Biomedical subjects

Masayuki Imamura

Publications and source records attributed to Masayuki Imamura.

At least 37 records · Page 2Linked to original sources

PubMed2005

Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma.

PURPOSE: Fascin, an actin bundling protein, induces membrane protrusions and increased cell motility in various transformed cells. The expression of fascin in epithelial neoplasms has been described only recently, and the role of fascin in esophageal squamous cell carcinoma (ESCC) is still unknown. EXPERIMENTAL DESIGN: Paraffin sections of 200 patients with ESCC were immunohistochemically investigated. The expression levels of fascin mRNA in 20 ESCC tissues were compared with that in corresponding normal esophageal epithelium by semiquantitative reverse transcription-PCR. We also examined fascin protein expression in 33 ESCC cell lines. The role of fascin in cell motility and invasiveness in ESCC cells was assessed by the vector-based small interfering RNA. RESULTS: In immunohistochemical study, the intensity of fascin expression was usually increased in the tumor compared with that in normal epithelium. Fascin overexpression was significantly associated with a poor prognosis (immunoreactive rate, P = 0.033; immunoreactive intensity, P = 0.031). The fascin immunoreactive rate was associated with extent of the tumor (P = 0.002) and lymph node metastasis (P = 0.003). Multivariate analysis showed that fascin expression intensity was an independent prognostic factor, but the immunoreactive rate was not. In addition, up-regulation of fascin mRNA was found in 60% (12 of 20) of patients. In vitro study revealed that all 33 ESCC cell lines expressed fascin protein at a certain level. KYSE170, one of the fascin-overexpressed cells, decreased its motile and invasive properties after down-regulation of fascin expression. CONCLUSION: Our findings suggest that fascin overexpression may play an important role in the progression of ESCC.

Adult↗

PubMed2005

The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma.

PURPOSE: Aurora-A/STK15/BTAK (Aurora-A) encodes a Serine/Threonine kinase associated with chromosomal distribution, and its up-regulation induces chromosomal instability thereby leading to aneuploidy and cell transformation in several types of cancer. In this study, we investigated the role of Aurora-A in human esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: The expression levels of Aurora-A mRNA were compared in 33 ESCC tissues with that in corresponding normal esophageal epithelium by semiquantitative reverse transcription-PCR, and the distribution patterns and expression levels of Aurora-A protein were immunohistochemically investigated in the ESCC tumors of 142 patients. The results were then separately compared with the clinicopathologic findings of the patients, and the expression of Aurora-A was examined in nine ESCC cell lines and a normal esophageal epithelial cell line using Western blot analysis. RESULTS: The up-regulation of Aurora-A mRNA was found in 30% (10 of 33) of the tumors by semiquantitative reverse transcription-PCR, and protein up-regulation was found in 53% (75 of 142) of the patients by immunohistochemistry. mRNA and protein up-regulation of Aurora-A were correlated with distant lymph node metastasis (P = 0.05 and P = 0.04, respectively), and patients with Aurora-A mRNA or protein up-regulation had a poorer prognosis (P = 0.003 and P = 0.0009, respectively). Furthermore, multivariate analysis revealed that up-regulation of the Aurora-A protein was an independent prognostic factor. In addition, Aurora-A expression in all ESCC cell lines was higher than that in a normal esophageal epithelial cell line. CONCLUSIONS: The up-regulation of Aurora-A expression may reflect the malignant behavior of ESCC and may prove useful information as a prognostic factor for ESCC patients.

Aged↗

PubMed2005

New pancreas-preserving total duodenectomy technique.

