Research and Clinical Trials News

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Low T3 syndrome predicts unfavorable outcomes in surgical patients with brain tumor

• Tuesday, 12 March 2013 20:05

Charlottesville, VA (March 12, 2013). In a study of 90 patients undergoing surgery for brain Tumor, researchers in Lithuania (Lithuanian University of Health Sciences) and the United States (University of North Carolina at Chapel Hill and Brigham & Women's Hospital, Harvard University) have discovered that the finding of low T3 (triiodothyronine) syndrome is predictive of unfavorable clinical outcomes and depressive symptoms. Details of this study are furnished in the article "Low triiodothyronine syndrome as a predictor of poor outcomes in patients undergoing brain tumor surgery: a pilot study. Clinical article," by Adomas Bunevicius, M.D., Ph.D., and colleagues, published today online, ahead of print, in the Journal of Neurosurgery.

Low T3 syndrome is a term used to describe the finding of low blood serum concentrations of T3, which can be accompanied by abnormal T4 (thyroxine) to T3 conversion and high concentrations of reverse T3 (rT3) without any obvious sign of thyroid disease. Previous reports have shown that the finding of low levels of T3 in critically ill patients and patients undergoing surgery for some disorders is widespread and associated with unfavorable clinical outcomes. To see if this was true for patients undergoing brain tumor surgery, Dr. Bunevicius and colleagues performed perioperative thyroid function tests. (Surgery is the most common treatment for brain tumors.) The researchers also examined whether there was an association between low T3 syndrome and symptoms of anxiety and depression, which in patients harboring brain tumors are common complications and are associated with poor prognoses.

The researchers evaluated thyroid function profiles in 90 patients (median age 55 years, 71% women) on the morning of brain surgery and again on the following morning. If patients were found to have a free T3 level of 3.1 picomoles per liter (pmol/L) or less, they were given a diagnosis of low T3 syndrome. The Hospital Anxiety and Depression Scale was used pre- and postoperatively to identify cases of anxiety and depression. The Glasgow Outcome Scale was used at the time of hospital discharge to determine clinical outcomes.

The researchers identified a high prevalence of low T3 syndrome in this patient cohort: 38% of patients before brain tumor surgery and 54% of patients after surgery. In a comparison of preoperative and postoperative thyroid hormone profiles, the researchers found significant decreases in the concentrations of free T3 and thyroid-stimulating hormone (TSH) as well as in the T4 to T3 conversion; they also found significant increases in the concentration of free T4 (all p < 0.001). Perioperative low T3 syndrome was associated with a five-fold increased risk of unfavorable outcome at the time of hospital discharge, compared to patients with normal T3 concentrations. A significantly increased risk of unfavorable outcome was associated with preoperative and postoperative low T3 syndrome in a univariate binary regression analysis as well as in a multivariate binary regression analysis in which adjustments were made for patient age and sex, preoperative impairments in function, histological type of brain tumor, and previous treatment for brain tumor.

There were significant improvements in postoperative scores for symptoms of depression and anxiety, when compared with scores obtained preoperatively. The researchers found a four-fold increased risk of preoperative symptoms of depression in patients with preoperative low T3 syndrome. The association between these two factors was verified in a univariate regression analysis and in a multivariate regression analysis in which adjustments were made for sociodemographic and clinical factors.

The researchers note: "this is the first study to examine perioperative thyroid axis function in patients undergoing brain tumor surgery." The primary finding of the study is that low T3 syndrome is a clear biomarker for unfavorable clinical outcomes in this patient group. Diagnosis and preoperative management of low T3 syndrome should therefore be a consideration in patients undergoing surgery for brain tumor. Adds Dr. Adomas Bunevicius, the first author, "Thyroid hormone concentrations can easily be investigated in routine clinical settings. The tests are inexpensive and readily available worldwide. Thyroid hormone concentrations can be potentially relevant for risk stratification in patients undergoing surgery for brain tumors."

Bunevicius A, Deltuva V, Tamasauskas S, Tamasauskas A, Laws ER Jr., Bunevicius R. Low triiodothyronine syndrome as a predictor of poor outcomes in patients undergoing brain tumor surgery: a pilot study. Clinical article. Journal of Neurosurgery, published online, ahead of print, March 12, 2013; DOI: 10.3171/2013.1.JNS121696.

