JaLCDOI 10.18926/AMO/48564
FullText URL 66_3_245.pdf
Author Okada, Toshiaki| Takigawa, Nagio| Kishino, Daizo| Katayama, Hideki| Kuyama, Shouichi| Sato, Ken| Mimoto, Junko| Ueoka, Hiroshi| Tanimoto, Mitsune| Kiura, Katsuyuki|
Abstract Cisplatin is used to treat lung cancer;however, it is also a known carcinogen. Cyclooxygenase-2 (COX-2) inhibitors have been shown to prevent carcinogen-induced experimental tumors. We investigated the effect of a COX-2 inhibitor, celecoxib, on cisplatin-induced lung tumors. One hundred twenty 4-week-old A/J mice were divided into 6 groups:group 1, no treatment;group 2, low-dose celecoxib (150mg/kg);group 3, high-dose celecoxib (1,500mg/kg);group 4, cisplatin alone;group 5, cisplatin plus low-dose celecoxib;and group 6, cisplatin plus high-dose celecoxib. Mice in groups 4-6 were administered cisplatin (1.62mg/kg, i.p.) once a week for 10 weeks between 7 and 16 weeks of age. All mice were sacrificed at week 30. Tumor incidence was 15.8% in group 1, 25% in group 2, 26.3% in group 3, 60% in group 4, 50% in group 5, and 50% in group 6. Tumor multiplicity was 0.2, 0.3, 0.3, 1.3, 1.0, and 0.6 in groups 1-6, respectively. Tumor multiplicity in the cisplatin-treated mice was reduced by celecoxib treatment in a dose-dependent manner (p<0.05, group 4 vs. group 6). Celecoxib significantly reduced COX-2 expression in cisplatin-induced tumors (p<0.01, group 4 vs. group 6).
Keywords cisplatin non-small cell lung cancer celecoxib cyclooxygenase-2 chemoprevention
Amo Type Original Article
Published Date 2012-06
Publication Title Acta Medica Okayama
Volume volume66
Issue issue3
Publisher Okayama University Medical School
Start Page 245
End Page 251
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2012 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 22729105
Web of Science KeyUT 000305669700008
Author Nogami, Naoyuki| Hotta, Katsuyuki| Kuyama, Shoichi| Kiura, Katsuyuki| Takigawa, Nagio| Chikamori, Kenichi| Shibayama, Takuo| Kishino, Daizo| Hosokawa, Shinobu| Tamaoki, Akihiko| Harita, Shingo| Tabata, Masahiro| Ueoka, Hiroshi| Shinkai, Tetsu| Tanimoto, Mitsune|
Published Date 2011-10
Publication Title Lung Cancer
Volume volume74
Issue issue1
Content Type Journal Article
JaLCDOI 10.18926/AMO/46851
FullText URL 65_4_259.pdf
Author Ogata, Yoshiko| Aoe, Keisuke| Hiraki, Akio| Murakami, Kazuo| Kishino, Daizo| Chikamori, Kenichi| Maeda, Tadashi| Ueoka, Hiroshi| Kiura, Katsuyuki| Tanimoto, Mitsune|
Abstract The objective of this study was to evaluate the utility of the determination of adenosine deaminase (ADA) level in pleural fluid for the differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in Japan, a country with intermediate incidence of tuberculosis (TB). We retrospectively reviewed the clinical records of 435 patients with pleural effusion and investigated their pleural ADA levels as determined by an auto analyzer. ROC analysis was also performed. The study included patients with MPE (n=188), TPE (n=124), benign nontuberculous pleural effusion (n=94), and pleural effusion of unknown etiology (n=29). The median ADA level in the TPE group was 70.8U/L, which was significantly higher than that in any other groups (p<0.05). The area under the curve (AUC) in ROC analysis was 0.895. With a cut-off level for ADA of 36U/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 85.5%, 86.5%, 69.7%, and 93.6%, respectively. As many as 9% of patients with lung cancer and 15% of those with mesothelioma were false-positive with this ADA cutoff setting. Although the ADA activity in pleural fluid can help in the diagnosis of TPE, it should be noted that some cases of lung cancer or mesothelioma show high ADA activity in geographical regions with intermediate incidence of TB, in contrast to high prevalence areas.
