February 1, 2010, 7:39 AM CT

Assessing risks associated with low-dose radiation

There remains a lack of consensus amongst the medical and scientific communities about any cancer risk from low level radiation, especially low-dose radiation delivered from computed tomography (CT) scans. However, the study of epigenetics may play a role in determining whether or not future trends of diseases can in fact be associated with utilization of CT, as per an article in the recent issue of the Journal of the American College of Radiology (JACR).

The term epigenetics refers to changes in the phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence. These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations.

"Radiation safety is, without a doubt, a large concern for practicing radiologists today," said Shella Farooki, MD, author of the article and radiologist and director of research for Columbus Radiology Corp in Columbus, OH. "However, the current focus does not account for the possibility of harm to future generations from radiation delivered today. I think that it is equally, if not more important, to consider potential harm to the patient's offspring and their offspring's offspring," she said.

"The effects of ionizing radiation have been demonstrated in neighboring cells (non-targeted radiation), known as the bystander effect. In addition, ionizing radiation effects have been shown to span generations, resulting in heritable defects in mice. However, we need to bridge the gap between understanding the epigenome functionality and radiation exposure before assuming anything," said Farooki......... Posted by: Jesmi24      Read more         Source

January 28, 2010, 7:54 AM CT

Targeting stem cells to fight ovarian cancer

Eliminating cancer stem cells (CSCs) within a tumor could hold the key to successful therapys for ovary cancer, which has been notoriously difficult to detect and treat, as per new findings published this week in the journal Oncogene by Yale School of Medicine researchers.

"We observed that stopping the expression of two genesLin28 and Oct4reduces ovary cancer cell growth and survival," said Yingqun Huang, M.D., assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.

Ovary cancer has been challenging to treat because it tends to recur frequently and develop resistance to therapy. The poor outcome for women with ovary cancer has been linked to subtle and nonspecific symptomsearning it the moniker the "disease that whispers."

"This recurrence and drug resistance appears to be due to the presence of CSCs within the tumors that have the capacity to reproduce and to differentiate into non-CSC tumor cells that repopulate the tumor mass," said Huang, who is a member of Yale Stem Cell Center and Yale Cancer Center. "Eliminating these CSCs appears to be key to successful therapys".

While in the process of studying the functions of stem cell proteins in human embryonic stem cells, Huang and her colleagues unexpectedly discovered that a sub-population of ovary cancer cells express stem cell proteins Lin28 and Oct4. They also observed that the two proteins appear to act together in ovary cancer tissue cells to produce more advanced tumors. Inhibiting their combined expression led to a significant decrease in the growth and survival of cancer cells. A larger-scale ovary cancer study is currently underway to confirm the significance of the findings......... Posted by: Jesmi24      Read more         Source

January 25, 2010, 8:11 AM CT

Reversing Cancer Cell Metabolism And Tumor Growth

A team of researchers led by Professor Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory has discovered molecular factors in cancer cells that boost the production of an enzyme that helps alter the cells' glucose metabolism. The altered metabolic state, called the Warburg effect, promotes extremely rapid cell proliferation and tumor growth.

Discovered eighty years ago by Nobel Prize-winning scientist Otto Warburg, this altered metabolism in cancer cells is most critically mediated by a protein called PK-M2 (pyruvate kinase M2). This is one of two versions - or isoforms - of the enzyme pyruvate kinase, whose other isoform, PK-M1, is harmless.

As per a research findings published online ahead of print in the Proceedings of the National Academy of Sciences, Krainer and his colleagues report their discovery of three factors that contribute to high levels of PK-M2 in cancer cells, in part by suppressing production of PK-M1.

"These findings suggest a new way in which cancer's altered glucose metabolism might be targeted for therapeutic benefit," explains Krainer. "Drugs that inhibit these factors and reverse the Warburg effect might work as anti-cancer agents." The study waccording toformed in collaboration with Professor Lewis Cantley, Ph.D., and colleagues at Harvard Medical School and The Broad Institute, in Cambridge, Mass......... Posted by: Jesmi24      Read more         Source

April 27, 2009, 5:22 AM CT

Improved detection of bladder tumors

Making tumors inside the bladder fluoresce red under blue light allows physicians to more easily find and remove them, substantially reducing the rate at which these cancers come back, says a Mayo Clinic doctor who is presenting results of a large, multicenter international clinical trial.

VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Lance Mynderse describing the research, are available on the Mayo Clinic News Blog (http://newsblog.mayoclinic.org/)Mayo Clinic News Blog. These materials are also subject to embargo, but appears to be accessed in advance by journalists for incorporation into stories. The password for the post is hvxaua1.

