Genomic Profile Can Improve Confidence in Active Surveillance of Prostate Cancer

MedicalResearch.com Interview with:

Bela S. Denes, MD, FACS Senior Director Medical Affairs UROLOGY Genomic Health Inc. Redwood City, CA. 94063

Dr. Bela S. Denes

Bela S. Denes, MD, FACS
Senior Director Medical Affairs
UROLOGY
Genomic Health Inc.
Redwood City, CA. 94063

MedicalResearch.com: What is the background for this study?

Response: This is a prospective community based non-interventional study designed to provide information on the utility of Oncotype GPS in the management of men presenting with a new diagnosis of clinically localized low risk prostate cancer. We sought to understand the impact of incorporating a molecular marker into the shared treatment decision in practices already well versed in Active Surveillance (AS) as measured by persistence on surveillance at 2 years as well as a number of patient reported outcomes. The current publication reports on the results of a one year pre-specified interim analysis.

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Salivary Biomarker May Lead To Spit Test For Early Diagnosis of Alzheimer’s Disease

MedicalResearch.com Interview with:

Ali Yilmaz, PhD Beaumont Research Institute Beaumont Health, Royal Oak, MI

Dr. Yilmaz

Ali Yilmaz, PhD
Beaumont Research Institute
Beaumont Health, Royal Oak, MI

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by the accumulation of β-amyloid plaques and tau tangles. Mild cognitive impairment (MCI) is progressive degree of impairment that is greater than might be attributed to normal age-related cognitive decline, but is not so severe as to merit a diagnosis of dementia. MCI is thought to be a transitional state between normal aging and AD sufferers phenotypically converting to AD at a rate of 10% per year. Currently there is no cure and few reliable diagnostic biomarkers for AD. As we live longer there is an ever increasing demand for valid and reliable biomarkers of Alzheimer’s disease; not only because it will help clinicians recognize the disease in its earliest symptomatic stages but will also be important for developing novel treatment of AD. Using 1D H NMR metabolomics, we biochemically profiled saliva samples collected from healthy-controls (n = 12), mild cognitive impairment (MCI) sufferers (n = 8), and Alzheimer’s disease (AD) patients (n = 9). We accurately identified significant concentration changes in 22 metabolites in the saliva of MCI and AD patients compared to controls.

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New Prostate Cancer Specific Assay May Reduce Need For Biopsies

MedicalResearch.com Interview with:

Eric A. Klein, MD</strong> Chairman, Glickman Urological and Kidney Institute Cleveland Clinic

Dr. Klein

Eric A. Klein, MD
Chairman, Glickman Urological and Kidney Institute
Cleveland Clinic

MedicalResearch.com: Which of these results did you find most interesting or surprising?

Response: What’s most interesting is that the IsoPSA assay redefines how PSA is measured, which links it more closely to the underlying biology of cancer. Current assays measure only the concentration of PSA, which can be affected by conditions other than cancer – BPH most commonly, but also infection and inflammation – which limits its diagnostic accuracy for finding cancer. Its been known for several decades that PSA exists in multiple different forms in the bloodstream in patients with prostate cancer.

These novel molecules arise because cancer cells have deranged cellular metabolism that result in the generation of new species of PSA, making their measurement more tightly linked to the presence or absence of cancer and even the presence of high grade cancer (where cellular metabolism is even more disordered).

The IsoPSA assay is the first assay to measure all of these isoforms and thus has better diagnostic accuracy for cancer.

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TeloView Measures Genomic Stability To Predict Disease Aggressiveness

MedicalResearch.com Interview with:

3D SignaturesJason Flowerday, CEO
Director of 3D Signatures 

MedicalResearch.com: What is the background for 3D Signatures?

Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level.

By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date.

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Saliva Test Can Predict Concussion Duration in Children

MedicalResearch.com Interview with:

Steven Daniel Hicks, MD, PhD Assistant Professor, Division of Academic General Pediatrics College of Medicine Penn State Health

Dr. Hicks

Steven Daniel Hicks, MD, PhD
Assistant Professor, Division of Academic General Pediatrics
College of Medicine
Penn State Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are about 3 million concussions in the US each year and the majority occur in children. Parents of children with concussions commonly cite length of recovery as a major concern, but pediatricians have no objective or accurate tests for addressing this concern.

Our research group previously identified small regulatory molecules called microRNAs that were altered in both the spinal fluid and saliva in children with traumatic brain injuries. In this study we investigated whether those microRNAs could predict duration of concussion symptoms. In 52 children with concussion we found a set of microRNAs that predict whether concussion symptoms would last beyond one month with over 80% accuracy. This was significantly more accurate than survey based tools such as the sports concussion assessment tool or a modified concussion clinical risk score. Interestingly, the microRNAs with predictive accuracy targeted pathways involved in brain repair and showed correlations with specific concussion symptoms.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy

MedicalResearch.com Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:
Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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GeneStrat Test Provides Quick Analysis of Genetic Lung Cancer Mutations

MedicalResearch.com Interview with:
Hestia Mellert, PhD

Director, Molecular Product Development
Biodesix: Making Medicine Personal
Boulder, CO

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies.

This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians.

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Xpert HCV Viral Load Test Can Detect Active Hepatitis C Infection From Fingerstick

MedicalResearch.com Interview with:

Jason Grebely PhD Associate Professor Senior Research Fellow (UNSW) Viral Hepatitis Clinical Research Program

Dr. Grebely

Jason Grebely PhD
Associate Professor
Senior Research Fellow (UNSW)
Viral Hepatitis Clinical Research Program

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Globally, testing and diagnosis of hepatitis C virus infection remain low. Although point of care tests for HCV infection exist, but many of these tests only measure HCV antibodies (previous exposure), not HCV RNA (active infection). Given that 25% of individuals spontaneously clear HCV infection, efforts to enhance diagnosis of chronic HCV infection and improve the HCV care cascade requires enhanced uptake of HCV RNA testing.

We conducted the first evaluation of the Xpert HCV Viral Load test (manufactured by Cepheid) – a point-of-care hepatitis C virus test that can detect active infection – from a finger-stick sample of blood. We established that there is good sensitivity and specificity of the Xpert HCV Viral Load point-of-care test using blood samples collected by finger-stick in participants attending drug health and homelessness services in Australia.

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New Platform Aims To Improve Cancer Markers Braf p.V600E/K Mutations

MedicalResearch.com Interview with:

Thurai Moorthy Ph.D.</strong> President, MultiGEN Diagnostics Greensboro, NC 27405

Dr. Moorthy

Thurai Moorthy Ph.D.
President, MultiGEN Diagnostics
Greensboro, NC 27405

MedicalResearch.com: What is the background for this study?

Response: As more cancer related genetic markers are reported, there is a need for appropriate molecular tests to meet clinical expectations. These expectations include detection at very low amount in a heterogeneous cell population, such as Formalin Fixed Paraffin embedded (FFPE) tumor biopsies.

Braf p.V600E/K mutations are cancer-specific markers found in a variety of cancers. There are several drugs in use, and more drugs are being developed, which are prescribed only to those patients whose tumor carries either of these (Braf p.V600E/K) mutations.

Hence, detection of Braf p. V600E/K is critical in the treatment of cancer patients. In this regard, we developed a new platform technology, Allele Specific Multiplex Sequencing (ASMS, for the detection of cancer markers from biopsy samples. As a demonstration project, we tested the new platform technology for the detection of Braf p.V600E/K using tumor samples (FFPE) previously tested by two presently used methods.

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Rapid Rule-Out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement

MedicalResearch.com Interview with:
Martin P. Than, MBBS
Emergency Department, Christchurch Hospital and
Dr John W Pickering, PhD
Associate Professor Senior Research Fellow in Acute Care
Emergency Care Foundation, Canterbury Medical Research Foundation, Canterbury District Health Board | Christchurch Hospital
Research Associate Professor | Department of Medicine | University of Otago
Christchurch New Zealand

MedicalResearch.com: What is the background for this study?

Response: Patients being investigated for possible acute coronary syndrome comprise one of the largest groups of patients presenting to emergency rooms. Troponin assays have developed such that they can now measure with greater accuracy much lower concentrations of troponin. A large retrospective registry based study and a couple of smaller prospective studies suggested that patients with a very low concentrations of troponin T (below the current limit of detection of 5 ng/L) measured with Roche Diagnostic’s high-sensitivity troponin T (hsTnT) assay on presentation to the emergency department (ie single blood draw) are very unlikely to be having a myocardial infarction (MI).

Our study gathers the current best evidence for using concentrations below the limit of detection in conjunction with no evidence of new ischaemia on ECG to safely risk stratify patients to a very low-risk group for MI and, therefore, potentially identify patients safe for early discharge.

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Pre-Clinical Study of Tbit™ System for Detection of Traumatic Brain Injury

MedicalResearch.com Interview with:

Sergey A. Dryga, PhD, MBA Chief Scientific Officer BioDirection, Inc.

Dr. Sergey Dryga

Sergey A. Dryga, PhD, MBA
Chief Scientific Officer
BioDirection, Inc. 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: When patients have suffered a head injury, they typically undergo a series of subjective cognitive tests to confirm a diagnosis of a concussion or other traumatic brain injury. In many cases these tests are inaccurate and inconsistent, increasing the risk of misdiagnosis. In other cases, patients may undergo an unnecessary CT scan, which is costly and exposes them to radiation. Early, objective diagnostic testing of patients who have experienced a head injury can support more rapid and appropriate treatment decisions while potentially reducing the use of unnecessary CT scans or other forms of intervention.

We know that protein biomarkers, including S100 calcium binding protein beta (S100β) and glial fibrillary acidic protein (GFAP), are released from the brain into the bloodstream immediately following a concussion or other traumatic brain injury. The Tbit™ System is a new medical device based on a nanotechnology biosensor that rapidly detects and accurately measures these protein biomarkers. The system includes a disposable cartridge and portable analyzer designed for testing using a single drop of blood at the earliest stages of a concussion.

This pre-clinical study was designed to evaluate the ability of the Tbit System to screen traumatic brain injury patients for a CT positive or CT negative test. Frozen plasma samples were collected from a total of 100 patients who had undergone CT scans post hospital admission. The Tbit System demonstrated 100% sensitivity with no false negative results, and a 41% specificity level.

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Model of RAF Inhibitor Action Provides Roadmap For Resistant Colon and Thyroid Cancer Treatment

MedicalResearch.com Interview with:

Poulikos I. Poulikakos, PhD Assistant Professor Department of Oncological Sciences Department of Dermatology The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai

Dr. Poulikakos

Poulikos I. Poulikakos, PhD
Assistant Professor
Department of Oncological Sciences
Department of Dermatology
The Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai

MedicalResearch.com: What is the background for this study?

Response: Mutations in the oncoprotein kinase BRAF are found in about 8% of human tumors, including more than 50% of melanomas. Small molecule RAF inhibitors prolonged survival of melanoma patients with mutant-BRAF tumors, but resistance limits their effectiveness. Further, RAF inhibitors showed only modest efficacy in patients with colorectal and thyroid mutant-BRAF tumors. Previous studies have suggested that the complex biochemical mechanisms of action of RAF inhibitors account for both sensitivity and major mechanisms of resistance to these drugs. Recently, a number of next generation RAF inhibitors have entered preclinical or clinical development, but the most appropriate clinical context for their use remained elusive.

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