oncology should champion a task force to revisit the Best Practice in use in this domain and issue a revised version or a new effort for a a new classification system for Clinical Response to treatment in Cancer.

  5. I’m sorry that I was looking for this paper again earlier and didn’t find it. I answered my view on your article earlier.

    This is a method demonstration, but not a proof of concept by any means. It adds to the cacophany of approaches, and in a much larger study would prove to be beneficial in treatment, but not a cure for serious prostate cancer because it is unlikely that it can get beyond the margin, and also because there is overtreatment at the cutoff of PSA at 4.0. There is now a proved prediction model that went to press some 4 months ago. I think that the pathologist has to see the tissue, and the standard in pathology now is for any result that is cancer, two pathologist or a group sitting together should see it. It’s not an easy diagnosis.

    Björn LDM Brücher, Anton Bilchik, Aviram Nissan, Itzhak Avital, & Alexander Stojadinovic. Tumor response criteria: are they appropriate? Future Oncol. (2012) 8(8), 903–906. 10.2217/FON.12.78. ISSN 1479-6694.

    ..Tumor heterogeneity is a ubiquitous phemomenon. In particular, there are important differences among the various types of gastrointestinal (GI) cancers in terms of tumor biology, treatment response and prognosis.

    ..This forms the principal basis for targeted therapy directed by tumor-specific testing at either the gene or protein level. Despite rapid advances in our understanding of targeted therapy for GI cancers, the impact on cancer survival has been marginal.

    ..Can tumor response to therapy be predicted, thereby improving the selection of patients for cancer treatment?

    ..In 2000 theNCI with the European Association for Research and Treatment of Cancer, proposed a replacement of 2D measurement with a decrease in the largest tumor diameter by 30% in one dimension. Tumor response as defined would translate into a 50% decrease for a spherical lesion

    ..We must rethink how we may better determine treatment response in a reliable, reproducible way that is aimed at individualizing the therapy of cancer patients.

    ..we must change the tools we use to assess tumor response. The new modality should be based on empirical evidence that translates into relevant and meaningful clinical outcome data.

    ..This becomes a conundrum of sorts in an era of ‘minimally invasive treatment’.

    ..integrated multidisciplinary panel of international experts – not sure that that will do it

    Several years ago i heard Stamey present the totality of his work at Stanford, with great disappointment over hsPSA that they pioneered in. The outcomes were disappointing.

    I had published a review of all of our cases reviewed for 1 year with Marguerite Pinto.
    There’s a reason that the physicians line up outside of her office for her opinion.
    The review showed that a PSA over 24 ng/ml is predictive of bone metastasis. Any result over 10 was as likely to be prostatitis, BPH or cancer.

    I did an ordinal regression in the next study with Gustave Davis using a bivariate ordinal regression to predict lymph node metastasis using the PSA and the Gleason score. It was better than any univariate model, but there was no followup.

    I reviewed a paper for Clin Biochemistry (Elsevier) on a new method for PSA, very different than what we are familiar with. It was the most elegant paper I have seen in the treatment of the data. The model could predict post procedural time to recurrence to 8 years.

    • I hope we are in agreement on the fact that imaging guided interventions are needed for better treatment outcome. The point I’m trying to make in this post is that people are investing in developing imaging guided intervention and it is making progress.

      Over diagnosis and over treatment is another issue altogether. I think that many of my other posts are dealing with that.

  6. Tumor response criteria: are they appropriate?
    Future Oncology 2012; 8(8): 903-906 , DOI 10.2217/fon.12.78 (doi:10.2217/fon.12.78)
    Björn LDM Brücher, Anton Bilchik, Aviram Nissan, Itzhak Avital & Alexander Stojadinovic
    Tumor heterogeneity is a problematic because of differences among the metabolic variety among types of gastrointestinal (GI) cancers, confounding treatment response and prognosis.
    This is in response to … a group of investigators from Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada who evaluate the feasibility and safety of magnetic resonance (MR) imaging–controlled transurethral ultrasound therapy for prostate cancer in humans. Their study’s objective was to prove that using real-time MRI guidance of HIFU treatment is possible and it guarantees that the location of ablated tissue indeed corresponds to the locations planned for treatment.
    1. There is a difference between expected response to esophageal or gastric neoplasms both biologically and in expected response, even given variability within a class. The expected time to recurrence is usually longer in the latter case, but the confounders are – age at time of discovery, biological time of detection, presence of lymph node and/or distant metastasis, microscopic vascular invasion.
    2. There is a long latent period in abdominal cancers before discovery, unless a lesion is found incidentally in surgery for another reason.
    3. The undeniable reality is that it is not difficult to identify the main lesion, but it is difficult to identify adjacent epithelium that is at risk (transitional or pretransitional). Pathologists have a very good idea about precancerous cervical neoplasia.

    The heterogeneity rests within each tumor and between the primary and metastatic sites, which is expected to be improved by targeted therapy directed by tumor-specific testing. Despite rapid advances in our understanding of targeted therapy for GI cancers, the impact on cancer survival has been marginal.

    The heterogeneity is a problem that will take at least another decade to unravel because of the number of signaling pathways and the crosstalk that is specifically at issue.

