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Archive for the ‘Diagnostics and Lab Tests’ Category


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

 

Scientists think excessive population growth is a cause of scarcity and environmental degradation. A male pill could reduce the number of unintended pregnancies, which accounts for 40 percent of all pregnancies worldwide.

 

But, big drug companies long ago dropped out of the search for a male contraceptive pill which is able to chemically intercept millions of sperm before they reach a woman’s egg. Right now the chemical burden for contraception relies solely on the female. There’s not much activity in the male contraception field because an effective solution is available on the female side.

 

Presently, male contraception means a condom or a vasectomy. But researchers from Center for Drug Discovery at Baylor College of Medicine, USA are renewing the search for a better option—an easy-to-take pill that’s safe, fast-acting, and reversible.

 

The scientists began with lists of genes active in the testes for sperm production and motility and then created knockout mice that lack those genes. Using the gene-editing technology called CRISPR, in collaboration with Japanese scientists, they have so far made more than 75 of these “knockout” mice.

 

They allowed these mice to mate with normal (wild type) female mice, and if their female partners don’t get pregnant after three to six months, it means the gene might be a target for a contraceptive. Out of 2300 genes that are particularly active in the testes of mice, the researchers have identified 30 genes whose deletion makes the male infertile. Next the scientists are planning a novel screening approach to test whether any of about two billion chemicals can disable these genes in a test tube. Promising chemicals could then be fed to male mice to see if they cause infertility.

 

Female birth control pills use hormones to inhibit a woman’s ovaries from releasing eggs. But hormones have side effects like weight gain, mood changes, and headaches. A trial of one male contraceptive hormone was stopped early in 2011 after one participant committed suicide and others reported depression. Moreover, some drug candidates have made animals permanently sterile which is not the goal of the research. The challenge is to prevent sperm being made without permanently sterilizing the individual.

 

As a better way to test drugs, Scientists at University of Georgia, USA are investigating yet another high-tech approach. They are turning human skin cells into stem cells that look and act like the spermatogonial cells in the testes. Testing drugs on such cells might provide more accurate leads than tests on mice.

 

The male pill would also have to start working quickly, a lot sooner than the female pill, which takes about a week to function. Scientists from University of Dundee, U.K. admitted that there are lots of challenges. Because, a women’s ovary usually release one mature egg each month, while a man makes millions of sperm every day. So, the male pill has to be made 100 percent effective and act instantaneously.

 

References:

 

https://www.technologyreview.com/s/603676/the-search-for-a-perfect-male-birth-control-pill/

 

https://futurism.com/videos/the-perfect-male-birth-control-pill-is-coming-soon/?utm_source=Digest&utm_campaign=c42fc7b9b6-EMAIL_CAMPAIGN_2017_03_20&utm_medium=email&utm_term=0_03cd0a26cd-c42fc7b9b6-246845533

 

http://www.telegraph.co.uk/women/sex/the-male-pill-is-coming—and-its-going-to-change-everything/

 

http://www.mensfitness.com/women/sex-tips/male-birth-control-pill-making

 

http://health.howstuffworks.com/sexual-health/contraception/male-bc-pill.htm

 

http://europe.newsweek.com/male-contraception-side-effects-study-pill-injection-518237?rm=eu

 

http://edition.cnn.com/2016/01/07/health/male-birth-control-pill/index.html

 

http://www.nhs.uk/Conditions/contraception-guide/Pages/male-pill.aspx

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Evaluating the Genetic Profiles of Tumor Cells circulating in the Bloodstream could transform Cancer Care: A Blood Test for managing Lung Cancer @Stanford University Medical School

Reporter: Aviva Lev-Ari, PhD, RN

 

A Legacy of Innovation @Stanford University Medical School

  1. 1967

    First synthesis of biologically active DNA in test tube

  2. 1968

    First adult human heart transplant in the United States

    Norman Shumway successfully transplants a heart into 54-year-old steelworker Mike Kasperak, who survives for 14 days.

