New depression research

For the more than 18 million Americans who suffer from depressive illnesses, the best pharmacological treatments are those that increase levels of serotonin, the brain chemical that regulates mood, sleep and memory. New research by an international team of scientists, led by Rockefeller University researchers in Paul Greengard’s laboratory of Molecular and Cellular Neuroscience, shows that a gene called p11 is closely related to serotonin transmission in the brain — and may play a key role in determining a person’s susceptibility to depression.

The newly discovered link between depression and the serotonin system, reported in the January 6 issue of the journal Science, could lead to new treatments for these mental disorders.

“We have shown that a gene called p11 is involved in the multiple complex changes that underlie depression,” says Per Svenningsson, a research assistant professor and first-author on the paper. “Our findings demonstrate that patients with depression, and mice that model this disease, have decreased levels of p11 protein, and they suggest that drugs that increase p11 are likely to have anti-depressant properties.”

Serotonin binds to 14 different receptors on a cell’s surface. One receptor in particular, known as 1B, plays a crucial role in regulating serotonin transmission in the brain. Recent studies have suggested a role for the serotonin 1B receptor in depression, as well as in obsessive-compulsive disorder, drug addiction, anxiety, aggression and sleep.

Intrigued by these studies, Svenningsson and colleagues at Rockefeller, the Karolinska Institute, the University of Rouen in France and Eli Lilly and Company, used a blind screen called a yeast two-hybrid screen to identify proteins that associate with the serotonin 1B receptor. They found an association with a protein called p11, a protein previously identified as a regulator of the localization of several proteins on the cell’s surface.

The researchers analyzed tissue from a mouse model of depression as well as post-mortem tissue from depressed human patients, and found decreased levels of p11 protein in both cases. On the other hand, p11 levels increased in rats and mice that were treated with anti-depressant medications or electroconvulsive therapy.

To further test the connection, Svenningsson and his colleagues genetically engineered two strains of mice: one that produced more p11 than normal and another that produced no p11 at all. They found that mice that overexpress p11 were hyperactive and, in a test designed to identify depression in rodents, acted just like mice that were on anti-depressant medication. Mice that lacked p11, meanwhile, acted depressed and showed less responsivity to anti-depressant medications.

Taken together, the findings point to p11 as a new target for developing depression treatments.

“In addition to exploring ways to increase p11 in depressed patients, it may also be possible to develop peptide-based compounds that can mimic the action of p11 to achieve a new class of anti-depressant compounds,” Svenningsson says.

January 6th, 2006 by Rachel Cunliffe | Comments Off

Study: Exercise helps speed wound healing in older adults

The body’s ability to heal even small skin wounds normally slows down as we age. But a new study in older adults finds that regular exercise may speed up the wound-healing process by as much as 25 percent.

“This is the first time we’ve been able to document this kind of enhancement associated with exercise,” said Charles Emery, a professor of psychology and the lead author of the Ohio State University study.

The faster that a wound heals, the less chance it will become infected.

The results appear in a recent issue of the Journal of Gerontology: Medical Sciences.

The study included 28 healthy older adults ranging in age from 55 to 77 (average age was 61). The participants hadn’t exercised regularly for at least six months prior to the study. For the research, about half (13) of them exercised three times a week for three months. The other 15 participants served as controls and were asked not to change their physical activity habits during the study period.

Each subject received a small puncture wound on the back of the upper arm. Adults in the exercise group started working out about a month before the wound procedure; this gave their bodies enough time to adapt to a regular exercise program.

The wounds were about 1/8-inch across and deep. The researchers photographed the wounds three times a week until the wounds were no longer visible (about six to seven weeks).

The exercise sessions began with 10 minutes of warm-up floor exercises and stretching followed by 30 minutes of pedaling on a stationary bike. After that, participants either jogged or walked briskly on a treadmill for 15 minutes, followed by about 15 minutes of strength training. All sessions ended with five minutes of cool-down exercises.

Each participant completed assessments of exercise endurance and stress at the beginning and end of the study. The exercise endurance test, completed on a treadmill, measured each subject’s aerobic fitness level by measuring how much oxygen he or she consumed while working out.

The researchers also collected saliva samples from each participant in order to measure levels of cortisol, a primary stress hormone. High cortisol levels indicate that the body is under stress; prior studies have suggested that exercise is associated with lower levels cortisol.

Lastly, each subject completed a questionnaire called the Perceived Stress Scale. This scale let the researchers determine how stressful the respondents perceived their lives to be.

At the end of the study, the researchers found that skin wounds healed an average of 10 days faster in the people who exercised (29 days in the exercise group vs. 39 days in the non-exercise group.)

Not surprisingly, exercise endurance increased in the group that worked out, but remained the same in the non-exercise group.

The researchers were somewhat surprised to find a sharp increase in cortisol levels in the exercise group. The hormone is typically boosted by stress, and other studies have suggested that exercise may lower levels of stress.

“The stress of exercise may enhance the regulation of cortisol,” Emery said. “This increase in cortisol levels may represent a biological pathway by which exercise helps wounds heal.”

There were no changes in perceived stress in either group but none of the adults in this study reported any significant distress in their lives at the beginning of the study.

The current study supports the results of a related study on wound healing conducted at Ohio State a few years ago. That work compared wound-healing rates between older adults caring for a loved one with Alzheimer’s disease to rates of older adults who weren’t caregivers.

