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REAL TIME Cancer Conference Coverage: A Novel Methodology for Authentic Reporting on Presentations and Discussions launched via Twitter.com @ The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

March 21, 2014 by 2012pharmaceutical

REAL TIME Cancer Conference Coverage: A Novel Methodology for Authentic Reporting on Presentations and Discussions launched via Twitter.com @ The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

Author, Curator, Life Sciences Reporter: Aviva Lev-Ari, PhD, RN

Article ID #123: REAL TIME Cancer Conference Coverage: A Novel Methodology for Authentic Reporting on Presentations and Discussions launched via Twitter.com @ The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum in Drug Development, 19th March 2014 • New York Academy of Sciences • USA. Published on 3/21/2014

WordCloud Image Produced by Adam Tubman

This article is by the same Curator as the following published on 1/4/2014:

conceived: NEW Definition for Co-Curation in Medical Research

RELATED ARTICLES

Cancer Biology and Genomics for Disease Diagnosis, Volume One Pre-ePub Announcement

Volatile Organic Compounds (VOCs) as Biomarkers in Cancer Detection: • Alnion Ranked #1 in “Top 10 Israeli medical advances to watch in 2014”.

Investing and inventing: Is the Tango of Mars and Venus Still on

Curator’s Position Statement

The complexity of presentations in Scientific Conferences requires a different Reporting methodology than the idea summarization by Science Journalists.

A Novel Methodology was applied @ The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoting Public & Private Sector Collaboration & Investment in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

Launched a novel methodology for Authentic Reporting on Presentations and Discussions in my quest to achieve REAL TIME Cancer Conference Coverage of content and Q&A.

Of all Social Media modalities I used the following:

  • Primary: Tweeting key idea by EVERY SPEAKER
  • Secondary: Tweeting all Q&A and Discussions
  • FaceBook posting
  • LinkedIn posting
  • WordPress.com e-Publishing @ http://pharmaceuticalinteligence.com

Below I present ALL the Tweets and the Retweets for 3/19/2014

Public and Private Partnership @ The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoting Public & Private Sector Collaboration & Investment in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

March 19, 2014 by 2012pharmaceutical

March 19, 2014 5PM
Public & Private Partnerships
Co-Chaired by:
  • Louis J. DeGennaro, Interim President and CEO, Chief Mission Ocer, The Leukemia and Lymphoma Society
  • Beth Jacobs, Managing Partner, Excellentia Global Partners Featuring:
  • Darryl Mitteldorf, Executive Director, Global Prostate Cancer Alliance
  • Dov Hass, Associate, Morgan, Lewis & Bockius LLP
  • Kristina Khodova, Head of Oncology Projects, Biomed Cluster, Skolkovo Foundation
  • Louise M. Perkins, Chief Science Ocer, Melanoma Research Alliance
  • Peter L. Hoang, Managing Director, Oce of Innovations, Technology Based Ventures, The University of Texas MD Anderson Cancer Center
  • Steven Young, President & COO, Addario Lung Cancer Medical Institute
  • Walter M. Capone, President, Multiple Myeloma Research Foundation
Public & Private Partnership
  • Foundation are playing a new role: The enable Cancer Research, links to biopharma, Scientific staff, understanding of the commercial landscape
  • Universities: Public & Private

Question #1: Difficulties in working with small biotech companies Non-Profits are disease focus, Biotech have expectation to gain capital funding from the Non-Profits Non-Profit has access to Patients information and disease condition in the pre-approval period, Consortia: addresses access to Resources do not invest or fund pharma companies, they fund diagnostics lab, stem cell companies Foundations  have right to publish data, IP ownership is still unresolved an issue, Dana Farber can’t be encouraged to give away its IP but a Foundation can accelerate the process.

IP Licensing Academic institution as LICENSORS WHILE HAVING having bond obligation, Tax exempt status is exclusive, while the bond owner status is non-exclusive Appetite for Risk – Venture Capital vs Foundation

  • Louis J. DeGennaro, Interim President and CEO, Chief Mission Ocer, The Leukemia and Lymphoma Society – provides $60 millions a year for R&D – they do take significant Risk. Size of population of patients is not a factor, serving all is. No detection, No screening, Patients present with full blown disease
  • Darryl Mitteldorf, Executive Director, Global Prostate Cancer Alliance — Risk does not belong to this organization. Foundation funded research on the disparity between Black and White patients.
  • Louise M. Perkins, Chief Science Officer, Melanoma Research Alliance – UV cause, funding research for personalized. medicine. Foundation has educated FDA, Sequencing of melanoma larger that sequencing of the Genome
  • Steven Young, President & COO, Addario Lung Cancer Medical Institute 70% of Lung Cancer Patients were not Smokers

__________________

8:00 AM –

On the 40th Floor of 7 World Trade Center in NYC @  The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoting Public & Private Sector Collaboration & Investment in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

Follow me @pharma_BI and @AVIVA1950

  • Event Coverage
  • Cancer & Genomic – Volume One in LPBI’s BioMed e-Series C: Cancer
  • Alnion Venture Funding Prospecting & Negotiation

Aviva Lev-Ari, PhD, RN Founder and Director Leaders in Pharmaceutical Business Intelligence

Editor-in-Chief http://pharmaceuticalintelligence.com

 TWEET LOG for 3/19/2014

  1. TODAY follow my Tweets @pharma_BI coverage for The 2nd ANNUAL Sachs Cancer Bio Partnering &… http://fb.me/1dvGXjXQC 

  2. Checkpoint inhibitors: Portfolio of antigens for a small # Tumors. Adjuvant combinations Risks: immune disease vs Cancer

  3. Argos Therapeutics: Leader in immunotherapy for Advanced Kidney cancer, vaccine development effort

  4. Tumor blockade via immunotherapy: active therapy, autologos, T cells depleted by kidney and tumor removal, healthy kidney was protected

