Tadao Tanaka

The Jikei University School of Medicine, Edo, Tōkyō, Japan

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Publications (93)201.84 Total impact

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    ABSTRACT: Placental mesenchymal dysplasia (PMD) is a rare vascular anomaly characterized by mesenchymal stem villous hyperplasia. Accurate differential diagnosis of PMD is crucial to predict fetal outcomes associated with serious obstetrical complications. We reviewed the clinical and pathological features and immunohistochemical and imaging findings of three patients with PMD. First trimester sonographic cystic findings identified molar pregnancy or PMD. However, PMD was highly suspected according to the maternal serum human chorionic gonadotropin (hCG) titers, fetal karyotypes, and imaging findings. The outcome of patient 1, in whom placental multicystic areas decreased as pregnancy progressed, was a live birth. In contrast, the babies of patients 2 and 3 were stillborn, and multicystic formations detected during the first trimester completely and consistently occupied the placentas. Pathological and immunohistochemical analyses using anti-CD34 and anti-D2-40 antibodies distinguished the cisternae from multiple small vessels in the villi. Immunohistochemical analyses using anti-CK7 and anti-Ki-67 antibodies did not detect excessive proliferation of trophoblasts. Most abnormal villi associated with PMD comprised stromal cells that did not react with an anti-p57 In patients with PMD, if the percentage of the normal placental area decreases as pregnancy progresses, the possibility of fetal growth restriction and intrauterine fetal demise should always be considered. The immunostaining pattern of CD34 and D2-40 may represent a unique feature of PMD and can provide supporting evidence for the differential diagnosis of PMD.
    No preview · Article · Jan 2015

  • No preview · Article · Oct 2013 · Placenta
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    ABSTRACT: Despite the use of retroviral vectors, efficiently introducing target genes into immunocytes such as T cells is difficult. In addition, retroviral vectors carry risks associated with the oncogenicity of the native virus and the potential for introducing malignancy in recipients due to genetic carryover from immortalized cells used during vector production. To address these issues, we have established a new virus vector that is based on human herpesvirus 6 (HHV-6), a non-oncogenic lymphotropic herpesvirus that infects CD4(+) T cells, macrophages, and dendritic cells. In the present study, we have altered the cell specificity of the resulting recombinant HHV-6 by knocking out the U2-U8 genes. The resulting virus proliferated only in activated cord blood cells and not in peripheral blood cells. Umbilical cord blood cells produced replication-defective recombinant virus in sufficiently high titer to omit the use of immortalized cells during vector production. HHV-6 vectors led to high rates (>90%) of gene transduction in both CD4(+) and CD8(+) T cells. These viruses showed low-level replication of viral DNA that supported greater expression of the induced genes than that of other methods but that was insufficient to support the production of replication-competent virus. Furthermore, HHV-6 vectors containing short hairpin RNAs against CD4 and HIV Gag remarkably inhibited the production of these proteins and HIV particles. Here we demonstrate the utility of HHV-6 as a new non-carcinogenic viral vector for immunologic diseases and immunotherapy.
    Full-text · Article · Feb 2013 · PLoS ONE
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    ABSTRACT: The pentaspan membrane glycoprotein CD133 (also known as prominin-1) has been widely used as a marker for both cancer and normal stem cells. However, the function of CD133 has not been elucidated. Here we describe a cancer stem cell line established from clear cell carcinoma of the ovary (CCC) and show that CD133 interacts with plakoglobin (also known as γ-catenin), a desmosomal linker protein. We further demonstrate that knockdown of CD133 by RNA interference (RNAi) results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. We speculate that CD133 may be a promising target for cancer chemotherapy.
    Full-text · Article · Jan 2013 · PLoS ONE
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    ABSTRACT: Cytokine expression in a tumor microenvironment can impact both host defense against the tumor and tumor cell survival. In this study, we sought to clarify whether the cytokine gene expression profile could have clinical associations with ovarian cancer. We analyzed the expression of 16 cytokine genes (IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-γ, TNF-α, IL-6, HLA-DRA, HLA-DPA1 and CSF1) in 50 ovarian carcinomas. Hierarchical clustering analysis of these tumors was carried out using Cluster software and differentially expressed genes were examined between clear cell carcinoma (CCC) and other subtypes. Following this examination we evaluated the biological significance of IL-6 knockdown in CCC. Unsupervised hierarchical clustering analysis of cytokine gene expression revealed two distinct clusters. The relationship between the two clusters and clinical parameters showed statistically significant differences in CCC compared to other histologies. CCC showed a dominant Th-2 cytokine expression pattern driven largely by IL-6 expression. Inhibition of IL-6 in CCC cells suppressed Stat3 signaling and rendered cells sensitive to cytotoxic agents. The unique cytokine expression pattern found in CCC may be involved in the pathogenesis of this subtype. In particular, high IL-6 expression appears likely to be driven by the tumor cells, fueling an autocrine pathway involving IL-6 expression and Stat3 activation and may influence survival when exposed to cytotoxic chemotherapy. Modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for CCC.
    Preview · Article · Jun 2012 · International Journal of Oncology

