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Researchers Discover Biomarker, Potential Targeted Therapy for Pancreatic Cancer

University of Cincinnati (UC) researchers have discovered a biomarker, known as phosphatidylserine (PS), for pancreatic cancer that could be effectively targeted, creating a potential therapy for a condition that has a small survival rate.

Brain Inflammation Linked to More Severe Parkinson’s Symptoms

Reversing inflammation in the fluid surrounding the brain’s cortex may provide a solution to the complex riddle of Parkinson’s, according to researchers who have found a link between pro-inflammatory biomarkers and the severity of symptoms such as fatigue, depression and anxiety in patients with the chronic disease.

Lena Brundin of Michigan State University’s College of Human Medicine was part of a research team that measured inflammatory markers found in cerebrospinal fluid samples of Parkinson’s patients and members of a control group.

“The degree of neuroinflammation was significantly associated with more severe depression, fatigue, and cognitive impairment even after controlling for factors such as age, gender and disease duration,” said Brundin, an associate professor in the college and a researcher with the Van Andel Institute.

“By investigating associations between inflammatory markers and non-motor symptoms we hope to gain further insight into this area, which in turn could lead to new treatment options.”

The results of the study were published in the journal Brain, Behavior, and Immunity.

Inflammation in the brain long has been suspected to be involved in the development of Parkinson’s disease, specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. Recent research suggests inflammation could drive cell death and that developing new drugs that target this inflammation might slow disease progression.

Parkinson´s disease is the second most common degenerative disorder of the central nervous system; the causes of the disease and its development are not yet fully understood.

“The few previous studies investigating inflammatory markers in the cerebrospinal fluid of Parkinson’s patients have been conducted on comparatively small numbers of subjects, and often without a healthy control group for comparison,” Brundin said.

In the study, 87 Parkinson’s patients were enrolled between 2008 and 2012. For the control group, 37 individuals were recruited. Participants underwent a general physical exam and routine blood screening. Researchers looked at the following markers: C-reactive protein, interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 and macrophage inflammatory protein 1-β.

The study was carried out in collaboration with researchers from Lund University in Sweden, Skåne University Hospital in Sweden and the Mayo Clinic College of Medicine in Florida.

Study: Cerebrospinal fluid inflammatory markers in Parkinson’s disease – Associations with depression, fatigue, and cognitive impairment [Brain, Behavior, and Immunity]

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

Cell Reports Publication Elucidates Role of FACT as Accelerator of Tumor Transformation and Potential Marker and Target of Aggressive Cancers

Cleveland BioLabs, Inc. (Nasdaq:CBLI), Incuron, LLC, a joint venture between CBLI and Bioprocess Capital Ventures, and Roswell Park Cancer Institute (RPCI) today announced the publication of studies describing the Facilitates Chromatin Transcription (FACT) complex as an accelerator of tumor transformation and a potential marker and target for aggressive cancers in Cell Reports, a peer-reviewed journal. FACT is the molecular target for Curaxins, a new class of anti-cancer compounds being developed by Incuron. The reported studies were led by scientists at RPCI.

The FACT complex is involved in chromatin remodeling during transcription, replication, and DNA repair. These studies confirm an association between FACT and cancer by showing that FACT is expressed at higher levels in tumor cell lines than in normal cells in vitro and that elimination of FACT expression leads to reduced growth and decreased survival of tumor cells. The published work concludes that FACT’s role in cancer likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses, making it an enabler of oncogene-induced transformation.

In addition, the studies establish a statistically significant association between the frequency and level of FACT expression and tumor aggressiveness. The studies demonstrated that FACT is predominantly expressed in aggressive undifferentiated cancers that result in poor overall patient survival because of the development of metastatic disease, irrespective of tumor size at the time of diagnosis. This increases the potential value of FACT as a prognostic marker, as FACT positivity of a primary tumor could be used at a very early stage to determine the risk of future metastatic disease.