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Wayne State researcher gives new name to exhaustion suffered by cancer patients

• Friday, 08 March 2013 19:39

DETROIT — The fatigue experienced by patients undergoing Cancer treatments has long been recognized by health care providers, although its causes and ways to manage it are still largely unknown.

A Wayne State University researcher believes the condition affects some patients much more than others and is trying to determine the nature of that difference.

Horng-Shiuann Wu, Ph.D., assistant professor of nursing in the College of Nursing, has made an effort to chronicle the parameters of what she calls sudden exhaustion syndrome. Her study, "Definition, Prevalence and Characteristics of Sudden Exhaustion: A Possible Syndrome of Fatigue in Cancer," recently published in the journal Supportive Care in Cancer, is an effort to differentiate between types of cancer-related fatigue (CRF), a condition that affects upwards of 90 percent of patients who undergo major treatments and 30 to 67 percent of cancer survivors.

"CRF is something that goes far beyond just being tired," Wu said. "It's more draining, more intense, lasts longer than typical fatigue and is often unexpected."

As a graduate student, Wu became interested in a subset of patients who reported fatigue as a "hit-the-wall" moment that came on suddenly, left them barely able to move and often forced them to lie down immediately until the episode passed.

CRF has been well documented, but while many clinicians and researchers have heard anecdotally from patients about suddenly "hitting the wall," such reports have not been addressed directly by studies.

Wu's team studied 114 breast cancer Chemotherapy patients aged 31 to 67 from a Midwestern clinic and an urban teaching hospital. Participants were screened for sudden fatigue and completed a questionnaire on the day of their chemotherapy treatment. Descriptive statistics were used to examine the prevalence and clinical characteristics of sudden fatigue episodes, including an intensity rating system from one to 10, the latter level being the highest.

Just under half (46 percent) of participants experienced sudden fatigue. Of those, 81 percent reported more than one episode per day, with 77 percent of episodes taking place during activities between 10 a.m. and 5 p.m. Ninety percent of patients described the intensity as severe.

Most episodes lasted an hour or less, but some lasted up to eight hours. Some patients had to sleep; others did not. Many reported concurrent symptoms including weakness, dizziness, pain, sweating, Nausea and shortness of breath.

"We learned that this is something that's really happening and most patients' lives are affected by it," Wu said.

Because the sudden onset of such episodes distinguishes them from what's normally thought of as CRF, she believes "sudden exhaustion syndrome" is a better description.

"Patients can suddenly become so exhausted they cannot move at all," Wu said. One participant experienced an onset while being surveyed, causing her eyelids to droop and rendering her unable to form words.

She said the study shows that patients undergoing treatment endure a lot, and she is interested in looking at which syndrome characteristics particular patients experience, along with degrees of intensity and concurrence.

Wu also would like to know why some patients feel compelled to sleep and others do not, and what symptom changes signal to each person that an episode is ending. She is especially curious about patients who seem to experience little or no CRF.

The condition may even continue for many cancer survivors even after they've finished treatment. Wu believes, however, that in the absence of empirical evidence of that continuation, further research is needed.

For now, Wu said oncology professionals need to recognize the syndrome and educate patients to enhance a sense of control and prevent harm.

"Cancer is not going away anytime soon," she said. "Most people experience their illness through the symptoms, not the illness per se. But we can manage a symptom, even if we can't cure the illness yet."

Wu's study was funded by an Oncology Nursing Foundation/Novartis Nursing Research Grant.

Wayne State University is one of the nation's pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the Quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit http://www.research.wayne.edu.

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Nuvilex Focused on Positioning Subsidiary, Medical Marijuana Sciences, Inc., to be a Leading Medical Marijuana Entity by Developing Brain and Pancreatic Cancer Treatments

• Friday, 01 March 2013 22:38
• Last Updated ( Friday, 01 March 2013 22:44 )

SILVER SPRING, Md., Feb. 27, 2013 —Nuvilex, Inc. (NVLX), an international biotechnology and clinical stage provider of natural products and cell and gene therapy solutions for the treatment of diseases, announced today that it is focused on positioning its subsidiary, Medical Marijuana Sciences, Inc., as a leader among entities in the medical marijuana field by virtue of its goal of using Cannabis constituents in the development of treatments for brain and pancreatic Cancer.

