Cavernous Hemangioma of the Gallbladder Masquerading as a Carcinoma

Cavernous hemangioma arising from the gallbladder is extremely rare. Here, we report a cavernous hemangioma of the gallbladder masquerading as a carcinoma. A 75-year-old man was referred to our institution for a follow-up study after gastrectomy. Abdominal computed tomography revealed that the gallbladder was filled with a low-density mass with calcification of the wall. The patient underwent extended cholecystectomy. Histologically, the tumor consisted of vascular endothelial cellular elements and hematomas. The postoperative course was uneventful without complications. Presently, only 7 cases of cavernous hemangioma of the gallbladder have been previously reported. This case serves as an important reminder to consider benign tumors including cavernous hemangioma when investigating all possible causes of a gallbladder tumor

Tetrahydrouridine Inhibits Cell Proliferation through Cell Cycle Regulation Regardless of Cytidine Deaminase Expression Levels

Tetrahydrouridine (THU) is a well characterized and potent inhibitor of cytidine deaminase (CDA). Highly expressed CDA catalyzes and inactivates cytidine analogues, ultimately contributing to increased gemcitabine resistance. Therefore, a combination therapy of THU and gemcitabine is considered to be a potential and promising treatment for tumors with highly expressed CDA. In this study, we found that THU has an alternative mechanism for inhibiting cell growth which is independent of CDA expression. Three different carcinoma cell lines (MIAPaCa-2, H441, and H1299) exhibited decreased cell proliferation after sole administration of THU, while being unaffected by knocking down CDA. To investigate the mechanism of THU-induced cell growth inhibition, cell cycle analysis using flow cytometry was performed. This analysis revealed that THU caused an increased rate of G1-phase occurrence while S-phase occurrence was diminished. Similarly, Ki-67 staining further supported that THU reduces cell proliferation. We also found that THU regulates cell cycle progression at the G1/S checkpoint by suppressing E2F1. As a result, a combination regimen of THU and gemcitabine might be a more effective therapy than previously believed for pancreatic carcinoma since THU works as a CDA inhibitor, as well as an inhibitor of cell growth in some types of pancreatic carcinoma cells

DPEP1 Inhibits Tumor Cell Invasiveness, Enhances Chemosensitivity and Predicts Clinical Outcome in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. To identify biologically relevant genes with prognostic and therapeutic significance in PDAC, we first performed the microarray gene-expression profiling in 45 matching pairs of tumor and adjacent non-tumor tissues from resected PDAC cases. We identified 36 genes that were associated with patient outcome and also differentially expressed in tumors as compared with adjacent non-tumor tissues in microarray analysis. Further evaluation in an independent validation cohort (N = 27) confirmed that DPEP1 (dipeptidase 1) expression was decreased (T: N ratio ∼0.1, P<0.01) in tumors as compared with non-tumor tissues. DPEP1 gene expression was negatively correlated with histological grade (Spearman correlation coefficient = −0.35, P = 0.004). Lower expression of DPEP1 in tumors was associated with poor survival (Kaplan Meier log rank) in both test cohort (P = 0.035) and validation cohort (P = 0.016). DPEP1 expression was independently associated with cancer-specific mortality when adjusted for tumor stage and resection margin status in both univariate (hazard ratio = 0.43, 95%CI = 0.24–0.76, P = 0.004) and multivariate analyses (hazard ratio = 0.51, 95%CI = 0.27–0.94, P = 0.032). We further demonstrated that overexpression of DPEP1 suppressed tumor cells invasiveness and increased sensitivity to chemotherapeutic agent Gemcitabine. Our data also showed that growth factor EGF treatment decreased DPEP1 expression and MEK1/2 inhibitor AZD6244 increased DPEP1 expression in vitro, indicating a potential mechanism for DPEP1 gene regulation. Therefore, we provide evidence that DPEP1 plays a role in pancreatic cancer aggressiveness and predicts outcome in patients with resected PDAC. In view of these findings, we propose that DPEP1 may be a candidate target in PDAC for designing improved treatments

MicroRNA-200b and -301 are associated with gemcitabine response as biomarkers in pancreatic carcinoma cells

Chemotherapy resistance (congenital or acquired) is one of the principal challenges for the treatment of pancreatic carcinoma. Recent evidence has demonstrated that epithelial to mesenchymal transition (EMT) is associated with chemoresistance in pancreatic carcinoma cells. However, the molecular mechanism underlying the development of chemoresistance remains unknown, and limited therapeutic options are available. Therefore, to anticipate individual chemosensitivity or acquired chemoresistance for patients with pancreatic carcinoma, predictive biomarkers are urgently required. Extensive evidence suggests that microRNAs (miRNAs) serve a crucial role in regulating EMT. The aim of this study was to examine the potential role of miRNA (miR)-200b and miR-301 in predicting the chemo-responses to treatment for pancreatic carcinoma. The present results demonstrate that miR-200b expression predicted chemo-sensitivity and may have potential as a biomarker. In six different pancreatic carcinoma cell lines (Capan-1, Capan-2, Panc-1, MIAPaCa-2, BxPC-3 and PL45 cells), the expression of miR-200b correlated positively with chemosensitivity. Moreover, the enhanced expression of miR-200b increased chemosensitivity and induced mesenchymal to epithelial transition. Conversely, miR-301 modulated gemcitabine resistance and induced EMT through the downregulation of cadherin 1 expression. In addition, gemcitabine-resistant cells (Capan-2 and Panc-1) exhibited upregulated miR-301 expression and downregulated gemcitabine-induced apoptosis. In summary, these two miRNAs may serve roles as biomarkers in pancreatic carcinoma, miR-200b expression may predict chemosensitivity, and elevated miR-301 expression may have potential applications in the prediction of acquired gemcitabine resistance

Prognostic Role of the Intrahepatic Lymphatic System in Liver Cancer

Although several prognosticators, such as lymph node metastasis (LNM), were reported for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the prognostic impact of intrahepatic lymphatic vessel invasion (LVI) in liver cancer has rarely been reported. We sought to clarify the prognostic impact of intrahepatic lymphatic system involvement in liver cancer. We systematically reviewed retrospective studies that described LVI and clinical outcomes of liver cancer and also included studies that investigated tumor-associated lymphangiogenesis. We conducted a meta-analysis using RevMan software (version 5.4.1; Cochrane Collaboration, Oxford, UK). The prognostic impact of intrahepatic LVI in HCC was not reported previously. However, tumor-associated lymphangiogenesis reportedly correlates with prognosis after HCC resection. The prognostic impact of intrahepatic LVI was reported severally for ICC and a meta-analysis showed that overall survival was poorer in patients with positive LVI than with negative LVI after resection of ICC. Lymphangiogenesis was also reported to predict unfavorable prognosis in ICC. Regarding colorectal liver metastases, LVI was identified as a poor prognosticator in a meta-analysis. A few reports showed correlations between LVI/lymphangiogenesis and LNM in liver cancer. LVI and lymphangiogenesis showed worse prognostic impacts for liver cancer than their absence, but further study is needed