Pancreas-preserving total duodenectomy (PPTD) was first described by Chung et al. in 1994. Since then, several surgeons have used PPTD to treat diseases that involve the duodenum diffusely but not the head of the pancreas, mostly familial adenomatous polyposis (FAP). The PPTD method has been changed in each report and seems to have improved over time. We performed PPTD on three patients with different diseases--one with intestinal hemorrhage due to small intestinal amyloidosis; another with numerous duodenal gastrinomas in a patient with multiple endocrine neoplasia type 1 (MEN-1) and Zollinger-Ellison syndrome (ZES); and the third with numerous duodenal polyposis and FAP--using a new method that is simpler and safer than those previously reported. When resecting the whole duodenum, we performed mucosectomy of the major papillar portion and saved the structure of the major papilla. After an approximately 8 mm long sphincteropapillotomy, the opened major papilla was anastomosed to an incisional opening of the small intestine. The orifice of the main pancreatic duct (MPD) was stented by a catheter, and the MPD was kept intact under direct vision during the operative procedures. The head of the pancreas was fixed with the small intestine by interrupted 4-0 silk sutures. Reconstruction of the alimentary tract was performed after either the Billroth I or the Billroth II method. This is the first report of PPTD in which the entire MPD was preserved to simplify the biliopancreatic-ductal reconstruction.

Adenomatous Polyposis Coli↗

PubMed2005

Impact of reconstruction methods on outcome of pancreatoduodenectomy in pancreatic cancer patients.

Local recurrence is one of the most frequent forms of pancreatic cancer recurrence, although local recurrence is rare for other periampullary cancers. Because the type of recurrence and outcome differ depending on the type of cancer, these factors should be considered when the type of reconstruction is chosen. Fifty-four pancreatoduodenectomies were performed in patients with ductal adenocarcinoma of the pancreas from 1994 to 2001. Billroth I reconstruction was performed in 27 consecutive patients before 1999, and thereafter Billroth II reconstruction was performed in another consecutive 27 patients. Postoperative nasogastric intubation and the duration before oral ingestion were longer for Billroth I patients than Billroth II patients. Seven complications occurred in Billroth I patients, whereas there were two complications in Billroth II patients. Disease-free survival and overall survival were not different between the two groups; however, bypass operations were required in nine patients of the Billroth I group and in one patient of the Billroth II group. Percutaneous transhepatic cholangio-drainage (PTCD) procedures were required in six patients of the Billroth I goup and in two patients of the Billroth II group. The Billroth II reconstruction may have some advantages over the Billroth I reconstruction in terms of postoperative oral ingestion and avoiding bypass surgery and PTCD at the time of recurrence.

Aged↗

PubMed2005

A strategy for determining which thoracic esophageal cancer patients should undergo cervical lymph node dissection.

BACKGROUND: There is controversy about performing cervical lymph node dissections in all middle and lower thoracic esophageal squamous cell carcinoma patients. The purpose of this study was to evaluate whether intraoperative examination of thoracic paratracheal lymph node by real-time reverse transcription-polymerase chain reaction was worthwhile for selecting patients for cervical lymph node dissection. METHODS: Under informed consent, 30 middle and lower thoracic esophageal squamous cell carcinoma patients were examined for thoracic paratracheal lymph node metastasis intraoperatively by hematoxylin-eosin staining and real-time reverse transcription-polymerase chain reaction for messenger RNA encoding squamous cell carcinoma antigen. When thoracic paratracheal lymph node metastasis was found, cervical lymph node dissection was performed. If the patients had no thoracic paratracheal lymph node metastasis, a randomized study for selection of cervical lymph node dissection was performed. RESULTS: Eleven of 30 patients with middle or lower third thoracic esophageal squamous cell carcinoma had thoracic paratracheal lymph node metastasis. Five of these 11 patients had cervical lymph node metastasis. Nineteen patients who had no metastasis in the thoracic paratracheal lymph nodes were enrolled in a randomized study. Eight of the 19 patients received cervical lymph node dissection and they were found not to have cervical lymph node metastasis. The other 11 patients did not receive cervical lymph node dissection, and there was no cervical lymph node recurrence. CONCLUSIONS: The intraoperative diagnosis of metastasis in the thoracic paratracheal lymph node may be used as an indicator for cervical lymph node dissection in middle and lower thoracic esophageal cancer patients.

