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Biomedical subjects

Minoru Yamamoto

Publications and source records attributed to Minoru Yamamoto.

At least 19 recordsLinked to original sources

Malignant solitary fibrous tumor originating from the peritoneum and review of the literature.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare neoplasm frequently involving the pleura. Benign and malignant forms of the tumor occur, the benign variant being three to four times more common than the malignant. CASE REPORT: We present herein a rare case of large malignant solitary fibrous tumor (SFT) originating from the peritoneum. An abdominal computed tomography scan revealed a well-defined solid tumor with mixed density. An abdominal ultrasonography (US) revealed a well-circumscribed solid tumor containing a partially cystic lesion. T1-weighted abdominal magnetic resonance imaging demonstrated a hypo- to isointensity, which was a hypo- to hyperintensity on T2-weighted images. Liposarcoma originating from the retroperitoneum was suggested, and the patient underwent a complete resection of the tumor as well as the left kidney because tumor invasion of the upper left kidney was suspected. Immunohistochemically, the spindle-shaped cells were positive for CD34, and the diagnosis was SFT originating from the peritoneum. At the 14-month follow-up evaluation, no recurrence or metastasis was detected. CONCLUSIONS: This case gave us some difficulty, and the correct diagnosis of the peritoneal mass was valuable. To diagnose the malignant potential of this type of tumor accurately may have value to direct the appropriate therapeutic operations after surgery and postoperative progress observation.

Adult↗

A new method for constructing an ileal J pouch without an enterotomy.

The conventional methods of making an ileal J pouch require an enterotomy to introduce a linear stapler. We devised a new surgical technique that removes any need for this enterotomy by using both circular and linear staplers. We applied this method to two patients who underwent a total colectomy for ulcerative colitis and succeeded in making a J pouch without difficulty. This procedure may represent an improved method of making a J pouch.

Colectomy↗

Interleukin-1alpha enhances IL-8 secretion through p38 mitogen-activated protein kinase and reactive oxygen species signaling in human pancreatic cancer cells.

BACKGROUND: Interleukin (IL)-1alpha plays an important role in modulating the expression of various growth factors and angiogenic factors in tumor cells. In here, we investigated effect of IL-1alpha on IL-8 secretion in human pancreatic cancer cells and underlying signal transduction pathways. MATERIAL/METHODS: IL-8 expression and secretion by pancreatic cancer cells was measured by Western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Activation of extracellular signal regulated kinases-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), c-jun aminoterminal kinase, Akt, and nuclear factor-kappaB (NF-kappaB) was determined by Western blot. Involvement of reactive oxygen species (ROS) were examined by measuring the H2O2. Activity of activator factor-1 (AP-1) and NF-kappaB was examined by electrophoretic mobility sift assay (EMSA). Proliferation of human umbilical vein endothelial cells (HUVECs) was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method and cell count. RESULTS: IL-1alpha modulated IL-8 secretion and induced activation of ERK-1/2 and p38 MAPK. Specific inhibitors for MEK-1 and p38 MAPK suppressed IL-8 secretion. IL-1alpha also induced production of ROS. Exogenous H2O2 enhanced IL-8 secretion and N-acetyl cysteine (NAC) prevented IL-1alpha-induced ROS production and IL-8 secretion. EMSA confirmed that IL-1alpha increased DNA-binding activity of AP-1 and NF-kappaB. Inhibitors and ROS scavenger studies revealed that upstream signalings for AP-1 and NF-kappaB were MAPK and ROS, respectively. Conditioned media from pancreatic cancer cells pretreated with IL-1alpha remarkably stimulated in vitro HUVECs growth. CONCLUSIONS: These results suggest that MAPK/AP-1 and ROS/NF-kappaB signaling pathways are involved in IL-1alpha-induced IL-8 secretion and that these paracrine signaling pathways enhance endothelial cell proliferation.

Blotting, Western↗

An anti-stray stylet for subclavian catheterization by the infraclavicular approach.

