Yukihiro Hasegawa

Hirosaki University, Khirosaki, Aomori Prefecture, Japan

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Publications (12)41.84 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To clarify the reason why central fibrosis (CF) is an important histological prognostic factor in small adenocarcinoma (SA) of the lung, tumor tissues from 50 patients with SA < or = 2 cm in diameter were investigated using immunohistochemical and in situ hybridization analysis for factors relating to extracellular matrix and vessels. CF was observed in 33/50 cases (66%). In adenocarcinoma areas, positive activity was observed with both primary antibodies and probes for matrix metalloproteinase-2 (MMP-2) in 11/50 patients (22%), membrane-type 1 matrix metalloproteinase (MT1-MMP) in 39/50 patients (78%) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 49/50 patients (98%). In CF areas, the positive activity of fibroblastic cells was seen for only TIMP-2 in 32/33 patients (97%). In CF areas, both CD34-positive (blood and lymphatic) vessels and D2-40-positive lymphatic vessels were semiquantitatively increased in 16/33 patients (48.5%) by immunohistochemistry. Tumors with increased vessel density were associated with statistically lower disease-free survival curves compared with tumors without increased vessels. Lymphatic vessels in some CF showed intravasation by carcinoma cells. In conclusion, CF could be an important histological prognostic factor in SA chiefly because of its association with angiogenesis and lymphangiogenesis.
    Pathology International 10/2006; 56(9):494-502. · 1.72 Impact Factor
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    ABSTRACT: Diagnosing tuberculous pleural effusion (pTB) is often difficult because the culturing of tubercle bacilli results in a negative test in the majority of cases. Serological tests for the detection of antibodies to tuberculous glycolipid (TBGL) and lipoarabinomannan (LAM) have been introduced for the diagnosis of pulmonary tuberculosis. We examined the levels of these antibodies, adenosine deaminase (ADA) and interferon-gamma (IFN-gamma) in the pleural effusion and compared their diagnostic values in pTB. We studied 65 patients with pleural effusion. Of those, 19 patients were diagnosed as having pTB according to our broad case definition. The etiologies in the other 46 patients were malignant effusion, transdative effusion and miscellaneous diseases. Determiner TBGL antibody (D-TBGL-Ab) and MycoDot were used for the detection of anti-LAM and anti-TBGL antibodies, respectively, in the pleural effusion. The sensitivity of ADA was 78.9% (15/19) and the specificity 97.8% (45/46). The sensitivity of IFN-gamma was 84.2% (16/19) and the specificity 93.5% (43/46). The sensitivities of D-TBGL-Ab and MycoDot were both 52.6% (10/19) and their specificities were 95.7% (44/46) and 97.8% (45/46), respectively. When DTBGL-Ab (cutoff point: 2.0 U/ml) and ADA activity (cutoff point: 57 IU/l) were combined, the sensitivity was 94.7% (18/19) and the specificity 93.5% (43/46). In the diagnosis of pTB, D-TBGL-Ab and MycoDot each have low sensitivity but high specificity. When D-TBGL-Ab is used in combination with ADA, the sensitivity and specificity are both >90%. We conclude that D-TBGL-Ab and ADA in combination are useful in the diagnosis of pTB.
    Respiratory Medicine 10/2006; 100(10):1775-80. · 2.59 Impact Factor
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    ABSTRACT: To clarify the clinical significance of vascular endothelial growth factor (VEGF) in Japanese patients with small cell lung cancer (SCLC). We measured serum VEGF levels using an enzyme-linked immunosorbent assay in 45 patients with SCLC before treatment and in 38 patients with benign pulmonary disease and in 32 healthy subjects (71 non-malignant subjects). VEGF immunostaining was performed in tissue biopsies obtained from 23 SCLC patients during bronchoscopic examination. Median serum VEGF level was 332 pg/ml in patients with SCLC and 160 pg/ml in non-malignant subjects, respectively. The 95% cut-off level to exclude non-malignant subjects was 500 pg/ml. An elevated VEGF level (>500 pg/ml) was found more frequently in patients with extensive disease of SCLC than in those with the limited disease (p<0.01). A significant positive correlation was found between the serum VEGF level and platelet count in SCLC patients (r=0.389; p=0.0083). Serum VEGF level also correlated with serum lactate dehydrogenase in SCLC patients (r=0.381; p=0.0098). However, it did not correlate with serum neuron-specific enolase and pro-gastrin-releasing peptide level. Patients with the elevated VEGF levels had significantly shorter progression-free time than those with the normal VEGF levels (p<0.05). Patients with the elevated VEGF levels had a significantly shorter overall survival time than those with the normal VEGF levels in univariate survival analysis (p<0.05). Further, the elevated VEGF level remained as a significant determinant of poor survival in multivariate analysis (p<0.01). Serum VEGF level was significantly higher in patients with positive VEGF protein immunoreactivity in tumor tissue in SCLC. Elevated serum VEGF levels were associated with poor outcome in SCLC.
