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National Resilience, Inc. is a first-of-its-kind manufacturing and technology company dedicated to broadening access to complex medicines and protecting biopharmaceutical supply chains against disruption – the Acquisition of Two Premier Biologics Manufacturing Facilities: Boston and in Ontario, Canada

 

Reporter: Aviva Lev-Ari, PhD, RN

Resilience’s new facility, located at 500 Soldiers Field Rd., Boston, MA. (Photo: Business Wire) – The Genzyme-Sanofi Building

 

SAN DIEGO & BOSTON–(BUSINESS WIRE)–Resilience (National Resilience, Inc.), a new company building the world’s most advanced biopharmaceutical manufacturing ecosystem, announced it has acquired two premier commercial manufacturing facilities in North America, joining other facilities already in Resilience’s network to boost total capacity under management to more than 750,000 square feet.

“These locations will serve as hubs for the future of biopharma manufacturing, leading the way and shaping the future of Resilience.”

  • The acquired facilities include a 310,000-square-foot plant in Boston, MA, purchased from Sanofi; and in a separate transaction,
  • a 136,000-square-foot plant in Mississauga, Ontario, Canada.

Both facilities, which currently produce commercial, marketed products, will see significant investments as Resilience adds capacity and capabilities to produce new therapies at these locations. In addition, the company has offered employment to the existing plant staff and intends to add more jobs at each facility.

“We have big plans for these facilities including investing in new capacity, applying new manufacturing technologies, creating jobs and bringing in new customers,” said Rahul Singhvi, Sc.D, Chief Executive Officer of Resilience. “These locations will serve as hubs for the future of biopharma manufacturing, leading the way and shaping the future of Resilience.”

As part of its agreement with Sanofi, Resilience will continue to manufacture a marketed product at the Boston location. The facility plan includes a build out to facilitate multi-modality manufacturing and state-of-the-art quality laboratories to ensure safe, reliable supply to patients. The facility itself is certified ISO 14001 (Environmental management system), OSHAS 18001 (Health & safety management system) and ISO 50001 (Energy management system).​

This is currently the largest of several facilities in Resilience’s growing biologics and advanced therapeutics manufacturing network, with plans to acquire and develop other sites in the U.S. this year. The facility offers 24/7/365 production, multiple 2000L bioreactors capacity and multiple downstream processing trains, with investment in additional capabilities to come.

Our state-of-the-art flexible facility in Mississauga, Ontario, provides upstream, downstream and aseptic fill finish, and is designed to comply with cGMP. The plant has been inspected and approved by multiple regulatory bodies, and handles development and commercialized products.

About Resilience

Resilience (National Resilience, Inc.) is a first-of-its-kind manufacturing and technology company dedicated to broadening access to complex medicines and protecting biopharmaceutical supply chains against disruption. Founded in 2020, the company is building a sustainable network of high-tech, end-to-end manufacturing solutions to ensure the medicines of today and tomorrow can be made quickly, safely, and at scale. Resilience offers the highest quality and regulatory capabilities, and flexible and adaptive facilities to serve partners of all sizes. By continuously advancing the science of biopharmaceutical manufacturing and development, Resilience frees partners to focus on the discoveries that improve patients’ lives.

For more information, visit www.Resilience.com.

Contacts

Ryan Flinn
Head of Communications
Ryan.flinn@Resilience.com
510-207-7616

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Happy 80th Birthday: Radioiodine (RAI) Theranostics: Collaboration between Physics and Medicine, the Utilization of Radionuclides to Diagnose and Treat: Radiation Dosimetry by Discoverer Dr. Saul Hertz, the early history of RAI in diagnosing and treating Thyroid diseases and Theranostics

 

Guest Author: Barbara Hertz

 203-661-0777

htziev@aol.com

Celebrating eighty years of radionuclide therapy and the work of Saul Hertz

First published: 03 February 2021

Both authors contributed to the development, drafting and final editing of this manuscript and are responsible for its content.

Abstract

March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. The breakthrough of Dr. Hertz and collaborator physicist Arthur Roberts was made possible by rapid developments in the fields of physics and medicine in the early twentieth century. Although diseases of the thyroid gland had been described for centuries, the role of iodine in thyroid physiology had been elucidated only in the prior few decades. After the discovery of radioactivity by Henri Becquerel in 1897, rapid advancements in the field, including artificial production of radioactive isotopes, were made in the subsequent decades. Finally, the diagnostic and therapeutic use of radioactive iodine was based on the tracer principal that was developed by George de Hevesy. In the context of these advancements, Hertz was able to conceive the potential of using of radioactive iodine to treat thyroid diseases. Working with Dr. Roberts, he obtained the experimental data and implemented it in the clinical setting. Radioiodine therapy continues to be a mainstay of therapy for hyperthyroidism and thyroid cancer. However, Hertz struggled to gain recognition for his accomplishments and to continue his work and, with his early death in 1950, his contributions have often been overlooked until recently. The work of Hertz and others provided a foundation for the introduction of other radionuclide therapies and for the development of the concept of theranostics.

SOURCE

https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/acm2.13175

 

 

SOURCE

https://www.youtube.com/watch?v=34Qhm8CeMuc

 

http://www.wjnm.org/article.asp?issn=1450-1147;year=…

http://www.wjnm.org/text.asp?2019/18/1/8/250309

Abstract

Dr. Saul Hertz was Director of The Massachusetts General Hospital’s Thyroid Unit, when he heard about the development of artificial radioactivity. He conceived and brought from bench to bedside the successful use of radioiodine (RAI) to diagnose and treat thyroid diseases. Thus was born the science of theragnostics used today for neuroendocrine tumors and prostate cancer. Dr. Hertz’s work set the foundation of targeted precision medicine.

Keywords: Dr. Saul Hertz, nuclear medicine, radioiodine

 

How to cite this article:
Hertz B. A tribute to Dr. Saul Hertz: The discovery of the medical uses of radioiodine. World J Nucl Med 2019;18:8-12

 

How to cite this URL:
Hertz B. A tribute to Dr. Saul Hertz: The discovery of the medical uses of radioiodine. World J Nucl Med [serial online] 2019 [cited 2021 Mar 2];18:8-12. Available from: http://www.wjnm.org/text.asp?2019/18/1/8/250309

 

 

  • Dr Saul Hertz (1905-1950) discovers the medical uses of radioiodine

Barbara Hertz, Pushan Bharadwaj, Bennett Greenspan»

Abstract » PDF» doi: 10.24911/PJNMed.175-1582813482

 

SOURCE

http://saulhertzmd.com/home

 

  • Happy 80th Birthday: Radioiodine (RAI) Theranostics

Thyroid practitioners and patients are acutely aware of the enormous benefit nuclear medicine has made to mankind. This month we celebrate the 80th anniversary of the early use of radioiodine(RAI).

Dr. Saul Hertz predicted that radionuclides “…would hold the key to the larger problem of cancer in general,” and may just be the best hope for diagnosing and treating cancer successfully.  Yes, RAI has been used for decades to diagnose and treat disease.  Today’s “theranostics,” a term that is a combination of “therapy” and “diagnosis” is utilized in the treatment of thyroid disease and cancer. 

            This short note is to celebrate Dr. Saul Hertz who conceived and brought from bench to bedside the medical uses of RAI; then in the form of 25 minute iodine-128.  

On March 31st 1941, Massachusetts General Hospital’s Dr. Saul Hertz (1905-1950) administered the first therapeutic use of Massachusetts Institute of Technology (MIT) cyclotron produced RAI.  This landmark case was the first in Hertz’s clinical studies conducted with MIT, physicist Arthur Roberts, Ph.D.

[Photo – Courtesy of Dr Saul Hertz Archives ]

Dr Saul Hertz demonstrating RAI Uptake Testing

            Dr. Hertz’s research and successful utilization of radionuclides to diagnose and treat diseases and conditions, established the use of radiation dosimetry and the collaboration between physics and medicine and other significant practices.   Sadly, Saul Hertz (a WWII veteran) died at a very young age.  

 

About Dr. Saul Hertz

Dr. Saul Hertz (1905 – 1950) discovered the medical uses of radionuclides.  His breakthrough work with radioactive iodine (RAI) created a dynamic paradigym change integrating the sciences.  Radioactive iodine (RAI) is the first and Gold Standard of targeted cancer therapies.  Saul Hertz’s research documents Hertz as the first and foremost person to conceive and develop the experimental data on RAI and apply it in the clinical setting.

Dr. Hertz was born to Orthodox Jewish immigrant parents in Cleveland, Ohio on April 20, 1905. He received his A.B. from the University of Michigan in 1925 with Phi Beta Kappa honors. He graduated from Harvard Medical School in 1929 at a time of quotas for outsiders. He fulfilled his internship and residency at Mt. Sinai Hospital in Cleveland. He came back to Boston in 1931 as a volunteer to join The Massachusetts General Hospital serving as the Chief of the Thyroid Unit from 1931 – 1943.

Two years after the discovery of artifically radioactivity, on November 12, 1936 Dr. Karl Compton, president of the Massachusetts Institute of Technology (MIT), spoke at Harvard Medical School.  President Compton’s topic was What Physics can do for Biology and Medicine. After the presentation Dr. Hertz spontaneously asked Dr. Compton this seminal question, “Could iodine be made radioactive artificially?” Dr. Compton responded in writing on December 15, 1936 that in fact “iodine can be made artificially radioactive.”

Shortly thereafter, a collaboration between Dr. Hertz (MGH) and Dr. Arthur Roberts, a physicist of MIT, was established. In late 1937, Hertz and Roberts created and produced animal studies  involving 48 rabbits that demonstrated that the normal thyroid gland concentrated Iodine 128 (non cyclotron produced), and the hyperplastic thyroid gland took up even more Iodine.  This was a GIANT step for Nuclear Medicine.

In early 1941, Dr. Hertz administer the first therapeutic treatment of MIT Markle Cyclotron produced radioactive iodine (RAI) at the Massachusetts General Hospital.  This  led to the first series of twenty-nine patients with hyperthyroidism being treated successfully with RAI. ( see “Research” RADIOACTIVE IODINE IN THE STUDY OF THYROID PHYSIOLOGY VII The use of Radioactive Iodine Therapy in Hyperthyroidism, Saul Hertz and Arthur Roberts, JAMA Vol. 31 Number 2).

In 1937, at the time of the rabbit studies Dr Hertz conceived of RAI in therapeutic treatment of thyroid carsonoma.  In 1942 Dr Hertz gave clinical trials of RAI to patients with thyroid carcinoma.

After serving in the Navy during World War II, Dr. Hertz wrote to the director of the Mass General Hospital in Boston, Dr. Paxon on March 12, 1946, “it is a coincidence that my new research project is in Cancer of the Thyroid, which I believe holds the key to the larger problem of cancer in general.”

Dr. Hertz established the Radioactive Isotope Research Institute, in September, 1946 with a major focus on the use of fission products for the treatment of thyroid cancer, goiter, and other malignant tumors. Dr Samuel Seidlin was the Associate Director and managed the New York City facilities. Hertz also researched the influence of hormones on cancer.

Dr. Hertz’s use of radioactive iodine as a tracer in the diagnostic process, as a treatment for Graves’ disease and in the treatment of cancer of the thyroid remain preferred practices. Saul Hertz is the Father of Theranostics.

Saul Hertz passed at 45 years old from a sudden death heart attack as documented by an autopsy. He leaves an enduring legacy impacting countless generations of patients, numerous institutions worldwide and setting the cornerstone for the field of Nuclear Medicine. A cancer survivor emailed, The cure delivered on the wings of prayer was Dr Saul Hertz’s discovery, the miracle of radioactive iodine. Few can equal such a powerful and precious gift. 

