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Archive for the ‘Genomic Expression’ Category


Live 12:00 – 1:00 P.M  Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health : October 19, 2018

Reporter: Stephen J. Williams, Ph.D.

12.00 The Italian Mediterranean Diet as a Model of Identity of a People with a Universal Good to Safeguard Health?

Prof. Antonino De Lorenzo, MD, PhD.

Director of the School of Specialization in Clinical Nutrition, University of Rome “Tor Vergata”

It is important to determine how our bodies interacts with the environment, such as absorption of nutrients.

Studies shown here show decrease in life expectancy of a high sugar diet, but the quality of the diet, not just the type of diet is important, especially the role of natural probiotics and phenolic compounds found in the Mediterranean diet.

The WHO report in 2005 discusses the unsustainability of nutrition deficiencies and suggest a proactive personalized and preventative/predictive approach of diet and health.

Most of the noncommunicable diseases like CV (46%) cancer 21% and 11% respiratory and 4% diabetes could be prevented and or cured with proper dietary approaches

Italy vs. the US diseases: in Italy most disease due to environmental contamination while US diet plays a major role

The issue we are facing in less than 10% of the Italian population (fruit, fibers, oils) are not getting the proper foods, diet and contributing to as we suggest 46% of the disease

The Food Paradox: 1.5 billion are obese; we notice we are eating less products of quality and most quality produce is going to waste;

  •  growing BMI and junk food: our studies are correlating the junk food (pre-prepared) and global BMI
  • modern diet and impact of human health (junk food high in additives, salt) has impact on microflora
  • Western Diet and Addiction: We show a link (using brain scans) showing correlation of junk food, sugar cravings, and other addictive behaviors by affecting the dopamine signaling in the substantia nigra
  • developed a junk food calculator and a Mediterranean diet calculator
  • the intersection of culture, food is embedded in the Mediterranean diet; this is supported by dietary studies of two distinct rural Italian populations (one of these in the US) show decrease in diet
  • Impact of diet: have model in Germany how this diet can increase health and life expectancy
  • from 1950 to present day 2.7 unit increase in the diet index can increase life expectancy by 26%
  • so there is an inverse relationship with our index and breast cancer

Environment and metal contamination and glyphosate: contribution to disease and impact of maintaining the healthy diet

  • huge problem with use of pesticides and increase in celiac disease

12:30 Environment and Health

Dr. Iris Maria Forte, PhD.

National Cancer Institute “Pascale” Foundation | IRCCS · Department of Research, Naples, Italy

Cancer as a disease of the environment.  Weinberg’s hallmarks of Cancer reveal how environment and epigenetics can impact any of these hallmarks.

Epigenetic effects

  • gene gatekeepers (Rb and P53)
  • DNA repair and damage stabilization

Heavy Metals and Dioxins:( alterations of the immune system as well as epigenetic regulations)

Asbestos and Mesothelioma:  they have demonstrated that p53 can be involved in development of mesothelioma as reactivating p53 may be a suitable strategy for therapy

Diet, Tomato and Cancer

  • looked at tomato extract on p53 function in gastric cancer: tomato extract had a growth reduction effect and altered cell cycle regulation and results in apoptosis
  • RBL2 levels are increased in extract amount dependent manner so data shows effect of certain tomato extracts of the southern italian tomato (     )

Antonio Giordano: we tested whole extracts of almost 30 different varieties of tomato.  The tomato variety  with highest activity was near Ravela however black tomatoes have shown high antitumor activity.  We have done a followup studies showing that these varieties, if grow elsewhere lose their antitumor activity after two or three generations of breeding, even though there genetics are similar.  We are also studying the effects of different styles of cooking of these tomatoes and if it reduces antitumor effect

please see post https://news.temple.edu/news/2017-08-28/muse-cancer-fighting-tomatoes-study-italian-food

 

To follow or Tweet on Twitter please use the following handles (@) and hashtags (#):

@ handles


@S_H_R_O 

@SbarroHealth

@Pharma_BI 

@ItalyinPhilly

@WHO_Europe

@nutritionorg

# hashtags


#healthydiet

#MediterraneanDiet

#health

#nutrition

Please see related articles on Live Coverage of Previous Meetings on this Open Access Journal

Real Time Conference Coverage for Scientific and Business Media: Unique Twitter Hashtags and Handles per Conference Presentation/Session

LIVE – Real Time – 16th Annual Cancer Research Symposium, Koch Institute, Friday, June 16, 9AM – 5PM, Kresge Auditorium, MIT

Real Time Coverage and eProceedings of Presentations on 11/16 – 11/17, 2016, The 12th Annual Personalized Medicine Conference, HARVARD MEDICAL SCHOOL, Joseph B. Martin Conference Center, 77 Avenue Louis Pasteur, Boston

Tweets Impression Analytics, Re-Tweets, Tweets and Likes by @AVIVA1950 and @pharma_BI for 2018 BioIT, Boston, 5/15 – 5/17, 2018

BIO 2018! June 4-7, 2018 at Boston Convention & Exhibition Center

LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

HUBweek 2018, October 8-14, 2018, Greater Boston – “We The Future” – coming together, of breaking down barriers, of convening across disciplinary lines to shape our future

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2018 Nobel Prize in Physiology or Medicine for contributions to Cancer Immunotherapy to James P. Allison, Ph.D., of the University of Texas, M.D. Anderson Cancer Center, Houston, Texas. Dr. Allison shares the prize with Tasuku Honjo, M.D., Ph.D., of Kyoto University Institute, Japan

Reporter: Aviva Lev-Ari, PhD, RN

 

See

Immune System Stimulants: Articles of Note @pharmaceuticalintelligence.com

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/05/01/immune-system-stimulants-articles-of-note-pharmaceuticalintelligence-com/

 

Immune-Oncology Molecules In Development & Articles on Topic in @pharmaceuticalintelligence.com

Curators: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/11/articles-on-immune-oncology-molecules-in-development-pharmaceuticalintelligence-com/

 

 

Monday, October 1, 2018

NIH grantees win 2018 Nobel Prize in Physiology or Medicine.

