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Researchers to Identify Genetic Biomarkers for Aggressive Breast Cancer

The Avon Foundation for Women recently awarded a $300,000 grant to Dolores Di Vizio, MD, PhD, associate professor in the Department of Surgery and the Department of Pathology and Laboratory Medicine and a member of the Cancer Biology and Urologic Oncology Research Programs at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute to advance scientific research in aggressive breast cancer.

Di Vizio will collaborate with the Cedars-Sinai Women’s Cancer Program to investigate biomarkers in patient blood samples that may identify individuals with aggressive breast cancer. Biomarkers are genes or other molecules that can indicate a person’s predisposition to specific medical conditions.

Research findings have the potential to create a novel standard of care and a new source of biomarkers. The possible new source of biomarkers, known as large oncosomes, are tumor-derived vesicles that transmit signaling complexes between cell compartments, providing valuable insight into the progression of disease. Findings may also help researchers and clinicians predict the aggressiveness of breast cancer earlier in the diagnostic process.

“This kind of research is the essential foundation to get us to our real goal, which is to improve diagnostic and prognostic capabilities and find effective treatments for breast cancer,” said Di Vizio. “With this study, we hope to identify previously unrecognized large oncosomes as potential biomarkers in advanced tumors that can be visualized, quantified and isolated using methods easily translatable to the clinic.”

Funding from the Avon Foundation for Women, a nonprofit organization and longtime supporter of Cedars-Sinai, will provide an opportunity for researchers to further spearhead new technologies, therapies and surgical interventions that may provide better patient outcomes, beginning at diagnosis.

Working with Di Vizio to provide these advancements is collaborator Beth Y. Karlan, MD, director of the Women’s Cancer Program, director of the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology, the Cedars-Sinai Board of Governors Chair in Gynecologic Oncology and the director of the Cedars-Sinai Gilda Radner Hereditary Cancer Program.

“I’m excited to be a collaborator on this research study, as it holds promise to provide tangible improvements in earlier diagnostics and detection in aggressive breast cancer and is perfectly aligned with the program goals of the Cedars-Sinai Women’s Cancer Program,” said Karlan. “This Avon Foundation for Women grant will further our program’s commitment to studying cancer biology, developing new approaches to early detection and preventing and improving cancer survival for all patients.”

This is the first study on large oncosomes analyses in patients with breast cancer. Pilot funding for this grant is supported by the Martz Breast Cancer Discovery Fund.

Source: EurekAlert!

Study Says New Biomarker May Predict Mesothelioma Survival, According to Surviving Mesothelioma

A team of researchers at Australia’s University of New South Wales say MUC1, a glycoprotein found on the outer surface of epithelial cells, is overexpressed in peritoneal mesothelioma. MUC1 is a mucin, a type of protein that helps protect the body against infection by binding with pathogens in the extracellular space and preventing them from entering cells.

Although MUC1 overexpression can predict poor survival in most cancers, and is often used to help diagnose mesothelioma, the Australian study is the first to measure its prognostic significance in mesothelioma, a rare cancer brought on by asbestos exposure. Mesothelioma most often occurs on the membrane that lines the lungs but peritoneal mesothelioma affects the lining of the abdomen. It accounts for about 25 to 30 percent of mesothelioma cases and, like all types of mesothelioma, is usually deadly.

Of the 42 peritoneal mesothelioma patients in the new study, 38 showed overexpression of MUC1. The significance of that overexpression was measured using the Kaplan-Meier method. Mesothelioma patients with a MUC1 level (based on immunohistochemical tests) between 5 and 8 had the lowest survival in all subtypes of tumors. Of the different variables tested – including tumor subtype, patient gender, peritoneal cancer index, and age at diagnosis – only a high MUC1 level and being over 60 years old at the time of diagnosis were consistently associated with poor outcomes.

Writing on their findings in the International Journal of Biological Markers, the authors conclude, “MUC1 evaluation by immunohistochemistry may serve as a useful prognostic tool in malignant peritoneal mesothelioma, but may need further confirmation in larger patients’ cohort.” Earlier this year, the same team of researchers determined that high expression of BCL2, a protein that helps regulate cell death (apoptosis), is associated with a good prognosis for patients with peritoneal mesothelioma.