Keywords pleural effusion adenosine deaminase tuberculosis lung cancer mesothelioma
Amo Type Original Article
Published Date 2011-08
Publication Title Acta Medica Okayama
Volume volume65
Issue issue4
Publisher Okayama University Medical School
Start Page 259
End Page 263
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2011 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 21860532
Web of Science KeyUT 000294236700006
JaLCDOI 10.18926/AMO/32866
FullText URL fulltext.pdf
Author Fujimoto, Nobukazu| Kiura, Katsuyuki| Takigawa, Nagio| Fujiwara, Yoshiro| Toyooka, Shinichi| Umemura, Shigeki| Tabata, Masahiro| Ueoka, Hiroshi| Tanimoto, Mitsune|
Abstract <p>We examined the feasibility of triplet chemotherapy using cisplatin, docetaxel, and irinotecan for patients with recurrent or refractory non-small cell lung cancer (NSCLC), retrospectively. Twenty-five patients (21 men and 4 women) with NSCLC and good performance status who were &#60;70 years old were analyzed. The median age was 58 years. Most patients had performance status 1 (16/25), stage IV disease (18/25) and adenocarcinoma-histology (16/25). Cisplatin and docetaxel were given on day 1 and irinotecan on day 2;the cycle was repeated every 3 weeks. The objective response rate was 39.1% (95% confidence interval:18.7-59.5%). The median survival time and actual 2-, 3-, and 5-year survival rates were 14.3 months, 32%, 20%, and 8%, respectively. Of note, only 6 patients were treated with gefitinib at the recurrence after triplet chemotherapy;of these, 4 (67%) achieved a partial response, which might result in favorable survival. Grade 3/4 toxicities consisted of neutropenia (100%), neutropenic fever (56%), nausea/vomiting (40%), and diarrhea (16%);no cases of treatment-related death occurred. Triplet chemotherapy showed impressive survival data in our clinical trial, but proved too toxic for use in treating patients with NSCLC in the clinical practice.</p>
Keywords cisplatin docetaxel irinotecan triplet chemotherapy gefitinib
Amo Type Original Article
Published Date 2010-02
Publication Title Acta Medica Okayama
Volume volume64
Issue issue1
Publisher Okayama University Medical School
Start Page 33
End Page 37
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 20200582
Web of Science KeyUT 000274868300005
JaLCDOI 10.18926/AMO/32676
FullText URL fulltext.pdf
Author Hosoya, Shigee| Kataoka, Mikio| Nakata, Yasunari| Maeda, Tsuyoshi| Nishizaki, Hiroshi| Hioka, Tohru| Mori, Yoshihiro| Ejiri, Tougo| Shiomi, Katsuhiko| Ueoka, Hiroshi| Numata, Takeyuki| Nishii, Kenji| Kodani, Tsuyoshi| Moritani, Yoshiaki| Ohnoshi, Taisuke| Kimura, Ikuro|
Abstract <p>Clinical features were studied in 125 patients with sarcoidosis (72 females and 53 males) diagnosed at Okayama University Hospital during a recent 10-year period. The age distribution had two peaks in patients in their 20s and the 50s. Over half of the patients were detected at health screening check and were asymptomatic, while the remaining were symptomatic. Twelve patients were in stage 0, 41 were in stage I, 54 were in stage II, 16 were in stage III, and 2 were in stage IV according to the chest x-ray findings. Serum angiotensin converting enzyme levels and serum lysozyme levels were elevated in 60% and 76% of the patients, respectively. The bronchoalveolar lavage fluid showed lymphocytosis, especially of helper T-cells. The clinical features of sarcoidosis appear to depend on the duration of the disease.</p>
Keywords sarcoidosis serum angiotesin converting enzyme bronchoalveolar lavage
Amo Type Article
Published Date 1992-02
Publication Title Acta Medica Okayama
Volume volume46
Issue issue1
Publisher Okayama University Medical School
Start Page 31
End Page 36
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 1561903
Web of Science KeyUT A1992HH01700006
JaLCDOI 10.18926/AMO/32669
FullText URL fulltext.pdf
Author Takigawa, Nagio| Ohnoshi, Taisuke| Ueoka, Hiroshi| Kiura, Katsuyuki| Kimura, Ikuro|