Many companies in the medical marijuana arena are technology enterprises concerned with growth and distribution of marijuana or the production of numerous products containing marijuana or forms of its extracts. In contrast, Medical Marijuana Sciences, Inc. is utilizing a number of compounds found in marijuana plants and utilizing them to develop treatments for serious diseases. More specifically, using cannabinoids isolated from Cannabis sativa, Nuvilex's subsidiary will concentrate on the development of treatments for some of the deadliest forms of cancer that have historically shown that they are very difficult to treat with great success. Thus, this effort will initially involve pancreatic cancer and cancers of the brain, particularly glioblastomas.

Nuvilex's COO, Dr. Gerald Crabtree commented "Nuvilex's "in-house" experience in drug development, particularly in the cancer area, coupled with the knowledge gleaned during the development of our pancreatic cancer treatment, serves as a strong foundation upon which Medical Marijuana Sciences can build treatments, using constituents of Cannabis, for deadly forms of cancer. By pursuing "hard targets" like cancers of the pancreas and brain, Medical Marijuana Sciences can position itself to become a leader among entities involved in the use of marijuana for medicinal purposes."

Nuvilex is a true biotechnology company by virtue of the development of a treatment for advanced, Inoperable pancreatic cancer, through its subsidiary Austrianova Singapore (ASPL), involving the use of its proprietary cell encapsulation technology together with the well-known anticancer drug, ifosfamide. On the foundation of very promising results from two independent clinical trials by ASPL, wherein the pancreatic cancer treatment was found to double both the Median survival time of patients as well as their one-year- Survival Rate, preparations are underway for a "late-phase" clinical study that if successful, will ultimately lead to approval by drug regulatory agencies for marketing of Nuvilex's pancreatic cancer treatment.

Dr. Robert Ryan, President and CEO of Nuvilex stated, "Through building on the experience and expertise obtained during the development of its pancreatic cancer treatment by Austrianova Singapore combined with that gained over many years of involvement by principals within Nuvilex toward the development of drugs and treatments for serious diseases, notably cancer, our new subsidiary, Medical Marijuana Sciences, Inc. will build on our knowledge and position itself to become a leading biotechnology contributor in the medical marijuana arena. It is our intention that the utilization of these and other natural source compounds will lead to valuable treatments for patients with serious diseases."

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About Nuvilex

Nuvilex, Inc. (OTCQB:NVLX) has been a provider of all-natural products for many years. The company has been expanded to increase its natural product-based footprint through medical marijuana studies. We are an international biotechnology provider of live, therapeutically valuable, encapsulated cells and services for research and medicine. New developments by our company and subsidiaries will be substantial as we have been working on many fronts to move us forward. Our company's offerings will ultimately include cancer, diabetes and other treatments using the Company's natural product knowledge, product base, cell and gene therapy expertise, and live-cell encapsulation technology in addition to other new products currently under development.

The Nuvilex, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=13494

Safe Harbor Statement

This press release contains forward-looking statements described within the 1995 Private Securities Litigation Reform Act involving risks and uncertainties including product demand, market competition, and meeting current or future plans which may cause actual results, events, and performances, expressed or implied, to vary and/or differ from those contemplated or predicted. Investors should study and understand all risks before making an investment decision. Readers are recommended not to place undue reliance on forward-looking statements or information. Nuvilex is not obliged to publicly release revisions to any forward-looking statement, reflect events or circumstances afterward, or disclose unanticipated occurrences, except as required under applicable laws.

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Study identifies growth factor essential to the most common malignant pediatric brain tumor

• Thursday, 28 February 2013 21:18

Interaction between signaling protein and receptor could be attractive treatment target

		IMAGE: Medulloblastoma cells secrete the developmental protein Shh, which binds to receptors in stromal cells and triggers signaling that leads to the production of PlGF. Stromal-derived PlGF then binds to Nrp1... Click here for more information.