    I must refer back to the work of Frank Dixon, Herschel Sidransky, and others, who did much to develop a concept of neoplasia occurring in several stages – minimal deviation and fast growing. These have differences in growth rates, anaplasia, and biochemical. This resembles the multiple “hit” theory that is described in “systemic inflammatory” disease leading to a final stage, as in sepsis and septic shock.
    In 1920, Otto Warburg received the Nobel Prize for his work on respiration. He postulated that cancer cells become anaerobic compared with their normal counterpart that uses aerobic respiration to meet most energy needs. He attributed this to “mitochondrial dysfunction. In fact, we now think that in response to oxidative stress, the mitochondrion relies on the Lynen Cycle to make more cells and the major source of energy becomes glycolytic, which is at the expense of the lean body mass (muscle), which produces gluconeogenic precursors from muscle proteolysis (cancer cachexia). There is a loss of about 26 ATP ~Ps in the transition.
    The mitochondrial gene expression system includes the mitochondrial genome, mitochondrial ribosomes, and the transcription and translation machinery needed to regulate and conduct gene expression as well as mtDNA replication and repair. Machinery involved in energetics includes the enzymes of the Kreb’s citric acid or TCA (tricarboxylic acid) cycle, some of the enzymes involved in fatty acid catabolism (β-oxidation), and the proteins needed to help regulate these systems. The inner membrane is central to mitochondrial physiology and, as such, contains multiple protein systems of interest. These include the protein complexes involved in the electron transport component of oxidative phosphorylation and proteins involved in substrate and ion transport.
    Mitochondrial roles in, and effects on, cellular homeostasis extend far beyond the production of ATP, but the transformation of energy is central to most mitochondrial functions. Reducing equivalents are also used for anabolic reactions. The energy produced by mitochondria is most commonly thought of to come from the pyruvate that results from glycolysis, but it is important to keep in mind that the chemical energy contained in both fats and amino acids can also be converted into NADH and FADH2 through mitochondrial pathways. The major mechanism for harvesting energy from fats is β-oxidation; the major mechanism for harvesting energy from amino acids and pyruvate is the TCA cycle. Once the chemical energy has been transformed into NADH and FADH2 (also discovered by Warburg and the basis for a second Nobel nomination in 1934), these compounds are fed into the mitochondrial respiratory chain.
    The hydroxyl free radical is extremely reactive. It will react with most, if not all, compounds found in the living cell (including DNA, proteins, lipids and a host of small molecules). The hydroxyl free radical is so aggressive that it will react within 5 (or so) molecular diameters from its site of production. The damage caused by it, therefore, is very site specific. The reactions of the hydroxyl free radical can be classified as hydrogen abstraction, electron transfer, and addition.
    The formation of the hydroxyl free radical can be disastrous for living organisms. Unlike superoxide and hydrogen peroxide, which are mainly controlled enzymatically, the hydroxyl free radical is far too reactive to be restricted in such a way – it will even attack antioxidant enzymes. Instead, biological defenses have evolved that reduce the chance that the hydroxyl free radical will be produced and, as nothing is perfect, to repair damage.
    Currently, some endogenous markers are being proposed as useful measures of total “oxidative stress” e.g., 8-hydroxy-2’deoxyguanosine in urine. The ideal scavenger must be non-toxic, have limited or no biological activity, readily reach the site of hydroxyl free radical production (i.e., pass through barriers such as the blood-brain barrier), react rapidly with the free radical, be specific for this radical, and neither the scavenger nor its product(s) should undergo further metabolism.
    Nitric oxide has a single unpaired electron in its π*2p antibonding orbital and is therefore paramagnetic. This unpaired electron also weakens the overall bonding seen in diatomic nitrogen molecules so that the nitrogen and oxygen atoms are joined by only 2.5 bonds. The structure of nitric oxide is a resonance hybrid of two forms.
    In living organisms nitric oxide is produced enzymatically. Microbes can generate nitric oxide by the reduction of nitrite or oxidation of ammonia. In mammals nitric oxide is produced by stepwise oxidation of L-arginine catalyzed by nitric oxide synthase (NOS). Nitric oxide is formed from the guanidino nitrogen of the L-arginine in a reaction that consumes five electrons and requires flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) tetrahydrobiopterin (BH4), and iron protoporphyrin IX as cofactors. The primary product of NOS activity may be the nitroxyl anion that is then converted to nitric oxide by electron acceptors.
    The thiol-disulfide redox couple is very important to oxidative metabolism. GSH is a reducing cofactor for glutathione peroxidase, an antioxidant enzyme responsible for the destruction of hydrogen peroxide. Thiols and disulfides can readily undergo exchange reactions, forming mixed disulfides. Thiol-disulfide exchange is biologically very important. For example, GSH can react with protein cystine groups and influence the correct folding of proteins, and it GSH may play a direct role in cellular signaling through thiol-disulfide exchange reactions with membrane bound receptor proteins (e.g., the insulin receptor complex), transcription factors (e.g., nuclear factor κB), and regulatory proteins in cells. Conditions that alter the redox status of the cell can have important consequences on cellular function.
    So the complexity of life is not yet unraveled.

    Can tumor response to therapy be predicted, thereby improving the selection of patients for cancer treatment?
    The goal is not just complete response. Histopathological response seems to be related post-treatment histopathological assessment but it is not free from the challenge of accurately determining treatment response, as this method cannot delineate whether or not there are residual cancer cells. Functional imaging to assess metabolic response by 18-fluorodeoxyglucose PET also has its limits, as the results are impacted significantly by several variables:

    • tumor type
    • sizing
    • doubling time
    • anaplasia?
    • extent of tumor necrosis
    • type of antitumor therapy and the time when response was determined.
    The new modality should be based on individualized histopathology as well as tumor molecular, genetic and functional characteristics, and individual patients’ characteristics, a greater challenge in an era of ‘minimally invasive treatment’.
    This listing suggests that for every cancer the following data has to be collected (except doubling time). If there are five variables, the classification based on these alone would calculate to be very sizable based on Eugene Rypka’s feature extraction and classification. But looking forward, time to remission and disease free survival are additionally important. Treatment for cure is not the endpoint, but the best that can be done is to extend the time of survival to a realistic long term goal and retain a quality of life.

    Brücher BLDM, Piso P, Verwaal V et al. Peritoneal carcinomatosis: overview and basics. Cancer Invest.30(3),209–224 (2012).
    Brücher BLDM, Swisher S, Königsrainer A et al. Response to preoperative therapy in upper gastrointestinal cancers. Ann. Surg. Oncol.16(4),878–886 (2009).
    Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer47(1),207–214 (1981).
    Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl Cancer Inst.92(3),205–216 (2000).
    Brücher BLDM, Becker K, Lordick F et al. The clinical impact of histopathological response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas. Cancer106(10),2119–2127 (2006).

    • Dr. Larry,

      Thank you for this comment.

      Please carry it as a stand alone post, Dr. Ritu will refer to it and reference it in her FORTHCOMING pst on Tumor Response which will integrate multiple sources.

      Please execute my instruction

      Thank you

    • Thank you Larry for this educating comment. It explains very well why the Canadian investigators did not try to measure therapy response!

      What they have demonstrated is the technological feasibility of coupling a treatment device to an imaging device and use that in order to guide the treatment to the right place.

      the issue of “choice of treatment” to which you are referring is not in the scope of this publication.
      The point is: if one treatment modality can be guided, other can as well! This should encourage others, to try and develop imaging-based treatment guidance systems.

  7. The crux of the matter in terms of capability is that the cancer tissue, adjacent tissue, and the fibrous matrix are all in transition to the cancerous state. It is taught to resect leaving “free margin”, which is better aesthetically, and has had success in breast surgery. The dilemma is that the patient may return, but how soon?

    • Correct. The philosophy behind lumpectomy is preserving quality of life. It was Prof. Veronesi (IEO) who introduced this method 30 years ago noticing that in the majority of cases, the patient will die from something else before presenting recurrence of breast cancer..

      It is well established that when the resection margins are declared by a pathologist (as good as he/she could be) as “free of cancer”, the probability of recurrence is much lower than otherwise.

  8. Dr. Larry,

    To assist Dr. Ritu, PLEASE carry ALL your comments above into a stand alone post and ADD to it your comment on my post on MIS

    Thank you

  9. Great post! Dr. Nir, can the ultrasound be used in conjunction with PET scanning as well to determine a spatial and functional map of the tumor. With a disease like serous ovarian cancer we typically see an intraperitoneal carcimatosis and it appears that clinicians are wanting to use fluorogenic probes and fiberoptics to visualize the numerous nodules located within the cavity Also is the technique being used mainy for surgery or image guided radiotherapy or can you use this for detecting response to various chemotherapeutics including immunotherapy.

    • Ultrasound can and is actually used in conjunction with PET scanning in many cases. The choice of using ultrasound is always left to the practitioner! Being a non-invasive, low cost procedure makes the use of ultrasound a non-issue. The down-side is that because it is so easy to access and operate, nobody bothers to develop rigorous guidelines about using it and the benefits remains the property of individuals.

      In regards to the possibility of screening for ovarian cancer and characterising pelvic masses using ultrasound I can refer you to scientific work in which I was involved:

      1. VAES (E.), MANCHANDA (R), AUTIER, NIR (R), NIR (D.), BLEIBERG (H.), ROBERT (A.), MENON (U.). Differential diagnosis of adnexal masses: Sequential use of the Risk of Malignancy Index and a novel computer aided diagnostic tool. Published in Ultrasound in Obstetrics & Gynecology. Issue 1 (January). Vol. 39. Page(s): 91-98.

      2. VAES (E.), MANCHANDA (R), NIR (R), NIR (D.), BLEIBERG (H.), AUTIER (P.), MENON (U.), ROBERT (A.). Mathematical models to discriminate between benign and malignant adnexal masses: potential diagnostic improvement using Ovarian HistoScanning. Published in International Journal of Gynecologic Cancer (IJGC). Issue 1. Vol. 21. Page(s): 35-43.

      3. LUCIDARME (0.), AKAKPO (J.-P.), GRANBERG (S.), SIDERI (M.), LEVAVI (H.), SCHNEIDER (A.), AUTIER (P.), NIR (D.), BLEIBERG (H.). A new computer aided diagnostic tool for non-invasive characterisation of malignant ovarian masses: Results of a multicentre validation study. Published in European Radiology. Issue 8. Vol. 20. Page(s): 1822-1830.

      Dror Nir, PhD
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  10. totally true and i am very thankfull for these briliant comments.

    Remember: 10years ago: every cancer researcher stated: “look at the tumor cells only – forget the stroma”. The era of laser-captured tumor-cell dissection started. Now , everyone knows: it is a system we are looking at and viewing and analyzing tumor cells only is really not enough.

    So if we would be honest, we would have to declare, that all data, which had been produced 13-8years ago, dealing with laser capture microdissection, that al these data would need a re-scrutinization, cause the influence of the stroma was “forgotten”. I ‘d better not try thinking about the waisted millions of dollars.

    If we keep on being honest: the surgeon looks at the “free margin” in a kind of reductionable model, the pathologist is more the control instance. I personally see the pathologist as “the control instance” of surgical quality. Therefore, not the wish of the surgeon is important, the objective way of looking into problems or challenges. Can a pathologist always state, if a R0-resection had been performed ?

    The use of the Resectability Classification:
    There had been many many surrogate marker analysis – nothing new. BUT never a real substantial well tought through structured analysis had been done: mm by mm by mm by mm and afterwards analyzing that by a ROC analysis. BUt against which goldstandard ? If you perform statistically a ROC analysis – you need a golstandard to compare to. Therefore what is the real R0-resectiòn? It had been not proven. It just had been stated in this or that tumor entity that this or that margin with this margin free mm distance or that mm distance is enough and it had been declared as “the real R0-classification”. In some organs it is very very difficult and we all (surgeons, pathologists, clinicians) that we always get to the limit, if we try interpretating the R-classification within the 3rd dimension. Often it is just declared and stated.

    Otherwise: if lymph nodes are negative it does not mean, lymph nodes are really negative, cause up to 38% for example in upper GI cancers have histological negative lymph nodes, but immunohistochemical positive lymph nodes. And this had been also shown by Stojadinovic at el analyzing the ultrastaging in colorectal cancer. So the 4th dimension of cancer – the lymph nodes / the lymphatic vessel invasion are much more important than just a TNM classification, which unfortunately does often not reflect real tumor biology.

