National Cancer Center HospitalTokyo

Stem, Japan

National Cancer Center HospitalTokyo

Stem, Japan
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Makino Y.,National Cancer Center HospitalTokyo | Makino Y.,Showa UniversityTokyo | Watanabe M.,National Cancer Center HospitalTokyo | Watanabe M.,Showa UniversityTokyo | And 7 more authors.
Asia-Pacific Journal of Clinical Oncology | Year: 2016

Aim: Limited sampling points for both amrubicin (AMR) and its active metabolite amrubicinol (AMR-OH) were simultaneously optimized using Akaike's information criterion (AIC) calculated by pharmacokinetic modeling. Methods: In this pharmacokinetic study, 40 mg/m2 of AMR was administered as a 5-min infusion on three consecutive days to 21 Japanese lung cancer patients. Blood samples were taken at 0, 0.08, 0.25, 0.5, 1, 2, 4, 8 and 24 h after drug infusion, and AMR and AMR-OH concentrations in plasma were quantitated using a high-performance liquid chromatography. The pharmacokinetic profile of AMR was characterized using a three-compartment model and that of AMR-OH using a one-compartment model following a first-order absorption process. These pharmacokinetic profiles were then integrated into one pharmacokinetic model for simultaneous fitting of AMR and AMR-OH. After fitting to the pharmacokinetic model, 65 combinations of four sampling points from the concentration profiles were evaluated for their AICs. Stepwise regression analysis was applied to select the sampling points for AMR and AMR-OH to predict the area under the concentration–time curves (AUCs) at best. Results: Of the three combinations that yielded favorable AIC values, 0.25, 2, 4 and 8 h yielded the best AUC prediction for both AMR (R2 = 0.977) and AMR-OH (R2 = 0.886). The prediction error for AUC was less than 15%. Conclusion: The optimal limited sampling points of AMR and AMR-OH after AMR infusion were found to be 0.25, 2, 4 and 8 h, enabling less frequent blood sampling in further expanded pharmacokinetic studies for both AMR and AMR-OH. © 2016 John Wiley & Sons Australia, Ltd


PubMed | Kyoto Prefectural University of Medicine and National Cancer Center HospitalTokyo
Type: Journal Article | Journal: American journal of cancer research | Year: 2016

Several studies have demonstrated that YWHAZ (14-3-3), included in the 14-3-3 family of proteins, is implicated in the initiation and progression of cancers. To detect a novel treatment target for adenocarcinoma of the esophagogastric junction (AEG), we tested whether YWHAZ acted as a cancer-promoting gene through its overexpression in AEG. We analyzed YWHAZ protein expression in 92 consecutive primary AEG tumors, which had been curatively resected in our institution between 2000 and 2010. Overexpression of the YWHAZ protein was frequently detected in primary AEG tumor samples (46% (42/92)). Overexpression of YWHAZ was significantly correlated with Siewert type III tumor, larger tumor size (40 mm) and higher rates of lymph node metastasis and recurrence. Patients with YWHAZ-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (


Arai Y.,Kyoto University | Aoki K.,Kyoto University | Takeda J.,Kyoto University | Kondo T.,Kyoto University | And 14 more authors.
Journal of Hematology and Oncology | Year: 2015

Background: Addition of high-dose cytarabine (HDCA) to the conventional cyclophosphamide/total-body irradiation (CY/TBI) regimen significantly improved prognosis after cord blood transplantation (CBT) for adult acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The efficacy of HDCA in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT), however, has not yet been elucidated. Findings: We conducted a cohort study to compare the prognosis of HDCA/CY/TBI (N = 435) and CY/TBI (N = 1667) in BMT/PBSCT for AML/MDS using a Japanese transplant registry database. The median age was 38 years, and 86.0 % of the patients had AML. Unrelated donors comprised 54.6 %, and 63.9 % of donors were human leukocyte antigen (HLA)-matched. Overall survival (OS) was not improved in the HDCA/CY/TBI group (adjusted hazard ratio (HR), 1.14; p = 0.13). Neutrophil engraftment was inferior (HR, 0.80; p < 0.01), and the incidence of hemorrhagic cystitis and thrombotic microangiopathy increased in HDCA/CY/TBI (HR, 1.47 and 1.60; p = 0.06 and 0.04, respectively), leading to significantly higher non-relapse mortality (NRM; HR, 1.48; p < 0.01). Post-transplant relapse and tumor-related mortality were not suppressed by the addition of HDCA. Conclusions: This study indicated the inefficacy of HDCA/CY/TBI in BMT/PBSCT for AML/MDS. Our results should be validated in large-scale prospective studies. © 2015 Arai et al.


Kitazono S.,National Cancer Center Hospital | Kitazono S.,Cancer Institute Hospital | Fujiwara Y.,National Cancer Center Hospital | Fujiwara Y.,National Cancer Center HospitalTokyo | And 12 more authors.
Clinical Lung Cancer | Year: 2015

Background Several studies have assessed the expression of programmed death-ligand 1 (PD-L1) in resected surgical specimens of non-small-cell lung cancer (NSCLC). However, the expression of PD-L1 in smaller biopsy samples of advanced NSCLC has not been reported. Patients and Methods A total of 79 patients with NSCLC at our institution with available biopsy samples and resected specimens were retrospectively enrolled in the present study. PD-L1 expression was assessed by immunohistochemistry and scored using the hybrid scoring method. The concordance rates for the expression of PD-L1 between the 2 samples were analyzed. Results The pathologic stage of the patients (51 men, 28 women; median age, 68 years) was stage I in 37, stage II in 18, and stage III in 24. The diagnostic procedures included transbronchial biopsy in 59, transbronchial needle aspiration biopsy in 14, and computed tomography (CT)-guided needle biopsy in 6. The positivity rate of PD-L1 in these samples was 38.0% (27 transbronchial biopsies, 6 transbronchial needle aspiration biopsies, 3 CT-guided needle biopsies) versus 35.4% in the resected specimens. The median hybrid score was 0 (range, 0-170), and the mean score was 28.7 ± 43.4. Comparing the biopsy samples and resected specimens with a score of ≥ 1 as positive for PD-L1 staining, 6 tumors were discordant for PD-L1 expression and 73 were concordant, for a concordance rate of 92.4% and κ value of 0.8366. Conclusion PD-L1 status showed good concordance between the biopsy samples and resected specimens. These small samples, even those derived from transbronchial needle aspiration biopsies, appear adequate for the assessment of PD-L1 expression. © 2015 Elsevier Inc.

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