A multi-institutional team led by Massachusetts General Hospital (MGH) researchers has identified a molecular pathway that appears to be essential for the growth and spread of medulloblastoma, the most common Malignant brain Tumor in children. In their report in the Feb. 28 issue of Cell, they show that blocking this pathway – which involves interactions between tumor cells and the surrounding tissues – leads to regression of all four molecular subtypes of medulloblastoma in several mouse models.

"Our finding that a pathway carrying signals from host cells to tumor cells via placental growth factor and its receptor neuropilin 1 is critical to the growth of medulloblastoma, regardless of molecular subtype, strongly supports evaluating antibodies against these proteins as a novel therapeutic approach to this pediatric Cancer," says Rakesh K. Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and corresponding author of the study.

A highly malignant tumor that originates in the Cerebellum, medulloblastoma accounts for about 20 percent of all pediatric brain tumors and is ten times more common in children than in adults. While aggressive treatment with surgery, Chemotherapy and radiation significantly improves patient survival, those treatments can have long-term developmental, behavioral, and neurological side effects, particularly in the youngest patients, making the need for less damaging therapies essential.

Impetus for the current investigation began with studies by Peter Carmeliet, MD, PhD, of the Vesalius Research Center in Belgium, a co-author of the current study. Carmeliet found that an antibody against placental growth factor (PlGF) could block angiogenesis in a number of adult tumors. Since PlGF, unlike other angiogenic proteins, is not required for normal postnatal development, Jain and his Steele Lab colleague Lei Xu, MD, PhD, proposed targeting PlGF as anti-angiogenic treatment for pediatric tumors. Matija Snuderl, MD, of the Steele Lab, a co-lead author of the current study, then found that PlGF was highly expressed in all types of medulloblastoma. Other members of Jain's team found that high expression of the P1GF receptor neuropilin 1 (Nrp1) was associated with poor survival in medulloblastoma patients.

To investigate mechanisms behind the potential role of PlGF in medulloblastoma, the MGH investigators collaborated with colleagues in the U.S., Belgium, Canada and Germany. They first confirmed that PlGF is expressed in patient samples of all subtypes of medulloblastoma and that expression of Nrp1 was more significant than that of PlGF's more common receptor, VEGFR1. Experiments in several mouse models revealed that the presence of PlGF is essential for the progression of medulloblastoma and that treatment with several antibodies against the growth factor reduced tumor growth and spread, increasing animal survival even without substantially inhibiting angiogenesis

The researchers were surprised to find that most PlGF was produced by surrounding supportive tissue called stroma and not by the tumor cells. Further investigation revealed that release of the developmental protein Shh (sonic hedgehog) by tumor cells induces expression in nearby stromal cells of PlGF, which then binds to the Nrp1 receptor on tumor cells, leading to further tumor growth. The authors note that therapies that block the interaction between PlGF and Nrp1 are less likely to lead to treatment resistance than are therapies directly targeting mutations that drive tumor growth.

"The importance of tumor-stromal interactions has been recognized for decades, especially the formation of new blood vessels to supply tumors," says Jain, the Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School. "Our discovery of an entirely different way that tumor-stromal interactions drive cancer progression supports the exciting possibility that targeting that pathway in medulloblastoma could be more broadly effective with fewer side effects for patients. Antibodies against both PlGF and Nrp1 have been developed and tested in adult patients. There is hope that they could be safe in pediatric patients, but that needs to be established in clinical trials."

In addition to Snuderl, co-lead authors of the Cell article are Ana Batista, PhD, and Nathaniel D. Kirkpatrick, PhD, of the Steele Lab, and Carmen Ruiz de Almodovar, PhD, of the Vesalius Research Center. Collaborating institutions include Children's Hospital Boston, the Vesalius Research Center, University of Leuven, Belgium; Genentech, Inc.; the University of British Columbia; and University Hospital, Münster, Germany. Support for this study includes a grant from Hoffmann-La Roche and National Institutes of Health grant R01CA163815. Carmeliet has patent applications for intellectual property related to this study, and Jain is on the boards of trustees of H&Q Healthcare Investors and H&Q Life Science Investors.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."