Long-term side-effects in testicular cancer could be reduced by chemotherapy before radiotherapy

Main Category: Cancer / Oncology
Also Included In: Radiology / Nuclear Medicine
Article Date: 20 Aug 2013 - 0:00 PDT Current ratings for:
Long-term side-effects in testicular cancer could be reduced by chemotherapy before radiotherapy

Giving men with testicular cancer a single dose of chemotherapy alongside radiotherapy could improve the effectiveness of treatment and reduce the risk of long-term side-effects, a new study reports. As many as 96% of men with testicular cancer now survive at least ten years from diagnosis (1), but more advanced forms need to be treated with combination chemotherapy - which can have serious long-term complications. Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust have therefore been searching for new treatments that would reduce the risk of relapse after initial treatment and so spare as many men as possible from needing combination chemotherapy.

The new pilot study, published in the August issue of prestigious journal the Annals of Oncology, tested a new treatment in a pilot study of men with stage IIA and IIB testicular seminoma - where the cancer has spread to the lymph nodes in the abdomen.

The researchers showed that giving chemotherapy drug carboplatin before radiotherapy could reduce relapse rates compared with radiotherapy alone - cutting the numbers of men who would need follow-up treatment. It also allowed radiation doses to be reduced. The study was funded by The Institute of Cancer Research (ICR), the Bob Champion Cancer Trust and Cancer Research UK, as well as through the NIHR Biomedical Research Centre at The Royal Marsden and the ICR.

Researchers gave 51 men with stage IIA and IIB testicular seminoma a single cycle of carboplatin - a low toxicity form of chemotherapy - followed three to four weeks later by radiotherapy. Most of the men were aged below 50, over a range of 18-73 years.

Adding carboplatin to patients' treatment plans allowed doctors to give a lower dose of radiation over a smaller area of the body for most of the men in the study. Some 39 of the men in the study had their prescription of radiation reduced from the standard 35 Grays (Gy) of radiation to 30 Gy, delivered to a smaller area of the abdomen.

After an average of 4.5 years of follow-up, there were no relapses of the cancer compared with a relapse risk of 5-11% after radiotherapy alone. The side-effects from treatment were mild and only lasted a short time.

Dr Robert Huddart, Team Leader in the Division of Radiation and Imaging at the Institute of Cancer Research, London, and Consultant at The Royal Marsden, who led the study, said:

"The results of this study show great promise. Men who have this stage of testicular seminoma are normally treated with just radiotherapy, or in some countries with intensive combination chemotherapy, where several anticancer drugs are given at once. Relapse occurs in 5-11% of men after radiotherapy alone, and these recurrences have to be treated with combination chemotherapy, which is associated with a risk of serious long-term complications such as cardiovascular disease or second cancers.

"The aim of the study was to develop an effective non-toxic treatment with low risk of long-term treatment complications, and our findings suggest that a single cycle of carboplatin before radiotherapy may reduce the chances of cancer reappearing compared with radiotherapy alone. This will reduce the risk that these patients would need combination chemotherapy. Not only that, but by adding carboplatin to the therapy, the radiation dose and volume can be lowered."

As this was a small, single-centre study, the researchers are recommending the approach is evaluated more widely.

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(1) Cancer Research UK Testicular cancer survival statistics (2009). Accessed online 15 August 2013.

Neoadjuvant carboplatin before radiotherapy in stage IIA and IIB seminoma

Ann Oncol (2013) 24 (8): 2104-2107. doi: 10.1093/annonc/mdt148

Institute of Cancer Research

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Joint symptoms in postmenopausal women not reduced by calcium plus vitamin D supplementation

Main Category: Arthritis / Rheumatology
Also Included In: Menopause;  Nutrition / Diet
Article Date: 20 Aug 2013 - 0:00 PDT Current ratings for:
Joint symptoms in postmenopausal women not reduced by calcium plus vitamin D supplementation

A team of investigators systematically analyzed the effect of calcium and vitamin D supplementation on joint symptoms in a rigorous and controlled study of postmenopausal women. They found that supplementation did not reduce the severity of joint symptoms reported by the participants. Their results are published in the Journal of the Academy of Nutrition and Dietetics.

The influence of low calcium and vitamin D deficiency on joint symptoms has been studied with mixed results. Only some observational studies have associated vitamin D with knee osteoarthritis and results from full-scale randomized trials have been sparse. "In the current study, we addressed for the first time in a full-scale, randomized clinical trial setting, the clinically relevant question of whether postmenopausal women using calcium and vitamin D supplements in currently recommended dosage would experience any favorable effect on joint pain or swelling, common symptoms in postmenopausal women," says lead investigator Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrance, California.

Using data from the Women's Health Initiative (WHI) calcium plus vitamin D supplementation trial, researchers identified a subgroup of 1,911 postmenopausal women for the current study, who had been randomized to receive calcium carbonate with vitamin D3 daily or placebo and had undergone serial joint symptom assessment. Responses to a questionnaire provided qualitative information on joint pain and joint swelling before entry and two years after randomization.

Between the daily supplement use and placebo groups, joint pain and swelling at baseline entry was comparable, at more than 70 percent. After two years, analysis revealed no statistically significant difference for the frequency or severity of joint pain or swelling.

The research team also evaluated data to determine the potential for interaction with age, BMI (body mass index), physical activity, non-protocol calcium and vitamin D supplement use, race/ethnicity, and hormone therapy. Investigators found no interaction with age, BMI, race/ethnicity, or physical activity. No significant interaction was evident with non-protocol vitamin D supplement use at entry. However, participants using non-protocol calcium supplements at entry reported less joint pain compared with those in the placebo group. The influence of calcium and vitamin D supplementation individually on joint symptoms was not determined because both were provided combined in a single pill in this trial.

Dr. Chlebowski concludes, "Joint symptoms are relatively common in postmenopausal women. However, daily supplementation with 1,000 mg of calcium carbonate and 400 IU of vitamin D3 in a randomized, placebo-controlled clinical trial setting did not reduce the self-reported frequency or severity of joint symptoms."

Dr. Chlebowski and his team add that these findings do not speak against current recommendations for vitamin D intakes for bone health and fracture risk reduction.

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Binge drinking for all students reduced by anti-homophobia measures

Main Category: Alcohol / Addiction / Illegal Drugs
Also Included In: Pediatrics / Children's Health;  Psychology / Psychiatry
Article Date: 19 Aug 2013 - 0:00 PDT Current ratings for:
Binge drinking for all students reduced by anti-homophobia measures

Canadian high schools with anti-homophobia policies or gay-straight alliances (GSAs) that have been in place for three years or more have a positive effect on both gay and straight students' problem alcohol use, according to a new study by University of British Columbia researchers.

GSAs are student-led clubs of lesbian, gay, bisexual, transgender, queer or questioning (LGBTQ) youth and their straight allies. Their purpose is to provide support and advocacy and help make schools more inclusive.

"These strategies appear to be helpful not only for LGBTQ students, but all students," says Elizabeth Saewyc, senior author and professor with the UBC School of Nursing. "Interventions that can make schools safer for LGBTQ youth may actually reduce harassment for straight students, too. Schools should consider including GSAs and anti-homophobia policies as part of their alcohol and drug abuse prevention strategies."

In schools with established GSAs, lesbian and bisexual girls and heterosexual boys and girls, all were less likely to binge drink and experience problems associated with alcohol or drug use such as blacking out, car accidents, problems at school or family arguments about alcohol use. There were no significant effects for gay or bisexual boys. Both heterosexual boys and girls also had lower odds of binge drinking in schools with anti-homophobia policies.

Published recently in the journal Preventive Medicine, and funded by the Canadian Institutes of Health Research, the study used data from the British Columbia Adolescent Health Survey to look at whether students' odds of recent substance use were lower in schools with recent or more established anti-homophobia policies and gay straight alliances compared to schools without these strategies.

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MAPS technology may generate vaccines conferring strong immunity at reduced cost and risk

Main Category: Immune System / Vaccines
Article Date: 30 Jul 2013 - 2:00 PDT Current ratings for:
MAPS technology may generate vaccines conferring strong immunity at reduced cost and risk

A new method of vaccine design, called the Multiple Antigen Presentation System (MAPS), may result in vaccines that bring together the benefits of whole-cell and acellular or defined subunit vaccination. The method, pioneered by researchers at Boston Children's Hospital, permits rapid construction of new vaccines that activate mulitple arms of the immune system simultaneously against one or more pathogens, generating robust immune protection with a lower risk of adverse effects.

As reported by Fan Zhang, PhD, Ying-Jie Lu, PhD, and Richard Malley, MD, from Boston Children's Division of Infectious Disease, in the Proceedings of the National Academy of Sciences on July 29, the method could speed development of new vaccines for a range of globally serious pathogens, or infectious agents.

