Tatsuhiko Kashii

Kinki University, Ōsaka-shi, Osaka-fu, Japan

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Publications (19)67.82 Total impact

  • Article: Miliary brain metastasis presenting with calcification in a patient with lung cancer: a case report.
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    ABSTRACT: Miliary brain metastasis is an extremely rare form of brain metastasis which can present with atypical imaging findings. We report the case of a patient with miliary brain metastasis of lung cancer showing calcification in metastatic lesions. A 68-year-old Japanese woman was diagnosed with lung adenocarcinoma. Brain computed tomography revealed multiple small calcified lesions in both cerebral hemispheres. Mutation of the epidermal growth factor receptor gene (exon 21, L858R) in lung cancer cells was detected, and treatment with gefitinib was initiated. A partial response was observed; however, the patient was readmitted to our hospital because of regrowth of the primary lesion and complaints of nausea, headache, and difficulty walking. Brain magnetic resonance imaging revealed scattered tiny nodules enhanced by gadolinium. A diagnosis of leptomeningeal carcinomatosis was made on the basis of cerebrospinal fluid cytology. The patient's general status worsened, and she died 356 days after the day of first medical examination. Upon autopsy, the brain was found to be edematous and swollen. Lung carcinoma cells were diffusely disseminated on the meningeal surface. Metastatic foci of small nodular form, accompanied by calcifications, were also found in the brain parenchyma. We diagnosed miliary metastasis of lung carcinoma. To the best of our knowledge, this is the third report of calcified miliary brain metastasis confirmed by autopsy. We describe calcified lesions that increased in size during the clinical course of nine months. Brain computed tomography findings that reveal multiple small calcified lesions in patients with malignancy should raise suspicion of miliary brain metastasis.
    Journal of Medical Case Reports 09/2012; 6(1):279.
  • Article: [Synchronous pulmonary hamartoma and lung cancer in a young patient].
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    ABSTRACT: A 23-year-old man was admitted for examination of an abnormal shadow in the right lower lung field. A chest CT scan revealed a nodule in the right lower lobe and a calcified nodule in the right upper lobe. A diagnosis of lung adenocarcinoma in the right lower lobe was made by transbronchial cytology. After resection of the right lower lobe and partial resection of the nodule in the right upper lobe were performed, we diagnosed lung adenocarcinoma in the right lower lobe (pathological stage IIIA) and hamartoma in the right upper lobe. Although several authors have reported cases of synchronous pulmonary hamartoma and lung cancer, it is uncommon in young patients. Since patients with hamartoma could also have lung carcinoma, careful observation is needed.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 05/2011; 49(5):349-54.
  • Article: Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a west Japan thoracic oncology group trial (WJTOG0203).
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    ABSTRACT: PURPOSE Gefitinib is a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase. We conducted a phase III trial to evaluate whether gefitinib improves survival as sequential therapy after platinum-doublet chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Chemotherapy-naïve patients with advanced stage (IIIB/IV) NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate organ function were randomly assigned to either platinum-doublet chemotherapy up to six cycles (arm A) or platinum-doublet chemotherapy for three cycles followed by gefitinib 250 mg orally once daily, until disease progression (arm B). Patients were stratified by disease stage, sex, histology, and chemotherapy regimens. The primary end point was overall survival; secondary end points included progression-free survival, tumor response, safety, and quality of life. Results Between March 2003 and May 2005, 604 patients were randomly assigned. There was a statistically significant improvement in progression-free survival in arm B (hazard ratio [HR], 0.68; 95% CI, 0.57 to 0.80; P < .001); however, overall survival results did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.03; P = .11). In an exploratory subset analysis of overall survival by histologic group, patients in arm B with adenocarcinoma did significantly better than patients in arm A with adenocarcinoma (n = 467; HR, 0.79; 95% CI, 0.65 to 0.98; P = .03). CONCLUSION This trial failed to meet the primary end point of OS in patients with NSCLC. The exploratory subset analyses demonstrate a possible survival prolongation for sequential therapy of gefitinib, especially for patients with adenocarcinoma.
    Journal of Clinical Oncology 02/2010; 28(5):753-60. · 18.37 Impact Factor
  • Article: [Two cases of pulmonary sarcomatoid carcinoma mimicking malignant mesothelioma].