OBJECTIVE: Misplacement of subclavian vein catheters has been reported. We assessed the rate of misplacement of a subclavian vein catheter with and without a novel stylet. METHODS: A prospective, randomized, controlled clinical trial was conducted between September 2001 and June 2003 in a university hospital. Two hundred sixteen adult patients were enrolled to receive subclavian vein catheterization under non-emergency conditions. Patients were randomly assigned to undergo right subclavian vein catheterization with the stylet (n = 109, stylet group) or without the stylet (n = 107, control group). The rate of subclavian vein catheter misplacement was determined and risk factors for failure and complications were analyzed. RESULTS: There was no incidence of catheter misplacement in the stylet group, but this occurred in 12 patients in the control group in whom the catheter was misplaced into the ipsilateral internal jugular vein (0% versus 11.2%, P = 0.0003). In multivariate analyses, use of the stylet (odds ratio = 0.062, 95% confidence interval = 0.008 to 0.495, P = 0.009) and a close to average body mass index (odds ratio = 0.73, 95% confidence interval = 0.54 to 0.98, P = 0.038) were associated with low risks of complications and failure, respectively. CONCLUSIONS: This stylet is useful for decreasing the incidence of misplacement of subclavian vein catheters. Body mass index is predictive of failed vein puncture.

Aged↗

Enhanced angiogenesis due to inflammatory cytokines from pancreatic cancer cell lines and relation to metastatic potential.

OBJECTIVES: To investigate the mechanisms of metastasis formation in human pancreatic carcinoma, we examined the angiogenic capabilities of human pancreatic cancer cell lines with different metastatic potentials and the roles of inflammatory cytokines. METHODS: Interleukin (IL)-8 secretion by human pancreatic cancer cells stimulated with IL-1alpha or IL-1 receptor antagonist (IL-1ra) was measured by enzyme-linked immunosorbent assay (ELISA). We then examined how cancer cells with different metastatic potentials influenced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method (MTT assay) and an angiogenesis assay, respectively. We also examined the role of inflammatory cytokines in relation to tumor metastatic potential and angiogenesis. RESULTS: IL-8 secretion levels by pancreatic cancer cells were regulated by IL-1alpha and correlated with metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with metastatic pancreatic cancer cells and were enhanced to a similar extent by culture in the presence of IL-1alpha and IL-8. In contrast, blockade of IL-1alpha or IL-8 inhibited HUVEC proliferation and angiogenesis. CONCLUSIONS: The inflammatory cytokines IL-1alpha and IL-8 may have an important role in metastasis via vascular endothelial cell proliferation and angiogenesis.

Cell Division↗

Glial cell line-derived neurotrophic factor enhances nuclear factor-kappaB activity and invasive potential in human pancreatic cancer cells.

OBJECTIVES: The invasive potential is increased by glial cell line-derived neurotrophic factor (GDNF) in human pancreatic cancer cell lines. We researched whether the signaling pathway activated by GDNF correlates with the nuclear factor-kappaB (NF-kappaB) in human pancreatic cancer cell lines and whether the inhibition of NF-kappaB activity is associated with suppression of invasive potential. METHODS: Proliferation of human pancreatic cancer cell lines (BxPC-3 and MIA PaCa-2) was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays (MTT assay). NF-kappaB activity was examined by dual luciferase assay and electrophoretic mobility shift assay. In addition, to investigate the invasive potential, an in vitro invasion assay was performed. RESULTS: Proliferation of both cell lines was decreased by a proteasome inhibitor, MG132, in a dose-dependent manner, but proliferation of control and IkappaBalphaM vector-transfected BxPC-3 cells was similar. The invasion cell number and the NF-kappaB activity were increased by GDNF stimulation. However, in the presence of MG132 or IkappaBalphaM, which blocks the nuclear localization of NF-kappaB, both were significantly suppressed. Furthermore, reduced activity of both remained unchanged by GDNF stimulation. CONCLUSION: These results indicate that GDNF promotes NF-kappaB activation and that the latter is involved in the invasive potential of human pancreatic cancer cells.

Cell Division↗

Expression of integrins in tumour tissue of a patient with cancer of the Vater's ampulla complicated by pancreas divisum.

