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Hitoshi Funahashi

Publications and source records attributed to Hitoshi Funahashi.

30 records · Page 2Linked to original sources

Enhancement of integrins by interleukin-1alpha, and their relationship with metastatic and invasive behavior of human pancreatic ductal adenocarcinoma cells.

BACKGROUND AND OBJECTIVES: Adhesion and invasion of tumor cells to extracellular matrix (ECM) proteins play an important role in tumor metastasis formation. We investigated the enhancement of adhesive and invasive behavior to ECM proteins of human pancreatic cancer cells by interleukin-1alpha (IL-1alpha) to examine the mechanism of adhesion and invasion of metastatic human pancreatic cancer cells to ECM proteins. METHODS: The enhancement of integrin subunits by IL-1alpha was examined by cellular enzyme-linked immunosorbent assay (CELISA) in two metastatic human pancreatic cancer cell lines (BxPC-3 and SW1990) and two nonmetastatic pancreatic cancer cell lines (PaCa-2 and PANC-1). In addition, assays of cancer cell adhesion and invasion to ECM proteins were performed to investigate whether increased integrin expression affected the invasive interaction between cancer cells and the putative integrin ECM ligands. RESULTS: Expression of the alpha6 subunit by metastatic cancer cells was enhanced by IL-1alpha. Metastatic cancer cells also exhibited preferential adherence and invasion to laminin compared with nonmetastatic cancer cells, and this was enhanced by IL-1alpha. CONCLUSIONS: The enhancement of alpha6beta1-integrin by Il-1alpha acting through IL-1RI, as well as the expression of alpha6beta1-integrin, plays an important role in metastasis formation in pancreatic cancer

Carcinoma, Ductal, Breast↗

Expression and prognostic roles of integrins and interleukin-1 receptor type I in patients with ductal adenocarcinoma of the pancreas.

To investigate the prognostic indicator, we examined the expression of alpha6- and alpha5-integrin and interleukin-1 receptor type I (IL-1RI) immunohistochemically, and analyzed the correlation between immunohistochemical findings and clinicopathological factors in pancreatic cancer. In patients with a strongly expressing alpha6-integrin subunit or weakly expressing alpha5beta1-integrin in pancreatic cancer tissues there was a significant association with advanced TNM stage (P = 0.027 and 0.014, respectively), presence of liver metastases (P = 0.032 and 0.002, respectively), and poor prognosis (P = 0.0155 and 0.0056, respectively). In patients with a weakly expressing alpha6 integrin subunit or weakly expressing alpha5beta1-integrin in noncancerous pancreatic tissues there was a significant association with poor prognosis (P = 0.0324 and 0.0396, respectively). Multivariate analysis demonstrated that strong expression of alpha6- and weak expression of alpha5beta1-integrin were found to be independent prognosticators in pancreatic cancer patients. Our present results indicate that alpha6beta1- and alpha5beta1-integrin expression can be a significant prognostic indicator in pancreatic cancer.

Aged↗

Alteration of integrin expression by glial cell line-derived neurotrophic factor (GDNF) in human pancreatic cancer cells.

INTRODUCTION: Pancreatic cancer cells express a number of functionally active integrins that are related to their adhesive and invasive abilities. AIMS: To determine whether glial cell line-derived neurotrophic factor (GDNF) influences the expression of integrins in pancreatic cancer cell lines and to elucidate the mechanisms of adhesion and invasion to extracellular matrix (ECM) proteins. METHODOLOGY: The expression of integrin subunits and the alteration of their expression by GDNF were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in pancreatic cancer cell lines (MIA PaCa-2 and BxPC-3). Assays of adhesion and invasion of cancer cells to ECM proteins were conducted to investigate whether increased integrin expression affects the interaction between cancer cells and putative integrin ECM ligands. RESULTS: Expression of some of the integrin subunits in pancreatic cancer cells was enhanced by GDNF. The enhancement and associated increase in adhesive and invasive ability by GDNF were inhibited by blocking the GDNF receptor or the integrin beta1 subunit. CONCLUSIONS: In pancreatic cancer, the enhancement of integrin expression by GDNF signaling through the GDNF receptor strongly influences adhesion and invasion to ECM proteins.