     

  3. 1973

    First expression of a foreign gene implanted in bacteria by recombinant DNA methods

  4. 1981

    First successful human combined heart/lung transplant in the world (fourth attempted worldwide)

  5. 1984

    Isolation of a gene coding for part of the T-cell receptor, a key to the immune system’s function

  6. 1988

    Isolation of pure hematopoietic stem cells from mice

  7. 2002

    First use of gene expression profiling to predict cancer outcomes

  8. 2007

    Application and expansion of optogenetics, a technique to control brain cell activity with light

SOURCE

Evaluating the Genetic Profiles of Tumor Cells circulating in the Bloodstream could transform Cancer Care: A Blood Test for managing Lung Cancer @Stanford University Medical School

The approach that the team developed could be used to look at mutations in three or four genes, and it requires no more than 2 milliliters of blood — about half a teaspoon. The test can be completed in about five hours, the researcher said, and costs less than $30. For comparison, a single state-of-the art biopsy of lung tissue with DNA sequencing costs about $18,000 and takes as long as three weeks to furnish results. Johnson & Johnson’s CellSearch — another blood test, already approved by the FDA — costs about $900 and takes a week to deliver results.

The researchers created a system for isolating circulating tumor cells from the blood of cancer patients and reading a handful of genes from inside each tumor cell. Thus, they were able to obtain genetic information about the original cancer tumor that resides deep in the lungs without doing a biopsy, which can be dangerous for the patient.

“We are trying to make minimally invasive technology that allows us to continuously monitor one person’s health over time,” said radiology instructor Seung-min Park, PhD, a lead author of the new study, which was published online Dec. 12 in the Proceedings of the National Academy of Sciences. Park shares lead authorship of the study with former Stanford graduate students Dawson Wong, PhD, and Chin Chun Ooi.

A MagSifter chip, shown here fastened to an acrylic holder, can purify circulating tumor cells from the blood of cancer patients.

The MagSifter is an electromagnetic sieve that can be turned on and off. When the MagSifter is on, it pulls the nanoparticle-labeled CTCs from the blood sample and allows the rest of the blood to flow through the sifter. The CTCs pulled from the blood are then deposited into a flat array of tiny wells, each large enough for only one cell. Now the tumor cells are ready for genetic analysis. Each flat of 25,600 wells looks like a miniature muffin tin, with room for a lot of tiny muffins.

SOURCE

http://med.stanford.edu/news/all-news/2016/12/blood-test-could-provide-cheaper-way-to-evaluate-lung-tumors.html

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FDA cleared Clever Culture Systems’ artificial intelligence tech for automated imaging, analysis and interpretation of microbiology culture plates speeding up Diagnostics

Reporter: Aviva Lev-Ari, PhD, RN

 

 

FDA clears automated imaging AI that speeds up infectious disease Dx

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Milestones in Physiology & Discoveries in Medicine and Genomics: Request for Book Review Writing on Amazon.com


physiology-cover-seriese-vol-3individualsaddlebrown-page2

Milestones in Physiology

Discoveries in Medicine, Genomics and Therapeutics

Patient-centric Perspective 

http://www.amazon.com/dp/B019VH97LU 

2015

 

 

Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Chief Scientific Officer

Leaders in Pharmaceutical Business Intelligence

Larry.bernstein@gmail.com

Preface

Introduction 

Chapter 1: Evolution of the Foundation for Diagnostics and Pharmaceuticals Industries

1.1  Outline of Medical Discoveries between 1880 and 1980

1.2 The History of Infectious Diseases and Epidemiology in the late 19th and 20th Century

1.3 The Classification of Microbiota

1.4 Selected Contributions to Chemistry from 1880 to 1980

1.5 The Evolution of Clinical Chemistry in the 20th Century

1.6 Milestones in the Evolution of Diagnostics in the US HealthCare System: 1920s to Pre-Genomics

 

Chapter 2. The search for the evolution of function of proteins, enzymes and metal catalysts in life processes

2.1 The life and work of Allan Wilson
2.2  The  evolution of myoglobin and hemoglobin
2.3  More complexity in proteins evolution
2.4  Life on earth is traced to oxygen binding
2.5  The colors of life function
2.6  The colors of respiration and electron transport
2.7  Highlights of a green evolution

