Biomarker detects graft-versus-host-disease in cancer patients after bone marrow transplant

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ScienceDaily (Oct. 21, 2011) — A University of Michigan Health System-led team of researchers has found a biomarker they believe can help rapidly identify one of the most serious complications in patients with leukemia, lymphoma and other blood disorders who have received a transplant of new, blood-forming cells.

Known as a hematopoietic stem cell transplant, these patients receive bone marrow or peripheral blood stem cells from a matched donor who is either a family member or an unrelated volunteer.

The most common fatal complication of this type of transplant is graft-versus-host disease (GVHD), where the newly transplanted immune system of the donor attacks the patient's skin and internal organs. Up to 30 percent of recipients develop GVHD in their gastrointestinal tract, which is the organ most resistant to treatment.

Without invasive tests such as biopsies, however, GVHD can be difficult to distinguish from other causes of gastrointestinal distress, such as infection or side effects from medication.

The U-M team tested blood samples from over 1,000 patients who were treated in Ann Arbor, Germany and Japan.

"We believe we've found a reliable biomarker in the patients' blood that is specific to graft-versus-host disease and therefore can help us to rapidly identify patients for whom standard treatment is likely to be insufficient," says James L.M. Ferrara, M.D., co-lead author of the study and director of the U-M Combined Blood and Marrow Transplant Program. "This marker can also tell us whether a patient is likely to respond to therapy and may lead to an entirely new risk assessment for the disease. The findings were recently published online ahead of print publication in the journal Blood.

The marker, known as regenerating islet-derived 3-alpha (REG3-alpha), doesn't prevent patients from still needing a biopsy, Ferrara cautions, but taken with other predictive indicators, it could help doctors to ensure patients get the most appropriate treatment as early as possible.

Doctors at U-M hope to start using the test clinically in early 2012.

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The above story is reprinted from materials provided by University of Michigan Health System.

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Journal Reference:

J. L. M. Ferrara, A. C. Harris, J. K. Greenson, T. M. Braun, E. Holler, T. Teshima, J. E. Levine, S. W. J. Choi, E. Huber, K. Landfried, K. Akashi, M. Vander Lugt, P. Reddy, A. Chin, Q. Zhang, S. Hanash, S. Paczesny. Regenerating islet-derived 3 alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood, 2011; DOI: 10.1182/blood-2011-08-375006

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New mechanism inhibiting the spread and growth of cancer found in motile cells

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ScienceDaily (Oct. 21, 2011) — A revolutionary discovery regarding motile cancer cells made by research scientists at VTT Technical Research Centre of Finland and the University of Turku is challenging previous conceptions.

The results have been published on 25 July 2011 in the Journal of Cell Biology.

It has long been held that cells use different mechanisms for regulating migration and growth. This conception was proven false by research scientists Anja Mai and Stefan Veltel from the research team of Professor Johanna Ivaska. Their findings on aggressively spreading breast cancer cells revealed -- completely contrary to previous expectations -- that a single cell protein (p120RasGAP) acts as an important inhibitor of both cell migration and growth.

Cancer cells are characterised by traits such as uncontrollable growth and the ability to metastasise. The findings of the research team now show that the regulation of these two deadly traits in cells is interconnected, which may be an important piece of information in the future development of medicines.

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The above story is reprinted from materials provided by Technical Research Centre of Finland (VTT).

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A. Mai, S. Veltel, T. Pellinen, A. Padzik, E. Coffey, V. Marjomaki, J. Ivaska. Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration. The Journal of Cell Biology, 2011; 194 (2): 291 DOI: 10.1083/jcb.201012126

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Trio of studies support use of PET/CT scans as prostate cancer staging tool

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ScienceDaily (Oct. 21, 2011) — Recent studies have suggested that C-11 choline positron emission tomography/computerized tomography (PET/CT) scans can be utilized as a staging and potentially therapeutic tool in prostate cancer. The results of three studies, released during a meeting of the North Central Section of the American Urological Association, validate findings in Europe and expand the potential use of C-11 choline PET scans.

One study found that C-11 choline PET/CT scans can be used as a staging tool rather than multiple x-rays, but is not necessarily better. Two additional studies support the favorable claims made in recent medical literature about the use of PET scans to evaluate patients with recurrent prostate cancer. These findings are important because distinguishing localized disease recurrence from systemic recurrence is a vital step in optimizing treatment following primary treatment failure.