The 2018 Nobel Prize in Physiology or Medicine has been awarded to National Institutes of Health grantee James P. Allison, Ph.D., of the University of Texas, M.D. Anderson Cancer Center, Houston, Texas. Dr. Allison shares the prize with Tasuku Honjo, M.D., Ph.D., of Kyoto University Institute, Japan, for their discovery of cancer therapy by inhibition of negative immune regulation.

The Royal Swedish Academy of Sciences said, “by stimulating the inherent ability of our immune system to attack tumor cells this year’s Nobel Laureates have established an entirely new principle for cancer therapy.”

Dr. Allison discovered that a particular protein (CTLA-4) acts as a braking system, preventing full activation of the immune system when a cancer is emerging. By delivering an antibody that blocks that protein, Allison showed the brakes could be released. The discovery has led to important developments in cancer drugs called checkpoint inhibitors and dramatic responses to previously untreatable cancers. Dr. Honjo discovered a protein on immune cells and revealed that it also operates as a brake, but with a different mechanism of action.

“Jim’s work was pivotal for cancer therapy by enlisting our own immune systems to launch an attack on cancer and arrest its development,” said NIH Director Francis S. Collins, M.D., Ph.D. “NIH is proud to have supported this groundbreaking research.”

Dr. Allison has received continuous funding from NIH since 1979, receiving more than $13.7 million primarily from NIH’s National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID).

“This work has led to remarkably effective, sometime curative, therapy for patients with advanced cancer, who we were previously unable to help,” said NCI Director Ned Sharpless, M.D. “Their findings have ushered in the era of cancer immunotherapy, which along with surgery, radiation and cytotoxic chemotherapy, represents a ‘fourth modality’ for treating cancer. A further understanding of the biology underlying the immune system and cancer has the potential to help many more patients.”

“Dr. Allison’s elegant and groundbreaking work in basic immunology over four decades and its important applicability to cancer is a vivid demonstration of the critical nature of interdisciplinary biomedical research supported by NIH,” says NIAID Director Anthony S. Fauci, M.D.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

SOURCE

https://www.nih.gov/news-events/news-releases/nih-grantees-win-2018-nobel-prize-physiology-or-medicine

 

Dr. Lev-Ari covered in person the following curated articles about James Allison, PhD since his days at University of California, Berkeley, including the prizes awarded prior to the 2018 Nobel Prize in Physiology.

 

2018 Albany Medical Center Prize in Medicine and Biomedical Research goes to NIH’s Dr. Rosenberg and fellow immunotherapy researchers James P. Allison, Ph.D., and Carl H. June, M.D.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/08/15/2018-albany-medical-center-prize-in-medicine-and-biomedical-research-goes-to-nihs-dr-rosenberg-and-fellow-immunotherapy-researchers-james-p-allison-ph-d-and-carl-h-june-m-d/

 

Lectures by The 2017 Award Recipients of Warren Alpert Foundation Prize in Cancer Immunology, October 5, 2017, HMS, 77 Louis Paster, Boston

REAL TIME Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/09/08/lectures-by-the-2017-award-recipients-of-warren-alpert-foundation-prize-in-cancer-immunology-october-5-2017-hms-77-louis-paster-boston/

 

Cancer-free after immunotherapy treatment: Treating advanced colon cancer – targeting KRAS gene mutation by tumor-infiltrating lymphocytes (TILs) and Killer T-cells (NK)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/08/cancer-free-after-immunotherapy-treatment-treating-advanced-colon-cancer-targeting-kras-gene-mutation-by-tumor-infiltrating-lymphocytes-tils-and-killer-t-cells-nk/

 

New Class of Immune System Stimulants: Cyclic Di-Nucleotides (CDN): Shrink Tumors and bolster Vaccines, re-arm the Immune System’s Natural Killer Cells, which attack Cancer Cells and Virus-infected Cells

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/24/new-class-of-immune-system-stimulants-cyclic-di-nucleotides-cdn-shrink-tumors-and-bolster-vaccines-re-arm-the-immune-systems-natural-killer-cells-which-attack-cancer-cells-and-virus-inf/

 

UC Berkeley research led to Nobel Prize-winning immunotherapy

Immunologist James P. Allison today shared the 2018 Nobel Prize in Physiology or Medicine for groundbreaking work he conducted on cancer immunotherapy at UC Berkeley during his 20 years as director of the campus’s Cancer Research Laboratory.

James Allison

James Allison, who for 20 years was a UC Berkeley immunologist conducting fundamental research on cancer, is now at the M.D. Anderson Cancer Center in Houston, Texas.

Now at the University of Texas M.D. Anderson Cancer Center in Houston, Allison shared the award with Tasuku Honjo of Kyoto University in Japan “for their discovery of cancer therapy by inhibition of negative immune regulation.”