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    ABSTRACT: We report 2 cases of pulmonary sarcomatoid carcinoma mimicking malignant mesothelioma. Case 1: A 69 year-old man presented, complaining of right chest pain. The chest X ray film and CT showed tumors in the right chest wall and pleura. Histological findings of specimens obtained from a percutaneous biopsy revealed spindle tumor cells, and the immunohistochemistry showed that the tumor cells were positive for CK-7, AE1/AE3, and vimentin and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel, but it was ineffective. Case 2: A 68 year-old man was admitted complaining of general malaise. The chest X ray film and CT revealed tumors in the right chest wall. Histological findings showed necrosis and spindle tumor cells which were positive for AE1/AE3 and vimentin, and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel. However the disease continued to progress and he died 2 months after admission. The pulmonary sarcomatoid carcinoma was reported to have spred to the pleural and chest wall. The present two cases showed prominent chest wall and pleural tumors with obscure primary lung tumors. Therefore, we needed to differentiate sarcomatoid carcinoma from malignant pleural mesothelioma.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 01/2010; 48(1):33-8.
  • Article: Phase I/II study of S-1 plus carboplatin in patients with advanced non-small cell lung cancer.
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    ABSTRACT: The objective of this phase I/II study was to determine the recommended dose (RD) of S-1 and carboplatin (CBDCA), and to evaluate the efficacy and safety of this combination in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients were treated with S-1 given orally on days 1-14, and CBDCA infused intravenously on day 1, repeated every 3 weeks. RD was AUC5 of CBDCA and 80 mg/m(2) of S-1. Nineteen patients were treated at the RD. The overall response was 30.8% (95% confidence interval: 17.1-58.3%). The response rate in the RD was 36.8% (95% CI: 16.3-61.6%). The median overall survival time was 11.1 months (95% CI: 8.1-15.3 months) and the median progression-free survival time was 5.0 months (95% CI: 3.6-6.0 months). Major grades 3-4 toxicities were thrombocytopaenia (47%), anaemia (26%) and infection (16%). This is the first report to show promising activity of this combination in phase II, including survival data and manageable toxicity, especially in outpatients receiving treatment for advanced NSCLC.
    European journal of cancer (Oxford, England: 1990) 05/2009; 45(12):2132-7. · 4.12 Impact Factor
  • Article: A phase I study of topotecan plus carboplatin for relapsed SCLC: WJTOG trial.
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    ABSTRACT: A phase I study on relapsed small cell lung cancer (SCLC) was conducted to establish the toxicity and maximum tolerated dose of carboplatin with topotecan, and to observe the antitumor activity. Thirty-two SCLC patients who had received one previous line of chemotherapy were enrolled. Topotecan was infused for 30 minutes on days 1 to 5, and carboplatin for 60 minutes after the topotecan infusion on day 5 every 3 weeks. Granulocyte colony-stimulating factor prophylaxis was administered from day 8 to white blood cell or neutrophil recovery. The most frequent toxicities were neutropenia and thrombocytopenia. Nonhematological toxicities were generally mild. Three of six patients experienced a dose-limiting toxicity, thrombocytopenia, at dose level 6: 0.85 mg/m topotecan with area under curve 5 carboplatin (maximum tolerated dose). Of 29 evaluable patients, 5 (17.2%) had partial responses. Of 21 patients who relapsed more than 90 days after completion of first-line chemotherapy, 5 (23.8%) had partial responses. Median overall survival time and 1-year survival rate were 11.3 months and 50.0%, respectively. The recommended dose for further studies is 0.75 mg/m of topotecan on days 1 to 5 with area under curve 5 of carboplatin on day 5 every 3 weeks. This combination is well tolerated, and is promising for sensitive relapsed SCLC. A comparative study against single-agent topotecan for sensitive relapsed SCLC is warranted.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2009; 4(5):644-8. · 4.55 Impact Factor
  • Article: [A case of sarcoidosis who showed rapid swelling of mediastinal and abdominal lymph nodes].
