Pancreatic cancer is one of the most aggressive cancers worldwide with a high mortality rate. Prognosis remains poor even in this era of advanced medicine mainly due to early metastasis and invasion. The present study aimed to explore and validate predictors of distant metastasis and prognosis in pancreatic cancer. In our preliminary experiment, we established a novel metastatic pancreatic cancer cell line BxPC-M8 from parent BxPC-3 cells. Via whole genome sequencing, RT-qPCR, western blotting, migration and invasion assays, we initially found that BxPC-M8 shared similar biological characteristics to BxPC-3, but only differed in enhanced metastatic and invasive capabilities with a significant increase in collagen type VI α1 chain (COL6A1) expression. Knockdown of COL6A1 via small interfering RNA led to a significant decrease in migration and invasion of BxPC-M8 cells, suggesting suppressed epithelial-mesenchymal transition. Furthermore, a significant increase in COL6A1 expression was observed in cancerous tissue compared with paracancerous tissue (40.7 vs 3.7, P=0.001). Additionally, its expression was observed to be significantly associated with distant metastasis and vascular invasion at the time of surgery. Multivariate analysis revealed that COL6A1 expression (hazard ratio 1.90, 95% confidence interval 1.04-3.47, P=0.037) is an independent predictor of overall survival (OS). The median OS observed for COL6A1 + and COL6A1patients was found to be 8±4 and 14±7 months (P= 0.021), respectively. Of note, we identified that COL6A1 expression in tissue samples was associated with significantly reduced OS (P= 0.001), demonstrating that COL6A1 may serve an important role in the metastatic process and could be considered as a predictor of poor outcomes in patients with pancreatic cancer. In addition, our findings suggest that COL6A1 could be an indicator of distant metastasis and a valid prognostic predictor in such patients; however, further investigation is required.
Aim. The primary aim of this study is to compare the short- and long-term outcomes between ABO-incompatible (ABOi) adult living donor liver transplantation (ALDLT) with rituximab prophylaxis and ABO-compatible (ABOc) ALDLT. Background. The strategy of ABOi liver transplantation (LT) was originated initially to increase the donor pool and to enable liver transplantation in emergency conditions. However, ABOi ALDLT remains a controversial approach in comparison to ABOc ALDLT. Methods. PubMed, Embase, and the Cochrane Library study search were accomplished to recognize studies comparing ABOi and ABOc ALDLT. Meta-analyses were conducted based on the evaluation of heterogeneity using a fixed-effect model and a random-effect model to assess the short- and long-term outcomes following ABOi ALDLT with rituximab prophylaxis. Results. Nine studies comprising a total of 3,922 patients (ABOi=671 and ABOc=3,251) were identified. There was no significant difference between ABOi and ABOc groups for 1-year, 3-year, and 5-year OS and graft survival, respectively. Moreover, 1-year and 3-year OS and DFS were similar between both groups for HCC patients. However, ABOi ALDLT had higher incidences of CMV infection, AMR, overall biliary complications, and biliary stricture than ABOc ALDLT and had other comparable postoperative complications. Conclusion. Our meta-analysis included studies comparing ABOi and ABOc ALDLT after the introduction of rituximab in a desensitization protocol for ABOi ALDLT. The results of ABOi ALDLT were comparable with those of ABOc ALDLT. However, biliary complications, CMV infection, and AMR remain a concern in the era of rituximab.
Background: Current opinion suggests that expansion of cancer stem cells (CSCs) and activation of pro-tumoral inflammation cascade correlate with cancer progression.Materials and methods: We explored the possible contributions of MRC-5 cancer-associated fibroblasts to the expression profiles of CSC markers and inflammation-associated cell surface molecules. The liver cancer cell lines Bel-7402, SMMC-7721, MHCC-LM3, and HepG2 cultured in conditioned medium (CM) from MRC-5 served as test groups, whereas the liver cancer cell lines cultured in normal medium served as control groups.Results: Flow cytometry revealed that the proportions of CD90+ cells were significantly higher in MHCC-LM3-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, and moderately higher in Bel-7402-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, than in controls. The CD90+/CD45- proportions were elevated in Bel-7402-(MRC-5)-CM and MHCC-LM3-(MRC-5)-CM cells, but reduced in HepG2-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, as compared to controls. Western blotting indicated that Nanog was downregulated in MHCC-LM3-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, compared to controls; that POU5F1 (OCT4/3) was downregulated in MHCC-LM3-(MRC-5)-CM, but upregulated in Bel-7402-(MRC-5)-CM and HepG2-(MRC-5)-CM cells, compared to controls, and that CK19 was upregulated in Bel-7402-(MRC-5)-CM and MHCC-LM3-(MRC-5)-CM cells, compared to controls. Proportions of cells expressing Toll-like receptor-1+ (TLR1) and TLR4 were significantly higher in MHCC-LM3-(MRC-5)-CM cells, and moderately higher in HepG2-(MRC-5)-CM cells, than controls. However, the TLR1+ and TLR4+ proportions were lower in Bel-7402-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells than controls. Proportions of CD25+ cells were reduced in HepG2-(MRC-5)-CM and SMMC-7721-(MRC-5)-CM cells, but elevated in MHCC-LM3-(MRC-5)-CM and Bel-7402-(MRC-5)-CM cells, compared to controls. Proportion of CD61+ cells was higher in liver cancer cells cultured in MRC-5-CM than in controls. Proportion of CD14+ cells was lower in HCC cells cultured in MRC-5-CM than in controls.Conclusion: MRC-5 extensively affected the production of CSC markers and inflammation-associated cell surface molecules. Tumor-targeting molecular therapies should consider these findings.
Background: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has become an important modality for identification of intra-abdominal masses. This study analyzed the accuracy of EUS-FNAB in a single medical center and explored factors related to positive diagnosis. Materials and methods: In total, 77 patients with EUS-FNAB were retrospectively reviewed from July 2016 to February 2020. "Atypical (tends to be neoplasm/malignancy)," "suspicious (first consider neoplasm/malignancy)," and "malignant" were defined as positive cytology. The final diagnoses were based on histopathologic examination. The positive rate of EUS-FNAB for the diagnosis of neoplasm and its associations with age, sex, target puncture mass size, liver function, tumor markers, albumin, hypertension, and diabetes were examined. Results: Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB cytologic diagnoses in all patients were 77.9% (60/77), 76.1% (54/71), 100%, 100%, and 26.1% (6/23), respectively. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB cytologic diagnoses in the pancreas were 80.0% (48/60), 79.3% (46/58), 100%, 100%, and 14.3% (2/14), respectively. The results of EUS-FNAB in pancreatic masses showed that the level of CA19-9 was higher in the true positive group than in the false-negative group (p<0.05). There were no factors associated with the true positive cytologic diagnoses (p>0.05). Conclusions: Our single-medical center study showed that EUS-FNAB is an accurate diagnostic procedure for the evaluation of intra-abdominal masses. Further follow-up is required to explore factors associated with the true positive cytology.
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