Allison, 70, conducted basic research on how the immune system – in particular, a cell called a T cell – fights infection. His discoveries led to a fundamentally new strategy for treating malignancies that unleashes the immune system to kill cancer cells. A monoclonal antibody therapy he pioneered was approved by the Food and Drug Administration in 2011 to treat malignant melanoma, and spawned several related therapies now being used against lung, prostate and other cancers.

“Because this approach targets immune cells rather than specific tumors, it holds great promise to thwart diverse cancers,” the Lasker Foundation wrote when it awarded Allison its 2015 Lasker-DeBakey Clinical Medical Research Award.

Allison’s work has already benefited thousands of people with advanced melanoma, a disease that used to be invariably fatal within a year or so of diagnosis. The therapy he conceived has resulted in elimination of cancer in a significant fraction of patients for a decade and counting, and it appears likely that many of these people are cured.

“Targeted therapies don’t cure cancer, but immunotherapy is curative, which is why many consider it the biggest advance in a generation,” Allison said in a 2015 interview. “Clearly, immunotherapy now has taken its place along with surgery, chemotherapy and radiation as a reliable and objective way to treat cancer.”

“We are thrilled to see Jim’s work recognized by the Nobel Committee,” said Russell Vance, the current director of the Cancer Research Laboratory and a UC Berkeley professor of molecular and cell biology. “We congratulate him on this highly deserved honor. This award is a testament to the incredible impact that the fundamental research Jim conducted at Berkeley has had on the lives of cancer patients”

“I don’t know if I could have accomplished this work anywhere else than Berkeley,” Allison said. “There were a lot of smart people to work with, and it felt like we could do almost anything. I always tell people that it was one of the happiest times of my life, with the academic environment, the enthusiasm, the students, the faculty.”

In this video about UC Berkeley’s new Immunotherapeutics and Vaccine Research Initiative (IVRI), Allison discusses his groundbreaking work on cancer immunotherapy.

In fact, Allison was instrumental in creating the research environment of the current Department of Molecular and Cell Biology at UC Berkeley as well as the department’s division of immunology, in which he served stints as chair and division head during his time at Berkeley, said David Raulet, director of Berkeley’s Immunotherapeutics and Vaccine Research Initiative (IVRI).

“His actions helped create the superb research environment here, which is so conducive to making the fundamental discoveries that will be the basis of the next generation of medical breakthroughs,” Raulet said.

Self vs. non-self

Allison joined the UC Berkeley faculty as a professor of molecular and cell biology and director of the Cancer Research Laboratory in 1985. An immunologist with a Ph.D. from the University of Texas, Austin, he focused on a type of immune system cell called the T cell or T lymphocyte, which plays a key role in fighting off bacterial and viral infections as well as cancer.

Supercharging the immune system to cure disease: immunotherapy research at UC Berkeley. (UC Berkeley video by Roxanne Makasdjian and Stephen McNally)

At the time, most doctors and scientists believed that the immune system could not be exploited to fight cancer, because cancer cells look too much like the body’s own cells, and any attack against cancer cells would risk killing normal cells and creating serious side effects.

“The community of cancer biologists was not convinced that you could even use the immune system to alter cancer’s outcome, because cancer was too much like self,” said Matthew “Max” Krummel, who was a graduate student and postdoctoral fellow with Allison in the 1990s and is now a professor of pathology and a member of the joint immunology group at UCSF. “The dogma at the time was, ‘Don’t even bother.’ ”

“What was heady about the moment was that we didn’t really listen to the dogma, we just did it,” Krummel added. Allison, in particular, was a bit “irreverent, but in a productive way. He didn’t suffer fools easily.” This attitude rubbed off on the team.

Trying everything they could in mice to tweak the immune system, Krummel and Allison soon found that a protein receptor called CTLA-4 seemed to be holding T cells back, like a brake in a car.

Postdoctoral fellow Dana Leach then stepped in to see if blocking the receptor would unleash the immune system to actually attack a cancerous tumor. In a landmark paper published in Science in 1996, Allison, Leach and Krummel showed not only that antibodies against CTLA-4 released the brake and allowed the immune system to attack the tumors, but that the technique was effective enough to result in long-term disappearance of the tumors.

“When Dana showed me the results, I was really surprised,” Allison said. “It wasn’t that the anti-CTLA-4 antibodies slowed the tumors down. The tumors went away.”

After Allison himself replicated the experiment, “that’s when I said, OK, we’ve got something here.”

Checkpoint blockade

The discovery led to a concept called “checkpoint blockade.” This holds that the immune system has many checkpoints designed to prevent it from attacking the body’s own cells, which can lead to autoimmune disease. As a result, while attempts to rev up the immune system are like stepping on the gas, they won’t be effective unless you also release the brakes.

Allison in 1993

James Allison in 1993, when he was conducting research at UC Berkeley on a promising immunotherapy now reaching fruition. (Jane Scherr photo)

“The temporary activation of the immune system though ‘checkpoint blockade’ provides a window of opportunity during which the immune system is mobilized to attack and eliminate tumors,” Vance said.

Allison spent the next few years amassing data in mice to show that anti-CTLA-4 antibodies work, and then, in collaboration with a biotech firm called Medarex, developed human antibodies that showed promise in early clinical trials against melanoma and other cancers. The therapy was acquired by Bristol-Myers Squibb in 2011 and approved by the FDA as ipilimumab (trade name Yervoy), which is now used to treat skin cancers that have metastasized or that cannot be removed surgically.