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    ABSTRACT: A 49-year-old woman noticed hoarseness and facial palsey three months prior to her visit to our hospital. Chest radiograph and CT scanning revealed bilateral mediastinal and hilar lymphadenopathy. Bronchofiberoptic biopsy showed sarcoidosis. Her symptoms improved under no treatment. However, she showed rapid increase of mediastinal and abdominal lymph nodes swelling and elevation of serum level of sIL-2R during observation. Therefore, we must discriminate sarcoidosis-lymphoma syndrome from exacerbation of sarcoidosis. Mediastinoscopic biopsy was conducted for diagnosis, and it revealed exacerbation of sarcoidosis. We reported this rare case of rapid increase of mediastinal and abdominal lymph node swelling due to sarcoidosis.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 02/2007; 45(1):54-8.
  • Article: [A case of intravascular lymphomatosis with no abnormal findings on chest computed tomography and with diffuse pulmonary uptake of 67Ga on scintigraphy].
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    ABSTRACT: A 45-year-old man was admitted to our hospital with high-grade fever uncontrolled by antipyretic drugs, and elevation of the serum LDH and sIL-2R levels, and decrease of diffusing capacity for carbon monoxide. Chest computed tomography (CT) showed no abnormal findings but 67Ga scintigraphy revealed diffuse pulmonary uptake. He was given a diagnosis of intravascular lymphomatosis (IVL) based on transbronchial lung biopsy (TBLB) and immunohistochemical analysis. The prognosis of IVL is generally bad, because antemortem diagnosis is difficult. In this case early TBLB enabled satisfactory curative effect of IVL.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 01/2007; 44(12):923-7.
  • Article: Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) 0104.
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    ABSTRACT: Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity. One hundred twenty-eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks. Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The median progression-free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057). Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study.
    Cancer 09/2006; 107(3):599-605. · 4.77 Impact Factor
  • Article: Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer
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    ABSTRACT: BACKGROUND.Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity.METHODS.One hundred twenty-eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks.RESULTS.Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The median progression-free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057).CONCLUSIONS.Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study. Cancer 2006. © 2006 American Cancer Society.
    Cancer 06/2006; 107(3):599 - 605. · 4.77 Impact Factor
  • Article: EGFR mutation of tumor and serum in gefitinib-treated patients with chemotherapy-naive non-small cell lung cancer.
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    ABSTRACT: The authors evaluate the efficacy and safety of gefitinib monotherapy in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). A secondary endpoint is to evaluate the relationship between clinical manifestations and epidermal growth factor receptor (EGFR) mutation status. Japanese chemotherapy-naive NSCLC patients were enrolled. They had measurable lesions, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ and bone marrow function. Patients received 250 mg of oral gefitinib daily. EGFR mutations in exon 18, 19, and 21 of DNA extracted from tumor and serum were analyzed by genomic polymerase chain reaction and direct sequence. All 30 patients were eligible for the assessment of efficacy and safety. An objective response and stable disease were observed in 10 patients (33.3%) and nine patients (30.0%), respectively. The median time to progression was 3.3 months and the median overall survival was 10.6 months. The 1-year survival rate was 43.3%. Grade 3 toxicities were observed in seven patients. EGFR mutation was observed in four of 13 (30.8%) tumors, and two of them achieved partial response. In serum samples, three of 10 patients with EGFR mutations in the serum before treatment had a response to gefitinib. EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment samples from patients with a partial response or stable disease than in those from patients with progressive disease (p = 0.006). Gefitinib monotherapy in chemotherapy-naive NSCLC patients was active, with acceptable toxicities. These results warrant further evaluation of gefitinib monotherapy as a first-line therapy. The EGFR mutation in serum DNA may be a biomarker for monitoring the response to gefitinib during treatment.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2006; 1(3):260-7. · 4.55 Impact Factor
  • Article: EGFR Mutation of Tumor and Serum in Gefitinib-Treated Patients with Chemotherapy-Naive Non-small Cell Lung Cancer
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    ABSTRACT: Background: The authors evaluate the efficacy and safety of gefitinib monotherapy in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). A secondary endpoint is to evaluate the relationship between clinical manifestations and epidermal growth factor receptor (EGFR) mutation status. Methods: Japanese chemotherapy-naive NSCLC patients were enrolled. They had measurable lesions, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ and bone marrow function. Patients received 250 mg of oral gefitinib daily. EGFR mutations in exon 18, 19, and 21 of DNA extracted from tumor and serum were analyzed by genomic polymerase chain reaction and direct sequence. Results: All 30 patients were eligible for the assessment of efficacy and safety. An objective response and stable disease were observed in 10 patients (33.3%) and nine patients (30.0%), respectively. The median time to progression was 3.3 months and the median overall survival was 10.6 months. The 1-year survival rate was 43.3%. Grade 3 toxicities were observed in seven patients. EGFR mutation was observed in four of 13 (30.8%) tumors, and two of them achieved partial response. In serum samples, three of 10 patients with EGFR mutations in the serum before treatment had a response to gefitinib. EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment samples from patients with a partial response or stable disease than in those from patients with progressive disease (p = 0.006). Conclusions: Gefitinib monotherapy in chemotherapy-naive NSCLC patients was active, with acceptable toxicities. These results warrant further evaluation of gefitinib monotherapy as a first-line therapy. The EGFR mutation in serum DNA may be a biomarker for monitoring the response to gefitinib during treatment.
