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July 2, 2010, 7:23 AM CT

DNA mutation as cause of cancer

DNA mutation as cause of cancer
What if we could understand why cancer develops? We know that certain risk factors, such as smoking or excessive sun exposure, can increase the chances of developing this terrible disease, but cancer can form in any tissue, and the cause is not always clear. One idea that has emerged is that for a cell to transform into a cancer cell it must suffer a large number of mutations affecting different genes needed to control cell growth. As per a research findings published this week in Science, Brandeis University scientists have observed that the process of repairing DNA damage also unexpectedly increases the rate of mutations and changes the kinds of mutations that arise.

Surprisingly, as cells progress toward full-blown cancer they begin to suffer alterations of the normal DNA replication process, leading to an increased amount of DNA damage, particularly chromosome breaks. Thus there is an increased need for cells to accurately repair these breaks.

Biologist James Haber, graduate student Wade Hicks and undergraduate Minlee Kim report that the repair of damaged strands of DNA, specifically by a process known as gene conversion, can cause higher-than-normal levels of mutation; in fact, 1,400 times as high as spontaneous mutations in cells.

"It has been hard to imagine how cells could accumulate so a number of mutations in the few generations that they undergo cell division on the way to becoming malignant," Haber said. "We believe that the elevated rate of mutation at sites where DNA has been broken appears to be an important source of these gene changes." .........

Posted by: Janet      Read more         Source


July 2, 2010, 7:20 AM CT

Loss of key protein promotes aggressive form of leukemia

Loss of key protein promotes aggressive form of leukemia
Cold Spring Harbor, NY New research by researchers at Cold Spring Harbor Laboratory (CSHL) has illuminated in fine detail one of the genetic paths that leads to a especially aggressive form of leukemia.

CSHL Professor Scott W. Lowe. Ph.D., an Investigator of the Howard Hughes Medical Institute, led a team of researchers who wanted to know more about how the absence of an important tumor-suppressing protein called p53 combines with another genetic "hit" in immature blood cells to give rise to acute myeloid leukemia, or AML. In experiments in living mice, the team discovered that if p53 is disabled in immature blood-cell "precursors" in which a mutation in a gene called Kras is also present, a built-in braking mechanism fails to engage and the cells proliferate out of control.

Mutations in p53, the gene that encodes the p53 "master tumor-suppressor" protein, had previously been linked to drug resistance and adverse outcome in AML. The mechanism, however, was a matter of conjecture previous to the new results, which are reported in the July 1 issue of Genes & Development

"Our team has shown how mutations in Kras and p53 act to reinforce one another to change the character of blood precursor cells, transforming them into cells that can renew themselves and thus proliferate indefinitely, somewhat as cancer stem cells are theorized to do," says Lowe.........

Posted by: Janet      Read more         Source


June 28, 2010, 7:36 AM CT

Statins may lower cancer recurrence

Statins may lower cancer recurrence
Men who use statins to lower their cholesterol are 30 percent less likely to see their prostate cancer come back after surgery in comparison to men who do not use the drugs, as per scientists at Duke University Medical Center. Scientists also observed that higher doses of the drugs were linked to lower risk of recurrence.

The findings appear in the journal CANCER.

"The findings add another layer of evidence suggesting that statins may have an important role in slowing the growth and progression of prostate cancer," says Stephen Freedland, M.D., a member of the Duke Prostate Center and the Urology Section at the Durham Veterans Affairs Medical Center, and the senior author of the study. "Prior studies have shown that statins have anti-cancer properties, but it's not entirely clear when it's best to use them or even how they work".

Scientists examined the records of 1319 men who underwent radical prostatectomy included in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. They observed that 18 percent of the men 236 were taking statins at the time of surgery.

Scientists followed the patients after surgery to evaluate recurrence rates, measured by slight rises in the PSA levels after surgery, a development known as "biochemcical recurrence." Time to biochemical recurrence is viewed as an important clinical factor because it is correlated with the risk of disease progression and death.........

Posted by: Janet      Read more         Source


June 24, 2010, 11:01 PM CT

Polarized arguments about breast screening

Polarized arguments about breast screening
Polarised arguments about the benefits and harms of breast screening are not helping women to make an informed decision, argues a senior doctor on bmj.com today.

Klim McPherson, Professor of Public Health Epidemiology at the University of Oxford looks at the evidence and calls for dispassionate analysis of all available data.

The burden of breast cancer is unremitting and we must do anything we can to contain it, he says. But screening for a progressive disease is justified only if earlier diagnosis and therapy improve disease progression.