Antibodies↗

Interleukin-1alpha enhances integrin alpha(6)beta(1) expression and metastatic capability of human pancreatic cancer.

OBJECTIVE: To investigate the mechanisms of metastasis formation in metastatic human pancreatic cancer, we examined the enhancement in integrin expression, and adherence to and invasiveness into extracellular matrix (ECM) proteins of human pancreatic cancer cells after exposure to interleukin (IL)-1alpha. METHODS: Expression of IL-1 receptor type I (IL-1RI) and alterations in integrin subunits by IL-1alpha were examined by flow-cytometric analysis and by cellular enzyme-linked immunosorbent assay in four human pancreatic cancer cell lines (BxPC-3, PaCa-2, PANC-1, and SW1990), respectively. In addition, assays of cancer cell adhesion and invasion to ECM proteins were performed to investigate whether increased integrin expression affected the adhesive and invasive interaction between cancer cells and the putative integrin ECM ligands. Furthermore, immunohistochemistry was used to assess integrins and IL-1R1 expression in pancreatic tissues. RESULTS: In metastatic cancer cells, expression of the alpha(6) subunit was enhanced by IL-1alpha treatment. While metastatic cancer cells exhibited preferential adherence to and invasion into laminin, these properties were enhanced by IL-1alpha. The alpha(6) subunit and IL-1RI were strongly expressed in pancreatic tissues from pancreatic cancer patients with liver metastasis. CONCLUSIONS: In pancreatic cancer, IL-1alpha enhanced alpha(6)beta(1)-integrin expression, probably via increased IL-1RI levels. Our results indicated that alpha(6)beta(1)-integrin and IL-1RI expression may play important roles in metastasis formation.

Enzyme-Linked Immunosorbent Assay↗

[Efficacy of intraperitoneal chemotherapy for advanced Borrmann type IV gastric carcinoma].

We report four patients with advanced Borrmann type IV gastric carcinoma, in whom intraperitoneal chemotherapy with low-dose CDDP and 5-FU plus MMC via a peritoneal port was effective against peritoneal metastasis. However, none of the four patients survived for a long period. During treatment, they were followed on an outpatient basis and received intraperitoneal chemotherapy biweekly with good control of peritoneal metastasis. The ratio of the outpatient follow-up period was more than 50% in all these patients. Intraperitoneal chemotherapy may be effective for controlling peritoneal metastasis of advanced Borrmann type IV gastric carcinoma, and contribute to maintaining the patient's quality of life.

Aged↗

Biological effect of irradiation on adhesion molecules in human colon cancer cells in vitro.

BACKGROUND: Carbohydrate antigens, such as sialyl Lewis(a) antigen (s-Le(a)) and sialyl Lewis(x) antigen (s-Le(x)), play an important role in cancer metastasis in vitro and in vivo. Currently, preoperative radiotherapy is used to prevent local recurrence of rectal cancer. We investigated the effects of X-ray irradiation on the carbohydrate antigens s-Le(a) and s-Le(x) in vitro. MATERIALS AND METHODS: The cell surface expressions of s-Le(a) and s-Le(x) were determined by flow cytometric analysis at 24 hours after X-ray irradiation of 4 human cancer cell lines. s-Le(a) and s-Le(x) functions were quantitated using a monolayer cell adhesion assay with human umbilical vein endothelial cells (HUVECs). RESULTS: The cell surface expressions of s-Le(a) and s-Le(x) decreased at 24 hours after irradiation. s-Le(a) adhesion to HUVECs monolayers similarly decreased at 24 hours after irradiation. CONCLUSION: These results may indicate a role for X-ray irradiation in the reduction of liver metastasis in patients with colon cancer.

CA-19-9 Antigen↗

Serous cystadenoma of the pancreas has abnormal imaging characteristics: report of a case.