Carcinoma, Squamous Cell↗

PubMed2005

Downregulation of survivin by siRNA diminishes radioresistance of pancreatic cancer cells.

BACKGROUND: Survivin is a member of the inhibitor of apoptosis protein family, which inhibits apoptosis and regulates cell division. Survivin is expressed by the majority of human cancers, including pancreatic adenocarcinoma. We have reported that its expression is correlated with shorter survival of pancreatic cancer patients, so regulation of this molecule could be a new strategy for fighting pancreatic cancer. METHODS: In 3 pancreatic cancer cell lines (AsPC-1, SUIT-2, and Panc-1), survivin promoter activity was determined by the luciferase reporter assay, and survivin messenger RNA (mRNA) expression was examined by quantitative reverse transcriptase-polymerase chain reaction. The dose-dependent cytotoxity of radiation was also assessed, while caspase-3 activity and induction of DNA fragmentation were evaluated. Furthermore, the effect of silencing or nonsilencing short interfering RNA (siRNA) expression plasmids directed against the survivin gene on AsPC-1 cells, the most radioresistant cell line, was evaluated. RESULTS: Pancreatic cancer cell lines expressed varying levels of survivin mRNA in association with transcriptional activity of the survivin promoter. Both survivin promoter activity and mRNA expression were correlated with tumor cell radiosensitivity. Radiation significantly increased survivin promoter activity and survivin mRNA expression in all cell lines. Radiation induced a significant increase in caspase-3 activity and DNA fragmentation in AsPC-1 cells. After silencing siRNA treatment of AsPC-1 cells (AS-S cells), there was a significant decrease in survivin mRNA expression and increase in caspase-3 activity, compared with the effect of nonsilencing scramble siRNA on AsPC-1 cells (AS-NS cells). AS-S cells were more radiosensitive than AS-NS cells. Radiation induced higher caspase-3 activity and more DNA fragmentation in AS-S cells, compared with AS-NS cells. CONCLUSIONS: Survivin may play an important role as 1 of the radioresistance factors. Downregulation of survivin by siRNA can diminish the radioresistance of pancreatic cancer cells, so combined therapy with survivin inhibition and radiation may be useful for the treatment of pancreatic cancer.

Cell Line, Tumor↗

PubMed2005

Pancreatic epithelial cells can be converted into insulin-producing cells by GLP-1 in conjunction with virus-mediated gene transfer of pdx-1.

BACKGROUND: Glucagonlike peptide-1 (GLP-1) stimulates insulin secretion and proliferation by islet cells in vitro and in vivo, associated with an activation of pancreatic duodenal homeobox gene-1 (pdx-1) function. The effect of GLP-1 on the conditionally immortalized pancreatic epithelial cells (IMPE cells) is not clear when they are treated in conjunction with the adenovirus-mediated gene transfer of pdx-1. METHODS: IMPE cells were established from the pancreas of H-2K(b)-tsA58 transgenic mice. IMPE cells were maintained at 33 degrees C with 10 U/mL interferon (IFN)-gamma and the experiments were performed at 39 degrees C without IFN-gamma. IMPE cells were infected with 20 multiplicities of Ad-pdx-1 or control Ad-lacZ at 39 degrees C without IFN-gamma and were incubated with various concentrations of GLP-1. After 48 hours, immunofluorescence and reverse transcriptase-polymerase chain reaction for insulin and pdx-1 expression were examined. Immunoreactive insulin in the cell lysate and supernatant was also analyzed. The glucose concentration in the culture medium was changed to test the insulin secretory responsiveness of the IMPE cells. RESULTS: The treatment with GLP-1 in conjunction with Ad-pdx-1 induced insulin production by IMPE cells, but the treatment with either GLP-1 or Ad-pdx-1 alone failed to induce insulin production. Insulin production and secretion were increased by GLP-1 and by glucose in a dose-dependent manner. In addition, the insulin-producing IMPE cells acquired a rapid insulin secretory responsiveness to the changes of extracellular glucose concentration. CONCLUSIONS: GLP-1 and pdx-1 work together to induce insulin-producing cells from IMPE cells, which bear unique characteristics of pancreatic ductal cells. The results suggest that GLP-1 may be another important determiner of pancreatic endocrine differentiation as is pdx-1.

