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September 10, 2009, 7:04 AM CT

Toward a nanomedicine for brain cancer

Toward a nanomedicine for brain cancer
Brain cancer cells like those in this tumor could someday become the target of nanoparticles that in lab experiments seek out and destroy brain cancer cells without harming healthy cells.
In an advance toward better therapys for the most serious form of brain cancer, researchers in Illinois are reporting development of the first nanoparticles that seek out and destroy brain cancer cells without damaging nearby healthy cells. The study is scheduled for the Sept. 9 issue of ACS' Nano Letters, a monthly journal.

Elena Rozhkova and his colleagues note the pressing need for new ways to treat the disease, glioblastoma multiforme (GBM), which often causes death within months of diagnosis. Recent studies show that titanium dioxide nanoparticles, a type of light-sensitive material widely used in sunscreens, cosmetics, and even wastewater therapy, can destroy some cancer cells when the chemical is exposed to ultraviolet light. However, researchers have had difficulty getting nanoparticles, each about 1/50,000th the width of a human hair, to target and enter cancer cells while avoiding healthy cells.

The scientists' solution involves chemically linked titanium dioxide nanoparticles to an antibody that recognizes and attaches to GMB cells. When they exposed cultured human GMB cells to these so-called "nanobio hybrids," the nanoparticles killed up to 80 percent of the brain cancer cells after 5 minutes of exposure to focused white light. The results suggest that these nanoparticles could become a promising part of brain cancer treatment, when used during surgery, the scientists say.........

Posted by: Janet      Read more         Source


September 9, 2009, 7:39 AM CT

Lapatinib shows effect against liver cancer

Lapatinib shows effect against liver cancer
Tanios Bekaii-Saab, M.D., is an assistant professor of medicine and pharmacology and medical director of gastrointestinal oncology at the Ohio State University Comprehensive Cancer Center.

Credit: Tanios Bekaii-Saab, M.D.

Use of the molecularly targeted agent lapatinib to delay tumor growth and improve the survival of patients with inoperable hepatocellular carcinoma, or liver cancer, only benefited certain subgroups of patients. While results of this study were largely negative, patients that exhibited toxicity from the drug in the form of a skin rash appeared to have a greater tumor response and longer survival.

Findings of this phase II, multi-institutional study are published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

"These results may not be practice changing, but they do emphasize the need to continue developing strategies targeting epidermal growth factor receptor [EGFR] in hepatocellular carcinoma," said lead researcher Tanios Bekaii-Saab, M.D., assistant professor of medicine and pharmacology and medical director of gastrointestinal oncology at the Ohio State University Comprehensive Cancer Center.

The prevalence of hepatocellular carcinoma is increasing worldwide, and since this form of cancer typically responds poorly to chemotherapy, new therapys are necessary to help curb its rise. The current standard therapy for advanced hepatocellular carcinoma is sorafenib.

This study is one of the first trials to test the tolerability and efficacy of lapatinib in patients with advanced hepatocellular carcinoma. Lapatinib targets both EGFR and Human EGFR type 2 (HER2/neu) signaling pathways. The FDA approved this drug in March of 2007 for breast cancer patients who were already using the chemotherapeutic agent capecitabine. Lapatinib works by inhibiting the tyrosine kinase activity linked to the two oncogenes EGFR and HER2/neu.........

Posted by: Janet      Read more         Source


September 3, 2009, 7:35 AM CT

Novel anti-cancer drug yields positive response

Novel anti-cancer drug yields positive response
The Hedgehog signaling pathway is involved in a preliminary study and case report describing positive responses to an experimental anticancer drug in a majority of people with advanced or metastatic basal cell skin cancers. One patient with the most common type of pediatric brain cancer, medulloblastoma, also showed tumor shrinkage.

Initial results of the drug trial, conducted at Johns Hopkins (Baltimore), the Karmanos Cancer Center (Detroit) and the Translational Genomics Research Institute (Scottsdale) are published online September 3 in the New England Journal (NEJM) (NEJM). The publication also details side effects of the drug, including muscle cramping, hair loss, fatigue and low blood sodium.

The compound, known as GDC-0449, is designed to inhibit the Hedgehog signaling pathway, thought to fuel growth of some cancers. The pathway was originally named for the oblong hedgehog like shape of fly embryos when a key gene in the pathway is disrupted.

Related research by Johns Hopkins and Genentech researchers reported online in the September 3 issue of Science Express reveals more findings on the medulloblastoma case.

"We know that both of these cancer types have mutations in Hedgehog pathway genes, and our results with Hedgehog inhibitors could be the starting point for developing a new type of treatment for these intractable cancers," says Charles Rudin, M.D., Ph.D., associate director for Clinical Research at the Johns Hopkins Kimmel Cancer Center.........

Posted by: Janet      Read more         Source


September 3, 2009, 7:27 AM CT

Canadian research breakthrough for cancer therapies

Canadian research breakthrough for cancer therapies
Scientists Dr. Marc Therrien at the Institute for Research in Immunology and Cancer (IRIC) of the Universit de Montral, and Dr. Frank Sicheri, at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, have discovered a new target that appears to be instrumental in the development of new, more effective cancer therapies.

