Long-term outcomes of pelvic exenterations for gynecological malignancies: a single-center retrospective cohort study.

BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.

Regular gastroscopy and colonoscopy during the evaluation of urachal cancer: do we really need them?

PURPOSE: Urachal cancer is similar to gastrointestinal adenocarcinoma in histology, and gastroscopy/colonoscopy is often administered during perioperative evaluation. However, gastroscopy and colonoscopy have corresponding disadvantages. This study discusses whether gastroscopy/colonoscopy is truly necessary for patients with urachal cancer. PATIENTS AND METHODS: A total of 166 bladder adenocarcinoma cases diagnosed at Sun Yat-sen University Cancer Center were retrospectively reviewed and divided into two groups (urachal cancer and nonurachal cancer), and perioperative evaluations were retrieved. RESULTS: There were 78 patients with urachal cancer, the median age was 48 years, and 59 were male. Perioperative gastroscopy/colonoscopy revealed 5 intestinal polyps and 1 adenoma during these evaluations, and no primary gastrointestinal cancer was found. Meanwhile, preoperative imaging evaluation did not detect significant gastrointestinal lesions. For 88 patients with nonurachal cancer, including primary bladder adenocarcinoma and metastatic tumors from gastrointestinal cancer, the median age was 56 years, and 64 were male. Preoperative imaging evaluation demonstrated 36 cases of gastrointestinal lesions, and 32 were confirmed by gastroscopy/colonoscopy; the other 4 were negative. Another 4 cases of colon cancer were detected by regular colonoscopy for suspected primary bladder adenocarcinoma. In all, 35 cases of colon cancer and 1 case of gastric cancer were identified by endoscopic examination. The diagnostic consistency of imaging and gastrointestinal endoscopy was favorable (P < 0.001), and the negative predictive value and diagnostic efficiency of imaging were 96.9% and 94.6%, respectively. CONCLUSIONS: The vast majority of gastrointestinal cancer cases can be identified by assessment of the patient's clinical symptoms, meticulous physical examination, and imaging evaluation. We recommend that gastroscopy/colonoscopy only be applied to patients with urachal cancer when the above examinations are positive.

A panel of eight autophagy-related long non-coding RNAs is a good predictive parameter for clear cell renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) carries a variable prognosis. Prognostic biomarkers can stratify patients according to risk, and can provide crucial information for clinical decision-making. We screened for an autophagy-related long non-coding lncRNA (lncRNA) signature to improve postoperative risk stratification in The Cancer Genome Atlas (TCGA) database. We confirmed this model in ICGC and SYSU cohorts as a significant and independent prognostic signature. Western blotting, autophagic-flux assay and transmission electron microscopy were used to verify that regulation of expression of 8 lncRNAs related to autophagy affected changes in autophagic flow in vitro. Our data suggest that 8-lncRNA signature related to autophagy is a promising prognostic tool in predicting the survival of patients with ccRCC. Combination of this signature with clinical and pathologic parameters could aid accurate risk assessment to guide clinical management, and this 8-lncRNAs signature related to autophagy may serve as a therapeutic target.

[Expressions of FOXO1/3a/4/6 in human testis and their roles in testicular aging].