The healing rates of those who weren’t caregivers was similar to the healing rates of the non-exercisers in the current studying – wounds in both groups healed in about 40 days. Wounds among older caregivers took about 20 percent longer to completely heal.

“The findings from both studies indicate that the effect of exercise we found in the current study truly represents an enhanced rate of wound healing in older adults,” Emery said.

The next step is to determine if older adults who report a fair amount of stress in their lives – such as dealing with the death of a spouse or financial troubles – get the same kind of benefit from exercise.

January 6th, 2006 by Rachel Cunliffe | Comments Off

Gold nanoparticles, radiation combo may slow Alzheimer’s

Chemists in Chile and Spain have identified a new approach for the possible treatment of Alzheimer’s disease that they say has the potential to destroy beta-amyloid fibrils and plaque — hypothesized to contribute to the mental decline of Alzheimer’s patients. The researchers say the new technique, which they call a type of “molecular surgery,” could halt or slow the disease’s progress without harming healthy brain cells. The research is scheduled for publication in the Jan. 11 issue of the American Chemical Society’s Nano Letters.

Using test tube studies, the scientists attached gold nanoparticles to a group of beta amyloid fibrils, incubated the resulting mixture for several days and then exposed it to weak microwave fields for several hours. The energy levels of the fields were six times smaller than that of conventional cell phones and unlikely to harm healthy cells, the researchers say. The fibrils subsequently dissolved and remained dissolved for at least one week after being irradiated, indicating that the treatment was not only effective at breaking up the fibrils but also resulted in a lower tendency of the proteins to re-aggregate, according to the researchers.

The same approach also holds promise for treating other neurodegenerative diseases that involve protein aggregation, including Parkinson’s and Huntington’s, says study leader Marcelo J. Kogan, of the University of Chile in Santiago. He says that the approach is similar to that of another experimental technique that uses metallic nanoparticles to label and destroy cancer cells. Animal studies are planned, Kogan says.

There’s currently no cure for Alzheimer’s disease and no one is sure of its exact causes. The disease affects an estimated 4.5 million people in the United States, according to the National Institute on Aging. That figure is expected to rise dramatically as the population ages, experts predict.

January 6th, 2006 by Rachel Cunliffe | Comments Off

Years of loud noise may lead to tumor

New research suggests that years of repeated exposure to loud noise increases the risk of developing a non-cancerous tumor that could cause hearing loss.

“It doesn’t matter if the noise comes from years of on-the-job exposure or from a source that isn’t job-related,” said Colin Edwards, a doctoral student in the School of Public Health at Ohio State University.

In the current study, people who were repeatedly exposed to loud noise over the span of several years were on average one-and-a-half times as likely to develop this type of tumor compared to people who weren’t exposed to such noise on a regular basis.

The tumor, called acoustic neuroma, grows slowly and symptoms typically become noticeable around age 50 or older. Of the 146 people with acoustic neuroma in this study, nearly two out of three were 50 or older.

An acoustic neuroma tumor slowly presses the cranial nerve that is responsible for sensing sound and helping with balance. Symptoms include hearing loss and a constant ringing in the ears, or tinnitus.

The study is currently in the online advance access edition of the American Journal of Epidemiology.

Edwards and his colleagues gathered four years of data from the Swedish portion of the INTERPHONE Study, an international study of cell phone use and tumors that affect the brain and head.

The researchers used the Swedish portion of the study because health officials there keep meticulous data on rates of acoustic neuroma development in the country’s population, said Judith Schwartzbaum, a study co-author and an associate professor of epidemiology in the School of Public Health at Ohio State .

In addition to the 146 study participants with acoustic neuroma, another 564 people without the tumor who served as controls were also interviewed by a nurse. The participants in this group were randomly selected from the continuously updated Swedish population registry. Study participants ranged in age from 20 to 69.

All participants were asked if they were regularly exposed to occupational and non-occupational loud noise and, if so, for how many years. “Loud noise” was defined as at least 80 decibels – the sound of city traffic.

If the subjects said that they had been regularly exposed to loud noise, they were then asked to describe the activities during which they were exposed to that noise.

Categories for loud noise exposure included: exposure to machines, power tools and/or construction noise; exposure to motors, including airplanes; exposure to loud music, including employment in the music industry; and exposure to screaming children, sports events and/or restaurants or bars.

The researchers also collected data on the use of hearing protection.

The two types of loud noise posing the highest risk of acoustic neuroma development were exposure to machines, power tools and/or construction (1.8 times more likely to develop the tumor) and exposure to music, including employment in the music industry (2.25 times more likely to develop the tumor.)

Exposure to motors, including airplanes increased acoustic neuroma risk by 1.3 times, while regular exposure to screaming children, sports events and/or bars and restaurants increased the risk by 1.4 times.

The number of years that a person was exposed to any category of loud noise also contributed to the development of acoustic neuroma. Just five years of regular exposure to loud noise increased the chance that a person would develop acoustic neuroma by one-and-a-half times.

“It’s not surprising that the longer that people are exposed to loud noise, the greater their chances become for developing the tumor,” Edwards said.

The study results also suggest the importance of wearing ear protection when exposed to loud noises. People who reported that they protected their ears from loud noise had about the same risk of developing acoustic neuroma as people who were not exposed to loud noise. People who protected their hearing were also half as likely to develop acoustic neuroma as people who didn’t wear ear protection.

The tumor is fairly rare, accounting for only about 6 to 10 percent of tumors that develop inside the skull. Depending on the population, anywhere from one to 20 people per 100,000 develop acoustic neuroma each year. The people with the tumor in this study had the most common type – unilateral acoustic neuroma. About 95 percent of all cases of acoustic neuroma affect only one ear. The other kind, bilateral acoustic neuroma, is inherited and affects both ears.

If the tumor is caught early enough through a thorough examination and hearing tests, a physician may be able to surgically remove it. But as the tumor grows larger, it may become attached to the nerves that control facial movement, balance and hearing, making it far more difficult to remove the entire tumor.

January 6th, 2006 by Rachel Cunliffe | Comments Off

Treating gum disease may reduce the risk of cardiovascular disease

The Journal of Dental Research has just published the results of a study showing that treatment of gum disease may reduce the risk of cardiovascular disease.

Researchers from Australia (Sydney Dental Hospital and Royal North Shore Hospital) and Norway (University of Oslo) collaborated in the PERICAR clinical trial, providing strong evidence linking periodontal (gum) disease to an increased risk of developing blood clots, which could lead to the onset of heart attack and stroke.

In recent years, many studies throughout the world have linked periodontal disease to increased cardiovascular risk, although the reasons for this link have not been fully explained, nor has it been proven that the link is a direct causal one. One explanation is that inflammation and infection have also been related to increased atherosclerosis and cardiovascular risk. Periodontal disease is the most common chronic infection in humans, and symptoms include bleeding, swollen or receding gums, and bad breath. In severe cases, the teeth become loose and may eventually fall out.

Individual participants who were involved in the trial had blood tests before and after treatment of gum disease that was so severe that all their teeth had to be extracted. The blood tests were for blood-clot risk factors and signs of inflammation.

The average level of factors fell when the gum infection was eradicated, suggesting that the risk of heart attacks and clots in the future had reduced. This also indicates that inflammation in the mouth has a measurable effect in the bloodstream, and therefore the rest of the body.

Although these results are exciting they do not yet provide proof of a direct link and more research is needed. With grants from the National Health and Medical Research Council of Australia and the Ramaciotti Foundation, the researchers are currently studying the relationship between gum and heart disease in people with less severe periodontal disease who do not need to have all their teeth extracted.

Dental disease impacts on people’s general health and well-being. Periodontal disease is common, preventable, and treatable. This study suggests that improving periodontal health could significantly reduce the risk of cardiovascular disease.

January 6th, 2006 by Rachel Cunliffe | Comments Off

Ovarian cancer treatment - new research

A study featured in this month’s edition of Gynecologic Oncology examines the challenges associated with the administration of intra-abdominal chemotherapy, also known as intraperitoneal (IP) chemotherapy. This is a companion study to a paper released today in the New England Journal of Medicine showing longer survival for women who received IP chemotherapy compared with those who received the standard intravenous (IV) regimen.

The New England Journal of Medicine study, “Intravenous Cisplatin and Paclitaxel Versus an Intensive Regimen of Intravenous Paclitaxel, Intraperitoneal Cisplatin and Intraperitoneal Paclitaxel in Stage III Ovarian Cancer: A Gynecologic Oncology Group (GOG) Study,” found that women who received part of their chemotherapy via an IP route had a median survival 16 months longer than women who received IV chemotherapy alone (65.6 months versus 49.7 months). Women could only be enrolled in this study if they had undergone thorough surgery resulting in optimal resection of their cancers such that the largest residual tumor nodules were less than 1 cm in diameter prior to initiation of chemotherapy. Segmental bowel resections were required to remove large tumor nodules in 32% of the women treated with IP chemotherapy. This finding highlights the importance of referral of women with known or suspected ovarian cancer to physicians with special expertise and training in the surgical management of ovarian cancer.

The IP therapy was shown to improve survival even though only 42% of patients in the IP therapy arm of the study completed all the prescribed IP treatments. This highlights the importance of continuing efforts to optimize techniques for IP chemotherapy administration.

The companion study published in Gynecologic Oncology, “Intraperitoneal Catheter Outcomes: A Phase III Trial of Intravenous Versus Intraperitoneal Chemotherapy in Optimal Stage III Ovarian and Primary Peritoneal Cancer: A Gynecologic Oncology Group Study,” by Joan L. Walker, MD and colleagues identifies issues and challenges associated with the administration of IP chemotherapy in conjunction with IV chemotherapy. These include proper surgical insertion and maintenance of IP catheters, as well as management of adverse events such as catheter obstruction, infection and bowel complications.

“IP chemotherapy’s success is dependent upon appropriate surgical resection, patient selection, and training of the physicians and nurses,” said Dr. Walker, Chief, Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Oklahoma. “We hope intraperitoneal chemotherapy will be embraced by the oncology community treating ovarian cancer, and will be translated into an improvement in overall survival and quality of life for these women.”

“The Society of Gynecologic Oncologists (SGO) and its members are encouraged by the latest findings on IP chemotherapy,” said Beth Karlan, MD, SGO President and Director of the Women’s Cancer Research Institute and the Division of Gynecologic Oncology at the Cedars-Sinai Medical Center. “IP chemotherapy should be considered by oncologists in women who have had optimal surgical resection for ovarian cancer.”

Ovarian cancer is the leading cause of death from a gynecologic malignancy in the United States. In 2005, the American Cancer Society estimates that there will be approximately 22,000 new cases of ovarian cancer identified in this country and more than 16,000 women will die from the disease.

