An integrated analysis of the anticarcinogenic role of forkhead box protein 1 in oesophageal squamous cell carcinoma.

Forkhead box protein 1 (FOXP1) serves as a tumour promoter or suppressor depending on different cancers, but its effect in oesophageal squamous cell carcinoma has not been fully elucidated. This study investigated the role of FOXP1 in oesophageal squamous cell carcinoma through bioinformatics analysis and experimental verification. We determined through public databases that FOXP1 expresses low in oesophageal squamous cell carcinoma compared with normal tissues, while high expression of FOXP1 indicates a better prognosis. We identified potential target genes regulated by FOXP1, and explored the potential biological processes and signalling pathways involved in FOXP1 in oesophageal squamous cell carcinoma through GO and KEGG enrichment, gene co-expression analysis, and protein interaction network construction. We also analysed the correlation between FOXP1 and tumour immune infiltration levels. We further validated the inhibitory effect of FOXP1 on the proliferation of oesophageal squamous cell carcinoma cells through CCK-8, colony formation and subcutaneous tumour formation assays. This study revealed the anticarcinogenic effect of FOXP1 in oesophageal squamous cell carcinoma, which may serve as a novel biological target for the treatment of tumour.

Exosomal miR-105-5p derived from bladder cancer stem cells targets for GPR12 to promote the malignancy of bladder cancer.

Bladder cancer stem cells (BCSCs) are considered as the root cause of BC initiation and recurrence, and exosomes derived from BCSCs (CSCs-exo) are the vital tool for establishing a stable tumor microenvironment. miR-105-5p has been revealed to promote tumor growth in a variety of cancers, but the effects on BC are still not included.Characteristics of CSCs-exo were examined by transmission electron microscope and nanoparticle tracking analysis. PKH67 dye was used to observe the cellular uptake of exosomes. Cell viability, migration and invasion were detected by CCK-8, wound healing and transwell invasion assays, respectively. The interaction between miR-105-5p and GPR12 was verified by luciferase activity assay. Xenografts were induced in the nude mice, and H&E staining method was applied to analyze the histological changes of xenografts. CSCs-exo efficiently promoted BC cell viability, migration and invasion. miR-105-5p was highly expressed in CSCs and CSCs-exo treatment significantly upregulated the expression of miR-105-5p in BC cells.GPR12 was subsequently verified to be the target gene of miR-105-5p, and overexpression of GPR12 abrogated the effects of miR-105-5p on BC cell growth and metastasis. Reversely, the anti-tumor function of miR-105-5p antagomir was observed in the xenograft mice.CSCs aggravated the malignancy of BC partly through transmitting exosomal miR-105-5p to BC cells to inhibit the expression of GPR12, which developed a novel aspect for CSC-targeted therapies.

Metastatic patterns of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma without neoadjuvant therapy.

PURPOSE: This research aimed to clarify the metastatic patterns of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma and to investigate appropriate strategies for lymph node dissection. METHODS: Patients with thoracic esophageal squamous cell carcinoma receiving esophagectomy from December 2020 to April 2024 were retrospectively analyzed. Risk factors for subcarinal, right and left recurrent laryngeal nerve lymph nodes metastasis were determined by chi-square test and multivariate logistic regression analysis. We visualized the metastasis rates of these specific lymph nodes based on the different clinicopathological characteristics. Correlation between subcarinal, right and left recurrent laryngeal lymph nodes metastasis and postoperative complications were also analyzed. RESULTS: A total of 503 thoracic esophageal squamous carcinoma patients who underwent esophagectomy were enrolled. The metastasis rates of subcarinal, right and left recurrent laryngeal nerve lymph nodes were 10.3%, 10.3%, and 10.9%, respectively. The lymphovascular invasion status and tumor location were the significant predictors for subcarinal and right recurrent laryngeal nerve lymph nodes metastasis, respectively (P < 0.001 and P = 0.013). For left recurrent laryngeal nerve lymph node metastasis, younger age (P = 0.020) and presence of lymphovascular invasion (P = 0.009) were significant risk factors. Additionally, pulmonary infection is the most frequent postoperative complication in patients with dissection of subcarinal, right and left recurrent laryngeal lymph nodes. There was no significant difference in the incidence of anastomotic leakage (P = 0.872), pulmonary infection (P = 0.139), chylothorax (P = 0.702), and hoarseness (P = 0.179) between the subcarinal lymph node dissection cohort and the reservation cohort. The incidence of hoarseness significantly increased in both right (P = 0.042) and left (P = 0.010) recurrent laryngeal nerve lymph nodes dissection cohorts compared by the reservation cohorts, with incidence rates of 5.9% and 6.7%, respectively. CONCLUSIONS: The metastasis rates of subcarinal, right and left recurrent laryngeal nerve lymph nodes in thoracic esophageal squamous cell carcinoma were all over 10%. The dissection of subcarinal lymph nodes does not increase postoperative complications risk, while recurrent laryngeal nerve lymph nodes dissection significantly increases the incidence of hoarseness. Thus, lymph node dissection of subcarinal lymph nodes should be conducted routinely, while recurrent laryngeal nerve lymph nodes dissection may be selectively performed in specific patients.