OBJECTIVE: To investigate the expression rules of FOXO1a, FOXO3a, FOXO4 and FOXO6 proteins in the human testis, and explore their roles in the development and progression of testicular aging. METHODS: We collected the para-carcinoma testis tissue from 4 testis cancer patients aged 28, 31, 32 and 46 years, and the testis tissue from another 2 PCa patients aged 66 and 81 years after castration surgery from January 2018 to December 2020. We detected the expressions of FOXO1a, FOXO3a, FOXO4 and FOXO6 proteins in the testis tissue by Western blot, determined the locations of FOXO1a, FOXO3a, FOXO4 and FOXO6 in the testis cells by immunofluorescence staining, and performed semi-quantitative and statistical analyses using image J and SPSS 23.0 software, respectively. RESULTS: The expression levels of FOXO1a and FOXO3a proteins were significantly decreased in the testis tissue of the elderly patients (P < 0.01), with an age-dependent reduction in the proportion of the positive cells. No statistically significant difference was observed in the expression levels of FOXO4 and FOXO6 between different age groups. FOXO1a was mainly expressed at the base of the seminiferous tubules, FOXO3a and FOXO4 in the Leydig cells, and FOXO6 in the seminiferous tubules. In addition, FOXO4 underwent age-related nuclear translocation in the senescent Leydig cells, suggesting its involvement in the aging of Leydig cells. CONCLUSION: FOXO1a/3a/4 may be closely related to human testicular aging and corresponding pathological changes, but its underlying mechanism remains to be further explored.

Predictive value of cadherin-11 for subsequent recurrence and progression in non-muscle invasive bladder cancer.

BACKGROUND: Cadherin-11 (CDH11) is a type II cadherin and reported to function as an oncogene in various cancers. Our present study aims to investigate the role of CDH11 in bladder cancer (BCA). METHODS: Bioinformatics analysis was performed in four independent microarray data including 56 non-muscle-invasive bladder cancer (NMIBC) and 132 muscle-invasive bladder cancer (MIBC) tissues from Gene Expression Omnibus to screen out differentially expressed genes. Next, we detected CDH11 expression in BCA specimens and cell lines by qPCR and western blotting assays. Immunohistochemical analyses were performed in 209 paraffin-embedded BCA samples and 30 adjacent normal bladder tissues. RESULTS: Bioinformatics analysis revealed that CDH11 had a higher expression level in MIBC tissues than in NMIBC, which was consistent with our clinical BCA specimens and cell lines at both mRNA and protein levels. Immunohistochemical analysis demonstrated that over-expression of CDH11 was closely related to the histological grade, pT status, tumour size and poor outcomes of BCA patients. What's more, CDH11 (area under curve (AUC) = 0.673 and 0.735) had a better predictive value than E-cadherin (AUC = 0.629 and 0.629) and a similar discrimination with the European Organization for Research and Treatment of Cancer (EORTC) score system (AUC = 0.719 and 0.667) in evaluating potential recurrence and progression of NMIBC. Moreover, combination of CDH11 and EORTC score system was the best predictive model in predicting recurrence of NMIBC (AUC = 0.779) among the three models. CONCLUSIONS: CDH11 was a reliable therapeutic target in BCA and a useful index to predict the possibilities of recurrence and progression in NMIBC patients.

Risk-adapted treatment reduced chemotherapy exposure for clinical stage I pediatric testicular cancer.

BACKGROUND: Different from adult clinical stage I (CS1) testicular cancer, surveillance has been recommended for CS1 pediatric testicular cancer. However, among high-risk children, more than 50% suffer a relapse and progression during surveillance, and adjuvant chemotherapy needs to be administered. Risk-adapted treatment might reduce chemotherapy exposure among these children. METHODS: A decision model was designed and calculated using TreeAge Pro 2011 software. Clinical utilities such as the relapse rates of different groups during surveillance or after chemotherapy were collected from the literature. A survey of urologists was conducted to evaluate the toxicity of first-line and second-line chemotherapy. Using the decision analysis model, chemotherapy exposure of the risk-adapted treatment and surveillance strategies were compared based on this series of clinical utilities. One-way and two-way tests were applied to check the feasibility. RESULTS: In the base case decision analysis of CS1 pediatric testicular cancer, risk-adapted treatment resulted in a lower exposure to chemotherapy than surveillance (average: 0.7965 cycles verse 1.3419 cycles). The sensitivity analysis demonstrated that when the relapse rate after primary chemotherapy was ≤ 0.10 and the relapse rate of the high-risk group was ≥ 0.40, risk-adapted treatment would result in a lower exposure to chemotherapy, without any association with the proportion of low-risk patients, the relapse rate of the low-risk group, the relapse rate after salvage chemotherapy or the toxicity utility of second-line chemotherapy compared to first-line chemotherapy. CONCLUSIONS: Based on the decision analysis, risk-adapted treatment might decrease chemotherapy exposure for these high-risk patients, and an evaluation after orchiectomy was critical to this process. Additional clinical studies are needed to validate this statement.

Kinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial-mesenchymal transition via Akt/GSK3ß signaling.

Kinesin family member C1 (KIFC1) is implicated in the clustering of multiple centrosomes to maintain tumor survival and is thought to be an oncogene in several kinds of cancers. In our experiments, we first performed bioinformatics analysis to investigate the expression levels of KIFC1 in bladder cancer (BC) specimens and normal bladder epitheliums and then, using our samples, verified findings by quantitative real-time PCR and western blotting assays. All data showed that KIFC1 was significantly upregulated in BC specimens at both the mRNA and protein levels. Immunohistochemical studies in a cohort of 152 paraffin-embedded BC tissues displayed that upregulated expression of KIFC1 clearly correlated with pT status (P = .014) and recurrent status (P = .002). Kaplan-Meier survival analysis and log-rank test indicated that patients with BC with high KIFC1 expression had both shorter cancer-specific survival (P < .001) and recurrence-free survival time (P < .001) than those with low KIFC1 expression. Furthermore, ectopic downregulation of KIFC1 weakened BC cell proliferation and migration both in vitro and in vivo, whereas upregulation of KIFC1 enhanced this in vitro. Overexpression of KIFC1 phosphorylated GSK3ß and promoted Snail through activating AKT (protein kinase B0) to induce proliferation and epithelial-mesenchymal transition (EMT) and, therefore, substantially promoted BC migration and metastasis. Our study revealed an oncogenic role for KIFC1 to promote BC cell proliferation and EMT via Akt/GSK3ß signaling; KIFC1 might be a promising prognostic biomarker as well as a therapeutic target for BC.

Conservative treatment for urinary fistula following ileal conduit urinary diversion: a simple method.

BACKGROUND: The presence of urinary fistula after ileal conduit urinary diversion is a challenging complication, and this study investigated the role of the intra-conduit negative pressure system (NPS) in the presence of urinary fistula following ileal conduit (IC) urinary diversion as a conservative treatment. METHODS: Using the intra-conduit NPS, a minor drainage tube was placed within a silicon tube to suck urine from the conduit with consistent negative pressure. Patients with urinary fistula following IC from August 2012 to July 2017 were recorded, and the clinical characteristics and outcome were retrospectively analyzed. RESULTS: The intra-conduit NPS was used as a primarily conservative treatment for 13 patients who suffered from urinary fistula and presented with a large amount of abdominal/pelvic drainage without other significant morbidities. The median age was 60 years old (42-74 years), and 7patients were male. The median duration between the IC operation and the presence of urinary fistula was 15 days (2-28 days), and elevated creatinine levels were detected in the abdominal/pelvic drainage with a median level of 2114 µmol/L (636-388 µmol/L). A significant decrease in abdominal/pelvic drainage was identified in 12 patients. The median time that the NPS was used was 9 days (7-11 days). The other patient did not show any improvements after 2 days of observation and then underwent open surgery. With ureteral stenting, 2 abdominal drainage tubes and the intra-conduit NPS were placed during operation, no urine leakage was observed in the abdominal/pelvic field, and the patient was cured in 9 days. With a median follow-up of 22 months, no fistula recurrence or hydronephrosis was detected. CONCLUSION: The intra-conduit negative pressure system is a feasible and promising way to cure urinary fistula following ileal conduit urinary diversion. Because this procedure is a mini-invasive and simple approach, it might represent an alternative in selected patients.

Relapse in children with clinical stage I testicular yolk sac tumors after initial orchiectomy.

