Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.     

Fundus lesions in malignant hypertension. III. Arterial blood pressure, biochemical, and fundus changes

Malignant (accelerated) renovascular arterial hypertension was produced in 57 adult rhesus monkeys by clamping the renal artery (one-kidney model in 25 animals and two-kidney model in 32). The animals were investigated before renal artery clamping and serially thereafter by recording systolic arterial blood pressure (BP), biochemical changes, and changes in the fundus of the eye; the latter was evaluated by ophthalmoscopy, stereoscopic color fundus photography, and fluorescein fundus angiography. All of the animals developed arterial hypertension. The data on BP, biochemical, and fundus findings were analyzed and correlated. The findings of this study clearly showed that the various fundus lesions seen in these hypertensive animals fall into three distinct categories: (1) hypertensive retinopathy, (2) hypertensive choroidopathy, and (3) hypertensive optic neuropathy. The appearance of the retinopathy was significantly earlier than that of the choroidopathy or optic neuropathy (P less than 0.01), but the difference between the times of appearance of the choroidopathy and neuropathy was not significant. There was no significance in the order in which the three types of fundus changes reached their maximum severity. There was no significant difference between the mean BPs when the retinopathy, choroidopathy, or optic neuropathy first appeared, nor between the BPs at the time of their appearance and at the time when they were most marked. In monkeys of the one-kidney model, the rise in BP developed significantly (P = 0.01) faster and the fundus lesions appeared significantly (P = 0.00001) earlier than in those with the two-kidney model.     

Role of oxidative stress,angiogenesis and chemo-attractant cytokines in the pathogenesis of ischaemic protection induced by remote ischaemic conditioning: Study of a human model of ischaemia-reperfusion induced vascular injury

Aims

We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.

A patient with testis seminoma, sarcoidosis, and neutropenic enterocolitis

Seminoma and sarcoidosis do not seem to be associated diseases, judging from epidemiologic data. The presence of these two diseases in the patient whose case is reported may have been coincidental. It was observed, however, that when the testis tumor appeared in this patient, the longstanding sarcoid lesions significantly increased. The patient developed neutropenic enterocolitis after chemotherapy for a non-hematologic malignancy.     

In vitro influence of thymopentin on proliferative responses and phytohemagglutinin-induced interleukin 2 production in normal human lymphocyte cultures

Immunologic Research - Peripheral human blood lymphocytes from healthy blood donors were investigated in vitro to observe the influence of different doses of thymopentin on nonstimulated...     

Event-related potentials (ERPs) in ecstasy (MDMA) users during a visual oddball task

Ecstasy is the common name for a drug mainly containing a substance identified as 3,4-methylenedioxymethamphetamine (MDMA). It has become popular with participants in “raves”, because it enhances energy, endurance and sexual arousal, together with the widespread belief that MDMA is a safe drug [Byard, R.W., Gilbert, J., James, R., Lokan, R.J., 1998. Amphetamine derivative fatalities in South Australia. Is “ecstasy” the culprit? Am. J. Forensic Med. Pathol. 19, 261–265]. However, it is suggested that this drug causes a neurotoxicity to the serotonergic system that could lead to permanent physical and cognitive problems.In order to investigate this issue, and during an ERP recording with 32 channels, we used a visual oddball design, in which subjects (14 MDMA abusers and 14 paired normal controls) saw frequent stimuli (neutral faces) while they had to detect as quickly as possible rare stimuli with happy or fearful expression.At a behavioral level, MDMA users imply longer latencies than normal controls to detect rare stimuli. At the neurophysiological level, ERP data suggest as main result that the N200 component, which is involved in attention orienting associated to the detection of stimulus novelty (e.g. [Campanella, S., Gaspard, C., Debatisse, D., Bruyer, R., Crommelinck, M., Guérit, J.M., 2002. Discrimination of emotional facial expression in a visual oddball task: an ERP study. Biol. Psychol. 59, 171–186]), shows shorter latencies for fearful rare stimuli (as compared to happy ones), but only for normal controls. This absence of delay was interpreted as an attentional deficit due to MDMA consumption.     

Simple DNA extraction method for dried blood spots and comparison of two PCR assays for diagnosis of vertical human immunodeficiency virus type 1 transmission in Rwanda

Dried blood spots (DBS) on filter paper facilitate the collection, transport, and storage of blood samples for laboratory use. A rapid and simple DNA extraction procedure from DBS was developed and evaluated for the diagnosis of human immunodeficiency virus type 1 (HIV-1) infection in children by an in-house nested-PCR assay on three genome regions and by the Amplicor HIV-1 DNA prototype assay version 1.5 (Roche Molecular Systems). A total of 150 samples from children born to HIV-1-infected mothers were collected in Kigali, Rwanda, in parallel as DBS and as peripheral blood mononuclear cell (PBMC) pellets. The results obtained on DBS by the two PCR assays were compared to the results of nested PCR on PBMCs. Of 150 PBMC samples, 10 were positive, 117 were negative, and 23 were indeterminate for HIV-1 infection. In DNA extracted from filter papers and amplified by using the in-house nested PCR, 9 of these 10 positive samples (90%) were found to be positive, and 1 was found to be indeterminate (only the pol region could be amplified). All of the negative samples and all of the 23 indeterminate samples tested negative for HIV-1 infection. When we used the Amplicor DNA test on DBS, all of the 10 PBMC-positive samples were found to be positive and all of the 23 indeterminate samples were found to be negative. Of the PBMC-negative samples, 115 were found to be negative and 2 were found to be indeterminate. We conclude that this simple rapid DNA extraction method on DBS in combination with both detection methods gave a reliable molecular diagnosis of HIV-1 infection in children born to HIV-infected mothers.