A recent article co-authored by Drs. Therrien and Sicheri and reported in the leading scientific journal Nature sheds new light on the activation mechanism of the RAF protein kinase which, when mutated, is responsible for more than 25 per cent of cancers. Understanding this mechanism may lead to novel anti-cancer agents designed to minimize the toxic side effects caused by chemotherapy.

The RAF family of kinases regulates various cellular processes including cell growth, differentiation and survival. The Therrien-Sicheri team is the first to show that the dimerization, or combination, of two RAF proteins is essential to its activation. Inhibiting the dimerization of RAF may therefore block its activation, thus stopping cancer cells from growing. The study exposes not only the activation mechanism of RAF, but potentially the mechanisms that control other protein kinases, a large number of which are associated with cancer and other diseases such as diabetes, high blood pressure and neurodegeneration.........

Posted by: Janet      Read more         Source


September 1, 2009, 11:18 PM CT

Computational Process Zeroes in

Computational Process Zeroes in
Rachel Karchin, right, an assistant professor of biomedical engineering, and doctoral student Hannah Carter led a Johns Hopkins team that developed software to narrow the search for mutations linked to cancer. Photo by Will Kirk.
Johns Hopkins engineers have devised innovative computer software that can sift through hundreds of genetic mutations and highlight the DNA changes that are most likely to promote cancer. The goal is to provide critical help to scientists who are poring over numerous newly discovered gene mutations, a number of of which are harmless or have no connection to cancer. As per its inventors, the new software will enable these researchers to focus more of their attention on the mutations most likely to trigger tumors.

A description of the method and details of a test using it on brain cancer DNA were reported in the August 15 issue of the journal Cancer Research.

The new process focuses on missense mutations, meaning protein sequences that each possess a single tiny variation from the normal pattern. A small percentage of these genetic errors can reduce the activity of proteins that commonly suppress tumors or hyperactivate proteins that make it easier for tumors to grow, thereby allowing cancer to develop and spread. But finding these genetic offenders can be difficult.

"It's very expensive and time-consuming to test a huge number of gene mutations, trying to find the few that have a solid link to cancer," said Rachel Karchin, an assistant professor of biomedical engineering who supervised the development of the computational sorting approach. "Our new screening system should dramatically speed up efforts to identify genetic cancer risk factors and help find new targets for cancer-fighting medications".........

Posted by: Janet      Read more         Source


August 31, 2009, 9:56 PM CT

Natural compounds, chemotherapeutic drugs may become partners

Natural compounds, chemotherapeutic drugs may become partners
Research in the Linus Pauling Institute at Oregon State University suggests that some natural food compounds, which previously have been studied for their ability to prevent cancer, appears to be able to play a more significant role in treating it - working side-by-side with the conventional drugs that are now used in chemotherapy.

A newly released study just reported in the International Journal of Cancer examined the activity of chlorophyllin and observed that, on a dose-by-dose basis, it was 10 times more potent at causing death of colon cancer cells than hydroxyurea, a chemotherapeutic drug usually used in cancer therapy.

Beyond that, chlorophyllin kills cancer cells by blocking the same phase of cellular division that hydroxyurea does, but by a different mechanism. This suggests that it - and possibly other "cocktails" of natural products - might be developed to have a synergistic effect with conventional cancer drugs, helping them to work better or require less toxic dosages, scientists said.

"We conclude that chlorophyllin has the potential to be effective in the clinical setting, when used alone or in combination with currently available cancer therapeutic agents," the scientists wrote in their study.

The concept of combining conventional or new cancer drugs with natural compounds that have been shown to have anti-cancer properties is very promising, said Rod Dashwood, professor and director of the Cancer Chemoprotection Program in the Linus Pauling Institute.........

Posted by: Janet      Read more         Source


August 31, 2009, 9:24 PM CT

Breast cancer intervention reduces depression

Breast cancer intervention reduces depression
A psychological intervention for newly diagnosed patients with breast cancer with symptoms of depression not only relieves patients' depression but also lowers indicators of inflammation in the blood.

Those are the findings of a newly released study by scientists at the Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute (OSUCCC-James) and the Ohio State University Department of Psychology involving patients with stage II or III breast cancer.

Patients who received a psychological treatment that reduced stress and enhanced their ability to cope experienced significant relief of depressive symptoms. Moreover, that improvement was followed by a reduction in markers of inflammation.

"Previously, we knew that inflammation was linked to depression-like symptoms among cancer patients, and that both are problematic, but we did not know whether treating depression would affect inflammation," says co-author Barbara L. Andersen, professor of psychology and an OSUCCC-James researcher.

"Inflammation is considered to be a cancer promoting factor, and both depression and inflammation predict increased risk of cancer death".

Patients in the control group received only health and psychological evaluations of their condition over the 12-month study period and showed no improvement in depression or inflammation indicators.........