Abstract <p>An etoposide-resistant subline, SBC-3/ETP, from a human small cell lung cancer cell line, SBC-3, was developed by continuous exposure to increasing concentrations of etoposide in culture. The SBC-3/ETP was 52.1-fold more resistant to etoposide than the parent cell line. The SBC-3/ETP was highly cross-resistant to teniposide, adriamycin, vinca alkaloids, 4-hydroperoxycyclophosphamide, CPT-11 and mitomycin C, and marginally cross-resistant to cisplatin, while the subline showed a collateral sensitivity to bleomycin. Topoisomerase I activity in the SBC-3/ETP was reduced to an extent of one half and topoisomerase II activity to an extent of one eighth in comparison with those of the SBC-3. Intracellular accumulation of [3H]-etoposide in the SBC-3/ETP was significantly lower in comparison to the SBC-3. An overexpression of MDR1 mRNA, and the presence of its product, P-glycoprotein, were detected in the SBC-3/ETP by Northern blotting and flowcytometry using a monoclonal antibody of the protein, MRK16. These results indicate that a decreased activity of topoisomerase II is the major factor for the development of etoposide resistance, and that an overexpression of the MDR1 gene is responsible, in part, for the development of resistance to the drug and some structurally unrelated compounds such as adriamycin and vinca alkaloids.</p>
Keywords small cell lung cancer etoposide-resistant cell line P-glycoprotein topoisomerase
Amo Type Article
Published Date 1992-06
Publication Title Acta Medica Okayama
Volume volume46
Issue issue3
Publisher Okayama University Medical School
Start Page 203
End Page 212
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 1354408
Web of Science KeyUT A1992JB50400009
JaLCDOI 10.18926/AMO/32631
FullText URL fulltext.pdf
Author Takigawa, Nagio| Ohnoshi, Taisuke| Ueoka, Hiroshi| Kiura, Katsuyuki| Kimura, Ikuro|
Abstract <p>In an attempt to predict the clinical activity of newly developed anthracycline analogues, ME2303, KRN8602, and SM5887 in the treatment of lung cancer, we compared antitumor activity of these drugs with that of adriamycin, using six human lung cancer cell lines and two drug-resistant human lung cancer sublines. Taking the pharmacokinetic data into consideration, we evaluated the relative antitumor activity: the ratio of area under the concentration-time curve of each drug to the 50% inhibitory concentration of the drug. Regarding this ratio, ME2303 was more potent than adriamycin, SM5887, and KRN8602. Cross-resistance of the new analogues to adriamycin was investigated using an adriamycin-resistant small cell lung cancer subline, SBC-3/ADM100 and an etoposide-resistant subline, SBC-3/ETP. SBC-3/ADM100 being 106-fold more resistant to adriamycin than the parent SBC-3 showed less resistance to the analogues: 1.80-fold to KRN8602, 3.80-fold to SM5887, and 8.60-fold to ME2303. SBC-3/ETP which was 52.1-fold more resistant to etoposide and 39.5-fold more resistant to adriamycin were also less resistant to the new analogues: 3.27-fold to KRN8602, 9.07-fold to SM5887, and 17.3-fold to ME2303. In conclusion, ME2303 was found to be the most potent agent among drugs tested for the treatment of lung cancer, and KRN8602 can be expected to be beneficial for the treatment of drug-resistant small cell lung cancer.</p>
Keywords new anthracycline analogues ME2303 KRN8602 SM5887 lung cancer cell line
Amo Type Article
Published Date 1992-08
Publication Title Acta Medica Okayama
Volume volume46
Issue issue4
Publisher Okayama University Medical School
Start Page 249
End Page 256
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 1442149
Web of Sience KeyUT A1992JL44200004
JaLCDOI 10.18926/AMO/32200
FullText URL fulltext.pdf
Author Ohnoshi, Taisuke| Hiraki, Shunkichi| Ueda, Nobuo| Fujii, Masafumi| Machida, Ken-ichi| Ueoka, Hiroshi| Kawahara, Shin| Kozuka, Akira| Kiura, Katsuyuki| Moritaka, Tomonori| Kodani, Tsuyoshi| Kamei, Haruhito| Kimura, Ikuro|
Abstract <p>Twenty-seven previously untreated patients with unresectable non-small cell lung cancer were treated with a 3-drug combination of ifosfamide, cisplatin, and vindesine as a phase II study. Patients received ifosfamide, 1.3g/m2, on days 1 to 5; cisplatin, 20mg/m2, on days 1 to 5; and vindesine, 3mg/m2, on days 1 and 8; with a sufficient parenteral hydration. Courses were repeated every 4 weeks. Twenty males and seven females with a median age of 61 years were treated and fully evaluated. Five patients had stage IIIA, seven had stage IIIB, and 15 had stage IV disease. One patient with adenocarcinoma achieved a complete response and 16 achieved a partial response, for an overall response rate of 63% (95% confidence limit: 45% to 81%). The median duration of response was 34 weeks (range: 9 to 52 weeks). The median survival time was 58 weeks for patients with IIIA/B disease, and 33 weeks for those with IV disease. The major toxicity was myelosuppression, however, it was generally well-tolerated. These results indicate that the 3-drug combination is active against non-small cell lung cancer and warrants further clinical trials.</p>