 

Chapter 3. Evolution of New Relationships in Neuroendocrine States
3.1 Pituitary endocrine axis
3.2 Thyroid function
3.3 Sex hormones
3.4 Adrenal Cortex
3.5 Pancreatic Islets
3.6 Parathyroids
3.7 Gastointestinal hormones
3.8 Endocrine action on midbrain
3.9 Neural activity regulating endocrine response

3.10 Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression

 

Chapter 4.  Problems of the Circulation, Altitude, and Immunity

4.1 Innervation of Heart and Heart Rate
4.2 Action of hormones on the circulation
4.3 Allogeneic Transfusion Reactions
4.4 Graft-versus Host reaction
4.5 Unique problems of perinatal period
4.6. High altitude sickness
4.7 Deep water adaptation
4.8 Heart-Lung-and Kidney
4.9 Acute Lung Injury

4.10 Reconstruction of Life Processes requires both Genomics and Metabolomics to explain Phenotypes and Phylogenetics

 

Chapter 5. Problems of Diets and Lifestyle Changes

5.1 Anorexia nervosa
5.2 Voluntary and Involuntary S-insufficiency
5.3 Diarrheas – bacterial and nonbacterial
5.4 Gluten-free diets
5.5 Diet and cholesterol
5.6 Diet and Type 2 diabetes mellitus
5.7 Diet and exercise
5.8 Anxiety and quality of Life
5.9 Nutritional Supplements

 

Chapter 6. Advances in Genomics, Therapeutics and Pharmacogenomics

6.1 Natural Products Chemistry

6.2 The Challenge of Antimicrobial Resistance

6.3 Viruses, Vaccines and immunotherapy

6.4 Genomics and Metabolomics Advances in Cancer

6.5 Proteomics – Protein Interaction

6.6 Pharmacogenomics

6.7 Biomarker Guided Therapy

6.8 The Emergence of a Pharmaceutical Industry in the 20th Century: Diagnostics Industry and Drug Development in the Genomics Era: Mid 80s to Present

6.09 The Union of Biomarkers and Drug Development

6.10 Proteomics and Biomarker Discovery

6.11 Epigenomics and Companion Diagnostics

 

Chapter  7

Integration of Physiology, Genomics and Pharmacotherapy

7.1 Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

7.2 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

7.3 Diagnostics and Biomarkers: Novel Genomics Industry Trends vs Present Market Conditions and Historical Scientific Leaders Memoirs

7.4 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

7.5 Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

7.6 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

7.7 Neuroprotective Therapies: Pharmacogenomics vs Psychotropic drugs and Cholinesterase Inhibitors

7.8 Metabolite Identification Combining Genetic and Metabolic Information: Genetic association links unknown metabolites to functionally related genes

7.9 Preserved vs Reduced Ejection Fraction: Available and Needed Therapies

7.10 Biosimilars: Intellectual Property Creation and Protection by Pioneer and by

7.11 Demonstrate Biosimilarity: New FDA Biosimilar Guidelines

 

Chapter 7.  Biopharma Today

8.1 A Great University engaged in Drug Discovery: University of Pittsburgh

8.2 Introduction – The Evolution of Cancer Therapy and Cancer Research: How We Got Here?

8.3 Predicting Tumor Response, Progression, and Time to Recurrence

8.4 Targeting Untargetable Proto-Oncogenes

8.5 Innovation: Drug Discovery, Medical Devices and Digital Health

8.6 Cardiotoxicity and Cardiomyopathy Related to Drugs Adverse Effects

8.7 Nanotechnology and Ocular Drug Delivery: Part I

8.8 Transdermal drug delivery (TDD) system and nanotechnology: Part II

8.9 The Delicate Connection: IDO (Indolamine 2, 3 dehydrogenase) and Cancer Immunology

8.10 Natural Drug Target Discovery and Translational Medicine in Human Microbiome

8.11 From Genomics of Microorganisms to Translational Medicine

8.12 Confined Indolamine 2, 3 dioxygenase (IDO) Controls the Homeostasis of Immune Responses for Good and Bad

 