    Internal Medicine 02/2005; 44(1):26-34. · 0.97 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the safety and efficacy of nedaplatin and paclitaxel when given concurrently with radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC). Nedaplatin was administered at a fixed dose of 20 mg/m(2), and paclitaxel was administered at a starting dose of 30 mg/m(2) with an incremental increase of 5 mg/m(2) until dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered once a week for 6 weeks. The RT was given at a single daily dose of 2 Gy for 5 days per week. The pharmacokinetics of nedaplatin and paclitaxel were investigated. Overall, 20 patients were recruited and assigned to three different treatment groups: group 1 (paclitaxel 30 mg/m(2)), group 2 (paclitaxel 35 mg/m(2)) and group 3 (paclitaxel 40 mg/m(2)). Pulmonary toxicity was the main toxicity which occurred in 16 of 20 patients. In group 3, grades 3 and 4 pulmonary toxicity occurred in two of six patients and grade 3 esophagitis in one patient. The maximum tolerated dose of paclitaxel in this study was 40 mg/m(2) and the recommended dose of paclitaxel was therefore 35 mg/m(2). Four complete and 11 partial responses were observed, resulting in a 75% overall response rate. The area under the concentration-time curve of paclitaxel in group 3 was significantly higher than that in group 1. Nedaplatin 20 mg/m(2) and paclitaxel 35 mg/m(2) could be safely administered for NSCLC with concurrent thoracic RT, and this regimen was effective. The most important DLT was pulmonary toxicity.
    Japanese Journal of Clinical Oncology 12/2004; 34(11):647-53. · 1.90 Impact Factor
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    Journal of Clinical Oncology 07/2004; 22(12):2504-5. · 18.04 Impact Factor
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    ABSTRACT: Airway eosinophilia is one of the hallmarks of asthma. Eotaxin may play an important role in eosinophil recruitment. To examine the relationship between eotaxin levels in the sputum and eosinophilic inflammation. The sputum was obtained from 11 non-smokers, 14 smokers and 13 asthmatic patients using a sputum induction method. Eotaxin and interleukin (IL)-5 levels in the sputum were determined by ELISA and immunocytochemical analysis. Asthmatic patients had eosinophilia and smokers showed neutrophilia in their sputum. The eotaxin level in the sputum was significantly higher in smokers (median 412.5, range 91.1-872.2 pg/ml) and asthmatic patients (351.0, 185.0-928.0 pg/ml) compared with non-smokers (123.2, 0-369.0 pg/ml; both p < 0.05). IL-5 was detected in the sputum of 1 non-smoker, none of the smokers and 4 asthmatic patients. The percentage of eotaxin-positive cells was higher in smokers and asthmatic patients than in non-smokers, but the percentage of IL-5-positive cells was significantly higher only in asthmatic patients (p < 0.05). These findings suggest that the elevated eotaxin level in the sputum does not always accompany the increase in eosinophils, and cooperation with another cytokine such as IL-5 may be required for the recruitment of eosinophils.
    Respiration 01/2003; 70(6):600-5. · 2.62 Impact Factor
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    ABSTRACT: We experienced combustion of a fiberoptic bronchoscope and an endotracheal tube, as well as tracheo-bronchial burn during a diode laser treatment in a hypoxemic patient requiring continuous oxygen administration. Total intravenous anesthesia and a high concentration of inspired oxygen (FIO2 0.60) were used for the procedure. The complication occurred abruptly at the beginning of the second treatment after the first uneventful 15 min treatment. Several reports suggest that laser treatment can be performed even under FIO2 1.0 without firing in the airway, and a high FIO2 itself would not consistently play a key role in developing combustion in the airway, even though combustion is more vigorous when a higher FIO2 is used. Based on our experience and reports of firing in the airway during laser treatment, the following recommendations are presented. The laser treatment should be done (1) at the FIO2 just enough to maintain adequate oxygenation in each individual patient, (2) at the greatest possible distance between a bronchoscope and an endotracheal tube, and (3) after removing small pieces of carbonized tissues produced by each laser treatment.
