Cancer
P Rex-1 protein key to melanoma metastasis
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Researchers from UNC Lineberger Comprehensive Cancer Center are part of a team that has identified a protein, called P-Rex1, that is key to the movement of cells called melanoblasts. When these cells experience uncontrolled growth, melanoma develops.
Melanoma is one of the only forms of cancer that is still on the rise and is one of the most common forms of cancer in young adults. The incidence of melanoma in women under age 30 has increased more than 50 percent since 1980. Metastases are the major cause of death from melanoma.
The team found that mice lacking the P-Rex1 protein are resistant to melanoma metastases. When researchers tested human melanoma cells and tumor tissue for the protein, P-Rex1 was elevated in the majority of cases – a clue that the protein plays an important role in the cancer’s spread. Their findings were published today in the journal Nature Communications.
How cancer cells get by on a starvation diet
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Cancer cells usually live in an environment with limited supplies of the nutrients they need to proliferate — most notably, oxygen and glucose. However, they are still able to divide uncontrollably, producing new cancer cells.
A new study from researchers at MIT and the Massachusetts General Hospital (MGH) Cancer Center helps to explain how this is possible. The researchers found that when deprived of oxygen, cancer cells (and many other mammalian cells) can engage an alternate metabolic pathway that allows them to use glutamine, a plentiful amino acid, as the starting material for synthesizing fatty molecules known as lipids. These lipids are essential components of many cell structures, including cell membranes.
The finding, reported in the Nov. 20 online edition of Nature, challenges the long-held belief that cells synthesize most of their lipids from glucose, and raises the possibility of developing drugs that starve tumor cells by cutting off this alternate pathway.
Newly identified gene mutation adds to melanoma risk
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A major international study has identified a novel gene mutation that appears to increase the risk of both inherited and sporadic cases of malignant melanoma, the most deadly form of skin cancer. The identified mutation occurs in the gene encoding MITF, a transcription factor that induces the production of several important proteins in melanocytes, the cells in which melanoma originates. While previous research has suggested that MITF may act as a melanoma oncogene, the current study identifies a mechanism by which MITF mutation could increase melanoma risk.
The report from researchers from the U.S., the U.K. and Australia is receiving advance online publication in Nature. It is expected to appear in a print issue along with a study from French researchers finding that the same mutation increased the risk for the most common form of kidney cancer, for melanoma or for both tumors.
“We previously knew that MITF is a master regulator for production of the pigment melanin; and several years ago we identified a chemical modification, called sumoylation, that represses MITF activity,” says David Fisher, MD, PhD, chief of Dermatology at Massachusetts General Hospital (MGH), director of the MGH Cutaneous Biology Research Center and co-senior author of the Nature paper. “The currently discovered mutation appears to block sumoylation of MITF, and the resulting overactivity of MITF significantly increases melanoma risk.”
Scientists prove regular aspirin intake halves cancer risk
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Scientists including those from Queen’s University have discovered that taking regular aspirin halves the risk of developing hereditary cancers.
Hereditary cancers are those which develop as a result of a gene fault inherited from a parent. Bowel and womb cancers are the most common forms of hereditary cancers. Fifty thousand people in the UK are diagnosed with bowel and womb cancers every year; 10 per cent of these cancers are thought to be hereditary.
The decade-long study, which involved scientists and clinicians from 43 centres in 16 countries and was funded by Cancer Research UK, followed nearly 1,000 patients, in some cases for over 10 years. The study found that those who had been taking a regular dose of aspirin had 50 per cent fewer incidences of hereditary cancer compared with those who were not taking aspirin.
The research focused on people with Lynch syndrome which is an inherited genetic disorder that causes cancer by affecting genes responsible for detecting and repairing damage in the DNA. Around 50 per cent of those with Lynch syndrome develop cancer, mainly in the bowel and womb. The study looked at all cancers related to the syndrome, and found that almost 30 per cent of the patients not taking aspirin had developed a cancer compared to around 15 per cent of those taking the aspirin.
Preventing cancer development inside the cell cycle
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Researchers from the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, have identified a cell cycle-regulated mechanism behind the transformation of normal cells into cancerous cells. The study shows the significant role that protein networks can play in a cell leading to the development of cancer. The study results, published in the October 21 issue of the journal Molecular Cell, suggest that inhibition of the CK1 enzyme may be a new therapeutic target for the treatment of cancer cells formed as a result of a malfunction in the cell’s mTOR signaling pathway.
In the study, NYU Cancer Institute researchers examined certain multi-protein complexes and protein regulators in cancer cells. Researchers identified a major role for the multi-protein complex called SCFβTrCP . It assists in the removal from cancer cells the recently discovered protein DEPTOR, an inhibitor of the mTOR pathway. SCF (Skp1, Cullin1, F-box protein) ubiquitin ligase complexes are responsible for the removal of unnecessary proteins from a cell. This degradation of proteins by the cell’s ubiquitin system controls cell growth and prevents malignant cell transformation. Researchers show that inhibiting the ability of SCFβTrCP to degrade DEPTOR in cells can result in blocking the proliferation of cancer cells. In addition, researchers discovered that the activity of CK1 (Casein Kinase 1), a protein that regulates signaling pathways in most cells, is needed for SCFβTrCP to successfully promote the degradation of DEPTOR.
“Low levels of DEPTOR and high levels of mTOR activity are found in many cancers, including cancers of the breast, prostate, and lung,” said senior study author Michele Pagano, MD, the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU Langone Medical Center and a Howard Hughes Medical Institute Investigator. “It is critical for researchers to better understand how the protein DEPTOR is regulated. Our study shows it would be advantageous to increase the levels of DEPTOR in many types of cancer cells to inhibit mTOR and prevent cell proliferation.”
Diabetes again linked to colon cancer risk
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A new research review confirms that people with diabetes have a somewhat increased risk of colon cancer—but the reasons for the connection, and what should be done about it, remain unclear.
Combining the results of 14 international studies, researchers found that overall, people with diabetes were 38 percent more likely to be diagnosed with colon cancer than those who were diabetes-free.
There was also a 20 percent increase in the risk of rectal cancer, though that appeared to be confined to men.
Gene defect that predisposes people to leukemia discovered
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A new genetic defect that predisposes people to acute myeloid leukemia and myelodysplasia has been discovered. The mutations were found in the GATA2 gene. Among its several regulatory roles, the gene acts as a master control during the transition of primitive blood-forming cells into white blood cells.
The researchers started by studying four unrelated families who, over generations, have had several relatives with acute myeloid leukemia, a type of blood cancer. Their disease onset occurred from the teens to the early 40s. The course was rapid.
The findings will be reported Sept. 4 in Nature Genetics. The results come from an international collaboration of scientists and the participation of families from Australia, Canada, and the United States.
New process that may save lives of cancer patients is effective and significantly less costly
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People who are at risk for a certain form of colon and other types of cancer may soon have a better chance at surviving or even avoiding the diseases, thanks to a new study done by the Intermountain Clinical Genetics Institute at LDS Hospital.
The Intermountain Heathcare group of scientists used sophisticated computer modeling to develop a reliable and cost-effective way to identify patients who may have Lynch syndrome, an inherited cancer syndrome that occurs in people who carry a genetic mutation in one of the DNA mismatch repair genes. The mismatch repair (MMR) genes usually help to repair DNA damage that happens to all of us as a part of daily life. But patients who have genetic mutations in these genes have a substantially increased risk of developing colon, uterine, pancreatic and urologic cancers. For some patients, the lifetime risk approaches 80 percent.
“Being able to identify people who carry a gene change is profoundly important because earlier and more frequent screening - not just for colon cancer, but also for other cancers — could save their lives. It could also save the lives of relatives who have no idea that they may share the increased risk for cancer,” says Marc S. Williams, MD, director of the Clinical Genetics Institute at LDS Hospital, and a member of the team that conducted the study, which is published in the August edition of the American Journal of Managed Care.