Meanwhile, Allison left UC Berkeley in 2004 for Memorial Sloan Kettering research center in New York to be closer to the drug companies shepherding his therapy through clinical trials, and to explore in more detail how checkpoint blockade works.

“Berkeley was my favorite place, and if I could have stayed there, I would have,” he said. “But my research got to the point where all the animal work showed that checkpoint blockade had a lot of potential in people, and working with patients at Berkeley wasn’t possible. There’s no hospital, no patients.”

Thanks to Allison’s doggedness, anti-CTLA-4 therapy is now an accepted therapy for cancer and it opened the floodgates for a slew of new immunotherapies, Krummel said. There now are several hundred ongoing clinical trials involving monoclonal antibodies to one or more receptors that inhibit T cell activity, sometimes combined with lower doses of standard chemotherapy.

Antibodies against one such receptor, PD-1, which Honjo discovered in 1992, have given especially impressive results. Allison’s initial findings can be credited for prompting researchers, including Allison himself, to carry out the studies that have demonstrated the potent anti-cancer effects of PD-1 antibodies. In 2015, the FDA approved anti-PD-1 therapy for malignant melanoma, and has since approved it for non-small-cell lung, gastric and several other cancers.

Science magazine named cancer immunotherapy its breakthrough of 2013 because that year, “clinical trials … cemented its potential in patients and swayed even the skeptics. The field hums with stories of lives extended: the woman with a grapefruit-size tumor in her lung from melanoma, alive and healthy 13 years later; the 6-year-old near death from leukemia, now in third grade and in remission; the man with metastatic kidney cancer whose disease continued fading away even after treatment stopped.”

Allison pursued more clinical trials for immunotherapy at Sloan-Kettering and then in 2012 returned to his native Texas.

Born in Alice, Texas, on Aug. 7, 1948, Allison earned a B.S. in microbiology in 1969 and a Ph.D. in biological science in 1973 from the University of Texas, Austin.

RELATED INFORMATION

SOURCE

http://news.berkeley.edu/2018/10/01/uc-berkeley-research-led-to-nobel-prize-winning-immunotherapy/

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Centers for Medicare & Medicaid Services announced that the federal healthcare program will cover the costs of cancer gene tests that have been approved by the Food and Drug Administration

 

Reporter: Aviva Lev-Ari, PhD, RN

genetic testing just became routine care for patients with advanced cancers. And that means precision medicine has finally broken into the mainstream.

Any tests that gain FDA clearance in the future will automatically receive full coverage.

In 3/2018 there are three FDA approved Genetic Tests for Cancer:

UNDER development and not included in the agreement , above, includes:

  • Olivier Elemento, Director of the Caryl and Israel Englander Institute for Precision Medicine at Cornell, the team at Cornell, for example, has developed a whole exome test that compares mutations in tumors against healthy cells across 22,000 genes. To date, it’s been used to help match more than 1,000 patients in New York state with the best available treatment options.

Under the final decision, doctors are still free to order non-FDA approved tests, but coverage isn’t guaranteed; each case will be evaluated by local Medicare administrative contractors. Which means Elemento’s test could still be covered. “To me this is a vote of confidence that next generation sequencing is useful for cancer patients,” says Elemento.

So far, CMS is only covering these tests for stage three and stage four metastatic cancer sufferers. Most of them aren’t going to be cured. They might get a few more good months, maybe a year, tops.

Cancerous Genes

SOURCE

WITH MEDICARE SUPPORT, GENETIC CANCER TESTING GOES MAINSTREAM

https://www.wired.com/story/with-medicare-support-genetic-cancer-testing-goes-mainstream/?mbid=social_twitter_onsiteshare

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Emerging STAR in Molecular Biology, Synthetic Virology and Genomics: Clodagh C. O’Shea: ChromEMT – Visualizing 3D chromatin structure

 

Curator: Aviva Lev-Ari, PhD, RN

 

On 8/28/2017, I attend and covered in REAL TIME the CHI’s 5th Immune Oncology Summit – Oncolytic Virus Immunotherapy, August 28-29, 2017 Sheraton Boston Hotel | Boston, MA

https://pharmaceuticalintelligence.com/2017/08/28/live-828-chis-5th-immune-oncology-summit-oncolytic-virus-immunotherapy-august-28-29-2017-sheraton-boston-hotel-boston-ma/

 

I covered in REAL TIME this event and Clodagh C. O’Shea talk at the conference.

On that evening, I e-mailed my team that

“I believe that Clodagh C. O’Shea will get the Nobel Prizebefore CRISPR

 

11:00 Synthetic Virology: Modular Assembly of Designer Viruses for Cancer Therapy

Clodagh_OShea

Clodagh O’Shea, Ph.D., Howard Hughes Medical Institute Faculty Scholar; Associate Professor, William Scandling Developmental Chair, Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies

Design is the ultimate test of understanding. For oncolytic therapies to achieve their potential, we need a deep mechanistic understanding of virus and tumor biology together with the ability to confer new properties.

To achieve this, we have developed

  • combinatorial modular genome assembly (ADsembly) platforms,
  • orthogonal capsid functionalization technologies (RapAd) and
  • replication assays that have enabled the rational design, directed evolution, systematic assembly and screening of powerful new vectors and oncolytic viruses.

