Archive | January, 2011

Antibiotic May Slow Bladder and Breast Cancer Cell Growth

Researchers have recently found that a common antibiotic prescribed for urinary tract infections may additionally slow and even stop the growth of breast and bladder cancer cells.  The study was performed by researchers at John Hopkins University School of Medicine.

Nitroxoline is the antibiotic of interest.  Traditionally, nitroxoline is used as a urinary antibacterial agent to combat the organisms commonly found in urinary tract infections.  However, the John Hopkins’ findings show that the antibiotic also blocks the formation of new blood vessels that fuel tumors.  With these results, nitroxoline may become a potential therapeutic agent for cancer.

“Angiogenesis, the growth of new blood vessels, plays an important role in tumor growth and metastasis, so inhibiting angiogenesis is a promising strategy for developing new anticancer drugs,” Dr. Jun O. Liu, a professor of pharmacology and molecular sciences at John Hopkins, said in regards to the findings.

More than 177,000 chemical compounds and drugs were tested.  The researchers were studying each drug’s ability to block the activity of a protein in order to inhibit the formation of new blood vessels.  The results were astonishing:  nitroxoline blocked more than 99 percent of the blood vessels at a low and safe concentration.

Even more promising is the fact that when the antibiotic was tested in mice, the treatment reduced breast cancer cell tumor volume by 60 percent and bladder cancer cell tumor by more than 50 percent.

Although the usage of nitroxoline to prevent the growth of bladder and breast cancer cells is promising, more clinical trials need to be conducted before a serious recommendation for treatment of bladder and breast cancer may be made.

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MicroRNA Treatment for Prostate Cancer

According to a recent study, a small slice of RNA has been found to inhibit the spread of prostate cancer, or prostate cancer metastasis.  This special type of RNA, called microRNA (miRNA), suppresses a surface protein commonly found on prostate cancer stem cells.

According to lead author Dean Tang, PhD, professor in MD Anderson Cancer Center’s Department of Molecular Carcinogenesis, the research results are the first of its kind to profile a microRNA expression pattern in prostate cancer stem cells, while also establishing a strong rationale for developing the microRNA miR-34a as new prostate cancer treatment options.

MicroRNA consists of short, single-stranded bits of RNA that regulate the messenger RNA expressed by genes to create a protein.  The issue with cancer stem cells is that they have an enhanced ability to initiate tumors.  Further, they are capable of self-renewal and are more resistant to treatment than other cancer cells.  In fact, tumor recurrence and metastasis are highly associated with cancer stem cells.  Such capacities are even more prevalent in cancer cells that feature CD44, which is a specific cell surface protein.

CD44 has long been associated with tumor development and cancer metastasis.  Cancer stem cells over-express this protein, making the process of identifying a target easier.  Dr. Tang’s study identified CD44 as a “direct and functional target of miR-34a.”

Through a set of lab experiments with cell lines, human xenograft tumors in mice and primary human prostate cancer samples, scientists were able to demonstrate that miR-34a suppresses CD44, thereby inhibiting prostate cancer stem cells.  The study also found that miR-34a is significantly reduced in prostate cancer cells that express high levels of CD44 on the cell surface.  The results show that prostate tumors in mice that received miR-34a treatment were one-third to half the average size of those in control group mice.

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Sexual Function May Improve After Prostate Surgery

Hope is still alive for men’s sexual function after prostatectomy.  Mainly, those men who are still experiencing erectile function two years after surgery may still see an improvement in function.  This improvement may leave men able to sufficiently function during sexual intercourse.

“The message to patients who have erectile dysfunction—even those who have failed to have erections after surgery—is that improvement does occur in a substantial number of men,” says researcher Jeffrey  Schiff, MD, a resident in urology at the State University of New York Downstate Center in Brooklyn, New York.

According to Dr. Schiff, nearly one-third of men with marginal erectile function and one-fourth of men with serious erectile dysfunction after surgery continue to have improvement in erectile function on follow-up visits, even 24 months after the surgery was performed.

Schiff and fellow researchers examined the medical records of 128 men who had a radical prostatectomy and were evaluated for erectile function at follow-up visits to the doctor.  The men were asked to rate their level of erectile function on a 5-level scale, with 1 corresponding to normal function and 5 representing no erections.