The findings, which are being reported at the annual meeting of the American Urological Association, show that this new diagnostic technique found more of the most common bladder tumors than the traditional white-light detection method in almost 17 percent of the patients, and demonstrated a 22 percent relative reduction in the recurrence rate within nine months of the procedure.

"This is the first demonstration that photodynamic diagnosis (PDD) cystoscopy along with the study drug (hexaminolevulinate) improves immediate detection, but more importantly reduces tumor recurrence rates of papillary bladder tumors; this is a significant improvement in therapy for our patients," says urologist Lance Mynderse, M.D., (http://www.mayoclinic.org/bio/10475311.html), who practices at Mayo Clinic's campus in Rochester, Minn. The 766-patient phase III study was conducted in 28 U.S. and European centers, and its principal investigator is Barton Grossman, M.D., of The University of Texas M.D. Anderson Cancer Center. Dr. Mynderse is presenting study results as spokesman for the lead enrolling site in North America......... Posted by: Jesmi24      Read more         Source

April 27, 2009, 5:17 AM CT

Robotic surgery for kidney cancer

Fox Chase Cancer Center scientists find that outcomes of robotic assisted kidney cancer surgery, when performed by experienced surgeons at high volume centers, prove more beneficial to patients when in comparison to open surgery. The study, authored by Fox Chase robotic surgeon Rosalia Viterbo, MD, was presented today at the American Urological Association's Annual Meeting, .

The standard therapy for kidney cancer is to surgically remove the entire or a portion of the kidney. This is known as nephron-sparing surgery, or partial nephrectomy, and is usually performed using traditional open surgery. Recently, there has been interest in applying a laparoscopic approach for this procedure, however it has proven to be technically challenging to a number of surgeons.

Experienced laparoscopic surgeons at high volume centers, such as Fox Chase, are now using the da Vinci robot assisted surgical system for patients with kidney cancer, or renal cell carcinoma. The advanced technology has enabled faster and greater technical proficiency allowing for completion of complex surgical procedures, facilitating a minimally invasive approach for partial nephrectomy.

"Our patients have experienced a number of benefits from the robot assisted approach, including shorter hospital stays (average 3 days), preserved kidney function (reduced need for dialysis), smaller scars with optimal cosmetic results, lower blood loss and easier and earlier return to normal activity," says Viterbo......... Posted by: Jesmi24      Read more         Source

April 13, 2009, 1:32 PM CT

SIRT1 takes down tumors

Yuan et al. have identified another anti-cancer effect of the "longevity" protein SIRT1. By speeding the destruction of the tumor promoter c-Myc, SIRT1 curbs cell division. The study will be published online April 13 (www.jcb.org) and will appear in the April 20 print issue of the Journal of Cell Biology

The yeast and nematode equivalents of SIRT1 are fountains of youth that stretch lifespan. Whether SIRT1 slows aging in mammals isn't certain, but it's beneficial in other ways. The protein tunes up metabolism, reducing blood levels of glucose and insulin, and might forestall neurodegenerative illnesses such as Alzheimer's disease and ALS. Given its pro-life credentials, you might expect SIRT1 to inhibit cancer. And several studies suggest that it does. But other work indicates that the protein aids tumors. For example, SIRT1 chops off acetyl groups, which can inactivate the tumor suppressor p53.

Yuan et al. determined SIRT1's effect on the transcription factor c-Myc, whose expression surges in a number of breast, colon, and liver cancers. The two proteins are tangled in a regulatory loop, the team found. c-Myc latched onto SIRT1's promoter, spurring cells to manufacture more SIRT1. In turn, SIRT1 detached acetyl groups from c-Myc, hastening its breakdown. To test SIRT1's effects on tumor growth, the scientists implanted malignant cells expressing c-Myc into nude mice that lack immune defenses. Boosting production of SIRT1 blocked tumor formation......... Posted by: Jesmi24      Read more         Source

December 24, 2008, 5:11 AM CT

How radiation therapy causes chronic inflammation of bowels

The use of radiation treatment to treat cancer inevitably involves exposure of normal tissues. Eventhough the benefits of this therapy have been well established, many patients experience distressing complications as a result injury to normal tissue These side effects correlation to inflammatory process cause discomfort and decreases the therapeutic benefit by increasing the overall therapy time.

A research article would be published on December 14, 2008 in the World Journal of Gastroenterology addresses the question. The research led by Dr. Christine Linard and her colleagues from the Institute for Radioprotection and Nuclear safety (IRSN) in France used experimentally a fractionated colorectal irradiation model to demonstrate an immune imbalance during the radiotherapy protocol and persisting in long term.