January 6th, 2006 by Rachel Cunliffe | Comments Off

Link between esophageal cancer and soft drinks debunked

Carbonated soft drink consumption was previously suggested to be linked to the 350 percent increase of adenocarcinoma of the esophagus since the mid-1970s, but researchers at Yale School of Medicine report that the link is unfounded and that there may, in fact, be a decreased risk of this cancer for diet soda drinkers.

The researchers warn that diet soft drink consumers might differ from other groups because they may engage in other unmeasured healthy behaviors. The study is published in the January 4 issue of Journal of the National Cancer Institute (JNCI).

It was hypothesized by others that carbonated soft drinks might have contributed to the development of adenocarcinoma of the esophagus. The theory was based on factors including similar time trends; acidic carbonated soft drinks causing gastric distension that might affect the lower esophagus; and association of carbonated soft drinks with heartburn at night, a known risk factor for esophageal adenocarcinoma.

“The theory that soft drinks could be causing this cancer was picked up by the media and widely disseminated,” said lead author of the Yale study Susan Mayne, professor in the Department of Epidemiology and Public Health at Yale School of Medicine and associate director of the Yale Cancer Center. “However, there was no direct evidence to bear on this hypothesis, until we initiated our analysis.”

Potential causes of esophageal adenocarcinoma were identified by Mayne and her colleagues in a previously completed population-based, multi-center study of 1,095 cancer patients and 687 control subjects. As part of that study, they conducted a full dietary interview and had access to available data on consumption of both regular and diet soft drinks.

“Our team analyzed that data as the first direct test of the hypothesis that soft drinks might have contributed to the increase in this cancer,” said Mayne. “We found that contrary to the hypothesis put forth by other researchers, carbonated soft drink consumption was inversely associated with esophageal adenocarcinoma risk, mainly attributable to diet soda, and that high intake did not increase risk of any esophageal or gastric cancer subtype in men or women.”

January 6th, 2006 by Rachel Cunliffe | Comments Off

Birth control pill could cause long-term problems with testosterone

In the January issue of The Journal of Sexual Medicine, researchers have published a new investigation measuring sex hormone binding globulin (SHBG) before and after discontinuation of the oral contraceptive pill. The research concluded that women who used the oral contraceptive pill may be exposed to long-term problems from low values of “unbound” testosterone potentially leading to continuing sexual, metabolic, and mental health consequences.

Sex hormone binding globulin (SHBG) is the protein that binds testosterone, rendering it unavailable for a woman’s physiologic needs. The study showed that in women with sexual dysfunction, elevated SHBG in “Oral Contraceptive Discontinued-Users” did not decrease to values consistent with those of “Never-Users of Oral Contraceptive”. Thus, as a consequence of the chronic elevation in sex hormone binding globulin levels, pill users may be at risk for long-standing health problems, including sexual dysfunction.

Oral contraceptives have been the preferred method of birth control because of their ease of use and high rate of effectiveness. However, in some women oral contraceptives have ironically been associated with women’s sexual health problems and testosterone hormonal problems. Now there are data that oral contraceptive pills may have lasting adverse effects on the hormone testosterone.

The research, in an article entitled: “Impact of Oral Contraceptives on Sex Hormone Binding Globulin and Androgen Levels: A Retrospective Study in Women with Sexual Dysfunction” published in The Journal of Sexual Medicine, involved 124 premenopausal women with sexual health complaints for more than 6 months. Three groups of women were defined: i) 62 “Oral Contraceptive Continued-Users” had been on oral contraceptives for more than 6 months and continued taking them, ii) 39 “Oral Contraceptive Discontinued-Users” had been on oral contraceptives for more than 6 months and discontinued them, and iii) 23 “Never-Users of Oral Contraceptives” had never taken oral contraceptives. SHBG values were compared at baseline (groups i, ii and iii), while on the oral contraceptive (groups i and ii), and well beyond the 7 day half-life of sex hormone binding globulin at 49-120 (mean 80) days and more than 120 (mean 196) days after discontinuation of oral contraceptives (group ii).

The researchers concluded that SHBG values in the “Oral Contraceptive Continued-Users” were 4 times higher than those in the “Never-Users of Oral Contraceptives”. Despite a decrease in SHBG values after discontinuation of oral contraceptive pill use, SHBG levels in “Oral Contraceptive Discontinued-Users” remained elevated when compared to “Never-Users of Oral Contraceptives”. This led to the question of whether prolonged exposure to the synthetic estrogens of oral contraceptives induces gene imprinting and increased gene expression of SHBG in the liver in some women who have used the oral contraceptives.

Dr. Claudia Panzer, an endocrinologist in Denver, CO and lead author of the study, noted that “it is important for physicians prescribing oral contraceptives to point out to their patients potential sexual side effects, such as decreased desire, arousal, decreased lubrication and increased sexual pain. Also if women present with these complaints, it is crucial to recognize the link between sexual dysfunction and the oral contraceptive and not to attribute these complaints solely to psychological causes.”

“An interesting observation was that the use of oral contraceptives led to changes in the synthesis of SHBG which were not completely reversible in our time frame of observation. This can lead to lower levels of ‘unbound’ testosterone, which is thought to play a major role in female sexual health. It would be important to conduct long-term studies to see if these increased SHBG changes are permanent,” added Dr. Panzer.

