Targeted anti-vascular therapies for ovarian cancer: current evidence

Ovarian cancer presents at advanced stage in around 75% of women, and despite improvements in treatments such as chemotherapy, the 5-year survival from the disease in women diagnosed between 1996 and 1999 in England and Wales was only 36%. Over 80% of patients with advanced ovarian cancer will relapse and despite a good chance of remission from further chemotherapy, they will usually die from their disease. Sequential treatment strategies are employed to maximise quality and length of life but patients eventually become resistant to cytotoxic agents. The expansion in understanding of the molecular biology that characterises cancer cells has led to the rapid development of new agents to target important pathways but the heterogeneity of ovarian cancer biology means that there is no predominant defect. This review attempts to discuss progress to date in tackling a more general target applicable to ovary cancer-angiogenesis

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Full-wave modeling of broadband near field scanning microwave microscopy

The authors would like to thank professor Dr. Gabriel Gomila from Institut de Bioenginyeria de Catalunya (IBEC) and Universitat de Barcelona for the fruitful discussion and support, as well as to Dr. Georg Gramse from Johannes Kepler University Linz for the experimental data. B.W. thanks the funding from the China Scholarship Council (CSC) for the support of his research at Queen Mary University of London, UK. Y.H. would like to thank EU-FP7 Nanomicrowave project for the financial support

Organization of high-level visual cortex in human infants

How much of the structure of the human mind and brain is already specified at birth, and how much arises from experience? In this article, we consider the test case of extrastriate visual cortex, where a highly systematic functional organization is present in virtually every normal adult, including regions preferring behaviourally significant stimulus categories, such as faces, bodies, and scenes. Novel methods were developed to scan awake infants with fMRI, while they viewed multiple categories of visual stimuli. Here we report that the visual cortex of 4–6-month-old infants contains regions that respond preferentially to abstract categories (faces and scenes), with a spatial organization similar to adults. However, precise response profiles and patterns of activity across multiple visual categories differ between infants and adults. These results demonstrate that the large-scale organization of category preferences in visual cortex is adult-like within a few months after birth, but is subsequently refined through development.National Science Foundation (U.S.) (CCF-1231216

Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis

<p>Abstract</p> <p>Background</p> <p>Gluten sensitive enteropathy (GSE) is an autoimmune enteropathy triggered by the ingestion of gluten-containing grains in susceptible individuals. Recurrent aphthous stomatitis (RAS) may be the sole manifestation of GSE. The aim of this study was to determine the prevalence of gluten sensitivity enteropathy (GSE) in a large group of patients with RAS and assess the efficacy of gluten free diet (GFD) on the improvement of aphthous lesions in those who were diagnosed with GSE.</p> <p>Methods</p> <p>Two hundred and forty seven patients with RAS were included. The patients had at least three aphthous attacks per year. Patients were screened by IgA anti-endomysial antibody (EMA), IgA anti tissue transglutaminase (TTG) and serum IgA level. Those with a positive serology underwent endoscopic biopsies of the duodenal mucosa and patients with negative serology were excluded. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. For patients with GSE, gluten free diet was recommended.</p> <p>Results</p> <p>Six out of 247 RAS patients had positive TTG test alone, and one had positive EMA and TTG. All 7 patients with positive serologic tests underwent duodenal biopsies. Histological findings were compatible with GSE in all of them (Marsh I in four patients, Marsh II in two patients and Marsh IIIB in one another.). The mean age of GSE patients was 27.42 ± 10.56 (range, 13 to 40) years old. They were suffering from RAS for an average duration of 4.5 years. All of the 7 GSE patients had not responded to the routine anti-aphthae medications, including topical corticosteroids, tetracycline and colchicine. Four patients who adhered to a strict gluten-free diet showed noticeable improvement in their aphthous lesions over a period of 6 months.</p> <p>Conclusion</p> <p>A significant minority (e.g. 2.83%) of RAS patients have GSE. This could be compared with the 0.9% prevalence of GSE in the general population of Iran. This study suggests that evaluation for celiac disease is appropriate in patients with RAS. Additionally, the unresponsiveness to conventional anti-aphthae treatment could be an additional risk indicator.</p

Sampling circulating tumor cells for clinical benefits: how frequent?

Circulating tumor cells (CTCs) are cells shed from tumors or metastatic sites and are a potential biomarker for cancer diagnosis, management, and prognostication. The majority of current studies use single or infrequent CTC sampling points. This strategy assumes that changes in CTC number, as well as phenotypic and molecular characteristics, are gradual with time. In reality, little is known today about the actual kinetics of CTC dissemination and phenotypic and molecular changes in the blood of cancer patients. Herein, we show, using clinical case studies and hypothetical simulation models, how sub-optimal CTC sampling may result in misleading observations with clinical consequences, by missing out on significant CTC spikes that occur in between sampling times. Initial studies using highly frequent CTC sampling are necessary to understand the dynamics of CTC dissemination and phenotypic and molecular changes in the blood of cancer patients. Such an improved understanding will enable an optimal, study-specific sampling frequency to be assigned to individual research studies and clinical trials and better inform practical clinical decisions on cancer management strategies for patient benefits

Parallels between Pathogens and Gluten Peptides in Celiac Sprue

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights

Genome Wide DNA Copy Number Analysis of Serous Type Ovarian Carcinomas Identifies Genetic Markers Predictive of Clinical Outcome

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups