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.

Continue reading

Frequency of Retinal Screening in Diabetes May Be Tailored to Individual

MedicalResearch.com Interview with:
John M. Lachin, Sc.D.
Research Professor of Biostatistics and of Epidemiology, and of Statistics
The George Washington University Biostatistics Center and
David Matthew Nathan, M.D.
Professor of Medicine, Diabetes Unit
Massachusetts General Hospital 

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

Response: Traditional guidelines for screening for retinopathy, based on indirect evidence, call for annual examinations. The automatic annual screening for retinopathy, without considering potential risk factors for progression,  appears excessive based on the slow rate of progression through sub-clinical states of retinopathy.

Continue reading

Genetic Variant of p53 Gene May Explain Increased Breast Cancer Risk in African American Women

MedicalResearch.com Interview with:

Maureen E. Murphy, Ph.D. Professor and Program Leader, Molecular and Cellular Oncogenesis Program Associate Vice President for Faculty Affairs Associate Director for Education and Career Development The Wistar Institute Philadelphia, PA 19104

Dr. Murphy

Maureen E. Murphy, Ph.D.
Professor and Program Leader, Molecular and Cellular Oncogenesis Program
Associate Vice President for Faculty Affairs
Associate Director for Education and Career Development
The Wistar Institute
Philadelphia, PA 19104

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

Response: The Murphy group discovered a coding-region variant of the p53 tumor suppressor gene, called Pro47Ser, that exists in individuals of African descent. In previous studies this group reported that this amino acid change reduces the ability of p53 to function as a tumor suppressor.

In this study, African American women from two different large cohorts were assessed for the incidence of the Pro47Ser variant in pre-menopausal breast cancer. A modest but statistically significant association was found between Pro47Ser and pre-menopausal breast cancer.

Continue reading

Precision Therapy In Early Stages For Triple Negative Breast Cancer

MedicalResearch.com Interview with:
Eran Andrechek, PhD

Eran Andrechek, PhD Associate Professor Department of Physiology Michigan State University East Lansing, MI

Associate Professor
Department of Physiology
Michigan State University
East Lansing, MI 

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

Response: Of the various types of breast cancer, triple negative breast cancer (lacking estrogen receptor, progesterone receptor and HER2) has the worst outcome and is largely limited to chemotherapy for treatment.  Other types can be treated with personalized medicine, resulting in better outcome.  For instance, a HER2+ve breast cancer can be treated with Herceptin, which targets HER2 itself.  The fact that triple negative breast cancer lacks these sort of targeted treatments presents a clear need in breast cancer therapy.

The goal of this study was to bring together our computational work using large databases from breast cancer with research into therapeutic options.  Essentially we wanted to ask if we could use patterns in what genes were being expressed to predict optimal therapy for triple negative breast cancer.  Continue reading

Biomarker May Predict Response to Common Leukemia Treatment

MedicalResearch.com Interview with:

Dr Laura Eadie PhD Post Doctoral Researcher Affiliate Lecturer Discipline of Medicine University of Adelaide

Dr. Laura Eadie

Dr Laura Eadie PhD
Post Doctoral Researcher
Affiliate Lecturer Discipline of Medicine
University of Adelaide

Summary: Researchers based at SAHMRI (South Australian Health and Medical Research Institute) in Adelaide, South Australia have recently demonstrated the significance of early increases in the expression of ABCB1 in predicting long-term response to imatinib therapy. Lead researcher, Dr Laura Eadie, has recently had these findings published in the journal Leukemia and says that she hopes “the evidence provided by the study could be used to inform better patient treatment in the future”.

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

Response: ABCB1 (p-glycoprotein) is a membrane transporter known to be involved in the efflux of the tyrosine kinase inhibitors (TKIs) that are used to treat chronic myeloid leukaemia (CML). Overexpression of ABCB1 has also been demonstrated to cause resistance to the TKIs imatinib, nilotinib and dasatinib in vitro. Although studied previously in CML patients, the predictive value of ABCB1 in determining a patient’s long-term response to imatinib had not been realized … until now.

Previous studies investigating ABCB1 as a predictive biomarker focused on expression levels of ABCB1 at one time point in isolation. For our study, we have measured the levels of ABCB1 at two separate time points specified in the TIDEL II trial protocol: day 1 (prior to the start of imatinib therapy) and day 22 (three weeks on imatinib). We then calculated the fold rise in ABCB1 expression levels at day 22 compared with day 1 and grouped patients about the median into high and low fold rise. When we compared molecular outcomes for patients within these two ABCB1 expression groups we noticed a striking difference in outcome to imatinib therapy.