To read and hear more about Dr. Hertz and the early history of RAI in diagnosing and treating thyroid diseases and theranostics see –

http://saulhertzmd.com/home

 

   References in https://www.wjnm.org/article.asp?issn=1450-1147;year=2019;volume=18;issue=1;spage=8;epage=12;aulast=Hertz

 

Top

 

1.
Hertz S, Roberts A. Radioactive iodine in the study of thyroid physiology. VII The use of radioactive iodine therapy in hyperthyroidism. J Am Med Assoc 1946;131:81-6.  Back to cited text no. 1
2.
Hertz S. A plan for analysis of the biologic factors involved in experimental carcinogenesis of the thyroid by means of radioactive isotopes. Bull New Engl Med Cent 1946;8:220-4.  Back to cited text no. 2
3.
Thrall J. The Story of Saul Hertz, Radioiodine and the Origins of Nuclear Medicine. Available from: http://www.youtube.com/watch?v=34Qhm8CeMuc. [Last accessed on 2018 Dec 01].  Back to cited text no. 3
4.
Braverman L. 131 Iodine Therapy: A Brief History. Available from: http://www.am2016.aace.com/presentations/friday/F12/hertz_braverman.pdf. [Last accessed on 2018 Dec 01].  Back to cited text no. 4
5.
Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): A single-centre, single-arm, phase 2 study. Lancet Oncol 2018;19:825-33.  Back to cited text no. 5
6.
Krolicki L, Morgenstern A, Kunikowska J, Koiziar H, Krolicki B, Jackaniski M, et al. Glioma Tumors Grade II/III-Local Alpha Emitters Targeted Therapy with 213 Bi-DOTA-Substance P, Endocrine Abstracts. Vol. 57. Society of Nuclear Medicine and Molecular Imaging; 2016. p. 632.  Back to cited text no. 6
7.
Baum RP, Kulkarni HP. Duo PRRT of neuroendocrine tumours using concurrent and sequential administration of Y-90- and Lu-177-labeled somatostatin analogues. In: Hubalewska-Dydejczyk A, Signore A, de Jong M, Dierckx RA, Buscombe J, Van de Wiel CJ, editors. Somatostatin Analogues from Research to Clinical Practice. New York: Wiley; 2015.  Back to cited text no. 7

 

SOURCE

From: htziev@aol.com” <htziev@aol.com>

Reply-To: htziev@aol.com” <htziev@aol.com>

Date: Tuesday, March 2, 2021 at 11:04 AM

To: “Aviva Lev-Ari, PhD, RN” <AvivaLev-Ari@alum.berkeley.edu>

Subject: Dr Saul Hertz : Discovery for the Medical Uses of RADIOIODINE (RAI) MARCH 31ST: 80 Years

 

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

 

Experience with Thyroid Cancer

Author: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/11/23/my-experience-with-thyroid-cancer/

 

New Guidelines and Meeting Information on Advanced Thyroid Cancer as Reported by Cancer Network (Meeting Highlights)

Reporter: Stephen J. Williams, Ph.D.

https://pharmaceuticalintelligence.com/2015/10/20/new-guidelines-and-meeting-information-on-advanced-thyroid-cancer-as-reported-by-cancer-network-meeting-highlights/

The Experience of a Patient with Thyroid Cancer

Interviewer and Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2014/07/14/the-experience-of-a-patient-with-thyroid-cancer/

 

Parathyroids and Bone Metabolism

Writer and Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/02/10/parathyroids-and-bone-metabolism/

 

Thyroid Function and Disorders

Writer and Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/02/05/thyroid-function-and-disorders/

Summary and Perspectives: Impairments in Pathological States: Endocrine Disorders, Stress Hypermetabolism and Cancer

Author and Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2014/11/09/summary-and-perspectives-impairments-in-pathological-states-endocrine-disorders-stress-hypermetabolism-cancer/

Introduction to Impairments in Pathological States: Endocrine Disorders, Stress Hypermetabolism and Cancer

Author and Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2014/11/08/introduction-to-impairments-in-pathological-states-endocrine-disorders-stress-hypermetabolism-cancer/

Metformin, Thyroid-Pituitary Axis, Diabetes Mellitus, and Metabolism

Larry H, Bernstein, MD, FCAP, Author and Curator
and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/9/27/2014/Metformin,_thyroid-pituitary_ axis,_diabetes_mellitus,_and_metabolism

Autophagy-Modulating Proteins and Small Molecules Candidate Targets for Cancer Therapy: Commentary of Bioinformatics Approaches

Author and Curator: Larry H Bernstein, MD, FCAP and Article Architect: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/09/18/autophagy-modulating-proteins-and-small-molecules-candidate-targets-for-cancer-therapy-commentary-of-bioinformatics-approaches/

 

Neural Activity Regulating Endocrine Response

Writer and Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/02/13/neural-activity-regulating-endocrine-response/

 

Pituitary Neuroendocrine Axis

Writer and Curator: Larry H. Bernstein, MD, FCA

https://pharmaceuticalintelligence.com/2015/02/04/pituitary-neuroendocrine-axis/

On the Influence of Hormones on Cancer

VOLUME 4: Human Reproductive System, Genomic Endocrinology and Cancer Types

(Series D: BioMedicine & Immunology) Kindle Edition. On Amazon.com  since February 2, 2021

http://www.amazon.com/dp/B08VTFWVKM

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Biomolecular Condensates: A new approach to biology originated @MIT – Drug Discovery at DewPoint Therapeutics, Cambridge, MA gets new leaders, Ameet Nathwani, MD (ex-Sanofi, ex-Novartis) as Chief Executive Officer and Arie Belldegrun, PhD (ex-Kite Therapeutics) on R&D

Curator & Reporter: Aviva Lev-Ari, PhD, RN

 

Hooked by the science, Arie Belldegrun joins a group of influentials who believe Dewpoint may have the key to the next big thing in biotech

A new approach to biology

“The real voyage of discovery consists, not in seeking new landscapes, but in having new eyes.” Marcel Proust

Starting with the study of P granules in C.elegans embryos in 2009, Tony Hyman, working with his collaborators like Frank Julicher, Cliff Brangwynne, Simon Alberti, Mike Rosen, and Rohit Pappu, began to unravel the mysteries of biomolecular condensates. These scientists realized that P granules behave like liquid droplets that form by phase separation (think of oil droplets in salad dressing) and called them condensates.

In subsequent studies, they found to their surprise that many compartments inside cells had the behavior of condensates: they are liquid-like and form by phase separation.

Inspired by the work of Tony and his colleagues, Richard Young, Phillip Sharp, and Arup Chakraborty at MIT applied these approaches to the study of gene expression, similarly shedding light on many important questions in gene control.

a video thumbnail

 

Press releases and Dewpoint in the news

 
  • Dewpoint Therapeutics Appoints Ameet Nathwani as Chief Executive Officer

    Dewpoint

  • New York Times interviews Rick Young and Amy Gladfelter on the role of condensate “droplets” in COVID-19

    New York Times

  • Dewpoint Therapeutics raises $77 million to go after ‘undruggable’ diseases

    Boston Globe

  • Hooked by the science, Arie Belldegrun joins a group of influentials who believe Dewpoint may have the key to the next big thing in biotech

    Endpoint News

  • Dewpoint Therapeutics to put ‘pedal to the metal’ with $77M round

    FierceBiotech

  • Dewpoint Therapeutics Raises $77M Series B Financing to Advance the Development of Drugs That Target Biomolecular Condensates

    Dewpoint

  • 21 biotech startups that are set to take off, according to top VCs

    Business Insider

  • Proteins — and labs — coming together to prevent Rett Syndrome

    Whitehead Institute

  • Dewpoint Therapeutics Collaborates with Merck to Evaluate Novel Approach for the Treatment of HIV

    Dewpoint

  • Discovery of how cancer drugs find their targets could lead to a new toolset for drug development

    Whitehead Institute

SOURCE

https://dewpointx.com/news/

Other related article published in this Online Open Access Scientific Journal include: 

Economic Potential of a Drug Invention (Prof. Zelig Eshhar, Weitzman Institute, registered the patent) versus a Cancer Drug in Clinical Trials: CAR-T as a Case in Point, developed by Kite Pharma, under Arie Belldegrun, CEO, acquired by Gilead for $11.9 billion, 8/2017.

https://pharmaceuticalintelligence.com/2017/10/04/economic-potential-of-a-drug-invention-prof-zelig-eshhar-weitzman-institute-registered-the-patent-versus-a-cancer-drug-in-clinical-trials-car-t-as-a-case-in-point-developed-by-kite-pharma-unde/

Read Full Post »

Live Conference Coverage AACR 2020 in Real Time: Monday June 22, 2020 Mid Day Sessions

Reporter: Stephen J. Williams, PhD

This post will be UPDATED during the next two days with notes from recordings from other talks

Follow Live in Real Time using

#AACR20

@pharma_BI

@AACR

 

 

 

 

 

 

 

Register for FREE at https://www.aacr.org/

 

AACR VIRTUAL ANNUAL MEETING II

 

June 22-24: Free Registration for AACR Members, the Cancer Community, and the Public
This virtual meeting will feature more than 120 sessions and 4,000 e-posters, including sessions on cancer health disparities and the impact of COVID-19 on clinical trials

 

This Virtual Meeting is Part II of the AACR Annual Meeting.  Part I was held online in April and was centered only on clinical findings.  This Part II of the virtual meeting will contain all the Sessions and Abstracts pertaining to basic and translational cancer research as well as clinical trial findings.

 

REGISTER NOW

 

Pezcoller Foundation-AACR International Award for Extraordinary Achievement in Cancer Research

The prestigious Pezcoller Foundation-AACR International Award for Extraordinary Achievement in Cancer Research was established in 1997 to annually recognize a scientist of international renown who has made a major scientific discovery in basic cancer research OR who has made significant contributions to translational cancer research; who continues to be active in cancer research and has a record of recent, noteworthy publications; and whose ongoing work holds promise for continued substantive contributions to progress in the field of cancer. For more information regarding the 2020 award recipient go to aacr.org/awards.

John E. Dick, Enzo Galligioni, David A Tuveson

DETAILS

Awardee: John E. Dick
Princess Anne Margaret Cancer Center, Toronto, Ontario
For determining how stem cells contribute to normal and leukemic hematopoeisis
  • not every cancer cell equal in their Cancer Hallmarks
  • how do we monitor and measure clonal dynamics
  • Barnie Clarkson did pivotal work on this
  • most cancer cells are post mitotic but minor populations of cells were dormant and survive chemotherapy
  •  only one cell is 1 in a million can regenerate and transplantable in mice and experiments with flow cytometry resolved the question of potency and repopulation of only small percentage of cells and undergo long term clonal population
  • so instead of going to cell lines and using thousands of shRNA looked at clinical data and deconvoluted the genetic information (RNASeq data) to determine progenitor and mature populations (how much is stem and how much is mature populations)
  • in leukemic patients they have seen massive expansion of a single stem cell population so only need one cell in AML if the stem cells have the mutational hits early on in their development
  • finding the “seeds of relapse”: finding the small subpopulation of stem cells that will relapse
  • they looked in BALL;;  there are cells resistant to l-aspariginase, dexamethasone, and vincristine
  • a lot of OXPHOS related genes (in DRIs) that may be the genes involved in this resistance
  • it a wonderful note of acknowledgement he dedicated this award to all of his past and present trainees who were the ones, as he said, made this field into what it is and for taking it into directions none of them could forsee

Monday, June 22

1:30 PM – 3:30 PM EDT

Virtual Educational Session

Experimental and Molecular Therapeutics, Drug Development, Cancer Chemistry

Chemistry to the Clinic: Part 1: Lead Optimization Case Studies in Cancer Drug Discovery

