S Hirohashi

..Actinin-4 is an actin-binding protein associated with enhanced cell motility, invasive growth, and lymph node metastasis. Actinin-4 might play an important role in the development and progression of pancreatic cancer...

..In conclusion, inactivation of the E-cadherin system by multiple mechanisms, including both genetic and epigenetic events, plays a significant role in multistage carcinogenesis...

..Some IPMCs might progress to invasive carcinoma via pathways that are different from those followed by ductal adenocarcinomas...

..Therefore, selective inhibition of Ras activation may be useful for preventing cancer metastasis...

..These findings indicate that c-Src activation is critically involved in carcinoma cell migration and metastasis...

..In addition, the wild-type allele of the E-cadherin locus was lost, suggesting that the E-cadherin gene had been inactivated by two hits (mutation and allele loss), similar to the mechanism for inactivation of tumor suppressor genes...

..These findings confirm the importance of the Rho/p160ROCK signaling pathway in intrahepatic metastasis of human HCC, and indicate that Y-27632 may be useful for the prevention of intrahepatic metastasis of human HCC...

..Although the function of DRH1 protein is still unknown, our findings suggest that DRH1 is related to the progression of HCC and may provide a new prognostic factor...

..Although structurally related to radixin and moesin, ezrin may have a distinct function in tumor-cell invasion...

..CONCLUSIONS: These data suggest that DNA methylation may play a role in human multistage carcinogenesis through direct or indirect regulation of multiple tumor-related genes...

..Our study showed that DEK overexpression, partly through an increase in its gene dose, mediates the activity of global transcriptional regulators and is associated with tumor initiation activity and poor prognosis in HGNEC...

..The absence of KRAS mutation and the presence of EGFR amplification may be potential predictive molecular marker of sensitivity to EGFR-targeted therapy in cholangiocarcinoma...

..The study concluded that overexpression of laminin-5 may be a useful prognostic factor in patients with small-sized lung adenocarcinoma, especially in Stage I cases...

..05). We conclude that immunohistochemical positivity for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and adenocarcinoma in pleomorphic adenoma of the major salivary glands...

..These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers...

..On the other hand, point-mutational activation of the c-Ki-ras proto-oncogene may be involved in cholangiocarcinogenesis in liver without preexisting liver-fluke or viral infection...

..The loss of epithelial cell polarity may be a critical cellular event driving beta-catenin/TCF4-mediated intestinal tumorigenesis...

..002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression...

..This monoclonal antibody potentially discriminates mesothelium from epithelium and may become a tool for differential diagnosis of mesothelioma...

..Int. J. Cancer (Pred. Oncol.) 84:381-387, 1999...

..Because alterations of integrin expression in cancers contribute to cancer cell biology, we analyzed the association between the potential for peritoneal dissemination and integrin expression...

..Finally, proliferation of lymphatic endothelial cells may occur in association with lymphatic invasion by cancer cells...

..Transarterial chemotherapy with SMANCS, which is well tolerated, appears to have moderate antitumor effect in patients with HCC...

..CONCLUSIONS. An anatomic and extensive liver resection should be performed for mass-forming ICC, whereas a hepatectomy with excision of the extrahepatic bile duct and hilar lymph nodal dissection is recommended for infiltrating ICC...

..Modulation of this interaction might provide a new approach to prevent metastasis and recurrence of HCC...

..5% at 3 years, and 40.5% and 40.1% at 5 years, respectively. There was no significant difference between the survival rates of those who underwent operations for PLC and extrahepatic primary cancer(s) synchronously and metachronously...

..These results suggest that plakoglobin could play a role in mediating the signals of APC by mutual interaction and that this may be regulated by tyrosine phosphorylation...

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..89; 95% CI, 1.05-3.39, P=0.0335) in IHCC. These results suggest that EGFR expression is associated with tumour progression and VEGF expression may be involved in haematogenic metastasis in cholangiocarcinoma...

..05). der(16)t(1;16)/der(1;16) detected by FISH is considered helpful in identifying patients with a better prognosis and for stratification of patients in randomized clinical trials of adjuvant chemo-endocrine therapies...

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..These deletions were probably produced by an error of RNA splicing, presenting one possible mechanism for the loss of intact alpha-catenin expression...

