Nuclear-cytoplasmic translocation of SQSTM1/p62 protein enhances ESCC cell migration and invasion by stabilizing EPLIN expression.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant disease with a poor prognosis. We previously found that p62 presented a marked nuclear-cytoplasmic translocation in ESCC cells as compared that in normal esophageal epithelial cells, but its effects on ESCC cells remain unclear. This study aims to clarify the impacts of different cellular localization of p62 on the function of ESCC cells and the underlying molecular mechanisms. We here demonstrated that cytoplasmic p62 enhances the migration and invasion abilities of esophageal cancer cells, whereas nuclear p62 has no effect. We further explored the interaction protein of p62 by using GST pull-down experiment and identified EPLIN as a potential protein interacting with p62. In addition, reducing EPLIN expression significantly inhibited the migration and invasion of ESCC cells, which were rescued when EPLIN expression was restored after the p62 knockdown. At a molecular level, p62 in cytoplasm positively regulated the expression of EPLIN via enhancing its protein stability. Data from the TCGA and GEO database displayed a significant up-regulation of EPLIN mRNA expression in ESCC tissues compared with corresponding paired esophageal epithelial samples. Our findings present evidence that the nuclear-cytoplasmic translocation of p62 protein contributes to an aggressive malignancy phenotype, providing candidate molecular biomarkers and potential molecular targets for the diagnosis and treatment of ESCC.

Exosomal MEF2C's Association With the Progression of CRC in Regulating CD36 Transcription.

Context: Exosomes are biologically active, extracellular vesicles that are involved in tumor-related processes, including activating tumors, facilitating tumor growth, and promoting inflammation. Objective: The study intended to investigate microRNAs (miRNAs) in exosomes that are associated with colorectal cancer (CRC). Design: The research team performed bioinformatics analysis, extracting RNA-sequencing (RNA-seq) datasets from the Cancer Genome Atlas (TCGA); ExoRBase, a database of different types of RNA information that scientists have extracted from human exosomes; and the Gene Expression Omnibus (GEO) databases, and analyzed the data. Setting: The study took place at the Department of Colorectal Surgery at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China. Participants: From October 2020 to March 2021, a total of 28 CRC patients who underwent curative resection at the National Cancer Center were enrolled. Tumor samples and tumor-adjacent normal sample were obtained from these CRC patients. Postoperative pathological characteristics all shown adenocarcinoma. The research team recruited participants from the hospitals connected with CAMS and PUMC and obtained written informed consent from them for publication of a case report and any accompanying images. The Ethics Committee of the Cancer Institute (Hospital), CAMS & PUMC has officially recognized the study (NCC 2017-YZ-026). Outcome Measures: The research team: (1) extracted RNA-seq datasets from the TCGA, exoRBase and GEO and analyzed the differentially expressed genes (DEGs); (2) performed a cluster analysis of variant genes using weighted gene co-expression network analysis (WGCNA);(3) verified expression of myocyte enhancer factor 2C-genecards (MEF2C) and cluster of differentiation 36 (CD36) in CRC tissues; (4) explored the biological function of the MEF2C by performing proliferation, migration, and invasion assays; and (5) used a chromatin immunoprecipitation (ChIP) experiment to analyze mechanisms to reveal CD36 transcription regulated by exosomal MEF2C. Results: A significant mean difference in exosomal MEF2C existed between normal and tumor tissues. By performing a correlation analysis, the research team found 609 potential target points of exosomal MEF2C (r > 0.5, P < .05). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) network analysis indicated that CD36 may be the target of exosomal MEF2C. Univariate, multivariate, and Kaplan-Meier analyses showed that CD36 was closely related to the overall survival (OS) of CRC patients. Obvious differences existed in the expression levels of MEF2C and CD36 in CRC and normal tissues according to qPCR and immunohistochemical assays. Functional-experiments analysis in vitro showed that exosomal-MEF2C could be considered as an antioncogene. Mechanistically, ChIP assays showed that MEF2C regulated the transcriptional level of CD 36; thus, the expression of CD36 increased significantly. Conclusion: MEF2C is a potential biomarker of a favorable prognosis in CRC and is related to the progression of CRC. Moreover, the MEF2C-CD36 pathway may reveal the tumor regulation mechanism in CRC. The exosomal MEF2C was the hub gene in exosomes, with CD36 was identified as the potential target. Exosomal MEF2C may be a promising molecular biomarker for predicting a good prognosis and may have potential as a medical target for CRC.

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

NEFL promotes invasion and migration of esophageal squamous carcinoma cells via the EGFR/AKT/S6 pathway.

