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Hirokuni Taguchi

Publications and source records attributed to Hirokuni Taguchi.

98 records · Page 6Linked to original sources

Prediction of sensitivity to STI571 among chronic myeloid leukemia patients by genome-wide cDNA microarray analysis.

One of the most critical issues to be solved in regard to cancer chemotherapy is the establishment of ways to predict the efficacy of anti-cancer drugs for individual patients. To develop a prediction system based on expression of specific genes, we analyzed expression profiles of mononuclear cells from 18 chronic myeloid leukemia (CML) patients who were treated with the tyrosine kinase inhibitor STI571. cDNA microarrays representing 23 040 genes identified 79 genes that were expressed differentially between responders and non-responders to STI571. On the basis of the expression patterns of 15 or 30 of these genes among the patients, we developed a "Prediction Score" system that could clearly separate the responder group from the non-responder group. Verification of this system using four additional ("test") cases succeeded in predicting the response of each of those four patients to the drug. These results provide the first evidence that gene-expression profiles can predict sensitivity of CML cells to STI571, and may eventually lead to the achievement of "personalized therapy" for this disease.

Adult↗

Inflammatory abdominal aortic aneurysm followed by disseminated intravascular coagulation and immune thrombocytopenia.

A 71-year-old man was diagnosed as having an abdominal aortic aneurysm when he was treated for idiopathic interstitial pneumonia (IIP). Three years later, he developed severe thrombocytopenia and had disseminated intravascular coagulation (DIC) that was associated with the inflammatory abdominal aortic aneurysm (IAAA). The coagulation abnormalities were corrected by low-molecular weight heparin, however the platelet count remained low. Bone marrow showed normocellularity with an increase of immature and mature forms of megakaryocytes. Platelet-associated IgG level was high. These findings suggested that the patient had severe thrombocytopenia caused by unusual complications of immune thrombocytopenic purpura and IAAA-associated DIC.

Aged↗

[beta 2-adrenoceptor polymorphism and effect of inhaled beta 2-stimulant (procaterol) on airway resistance measured by body plethysmography in healthy volunteers].

This study was designed to evaluate, in healthy volunteers, differences of bronchodilator responsiveness to a beta 2-agonist between those with the Arg 16/Gly 16 allele and those with the Gly 16/Gly 16 allele at codon 16 of beta 2 adrenoceptor polymorphism. Peak flow and pulmonary functions were measured by body plethysmography after the inhalation of procaterol. In the Arg 16/Gly 16 group, the resulting acute increase of V 25 and acute decrease of airway resistance were greater, and the bronchodilator effect of a single inhaled beta 2-agonist was longer, than those observed in the Gly 16/Gly 16 group. The present study showed that a single inhalation of procaterol has a varying bronchodilator effect on healthy adults, depending on the genotype of beta 2 adrenoceptor polymorphism at codon 16.

Administration, Inhalation↗

Prediction of chemosensitivity for patients with acute myeloid leukemia, according to expression levels of 28 genes selected by genome-wide complementary DNA microarray analysis.

To identify genes involved in the sensitivity of acute myeloid leukemia (AML) cells to chemotherapy, we monitored gene-expression profiles of cancer cells from 76 AML patients using a cDNA microarray consisting of 23,040 genes. We identified 63 genes that were commonly overexpressed and 372 genes suppressed in AML. Because these genes represent key molecules for disclosing the molecular mechanisms of AML, they may be potential targets for drug development. We also found 28 that revealed different expression levels between good and poor responders to chemotherapy and appeared to be associated with chemosensitivity. On that basis, we developed a "Drug Response Scoring" system that was correlated well with individual sensitivity to an anticancer drug regimen. Among the 44 cases with positive drug-response scores by our definition, 40 achieved complete remission after treatment, whereas the only 3 of the 20 cases with negative scores responded well to the treatment. An ability to predict chemosensitivity should eventually lead to achievement of our goal of "personalized therapy."

Adult↗

[Malignant lymphoma of the lung aassociated with Evans' syndrome: report of a case].

A 77 year-old woman who had been treated for Evans' syndrome was admitted to our hospital because of the development of bilaterally-enlarging abnormal lung shadows. She had been diagnosed as having Evans' syndrome since she was 64 years old, and had been treated with corticosteroids. She had also been found positive for hepatitis C virus, and was suffering from chronic hepatitis. The pathological examination of a transbronchial biopsy specimen revealed B-cell malignant lymphoma of the diffuse large-cell type. A computed tomography (CT) scan showed lung tumors, hilar lymph node swelling, but no other definite tumors. Gallium scintigraphy showed positive accumulation only in the lungs, and so a diagnosis of primary pulmonary lymphoma was made. She received several courses of standard CHOP therapy and achieved a partial remission. She died 8 months later, however, of bleeding from esophageal varices associated with liver cirrhosis. To our knowledge, primary pulmonary lymphoma associated with Evans' syndrome is extremely rare. Although the underlying mechanism remains to be clarified, it is likely that immunological disorders complicating Evans' syndrome lead to the development of malignant lymphoma in some cases.