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..Since ACPs harbour beta-catenin mutation, the inappropriate activation of beta-catenin/LEF1 complex-dependent transcription may play a critical role in ACP tumorigenesis...

..The molecules involved in the progression of hepatocellular carcinoma (HCC) are not fully understood. The aim of this study was to elucidate the crucial genes involved in cancer progression and metastasis...

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..These results indicate that ISH is an excellent technique for systemic screening of genes expressed in a region specific manner...

..The purpose of the study was to evaluate the safety and efficacy of Gd-BOPTA for liver imaging and to determine the most appropriate clinical dose to administer...

..CONCLUSION: Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery...

..These results suggest that not only the expression of VLDLR but also genetic or epigenetic silencing of this gene may contribute to tumor formation and be involved in gastric carcinogenesis...

..hum pathol 32:257-263...

..We conclude that MRP3 could be a novel molecular marker for LNMBAC, whose expression increases during the early progression of tumourigenesis...

..Laminin-5-gamma-2 expression in the intraductal components of IPMTs tends to increase as tumors develop and may be a indicator of the potential invasiveness of the tumor cells...

..Although atypical proliferative lesions were frequently confirmed to be of clonal nature with LOH on 16q, these lesions and carcinomas were considered to be clones, probably originated from a field with these clones...

..0028, log-rank test for overall and recurrence-free survival rate, respectively). These results suggest that increased dysadherin expression is a significant indicator of poor prognosis for patients with advanced colorectal carcinoma...

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..It is possible that the adenoma-carcinoma sequence occurs in biliary tumours...

..We suggest that the HFREP-1 gene is a new member of the fibrinogen family and that further data on the gene are important for a better understanding of the development of hepatocellular carcinomas...

..These findings should facilitate our understanding of the regulation of beta4-integrin gene expression in processes such as cell growth and differentiation, apoptosis, and cancer development and metastasis...

..The reduction rate in serum AFP levels was also useful in patients with AFP levels >200 ng/ml before treatment...

..High-level estrogens and / or sensitivity of mammary glandular cells to estrogens might induce breast cancers with structural changes of chromosome 16...

..Therefore, in contrast to the ras oncogenes, mutation of the p53 gene was frequently involved in the development of CCCs in both Japanese and Thai patients, irrespective of any difference in etiology...

..001) and survival rate (log rank = 0.0014), confirming the mapping of PAS1 and pointing to the role of this locus in human lung cancer...

..Furthermore, mechanisms other than mutation of exon 3 of the beta-catenin gene may activate the Wnt/Wingless signaling pathway in this type of tumor...

..Cadherin-14 is a novel neurally specific cell-cell adhesion molecule and may regulate neural morphogenesis...

..These data suggest that c-erbB-2-induced signaling is also directly liked to the cadherin-mediated cell adhesion and "invasion-suppressor" system through beta-catenin and plakoglobin in cancers...

..The histological grade and c-erbB-2 overexpression appeared to be largely established during the early microscopic stages of a DCIS or invasive carcinoma...

..As a supportive diagnostic procedure, FISH analysis may give information about the nature of lesions, when the lesions are clinically or pathologically equivocal for cancer...

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..These findings suggest that reduced p27Kip1 expression may be at least partly responsible for human hepatocarcinogenesis...

..0019 by log-rank test). These data suggest that the HGF/c-MET system constitutes an autocrine activation loop in cancer-stromal myofibroblasts. This autocrine system may play a role in invasion and metastasis of lung adenocarcinoma...

..CONCLUSIONS: This study showed that tumor nest configuration, which corresponded to the behavior of tumor cells against stromal cells, correlated well with the aggressiveness of the tumor...

..These tumors, when arising in proximal locations, have a much worse prognosis than those arising in distal locations...

..In addition, the CISH method was superior in the detection of numerical alterations in carcinoma cells by referring to the morphology of cells and in the detection of significant clones which might be missed under dark-field microscopy...

..Appropriate immunohistochemical studies and laboratory examination enable pathologists to distinguish ANB from other differential diagnoses, especially PNET...

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..Nonetheless, the identification of "immature glandular features" was effective in predicting the radiotherapy resistance of cervical SCC and poorer patient prognosis...

..046). These results suggested that inactivation of tumor suppressor genes on chromosome 2 is involved in the phenotypic alterations of NSCLC cells into more aggressive ones...

..The IGSF4 gene, a novel gene that is shown to be located in the common loss of heterozygosity region, possesses a number of interesting features and may be good candidate for a tumor suppressor gene...

..This mutation may abolish the E-cadherin-mediated cell-cell adhesion and be at least partly responsible for the weak intercellular adhesiveness and scattered histological pattern of the tumor...

..Recently, another member of the semaphorin family, CD100, was shown to significantly improve the viability of B lymphocytes. These results suggest the involvement of semaphorins in diverse cell survival mechanisms...

..Moreover, immunohistochemical examination of 44 lung carcinomas showed that both molecules were coexpressed in all of them, and suggested that expression of P-cadherin was closely related to the differentiation of carcinoma cells...

..Dysadherin expression is considered to be one of the determinants of histologic subtype in synovial sarcoma. Moreover, dysadherin expression is an excellent and independent prognostic indicator...

..This study shows that dysadherin has prometastatic effects that are independent of E-cadherin expression and that CCL2 could play an important role in mediating the prometastatic effect of dysadherin in ER-negative breast cancer...

..The aim of this study was to investigate the clinical significance and roles of TR in the progression and multistep carcinogenesis of pancreatic ductal adenocarcinoma...

..These results suggest that epigenetic silencing by hypermethylation of the CpG-rich promoter region of PCDH20 leads to loss of PCDH20 function, which may be a factor in the carcinogenesis of NSCLC...

..Shutting down the signals mediating this association may be worth considering as a therapeutic approach to cancer invasion and metastasis...

..In combination with gene expression profiling, it was indicated that CD74 could be a candidate molecule involved in perineural invasion. These models provide new approaches for study of perineural invasion in pancreatic cancer...

..Our results have clinical relevance because epigenetic instability-dependent HCCs may respond well to methylation inhibitory therapies...

..39 and correlation coefficient of over 0.92 between duplicates), and accurate quantification with a wide dynamic range (over 10(3)) of our platform warrant its application to various types of experimental and translational proteomics...

..Regional DNA hypermethylation may be associated with renal tumorigenesis from a precancerous condition to malignant progression and become a predictor of patient prognosis...

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..Our results contribute to a complete description of genomic structural aberrations and the identification of potential therapeutic targets and genetic indicators that predict patient outcome in pancreatic adenocarcinoma...

..Identification of the functional interaction of Ku70 as well as PARP-1 with the TCF-4 and beta-catenin transcriptional complex may provide insights into a novel linkage between DNA damage recognition/repair and Wnt signaling...

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..We attempted to examine whether deregulation of Nrf2, a master transcriptional factor of various cytoprotective genes against oxidative stress, plays a role in the carcinogenesis of BTC...

..These results suggest that, at least partly, epigenetic silencing by hypermethylation of the ANGPTL2 promoter leads to a loss of ANGPTL2 function, which may be a factor in the carcinogenesis of OC in a stage-dependent manner...

..90, 95% CI = 1.56-2.33, P = 8.01 x 10(-11)). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer...

..However, beta-catenin has no nuclear localization signal, and the mechanisms by which beta-catenin is imported into the nucleus and forms a complex with the TCF-4 nuclear protein are poorly understood...

..We aimed to develop prognostic biomarkers for gastrointestinal stromal tumors (GIST) using a proteomic approach...

..Thus, inhibition of NRF2 may provide new therapeutic approaches in lung cancers with activation of Nrf2...

..There is no consensus on the strategy for follow-up. Identification of the molecular mechanisms that are associated with the natural history of lung adenocarcinoma should provide useful information...

..DNA topoisomerase IIalpha (Topo IIalpha) is a component of the beta-catenin/T-cell factor-4 (TCF-4) nuclear complex. We examined the functional significance of Topo IIalpha in Wnt signaling...

..Correction of DNA methylation status may offer a new strategy for prevention and therapy of cancers...

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..This protocol allows the execution of large-scale proteomics in a more efficient, accurate and reproducible way. The protocol can be used to examine a single sample in 5 d or to examine hundreds of samples in large-scale proteomics...

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..These results suggest that genetic or epigenetic silencing by hypermethylation of the ADAM23 CpG-rich promoter region leads to loss of ADAM23 function, which may be a factor in gastric carcinogenesis...