Low-dose LBH589 increases the sensitivity of cisplatin to cisplatin-resistant ovarian cancer cells

ObjectiveThere is a need to develop alternative therapeutic strategies to overcome cisplatin-associated resistance in patients with ovarian cancer. Histone deacetylation (HDAC) associated with inactivation of genes has been implicated in the epigenetic silencing of tumor suppressor genes affecting critical biological activities in cancer cells and may be an important factor in acquired cisplatin-associated resistance. In this report, we tested a combination of cisplatin and LBH589 (histone deacetylation inhibitor) in cisplatin-resistant ovarian cancer cells to explore the reversal effect of cisplatin resistance and changes of gene expression.Materials and MethodsTo detect the synergistic effects of antiproliferation between cisplatin and LBH589 in ovarian cancer cells, we performed a cell viability assay and a clonogenic assay. To investigate the differences of gene expression between cells treated by cisplatin alone and cotreated with cisplatin and LBH589, a microarray mRNA analysis was performed.ResultsIn the presence of low-dose LBH589, the inhibition concentration value of cisplatin for A2780-cp70 cells was much lower than with cisplatin treatment alone. Gene expression profiles identified that a total of 354 genes had been significantly upregulated and a total of 63 genes been downregulated with LBH589 cotreatment.ConclusionWe hypothesized that combination of cisplatin and LBH589 can override cisplatin-associated resistance in ovarian cancer cells. These results provide initial evidence for testing this combination in clinical use.     

Significance of seemingly intact urothelium in patients with bladder cancer

During 9 years (from 1979 to 1988) the authors performed 412 multiple cold biopsies taken from 9 different points of the cancerous bladder in 263 patients. In 42 per cent of the patients the hystopathological examination of biopsy materials discovered dysplasia, carcinoma in situ or tumor of the grossly normal urothelium. The frequency of these proliferative lesions is closely connected with number, configuration, grading and depth of infiltration of overt bladder tumor. These lesions indicate the probable recurrence-rate as well as danger of the more progressive recurrence.     

Cytokines as Prognostic Biomarkers of Epithelial Ovarian Cancer (EOC): A Systematic Review and Meta-Analysis

Objectives: The value of cytokines as epithelial ovarian cancer (EOC) prognostic factors has been widely investigated. This study aimed to determine the role of single cytokine as a biomarker prognosis in EOC. Materials and Methods: We conducted a systematic review and meta-analysis of studies reporting cytokine as the prognostic predictor in EOC based on PRISMA guideline. We included English articles investigating associations of preoperative cytokines level in tissue, blood or ascites with overall survival (OS) or disease-free survival (DFS) from PUBMED and EBSCO. Summary hazard ratios (HRs) and confidence intervals (CIs) were calculated. Results: Fifty studies investigating twenty types of cytokines in tumor tissue, serum, and ascites from 5,376 patients were included. Pre-operative high VEGF level was associated with poor OS (HR 2.28, 95%CI [1.28, 3.28]) and DFS (HR 2.13, 95%CI [1.63, 2.78]) in serum and OS (HR 1.80, 95%CI [1.45, 2.23]) in tissue. IL-6 level in blood was associated with DFS (HR 1.60, 95%CI [1.21, 2.11]). There was no single cytokine which investigated by at least 2 studies reporting hazard ratio in ascites, so we did not conduct the meta-analysis. Other cytokines (serum IL-8; ascites fluid IL-8, IL-10, IFN-γ, TNF-α; and ovarian tissue TGF-α, CSF-1, IL-10 ,TGF-β1, IL-17) associated with the poorer prognosis, could not be pooled due to lack of studies. Conclusion: Pre-operative VEGF level in serum and tissue specimen seem to be the potential candidate of an unfavorable prognostic biomarker for EOC. The evidence was lacking to support the other cytokines investigated in blood, tissue and ascites as prognostic biomarkers for EOC.     

Wireless oesophageal pH monitoring: Establishing values in a multiracial cohort of asymptomatic Asian subjects

BackgroundWireless oesophageal (Bravo) readings in healthy European and American subjects show varied results. Values in Asians remain unstudied.AimsWe performed Bravo studies in healthy Asians to determine if values differed from previously published and identified reflux parameters to differentiate healthy volunteers from patients.MethodsFifty healthy volunteers were recruited between August 2009 and August 2011 to undergo 48 h wireless pH monitoring. Bravo capsule was introduced transorally and placed 6 cm above the squamocolumnar junction. Acid reflux parameters were compared against 41 patients previously evaluated for non-erosive reflux disease.ResultsFive volunteers were excluded. Capsule dislodgement occurred in four and three volunteers on study days 1 and 2 respectively. Forty and 37 volunteers (73% male, mean age 33.0 ± 7.6 years) had interpretable readings at 24 and 48 h, respectively. Percentage of time oesophageal pH < 4 in 37 volunteers who completed 48 h recordings was 1.6% (7.5%), 1.5% (6.3%) and 1.9% (5.8%) on days 1, 2 and overall study duration, respectively.ConclusionBravo readings in Asians differed from previously published. Percentage of time oesophageal pH < 4 on day 2 and DeMeester score on day 2 (95th percentile 22.9) best discriminated healthy volunteers from patients.     

Three cases of mycobacteriosis with gastrointestinal localization

The authors present three patients having primary microbacterial infections which involved the gastrointestinal tract. A short survey of the clinical features and the difficulties arriving at definitive diagnosis is given. They discuss the differential diagnostic problems in each case--without an unequivocal bacterial findings--on the basis of histologyc data and of therapeutic response which ultimately proved the mycobacterial nature of the infection.     

Lumbar facet anatomy changes in spondylolysis: a comparative skeletal study

Opinions differ as to the exact mechanism responsible for spondylolysis (SP) and whether individuals with specific morphological characteristics of the lumbar vertebral neural arch are predisposed to SP. The aim of our study was to reveal the association between SP and the architecture of lumbar articular facets and the inter-facet region. Methods: Using a Microscribe three-dimensional apparatus (Immersion Co., San Jose, CA, USA), length, width and depth of all articular facets and all inter-facet distances in the lumbar spine (L1–L5) were measured. From the Hamann-Todd Human Osteological Collection (Cleveland Museum of Natural History, OH, USA) 120 normal male skeletons with lumbar spines in the control group and 115 with bilateral SP at L5 were selected. Analysis of variance was employed to examine the differences between spondylolytic and normal spines. Results: Three profound differences between SP and the norm appeared: (1) in individuals with SP, the size and shape of L4’s neural arch had significantly greater inter-facet widths, significantly shorter inter-facet heights and significantly shorter and narrower articular facets; (2) only in the L4 vertebra in individuals with SP was the inferior inter-facet width greater in size than the superior inter-facet width of the vertebra below (L5) (38.7 mm versus 40 mm); (3) in all lumbar vertebrae, the right inferior articular facets in individuals with SP were flatter compared to the control group. Conclusions: Individuals with L4 “SP” characteristics are at a greater risk of developing fatigue fractures in the form of spondylolysis at L5.