New class of cancer drugs in making
The compounds are the first selective inhibitors of the protein phospholipase D (PLD), an enzyme that has been implicated in multiple human cancers including breast, renal, gastric and colorectal.
The new inhibitors, published in the recent issue of Nature Chemical Biology, block the invasive migration of breast cancer cells, supporting their further development as antimetastatic agents. They will also be useful tools for understanding the complex roles of PLD in cellular physiology, said H. Alex Brown, Ph.D., professor of Pharmacology and one of the team leaders.
"PLD is linked to a number of fundamental cellular processes like secretion, migration, growth and proliferation. But the absence of selective inhibitors has really interfered with the ability of biologists to study this important enzyme," Brown said.
There are two related "isoforms" of PLD: PLD1 and PLD2. Both PLD enzymes produce phosphatidic acid, a key lipid metabolic and signaling molecule. But whether the two PLDs have different roles is an open question, one that the new isoform-selective inhibitors can now be used to address.........
Statins do not interfere with rituximab treatment
50th Annual Meeting of the American Society of Hematology (http://www.hematology.org/meetings/2008/) in San Francisco. In fact, statins may slow the progression of certain types of lymphoma.
The study focused on the impact of statin use on outcomes of patients with two most common lymphoma types, diffuse large B-cell lymphoma and follicular lymphoma. Both are cancers of the immune system. Examples of usually used statins in the U.S. include Lipitor, Zocor, Parvachol, Lescol, Mevacor and Crestor.
Rituximab (Rituxan), a monoclonal antibody, is often used alone or in conjunction with chemotherapy drugs to treat lymphomas. When administered to patients with lymphoma, rituximab attaches to CD20, a protein found on lymphoma cells. Addition of rituximab to chemotherapy improves outcomes in a number of lymphoma types.
A laboratory-based study by Winiarska and his colleagues published this year in The Public Library of Science Medicine journal suggested that statins may inhibit rituximab binding to CD20. "That finding raised questions about maintaining or stopping cholesterol therapy with statins for patients with lymphoma," says Grzegorz Nowakowski, M.D. (http://www.mayoclinic.org/bio/13657551.html), Mayo Clinic hematologist and lead researcher on the Mayo study.........
New tool to speed cancer therapy approval available
The National Cancer Institute's Translational Research Working Group (TRWG) developed a set of tools that it believes will improve that process. The tools, known as.
"Pathways to Clinical Goals" are reported in the September 15 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research.
"The NCI supports a great deal of excellent translational research, but inefficiencies arising from a lack of communication and coordinated effort prevent a number of promising leads from reaching clinical trials and eventual approval," said Lynn Matrisian, Ph.D, a special assistant in the Office of the Director, NCI. Matrisian co-chaired the TRWG, which was formed in 2005 with the goal of accelerating the pace of translational cancer research. Publication of the Pathways is expected to be a major step forward in this process.
There are six Pathways that address the following categories: anti-cancer agents (drugs or biologics), biospecimen-based assessment methods, immune response modifiers, image-based assessment modalities, intervention devices, and lifestyle alterations.........
Patients 75 years and older with brain tumors
Using the Surveillance, Epidemiology and End Results (SEER) Medicare-linked database, the scientists led by Jill S. Barnholtz-Sloan, Ph.D., of the Comprehensive Cancer Center at Case Western Reserve University and University Hospitals, looked at the records of 1753 patients who were treated for glioblastoma multiforme (GBM) and of 205 patients treated for anaplastic astrocytoma (AA) between 1991 and 1999. GBMs are the most common cancerous brain tumors in adults. AAs are less common, but are treated similarly to GBMs. Both have a poor prognosis, and as the American population ages, the occurence rate of these brain tumors is on the rise.
The scientists looked at whether patients received a biopsy only, surgery only, biopsy and radiation, surgery and radiation, or surgery, radiation and chemotherapy.
The odds of undergoing aggressive therapy surgery followed by radiation with or without chemotherapy, which is the standard of care in the United States in younger individuals decreased significantly in individuals who were 75 years old or older, said Dr. Barnholtz-Sloan.........
The cancer-related protein Akt
The study was published online Feb. 21 in the Proceedings of the National Academy of Sciences of the United States of America.
The findings may provide another piece of the puzzle in figuring out how tau proteins can poison nerve cells in the brain.