Before the surgery, two-thirds of the men evaluated themselves at level 1, meaning they had normal erectile function.  The remaining one-third said they had diminished erections, but were still able to have intercourse.

After surgery, however, 51 men had rated themselves at level 3, meaning “partial erections occasionally satisfactory for intercourse.”  At subsequent follow-up visits, 10% of these men had normal functioning and 22% recovered enough to have intercourse, although they did have diminished erections.

Eighty-seven men rated themselves at level 4 or 5, corresponding to partial erections not sufficient for intercourse, or no erections two years after surgery.  Of these men, 1.1% recovered to normal erections and 10% recovered diminished erections, routinely sufficient for intercourse.  Thirteen percent recovered partial erections occasionally satisfactory for intercourse.

Although those men who experienced the most severe erectile dysfunction still did not see any improvement after three years, men who had partial erections that were occasionally sufficient for intercourse continued to make progress for up to four years after surgery, explains Schiff.

“It’s common for men to have erectile dysfunction after prostatectomy and this shows they shouldn’t get discouraged if sexual functioning doesn’t come back right away,” says AUA spokesman Ira Sharlip, MD, of the University of California, San Francisco.  “Even after two years, many will still improve.”

One confounding factor of the study is that about half the men in the study who suffered from sexual dysfunction took ED drugs like Viagra.

“This was not a controlled experiment, so we don’t’ know if these drugs were helpful in overcoming erectile dysfunction,” says the study’s head, Farhang Rabbani, MD, associate professor of urology at Montefiore Medical Center.

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How to Manage the Side Effects of Androgen Deprivation Therapy

With modern advancements in medical technology, prostate cancer can now be detected much earlier, thus allowing treatments to start sooner.  Before, cancer was not diagnosed until the patient was symptomatic, so the side effects of cancer had to be endured.  Today, patients do not need to suffer from prostate cancer but, instead, the side effects of androgen deprivation therapy are more prevalent.

Researchers and medical practitioners have agreed that supportive care needs to be given to both prostate cancer patients and their partners when patients begin ADT.  The consensus came about after an in-depth review of strategies for managing the side effects of the treatment.

Many studies have been conducted in regards to the physiological side effects of ADT; however, the new study focused mainly on the psycho-social and sexual problems associated with androgen deprivation.  These problems are often understated, despite the severity and the significant decrease in quality of life in those patients experiencing the side effects.  Unfortunately, patients are not informed of the full extent of such psycho-social issues before they seek out ADT.

Evidence suggests that the partners of patients who are androgen-deprived are often more distressed than the patients themselves.  This means that ADT has epidemiological impacts on others.  More attention needs to be given to the patients’ partners in order to help mitigate the negative side-effects of the treatment.

The partners of ADT patients feel emotionally abandoned when the libido of the patient decreases.  This often leads to tension in the relationship, which is only exacerbated by the differences in coping mechanisms in men and women.  While women normally adopt strategies that involve discussing the issue, men prefer strategies that include denial or avoidance.

Ignoring the psychological challenges that ADT brings to the partners compromises the health and welfare of the patients themselves.  According to one study conducted in 2008, psychological distress of the female partners actually predicts the ultimate health of male patients.  “Women’s distress predicts men’s physical health, over and above the men’s distress…age, and cancer stage,” explains Dr. Kim, one of the authors of the 2008 study.  Such effects on the patients’ health are detrimental, and prove that the health and welfare of the partners of prostate cancer patients on ADT should be a concern of the prescribing physician.

In order to provide the best medical care for prostate cancer patients, support must be given to both the patient and his partner.  If psychological support programs are not available at a referring physician’s clinic, then referrals for mental health professionals or community-based organizations in the area must be given to the patient and partner.  Then, strategies may be given for maintaining intimacy (both sexual and non-sexual) during ADT.

Many prostate cancer patients’ partners are reluctant to admit problems in front of their partners.  Because of this, suggestions or inquiries should be given individually in order to locate an issue.  But what a physician cannot do is simply ignore or allow such intimacy problems to remain undiagnosed.  Those couples who are fully informed at the time that ADT is prescribed and are aware of what to expect from the treatment can be provided with effective strategies to manage the side effects and fare better than couples provided with usual care.