    Masui. The Japanese journal of anesthesiology 01/2003; 51(12):1359-62.
  • Journal of Bronchology 01/2003; 10(3):198-200.
  • Nihon Naika Gakkai Zasshi 04/2002; 91(3):1022-4.
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    ABSTRACT: Ignition accidents during bronchoscopic laser irradiation have occasionally been reported, but the mechanisms responsible for the ignition accidents are not fully understood. We examined causative factors including ignition site, oxygen concentration, and role of airflow through the laser fiber. Porcine muscle tissue was placed in a bottle and irradiated by laser under various conditions. Also, a piece of porcine muscle was wedged in a main bronchus of the isolated porcine lungs and irradiated by laser in the same way. Flashing occurred on the tissue exposed to the laser, and this flashing reached the ignition when the oxygen concentration was above 30%. Increasing airflow through the laser fiber prevented the ignition even at an oxygen concentration at 100%. In laser irradiation, the tissue exposed to the laser can be the ignition site of fire. Increasing airflow through the laser fiber was an effective technique to prevent airway fire.
    Lasers in Surgery and Medicine 02/2002; 31(3):211-5. · 2.46 Impact Factor
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    ABSTRACT: Transforming growth factor-beta1 (TGF- beta1) is a multifunctional factor and is known to affect tumor growth in malignant tumors. The effects of TGF-beta1 on angiogenesis, stromal formation, and immune function suggest its possible involvement in tumor progression. The authors examined whether TGF-beta1 levels may be correlated with angiogenesis, clinicopathologic factors, and survival in patients with surgically resected lung carcinoma. TGF-beta1 protein was extracted from 53 nonsmall cell lung carcinoma tissue samples (19 squamous cell carcinomas, 33 adenocarcinomas, and 1 adenosquamous cell carcinoma), and its level was measured by enzyme-linked immunosorbent assay. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD31 immunostaining. The protein level of TGF-beta1 was 289 picograms per milligram of protein (pg/mg protein), ranging from 94 pg/mg protein to 584 pg/mg protein. The TGF-beta1 protein level was significantly higher in patients with lymph node metastasis compared with patients who were without lymph node metastasis (P = 0.02), and the TGF-beta1 protein level was significantly higher in patients with Stage III disease (TNM classification) compared with patients who had Stage I and II disease (P = 0.03). There was no significant correlation between the TGF-beta1 protein level and any of the other clinicopathologic factors that were considered. A significant positive correlation between TGF-beta1 protein level and MVD was noted (P < 0.01). Furthermore, in patients with adenocarcinoma, a significant correlation between TGF-beta1 protein level and prognosis was detected by multivariate analysis (P = 0.028). TGF-beta1 seems to affect tumor angiogenesis and to play an important role in tumor progression in patients with nonsmall cell lung carcinoma. Furthermore, the TGF-beta1 protein level may be an independent predictor of survival in patients with adenocarcinoma of the lung.
    Cancer 03/2001; 91(5):964-71. · 5.20 Impact Factor
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    ABSTRACT: Interleukin (IL)-10 is a potent regulatory cytokine that decreases inflammatory responses. This study investigated whether IL-10 levels in the airway are decreased in chronic airway inflammation associated with asthma or chronic obstructive pulmonary disease (COPD). Sputum was obtained from 12 healthy nonsmokers, 10 healthy smokers, 16 asthmatic patients and seven patients with COPD by means of the sputum-induction method. The IL-10 level was measured via enzyme-linked immunosorbent assay and immunocytochemical analysis. The IL-10 level in sputum was significantly lower in asthma and COPD patients and healthy smokers compared with that in healthy nonsmokers (nonsmokers, 68.0+/-11.3; smokers, 45.3+/-7.8; asthma, 26.7+/-4.0; COPD, 18.0+/-2.3 pg x mL(-1); p<0.05 for nonsmokers versus the other groups). The percentage of IL-10-positive cells in the sputum was also significantly lower in asthma and COPD and in smokers (nonsmokers, 13.2+/-1.7; smokers, 6.4+/-1.8; asthma, 5.4+/-3.5; COPD, 3.5+/-1.6%; p<0.05 for nonsmokers versus the other groups). The IL-10-positive cell appeared morphologically to be the macrophage. These data suggest that the reduced level of interleukin-10 within the airways plays a role in the pathogenesis of chronic airway inflammation in asthma and chronic obstructive pulmonary disease.
    European Respiratory Journal 09/1999; 14(2):309-14. · 6.36 Impact Factor