Discovery Could Lead To Novel Drugs To Prevent Cancer Metastasis

A Loyola University Chicago Stritch School of Medicine study has revealed details of the complex molecular process involving a protein that enables cancer cells to establish tumors in distant parts of the body.

The finding could lead the way to new drugs to prevent breast cancer and other cancers from spreading to new sites.

The study by Adriano Marchese, PhD, and colleagues is published in the March 16 issue of the Journal of Biological Chemistry.

The study involves a molecule on the surface of cells called CXCR4. There is an abnormal abundance of this molecule in 23 types of cancer, including cancers of the breast, lung, pancreas and thyroid.

What usually kills patients is the spread of cancer from the primary site to other sites. A tumor cell breaks away from the primary site and circulates through the body. A molecule called CXCL12 acts like a beacon to CXCR4, signaling the cancer cell to land and start a new tumor.

The goal of the study was to better understand this complex signaling pathway. (A signaling pathway involves a group of molecules that work together in a cell. After the first molecule in the pathway receives a signal, it activates another molecule, and the process is repeated until the last molecule is activated.)

"We understand the final outcome of this signaling pathway," Marchese said. "What we are trying to do now is understand the molecular details."

In the study, Marchese and colleagues used a line of human cancer cells called HeLa. (The cell line is the subject of the best-selling book "The Immortal Life of Henrietta Lacks".)

Using HeLa cancer cells, the researchers identified a molecule that is a critical link in the signaling pathway. Researchers hope to target this molecule, thereby disabling the signaling pathway and preventing the cancer cell from setting up shop in a new site, Marchese said.

The next step will be to develop a drug that blocks the target molecule. Researchers then would test the drug on an animal model. If the drug worked in animals, it later could be tested in a clinical trial of cancer patients, Marchese said.

"We are laying the groundwork for the development of new drugs to stop cancer from spreading," Marchese said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our breast cancer section for the latest news on this subject. Marchese is an associate professor in the Department of Molecular Pharmacology and Therapeutics of Loyola University Chicago Stritch School of Medicine. His co-authors are Rohit Malik, PhD (first author); Unice J.K. Soh, PhD; and JoAnn Trejo, PhD.
The study was supported by a grant from the National Institutes of Health. Malik was supported by a predoctoral fellowship from the American Heart Association. He graduated in December 2011 and is doing postdoctoral training at the University of Michigan.
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Gene Chip May Help Prevent Heart Disease

Worldwide, coronary heart disease (CHD) is the leading cause of death. According to a study published online in The Lancet, anti-inflammatory medications may become a new way to prevent and treat the disease.

Using a gene analysis tool called the Cardiochip, the researchers examined a specific gene variant associated with inflammation and heart disease. The chip was designed by Brendan J. Keating, Ph.D., co-author of the study and a researcher in the Center for Applied Genomics at The Children's Hospital of Philadelphia.

Even though researchers are aware of the association between inflammation and atherosclerosis - a disorder in which fat, cholesterol, and other fatty deposits build up in the walls of arteries - they have been unable to find an inflammatory agent that causes the diseases, until now. In addition, researchers did not know whether a drug targeted at reducing inflammation might treat the disease.

The team focused on the signaling protein interleukin-6 receptor (IL6R). IL6R is found in the blood and increases inflammatory responses.

Keating explained:

"This study provides robust evidence that IL6R is implicated in coronary heart disease. Furthermore, our analysis showed that an existing anti-inflammatory drug, acting on this receptor, may offer a new potential approach for preventing CHD."

The meta-analysis study was conducted by the IL6R Mendelian Randomization Analysis Consortium, and international team of investigators led by Dr. Juan Pablo Casas, Professor Aroon. D. Hingorani, and Dr. Daniel I. Swerdlow, all of University College London, UK.

The researchers examined data from 40 previous studies that involved almost 133,500 individuals from Europe and the United States. Mendelian randomization is a research technique that utilizes knowledge of genes and biological mechanisms in order to figure out the likely effects of a new medication before a clinical trial is conducted, with its potential risk of adverse effects and high cost.

In the same issue of The Lancet, an associated report conducted by the IL6R Genetics Consortium and Emerging Risk Factors Collaboration, discovered that a genetic variant of the IL6R gene, which carries the code for the IL6R protein, decreases inflammation and therefore reduces the risk of heart disease.

The primary focus of the study Keating participated in was on SNPs (single nucleotide polymorphisms) single-base changes in the IL6R gene that codes for the IL6R protein.

The researchers used the IBC Human CVD BeadChip (a DNA array), also called the Cardiochip. The chip, which contains DNA markers for 2,000 gene variants implicated in cardiovascular disease, was developed in 2006 by Keating and has been used in several large gene studies.