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New Prostate Cancer Recurrence Prediction Method

A new test to determine prostate cancer recurrence has been developed by Myriad Genetics, Inc.  The 46-gene prognostic test is called Prolaris™, and works by quantitatively determining the risk of recurrence in patients who have undergone prostatectomy surgery.  With this new launching, physicians now have a direct molecular measure of a prostate tumor’s capacity to divide and grow by examining the mechanics of growth at the molecular level.

“After undergoing a radical prostatectomy, men often worry about their continuing risk of cancer recurrence,” said Peter R. Carroll, M.D., M.P.H., Professor and Chair, Urology, University of California, San Francisco.  “Prolaris may offer very important information to the patient and his physician about the risk of his cancer recurring.”

Prolaris is actually a molecular diagnostic assay that provides urologists with more accurate results that can be used to determine the risk of recurrence of prostate cancer.  This new technology is based on cell growth and tumor biology and provides quantitative measures of the expression levels of multiple genes related to progression of the cell cycle.

The test provides results at a 95% accuracy level, which can give men the confidence they need for aggressive treatment.  Men with high Prolaris scores can then be considered for more intensive screening and therapy to address the disease.  Additional clinical tests and studies will be performed in order to expand the utility of Prolaris.

“Prolaris is a valuable additional tool that will enable urologists to provide an accurate, individualized recurrence risk score to men who have undergone a radical prostatectomy,” stated Mark C. Capone, President, Myriad Genetic Laboratories, Inc.  “We view Prolaris as the first of a strong emerging stable of RNA signature tools based on fundamental tumor biology which Myriad will offer to the urology/oncology community.”

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Are Phytoestrogens Safe for Women?

Phytoestrogens are a group of naturally occurring, plant-derived compounds that have either a weak estrogenic or anti-estrogenic effect.  Recently, these compounds have gained popularity among women as dietary estrogens or as menopause treatment regimes.  Further, several large women’s health trials have suggested health risks in women taking hormone replacement therapy for menopausal symptoms, thus increasing the demand for alternative treatments, such as phytoestrogens.

Four major groups of phytoestrogens exist.  The first group contains the flavonoids, including genistein, naringenin, and kaempferol.  Coumestans, such as coumestrol, make up the second group.  The third group is the lignans, such as enterodiol and enterolactone.  Finally, the fourth group includes the most widely known and studied phytoestrogens:  the isoflavones.  Isoflavones are found in red clover and soy and include formononentin, biochanin, and daidzein.

Previous urological studies have suggested that diets high in soy, like those in Asia, have a protective effect on men against development of prostate cancer.  But studies conducted for the effect in women generate conflicting results.  Some results indicate a protective effect against breast cancer, while some in vitro studies differ on whether they hinder or help tumor cell growth.

The differences in results may be due to the wide variety of phytoestrogens.  For example, some of these compounds are weakly estrogenic and bind the estrogen receptor about 1,000 times weaker than estradiol.  And other phytoestrogens block the effect on the estrogen receptor.  Even the well-known isoflavones in soy show mainly an agonist, yet weak, estrogen effect.

Whether or not soy compounds can lead to side effects such as endometrial hyperplasia or cancer is not known.  In addition, it still remains unclear as to whether or not genistein antagonizes the inhibitory effect of tamoxifen on breast cancer cell growth in vivo.

A recent study from Austria has attempted to clarify the safety of phytoestrogens by analyzing all known English studies.  The researchers analyzed 174 randomized controlled trials that compared phytoestrogens to placebos.  In 82 of these trials, no side effects were discussed.

For the remaining studies, the researches focused on several categories of side effects, including gastrointestinal, gynecological, urinary, neurological, and musculoskeletal.  The most common side effects found among women were GI complaints like nausea, vomiting, heartburn, gastric irritation, or pain.  Women older than 55 had a higher rate of these GI symptoms.  U.S. and European studies were less likely to indicate the GI side effects.  In addition, the length of the trial did not lead to a higher incidence of side effects.  Instead, fewer side effects were actually observed the longer the women remained taking phytoestrogens.  Other side effects found in the trials were muscle pain and sleepiness.

The potential gynecological side effects the women reported were vaginal spotting, nipple discharge, breast pain/enlargement, breast cancer, endometrial hyperplasia, and pelvic pain.  One study showed a higher rate of endometrial hyperplasia with atypia after five years of phytoestrogen supplementation.  However, no increased risk of endometrial cancer or breast cancer was found.  Further, the researchers found no indication of other side effects that occur with hormone replacement such as stroke, blood clots, heart attack, and breast cancer.