Akt is known to increase cancer cell survival capability and has become a target in the development of some cancer-inhibitor drugs. The abnormal accumulation of tau protein tangles kills nerve cells and is considered one of the hallmarks of Alzheimer's disease.
"This study describes for the first time a new function for the cancer-related protein Akt - one that may help promote Alzheimer's disease pathology," said lead author Chad Dickey, PhD, assistant professor of molecular pharmacology and physiology at USF. "We observed that increased amounts of Akt may prevent the removal of abnormal proteins, such as tau, causing these proteins to accumulate and disrupt the balance within the cells."
While this Akt-induced imbalance might result in cancer cells continuing to divide uncontrollably, Dr. Dickey suggests it likely has a different effect in Alzheimer's disease. "The nerve cells may try to divide in the brain, but cannot, and therefore die," he said. "Thus regulating levels of Akt, rather than its activity, may be beneficial to sufferers of diseases of aging, such as cancer, Alzheimer's and even diabetes."........
Cell phone-cancer link found
Dr. Sadetzki, a physician, epidemiologist and lecturer at Tel Aviv University, published the results of a study recently in the American Journal of Epidemiology, in which she and her colleagues observed that heavy cell phone users were subject to a higher risk of non-malignant and cancerous tumors of the salivary gland.
Those who used a cell phone heavily on the side of the head where the tumor developed were found to have an increased risk of about 50% for developing a tumor of the main salivary gland (parotid), in comparison to those who did not use cell phones.
The fact that the study was done on an Israeli population is significant. Says Sadetzki, Unlike people in other countries, Israelis were quick to adopt cell phone technology and have continued to be exceptionally heavy users. Therefore, the amount of exposure to radiofrequency radiation found in this study has been higher than in prior cell phone studies.
This unique population has given us an indication that cell phone use is linked to cancer, adds Sadetzki, whose study investigated nearly 500 people who had been diagnosed with non-malignant and cancerous tumors of the salivary gland.........
4 health behaviors can add 14 extra years of life
Rather than focusing on how an individual factor is related to health, the study calculates the combined impact of these four simply-defined forms of behaviour. The results suggest that several small changes in lifestyle could have a marked impact on the health of populations.
There is overwhelming evidence showing that lifestyles such as smoking, diet and physical activity influence health and longevity but there is little information about their combined impact. Furthermore the huge amount of information provided by these studies and the varying definitions of a health behaviour that these studies use can often make them confusing for public health professionals and for the general public. For example: small amounts of alcohol appear to be related to lower risk of cardiovascular disease health but what is the overall impact on longevity ".
In order to examine the combined impact of changes in lifestyle, Kay-Tee Khaw and colleagues from the University of Cambridge and the Medical Research Council used a health behaviour score that is easy to understand in order to assess the participants in the study (who were from Norfolk, United Kingdom). Between 1993 and 1997, 20,000 men and women between the ages of 45 and 79, none of whom had known cancer or heart or circulatory disease, completed a questionnaire that resulted in a score between 0 and 4. A point was awarded for each of the following: not currently smoking; not being physically inactive (physical inactivity was defined as having a sedentary job and not doing any recreational exercise); a moderate alcohol intake of 1-14 units a week (a unit is half a pint of beer or a glass of wine); and a blood vitamin C level consistent with eating five servings of fruit or vegetables a day. Deaths among the participants were recorded unti l 2006.........
Silencing small but mighty cancer inhibitors
Whats more, in several instances, re-introducing repressed miRNAs into Myc-containing cancer cells suppressed tumor growth in mice, raising the possibility that a sort-of gene treatment approach could be effective treatment for treating certain cancers.
A research team led by Joshua Mendell, M.D., Ph.D., assistant professor at the McKusick-Nathans Institute of Genetic Medicine, previously observed that Myc could turn on one particular group of growth-promoting miRNAs called the miR-17-92 cluster in lymphoma cells. His team, along with Andrei Thomas-Tikhonenkos lab at the University of Pennsylvania, now took a broader approach and analyzed more than 300 miRNAs in both human and mouse lymphoma cells.
In those cells that had high amounts of Myc protein, the scientists found significant changes in the quantities of at least 13 miRNAs. The surprising aspect, considering our miR-17-92 results, says Tsung-Cheng Chang, lead author on the study, is that lots of Myc turns everything off, not on.........
