Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a premalignant biliary-type epithelial neoplasm with intraductal papillary or villous growth. Currently reported local palliative therapeutic modalities, including endoscopic nasobiliary drainage, stenting and biliary curettage, endoscopic biliary polypectomy, percutaneous biliary drainage, laser ablation, argon plasma coagulation, photodynamic therapy, and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages. We have applied percutaneous transhepatic cholangioscopy (PTCS)-assisted biliary polypectomy (PTCS-BP) technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010. AIM: To assess the technical feasibility, efficacy, and safety of PTCS-BP for local palliative treatment of IPNB. METHODS: Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included. PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire, and the tumor was snared and resected with electrocautery. The primary outcome was its feasibility, indicated by technical success. The secondary outcomes were efficacy, including therapeutic success, curative resection, and clinical success, and safety. RESULTS: Five patients (four with mucin-hypersecreting cast-like type and one with polypoid type IPNB) were included. Low- and high-grade intraepithelial neoplasia (HGIN) and recurrent IPNB with invasive carcinoma were observed in one, two, and two patients, respectively. Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB. All five patients achieved technical success of PTCS-BP. Four patients (three with mucin-hypersecreting cast-like type and one with polypoid type IPNB) obtained therapeutic success; one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors. All four patients with mucin-hypersecreting IPNB achieved clinical success. The patient with polypoid type IPNB achieved curative resection. There were no PTCS-BP-related serious adverse events. CONCLUSION: PTCS-BP appears to be feasible, efficacious, and safe for local palliative treatment of both mucin-hypersecreting cast-like and polypoid type IPNB.

Stem cell gene Girdin: a potential early liver metastasis predictor of colorectal cancer.

The objective of this study is to investigate the liver's metastasis-related genes and the relationship between Girdin protein expression and clinical and pathological characteristics and prognosis in colorectal cancer. The differential expression of genes between tumor cells from cases with liver metastasis and those from cases without liver metastasis were detected using an RT(2) Profiler™ PCR Array. The expression of the stem cell gene Girdin was analyzed using immunohistochemistry staining. Subsequently, the relationship between Girdin and clinicopathological parameters of colorectal cancer was determined. The Girdin protein was verified as a gene related to liver metastasis and was expressed positively in 161 (37.01 %) of the 435 cases examined. The expression of Girdin protein was related to histological grade and distant metastasis (P = 0.007 and 0.007, respectively). After analyzing survival rates, cases with highly expressed Girdin protein were shown to attain a significantly higher rate of liver metastasis and poorer postoperative, disease-specific survival than those with no or low expressed Girdin protein (P = 0.001). In the Cox regression test, the depth of tumor invasion, histological grade, duke's stage, distant metastasis, and the Girdin protein were detected as an independent prognostic factor (0.020, 0.032, 0.001, 0.001, and 0.010, respectively). The Girdin protein may be a potential new early liver metastasis biomarker of colorectal cancer.

Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5.

The abnormal expression of long noncoding RNAs (lncRNAs) is frequently observed in gastric cancer (GC) and considered an important driving force in GC progression. However, little is known regarding the involvement of TMEM147-AS1 in GC. Therefore, we examined TMEM147-AS1 expression in GC and determined its prognostic value. In addition, TMEM147-AS1 expression was depleted to identify the functional changes in response to TMEM147-AS1 deficiency. Using the cancer genome atlas dataset and our own cohort, we identified a strong expression of TMEM147-AS1 in GC. Increased TMEM147-AS1 levels in GC showed a significant association with poor prognosis. TMEM147-AS1 interference resulted in the inhibition of GC cell proliferation, colony-forming, migration, and invasion in vitro. Additionally, depletion of TMEM147-AS1 restricted the growth of GC cells in vivo. Mechanistically, TMEM147-AS1 functioned as a microRNA-326 (miR-326) sponge. Furthermore, SMAD family member 5 (SMAD5) was experimentally validated as the functional effector of miR-326. TMEM147-AS1 was demonstrated to sequester miR-326 away from SMAD5; consequently, knocking down TMEM147-AS1 downregulated SMAD5 levels in GC cells. The functional suppression of miR-326 or reintroduction of SMAD5 effectively reversed the attenuated behavior of GC cells caused by TMEM147-AS1 downregulation. In summary, TMEM147-AS1 exhibits tumorigenic activities in GC, which is likely the result of an altered miR-326/SMAD5 axis. Therefore, targeting TMEM147-AS1/miR-326/SMAD5 may represent a target for the treatment of GC.

MicroRNA-103a inhibits gastric cancer cell proliferation, migration and invasion by targeting c-Myb.

OBJECTIVES: There have been no previous reports concerning functions of miR-103a in gastric cancer (GC) cells. Thus the aim of the study was to investigate its expression and role in development of this tumour. MATERIALS AND METHODS: Real-time RT-PCR was performed to detect expression of miR-103a in GC cell lines and clinical cancer specimens. To further understand its role, we restored expression of miR-103a in MGC-803 cell line by transfection with miR-103a mimics or inhibitors. Effects of miR-103a on cell proliferation, migration and invasion on targets were also determined. RESULTS: miR-103a was down-regulated in both GC cell lines and clinical cancer specimens. Meanwhile, its level was closely associated with pM or pTNM stage of GC. Overexpression of miR-103a markedly suppressed proliferation, migration, and invasion of GC cells, while its inhibition significantly accelerated cell proliferation, migration and invasion. Moreover, c-Myb was identified to be a functional downstream target of miR-103a, ectopic expression of which partially reversed suppression of cell proliferation and invasion. CONCLUSIONS: Thus our observations suggest that miR-103a functioned as a tumour suppressor by targeting c-Myb. These findings indicate that miR-103a might play a significant role in pathogenesis of GC.