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  • 1
    Online Resource
    Online Resource
    Phase II study of amrubicin (AMR) combined with carboplatin (CBDCA) for refractory relapsed small cell lung cancer (SCLC): North Japan Lung Cancer Group 0802.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 7086-7086
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 7086-7086
    Abstract: 7086 Background: AMR, a new anthracycline agent, has achieved some promising results for advanced SCLC both in the first-line and the second-line setting. However the efficacy of AMR alone against refractory relapsed SCLC was relatively low in previous studies. This study was conducted to evaluate the safety and efficacy of the combination of AMR plus CBDCA in patients with refractory relapsed SCLC. Methods: Patients with advanced SCLC who relapsed within 90 days after the completion of first-line chemotherapy received AMR (30 mg/m 2 , day1-3) and CBDCA (AUC 4.0, day 1) every 3 weeks. The primary endpoint of this study was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 45% in eligible patients would indicate potential usefulness while ORR of 20% would be the lower limit of interest, with alpha = 0.10 and beta = 0.10, at least 24 patients were required. Results: From September 2008 to May 2011, 30 patients were enrolled from 10 institutions. One patient was excluded because of ineligible histology. Patient characteristics were: Male/Female 26/3; median age 67 (range 50-81); Performance status 0/1/2 9/16/4. The median number of treatment cycles were 4 (range 1-7). The objective responses evaluated by RECIST were: CR 0, PR 10, SD 14, PD 5. The ORR was 34% and the disease control rate was 83%. Median PFS was 3.5 months and median survival time was 7.3 months. Grade 3-4 neutropenia was observed in 23 patients (79%) and grade 3-4 thrombocytopenia was observed in 7 patients (24%). One patient (3%) suffered from grade 3-4 febrile neutropenia. Other grade 3 non-hematological toxicities such as infection, interstitial lung disease, hyponatremia, hypoglycemia, were observed in 7 patients (24%). No treatment related death was observed. Conclusions: This is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated. Further investigation of this treatment is warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.7086
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Phase II study of amrubicin (AMR) and carboplatin (CBDCA) for invasive thymoma (IT) and thymic carcinoma (TC): NJLCG0803.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 7530-7530
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 7530-7530
    Abstract: 7530 Background: There has been no standard chemotherapy for advanced thymic malignancies including IT and TC although anthracycline or platinum agents have been commonly used for them. AMR, a new anthracycline agent, was approved for lung cancer in Japan and we had previously conducted some prospective studies of AMR combined with CBDCA for patients with small-cell lung cancer, which revealed this regimen was active with acceptable toxicity. The objective of this study is to evaluate the efficacy and safety of this combination for patients with advanced thymic malignancies. Methods: Patients with histologically confirmed thymic malignancies received AMR (35 mg/m2, day1-3) and CBDCA (AUC 4.0, day1) every 3 weeks. Patients who underwent previous chemotherapy received reduced dose of AMR (30 mg/m2). The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 75% and 45% would indicate the potential usefulness while ORR of 50% and 20% would be the lower limit of interest, with alpha = 0.10 and beta = 0.20, for IT patients and TC patients, respectively, 18 IT patients and 16 TC patients were at least required. Results: From December 2008 to October 2012, 51 patients (18 IT and 33 TC) were enrolled from 20 institutions in Japan. Patients’ characteristics are as follows; male/female 35/16; median age 66 (range 39-78); performance status 0/1 24/27. The ORR and disease control rate were 17% and 89% in IT, and 30% and 85% in TC. Preliminary median PFS was 7.6 months in both groups. Toxicity was generally moderate and no treatment related death was observed. Conclusions: This is the largest prospective study of chemotherapy for advanced thymic malignancies. AMR combined with CBDCA was effective for TC patients with acceptable toxicities. Clinical trial information: R000001598.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.7530