Adenoviridae↗

PubMed2005

Analysis of E-, N-cadherin, alpha-, beta-, and gamma-catenin expression in human pancreatic carcinoma cell lines.

OBJECTIVES: Cadherins are cell surface glycoproteins that mediate Ca2+-dependent, homophilic cell-cell adhesion. The classic cadherins interact with either beta-catenin or gamma-catenin, which is bound to alpha-catenin that links the complex to the actin cytoskeleton. It has been reported that alteration in cadherins/catenins function or expression is found in the neoplastic process as a step in metastasis. The aim of this study was to analyze the expressions of E- and N-cadherins and catenins in human pancreatic cancer cell lines. METHODS: We examined the expression of cadherins and catenins in 7 human pancreatic cancer cells by RT-PCR, Western blotting, and immunocytochemistry. The interactions between cadherins and beta-catenin were assessed by immunoprecipitation. RESULTS: E-cadherin was expressed in all cell lines except for MIAPaCa-2, whereas N-cadherin was expressed in Capan-2, CFPAC-1, BxPC-3, and PANC-1. The alpha-, beta-, and gamma-catenins were expressed and cadherins/beta-catenin interactions were detected in all cadherin-expressing cells. Immunocytochemical analysis showed membranous expression of cadherins and catenins. CONCLUSION: The decreased or loss of cadherins and catenins expression could be involved in the tumor progression and metastasis, although these events may occur in in vivo conditions by interaction between cancer cells and extracellular matrices.

Adenocarcinoma↗

PubMed2005

[Recent trend of diagnosis and treatment for Zollinger-Ellison syndrome].

Since 1955 it has been difficult to cure gastrinomas in patients with Zollinger-Ellison Syndrome (ZES), because gastrinomas exhibit symptoms when they are still small. Besides they are often multiple and metastatic. Development of the SASI test and SRS has changed the situation, and now, based on these two techniques, curative resection of gastrinomas in ZES can be routinely performed. As the cases of resection increase, more accurate pathological findings have accumulated. We know now that duodenal gastrinomas have been a cause of ZES in more patients than pancreatic gastrinomas. In most patients with MEN-1 and ZES, duodenal gastrinomas, which are often multiple, bring about ZES.

Diagnosis, Differential↗

PubMed2005

Multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas in Japan.

The molecular mechanisms responsible for the development and/or progression of gastrinomas are largely unknown. Studies involving sporadic enteropancreatic neuro-endocrine tumors suggest that mutations in the MEN1 gene occur in some tumors and probably play an important role in their pathogenesis. In this study, we examined whether somatic mutations in the MEN1 gene are also responsible for sporadic gastrinomas and correlate with clinical manifestations of gastrinomas in Japanese patients. Genomic DNA was extracted from paraffin-embedded gastrinoma tissues from 12 patients. Nucleotide sequences in the MEN1 genes were determined by direct sequencing. We identified 6 mutations in 7 out of 12 examined gastrinomas (58%). The identified mutations were 1 non-sense, 2 missense, 1 deletion leading to frame shifts, 1 insertion and 1 splicing mutation. Identical mutations were found in three gastrinoma tissues. The age at surgery, the rate of hepatic metastasis, and tumor status were not significantly different in the 2 groups. This study demonstrates that alterations in the MEN1 gene are involved in about half of all sporadic gastrinomas, although no correlation between the presence of mutations and location and clinical phenotype or severity of disease has been found.