“This recent publication builds upon our previous work showing that FACT is the molecular target of Curaxins,” noted Katerina Gurova, M.D., Ph.D., a researcher in the Department of Cell Stress Biology at RPCI and lead author. “The data presented in the Cell Reports publication indicate that FACT is a promising marker and target for subtypes of cancer characterized by high grade and aggressiveness, and poor prognosis. This, together with the absence of FACT expression in most normal tissues, suggests that pharmacological inhibition of FACT using Curaxins could be an effective strategy to treat types of cancer for which there are currently few treatment options.”

Jean Viallet, M.D., Chief Development Officer at Cleveland BioLabs, stated, “We are evaluating the enormous body of data collected by our collaborators on FACT expression and its role in cancer progression in an effort to focus our next trials with our lead Curaxin drug candidate, CBL0137. Our plan is to enrich the upcoming study of the intravenous administration of CBL0137 in patients with metastatic or unresectable advanced solid tumors and lymphomas by including patients whose tumor types are dependent on transcriptional oncogenes.”

In March 2013, a Notice of Allowance was received from the U.S. Food and Drug Administration for an Investigational New Drug Application for intravenous administration of CBL0137. A Phase 1 single-agent dose-escalation study of oral administration of CBL0137 in patients with advanced solid tumors that are resistant or refractory to standard-of-care treatment is ongoing in the Russian Federation.

Study: Facilitates Chromatin Transcription Complex Is an “Accelerator” of Tumor Transformation and Potential Marker and Target of Aggressive Cancers

Source: Cleveland BioLabs

EMD Serono Establishes Immuno-Oncology Research and Early Development Platform to Advance Innovation in Cancer Therapies

EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany, recently announced its commitment to the field of cancer immunotherapy by creating a fully dedicated immuno-oncology innovation platform integrating research, early development and biomarker strategies. In addition to the company’s existing oncology platform, this new immuno-oncology platform will focus on developing therapies that leverage the immune system’s natural ability to fight tumors, and work in combination with existing and future therapies.

“We are pleased to announce our commitment to immuno-oncology, recognizing that the complexity of cancer requires diverse approaches that will enable alternative therapeutic interventions,” said Bernhard Kirschbaum, Head of Global Research and Early Development at Merck Serono, a division of Merck KGaA, Darmstadt, Germany. “In order to spur research and early development in this specialized area, we have created an innovative environment where researchers and clinicians work side-by-side to advance potential new cancer immunotherapies.”

The new immuno-oncology platform includes three innovation clusters, each of which is focused on discovery research and the advancement of molecules into the clinic through proof of confidence:

  • Therapeutic cancer vaccines: targeting tumor antigens to elicit a tumor-specific immune response
  • Cancer stem cells: targeting cancer stem cells to prevent or reduce tumor formation and inhibit metastases
  • Immunotolerance: eliminating or circumventing inhibitory mechanisms in the immune system that prevent cancer cells from being recognized and attacked by the body

To ensure a broad immuno-oncology research and early development platform, EMD Serono has assembled an in-house team of preeminent researchers and clinicians who will focus resources and technologies to build a portfolio of investigational immunotherapies, while collaborating with premier academia, research and industry organizations to complement internal capabilities.

The current immuno-oncology portfolio comprises therapeutic candidates in early clinical development and a robust pipeline of pre-clinical molecules. Leading therapeutic concepts in the clinic are:

  • A monoclonal antibody targeting PD-L1 (programmed cell death ligand) expressed by various tumors, currently in Phase I in solid tumors
  • NHS-IL12, a cancer immunotherapy targeting IL-12 to the necrotic regions of tumors, sponsored by the United States National Cancer Institute (NCI), currently in Phase I in solid tumors
  • NHS-IL2, targeting IL-2 to the necrotic regions of tumors, completed Phase I and currently preparing for Phase II in solid tumors

“Our goal is to develop leading immunotherapies that work in combination with other therapeutic modalities, understanding that attacking multiple cancer targets simultaneously increases the possibility of therapeutic success,” said Helen Sabzevari, Head of Immuno-Oncology, Global Research and Early Development at Merck Serono, a division of Merck KGaA, Darmstadt, Germany. “We are committed to delivering on the promise of immuno-oncology by combining creative thinking with strong research and clinical excellence, and, more importantly, by keeping patient needs at the heart of our efforts.”

Source: EMD Serono