Stereo Mammography Improves Cancer Detection
The findings from a clinical trial underway at Emory University were presented today at the annual meeting of the Radiological Society of North America held in Chicago.
In the study, stereoscopic digital mammography reduced false-positive findings by 49 percent compared to standard digital mammography, and reduced missed lesions by 40 percent, according to Dr. Carl DOrsi, MD, professor of radiology, Emory University School of Medicine, and director of breast imaging.
This finding is very significant because it shows the technology cuts by almost half the number of women who are recalled for additional tests, reduces the number of false positives that typically occur in standard mammograms and eliminates significant anxiety in patients and their loved ones, says Dr. DOrsi.
Standard mammography is widely considered to be one of the most difficult exams to read because lesions may be disguised by normal tissue," says Dr. D'Orsi. "At the same time, false-positives can also occur because of the two dimensional images provided by the existing technology.........
New Therapeutic Molecular Target to Fight Cancer
In the Nov. 1 issue of the journal Cancer Research, scientists examined human colon and breast cancer cells and established a role of sphingosine kinase 2 (SphK2), an enzyme that forms the potent lipid mediator sphingosine-1-phosphate in the death of cancer cells mediated by the chemotherapeutic drug, doxorubicin.
Doxorubicin is able to kill cancer cells by working with p53, one of the most protective anti-cancer proteins in the human body. However, doxorubicin also relies on p53- independent mechanisms to induce death in colon and breast cancer cells.
"Understanding how doxorubicin kills in a p53-independent manner is a major goal of cancer scientists because most cancer cells have mutated p53," said lead author Sarah Spiegel, Ph.D., chair and professor in the VCU Department of Biochemistry and Molecular Biology and co-leader of the cancer center's cancer cell biology program.
As per Spiegel, the study demonstrated that SphK2 is important for p53-independent induction of expression of p21, a cyclin-dependent kinase inhibitor. This p21 regulates the cell cycle, and apoptosis or programmed cell suicide, mediated by doxorubicin. Human colon and breast cancer cells were killed more efficiently by doxorubicin when SphK2 was removed from the cells.........
New treatment option for bladder cancer
The unfortunate reality is that kidney problems often result from bladder cancer which precludes the usual chemotherapy package of cisplatin and gemcitabine, says Dr. Teresa A. Coleman, hematologist-oncologist at the MCG Cancer Center.
A Phase II study at about 120 sites in North America, Europe and Asia will determine if those patients can benefit from vinflunine, which is in the same vinca alkaloid family as Navelbine®, used for lung cancer.
These vinca alkaloids keep cells from dividing properly so the tumor can't grow and existing tumor regresses, says Dr. Coleman, a principal investigator on the study sponsored by Bristol-Myers Squibb.
Patients with stage two disease, which has spread beyond its origin in the bladder's lining, typically get cisplatin and gemcitabine before or after surgery or in conjunction with radiation treatment. However, a major side effect of cisplatin is kidney failure, and gemcitabine alone is believed not to be nearly as effective. "The most effective drug we have can't be used in some patients," Dr. Coleman says.
Bladder cancer, the sixth most common cancer, often obstructs tubules that connect the kidney to the bladder, says Dr. Coleman. While the cancer typically doesn't spread upward, tubule blockage damages the kidneys. Additionally, bladder cancer incidence peaks in the 60s and 70s when other diseases, such as type 2 diabetes and uncontrolled blood pressure, may also have damaged the kidneys, she says. These scenarios make more than 50 percent of patients age 70 to 80 and an estimated 30 percent of all bladder cancer patients are ineligible for cisplatin.........
Post-traumatic Stress Symptoms In Adolescent Children Of Cancer Patients
A cancer diagnosis is among those life experiences that can be so stressful that it is traumatic. While only a fraction of people who develop post-traumatic stress symptoms (PTSS) go on to develop post-traumatic stress disorder (PTSD), the symptoms can cause emotional problems during the later part of life. Much is known about the psychological effect that cancer has on a patient and a spouse, but the consequences of a parent's cancer on children are more poorly understood.
The study, presented today (Wednesday) at the European Cancer Conference (ECCO 14) in Barcelona, is the first to examine PTSS over time in adolescent children of cancer patients.