Adult↗

PubMed2005

[Treatment for pancreatic endocrine tumors with or without multiple endocrine neoplasia type 1].

Recent strategies for the treatment of pancreatic endocrine tumors are described. Most cases are metastatic, and liver metastasis is the most significant prognostic factor. Thus curative resection before liver metastasis develops based on the localization of the tumors with the SASI test is the standard strategy. Subtotal distal pancreatectomy or pancreas-preserving total duodenectomy is indicated for multiple pancreatic endocrine tumors and multiple duodenal gastrinomas, respectively, for patients with multiple endocrine neoplasia type 1.

Gastrinoma↗

PubMed2004

Prediction of lymph node metastasis with use of artificial neural networks based on gene expression profiles in esophageal squamous cell carcinoma.

BACKGROUND: The aim of the study was (1) to detect candidate genes involved in lymph node metastasis in esophageal cancers and (2) to investigate whether we can estimate and predict occurrence of lymph node metastasis by analyzing artificial neural networks (ANNs) using these gene subsets. METHODS: Twenty-eight primary esophageal squamous cell carcinomas were used. Gene expression profiles of all primary tumors were obtained by cDNA microarray. Lymph node metastasis-related genes were extracted with use of Significance Analysis of Microarrays (SAM). Predictive accuracy for lymph node metastasis was calculated by evaluation of 28 cases by ANNs with leave-one-out cross-n. The results were compared with those of other analyses such as clustering or predictive scoring (LMS). RESULTS: Our ANN model could predict lymph node metastasis most accurately with 60 clones. The highest predictive accuracy for lymph node metastasis by ANN was 10 of 13 (77%) in newly added cases that were not used for gene selection by SAM and 24 of 28 (86%) in all cases (sensitivity: 15/17, 88%; specificity: 9/11, 82%). Predictive accuracy of LMS was 9 of 13 (69%) in newly added cases and 24 of 28 (86%) in all cases (sensitivity: 17/17, 100%; specificity: 7/11, 67%). It was difficult to extract useful information for the prediction of lymph node metastasis by clustering analysis. CONCLUSIONS: ANN had superior potential in comparison with other methods of analysis for the prediction of lymph node metastasis. This systematic analysis combining SAM with ANN was very useful for the prediction of lymph node metastasis in esophageal cancers and could be applied clinically in the near future.

Adult↗

PubMed2004

Dual-phase 18F-fluoro-2-deoxy-D-glucose positron emission tomography as a prognostic parameter in patients with pancreatic cancer.

PURPOSE: Recently, dual-phase 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) was shown to be useful in the differentiation between malignant and benign pancreatic lesions. The aim of this prospective study was to evaluate the value of dual-phase FDG-PET as a prognostic parameter in patients with pancreatic cancer. METHODS: Sixty-five consecutive patients with pancreatic cancer underwent dual-phase FDG-PET. Standardised uptake values at 1 h (SUV1) and 2 h (SUV2) following the injection of FDG were determined, and the retention index (RI) was calculated by dividing the difference between SUV2 and SUV1 by SUV1. The prognostic value of SUV1, SUV2 and RI was analysed, along with the various clinical and biochemical parameters. RESULTS: Multivariate analysis showed that only three factors had an independent association with longer patient survival: female gender (p<0.01), TNM stage I-III (p<0.05) and RI>10% (p<0.01). Neither SUV1 nor SUV2 showed any prognostic significance. Combination of tumour stage and RI allowed more accurate prognostic evaluation. Patients at stage I-III with RI>10% survived longer than did patients at the same stage with RI<10% (15.3 vs 11.5 months, p<0.01). Patients at stage IV with RI>10% had an intermediate prognosis, with a median survival of 9.5 months; patients at stage IV with RI<10% showed the worst prognosis, with a median survival of 4.9 months (p<0.05). CONCLUSION: RI calculated with dual-phase FDG-PET can be used not only as a tool for initial diagnosis and staging of pancreatic cancer but also as a strong independent prognostic parameter that can allow accurate identification of those patients who will benefit from intensive anticancer treatment at different stages of the disease.