    AS we see: cancer has multifactorial reasons and it is necessary taking the challenge performing high sophisticated research by a multifactorial and multidisciplinary manner.

    Again my deep and heartly thanks for that productive and excellent discussion !

    • Dr. BB,

      Thank you for your comment.

      Multidisciplinary perspectives have illuminated the discussion on the pages of this Journal.

      Eager to review Dr. Ritu’s forthcoming paper – the topic has a life of its own and is embodied in your statement:

      “the 4th dimension of cancer – the lymph nodes / the lymphatic vessel invasion are much more important than just a TNM classification, which unfortunately does often not reflect real tumor biology.”

    • Thank you BB for your comment. You have touched the core limitation of healthcare professionals: how do we know that we know!

      Do we have a reference to each of the test we perform?

      Do we have objective and standardise quality measures?

      Do we see what is out-there or are we imagining?

      The good news: Everyday we can “think” that we learned something new. We should be happy with that, even if it is means that we learned that yesterday’s truth is not true any-more and even if we are likely to be wrong again…:)

      But still, in the last decades, lots of progress was made….

  11. Dr. Nir,
    I thoroughly enjoyed reading your post as well as the comments that your post has attracted. There were different points of view and each one has been supported with relevant examples in the literature. Here are my two cents on the discussion:
    The paper that you have discussed had the objective of finding out whether real-time MRI guidance of treatment was even possible and if yes, and also if the treatment could be performed in accurate location of the ROI? The data reveals they were pretty successful in accomplishing their objective and of course that gives hope to the imaging-based targeted therapies.
    Whether the ROI is defined properly and if it accounts for the real tumor cure, is a different question. Role of pathologists and the histological analysis they bring about to the table cannot be ruled out, and the absence of a defined line between the tumor and the stromal region in the vicinity is well documented. However, that cannot rule out the value and scope of imaging-based detection and targeted therapy. After all, it is seminal in guiding minimally invasive surgery. As another arm of personalized medicine-based cure for cancer, molecular biologists at MD Anderson have suggested molecular and genetic profiling of the tumor to determine genetic aberrations on the basis of which matched-therapy could be recommended to patients. When phase I trial was conducted, the results were obtained were encouraging and the survival rate was better in matched-therapy patients compared to unmatched patients. Therefore, everytime there is more to consider when treating a cancer patient and who knows a combination of views of oncologists, pathologists, molecular biologists, geneticists, surgeons would device improvised protocols for diagnosis and treatment. It is always going to be complicated and generalizations would never give an answer. Smart interpretations of therapies – imaging-based or others would always be required!

    Ritu

    • Dr. Nir,
      One of your earlier comments, mentioned the non invasiveness of ultrasound, thus, it’s prevalence in use for diagnosis.

      This may be true for other or all areas with the exception of Mammography screening. In this field, an ultrasound is performed only if a suspected area of calcification or a lump has been detected in the routine or patient-initiated request for ad hoc mammography secondery to patient complain of pain or patient report of suspected lump.

      Ultrasound in this field repserents ascalation and two radiologists review.

      It in routine use for Breast biopsy.

    • Thanks Ritu for this supporting comment. The worst enemy of finding solutions is doing nothing while using the excuse of looking for the “ultimate solution” . Personally, I believe in combining methods and improving clinical assessment based on information fusion. Being able to predict, and then timely track the response to treatment is a major issue that affects survival and costs!

Case Study #4:

  • Judging the ‘Tumor response’-there is more food for thought

https://pharmaceuticalintelligence.com/2012/12/04/judging-the-tumor-response-there-is-more-food-for-thought/

13 Responses

  1. Dr. Sanexa
    you have brought up an interesting and very clinically relevant point: what is the best measurement of response and 2) how perspectives among oncologists and other professionals differ on this issues given their expertise in their respective subspecialties (immunologist versus oncologist. The advent of functional measurements of tumors (PET etc.) seems extremely important in the therapeutic use AND in the development of these types of compounds since usually a response presents (in cases of solid tumors) as either a lack of growth of the tumor or tumor shrinkage. Did the authors include an in-depth discussion of the rapidity of onset of resistance with these types of compounds?
    Thanks for the posting.

  2. Dr. Williams,
    Thanks for your comment on the post. The editorial brings to attention a view that although PET and other imaging methods provide vital information on tumor growth, shrinkage in response to a therapy, however, there are more aspects to consider including genetic and molecular characteristics of tumor.
    It was an editorial review and the authors did not include any in-depth discussion on the rapidity of onset of resistance with these types of compounds as the focus was primarily on interpreting tumor response.
    I am glad you found the contents of the write-up informative.
    Thanks again!
    Ritu

  3. Thank you for your wonderful comment and interpretation. Dr.Sanexa made a brilliant comment.

    May I allow myself putting my finger deeper into this wound ? Cancer patients deserve it.

    It had been already pointed out by international experts from Munich, Tokyo, Hong-Kong and Houston, dealing with upper GI cancer, that the actual response criteria are not appropriate and moreover: the clinical response criteria in use seem rather to function as an alibi, than helping to differentiate and / or discriminate tumor biology (Ann Surg Oncol 2009):

    http://www.ncbi.nlm.nih.gov/pubmed/19194759

    The response data in a phase-II-trial (one tumor entity, one histology, one treatment, one group) revealed: clinical response evaluation according to the WHO-criteria is not appropriate to determine response:

    http://www.ncbi.nlm.nih.gov/pubmed/15498642

    Of course, there was a time, when it seemed to be useful and this also has to be respected.

