To evaluate the prognostic significance of the novel index combining preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) in renal cell carcinoma (RCC) patients. We enrolled 1360 patients who underwent nephrectomy in our institution from 2001 to 2010. The cutoff values for HALP, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were defined by using X-tile software. Survival was analyzed by the Kaplan–Meier method, with differences analyzed by the log-rank test. Multivariate Cox proportional-hazards model was used to evaluate the prognostic significance of HALP for RCC. Low HALP was significantly associated with worse clinicopathologic features. Kaplan-Meier and log-rank tests revealed that HALP was strongly correlated with cancer specific survival (P < 0.001) and Cox multivariate analysis demonstrated that preoperative HALP was independent prognostic factor for cancer specific survival (HR = 1.838, 95%CI:1.260–2.681, P = 0.002). On predicting prognosis by nomogram, the risk model including TNM stage, Fuhrman grade and HALP score was more accurate than only use of TNM staging. HALP was closely associated with clinicopathologic features and was an independent prognostic factor of cancer-specific survival for RCC patients undergoing nephrectomy. A nomogram based on HALP could accurately predict prognosis of RCC.

5-Hydroxymethylcytosine (5hmC) is converted from 5-methylcytosine (5mC) by a group of enzymes termed ten-eleven translocation (TET) family dioxygenases. The loss of 5hmC has been identified as a hallmark of most types of cancer and is related to tumorigenesis and progression. However, the role of 5hmC in bladder cancer is seldom investigated. Vitamin C was recently reported to induce the generation of 5hmC by acting as a cofactor for TET dioxygenases. In this study, we explored the role of 5hmC in bladder cancer and the therapeutic efficacy of vitamin C in increasing the 5hmC pattern. 5hmC was decreased in bladder cancer samples and was related to patient overall survival. Genome-wide mapping of 5hmC in tumor tissues and vitamin C-treated bladder cancer cells revealed that 5hmC loss was enriched in cancer-related genes and that vitamin C treatment increased 5hmC levels correspondingly. Vitamin C treatment shifted the transcriptome and inhibited the malignant phenotypes associated with bladder cancer cells in both in vitro cell lines and in vivo xenografts. This study provided mechanistic insights regarding the 5hmC loss in bladder cancer and a rationale for exploring the therapeutic use of vitamin C as a potential epigenetic treatment for bladder cancer.

Background Different genomic characterization in urothelial carcinoma (UC) by site of origin, may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity. Materials and Methods We prospectively sequenced 118 tumors and matched blood DNA from Chinese UC patients using next-generation sequencing (NGS) techniques, including 45 UTUC and 73 UCB. 226 UTUC and 350 UCB patients for TCGA were acquired from the cbioportal. Results There were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared to UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. UTUC patients had lower PD-L1 than UCB patients. There was no significant difference in the number of DDR mutations, copy number variation (CNV) counts, and tumor mutational burden (TMB) between UTUC and UCB. Conclusions UTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB. Implications for Practice Our findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between UTUC and UCB and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.

Previous reports about laparoscopic total pelvic exenteration (LTPE) are still limited. In the present study, we described our single-center experience of the initial 11 cases. Between April 2011 and September 2015, eight males and three females diagnosed as pelvic malignancies underwent LTPE by the same operation team. We retrospectively collected all cases’ parameters about surgical technique. Thirty-seven patients who received open surgery were also retrospectively collected. A comparison between LTPE and open surgery was performed to evaluate the feasibility and safety of LTPE. Eleven cases successfully underwent the LTPE without any intraoperative complication. No open conversion was required. Eight patients underwent Bricker’s procedure. Three patients were performed with the cutaneous ureterostomy. Anus preservation operation was performed in three patients. Compared with open surgery, LTPE had longer mean operative time (565.2 vs 468.2 min, p = 0.004) but less mean blood loss (547.3 vs 1033.0 ml, p < 0.001) and shorter postoperative hospitalization time (15.3 vs 22.4 days, p = 0.004). One patient died of pulmonary embolism in the 7th month of follow-up time. One patient died of recurrence in the 12th month of follow-up time. Nine patients are still alive without recurrence and metastasis. The mean follow-up time was 11.1 months. The technique of LTPE seems to be feasible and safe in the treatment of carefully selected patients of pelvic malignancies. LTPE can also decrease the blood loss, the recovery time, and the hospital stay. But the oncological safety and long-term outcome of LTPE still need to be explored.

Healing of full-thickness skin wounds remains a major challenge. Recently, human umbilical cord mesenchymal stem cells (hUC-MSCs) were shown to possess an extraordinary potential to promote skin repair in clinical settings. However, their low survival rate after transplantation limits their therapeutic efficiency in treating full-thickness skin wounds. Hydrogels are considered an ideal cell transplantation vector owing to their three-dimensional mesh structure, good biosafety, and biodegradation. The objective of this study was to investigate the skin wound healing effect of a fibrin hydrogel scaffold loaded with hUC-MSCs. We found that the fibrin hydrogel had a three-dimensional mesh structure and low cytotoxicity and could prolong the time of cell survival in the peri-wound area. The number of green fluorescent protein (GFP)-labeled hUC-MSCs was higher in the full-thickness skin wound of mice treated with hydrogel–hUC-MSCs than those of mice treated with cell monotherapy. In addition, the combination therapy between the hydrogel and hUC-MSCs speed up wound closure, its wound healing rate was significantly higher than those of phosphate-buffered saline (PBS) therapy, hydrogel monotherapy, and hUC-MSCs monotherapy. Furthermore, the results showed that the combination therapy between hydrogel and hUC-MSCs increased keratin 10 and keratin 14 immunofluorescence staining, and upregulated the relative gene expressions of epidermal growth factor (EGF), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor A (VEGFA), promoting epithelial regeneration and angiogenesis. In conclusion, the fibrin hydrogel scaffold provides a relatively stable sterile environment for cell adhesion, proliferation, and migration, and prolongs cell survival at the wound site. The hydrogel–hUC-MSCs combination therapy promotes wound closure, re-epithelialization, and neovascularization. It exhibits a remarkable therapeutic effect, being more effective than the monotherapy with hUC-MSCs or hydrogel.

Despite advances in our understanding of the molecular landscape of prostate cancer and the development of novel biomarker-driven therapies, the prognosis of patients with metastatic prostate cancer that is resistant to conventional hormonal therapy remains poor. Data suggest that a significant proportion of patients with metastatic castration-resistant prostate cancer (mCRPC) have mutations in homologous recombination repair (HRR) genes and may benefit from poly(ADP-ribose) polymerase (PARP) inhibitors. However, the adoption of HRR gene mutation testing in prostate cancer remains low, meaning there is a missed opportunity to identify patients who may benefit from targeted therapy with PARP inhibition, with or without novel hormonal agents. Here, we review the current knowledge regarding the clinical significance of HRR gene mutations in prostate cancer and discuss the efficacy of PARP inhibition in patients with mCRPC. This comprehensive overview aims to increase the clinical implementation of HRR gene mutation testing and inform future efforts in personalized treatment of prostate cancer.