Thanks to the development of image diagnosis and the spread of screening by ultrasonography, an increasing number of cystic lesions of the pancreas are being recognized. Serous cystadenoma of the pancreas is relatively rare among the cystic tumors of the pancreas in Japan. Herein, we report a case of serous cystadenoma that was difficult to diagnose. The tumor was located in the head of the pancreas, and it was indicated hypovascularity by enhanced computed tomography. These images did not indicate serous cystadenoma. After operation, we diagnosed correctly from the immunohistochemical examination. Although serous cystadenoma was believed to be in benign tumors, it has recently been revealed that serous cystadenoma has malignant potential. Therefore, serous cystadenoma that is difficult to diagnose should be completely resected.

Cystadenoma, Serous↗

Clinicopathological and immunohistochemical analysis of malignant features in mucinous cystic tumors of the pancreas.

BACKGROUND/AIMS: To investigate the malignancy of mucinous cystic tumors (MCTs) of the pancreas, we examined clinicopathological features and immunohistochemical findings of MCT. METHODOLOGY: We analyzed the expression of p53 protein, proliferating cell nuclear antigen, alpha6-integrin subunit, alpha5beta1-integrin, and interleukin-1 receptor type I in tumor specimens from eight patients with MCT. RESULTS: The tumors were classified as mucinous cyst adenoma (n=6) or mucinous cyst adenocarcinoma (n=2). The actuarial five-year survival rate was 83.3%. All in eight MCTs had 'ovarian-type' stroma in the cyst wall. The alpha6-integrin subunit and p53 protein were expressed in adenocarcinoma tissues of MCTs, and in two adenomas the alpha6-integrin subunit and p53 protein were also co-expressed. CONCLUSIONS: Our present results indicate that coexpression of the alpha6-integrin subunit and p53 protein should be appreciated as an indicator of malignancy in MCTs.

Adult↗

Surgical treatment for relief of severe pain with chronic pancreatitis that is resistant to conservative treatment.

BACKGROUND/AIMS: To evaluate the surgical treatment, we investigated that performed for chronic pancreatitis patients suffering from severe pain resistant to conservative treatments. METHODOLOGY: Nineteen chronic pancreatitis patients with severe pain resistant for a long time to previous conservative medical and/or interventional treatments underwent surgery retrospectively. We evaluated a difference of postoperative improvement of symptoms in patients with surgical treatment including nerve plexus resection. RESULTS: The mean follow-up interval after surgery was 59.7 months (range, 3.0-187.3 months). Of 19 patients, 14 (73.7%) underwent nerve plexus resection. Relief of symptoms was observed in 16 of 19 patients (84.2%). Fourteen of the 15 patients (93.3%) in the nerve plexus resection group were relieved of symptoms after surgery, compared to only two of four (50.0%) patients in the nerve plexus non-resection group. CONCLUSIONS: Surgical treatments with nerve plexus resection appropriately matched with individual patients are very safe and contribute to the improvement of the quality of life for chronic pancreatitis patients resistant to conservative treatments.

Adult↗

Clinicopathologic study of intraductal papillary-mucinous tumors and mucinous cystic tumors of the pancreas.

BACKGROUND/AIMS: We analyzed clinicopathologic and imaging findings of intraductal papillary-mucinous tumors (IPMTs) and mucinous cystic tumors (MCTs) of the pancreas to evaluate the difference between IPMTs and MCTs, and to identify the signs indicative of malignancy in IPMTs. METHODOLOGY: Clinicopathological features of 20 patients with IPMT and six patients with MCT of the pancreas were studied. RESULTS: The patients with IPMT comprised 16 males and four females with a mean age of 62.9 years. Eighty percent of IPMTs were located in the pancreatic head, and the mean tumor size was 38.6mm. Recurrence was observed in one patient, who died of IPM adenocarcinoma. In contrast, all patients with MCT were females, with a mean age of 53.0 years. None of the MCTs arose in the pancreatic head, and the mean tumor size was 42.7mm. One patient died of MC adenocarcinoma, but all of the others survived without recurrence. The difference in gender, location of the tumor, and connection to the pancreatic duct reached statistical significance between IPMTs and MCTs. A significant connection to the pancreatic duct and high level of serum carbohydrate antigen 19-9 (CA19-9) was observed in the adenocarcinoma and moderate dysplasia groups of IPMT. CONCLUSIONS: The main duct type and an elevation of serum CA19-9 level suggested malignancy in IPMTs.

Adenocarcinoma, Mucinous↗