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Archives for August 2013

Breakthrough Case Study Highlights New Biomarker for Cancer and Inflammation

A groundbreaking peer reviewed case report by Dr. Isaac Eliaz, M.D. of Amitabha Medical Clinic, demonstrates for the first time the clinical use of novel biomarker galectin-3 to assess cancer progression and inflammation. The case study titled, “The Role of Galectin-3 as a Marker of Cancer and Inflammation in a Stage IV Ovarian Cancer Patient with Underlying Pro-Inflammatory Comorbidities,” was published in the July 2013 issue of Case Reports in Oncology. This report is the first of its kind to expand the diagnostic and prognostic applications of the galectin-3 blood serum test, introducing an important clinical tool to assess risk and progression of metastatic cancer and inflammatory diseases.

In 2011, the galectin-3 blood test was approved by the U.S. Food and Drug Administration for the screening and prognosis of congestive heart failure and cardiovascular disease. Approval was granted after an extensive body of published data, including long-term population studies, demonstrated the active role of elevated galectin-3 in cardiovascular conditions, fibrosis and early mortality. However, a rapidly expanding field of published galectin-3 research also highlights the significance of this rogue molecule as a novel biomarker that is both an active culprit as well as a byproduct of numerous inflammatory and malignant cellular processes beyond cardiovascular disease.

An expert on galectin-3, Dr. Eliaz applies the data obtained in this case study to shed further light on excess galectin-3’s mechanisms of action, specifically inflammatory response to injury and cancer progression. In this report, Dr. Eliaz presents the first published case documenting the clinical use of galectin-3 to monitor cancer progression and treatment response, as well as inflammatory conditions. These findings point to an expanded clinical model using galectin-3 testing in the diagnostic and prognostic assessment of numerous chronic, inflammatory diseases.

Unlike biomarkers such as C-reactive protein (CRP), which only indicate the presence of inflammation, galactin-3 is shown to play a direct role in initiating disease progression. It is a protein normally present in the body at low concentrations, where it is involved in numerous functions including cell growth and communication. At elevated levels, however, galectin-3 fuels numerous pathologic processes including chronic inflammation and the progression of inflammation to fibrosis; cancer cell adhesion, migration, angiogenesis, and metastasis. Elevated galectin-3 also allows cancer cells to evade immune response. Research demonstrates elevated galectin-3 levels in patients with melanoma, lung, breast, prostate, colorectal, ovarian, and head and neck cancers as well as non-Hodgkin’s lymphoma and others. Galectin-3 levels are also found to be higher in patients with metastatic disease than in patients with localized tumors.

Dr. Eliaz states, “This new case report and significant clinical observation supports the need for further research on the role of galectin-3. The galectin-3 test could well become one of our most important clinical tools in assessing and monitoring a wide range of conditions beyond cardiovascular disease, including metastatic cancer and inflammatory conditions.”

Study: The Role of Galectin-3 as a Marker of Cancer and Inflammation in a Stage IV Ovarian Cancer Patient with Underlying Pro-Inflammatory Comorbidities [Case Reports in Oncology]

Source: PR Newswire

Faster, Simpler Diagnosis for Fibromyalgia May be on the Horizon

Researchers have developed a reliable way to use a finger-stick blood sample to detect fibromyalgia syndrome, a complicated pain disorder that often is difficult to diagnose.

If it were someday made available to primary care physicians, the test could knock up to five years off of the wait for a diagnosis, researchers predict.

In a pilot study, the scientists used a high-powered and specialized microscope to detect the presence of small molecules in blood-spot samples from patients known to have fibromyalgia.

By “training” the equipment to recognize that molecular pattern, the researchers then showed that the microscope could tell the difference between fibromyalgia and two types of arthritis that share some of the same symptoms.

Though more analysis is needed to identify exactly which molecules are related to development of the disorder itself, the researchers say their pilot data are promising.

“We’ve got really good evidence of a test that could be an important aid in the diagnosis of fibromyalgia patients,” said Tony Buffington, professor of veterinary clinical sciences at The Ohio State University and senior author of the study. “We would like this to lead to an objective test for primary care doctors to use, which could produce a diagnosis as much as five years before it usually occurs.”

Patients with fibromyalgia are often desperate by the time they receive treatment because of the lengthy process required to make a diagnosis. The main symptoms, persistent pain and fatigue, mimic many other conditions, so physicians tend to rule out other potential causes before diagnosing fibromyalgia. Additional symptoms include disrupted sleep and memory or thought problems. An estimated 5 million American adults have the disorder, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

“The importance of producing a faster diagnosis cannot be overstated, because patients experience tremendous stress during the diagnostic process. Just getting the diagnosis actually makes patients feel better and lowers costs because of reductions in anxiety,” said Kevin Hackshaw, associate professor of medicine, division of rheumatology and immunology, at Ohio State’s Wexner Medical Center and lead author of the study.

The study is published in the Aug. 21, 2013, issue of the journal Analyst.

The technology used in this work is infrared microspectroscopy, which identifies the biochemical content of a blood sample based on where peaks of molecules appear in the infrared spectrum. The technology offers hints at the molecules present in the samples based on how molecular bonds vibrate when they are struck by light.

