Multiple primary cancers of the duodenum and sigmoid colon: report of two cases.
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Adenocarcinoma↗
Biomedical subjects
Yuji Okada
Publications and source records attributed to Yuji Okada.
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↗
Glial cell-derived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase-9 in human pancreatic cancer.
BACKGROUND: We have previously reported that the glial cell-derived neurotrophic factor (GDNF) promotes pancreatic cancer cell invasion in vitro. The purpose of this study was to determine whether GDNF regulates the expression and activation of matrix metalloproteinase-9 (MMP-9) in human pancreatic cancer cells. METHODS: We used human pancreatic cancer cell line MIA PaCa-2. The effect of GDNF on mRNA and protein expression was measured by Northern blot, Western blot and enzyme-linked immunosorbent assay. MMP proteolytic activity was detected by gelatin zymography. To determine which intracellular pathways were involved, we used the following inhibitors: tyrosine kinase inhibitor Genistein, MEK-1 inhibitor PD98059 and PI3-K inhibitor Wortmannin. RESULTS: GDNF increased MMP-9 mRNA and protein expression in MIA PaCa-2 cells in a dose-dependent manner. Treatment with GDNF enhanced gelatinolytic activity of the pro and active form of MMP-9. Inhibitor experiments showed that the expression and activity of pro MMP-9 was totally inhibited by Genistein and partially by Wortmannin, whereas PD98059 had no effect. All three compounds inhibited the activity of the active form of MMP-9. CONCLUSIONS: GDNF upregulates the expression and enzymatic activity of MMP-9 through different signaling pathways in MIA PaCa-2. These findings suggest that GDNF modulates MMP-9 expression and activation, and this may promote pancreatic cancer invasion.
Culture Media↗
Tumor-forming pancreatitis diagnosed preoperatively as intraductal papillary-mucinous tumor: report of a case.
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Adenocarcinoma, Mucinous↗
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↗
Effects of the prostanoids on the proliferation or hypertrophy of cultured murine aortic smooth muscle cells.
Effects of the prostanoids on the growth of cultured aortic vascular smooth muscle cells (VSMCs) were examined using mice lacking prostanoid receptors. Proliferation of VSMCs was assessed by measuring [(3)H]-thymidine incorporation and the cell number, and their hypertrophy by [(14)C]-leucine incorporation and protein content. In VSMCs from wild-type mice, expressions of mRNAs for the EP(4) and TP were most abundant, followed by those for the IP, EP(3) and FP, when examined by competitive reverse transcriptase-PCR. Those for the EP(1), EP(2) and DP, however, could not be detected. AE1-329, an EP(4) agonist, and cicaprost, an IP agonist, inhibited platelet derived growth factor (PDGF)-induced proliferation of VSMCs from wild-type mice; these inhibitory effects disappeared completely in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. In accordance with these effects, AE1-329 and cicaprost stimulated cAMP production in VSMCs from wild-type mice, which were absent in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. Effects of PGE(2) on cell proliferation and adenylate cyclase were almost similar with those of AE1-329 in VSMCs from wild-type mice, which disappeared in VSMCs from EP(4)(-/-) mice. PGD(2) inhibited PDGF-induced proliferation of VSMCs from both wild-type and DP(-/-) mice to a similar extent. This action of PGD(2) was also observed in VSMCs from EP4(-/-) and IP(-/-) mice. In VSMCs from wild-type mice, I-BOP, a TP agonist, showed potentiation of PDGF-induced hypertrophy. I-BOP failed to show this action in VSMCs from TP(-/-) mice. The specific agonists for the EP(1), EP(2) or EP(3), and PGF(2)alpha showed little effect on the growth of VSMCs. These results show that PGE(2), PGI(2) and TXA(2) modulate PDGF-induced proliferation or hypertrophy of VSMCs via the EP(4), IP and TP, respectively, and that the inhibitory effect of PGD(2) on PDGF-induced proliferation is not mediated by the DP, EP(4) or IP.
Animals↗
Effects of topically instilled bunazosin hydrochloride and other ocular hypotensive drugs on endothelin-1-induced constriction in rabbit retinal arteries.
PURPOSE: To compare the inhibitory effect of topically instilled bunazosin hydrochloride (bunazosin), a selective alpha(1)-adrenoceptor antagonist, on the endothelin (ET)-1-induced vasoconstriction in rabbit retinal arteries with the effects of other ocular hypotensive drugs. METHODS: ET-1 was injected into the central part of the vitreous of both eyes of pigmented rabbits. Color fundus photographs were taken 5 min before and 60 min after the injection. The average diameters of the two major retinal arteries at the rim of the optic nerve head (ONH) were normalized with respect to ONH diameter. Fifty microliters of 0.01% bunazosin, or 0.12% isopropyl unoprostone (unoprostone), 1% dorzolamide hydrochloride (dorzolamide), 0.25% nipradilol, 0.5% betaxolol hydrochloride (betaxolol), or 0.5% timolol maleate (timolol) was instilled into one eye of each rabbit 60 min before the ET-1 injection. The series of experiments was performed as masked tests. RESULTS: Bunazosin and unoprostone inhibited the ET-1-induced constriction of retinal arteries by 103% (P = 0.012 versus contralateral eyes) and 50% (P = 0.037), respectively. Dorzolamide, nipradilol, betaxolol, and timolol had no significant effects in this experiment. CONCLUSIONS: Under our experimental conditions, bunazosin and unoprostone inhibited the ET-1-induced constriction. Hence, bunazosin and unoprostone may be clinically more effective against ET-1-related retinal diseases.
Administration, Topical↗
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↗
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↗