DLGAP5 promotes gallbladder cancer migration and tumor-associated macrophage M2 polarization by activating cAMP.

BACKGROUND: Although disc large associated protein family (DLGAP5) has been reported to be involved in a variety of tumor pathologic processes, its expression and mechanism in gallbladder cancer (GBC) are still uncertain. Macrophages were divided into M1 and M2 macrophages. TAM is more closely defined as M2 polarized macrophages, which plays a key role in cancer progression. OBJECTIVE: To clarify the role of disc large associated protein family (DLGAP5) in gallbladder cancer (GBC) progression and investigate the mechanism. METHODS: Differential genes in 10 normal paracancer tissues and 10 GBC tissues in GSE139682 from NCBI-GEO were analyzed by R language. Bioinformation analysis and clinical sample analysis were performed to detect DLGAP5 expression in GBC and its correlation with prognosis. CCK-8, EDU, transwell, wound closure, and Immunoblot were performed to detect its effects on the function of GBC cells. GST-pulldown showed the direct interact between DLGAP5 and cAMP. Macrophage polarization assay was further conducted to detect the effects of DLGAP5 on macrophage M2 polarization. The tumor growth assays were further conducted to confirm its role in mice. RESULTS: Biological analysis and clinical samples confirmed that DLGAP5 was increased in GBC and strongly related to poor prognosis in patients with GBC. After overexpression of DLGAP5 in GBC cell lines, such as GBC-SD and NOZ cells, cell proliferation and migration were enhanced, and macrophages were polarized to M2. However, after DLGAP5 is knocked down, there is opposite effect. Mechanistically, DLGAP5 promotes the growth and migration of GBC-SD and NOZ cells and the M2 polarization of THP-1-derived macrophages by activating cyclic adenosine monophosphate (cAMP) pathway. In vivo, GBC-SD with DLGAP5 knockdown was subcutaneously injected into nude mice. It was found that after DLGAP5 knockdown, both tumor volume and tumor were reduced, and indicators related to proliferation and M2 polarization decreased. CONCLUSION: Our study shows that DLGAP5 is significantly elevated in GBC and is strongly related to poor prognosis in patients with GBC. DLGAP5 promotes GBC proliferation, migration, and M2 polarization of macrophages through cAMP pathway, which provides a theoretical basis for the treatment of GBC and may become a promising therapeutic target.

Pancreaticoduodenal and choledochal hemangiomatosis with vascular variation in a child: a rare disease with challenge starts from diagnosis-a case report.

BACKGROUND: Visceral hemangiomatosis is a benign tumor (rarer than hemangioma) that has not been reported to occur in the pancreas, duodenum, or choledoch. It can be easily confused with other pancreatic tumors or choledocholithiasis. Herein, we describe a case of a child with pancreaticoduodenal and choledochal hemangiomatosis and the key characteristics for the accurate diagnosis of pancreatic tumors based on previous reports and our findings. CASE PRESENTATION: We report a case of a 2-year and 9-month-old child who presented with repeated and fluctuating jaundice for 3 months with a history of endoscopic stone removal in a local hospital, following the diagnosis of choledocholithiasis. An abdominal computed tomography revealed a previously undiagnosed pancreatic head tumor and celio-mesenteric trunk (a rare vascular variation). This was misdiagnosed as a pancreatic neuroendocrine tumor. Since the patient's parents refused FNA biopsy and insisted on surgery, pancreaticoduodenectomy was performed; however, postoperatively, the child was correctly diagnosed with pancreaticoduodenal and choledochal hemangiomatosis. Although the patient was in good condition and had gained 4 kg in weight 3 months postoperatively, pancreaticoduodenectomy could have been avoided if an accurate diagnosis had been established before or during the operation. CONCLUSION: Our report highlights the difficulty in diagnosing visceral hemangiomatosis. Radiologists, endoscopists, and surgeons should consider this possibility in cases of repeated and fluctuating jaundice that cannot be explained by choledocholithiasis alone.

RNF126 contributes to stem cell-like properties and metastasis in hepatocellular carcinoma through ubiquitination and degradation of LKB1.

Hepatocellular carcinoma (HCC) is one of the malignant tumors with the worst prognosis, and tumor recurrence and metastasis are the main factors leading to poor prognosis of HCC patients. Accumulating studies show that RNF126, ring finger protein 126, is involved in the pathological process of many tumors. However, the biological function and exact molecular mechanism of RNF126 in HCC remain unclear. In this study, we investigated the role of RNF126 in the pathogenesis of HCC. By analyzing database and verifying with our clinical specimens, it was found that RNF126 was highly expressed in HCC tissues, which is associated with shorter overall survival and higher recurrence rate. Overexpressed RNF126 can significantly promote the proliferation, migration, invasion and angiogenesis of HCC cells, whereas knockdown RNF126 can reverse this effect. Mechanically, RNF126 down-regulates liver kinase B1 (LKB1) expression by ubiquitination of LKB1 to weaken its stability, thereby significantly promoting stem-cell-like activity, migration, and angiogenesis of HCC. Notably, consistent with in vitro results, RNF126 was stably transformed in Hep3B and subcutaneously injected into nude mice. In established mouse xenograft models, tumor growth can be effectively inhibited and the occurrence of lung metastasis is reduced. In HCC, RNF126 may down-regulate LKB1 through ubiquitination, thus becoming a powerful prognostic biomarker and a recognized tumor suppressor. Therefore, our study may provide a promising new therapeutic strategy for targeting RNF126 for HCC patients.

Hybrid Laparoendoscopic-Radiologic Procedure for Laparoscopic Cholecystectomy Complicated With Choledocolithiasis.

PURPOSE: The removal of common bile duct stones (CBDS) is routinely performed as either a 1-stage or 2-stage procedure. Despite many developments in both methods, the optimal approach has not been established to date. This study aimed to investigate the value and short-term outcomes of hybrid laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) combined with intraoperative endoscopic nasobiliary drainage (IO-ENBD) after primary duct closure (PDC) and intraoperative cholangiography (IOC) in patients with concomitant gallbladder stones (GBS) and CBDS. MATERIALS AND METHODS: Forty-seven patients with GBS and CBDS who underwent LC and LCBDE, PDC with IO-ENBD, and IOC were retrospectively enrolled. Stone characteristics and removal, operative data, and postoperative outcomes were recorded and analyzed. RESULTS: A total of 46 (97.87%) procedures were completed without conversion to open surgery. The mean operating time was 127.15±8.36 minutes (range, 97 to 158 min). Three patients (6.38%) had residual stones during IOC but achieved 100% stone clearance eventually. Postoperative pancreatitis and bile leakage rates were 4.26% and 2.13%, respectively. CONCLUSION: A hybrid procedure combining LC and LCBDE, PDC with IO-ENBD, and IOC is safe and feasible for concomitant GBS and CBDS.

LncRNA-SNHG3 is an independent prognostic biomarker of intrahepatic cholangiocarcinoma.

BACKGROUND: Numerous deregulated long non-coding RNAs (lncRNAs) accompany the initiation and progression of carcinogenesis. The present study aimed to explore the prognostic significance of lncRNA-SNHG3 on intrahepatic cholangiocarcinoma (ICC) patients. METHODS: LncRNA microarray assays were used to evaluate lncRNA expression profiling in three pairs of ICC tissues and adjacent non-tumorous tissues. RT-qPCR was performed to further validate the accuracy of the microarray results. RESULTS: lncRNA microarray and RT-qPCR assays revealed that SNHG3 expression levels were significantly increased in ICC tissues compared to the adjacent non-tumor tissues. A high SNHG3 expression level was significantly correlated with shorter OS in ICC patients. A multivariate regression analysis discovered that SNHG3 could serve as an independent prognostic factor for predicting the OS of ICC patients. CONCLUSION: We found SNHG3 to be an independent risk factor for predicting the prognosis of ICC. SNHG3 shows a strong promise in the development of novel therapeutic targets for the treatment of ICC.

Donor denervation and elimination of Kupffer cells affect expression of P-selectin and ICAM-1 in liver graft.

BACKGROUND: The non-function and dysfunction of primary liver graft likely involves dependence on Kupffer cells and hepatic innervation. The present experiment was designed to study the expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) mRNA in liver graft and to elucidate the role of Kupffer cells and the sympathetic nerve of the liver in down-regulating this expression. METHODS: Donor rats were given hexamethonium, a sympathetic ganglionic blocking agent, and/or gadolinium chloride, an inhibitor of Kupffer cells. Then the changes of graft P-selectin and ICAM-1 mRNA expression were measured after liver transplantation. RESULTS: The expressions of P-selectin and ICAM-1 mRNA were increased after liver transplantation, and down-regulated by liver denervation and elimination of Kupffer cells. CONCLUSIONS: Live donor denervation and elimination of Kupffer cells down-regulated the expressions of P-selectin and ICAM-1 mRNA in grafts. This may decrease graft ischemia/reperfusion injury.