When the chip is brought into contact with test samples of DNA from study participants, it identifies specific SNPs in the sample - gene variants that could potentially affect biological functions as well as risks of cardiovascular disease among the study participants.

The researchers discovered that one SNP, the gene variant rs8192284, changed numerous biological markers linked to inflammation. These results were comparable to results found in studies of tocilizumab, an anti-inflammatory drug currently used to treat individuals suffering with rheumatoid arthritis. This medication decreased the painful inflammation common in rheumatoid arthritis by preventing the action of IL6R.

After examining data from patients with CHD and controls, the researchers also found that individuals carrying the gene variant had a lower risk of developing CHD.

Keating said:

"What this tells us is that IL6R blockers such as tocilizumab mimic the benefits of having this gene variant. A next step will be for cardiology researchers to design and carry out clinical trials to determine whether tocilizumab or similar anti-inflammatory drugs will prevent heart disease."

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our heart disease section for the latest news on this subject. “The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomization analysis” The Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium
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Help Your Child Lose Weight By Losing Weight Yourself

A study by researchers at the University of California, San Diego School of Medicine and The University of Minnesota indicates that a parent's weight change is a key contributor to the success of a child's weight loss in family-based treatment of childhood obesity. The results were published in the advanced online edition of the journal Obesity.

"We looked at things such as parenting skills and styles, or changing the home food environment, and how they impacted a child's weight," said Kerri N. Boutelle, PhD, associate professor of pediatrics and psychiatry at UC San Diego and Rady Children's Hospital-San Diego. "The number one way in which parents can help an obese child lose weight? Lose weight themselves. In this study, it was the most important predictor of child weight loss."

Recent data suggests that 31 percent of children in the United States are overweight or obese, or between four and five million children. Current treatment programs generally require participation by both parents and children in a plan that combines nutrition education and exercise with behavior therapy techniques.

"Parents are the most significant people in a child's environment, serving as the first and most important teachers," said Boutelle "They play a significant role in any weight-loss program for children, and this study confirms the importance of their example in establishing healthy eating and exercise behaviors for their kids."

The researchers looked at eighty parent-child groups with an 8 to 12-year-old overweight or obese child, who participated in a parent-only or parent + child treatment program for five months.

The study focused on evaluating the impact of three types of parenting skills taught in family-based behavioral treatment for childhood obesity, and the impact of each on the child's body weight: the parent modeling behaviors to promote their own weight loss, changes in home food environment, and parenting style and techniques (for example, a parent's ability to help limit the child's eating behavior, encouraging the child and participating in program activities).

Consistent with previously published research, parent BMI change was the only significant predictor of child's weight loss.

The researchers concluded that clinicians should focus on encouraging parents to lose weight to help their overweight or obese child in weight management.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our obesity / weight loss / fitness section for the latest news on this subject. For more information about weight loss programs for children and adolescents at UC San Diego, visit http://www.obesitytreatment.ucsd.edu/.
Additional contributors to the study include Guy Cafri, UCSD Child and Adolescent Services Research Center, and Scott J. Crown, University of Minnesota.
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Black Men Who Confront Racial Discrimination And Hide Their Emotions At Greater Risk Of Depression

Enduring subtle, insidious acts of racial discrimination is enough to depress anyone, but African-American men who believe that they should respond to stress with stoicism and emotional control experience more depression symptoms, according to new findings from the University of North Carolina at Chapel Hill.

The study, "Taking It Like a Man: Masculine Role Norms as Moderators of the Racial Discrimination - Depressive Symptoms Association Among African-American Men," was published online in the American Journal of Public Health.

"We know that traditional role expectations are that men will restrict their emotions - or 'take stress like a man,'" said study author Wizdom Powell Hammond, Ph.D., assistant professor of health behavior in UNC's Gillings School of Global Public Health. "However, the more tightly some men cling to these traditional role norms, the more likely they are to be depressed.

"It also is clear that adherence to traditional role norms is not always harmful to men," Hammond said. "But we don't know a lot about how these norms shape how African-American men confront stressors, especially those that are race-related."

Hammond studied the phenomenon researchers call everyday racism, which is marked not so much by magnitude or how egregious the prejudice and torment were, but by persistence and subtlety.

"It chips away at people's sense of humanity and very likely at their hope and optimism," Hammond said. "We know these daily hassles have consequences for men's mental health, but we don't know why some men experience depression while others do not."

Hammond studied data collected from surveys of 674 African-American men, aged 18 and older, carried out at barber shops in four U.S. regions between 2003 and 2010.

