Association of microRNA-21 expression with its targets, PDCD4 and TIMP3, in pancreatic ductal adenocarcinoma.

Since the discovery of small non-coding RNAs, the analyses of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. miRNA-21 has been suggested to be one of the miRNAs that have an important role in the development or biological behavior of a variety of malignancies, including pancreatic cancer. This study was conducted to evaluate the relationship between the expression of miRNA-21 and that of its molecular targets, programmed cell death 4 (PDCD4) and tissue inhibitor of metalloproteinase (TIMP3), in pancreatic ductal adenocarcinoma. The study included 65 pancreatic ductal adenocarcinomas and 5 normal pancreatic tissue specimens for comparison. The miRNA expression profiling of five selected pancreatic ductal adenocarcinomas and five normal pancreatic specimens was performed using a microarray platform, and was evaluated by a hierarchical clustering analysis. The miRNA most highly expressed in pancreatic ductal adenocarcinomas (ie, miRNA-21) was further assessed by quantitative real-time reverse transcription PCR (RT-PCR) assays in the 65 pancreatic ductal adenocarcinoma cases. The expression pattern of its molecular targets (eg, PDCD4 and TIMP3) in pancreatic ductal adenocarcinoma was examined immunohistochemically. In the microarray analyses, 28 miRNAs were upregulated in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue, whereas 48 miRNAs were downregulated. miRNA-21 was the most significantly overexpressed miRNA in the pancreatic ductal adenocarcinomas analyzed, and was also highly expressed in 75% of the 65 pancreatic ductal adenocarcinomas examined by real-time RT-PCR. High miRNA-21 expression was correlated with a worse prognosis in the pancreatic ductal adenocarcinoma patients (P=0.045). The immunohistochemical expression patterns of PDCD4 (reduced nuclear staining pattern) and TIMP3 (downregulated expression) were significantly associated with both the upregulated miR-21 expression (P<0.05) and the poor survival of the patients (P<0.001 and P=0.001, respectively). Our data suggest that an overexpression of miRNA-21 is, therefore, associated with the biological behavior of pancreatic ductal adenocarcinoma via the downregulation of the expression of tumor suppressors, PDCD4 and TIMP3, thus resulting in tumor progression and the adverse clinical course of pancreatic ductal adenocarcinoma.

Lymphoepithelioma-Like Carcinoma of the Stomach with Epithelioid Granulomas.

An 83-year-old Japanese man was admitted to our hospital for gastric adenocarcinoma mimicking a submucosal tumor in the gastric body. Considering his general condition, partial resection of the stomach and dissection of regional lymph nodes were performed; a dome-shaped tumor that was largely covered by normal mucosa and having a shallow central stellate ulcer was removed. Histopathologically, the carcinoma cell nests were surrounded by prominent lymphoid stroma. Sarcoid-like epithelioid granulomas were noted both in the tumor stroma and in the regional lymph node with metastasis. Epstein-Barr virus (EBV)-encoded RNA (EBER) in situ hybridization showed an intense and diffuse positive reaction in the carcinoma cells and no reaction in the surrounding gastric and lymphoid tissues. While the presence of lymphoid stroma is a characteristic finding in EBV-associated lymphoepithelioma-like carcinoma, sarcoid-like epithelioid granulomas might be associated with latent EBV infection.

[A case of sigmoid colon cancer with peritoneal dissemination responding to third-line therapy employing bevacizumab combination therapy after failure of FOLFOX and FOLFIRI].

A58 -year-old man with sigmoid colon cancer with peritoneal dissemination was treated with bevacizumab (BV) plus mFOLFOX6 therapy as third-line chemotherapy after treatment failures with FOLFOX4 and FOLFIRI regimen. BV combination therapy resulted in a decrease in ascites and disappearance of the primary lesion. His ECOG performance status (PS) recovered from level 3 to level 1, and BV combination therapy improved his quality of life. This case suggested that BV in combination with chemotherapy could be a promising systemic chemotherapy for patients with colorectal cancer with peritoneal dissemination, and this regimen may be useful for patients progressing after receiving FOLFOX, FOLFIRI regimen.

[A long-term survivor case with good quality of life due to biliary bypass and gemcitabine for advanced pancreatic cancer].

A 54-year-old man was admitted to the hospital because of upper abdominal pain and anorexia. Physical examination revealed jaundice, and abdominal CT demonstrated a pancreatic mass and dilatation of bile duct. The patient was operated with the diagnosis of pancreatic cancer. However, the pancreatic cancer was unresectable because of invasion of the surrounding organs and metastasis to paraaortic lymph nodes, so a biliary bypass was performed. After operation, chemotherapy using gemcitabine was performed in the outpatient clinic. He survived for more than two years and eleven months without recurrence of jaundice. Combination of biliary bypass and gemcitabine is considered helpful for good quality of life and long-term survival of a patient with advanced pancreatic cancer.