Abstract c-jun mRNA levels were increased in rat hepatoma cells (H4-II-E-C3) when exposed to hypotonie medium (205 mosmoll) with a maximal induction observed after 1 h of hypotonie exposure. At this time point an approximate 5-fold increase in c-jun expression could be detected in relation to nonnotonic control incubations (305 mosmoll). Hypertonic exposure (405 mosmol/1) had only a slight effect on c-jun expression. In contrast to the increased c-jun mRNA levels under hypotonic conditions, expression of the c-fos proto-oncogene was unaffected by changes in the osmolarity. The hypotonicity-induced increase in c-jun expression was also detectable in the presence of a protein kinase C (PKC) inhibitor. This indicates that PKC is not involved in the signal transduction pathway leading to c-jun expression upon hypotonic cell swelling in these cells.

Purpose We examined the clinical significance of long-term serum testosterone monitoring to predict the prognosis of patients with prostate cancer treated with combined androgen blockade. Materials and Methods We retrospectively analyzed the records of 225 patients who underwent combined androgen blockade as first line therapy for prostate cancer. The prognostic values of testosterone and other clinical factors were evaluated with respect to prostate specific antigen progression-free and overall survival. Results Median patient age was 73.0 years, median prostate specific antigen was 42.6 ng/ml and median followup was 45.8 months. No variable associated with testosterone was predictive of progression-free survival. With regard to overall survival on univariate analysis nadir testosterone less than 16 ng/dl (p = 0.0190), less than 20 ng/dl (p = 0.0020) and less than 32 ng/dl (p = 0.0146) were significant together with other clinical factors. In contrast, nadir testosterone less than 8 and less than 12 ng/dl were not significant. Multivariate analysis showed that nadir testosterone less than 20 ng/dl was the significant prognostic factor (p = 0.0048). In addition, time to nadir testosterone was about 1 year (11.3 months). Patients were divided into rapid and slow types based on time to testosterone less than 20 ng/dl before and after 6 months, respectively. No significant difference in overall survival was observed between the 2 types. The current results suggest that the critical factor for prognosis was not a rapid decrease but whether nadir testosterone achieved a level of less than 20 ng/dl. Conclusions Nadir testosterone 20 ng/dl was the most significant cutoff level for overall survival in Japanese patients with prostate cancer treated with combined androgen blockade.

Curcumin, a natural yellow phenolic compound, is present in many kinds of herbs, particularly in Cur- cuma longa Linn. (turmeric). It is a natural antioxidant and has shown many pharmacological activities such as anti-inflammatory, anti-microbial, anti-cancer, and anti-Alzheimer in both preclinical and clinical studies. Moreover, curcumin has hepatoprotective, nephroprotective, cardioprotective, neuroprotective, hypoglycemic, antirheumatic, and antidiabetic activities and it also suppresses thrombosis and protects against myocardial infarction. Particularly, curcumin has demonstrated efficacy as an anticancer agent, but a limiting factor is its extremely low aqueous solubility which hampers its use as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. In this re- view, we summarize the recent works on the design and development of nano-sized delivery systems for curcumin, including liposomes, polymeric nanoparticles and micelles, conjugates, peptide carriers, cy- clodextrins, solid dispersions, lipid nanoparticles and emulsions. Efficacy studies of curcumin nano- formulations using cancer cell lines and in vivo models as well as up-to-date human clinical trials are also discussed.

Purpose We determined the incidence of pathological upgrading and up staging for contemporary, clinically low risk patients, and identified predictors of having occult, advanced disease to inform the selection of patients for active surveillance. Materials and Methods We studied 10,273 patients in the SEER database diagnosed with clinically low risk disease (cT1c/T2a, prostate specific antigen less than 10 ng/ml, Gleason 3+3=6) in 2010 to 2011 and treated with prostatectomy. The primary outcome was the incidence of upgrading to pathological Gleason score 7-10 or up staging to pathological T3-T4/N1 disease. Multivariable logistic regression of cases with complete biopsy data (5,581) identified significant predictors of upgrading or up staging, which were then used to create a risk stratification table. Results At prostatectomy 44% of cases were upgraded and 9.7% were up staged. Multivariable analysis of 5,581 patients showed age, prostate specific antigen and percent positive cores (all p <0.001) but not race were associated with occult, advanced disease. With these variables dichotomized at the median, age older than 60 years (AOR 1.39), prostate specific antigen greater than 5.0 ng/ml (AOR 1.28) and more than 25% positive cores (AOR 1.76) were significantly associated with upgrading (all p <0.001). Similarly, age older than 60 years (AOR 1.42), prostate specific antigen greater than 5.0 ng/ml (AOR 1.44) and more than 25% positive cores (AOR 2.26) were associated with up staging (all p <0.001). Overall 60% of 5,581 low risk cases with prostate specific antigen 7.5 to 9.9 ng/ml and more than 25% positive cores were upgraded. This study is limited by possible bias introduced by only using patients selected for prostatectomy. Conclusions Nearly half of clinically low risk patients harbor Gleason 7 or greater, or pT3 or greater disease, and should be risk stratified by prostate specific antigen and percent positive cores for consideration of further testing before deciding on active surveillance.