 

Clodagh O’Shea’s Talk In Real Time:

  • Future Cancer therapies to be sophisticated as Cancer is
  • Targer suppresor pathways (Rb/p53)
  • OV are safe their efficacy ishas been limited
  • MOA: Specify Oncolytic Viral Replication in Tumor cells Attenuate – lack of potency
  • SOLUTIONS: Assembly: Assmble personalized V Tx fro libraries of functional parts
  • Adenovirus – natural & clinical advantages
  • Strategy: Technology for Assmbling Novel Adenovirus Genomes using Modular Genomic Parts
  • E1 module: Inactives Rb & p53
  • core module:
  • E3 Module Immune Evasion Tissue targeting
  • E4 Module Activates E2F (transcription factor TDP1/2), PI3K
  • Adenovirus promoters for Cellular viral replication — Tumor Selective Replication: Novel Viruses Selective Replicate in RB/p16
  • Engineering Viruses to overcome tumor heterogeneity
  • Target multiple & Specific Tumor Cel Receptors – RapAd Technology allows Re-targeting anti Rapamycin – induced targeting of adenovirus
  • Virus Genome: FKBP-fusion FRB-Fiber
  • Engineer Adenovirus Caspids that prevent Liver uptake and Sequestration – Natural Ad5 Therapies 
  • Solution: AdSyn335 Lead candidat AdSyn335 Viruses targeting multiple cells
  • Engineering Mutations that enhanced potency
  • Novel Vector: Homes and targets
  • Genetically engineered PDX1 – for Pancreatic Cancer Stroma: Early and Late Stage
On Twitter:

Engineer Adenovirus Caspids prevent Liver uptake and Sequestration – Natural Ad5 Therapies C. O’Shea, HHDI

Scientist’s Profile: Clodagh C. O’Shea

http://www.salk.edu/scientist/clodagh-oshea/

EDUCATION

BS, Biochemistry and Microbiology, University College Cork, Ireland
PhD, Imperial College London/Imperial Cancer Research Fund, U.K.
Postdoctoral Fellow, UCSF Comprehensive Cancer Center, San Francisco, U.S.A

VIDEOS

http://www.salk.edu/scientist/clodagh-oshea/videos/

O’Shea Lab @Salk

http://oshea.salk.edu/

AWARDS & HONORS

  • 2016 Howard Hughes Medical Institute Faculty Scholar
  • 2014 W. M. Keck Medical Research Program Award
  • 2014 Rose Hills Fellow
  • 2011Science/NSF International Science & Visualization Challenge, People’s Choice
  • 2011 Anna Fuller Award for Cancer Research
  • 2010, 2011, 2012 Kavli Frontiers Fellow, National Academy of Sciences
  • 2009 Sontag Distinguished Scientist Award
  • 2009 American Cancer Society Research Scholar Award
  • 2008 ACGT Young Investigator Award for Cancer Gene Therapy
  • 2008 Arnold and Mabel Beckman Young Investigator Award
  • 2008 William Scandling Assistant Professor, Developmental Chair
  • 2007 Emerald Foundation Schola

READ 

Clodagh C. O’Shea: ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells | Science

http://science.sciencemag.org/content/357/6349/eaag0025

and 

https://www.readbyqxmd.com/keyword/93030

Clodagh C. O’Shea

In Press

Jul 27, 2017 – Salk scientists solve longstanding biological mystery of DNA organization

Sep 22, 2016 – Clodagh O’Shea named HHMI Faculty Scholar for groundbreaking work in designing synthetic viruses to destroy cancer

Oct 05, 2015 – Clodagh O’Shea awarded $3 million to unlock the “black box” of the nucleus

Aug 27, 2015 – The DNA damage response goes viral: a way in for new cancer treatments

Apr 12, 2013 – Salk Institute promotes three top scientists

Oct 16, 2012 – Cold viruses point the way to new cancer therapies

Aug 25, 2010 – Use the common cold virus to target and disrupt cancer cells?

Oct 22, 2009 – Salk scientist receives The Sontag Foundation’s Distinguished Scientist Award

May 15, 2008 – Salk scientist wins 2008 Beckman Young Investigator Award

Mar 24, 2008 – Salk scientist wins 2007 Young Investigator’s Award in Gene Therapy for Cancer

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Reporter and Curator: Irina Robu, PhD

Monitoring cancer patients and evaluating their response to treatment can sometimes involve invasive procedures, including surgery.

The liquid biopsies have become something of a Holy Grail in cancer treatment among physicians, researchers and companies gambling big on the technology. Liquid biopsies, unlike traditional biopsies involving invasive surgery — rely on an ordinary blood draw. Developments in sequencing the human genome, permitting researchers to detect genetic mutations of cancers, have made the tests conceivable. Some 38 companies in the US alone are working on liquid biopsies by trying to analyze blood for fragments of DNA shed by dying tumor cells.

Premature research on the liquid biopsy has concentrated profoundly on patients with later-stage cancers who have suffered treatments, including chemotherapy, radiation, surgery, immunotherapy or drugs that target molecules involved in the growth, progression and spread of cancer. For cancer patients undergoing treatment, liquid biopsies could spare them some of the painful, expensive and risky tissue tumor biopsies and reduce reliance on CT scans. The tests can rapidly evaluate the efficacy of surgery or other treatment, while old-style biopsies and CT scans can still remain inconclusive as a result of scar tissue near the tumor site.

As recently as a few years ago, the liquid biopsies were hardly used except in research. At the moment, thousands of the tests are being used in clinical practices in the United States and abroad, including at the M.D. Anderson Cancer Center in Houston; the University of California, San Diego; the University of California, San Francisco; the Duke Cancer Institute and several other cancer centers.

