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Masanori Asada

Publications and source records attributed to Masanori Asada.

At least 19 recordsLinked to original sources
PubMed2006

Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

PURPOSE: Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. EXPERIMENTAL DESIGN: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. RESULTS: The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. CONCLUSIONS: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Acute cerebral infarction during combination chemotherapy with s-1 and cisplatin for a young patient with a mucin-producing adenocarcinoma of the stomach.

We report a 29-year-old woman with gastric cancer who developed Trousseau's syndrome, a malignancy-related thromboembolism, during chemotherapy. She was diagnosed with a mucin-producing adenocarcinoma of the stomach, and chemotherapy with S-1 and cisplatin was commenced. During treatment, she developed a sudden onset of right hemiplegia. Magnetic resonance imaging showed an acute cerebral infarction of the left cerebral hemisphere. The underlying pathophysiology is thought to be chronic disseminated intravascular coagulation due to mucin-producing adenocarcinomas. However, cisplatin-induced vascular toxicity and hypercoagulability caused by decreased plasma protein C activity, elevated plasma von-Willebrand factor levels, and hypomagnesemia has also been proposed to be associated with thrombogenicity.

Acute Disease↗
PubMed2006

Human thioredoxin-1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production.

BACKGROUND & AIMS: Thioredoxin-1 (TRX) is a small multifunctional protein with antioxidative and redox-regulating functions. In this study, we investigated the significance of TRX in patients with inflammatory bowel disease (IBD) and the ability and mechanism to ameliorate experimental colitis. METHODS: Serum TRX and macrophage migration inhibitory factor (MIF) levels were measured in patients with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)-induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and control mice. We further evaluated the effect of recombinant human TRX (rhTRX) administration on DSS-induced colitis and colonic inflammation of interleukin (IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically and histologically. Proinflammatory cytokine levels were examined in colonic tissues, and MIF levels were measured in colonic tissues and sera in mice. The effect of TRX on MIF production was also analyzed in vitro. RESULTS: Serum TRX and MIF levels were significantly higher in patients with IBD than normal controls, and TRX levels correlated with disease activity. TRX significantly ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice. Increase of tumor necrosis factor-alpha and interferon-gamma in colonic tissues was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF levels in colonic tissues and sera were significantly lower in TRX-TG mice than in wild-type mice, irrespective of DSS administration. Anti-TRX treatment exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX suppressed MIF production in human monocyte cells. CONCLUSIONS: TRX might have a potential as a novel therapeutic agent for the treatment of IBD.

Animals↗
PubMed2006

Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non-small-cell lung cancer.

PURPOSE: To investigate the efficacy and safety of nitroglycerin plus vinorelbine and cisplatin in patients with previously untreated stage IIIB/IV non-small-cell lung cancer (NSCLC) as the experimental arm for the next phase III trial. PATIENTS AND METHODS: One hundred twenty patients with stage IIIB/IV NSCLC were randomly assigned to vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1, with transdermally applied nitroglycerin (25 mg/patient daily for 5 days; arm A) or with placebo patch (arm B) every 3 weeks for a maximum of four cycles in a double-blind and controlled trial. Primary efficacy end points were the best confirmed response rate and time to disease progression (TTP). RESULTS: The response rate in arm A (72%; 43 of 60 patients) was significantly higher than that for patients in arm B (42%; 25 of 60 patients; P < .001). Median TTP in arm A was longer than that in arm B (327 v 185 days). No severe adverse effect was recognized for either arm. The rate of grade 1 to 2 headache in arm A (30%; 18 of 60 patients) was significantly higher than that in arm B (2%; one of 60 patients; P < .001, chi(2) test). CONCLUSION: Use of nitroglycerin combined with vinorelbine and cisplatin may improve overall response and TTP in patients with stage IIIB/IV NSCLC. The arm A regimen is being evaluated in a large phase III trial.

Adult↗
PubMed2006

Specific antibodies against recombinant protein of insertion element 900 of Mycobacterium avium subspecies paratuberculosis in Japanese patients with Crohn's disease.