PURPOSE: To evaluate risk factors of relapse in pediatric patients with clinical stage I (CS1) testicular yolk sac tumors. METHODS: With retrospective analysis, the medical records of children with pure testicular yolk sac tumors who were referred to Sun Yat-sen University Cancer Center and The First Affiliated Hospital from January 1995 to December 2015 were selected and recorded. Histopathology and staging were retrieved and multivariate analysis was performed with SPSS 20.0 software. RESULTS: 90 children with CS1 testicular yolk sac tumors were selected, and 21 of them underwent chemotherapy following initial orchiectomy. The median age of them was 17 months. With a median follow-up of 61 months (range 11-183 months), 84 patients were alive and 3 patients died, whereas the status was unknown in 3 patients. 30 patients experienced relapse within a median time of 4 months, including only 1 patient who underwent primary chemotherapy, and 28 of these patients underwent salvage chemotherapy. According to adjusted analysis, lymphovascular invasion (LVI) (P < 0.001), necrosis (P = 0.003) and primary chemotherapy (P = 0.008) were independent predictors of event-free survival. The 4-year event-free survival of high- and low-risk patients was 46.5% and 85.1%, respectively (P < 0.001). CONCLUSIONS: LVI and necrosis were independent risk factors for relapse in pediatric patients with CS1 testicular yolk sac tumors, and primary chemotherapy was effective. Thus, individualized management might be feasible for these patients according to risk classification.

Trends of testis-sparing surgery for pediatric testicular tumors in South China.

BACKGROUND: Testis-sparing surgery is not popular in South China. This study aimed to investigate this procedure for pediatric testicular tumors. METHODS: Children with testicular benign tumors were retrospectively analyzed from January 2001 to June 2015 in the Sun Yat-sen University Cancer Center (SYSUCC) and the First Affiliated Hospital (SYSU-1st). Follow-up was performed until June 2016, and the proportions of TSS in the two hospitals during the different periods were compared. RESULTS: Forty-seven children with testicular benign tumors were enrolled, and 16 cases underwent testis-sparing surgery. All patients were cured and discharged, which included mature teratoma (n = 37), testicular adrenal rest tumors (n = 4), epidermal cysts (n = 3), granulomatous inflammation (n = 2) and adenomatoid tumors (n = 1). Inguinal testis-sparing surgery was performed in 16 children, and no recurrence was detected during follow-up. It was performed more frequently in SYSUCC than in SYSU-1st (P = 0.031), and the tumor size of these patients was smaller than those of patients who underwent radical orchiectomy (P = 0.044). Moreover, testis-sparing surgery has become more common in the past 5 years, although differences over time have not reached significance (P = 0.051). CONCLUSIONS: Testis-sparing surgery is reliable, and tumor size and special hospitals affect its success. Additionally, its use has become more popular in recent years. However, advocacy is still needed for the use of this technique in pediatric testicular benign tumors that are small sized.

Management of adrenal incidentaloma: the role of adrenalectomy may be underestimated.

BACKGROUND: To demonstrate clinical characteristics of adrenal incidentaloma in South China and explore its comprehensive management. METHODS: The clinical data of patients with adrenal neoplasm from Jan 1998 to Dec 2012 were retrospectively analysed. Patients with suspicion of adrenal abnormalities or those in whom adrenal abnormalities were detected in the staging procedures of other cancers were excluded. Most patients with adrenal incidentaloma chose to have adrenalectomy, and some chose surveillance. The relationships between clinical features were analysed with a chi-square test and rank sum test. RESULTS: In total, 634 patients with adrenal incidentaloma were studied. Their age ranged from 17 to 85 years old with a median age of 50 years. Of 478 cases with pathological results, adenoma was the most common tumour (233/478), with 84 cases of pheochromocytoma and 36 cases of adrenocortical carcinoma were 84 and 36. When the tumour size was ≤4 cm, >95 % were benign; when the tumour size was >6 cm, 33 % were malignant. For patients with a tumour size ≤4 cm, 249/376 cases had an adrenalectomy performed. Due to anxiety over a potential malignant transformation and enlargement, most patients (>80 %) under surveillance preferred to undergo adrenalectomy. CONCLUSIONS: Pheochromocytoma and adrenocortical carcinoma were not rare tumours of adrenal incidentaloma, and 4 cm is a good size cutoff to use in the diagnosis of an adrenal incidentaloma. Other than surveillance, laparoscopic adrenalectomy may become the method of choice for management of small adrenal incidentaloma.