    There is another challenge: using statistically a ROC and resulting in thresholds. This was, is and always be “a clinical decision only” and not the decision of the statistician. The clinician tells the statistician, what decision, he wants to make – the responsibility is enormous. Getting back to the roots:
    After the main results of the Munich-group had been published 2001 (Ann Surg) and 2004 (J Clin Oncol):

    http://www.ncbi.nlm.nih.gov/pubmed/11224616

    http://www.ncbi.nlm.nih.gov/pubmed/14990646

    the first reaction in the community was: to difficult, can’t be, not re-evaluated, etc.. However, all evaluated cut-offs / thresholds had been later proven to be the real and best ones by the MD Anderson Cancer Center in Houston, Texas. Jaffer Ajani – a great and critical oncologist – pushed that together with Steve Swisher and they found the same results. Than the upper GI stakeholders went an uncommon way in science: they re-scrutinized their findings. Meanwhile the Goldstandard using histopathology as the basis-criterion had been published in Cancer 2006.

    http://www.ncbi.nlm.nih.gov/pubmed/16607651

    Not every author, who was at the authorlist in 2001 and 2004 wanted to be a part of this analysis and publication ! Why ? Everyone should judge that by himself.

    The data of this analysis had been submitted to the New England Journal of Medicine. In the 2nd review stage process, the manuscript was rejected. The Ann Surg Oncol accepted the publication: the re-scrutinized data resulted in another interesting finding: in the future maybe “one PET-scan” might be appropriate predicting the patient’s response.

    Where are we now ?

    The level of evidence using the response criteria is very low: Miller’s (Cancer 1981) publication belonged to ”one single” experiment from Moertel (Cancer 1976). During that time, there was no definition of “experiences” rather than “oncologists”. These terms had not been in use during that time.

    Additionally they resulted in a (scientifically weak) change of the classification, published by Therasse (J Natl Cancer Inst 2000). Targeted therapy did not result in a change so far. In 2009, the international upper GI experts sent their publication of the Ann Surg Oncol 2009 to the WHO but without any kind of reaction.

    Using molecular biological predictive markers within the last 10years all seem to have potential.

    http://www.ncbi.nlm.nih.gov/pubmed/20012971

    http://www.ncbi.nlm.nih.gov/pubmed/18704459

    http://www.ncbi.nlm.nih.gov/pubmed/17940507

    http://www.ncbi.nlm.nih.gov/pubmed/17354029

    But, experts are aware: the real step breaking barriers had not been performed so far. Additionally, it is very important in trying to evaluate and / predict response, that not different tumor entities with different survival and tumor biology are mixed together. Those data are from my perspective not helpful, but maybe that is my own Bias (!) of my view.

    INCORE, the International Consortium of Research Excellence of the Theodor-Billroth-Academy, was invited publishing the Editorial in Future Oncology 2012. The consortium pointed out, that living within an area of ‘prove of principle’ and also trying to work out level of evidence in medicine, it is “the duty and responsibility” of every clinician, but also of the societies and institutions, also of the WHO.

    Complete remission is not the only goal, as experts dealing with ‘response-research’ are aware. It is so frustrating for patients and clinicians: there is a rate of those patients with complete remission, who develop early recurrence ! This reflects, that complete remission cannot function as the only criterion describing response !

    Again, my heartly thanks, that Dr.Sanexa discussed this issue in detail.
    I hope, I found the way explaining the way of development and evaluating response criteria properly and in a differentiated way of view. From the perspective of INCORE:

    “an interdisciplinary initiative with all key stake¬holders and disciplines represented is imperative to make predictive and prognostic individualized tumor response assessment a modern-day reality. The integrated multidisciplinary panel of international experts need to define how to leverage existing data, tissue and testing platforms in order to predict individual patient treatment response and prognosis.”

  4. Dr. Brucher,

    First of all thanks for expressing your views on the ‘tumor response’ in a comprehensive way. You are the first author of the editorial review one of the prominent people who has taken part in the process of defining tumor response and I am glad that you decided to write a comment on the writeup.
    The topic has been explained well in an immaculate manner and that it further clarifies the need for the perfect markers that would be able to evaluate and predict tumor response. There are, as you mentioned, some molecular markers available including VEGF, cyclins, that have been brought to focus in the context of squamous cell carcinoma.

    It would be great if you could be the guest author for our blog and we could publish your opinion (comment on this blog post) as a separate post. Please let us know if it is OK with you.

    Thanks again for your comment
    Ritu

  5. Thank you all to the compelling discussions, above.

    Please review the two sources on the topic I placed at the bottom of the post, above as post on this Scientific Journal,

    All comments made to both entries are part of thisvdiscussion, I am referring to Dr. Nir’s post on size of tumor, to BB comment to Nir’s post, to Larry’ Pathologist view on Tumors and my post on remission and minimally invasive surgery (MIS).

    Great comments by Dr. Williams, BB and wonderful topic exposition by Dr. Ritu.

  6. Aviva,
    Thats a great idea. I will combine all sources referred by you, the post on tumor imaging by Dr. Nir and the comments made on the these posts including Dr. Brucher’s comments in a new posts.
    Thanks
    Ritu

    • Great idea, ask Larry, he has written two very long important comments on this topic, one on Nir’s post and another one, ask him where, if it is not on MIS post. GREAT work, Ritu, integration is very important. Dr, Williams is one of our Gems.

    • Assessing tumour response it is not an easy task!Because tumours don’t change,but happilly our knowlege(about them) does really change,is everchanging(thans god!).In the past we had the Recist Criteria,then the Modified Recist Criteria,becausa of Gist and other tumors.At this very moment,these are clearly insuficient.We do need more new validated facing the reality of nowadays. A great, enormoust post Dr. Ritu! Congratulations!

 

Conclusions

The Voice of Aviva Lev-Ari, PhD, RN:

The relevance of the Scientific Agora to Medical Education is vast. The Open Access Journal allows EVERY Scientist on the internet the GLOBAL reach and access to Open Access published scientific contents NOT only to the subscription payer base of Journals. If you don’t have a HIGH FEE subscription you get NO access to content in the Journal, you can’t participate in Multiple Comment Exchanges. In the Medical Education context – COMMENTS are the medium to debate with peers. 