How can one continue to deliver innovative medicines to patients when biological targets are becoming ever scarcer and less amenable to therapeutic intervention? Are there sound strategies in place that can clear the path to targets previously considered “undruggable”? Recent advances in lead finding methods and novel technologies such as covalent screening and targeted protein degradation have enriched the toolbox at the disposal of drug discovery scientists to expand the druggable ta

Stefan N Gradl, Elena S Koltun, Scott D Edmondson, Matthew A. Marx, Joachim Rudolph

DETAILS

Monday, June 22

1:30 PM – 3:30 PM EDT

Virtual Educational Session

Bioinformatics and Systems Biology, Molecular and Cellular Biology/Genetics

Informatics Technologies for Cancer Research

Cancer researchers are faced with a deluge of high-throughput data. Using these data to advance understanding of cancer biology and improve clinical outcomes increasingly requires effective use of computational and informatics tools. This session will introduce informatics resources that support the data management, analysis, visualization, and interpretation. The primary focus will be on high-throughput genomic data and imaging data. Participants will be introduced to fundamental concepts

Rachel Karchin, Daniel Marcus, Andriy Fedorov, Obi Lee Griffith

DETAILS

  • Variant analysis is the big bottleneck, especially interpretation of variants
  • CIVIC resource is a network for curation, interpretation of genetic variants
  • CIVIC curators go through multiple rounds of editors review
  • gene summaries, variant summaries
  • curation follows ACSME guidelines
  • evidences are accumulated, categories by various ontologies and is the heart of the reports
  • as this is a network of curators the knowledgebase expands
  • CIVIC is linked to multiple external informatic, clinical, and genetic databases
  • they have curated 7017 clinical interpretations, 2527 variants, using 2578 papers, and over 1000 curators
  • they are currently integrating with COSMIC ClinVar, and UniProt
  • they are partnering with ClinGen to expand network of curators and their curation effort
  • CIVIC uses a Python interface; available on website

https://civicdb.org/home

The Precision Medicine Revolution

Precision medicine refers to the use of prevention and treatment strategies that are tailored to the unique features of each individual and their disease. In the context of cancer this might involve the identification of specific mutations shown to predict response to a targeted therapy. The biomedical literature describing these associations is large and growing rapidly. Currently these interpretations exist largely in private or encumbered databases resulting in extensive repetition of effort.

CIViC’s Role in Precision Medicine

Realizing precision medicine will require this information to be centralized, debated and interpreted for application in the clinic. CIViC is an open access, open source, community-driven web resource for Clinical Interpretation of Variants in Cancer. Our goal is to enable precision medicine by providing an educational forum for dissemination of knowledge and active discussion of the clinical significance of cancer genome alterations. For more details refer to the 2017 CIViC publication in Nature Genetics.

U24 funding announced: We are excited to announce that the Informatics Technology for Cancer Research (ICTR) program of the National Cancer Institute (NCI) has awarded funding to the CIViC team! Starting this year, a five-year, $3.7 million U24 award (CA237719), will support CIViC to develop Standardized and Genome-Wide Clinical Interpretation of Complex Genotypes for Cancer Precision Medicine.

Informatics tools for high-throughput analysis of cancer mutations

Rachel Karchin
  • CRAVAT is a platform to determine, categorize, and curate cancer mutations and cancer related variants
  • adding new tools used to be hard but having an open architecture allows for modular growth and easy integration of other tools
  • so they are actively making an open network using social media

Towards FAIR data in cancer imaging research

Andriy Fedorov, PhD

Towards the FAIR principles

While LOD has had some uptake across the web, the number of databases using this protocol compared to the other technologies is still modest. But whether or not we use LOD, we do need to ensure that databases are designed specifically for the web and for reuse by humans and machines. To provide guidance for creating such databases independent of the technology used, the FAIR principles were issued through FORCE11: the Future of Research Communications and e-Scholarship. The FAIR principles put forth characteristics that contemporary data resources, tools, vocabularies and infrastructures should exhibit to assist discovery and reuse by third-parties through the web. Wilkinson et al.,2016. FAIR stands for: Findable, Accessible, Interoperable and Re-usable. The definition of FAIR is provided in Table 1:

Number Principle
F Findable
F1 (meta)data are assigned a globally unique and persistent identifier
F2 data are described with rich metadata
F3 metadata clearly and explicitly include the identifier of the data it describes
F4 (meta)data are registered or indexed in a searchable resource
A Accessible
A1 (meta)data are retrievable by their identifier using a standardized communications protocol
A1.1 the protocol is open, free, and universally implementable
A1.2 the protocol allows for an authentication and authorization procedure, where necessary
A2 metadata are accessible, even when the data are no longer available
I Interoperable
I1 (meta)data use a formal, accessible, shared, and broadly applicable language for knowledge representation.
I2 (meta)data use vocabularies that follow FAIR principles
I3 (meta)data include qualified references to other (meta)data
R Reusable
R1 meta(data) are richly described with a plurality of accurate and relevant attributes
R1.1 (meta)data are released with a clear and accessible data usage license
R1.2 (meta)data are associated with detailed provenance
R1.3 (meta)data meet domain-relevant community standards

A detailed explanation of each of these is included in the Wilkinson et al., 2016 article, and the Dutch Techcenter for Life Sciences has a set of excellent tutorials, so we won’t go into too much detail here.