A recent US report on screening for breast cancer estimated that the mortality reductions attributable to breast screening are 15% for women aged 39-49, 14% for those aged 50-59, and 32% for those aged 60-69. Worse still, estimated numbers of women needed to be invited to a US screening programme in order to save one life are high. For the younger group it is nearly 2,000 while in those aged 60-69 it is still nearly 400. In the UK, the figure is 1,610 for women aged 40-55.

A recent analysis from the Nordic Cochrane Centre also claimed that one in three breast cancers detected in screening programmes is overdiagnosed, eventhough others argue that the lives saved by screening greatly outnumber overdiagnosed cases.........

Posted by: Janet      Read more         Source


June 24, 2010, 10:54 PM CT

Treatment of pancreatic adenocarcinoma

Treatment of pancreatic adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a highly cancerous digestive tumor with a very poor prognosis. Hypoxia-inducible transcription factor-1α (HIF-1α) is involved in cancerous progression in a number of solid tumors, including PDAC, upregulation of HIF-1α accelerates PDAC progression, but the exact regulatory mechanisms of HIF-1αin PDAC has not been unequivocally addressed. Recently, an increasing number of studies reported that toll-like receptors (TLRs) were upregulated in epithelial malignancies and involved in tumor progression, but whether TLRs, such as TLR4, is expressed on PDAC cells remains unknown. In immune-related cells, TLR signal pathway may induce expression of HIF-1α, but it is also still unclear whether there exists some association between TLR4 and HIF-1α in tumor microenviroment, such as PDAC.

A research article to be published on June 21, 2010 in the World Journal of Gastroenterology addresses this question. The research team led by He-Shui Wu, MD, from Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, used real time polymerase chain reaction and immunohistochemistry, to detect TLR4, NF-κB p65 and HIF-1α expression in 65 cases of PDAC tissues and 38 cases of corresponding adjacent tissues.........

Posted by: Sue      Read more         Source


June 24, 2010, 10:29 PM CT

Hepatitis B virus and liver cancer

Hepatitis B virus and liver cancer
Prior studies have shown that antiviral therapy reduces the occurence rate of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). But now, scientists from the Division of Gastroenterology and Hepatology at Thomas Jefferson University are reporting that the antiviral treatment also prevents recurrence of HCC and extends patients' lives.

The standard of care for patients with HCC is local ablation of the tumor, unless it is large or has metastasized. However, HCC tumors often recur, or new lesions develop. In the International Journal of Cancer, Hie-Won Hann, M.D., professor of Medicine at Jefferson Medical College of Thomas Jefferson University, and his colleagues reported that the median survival in patients who received antiviral treatment after HCC diagnosis was 60 months in patients. In those who did not receive antiviral treatment, the median survival was 12.5 months.

"Before the antiviral drugs were developed, patients would often develop new lesions within a few months of tumor ablation because we were not treating the underlying virus that is causing the liver cancer," Dr. Hann said. "The virus drives the cancer, and by suppressing the virus and making it undetectable we can extend the survival for these patients".

The small study included 15 CHB patients who received local ablation of a single HCC tumor that was less than four cm. The first six patients were diagnosed between 1991 and 1997, previous to the development of antiviral treatment. These patients were considered historical controls.........

Posted by: Sue      Read more         Source


June 22, 2010, 7:11 AM CT

Reduce number of breast biopsies

Reduce number of breast biopsies
By combining two relatively inexpensive technologies based on sound and light waves, scientists hope to lower the rate at which women undergo breast biopsies for suspicious lesions. Results of the study on ultrasound-guided optical tomography are reported in the online edition and the August print issue of Radiology

"The goal of our study was to investigate the potential of diffuse optical tomography in the near infrared spectrum with ultrasound localization as a means of differentiating early-stage cancers from non-malignant lesions of the breast," said lead researcher Quing Zhu, Ph.D., professor of bioengineering at the University of Connecticut.

When mammography and ultrasound cannot determine whether a suspicious breast lesion is cancerous or benign, physicians typically recommend a needle biopsy to extract samples of the suspicious tissue for laboratory testing. In current clinical practice, 70 to 80 percent of biopsies performed reveal non-malignant lesions, leading to unnecessary cost and anxiety for women.

Diffuse optical tomography is an emerging noninvasive imaging technique that measures light absorption within tissue to quantify blood content (hemoglobin level) and blood oxygen levels. Because malignant lesions have a number of more blood vessels than normal tissue, hemoglobin levels can help distinguish cancerous from non-malignant lesions.........