Multiple Comment Exchanges on Four articles in the Journal, above, demonstrate the vibrancy of the scientific discussion, the multiplicity of perspectives, the subjectivity of the contribution to the debate and the unique expertise and clinical experience expressed by each Scientist.

 .

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Three Genres in e-Scientific Publishing AND Three Scientists’ Dilemmas

Curator: Aviva Lev-Ari, PhD, RN

 

That’s what I tell students. The way to succeed is to get born at the right time and in the right place. If you can do that then you are bound to succeed. You have to be receptive and have some talent as well.

Professor Sydney Brenner, a professor of Genetic medicine at the University of Cambridge and Nobel Laureate in Physiology or Medicine in 2002

 

 

Cell/Nature/Science

[CNS]

 Subscription-based Access

Open Access

  1. Online journals, to which scientists pay an upfront free to cover editing costs, which then ensure the work is available free to access for anyone in perpetuity

 

Curation of Scientific Findings

i.e., Kindle Direct Publishing [KDP] – Royalty-based system

  1. Free content to e-Readers
  2. Expert, Authors, Writers -Volunteers
  3. Editor -Voluneers
Confirming or disproving past studies Confirming or disproving past studies
Decades-long pursuit of a risky “moonshot” Decades-long pursuit of a risky “moonshot”
Trendy topics with Editors Trendy topics with Editors

 

Genres in e-Scientific Publishing

(A) Cell/Nature/Science

 – June 27, 2017

Elizabeth Dzeng — Feb 24th, 2014

  • http://www.cell.com/
  • http://www.sciencemag.org/
  • https://www.nature.com/
  • In 1998, Elsevier rolled out its plan for the internet age, which would come to be called “The Big Deal”. It offered electronic access to bundles of hundreds of journals at a time: a university would pay a set fee each year – according to a report based on freedom of information requests, Cornell University’s 2009 tab was just short of $2m – and any student or professor could download any journal they wanted through Elsevier’s website. Universities signed up en masse. …. Elsevier owned 24% of the scientific journal market, while Maxwell’s old partners Springer, and his crosstown rivals Wiley-Blackwell, controlled about another 12% each. These three companies accounted for half the market. (An Elsevier representative familiar with the report told me that by their own estimate they publish only 16% of the scientific literature.)  – June 27, 2017.  Elsevier published 420,000 papers last year, after receiving 1.5m submissions  – June 28, 2017 [numbers correction to 6/27/2017.]

(B) Open Access Journals and the Phenomenon

  1. Biochemistry
  2. Biophysics and Structural Biology
  3. Cancer Biology
  4. Cell Biology
  5. Computational and Systems Biology
  6. Developmental Biology and Stem Cells
  7. Epidemiology and Global Health
  8. Genomics and Evolutionary Biology
  9. Microbiology and Infectious Disease
  10. Neuroscience

(C) Curation of Scientific Findings

Scientists’ Dilemmas

(1) Confirming or disproving past studies

(2) Decades-long pursuit of a risky “moonshot”

(3) Trendy Topics with Editors 

 

@ PharmaceuticalIntelligence.com –  A Case Study on the LEADER in Curation of Scientific Findings

https://pharmaceuticalintelligence.com/2017/06/29/pharmaceuticalintelligence-com-a-case-study-on-the-leader-in-curation-of-scientific-findings/

Product Details

Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation: The Art of Scientific & Medical Curation

Nov 29, 2015 | Kindle eBook

by Larry H. Bernstein MD FCAP and Aviva Lev-Ari PhD RN
Subscribers read for free.
Auto-delivered wirelessly
Sold by: Amazon Digital Services LLC

 

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How Will FDA’s new precisionFDA Science 2.0 Collaboration Platform Protect Data?

Reporter: Stephen J. Williams, Ph.D.

As reported in MassDevice.com

FDA launches precisionFDA to harness the power of scientific collaboration

FDA VoiceBy: Taha A. Kass-Hout, M.D., M.S. and Elaine Johanson

Imagine a world where doctors have at their fingertips the information that allows them to individualize a diagnosis, treatment or even a cure for a person based on their genes. That’s what President Obama envisioned when he announced his Precision Medicine Initiative earlier this year. Today, with the launch of FDA’s precisionFDA web platform, we’re a step closer to achieving that vision.

PrecisionFDA is an online, cloud-based, portal that will allow scientists from industry, academia, government and other partners to come together to foster innovation and develop the science behind a method of “reading” DNA known as next-generation sequencing (or NGS). Next Generation Sequencing allows scientists to compile a vast amount of data on a person’s exact order or sequence of DNA. Recognizing that each person’s DNA is slightly different, scientists can look for meaningful differences in DNA that can be used to suggest a person’s risk of disease, possible response to treatment and assess their current state of health. Ultimately, what we learn about these differences could be used to design a treatment tailored to a specific individual.

The precisionFDA platform is a part of this larger effort and through its use we want to help scientists work toward the most accurate and meaningful discoveries. precisionFDA users will have access to a number of important tools to help them do this. These tools include reference genomes, such as “Genome in the Bottle,” a reference sample of DNA for validating human genome sequences developed by the National Institute of Standards and Technology. Users will also be able to compare their results to previously validated reference results as well as share their results with other users, track changes and obtain feedback.

Over the coming months we will engage users in improving the usability, openness and transparency of precisionFDA. One way we’ll achieve that is by placing the code for the precisionFDA portal on the world’s largest open source software repository, GitHub, so the community can further enhance precisionFDA’s features.Through such collaboration we hope to improve the quality and accuracy of genomic tests – work that will ultimately benefit patients.

precisionFDA leverages our experience establishing openFDA, an online community that provides easy access to our public datasets. Since its launch in 2014, openFDA has already resulted in many novel ways to use, integrate and analyze FDA safety information. We’re confident that employing such a collaborative approach to DNA data will yield important advances in our understanding of this fast-growing scientific field, information that will ultimately be used to develop new diagnostics, treatments and even cures for patients.

fda-voice-taha-kass-1x1Taha A. Kass-Hout, M.D., M.S., is FDA’s Chief Health Informatics Officer and Director of FDA’s Office of Health Informatics. Elaine Johanson is the precisionFDA Project Manager.