Keywords non-small cell lung cancer ifosfamide cisplatin vindesine
Amo Type Article
Published Date 1991-10
Publication Title Acta Medica Okayama
Volume volume45
Issue issue5
Publisher Okayama University Medical School
Start Page 357
End Page 361
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 1661559
Web of Sience KeyUT A1991GN53800010
JaLCDOI 10.18926/AMO/31714
FullText URL fulltext.pdf
Author Kawada, Kazuhiko| Yonei, Toshiro| Ueoka, Hiroshi| Kiura, Katsuyuki| Tabata, Masahiro| Takigawa, Nagio| Harada, Mine| Tanimoto, Mitsune|
Abstract <p>When the development of chemotherapeutic agents reaches the clinical trial stage, it is necessary to perform drug sensitivity tests quickly in order to select the most promising agents for the treatment of cancer. In order to assess the possibility of using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as a substitute for the human tumor clonogenic assay (HTCA), we evaluated the correlation between the results obtained by these 2 assays in 5 human lung cancer cell lines. The correlation coefficient between the results of the HTCA and the MTT assay was 0.673, indicating a relatively good correlation. The correlation was most prominent in platinum analogues (r = 0.939) and good in anthracyclines/anthracenedione (r = 0.611). However, no significant correlation was observed in vinca alkaloids, etoposide, irinotecan, SN-38 (an active metabolite of irinotecan), and rhizoxin. The results of the MTT assay showed a high degree of correlation with those of the HTCA in predicting the sensitivity of cancer cell lines to platinum analogues, and anthracyclines/anthracenedione. These results suggest that the MTT assay may be more convenient and quickly performed than the HTCA and can replace HTCA in evaluating the effects of anticancer agents, especially the platinum analogues and anthracyclines/anthracenedione.</p>
Keywords chemosensitivity test 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltertrazolium bromide (MTT) assay clonogenic assay
Amo Type Article
Published Date 2002-06
Publication Title Acta Medica Okayama
Volume volume56
Issue issue3
Publisher Okayama University Medical School
Start Page 129
End Page 134
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 12108583
Web of Science KeyUT 000176521200002
JaLCDOI 10.18926/AMO/31705
FullText URL fulltext.pdf
Author Takata, Ichiro| Ueoka, Hiroshi| Kiura, Katsuyuki| Tabata, Masahiro| Takigawa, Nagio| Katayama, Hideki| Takemoto, Mitsuhiro| Hiraki, Yoshio| Harada, Mine| Tanimoto, Mitsune|
Abstract <p>A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC). Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2) was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy) was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0%) or stage IIIB (60.0%) disease. Fifteen patients (60.0%) completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0%) due to poor response, and 7 patients (28.0%) partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0%) and 10 patients (40.0%), respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0%) and 2 patients (8.0%), respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.</p>
Keywords non-small-cell lung cancer concurrent chemoradiotherapy low-dose cisplatin poor-risk factor
Amo Type Article
Published Date 2002-10
Publication Title Acta Medica Okayama
Volume volume56
Issue issue5
Publisher Okayama University Medical School
Start Page 261
End Page 266
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 12530510
Web of Sience KeyUT 000178668100007
JaLCDOI 10.18926/AMO/31626
FullText URL fulltext.pdf
Author Matsushita, Akio| Tabata, Masahiro| Ueoka, Hiroshi| Kiura, Katsuyuki| Shibayama, Takuo| Aoe, Keisuke| Kohara, Hiroyuki| Harada, Mine|