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Abstract 1793: Imatinib treatment for gefitinib-resistant lung cancer harboring epidermal growth factor receptor mutation
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 1793-1793
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 1793-1793
    Abstract: Background: Epidermal growth factor receptor (EGFR) mutant-lung cancer showed significant response to EGFR-tyrosine kinase inhibitor (TKI) treatment, however, treatment failure due to acquired resistance to EGFR-TKI become important clinical problem for long-term survivors. Our purpose is to develop the new treatment for EGFR-TKI resistance. Methods: We used PC9 human lung cancer cell line harboring EGFR exon 19 deletion (E746-A750). When PC9 cells were cultured with 2 μM gefitinib solved in dimethylsulfoxide (DMSO), most of cells died and surviving cells proliferated slowly. By 90 days-culture with 2 μM gefitinib, PC9 gefitinib resistant cells (PC9GR90) were established and confirmed that EGFR-T790M resistance-related mutation was negative. In PC9GR90, an immunoblot assay revealed MET (hepatocyte growth factor receptor) amplification and alternative EGFR3 tyrosine phosphorylation, which is known as one of the major resistant mechanisms. Results: When PC9GR90 were cultured with 2 μM gefitinib and one inhibitor (histone deacetylase inhibitor, insulin-like growth factor receptor inhibitor, gamma secretase inhibitor, or imatinib known as bcr-abl, c-kit and platelet derived growth factor receptor inhibitor), 10 μM imatinib treatment with gefitinib showed significant suppression of cell growth. The ratio of cell count of 2 μM gefitinib/DMSO and 10 μM imatinib with 2 μM gefitinib/DMSO were 91.7% and 6.0%, respectively. When imatinib concentration was decreased to 1 μM known as appropriate concentration for chronic myeloid leukemia treatment, there was no effect. The imatinib effect was not shown for NCI-H1975 lung cancer cells harboring both EGFR-L858R and -T790M. By immunoblot, we found EGFR3 phosphorylation was inhibited by imatinib treatment. Conclusion: It is the first report that imatinib inhibits EGFR3 phophorylation and induce cell death in the EGFR-TKI resistant lung cancer with MET amplification and EGFR3 phophorylation. Although further studies are required to apply this strategy to a clinical setting, we demonstrate a hopeful data to conquer one important resistant mechanism. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1793. doi:1538-7445.AM2012-1793
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-1793
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    Online Resource
    Online Resource
    Randomized phase II trial of carboplatin combined with weekly paclitaxel (CP) and docetaxel alone (D) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): NJLCG 0801.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 7565-7565
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 7565-7565
    Abstract: 7565 Background: Standard first-line chemotherapy for elderly NSCLC pts has been considered as a monotherapy with vinorelbine or gemcitabine globally. However, we have demonstrated the high efficacy of CP for elderly pts in our previous trial (Ann Oncol 2010). Meanwhile, D has been considered as an alternative option for this population in Japan according to the result of WJTOG9904 (JCO 2006). Thus we compared the two regimens to select the proper candidate for future phase III trial. Methods: Eligible pts were aged 70 years or older with newly diagnosed stage IIIB/IV NSCLC; ECOG performance status 0-1; adequate organ function; written informed consent. Pts were randomized to receive carboplatin (AUC 6) on day 1 and paclitaxel (70mg/m 2 on day 1, 8, and 15) every 4 weeks or D (60mg/m 2 on day 1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival, and toxicity profile. Assuming that ORR of 40% would be potential usefulness while ORR of 20% would be the lower limit of interest, 40 pts in each arm were required if expect 10% loss to follow up. Results: Between July 2006 and September 2010, 84 pts were enrolled