"Taken together, the three studies presented today represent an important validation of the C-11 choline PET/CT scan as a staging tool for patients with prostate cancer," says R. Jeffrey Karnes, M.D., senior author of all three papers. "We believe the use of these scans can improve the staging and treatment of this common form of cancer, while potentially reducing the cost of delivering the best possible care."

Positron emission tomography is an imaging test that uses a small amount of radioactive material to reveal how tissues and organs are functioning. A C-11 choline PET scan involves the injection into a vein of a small amount of C-11 choline, a radioactive form of the vitamin choline. Clinicians then use a scanner and computer to make detailed pictures of areas where the C-11 choline collects. Since cancer cells take up more C-11 choline than normal cells, the pictures can be used to find cancer in the body.

Summary of the Three Studies

"Initial Staging for High-Risk Prostate Cancer: Is there a Role for C-11 Choline PET Scan?" -- The findings suggest that C11-choline PET is an accurate diagnostic tool when used as the initial staging modality prior to definitive treatment and could potentially eliminate the need for CT and/or bone scans."Detection of Consolidated Disease Recurrences of Prostate Cancer by C-11 Choline PET Scan: Results Confirmed by Surgical Resection" -- This study found that a C-11 choline PET scan is an accurate diagnostic tool for detecting localized disease recurrences that, in select cases, are suitable for salvage surgical resection."Operational Characteristics of C-11 Choline PET Scan for Prostate Cancer Patients with Biochemical Recurrence Following Initial Treatment" -- The operational performance of C11-choline PET for evaluating patients with recurrent prostate cancer supports the favorable claims regarding this technology. The use of C-11-choline PET substantially enhances the rate of prostate cancer lesion detection by approximately 30% beyond what can be garnered using conventional imaging technologies.

About Prostate Cancer

According to the American Cancer Society, prostate cancer affects approximately one in six American men, and is the second most common cancer among this patient group, behind skin cancer. While death from prostate cancer is the second-leading cause of cancer death in American men, and more than 240,000 men will be diagnosed with the disease this year, it is treatable. More than 2 million prostate cancer survivors live in the United States today.

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The above story is reprinted from materials provided by Mayo Clinic.

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Elevated hormone levels add up to increased breast cancer risk, research finds

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ScienceDaily (Oct. 21, 2011) — Post-menopausal women with high levels of hormones such as estrogen or testosterone are known to have a higher risk of breast cancer. New research published in BioMed Central's open access journal Breast Cancer Research looked at eight different sex and growth hormones and found that the risk of breast cancer increased with the number of elevated hormones -- each additional elevated hormone level increased risk by 16%.

Researchers from the Brigham and Women's Hospital and Harvard Medical School used blood samples collected from nurses up to nine years before health information, including their breast cancer status, was recorded. Post-menopausal women who were diagnosed with breast cancer were matched to two controls of a similar age.

The highest levels of circulating estrogens (estrone and estrogen), prolactin, and androgens (testosterone, androstenedione, DHEA, or DHEA-sulfate) were individually associated with between 50 and 200% increase in breast cancer risk. The number of different hormones elevated above normal further increased risk, so that women with one elevated hormone had an increased risk of 10% (compared to normal levels), but the risk for women with five or six elevated hormone levels was doubled, and that for women with seven or eight was tripled. All these risks were slightly higher for women with ER positive disease.

Dr Shelley Tworoger, from Brigham and Women's Hospital, commented that "Elevated estrogens had the biggest effect on risk, especially for ER positive cancer. However, androgens, and prolactin also contribute to increasing risk of breast cancer. These hormones are known to stimulate the growth of breast cancer cells in the lab and, while androgens can be converted to estrogen in the body, these hormones have also been found to stimulate cancer cell growth in the absence of ER. Our results suggest that models used to assess breast cancer risk could be improved by taking into account multiple sex hormone and growth hormone levels."

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Shelley S Tworoger, Bernard A Rosner, Walter C Willett and Susan E Hankinson. The combined influence of multiple sex and growth hormones on risk of postmenopausal breast cancer: a nested case-control study. Breast Cancer Research, 2011; 13: R99 DOI: 10.1186/bcr3040

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