JaLCDOI 10.18926/AMO/31598
FullText URL fulltext.pdf
Author Kiura, Katsuyuki| Ohnoshi, Taisuke| Tabata, Masahiro| Shibayama, Takuo| Kimura, Ikuro|
Abstract A subline highly resistant to Adriamycin (SBC-3/ADM100) was isolated in vitro from the human small cell lung cancer cell line, SBC-3, by culturing in progressively higher concentrations of Adriamycin. The SBC-3/ADM100 cells were 106-fold more resistant to the drug than the parent cells in an inhibitory concentration of 50% determined by the MTT assay. The population-doubling time was much longer in SBC-3/ADM100 than in the parent cells. Northern blot hybridization revealed marked overexpression of the MDR1 mRNA in the resistant cells. P-glycoprotein overexpression and a decrease in intracellular accumulation of Adriamycin were demonstrated in SBC-3/ADM100, indicating that outward drug transport was the major mechanism of resistance in this subline. Additionally, a significant elevation of the intracellular glutathione content coupled with the glutathione S-transferase (GST) pi level and a decrease in DNA topoisomerase II (Topo II) activity were noted in this resistant subline. These results indicate that the mechanism of resistance to Adriamycin is multifactorial; involving altered growth characteristics, an enhanced outward transport, enhanced drug detoxification process, and decreased target enzyme activity. The resistant subline will serve as a useful tool in the search for ways to overcome drug resistance.
Keywords Adriamycin-resistant cell line MDR1 mRNA glutathione glutathione S-transferasse π DNA topoisomerase II
Amo Type Article
Published Date 1993-06
Publication Title Acta Medica Okayama
Volume volume47
Issue issue3
Publisher Okayama University Medical School
Start Page 191
End Page 197
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders Copyright © 1999 Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 8104372
Web of Science KeyUT A1993LL12400008
Related Url http://ousar.lib.okayama-u.ac.jp/metadata/6296
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/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 Science 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/53671
FullText URL 69_5_261.pdf
Author Nojima, Daisuke| Fujimoto, Nobukazu| Kato, Katsuya| Fuchimoto, Yasuko| Kiura, Katsuyuki| Kishimoto, Takumi| Tanimoto, Mitsune|
Abstract We investigated the clinical features of asbestos-induced diffuse pleural thickening (DPT) with severe respiratory compromise. We conducted a retrospective study of consecutive subjects with asbestos-induced DPT. Medical data such as initial symptoms, radiological findings, respiratory function test results, and clinical course were collected and analyzed. There were 24 patients between 2003 and 2012. All were men, and the median age at the development of DPT was 74 years. The top occupational category associated with asbestos exposure was dockyard workers. The median duration of asbestos exposure was 35.0 years, and the median latency from first exposure to the onset of DPT was 49.0 years. There were no significant differences in respiratory function test results between the higher and lower Brinkman index groups or between unilateral and bilateral DPT. Thirteen patients had a history of benign asbestos pleural effusion (BAPE), and the median duration from pleural fluid accumulation to DPT with severe respiratory compromise was 28.4 months. DPT with severe respiratory compromise can develop after a long latency following occupational asbestos exposure and a history of BAPE.