BACKGROUND: Mycobacterial avium subspecies paratuberculosis (MAP) infection has been hypothesized as an etiological factor of Crohn's disease (CD). However, the involvement of MAP in the pathophysiology of CD is controversial. The aim of this study is to investigate whether MAP is involved in the pathogenesis of CD with the glutathione S-transferase fusion recombinant protein encoding a portion of insertion element (IS) 900 (IS900-GST), which is specific for MAP. METHODS: Serum samples from the patients with CD (n = 50), ulcerative colitis (n = 40), colonic tuberculosis (n = 20), and non-IBD controls (n = 44), were applied for solid-phase enzyme-linked immunosorbent assay (ELISA) to detect antibodies against MAP and Saccharomyces cerevisiae. IS900-GST, which was made by the pGST-4T-2 vector inserted with polymerase chain reaction-amplified IS900DNA, was used as an antigen of MAP. Moreover, we studied the relationship between antibodies against IS900-GST and clinical characteristics. RESULTS: ELISA showed that the serum level of immunoglobulin G and immunoglobulin A antibodies against IS900-GST (anti-IS900) in patients with CD were significantly higher than those with ulcerative colitis, colonic tuberculosis, and control subjects. The levels of anti-IS900 tended to be higher in CD patients with small intestinal involvement than with colonic involvement alone. Anti-IS900 in patients with penetrating- and stricture-type CD was significantly higher than with inflammatory-type CD. Furthermore, a negative correlation was found between the titer of anti-IS900 and disease duration. Anti-IS900 was not associated with surgical treatment nor was it associated with the use of immunosuppressants. No significant correlation was observed between the serum levels of anti-IS900 and anti-S cerevisiae antibody. CONCLUSIONS: This is the first demonstration of the ELISA system of detecting antibodies against IS900 in IBD patients. MAP could be involved in the pathophysiology of Japanese patients with CD.

Adult↗
PubMed2006

Clinical significance of serum thioredoxin 1 levels in patients with acute pancreatitis.

OBJECTIVE: Thioredoxin 1 (TRX-1), a redox-regulating protein with antioxidant activity, is induced by oxidative stress, and serum TRX-1 levels are recognized as an oxidative-stress marker. The aim of this study was to clarify the clinical significance of serum TRX-1 levels in patients with acute pancreatitis (AP) and evaluate the usefulness of this measurement in assessing disease severity. METHODS: Serum TRX-1 levels were determined on admission in 18 patients with severe AP and 36 patients with mild AP. We also investigated the relationship between serum TRX-1 levels and clinical and laboratory data. RESULTS: The median serum TRX-1 levels on admission were 54.9 ng/mL in mild AP and 118.8 ng/mL in severe AP. When the cutoff value for TRX-1 in predicting severe AP was determined to be 100 ng/mL, its sensitivity, specificity, and accuracy were 83.3%, 94.4%, and 90.7%, respectively. A significant correlation was observed between serum TRX-1 levels and Ranson score (r = 0.674), C-reactive protein (r = 0.718), interleukin 6 (r = 0.712), leukocyte count (r = 0.642), and serum amylase (r = 0.436). CONCLUSIONS: Serum TRX-1 levels significantly correlate with AP severity. TRX-1 should constitute a reliable oxidative-stress marker for the evaluation of AP severity in relation to oxidative stress.

Acute Disease↗
PubMed2006

Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis.

OBJECTIVES: Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients. METHODS: We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies. RESULTS: We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies. CONCLUSIONS: These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.

Aged↗
PubMed2006

Effects of menthol on the triggering of the swallowing reflex in elderly patients with dysphagia.

AIMS: To investigate the effect of menthol on swallowing reflex sensitivity in elderly patients with dysphagia. METHODS AND RESULTS: The swallowing reflex sensitivity of institutionalized elderly patients was evaluated as a latent time of swallowing reflex (LTSR), induced by the injection of 1 ml solution into the pharynx. LTSR was significantly shortened in a concentration-dependent manner, from 13.8 s [95% confidence interval (CI) 11.1, 16.5] by distilled water to 9.4 s (95% CI 7.1. 11.8) by 10(-2)m menthol. CONCLUSION: Using menthol with elderly patients with dysphagia may improve the sensitivity of their swallowing reflex, resulting in prevention of aspiration pneumonia.

Aged, 80 and over↗
PubMed2005

Granulocyte colony-stimulating factor promotes tumor angiogenesis via increasing circulating endothelial progenitor cells and Gr1+CD11b+ cells in cancer animal models.