Dr. Andre Guay, study co-author and Director of the Center for Sexual Function/Endocrinology in Peabody, MA affirmed that this study is a revelation and that the results have been remarkable. “For years we have known that a subset of women using oral contraceptive agents suffer from decreased sex drive,” states Dr. Guay. “We know that the birth control pill suppresses both ovulation and also the male hormones that the ovaries make in larger amounts during the middle third of the menstrual cycle. SHBG binds the testosterone, therefore, these pills decrease a woman’s male hormone availability by two separate mechanisms. No wonder so many women have had symptoms.”

“This work is the culmination of 7 years of observational research in which we noted in our practice many women with sexual dysfunction who had used the oral contraceptive but whose sexual and hormonal problems persisted despite stopping the birth control pill,” said Dr. Irwin Goldstein, a urologist and senior author of the research. “There are approximately 100 million women worldwide who currently use oral contraceptives, so it is obvious that more extensive research investigations are needed. The oral contraceptive has been around for over 40 years, but no one had previously looked at the long-term effects of SHBG in these women. The larger problem is that there have been limited research efforts in women’s sexual health problems in contrast to investigatory efforts in other areas of women’s health or even in male sexual dysfunction.”

To better appreciate the scope of the problem, oral contraceptives were introduced in the USA in 1960 and are currently used for reversible pharmacologic birth control by over 10 million women in the US, including 80% of all American women born since 1945 and, more specifically, 27% of women ages 15-44 and 53% of women age 20-24 years. By providing a potent synthetic estrogen (ethinyl estradiol) and a potent synthetic progesterone (for example – norethindrone), highly effective contraception is achieved by diminishing the levels of FSH and LH, thereby reducing metabolic activity of the ovary including the suppression of ovulation.

Several studies over the last 30 years reported negative effects of oral contraceptives on sexual function, including diminished sexual interest and arousal, suppression of female initiated sexual activity, decreased frequency of sexual intercourse and sexual enjoyment. Androgens such as testosterone are important modulators of sexual function. Oral contraceptives decrease circulating levels of androgens by direct inhibition of androgen production in the ovaries and by a marked increase in the hepatic synthesis of sex-hormone binding globulin, the major binding protein for gonadal steroids in the circulation. The combination of these two mechanisms leads to low circulating levels of “unbound” or “free” testosterone.

January 6th, 2006 by Rachel Cunliffe | Comments Off

Radiation treatment for breast cancer - new research

Doctors in Canada are studying the effectiveness of permanent radiation seed implants following lumpectomy as an alternative to whole or partial breast irradiation for early-stage breast cancer patients, according to a study published in the January 1, 2006, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology. This type of radiation would cut treatment time for certain patients from several weeks to one day.

For early stage breast cancer, women often undergo a lumpectomy to remove the tumor followed by radiation therapy to kill any cancer cells that may remain. Most women undergo external beam radiation, which is given every day, Monday through Friday, for six to eight weeks. Doctors have been experimenting with ways to shorten this treatment. One technique used by a growing number of radiation oncologists involves the use of temporary radiation implants. These radiation sources are delivered through a catheter into the breast, usually twice a day for one week.

In this study, the first of its kind in the world, doctors wanted to see if it was possible to use permanent implants, like what many men receive to treat prostate cancer, to combat the cancer with only one treatment. These implants, about the size of a grain of rice, would not be removed daily like with the temporary implants. Rather, the radioactive seeds would deliver radiation to the breast area for a number of weeks until they were no longer radioactive. The advantage over the temporary implants is that the patient only has to undergo one surgical procedure to receive the radiation, versus 10 treatments over one week for temporary implants.

The current treatment standard of lumpectomy followed by external beam radiation therapy is proven to keep the cancer from returning, but 38 percent of women develop significant toxicity, which can compromise their quality of life. According to early returns from the study, which began in May 2004, 44 patients have been treated successfully with the permanent implants. So far, none have evidence of their cancer returning and acute skin irritation is six times less frequent when compared to external beam radiation.

“The main motivation was to see if we could reduce the burden of treatment for women suffering from early-stage breast cancer,” said Jean-Philippe Pignol, M.D., Ph.D., lead author of the study and radiation oncologist at Sunnybrook and Women’s College Health Sciences Centre in Toronto, Ontario, Canada. “The seed implants reduce the treatment to a one-time event compared to the current standard of daily treatments over many weeks. The seeds also reduce the amount of radiation the normal breast tissue receives, which lessens the chance of the patient developing problems that affect their post-cancer quality of life. The great thing is that the patient can go home right after the procedure and live a normal life while receiving her radiation.”

January 6th, 2006 by Rachel Cunliffe | Comments Off

DNA polymerase zeta

The DNA in our cells is constantly being bombarded by environmental, chemical and cellular insults. Fortunately, our cells contain many enzymes devoted strictly to detecting and repairing any damage caused by these insults. In fact, failure of these enzymes to make needed repairs to genes can lead to the accumulation of mutations and, eventually, cell death or possibly cancer. However, it appears that the activity of some DNA repair enzymes is more critical than others, particularly in developing embryos. University of Pittsburgh researchers report in the Jan. 1 edition of Cancer Research that a poorly understood enzyme, known as DNA polymerase zeta, or pol zeta, has the uncanny ability to give cells with even heavily damaged DNA a new lease on life. Furthermore, when the enzyme is absent in cells that already have growth control problems, the consequences to chromosomes are catastrophic and may lead to cancer.