She found that everyday racial discrimination was associated with depression across all age groups. Younger men (aged under 40) were more depressed, experienced more discrimination and had a stronger allegiance to norms encouraging them to restrict their emotions than men over 40 years old. Furthermore, some men who embraced norms encouraging more self-reliance reported less depression.

The results showed associations, not necessarily causation, Hammond noted.

The data also showed that when men felt strongly about the need to shut down their emotions, then the negative effect of discrimination on their mental health was amplified. The association was particularly apparent for men aged 30 years and older.

"It seems as though there may be a cumulative burden or long-term consequences of suffering such persistent discriminatory slights and hassles in silence," Hammond said. "Our next task is to determine when embracing traditional role norms are harmful or helpful to African American men's mental health."

The information will help target future interventions to subgroups of men, rather than try to reach all men with one general approach.

"African-American men are not all alike, just as all people in any group are not alike," Hammond said. "The way they feel, respond and react changes over time as they normally develop. The slings and arrows of everyday racism still exist, and we need to find targeted ways to help men defend against them while also working to address the policy structures that project them."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our depression section for the latest news on this subject. Currently, Hammond is part of the 2011-2012 class of White House Fellows. Founded in 1964, the leadership and public service program offers fellows a first-hand experience working at the highest levels of the federal government.
Hammond also is a member of the UNC Lineberger Comprehensive Cancer Center.
The study is available at http://ajph.aphapublications.org/doi/abs/10.2105/ajph.2011.300485.
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HRT With Estrogen Added Raises Breast Cancer Risk

According to a study published March 15 in the Journal of the National Cancer Institute, thoughts about how estrogen alone or estrogen in addition to progestin influence the risk of developing breast cancer has considerably changed in the past 10 years due to results from the Women's Health Initiative (WHI) randomized placebo-controlled hormone therapy trials, and from large prospective cohort studies.

At present, concerns are still being raised regarding hormone therapy-induce breast cancer risk, even though the therapy is used for menopausal symptoms by millions of women. Furthermore, researchers are still not clear on the effects of estrogen in addition to progestin vs estrogen alone on breast cancer.

Rowan T. Chlebowski, M.D., Ph.D., of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Garnet Anderson, Ph.D., at Fred Hutchinson Cancer Research Center, examined data from 2 randomized, placebo-controlled clinical trials carried out in the WHI, in order to examine the effects of estrogen in addition progestin vs estrogen alone on the risk of developing breast cancer.

The first study assessed estrogen alone in post-menopausal women with prior hysterectomy, and the second study assessed estrogen plus progestin in post-menopausal women who had not undergone hysterectomy.

The researchers found that the risk of developing breast cancer was statistically considerably increased by using estrogen in addition to progestin, while the risk was statistically significantly decreased in post-menopausal women with previous hysterectomy who took estrogen alone.

According to the researchers, findings from the randomized human trial and those from the majority of observational studies differ, with the observational studies indicating that both estrogen alone and estrogen plus progestin increase the risk of developing breast cancer.

The researchers explain that:

"An imbalance in the use of mammography with greater screening for hormone users could explain some of the increase in breast cancer incidence with estrogen alone seen in cohort studies because screened populations have more cancers detected than unscreened populations."

Even though the authors do not fully understand the mechanisms underlying the different effects of estrogen alone and estrogen in addition to progestin, they said:

"The findings in the clinic, taken together with preclinical evidence, indicate that many breast cancers in post-menopausal women can survive only a limited range of estrogen exposures."

Written by Grace Rattue
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Menopause Linked To Memory Loss

A study published today in the journal Menopause, from the North American Menopause Society, confirms the frustration that many women feel with memory problems as they approach menopause.

Scientists at the University of Rochester Medical Center and the University of Illinois at Chicago finally validated the claims of many women in their 40s and 50s who complain of "brain fog" or forgetfulness. 75 women from ages 40 to 60 were give an array of cognitive tests which not only confirm the problem but also provide some explanation as to its occurrence and explain what is happening in the brain during menopause.

Miriam Weber, Ph.D., the neuropsychologist at the University of Rochester Medical Center who led the study explains :

"The most important thing to realize is that there really are some cognitive changes that occur during this phase in a woman's life ... If a woman approaching menopause feels she is having memory problems, no one should brush it off or attribute it to a jam-packed schedule. She can find comfort in knowing that there are new research findings that support her experience. She can view her experience as normal."

The tests included attention span over time as well as the ability to learn and manipulate new information. The researchers found that only some of the problems were linked to memory deficit. The women were also questioned about their menopause symptoms, including depression, anxiety, hot flashes, and sleep difficulties. Blood levels of the hormones estradiol and follicle-stimulating hormone were measured.

