Vitamin D supplements could improve fertility

Vitamin D, a hormone produced by the body through exposure to sunshine or obtained from foods such as fatty fish and egg yolk, helps the body control calcium and phosphate levels. Previous studies have linked vitamin D levels with a range of health problems including cardiovascular disease and cancer.

Up to 80% of the population in Europe are affected by low vitamin D levels. As this is particularly common amongst people who lead unhealthy, sedentary lifestyles, low vitamin D levels have been associated with obesity; at the same time as obesity is rising, vitamin D levels are falling. In addition, female fertility and semen quality have deteriorated in the recent years due to largely unknown causes. Infertility rates amongst couples who want to have children are at 10-15%, and up to 10% of women of reproductive age suffer from polycystic ovary syndrome (PCOS), a condition which may hinder fertility.

Dr Elisabeth Lerchbaum, from the Medical University of Graz, has led much research on the effects of vitamin D supplementation in different aspects of male and female fertility. Research from her group and others suggests vitamin D affects many aspects of fertility in both genders, including influencing production and maturation of sperm cells in men, egg cell and uterine lining maturation in women, and sex hormone production in both sexes. Vitamin D levels have been associated with in-vitro fertilisation (IVF) outcome, some features of PCOS and endometriosis in women. In men, levels of vitamin D have been linked to semen quality and male hormone levels in both fertile and infertile men.

Bare bones: Making bones transparent

The research was done in the laboratory of Viviana Gradinaru (BS ’05), assistant professor of biology and biological engineering and a Heritage Medical Research Institute Investigator. It appears in a paper in the April 26 issue of Science Translational Medicine.

In healthy bone, a delicate balance exists between the cells that build bone mass and the cells that break down old bone in a continual remodeling cycle. This process is partially controlled by stem cells in bone marrow, called osteoprogenitors, that develop into osteoblasts or osteocytes, which regulate and maintain the skeleton. To better understand diseases like osteoporosis, which occurs when loss of bone mass leads to a high risk of fractures, it is crucial to study the behavior of stem cells in bone marrow. However, this population is rare and not distributed uniformly throughout the bone.

“Because of the sparsity of the stem cell population in the bone, it is challenging to extrapolate their numbers and positions from just a few slices of bone,” says Alon Greenbaum, postdoctoral scholar in biology and biological engineering and co-first author on the paper. “Additionally, slicing into bone causes deterioration and loses the complex and three-dimensional environment of the stem cell inside the bone. So there is a need to see inside intact tissue.”

To do this, the team built upon a technique called CLARITY, originally developed for clearing brain tissue during Gradinaru’s postgraduate work at Stanford University. CLARITY renders soft tissues, such as brain, transparent by removing opaque molecules called lipids from cells while also providing structural support by an infusion of a clear hydrogel mesh. Gradinaru’s group at Caltech later expanded the method to make all of the soft tissue in a mouse’s body transparent. The team next set out to develop a way to clear hard tissues, like the bone that makes up our skeleton.

High rates of satisfaction for applicator free local estrogen softgel ovule

“These survey results show that something as simple as a change to a more elegant delivery system that is easier to use and not messy might empower more post-menopausal women to seek prescription treatment for VVA, and perhaps help them stay with the application guidelines for longer,” said study first author Sheryl Kingsberg, PhD, Division Chief, OB/GYN Behavioral Medicine, UH Cleveland Medical Center; Professor of Obstetrics and Gynecology and Psychiatry, Case Western Reserve University School of Medicine; and first author of the survey analysis. “We still have to find better ways to educate the millions of women suffering with VVA about the symptoms, however, so that more of them know it is common, decide to discuss treatment with their healthcare professional, and seek symptom relief with appropriate treatment.”

The new results were part of a multi-center randomized, placebo-controlled phase 3 clinical trial for TX004HR, an investigational bio-identical 17?-estradiol applicator free vaginal softgel capsule. Previous publications have shown TX004HR to be safe and effective at alleviating symptoms of VVA. The survey, which included 731 respondents with a 96 percent response rate, sought to quantify participants’ satisfaction with the application method and overall treatment delivery system. The majority of women taking either TX004HR or placebo (85.4 — 92.1 percent) found the product easy to use.

VVA is a chronic condition associated with genitourinary syndrome of menopause (GSM). VVA affects 50 to 70 percent of post-menopausal women, and is characterized by pain with sexual activity, dryness, and discomfort. Current on-the-market treatments for VVA include both over-the-counter creams and moisturizers as well as several safe and effective prescription treatments in cream, tablet, ring or oral form.

Previous survey research completed by Dr. Kingsberg and others has shown that while 32 million women may be experiencing symptomatic VVA and suffering from related impacts on sexual function, interpersonal relationships, self-esteem and overall quality of life, only 7 percent are currently using a prescription therapy to alleviate symptoms. Though they may suffer from physical and emotional pain as a result of VVA, women may not feel comfortable discussing these symptoms with a healthcare professional, may not recognize the symptoms as treatable, may not fully understand the treatment options available, or if they did receive treatment, found the current prescription treatment options inconvenient, messy, or uncomfortable to use.

Potential breakthrough in determining who’s at risk for heart attacks

The notion that soft plaque is more likely to rupture and cause heart attacks than hard calcium deposits in coronary arteries may be wrong, according to the new study that will be presented at the American College of Cardiology Scientific Sessions in Washington, D.C., on March 18.

Atherosclerosis is caused when plaque builds up in the arteries, narrowing and hardening them.

“We previously thought the lipid-laden soft plaque was more likely to rupture and cause heart attacks, but based on our new research, it’s more the calcified plaque that appears to be associated with adverse cardiovascular events” said Brent Muhlestein, MD, one of the study’s authors and co-director of cardiology research at the Intermountain Medical Center Heart Institute in Salt Lake City.

Intermountain Medical Center Heart Institute researchers had earlier teamed with Johns Hopkins School of Medicine and National Institutes of Health scientists to analyze the composition of plaque from 224 patients who had diabetes, but no heart symptoms.

This new research reflects more long-term findings after patients were followed for an average of nearly seven years to see if their plaque composition had predicted whether they’d have a cardiac event.

In this study, through careful quantitative evaluation, the composition of coronary artery plaque identified in the subjects through CT coronary angiography was stratified proportionately into amounts of soft, calcified, and fibrous plaque and compared with future risk of unstable angina, heart attack or death.

Color change test to help cancer research advance

Researchers know that patients with several types of cancer, including prostate cancer, have higher than normal levels of a protein called AMACR, and that the protein is linked to the aggressiveness of the cancer. Lowering levels of AMACR reduces the growth of cancer cells, and these cells revert to more ‘normal’ behaviour.

However exploitation of these discoveries has been slow because of the lack of a test to easily measure functional levels of AMACR.

Now scientists from the Department of Pharmacy & Pharmacology have created a simple and cheap test that turns a clear liquid bright yellow in the presence of the functional protein, within minutes. The research is published in the leading journal Chemical Communications.

Lead author Dr Matthew Lloyd, from the University of Bath Department of Pharmacy & Pharmacology, said: “The research suggests new ways of treating cancer can be developed based on reducing AMACR function, which is exciting, but progress has been extremely limited because of the technical difficulties in measuring function.

“One of the important things about our test is that we can now quickly analyse samples and start investigating the development of new treatments based on reducing AMACR function. It will also allow investigation of the underlying biology, which is currently poorly understood. There is also potential for developing the method into a new way of monitoring the cancer. This is an extremely significant step forwards in the field.”

Using the new test many samples can be analysed quickly and at the same time, and the functional level of AMACR can be measured much more accurately than by previous methods.

Dr Iain Frame, Director of Research at Prostate Cancer UK said: “The development of new treatments to halt the spread of prostate cancer is crucial if we are to stop thousands of men dying from the disease every year. It has been known for some time that a protein called AMACR is involved in prostate cancer development. This makes it an exciting drug target, but until now, it has been difficult to test the effectiveness of potential new drugs on blocking the protein.

“Dr Lloyd’s research provides a key part of the puzzle which means we can start the process of developing drugs to target AMACR and ultimately fight the disease in men. We are proud to have funded this research and look forward to seeing further developments.”

Experts encourage prostate cancer patients to weigh long-term impact of treatment options with their doctors

Ten-year findings from the trial indicate that for men with early stage prostate cancer, there is no difference in mortality rates following active monitoring, surgery or RT, and moreover, that cancer-specific deaths at ten years following diagnosis averaged only one percent for all men enrolled in the trial.

Growth of the cancer outside of the prostate did vary between monitoring and treatment groups. Rates of both regional spread and distant metastases were significantly higher for men who were monitored rather than treated for their early stage disease. Progression did not vary, however, between the surgery and RT groups, although patients in the trial reported different side effects with each modality.

“These findings underscore the essential role of dialogue in treatment selection,” said ASTRO President David C. Beyer, MD, FASTRO. “Men with prostate cancer are all different, and the relative costs and benefits associated with the multiple options to treat it can vary substantially between individuals. The best treatment decisions for prostate cancer, or any cancer, take into consideration the specifics of each individual patient’s disease, expectations and preferences. These options can be confusing, and patients should always make these decisions after consultation with a radiation oncologist and urologist”

ASTRO, the American Urological Association (AUA) and the American Society for Clinical Oncology (ASCO) are currently developing updated guidelines for the management of clinically localized prostate cancer. The recommendations, which update a 2007 collaborative guideline issued by the societies, are scheduled for publication in mid-2017.

Study finds first evidence that PD-1 antibody could help men with metastatic prostate cancer

It is a surprising turnaround because prior results in men with aggressive, advanced-stage prostate cancer showed no evidence of anti-tumor activity with immune therapies that work by blocking PD-1 signals.

In the study published in the journal Oncotarget, 10 men with metastatic prostate cancer resistant to androgen deprivation therapy and the androgen receptor antagonist enzalutamide were treated with pembrolizumab, a monoclonal antibody that binds to the PD-1 receptor.

Three of the first 10 participants enrolled in the ongoing clinical trial experienced rapid reductions in prostate specific antigen, or PSA, an early measure of treatment effect. Subsequent imaging scans showed that tumors shrank in two of these three men, including metastatic liver tumors in one patient. Two of the three participants who responded to the treatment gained relief from cancer pain and were able to stop taking opiate pain medication.

The research team led by Julie Graff, M.D.,says the data provide, for the first time, evidence for meaningful clinical activity for PD-1 blockade in men with metastatic prostate cancer that is resistant to androgen deprivation.

“It’s pretty remarkable, especially in light of the fact that many people doubted this approach could work at all,” said Graff, lead study author and an oncologist specializing in prostate cancer at the OHSU Knight Cancer Institute. “You don’t get responses like this with almost any other treatment.”

Protein ZMYND8 tied to suppression of prostate cancer tumor metastasis

“These findings are important as cancer metastasis is a complicated process and is both devastating and clinically challenging,” said Min Gyu Lee, Ph.D., associate professor of Molecular and Cellular Oncology. “For metastasis, cancer cells acquire migratory and invasive abilities and so gaining new insight into how this occurs and how to stop metastasis is crucial. We believe this study opens a window into this process.”

Lee’s study centered on modification of proteins crucial to gene regulation, known as histones. Alterations in histone modifications, including acetylation and methylation, are frequently associated with cancer development. Lee’s group looked at ZMYND8 as a histone “reader” that could possibly impact gene expression by recognizing these histone modifications known as histone “marks.”

“It has been well documented that the effects of histone acetylation and methylation on gene expression can be mediated by specific binding proteins called ‘readers,'” said Lee. “We identified ZMYND8 as a reader for histone marks called H3K4me1 and H3K14ac, both of which are tied to metastasis-linked genes.”

The research group also noted that ZMYND8 cooperated with a type of histone mark “eraser” called JARID1D to suppress metastasis-linked genes.

“These findings are of special interest in light of our earlier study that JARID1D levels are lower in metastasized prostate tumors than in normal prostate and primary prostate tumors,” said Lee. “This study revealed a previously unknown metastasis-suppressive mechanism in which ZMYND8 counteracts the expression of metastasis-linked genes by reading dual histone marks H3K4me1 and H3K14ac and cooperating with JARID1D.”

New test distinguishes ‘tigers’ from ‘pussycats’ in prostate cancer

Each year 46,000men in the UK develop prostate cancer and many cancers progress after diagnosis to become life threatening. 11,000 men will die from the disease every year.

However, unlike many cancers, more than 50 per cent of prostate cancer cases cause no symptoms and are never life threatening. But it is not possible at the point of diagnosis reliably distinguish these from clinically important cancers.

Prof Colin Cooper, professor of cancer genetics at UEA’s Norwich Medical School, said: “Previously, distinguishing the dangerous ‘tigers’ from the less threatening ‘pussycats’ has not been possible for many men.

“Curative treatment of early prostate cancer by surgery or radiotherapy needs to ideally be targeted to the minority of men with significant cancers, so that the remainder are spared the side-effects of treatment, which frequently includes impotence.

“Improved clinical markers are therefore required to predict behaviour allowing radical therapies to be targeted to men with significant cancers, so that the remainder, with biologically unimportant disease, are spared the side-effects of treatment.”

Funded by donations to The Difference Campaign, including support from the Bob Champion Cancer Trust and The Masonic Charitable Foundation, Prof Colin Cooper and Dr Daniel Brewer from Norwich Medical School collaborated with Prof Vincent Moulton and Dr Bogdan Luca from UEA’s School of Computing Sciences to devise a new framework for classifying human prostate cancer using a mathematical approach.

Fusion targeted prostate biopsy proves more accuratein diagnosis of prostate cancer

Using specialized equipment needed, physicians at UT Southwestern Medical Center’s Harold C. Simmons Comprehensive Cancer Center began using the fusion biopsy procedure about three years ago for its ability to blend live ultrasound images with captured MRI images. The fused image creates the 3D model, and flags anomalies that could be areas of concern. That helps guide urologists to get tissue samples called biopsies to determine whether cancer is present.

UT Southwestern’s early adoption of the cutting-edge technology allowed researchers to report on the superior diagnostic performance of this novel approach compared to traditional methods for diagnosing prostate cancer. Furthermore, these researchers have partnered with colleagues in Brazil to conduct follow up studies that now show the technique consistently improved detection of clinically significant prostate cancer under a wide variety of conditions, even when radiologists were using different equipment and protocols.

“In the past, we diagnosed prostate cancer by random biopsies of the prostate in men with elevated PSA values. With fusion biopsy, we actually find more cancer, we can differentiate between dangerous tumors and less aggressive tumors, and in some cases we perform fewer biopsies,” said Dr. Daniel Costa, Assistant Professor of Radiology and with the Advanced Imaging Research Center (AIRC) at UT Southwestern.

Prostate cancer is the second most common cancer diagnosed in men, after skin cancer. Prostate cancer risk increases with age, with most cases occurring after age 60. According to the National Cancer Institute (NCI), about 180,890 men will be diagnosed this year, and about 14 percent of men will be diagnosed sometime during their lifetime.