Chapter 9. BioPharma – Future Trends

9.1 Artificial Intelligence Versus the Scientist: Who Will Win?

9.2 The Vibrant Philly Biotech Scene: Focus on KannaLife Sciences and the Discipline and Potential of Pharmacognosy

9.3 The Vibrant Philly Biotech Scene: Focus on Computer-Aided Drug Design and Gfree Bio, LLC

9.4 Heroes in Medical Research: The Postdoctoral Fellow

9.5 NIH Considers Guidelines for CAR-T therapy: Report from Recombinant DNA Advisory Committee

9.6 1st Pitch Life Science- Philadelphia- What VCs Really Think of your Pitch

9.7 Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for Non-Small Cell Lung Cancer

9.8 Heroes in Medical Research: Green Fluorescent Protein and the Rough Road in Science

9.9 Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

9.10 The SCID Pig II: Researchers Develop Another SCID Pig, And Another Great Model For Cancer Research

Epilogue

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BIO-RAD – a Leader in Lab Diagnostics

Reporters: David Orchard-Webb and Aviva Lev-Ari, PhD, RN

 

  • Corporate History Timeline

http://www.bio-rad.com/en-us/corporate/bio-rad-history

 

  • Life Sciences Research

http://www.bio-rad.com/en-us/life-science-research

 

 

  • Applications and Products
Kits and Consumables

  Lab Equipment

http://www.bio-rad.com/en-us/life-science-research

 

  • Clinical Diagnostics

http://www.bio-rad.com/en-us/clinical-diagnostics

 

  • Spectroscopy

http://www.bio-rad.com/en-us/spectroscopy

 

  • Process Separation

http://www.bio-rad.com/en-us/process-separations

 

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

 

Trovagene’s ctDNA Liquid Biopsy urine and blood tests to be used in Monitoring and Early Detection of Pancreatic Cancer

Reporters: David Orchard-Webb, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/06/trovagenes-ctdna-liquide-biopsy-urine-and-blood-tests-to-be-used-in-monitoring-and-early-detection-of-pancreatic-cancer/

 

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/

 

Fluidigm Microfluidic Technology: Contributions to Life Science Industry – the Biomark™ HD and C1™systems.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/12/fluidigm-microfluidic-technology-contributions-to-life-science-industry-the-biomark-hd-and-c1systems/

 

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Trovagene’s ctDNA Liquid Biopsy urine and blood tests to be used in Monitoring and Early Detection of Pancreatic Cancer

Reporters: David Orchard-Webb, PhD and Aviva Lev-Ari, PhD, RN

UPDATED on 7/29/2016

Trovagene’s Dual-Sample Liquid Biopsy Performs Well in First Peer-Reviewed Study

https://www.genomeweb.com/trovagenes-dual-sample-liquid-biopsy-performs-well-first-peer-reviewed-study?utm_source=SilverpopMailing&utm_medium=email&utm_campaign=Daily%20News:%20NIH%20Seeks%20New%20Centers%20for%20Precision%20Medicine%20Initiative%20Participant%20Enrollment,%20Management%20-%2007/29/2016%2004:15:00%20PM

Detection and quantitation of ctDNA KRAS mutations from patients with unresectable pancreatic cancer

Inna Chen 1 , Victoria M. Raymond 2 , Jennifer Geis 2 , Sandeep Pingle 2 , Fernando F. Blanco 2 Eric A. Collisson 3 , Vlada Melnikova 2 , Margaret Tempero 3 , Mark G. Erlander 2 , and Julia S. Johansen 1 1Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Denmark; 2Trovagene, Inc, San Diego, California, USA; 3Department of Oncology, University of California San Francisco, California, USA

Conclusions

• This is the largest, prospective dataset exploring ctDNA KRAS in unresectable pancreatic cancer.

• 92.9% of 210 patients with unresectable pancreatic cancer were positive for ctDNA KRAS.

• This detection rate closely matches the published prevalence of KRAS in pancreatic cancer (90%), and out performs previous studies, demonstrating the superior assay sensitivity.

• ctDNA analysis offers a viable tissue biopsy alternative for determining KRAS mutation status, especially in late stage patients.

