Hiroshi Tsubamoto

Hyogo College of Medicine, Nishinomiya, Hyōgo, Japan

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Publications (58)88.18 Total impact

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    ABSTRACT: Fig. 1. Treatment course for a patient with ovarian clear cell carcinoma (December 2014 to November 2015). PLD, pegylated liposomal doxorubicin at 40 mg/m2 every 28 days; wPTX, weekly paclitaxel at 80 mg/m2; VP-16, 50 mg of oral etoposide daily; Bev, 15 mg/kg of bevacizumab; Bev + wPTX, 15 mg/kg of bevacizumab every 21 days and weekly paclitaxel at 80 mg/m2; PE, pulmonary embolization.
    Preview · Article · Feb 2016
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    ABSTRACT: Purpose: The aim of this study was to establish a simple tool to predict good-quality embryos in in vitro fertilization (IVF) by using cumulus cells (CCs) or peripheral blood cells (PBCs). Methods: Mitochondrial DNA was extracted from CCs and PBCs in patients undergoing IVF. Using real-time polymerase chain reaction, mtDNA copy number in a single cell was calculated. Embryo quality was assessed when it was transferred or frozen. Results: CCs were obtained from 60 oocyte cumulus-cell complexes (OCCCs) in 30 women, and PBCs were collected from 18 women. For the 30 women in the study, the median age was 37 years old (range, 24-43), and the mean body mass index was 21.4 (standard error, 2.0). mtDNA content of CCs and PBCs was highly correlated (Pearson's r = 0.900, p < 0.0001). The median mtDNA content of CCs for good- and poor-quality embryos was 140 and 57, respectively (p < 0.0001). The median mtDNA content of PBCs for good- and poor-quality embryos was 36 and 13, respectively (p = 0.604). The logistic regression model indicated that mtDNA content in CCs was the only parameter that predicted good-quality embryos (p = 0.020). The receiver operating characteristic curve for obtaining good-quality embryos by mtDNA copy number in CCs had an area under the curve of 0.823, and using a threshold of 86, positive and negative predictive values were 84.4 and 82.1 %, respectively. Conclusions: The determination of mtDNA content in CCs can be used to predict good-quality embryos.
    No preview · Article · Jan 2016 · Journal of Assisted Reproduction and Genetics
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    ABSTRACT: Background: There exist limited therapeutic opportunities for the treatment of endometrial cancer (EC). Itraconazole, a common anti-fungal agent and a potent inhibitor of the Hedgehog pathway, has been shown to be clinically effective for various types of cancers, but its clinical efficacy for EC is unknown. Herein, we evaluated the efficacy of itraconazole in treating EC. Materials and Methods: We performed immunohistochemistry on EC tumour samples including serous endometrial intraepithelial carcinoma (SEIC). We further evaluated the in vitro efficacy of itraconazole for inhibiting proliferation and migration of EC cell lines. Results: Sonic Hedgehog and glioma-associated oncogene homolog 1 (GLI1) were expressed in SEIC and endometrioid adenocarcinoma. We found that itraconazole significantly inhibited tumour cell growth in both dose-dependent and time-dependent manners and inhibited migration of HEC-1A cells. Conclusion: Hedgehog signaling plays a role in carcinogenesis and malignant progression in EC. Itraconazole at a physiological dose may suppress progression of EC.
    No preview · Article · Jan 2016 · Anticancer research
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    ABSTRACT: Background: There exist limited therapeutic opportunities regarding the treatment of endometrial cancer (EC), and novel therapies based on the molecular profiling of EC cells are required. Materials and Methods: We used microarray analysis of EC tumour samples in order to identify tumour-specific changes regarding gene expression. Results: It was found that gremlin 2, an inhibitor of bone morphogenetic protein (BMP) signaling, was repressed in EC samples, and that gremlin 2 inhibited tumour cell growth. Conclusion: Down-regulation of gremlin 2 may lead to carcinogenesis and progression of EC. We suggest that reactivation of gremlin 2-associated pathways could suppress EC progression and should thus be explored as a potential novel therapeutic approach.
    No preview · Article · Jan 2016 · Anticancer research

  • No preview · Article · Nov 2015
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    ABSTRACT: We evaluated the efficacy and safety of itraconazole after first-line chemotherapy in patients with metastatic biliary tract cancer (BTC). We retrospectively reviewed data from patients with histologically-diagnosed BTC with distant metastases who had received one or more lines of chemotherapy and subsequent itraconazole chemotherapy. Among 28 enrolled patients, 26 (93%) received docetaxel (35 mg/m(2)), gemcitabine (1,000 mg/m(2)), and carboplatin (AUC4) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2, repeated every 2 weeks. Two patients received docetaxel plus itraconazole with irinotecan. Two complete responses and 14 partial responses were observed, with a response rate of 57%. The median overall survival was 12.0 months. During 160 cycles, 21 (75%) and 17 (61%) patients had grade 3/4 neutropenia and thrombocytopenia, respectively. Two patients (7%) experienced febrile neutropenia. Combination chemotherapy with itraconazole after first-line chemotherapy is promising for patients with metastatic BTC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    No preview · Article · Sep 2015 · Anticancer research
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    ABSTRACT: We experienced a rare case of uterine metastasis of non-small cell lung cancer in an 82-year-old Japanese woman revealed by detecting the same epidermal growth factor receptor (EGFR) gene mutation in both lung and endometrial biopsy specimens. The patient noticed abnormal genital bleeding at the first presentation. Further examination revealed huge masses in both lung and uterus. Biopsies from the lung and endometrium were performed. Although the pathological findings of both specimens showed similar adenocarcinomatous features including intracytoplasmic luminas, immunohistochemical analyses could not clarify whether these two tumors are lung metastasis of endometrial adenocarcinoma, uterine metastasis of lung adenocarcinoma or double primary adenocarcinomas of the lung and endometrium. Mutational analyses of EGFR gene using genomic DNA revealed that both lung and endometrial tumors had the same substitution mutation (L858R) at exon 21 which is often observed in lung adenocarcinomas. Since EGFR mutations are rarely detected in primary endometrial cancers and especially L858R mutation has not been reported in them, detection of the same L858R EGFR gene mutation in both lung and endometrial tumors strongly suggested that uterine tumor is the metastasis of lung adenocarcinoma. Mutational analyses might be useful to determine whether the tumor is primary or metastatic when the particular mutational types are observed in particular tumor types and/or particular organs.
    No preview · Article · Aug 2015 · Cancer Treatment Communications
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    ABSTRACT: We evaluated chemotherapy with itraconazole (a common anti-fungal agent that is a potent inhibitor of the Hedgehog pathway, P-glycoprotein, and angiogenesis) for treating progressive pancreatic cancer. We retrospectively reviewed the medical charts of patients with histologically-diagnosed pancreatic cancer who had received first- or second-line chemotherapy and subsequent chemotherapy with itraconazole. A total of 38 patients received docetaxel (35 mg/m(2)), gemcitabine (1,000 mg/m(2)), and carboplatin (area under the curve, 4 mg/min/ml) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2, repeated every 2 weeks. One complete response and 13 partial responses were observed, for a response rate of 37%. Eight (21%) patients experienced febrile neutropenia. The median overall survival was 11.4 months (95% confidence interval=8.5-21.2 months). Combination chemotherapy with itraconazole is promising for prolonging overall survival, with acceptable toxicities in the second-line setting of pancreatic cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    No preview · Article · Jul 2015 · Anticancer research
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    ABSTRACT: Highlights • Endometrial stromal sarcoma disseminated after morcellation • Complete remission of pelvic recurrence was achieved by oophorectomy. • Laparoscopic confirmation of remission of recurrent disease
    Preview · Article · Jan 2015
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    ABSTRACT: Background/aim: The identification of novel molecules associated with endometrial cancer (EC) development might offer less invasive surgery, better fertility preservation, and avoidance of unnecessary adjuvant therapy. Materials and methods: Microarray analysis was conducted using fresh surgically-obtained specimens from five EC patients and five cases with benign tumours. Additionally, immunohistochemical studies of the most highly expressed molecules were performed on paraffin-embedded tissues from these patients and others with stage IA, grade 1-2 EC (n=3) with or without (n=7) recurrent disease. Results: The most highly expressed gene in EC was chemokine ligand 18 (CCL18), with a 35.6-fold change compared to benign tumors. CCL18 expression was observed in tumor cells at the myometrial invasive front in 9 out of 11 tested samples. Conclusion: CCL18 expression was positively correlated with malignancy in EC. Further investigation with a larger number of samples or examination of serum CCL18 levels is warranted.
    No preview · Article · Oct 2014 · Anticancer research
  • Atsushi Morimoto · Hiroshi Tsubamoto · Kayo Inoue · Yuuki Ikeda · Seiichi Hirota
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    ABSTRACT: Several cases of the uterus being preserved after diagnosis of endometrial stromal sarcoma (ESS) have been reported. Most of these patients were alive and did not experience relapse, but this might have reflected the short follow-up period, given the indolent recurrence of ESS. We report the first fatal case of ESS 10 years after fertility-sparing management. A specimen obtained from the last operation showed loss of estrogen receptor status and expression of c-kit without c-kit or PDGFR-α gene mutations.
    No preview · Article · Sep 2014 · Journal of Obstetrics and Gynaecology Research
  • H Tsubamoto · S Takeuchi · K Ito · Y Miyagi · S Toyoda · K Inoue · R Kanazawa · Y Hosoda · H Shibahara
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    ABSTRACT: Ovarian and endometrial cancers diagnosed at advanced stages are often associated with malignant ascites. This study aimed to determine the safety, feasibility and efficacy of intraperitoneal (IP) docetaxel (TXT) for the treatment of ascites. A phase I study, including nine patients, was undertaken to determine the maximum tolerable dose. Efficacy was retrospectively assessed in 18 patients treated with 40-70 mg/m(2) IP TXT between 2005 and 2012. In a phase I study, the dose was safely escalated to a maximum of 70 mg/m(2), at which level no patients had grade -3 haematological adverse events. In a retrospective study of 18 patients, seven had an Eastern Cooperative Oncology Group performance status of 3; 16 had prior paclitaxel administration and two, with doses of 40 and 70 mg/m(2), experienced a serological response and a decrease in paracentesis. Thus, palliative treatment of recurrent OC should be further studied with 40 mg/m(2) among more patients, and 70 mg/m(2) could be evaluated for first-line IP chemotherapy.
    No preview · Article · Jul 2014 · Journal of Obstetrics and Gynaecology
  • Hiroshi Tsubamoto · Takashi Sonoda · Kayo Inoue
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    ABSTRACT: Background/aim: Recurrent triple-negative breast cancer (TNBC) patients have poor prognoses and limited treatment options, especially after progression during prior chemotherapy. The present study aimed to determine the impact of itraconazole with chemotherapy in these patients. Patients and methods: Medical records of recurrent TNBC patients receiving itraconazole with chemotherapy between 2008 and 2012 were retrospectively reviewed. Results: Thirteen patients who progressed during prior chemotherapy (12 with visceral organ metastases) were enrolled. All patients had received docetaxel, carboplatin, and gemcitabine with itraconazole. Additionally, 3 patients with pleural effusion and 2 with inflammatory breast cancer received bevacizumab. No febrile neutropenia, platelet transfusion, or chemotherapy-related death was observed during treatment with itraconazole. The response rate, median progression-free survival, and median overall survival were 62% (95% confidence interval (CI): 35-88%), 10.8 months (95%CI: 7.6-15.3 months), and 20.4 months (95%CI: 13.1-41.4 months), respectively. Conclusion: Chemotherapy with itraconazole is promising for heavily pre-treated TNBC patients.
    No preview · Article · Jul 2014 · Anticancer research
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    ABSTRACT: Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥50 mg/m(2)). Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy). Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each). Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV.
    Full-text · Article · May 2014 · Supportive Care in Cancer
  • Hiroshi Tsubamoto · Takashi Sonoda · Masaaki Yamasaki · Kayo Inoue
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    ABSTRACT: After progression during chemotherapy, persistent ovarian cancer rarely responds to cytotoxic agents. We evaluated the use of adjunctive itraconazole for treating refractory ovarian cancer. Medical records of patients with ovarian cancer were retrospectively reviewed to select those with a history of platinum and taxane administration, clinical progression within six months of the last platinum administration, continuation of chemotherapy after the first progression during chemotherapy. Among 55 patients, itraconazole in combination with chemotherapy was administered to 19 patients. The median progression-free survival (PFS) was 103 days and 53 days for chemotherapy with and without itraconazole, respectively (p=0.014). The corresponding median overall survival was 642 days and 139 days, respectively (p=0.006). The hazard ratio for PFS was 0.24 (p=0.002) and for overall survival was 0.27 (p=0.006) for therapy with itraconazole. Adjunctive itraconazole is promising for patients with refractory ovarian cancer.
    No preview · Article · May 2014 · Anticancer research
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    ABSTRACT: •Endometrioid adenocarcinoma may develop during the long-term follow-up of APA.•Atypical polypoid adenomyoma is a precursor of endometrioid adenocarcinoma.•Careful follow-up is needed for the conservative management of APA.
