Loss of aquaporin-4 expression and putative function in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs.</p> <p>Methods</p> <p>We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue.</p> <p>Conclusions</p> <p>Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets.</p

First data concerning the medical supply of patients with non-alcoholic fatty liver disease in Germany - a survey in university hospital centers of hepatology

Background: Non-alcoholic fatty liver disease (NAFLD) currently is one oft the most common reasons for chronic liver injury in the western world. In the European and American population the prevalence is up to 30 %. The medical supply of German patients with NAFLD is variable and has not been analyzed to date. Methods: We sent questionnaires to all university liver centers in Germany (11 questions) concerning the medical supply of patients with NAFLD. Questions included the rate of patients with fatty liver disease in the outpatient clinics, metabolic comorbidities and the kind of assignment. Besides that, individual clinical standards were documented. We compared longitudinal changes between 2008 and 2013. Results: The return rate of questionnaires was 65 % (n = 20). Analysis showed that the portion of NAFLD patients in the university outpatient clinics had increased between 2008 and 2013 with the predominant part of patients being assigned from external practitioners and not from internal departments of the hospital. Only few patients were assigned by diabetologists or endocrinologists, but on the other hand most liver outpatient clinics investigated their NAFLD patients for metabolic disorders. Cooperation between liver outpatient clinics and other medical services was moderate and was rated average, joint conferences were held rarely. Follow-up visits of patients with NAFLD take place regularly in all centers, however based on different criterions. A consistent algorithm concerning risk assessment and invasive workup does not exist. Conclusion: The awareness concerning patients with NAFLD seems to have grown in recent years. Nevertheless, the medical supply of these patients is quite heterogenous and consistent standards do not exist. Therefore, a common guidline is urgently required

Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus-infected patients with renal impairment: results from a 7-year, multicentre retrospective cohort study

Background: Limited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus\u2013infected (CHB) patients with renal impairment (RI). Aims: To compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI. Methods: Retrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60&nbsp;mL/min [Cockcroft-Gault]) either before TDF/ETV initiation (\u2018before\u2019 subgroup [baseline&nbsp;=&nbsp;treatment initiation]) or after TDF/ETV initiation (\u2018after\u2019 subgroup [baseline&nbsp;=&nbsp;first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting. Results: \u2018Before\u2019 subgroup included 107 TDF- and 91 ETV-treated patients; \u2018after\u2019 subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1&nbsp;years (both treatments). AESI were more frequent with TDF vs ETV (\u2018before\u2019: 18.7% vs 8.8%; \u2018after\u2019: 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% \u2018before\u2019; 1.9% \u2018after\u2019) as well as renal adverse events leading to treatment discontinuation (8.4% \u2018before\u2019; 7.1% \u2018after\u2019). Effectiveness was similar between treatments. Conclusions: Overall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI