Nishisaitama Chuo National Hospital

Tokorozawa, Japan

Nishisaitama Chuo National Hospital

Tokorozawa, Japan
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Ikeda Y.,Ohki Memorial Kikuchi Cancer Center for Women | Ikeda Y.,University of Tokyo | Ikeda Y.,Kawakita General Hospital | Takano M.,Ohki Memorial Kikuchi Cancer Center for Women | And 11 more authors.
International Journal of Gynecological Cancer | Year: 2013

Combination therapy using gemcitabine with oxaliplatin (GEMOX) showed moderate activity in recurrent ovarian cancers. However, severe toxicities have been observed in patients who received full-dose therapy of GEMOX. On the other hand, bevacizumab enhances chemotherapeutic efficacy in various cancers. Here, we evaluated the effect of weekly low-dose administration of GEMOX in combination with bevacizumab (B-GEMOX) for patients with recurrent and refractory ovarian cancers (ROCs). Methods: A total of 19 patients with ROC were treated with B-GEMOX: 2 mg/kg of bevacizumab, 300 mg/m2 of gemcitabine, and 30 mg/m2 of oxaliplatin, 3 weeks on and 1 week off, q4weeks. The treatment was continued until development of severe toxicities or progressive disease. Tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors and Gynecologic Cancer Intergroup criteria. Results: Median number of the B-GEMOX therapy was 5 cycles. Response was observed in 4 (34%) cases by Response Evaluation Criteria in Solid Tumors, and in 2 (29%) cases by Gynecologic Cancer Intergroup criteria, resulting in overall response rate of 32%. Clinical benefit excluding progressive disease was obtained in 79% of the patients. Median progression-free survival was 4.5 months (range, 2Y16+ months). Toxicities were mild and mainly consisted of hematologic, gastrointestinal, and neuropathy; however, there were no nonhematologic toxicities more than grade 1. Conclusions: Weekly administration of B-GEMOX was active for patients with ROC and showed mild toxicities. These resultswarrant further prospective studies for patients withROC. © 2013 by IGCS and ESGO.


Takano M.,National Defense Medical College | Goto T.,National Defense Medical College | Hirata J.,National Defense Medical College | Furuya K.,National Defense Medical College | And 6 more authors.
European Journal of Gynaecological Oncology | Year: 2013

Introduction: Genotyping of UGT1A1 could be useful for prediction of severe toxicities for patients treated with irinotecan; however, genotype-based recommended dose (RD) has not been established. The aim of the present study was to determine the RD of irinotecan in combination with cisplatin (CPT-P) for individuals with or without UGT1A1 polymorphisms. Materials and Methods: According to polymorphisms of UGT1A1*28,*6, and*27, RDs were determined by three-case cohort methods for patients with wild-type and heterotype, and by inter-patient dose escalation for homotype patients. Pharmacokinetic studies were also evaluated. During May 2009 and July 2011, 18 Japanese patients were enrolled; 16 patients with ovarian carcinoma, and two cases with cervical cancer. The RD of irinotecan was determined as 50 mg/m 2 for the patients with wild-type, 40 mg/m2 for those with heterotype, and 30 mg/m2 for homotype UGT1A1 genotype. Results: Patients with homotype UGTlAl alleles had a significantly lower glucuronidation ratio in comparison with UGT1A1 wild-type and heterotype cases. Conclusion: UGT1A1 genotype-based RDs of irinotecan in CPT-P therapy were determined. Further studies to investigate efficacy of the RD including response evaluation are needed to confirm the present results.


Kobayashi H.,Nishisaitama Chuo National Hospital | Reid G.,University of Manitoba | Hadfield M.,University of Manitoba
Thrombosis Research | Year: 2014

Introduction: This study was undertaken to assess the influence of labor and cesarean section on endothelial function. Materials and Methods: Flow-mediated vasodilatation (FMD) was measured before and after delivery for an assessment of endothelial function in three groups: (1) the Vaginal delivery group (with spontaneous labor or induction of labor, n = 48), (2) the Elective C/S group (with a cesarean planned, n = 20), and (3) the C/S after FP group (scheduled for vaginal delivery but required to have an emergency cesarean section because of failure in progress, n = 11). Results: There were statistically significant changes between the antepartum and postpartum FMD values in the Vaginal delivery group and the Elective C/S group but not inthe C/S after FP group(P < 0.001, P = 0.023 and P = 0.22 respectively). Conclusions: These observations suggest that labor may enhance endothelial function and that cesarean section may impair endothelial function. © 2014 Elsevier Ltd. All rights reserved.


Yoshida A.,National Defense Medical College | Saito K.,Nishisaitama Chuo National Hospital | Ishii K.,Nishisaitama Chuo National Hospital | Azuma I.,Nishisaitama Chuo National Hospital | And 2 more authors.
Medical Devices: Evidence and Research | Year: 2013

Purpose: Using the Pronto-7® analyzer, we measured percutaneous hemoglobin (SpHb) noninvasively in pregnant and early postpartum women, and assessed the accuracy of the measurements by comparing them with laboratory measurements of hemoglobin. Methods: We obtained SpHb measurements from 193 pregnant women, 269 early postpartum women, and 76 nonpregnant women. A laboratory total hemoglobin (tHb) measurement, from venous blood sampling, was obtained immediately prior to the SpHb measurement. The total number of measurements obtained from the nonpregnant, pregnant, and postpartum women was 76, 438, and 347, respectively. Results: The mean biases (SpHb-tHb) among the nonpregnant, first trimester, second trimester, third trimester, and early postpartum women were -0.20, 0.19, 1.01, 1.32, and 1.10 g/dL, respectively. The Bland-Altman comparison showed neither the tendency of a fixed bias nor proportional biases among the measurements in the category of nonpregnant and first trimester women. But in the second and third trimester and postpartum category, a significant fixed bias was noted, without any tendencies of proportional bias. Conclusion: In this study, we found higher hemoglobin values with the Pronto-7 analyzer than were measured in the laboratory. We consider that the device has certain limitations in obstetrical utility and requires further modifications for use in the perinatal period. © 2014 Yoshida et al.


Takano M.,National Defense Medical College | Kikuchi Y.,Ohki Memorial Kikuchi Cancer Clinic for Women | Kudoh K.,Nishisaitama chuo National Hospital | Goto T.,National Defense Medical College | And 6 more authors.
International Journal of Clinical Oncology | Year: 2011

Clear cell carcinoma (CCC) of the ovary is well-known to be chemotherapy resistant compared with other histologic subtypes. An inhibitor against the mammalian target of rapamycin, temsirolimus (TEM) has been reported to be effective in renal CCC. Therefore, we investigated the effects of TEM in patients with CCC of the ovary. Six patients with CCC of the ovary who had been heavily pretreated by more than 4 regimens were given TEM: the cycle consisted of weekly TEM (10 mg/m 2) for 3 weeks followed by 1 week off. The treatment was continued until development of either progressive disease, or unmanageable adverse effects. Response evaluation was based upon the Response Evaluation Criteria in Solid Tumors version 1.0. Adverse effects were analyzed according to Common Terminology Criteria for Adverse Events version 3.0. The median cycle of weekly TEM was 3 (range 2-14). Among five cases in which responses could be evaluated, partial response was observed in one case (20%) and stabilized disease was seen in another case (20%). There were no toxicities greater than grade 3, and no case developed severe toxicity requiring discontinuation of weekly TEM. The patient who showed a partial response obtained a progression-free period of 14 months. In conclusion, weekly TEM shows a potential therapeutic benefit for patients with CCC of the ovary. Further studies including a translational approach are needed to select candidates for whom TEM therapy would be beneficial. © Japan Society of Clinical Oncology 2011.


Kudoh K.,Ohki Memorial Kikuchi Cancer Clinic for Women | Kudoh K.,Nishisaitama Chuo National Hospital | Takano M.,Ohki Memorial Kikuchi Cancer Clinic for Women | Takano M.,National Defense Medical College | And 9 more authors.
Gynecologic Oncology | Year: 2011

Objectives: Currently, pegylated liposomal doxorubicin (PLD) is regarded as one of the standard treatment options in recurrent ovarian cancers (ROC). Bevacizumab has shown significant antitumor activity for ROC in single-agent or in combination with cytotoxic agents. We have conducted a preliminary study to investigate effects of combination of bevacizumab and PLD for heavily pretreated patients with ROC. Methods: Thirty patients with ROC were treated with combination therapy with weekly bevacizumab and PLD, 2 mg/kg of continuous weekly bevacizumab and 10 mg/m2 of PLD (3 weeks on, 1 week off). The treatment was continued until development of disease progression, or unmanageable adverse effects. Response evaluation was based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and Gynecologic Cancer Intergroup (GCIG) CA125 response criteria. Adverse effects were analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Results: Overall response rate was 33%, and clinical benefit rate (CR + PD + SD) was 73%. Median progression-free survival was 6 months (range: 2-20 months), and a 6-months progression-free survival was 47%. Any hematological toxicities more than grade 3 were not observed. Two cases developed non-hematologic toxicities more than grade 2; a case with grade 3 hand-foot syndrome, another with grade 3 gastrointestinal perforation (GIP). The case with GIP was conservatively treated and recovered after 2 months, and there was no case with treatment-related death. Conclusion: The present investigation suggested that combination therapy with bevacizumab and PLD was active and well tolerated for patients with ROC. We recommend the regimen be evaluated in further clinical studies. © 2011 Elsevier Inc.


Nakamura A.,Hokkaido University | Hotsubo T.,Nippon Telegraph and Telephone | Kobayashi K.,Nishisaitama chuo National Hospital | Mochizuki H.,Saitama Childrens Medical Center | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Objective: Activating mutations in the calcium-sensing receptor (CASR) gene cause autosomal dominant hypoparathyroidism, and heterozygous inactivating CASR mutations cause familial hy-pocalciuric hypercalcemia. Recently, there has been a focus on the use of allosteric modulators to restore thefunctional activity of mutant CASRs. In this study, the effect of all osteric modulators NPS R-568 and NPS 2143 on CASR mutants was studied in vitro. Methods: DNA sequence analysis of the CASR gene was undertaken in autosomal dominant hy-poparathyroidism and familial hypocalciuric hypercalcemia Japanese patients, and the functional consequences for the Gi-MAPK pathway and cell surface expression of CASR were determined. Furthermore, we studied the effect of NPS R-568 and NPS 2143 on the signal transduction activity and cell surface expression of each mutant CASR. Results: We identified 3 activating mutations (S122C, P569H, and I839T) and 2 inactivating mutations (A110T and R172G) in patients. The activating and inactivating mutations caused leftward and rightward shifts, respectively, in the dose-response curves of the signaling pathway. NPS R-568 rescued the signal transduction capacity of 2 inactivating mutants without increasing cell surface expression levels. NPS 2143 suppressed the enhanced activity of the activating mutants without altering cell surface expression levels, although A843E, which is aconstitutively active mutant, was suppressed to a lesser degree. Conclusions: We have identified 4 novel mutations of CASR. Moreover, our results indicate that allosteric modulators can restore the activity of the loss- and gain-of-function mutant CASRs, identified in this study. Copyright © 2013 by The Endocrine Society.


PubMed | Nishisaitama Chuo National Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

5018 Background: Currently, pegylated liposomal doxprubicin (D) is used as one of the standard treatment options in recurrent or refractory ovarian cancer. Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded as a promising therapeutic target against ovarian cancers. Thus, we attempted to determine therapeutic effects of bevacizumab (B) on D in heavily pretreated patients with recurrent and progressed ovarian cancer.Thirty-eight patients with platinum-resistant recurrent or refractory ovarian cancers received at least more than 3 cycles of weekly B-D consisting of B: 2mg/kg and D: 10mg/mIn 24 RECIST-assessable cases, 2 (8%) had complete remission (CR) and 9 (38%) had partial remission (PR), resulting in response rate of 46%. Clinical benefit rate (CR+PR+SD) was 75%. Of 30 patients evaluable for CA125 response, 13 (43%) had a response (decrease of >50%), and 11 (37%) patients had not progressed (within doubling of CA125) following 6 months on treatment. Median progression-free survival (PFS) was 8 months. Any hematological adverse effect was not observed in the present study. Gastrointestinal perforation was observed in one case and was conservatively treatable. Although nasal bleeding was frequently observed, no treatment was required. An induced hypertension was also observed and manageable. Hand-foot syndrome was seen in 6 (16%) of 38 patients and treatment was required in three cases. Of note, Six (75%) of 8 cases with that did not respond to previous monthly D (50mg/m2) showed response to following weekly B-D.B seemed to enhance effect of D in platinum-resistant recurrent or refractory ovarian cancer patients. Weekly B-D warrants further clinical study in such clinical settings.


PubMed | Nishisaitama Chuo National Hospital
Type: | Journal: ISRN obstetrics and gynecology | Year: 2011

It was previously reported that the brachial-ankle pulse wave velocity (baPWV) is elevated in preeclamptic women. However, baPWV is strongly affected by blood pressure. Recently, a new index of vascular stiffness, the cardioankle vascular index (CAVI), was developed. CAVI is thought to be an index independent of blood pressure. We assessed CAVI in normotensive and hypertensive pregnant women. We studied a total of 109 Japanese women consisting of 23 nonpregnant healthy women (group A), 45 normotensive pregnant women (group B), 28 pregnant women complicated with established preeclampsia (group C), and 13 pregnant women with chronic hypertension (group D). The subject remained supine while the blood pressure, baPWV, and CAVI were recorded. No significant difference in baPWV was present between groups C and D, but the difference in CAVI was significantly high in group D. We believe that we can distinguish the vessel structural change between chronic hypertension and preeclampsia through simultaneous baPWV and CAVI measurements.


PubMed | University of Manitoba and Nishisaitama chuo National Hospital
Type: Journal Article | Journal: Thrombosis research | Year: 2014

This study was undertaken to assess the influence of labor and cesarean section on endothelial function.Flow-mediated vasodilatation (FMD) was measured before and after delivery for an assessment of endothelial function in three groups: (1) the Vaginal delivery group (with spontaneous labor or induction of labor, n = 48), (2) the Elective C/S group (with a cesarean planned, n = 20), and (3) the C/S after FP group (scheduled for vaginal delivery but required to have an emergency cesarean section because of failure in progress, n = 11).There were statistically significant changes between the antepartum and postpartum FMD values in the Vaginal delivery group and the Elective C/S group but not in the C/S after FP group (P < 0.001, P = 0.023 and P = 0.22 respectively).These observations suggest that labor may enhance endothelial function and that cesarean section may impair endothelial function.

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