 

The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of MassDevice.com or its employees.

So What Are the Other Successes With Such Open Science 2.0 Collaborative Networks?

In the following post there are highlighted examples of these Open Scientific Networks and, as long as

  • transparancy
  • equal contributions (lack of heirarchy)

exists these networks can flourish and add interesting discourse.  Scientists are already relying on these networks to collaborate and share however resistance by certain members of an “elite” can still exist.  Social media platforms are now democratizing this new science2.0 effort.  In addition the efforts of multiple biocurators (who mainly work for love of science) have organized the plethora of data (both genomic, proteomic, and literature) in order to provide ease of access and analysis.

Science and Curation: The New Practice of Web 2.0

Curation: an Essential Practice to Manage “Open Science”

The web 2.0 gave birth to new practices motivated by the will to have broader and faster cooperation in a more free and transparent environment. We have entered the era of an “open” movement: “open data”, “open software”, etc. In science, expressions like “open access” (to scientific publications and research results) and “open science” are used more and more often.

Curation and Scientific and Technical Culture: Creating Hybrid Networks

Another area, where there are most likely fewer barriers, is scientific and technical culture. This broad term involves different actors such as associations, companies, universities’ communication departments, CCSTI (French centers for scientific, technical and industrial culture), journalists, etc. A number of these actors do not limit their work to popularizing the scientific data; they also consider they have an authentic mission of “culturing” science. The curation practice thus offers a better organization and visibility to the information. The sought-after benefits will be different from one actor to the next.

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

  • Using Curation and Science 2.0 to build Trusted, Expert Networks of Scientists and Clinicians

Given the aforementioned problems of:

        I.            the complex and rapid deluge of scientific information

      II.            the need for a collaborative, open environment to produce transformative innovation

    III.            need for alternative ways to disseminate scientific findings

CURATION MAY OFFER SOLUTIONS

        I.            Curation exists beyond the review: curation decreases time for assessment of current trends adding multiple insights, analyses WITH an underlying METHODOLOGY (discussed below) while NOT acting as mere reiteration, regurgitation

 

      II.            Curation providing insights from WHOLE scientific community on multiple WEB 2.0 platforms

 

    III.            Curation makes use of new computational and Web-based tools to provide interoperability of data, reporting of findings (shown in Examples below)

 

Therefore a discussion is given on methodologies, definitions of best practices, and tools developed to assist the content curation community in this endeavor

which has created a need for more context-driven scientific search and discourse.

However another issue would be Individual Bias if these networks are closed and protocols need to be devised to reduce bias from individual investigators, clinicians.  This is where CONSENSUS built from OPEN ACCESS DISCOURSE would be beneficial as discussed in the following post:

Risk of Bias in Translational Science

As per the article

Risk of bias in translational medicine may take one of three forms:

  1. a systematic error of methodology as it pertains to measurement or sampling (e.g., selection bias),
  2. a systematic defect of design that leads to estimates of experimental and control groups, and of effect sizes that substantially deviate from true values (e.g., information bias), and
  3. a systematic distortion of the analytical process, which results in a misrepresentation of the data with consequential errors of inference (e.g., inferential bias).

This post highlights many important points related to bias but in summarry there can be methodologies and protocols devised to eliminate such bias.  Risk of bias can seriously adulterate the internal and the external validity of a clinical study, and, unless it is identified and systematically evaluated, can seriously hamper the process of comparative effectiveness and efficacy research and analysis for practice. The Cochrane Group and the Agency for Healthcare Research and Quality have independently developed instruments for assessing the meta-construct of risk of bias. The present article begins to discuss this dialectic.

  • Information dissemination to all stakeholders is key to increase their health literacy in order to ensure their full participation
  • threats to internal and external validity  represent specific aspects of systematic errors (i.e., bias)in design, methodology and analysis

So what about the safety and privacy of Data?

A while back I did a post and some interviews on how doctors in developing countries are using social networks to communicate with patients, either over established networks like Facebook or more private in-house networks.  In addition, these doctor-patient relationships in developing countries are remote, using the smartphone to communicate with rural patients who don’t have ready access to their physicians.

Located in the post Can Mobile Health Apps Improve Oral-Chemotherapy Adherence? The Benefit of Gamification.

I discuss some of these problems in the following paragraph and associated posts below:

Mobile Health Applications on Rise in Developing World: Worldwide Opportunity

According to International Telecommunication Union (ITU) statistics, world-wide mobile phone use has expanded tremendously in the past 5 years, reaching almost 6 billion subscriptions. By the end of this year it is estimated that over 95% of the world’s population will have access to mobile phones/devices, including smartphones.

This presents a tremendous and cost-effective opportunity in developing countries, and especially rural areas, for physicians to reach patients using mHealth platforms.

How Social Media, Mobile Are Playing a Bigger Part in Healthcare

E-Medical Records Get A Mobile, Open-Sourced Overhaul By White House Health Design Challenge Winners

In Summary, although there are restrictions here in the US governing what information can be disseminated over social media networks, developing countries appear to have either defined the regulations as they are more dependent on these types of social networks given the difficulties in patient-physician access.

Therefore the question will be Who Will Protect The Data?

For some interesting discourse please see the following post

Atul Butte Talks on Big Data, Open Data and Clinical Trials

 

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Twitter, Google, LinkedIn Enter in the Curation Foray: What’s Up With That?

 

Reporter: Stephen J. Williams, Ph.D.

Recently Twitter has announced a new feature which they hope to use to increase engagement on their platform. Originally dubbed Project Lightning and now called Moments, this feature involves many human curators which aggregate and curate tweets surrounding individual live events(which used to be under #Live).