    Journal of Thoracic Oncology 02/2006; 1(3):260-267. · 3.66 Impact Factor
  • Article: Some biochemical and histochemical properties of human liver serine dehydratase.
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    ABSTRACT: In rat, serine dehydratase (SDH) is abundant in the liver and known to be a gluconeogenic enzyme, while there is little information about the biochemical property of human liver serine dehydratase because of its low content and difficulty in obtaining fresh materials. To circumvent these problems, we purified recombinant enzyme from Escherichia coli, and compared some properties between human and rat liver serine dehydratases. Edman degradation showed that the N-terminal sequence of about 75% of human serine dehydratase starts from MetSTART-Met2-Ser3- and the rest from Ser3-, whereas the N-terminus of rat enzyme begins from the second codon of MetSTART-Ala2-. The heterogeneity of the purified preparation was totally confirmed by mass spectrometry. Accordingly, this observation in part fails to follow the general rule that the first Met is not removed when the side chain of the penultimate amino acid is bulky such as Met, Arg, Lys, etc. There existed the obvious differences in the local structures between the two enzymes as revealed by limited-proteolysis experiments using trypsin and Staphylococcus aureus V8 protease. The most prominent difference was found histochemically: expression of rat liver serine dehydratase is confined to the periportal region in which many enzymes involved in gluconeogenesis and urea cycle are known to coexist, whereas human liver serine dehydratase resides predominantly in the perivenous region. These findings provide an additional support to the previous notion suggested by physiological experiments that contribution of serine dehydratase to gluconeogenesis is negligible or little in human liver.
    The International Journal of Biochemistry & Cell Biology 04/2005; 37(3):574-89. · 4.63 Impact Factor
  • Article: [Marked improvement of Lambert-Eaton myasthenic syndrome resulting from treatment for small cell lung carcinoma].
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    ABSTRACT: A 68-year-old man was admitted to our hospital because of muscle weakness. A complete medical examination led to a diagnosis of small cell lung carcinoma (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS) and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Four courses of chemotherapy (carboplatin + etoposide) and one of radiotherapy with a total dose of 45 Gy to the mediastinum were performed and resulted in a partial response in the SCLC. After the second course of chemotherapy, the serum level of antivoltage-gated Ca2+ channel (VGCC) antibody decreased from 190 pg/ml to 120 pg/ml. Marked improvement of the muscle weakness was recognized only after 3 courses of chemotherapy. The patient, who had had difficulty in standing, recovered enough to be able to climb stairs after 4 courses of chemotherapy. Marked improvement of LEMS was achieved by treatment for small cell lung carcinoma.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 06/2003; 41(5):331-5.
  • Article: Sensitivity of non-small-cell lung cancer cell lines established from patients treated with prolonged infusions of Paclitaxel.