• ctDNA KRAS analysis identified 52% more patients as positive than CA19-9, demonstrating KRAS as an improved diagnostic tool.

• Individuals with metastatic disease had a 8.2 fold difference in median ctDNA KRAS mutation load at baseline versus a 3.9 fold difference in baseline CA19-9. KRAS may represent an improved biomarker for metastatic disease over CA19-9.

• In two representative patients, dynamic changes in KRAS mutation load were consistent with response by imaging and predicted progressive disease months in advance of progression by imaging.

• Quantitation of KRAS mutant copy load may provide a more informative biomarker for prognosis and monitoring for therapeutic response

http://www.trovagene.com/wp-content/uploads/Posters/20160512%20AACR%20PancreasPoster(1).pdf

 

Trovagene and University of Michigan Enter into Collaboration for Monitoring and Early Detection of Pancreatic Cancer

Trovagene’s KRAS ctDNA liquid biopsy test will be at the forefront of research partnership with Dr. Diane Simeone at University of Michigan Health System

SAN DIEGO, July 6, 2016 /PRNewswire/ — Trovagene, Inc. (NASDAQ: TROV), a developer of circulating tumor DNA (ctDNA) molecular diagnostics, today announced the initiation of a multi-phased collaborative research program with the University of Michigan Comprehensive Cancer Center utilizing the Trovera™ KRAS ctDNA liquid biopsy test.

 

About Pancreatic Cancer and KRAS Mutations

The relative 1-year survival rate for patients with pancreatic cancer is only 28%, and the overall 5-year survival rate is 8%; stage IV pancreatic cancer has a 5-year survival rate of about 1%. At present, surgery offers the only therapeutic means of cure, but less than 20% of patients present with tumors amenable to resection.

The significant mortality rate of pancreatic cancer is due to the high incidence of metastases at the time of diagnosis, its fulminant clinical course, and the lack of adequate systemic therapies. Patients who undergo resection for localized pancreatic carcinoma have a long-term survival of approximately 20% and a median survival of 13 to 20 months. At the other end of the clinical spectrum, a high percentage (40% to 45%) of patients present with unresectable metastatic disease, with a short survival of only 3 to 6 months.

Mutations of the KRAS gene occurs in over 90% of pancreatic carcinomas – no other human tumor comes close in mutational frequency of this particular gene.

SOURCE

http://www.prnewswire.com/news-releases/trovagene-and-university-of-michigan-enter-into-collaboration-for-monitoring-and-early-detection-of-pancreatic-cancer-300294646.html?tc=portal_CAP

http://www.trovagene.com/

 

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

 

 

Hyaluronidase treatment of high HA pancreatic cancer increased progression-free survival

Author: David Orchard-Webb, PhD

https://pharmaceuticalintelligence.com/2016/07/03/hyaluronidase-treatment-of-high-ha-pancreatic-cancer-increased-progression-free-survival/

 

Targeting paclitaxel to the pancreas with a biodegradable drug-eluting device

Author: David Orchard-Webb, PhD

https://pharmaceuticalintelligence.com/2016/07/03/targeting-paclitaxel-to-the-pancreas-with-a-biodegradable-drug-eluting-device/

 

Recent Research On SMAD4 In Pancreatic Cancer

Curator: David Orchard-Webb, PhD

https://pharmaceuticalintelligence.com/2016/06/27/recent-research-on-smad4-in-pancreatic-cancer/

 

Pancreatic Cancer Modeling using Retrograde Viral Vector Delivery and IN-Vivo CRISPR/Cas9-mediated Somatic Genome Editing

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

https://pharmaceuticalintelligence.com/2016/06/10/pancreatic-cancer-modeling-using-retrograde-viral-vector-delivery-and-in-vivo-crisprcas9-mediated-somatic-genome-editing/

 

Mutations in RAS genes

Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/04/23/mutations-in-ras-genes/

 

TP53 tumor Drug Resistance Gene Target

Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/12/27/p53-tumor-drug-resistance-mechanism-target/

 

Pancreatic Cancer Targeted Treatment?

Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/05/18/pancreatic-cancer-targeted-treatment/

 

Aduro Biotech Phase II Pancreatic Cancer Trial CRS-207 plus cancer vaccine GVAX Fails

Reporter: Stephen J Williams, PhD

https://pharmaceuticalintelligence.com/2016/05/16/aduro-biotech-phase-ii-pancreatic-cancer-trial-crs-207-plus-cancer-vaccine-gvax-fails/

 

The “Guardian Of The Genome” p53 In Pancreatic Cancer

Curator: David Orchard-Webb, PhD

https://pharmaceuticalintelligence.com/2016/05/09/the-guardian-of-the-genome-p53-in-pancreatic-cancer/

 

Targeting Epithelial To Mesenchymal Transition (EMT) As A Therapy Strategy For Pancreatic Cancer

Curator: David Orchard-Webb, PhD

https://pharmaceuticalintelligence.com/2016/04/19/targeting-emt-as-a-therapy-strategy-for-pancreatic-cancer/

 

Pancreatic Cancer at the Crossroads of Metabolism

Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/10/13/pancreatic-cancer-at-the-crosroad-of-metabolism/

 

Using CRISPR to investigate pancreatic cancer

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/07/31/using-crispr-to-investigate-pancreatic-cancer/

 

Prostate Cancer Cells: Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition

Reporter-Curator: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2012/11/30/histone-deacetylase-inhibitors-induce-epithelial-to-mesenchymal-transition-in-prostate-cancer-cells/

 

@Mayo Clinic: Inhibiting the gene, protein kinase D1 (PKD1), and its protein could stop spread of this form of Pancreatic Cancer

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/02/24/inhibiting-the-gene-protein-kinase-d1-pkd1-and-its-protein-could-stop-spread-of-this-form-of-pancreatic-cancer/

 

Locally Advanced Pancreatic Cancer: Efficacy of FOLFIRINOX

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/06/01/locally-advanced-pancreatic-cancer-efficacy-of-folfirinox/

 

Consortium of European Research Institutions and Private Partners will develop a microfluidics-based lab-on-a-chip device to identify Pancreatic Cancer Circulating Tumor Cells (CTC) in blood

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/10/consortium-of-european-research-institutions-and-private-partners-will-develop-a-microfluidics-based-lab-on-a-chip-device-to-identify-pancreatic-cancer-circulating-tumor-cells-ctc-in-blood/

 

What`s new in pancreatic cancer research and treatment?

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/10/21/whats-new-in-pancreatic-cancer-research-and-treatment/

 

Pancreatic Cancer: Genetics, Genomics and Immunotherapy

Author: Tilda Barliya, PhD

https://pharmaceuticalintelligence.com/2013/04/11/update-on-pancreatic-cancer/

 

Targeting the Wnt Pathway

Writer and Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/04/10/targeting-the-wnt-pathway-7-11/

 

Gene Amplification and Activation of the Hedgehog Pathway

Curator: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/10/29/gene-amplification-and-activation-of-the-hedgehog-pathway/

 

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Previously undiscerned value of hs-troponin

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

LPBI

 

Troponin Rise Predicts CHD, HF, Mortality in Healthy People: ARIC Analysis

Veronica Hackethal, MD

Increases in levels of cardiac troponin T by high-sensitivity assay (hs-cTnT) over time are associated with later risk of death, coronary heart disease (CHD), and especially heart failure in apparently healthy middle-aged people, according to a report published June 8, 2016 in JAMA Cardiology[1].

The novel findings, based on a cohort of >8000 participants from the Atherosclerosis Risk in Communities (ARIC) study followed up to 16 years, are the first to show “an association between temporal hs-cTnT change and incident CHD events” in asymptomatic middle-aged adults,” write the authors, led by Dr John W McEvoy (Johns Hopkins University School of Medicine, Baltimore, MD).

Individuals with the greatest troponin increases over time had the highest risk for poor cardiac outcomes. The strongest association was for risk of heart failure, which reached almost 800% for those with the sharpest hs-cTnT rises.

Intriguingly, those in whom troponin levels fell at least 50% had a reduced mortality risk and may have had a slightly decreased risk of later HF or CHD.