The spectroscopy works on dried blood, so just a few drops from a finger stick produce enough blood to run this test.

Researchers first obtained blood samples from patients diagnosed with fibromyalgia (14), rheumatoid arthritis (15) and osteoarthritis (12). These other conditions were chosen for comparison because they produce similar symptoms as fibromyalgia, but are easier to diagnose.

The scientists analyzed each sample with the infrared microspectroscopy to identify the molecular patterns associated with each disease. This functioned as a “training” phase of the study.

When the researchers then entered blinded blood samples into the same machinery, each condition was accurately identified based on its molecular patterns.

“It separated them completely, with no misclassifications,” Buffington said. “That’s very important. It never mistook a patient with fibromyalgia for a patient with arthritis. Clearly we need more numbers, but this showed the technique is quite effective.”

The researchers also analyzed some of the potential chemicals that could someday function as biomarkers in the fibromyalgia blood samples, but further studies are needed to identify the molecules responsible for the spectral patterns, he said.

Though an infrared microscope can be expensive, Buffington said the testing could be affordable if a central lab existed to run the samples. That the method can use dried blood samples makes this concept feasible because dried blood can be legally sent via U.S. mail, he noted.

Why is a veterinarian pursuing this type of research? Buffington is a renowned expert on domestic cats, including a painful bladder disorder they suffer called interstitial cystitis (IC). This syndrome also occurs in humans.

It turns out that the origins of IC, like such human disorders as irritable bowel syndrome and fibromyalgia, cannot be traced to the specific area of the anatomy most affected by the syndrome. These disorders are categorized as medically unexplained or functional syndromes, and Buffington has explored the possibility that a common link exists among these types of diseases, and that they might have origins in the central nervous system.

Buffington has filed two invention disclosures with the university, and Ohio State has filed multiple patent applications for the testing method, in the United States and internationally. In November, Ohio State was issued U.S. Patent 8,309,931 on a rapid diagnostic method for functional syndromes in humans and cats.

Additional co-authors include Luis Rodriguez-Saona and Marçal Plans of the Department of Food Science and Technology at Ohio State, and Lauren Bell of Metabolon Inc., based in Durham, N.C.

Study: A bloodspot-based diagnostic test for fibromyalgia syndrome and related disorders [Analyst]

Source: Ohio State University Wexner Medical Center

Potential Clue Associated with Aggressive Prostate Cancer Identified by Rutgers Investigators

Prostate cancer is one of the most common forms of cancer in men and the leading cause of cancer deaths in white, African-American and Hispanic men, according to the Centers for Disease Control. Current treatment of prostate cancer targets androgens, hormones which promote the growth and spread of cancer cells. However, it remains unclear why, despite treatment, some prostate cancers progress and may become fatal. Researchers at Robert Wood Johnson Medical School, part of Rutgers, The State University of New Jersey, who are studying the underlying mechanisms that cause invasive tumor growth have identified a key transcription factor, a protein which regulates the flow of information from DNA, that is over-produced in treatment-resistant prostate cancer, as well as the two protein kinases that trigger the process. This finding, published and highlighted on the cover of the July issue of Molecular Cancer Research, a journal of the American Association for Cancer Research (AACR) could be utilized to develop treatments for prostate cancer that is resistant to current therapies.

The research team, led by Joseph Fondell, PhD, associate professor of pharmacology, found that in clinically localized human prostate cancer — cancer that is confined to the prostate and pelvic area — the key transcription factor termed MED1 is overexpressed, meaning that significantly more MED1 is produced than is typical. According to Fondell, the finding potentially could be used as a biomarker in cancer screenings, indicating to oncologists that the prostate cancer has become aggressive. “As MED1 is a known co-activator of androgen receptors, the overexpression of MED1 is thought to facilitate alternative gene expression patterns that drive treatment-resistant cancer cell growth in the prostate,” Fondell said.

“Our study showed for the first time that MED1 expression is elevated in malignant cells of a statistically significant number of patients with clinical prostate cancer and that this overexpression correlates with an increase in cancer cell growth and invasiveness,” said Feng Jin, PhD, a former graduate student in Fondell’s lab and first author on the study. “In addition to accelerated tumor growth, our study showed that overexpression of MED1 may also be involved with inflammation of the prostate.”

Further study of the process using mouse models that mimic human prostate cancer, showed that two protein kinases, ERK and PI3K/AKT, were overactive and responsible for MED1 overproduction, ultimately accelerating the progression and spread of prostate cancer.

“Whereas the current treatment approach for prostate cancer is to prohibit androgen production and signaling, our findings indicate that MED1 could represent a novel target for new therapies that stop the process at the molecular level, before prostate cancer can progress to an advanced stage,” added Fondell, who also is a member of Rutgers Cancer Institute of New Jersey.

