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

Heterochronic faecal transplantation boosts gut germinal centres in aged mice

Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system, however it is not clear if there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli

Clinical practice: Coeliac disease

Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100–200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. Conclusion: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted

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

Potential theory results for a class of PDOs admitting a global fundamental solution

We outline several results of Potential Theory for a class of linear par-tial differential operators L of the second order in divergence form. Under essentially the sole assumption of hypoellipticity, we present a non-invariant homogeneous Harnack inequality for L; under different geometrical assumptions on L (mainly, under global doubling/Poincar\ue9 assumptions), it is described how to obtainan invariant, non-homogeneous Harnack inequality. When L is equipped with a global fundamental solution \u393, further Potential Theory results are available (such as the Strong Maximum Principle). We present some assumptions on L ensuring that such a \u393 exists

Antiangiogenic drugs in ovarian cancer

Ovarian cancer continues to be a major cause of morbidity and mortality in women. Antiangiogenic treatments have emerged as a promising strategy to treat ovarian cancer. This article reviews the rationale supporting the use of antiangiogenic treatments in ovarian cancer, the clinical development of this group of drugs and the toxicities specific to this modality of treatment