Open Reading Frame brings together a selection of recent publication highlights from elsewhere in the open access ecosystem. This week we take a look at the past few weeks in medicine.
Exploring new therapeutic strategies for uterine cancer
Uterine serous carcinoma (USC) is an uncommon form of endometrial cancer that typically occurs in postmenopausal women. The HER2 gene is over-expressed in around 30 percent of USC cases, and new research has been carried out to assess whether the antibody-drug conjugate targeting HER2, T-DM1, could be used to treat USC. T-DM1 consists of the antibody therapy trastuzumab linked to mertansine, a cytotoxic agent. The authors showed that T-DM1 is more effective than trastuzumab in reducing cell proliferation in USC cell lines, and that T-DM1 reduces tumor formation in a mouse model of USC. T-DM1 has previously shown promising results in a clinical trial for HER2-positive advanced breast cancer, and these new findings indicate that it could also represent a novel treatment strategy for HER2-positive USC patients.
English et al. Cancer Medicine
Centenarians outlive chronic disease
The number of people who live to be over 100 years old is increasing steadily in the UK, and it is predicted that there will be over half a million centenarians by 2066. It is therefore important to understand the health needs of this unique group of elderly people, so that they can have the best possible end-of-life care. Now, an analysis of death registration data has been carried out to examine the causes of death among centenarians in the UK. Compared with younger elderly patients (aged 80-99), centenarians are more likely to die from pneumonia or frailty, and less likely to die as a result of cancer or heart disease. These findings suggest that many centenarians have outlived death from chronic diseases, but have a higher risk of dying from acute infection. The authors conclude that these findings should inform healthcare policy on caring for the growing number of centenarians, which should include an increase in care home provision to reduce the risk of infection and ensure that more centenarians can end their lives outside hospital.
Evans et al. PLOS Medicine
Choosing donors for stem cell transplants: the importance of NKp46
Hematopoietic stem cell transplantation (HSCT) is used as curative treatment for a range of hematological malignancies, including leukemia and myeloma. Selecting the best match between donor and recipient cells is crucial because transplanted cells can give rise to graft-versus-host disease (GVHD). A new study carried out in mice has revealed that GVHD is exacerbated in the absence of NKp46, a receptor expressed on the surface of natural killer immune cells, leading to death following HSCT. While these findings require further validation in humans, it is known that the expression of NKp46 varies between individuals, suggesting that choosing donors with high levels of NKp46 for treating hematological malignancies could lead to better tumor eradication with minimal GVHD.
Ghadially et al. Cell Reports
Hepatitis B infection: targeting immune cells
Hepatitis B virus (HBV) infection is a major cause of liver disease. In most people, HBV infection is cleared rapidly, but chronic infection persists in some patients, and can progress to liver cirrhosis or hepatocellular carcinoma. The immune system plays an important role in determining whether HBV infection is cleared quickly or persists. In a review article, Anita Schuch and colleagues discuss the role of two key immune system components, natural killer cells and CD8+ T cells, in HBV infection. The authors discuss the mechanisms of T cell dysfunction that contribute to chronic infection, and describe how they can be targeted therapeutically to limit the persistence of HBV and avoid the associated liver complications.
Schuch et al. Frontiers in Immunology
Autism linked to male hormones in the womb
New research suggests that exposure to high levels of male sex hormones in the womb can increase the risk of autism in boys. While autism affects both sexes, it is more common in boys, but the reasons for this male predominance are not fully understood. In this study, Simon Baron-Cohen and colleagues analyzed the levels of four steroid hormones – including testosterone – in amniotic fluid samples, and showed that hormone levels were particularly high for those boys who later developed autism. The authors caution that these hormones are essential for fetal development so cannot be blocked to prevent autism, but these findings pinpoint when autism might be triggered in the process of fetal development. As the hormones identified are produced in higher quantities in males than females, these altered levels could also help to explain why autism is more common in boys. Read more on the latest developments in autism research from Simon Baron-Cohen in a Biome Q&A here.
Baron-Cohen et al. Molecular Psychiatry
Sleep apnea in type 2 diabetes could be unrelated to obesity
Obstructive sleep apnea (OSA), a condition that causes disrupted breathing during sleep, is prevalent among people with type 2 diabetes. OSA is often considered to be obesity-linked, but a new study suggests that OSA could be linked to autonomic nervous system dysregulation, rather than obesity, in those with type 2 diabetes. In a comparison of over 100 non-obese diabetic patients with a group of age- sex- and body mass index-matched controls, those with type 2 diabetes scored higher in a questionnaire to assess the degree of autonomic dysfunction. The authors conclude that OSA could be linked to dysautonomy and unrelated to obesity in these patients, providing new insights into the mechanisms underlying OSA in diabetics.
Rizzi et al. Journal of Clinical & Translational Endocrinology
Written by Claire Barnard, Senior Editor for BMC Medicine.