Recombinant granulocyte colony-stimulating factor (G-CSF) is used for cancer patients with myelosuppression induced by chemotherapy. G-CSF has been reported to progress tumor growth and angiogenesis, but the precise mechanism of tumor angiogenesis activated by G-CSF has not been fully clarified. N-terminal-mutated recombinant human G-CSF administration increased WBCs and neutrophils in peripheral blood and reduced bone marrow stromal cell-derived factor-1 in mice, indicating its biological relevance. Mice were inoculated with Lewis lung carcinoma cells (LLCs) or KLN205 cells and treated with G-CSF. G-CSF accelerated tumor growth and intratumoral vessel density, while it did not accelerate proliferation of LLCs, KLN205 cells or human umbilical vein endothelial cells in vitro. In the absence of tumors, G-CSF did not increase circulating cells that displayed phenotypic characteristics of endothelial progenitor cells (EPCs). In the presence of tumors, G-CSF increased circulating EPCs. In addition, G-CSF treatment increased immune suppressor and endothelial cell-differentiating Gr1+CD11b+ cells in tumor-bearing mice. We conclude that G-CSF promotes tumor growth by activating tumor angiogenesis via increasing circulating EPCs and Gr1+CD11b+ cells in cancer animal models.

Animals↗
PubMed2005

Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis.

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of kappaB-alpha, thereby suppressing proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.

Acute Disease↗
PubMed2005

Macrophage colony-stimulating factor induces vascular endothelial growth factor production in skeletal muscle and promotes tumor angiogenesis.

Although M-CSF has been used for myelosuppression due to chemotherapy in patients with solid tumors, the effect of exogenous M-CSF on tumor angiogenesis has not been studied. In this study we showed that M-CSF has the ability to accelerate solid tumor growth by enhancing angiogenesis with a novel mechanism. M-CSF accelerated intratumoral vessel density in tumors inoculated into mice, although it did not accelerate the proliferation of malignant cells and cultured endothelial cells in vitro. In both the absence and the presence of tumors, M-CSF significantly increased the circulating cells that displayed phenotypic characteristics of endothelial progenitor cells in mice. Moreover, M-CSF treatment induced the systemic elevation of vascular endothelial growth factor (VEGF). VEGFR-2 kinase inhibitor significantly impaired the effect of M-CSF on tumor growth. In vivo, M-CSF increased VEGF mRNA expression in skeletal muscles. Even after treatment with carageenan and anti-CD11b mAb in mice, M-CSF increased VEGF production in skeletal muscles, suggesting that systemic VEGF elevation was attributed to skeletal muscle VEGF production. In vitro, M-CSF increased VEGF production and activated the Akt signaling pathway in C2C12 myotubes. These results suggest that M-CSF promotes tumor growth by increasing endothelial progenitor cells and activating angiogenesis, and the effects of M-CSF are largely based on the induction of systemic VEGF from skeletal muscles.

Animals↗
PubMed2005

A case of autoimmune pancreatitis associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome.

We report a very rare case of autoimmune pancreatitis (AIP) associated with sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome. The patient had an enlarged pancreas, and autoantibodies were detected in the serum. Serum IgG and IgG4 concentrations were also elevated. Endoscopic retrograde cholangiopancreatography revealed an irregular narrowing of the main pancreatic duct from the head to the body and sclerotic change in the intrapancreatic common bile duct, which later extended to the intrahepatic bile ducts. In addition, histological examination of the liver revealed lymphocytic sclerosis around the bile ducts, similar to the histology in the pancreas of AIP. Retroperitoneal tumors were diagnosed as retroperitoneal fibrosis by histological examination. Serological and functional abnormalities suggestive of Sjögren's syndrome were detected, and histological findings of the lip were compatible with Sjögren's syndrome. Immunohistochemistry of each lesion disclosed that most of the infiltrating lymphocytes were T cells with similar levels of both CD4+ and CD8+ cells. Moreover, some of the infiltrating plasma cells were positive for anti-IgG4 monoclonal antibody. These diseases were dramatically improved by steroid therapy. Although the pathophysiology of AIP is still unclear, the present case suggests a common pathophysiological mechanism for AIP, sclerosing cholangitis, retroperitoneal fibrosis and Sjögren's syndrome.

Aged↗