    Preview · Article · Apr 2014 · Gynecologic Oncology Reports
  • Hiroshi Tsubamoto · Takashi Sonoda · Masaaki Yamasaki · Kayo Inoue
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    ABSTRACT: Recurrent ovarian clear cell carcinoma (CCC) rarely responds to cytotoxic agents. Itraconazole is a potent inhibitor of the P-glycoprotein efflux pump, angiogenesis, and the Hedgehog pathway. We evaluated the efficacy of chemotherapy with itraconazole for CCC. Medical charts of patients with CCC who had received chemotherapy with itraconazole were retrospectively reviewed. Among nine patients with CCC, five had a history of progression with paclitaxel and carboplatin, and none had received prior treatment with bevacizumab or other targeted therapy. Eight patients received docetaxel (35 mg/m(2), day 1) and carboplatin-based (area under the curve, 4 mg·min(-1)·mL(-1); day 1) chemotherapy with an oral itraconazole solution (400 mg, days -2 to 2), repeated every two weeks. The response rate, median progression-free survival and overall survival were 44% (95% confidence interval [(CI)=12-77%], 544 days (95% CI=82-544 days) and 1,047 days (95% CI=462-1332 days), respectively. Chemotherapy with itraconazole is promising for patients with CCC.
    No preview · Article · Apr 2014 · Anticancer research
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    ABSTRACT: The ideal timing for transition to best supportive care (BSC) for ovarian cancer patients is not clear. We retrospectively assessed the survival benefit of continuing chemotherapy and hospice enrollment in late-stage ovarian cancer patients. Eligibility criteria included platinum and taxane treatment, clinical progression within 6 months of the last platinum dose, and progression during chemotherapy. Of the 55 eligible patients (median overall survival after first becoming refractory [1st Ref], 96 days), 22 received chemotherapy (Chemo group), two received radiation therapy, and 13 had medical contraindications for subsequent chemotherapy. The remaining 18 patients (BSC group) were compared with the Chemo group. The Chemo and BSC groups had similar background characteristics, except for the rate of consultation with a regional palliative care physician before or within 1 week of 1st Ref (9% vs 50%, respectively). In multivariate analysis, chemotherapy (hazard ratio 0.251, P = 0.005) and hospice enrollment (hazard ratio, 0.274, P = 0.023) were predictive factors of survival after 1st Ref. Chemotherapy after 1st Ref can be offered and hospice enrollment during the terminal stages is encouraged for recurrent ovarian cancer patients.
    No preview · Article · Mar 2014 · Journal of Obstetrics and Gynaecology Research
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    ABSTRACT: Patients with hereditary cancer need an integrated support system. A recently launched project was evaluated in terms of its efficacy in screening patients with hereditary cancer at the gynecologic service. The project team comprised gynecologists, surgeons, medical geneticists, and certified genetic counselors (CGCs) in our hospital. At the gynecologic service, a newly developed self-administered family history questionnaire (SAFHQ) was given to patients with ovarian, endometrial, or breast cancer as well as a history of multiple cancers. After an interview, a CGC constructed a pedigree and evaluated the risk for hereditary cancer. Patients at risk were recommended by a gynecologist to receive further genetic counseling at the Department of Genetics according to the modified Bethesda criteria, Amsterdam II criteria, and National Comprehensive Cancer Network (NCCN) guidelines 2012 for breast-ovarian cancer syndrome (HBOC). The numbers of newly screened patients were compared before and after the project launch. The SAFHQ was administered to 131 patients and 106 (81 %) pedigrees were constructed between August 2012 and July 2013. The number of newly screened patients according to the Bethesda criteria was 4 and 8 at 10 years before and 1 year after the project launch, respectively. Two and 31 patients met the NCCN criteria for HBOC excluding ovarian cancer alone, respectively, at these 2 time points. Of 54 patients who were recommended to undergo further counseling, 10 (19 %) visited the Department of Genetics. After the launch of an integrated support system, the number of patients with hereditary cancers who were screened increased. The gynecologic service played a pivotal role in patient and family care.
    No preview · Article · Dec 2013 · International Journal of Clinical Oncology
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    Yuji Ukita · Hiroshi Tsubamoto · Toru Kato · Shigeo Suno · Hiroaki Shibahara
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    ABSTRACT: Highlights • Glassy cell carcinoma (GCC) of the cervix is rare and aggressive. • A few case reports have described a response to intravenous chemotherapy for this malignancy. • This is the first report of a GCC case that responded to a combination of docetaxel and carboplatin.
    Preview · Article · Nov 2013 · Gynecologic Oncology Reports

Publication Stats

305 Citations
88.18 Total Impact Points

Institutions

  • 1995-2016
    • Hyogo College of Medicine
      • Department of Obstetrics and Gynecology
      Nishinomiya, Hyōgo, Japan
  • 2015
    • Meiwa Hospital
      Nishinomiya, Hyōgo, Japan