We present herein a rare case where cancer of the Vater's ampulla was complicated with pancreas divisum. Endoscopic retrograde cholangiopancreatography demonstrated the pancreas divisum and stenosis of the common channel due to the tumorous lesion of the Vater's ampulla. Magnetic resonance cholangiopancreatography demonstrated that the Wirsung duct and Santorini duct were unconnected. The biopsy specimen at the upper gastrointestinal endoscopy revealed moderately differentiated tubular adenocarcinoma. The patient was diagnosed with cancer of the Vater's ampulla complicated with pancreas divisum, and underwent a pylorus-preserving pancreaticoduodenectomy. Immunohistochemical examination showed that the p53 protein and the alpha5beta1-integrin were expressed in tumour cells, and the proliferating cell nuclear antigen test was positive. Furthermore, the alpha5beta1-integrin was expressed in chronic pancreatitis tissue. We demonstrate that there is a risk that pancreas divisum will co-exist with malignant disease in the pancreaticobiliary area, causing a potential risk of complicating malignant diseases in the pancreas.

Adenocarcinoma↗

[The QOL of the patient with advanced pancreatic carcinoma was changed for the better with combination therapy consisting of arterial chemotherapy and injection of interferon].

The prognosis of advanced pancreatic carcinoma with multiple liver metastases is extremely poor. The current methods of treating pancreatic carcinoma are far from satisfactory. The results of systemic and regional chemotherapies for pancreatic carcinoma are disappointing. The patient was a 68-year-old male with advanced pancreatic carcinoma. After an operation, he received a combination therapy consisting of arterial infusion (gemcitabine hydrochloride, GEM, 600 mg) and muscle injection of interferon (IFN, 300x10(4) U). A decrease in metastatic tumor of the liver was observed. In this report, we describe the case of a patient whose effective results were achieved by using a new combination of GEM and IFN.

Aged↗

Synthesis and structure-activity relationships of 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids as HB-EGF shedding inhibitors.

HB-EGF Shedding inhibitors have been expected to become effective medicines for skin diseases caused by the proliferation of keratinocytes. In order to discover novel HB-EGF shedding inhibitors and clarify their structure-activity relationships, 5,6,7,8-tetrahydronaphthylidine-based hydroxamic acid and 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids have been synthesized. Among the synthesized compounds, the ethoxyethoxy derivative 3o and the methoxypropoxy derivative 3p exhibited much more potent HB-EGF shedding inhibitory activity than CGS 27023A. The structural modification of 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids enabled us to establish the following structure-activity relationships; the existence of the hydroxamic acid, the sulfonamide, and the phenyl moieties are crucial for a potent HB-EGF shedding inhibitory activity, and the stereochemistry of the alpha carbon of hydroxamic acid is also important. In addition, from the comparison of their HB-EGF shedding inhibitory activities with their MMPs inhibitory activities, we found that the S1' pocket of the responsible enzyme for HB-EGF shedding is deep unlike that of MMP-1.

Epidermal Growth Factor↗

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↗

Keyhole procedure: a new technique for intestinal anastomosis with a large opening and less tissue trauma, using both circular and linear staplers.

BACKGROUND: We designed a new technique, termed the keyhole procedure, that uses a linear stapler to enlarge the anastomotic opening made with a circular stapler. The present study was performed to evaluate this technique in terms of maximum bursting pressure and area of anastomotic opening and compare it with conventional anastomosis using a circular stapler in an animal model. METHODS: Anastomoses were created by the new technique or by the conventional method in swine small intestine. Anastomosis integrity was assessed by the air leakage test. Anastomotic openings were photographed and measured with an image analyzer. RESULTS: It was found that the area of the anastomotic opening obtained with the new technique was more than 3 times that of the control (P <.001). There was no significant difference between the methods in maximum bursting pressure. CONCLUSIONS: The keyhole procedure provides a larger anastomotic opening than conventional anastomosis with a circular stapler, without impairing the integrity of anastomosis.

Anastomosis, Surgical↗

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↗

New type of metalloproteinase inhibitor: design and synthesis of new phosphonamide-based hydroxamic acids.

A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K(i) values against MMP-1, -3, -9, and TACE and also showed nanomolar IC(50) values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.

Amides↗