Overall, the study presented results that allowed the authors to conclude that phytoestrogens can safely be used over a two year period.  With only GI upset noted as the major category of significant side effects, and no endometrial or breast cancer risk was observed, the authors felt comfortable about the safety of phytoestrogen supplementation.

Although phytoestrogens are considered natural and safe, when it involves hormone manipulation caution should be taken.  Long term studies, or those that follow the patients for more than five years, still need to be conducted.  These compounds should be taken in moderation.  Just because compounds occur in nature doesn’t automatically make them safe or healthy in large, uncontrolled quantities.

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Risks of Gastric Bypass Surgery

In addition to the common risks associated with surgery in general, such as infection, blood clots, or even death, gastric bypass surgery may have an even more specific risk:  kidney stones.

Urological researchers at UT Southwestern Medical Center report that the urine composition of those patients who undergo gastric bypass surgery experience changes that may increase their risk of developing kidney stones.

The new study, published in the March issue of The Journal of Urology, found that some of these urinary changes place weight-loss surgery patients at higher risk for developing kidney stones than obese patients who do not undergo the procedure.

Investigators of the gastric bypass surgery study collected urine samples from 38 participants.  Among those participating were 16 women and three men in each of two groups.  One group had undergone Roux-en-Y gastric bypass (RYGB) surgery, while the second group contained normal obese individuals.  RYGB is one of the most commonly performed weight-loss procedures and involves the creation of a small gastric pouch that allows food to bypass part of the small intestine.

A material called oxalate was found in urine of RYGB patients at significantly elevated levels when compared with those participants who did not have the surgical procedure.  In addition, the amount of the chemical citrate in the urine was low in many gastric bypass patients when compared to the obese nonsurgical group.

The importance of these findings is that oxalate is found in the majority of kidney stones, while citrate inhibits stone formation.

“Almost half of the patients who had undergone gastric bypass and did not have a history of kidney stones showed high urine oxalate and low urine citrate—factors that lead to kidney-stone formation,” said Dr. Naim Maalouf, assistant professor of internal medicine in the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research and the study’s lead author.

Dr. Maalouf is concerned over the study’s result and feels that weight-loss surgery patients and their physicians should be alerted of the heightened risk of kidney stones.

“These findings illustrate that the majority of patients are at risk for kidney-stone formation after RYGB,” Dr. Maalouf said.  “This complication may not be well-recognized in part because it tends to occur months to years after the bypass surgery.”

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One-Size-Fits-All Kidney Disease Care Is Not Effective

Researchers have known that age, race, and diabetes status all affect an individual’s blood pressure and, consequently, the risk of premature death.  But previous research also indicates that mild to moderate hypertension may not actually increase dialysis patients’ risk of dying prematurely.  These findings conflict with those found in the general population and are generalized to diverse groups of patients with kidney disease.

In order to investigate this conflict, Philip Zager, MD, Orrin Myers, PhD, and colleagues began a new study.  The goal is to see if age, race, and the presence or absence of diabetes affects the relationship between blood pressure and risk of premature death among dialysis patients.  The researchers studied medical information from 16,283 dialysis patients.

The results show how important diversity is in managing care for patients.  First, low systolic blood pressure was found to be associated with increased risk of premature death, particularly among older patients and patients with diabetes.  Second, higher systolic blood pressure was associated with increased risk of premature death among younger patients, regardless of race or diabetes status.  Third, older black patients had a survival advantage over older patients of other races.  And fourth, diabetes was associated with increased risk of premature death mainly among older patients with low blood pressure.

The importance of these findings is that age and diabetes status have not been taken into as much consideration as needed when identifying optimal blood pressure ranges for dialysis patients with kidney disease.

“This is certainly one of the best observational studies to pay attention to how outcomes are different in certain patient groups,” note Deidra Crews, MD, and Neil Powe, MD, MPH, MBA.

These results raise a number of questions for clinicians as they address blood pressure in dialysis patients.

“Let’s hope that soon we will generate the evidence needed to guide the often complicated blood pressure management of our patients,” stated Dr. Crews and Dr. Powe.

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