A regulatory circuit of lncRNA NLGN1-AS1 and Wnt signalling controls clear cell renal cell carcinoma phenotypes through FZD4-modulated pathways.

BACKGROUND: Recent evidence has indicated that long non-coding RNAs (lncRNAs) were emerged as key molecules in clear cell renal cell carcinoma (ccRCC). TCGA database showed that the expression level of lncRNA NLGN1-AS1 was up-regulated in ccRCC; However, whether NLGN1-AS1 implicated in the malignant progression of ccRCC remained unclear. METHODS: Based on TCGA database, candidate lncRNAs were selected and quantitative real-time PCR (qRT-PCR) was utilized to verify the expression levels of candidate lncRNAs in human ccRCC tissues. Loss-of-function experiments were performed to examine the biological functions of NLGN1-AS1 both in vitro and in vivo. According to bioinformatics analysis, fluorescence reporter assays and rescue experiments, the underlying mechanisms of NLGN1-AS1 in ccRCC cell lines were so clearly understood. RESULTS: As a novel lncRNA, NLGN1-AS1 was up-regulated in ccRCC cell lines and associated with poor prognosis of and ccRCC patients, which was correlated with the progression of ccRCC. Functionally, the down-regulation of NLGN1-AS1 significantly decreased the proliferation of ccRCC cells both in vitro and in vivo. Bioinformatics analysis and luciferase report assays identified that miR-136-5p was a direct target of NLGN1-AS1. We also determined that FZD4 were inhibitory targets of miR-136-5p, and that Wnt/ß-catenin signaling was inhibited by both NLGN1-AS1 knockdown and miR-136-5p over-expression. In addition, we found that the suppression of proliferation and the inhibition of Wnt/ß-catenin pathway induced by NLGN1-AS1 knockdown would require the over-expression of FZD4. CONCLUSIONS: Our findings suggested that lncRNA NLGN1-AS1 could promote the progression of ccRCC by targeting miR-136-5p/FZD4 and Wnt/ß-catenin pathway, and might serve as a novel potential therapeutic target to inhibit the progression of ccRCC.

The performance of 18F-PSMA PET/CT in the detection of prostate cancer: a systematic review and meta-analysis.

This paper presents a meta-analysis regarding the detection rate (DR) of fluorine-18 (18F)-labeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) in the management of patients with prostate cancer (PCa). Relevant studies regarding 18F-PSMA PET/CT in the management of PCa published until June 1, 2021, were electronically searched in online databases including EMBASE, PubMed, and Web of Science. The primary outcome was the DR of 18F-PSMA PET/CT in managing PCa patients, while the secondary outcome was the DR of 18F-PSMA PET/CT according to Gleason scores and serum prostate-specific antigen (PSA) level. The pooled DR was calculated on a per-patient basis, with pooled odd ratios and 95% confidence intervals (CIs). In total, 17 observational studies evaluating 1019 patients with PCa met the inclusion criteria. The DR of 18F-PSMA PET/CT was 0.83 (95% CI: 0.78-0.88), in the random-effects model. Subsequently, the analysis of DR of 18F-PSMA PET/CT in PCa patients using Gleason score (≤7 vs ≥8), showed a significant difference in PCa patients. Based on the above results, the higher Gleason score of PCa patients, the higher DR of 18F-PSMA PET/CT. The DR of 18F-PSMA PET/CT in PCa was 0.57 for PSA <0.5 ng ml-1; 0.75 for PSA ≥0.5 ng ml-1 and <1.0 ng ml-1; 0.93 for PSA ≥1.0 ng ml-1 and <2.0 ng ml-1; and 0.95 for PSA ≥2.0 ng ml-1. Therefore, the significant diagnostic value was found in terms of the DR of 18F-PSMA PET/CT in managing PCa patients and was associated with Gleason score and serum PSA level.

Pneumoperitoneum preconditioning for the prevention of renal function after laparoscopic partial nephrectomy: protocol for a double-blind randomised controlled trial.

INTRODUCTION: Renal ischaemia reperfusion injury is an inevitable pathophysiology in different clinical situations including laparoscopic partial nephrectomy (LPN), which can obviously decrease the renal function after surgery. Pneumoperitoneum preconditioning (PP) is a promising approach that can yield a protective effect on kidney, which has already been demonstrated in some animal models. The present study is designed to assess whether the PP can yield a clinical renoprotective role after LPN. METHODS AND ANALYSIS: This study is a randomised, prospective, double-blind and parallel controlled clinical trial. Eligible participants will be patients with renal tumours and willing to choose elective LPN. Patients randomised to the treatment arm will receive PP consisted of three cycles of 5 min insufflation and 5 min desufflation before LPN, while the control arm will receive a sham operation. The primary endpoints are glomerular filtration rate and the level of serum cystatin C within 6 months after desufflation. The secondary endpoints are serum creatinine, estimated glomerular filtration rate, alanine transaminase, serum amylase, intestinal fatty acid binding protein, postoperative hospital stay, the incidence of adverse events and mortality in postoperative 6 months. ETHICS AND DISSEMINATION: This study has been approved by the institutional ethics committee of Nanjing First Hospital. The results of this study will be reported faithfully through scientific conferences or published articles. TRIAL REGISTRATION NUMBER: NCT03822338.