Continue reading

Monitoring Circulating Tumor Cells May Further Personalized Cancer Treatment

MedicalResearch.com Interview with:

Dr. Elodie Sollier
Chief Scientific Officer at Vortex Biosciences

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

Response: Circulating Tumor Cell (CTC) burden may be a useful biomarker of response to targeted therapy in PDX (Patient Derived Xenograft) mouse models. Vortex Biosciences’ technology has been proven to enrich CTCs from human blood, but use of the technology with mouse blood had not yet been explored. In this poster, human CTCs are isolated with both high efficiency and purity from xenograft model of breast cancer using Vortex’s technology. Circulating Tumor Cell enumeration increased as the tumor burden increased in the mouse demonstrating its utility as a biomarker for drug treatment response.

Continue reading

Cross Border Pharmaceutical Alliances Present Challenges and Opportunities

Diane Frenier Esq Reed Smith Corporate Partner Member of Corporate & Securities Group and Life Sciences Health Industry Group

Diana Frenier

MedicalResearch.com Interview with:
Diane Frenier Esq

Reed Smith Corporate Partner
Member of Corporate & Securities Group and Life Sciences Health Industry Group

Background: Diane Frenier Esq discusses the M&A boom in the pharmaceutical and retail drug industry including a the “global study of 100 senior executives at life sciences companies by global law firm Reed Smith, in partnership with Mergermarket, reveals that 94% are planning to make an acquisition in the next year”.

Medical Research: What are the main drivers behind the pursuit of cross-border life sciences deals?

Ms Frenier: I think companies are trying to strengthen their capabilities in areas that are a core focus for them (e.g., in certain therapeutic areas, or for orphan drugs), and that includes adding products in those core focus areas and, in some cases, broadening geographically so they can market products in those core focus areas on a more global basis.  This will allow them to use their resources more efficiently and take advantage of saving from reducing redundancies.

Continue reading

Targeted Melanoma Panel Identifies Genetic Subsets of Melanoma

Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NYMedicalResearch.com Interview with:
Melissa Wilson, MD, PhD
Assisstant Professor
Perlmutter Cancer Center
NYU Langone Medical Center
New York, NY

Medical Research: What is the background for this study? What are the main findings?

Dr. Wilson: Metastatic cutaneous melanoma is an extremely aggressive form of skin cancer.  Traditionally, it has been characterized by clinicopathologic characteristics.  More recently, melanoma tumors have also been stratified by common somatic mutations for which targeted therapies have been developed or are under investigation, including BRAF, NRAS and KIT.  In addition to somatic mutations, aberrant intracellular signaling pathways and cell cycle disruption contribute to melanoma pathogenesis.  Indeed, recent next generation sequencing studies have identified a number of new genes involved in melanomagenesis.  A comprehensive evaluation and understanding of concurrent and mutually exclusive mutations in tumors has been lacking.  Therefore, we developed a comprehensive custom targeted capture of 108 genes previously implicated in melanoma pathogenesis.  We used the targeted panel to perform massively parallel sequencing on 94 well-established human melanoma cell lines, 67 patient-derived xenografts (PDX), and 5 cell lines made from PDX, all untreated.

Samples were clustered based on deleterious mutations.  Eighty-three percent of samples had deleterious mutations in the MAPK signaling pathway (including BRAF, RAS) and NF1.  Ten percent of samples had PI3K pathway mutations which were predominantly associated with BRAF mutations.  TP53 was found to be mutated in 24% of the samples and were also associated with mutations in the MAPK pathway.  Mutations in chromatin remodeling genes were mutually exclusive with each other, but were associated with BRAF and NRAS mutations.  Of particular interest, five of the 10 NF1mutated samples harbored likely deleterious mutations in MAP3K5 or MAP3K9, suggesting the potential involvement of JNK signal transduction pathway in a cohort of samples.

Continue reading

Genetic Diversity of Pancreatic Cancer May Lead To Therapeutic Targets

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT SouthwesternMedicalResearch.com Interview with:
Dr. Agnieszka Witkiewicz MD
Associate Professor of Pathology
Harold C. Simmons Comprehensive Cancer Center
UT Southwestern

MedicalResearch: What is the background for this study?

Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts.

MedicalResearch: What are the main findings?

Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease.   Specifically, many cases harbored deregulation in pathways that are the target for drug development.   For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib.   Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors.  Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention.

Continue reading

Mobile Health Technologies Will Change Chronic Disease Management

Ryan Jeffrey Shaw, PhD, MS, RN Assistant Professor School of Nursing Center for Health Informatics Center for Precision Medicine Duke University MedicalResearch.com Interview with:
Ryan Jeffrey Shaw, PhD, MS, RN

Assistant Professor School of Nursing
Center for Health Informatics
Center for Precision Medicine
Duke University

Medical Research: What is the background for this study? What are the main findings?

Dr. Shaw: Primary care delivery revolves around a series of episodes, rather than functioning as a continuum. When patients come to a clinic data on their health is collected as a single data point. This model neglects potentially meaningful data from patients’ daily lives and results in less informed treatment and scheduling of follow-up visits. Lack of meaningful data further blinds clinicians to patients’ health outside of the clinic and can contribute to unnecessary emergency department visits and hospitalizations.

Personalized care through mobile health technologies inspires the transition from isolated snapshots based on serial visits to real time and trended data. By using technologies from cell phones to wearable sensors, providers have the ability to monitor patients and families outside of the traditional office visit.

Continue reading

Germline Mutations Studied In Patients With Family History Of Early Onset Colon Cancer

Matthew B. Yurgelun, MD Instructor in Medicine Harvard Medical SchoolMedicalResearch.com Interview with:
Matthew B. Yurgelun, MD
Instructor in Medicine
Harvard Medical School

Medical Research: What is the background for this study? What are the main findings?

Dr. Yurgelun: Germline mutations in the TP53 gene are linked to Li-Fraumeni syndrome, which is an inherited syndrome associated with a 73-100% lifetime risk of cancer. Classically, cancers linked to Li-Fraumeni syndrome include early-onset breast cancer, leukemias, soft tissue sarcomas, brain cancer, and adrenocortical cancer, although recent data have shown an increased risk of colorectal cancer as well.  Our study’s primary aim was to determine the frequency of germline TP53 mutations in patients with early-onset colorectal cancer.

We studied 457 patients from the multinational Colon Cancer Family Registry who were diagnosed with colorectal cancer at age 40 or younger, and found that 1.3% carried a germline alteration in the TP53 gene.  None of these individuals had personal or family histories of cancer that fulfilled clinical criteria for Li-Fraumeni syndrome. Continue reading

Gene Signature May Predict Risk of Metastases and Death From Melanoma

Pedram Gerami MD Associate Professor of Dermatology and Pathology Northwestern UniversityMedicalResearch.com Interview with:
Pedram Gerami MD
Associate Professor of Dermatology and Pathology
Northwestern University

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

Dr. Gerami: The outcomes for patients with cutaneous melanoma are highly variable and there are limitations to the conventional staging system for melanoma. For example while the status of the sentinel lymph node biopsy is considered the strongest prognosticator, approximately 2/3 of cutaneous melanoma patients that ultimately die from their melanoma will have a negative sentinel lymph node biopsy result. In this study we showed that using a technique known as mRNA expression profiling to determine which genes are highly active and which are not that a molecular prognostic assay with accuracy could be developed. This assay can accurately classify patients based on their gene signature as having a high or low risk for metastasis and death from their melanoma. In an independent validation cohort, patients with a class I or low risk signature had a 5 year disease free survival rate of 97% while those with a class II or high risk signature had a 5 year disease free survival rate of only 31%.

Continue reading

Study Examines Use Of Oncotype DX® Breast Cancer Test In Medicare Patients

Dr. Michaela A. Dinan Ph.D Department of Medicine Duke UniversityMedicalResearch.com Interview with:
Dr. Michaela A. Dinan Ph.D

Department of Medicine
Duke University

Medical Research: What is the background for this study? What are the main findings?

Dr. Dinan: We wanted to examine how  Oncotype DX® Breast Cancer Test (ODX) was being used in real-world practice at the population level. ODX has been examined in clinical trials and limited academic settings but we know that these patients are often younger, have fewer medical comorbidities, and do not necessarily accurately reflect the majority patients with cancer.  In our study, we observed that Oncotype DX® Breast Cancer Test was being used predominately in accordance with guidelines which recommend the test for women with estrogen-receptor positive, node negative disease. We also looked just at women under the age of 70 who met guideline criteria for testing, because this population would include those women who were more likely to be chemotherapy candidates, and we saw a rapid uptake of the test between 2005 and 2009, with use of the test increasing from 8% to 39%.