With patients for whom physicians cannot get a tissue biopsy, the liquid biopsy could prove a safe and effective alternative that could help determine whether treatment is helping eradicate the cancer. A startup, Miroculus developed a cheap, open source device that can test blood for several types of cancer at once. The platform, called Miriam finds cancer by extracting RNA from blood and spreading it across plates that look at specific type of mRNA. The technology is then hooked up at a smartphone which sends the information to an online database and compares the microRNA found in the patient’s blood to known patterns indicating different type of cancers in the early stage and can reduce unnecessary cancer screenings.

Nevertheless, experts warn that more studies are essential to regulate the accuracy of the test, exactly which cancers it can detect, at what stages and whether it improves care or survival rates.

SOURCE

https://www.fastcompany.com/3037117/a-new-device-can-detect-multiple-types-of-cancer-with-a-single-blood-test

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356857/

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

Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute, Micro and Nanotechnology Lab

Reporters: Tilda Barliya, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/28/liquid-biopsy-chip-detects-an-array-of-metastatic-cancer-cell-markers-in-blood-rd-worcester-polytechnic-institute-micro-and-nanotechnology-lab/

Liquid Biopsy Assay May Predict Drug Resistance

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/11/06/liquid-biopsy-assay-may-predict-drug-resistance/

One blood sample can be tested for a comprehensive array of cancer cell biomarkers: R&D at WPI

Curator: Marzan Khan, B.Sc

https://pharmaceuticalintelligence.com/2017/01/05/one-blood-sample-can-be-tested-for-a-comprehensive-array-of-cancer-cell-biomarkers-rd-wpi

 

 

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Pharmacotyping Pancreatic Cancer Patients in the Future: Two Approaches – ORGANOIDS by David Tuveson and Hans Clevers and/or MICRODOSING Devices by Robert Langer

Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 4/5/2018

Featured video: Magical Bob

A fascination with magic leads Institute Professor Robert Langer to solve world problems using the marvels of chemical engineering.Watch Video

MIT News Office
March 27, 2018

http://news.mit.edu/2018/featured-video-magical-bob-langer-0327

 

This curation provides the resources for edification on Pharmacotyping Pancreatic Cancer Patients in the Future

 

  • Professor Hans Clevers at Clevers Group, Hubrecht University

https://www.hubrecht.eu/onderzoekers/clevers-group/

  • Prof. Robert Langer, MIT

http://web.mit.edu/langerlab/langer.html

Langer’s articles on Drug Delivery

https://scholar.google.com/scholar?q=Langer+on+Drug+Delivery&hl=en&as_sdt=0&as_vis=1&oi=scholart&sa=X&ved=0ahUKEwixsd2w88TTAhVG4iYKHRaIAvEQgQMIJDAA

organoids, which I know you’re pretty involved in with Hans Clevers. What are your plans for organoids of pancreatic cancer?

Organoids are a really terrific model of a patient’s tumour that you generate from tissue that is either removed at the time of surgery or when they get a small needle biopsy. Culturing the tissue and observing an outgrowth of it is usually successful and when you have the cells, you can perform molecular diagnostics of any type. With a patient-derived organoid, you can sequence the exome and the RNA, and you can perform drug testing, which I call ‘pharmacotyping’, where you’re evaluating compounds that by themselves or in combination show potency against the cells. A major goal of our lab is to work towards being able to use organoids to choose therapies that will work for an individual patient – personalized medicine.

Organoids could be made moot by implantable microdevices for drug delivery into tumors, developed by Bob Langer. These devices are the size of a pencil lead and contain reservoirs that release microdoses of different drugs; the device can be injected into the tumor to deliver drugs, and can then be carefully dissected out and analyzed to gain insight into the sensitivity of cancer cells to different anticancer agents. Bob and I are kind of engaged in a friendly contest to see whether organoids or microdosing devices are going to come out on top. I suspect that both approaches will be important for pharmacotyping cancer patients in the future.

From the science side, we use organoids to discover things about pancreatic cancer. They’re great models, probably the best that I know of to rapidly discover new things about cancer because you can grow normal tissue as well as malignant tissue. So, from the same patient you can do a comparison easily to find out what’s different in the tumor. Organoids are crazy interesting, and when I see other people in the pancreatic cancer field I tell them, you should stop what you’re doing and work on these because it’s the faster way of studying this disease.

SOURCE

Other related articles on Pancreatic Cancer and Drug Delivery published in this Open Access Online Scientific Journal include the following:

 

Pancreatic Cancer: Articles of Note @PharmaceuticalIntelligence.com

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/05/26/pancreatic-cancer-articles-of-note-pharmaceuticalintelligence-com/

Keyword Search: “Pancreatic Cancer” – 275 Article Titles

https://pharmaceuticalintelligence.wordpress.com/wp-admin/edit.php?s=Pancreatic+Cancer&post_status=all&post_type=post&action=-1&m=0&cat=0&paged=1&action2=-1

Keyword Search: Drug Delivery: 542 Articles Titles

https://pharmaceuticalintelligence.wordpress.com/wp-admin/edit.php?s=Drug+Delivery&post_status=all&post_type=post&action=-1&m=0&cat=0&paged=1&action2=-1

Keyword Search: Personalized Medicine: 597 Article Titles

https://pharmaceuticalintelligence.wordpress.com/wp-admin/edit.php?s=Personalized+Medicine&post_status=all&post_type=post&action=-1&m=0&cat=0&paged=1&action2=-1

  • Cancer Biology & Genomics for Disease Diagnosis, on Amazon since 8/11/2015

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

 

 

VOLUME TWO WILL BE AVAILABLE ON AMAZON.COM ON MAY 1, 2017

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A novel 5-gene pancreatic adenocarcinoma classifier: Meta-analysis of transcriptome data – Clinical Genomics Research @BIDMC

Curator: Tilda Barliya, PhD

Analysis of  Bhasin et al paper and Literature search

Table 1: 5-genes classifiers as biomarkers for PDAC:

Gene symbol Gene name Subcellular localization
ECT2 Epithelial cell transforming sequence 2 oncogene Nucleus, cytoplasm
AHNAK2 AHNAKE nucleoprotein 2 Plasma membrane, cytoplasm
POSTN Periostin, osteoblast specific factor Extracellular space
TMPRSS4 Transmembrane protease, serine 4 Plasma membrane

 

SERPINB5 Serpin peptidase inhibitor, clade B (ovalbumin) member 5 Extracellular space


Introduction
:

  • Bhasin et al, conducted a beautiful study using a powerful meta-analysis from different sources to identify the “important/classifier” genes associated with Pancreatic Cancer (PDAC).
  • The authors identified 5 genes that were considered as good classifiers (table 1).
  • It is important to note that the meta-analysis was performed on tissue and microdissection samples.
  • In their summary, the authors aim to validate these genes in blood/urine samples.
  • While these genes might be over expressed in tissue samples it may not be true to their existence in blood and careful examination and validation is required.
  • Liquid biopsies are emerging as the go-to use tools for disease detection, mostly aimed for early diagnosis.
  • Liquid biopsies are non-invasive biopsies of blood, urine (potentially saliva) and their “exotic” components, i.e miRNA, exosomes etc.
  • Since Liquid biopsies are non-invasive, they are painless and patients are more complied.
  • It is important to note that there is a gap between the expression of a gene or a protein in tissue section and their expression in the blood and may not necessarily correlate.
  • It will be very interesting to follow their research and future outcomes.

Additional References:

  • TMPRSS4: an emerging potential therapeutic target in cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453593/

  • The tumour trail left in blood

http://www.nature.com/nature/journal/v532/n7598/full/532269a.html

Aashir Awan, PhD, wrote on 12/28/2016

I was wondering if these same 5 genes were upregulated in the pancreatic ductal adenocarcinoma cell lines that are available out there.  In doing cell biology work, there is always a dilemma whether cancer cell lines correctly re-capitulate in vivo tumors or not.  Personally, I prefer primary cell lines to do analysis but this finding can be used to test primary vs cell line.  In addition, I’ve attached the gene network for Ect2.  If you look carefully, the two big proteins that jump out are RACGAP1 and KIF23.  I think in designing therapies, combinatorial targets can yield the best outcomes.  Drugs directed towards two or more targets would seem ideal in my opinion.

ect2

Gene Network for Ect2

Original Research
Oncotarget. 2016 Apr 26;7(17):23263-81. doi: 10.18632/oncotarget.8139.

Meta-analysis of transcriptome data identifies a novel 5-gene pancreatic adenocarcinoma classifier.

Abstract

PURPOSE:

Pancreatic ductal adenocarcinoma (PDAC) is largely incurable due to late diagnosis. Superior early detection biomarkers are critical to improving PDAC survival and risk stratification.

EXPERIMENTAL DESIGN:

Optimized meta-analysis of PDAC transcriptome datasets identified and validated key PDAC biomarkers. PDAC-specific expression of a 5-gene biomarker panel was measured by qRT-PCR in microdissected patient-derived FFPE tissues. Cell-based assays assessed impact of two of these biomarkers, TMPRSS4 and ECT2, on PDAC cells.

RESULTS:

A 5-gene PDAC classifier (TMPRSS4, AHNAK2, POSTN, ECT2, SERPINB5) achieved on average 95% sensitivity and 89% specificity in discriminating PDAC from non-tumor samples in four training sets and similar performance (sensitivity = 94%, specificity = 89.6%) in five independent validation datasets. This classifier accurately discriminated PDAC from chronic pancreatitis (AUC = 0.83), other cancers (AUC = 0.89), and non-tumor from PDAC precursors (AUC = 0.92) in three independent datasets. Importantly, the classifier distinguished PanIN from healthy pancreas in the PDX1-Cre;LSL-KrasG12D PDAC mouse model. Discriminatory expression of the PDAC classifier genes was confirmed in microdissected FFPE samples of PDAC and matched surrounding non-tumor pancreas or pancreatitis. Notably, knock-down of TMPRSS4 and ECT2 reduced PDAC soft agar growth and cell viability and TMPRSS4 knockdown also blocked PDAC migration and invasion.

CONCLUSIONS:

This study identified and validated a highly accurate 5-gene PDAC classifier for discriminating PDAC and early precursor lesions from non-malignant tissue that may facilitate early diagnosis and risk stratification upon validation in prospective clinical trials. Cell-based experiments of two overexpressed proteins encoded by the panel, TMPRSS4 and ECT2, suggest a causal link to PDAC development and progression, confirming them as potential therapeutic targets.