Abstract Aim of study Incidence rates of melanoma, generated by cancer registries (CRs), are susceptible to reporting inconsistencies due to increasing decentralisation of diagnosis. We therefore independently assessed the burden of melanoma in Austria. Methods We collected histopathological reports on melanoma of all patients diagnosed in Austria in 2011. Demographic and clinical characteristics, histopathological tumour stages were assessed. Their regional distributions and incidence rates were analysed and compared with data of national and international CRs. Results A total of 5246 patients were diagnosed with 1951 in-situ and 3295 invasive melanomas in Austria in 2011 (population 8.4 million). Age, sex and anatomic distribution corresponded to findings in other European countries, however, the incidence of 25/100,000 (world age-standardised rate) for invasive melanomas was two-fold higher than published by the Austrian CR (12/100,000). Varying frequencies in diagnosing thin melanomas (≤1 mm; n = 4415) accounted exclusively for significant regional disparities, while advanced tumours (>1 mm; n = 761) were evenly distributed. Western Austria showed the highest rates (36/100,000). Patients from eastern Austria whose melanomas were diagnosed in laboratories in western Austria (n = 76) showed significantly higher proportions of in-situ lesions (n = 43; 57%) compared to those whose tumours were diagnosed in eastern Austria (n = 4014; in-situ = 1369; 34%) (p < 0.0001). Conclusions In Austria, the melanoma burden and its potential socio-economic implications are significantly underestimated. Similarities of incidences indicate this could affect other European countries with well-established CRs and compromise international comparability of data. Austrian regional disparities suggest overdiagnosis of thin melanomas due to the variability of pathologists' thresholds for the diagnosis of early stage tumours.

Abstract miR-410 acts as an oncogene or tumor suppressor gene in some malignancies. However, its role in NSCLC is still unknown. In this study, we showed that the expression of miR-410 was up-regulated in both human NSCLC tissues and cells. Overexpression of miR-410 promoted cell proliferation, migration, and invasion of NSCLC. In addition, bromodomain-containing protein 7 (BRD7) was a direct target of miR-410. MiR-410-mediated downregulation of BRD7 led to increase Akt phosphorylation. Inhibition of Akt phosphorylation can rescue the effect of miR-410 on NSCLC cell. The expression of BRD7 was downregulated in NSCLC and was inversely expressed with miR-410 in NSCLC. Our data provided new knowledge regarding the role of miR-410 in the lung cancer progression.

Lymphadenectomy is a well established practice for many urological malignancies but its role in renal cell carcinoma is less clear. Our primary objective was to determine whether lymphadenectomy impacted survival in patients with fully resected, high risk renal cell carcinoma.

Abstract Aberrant expression of miR-204 had been frequently reported in cancer studies; however, the mechanism of its function in retinoblastoma remained unknown. Here, we reported that miR-204 was frequently downregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-204 inhibited retinoblastoma cells’ proliferation and invasion. In vivo study indicated that restoration of miR-204 inhibited tumor growth. CyclinD2 and MMP-9 were identified as potential targets of miR-204. In addition, a reverse correlation between miR-204 and CyclinD2 or MMP-9 expression was noted in retinoblastoma tissues. Taken together, our results identified a crucial tumor suppressive role of miR-204 in the progression of retinoblastoma.

The presence of mechanical linkages between synergistic muscles and their common tendons may distribute forces among the involved structures. We review studies, using humans and other animals, examining muscle and tendon interactions and discuss the hypothesis that connections between muscle bellies and within tendons may serve as a mechanism to distribute forces and mitigate peak stresses.

Mitochondria regulate hepatic lipid metabolism and oxidative stress. Ultrastructural mitochondrial lesions, altered mitochondrial dynamics, decreased activity of respiratory chain complexes, and impaired ability to synthesize adenosine triphosphate are observed in liver tissues from patients with alcohol-associated and non-associated liver diseases. Increased lipogenesis with decreased fatty acid β-oxidation leads to the accumulation of triglycerides in hepatocytes, which, combined with increased levels of reactive oxygen species, contributes to insulin resistance in patients with steatohepatitis. Moreover, mitochondrial reactive oxygen species mediate metabolic pathway signaling; alterations in these pathways affect development and progression of chronic liver diseases. Mitochondrial stress and lesions promote cell death, liver fibrogenesis, inflammation, and the innate immune responses to viral infections. We review the involvement of mitochondrial processes in development of chronic liver diseases, such as nonalcoholic fatty, alcohol-associated, and drug-associated liver diseases, as well as hepatitis B and C, and discuss how they might be targeted therapeutically.