Broadly speaking, the vaccines available today fall into two categories: whole-cell vaccines, which rely on weakened or killed bacteria or viruses; and acellular or subunit vaccines, which include a limited number of antigens - portions of a pathogen that trigger an immune response. Both approaches have advantages and disadvantages.

"Whole-cell vaccines elicit a broad range of immune responses, often just as an infection would, but can cause side effects and are hard to standardize," said Malley. "Acellular vaccines can provide good early immunity with less risk of side effects, but the immune responses they induce wane with time."

The MAPS method may allow vaccine developers to take a middle ground, where they can link multiple protein and polysaccharide (sugar) antigens from one or more pathogens together in a modular fashion, much as one would connect Lego blocks.

The resulting complex - which resembles a scaffold of polysaccharides studded with proteins - can stimulate both antibody and T-cell responses simultaneously much like whole-cell vaccines, resulting in stronger immunity to the source pathogen(s). However, because the composition of a MAPS vaccine is well defined and based on the use of isolated antigens (as one would find with an acellular vaccine) the risk of side effects should be greatly reduced.

For instance, mice injected with a MAPS vaccine combining proteins from tuberculosis (TB) and polysaccharides from Streptococcus pneumoniae (pneumococcus) mounted vigorous antibody and T-cell responses against TB, whereas those vaccinated with TB protein antigens alone mounted only an antibody response.

Similarly, 90 percent of mice given a MAPS-based vaccine containing multiple pneumococcal polysaccharide and protein antigens were protected from a lethal pneumococcus infection, mounting strong antibody and T-cell responses against the bacteria. By contrast, 30 percent of mice vaccinated with the same antigens in an unbound state survived the same challenge.

"The MAPS technology gives you the advantages of: whole-cell vaccines while being much more deliberate about which antigens you include; doing it in a quantitative and precise way; and including a number of antigens so as to try to replicate the effectiveness of whole-cell vaccination," Malley explained. "The immunogenicity of these constructs is greater than the sum of their parts, somewhat because they are presented to the host as particles."

The system relies on the interactions of two compounds, biotin and rhizavidin, rather than covalent binding as is used in most of the current conjugate vaccines. To build a MAPS vaccine, biotin is bound to the polysaccharide(s) of choice and rhizavidin to the protein(s). The biotin and rhizavidin then bind together through an affinity interaction analogous to Velcro. The construction process is highly efficient, significantly reducing the time and cost of vaccine development and production.

While his team's initial work has focused on bacterial pathogens, Malley believes the technology could impact vaccine development for a broad range of pathogens, in particular those of importance in the developing world. "Technically, one could construct MAPS vaccines for viruses, parasites, even cancer antigens," he said. "And the modularity is such that one could include antigens from multiple pathogens into the same vaccine, allowing the development of combinatorial vaccines much more efficiently."

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Fan Zhang, Ying-Jie Lu, and Richard Malley "Multiple antigen-presenting system (MAPS) to induce comprehensive B- and T-cell immunity" Published online before print July 29, 2013, doi: 10.1073/pnas.1307228110

The study was supported by the National Institute for Allergy and Infectious Diseases (grant R01AI067737) and the Translational Research Program at Boston Children's Hospital.

Boston Children's Hospital

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Seizures reduced and progression of epilepsy slowed by adenosine therapy

Main Category: Epilepsy
Article Date: 29 Jul 2013 - 0:00 PDT Current ratings for:
Seizures reduced and progression of epilepsy slowed by adenosine therapy

Epilepsy is characterized by recurrent seizures that present in many different ways. In some cases epileptic patients exhibit a progressive increase in both frequency and severity of seizures. Epigenetic changes such as DNA methylation have recently been implied as an underlying cause of several neurologic disorders, including epilepsy.

In this issue of the Journal of Clinical Investigation, Detlev Boison and colleagues at Legacy Research show an increase of DNA methylation in the hippocampi of epileptic animals. They found that increased methyation corresponded with a decrease of adenosine (ADO), which is a known anticonvulsant.

The authors used bioengineered implants to transiently deliver ADO to the brains of epileptic rats. Targeted ADO delivery to the brain reversed DNA hypermethylation and resulted in a decrease in seizures and prevented epilepsy progression.

These data indicate that therapies aimed at reducing DNA methylation in the brain have potential for the treatment and prevention of epilepsy.

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TITLE: Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesis

View this article at: http://www.jci.org/articles/view/65636?key=b830cd2835e7b6acdd11

Journal of Clinical Investigation

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