PARP inhibition: A promising therapeutic target in ovarian cancer.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

Two consecutive twin and a singleton pregnancy in a patient with chronic myeloid leukemia.

Consecutive multiple pregnancies with Chronic myeloid leukemia is a rare event and little is known about its prevalence and management with or without chemotherapy. We present a case of three consecutive pregnancies in a woman with CML, two of which were multiple pregnancies.

Pharmacological prophylaxis for deep vein thrombosis in acute spinal cord injury: an Indian perspective.

STUDY DESIGN: Prospective randomized single blind study. OBJECTIVES: To find out the incidence of deep vein thrombosis (DVT) in Indian acute spinal cord injury (ASCI) subjects with and without pharmacological prophylaxis. SETTING: Indian Spinal Injuries Centre. METHODS: Seventy four ASCI subjects were randomly divided into two groups with 37 subjects each: group I received no antithrombotic prophylaxis, and only physical measures like compression stockings were employed for prophylaxis, whereas group II received antithrombotic prophylaxis with low-molecular weight heparin (LMWH) along with physical measures as in group I. DVT was monitored through daily clinical assessment and doppler venous ultrasonography at 2 weeks. RESULTS: Out of 37 subjects in each group, eight (21.6%) developed DVT in group I and two (5.4%) in group II. The difference was significant (P-value=0.041). Six out of eight subjects who developed DVT in group I were asymptomatic. There was no incidence of significant DVT-related complications including pulmonary embolism in any of the subjects. CONCLUSIONS: There is a significant incidence of DVT in Indian subjects with ASCI but definitely less than what has been reported in western literature. Pharmacological prophylaxis (LMWH in this study) significantly (P=0.041) decreases the incidence of DVT in subjects with ASCI. As there was no difference in the incidence of symptomatic DVT or related complications, a larger study would be required to conclude definitely on the role of pharmacological prophylaxis in the Indian population.

A simulator study of adverse wear with metal and cement debris contamination in metal-on-metal hip bearings.

OBJECTIVES: Third-body wear is believed to be one trigger for adverse results with metal-on-metal (MOM) bearings. Impingement and subluxation may release metal particles from MOM replacements. We therefore challenged MOM bearings with relevant debris types of cobalt-chrome alloy (CoCr), titanium alloy (Ti6Al4V) and polymethylmethacrylate bone cement (PMMA). METHODS: Cement flakes (PMMA), CoCr and Ti6Al4V particles (size range 5 µm to 400 µm) were run in a MOM wear simulation. Debris allotments (5 mg) were inserted at ten intervals during the five million cycle (5 Mc) test. RESULTS: In a clean test phase (0 Mc to 0.8 Mc), lubricants retained their yellow colour. Addition of metal particles at 0.8 Mc turned lubricants black within the first hour of the test and remained so for the duration, while PMMA particles did not change the colour of the lubricant. Rates of wear with PMMA, CoCr and Ti6Al4V debris averaged 0.3 mm(3)/Mc, 4.1 mm(3)/Mc and 6.4 mm(3)/Mc, respectively. CONCLUSIONS: Metal particles turned simulator lubricants black with rates of wear of MOM bearings an order of magnitude higher than with control PMMA particles. This appeared to model the findings of black, periarticular joint tissues and high CoCr wear in failed MOM replacements. The amount of wear debris produced during a 500 000-cycle interval of gait was 30 to 50 times greater than the weight of triggering particle allotment, indicating that MOM bearings were extremely sensitive to third-body wear. Cite this article: Bone Joint Res 2015;4:29-37.

Comprehensive microRNA expression profiling of the hematopoietic hierarchy.

The hematopoietic system produces a large number of highly specialized cell types that are derived through a hierarchical differentiation process from a common stem cell population. miRNAs are critical players in orchestrating this differentiation. Here, we report the development and application of a high-throughput microfluidic real-time quantitative PCR (RT-qPCR) approach for generating global miRNA profiles for 27 phenotypically distinct cell populations isolated from normal adult mouse hematopoietic tissues. A total of 80,000 RT-qPCR assays were used to map the landscape of miRNA expression across the hematopoietic hierarchy, including rare progenitor and stem cell populations. We show that miRNA profiles allow for the direct inference of cell lineage relations and functional similarity. Our analysis reveals a close relatedness of the miRNA expression patterns in multipotent progenitors and stem cells, followed by a major reprogramming upon restriction of differentiation potential to a single lineage. The analysis of miRNA expression in single hematopoietic cells further demonstrates that miRNA expression is very tightly regulated within highly purified populations, underscoring the potential of single-cell miRNA profiling for assessing compartment heterogeneity.

Fournier's gangrene in a female with spinal cord injury: a case report.

INTRODUCTION: We report the case of a woman with spinal cord injury (SCI) who presented to us with Fournier's gangrene. CASE REPORT: A 60-year-old patient with SCI, ASIA A, neurological level D6, on clean intermittent catheterization presented with rapid necrosis of the perineal region, including the labia and anus, which developed after traumatic catheterizations for clean intermittent catheterization. She required repeated debridement and loop colostomy for management. CONCLUSION: We conclude that patients with SCI are rarely at risk for Fournier's gangrene secondary to neurogenic bladder and bowel, as well as to impaired sensations and genital flora. Treating physicians need to be aware of this complication in order to prevent mortality.

Positive impact of selective outpatient management of high-risk acute myelogenous leukemia on the incidence of septicemia.

BACKGROUND: Curative intent chemotherapy for acute myelogenous leukemia (AML) leads to prolonged severe neutropenia, during which patients are highly susceptible to infection. Traditionally these high-risk patients were treated as inpatients. Our center recently implemented a selective ambulatory management policy for AML patients undergoing chemotherapy. MATERIALS AND METHODS: A retrospective analysis was conducted to assess the occurrence of septicemia in AML patients treated over a 5 years period with curative intent chemotherapy. This review encompasses a change in policy from primarily inpatient care to selective outpatient management coupled with prophylactic antibiotic therapy. RESULTS: A total of 294 patients, receiving 623 cycles of chemotherapy were identified. A significant decrease in septicemia was observed from the inpatient to outpatient cohort (22% to 13% P < 0.05), which correlated with the shift towards outpatient treatment of consolidation cycles. A shift from Gram-negative to Gram-positive organisms as the cause of septicemia was also detected in the outpatient cohort, likely due to the introduction of ciprofloxacin prophylaxis. No significant emerging resistance and no septicemia-related mortality were noted in the outpatient cohort. CONCLUSION: The observed decrease in the incidence of septicemia in the ambulatory cohort adds supportive evidence to the feasibility of selective outpatient management of AML patients with respect to infectious complications.