Continue reading

Personalized Medicine: Tailoring Surgical Approach To Ovarian Cancer

Dr. Anil Sood MD Professor of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer CenterMedicalResearch.com Interview with:
Dr. Anil Sood MD

Professor of Gynecologic Oncology and Reproductive Medicine
The University of Texas MD Anderson Cancer Center

Medical Research: What is the background for this study? What are the main findings?

MedicalResearch: What is the background for this approach? What are the main findings?

Dr. Sood: The background involves several different issues: management approaches have varied quite a bit across the US; definition of “optimal” surgery and rates of complete surgical removal of tumor (R0) have also varied. It is quite apparent that patients who benefit the most from surgery upfront are those who have removal of tumor resection. To address these issues, we have implanted a much more personalized approach whereby patients with suspected advanced ovarian cancer undergo laparoscopic assessment using a validated scoring system (based on the pattern and extent of disease noted during laparoscopic assessment); patients with a score <8 undergo upfront debulking surgery and those with a score ≥8 receive neoadjuvant chemotherapy followed by surgery after 3-4 cycles. To date, this program has been fully implemented as part of the Moonshot Program at M.D. Anderson. This program has already resulted in several benefits – for example, prior to this algorithm being put into place among all patients with suspected advanced ovarian cancer, around 20% would have removal of tumor resection; after the implementation of the algorithm, of those going to upfront debulking surgery (after laparoscopic assessment), almost 85% of times removal of tumor resection can be achieved. Also, this method of treatment is allowing for new and innovative clinical trial designs. Continue reading

MAPT locus on Chromosome 17 Links Parkinson’s and Alzheimer’s Diseases

Dr. Rahul S. Desikan MD, PhD Department of Radiologoy University of California, San Diego School of MedicineMedicalResearch.com Interview with:
Dr. Rahul S. Desikan MD, PhD
Department of Radiologoy
University of California, San Diego School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Desikan: The MAPT gene encodes the tau protein, which plays an integral role in Alzheimer’s disease (AD) neurodegeneration. Though a number of studies have investigated this issue, the role of the MAPT gene in Alzheimer’s disease is still unclear. In contrast, a number of studies have found a robust association between MAPT and increased risk for other ‘tauopathies’ like Parkinson’s disease (PD). In our study, rather than evaluating all possible genetic loci, we only assessed shared genetic variants between Alzheimer’s disease and PD. By using this type of approach, we were able to increase our statistical power for gene discovery in Alzheimer’s disease.

We found genetic overlap between Alzheimer’s disease and Parkinson’s disease at a locus on chromosome 17 within the MAPT region. Our findings demonstrate that this MAPT associated locus increases risk for Alzheimer’s disease, correlates with gene expression of MAPT and is associated with brain atrophy of the entorhinal cortex and hippocampus on longitudinal MRI scans.

Continue reading

Personalized Advice May Help Risky Drinkers Reduce Alcohol

Sean M. Murphy, Ph.D. Assistant Professor  Department of Health Policy & Administration Washington State University MedicalResearch.com Interview with:
Sean M. Murphy, Ph.D.
Assistant Professor  Department of Health Policy & Administration
Washington State University

Medical Research: What is the background for this study? What are the main findings?

Dr. Murphy: Professional healthcare advice regarding excessive alcohol consumption has been shown to reduce demand in a controlled setting. However, success in a clinical trial isn’t always indicative of an intervention’s effectiveness in everyday use. Studies testing the effect of provider advice on alcohol demand in a non-controlled environment are few, and have failed to control for non-moderate drinkers.  Therefore, it is possible that the estimated effect of professional-health advice primarily reflected moderate-drinkers’ responses. The distinction between moderate and non-moderate drinkers is an important one, as society bears a large cost for those who consume above-moderate quantities, while moderate drinkers have been shown to be relatively productive and healthy. Excise taxes may not be efficient given that they impose negative externalities on moderate drinkers, while excessive drinkers have been shown to be relatively unresponsive to price increases. We found that personalized information from a healthcare professional was negatively associated with reported alcohol consumption among both “risky” and “binge” drinkers. Moreover, we found that personalized drinking advice may have an impact on those who are reluctant to state that they were given such advice.