  5. Precursors of breast lesions, target antigen, vaccine for cancer MAY or not evolve into immune event in the future

  6. Immunotherapy in Cancer: Tolerance of Cancer, central (thymus) breast/ovarian vs peripheral by checkpoint: skin, lungs, kidney vs

  7. Florian Schodel, Philimmune, immunotherapy in Cancer Development: vaccine for Cancer for secondary prevention breast/ovarian cancer

  8. All Options on the table when financing, best package requires flexibility. Outcome, Output, Process originality do clinical trial, find what kills

  9. Partnering in Phase I is dangerous vs Stage IV, companion diagnostics, not enough money in the product to share.

  10. Future Trends in Oncology: preclinical going IPO, China for clinical trial at different standard of care than US or Europe

  11. Carole Nuechterlein, Head Roche Venture Fund: Big Pharma offers to biotech knowledge on combination drugs to select for development. Biotech tend to overestimate value of the assets

  12. Tim Herpin, Head Transactions (UK) BD AstraZeneca: Acquisition is preferred to partnership

  13. Stuart Barich, Oppenheimer & Co. Holding to assets vs. Partnering – HOLD as long as a biotech can

  14. Anne Altmeyer, VP Oncology, Novartis: Only 5% of all Cancer drugs move from Phase I to phase II – Oncology drugs 36% of all current cancer drugs are in Phase II

  15. Commercialization is only one factor in Transforming Patient life’s by drug response in clinical trials – repurposed drugs vs generic

  16. Regulatory affairs: 30% of applications are approved, most cancer indications requires orphan drug development – niche of patient

  17. Celgene partners with Foundation Medicine or Diagnostics development, Roche has own Diagnostics – small biotech vs big Pharma

  18. Guillaume Vignon, Dir BD, EMD Serono: Finding the right patient by selection for obtaining response – key for clinical study success & Translational Team

  19. Anne Altmeyer, VP Oncology Novartis: Strategies for Small Molecule and Biologicals Drug Development, 1/3 of top 100 drugs and 22% of drug approval are Biologicals this is the future

  20. Moffitt Total Cancer Care DB Solid Tumor signature – Cancer Vaccine, genotype—>>>>phenotype demographic histology over expression of genes

  21. M2GEN – Concortium with Community Hospitals: WORLD largest biorepository Moffitt/Merck/Community Hospital, Genomic Marker

  22. J. Mule, Moffitt Cancer Center: Translational Research for Personalized Medicine: M2GEN collaboration StateMerck/Moffitt 3rd largest in US

  23. BRAF inhibition: not enough patients for genetic mutation based clinical trial, BiomarkersDiagnostics in collaboration w/academia is optimal

  24. TODAY follow my Tweets @pharma_BI coverage for The 2nd ANNUAL Sachs Cancer Bio Partnering &… http://fb.me/1jxkUHMlJ 

  25. N.C. Dracopoli of Janssen R&D: Biomarkers for Diagnosis – Prognosis, Predicative test, pharmacodygnostic test FDA 32 genomics biomarkers approved

  26. Tx w/anti-IL-6 for ALL – Great Prognosis, Novartis and UPenn collaboration most promising big Pharma and Academia case

  27. Philip Gotwals, Oncology Novartis, Translational Research, collaboration with UPenn – Org clarity challenging

  28. TODAY follow my Tweets @pharma_BI coverage for The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoti…http://lnkd.in/dbHd85U

  29. TODAY follow my Tweets @pharma_BI coverage for The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum… http://wp.me/p2kEDv-5AX 

  30. Cancer Biology and Genomics for Disease Diagnosis, Volume One Pre-ePub Announcement http://lnkd.in/d83gUrY 

  31. Power of Analogy: Curation in Music, Music Critique as a Curation and Curation of Medical Research Findings – A Comp…http://lnkd.in/dBbahTf 

  32. Aviva Lev-Ari ‏@AVIVA1950  Mar 19

 Re-TWEETS

1. @pharma_BI ‏@Pharma_BI Mar 19

Future Trends in Oncology: preclinical gong IPO, China for clinical trial at different standard of care than US or Europe

  • Retweet 1: Gil Press
  • Favorite 1: Kimberly Ha
  • 8:23 AM – 19 Mar 2014 · Details

2. @pharma_BI ‏@Pharma_BI Mar 19

Big Pharma offers to biotech knowledge on combination drugs to select for development. Biotech tend to overestimate value of the assets

  • Retweet 1: Gil Press

8:35 AM – 19 Mar 2014 · Details

3. @pharma_BI ‏@Pharma_BI Mar 19

Only 5% of all Cancer drugs move from Phase I to phase II -Oncology drugs 36% of all current cancer drugs are in Phase II

7:51 AM – 19 Mar 2014 · Details

4. @pharma_BI ‏@Pharma_BI Mar 19

Commercial only one factor in Transforming Patient life’s by drug response in clinical trials – repurposed drugs vs generic

  • Retweet 1 – Gil Press

5. @pharma_BI ‏@Pharma_BI Mar 19

Celgene partners with Foundation Medicine or Diagnostics development, Roche has own Diagnostics – small biotech vs big Pharma

  • Retweet 1 – Gil Press

7:03 AM – 19 Mar 2014 · Details

6. @pharma_BI ‏@Pharma_BI Mar 19

TODAY follow my Tweets @pharma_BI coverage for The 2nd ANNUAL Sachs Cancer Bio Partnering &… http://fb.me/1jxkUHMlJ 

  • Retweet 1 – Gil Press

6:16 AM – 19 Mar 2014 · Details

7.  @pharma_BI ‏@Pharma_BI Mar 14

The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoting Public & Private Sector Col… http://wp.me/p2kEDv-55i  via @Pharma_BI

Retweeted by @pharma_BI

8. Sachs Associates Ltd ‏@SachsAssociates Dec 10

2nd Annual SachsCancerBioPartnering Forum, 19th March, New York. Info: http://goo.gl/GLD3Dg  Early Bird Registration:http://goo.gl/rX0RpW 

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Interviews with Scientific Leaders, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Technology Transfer: Biotech and Pharmaceutical, Translational Science | Leave a Comment »

What is the key method to harness Inflammation to close the doors for many complex diseases?