“Serial testing over time with high-sensitivity cardiac troponins provided additional prognostic information over and above the usual clinical risk factors, [natriuretic peptide] levels, and a single troponin measurement. Two measurements appear better than one when it comes to informing risk for future coronary heart disease, heart failure, and death,” McEvoy told heartwire from Medscape.

He cautioned, though, that the conclusion is based on observational data and would need to be confirmed in clinical trials. Moreover, high-sensitivity cardiac troponin assays are widely used in Europe but are not approved in the US.

An important next step after this study, according to an accompanying editorial from Dr James Januzzi (Massachusetts General Hospital, Boston, MA), would be to evaluate whether the combination of hs-troponin and natriuretic peptides improves predictive value in this population[2].

“To the extent prevention is ultimately the holy grail for defeating the global pandemic of CHD, stroke, and HF, the main reason to do a biomarker study such as this would be to set the stage for a biomarker-guided strategy to improve the medical care for those patients at highest risk, as has been recently done with [natriuretic peptides],” he wrote.

The ARIC prospective cohort study entered and followed 8838 participants (mean age 56, 59% female, 21.4% black) in North Carolina, Mississippi, Minneapolis, and Maryland from January 1990 to December 2011. At baseline, participants had no clinical signs of CHD or heart failure.

Levels of hs-cTnT, obtained 6 years apart, were categorized as undetectable (<0.005 ng/mL), detectable (≥0.005 ng/mL to <0.014 ng/mL), and elevated (>0.014 ng/mL).

Troponin increases from <0.005 ng/mL to 0.005 ng/mL or higher independently predicted development of CHD (HR 1.41; 95% CI 1.16–1.63), HF (HR 1.96; 95% CI 1.62–2.37), and death (HR 1.50; 95% CI 1.31–1.72), compared with undetectable levels at both measurements.

Hazard ratios were adjusted for age, sex, race, body-mass index, C-reactive protein, smoking status, alcohol-intake history, systolic blood pressure, current antihypertensive therapy, diabetes, serum lipid and cholesterol levels, lipid-modifying therapy, estimated glomerular filtration rate, and left ventricular hypertrophy.

Subjects with >50% increase in hs-cTnT had a significantly increased risk of CHD (HR 1.28; 95% CI 1.09–1.52), HF (HR 1.60; 95% CI 1.35–1.91), and death (HR 1.39; 95% CI 1.22–1.59).

Risks for those end points fell somewhat for those with a >50% decrease in hs-cTnT (CHD: HR 0.47; 95% CI 0.22–1.03; HF: HR 0.49 95% CI 0.23–1.01; death: HR 0.57 95% CI 0.33–0.99).

Among participants with an adjudicated HF hospitalization, the group writes, associations of hs-cTnT changes with outcomes were of similar magnitude for those with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).

Few biomarkers have been linked to increased risk for HFpEF, and few effective therapies exist for it. That may be due to problems identifying and enrolling patients with HFpEF in clinical trials, Dr McEvoy pointed out.

“We think the increased troponin over time reflects progressive myocardial injury or progressive myocardial damage,” Dr McEvoy said. “This is a window into future risk, particularly with respect to heart failure but other outcomes as well. It may suggest high-sensitivity troponins as a marker of myocardial health and help guide interventions targeting the myocardium.”

Moreover, he said, “We think that high-sensitivity troponin may also be a useful biomarker along with [natriuretic peptides] for emerging trials of HFpEF therapy.”

But whether hs-troponin has the potential for use as a screening tool is a question for future studies, according to McEvoy.

In his editorial, Januzzi pointed out several implications of the study, including the possibility for lowering cardiac risk in those with measurable hs-troponin, and that HF may be the most obvious outcome to target. Also, optimizing treatment and using cardioprotective therapies may reduce risk linked to increases in hs-troponin. Finally, long-term, large clinical trials on this issue will require a multidisciplinary team effort from various sectors.

“What is needed now are efforts toward developing strategies to upwardly bend the survival curves of those with a biomarker signature of risk, leveraging the knowledge gained from studies such as the report by McEvoy et al to improve public health,” he concluded.

 

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