As Madhu Muthukumar (@justmadhu), Twitter’s Product Manager, published a blog post describing Moments said:

“Every day, people share hundreds of millions of tweets. Among them are things you can’t experience anywhere but on Twitter: conversations between world leaders and celebrities, citizens reporting events as they happen, cultural memes, live commentary on the night’s big game, and many more,” the blog post noted. “We know finding these only-on-Twitter moments can be a challenge, especially if you haven’t followed certain accounts. But it doesn’t have to be.”

Please see more about Moments on his blog here.

Moments is a new tab on Twitter’s mobile and desktop home screens where the company will curate trending topics as they’re unfolding in real-time — from citizen-reported news to cultural memes to sports events and more. Moments will fall into five total categories, including “Today,” “News,” “Sports,” “Entertainment” and “Fun.” (Source: Fox)

Now It’s Google’s Turn

 

As Dana Blankenhorn wrote in his article Twitter, Google Try It Buzzfeed’s Way With Curation

in SeekingAlpha

What’s a challenge for Google is a direct threat to Twitter’s existence.

For all the talk about what doesn’t work in journalism, curation works. Following the news, collecting it and commenting, and encouraging discussion, is the “secret sauce” for companies like Buzzfeed, Vox, Vice and The Huffington Post, which often wind up getting more traffic from a story at, say The New York Times (NYSE:NYT), than the Times does as a result.

Curation is, in some ways, a throwback to the pre-Internet era. It’s done by people. (At least I think I’m a people.) So as odd as it is for Twitter (NYSE:TWTR) to announce it will curate live events it’s even odder to see Google (NASDAQ:GOOG) (NASDAQ:GOOGL) doing it in a project called YouTube Newswire.

Buzzfeed, Google’s content curation platform, made for desktop as well as a mobile app, allows sharing of curated news, viral videos.

The feel for both Twitter and Google’s content curation will be like a newspaper, with an army of human content curators determining what is the trendiest news to read or videos to watch.

BuzzFeed articles, or at least, the headlines can easily be mined from any social network but reading the whole article still requires that you open the link within the app or outside using a mobile web browser. Loading takes some time–a few seconds longer. Try browsing the BuzzFeed feed on the app and you’ll notice the obvious difference.

However it was earlier this summer in a Forbes article Why Apple, Snapchat and Twitter are betting on human editors, but Facebook and Google aren’t that Apple, Snapchat and Twitter as well as LinkedIn Pulse and Instragram were going to use human editors and curators while Facebook and Google were going to rely on their powerful algorithms. Google (now Alphabet) CEO Eric Schmidt has even called Apple’s human curated playlists “elitist” although Google Play has human curated playlists.

Maybe Google is responding to views on its Google News like this review in VentureBeat:

Google News: Less focused on social signals than textual ones, Google News uses its analytic tools to group together related stories and highlight the biggest ones. Unlike Techmeme, it’s entirely driven by algorithms, and that means it often makes weird choices. I’ve heard that Google uses social sharing signals from Google+ to help determine which stories appear on Google News, but have never heard definitive confirmation of that — and now that Google+ is all but dead, it’s mostly moot. I find Google News an unsatisfying home page, but it is a good place to search for news once you’ve found it.

Now WordPress Too!

 

WordPress also has announced its curation plugin called Curation Traffic.

According to WordPress

You Own the Platform, You Benefit from the Traffic

“The Curation Traffic™ System is a complete WordPress based content curation solution. Giving you all the tools and strategies you need to put content curation into action.

It is push-button simple and seamlessly integrates with any WordPress site or blog.

With Curation Traffic™, curating your first post is as easy as clicking “Curate” and the same post that may originally only been sent to Facebook or Twitter is now sent to your own site that you control, you benefit from, and still goes across all of your social sites.”

The theory the more you share on your platform the more engagement the better marketing experience. And with all the WordPress users out there they have already an army of human curators.

So That’s Great For News But What About Science and Medicine?

 

The news and trendy topics such as fashion and music are common in most people’s experiences. However more technical areas of science, medicine, engineering are not in most people’s domain so aggregation of content needs a process of peer review to sort basically “the fact from fiction”. On social media this is extremely important as sensational stories of breakthroughs can spread virally without proper vetting and even influence patient decisions about their own personal care.

Expertise Depends on Experience

In steps the human experience. On this site (www.pharmaceuticalintelligence.com) we attempt to do just this. A consortium of M.D.s, Ph.D. and other medical professionals spend their own time to aggregate not only topics of interest but curate on specific topics to add some more insight from acceptable sources over the web.

In Power of Analogy: Curation in Music, Music Critique as a Curation and Curation of Medical Research Findings – A Comparison; Dr. Larry Berstein compares a museum or music curator to curation of scientific findings and literature and draws similar conclusions from each: that a curation can be a tool to gain new insights previously unseen an observer. A way of stepping back to see a different picture, hear a different song.

 

For instance, using a Twitter platform, we curate #live meeting notes and tweets from meeting attendees (please see links below and links within) to give a live conference coverage

https://pharmaceuticalintelligence.com/press-coverage/

and curation and analysis give rise not only to meeting engagement butunique insights into presentations.

 

In addition, the use of a WordPress platform allows easy sharing among many different social platforms including Twitter, Google+, LinkedIn, Pinterest etc.

Hopefully, this will catch on to the big powers of Twitter, Google and Facebook to realize there exists armies of niche curation communities which they can draw on for expert curation in the biosciences.

Other posts on this site on Curation and include

 

Inevitability of Curation: Scientific Publishing moves to embrace Open Data, Libraries and Researchers are trying to keep up

The Methodology of Curation for Scientific Research Findings

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

The growing importance of content curation

Data Curation is for Big Data what Data Integration is for Small Data

Stem Cells and Cardiac Repair: Content Curation & Scientific Reporting

Cardiovascular Diseases and Pharmacological Therapy: Curations

Power of Analogy: Curation in Music, Music Critique as a Curation and Curation of Medical Research Findings – A Comparison

 

 

 

 

 

 

 

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