March 21, 2014 by Demet Sag, Ph.D., CRA, GCP

 What is the key method to harness Inflammation to close the doors for many complex diseases?

 

Author and Curator: Larry H Bernstein, MD, FCAP

 

The main goal is to  have a quality of a healthy life.

When we look at the picture 90% of main fluid of life, blood, carried by cardiovascular system with two main pumping mechanisms, lung with gas exchange and systemic with complex scavenger actions, collection of waste, distribution of nutrition and clean gases etc.  Yet without lymphatic system body can’t make up the 100% fluid.  Therefore, 10% balance is completed by lymphatic system as a counter clockwise direction so that not only the fluid balance but also mass balance is  maintained. Finally, the immune system patches the  remaining mechanism by providing cellular support to protect the body because it contains 99% of white cells to fight against any kinds of invasion, attack, trauma.

These three musketeers, ccardiovascular, lyphatic and immune systems, create the core mechanism of survival during human life.

However, there is a cellular balance between immune and cardiovascular system since blood that made up off 99% red cells and 1% white blood cells that are used to scavenger hunt circulating foreign materials.   These three systems are acting with a harmony not only defend the body but provide basic needs of life.  Thus, controlling angiogenesis and working mechanisms in blood not only helps to develop new diagnostic tools but more importantly establishes long lasting treatments that can harness Immunomodulation.

The word inflammation comes from the Latin “inflammo”, meaning “I set alight, I ignite”.

Medical Dictionary description is:

“A fundamental pathologic process consisting of a dynamic complex of histologically apparent cytologic changes, cellular infiltration, and mediator release that occurs in the affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by a physical, chemical, or biologic agent, including the local reactions and resulting morphologic changes; the destruction or removal of the injurious material; and the responses that lead to repair and healing.”

The five elements makes up the signature of  inflammation:  rubor, redness; calor, heat (or warmth); tumor swelling; and dolor, pain; a fifth sign, functio laesa, inhibited or lost function.   However, these indications may not be present at once.

Please click on to the following link for genetic association of autoimmune diseases (Cho Et al selected major association signals in autoimmune diseases) from Cho JH, Gregersen PK. N Engl J Med 2011;365:1612-1623.

Inflammatory diseases grouped under two classification: the immune system related due to  inflammatory disorders, such as both allergic reactions  and some myopathies, with many immune system disorders.  The examples of inflammatory disorders  include Acne vulgaris, asthma, autoimmune disorders, celiac disease, chronic prostatitis, glomerulonepritis, hypersensitivities, inflammatory bowel diseases, pelvic inflammatory diseases, reperfusion diseases, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, interstitial cyctitis, The second kind of inflammation are related to  non-immune diseases such as cancer, atherosclerosis, and ischaemic heart disease.

This seems simple yet at molecular physiology and gene activation levels this is a complex response as an innate immune response from body.  There can be acute lasting few days after exposure to bacterial pathogens, injured tissues or chronic inflammation continuing few months to years after unresolved acute responses such as non-degradable pathogens, viral infection, antigens or any  foreignmaterials, or autoimmune responses.

As the system responses arise from plasma fluid, blood vessels, blood plasma through vasciular changes, differentiation in plasma cascade systems like coagulation system, fibrinolysis, complement system and kinin system.  Some of the various mediators include bradykinin produced by kinin system, C3, C5, membrane attack system (endothelial cell activation or endothelial coagulation activation mechanism) created by the complement system; factor XII that can activate kinin, fibrinolysys and coagulation systems at the same time produced in liver; plasmin from fibrinolysis system to inactivate factor Xii and C3 formation, and thrombin of coagulation system with a reaction through protein activated receptor 1 (PAR1), which is a seven spanning membrane protein-GPCR.   This system is quite fragile and well regulated.  For example activation of inactive Factor XII by collagen, platelets, trauma such as cut, wound, surgery that results in basement membrane changes since it usually circulate in inactive form in plasma automatically initiates and alerts kinin, fibrinolysis and coagulation systems.

Furthermore, the changes reflected through receptors and create gene activation by cellular mediators to establish system wide unified mechanisms. These factors (such as IFN-gamma, IL-1, IL-8, prostaglandins, leukotrene B4,  nitric oxide, histamines,TNFa) target immune cells and redesign their responses, mast cells, macrophages, granulocytes, leukocytes, B cells, T cells) platelets, some neuron cells and endothelial cells.  Therefore, immune system can react with non-specific or specific mechanisms either for a short or a long term.

As a result, controlling of mechanisms in blood and prevention of angiogenesis answer to cure/treat many diseases  Description of angiogenesis is simply formation of new blood vessels without using or changing pre-existing capillaries.  This involves serial numbers of events play a central role during physiologic and pathologic processes such as normal tissue growth, such as in embryonic development, wound healing, and the menstrual cycle.  However this system requires three main elements:  oxygen, nutrients and getting rid of waste or end products.

Genome Wide Gene Association Studies, Genomics and Metabolomics, on the other hand, development of new technologies for diagnostics and non-invasive technologies provided better targeting systems.

In this token recent genomewide association studies showed a clear view on a disease mechanism, or that suggest a new diagnostic or therapeutic approach particularly these disorders are related to  genes within the major histocompatibility complex (MHC) that predisposes the most significant genetic effect.  Presumably, these genes are reflecting the immunoregulatory effects of the HLA molecules themselves. As a result, the working mechanism of pathological conditions are revisited or created new assumptions to develop new targets for diagnosis and treatments.