In clinical practice, biomarkers are often used to help plan a treatment strategy for mesothelioma and other hard-to-treat cancers.

The original study appears in a recent issue of the International Journal of Biological Markers. (Pillai, K, et al, “MUC1 has prognostic significance in malignant peritoneal mesothelioma”, July 4, 2013, International Journal of Biological Markers, Epub head of print. http://www.ncbi.nlm.nih.gov/pubmed/23828409)

Study: MUC1 has prognostic significance in malignant peritoneal mesothelioma [International Journal of Biological Markers]

Source: PR Web

Takeda and Zinfandel Pharmaceuticals Initiate Phase 3 TOMMORROW Trial of AD-4833 for the Delay of Onset of Mild Cognitive Impairment Due to Alzheimer’s Disease in Subjects Selected Using a Genetic-Based Biomarker Risk Assignment Algorithm

Takeda Pharmaceutical Company Limited (“Takeda”) and its partner, Zinfandel Pharmaceuticals, Inc. (“Zinfandel”), recently announced the initiation of TOMMORROW, a global Phase 3 clinical trial investigating a genetic-based biomarker risk assignment algorithm (risk assignment algorithm) to predict risk of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) within a five year period and to evaluate the efficacy of the investigational low dose pioglitazone (designated AD-4833 for this use) in delaying the onset of MCI due to AD in cognitively normal individuals at high risk as determined by the risk assignment algorithm.

The risk assignment algorithm is comprised of apolipoprotein E (APOE) and TOMM40 genotypes and age. Age and APOE genotype have previously been shown to indicate elevated risk of AD. The addition of TOMM40 is hypothesized to further refine the risk determination.

“To date, there have been a number of avenues investigated with the goal of altering the course of Alzheimer’s disease but results have been unsuccessful,” said Allen Roses, M.D., Chief Executive Officer, Zinfandel. “This is why the TOMMORROW trial is important. The potential to identify an individual’s risk for developing MCI due to AD warrants further investigation.”

AD is a devastating disease and diagnoses are increasing as the world’s population ages. Currently 35.6 million people worldwide are living with some form of dementia. Studies show that individuals with MCI are at an increased risk of developing AD or another dementia with conversion rates of approximately 15 percent per year.

“AD-4833 is a member of a class of drugs known as PPAR (peroxisome proliferator-activated receptor)-gamma agonists which available data show may have a beneficial role in delaying symptoms of MCI due to AD,” noted Stephen Brannan, M.D., Central Nervous System Development Therapeutic Area Head, Takeda. “TOMMORROW is a significant study and represents a novel clinical milestone and trial for the Alzheimer’s community as it evaluates pre-symptomatic patients.”

Source: Taleda Pharmaceutical Company Limited

Nodality, Inc. Reports Promising Rheumatoid Arthritis Study Results to Predict Patient Treatment Response to TNF Inhibitors

Nodality, Inc., an innovative biotechnology company advancing discovery, development and use of transformative therapies by revealing functional systems biology, recently announced results of the Company’s comprehensive research study to identify cell markers (biomarkers) of disease activity and treatment success in rheumatoid arthritis (RA) patients. The study findings demonstrated that Nodality’s SCNP technology, which measures functional pathways at the single cell level, can be used to identify biomarkers of responsiveness to treatment with tumor necrosis factor inhibitors (TNFIs). RA affects an estimated two million Americans, and TNFIs constitute the most commonly prescribed therapy. Approximately half of patients respond to treatments such as TNFIs, leaving a substantial unmet need to identify which patients are more likely to respond to current therapies. Optimizing use of currently available therapies could potentially delay tissue damage and progression of disease.