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    ABSTRACT: Regimens with prolonged infusions of taxanes have been developed for patients with cancer to overcome drug resistance. Our objective of the present study was to examine the impact of prolonged exposure on the cytotoxicity of taxanes against non-small-cell lung carcinoma (NSCLC) cell lines and the clinical response and outcome of the patients. Five cell lines (NCI-H2882, -H2887, -H2973, -H3122, -H3255) were derived from previously untreated patients with NSCLC who participated in clinical trials of continuous 96-hour infusions of paclitaxel followed by bolus cisplatin. Two additional cell lines (NCI-H838, -H1299) with previously published data were used as controls. Drug sensitivities were assessed by the MTS (Promega) assay. Multidrug resistance (MDR) phenotypes were assessed by quantitative real-time PCR and HER-2/NEU by both immunohistochemistry and ELISA. The median of mean IC(50) values of docetaxel at the exposure durations of 3, 24, 72 and 120 h were 0.52, 0.06, 0.03 and 0.06 microM, respectively. The median of mean IC(50) values of paclitaxel at the exposure duration of 3, 24, 72 and 120 h were 0.48, 0.13, 0.03 and 0.02 microM, respectively. In all cell lines studied, there was a less than 4-fold difference in the IC(50) values between docetaxel and paclitaxel at 3-, 72-, and 120-hour exposure times. The single cell line with moderate MDR1 expression (NCI-H2887) was the only cell line established from a patient with progressive disease when treated with paclitaxel. This study demonstrates prolonged exposure to both docetaxel and paclitaxel inhibits the growth of NSCLC cell lines in similar fashion.
    Oncology 02/2003; 64(4):399-406. · 2.27 Impact Factor
  • Article: Hydrogen peroxide induces upregulation of Fas in human airway epithelial cells via the activation of PARP-p53 pathway.
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    ABSTRACT: Fas mediates apoptosis following binding with Fas ligand. Fas is expressed in human airway epithelial cells and has a critical role in the pathophysiology of various pulmonary disorders. Hydrogen peroxide (H(2)O(2)) is an important mediator of airway epithelial injury. In this context, we hypothesized that H(2)O(2) would increase the expression of cell surface Fas in human airway epithelial cells. To test this hypothesis, the modulation of Fas expression with H(2)O(2) was assessed in normal human bronchial epithelial cells and A549 cells. The majority of Fas was cytoplasmic in both cell types without any stimulation. Hydrogen peroxide significantly increased Fas in the plasma membrane fraction, while decreasing Fas in the cytoplasmic fraction. Incubation with an agonistic antibody for Fas induced apoptosis in H(2)O(2)-treated cells in proportion to the level of surface Fas expression on those cells. Inhibitors of poly(ADP-ribose) polymerase abrogated the H(2)O(2)-induced Fas translocation to the plasma membrane and p53 activation. Expression of dominant-negative p53 also inhibited the Fas translocation induced by H(2)O(2) in A549 cells. These results indicate that H(2)O(2) induces Fas upregulation by promoting cytoplasmic transport of Fas to the cell surface in human airway epithelial cells, and that the activation of the poly(ADP-ribose) polymerase-p53 pathway may be involved in this mechanism.
    American Journal of Respiratory Cell and Molecular Biology 12/2002; 27(5):542-52. · 5.13 Impact Factor
  • Article: Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma.
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    ABSTRACT: The A to C transversion in the promoter region of the gene encoding leukotriene C4 synthase (LTC4S) is proposed to be associated with the development of aspirin-induced asthma (AIA). We investigated the frequency of the polymorphism in Japanese population and its association with clinical characteristics and cysteinyl leukotriene production. Genotyping of LTC4S gene promoter was performed on 60 patients with AIA, 100 patients with aspirin-tolerant asthma (ATA), and 110 control subjects. We assessed the basal levels of urinary LTE4, the increment of urinary LTE4 on venous aspirin challenge, and LTC4S activity in peripheral blood eosinophils. The frequency of the variant C allele was significantly higher in patients with AIA (frequency of allele [q] = 0.192) than in patients with ATA (q = 0.110, P =.042). Variant C-allelic carriers experienced asthma at a significantly younger age (31.8 +/- 2.9 years [mean +/- SEM]) than wild-type A homozygotes (41.3 +/- 2.2 years, P =.007). Basal levels of LTE4 and the increment of urinary LTE4 on venous aspirin challenge did not show a difference between wild-type A homozygotes and variant C-allelic carriers. There was no relationship between the polymorphism and the LTC4S activity in eosinophils, although LTC4S activities were significantly higher in patients with AIA than in patients with ATA. Our findings reveal the lack of functionality of the polymorphism in the LTC4S gene, whereas this polymorphism might have some effect on the development of AIA, probably in linkage disequilibrium with another causatively important mutation.
    Journal of Allergy and Clinical Immunology 07/2002; 109(6):936-42. · 11.00 Impact Factor
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