Even though B and T cells are reactive to initiate responses there are several level of mechanisms control the cell differentiation for designing rules during health or diseases. These regulators are in check for both T and B cells.  For example, during Type 1 diabetes there are presence of more limited defects in selection against reactivity with self-antigens like insulin, thus, T cell differentiation is in jeopardy.  In addition, B cells have many active checkpoints to modulate the immune responses like  pre-B cells in the bone marrow are highly autoreactive yet they prefer to stay  in naïve-B cell forms in the periphery through tyrosine phosphatase nonreceptor type 22 (PTPN22) along with many genes play a role in autoimmunity.  In a nut shell this is just peeling the first layer of the onion at the level of Mendelian Genetics.

There is a great work to be done but if one can harness the blood and immune responses many complex diseases patients may have a big relief and have a quality of life.  When we look at the picture 90% of main fluid of life, blood, carried by cardiovascular system with two main pumping mechanisms, lung with gas exchange and systemic with complex scavenger actions, collection of waste, distribution of nutrition and clean gases.  Yet, without lymphatic system body can’t make up the 100% fluid.  Therefore, 10% balance is completed by lymphatic system as a counter clockwise direction so that not only the fluid balance but also mass balance is  maintained. Finally, the immune system patches the  remaining mechanism by providing cellular support to protect the body because it contains 99% of white cells to fight against any kinds of invasion, attack, trauma.

FURTHER READINGS AND REFERENCES:

Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science (Wash DC)279:377–380.

 Brouty BD, Zetter BR (1980) Inhibition of cell motility by interferon.Science (Wash DC) 208:516–518.

Ferrara N, Alitalo K (1999) Clinical Applications of angiogenic growth factors and their inhibitors. Nat Med 5:1359–1364.

 

Ferrara N (1999) Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int 56:794–814.

 

Ferrara N (1995) Leukocyte adhesion: Missing link in angiogenesis. Nature (Lond) 376:467.

 

Kohn EC, Alessandro R, Spoonster J, Wersto RP, Liotta LA (1995) Angiogenesis: Role of calcium-mediated signal transduction. Proc Natl Acad Sci U S A 92:1307–1311

Meijer DKF, Molema G (1995) Targeting of drugs to the liver. Semin Liver Dis 15:202–256.

Sidky YA, Borden EC (1987) Inhibition of angiogenesis by interferons: Effects on tumor- and lymphocyte-induced vascular responses. Cancer Res47:5155–5161.

Anonymous (1999a) Genentech takes VEGF back to lab. SCRIP 2493:24.

Ziche M, Morbidelli L, Choudhuri R, Zhang HT, Donnini S, Granger HJ,Bicknell R (1997) Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99:2625–2634.

 

Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H, Kuwano M(1997) Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor α-dependent angiogenesis. Mol Cell Biol 17:4015–4023.

 

Vittet D, Prandini MH, Berthier R, Schweitzer A, Martin SH, Uzan G,Dejana E (1996) Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps. Blood 88:3424–3431.

 

Ruegg C, Yilmaz A, Bieler G, Bamat J, Chaubert P, Lejeune FJ (1998) Evidence for the involvement of endothelial cell integrin αvβ3 in the disruption of the tumor vasculature induced by TNF and IFN. Nat Med4:408–414

Patey N, Vazeux R, Canioni D, Potter T, Gallatin WM, Brousse N (1996) Intercellular adhesion molecule-3 on endothelial cells. Expression in tumors but not in inflammatory responses. Am J Pathol 148:465–472.

Oliver SJ, Banquerigo ML, Brahn E (1994) Supression of collagen-induced arthritis using an angiogenesis inhibitor AGM-1470 and microtubule stabilizer taxol. Cell Immunol 157:291–299

Molema G, Griffioen AW (1998) Rocking the foundations of solid tumor growth by attacking the tumor’s blood supply. Immunol Today 19:392–394.

 

Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M,Ashare AB, Lathi K, Isner JM (1998) Gene therapy for myocardial angiogenesis: Initial clinical results with direct myocardial injection of PhVEGF165 as sole therapy for myocardial ischemia. Circulation98:2800–2804.

Jain RK, Schlenger K, Hockel M, Yuan F  (1997) Quantitative angiogenesis assays: Progress and problems. Nat Med 3:1203–1208.

Jain RK (1996) 1995 Whitaker Lecture: Delivery of molecules, particles and cells to solid tumors. Ann Biomed Eng 24:457–473.

 

Giraudo E, Primo L, Audero E, Gerber H, Koolwijk P, Soker S,Klagsbrun M, Ferrara N, Bussolino F (1998) Tumor necrosis factor-alpha regulates expression of vascular endothelial growth factor receptor-2 and of its co-receptor neuropilin-1 in human vascular endothelial cells. J Biol Chem273:22128–22135.

Inflammation Genomics

Kocarnik JM, Pendergrass SA, Carty CL, Pankow JS, Schumacher FR, Cheng I, Durda P, Ambite JL, Deelman E, Cook NR, Liu S, Wactawski-Wende J, Hutter C, Brown-Gentry K, Wilson S, Best LG, Pankratz N, Hong CP, Cole SA, Voruganti VS, Bůžkova P, Jorgensen NW, Jenny NS, Wilkens LR, Haiman CA, Kolonel LN, Lacroix A, North K, Jackson R, Le Marchand L, Hindorff LA, Crawford DC, Gross M, Peters U. Multi-Ancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture using Genomics and Epidemiology (PAGE) Study. Circ Cardiovasc Genet. 2014 Mar 12

Ellis J, Lange EM, Li J, Dupuis J, Baumert J, Walston JD, Keating BJ, Durda P, Fox ER, Palmer CD, Meng YA, Young T, Farlow DN, Schnabel RB, Marzi CS, Larkin E, Martin LW, Bis JC, Auer P, Ramachandran VS, Gabriel SB, Willis MS, Pankow JS, Papanicolaou GJ, Rotter JI, Ballantyne CM, Gross MD, Lettre G, Wilson JG, Peters U, Koenig W, Tracy RP, Redline S, Reiner AP, Benjamin EJ, Lange LA. Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novelassociation at CD36 in African Americans. Hum Genet. 2014 Mar 19.