Study: ERK and AKT Signaling Drive MED1 Overexpression in Prostate Cancer in Association with Elevated Proliferation and Tumorigenicity [Molecular Cancer Research]

Source: Robert Wood Johnson Medical School

ITN Type 1 Diabetes Study Identifies Subset of Patients with Strong Response to Therapy

Primary results from a new clinical trial show that patients with type 1 diabetes treated with the monoclonal antibody teplizumab (MacroGenics, Inc.) exhibit greater preservation of C-peptide, a biomarker of islet cell function, compared to controls. Further analyses identified a discrete subset of the treatment group that demonstrated especially robust responses (“responders”), suggesting that these patients could be identified prior to treatment. The trial, entitled “Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes” (AbATE), was conducted by the Immune Tolerance Network (ITN). The results are available online and will be published in the November issue of the journal Diabetes.

The AbATE study, led by Kevan Herold, MD (Yale University), tested teplizumab, which targets the CD3 receptor found on T cells, in patients with new-onset type 1 diabetes. CD3 is required for T-cell activation, which can lead to the destruction of insulin-producing beta cells. A previous ITN study with teplizumab showed that a single course of the drug slowed C-peptide decline in new-onset patients for a year, after which the effects waned. The aim of the AbATE study was to test whether C-peptide preservation could be prolonged by administering two courses of teplizumab, one year apart.

In this open-label, Phase II study, 77 new-onset patients (ages 8 to 30 years old) were randomized to receive either teplizumab or a control. Those in the treatment arm received the scheduled treatment consisting of two 14-day courses of teplizumab, one year apart. Both arms received intensive diabetes care from certified diabetes educators and were followed for two years. The primary endpoint compared C-peptide preservation between the two groups.

After two years, the teplizumab-treated group showed significantly greater preservation of C-peptide (75-percent higher responses compared to the control group).

Further analysis revealed that within the treatment arm two groups of patients could be distinguished based on their C-peptide levels: one group, considered “responders” (22/49), showed very little C-peptide decline over the course of the study (only a 6 percent reduction from baseline), while the “non-responders” (27/49) exhibited a similar rate of C-peptide decline as the control group (less than 40-percent reduction from baseline).

Investigators measured various biomarkers and cell types that might distinguish between these two groups. They found that, at trial entry, “responders” had lower hemoglobin A1c levels (a marker of glucose concentration in the blood) and used less insulin at baseline, compared to “non-responders”. Differences in specific T-cell subsets also distinguished between the two groups at baseline, suggesting that immune status might contribute to drug responsiveness. However, further studies will be required to confirm these results.

“This overall approach to identifying characteristics of individuals most likely to respond to therapies shows great promise because the responders in this study experienced a robust and prolonged drug effect,” said Dr. Herold. “This type of response has not been seen in other studies of immune therapies.”

Type 1 diabetes is a disease marked by immune destruction of insulin-producing beta cells in the pancreas. New-onset patients usually have 20 to 40 percent of their normal beta cell mass remaining, which is still capable of producing insulin. Preserving this remaining mass, even temporarily, could improve long-term clinical outcomes.

Immune modulators, like teplizumab, represent a promising means of inducing tolerance; however, no drug has been shown to prevent or reverse disease, and only a few have temporarily delayed disease progression. The ability to identify a subgroup of patients who may be more responsive to therapy could greatly enhance the clinical use of immune modulators and improve outcomes for those patients. Further analyses with specimens collected from the AbATE study are ongoing to understand the mechanism of response.

Source: EurekAlert!

NEBA Health Earns Patent for Integration of NEBA Biomarker with Clinician’s ADHD Evaluation

NEBA Health, LLC recently announced that Dr. Steven M. Snyder, Research and Development Vice President, has earned US Patent 8,509,884. The patent protects a key aspect of the NEBA system: integrating the biomarker with a clinician’s workup for ADHD. “NEBA is not a standalone diagnostic,” said Dr. Snyder. “After the clinician’s ADHD evaluation, NEBA helps them determine if the symptoms are due to ADHD or if further testing is warranted.”

“Integrating the NEBA biomarker with a clinician’s initial diagnostic impression can bring a clinician’s diagnosis more in line with that of multidisciplinary team,” said Dr. Snyder. Research supports that compared to a clinician alone, a multidisciplinary team is better able to determine if ADHD-like symptoms are accounted for by another condition.

In order to diagnose ADHD, a clinician not only observes criteria regarding behavioral symptoms and impairment, but also must determine whether symptoms would be better accounted for by another condition. Because ADHD shares symptoms with other disorders, the diagnosis may be difficult. According to the US Center for Disease Control and Prevention (CDC), 9.5% of all children and adolescents have an ADHD diagnosis. The ADHD diagnosis rate is increasing. CDC states that rates of ADHD diagnosis increased an average of 3% per year from 1997 to 2006 and an average of 5.5% per year from 2003 to 2007.

“In their ADHD evaluation, clinicians may be challenged in the current medical environment to determine the primary diagnosis when overlapping symptoms are present,” said Howard Merry, President of NEBA Health. “We are delighted that the USPTO has awarded Dr. Snyder the patent. It covers NEBA’s core technology, and it’s another validation point for the 7 years we spent developing and validating NEBA.”

Source: PR Newswire