Abstract
Researchers at Fred Hutchinson Cancer Research Center (WA, USA) have found that women infected with two strains of HIV have more potent antibody responses that block the replication of the virus compared with women infected with one strain. The research was published recently in the journal PLOS Pathogens.
With a view to finding new HIV vaccine strategies, it is essential to identify naturally occurring neutralizing antibodies (NAbs) that are cross-reactive against all global HIV-1 subtypes. This study sought to investigate NAbs in HIV superinfected women.
The authors studied immune activity in 12 women from Mombasa (Kenya), who were infected with two HIV strains, over a 5-year period. Each woman was assigned to a control group of three women who were infected with only one strain. Antibody response in all the plasma samples was assessed in vitro for the duration of the study comparing responses in superinfected women with singly infected women, using a panel of eight viruses representing four different HIV-1 subtypes.
Results showed that the superinfected women developed significantly broader NAb responses, and significantly greater potency, compared with singly infected participants. The researchers controlled for variables such as antibody response prior to superinfection, and biomarkers of immunity such as CD4+ T-cell count and viral load. These findings suggest that NAb responses may be improved by multiple HIV-1 strains.
First author on the paper, Valerie Cortez, explains to Women's Health that “Superinfection can be viewed as sequential ‘natural’ immunizations, which gives us the opportunity to evaluate the subsequent immunological impact that occurs as a result of antigenic stimulation from two distinct viral variants.” Cortez continues. “Our current work aims to characterize the viral variants circulating in these women in order to determine the unique antigenic properties that led to their broad and potent antibody responses.”
The researchers hope that, with more data available on the role of superinfection in NAb responses, a new vaccination strategy that mimics this may lead to the development of broad NAbs in immunized individuals.
– Written by Sam Rose
Source: Cortez V, Odem-Davis K, McClelland RS, Jaoko W, Overbaugh J. HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response. PLOS Pathog. 8(3), e1002611 (2012).
Early life adiposity may indicate future cardiometabolic risk in women
A new study published in The Endocrine Society's Journal of Clinical Endocrinology and Metabolism has suggested that birth weight and body fat distribution in early childhood are associated with increased cardiometabolic risk factors in girls. The researchers aimed to study this correlation with a focus on sex differences.
Previous studies have shown that cardiovascular risk factors in childhood and adults are associated with increased birth weight. The current childhood obesity epidemic in the Western world warrants further investigation into a potential association with the increasing incidence of early onset Type 2 diabetes.
The study looked at a total of 1053 17 year olds from an Australian birth cohort. The individuals had measures of anthropometry, blood pressure and fasting insulin, glucose and lipids. It was found that the 17-year-old girls with metabolic risk factors including greater waist circumference, triglycerides and insulin and, lower high-density lipoprotein/cholesterol were also heavier from birth with consistently higher BMI thereafter. By contrast, birth weight had no statistical impact on metabolic risk factors in males.
Rae-Chi Huang (University of Western Australia, Perth, Australia), the study's lead author, explains that “What happens to a baby in the womb affects future heart disease and diabetes risk when the child grows up… We found that female babies are particularly prone to this increased risk and females who are at high risk of obesity and diabetes-related conditions at age 17 are showing increased obesity as early as 12 months of age.”
This study demonstrated that females in a modern-day population may be particularly prone to increased cardiometabolic risk when born heavier. The authors believe that this has implications for targeted prevention of obesity and metabolic diseases. Huang summarizes, “These findings are significant because in our modern western society, we are seeing increased maternal obesity and gestational diabetes, which means there will also be a rise in female newborns that are born large for their age … Our results can be applied to public health messages targeting both maternal health and measures in early infancy regarding the prevention of childhood obesity and its consequences.”
- Written by Sam Rose
Source: Huang RC, Mori TA, Burrows S et al. Sex dimorphism in the relation between early adiposity and cardiometabolic risk in adolescents. J. Clin. Endocrinol Metab. doi:10.1210/jc.2011-3007 (2012) (Epub ahead of print).
Alternative therapies can help alleviate symptoms of breast cancer treatment-induced menopause
Researchers from the Netherlands Cancer Institute (Amsterdam, The Netherlands) have found that menopausal symptoms induced by chemotherapy or hormonal therapy in younger women with breast cancer can be considerably alleviated through the use of cognitive behavioral therapy (CBT) and physical exercise (PE). These findings were presented at the 8th European Breast Cancer Conference in March 2012.
Many cancer patients are faced with irreversible changes resulting from cancer treatment. One such change some women face after breast cancer is treatment-induced menopause, involving distressing symptoms such as hot flushes, night sweats, vaginal dryness, weight gain, urinary incontinence and sexual dysfunction.
The researchers studied 411 breast cancer patients, averaging at 48 years of age, recruited from 14 hospitals in Amsterdam and Rotterdam (The Netherlands). The women were randomly assigned into four groups: CBT alone, PE alone, CBT and PE combined, and a control group. All patients receiving CBT and/or PE interventions showed an overall reduction in the levels of menopausal symptoms compared with the control group. Even after 6 months, the women receiving PPT and/or PE reported these improvements.