Abstract <p>We established a drug sensitivity panel consisting of 24 human lung cancer cell lines. Using this panel, we evaluated 26 anti-cancer agents: three alkylators, three platinum compounds, four antimetabolites, one topoisomerase I inhibitor, five topoisomerase II inhibitors, seven antimitotic agents and three tyrosine kinase inhibitors. This panel showed the following: a) Drug sensitivity patterns reflected their clinically-established patterns of action. For example, doxorubicin and etoposide were shown to be active against small cell lung cancer cell lines and mitomycin-C and 5-fluorouracil were active against non-small cell lung cancer cell lines, in agreement with clinical data. b) Correlation analysis of the mean graphs derived from the logarithm of IC50 values of the drugs gave insight into the mechanism of each drug's action. Thus, two drug combinations with reverse or no correlation, such as the combination of cisplatin and vinorelbine, might be good candidates for the ideal two drug combination in the treatment of lung cancer, as is being confirmed in clinical trials. c) Using cluster analysis of the cell lines in the panel with their drug sensitivity patterns, we could classify the cell lines into four groups depending on the drug sensitivity similarity. This classification will be useful to elucidate the cellular mechanism of action and drug resistance. Thus, our drug sensitivity panel will be helpful to explore new drugs or to develop a new combination of anti-cancer agents for the treatment of lung cancer.</p>
Keywords drug screening system MTT assay lung cancer cell line drug resistance
Amo Type Article
Published Date 1999-04
Publication Title Acta Medica Okayama
Volume volume53
Issue issue2
Publisher Okayama University Medical School
Start Page 67
End Page 75
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
Web of Sience KeyUT 000080058700002
JaLCDOI 10.18926/AMO/31591
FullText URL fulltext.pdf
Author Ohnoshi, Taisuke| Hiraki, Shunkichi| Fujii, Masafumi| Ueoka, Hiroshi| Yonei, Toshiro| Tamura, Makoto| Moritaka, Tomonori| Mima, Yuchi| Horiguchi, Takashi| Kiura, Katsuyuki| Kamei, Haruhito| Kodani, Tsuyoshi| Hiraki, Yoshio| Kimura, Ikuro|
Abstract <p>We evaluated the long-term outcome of 148 patients with small cell lung cancer (SCLC) who had been entered into clinical trials of chemotherapy with or without thoracic and prophylactic cranial irradiation (PCI) between 1981 and 1987. Eighteen patients (12%) survived for 2 or more years. With a minimum follow-up of 4.5 years, 10 of the 18 patients who remained disease-free at 2 years are currently alive and free of SCLC. Seven of these 10 patients currently function as they did before diagnosis. However, three suffer from central nervous system changes of varying degrees in severity which appeared 2-3 years after PCI. Eight of the 18 patients who were disease-free at 2 years have died. Two died of isolated relapse in the brain at 3.6 and 4.2 years after initiation of chemotherapy. Five died of other malignancies while continuing their complete response to SCLC; two of non-small cell lung cancer, two of acute myelogenous leukemia, and one of hepatocellular carcinoma. Another patient died of an unrelated disease without any evidence of SCLC. A small but substantial proportion of patients who underwent intensive treatment will achieve long-term survival; however, these patients remain at higher risk for second cancers and late toxicities. Therefore, attention must be directed to defining the safest way to employ such treatment in the management of SCLC.</p>
Keywords small cell lung cancer long-term survivors late relapse toxicities complications
Amo Type Article
Published Date 1993-06
Publication Title Acta Medica Okayama
Volume volume47
Issue issue3
Publisher Okayama University Medical School
Start Page 209
End Page 214
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 8397470
Web of Sience KeyUT A1993LL12400010
JaLCDOI 10.18926/AMO/31590
FullText URL fulltext.pdf
Author Segawa, Yoshihiko| Ohnoshi, Taisuke| Hiraki, Shunkichi| Ueoka, Hiroshi| Kiura, Katsuyuki| Kamei, Haruhito| Tabata, Masahiro| Shibayama, Takuo| Miyatake, Kazuyo| Genda, ken-ichi| Matsumura, Tadashi| Kimura, Ikuro|
Abstract <p>In an attempt to elucidate the tumor properties relating to responsiveness to chemotherapy, we examined immunohistochemically the expression of P-glycoprotein (P-gp) and carcinoembryonic antigen (CEA) in small cell lung cancer (SCLC) tumors. Tumor specimens from 33 patients were obtained at the time of diagnosis and relapse. Four patients expressed P-gp in their initial tumors, and 7 others did in recurrent tumors. The overall response rate to chemotherapy of the initial tumors was 75% for P-gp-positive initial tumors and 86% for P-gp-negative tumors, whereas the disease-free and overall survival times were significantly shorter in the former than the latter. Three patients showed CEA in their initial tumors, and 5 others did in recurrent tumors. The patients with CEA-positive initial tumors tended to relapse earlier than those with CEA-negative tumors. In addition, recurrent tumors expressing CEA were resistant to salvage chemotherapy. A clear correlation between CEA expression by tumors and the CEA level in the serum was observed at diagnosis as well as at relapse. These findings indicate that P-gp and/or CEA expression by a tumor and elevated CEA level in the serum may predict refractoriness of the tumor to chemotherapy.</p>
Keywords small cell lung cancer immunohistochemistry drug resistance P-glycoprotein carcinoembryonic antigen
Amo Type Article
Published Date 1993-06
Publication Title Acta Medica Okayama
Volume volume47
Issue issue3
Publisher Okayama University Medical School
Start Page 181
End Page 189
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 8104371
Web of Science KeyUT A1993LL12400007
JaLCDOI 10.18926/AMO/31555
FullText URL fulltext.pdf
Author Segawa, Yoshihiko| Ohnoshi, Taisuke| Ueoka, Hiroshi| Kimura, Ikuro|
Abstract <p>The neural cell adhesion molecule (NCAM) is a family of cell surface sialoglycoproteins mediating homotypic and heterotypic cell-cell adhesion. In tumors, NCAM is supposed to be involved with the malignant features characterized by invasive growth and metastasis. In the present study, we evaluated the correlation between NCAM expression of tumors obtained from small cell lung cancer (SCLC) patients and the clinical outcome. NCAM expression was determined semi-quantitatively by an immunogold-silver staining method using the SCLC cluster 1 monoclonal antibody NCC-LU-243. Of 20 SCLC patients studied, six patients with tumors with high NCAM expression had a poor response to chemotherapy, and a short disease-free (p = 0.011) and overall (p = 0.003) survival as compared with 14 patients having tumors with low NCAM expression. These findings indicate that the therapeutic outcome of SCLC may be partly predicted by determining the NCAM expression of the tumor.</p>
Keywords neural cell adhesion molecule small cell lung cancer metastatic potential cluster 1 monoclonal antibodies immunogold-silver staining method
Amo Type Article
Published Date 1993-08
Publication Title Acta Medica Okayama
Volume volume47
Issue issue4
Publisher Okayama University Medical School
Start Page 281
End Page 287
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 8213222
Web of Science KeyUT A1993LV73800010
Related Url http://ousar.lib.okayama-u.ac.jp/metadata/4330
JaLCDOI 10.18926/AMO/31553
FullText URL fulltext.pdf
Author Tabata, Masahiro| Ohnoshi, Taisuke| Ueoka, Hiroshi| Kiura, Katsuyuki| Kimura, Ikuro|
Abstract <p>We report a preliminary study to determine whether MDR1 gene expression level in small cell lung cancer (SCLC) tumors is a useful predictor of tumor response to chemotherapy and patient survival in association with myc amplification in the tumor. We analyzed 18 patients with SCLC receiving adriamycin and etoposide combination chemotherapy between August 1989 and November 1991; 16 males and 2 females, median age of 68 years, and 7 with limited disease and 11 with extensive disease. MDR1 mRNA expression level and myc family gene amplification were simultaneously determined by polymerase chain reaction using transbronchial biopsy specimens which were obtained at diagnosis. Patients with tumors expressing low MDR1 mRNA responded more favorably to chemotherapy than those with tumors expressing high MDRI mRNA, however, the difference in tumor response was statistically not significant (84.6% versus 40%). The overall survival was significantly shorter in the latter than in the former (7.2 months versus 11.7 months; p = 0.023). The survival of the 4 patients with tumor showing myc family gene amplification was almost identical to that of patients with tumors showing no amplification of the gene (8.2 months versus 8.8 months; p = 0.73). Multivariate Cox's regression analysis supports the notion that MDR1 may be a useful independent prognostic factor.</p>
