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The aim of the study was to evaluate prognosis for biochemical recurrence (BR) by analysing the pathological and biological characteristics of prostate cancer (PCa) after radical prostatectomy (RP). There were 130 men with clinically localized PCa in whom pretreatment serum PSA level and Ki-67, prostate specific membrane antigen (PSMA), glucose transporter-1 (GLUT-1), vascular endothelial growth factor (VEGF), microvessel density (MVD) and human telomerase reverse transcriptase (hTERT) proteins expression, based on number of immunohistochemically positive cells (labelling index), were retrospectively studied. In order to assess the prognostic significance of analysed variables in univariate and multivariate Cox analysis, patients were dichotomized based on cut-off points chosen by receiver operating characteristic (ROC) curves. There were 83 males (63.8%) at pT stage 1–2 and 47 (36.1%) at pT stage 3–4, respectively, with median (range) age of 62.8 years (49–77), and median follow-up of 78.5 months (12–148). In 42 (32.3%) men BR was found. In univariate analysis, tumour biological features: PSA ≤ 8 ng/mL (p = 0.006), Ki-67LI ≤ 12.7% (p = 0.015), VEGFLI>11.0% (p = 0.030), and hTERTLI>6.7% (p = 0.016), but not clinicopathological parameters, appeared to be positive prognosticators for BRFS. In the Cox analysis, Ki-67 lost its significance, and clinicopathological parameters appeared to be nonsignificant. The independent negative prognostic factors for BRFS were: PSA > 8.0 ng/mL, (Hazard ratio = 2.75, p = 0.003), GLUT-1 > 19.1% (HR = 2.1, p = 0.032), VEGF≤11.0% (HR = 1, p = 0.024) and hTERT≤6.7% (HR = 1, p = 0.017). High PSA level, and GLUT-1 expression and lower VEGF and nuclear hTERT expression may indicate the great role of hypoxia in BR induction in PCa.

Funder: Kjell och Märta Beijers Stiftelse (SE), Funder: Hjärnfonden; doi: http://dx.doi.org/10.13039/501100003792, Funder: Cancerfonden; doi: http://dx.doi.org/10.13039/501100002794, Funder: Vetenskapsrådet; doi: http://dx.doi.org/10.13039/501100004359, Funder: Alzheimerfonden; doi: http://dx.doi.org/10.13039/501100008599, Funder: Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (SE), Funder: Science for Life Laboratory (SE), Funder: Fundacja na rzecz Nauki Polskiej (PL), Funder: Uppsala University, Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer’s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a “genetic wasteland”, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.

BackgroundMosaic loss of chromosome Y (LOY) is the most common somatic mutation and is associated with all-cause mortality, non-haematological cancers and Alzheimer’s disease among other outcomes. The predominant method used for estimating LOY is the intensity data generated by SNP-arrays, which is difficult to interpret due to its logarithmic scale. Here we describe a new way to convert the LOY mosaicism into a non-logarithmic scale, which instead represents the percentage of affected cells.MethodsWe compared three independent LOY readouts from matched samples, generated by SNP-array, whole genome sequencing and droplet digital PCR. The SNP-array standardization was derived from this comparison and was applied in analyses of serially collected samples from a large cohort of aging men. The sampling was performed up to five times, spanning up to 22 years.ResultsWe observed a higher correlation between the LOY measurements from SNP-array and the two other readouts when using the standardized, instead of the logarithmic, SNP-array data. We also observed a pronounced intra-individual variation of changes in the frequency of LOY within individual males over time.ConclusionsDescribing LOY measurements generated from SNP-arrays in percentage of cells without the Y chromosome makes comparisons to WGS and ddPCR measurements more precise and easier to interpret. This standardization could be applied to the vast amount of SNP-array data already generated in the scientific community, allowing further discoveries of LOY associated disease and outcomes. Additionally, the frequency of LOY in this study changed profoundly within men over time, likely as a result of aberrant clonal expansions.

Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development. We showed that MCPIP1 expression depends on the proteasome activity; however, hypoxia and hypoxia inducible factor 2 alfa (HIF2α) are key factors lowering MCPIP1 expression. Furthermore, we found that MCPIP1 negatively regulates HIF1α and HIF2α levels and in the case of the last one, the mechanism is based on the regulation of the half time of transcript coding for HIF2α. Enhanced expression of MCPIP1 in Caki-1 cells results in a downregulation of transcripts encoding VEGFA, GLUT1, and IL-6. Furthermore, MCPIP1 decreases the activity of mTOR and protein kinase B (Akt) in normoxic conditions. Taken together, MCPIP1 contributes to the ccRCC development. Electronic supplementary material The online version of this article (doi:10.1007/s10456-017-9540-2) contains supplementary material, which is available to authorized users.

BACKGROUND Radiotherapy is explicitly indicated as one of the excluding factors in diagnosing overactive bladder syndrome (OAB). Nevertheless, symptoms of OAB such as urgent episodes, incontinence, pollakiuria, and nocturia, which are consequences of irradiation, led us to test the effectiveness of VESIcare®/Solifenacin in patients demonstrating these symptoms after radiation therapy of small pelvis organs due to malignant neoplasm. MATERIAL AND METHODS We conducted an observatory clinical study including 300 consecutive patients with symptoms of post-irradiation bladder; 271 of those patients completed the study. The observation time was 6 months and consisted of 3 consecutive visits taking place at 12-week intervals. We used VESIcare® at a dose of 5 mg a day. Every sixth patient was examined urodynamically at the beginning and at the end of the observation period, with an inflow speed of 50 ml/s. RESULTS We noticed improvement and decline in the average number of episodes a day in the following parameters: number of micturitions a day (-36%, P

Between 1990 and 1999, 182 men were treated for non-seminomatous germ cell testicular tumours. In 24 of them after chemotherapy a residual retroperitoneal mass was removed. In 14 of them additional immunohistochemical (IHC) examinations using antibodies against cytokeratins, vimentin, PLAP, CD30, AFP, βhCG, p53, and MIB-1 were performed. We compared the results of those additional studies with the results of routine histopathological examination. Histological assessment revealed most frequently (ca. 54% of cases) non-neoplastic lesions, i.e. fibro-cystic, necrotic or inflammatory tumours and lymphatic tissue. In about 33% of cases, surviving live neoplastic cells were found.