  • for outside vendors to access their data, vendors would need a signed Material Transfer Agreement but NCI had formulated a framework to facilitate sharing of data using a DIACOM standard for imaging data

Monday, June 22

1:30 PM – 3:01 PM EDT

Virtual Educational Session

Experimental and Molecular Therapeutics, Cancer Chemistry, Drug Development, Immunology

Engineering and Physical Sciences Approaches in Cancer Research, Diagnosis, and Therapy

The engineering and physical science disciplines have been increasingly involved in the development of new approaches to investigate, diagnose, and treat cancer. This session will address many of these efforts, including therapeutic methods such as improvements in drug delivery/targeting, new drugs and devices to effect immunomodulation and to synergize with immunotherapies, and intraoperative probes to improve surgical interventions. Imaging technologies and probes, sensors, and bioma

Claudia Fischbach, Ronit Satchi-Fainaro, Daniel A Heller

DETAILS

Monday, June 22

1:30 PM – 3:30 PM EDT

Virtual Educational Session

Survivorship

Exceptional Responders and Long-Term Survivors

How should we think about exceptional and super responders to cancer therapy? What biologic insights might ensue from considering these cases? What are ways in which considering super responders may lead to misleading conclusions? What are the pros and cons of the quest to locate exceptional and super responders?

Alice P Chen, Vinay K Prasad, Celeste Leigh Pearce

DETAILS

Monday, June 22

1:30 PM – 3:30 PM EDT

Virtual Educational Session

Tumor Biology, Immunology

Exploiting Metabolic Vulnerabilities in Cancer

The reprogramming of cellular metabolism is a hallmark feature observed across cancers. Contemporary research in this area has led to the discovery of tumor-specific metabolic mechanisms and illustrated ways that these can serve as selective, exploitable vulnerabilities. In this session, four international experts in tumor metabolism will discuss new findings concerning the rewiring of metabolic programs in cancer that support metabolic fitness, biosynthesis, redox balance, and the reg

Costas Andreas Lyssiotis, Gina M DeNicola, Ayelet Erez, Oliver Maddocks

DETAILS

Monday, June 22

1:30 PM – 3:30 PM EDT

Virtual Educational Session

Other Articles on this Open Access  Online Journal on Cancer Conferences and Conference Coverage in Real Time Include

Press Coverage

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Symposium: New Drugs on the Horizon Part 3 12:30-1:25 PM

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on NCI Activities: COVID-19 and Cancer Research 5:20 PM

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Evaluating Cancer Genomics from Normal Tissues Through Metastatic Disease 3:50 PM

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Novel Targets and Therapies 2:35 PM

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Hypertriglyceridemia: Evaluation and Treatment Guideline

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Severe and very severe hypertriglyceridemia increase the risk for pancreatitis, whereas mild or moderate hypertriglyceridemia may be a risk factor for cardiovascular disease. Individuals found to have any elevation of fasting triglycerides should be evaluated for secondary causes of hyperlipidemia including endocrine conditions and medications. Patients with primary hypertriglyceridemia must be assessed for other cardiovascular risk factors, such as central obesity, hypertension, abnormalities of glucose metabolism, and liver dysfunction. The aim of this study was to develop clinical practice guidelines on hypertriglyceridemia.

The diagnosis of hypertriglyceridemia should be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150–999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very severe hypertriglyceridemia (triglycerides of >1000 mg/dl) be considered a risk for pancreatitis. The patients with hypertriglyceridemia must be evaluated for secondary causes of hyperlipidemia and that subjects with primary hypertriglyceridemia be evaluated for family history of dyslipidemia and cardiovascular disease.

The treatment goal in patients with moderate hypertriglyceridemia should be a non-high-density lipoprotein cholesterol level in agreement with National Cholesterol Education Program Adult Treatment Panel guidelines. The initial treatment should be lifestyle therapy; a combination of diet modification, physical activity and drug therapy may also be considered. In patients with severe or very severe hypertriglyceridemia, a fibrate can be used as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis.

Three drug classes (fibrates, niacin, n-3 fatty acids) alone or in combination with statins may be considered as treatment options in patients with moderate to severe triglyceride levels. Statins are not be used as monotherapy for severe or very severe hypertriglyceridemia. However, statins may be useful for the treatment of moderate hypertriglyceridemia when indicated to modify cardiovascular risk.

 

References:

 

https://www.medpagetoday.com/clinical-connection/cardio-endo/77242?xid=NL_CardioEndoConnection_2019-01-21

https://www.ncbi.nlm.nih.gov/pubmed/19307519

https://www.ncbi.nlm.nih.gov/pubmed/23009776

https://www.ncbi.nlm.nih.gov/pubmed/6827992

https://www.ncbi.nlm.nih.gov/pubmed/22463676

https://www.ncbi.nlm.nih.gov/pubmed/17635890

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Over the past 20 years, studies have shown that girls and possibly boys have been experiencing puberty at progressively younger ages. This is troubling news, as earlier age at puberty has been linked with increased risk of mental illness, breast and ovarian cancer in girls and testicular cancer in boys. Researchers found that daughters of mothers who had higher levels of diethyl phthalate and triclosan in their bodies during pregnancy experienced puberty at younger ages. The same trend was not observed in boys. So, researchers suspected that girls exposed to chemicals commonly found in toothpaste, makeup, soap and other personal care products before birth may hit puberty earlier.

 

Diethyl phthalate is often used as a stabilizer in fragrances and cosmetics. The antimicrobial agent triclosan — which the FDA banned from use in hand soap in 2017 because it was shown to be ineffective — is still used in some toothpastes. Researchers suspected that many chemicals in personal care products can interfere with natural hormones in human bodies, and studies have shown that exposure to these chemicals can alter reproductive development in rats. Chemicals that have been implicated include phthalates, which are often found in scented products like perfumes, soaps and shampoos; parabens, which are used as preservatives in cosmetics; and phenols, which include triclosan.

 

However, few studies have looked at how these chemicals might affect the growth of human children. This present study at UC Berkeley, USA recruited pregnant women living in the farm-working, primarily Latino communities of Central California’s Salinas Valley between 1999 and 2000. While the primary aim of the study was to examine the impact of pesticide exposure on childhood development, the researchers used the opportunity to examine the effects of other chemicals as well. The scientists measured concentrations of phthalates, parabens and phenols in urine samples taken from mothers twice during pregnancy, and from children at the age of 9. They then followed the growth of the children — 159 boys and 179 girls — between the ages of 9 and 13 to track the timing of developmental milestones marking different stages of puberty.

 

The vast majority — more than 90 percent — of urine samples of both mothers and children showed detectable concentrations of all three classes of chemicals, with the exception of triclosan which was present in approximately 70 percent of samples. The researchers found that every time the concentrations of diethyl phthalate and triclosan in the mother’s urine doubled, the timing of developmental milestones in girls shifted approximately one month earlier. Girls who had higher concentrations of parabens in their urine at age 9 also experienced puberty at younger ages. However, it is unclear if the chemicals were causing the shift, or if girls who reached puberty earlier were more likely to start using personal care products at younger ages.

 

The limitations are that these chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable. But, this study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children.

 

References:

 

https://www.universityofcalifornia.edu/news/prenatal-exposure-chemicals-personal-care-products-may-speed-puberty-girls?utm_source=fiat-lux

 

https://www.ncbi.nlm.nih.gov/pubmed/30517665

 

https://www.ncbi.nlm.nih.gov/pubmed/24781428

 

https://www.ncbi.nlm.nih.gov/pubmed/30203993

 

https://www.ncbi.nlm.nih.gov/pubmed/25173057

 

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June 4, 2018 – Department of Defense Medical Innovation and Biodefense Forum, BIO 2018! at Boston Convention & Exhibition Center

Announcement

Aviva Lev-Ari, PhD, RN,

https://mybio.org/profile/member/2029564?profile_tabs=profile

Founder and Director of LPBI Group will be in attendance covering the event in REAL TIME

https://pharmaceuticalintelligence.com/2018/05/26/bio-2018-june-4-7-2018-at-boston-convention-exhibition-center/

@pharma_BI

@AVIVA1950

for

#BIO2018

@BIOConvention

  • How DoD can assist Industry to commercialize technologies
  • How the coordination in the Infectious disease takes place
  • Manufacturing for DoD
  • Infrastructure to manage across Government RFP Process
  • Devices requires detailed engineering for use in Field hospitals
  • Regulatory, Scheduling and Engineering problems
  • Development is for all the Forces of the US and for all the Forces of US Allies — design for CIvilian first respnders as well
  • Some partners are commercial Partners, they need to approach DoD with novel product concept
  • FDA approved vs Right to Try – DoD uses both
  • Small business Program, success in bringing product to market
  • 20 years ago: Communities of interest – 20 orgs community common goals in Health Care, rehabilitation after coming home,
  • MROC – Conference in Florida DoD to explain the Public the process of engagement with Do
  • Interagency partnership
  • DoD starts with good ideas, concept studies – innovators
  • Collaborations with Academia, we are available to be approached
  • DoD will partner with small businesses to avoid the Regulatory process  – to save time and resources in the commercialization process
  • How a civilian concept FITS the needs of DoD
  • Sustaining an innovation along the years
  • Need for small business to approach DoD to make the contact
  • Where is a small business in the Development cycle? DoD can help calibrate
  • A System of Systems: Diagnostics drive decisions
  • develop partnerships in consortia
  • Six month to vaccinate 17,000 with a Vaccine for EBOLA
  • DoD of respective countries are collaborating with US DoD
  • Threat environment changes over time vs modify known threats
  • Monoclonal antibody – the Industry developed the manufacturing technology and DoD is user of Industry products
  • All research for the Joint Force, Chemical, Biological,
  • Short time to market solutions are of interest for DoD to identify
  • Military relevance: Key for funding
  • Announcements of DoD on WHAT PROBLEMS DoD tries to solve
  • DoD and HHS — aligned for common solution to avoid redundancy
  • Development of profilaxix is very expensive, DoD budget has competing goals: Next soldier suit,
  • FDA and DoD need to collaborate for DoDs needs
  • Order transaction authority,
  • Congress set aside a budget for small businesses to use accounting systems for Small business to interact with DoD
  • How to get a digital signal to the brain: Expertise in many disciplines: EE, Ethomology
  • Delivery, test , evaluation, develop sensors, IS to manage threats, Diagnostics,
  • How to do Business with Industry?
  • Congress asked for a Consorsium to engage with Industry in a different form than we engaged before
  • Partnerships for out of the box thinking and going quickly – the appetite for is greater then evr before
  • Successful area: Diagnostics – adoptation of existing diagnostics for military applications
  • Platform technologies: Metabolic, Vaccines,
  • Leverage existing technologies to solve DoD concerns
  • involved with MCS help Government to learn how to build their Office
  • Genomic, Proteomics, therapeutics candidates, Prophylaxis as Vaccines
  • In the event of an outbreak: clinicians, 1st responders
Panel 2: Clay Holloway, Director of Strategic Initiatives, Joint Project Manager, Medical Countermeasure Systems (JPM-MCS)
  • Partnering is key
  • capability requirements: broad spectrum capabilities
  • Decision tools to be used at studies for data analysis for decision making
  • Risks in partnership: DoD needs to evaluate ideas for next generation to SKIP one generation
  • How to used different agreement strategically? Streamline DoD Methods
  • Have continuous access to assets

 

LOCATION

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Top TEN Graduate School Search – Biological Sciences Programs

Reporter: Aviva Lev-Ari, PhD, RN

 

School Program Rank
Massachusetts Institute of Technology – Department of Biology

Cambridge, MA

#1Tie
Stanford University – Department of Biology

Stanford, CA

#1Tie
University of California–Berkeley – College of Letters and Science

Berkeley, CA

#1Tie
California Institute of Technology – Division of Biology

Pasadena, CA

#4Tie
Harvard University – Programs in Biological and Biomedical Sciences

Boston, MA

#4Tie
Johns Hopkins University – Biology Department

Baltimore, MD

#6Tie
Princeton University – Department of Molecular Biology

Princeton, NJ

#6Tie
University of California–San Francisco – Graduate Division

San Francisco, CA

#6Tie
Yale University – Combined Program in the Biological and Biomedical Sciences

New Haven, CT

#6Tie
Cornell University

Ithaca, NY

#10Tie

SOURCE

https://www.usnews.com/best-graduate-schools/search?program=top-biological-sciences-programs&name=&sort=program_rank&sortdir=asc

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Anti-Müllerian Hormone (AMH), is secreted by growing follicles that contains the egg or ovum. According to regular practice low AMH and high Follicle Stimulating Hormone (FSH) are generally considered as indicators of diminished egg quantity in a female. But, there are several cases the female conceived absolutely normally without any support even after low AMH was reported.

 

Therefore, a new research published in the Journal of the American Medical Association declares that AMH doesn’t dictate a woman’s reproductive potential. Although AMH testing is one of the most common ways that doctors assess a woman’s fertility. Present research says that all it takes is one egg each cycle and AMH is not a marker of whether a female can or cannot become pregnant. So, for women who haven’t yet tried to get pregnant and who are wondering whether they are fertile, an AMH value isn’t going to be helpful in that context. In addition, AMH is not necessarily a good marker to predict that whether one has to cryopreserve her eggs. So, practically doctors don’t yet have a way to definitively predict egg quality or a woman’s long-term ability to conceive, but age is obviously one of the most important factors.

 

The above mentioned study followed 750 women between the ages of 30 and 44 who had been trying to conceive for three months or less. During the 12-month observation period, those with low AMH values of less than 0.7 were not less likely to conceive than those who had normal AMH values. The study had various limitations, however, that are worth noting. The researchers only included women who did not have a history of infertility. Women who sought fertility treatments (about 6 percent) were withdrawn. And only 12 percent of the women were in the 38-to-44 age range. In addition, the number of live births was unavailable.

 

Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood FSH tests or AMH levels to assess natural fertility for women with these characteristics. The researchers’ next want to see whether low AMH is associated with a higher risk of miscarriage among the women who conceived.

 

Although AMH testing isn’t designed to be an overall gauge of a woman’s fertility, it can still provide valuable information, especially for women who are infertile and seeking treatment. It can assist in diagnosing polycystic ovarian syndrome, and identify when a woman is getting closer to menopause. Previous research also showed that AMH is good predictor of a woman’s response to ovarian stimulation for in vitro fertilization and therefore it can predict the probability of conceiving via in vitro fertilization (I.V.F.).

 

References:

 

https://jamanetwork.com/journals/jama/article-abstract/2656811?JamaNetworkReader=True

 

https://www.nytimes.com/2017/10/16/health/fertility-test-ovarian-reserve.html

 

https://academic.oup.com/humrep/article/26/11/2925/656065

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339896/

 

https://www.ncbi.nlm.nih.gov/pubmed/27179263

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Scientists at the Stanford University School of Medicine have completed the first-ever characterization of the meticulously timed immune system changes in women that occur during pregnancy. The findings were published in Science Immunology revealed that there is an immune clock of pregnancy and suggest it may help doctors predict preterm birth.

 

The timing of immune system changes follows a precise and predictable pattern in normal pregnancy. Although physicians have long known that the expectant mother’s immune system adjusts to prevent her body from rejecting the fetus, no one had investigated the full scope of these changes, nor asked if their timing was tightly controlled.

 

Nearly 10 percent of U.S. infants are born prematurely, arriving three or more weeks early, but physicians lack a reliable way to predict premature deliveries. Previous research at Stanford and other places suggested that inflammatory immune responses may help in triggering early labor. It suggested that if scientists identify an immune signature of impending preterm birth, they should be able to design a blood test to detect it.

 

The researchers used mass cytometry, a technique developed at Stanford, to simultaneously measure up to 50 properties of each immune cell in the blood samples. They counted the types of immune cells, assessed what signaling pathways were most active in each cell, and determined how the cells reacted to being stimulated with compounds that mimic infection with viruses and bacteria.

 

The researchers developed an algorithm that captures the immunological timeline during pregnancy that both validates previous findings and sheds new light on immune cell interaction during gestation. By defining this immunological chronology during normal term pregnancy, they can now begin to determine which alterations associate with pregnancy-related pathologies.

 

With an advanced statistical modeling technique, introduced for the first time in this study, the scientists then described in detail how the immune system changes throughout pregnancy. Instead of grouping the women’s blood samples by trimester for analysis, the model treated gestational age as a continuous variable, allowing the researchers to account for the exact time during pregnancy at which each sample was taken. The mathematical model also incorporated knowledge from the existing scientific literature of how immune cells behave in nonpregnant individuals to help determine which findings were most likely to be important.

 

The study confirmed immune features of pregnancy that were already known. Such as the scientists saw that natural killer cells and neutrophils have enhanced action during pregnancy. The researchers also uncovered several previously unappreciated features of how the immune system changes, such as the finding that activity of the STAT5 signaling pathway in CD4+T cells progressively increases throughout pregnancy on a precise schedule, ultimately reaching levels much higher than in nonpregnant individuals. The STAT5 pathway is involved in helping another group of immune cells, regulatory T cells, to differentiate. Interestingly, prior research in animals has indicated that regulatory T cells are important for maintaining pregnancy.

 

The next step will be to conduct similar research using blood samples from women who deliver their babies prematurely to see where their trajectories of immune function differ from normal.

 

This study revealed a precisely timed chronology of immune adaptations in peripheral blood over the course of a term pregnancy. This finding was enabled by high-content, single-cell mass cytometry coupled with a csEN algorithm accounting for the modular structure of the immune system and previous knowledge. The study provided the conceptual backbone and the analytical framework to examine whether disruption of this chronology is a diagnostically useful characteristic of preterm birth and other pregnancy-related pathologies.

 

References:

 

http://immunology.sciencemag.org/content/2/15/eaan2946.full

 

http://med.stanford.edu/news/all-news/2017/09/immune-system-changes-during-pregnancy-are-precisely-timed.html

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078586/

 

http://www.nature.com/nm/journal/v19/n5/full/nm.3160.html?foxtrotcallback=true

 

https://www.ncbi.nlm.nih.gov/pubmed/14758358

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