“To our knowledge, this is the first study to investigate the efficacy of these two interventions specifically in women who have experienced acute, treatment-induced menopause,” said Marc van Beurden (The Netherlands Cancer Institute). “This is a very important issue for the quality of life of younger breast cancer patients. Unlike healthy women starting the menopause, they are unable to take hormone replacement therapy to alleviate their symptoms. There are other drugs available, but they are only moderately effective and have troublesome side-effects.”
The researchers noted that while the evidence that CBT and PE worked was convincing, compliance to CBT during the study was poor, and the frequency and intensity of the PE programme was also a challenge for many women. “We think that we have made an important step forward in improving the quality of life of these patients,” continued van Beurden. “Based on input from patients, we are now developing an internet-based version of the CBT programme. We hope that this will further increase the accessibility and convenience of the interventions and lead to more women benefiting from their results.”
– Written by Sam Rose
Source: European Cancer Organization/European Breast Cancer Conference press release: www.ecco-org.eu/Global/News/EBCC8-PR/2012/03/22_03-Non-drug-treatments-help-alleviate-symptoms-of-treatment.aspx
Study suggests that advanced breast cancer treatments may have beneficial effects on bone health
New results from the BOLERO-2 trial of everolimus and exemestane to treat hormone-resistant estrogen receptor-positive (ER+) breast cancer in postmenopausal women have suggested that the use of everolimus reduces bone turnover, leading to better bone strength and reduced metastasis.
Michael Gnant, one of the BOLERO-2 researchers (Medical University of Vienna, Austria), presented the results at the 8th European Breast Cancer Conference, which was held on 21–24 March in Vienna. Women from the Phase III trial were given a combination of everolimus and exemestane with a control group receiving only exemestane.
The results of the trial showed that markers of bone turnover decreased in women given the combination therapy, suggesting that bone turnover is slower and bones are therefore stronger and less prone to fracture in women receiving everolimus and exemestane.
Three markers of bone turnover and resorption were measured (BSAP, P1NP and CTX) at enrollment and at 6 and 12 weeks after the start of treatment. The markers were found at decreased levels at both time points in patients receiving everolimus and at increased levels in the control group.
The trial also showed positive results with respect to reducing metastasis in bone. The incidence of metastasis in women on the combinatorial therapy was only 3%, in contrast to 6% in women given the placebo. In addition, the recurrence of metastasis in women who previously had metastases decreased from 8% in the placebo group to 4% in the everolimus group.
Speaking on the results of the study, Gnant explains that they “show that the addition of everolimus to exemestane is greatly beneficial to bone health by reducing bone turnover and improving time to bone metastases. Everolimus appears to make it more difficult for metastases to occur and grow in bone.”
The results may have important implications for clinical practice. Speaking on the clinical implications of these results, Gnant said “after approval of everolimus by the authorities (expected later this year), this is likely to become a new standard of care in ER+ metastatic breast cancer.”
Everolimus, an inhibitor of mTOR, is currently used to treat advanced kidney cancer; however, it is also being trialed as a treatment for other cancers. The BOLERO-2 trial investigated the use of the drug in postmenopausal patients with ER+ breast cancer who had developed resistance to aromatase inhibitors, the standard treatment.
Aromatase inhibitors are known to reduce bone strength, meaning any treatment that can counteract this is of great benefit in the treatment of breast cancer. As Gnant explains, “Improving bone health is an important aspect of giving [breast cancer] patients the best possible treatment.”
Gnant further explained that “Everolimus is obviously bone-protective, in addition to the spectacular main effect described in BOLERO-2. This suggests its use in early breast cancer since bone health issues are a challenge there.” Future trials are now being designed to test whether everolimus could be an effective treatment for early breast cancer.
– Written by Alisa Crisp
Source: European Cancer Organisation/European Breast Cancer Conference press release: www.ecco-org.eu/Global/News/EBCC8-PR/2012/03/23_03-Everolimus-plus-exemestane-improves-bone-health-in-post-menopausal-women.aspx
In brief…
Researchers at the University of California at San Francisco School of Medicine (CA, USA) have performed a study examining the relationship between sociodemographic characteristics and the utilization of fertility preservation services in women of reproductive age diagnosed with cancer. It was concluded that sociodemographic health disparities, including age, parity, ethnicity and sexual orientation, are likely to affect access to these services. The authors believe that an unmet need remains for reproductive health counseling and fertility preservation in women of reproductive age diagnosed with cancer.
According to a study at Henry Ford Hospital, low bone density medications, such as Fosamax, Boniva and Actonel, may have a protective effect for endometrial cancer. From of a total of 29,254 women, the rate of endometrial cancer among women who had taken bisphosphonates was approximately half that of women who had never taken the medication (9.6 vs 18.7 per 10,000 person years). The researchers state that a clinical trial with closely monitored data needs to be performed for definitive results.