Ricaño-Ponce I, Wijmenga C. Mapping of immune-mediated disease genes. Annu Rev Genomics Hum Genet. 2013;14:325-53. doi: 10.1146/annurev-genom-091212-153450. Epub 2013 Jul 3. Review.

McKillop AM, Flatt PR. Emerging applications of metabolomic and genomic profiling in diabetic clinical medicine. Diabetes Care. 2011 Dec;34(12):2624-30. doi: 10.2337/dc11-0837. Review.

Ricaño-Ponce I, Wijmenga C. Mapping of immune-mediated disease genes. Annu Rev Genomics Hum Genet. 2013;14:325-53. doi: 10.1146/annurev-genom-091212-153450. Epub 2013 Jul 3.Review.

Chen YB, Cutler CS. Biomarkers for acute GVHD: can we predict the unpredictable? Bone Marrow Transplant. 2013 Jun;48(6):755-60. doi: 10.1038/bmt.2012.143. Epub 2012 Aug 6. Review.

Cho JH, Gregersen PK. Genomics and the multifactorial nature of human autoimmune disease. N Engl J Med. 2011 Oct 27;365(17):1612-23. doi: 10.1056/NEJMra1100030. Review.

Shikama N, Nusspaumer G, Hollander GA. Clearing the AIRE: on the pathophysiological basis of the autoimmune polyendocrinopathy syndrome type-1. Endocrinol Metab Clin North Am2009;38:273-288

Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med 2009;360:1646-1654

Posted in Biomarkers & Medical Diagnostics, Calcium Signaling, CANCER BIOLOGY & Innovations in Cancer Therapy, Genome Biology, Human Immune System in Health and in Disease, Human Sensation and Cellular Transduction: Physiology and Therapeutics, Immunodiagnostics, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacogenomics, Systemic Inflammatory Response Related Disorders, Translational Research, Translational Science | Tagged , , , , , , , , , , , , , , , , , , , , , | Leave a Comment »

From Genomics of Microorganisms to Translational Medicine

March 20, 2014 by Demet Sag, Ph.D., CRA, GCP

From Genomics of Microorganisms to Translational Medicine

Reporter and Curator: Demet Sag, PhD

Pharmacogenomics needs new materials that are inert against the host and specifically  active to modulate molecular metabolism towards wanted homeostasis of the physiological system.  These can come from natural resources or men-made.  That is why we must know the origin  to  improve.     Recently, Synthetic Biology, even though it is a developing upcoming field, it is generating mile stones for applications in the clinic, the biotechnology industry and in basic molecular research. As  a result, it created a multidisciplinary expertise from scientists to engineers.  Among other things extending the search to first life on Earth is one of the many alternatives.  Here I like to present how synthetic biology can be initiated onto Translational Medicine from adiscovery of molecules from the sea.

Microorganisms played a role in evolution to start a life.  99 % of our genome is related to microbial organisms. initially there was a classical  Microbiology, then evolved to Industrial Microbiology and Biotechnology then Microbial Genomics and now Microbiome and Health became the focus.  Finally,  the circle is getting tide into how microbiome involved with healthy and disease state of human? How they can be used that is what it really means to include microorganisms into human health for diagnostics and targeted therapies?

Or should we start from  scarcity?

Microbiology is my first formal education and  building block.  Simple but help to understand system biology and  the mechanism of life in a nut shell.   The closest field is embryonic stem cell biology for building “synthesizing” a whole new organism.  Then  system biology and developmental biology also gain interest.

The real  remember the month of October in 2001 when DOE reported that they sequenced 23 organisms in Walnut Creek.  Having seen presentation to identify microorganisms through complex crystal structure assays through chemical pathway  at the Microbial Genomics Meeting organized by ASM in Monterey, CA in 2001.

Discovery of microorganisms in marine life like in Mediterranean Sea, containing 38% salt,is very similar with finding circulating disease making cells.   Yet, they are similar since both search for a specific needle in the pile.  Furthermore, the unique behavior of enzymes from microbial organisms such as Taq polymerase or restriction enzymes made it possible for us to develop new technologies for copying and propagating significant sequences.  When these early molecular biology methods are combined with the power of genomics and knowledge of unique structures in molecular physiology, it is possible to design better and sensitive sensors or build an organism to rptect or fix the need of the body.  neither sensors nor synthesized organism model are complete since one is missing the basic element of life “transformation of information” the other is missing the integrity that once nature provided in a single simple cell.

Having sensory smart chip/band/nanomolecule to redesign the cells may also possible if only we know the combination.  Thus, we have options to deliver if we know what to be carried.

An external file that holds a picture, illustration, etc.<br /><br /><br /><br /><br /> Object name is marinedrugs-11-00700-g002.jpg

(Figure: The combined strategy of gene-based screening and bioactivity-based screening for marine microbial natural products (MMNPs) discovery, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705366/figure/marinedrugs-11-00700-f002/)

As we come across, novel pathways or primary pathways of physiology gain significant interest to determine marine microbial compound for therapeutics since they are further away from the evolution three that gives an advantage for biomedical/translational scientist to avoid most part of th eimmune responses such as inflammation, toxicity. Yes, indeed these are not scientific tails but true since currently, 16 of 20 marine antitumor compounds under clinical trial are derived from microbial sources because marine microorganisms are a major source for MMNP discovery.  However, isolation of these organisms.  For example, pretreatment methods, enrichment, physical, and chemical techniques (e.g., dry heat, exposure to 1%–1.5% phenol, sucrose-gradient centrifugation, and filtration through cellulose membrane filters) can be applied to increase especially the less abundant specific groups of marine microorganisms, . A variety of pretreatment methods including recovery of these microorganisms.  This reminds me ecosystem of the soil, since in soil the trouble is identifying the specific culture among millions of others.

