Addition of Prostate Volume and Prostate-specific Antigen Density to Memorial Sloan Kettering Cancer Center Prostate Cancer Nomograms

Prostate-specific antigen (PSA) density is an established prognostic marker for prostate cancer. We investigated whether the inclusion of PSA density or prostate volume in the Memorial Sloan Kettering Cancer Center nomograms improves the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Among the 11 725 men included, 2140 developed BCR. Neither PSA density nor prostate volume was associated with BCR when added to either the pre-RP or post-RP model (all p values ≥0.10) and changes in the C index were very small (largest change, 0.002). The results were robust to exclusion of outlying prostate volumes and restriction to patients treated after 2005. There is no justification for adding prostate volume or PSA density to BCR nomograms. Patient summary: Addition of prostate volume or prostate-specific antigen density to Memorial Sloan Kettering Cancer Center prediction schemes did not improve the prediction of recurrence of prostate cancer after removal of the prostate

β-catenin nuclear translocation induced by HIF-1α overexpression leads to the radioresistance of prostate cancer

Hypoxia-inducible factor-1α (HIF-1α) is known to play crucial roles in tumor radioresistance; however, the molecular mechanisms responsible for the promotion of tumor radioresistance by HIF-1α remain unclear. β-catenin is known to be involved in the metastatic potential of prostate cancer (PCa). In this study, to investigate the role of HIF-1α and β-catenin in the radioresistance of PCa, two PCa cell lines, LNCaP and C4-2B, were grouped as follows: Negative control (no treatment), HIF-1α overexpression group (transfected with HIF-1α overexpression plasmid) and β-catenin silenced group (transfected with HIF-1α plasmids and β-catenin-shRNA). Cell proliferation, cell cycle, cell invasion and radiosensitivity were examined under normal or hypoxic conditions. In addition, radiosensitivity was examined in two mouse PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Our results revealed that in both the LNCaP and C4-2B cells, transfection with HIF-1α overexpression plasmid led to an enhanced β-catenin nuclear translocation, while β-catenin silencing inhibited β-catenin nuclear translocation. The enhanced β-catenin nuclear translocation induced by HIF-1α overexpression resulted in an enhanced cell proliferation and cell invasion, an altered cell cycle distribution, decreased apoptosis, and improved non-homologous end joining (NHEJ) repair under normal and irradiation conditions. Similar results were observed in the animal models. HIF-1α overexpression enhanced β-catenin nuclear translocation, which led to the activation of the β-catenin/NHEJ signaling pathway and increased cell proliferation, cell invasion and DNA repair. These results thus suggest that HIF-1α overexpression promotes the radioresistance of PCa cells

β-catenin nuclear translocation induced by HIF-1a overexpression leads to the radioresistance of prostate cancer

Hypoxia-inducible factor-1a (HIF-1a) is known to play crucial roles in tumor radioresistance; however, the molecular mechanisms responsible for the promotion of tumor radioresistance by HIF-1a remain unclear. β-catenin is known to be involved in the metastatic potential of prostate cancer (PCa). In this study, to investigate the role of HIF-1a and β-catenin in the radioresistance of PCa, two PCa cell lines, LNCaP and C4-2B, were grouped as follows: Negative control (no treatment), HIF-1a overexpression group (transfected with HIF-1a overexpression plasmid) and β-catenin silenced group (transfected with HIF-1a plasmids and β-catenin-shRNA). Cell proliferation, cell cycle, cell invasion and radiosensitivity were examined under normal or hypoxic conditions. In addition, radiosensitivity was examined in two mouse PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Our results revealed that in both the LNCaP and C4-2B cells, transfection with HIF-1a overexpression plasmid led to an enhanced β-catenin nuclear translocation, while β-catenin silencing inhibited β-catenin nuclear translocation. The enhanced β-catenin nuclear translocation induced by HIF-1a overexpression resulted in an enhanced cell proliferation and cell invasion, an altered cell cycle distribution, decreased apoptosis, and improved non-homologous end joining (NHEJ) repair under normal and irradiation conditions. Similar results were observed in the animal models. HIF-1a overexpression enhanced β-catenin nuclear translocation, which led to the activation of the β-catenin/NHEJ signaling pathway and increased cell proliferation, cell invasion and DNA repair. These results thus suggest that HIF-1a overexpression promotes the radioresistance of PCa cells