Female↗

PubMed2004

Brain metastasis from colorectal cancer.

PURPOSE: The mechanism of brain metastasis is not well understood, but the affinity between cancer cells and neural tissues may be involved in the process. The aim of our study is to elucidate the involvement of neural cell adhesion molecule (NCAM) and therapeutic parameters in patients with brain metastasis from colorectal cancer. METHODS: We retrospectively identified 17 patients with brain metastasis from colorectal cancer. Data were collected with regard to patients' characteristics, location, and stage of primary tumor, and extent and location of metastatic disease. NCAM histochemical staining was undertaken using a paraffin block, and compared with 56 Dukes C patients and 13 Dukes D patients. RESULTS: Neural cell adhesion molecule expression was significantly higher in the primary tumors of the brain metastasis patients than in the lesions of the Dukes C and Dukes D control groups (p = 0.0004). Patients whose tumor was managed by radiosurgery survived longer than patients who had had whole brain radiation or those who had been left untreated. CONCLUSION: The fact that NCAM expression was high in the primary tumors of brain metastasis patients suggests that the affinity of cancer cells to a particular organ is important for circulation-mediated metastasis. Controlling local tumors using radiosurgery is certainly going to play an important role in extending survival and improving the patient's quality of life (QOL).

Adult↗

PubMed2004

Conditional transformation of mouse pancreatic epithelial cells: an in vitro model for analysis of genetic events in pancreatocarcinogenesis.

Pancreatic ductal adenocarcinomas arise through the accumulation of certain genetic alterations including ras, p16, p53, and DPC4. We found that activation of ras and inactivation of p53 could cooperatively induce in vitro tumorigenicity in conditionally immortalized pancreatic epithelial (IMPE) cells. IMPE cells were established from transgenic mice bearing a temperature-sensitive mutant SV40 Large T (LT) antigen. IMPE cells grew continuously under permissive conditions (33 degrees C with interferon-gamma), but rapidly suffered growth arrest under non-permissive conditions (39 degrees C without interferon-gamma). The cells showed strong expression of E-cadherin and beta-catenin as epithelial markers, and cytokeratin 19, a specific ductal cell marker. Cell proliferation under permissive conditions was associated with down-regulation of p21 expression through inactivation of p53 after overexpression of LT antigen. Intriguingly, the shift from the permissive to non-permissive culture conditions caused G2/M arrest of IMPE cells. Although the cells did not form colonies when cultured in soft agar without activation of ras, cells with ras activation via an adenovirus vector formed colonies under permissive conditions. These findings suggest that activation of ras and inactivation of p53 can cooperatively induce anchorage-independent growth of IMPE cells. This cell line might be useful for studying the processes involved in pancreatocarcinogenesis.

Animals↗

PubMed2004

N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma.

PURPOSE: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to-mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules. The purpose of the study presented here was to investigate whether a gain in N-cadherin in pancreatic cancer is involved in the process of metastasis via EMT and whether its expression is affected by growth factors. EXPERIMENTAL DESIGN: We immunohistochemically examined the expression of N- and E-cadherins and vimentin, a mesenchymal marker, in pancreatic primary and metastatic tumors. Correlations among the expressions of N-cadherin, transforming growth factor (TGF)beta, and fibroblast growth factor 2 was evaluated in both tumors, and the induction of cadherin and vimentin by growth factors was examined in cultured cell lines. RESULTS: N-cadherin expression was observed in 13 of 30 primary tumors and in 8 of 15 metastatic tumors. N-cadherin expression correlated with neural invasion (P = 0.008), histological type (P = 0.043), fibroblast growth factor expression in primary tumors (P = 0.007), and TGF expression (P = 0.004) and vimentin (P = 0.01) in metastatic tumors. Vimentin, a mesenchymal marker, was observed in a few cancer cells of primary tumor but was substantially expressed in liver metastasis. TGF stimulated N-cadherin and vimentin protein expression and decreased E-cadherin expression of Panc-1 cells with morphological change. CONCLUSION: This study provided the morphological evidence of EMT in pancreatic carcinoma and revealed that overexpression of N-cadherin is involved in EMT and is affected by growth factors.