Those who complained of a foggy memory did poorly on tests designed to gauge what is called "working memory", this gives a person the ability to take in new information as well as manipulate it mentally. An example might include adding up numbers in your head or adjusting an itinerary or schedule. Problems also included maintaining attention span on a long drive or getting through a long book.

Weber points out that what people consider memory, such recalling items needed on a shopping trip or remembering a phone number is only a small part of memory function, and most women were not having issues with these simpler traditional kinds of memory function.

Although there was no link found between hormone levels and memory function, researchers did note that those with memory problems were generally more prone to other symptoms of menopause, such as sleeping difficulty and anxiety.

Weber further explains that :

"If you speak with middle-aged women, many will say, yes, we've known this. We've experienced this ... But it hasn't been investigated thoroughly in the scientific literature ... Science is finally catching up to the reality that women don't suddenly go from their reproductive prime to becoming infertile. There is this whole transition period that lasts years. It's more complicated than people have realized."

The latest confirmation aligns with results from an earlier study that Weber did with Mark Mapstone, Ph.D., associate professor of Neurology, and results from a study involving hundreds of women, that only used less sensitive measures to look at cognitive performance. He concludes that :

"There really is something going on in the brain of a woman at this stage in her life ... There is substance to their complaints that their memory is a bit fuzzy."

Weber finishes with some advice for women experiencing these problems :

"When someone gives you a new piece of information, it might be helpful to repeat it out loud, or for you to say it back to the person to confirm it ... it will help you hold onto that information longer ... Make sure you have established that memory solidly in the brain ... You need to do a little more work to make sure the information gets into your brain permanently. It may help to realize that you shouldn't expect to be able to remember everything after hearing it just once."

Written by Rupert Shepherd

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20.14 | 0 komentar

HIV Risk 14 Times Higher Among Sex Workers In Poorer Nations

The risk of contracting HIV is 14 times higher for female sex workers in low- and middle-income countries (LMIC) than for women in the general population, according to a study published Online First in The Lancet Infectious Diseases.

Three decades have passed since the global HIV epidemic started, yet the knowledge about HIV amongst sex workers is still limited, despite these women's increased risk of infection because of higher exposure to biological, behavioral and structural risk factors.

Dr. Stefan Baral, from the Center for Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health in Baltimore, MD, USA, and his team decided to perform a meta-analysis of 102 studies that included nearly 100,000 female sex workers in 50 countries.

They discovered an overall HIV occurrence in 12% of female sex workers in LMIC, and that sex workers were 14 times more likely to be infected with the virus as compared with the general female population in those countries. 31% of female sex workers in 26 countries categorized as medium or high background HIV prevalence tested positive to the virus, with the risk for infection in these female sex workers being 12 times higher compared with women from the general population.

The worst region in terms of infection risk for female sex workers was Asia, with an increased risk of 29 times, whilst the risk in Africa and Latin America was 12-fold as compared to the general female population.

The researchers concluded:

"We identified consistent evidence of substantially higher levels of HIV among female sex workers compared with all women of reproductive age in low-income and middle-income countries in all regions with data.

Although female sex workers have long been understood to be a key affected population, the scope and breadth of their disproportionate risk for HIV infection had to date not been systematically documented. These findings suggest an urgent need to scale up access to quality HIV-prevention programming and services among female sex workers because of their heightened burden of disease and likelihood of onward transmission through high numbers of sexual partners as clients.

In view of the high burden of HIV among female sex workers and recent biomedical advances related to treatment as prevention, improvement of linkages to antiretroviral treatment, and retention in care, ongoing prevention for sex workers already living with HIV is crucial...Considerations of the legal and policy environments in which sex workers operate, and the important role of stigma, discrimination, and violence targeting female sex workers globally will be required to reduce the disproportionate disease burden among these women."

Dr. Kate Shannon of the Gender and Sexual Health Initiative, and Dr Julio S G Montaner from the British Columbia Centre for Excellence in HIV/AIDS and the University of British Columbia in Vancouver, BC, Canada, write in a linked comment:

"As the epidemic matures in many settings, with some countries already reporting over 50% of sex workers living with HIV, comprehensive initiatives simultaneously targeting HIV prevention, ART access, and care are increasingly vital. As highlighted in a recent report by the UNAIDS advisory on sex work and HIV, removal of structural barriers (e.g., criminalized laws and policies, violence) remains a necessary precondition to an effective HIV response in sex work worldwide."

Written by Petra Rattue
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17.13 | 0 komentar