Regardless of the case,  nutrients are the key for selecting and isolating any organisms but specifically, as a result any marine microbes have specific nutrient requirements for growth (e.g., sponge extract ) or chemical (e.g., siderophores, signal molecules, non-traditional electron donors, and electron acceptors.  This also should remind us subject of Biology 101 Essential Vitamins and Minerals.  What we eat who we are.

For example, Bruns et al. employed technique where they employed different carbon substrates (agarose, starch, laminarin, xylan, chitin, and glucose) at low concentrations (200 μM each) so that they can  improve the cultivation efficiency of bacteria from the Gotland Deep in the central Baltic Sea. As a result of this growth medium they were able to elevate yield, which is created higher cultivation efficiencies (up to 11% in fluid media) compared to other studies.

Yet, another component must be addressed that is culture medium such as ionic strength for a microbila growth. For example, Tsueng et al. study on marine actinomycete genus Salinispora that can produce bioactive secondary metabolites such as desferrioxamine, saliniketals, arenamides, arenimycin and salinosporamide.  However, they observed that  three species of Salinispora, S. arenicola, S. tropica, and S. pacifica require a high ionic strength but  S. arenicolahas a lower growth requirement for ionic strength than S. tropica and S. pacificaUsing after assaying them against sodium chloride-based and lithium chloride-based media. As  aresult, there is a specificity for growth. 

In addition, energy must be supported imagine that in marine organisms the metabolism is very unique, may be slow and possibly.  However, the main criteria is  most of them grow under low oxygen conditions like tumors.  Warburg effect posed a  problem for human but helped microorganisms to survive and evolve.  One’s weakness the other’s strength make a great teamwork for solving diseases of human kind es especially for cancer. 

This reminds us to utilize minerals, electrons specifically after all the simplest form of carbon metabolism based on biochemical pathways like Crebs cycle, one carbon metabolism and amino acid metabolism etc. Even though 90% of human body made up off microbial origin there are microorganisms that are not cultured yet.

The irony is less than 1% of microorganisms can be cultured.  Furthermore, they are not included for representing the total phylogenetic diversity. Therefore, majority of work concentrated on finding and cultivating the uncultured majority of the microbial world for MMNPs’.  For example,  an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei  producing many antitumor compounds such as pederin, mycalamide A, and onnamide A.

In any conditions if any living needs to be recognized and remembered, their place would be either on top or the bottom of the stack. Microbiome searches for specificity among tone of other organisms to recognize the disease, changes in cell differentiation and pathways or marine microbiologist search for uncommon scarce organisms. Yet, both of them are beneficial with their unique way.

Then what is the catch or fuss?  The catch is screening to identify what makes this organism unique that can be use for human health. Translational medicine may start from the beginning of life from microorganisms created.  This can be called with its newly coined named”synthetic biology” but if we go further than the conventional screening methods which include bioactivity-guided screening and gene-guided screening  and increase the power with genomics we may call it “synthetic genomics”.

As  a result these signature sequences establishes the “unique” biomarkers  or therpaeutics to be used for drug discovery, making vaccines, and remodulating the targeted cells. How?

These microorganisms secrete these metabolites or proteins to their growth medium just like a soluble protein, if you will like a inflammation factor or any other secreted protein of our human body cells. Collecting substrate or extract the pellet could be the choice.   in a nut shell this require at least three steps: First, finding the bioactivity, apply bioactivity-guided screening for direct detection of  the activity such as antimicrobial, antitumor, antiviral, and antiparasitic activities.  Second, a bioinformatic assessment of the secondary metabolite biosynthetic potential in the absence of fully assembled pathways or genome sequences. Third, application on cell lines and possible onto model organisms can improve the process of MMNP discovery so that allow us to prioritize strains for fermentation studies and chemical analysis. 

In summary, establish the culture growth, analyze bioactivity and discover the new gene product to be used.  Here is an example, first they  isolated Marinispora sp from the saline culture.  Next step,  identify new sources of bioactive secondary metabolites, gene-guided screening has been deployed to search target genes associated with NPs biosynthetic pathways, e.g., the fragments between ketosynthase and methylmalonyl-CoA transferase of polyketides (PKS) type I, enediyne PKS ketosynthase gene, O-methyltransferase gene, P450 monooxygenase gene, polyether epoxidase gene, 3-hydroxyl-3-methylglutaryl coenzyme A reductase gene, dTDP-glucose-4,6-dehydratase (dTGD) gene, and halogenase gene. The, apply bioinformatics that includes synthesizing the knowledge with  homology-based searches and phylogenetic analyses, gene-based screening  to predict new secondary metabolites discovered by isolates or environments.  Finally, identify the sequnce for PCR and use against a cell line or model organisms. In this case,  CNQ-140 based on significant antibacterial activities  against drug-resistant pathogens (e.g., MRSA) and impressive and selective cancer cell cytotoxicities (0.2–2.7 μM of MIC50 values) against six melanoma cell lines provided significant outcome. They are recognized as antitumor antibiotics with a new structural class, marinomycins A–D

This is a great method but there are two botle necks: 1. 99% of microbial organisms are not cultured in the labs. 2. Finding the optimum microbial growth and screening takes time. Thus, assesments can me done through metagenomics.  However, metagenomics has its shortcomings since on face of living unless applications applied in vivo in vitro results may not be valid.  The disadvantage of  metagenomics can be listed as:  1. inability of efficient acquisition of intact gene fragment,  2. incompatibility of expression elements such as promoter in a heterologous host.  On the pther hand, there can be possible resolution to avoid these factors  so metagenomics-based MMNP discovery can be plausable such as development  in  synthetic biology by large DNA fragment assembly techniques for artificial genome synthesis and synthetic microbial chassis suitable for different classes of MMNP biosynthesis.