Many advanced breast cancer patients do not receive recommended treatment
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Radiation after a mastectomy for women with advanced breast cancer saves lives, but almost half of these patients do not receive it. That is the conclusion of a new study published early online in CANCER, a peer-reviewed journal of the American Cancer Society. The study’s results indicate that treatments that have proven their life-saving potential in clinical trials may not be available to many patients.
After clinical trials in the 1990s revealed the benefits of radiation after mastectomy in advanced breast cancer patients, several major treatment guidelines were published that recommended radiation for these women after their surgery. To investigate whether these recommendations are being followed, Shervin Shirvani, MD, and Benjamin Smith, MD, of the MD Anderson Cancer Center in Houston, led a team that analyzed information from 38,322 women aged ≥ 66 years treated with mastectomy for invasive breast cancer between 1992 and 2005. (The researchers obtained data from the Surveillance, Epidemiology, and End Results [SEER]-Medicare database, which links cancer registry data to a master file of Medicare enrollment.)
While radiation use increased from 36.5 percent to 57.7 percent between 1996 and 1998 with the publication of landmark clinical trials, no further increase in use was observed between 1999 and 2005 despite the publication of multiple guidelines endorsing it.
American Cancer Society report finds continued progress in reducing cancer mortality
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A steady reduction in overall cancer death rates translates to the avoidance of about 898,000 deaths from cancer between 1990 and 2007, according to the latest statistics from the American Cancer Society. However, the report, Cancer Statistics 2011, and its companion consumer publication Cancer Facts & Figures 2011 find that progress has not benefitted all segments of the population equally. A special section of the report finds cancer death rates for individuals with the least education are more than twice those of the most educated and that closing that gap could have prevented 37%—or 60,370—of the premature cancer deaths that occurred in 2007 in people ages 25-64 years.
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries, and mortality data from the National Center for Health Statistics.
A total of 1,596,670 new cancer cases and 571,950 deaths from cancer are projected to occur in the U.S. in 2011. Overall cancer incidence rates were stable in men in the most recent time period after decreasing by 1.9% per year from 2001 to 2005; in women, incidence rates have been declining by 0.6% annually since 1998. Overall cancer death rates, which have been dropping since the early 1990s, continued to decrease in all racial/ethnic groups in both men and women since 1998 with the exception of American Indian/Alaska Native women, among whom rates were stable. African American and Hispanic men showed the largest annual decreases in cancer death rates during this time period, 2.6% and 2.5%, respectively. Lung cancer death rates showed a significant decline in women after continuously increasing since the 1930s.
New 3-D tumor model
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A team of scientists has developed a way to coax tumor cells in the lab to grow into 3-D spheres. Their discovery takes advantage of an earlier technique of producing spherical cavities in a common polymer and promises more accurate tests of new cancer therapies.
As team leader Michael R. King, Ph.D., of Cornell University explains, “Sometimes engineering research tends to be a case of a hammer looking for a nail. We knew our previous discovery was new and it was cool. And now we know it’s useful.”
Three years ago, the team—in collaboration with Lisa DeLouise, Ph.D., MPD, of Rochester, N.Y.—perfected a low-cost, easy fabrication technique to make spherical cavities in PDMS (polydimethylsiloxane), a widely used silicon organic polymer. More recently, the Cornell team discovered that these cavities could be used as a scaffolding to grow numerous tumor spheroids, which could serve as realistic models for cancer cells. The Cornell team’s work appears in the current issue of Biomicrofluidics, a publication of the American Institute of Physics.
Study identifies genetic mutations associated with cancer risk for hereditary cancer syndrome
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Among various genetic mutations for individuals with Lynch syndrome, a hereditary cancer syndrome that carries a high risk of colon cancer and an above-normal risk of other cancers, researchers have identified mutations associated with a lower cancer risk and mutations associated with an increased risk for ovarian and endometrial cancer, according to a study in the June 8 issue of JAMA, a theme issue on cancer. The study is being published early online to coincide with the American Society of Clinical Oncology 2011 Annual Meeting.
The Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer syndrome, accounts for 3 percent to 5 percent of all colorectal cancers. “Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome,” according to background information in the article. “Having more accurate knowledge of the age-dependent cancer risks associated with mismatch repair [MMR; a system within the cell for correcting errors in DNA] gene mutations would help in improving preventive strategies.”
Valerie Bonadona, M.D., Ph.D., of the Centre National de la Recherche Scientifique, Villeurbanne, France, and colleagues conducted a study to estimate the specific cancer risks associated with mutations in the genes MLH1, MSH2, and MSH6 by analyzing a large sample of families with Lynch syndrome. The study included 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6). The families were enrolled between January 2006 and December 2009 from 40 French cancer genetics clinics.
Arthritis patients taking newer treatments do not have an overall increased cancer risk
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Only three percent (n=181) of patients in the study cohort receiving anti-tumour necrosis factor agents (anti-TNFs) for treatment of their arthritis developed a first cancer within nine years and overall risk was not dependent on the type of arthritis.
The nine year follow-up study conducted at Gentofte University Hospital, Denmark demonstrated that relative risk ((RR)=1.03 (95%confidence interval 0.82-1.30)) was not increased in patients treated with anti-TNFs compared to patients who had never taken anti-TNFs during 23,965 person-years follow-up. Overall cancer risk was not dependent on the type of arthritis including rheumatoid arthritis (RA) (n=3,496) (RR=1.05, 95% CI 0.82-1.34), psoriatic arthritis (PsA) (n=670) (RR=1.98, 95% CI 0.24-16.18) or other arthritis (n=499) (RR=0.79 95% CI 0.08-8.33).
“Some studies have suggested that taking anti-TNFs may increase an individual’s risk of cancer however this study provides long term evidence that an overall risk of cancer is not associated with this group of treatments”, said Dr. PhD, Lene Dreyer from the Department of Rheumatology at Gentofte University Hospital. “TNF is a small signalling molecule called a cytokine and is able to inhibit the development of tumours by interfering with signalling pathways. Therefore drugs targeting TNF can influence the development of tumours, although the extent of this impact remains unclear.”
New treatment regimen shows clinical benefit in advanced colon cancer
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A new treatment regimen for patients with metastatic colon cancer appears to offer clinical benefit even when used after multiple other treatments have failed, say research physicians at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center.
The research team found that combining a PARP inhibitor with chemotherapy (temozolomide) offers significant benefit in patients who had no further treatment options. However, the study is small, and does not include a comparison arm, so further investigation is needed, they add. The study will be presented in an oral session on Saturday, June 4th, at the 2011 annual meeting of the American Society of Clinical Oncology in Chicago.
PARP, short for “poly (ADP-ribose) polymerase” is a key part of a cell’s DNA repair apparatus, and is important for protecting our normal cells against DNA damage. However, cancer cells become resistant to chemotherapy in part by increasing PARP expression and thus rapidly repairing DNA damage intentionally caused by chemotherapy. PARP inhibitors are designed to overcome a cancer cell’s ability to repair the damaged DNA. (They are showing promise in both breast and ovarian cancers, and are being studied in a variety of other cancer types).
Oncolytic viruses effectively target and kill pancreatic cancer stem cells
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Oncolytic viruses quickly infect and kill cancer stem cells, which may provide a treatment for tumors that are resistant to conventional chemotherapy and radiation, particularly pancreatic cancer, according to new research from Memorial Sloan-Kettering Cancer Center in New York. The findings are especially important since pancreatic cancer has a poor prognosis and is difficult to detect and treat at early stages.
Investigators led by Joyce Wong, MD, surgical researcher with Memorial Sloan-Kettering Cancer Center, investigated whether they could use oncolytic viruses, which are naturally occurring viruses that have been genetically engineered to be safe and express tracking genes, as a possible therapy against pancreatic cancer stem cells. These stem cells are thought to cause disease recurrence and metastasis, even after therapy, and oncolytic viruses may offer a new treatment strategy.
“What we learned is that oncolytic viruses have been engineered to selectively target cancer cells and have a low toxicity profile in animal studies,” said Dr. Wong. “Targeting the cancer stem cell may enhance our ability to eradicate tumors and prevent future recurrence of disease.”