“Pol zeta appears to be the only one of a group of specialized DNA polymerases that is critical for development in animals,” explained John P. Wittschieben, Ph.D., research instructor in the department of pharmacology, University of Pittsburgh School of Medicine, and first author of the study. “Moreover, its loss in animal cells plays a significant role in the development of chromosomal instability, which is a hallmark of cancer. Therefore, we believe its function may be to suppress the development of tumors.”

Although DNA polymerases–enzymes responsible for copying, editing and repairing genes and surrounding DNA–generally have the ability to make completely accurate copies of strands of DNA, in certain situations damaged areas, called lesions, can bring this replication machinery to a complete halt. In the last few years, scientists have learned of the existence of a variety of so-called lesion-replicating polymerases that can overcome these replication “stop signs” and keep cells dividing that would otherwise be killed off by their own suicide mechanisms.

First discovered in budding yeast cells, and later in plants and animals, pol zeta has the remarkable ability, in the test tube, to efficiently extend DNA with lesions that stop most other DNA polymerases in their tracks. Other research has shown that inactivation of this lesion-replicating enzyme in yeast leads to a dramatic decrease in the frequency of mutations induced by a wide range of DNA damaging agents.

In this study, Dr. Wittschieben–working in the laboratory of Richard D. Wood, Ph.D., professor of pharmacology, the Richard M. Cyert Chair in Molecular Oncology and director of the molecular and cellular oncology program at the University of Pittsburgh Cancer Institute–sought to determine pol zeta’s key role in mice cells. To do this, Drs. Wittschieben and Wood disabled, or “knocked out,” the gene for pol zeta’s Rev3L subunit, the part with the lesion-replicating capabilities. However, knocking out the Rev3L gene proved lethal to the mice embryos. The investigators nevertheless isolated fibroblasts from these embryos to see if they could be kept alive in culture. After repeated attempts, the mouse embryonic fibroblasts, or MEFs, failed to divide and died within a few weeks or months.

Suspecting that the MEFs were dying because they were self-destructing, or undergoing apoptosis, the investigators then knocked out the gene for a protein known as p53, which is a cell-suicide-signaling molecule. After matings between the p53 knockout mice and Rev3L knockout mice, the investigators isolated and cultured MEFs from all the offspring of the matings to see if any would grow. Unfortunately, the cells all failed to divide. However, three months later, some cells began to grow and at a surprisingly robust rate.

“Once the cells in which Rev3L and p53 had been knocked out began to divide, they did so very rapidly,” said Dr. Wittschieben. “Because the only Rev3L-deficient cells that began dividing also were p53 deficient, we believe that knocking out their apoptotic mechanism was key to this viability. However, they didn’t begin dividing right away, so something else must have happened. We are still not sure what that something else is.”

When the investigators looked for evidence that these cells were different from normal cells, they didn’t have to look far. Examination of the cells’ chromosomes showed not only a dramatic ten-fold increase in the incidence of swapping and fusing of genes and other genetic material between chromosomes, but also an increase in the number of chromosomes compared to normal cells.

The high frequency of DNA rearrangements in Rev3L/p53-deficient cells suggests that pol zeta in normal cells is responsible for preventing double-stranded breaks from occurring in chromosomes. When pol zeta is absent, it leads to a massive amount of double stranded breaks, some of which are repaired correctly and others that are repaired incorrectly by being fused to other genes or chromosomes.

According to Dr. Wood, these findings have significant implications for human cancer research, in that such a high degree of chromosomal instability is a characteristic of cancer cells. Furthermore, the human Rev3L gene is located in a segment of chromosome 6 where multiple tumor suppressor genes are believed to reside and a slew of human cancers, including a number of leukemias and lymphomas, are associated with chromosomal instabilities in this particular region of chromosome 6.

“Although it requires further investigation, we believe that mutations in this part of chromosome 6 could occur during the development of some cancers and this may have prognostic and therapeutic implications. We are now investigating this hypothesis by selectively deleting the Rev3L gene in adult mouse cells to study how the loss of DNA polymerase zeta influences the development and progression of spontaneous cancers,” explained Dr. Wood.