Aged↗

PubMed2004

Frequent silencing of low density lipoprotein receptor-related protein 1B (LRP1B) expression by genetic and epigenetic mechanisms in esophageal squamous cell carcinoma.

Low-density lipoprotein receptor-related protein 1B (LRP1B) is frequently deleted in tumors of various types, but its status and expression in esophageal squamous cell carcinomas (ESCs) have never been reported. In the course of a program to screen ESC cell lines for copy-number aberrations using array-based comparative genomic hybridization, we identified a homozygous deletion of LRP1B. Genomic PCR experiments revealed homozygous deletions of LRP1B in additional ESC cell lines (total, 6 of 43; 14.0%) and in primary esophageal tumors (30 of 70; 42.9%). Moreover, expression of LRP1B mRNA was frequently silenced in ESC lines without homozygous deletions (14 of 37; 37.8%). Using bisulfite-PCR analysis and sequencing, we found that LRP1B-nonexpressing cells without homozygous deletions were highly methylated at a CpG island of LRP1B, a sequence possessing promoter activity. Treatment with 5-aza-2'-deoxycytidine restored expression of LRP1B in those ESC lines. Histone acetylation status correlated directly with expression of LRP1B and inversely with the methylation status of the CpG island. Methylation of LRP1B was also detected in primary esophageal tumors. Restoration of LRP1B expression in ESC cells reduced colony formation. These results suggest that loss of LRP1B function in esophageal carcinogenesis most often occurs either by homozygous deletion or by transcriptional silencing through hypermethylation of its CpG island.

Acetylation↗

PubMed2004

Production of prostaglandinE2 via bile acid is enhanced by trypsin and acid in normal human esophageal epithelial cells.

Several reports suggest that duodenogastroesophageal reflux may produce esophagitis, Barrett's esophagus and esophageal carcinoma. And it is well known that the incidence of adenocarcinoma arising from Barrett's esophagus has been increasing during the past decade. On the other hand, cyclooxygenase-2 and prostaglandins, produced by the catalytic reaction of cyclooxygenase-2, are considered to relate to carcinogenesis of the digestive tract and other malignant tumors. Recent reports suggest that cyclooxygenase-2 is induced in Barrett's esophagus and esophageal carcinoma. The purpose of this study is to investigate the reaction of cyclooxygenase-2 expression and prostaglandinE2 production on normal human esophageal epithelial cells cultured with gastroduodenal components. Normal human esophageal epithelial cells were cultured with chenodeoxycholic acid, trypsin and in acidic condition, individually and with different combinations of these three factors. After culturing, cyclooxygenase-2 expression in the cells and amount of prostglandinE2 in culture media was evaluated by immunoblotting and enzyme-immunoassay, respectively after culturing the cells. Cyclooxygenase-2 expression was up-regulated by bile acid and prostaglandinE2 production was enhanced by bile acid with trypsin, acidic condition or both of these components, without a synergistic effect on cyclooxygenase-2 expression. Production of prostaglandinE2 via these factors was suppressed by the cyclooxygenase-2 selective inhibitor JTE-522. The results suggest that duodenogastroesophageal reflux may induce cyclooxygenase-2 expression and prostaglandinE2 production in esophageal epithelial cells, cyclooxygenase-2 specific inhibitors may have a chemopreventive effect on esophageal carcinoma.

Benzenesulfonates↗