However, many gene clusters have been identified by combined power of genomics and biioinformatics for MNP discovery.  This is  mainly necessary since  secondary metabolites usually biosynthesized by large multifunctional synthases that acts in a sequential assembly lines like adding carboxylic acid and amino acid building blocks into their products.  

 References

Simmons TL, Coates RC, Clark BR, Engene N, Gonzalez D, Esquenazi E, Dorrestein PC, Gerwick W

Proc Natl Acad Sci U S A. 2008 Mar 25; 105(12):4587-94.

Posted in Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Computational Biology/Systems and Bioinformatics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, Metabolomics, Personalized and Precision Medicine & Genomic Research, Pharmaceutical R&D Investment, Pharmacogenomics, Translational Science | Tagged , , , , , , , , , , , , , , , | Leave a Comment »

Public and Private Partnership @ The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoting Public & Private Sector Collaboration & Investment in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

March 19, 2014 by 2012pharmaceutical

March 19, 2014

5PM

Public & Private Partnerships

Co-Chaired by: Louis J. DeGennaro, Interim President and CEO, Chief Mission Ocer, The Leukemia and Lymphoma Society
Beth Jacobs, Managing Partner, Excellentia Global Partners
Featuring: Darryl Mitteldorf, Executive Director, Global Prostate Cancer Alliance
Dov Hass, Associate, Morgan, Lewis & Bockius LLP
Kristina Khodova, Head of Oncology Projects, Biomed Cluster, Skolkovo Foundation
Louise M. Perkins, Chief Science Ocer, Melanoma Research Alliance
Peter L. Hoang, Managing Director, Oce of Innovations, Technology Based Ventures, The University of Texas MD Anderson Cancer Center
Steven Young, President & COO, Addario Lung Cancer Medical Institute
Walter M. Capone, President, Multiple Myeloma Research Foundation

Public & Private Partnership

  • Foundation are playing a new role: The enable Cancer Research, links to biopharma, Scientific staff, understanding of the commercial landscape
  • Universities: Public & Private

Question #1: Difficulties in working with small biotech companies

Non-Profits are disease focus, Biotech have expectation to gain capital funding from the Non-Profits

Non-Profit has access to Patients information and disease condition in the pre-approval period, Consortia: addresses access to Resources do not invest or fund pharma companies, they fund diagnostics lab, stem cell companies

Foundations  have right to publish data, IP ownership is still unresolved an issue, Dana Farber can’t be encouraged to give away its IP but a Foundation can accelerate the process.

IP Licensing

Academic institution as LISENSORS WHILE HAVING having bond obligation, Tax exempt status is exclusive, while the bond owner status is non-exclusive

Appetite for Risk – Venture Capital vs Foundation

  • Louis J. DeGennaro, Interim President and CEO, Chief Mission Ocer, The Leukemia and Lymphoma Society – provides $60 millions a year for R&D – they do take significant Risk. Size of population of patients is not a factor, serving all is. No detection, No screening, Patients present with full blown disease
  • Darryl Mitteldorf, Executive Director, Global Prostate Cancer Alliance — Risk does not belong to this organization. Foundation funded research on the disparity between Black and White patients.
  • Louise M. Perkins, Chief Science Officer, Melanoma Research Alliance – UV cause, funding research for personalized. medicine. Foundation has educated FDA, Sequencing of melanoma larger that sequencing of the Genome
  • Steven Young, President & COO, Addario Lung Cancer Medical Institute 70% of Lung Cancer Patients were not Smokers

__________________

8:00 AM – On the 40th Floor of 7 World Trade Center in NYC

@  The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoting Public & Private Sector Collaboration & Investment in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

Follow me @pharma_BI

  • Event Coverage
  • Cancer & Genomic – Volume One in LPBI’s BioMed e-Series C: Cancer
  • Alnion Venture Funding Prospecting & Negotiation

Aviva Lev-Ari, PhD, RN

Founder and Director

Leaders in Pharmaceutical Business Intelligence

Editor-in-Chief

http://pharmaceuticalintelligence.com

Posted in Technology Transfer: Biotech and Pharmaceutical | Leave a Comment »

Cancer Biology and Genomics for Disease Diagnosis, Volume One Pre-ePub Announcement

March 17, 2014 by sjwilliamspa

Leaders in Pharmaceutical Business Intelligence announce their latest addition to the BioMed e-Series ebooks: Cancer Biology and Genomics for Disease Diagnosis, Volume One.

This ebook is a compendium of recent breakthroughs, articles, and commentary on cancer research, cancer detection and diagnosis and treatment, written and curated by a team of PhD, MD, MD/PhD, PharmD clinicians, scientists, and writers having expertise in oncology.

Leaders in Pharmaceutical Business Intelligence will demonstrate this e-book at  The Sachs Cancer Bio Partnering and Investment Forum, held March 19, 2014 at the New York Academy of Sciences in New York, USA.

A post on this site entitled The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum Promoting Public & Private Sector Collaboration & Investment in Drug Development, 19th March 2014 • New York Academy of Sciences • USA explains the program, agenda, a description of this investment conference.