Posted by: Janet      Read more         Source


June 21, 2010, 7:14 AM CT

New strategy to fight cancer drug resistance

New strategy to fight cancer drug resistance
By leveraging nature's solution to ligand selectivity, Stewart et al. developed a selective inhibitor of anti-apoptotic MCL-1, which has emerged as a formidable survival factor for a wide variety of cancers. By screening a panel of stapled peptide helices of BCL-2 family protein interaction domains, the team discovered that, ironically, MCL-1's own BH3 death domain helix is a uniquely exclusive MCL-1 inhibitor that resensitizes cancer cells to select apoptotic stimuli that are especially blunted by MCL-1 expression.

Credit: Dana-Farber Cancer Institute

Researchers at Dana-Farber Cancer Institute have found a way to disable a common protein that often thwarts chemotherapy therapy of several major forms of cancer.

The scientists discovered, surprisingly, that they could exploit a small portion of this anti-death protein, called MCL-1, to make a molecular tool that specifically blocked MCL-1's "pro-survival" action, allowing standard cancer drugs to kill the tumor cells by apoptosis, or programmed cell death.

"We think this is a very important step toward developing an inhibitor of MCL-1, which is emerging as a critical survival factor in a broad range of human cancers, including leukemia, lymphoma, multiple myeloma, melanoma, and poor-prognosis breast cancer to name just a few," said Loren Walensky, MD, PhD, a pediatric oncologist and chemical biologist at Dana-Farber and Children's Hospital Boston.

He is the senior author of the report being published June 20 on the website of Nature Chemical Biology The first author is Michelle Stewart, a graduate student in the Walensky lab.

The scientists showed in lab experiments that combining the MCL-1 inhibitor with a class of conventional agents that can be rendered ineffective by MCL-1 resensitized the cancer cells to the drugs. The MCL-blocking compound is now being advanced to testing in animal models.........

Posted by: Janet      Read more         Source


June 17, 2010, 7:23 AM CT

Early detection of ovarian cancer

Early detection of ovarian cancer
Joshua LaBaer
Despite a number of research advances, ovary cancer remains lethal in a majority of cases, due to late diagnosis of the disease. In a newly released study, Dr. Joshua LaBaer of the Biodesign Institute at Arizona State University, along with Arturo Ramirez and Paul Lampe, scientists at the Fred Hutchinson Cancer Research Center in Seattle, used a novel method for identifying biomarkers-proteins in blood that can identify ovary cancer before symptoms appear.

The work, which appeared recently in the journal Molecular and Cellular Proteomics, holds the potential for significant improvements in patient survival rate. The research is part of the Early Detection Research Network program of the National Cancer Institute.

As LaBaer notes, ovary cancer is an attractive target for biomarker study. "This is a disease for which an early diagnostic test would make an enormous difference in the health of women." Highly treatable in its early stage, ovary cancer is typically not identified until it has progressed to stage 3 or beyond. Often, it is detected accidentally, in the course of some other test or procedure, for example, during an oophorectomy. "By the time it's caught," LaBaer says, "it has commonly speckled the abdomen with advanced tumors".

At present, only one reliable biomarker for ovary cancer exists. Known as CA 125, this protein is produced on the surface of cells and released into the bloodstream. Elevated levels of CA 125 are indicative of ovary cancer, but testing for CA 125 alone is not adequate. Such tests can produce both false positive and false negative results. Further, the level of CA 125 tends to go up in proportion to tumor growth, sometimes providing good evidence only after the disease has reached its later, terminal stages.........

Posted by: Emily      Read more         Source


June 16, 2010, 7:22 AM CT

Personalized treatment for melanoma

Personalized treatment for melanoma
Identification of a key player in a signaling pathway involved in the development of melanoma the deadliest form of skin cancer may offer hope for new targeted melanoma therapies.

Ann Richmond, Ph.D., and his colleagues at Vanderbilt-Ingram Cancer Center report that a signaling molecule, known as IKKβ, is essential for melanoma tumor development in a mouse model of the disease. The results, published June 7 in the Journal of Clinical Investigation, also point to ways of targeting therapies that inhibit IKKβ toward the patients most likely to benefit from them based on their genetic profile.

Melanoma is the deadliest form of skin cancer and incredibly difficult to treat successfully once the tumor has spread beyond the skin.

Previous studies have shown that the NF-κB signaling pathway centered on the protein NF-κB, which regulates gene expression is abnormally activated in tumor cells; the pathway is turned "on" constantly, even at times it should be turned "off." This activation often results from abnormal activation of another enzyme in the pathway, IKKβ.

Just how NF-κB contributes to tumor progression has been unclear. And with drugs that inhibit this pathway entering clinical trials, a clearer picture of its function in tumor progression is needed.........

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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