Dr Gea Huizinga, a health scientist and research fellow at the University Medical Center in Groningen, The Netherlands, examined the prevalence of PTSS, emotional and behavioural problems in 49 adolescents during the first year after a parent's cancer diagnosis. The children and each of their parents completed questionnaires three times over the year - within four months after the diagnosis and at six and twelve months after the first survey.........
Shrinkage of prostate leads to overestimation of cancer
The study of the Prostate Cancer Prevention Trial, led by University of Illinois at Chicago professor of pathology Dr. Peter Gann, is reported in the Sept. 12 issue of the Journal of the National Cancer Institute.
The Prostate Cancer Prevention Trial reviewed the drug finasteride, which blocks production of a male hormone within the prostate and is proven effective in treating non-malignant prostatic hyperplasia, or enlargement of the prostate. The trial was stopped in 2003 when finasteride was found to reduce the risk of prostate cancer by nearly 25 percent. However, men assigned to the finasteride group had a greater prevalence of high-grade cancer.
Gann said the results were confusing for clinicians and patients because the drug appeared to retard the development of prostate cancer and decrease its prevalence, but the increased risk of high-grade cancer was unexplained and worrisome.
Scientists reasoned one possible explanation was that because finasteride shrinks the prostate gland, it increases the likelihood that a biopsy will detect high-grade cancer.........
Birth records hold pancreatic cancer clue
The research team drawn from the US and Israel and led by M. C. Perrin traced over 37,000 mothers who gave birth between 1964 and 1976 in Jerusalem as part of the Jerusalem Perinatal Study. Birth records revealed 410 women were diagnosed with gestational diabetes in one or more of their pregnancies. Of the 410 women with gestational diabetes, five eventually developed pancreas cancer. There were 54 cases of pancreas cancer overall in the cohort; and none of the women with type 1 diabetes at the time they gave birth went on to develop pancreas cancer.
Those with gestational diabetes often go on to develop type 2 diabetes mellitus. Medical debate surrounds the causal relationship between diabetes and pancreas cancer. On the one hand, patients with newly diagnosed pancreas cancer frequently have diabetes of recent onset and when the tumor is removed the symptoms of diabetes often improve. Conversely, individuals with long standing diabetes have also been shown to be at increased risk of pancreas cancer. In this study the gestational diabetes clearly came first, between 14 and 35 years before the pancreas cancer.........
Elevated Leukaemia Rates Near Nuclear Facilities
Researchers at the Medical University of South Carolina carried out a sophisticated meta-analysis of 17 research papers covering 136 nuclear sites in the UK, Canada, France, the USA, Germany, Japan and Spain.
They found that death rates for children up to the age of nine were elevated by between five and 24 per cent, depending on their proximity to nuclear facilities, and by two to 18 per cent in children and young people up to the age of 25.
Incidence rates were increased by 14 to 21 per cent in zero to nine year olds and seven to ten percent in zero to 25 year-olds.
Childhood leukaemia is a rare disease and nuclear sites are commonly found in rural areas, which means that sample sizes tend to be small says lead author Dr Peter J Baker.
The advantage of carrying out a meta-analysis is that it enables us to draw together a number of studies that have employed common methods and draw wider conclusions.
Eight separate analyses were performed including unadjusted, random and fixed effect models and the figures they produced showed considerable consistency.........
Skin Rash Actually Signifies Better Outcomes
The study, reported in the July 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, reports that for patients taking Tarceva who developed a moderate to severe rash, survival without progression of disease was 245 percent longer than in patients who had a mild rash or none at all. In fact, in the majority of cases, the more severe the rash, the longer a patient's cancer was held in check, scientists found.
This rash, which often looks like acne, can be unpleasant enough for some people to consider discontinuing therapy, but "it is important for physicians and patients to understand that this a positive event because it means there is likely to be a better clinical outcome," said the lead author, Bret Wacker, MS Director of Biostatistics at OSI Pharmaceuticals, Inc. "Further studies are needed to both identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy."........
Cigarette smoking impairs ligament healing
Studying mice with knee ligament injuries, the team discovered cigarette smoking impairs the recruitment of cells to the injury site and delays healing following ligament-repair surgery. They reported their findings in the Journal of Orthopaedic Research.
The scientists looked at the mouse medial collateral ligament (MCL), a ligament that supports the knee joint in both mice and people. Each year in the United States there are more than 20 million reported ligament injuries, and MCL injuries are the most common. They also are the most common injuries seen in competitive and recreational sports. It's not clear exactly how a number of MCL injuries occur annually because a number of go unreported.
"A lot of MCL injuries never make it to an emergency room because patients will have a sore knee but don't seek therapy," says Rick W. Wright, M.D., associate professor of orthopaedic surgery and a senior investigator on the MCL study.
Prior studies have demonstrated that the mouse provides a good paradigm for what happens in injured human knees.
"This is a good model for knee ligament injury, but it could be a model for ligament injuries anywhere in the body," says co-investigator Linda J. Sandell, Ph.D., professor of orthopaedic surgery. "It's likely the biology is transferable to other knee ligaments, elbow ligaments, shoulder ligaments, you name it".........
Antioxidant is selective killer of leukemia cells
Current therapys for leukemia, such as chemotherapy and radiation, often damage healthy cells and tissues and can produce unwanted side effects for a number of years afterward. So, there is an intensive search for more targeted therapies for leukemia worldwide, said corresponding author Xiao-Ming Yin, M.D., Ph.D., associate professor of pathology, University of Pittsburgh School of Medicine.
Leukemia is not a single disease but many related cancers that start in the blood-forming cells of the bone marrow. Meaning literally white blood in Greek, leukemia occurs when there is an excess of abnormal white blood cells. There are both acute and chronic forms of leukemia, each with a number of subtypes that vary in their response to therapy. As per the National Cancer Institute, about 44,000 new leukemia cases will be diagnosed in the United States in 2007, and there will be about 22,000 leukemia-related deaths.........
Is treatment for prostate cancer is working?
"Currently, we have no way of detecting bone tumor response to treatment, even with all of the imaging options we have available. The magnitude of this problem is huge as a number of as 500,000 people in the United States have metastatic breast or prostate cancer to the bone," says study author Brian D. Ross, Ph.D., professor of radiology and biological chemistry at the U-M Medical School and co-director of the Molecular Imaging Program at the U-M Comprehensive Cancer Center.
Results of the study, which was done in mice, appear in the April 15 issue of Cancer Research.
The imaging technique, called a functional diffusion map, uses a magnetic resonance imaging scan and special software to track the diffusion, or movement, of water through the cells. Scientists mapped the changes in diffusion over the course of therapy. The tumor cells slow the movement of water, so as those cells die, water diffusion increases.
Scientists studied metastatic prostate cancer in mice; half the mice were given chemotherapy to treat the cancer, which was in the bones, while the remaining mice served as an untreated control group. Scientists performed an MRI of bone tumors to collect diffusion data. A functional diffusion map analysis found the mice that did not receive therapy had little or no change in water diffusion, while the treated mice had progressively increasing changes in the functional diffusion map over the three weeks of therapy. Scientists could identify a statistically significant change in diffusion as early as seven days after therapy began.........
Researchers Wake Up Viruses Inside Tumors
Epstein-Barr virus modelIn the March 1 issue of Clinical Cancer Research, a team of radiologists and oncologists from Johns Hopkins Medical Institutions describe how they used two agents already on the market − one of which is the multiple myeloma drug Velcade − to light up tumor viruses on a gamma camera. The technique is the first in the new field of in vivo molecular-genetic imaging that doesn't require transfecting tumors with a "reporter" gene, the researchers say.
"The beauty of this is that you don't have to introduce any reporter genes into the tumor because they are already there," says radiologist Martin G. Pomper, M.D., Ph.D. "This is the only example we know of where it is possible to image activated endogenous gene expression without having to transfect cells".
A variety of blood and solid cancers are more likely to occur in people who have been infected with the Epstein-Barr virus (EBV), but not everyone with these cancers has such infections. For those who do, researchers, such as Hopkins oncologist and co-author Richard F. Ambinder, M.D., Ph.D., have been working on ways to activate the reproductive, or "lytic" cycle, within the virus to make it replicate within the tumor cell. When enough viral particles are produced, the tumor will burst, releasing the virus. In animal experiments, this experimental treatment, called lytic induction treatment, results in tumor death.........
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