Keywords small cell lung cancer MDR1 mRNA expression myc gene amplification prognostic factor
Amo Type Article
Published Date 1993-08
Publication Title Acta Medica Okayama
Volume volume47
Issue issue4
Publisher Okayama University Medical School
Start Page 243
End Page 248
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 8213218
Web of Science KeyUT A1993LV73800004
JaLCDOI 10.18926/AMO/31552
FullText URL fulltext.pdf
Author Yonei, Toshiro| Ohnoshi, Taisuke| Hiraki, Shunkichi| Ueoka, Hiroshi| Kiura, Katsuyuki| Moritaka, Tomonori| Shibayama, Takuo| Tabata, Masahiro| Segawa, Yoshihiko| Takigawa, Nagio| Kimura, Ikuro|
Abstract <p>Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC -3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer.</p>
Keywords platinum analogs antitumor activity lung cancer colony assay combination effect
Amo Type Article
Published Date 1993-08
Publication Title Acta Medica Okayama
Volume volume47
Issue issue4
Publisher Okayama University Medical School
Start Page 233
End Page 241
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 8213217
Web of Science KeyUT A1993LV73800003
JaLCDOI 10.18926/AMO/31310
FullText URL fulltext.pdf
Author Tamura, Makoto| Ueoka, Hiroshi| Kiura, Katsuyuki| Tabata, Masahiro| Shibayama, Takuo| Miyatake, Kazuyo| Genba, Kenichi| Hiraki, Shunkichi| harada, Mine|
Abstract <p>In order to elucidate factors influencing the prognosis of small-cell lung cancer (SCLC), we reviewed the records of 253 patients with SCLC and evaluated 20 pretreatment prognostic factors by univariate analysis and Cox's multiple regression analysis. Recursive partitioning and amalgamation (RPA) was employed to identify subgroups with similar survival rates. Cox's multiple regression analysis identified five significant factors: extent of disease, number of metastatic sites, serum albumin, serum lactate dehydrogenase, and presence of weight loss. Among these, extent of disease was the most influential factor. RPA analysis revealed three subgroups predicting significantly different prognoses. The median survival time and 3-year survival rate were 18.4 months and 20.6%, respectively for the good-risk group (limited disease without weight loss), 13.5 months and 9.1%, respectively for the intermediate-risk group (limited disease with weight loss or extensive disease with less than two metastatic sites), and 9.2 months and 0%, respectively for the poor-risk group (extensive disease with two or more metastatic sites). These results will be useful for development of new staging system or subsequent stratification for randomized trials.</p>
Keywords prognostic factors Cox's multiple regression analysis recursive partitioning and amalgamayion method small-sell lung canser
Amo Type Article
Published Date 1998-04
Publication Title Acta Medica Okayama
Volume volume52
Issue issue2
Publisher Okayama University Medical School
Start Page 105
End Page 111
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 9588226
Web of Sience KeyUT 000073363000006
JaLCDOI 10.18926/AMO/30795
FullText URL fulltext.pdf
Author Matsuo, Keisuke| Kiura, Katsuyuki| Ueoka, Hiroshi| Tabata, Masahiro| Shibayama, Takuo| Matsumura, Tadashi| Takigawa, Nagio| Hiraki, Shunkichi| Harada, Mine|