Continue reading

Cerebral Palsy Sometimes Due To Genetics, Not Birth Trauma

Prof. Jozef GECZMedicalResearch.com Interview with:
Prof. Jozef Gecz
NH&MRC Senior Principal Research Fellow
Professor of Human Genetics
School of Paediatrics and Reproductive Health
Faculty of Health Sciences The University of Adelaide at the Women’s and Children’s Hospital North Adelaide, SA

Medical Research: What is the background for this study? What are the main findings?

Prof. Gecz: Cerebral palsy is the most frequent movement disorder of children for many years considered to be due to brain injury. Given that cerebral palsy incidence has not changed dramatically over many years while medical care is constantly improving, we look for other causes and specifically genetic mutation. By investigating 183 children with cerebral palsy and for many also one or both of their parents we find that for at least 14% of these we can find plausible explanation in genetic mutation being involved in the causation of their cerebral palsy. Importantly, we find that 10% of these mutations are de novo, which means that these mutations are not present in the parents (specifically in their blood as that is the tissue source we tested). 4% of mutations were inherited from unaffected mothers to affected sons. Previous estimates suggested 2% genetic contribution to Cerebral palsy. We now know that it is at least 14% and likely more.

Continue reading

Order of Mutations Affects Disease Pattern in Chronic Blood Disorders

David G. Kent, Ph.D From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of CambridgeMedicalResearch.com Interview with:
David G. Kent, Ph.D

From the Cambridge Institute for Medical Research and Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge

Medical Research: What is the background for this study? What are the main findings?

Dr. Kent: Cancers are the result of the sequential acquisition of errors in the genetic code.  Most studies have focused on the sum of these mutations (e.g., A+B+C = cancer) but no study in patients has asked the question of whether or not the order of genetic mutations impacts the disease (e.g., does A to AB equal B to BA).  We studied patients with chronic blood disorders (known as myeloproliferative neoplasms, or MPNs) that are precursors to cancer to access the earliest stages of tumour development and studied whether or not the order of mutation acquisition impacted disease.  We studied patients with mutations in two genes (JAK2 and TET2) and showed that the order of acquisition of these mutations impacted timing of clinical presentation, disease subtype, frequency of thrombotic events, and differed in their response to targeted therapy in the lab. Continue reading

Parental Performance Influences Genetic Neurodevelopmental Disability

Andres Moreno De Luca, MD Investigator and Resident Physician Autism & Developmental Medicine Institute Department of Radiology Geisinger Health System Danville, PA 17822MedicalResearch.com Interview with:
Andres Moreno De Luca, MD
Investigator and Resident Physician
Autism & Developmental Medicine Institute
Department of Radiology Geisinger Health System
Danville, PA 17822

 

Medical Research: What is the background for this study? What are the main findings?

Response: The main finding of our study is that family background contributes to the variability in cognitive, behavioral, and motor performance seen in children with 16p11.2 deletions, and perhaps other genetic syndromes, and this may be attributed in part to genetic background effects.

In the general population the best predictor of a child’s outcomes in traits such as cognitive ability, height, BMI, etc. is the biparental mean performance in such domains and this is due in part to genetic background. For example, if a child’s parents have IQ scores of 130 and 110, it is expected that the child will have an IQ within 2 standard deviations of 120 (bi-parental mean). However, when studying individuals with genetic conditions, most researchers tend to overlook the influence of familial/genetic background on the affected child’s outcomes and commonly attribute the manifestations (or lack thereof) to the genetic mutation alone.

This creates confusion when studying children with neurodevelopmental disorders, such as autism, which show significant clinical variability, as some children with a specific genetic mutation (e.g. deletion 16p11.2) may have intellectual disability without autism, while other children with the same mutation may have autism without intellectual disability. Based on these observations, some researchers have argued that deletion 16p11.2 is incompletely penetrant. However, our study showed that the 16p11.2 deletion has a detrimental effect on cognitive and behavioral performance for all children, but the clinical status (affected vs. unaffected) and ultimate performance level is influenced by the parental performance.

Continue reading

Warfarin Dosing: Do Genotype-Based Algorithms Improve Outcomes?

MedicalResearch.com Interview with:
David Ldr_david_l_brown. Brown, MD, FACC
Professor of Medicine
Cardiovascular Division
Washington University School of Medicine
St. Louis, MO 63110

MedicalResearch: What are the main findings of the study?

Dr. Brown: This meta-analysis of randomized controlled trials showed that using a genotype-based warfarin dosing algorithm did not improve the process or outcomes of anticoagulation compared to using a clinical dosing algorithm.
Continue reading