KEYWORDS:

bioinformatics; biomarkers; meta-analysis; pancreatic cancer; transcriptome

PMID:
26993610
PMCID:
PMC5029625
DOI:
10.18632/oncotarget.8139

SOURCE

Oncotarget, Vol. 7, No. 17 – Referred as PDF, above

 

BIDMC Researchers Discover Early Indicators of Pancreatic Cancer

LibermannBhasin_PancreasCancerStudy

Markers may help doctors detect pancreatic cancer before it becomes deadly

In photo: First author Manoj Bhasin, PhD, and co-senior author Towia Libermann, PhD, Co-Director and Director of BIDMC’s Genomics, Proteomics, Bioinformatics and Systems Biology Center.

SOURCE

http://www.bidmc.org/News/PRLandingPage/2016/March/Libermann-Pancreatic-Cancer-Research-2016.aspx

BOSTON – Pancreatic cancer, the fourth leading cause of cancer death in the United States, is often diagnosed at a late stage, when curative treatment is no longer possible. A team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has now identified and validated an accurate 5-gene classifier for discriminating early pancreatic cancer from non-malignant tissue. Described online in the journal Oncotarget, the finding is a promising advance in the fight against this typically fatal disease.

“Pancreatic cancer is a devastating disease with a death rate close to the incidence rate,” said co-senior author Towia Libermann, PhD, Director of the Genomics, Proteomics, Bioinformatics and Systems Biology Center at BIDMC and Associate Professor of Medicine at Harvard Medical School (HMS). “Because more than 90 percent of pancreatic cancer cases are diagnosed at the metastatic stage, when there are only limited therapeutic options, earlier diagnosis is anticipated to have a major impact on extending life expectancy for patients. There has been a lack of reliable markers, early indicators and risk factors associated with pancreatic cancer, but this new way of differentiating between healthy and malignant tissue offers hope for earlier diagnosis and treatment.”

The investigators used a number of publicly available gene expression datasets for pancreatic cancer and developed a strategy to reanalyze these datasets together, applying rigorous statistical criteria to compare different datasets from different laboratories and different platforms with each other. The team then selected a subset of data for developing a panel for differentiating between pancreatic cancer and healthy pancreas tissue and thereafter applied this “Pancreatic Cancer Predictor” to the remaining datasets for independent validation to confirm the accuracy of the markers.

After demonstrating and independently validating that a 5-gene pancreatic cancer predictor discriminated between cancerous and healthy tissue, the researchers applied the predictor to datasets that also included benign lesions of the pancreas, including pancreatitis and early stage cancer. The predictor accurately differentiated pancreatic cancer, benign pancreatic lesions, early stage pancreatic cancer and healthy tissue. The predictor achieved on average 95 percent sensitivity and 89 percent specificity in discriminating pancreatic cancer from non-tumor samples in four training sets and similar performance (94 percent sensitivity, 90 percent specificity) in five independent validation datasets.

“Using innovative data normalization and gene selection approaches, we combined the statistical power of multiple genomic studies and masked their variability and batch effects to identify robust early diagnostic biomarkers of pancreatic cancer,” said first author Manoj Bhasin, PhD, Co-Director of BIDMC’s Genomics, Proteomics, Bioinformatics and Systems Biology Center and Assistant Professor of Medicine at HMS.

“The identification and initial validation of a highly accurate 5-gene pancreatic cancer biomarker panel that can discriminate late and early stages of pancreatic cancer from normal pancreas and benign pancreatic lesions could facilitate early diagnosis of pancreatic cancer,” said co-senior author Roya Khosravi-Far, PhD, Associate Professor of Pathology at BIDMC. “Our findings may open a window of opportunity for earlier diagnosis and, consequently, earlier intervention and more effective treatment of this deadly cancer, leading to higher survival rates.”

The first diagnostic application of the panel may be for analyses of fine needle biopsies routinely used for diagnosing pancreatic cancer and for determining the malignant potential of mostly benign pancreatic cysts that can sometimes be precursors of pancreatic cancer. In addition to providing a new tool for diagnoses, the research may also lead to new insights into how pancreatic cancer arises.

“Because these five genes are ‘turned on’ so early in the development of pancreatic cancer, they may play roles as drivers of this disease and may be exciting targets for therapies,” said Libermann. Most of the five genes—named TMPRSS4, AHNAK2, POSTN, ECT2 and SERPINB5—have been linked to migration, invasion, adhesion, and metastasis of pancreatic or other cancers.

The scientists next plan to evaluate the precise roles of the five genes and to validate the accuracy of their diagnostic assay in a prospective clinical study. “Moving forward, we will explore the potential to convert this tissue-based diagnostic into a noninvasive blood or urine test,” Libermann said.

“To further enhance the diagnostic power of this biomarker, we plan to expand it by including non-coding RNAs, proteins, metabolites and mutations associated with pancreatic cancer. This will result in development of the first of its kind biomarker that gauges pancreatic cancer alterations from multiple genomic angles for making highly accurate diagnoses,” added Bhasin. Such an inexpensive and simple test could help transform the landscape of pancreatic cancer and help prevent many of the estimated 330,000 deaths that it causes worldwide each year.

Study coauthors include BIDMC investigators Kenneth Ndebele, Octavian Bucur, Eric Yee, Jessica Plati, Andrea Bullock, Xuesong Gu, Eduardo Castan, Peng Zhang, Robert Najarian, Maria Muraru and Rebecca Miksad, and the University of Nebraska-Lincoln’s Hasan H. Otu. The work was supported by the National Institutes of Health, National Cancer Institute and Ben and Rose Cole Charitable Pria Foundation.

SOURCE

http://www.bidmc.org/News/PRLandingPage/2016/March/Libermann-Pancreatic-Cancer-Research-2016.aspx

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