Abstract <p>We have established an Adriamycin (ADM) -resistant small cell lung cancer (SCLC) cell line, SBC-3/ADM100, which shows multifactorial mechanisms of resistance to ADM, such as overexpression of P-glycoprotein, an enhanced detoxifying system and a decrease in topoisomerase II activity. In the present study, we confirmed that SBC-3/ADM 100 showed collateral sensitivity to methotrexate and TNP-351, a new antifolate, though this cell line showed a typical multidrug resistance (MDR) pattern. We also demonstrated a faster uptake and higher accumulation (1.3-fold) of TNP-351 in the SBC-3/ADM100 cells than those in the parent SBC-3 cells. These results explain one of the mechanisms for collateral sensitivity in the resistant cells. Furthermore, this cell line was found to have no cross-resistance to edatrexate and minimal cross-resistance to trimetrexate, 254-S (cisplatin analog), 5-fluorouracil and 4-hydroperoxyifosfamide. These drugs will have clinical importance in patients with SCLC who were previously treated with an ADM-containing regimen. Thus, antifolates, especially TNP-351 and edatrexate, can be expected to eradicate residual multidrug resistant SCLC cells selected by ADM.</p>
Keywords Adriamycin-resistant cell line antifolates small cell lung cancer
Amo Type Article
Published Date 1997-06
Publication Title Acta Medica Okayama
Volume volume51
Issue issue3
Publisher Okayama University Medical School
Start Page 121
End Page 127
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 9227790
Web of Science KeyUT A1997XJ12700002
JaLCDOI 10.18926/AMO/30751
FullText URL fulltext.pdf
Author Kitajima, Takuji| Nishii, Kenji| Ueoka, Hiroshi| Shibayama, Takuo| Gemba, Kenichi| Kodani, Tsuyoshi| Kiura, Katsuyuki| Tabata, Masahiro| Hotta, Katsuyuki| Tanimoto, Mitsune| Sobue, Tomotaka|
Abstract <p>To evaluate recent improvements in lung cancer screening, we compared the results of recently conducted lung cancer screening with those of a previous screening. This study compared the survival of lung cancer patients detected by lung cancer screening conducted between 1976 and 1984 (early period) with that conducted between 1989 and 1997 (late period). Two hundred seventy-six patients with lung cancer were detected in the early period and 541 patients with lung cancer were detected in the late period. The median survival time (late : 49.8 vs. early : 27.8 months) and the 5-year survival rate (late : 47.8 vs. early : 34.8%) of the patients with lung cancer detected in the late period were significantly better than those in the early period (p = 0.0054). Among patients undergoing resection, the proportion of pathological stage I patients in the late period was significantly higher than that in the early period (late : 60.8 vs. early : 54.9%, p = 0.005). Multivariate analysis showed that the screening time period was a significant prognostic factor (hazard ratio = 0.685, 95% confidence interval : 0.563-0.832, p = 0.0002). These results were consistent with the findings of case-control studies of lung cancer screening programs in the late period recently conducted in Japan, which also showed a greater efficacy for screening than for previous case-control studies in the early period.</p>
Keywords lung cancer screening survival lung cancer mortality
Amo Type Article
Published Date 2006-06
Publication Title Acta Medica Okayama
Volume volume60
Issue issue3
Publisher Okayama University Medical School
Start Page 173
End Page 179
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 16838046
Web of Science KeyUT 000238503600005
JaLCDOI 10.18926/AMO/30750
FullText URL fulltext.pdf
Author Hiraki, Akio| Murakami, Tomoyuki| Aoe, Keisuke| Matsuda, Eisuke| Maeda, Tadashi| Umemori, Yoshiki| Ueoka, Hiroshi|
Abstract <p>We describe here a patient with a recurrent hemangiopericytoma of the superior mediastinum 23 years after an initial complete resection. In the current biopsy specimen, the tumor cells were much more anaplastic than those seen 23 years ago. Although the patient was treated with chemotherapy, which consisted of ifosfamide and epirubicin, the tumor was unresponsive and he died 6 months later from disease progression. Careful long-term follow-up is mandatory for patients with hemangiopericytomas because recurrence with greater malignancy can develop following an extended disease-free interval.</p>
Keywords primary hemangiopericytoma recurrence mediastinal tumor
Amo Type Article
Published Date 2006-06
Publication Title Acta Medica Okayama
Volume volume60
Issue issue3
Publisher Okayama University Medical School
Start Page 197
End Page 200
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 16838049
Web of Science KeyUT 000238503600008