Posted by: Janet      Read more         Source


August 28, 2009, 7:02 AM CT

Predicting cancer prognosis

Predicting cancer prognosis
Scientists led by Dr. Soheil Dadras at the Stanford University Medical Center have developed a novel methodology to extract microRNAs from cancer tissues. The related report by Ma et al, "Profiling and discovery of novel miRNAs from formalin-fixed paraffin-embedded melanoma and nodal specimens," appears in the September 2009 issue of the Journal of Molecular Diagnostics

Cancer tissues from patients are often stored by a method that involves formalin fixation and paraffin embedding to retain morphological definition for identification; however, this method frequently prevents further molecular analysis of the tissue because of mRNA degradation. Even so, these tissues contain high numbers of microRNAs (miRNAs), which are short enough (~22 nucleotides) to not be broken down during the fixation process.

In this study, Dr. Dadras and his colleagues optimized a new protocol for extracting miRNAs from formalin-fixed paraffin-embedded tissues. Using their new procedure, they identified 17 new and 53 known miRNAs from normal skin, melanoma, and sentinel lymph nodes. These miRNAs were well-preserved in a 10-year-old specimen. This new protocol, therefore, will allow for the identification of novel miRNAs that may differ in malignant and healthy tissue, even from long-preserved tissue, leading to better predictions of disease prognosis and therapy response.........

Posted by: Janet      Read more         Source


August 28, 2009, 6:58 AM CT

New, cancer-causing role for protein

New, cancer-causing role for protein
Hui-Kuan Lin, Ph.D., is an assistant professor in M. D. Anderson's Department of Molecular and Cellular Oncology.

The mainstay immune system protein TRAF6 plays an unexpected, key role activating a cell signaling molecule that in mutant form is linked to cancer growth, scientists at The University of Texas M. D. Anderson Cancer Center report in the Aug. 28 edition of Science

"The mechanism that we discovered activates Akt and also contributes to hyperactivation of a mutant form of Akt found in breast, colon and other cancers," said senior author Hui-Kuan Lin, Ph.D., assistant professor in M. D. Anderson's Department of Molecular and Cellular Oncology.

Akt is a signaling protein that plays a central role in numerous biological functions, including cell growth and programmed cell death, or apoptosis, Lin said. Deregulated Akt expression has been found to contribute to cancer development.

"Our novel findings are that Akt undergoes ubiquitination to be activated, and that TRAF6 regulates that process. We've observed that TRAF6 is not just involved in the innate immune response, but plays a role in cell growth and carcinogenesis," Lin said.

Ubiquitins are regulatory proteins that work by binding to other proteins. While ubiquitins are best known for marking a defective protein for death by the cell's proteasome complex, Lin said, ubiquitination of Akt is not tied to the proteasome. Ubiquitins are transferred to target proteins by another set of proteins called ligases.........

Posted by: Janet      Read more         Source


August 24, 2009, 10:42 PM CT

New prognostic marker for breast cancer

New prognostic marker for breast cancer
Elevated levels of GLI1 (glioma-associated oncogene homolog 1) protein in human breast cancer are linked to unfavorable prognosis and progressive stages of disease. Scientists writing in the open access journal BMC Cancer found increased expression of GLI1 in samples taken from more advanced and less survivable tumors.

Edgar Dahl led a team of scientists from RWTH Aachen's University Hospital who sought to evaluate whether GLI1 could represent a new prognostic marker in breast cancer therapy. He said, "GLI1, a mediator of the so-called 'hedgehog' signaling pathway, has previously been implicated in the development of different human tumor entities. We've found a positive, significant association between overexpression of GLI1 and unfavorable overall survival outcome in human breast cancer. This association has not been reported anywhere else so far, but similar tendencies were recently shown in human esophageal cancer".

The scientists studied samples of 229 invasive breast carcinomas taken from patients at the hospital, along with samples of normal human breast tissue for comparison. As well as poor survival, overexpression of the GLI1 protein was linked to tumor stage and lymph node status of the breast tumors analyzed. Dahl said, "Taken together, these results support a role of GLI1 as a new prognostic biomarker in breast cancer. Future studies will determine whether GLI1 can be successfully included into multimarker panels for early cancer detection or molecular sub-typing of breast cancer. This could support personalized breast cancer medicine".........

Posted by: Janet      Read more         Source



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Cancer
Cancer is a very common disease, approximately one out of every two American men and one out of every three American women will have some type of cancer at some point during the course of their life. Cancer is more common in the elderly and 77 percent of cancers occur in people above age 55 or older. Cancer is also common in children. Cancer incidence is said to have two peaks once during early childhood and then during late years in life. No age period is completely exempted from development of cancers. Some cancers occur predominantly in the elderly, other types occur in children, Cancer occurs in all ethnic races, however the cancer rates and rates of specific cancer types may vary from group to group. Late stages of cancer may be incurable in most cases, but with the advancement of medicine, more and more cancers are becoming curable.

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