and 41 pts in CP arm and 42 pts in D arm were eligible (median age, 76 years; 75% male; 72% stage IV). Median treatment cycle was 4 in each arm (CP, range 1-6; D, range 1-8). ORRs were 51% (95%CI: 36-66%) and 26% (95%CI: 12-39%) in the CP and D arm, respectively. With a median follow-up of 18.4 months, median PFS were 6.5 and 3.9 months in the CP and D arm, respectively (Logrank, P=0.0027). Grade 3 or severer toxicities were as follows: neutropenia (CP, 56% and D, 79%), anemia (CP, 15% and D, 7%), thrombocytopenia (CP, 10% and D, 0%), infection (CP, 20% and D, 25%). One treatment-related death due to neutropenia, pneumonia, and lethal arrhythmia occurred in D arm but none in CP arm. Conclusions: The platinum doublet CP achieved higher activity with an acceptable toxicity profile for elderly pts with advanced NSCLC compared to monotherapy with D. The superiority of CP to the monotherapy in this trial is consistent with results of recent IFCT-0501 trial (Lancet 2011).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.7565
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Vaccination of Dendritic Cells Loaded with Interleukin-12-Secreting Cancer Cells Augments In vivo Antitumor Immunity: Characteristics of Syngeneic and Allogeneic Antigen-Presenting Cell Cancer Hybrid Cells
    American Association for Cancer Research (AACR) ; 2005
    In:  Clinical Cancer Research Vol. 11, No. 1 ( 2005-01-01), p. 58-66
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 11, No. 1 ( 2005-01-01), p. 58-66
    Abstract: Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-γ production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.58.11.1
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2005
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 6
    Online Resource
    Online Resource
    Bilateral Peripheral Infiltrates Refractory to Immunosuppressants were Diagnosed as Autoimmune Pulmonary Alveolar Proteinosis and Improved by Inhalation of Granulocyte/Macrophage-Colony Stimulating Factor
    Japanese Society of Internal Medicine ; 2012
    In:  Internal Medicine Vol. 51, No. 13 ( 2012), p. 1737-1742
    Details
    In: Internal Medicine, Japanese Society of Internal Medicine, Vol. 51, No. 13 ( 2012), p. 1737-1742
    Type of Medium: Online Resource
    ISSN: 0918-2918 , 1349-7235
    URL: Article
    DOI: 10.2169/internalmedicine.51.6093
    RVK:
    XA 49642
    Language: English
    Publisher: Japanese Society of Internal Medicine
    Publication Date: 2012
    detail.hit.zdb_id: 2202453-0
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  • 7
    Online Resource
    Online Resource
    Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice
    Rockefeller University Press ; 2003
    In:  The Journal of Experimental Medicine Vol. 197, No. 5 ( 2003-03-03), p. 669-674
    Details
    In: The Journal of Experimental Medicine, Rockefeller University Press, Vol. 197, No. 5 ( 2003-03-03), p. 669-674
    Abstract: Secretory leukoprotease inhibitor (SLPI) protects tissue against the destructive action of neutrophil elastase at the site of inflammation. Recent studies on new functions of SLPI have demonstrated that SLPI may play a larger role in innate immunity than merely as a protease inhibitor. To clarify the functions of SLPI in bacterial infections, we generated SLPI-deficient mice (SLPI−/− mice) and analyzed their response to experimental endotoxin shock induced by lipopolysaccharide (LPS). SLPI−/− mice showed a higher mortality from endotoxin shock than did wild type mice. This may be explained in part by our observation that SLPI−/− macro-phages show higher interleukin 6 and high-mobility group (HMG)-1 production and nuclear factor κB activities after LPS treatment than do SLPI+/+ macrophages. SLPI also affects B cell function. SLPI−/− B cells show more proliferation and IgM production after LPS treatment than SLPI+/+ B cells. Our results suggest that SLPI attenuates excessive inflammatory responses and thus assures balanced functioning of innate immunity.
    Type of Medium: Online Resource
    ISSN: 1540-9538 , 0022-1007
    URL: Article
    DOI: 10.1084/jem.20021824
    RVK:
    XA 10000
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2003
    detail.hit.zdb_id: 1477240-1
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