Aged↗

Combined effects of resveratrol and paclitaxel on lung cancer cells.

Resveratrol (3,4',5-trihydroxystilbene) is a phytoalexin found in grapes and other food products that can prevent cancer. We studied the in vitro biological activity of this compound by examining its effect on proliferation and inducing apoptosis in three lung cancer cell lines (A549, EBC-1, Lu65). Resveratrol inhibited the growth of A549, EBC-1 and Lu65 lung cancer cells by 50% (ED50) at concentrations between 5-10 microM. We also examined the combined effects in these cells of resveratrol and paclitaxel, an essential chemotherapeutic agent against lung cancer. Although simultaneous exposure to resveratrol plus paclitaxel did not result in significant synergy, resveratrol (10 microM, 3 days) significantly enhanced the subsequent antiproliferative effect of paclitaxel. In addition, resveratrol as well as paclitaxel induced apoptosis in EBC-1 and Lu65 cells, as measured by TUNEL and caspase assays, as well as flow cytometry. Resveratrol (10 microM, 3 days) similarly enhanced the subsequent apoptotic effects of paclitaxel. We examined the effects of resveratrol and paclitaxel on levels of p21waf1, p27kip1, E-cadherin, EGFR and Bcl-2 in EBC-1 cells. Resveratrol (10 microM, 3 days) prior to paclitaxel induced p21waf1 expression approximately 4-fold. These results suggest that resveratrol may be a promising alternative therapy for lung cancer and that lung cancer cells exposed to resveratrol have a lowered threshold for killing by paclitaxel.

Antineoplastic Combined Chemotherapy Protocols↗

Do Japanese take more folate from traditional Japanese dish than is conventionally estimated?-Actual folate contents in hospital diets and marketed lunch boxes.

Folic acid deficiency is very rare in Japan. However, recent concerns in relation to causal relationships between cancer and low folic acid levels necessitate information on actual folate intake by Japanese, which has hitherto not been well studied. We therefore evaluated folate contents of a hospital diet for 7 consecutive days and of 16 lunch boxes purchased at convenience stores. Dietary intake was assessed for weighed food items after cooking using our previously published data on folate contents of various foods and also by using Standard Tables of Food Composition in Japan (STFCJ). Mean daily folate intake from the hospital diet was 723.9 microg/day using our data but only 359.2 microg/day if calculated using the STFCJ. Twenty-nine % of the total daily folate intake was through rice. Mean folate intake through lunch boxes was 491.7 microg/day by our tabulation and 139.5 microg/day with the STFCJ. Folic acid intake of Japanese is far above the levels taken in other countries and over half of this amount is taken from rice. Levels of folic acid contents (especially in rice) listed in the STFCJ are too low and revision is strongly suggested.

Diet↗

Diffuse micronodular pulmonary metastasis of lung adenocarcinoma predicts gefitinib response in association with epidermal growth factor receptor mutations.

Female, non-smoker, Asian ethnicity and adenocarcinoma histology are the major clinical predictors of gefitinib response in non-small cell lung cancer, as shown in previous studies. Recently, response to gefitinib has been associated with epidermal growth factor receptor (EGFR) mutations. Higher rates of mutation were seen in females, patients with adenocarcinomas, the Asian population and never-smokers, which may explain the clinical response predictors. The presence of diffuse micronodular pulmonary metastasis on chest imaging as a novel clinical predictor of its response is proposed here. Two cases of lung adenocarcinomas in men presenting with diffuse micronodular pulmonary metastasis were encountered. Both patients showed a major response to gefitinib. The dramatic reduction of micronodular pulmonary nodules throughout both lungs on computed tomography scans was achieved after treatment for a couple of months with 250 mg of oral gefitinib. In the molecular analysis, one patient had a heterozygous delL746-A750 mutation and the other had a heterozygous L858R EGFR mutation. In conclusion, patients with lung adenocarcinoma, even men, who presented with bilateral diffuse micronodular metastatic spread to the lungs tended to have an activated EGFR mutation. Therefore, they are most likely to receive benefits from molecular target drugs such as gefitinib and possibly erlotinib.

Adenocarcinoma↗