They observed that without causing histological damage, fractionated radiation induced elevated expression of IL-1beta, TNF alpha, MCP-1, and iNOS in distal colonic mucosa during the early post-irradiation phase. At that time, a Th2 profile was confirmed by expression of both the Th2-specific transcription factor GATA-3 and the chemokine receptor CCR4 and by suppression of the Th1 cytokine IFN gamma/IP-10 throughout the irradiation protocol. After 6 mo, despite the 2-fold reduction of iNOS and MCP-1 levels, the Th2 profile persisted, as shown by a 50% reduction in the expression of the Th1 transcription factor T-bet, the chemokine receptor CCXCR3, and the IFNgamma /STAT1 pathway. At the same time-point, the immunosuppressive IL-10/STAT3 pathway, known to regulate the Th1/Th2 balance, was expressed, in irradiated rats, at approximately half its level as in comparison to controls. This suppression was linked to an overexpression of SOCS3, which inhibits the feedback of the Th1 polarization and regulates IL-10 production......... Posted by: Jesmi24      Read more         Source

December 9, 2008, 10:29 PM CT

New therapy prevents dangerous side effect for lymphoma patients

Patients respond well to a new three-drug combination for indolent B cell lymphoma that also spares them prolonged, potentially lethal, suppression of blood production in the bone marrow, scientists at The University of Texas M. D. Anderson Cancer Center report today at the 50th annual meeting of the American Society of Hematology.

Pentostatin, cyclophosphamide and rituximab together are providing the same remission rate as other combinations but with minimal long-term bone marrow suppression, said study presenter Felipe Samaniego, M.D., associate professor in M. D. Anderson's Department of Lymphoma and Melanoma.

Myelosuppression leads to production of fewer red blood cells, white blood cells and platelets. When prolonged, it can lead to myelodysplastic syndrome, which comprises several conditions that cause potentially lethal insufficient blood production.

"The worst outcome of long-term myelosuppression for indolent B cell lymphoma patients is myelodysplastic syndrome," Samaniego said. "In this study, out of 80 patients, none developed MDS".

And 77 of 80 (96 percent) experienced either complete remission or unconfirmed complete remission. Some did have low blood counts, but all were short-term. Overall, the combination is well-tolerated, the research team reported......... Posted by: Jesmi24      Read more         Source

November 19, 2008, 8:09 PM CT

New platinum-phosphate compounds kill ovarian cancer

A new class of compounds called phosphaplatins can effectively kill ovarian, testicular, head and neck cancer cells with potentially less toxicity than conventional drugs, as per a new study published this week in the journal Proceedings of the National Academy of Sciences.

The compounds could be less harmful than current cancer therapys on the market such as cisplatin and carboplatin because they don't penetrate the cell nucleus and attach to DNA, said lead author Rathindra Bose. Conventional drugs can interfere with the functions of the cell's enzymes, which lead to side effects such as hearing and hair loss and kidney dysfunction.

Though researchers don't fully understand the mechanism by which the phosphaplatins kill cancer cells, they suspect that the compounds bind to the cell surface membrane proteins and transmit a "death signal" to the interior of the cell, Bose said. The compounds are created by attaching platinum to a phosphate ligand, which can readily anchor to the cell membrane. Future studies will focus on identifying the exact process.

"The findings suggest a paradigm shift in potential molecular targets for platinum anticancer drugs and in their strategic development," said Bose, a professor of biomedical sciences and chemistry and vice president for research at Ohio University who conducted the work while at Northern Illinois University......... Posted by: Jesmi24      Read more         Source

July 1, 2008, 10:01 PM CT

Death, Division or Cancer?

Each day, a staggering number of cells perform a feat that still amazes scientists with its complexity: they divide to produce perfect replicas of each other. The process is called mitosis, and an inability to control it is one of the hallmarks of cancer.

Little is known about the biochemical processes that control mitosis, but now scientists from Fox Chase Cancer Center and Technion-Israel Institute of Technology in Haifa, Israel, have discovered a novel activity, called the mitotic checkpoint factor 2 (MCF2). This appears to be integral in preventing cells that are unable to equally separate their chromosomes from dividing. The identities of the proteins involved in MCF2 remain to be determined, however, their findings offer insight into a fundamental question of biology, which may also help to increase the efficiency of cancer drugs that disrupt DNA replication, like gemcitabine, or drugs that prevent mitosis, like paclitaxel.

They publish their findings today online in the Early Edition of the Proceedings of the National Academy of Sciences.

"At any given moment, 250 million cells in your body are undergoing mitosis in order to replenish cells that die as a result of normal turnover," says Tim J. Yen, Ph.D., senior member at Fox Chase. "The mitotic checkpoint is a complex series of quality control systems, just like in a factory assembly line, that ensures that each new cell gets their proper share of DNA." (Click here for illustration)......... Posted by: Jesmi24      Read more         Source