A flyer of the demonstration by Leaders in Pharmaceutical Intelligence is included below (please click on picture):

SACHS FLYER 2014 CANCER EBOOKjpeg-page1

SACHS FLYER 2014 CANCER EBOOKjpeg-page2

 

The flyer can be downloaded as a .pdf here: SACHS FLYER 2014 CANCER EBOOK

April 2014 will see LAUNCH of next VOLUME in Series C: e-Books on Cancer & Oncology Radiation Oncology & Immunotherapy in Cancer

Posted in Academic Publishing, CANCER BIOLOGY & Innovations in Cancer Therapy, Health Economics and Outcomes Research, HealthCare IT, Open Access Journals | Tagged , , , , , | Leave a Comment »

The Web at 25: The Value of Open

March 17, 2014 by 2012pharmaceutical

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Forensic Science Research Opportunity

March 13, 2014 by 2012pharmaceutical

Forensic Science Research Opportunity

Reporter: Aviva Lev-Ari, PhD, RN

From: Pierson, Steve [mailto:spierson@amstat.org]
Sent: Wednesday, March 12, 2014 9:16 AM
To: stat-acad-reps
Subject: Forensic Science opportunity

Dear Department Chairs/Representatives,

I write to request names of faculty who might be willing to serve on a standing review panel for the National Institute of Justice. The ASA forensic science committee cannot meet current demand for statisticians to be involved in forensic science and so suggested this email as an opportunity for younger faculty to learn about this funding agency and to be exposed to forensic science research challenges.

One of the standing review committee is an established one in Impression & Pattern Evidence (fingerprint, firearms, blood pattern, etc.) and the other is a new one in Trace Evidence (hair, fibers, paint, particles, etc.).  They ask reviewers for a 3-year commitment and hold an in-person review panel meeting annually in June in the DC area. Some of the ASA forensic science members have served on the established panel and describe as very interesting and less work than an NSF panel.

Please send any suggestions to me by Monday morning (and preferably sooner.)

Here’s additional information on the standing review panels that we’ve learned:
-Establishing scientifically valid foundations for assigning values to forensic comparisons is one of the top concerns in forensic science today.  We certainly feel that our funding decisions benefit when projects get adequate scrutiny of their statistical methods on the front end, and we hope to insure that by including the right expertise on our review panels.

– As to the question that your member had about subject matter expertise:  we’re not necessarily just looking for people with significant experience with a forensic science field.  If you’re able to refer qualified statisticians with that background, that would be great—but as you’ve said that list is rather short.  Primarily, we’re looking for statisticians who would be able to act as second reviewers of projects that rely to a large extent on statistical methods or that would only be successful if grounded in a statistically valid methodology.  For some particularly stats-heavy proposals, they may serve as lead reviewer, and would be appropriately paired with a technical expert. They would not be expected to weigh in on matters beyond the scope of their expertise (e.g., whether a specific FS technique is appropriate or practical).  Our panels will have 12-18 members, so there is plenty of room for a diversity of experience and background.

-Recusals from the panel are handled year by year. If they plan to apply this year to the solicitation “Research and Development in Forensic Science for Criminal Justice Purposes” (link below), it would be best if they didn’t offer to serve, as they would immediately be recused for COI. But once on the panel, there is nothing to prevent them from applying to the solicitation in a subsequent cycle, as long as they let us know that they will need to be recused. (FYI, here is the current solicitation: https://www.ncjrs.gov/pdffiles1/nij/sl001082.pdf.)

I should also give you a heads-up that we’ll be encouraging statisticians to apply for positions on the various committees of the newly established NIST forensic science oversight body called Organization of Scientific Area Committees (OSAC), to replace what has been known as the Scientific Working Groups. The OSAC and the ways to serve are described at http://www.nist.gov/forensics/upload/osac-021814.pdf. We expect the application process to open up within a month. If you open up those slides, you’ll see that “statistician” is mentioned 7 times.

Best Wishes,
Steve

Steve Pierson, Ph.D.
Director of Science Policy

American Statistical Association
Promoting the Practice and Profession of Statistics™
732 North Washington Street
Alexandria, VA 22314-1943
(703) 302-1841
http://www.amstat.org/policy <http://www.amstat.org/policy>
For ASA science policy updates, follow us on Twitter: @ASA_SciPol

http://www.amstat.org/asa175/index.cfm 

SOURCE

From: Tom Lane <Tom.Lane@mathworks.com>
Date: Thu, 13 Mar 2014 21:49:05 +0000
To: “tlane@alum.mit.edu” <tlane@alum.mit.edu>
Conversation: [BCASA] Forensic Science opportunity
Subject: [BCASA] Forensic Science opportunity

Posted in Scientist: Career considerations, Statistical Methods for Research Evaluation | Leave a Comment »

ENC Lawmaker Wants To Legalize Specific Type Of Medical Marijuana – WITN

March 12, 2014 by 2012pharmaceutical

See on Scoop.it – Cardiotoxicity

ENC Lawmaker Wants To Legalize Specific Type Of Medical Marijuana
WITN
That mom’s 5-year-old daughter has tried all other medicines and nothing has worked. “It’s the only hope they have right now,” says McElraft.

See on www.witn.com

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Reassessing the Role of Beta-Blockers in the Management of Hypertension – My Courses

March 12, 2014 by 2012pharmaceutical

See on Scoop.it – Cardiovascular Disease: PHARMACO-THERAPY

Experts agree that beta-blockers play an important and continuing role in the management of hypertensive patients; however, recent and conflicting …

See on healthxpressonline.net

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Beta adrenergic blockers lower… – ” Sudanese Young Pharmacists , Every Day One Drug ” | Facebook

March 12, 2014 by 2012pharmaceutical

See on Scoop.it – Cardiovascular Disease: PHARMACO-THERAPY

Beta adrenergic blockers lower intraocular tension by:
A.Down regulating adenylyl cyclase in ciliary body… http://t.co/AAf13VdEDP

See on www.facebook.com

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