Keywords asbestos pleural thickening MRC dyspnea scale respiratory function test costophrenic angle
Amo Type Original Article
Published Date 2015-10
Publication Title Acta Medica Okayama
Volume volume69
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
Copyright Holders CopyrightⒸ 2015 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 26490022
Web of Science KeyUT 000365519600001
Author Hayakawa, Hiromi| Ichihara, Eiki| Ohashi, Kadoaki| Ninomiya, Takashi| Yasugi, Masayuki| Takata, Saburo| Sakai, Katsuya| Matsumoto, Kunio| Takigawa, Nagio| Tanimoto, Mitsune| Kiura, Katsuyuki|
Published Date 2013-11
Publication Title Cancer Science
Volume volume104
Issue issue11
Content Type Journal Article
Author Ninomiya, Takashi| Takigawa, Nagio| Ichihara, Eiki| Ochi, Nobuaki| Murakami, Toshi| Honda, Yoshihiro| Kubo, Toshio| Minami, Daisuke| Kudo, Kenichiro| Tanimoto, Mitsune| Kiura, Katsuyuki|
Published Date 2013-05
Publication Title Molecular Cancer Therapeutics
Volume volume12
Issue issue5
Content Type Journal Article
Author Takeda, Hiromasa| Takigawa, Nagio| Ohashi, Kadoaki| Minami, Daisuke| Kataoka, Itaru| Ichihara, Eiki| Ochi, Nobuaki| Tanimoto, Mitsune| Kiura, Katsuyuki|
Published Date 2013-02-15
Publication Title Experimental Cell Research
Volume volume319
Issue issue4
Content Type Journal Article
Author Kiura, Katsuyuki|
Published Date 2013-08-01
Publication Title 岡山医学会雑誌
Volume volume125
Issue issue2
Content Type Journal Article
Author Kiura, Katsuyuki| Tanimoto, Mitsune|
Published Date 2013-04-01
Publication Title 岡山医学会雑誌
Volume volume125
Issue issue1
Content Type Journal Article
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
JaLCDOI 10.18926/AMO/47260
FullText URL 65_6_353.pdf
Author Ichihara, Eiki| Kiura, Katsuyuki| Tanimoto, Mitsune|
Abstract Angiogenesis is an essential process in tumor growth. The concept of angiogenesis, when proposed by Folksman in 1971, had a great impact on cancer research and therapy, as the survival and proliferation of cancer depend on angiogenesis, which could be a target of cancer therapy. In subsequent decades, numerous antiangiogenic agents were developed, and some of them have been applied clinically. However, angiogenesis includes a complex and multistep process that has not been sufficiently elucidated. In this review, we focus on signaling pathways related with tumor angiogenesis and several antiangiogenic agents approved by the United States Food and Drug Administration or under investigation.
Keywords angiogenesis cancer
Amo Type Review
Published Date 2011-12
Publication Title Acta Medica Okayama
Volume volume65
Issue issue6
Publisher Okayama University Medical School
Start Page 353
End Page 362
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 22189475
Web of Science KeyUT 000298516900001
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
Author Ichihara, Eiki| Ohashi, Kadoaki| Takigawa, Nagio| Osawa, Masahiro| Ogino, Atsuko| Tanimoto, Mitsune| Kiura, Katsuyuki|
Published Date 2011-04-01
Publication Title 岡山医学会雑誌
Volume volume123
Issue issue1
Content Type Journal Article
JaLCDOI 10.18926/AMO/40503
FullText URL 64_5_285.pdf
Author Nishimori, Hisakazu| Takahashi, Shunji| Kiura, Katsuyuki| Ennishi, Daisuke| Kobayashi, Takayuki| Sano, Koji| Shinozaki, Eiji| Yokoyama, Masahiro| Mishima, Yuko| Terui, Yasuhito| Chin, Keisho| Mizunuma, Nobuyuki| Ito, Yoshinori| Nishimura, Seiichiro| Takeuchi, Kengo| Ishikawa, Yuichi| Oguchi, Masahiko| Tanimoto, Mitsune| Hatake, Kiyohiko|
Abstract We evaluated the efficacy and toxicity of cisplatin/docetaxel (CDDP/TXT) chemotherapy and identified prognostic factors in Japanese patients with cancer of unknown primary site (CUP). Twenty-eight consecutive patients seen at a single institute were reviewed retrospectively. Sixteen patients were treated with TXT 80mg/m2, followed by CDDP 75mg/m2. The overall response rate to CDDP/TXT treatment was 62.5%, with a median survival time (MST) of 22.7 months. Common adverse reactions were myelosuppression and hyponatremia. The MST of all 28 patients with CUP was 8.3 months, and the 1-year overall survival rate was 45.6%. Univariate analysis identified 5 prognostic factors:performance status, liver involvement, bone involvement, pleural involvement, and lymph node involvement. In conclusion, CDDP/TXT chemotherapy is effective with tolerable toxicity in patients with CUP. Japanese patients with CUP might be chemosensitive and may survive longer.
Keywords cancer of unknown primary site (CUP) cisplatin docetaxel prognosis
Amo Type Original Article
Published Date 2010-10
Publication Title Acta Medica Okayama
Volume volume64
Issue issue5
Publisher Okayama University Medical School
Start Page 285
End Page 291
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2010 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 20975761
Web of Science KeyUT 000283563300003
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 Science KeyUT A1992JL44200004