SCNP provides the core technology foundation for Nodality’s programs dedicated to improving clinical medicine by increasing the efficiency of therapeutic R&D programs, enhancing life cycle management for commercialized drugs, and introducing new predictive diagnostics. The study results were featured in an oral presentation titled, Comparison of functional immune signaling profiles in peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis (RA) patients versus healthy donors (HD) using Single Cell Network Profiling (SCNP) (Abstract W7.02.04), at the 15th International Congress of Immunology (ICI) in Milan, Italy, taking place August 22 to 27, 2013. The findings were presented by S. Louis Bridges, Jr., M.D., Ph.D., Marguerite Jones Harbert-Gene V. Ball, MD Professor of Medicine, Director, Division of Clinical Immunology and Rheumatology, University of Alabama School of Medicine.

“Nodality’s research program demonstrates the great promise and potential in gaining a better understanding of disease biology and applying this to the development of prognostic and predictive biomarkers for autoimmune diseases such as RA,” commented Alessandra Cesano, M.D., Ph.D., Chief Medical Officer of Nodality. “I look forward to the final results of this program, one of the most comprehensive of its kind. Our technology, based on immune-biology, can predict which RA patients will respond to specific therapies and reveal the mechanisms of drug resistance, thus informing alternative therapeutic strategies.”

The Nodality research program compares healthy and diseased peripheral blood cells at the single cell level, studying samples obtained through the national Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository (TETRAD). Nodality anticipates completing its research program and announcing the key findings later this year.

Laura Brege, Nodality’s President and Chief Executive Officer, stated, “ICI has provided an important opportunity to showcase one of our key programs in immunology, further validating our broadly enabling SCNP platform. This platform has led to major collaborations in immunology addressing significant unmet needs among patients, as well as new predictive diagnostic modalities in blood cancers. Ultimately, Nodality’s goal is to accelerate and make more efficient the development of new therapeutic agents for serious diseases affecting large patient populations within immunology and oncology, two areas of continuing significant unmet clinical need.”

Additional program results were featured in a second oral presentation at the ICI Congress in a presentation titled, Functional proteomic interrogation of immune cell crosstalk and the effects of cytokine-targeted inhibitors using Single Cell Network Profiling (SCNP) (Abstract W7.02.03).

Source: Nodality, Inc

Key Assay Development at HUPO

Proteome Sciences presented novel data and key assay developments at the HUPO 12th Annual World Congress in Japan covering Tau in Alzheimer’s disease, SysQuant® in pancreatic cancer and a missing isoform in sugar structures of clusterin, a plasma protein biomarker for Alzheimer’s in brain atrophy.

pTau

The new Tau phosphorylation assay (pTau SRM) demonstrated powerful sensitivity and reproductivity measuring Tau phosphorylation on human and mouse models of Alzheimer’s disease from a much smaller sample amount.

In a different application the pTau SRM was successfully used to determine the effect of Tau kinase inhibitors PS110 and PS278-05 on CK1d on the Tau protein in a mouse model of Alzheimer’s. The results confirmed that Tau phosphorylation was reduced by the two compounds but not affected by the control substance.

SysQuant®

Over 5,000 different phosphorylation sites were quantified in tumour and healthy tissue in pancreas cancer with SysQuant®. In addition to major alterations in proteins related to cell morphology and motility, individual patterns of pathway activation were able to accurately predict the likelihood of tumour recurrence and to provide a truly personalised treatment regime.

Glycopreotomics

Novel data was presented that showed diagnostic changes in sugar structures attached to clusterin, a plasma marker for Alzheimer’s in brain atrophy. This revealed a unique isoform that lacked a specific branching pattern in patients with high levels of brain atrophy.

Commenting from Yokohama, Dr. Ian Pike, Chief Operating Officer, said: 

“We were delighted to be invited to the 12th HUPO congress to show results from the powerful biomarker services platform that we have developed from our TMT® mass tags for customers where we are at the forefront in proteomics. New assays for pTau and clusterin glycoprotein provide important additions to the range of assays and services that we offer our customers in Alzheimer’s The added power delivered by SysQuant® identifies thousands of phosphorylation sites across key signalling pathways that give clinicians the ability for the first time to provide real time patient management, in this case in pancreas cancer. These are exciting developments from proteomics that are fundamentally changing how clinicians identify and manage disease.”

Source: Proteome Sciences