ß-catenin nuclear translocation induced by HIF-1a overexpression leads to the radioresistance of prostate cancer

Hypoxia-inducible factor-1a (HIF-1a) is known to play crucial roles in tumor radioresistance\; however, the molecular mechanisms responsible for the promotion of tumor radioresistance by HIF-1a remain unclear. ß-catenin is known to be involved in the metastatic potential of prostate cancer (PCa). In this study, to investigate the role of HIF-1a and ß-catenin in the radioresistance of PCa, two PCa cell lines, LNCaP and C4-2B, were grouped as follows: Negative control (no treatment), HIF-1a overexpression group (transfected with HIF-1a overexpression plasmid) and ß-catenin silenced group (transfected with HIF-1a plasmids and ß-catenin-shRNA). Cell proliferation, cell cycle, cell invasion and radiosensitivity were examined under normal or hypoxic conditions. In addition, radiosensitivity was examined in two mouse PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Our results revealed that in both the LNCaP and C4-2B cells, transfection with HIF-1a overexpression plasmid led to an enhanced ß-catenin nuclear translocation, while ß-catenin silencing inhibited ß-catenin nuclear translocation. The enhanced ß-catenin nuclear translocation induced by HIF-1a overexpression resulted in an enhanced cell proliferation and cell invasion, an altered cell cycle distribution, decreased apoptosis, and improved non-homologous end joining (NHEJ) repair under normal and irradiation conditions. Similar results were observed in the animal models. HIF-1a overexpression enhanced ß-catenin nuclear translocation, which led to the activation of the ß-catenin/NHEJ signaling pathway and increased cell proliferation, cell invasion and DNA repair. These results thus suggest that HIF-1a overexpression promotes the radioresistance of PCa cells

ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: A multicentre, non-inferiority, adaptive, randomised controlled trial

Background: Use of medical devices represents a unique opportunity to facilitate scale-up of early infant male circumcision (EIMC) across sub-Saharan Africa. The ShangRing, a circumcision device prequalified by WHO, is approved for use in adults and adolescents and requires topical anaesthesia only. We aimed to investigate the safety and efficacy of the ShangRing versus the Mogen clamp for EIMC in infants across eastern sub-Saharan Africa. Methods: In this multicentre, non-inferiority, open-label, randomised controlled trial, we enrolled healthy male infants (aged Findings: Between Sept 17, 2018, and Dec 20, 2019, a total of 1420 infants were assessed for eligibility, of whom 1378 (97·0%) were enrolled. 689 (50·0%) infants were randomly assigned to undergo EIMC by ShangRing and 689 (50·0%) by Mogen clamp. 43 (6·2%) adverse events were observed in the ShangRing group and 61 (8·9%) in the Mogen clamp group (p=0·078). The most common treatment-related AE was intraoperative pain (Neonatal Infant Pain Scale score ≥5), with 19 (2·8%) events in the ShangRing and 23 (3·3%) in the Mogel clamp group. Rates of moderate and severe AEs were similar between both groups (29 [4·2%] in the ShangRing group vs 30 [4·4%] in the Mogen clamp group; difference –0·1%; one-sided 95% CI upper limit of 1·7%; p=0·89). No treatment-related deaths were reported. Interpretation: Use of the ShangRing device for EIMC showed safety, achieved high caregiver satisfaction, and did not differ from the Mogen clamp in other key measures. The ShangRing could be used by health systems and international organisations to further scale up EIMC across sub-Saharan Africa