January 6th, 2006 by Rachel Cunliffe | Comments Off


  • nintendo ds lite download music
  • tujhe yaad na meri aayee mp3 download songs pk
  • download house 8 temporada legendado
  • chicken invaders 4 download free full game
  • sony ericsson w705 games
  • norton antivirus download 90 days trial version
  • main aisa hi hoon songs download pk
  • baixar cd exaltasamba 25 anos
  • free download song chanda ki doli mein
  • free full hd bollywood movie download in hindi
  • download perreame jowell y randy ft wisin y yandel
  • pyar to hona hi tha hindi movie songs free download
  • 3r black cherry download free
  • download like a g6 getter remix
  • tweakui windows xp free download
  • download 8 ball pool multiplayer hack
  • download font thai th niramit
  • 945gct-hm motherboard drivers download
  • corel draw 13 download crack
  • zindagi ek jua mp3 songs free download
  • free download driver printer epson lx 800
  • virtual dj le software download
  • queen we will rock you remix mp3 free download
  • gangnam style official music video 3gp download
  • pokemon gold version free download pc
  • garmin gps 76 download
  • ik junoon video song download
  • download virtual dj home free 7.0.4
  • ek glassy do glassy mp3 download free
  • latest opera download windows 7 free
  • download map pb untuk cs
  • download pc games online uk
  • xem phim dong yi tap cuoi han quoc
  • download game hp nokia n-gage qd gratis
  • download megaman x7 pc free full version
  • corel draw x4 download portugues gratis baixaki
  • check if solaris 10 64 bit
  • windows update activex download
  • download big boi for your sorrows
  • kleerup until we bleed mp3 download
  • download videos youtube 3gp format
  • download cd rock nacional anos 80 90
  • download dragon ball z movie 8 broly legendary super saiyan
  • visual c 2008 express edition offline download
  • download software samsung yp-t7j
  • fifa 08 free download pc full version
  • download k-9 movie free
  • .net2.0 software free download
  • download music last fm xbox
  • baixar livro a ultima musica em pdf
  • minolta qms magicolor 2300dl driver download
  • yugioh ́5d para nintendo ds download
  • virtual dj download 5.2 free
  • how to download from youtube
  • download corel draw x4 completo portugues free
  • avast v4.8 download
  • wwe impact v3 downloadable content
  • game ft tyler creator martians vs goblins free download
  • vlc .9 download mac
  • skype nokia n97 mini free download
  • download keyshia cole woman to woman deluxe zip
  • driver hp laserjet 1010 windows 7
  • download blackberry os 7.1 for curve 8520
  • corel draw x5 free download full version with keygen
  • apple store 10 billion download
  • world war z download ebook
  • game.co.uk downloads mac
  • xl hate yourself mp3 download
  • hp officejet 6500 wireless download software
  • google sketchup free download pc
  • download chelsea smile kc blitz remix
  • free download hindi movie love aaj kal video songs
  • download cars tm nation forever
  • sony vegas movie studio platinum 9 free download
  • l's theme song b download
  • download power dvd player for windows xp
  • download google maps for android apk
  • download de filmes gratis avi
  • flash mx download completo portugues serial
  • mortal kombat 9 downloadable characters release date
  • 1920 evil returns aye khuda mp3 songs free download
  • sony psp emulator pc free download
  • windows xp sp3 download completo portugues gratis iso
  • 3 bachelors mp3 songs free download
  • rockstar games gta 4 download pc
  • windows live messenger download for winxp
  • how to download video from jw player for mac
  • 30 minutes less download link
  • dr. house download all seasons
  • how to download wp database
  • download youtube 2 mp3 converter free
  • no download itunes gift card generator
  • gta samp download 0.2x
  • animated themes for nokia 5310 xpressmusic free download
  • download b13 ultimatum movie
  • qb pdf converter download
  • how to download music onto your htc wildfire s
  • um beijo luan santana download busca mp3
  • top radio zu download iunie 2011
  • sap fico certification material free download
  • download fifa 09 game for pc
  • gta iv game free download for mobile
  • download game kung fu nguoi que
  • motogp 2 game free download for pc
  • alone - i.n blue mp3 download
  • fb password hacker free download-mediafire
  • dd-wrt download v24 sp2
  • jailbreak iphone 3g free download
  • how to download dd-214
  • hd writer ae 1.0 download free
  • go launcher ex theme xperia free download
  • download accelerator plus 8.7.0.5 full version free download
  • download crack megaman x8 pc
  • dota maphack 1.26a download
  • audi a3 repair manual download
  • download mp3 cutter java
  • spss download gratis
  • capital t - u be gone mp3 download
  • windows xp backup utility download free
  • 3gp to wmv video converter free download
  • ms office 2007 free download full version for windows xp
  • download break up ke baad song
  • free download 32 bit itunes windows 7
  • pspgodownloadcenter.com review
  • usher dj falling in love mp3 song download
  • download wwe cm punk new theme song 2011
  • download mustek dv4000 driver
  • download mp3 song aye mere watan ke logo
  • download google earth for free 2010 latest version
  • download itunes app for android
  • download gratis do navegador internet explorer 8
  • download filme glee live 3d legendado
  • download fifa 13 demo for pc origin
  • download grey's anatomy 8a temporada legendado
  • how do you download songs on a blackberry curve
  • nicky asu feat bobby pe cine iubesc download free
  • mp3 download app for galaxy s3
  • kc and jojo all my life free music download
  • php code generator free download full version
  • download kesha cannibal zip
  • download hack mii installer v0.5
  • mm karavani telugu songs download
  • written stars mp3 download free tinie
  • avaya ip office manager download software
  • ek niranjan songs download mp3
  • pinnacle hollywood fx volume 3 free download
  • p90x workout guide download
  • download 143 ray j bobby brackins
  • download songs of nsync
  • dedication 4 free mp3 download
  • download here am bryan adams mp3
  • flight radar 24 download free
  • 50 cent - ok you' are right download mp3
  • free download song jhonka hawa ka aaj bhi
  • woh lamhe mp3 free download songs
  • dr dre feat eminem need doctor free mp3 download
  • age empires 3 full version free download windows 7
  • best resume format download ms word
  • download facebook chat for nokia 2690
  • nokia c3 black list software free download
  • download theme blackberry 8520 curve free
  • ko tamil movie songs free download zip
  • ie9 download 64 bit vista
  • gta vice city game free download full version pc cnet
  • download free music htc wildfire s
  • how to download psp games for free full version
  • download map dota allstars v6.64
  • download full version adobe acrobat reader x
  • mozilla firefox download for mac os x 10.4.11
  • ios 6 itunes match download individual songs
  • am legend movie download mp4
  • vr holden commodore workshop manual download
  • she so high above me download mp3
  • baixar filme a era do gelo 4 dublado avi
  • ad-aware 2008 no connection to download server
  • descarga de videos de youtube gratis online
  • download entire website linux
  • laserjet 6l download driver
  • o diario de tati o filme download
  • hp officejet pro 8500 driver download windows xp
  • canon rebel xs driver download
  • songs.pk english songs mp3 free download akon
  • download twilight saga breaking dawn part 2 gratis
  • uc browser cloud download for nokia c2-01
  • fifa 11 download game free pc
  • iu new album download
  • download a origem legendado avi
  • free download football manager 2013
  • free download yaad piya ki aane lagi song
  • free download audi a4 repair manual
  • esto es lo que soy free download
  • cd will not import into itunes
  • download quick boot -v2.1
  • download web browser windows 98
  • fast can download 1gb file
  • how do you download music from itunes to iphone 4
  • meek mill rick ross ima boss mp3 download
  • ps2 games free download iso
  • download java compiler for mac
  • download blackberry software update bold 9000
  • adobe flash player free download for samsung galaxy s2
  • ver y descargar peliculas gratis en español 1 link
  • download adobe flash player 10 for linux
  • microsoft security essentials update download 64 bit
  • free mp3 download got your back t.i keri hilson
  • resident evil 6 download pc free
  • richard muller uz download mp3
  • turning 30 movie download dvd rip
  • download do internet explorer 8
  • download song sanu ek pal chain na aave mp3
  • ek deewana tha movie mp3 download
  • download windows 98 virtual machine vmware
  • herb black eh king download
  • download beautiful free fonts
  • free download bootable windows xp sp2
  • free download pari hoon main by sunita rao
  • jab tak hai jaan mp3 songs free download for mobile
  • free download fool you cee lo green
  • download brian lara international cricket 2007 full version pc
  • free pc educational games for kids download
  • c visual studio express download
  • download games xperia x10i free
  • download virtual dj setup
  • directx 11 download windows 7 32 bit
  • download need love ll cool j
  • redsnow 0.9. 8b4 download
  • uk top 100 music download
  • download xp home sp3
  • daughtry - tennessee line download mp3
  • download windows 98 plus themes windows xp
  • adobe photoshop mac download cracked
  • free download mobile games for nokia c2-01
  • yu-gi-oh download game
  • download hd writer ae 1.5
  • download clip bao cong xu ton ngo khong full
  • how do i download youtube videos to my blackberry playbook
  • download game dynasty warriors 7
  • download do filme amor alem da vida legendado
  • microsoft windows xp download games
  • lak 28 kudi da 47 weight kudi da mp3 free download
  • download de grand chase 3 season
  • ramanichandran tamil novels pdf free download
  • java 1.3 free download for windows xp
  • iphone 2g 3.9 bootloader download
  • free full movies online to watch now without downloading
  • download phim tan loc dinh ky - truong ve kien
  • final fantasy 13 free music download
  • rarbg software free download
  • a to z video converter download
  • virtual ti-83 plus rom download
  • download driver sato cx series
  • download musica dragon ball z budokai 3
  • patch v23 do cs 1.6 non steam download chomikuj
  • rc build 7100 download
  • garena client free download latest version
  • death note l's theme mp3 free download
  • download e72 games free
  • nba live 2003 demo free download
  • om shanti om hindi mp3 songs download free
  • lil wayne tha carter 3 album download zip
  • download lagu b'z don't wanna lie
  • avira antivirus update free download 2012
  • o universo history channel 2 temporada download
  • usb bootable xp software download
  • ajab prem ki ghazab kahani mp4 video songs free download
  • download tu dien lac viet 2008 mien phi
  • download hair sims 3 free mac
  • hp usb disk storage format tool download win 7
  • u2 live in chicago 2005 for download
  • corel draw x4 download free crack
  • free download opera for nokia c2-03
  • itunes 9.2 free download mac
  • pokemon season 15 free download
  • dil pardesi ho gaya film songs download
  • download hp laserjet 5n driver
  • download kk songs collection
  • rs agarwal download verbal nonverbal reasoning
  • canon eos 7d manual free download
  • download phan mem diet virus bkav 2011 mien phi
  • free download sql interview questions and answers pdf
  • manual sony h9 download
  • jailbreak ps3 firmware 3.56 download
  • microsoft sql server 2008 r2 service pack 2 download
  • download ps i love you movie in hindi
  • ld assistant free download
  • download games psp iso free
  • redsnow 0.9.6b1 download for windows
  • 50 cent feat. nate dogg - 21 questions download mp3
  • download lagu cn blue album first step
  • mp navigator download windows vista
  • windows 98 2nd edition update
  • youtube video mp3 converter free download mac
  • free download movie maker windows 7 starter
  • download four letter word by diggy simmons
  • windows live movie maker 2012 beta download
  • kolaveri di download 3gp hd
  • sd gundam online download malaysia
  • ptcl evdo drivers download
  • download videos from youtube online for free
  • 20 20 cabinet design software free download
  • download jlc internet tv 2010
  • g download xcode
  • mp3 player free downloads kids
  • vr-networld update 4 download
  • download nero 8 serial download
  • os 4.3.5 ipsw direct download links
  • xem phim song hung ky hiep tvb
  • ek dantaya mp3 song free download
  • ra one criminal full video songs free download mp4
  • cd luan santana ao vivo mp3 download
  • song lyrics n dubz morning star
  • download auto joiner 4.9.1
  • free download mere brother ki dulhan ringtones
  • play free online hidden object games no download required
  • can download windows xp mode
  • download pdf tutorial for photoshop