Influence of body mass index on oncological outcomes in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

OBJECTIVE: To investigate the association between body mass index and oncological outcomes in Chinese patients who had undergone radical nephroureterectomy for upper urinary tract urothelial carcinoma. METHODS: Between August 1998 and October 2009, 236 consecutive Chinese patients underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma at Sun Yat-sen University Cancer Center (Guangzhou, China). Body mass index data were available for 230 (97.5%) of these patients. All 230 patients were classified into three groups according to the body mass index criteria for Asians, issued by the Asia Cohort Consortium: underweight, body mass index <18.5 kg/m(2) (n = 21, 9.1%); normal weight, body mass index ≥18.5 and <25 kg/m(2) (n = 151, 65.7%); and obesity, body mass index ≥25 kg/m(2), (n = 58, 25.2%). Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Being underweight was significantly associated with lymph node metastasis (P = 0.017) and Eastern Cooperative Oncology Group performance status (P = 0.003). Univariate analysis showed recurrence-free survival and cancer-specific survival were significantly worse in underweight patients than in patients with normal weight or obese patients. After adjustments for other clinicopathological variables, multivariate analysis confirmed that recurrence-free survival and cancer-specific survival were significantly worse in underweight patients than in patients with normal weight or obese patients (recurrence-free survival P = 0.014, cancer-specific survival P = 0.015). CONCLUSIONS: Preoperative underweight is an independent predictor of unfavorable recurrence-free survival and cancer-specific survival in Chinese patients with upper urinary tract urothelial carcinoma treated by radical nephroureterectomy, whereas obesity is associated with superior recurrence-free survival and cancer-specific survival. Further studies, including a multi-institutional, prospective, Asian cohort study, are required to confirm these findings.

The risk factors for the presence of pelvic lymph node metastasis in penile squamous cell carcinoma patients with inguinal lymph node dissection.

OBJECTIVE: To evaluate factors in penile squamous cell carcinoma predictive of pelvic lymph node metastasis and survival. MATERIALS AND METHODS: Data were collected and analyzed retrospectively in 146 patients with squamous cell carcinoma of penis who underwent bilateral inguinal lymph node dissection in our center between January 1998 and April 2011. Variables recorded included serum squamous cell carcinoma antigen, primary tumor p53 immunoreactivity, histological grade, pathological tumor stage, lymphatic or vascular invasion, absent/unilateral or bilateral inguinal lymph node involvement, number of metastatic inguinal lymph nodes, presence of extracapsular growth and lymph node density. RESULTS: Seventy patients had inguinal lymph node metastasis (LNM). Of these, 33 (47.1%) had pelvic LNM. Primary tumor strong p53 expression, lymphatic or vascular invasion, involvement of more than two inguinal lymph nodes and 30% or greater lymph node density were significant predictors of pelvic LNM. Primary tumor strong p53 expression (odds ratio [OR] 5.997, 95% confidence intervals [CI] 1.615-22.275), presence of extracapsular growth (OR 2.209, 95% CI 1.166-4.184), involvement of more than two inguinal lymph nodes (OR 2.494, 95% CI 1.086-5.728) and pelvic lymph node involvement (OR 18.206, 95% CI 6.807-48.696) were independent prognostic factors for overall survival. CONCLUSIONS: Primary tumor expression of p53, lymphatic or vascular invasion, number of metastatic inguinal lymph nodes and lymph node density were all predictors of pathologic pelvic lymph node involvement. Patients with pelvic LNM had an adverse prognosis, with a 3-year overall survival rate of approximately 12.1%. Pelvic lymph node dissection should be considered in these cases.

Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma.

The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months (range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

Optimal interval timing between transurethral resection of bladder tumors and Bacillus Calmette-Guerin perfusion.

OBJECTIVE: There is no consensus regarding the best interval time between transurethral resection of a bladder tumor and Bacillus Calmette-Guerin (BCG) perfusion. This study was to explore whether the interval time has an impact on the prognosis and adverse effects. METHODS: We retrospectively reviewed the clinical data of patients who received BCG intravesical perfusion at Sun Yat-sen University Cancer Center (SYSUCC) from September 2015 to October 2021. Recurrence-free survival (RFS) and progression-free survival were the primary endpoints. Cox regression was used to explore independent predictors. The association between interval time and adverse effect grade was detected by logistic regression. Propensity score matching (PSM) was performed. RESULTS: A total of 403 patients were enrolled, the median interval time was 24 days (6-163 days), and the follow-up was 28 months (7-82 months). Eighty-eight (20.9%) patients relapsed, and 40 patients (10.0%) suffered progression. The multivariate Cox regression analysis confirmed that interval time was an independent predictor of RFS (p = 0.017). Notably, when the interval time was less than or equal to 26 days, there was a trend toward better RFS, PSM resulted in 65 matched pairs in each group, and Kaplan-Meier analysis showed that there was a significant difference in RFS between groups (p = 0.009). The logistic regression analysis showed that there was no correlation between interval time and adverse effects and their grades (p > 0.05). CONCLUSIONS: We considered that the first BCG perfusion could be performed within 2-4 weeks after surgery.

m5C-dependent cross-regulation between nuclear reader ALYREF and writer NSUN2 promotes urothelial bladder cancer malignancy through facilitating RABL6/TK1 mRNAs splicing and stabilization.

The significance of 5-methylcytosine (m5C) methylation in human malignancies has become an increasing focus of investigation. Here, we show that m5C regulators including writers, readers and erasers, are predominantly upregulated in urothelial carcinoma of the bladder (UCB) derived from Sun Yat-sen University Cancer Center and The Cancer Genome Atlas cohort. In addition, NOP2/Sun RNA methyltransferase family member 2 (NSUN2) as a methyltransferase and Aly/REF export factor (ALYREF) as a nuclear m5C reader, are frequently coexpressed in UCB. By applying patient-derived organoids model and orthotopic xenograft mice model, we demonstrate that ALYREF enhances proliferation and invasion of UCB cells in an m5C-dependent manner. Integration of tanscriptome-wide RNA bisulphite sequencing (BisSeq), RNA-sequencing (RNA-seq) and RNA Immunoprecipitation (RIP)-seq analysis revealed that ALYREF specifically binds to hypermethylated m5C site in RAB, member RAS oncogene family like 6 (RABL6) and thymidine kinase 1 (TK1) mRNA via its K171 domain. ALYREF controls UCB malignancies through promoting hypermethylated RABL6 and TK1 mRNA for splicing and stabilization. Moreover, ALYREF recognizes hypermethylated m5C site of NSUN2, resulting in NSUN2 upregulation in UCB. Clinically, the patients with high coexpression of ALYREF/RABL6/TK1 axis had the poorest overall survival. Our study unveils an m5C dependent cross-regulation between nuclear reader ALYREF and m5C writer NSUN2 in activation of hypermethylated m5C oncogenic RNA through promoting splicing and maintaining stabilization, consequently leading to tumor progression, which provides profound insights into therapeutic strategy for UCB.

[Efficacy of compound xuanju capsule combined with bromocriptine on hyperprolactinemia-induced erectile dysfunction].

OBJECTIVE: To investigate the effect of Compound Xuanju Capsule (CXC) combined with bromocriptine on hyperprolactinemia-induced erectile dysfunction (ED). METHODS: We randomly assigned 46 patients with hyperprolactinemia-induced ED to receive bromocriptine (trial group, n = 23) and bromocriptine plus CXC (control group, n = 23), respectively, both for 12 weeks. Then we compared the two groups of patients in erectile function and the levels of serum prolactin and testosterone. RESULTS: After 12 weeks of treatment, the IIEF-5 scores were significantly improved in both the trial and the control groups as compared with the baseline (19.5 +/- 4.1 vs 13.0 +/- 3.8 and 16.4 +/- 3.7 vs 13.7 +/- 3.5, P<0.05), the level of serum prolactin was remarkably decreased ([156.07 +/- 26.31] vs [478.35 +/- 62.28] mIU/L and [164.73 +/- 28.58] vs [445.26 +/- 57.83] mIU/L, P<0.05), while the level of serum testosterone was markedly increased ([15.34 +/- 5.27] vs [3.80 +/- 1.09] nmol/L and [12.02 +/- 2.36] vs [4.07 +/- 1.25] nmol/L, P<0.05). Post-treatment erectile function was significantly better in the trial than in the control group (P<0.05), and the post-treatment serum testosterone level remarkably higher in the former than in the latter (P<0.05), but there was no significant difference in the serum prolactin level after treatment between the two groups (P>0.05). CONCLUSION: The combination of Compound Xuanju Capsule and bromocriptine is highly effective in the treatment of hyperprolactinemia-induced ED, and its effect is even better than that of bromocriptine alone.

Primary mucinous adenocarcinoma of the renal pelvis with elevated CEA and CA19-9.

Primary adenocarcinoma of the renal pelvis is rarely reported in the literature. Here we present a case of primary mucinous adenocarcinoma of the renal pelvis with elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. A 56-year-old woman was referred to our center with intermittent fever and left-sided back pain for 1 month. Computed tomography showed bilateral nephrolithiasis, mild right hydronephrosis and left pyonephrosis accompanied with ambiguous soft tissues. A radionucleorenogram showed that the glomerular filtration rate of the left and right kidney was 0 and 79 ml/min, respectively. Left nephrectomy was performed without lymph node dissection. Histopathology revealed mucinous adenocarcinoma and elevated serum CEA and CA19-9 levels were found. She died of multiorgan metastasis after 5 months. A review of the literature is also reported.

BMI1 activates P-glycoprotein via transcription repression of miR-3682-3p and enhances chemoresistance of bladder cancer cell.

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.

LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis.

Reactive oxygen species (ROS) which are continuously generated mainly by mitochondria, have been proved to play an important role in the stress signaling of cancer cells. Moreover, pentatricopeptide repeat (PPR) proteins have been suggested to take part in mitochondrial metabolism. However, the mechanisms integrating the actions of these distinct networks in urothelial carcinoma of the bladder (UCB) pathogenesis are elusive. In this study, we found that leucine rich pentatricopeptide repeat containing (LRPPRC) was frequently upregulated in UCB and that it was an independent prognostic factor in UCB. We further revealed that LRPPRC promoted UCB tumorigenesis by regulating the intracellular ROS homeostasis. Mechanistically, LRPPRC modulates ROS balance and protects UCB cells from oxidative stress via mt-mRNA metabolism and the circANKHD1/FOXM1 axis. In addition, the SRA stem-loop interacting RNA binding protein (SLIRP) directly interacted with LRPPRC to protect it from ubiquitination and proteasomal degradation. Notably, we showed that LRPPRC modulated the tumorigenesis of UCB cells in a circANKHD1-FOXM1-dependent manner. In conclusion, LRPPRC exerts critical roles in regulating UCB redox homeostasis and tumorigenesis, and is a prognostic factor for UCB; suggesting that LRPPRC may serve as an exploitable therapeutic target in UCB.