GLUTATHIONE S-TRANSFERASE PLACENTAL FORM IS A MARKER FOR BILE DUCT CARCINOMA, BUT NOT HEPATOCELLULAR CARCINOMA, IN HUMANS.

Immunohistochemical studies using anti-human glutathione S-transferase placental form (GST-π) rabbit antibody were carried out to investigate various hepatobiliary diseases in humans. Hepatocytes in fetal and adult liver without disease were negatively or positively stained while intra-or extrahepatic bile duct epithelial cells were positively or strongly positively stained with GST-π. Hepatocytes in regenerated nodules in liver cirrhosis were positively stained. Hepatocellular carcinomas were not strongly positively stained, while cholangiocarcinomas and cancers of the biliary tract were positively or strongly positively stained. These results indicate that GST-π staining is a useful marker for the diagnosis of intra-or extra-hepatic bile duct carcinomas in humans, and that enzyme activity is not phenotypically expressed in hepatocellular carcinomas

9-Hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells

AbstractThere is increasing interest in identifying potent inhibitors of telomerase because the enzyme plays a crucial role in the development of cellular immortality and carcinogenesis. We hypothesized that 9-hydroxyellipticine (9-HE), an antitumor alkaloid, would inhibit telomerase activity because the drug has a unique mechanism of inhibiting phosphorylation of mutant p53 protein via inhibition of protein kinases, thereby restoring wild-type p53 function. This study was conducted to examine the effect of 9-HE on telomerase activity in human pancreatic cancer cells with differing p53 gene status. 9-HE treatment at relatively high concentrations resulted in rapid, complete inhibition of telomerase activity, irrespective of the p53 status. We conclude that 9-HE may exert a strong inhibitory effect on telomerase activity possibly through inhibition of protein kinases rather than through restoration of functional wild-type p53

MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation

<p>Abstract</p> <p>Background</p> <p>Recently, the microRNA-200 family was reported to affect cancer biology by regulating epithelial to mesenchymal transition (EMT). Especially, the expression of <it>miR-200c </it>has been shown to be associated with upregulating the expression of <it>E-cadherin</it>, a gene known to be involved in pancreatic cancer behavior. However, the significance of <it>miR-200c </it>in pancreatic cancer is unknown.</p> <p>Methods</p> <p>In the present study, we investigated the relationship between <it>E-cadherin </it>and <it>miR-200c </it>expression in a panel of 14 pancreatic cancer cell lines and in macro-dissected formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from 99 patients who underwent pancreatectomy for pancreatic cancer. We also investigated the effects of <it>miR-200c </it>on the proliferation and invasion of pancreatic cancer cells.</p> <p>Results</p> <p>We found that patients with high levels of <it>miR-200c </it>expression had significantly better survival rates than those with low levels of <it>miR-200c </it>expression. We also found a remarkably strong correlation between the levels of <it>miR-200c </it>and <it>E-cadherin </it>expression.</p> <p>Conclusions</p> <p>These data indicate that <it>miR-200c </it>may play a role in the pancreatic cancer biology and may be a novel marker for the prognosis of pancreatic cancer.</p

Repeated Pancreatectomy for Recurrent Pancreatic Carcinoma after Pylorus-Preserving Pancreatoduodenectomy: Report of Two Patients

Repeated pancreatectomy for pancreatic carcinoma is extremely rare. We report two such patients who underwent pancreatectomy for carcinoma developing in the pancreatic remnant after pylorus-preserving pancreatoduodenectomy (PpPD) for invasive pancreatic ductal carcinoma. One patient underwent PpPD for invasive pancreatic ductal carcinoma and received adjuvant chemotherapy. Follow-up computed tomography (CT) demonstrated a low-density mass in the remnant pancreas, which was diagnosed as a carcinoma by endoscopic ultrasound-guided fine-needle aspiration cytology 5 years 10 months after PpPD. She underwent curative resection of the remnant pancreas and is alive and well 13 months after the second operation. The other patient underwent PpPD for invasive pancreatic ductal carcinoma. Follow-up CT showed a low-density mass in the remnant pancreas after 2 years 11 months. He received systemic chemotherapy with S-1 for 3 months. The tumor shrank, and the patient underwent curative resection of the remnant pancreas 3 years 1 month after the initial operation. Repeated pancreatectomy may provide a chance of long survival for patients with carcinoma developing in the remnant pancreas after pancreatectomy if the recurrence occurring at long term is limited to the remnant pancreas

Inhibition of p600 Expression Suppresses Both Invasiveness and Anoikis Resistance of Gastric Cancer

BACKGROUND: Advanced gastric cancers often metastasize to distant organs and the peritoneum, leading to a poor prognosis. Both invasiveness and resistance to anchorage-independent cell death (anoikis) are important factors in the process of metastasis. p600 (600-kDa protein), recently identified from a cervical cancer cell line, plays a role in both anoikis resistance and cell migration. In this study, we examined whether p600 is involved in the progression of gastric cancer. METHODS: We used both normal gastric mucosal cells and cancer cells laser-microdissected from 42 gastric cancers and their normal counterparts, and compared their p600 mRNA expression levels with quantitative reverse transcriptase–polymerase chain reaction. We inhibited p600 expression in two gastric cancer cell lines with siRNA and examined its effect on the invasiveness and anoikis resistance both in vitro and in vivo. RESULTS: Expression of p600 mRNA was significantly higher in gastric cancer cells than in normal mucosal cells (P = 0.027). The invasion assay revealed that invasiveness was significantly reduced by inhibition of p600 (P < 0.01). In vitro experiments revealed that cell viability and colony-formation capacity under anchorage-independent conditions were significantly reduced by inhibition of p600 (P < 0.05). In vivo experiments also showed that the establishment of intraperitoneal disseminated tumors was significantly suppressed by transient inhibition of p600 (P < 0.001). CONCLUSIONS: Our results strongly suggest that p600 is involved in gastric cancer progression, and has a potential to be a new molecular target for gastric cancer therapy

Clustering of Lyman Break Galaxies at z=4 and 5 in The Subaru Deep Field: Luminosity Dependence of The Correlation Function Slope

We explored the clustering properties of Lyman Break Galaxies (LBGs) at z=4 and 5 with an angular two-point correlation function on the basis of the very deep and wide Subaru Deep Field data. We found an apparent dependence of the correlation function slope on UV luminosity for LBGs at both z=4 and 5. More luminous LBGs have a steeper correlation function. To compare these observational results, we constructed numerical mock LBG catalogs based on a semianalytic model of hierarchical clustering combined with high-resolution N-body simulation, carefully mimicking the observational selection effects. The luminosity functions for LBGs predicted by this mock catalog were found to be almost consistent with the observation. Moreover, the overall correlation functions of LBGs were reproduced reasonably well. The observed dependence of the clustering on UV luminosity was not reproduced by the model, unless subsamples of distinct halo mass were considered. That is, LBGs belonging to more massive dark haloes had steeper and larger-amplitude correlation functions. With this model, we found that LBG multiplicity in massive dark halos amplifies the clustering strength at small scales, which steepens the slope of the correlation function. The hierarchical clustering model could therefore be reconciled with the observed luminosity-dependence of the angular correlation function, if there is a tight correlation between UV luminosity and halo mass. Our finding that the slope of the correlation function depends on luminosity could be an indication that massive dark halos hosted multiple bright LBGs (abridged).Comment: 16 pages, 17 figures, Accepted for publication in ApJ, Full resolution version is available at http://zone.mtk.nao.ac.jp/~kashik/sdf/acf/sdf_lbgacf.pd