To explore the expression, the roles and the underlying mechanism of neurofilament light chain (NEFL) in esophageal squamous cell carcinoma (ESCC), we firstly analyzed the NEFL mRNA and protein expression in ESCC and paired normal tissues by using Gene Expression Omnibus (GEO) database, and real-time quantitative reverse transcription PCR (qRT-PCR). The results showed that NEFL mRNA level was significantly upregulated in ESCC tissues compared with that of normal tissues. Western blot analysis revealed that NEFL protein level was also significantly upregulated in ESCC tissues. CCK8 and transwell assays were performed to analyze the effect of NEFL overexpression on the malignant phenotypes of ESCC cells, and the results showed that NEFL knockdown significantly impaired the ESCC cell invasion and migration in vitro. Xenograft assay in nude mice indicated that NEFL silencing suppressed tumor growth in vivo. At the molecular level, NEFL knockdown significantly upregulated E-cadherin and downregulated N-cadherin expression, suggesting that NEFL overexpression might influence the epithelial-mesenchymal transition (EMT) process. Furthermore, we found that NEFL knockdown significantly reduced the mRNA and protein expression of epidermal growth factor receptor (EGFR) and the phosphorylation levels of protein kinase B (PKB; also known as AKT) and ribosomal protein S6 (S6). Ectopic expression of EGFR after NEFL knockdown significantly restored the phosphorylation levels of AKT and S6 as well as the invasion and migration of ESCC cells. These data indicate that NEFL overexpression might promote the EMT process of ESCC cells via the EGFR/AKT/S6 pathway, ultimately enhancing the invasion and migration of ESCC cells.

Remarkable inhibition effects of afatinib alone or combining with paclitaxel in esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Chemotherapy drugs do not work well in esophageal squamous cell carcinoma (ESCC), and none of the targeted drugs have been applied in clinic. This study aims to identify effective targeted drugs and related biomarkers for the treatment of ESCC. METHODS: The effect of 40 Food and Drug Administration-approved small-molecule inhibitors was first tested in five ESCC cell lines. CCK8 assays and xenografts derived from ESCC cell lines were performed to evaluate the anti-ESCC effects of inhibitors or chemotherapeutic agents in vitro and in vivo, respectively. Immunohistochemistry was utilized to analyze the p-EGFR expression in tissues. Western blot combining with gray analysis was conducted to detect the expression of interest protein. Flow cytometry and immunofluorescence assay were used to analyze apoptosis, cell cycle, and mitotic changes after drug treatment. RESULTS: Afatinib showed remarkable effects on inhibiting ESCC cells with higher expression of p-EGFR. Results from combinatorial screening in ESCC cells expressing lower phosphorylation level of EGFR showed that paclitaxel and afatinib presented a significant synergistic inhibitory effect (P < 0.001). Molecular analysis revealed that paclitaxel sensitized afatinib by activating EGFR, and afatinib in combination with paclitaxel effectively blocked MAPK pathway and induced G2/M cell arrest and apoptosis that is an indicator of mitotic catastrophe. CONCLUSIONS: Our data demonstrate that afatinib is an effective drug for patients with ESCC expressing higher phosphorylation level of EGFR. And for patients with lower p-EGFR in tumors, paclitaxel in combination with afatinib might be a promising therapeutic strategy in ESCC.

[A comparison of curative effects of percutaneous nephrostomy and open surgery in the management of postrenal acute renal failure].

OBJECTIVE: To investigate the effects and clinical value of percutaneous nephrostomy (PCN) in the management of postrenal acute renal failure (PARF). METHODS: The clinical data of 40 cases of PARF for the treatment of PCN and 20 cases with open surgery were retrospectively analyzed. RESULTS: The success rate of PCN was 100%, renal function of all patients was restored to normal range after 2-7 days of PCN, in whom 30 patients recovered. In 10 patients nephrostomy was prolonged, among them 2 patients had recurrent abdominal tumors, and 8 patients had cervical cancer in late phase. There was no death, and no complications except hematuria. In the open surgery group, renal function of 19 cases recovered to normal range after 2-7 days of drainage. Lung infection occurred in 3 patients after operation, and they recovered with antibiotic therapy. One patient died of multiple organ dysfunction failure (MOF). CONCLUSION: For PARF, PCN is preferable because of minimal trauma, less blood loss, as well as rapid recovery and better effect on recovery of renal function.

[Pneumoscrotum induced by spontaneous colon perforation: a case report and review of the literature].

One case of pneumoscrotum associated with spontaneous colon perforation was reported. The patient was a 66-year-old man, presented with high temperature, mild abdominal pain and an enlarged scrotum. Physical examination revealed scrotal swelling, abdominal tenderness Case Report and muscular defense. Computed tomography (CT) of the abdomen showed swelling and pneumatosis of the left major psoas and iliopsoas muscles, and ultrasound found subcutaneous emphysema of the scrotum. Surgical investigation discovered a retroperitoneal perforation in the descending colon connected with a huge retroperitoneal vomica and scrotal sac. Spontaneous colon perforation induced pneumoscrotum is rare clinically. It may present as colon perforation, which calls for special attention.

[Evaluation of absolute alcohol treatment for renal cyst with percutaneous puncture and catheterization under ultrasonographic guidance].

OBJECTIVE: To evaluate the effect of absolute alcohol treatment for renal cyst with percutaneous puncture and catheterization. METHODS: This report presented 64 cases of renal cysts, 34 cases were treated with percutaneous puncture (A group) and 30 cases with percutaneous catheterization (B group). According to the size, the cysts were divided into 2 groups, more than 6 cm in diameter and less than 6 cm in diameter. RESULTS: All the patients were followed up for 3 - 12 months by CT or B ultrasonography. Striking difference of the therapeutic results were existed when cystS were more than 6 cm in diameter. CONCLUSION: Percutaneous catheterization is applicable to the sclerosing treatment of renal cyst whose diameter is more than 6 cm.