  • No preview · Article · Jun 2012 · Nippon rinsho. Japanese journal of clinical medicine
  • Tadao Tanaka · Satoshi Yanagida · Nozomu Yanaihara

    No preview · Article · Jun 2012 · Nippon rinsho. Japanese journal of clinical medicine
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    ABSTRACT: Choriocarcinoma is a highly malignant tumor of trophoblastic origin. Most cases occur in association with preceding gestational events. However, on very rare occasions, nongestational choriocarcinoma arises from germ cell or trophoblastic differentiation in different types of carcinoma. This article reports the case of a 58-year-old woman with primary nongestational choriocarcinoma of the uterus that developed 19 years after her final pregnancy and 4 years after menopause. A total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological examination showed choriocarcinoma of the uterus without components of other germ cell tumors. Karyotype analysis of the tumor cells demonstrated XX. We confirmed its nongestational origin by DNA polymorphism analysis at 15 short tandem repeat loci. After surgery, the patient was given four courses of combination chemotherapy. She is still alive and there has been no evidence of recurrence 3 years after surgery.
    No preview · Article · May 2012 · International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists
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    ABSTRACT: Aim: The optimal chemotherapy regimen for patients with endometrial cancer has not been established. We assessed the feasibility of paclitaxel plus carboplatin (TC) for postoperative chemotherapy in patients with endometrial cancer. Material and Methods: Patients with newly diagnosed endometrial cancer received TC (paclitaxel 180 mg/m2, carboplatin AUC6 mg/mL/min) every three weeks. Treatment was continued until disease progression or completion of six cycles. Toxicities were evaluated every cycle according to NCI-CTCAE version 3.0. Results: Sixty patients were registered from December 2005 through November 2006. Forty-four of 60 (73.3%) cases completed all of the planned six cycles. Grades 3 and 4 hematologic toxicities were observed as follows: leukopenia (61.7%), neutropenia (95.0%), anemia (21.7%), and thrombocytopenia (5.0%). There were six patients who dropped out from the protocol by neutropenia. Grade 3 non-hematologic toxicities were observed as follows: nausea (3.3%), vomiting (1.7%), neuropathy (5.0%), myalgia (6.7%) and constipation (1.7%). No grade 4 non-hematologic toxicity was observed. Conclusion: This TC regimen is feasible for endometrial cancer patients.
    No preview · Article · May 2012 · Journal of Obstetrics and Gynaecology Research
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    ABSTRACT: Aim: Several previous reports showed that irinotecan hydrochloride plus cisplatin (CPT-P) was a candidate first-line chemotherapy regimen for clear cell adenocarcinoma of the ovary (CCC). However, long-term survival in CCC patients treated with CPT-P as first-line chemotherapy remains to be determined. The aim of the present study was to evaluate the long-term results of CPT-P as first-line chemotherapy for CCC. Material and Methods: We performed a retrospective review of 31 patients with CCC who were treated with CPT-P between 1996 and 2004. Results: The median follow-up period was 91 months. The estimated 8-year overall survival (OS) rate in all patients was 64.5%, while the rate in 18 stage I, 21 stage I/II, and 10 stage III/IV patients was 88.9%, 85.7%, and 20.0%, respectively. The estimated 8-year OS rate in patients with pT1/pT2 disease was 87.0%, while the 3-year OS rate in patients with pT3 disease was 0%. Univariate analysis using the log–rank test revealed that Eastern Cooperative Oncology Group performance-status 1, pT3 stage, and presence of residual disease (stage II-IV) were significantly correlated with shortened patient survival. Multiple regression analysis revealed that pT3 predicted worse OS in patients with CCC than pT1 (P < 0.001) or pT2 disease (P < 0.005). Conclusion: The long-term results suggest CPT-P as a candidate in first-line chemotherapy for CCC in not only stage I, but also in optimally debulked stage II-IV patients with pT1/pT2 disease.
    No preview · Article · May 2012 · Journal of Obstetrics and Gynaecology Research
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    ABSTRACT: CD147 is a membrane glycoprotein that is expressed in various cancer cells and is involved in tumor invasion and metastasis by inducing stromal fibroblastic cells to produce matrix metalloproteinases. This study was carried out to evaluate the correlation between CD147 expression and various clinicopathologic parameters, including histological grade and prognosis in a small sample set of human ovarian cancer patients. Paraffin-embedded surgical tissue samples from 25 patients with ovarian serous and endometrioid adenocarcinoma were stained with anti-CD147 antibody (monoclonal antibody 12C3: MoAb 12C3) for immunohistochemical analysis. CD147 protein was expressed in 84.0% (21 of 25 cases) of cancerous lesions, but not in normal lesions. CD147 expression by ovarian cancer cells was inversely correlated with overall survival. There was no correlation between CD147 expression and histological grade. These results suggest that measurement of CD147 expression may enhance the understanding of the pathophysiology of epithelial ovarian cancer.
    No preview · Article · May 2012 · Journal of Obstetrics and Gynaecology Research
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    ABSTRACT: A pregnant Japanese female was referred to our hospital due to intrauterine fetal growth restriction. A prenatal diagnosis of right pulmonary agenesis could be made using ultrasonography and fetal magnetic resonance imaging, and a Caesarian section was performed at 34 weeks of gestation. The infant developed a respiratory disorder immediately, received systemic management in the neonatal intensive care unit (NICU), and was discharged at age of 103 days without any severe sequelae.
    No preview · Article · Apr 2012 · Journal of Medical Ultrasonics
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    ABSTRACT: Female adnexal tumors of probable Wolffian origin (FATWOs) are rare neoplasms that originate from remnants of the Wolffian duct. These tumors often appear in the broad ligament and para-ovarian area where such remnants exist. FATWOs have specific pathological characteristics similar to those of remnants of the Wolffian duct. Since these tumors neither have any specific tumor markers nor specific features on scanning images, there has been no case report concerning the preoperative diagnosis of FATWOs. Diagnostic imaging technology has become remarkably developed nowadays, enabling physicians to make preoperative diagnosis more precisely. We report here a case of FATWO with detailed discussion of its MR images.
    No preview · Article · Apr 2012
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    ABSTRACT: Ovarian clear cell carcinoma (OCCC) has several significant characteristics based on molecular features that are distinct from those of ovarian high-grade serous carcinoma. Cellular glycogen accumulation is the most conspicuous feature of OCCC and in the present study its metabolic mechanism was investigated. The amount of glycogen in cells cultured under hypoxia increased significantly and approximately doubled after 48 h (P<0.01) compared to that under normoxic conditions. Periodic acid-Schiff positive staining also demonstrated intracellular glycogen storage. Western blot analysis revealed that HIF1α, which was overexpressed and stabilized under hypoxic conditions, led to an increase in the levels of cellular glycogen synthase 1, muscle type (GYS1), and conversely to a decrease in inactive phosphorylated GYS1 at serine (Ser) 641. Additional increases were observed in both protein phosphatase 1, which dephosphorylates and thereby induces GYS1 enzyme activity, and glycogen synthase kinase 3 beta (GSK3β) phosphorylated at Ser9, which is inactive on phosphorylation of GYS1 and subsequently induces its enzyme activity. By contrast, the level of PYGM-b decreased. These results indicated that the glycogen accumulation under a hypoxic environment resulted in the promotion of glycogen synthesis, but did not lead to inhibition of glycogen degradation and/or consumption. Under hypoxic conditions, HAC2 cells showed activation of the PI3K/AKT pathway caused by a mutation in exon 20 of PIK3CA, encoding the catalytic subunit p110α of PI3K. The resulting activation of AKT (phosphoSer473) also plays a role as a central enhancer in glycogen synthesis through suppression of GSK3β via phosphorylation at Ser9. Hypoxia decreased the cytocidal activity of cisplatin and doxorubicin to various degrees. In conclusion, the hypoxic conditions together with HIF1 expression and stabilization increased the intracellular glycogen contents and resistance to the anticancer drugs.
    Full-text · Article · Mar 2012 · International Journal of Oncology
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    ABSTRACT: Adenomyosis patients treated with dienogest are considered to be at higher risk of uterine bleeding; however, the mechanisms which cause severe uterine bleeding in those patients are unknown. This study aims to investigate the risk factors of uterine bleeding among adenomyosis patients treated with dienogest. Clinical data of 51 adenomyosis patients treated with dienogest were retrospectively collected from their medical records. The impact of potential risk factors (age, sagittal square area of the uterus before treatment, and estradiol at the third month of treatment) and confounders (hemoglobin before treatment and prior medical treatments) on the time to treatment discontinuation due to uterine bleeding was assessed using log-rank tests and a Cox proportional hazard model. Age (< 38 years, P = 0.004), hemoglobin before treatment (<12 g/dL, P = 0.047), and estradiol at the third month of treatment (≥ 60 pg/mL, P = 0.027) had statistically significant effects on the time to treatment discontinuation due to uterine bleeding. Age was still statistically significant after controlling for hemoglobin (P = 0.023). Adenomyosis patients treated with dienogest are at higher risk of treatment discontinuation due to uterine bleeding, especially when they are of younger age, have anemia before treatment, and/or have mildly suppressed or unsuppressed estradiol after they started dienogest treatment. Clinicians should pay special attention when they prescribe dienogest for such patients.
    No preview · Article · Mar 2012 · Journal of Obstetrics and Gynaecology Research
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    Nagayoshi Umehara · Tadao Tanaka
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    ABSTRACT: Objective. To investigate the incidence of various antiphospholipid antibodies (aPLs), measured by commercial-based laboratory, with recurrent spontaneous abortion (RSA) patients and the impact of the species, isotype, titer, and number of positive aPLs on reproductive outcome in Japanese. Method. In this retrospective cohort study, 263 patients with RSA without possible causes were investigated. Of 131 patients with one or more positive aPL, 82 pregnant women under anticoagulant therapy were evaluated. Results. The incidence of various aPLs was almost consistent with previous report. Overall, successful pregnancy rate with anticoagulant therapy was 91.4% regardless of aPL profiles. There was no significant difference in the pregnancy maintenance rate between IgG and IgM groups or single positive and multiple positive groups, but there was a tendency for the rate with aspirin to be lower than with aspirin plus heparin in IgG group. Conclusion. aPL profile did not affect the pregnancy maintenance rate when anticoagulant therapy was actively introduced, however in IgG group, we recommend combination therapy with aspirin and heparin.
    Preview · Article · Mar 2012 · ISRN obstetrics and gynecology
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    ABSTRACT: The objective of this study was to ascertain the evidence on ovarian cancer during pregnancy and compile recommendations derived from this information. This was a retrospective study, based on clinical histories from patients diagnosed and treated at 4 independent hospitals for ovarian cancer during pregnancy, between 1992 and 2009. The median age at diagnosis was 30 years (range, 24-41). Out of 10 cases of ovarian cancer, 2 patients showed either bleeding or abdominal pain, while 8 patients were asymptomatic. All 10 cases were diagnosed via ultrasound, and the masses were detected in the first trimester in 7 patients and in the second trimester in 2 patients. Of the diagnosed tumors, 8 cases were epithelial tumors including 6 adenocarcinomas and 2 borderline tumors, and 2 germ cell tumors. The primary ovarian malignancies were at stage I of the disease. Unilateral salpingo-oophorectomy was performed in 9 patients and cystectomy was performed in one patient. Chemotherapy was administered to 4 patients, in 1 case during pregnancy. Neonatal outcome analysis showed a full- or pre-term delivery in 6 cases, abortion in 1 case and therapeutic termination in 3 cases. The majority of cases of ovarian cancer in pregnancy were incidentally detected by ultrasound at an early stage, resulting in good prognosis for the mother and the neonate.
    Preview · Article · Mar 2012 · Oncology letters

  • No preview · Article · Jan 2012 · Nippon Laser Igakkaishi

  • No preview · Article · Jan 2012
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    ABSTRACT: Photodynamic therapy (PDT) has been established as a useful treatment for early stage cancer and dysplasia of uterine cervix. Multidisciplinary therapy is necessary for recurrent lesion of cervical cancer after hysterectomy. However, many cases are repeat recurrence, and it is difficult to complete treatment after radiation therapy. Occasionally surgical treatment such as total pelvic exenteration makes patient’s condition worse in terms of quality of life. PDT can be performed without systemic side effect, and it was suggested that PDT would become one of the effective treatment modalities for recurrent cervical cancer. We expect PDT could yield excellent result in recurrent cervical cancer as part of our new therapeutic strategy.
    No preview · Article · Jan 2012 · Nippon Laser Igakkaishi

Publication Stats

3k Citations
201.84 Total Impact Points

Institutions

  • 1998-2013
    • The Jikei University School of Medicine
      • Department of Obstetrics and Gynecology
      Edo, Tōkyō, Japan
  • 2004
    • Shonan Atsugi Hospital
      Atsuki, Kanagawa, Japan
  • 2001
    • Nippon Medical School
      • Department of Obstetrics and Gynecology
      Edo, Tokyo, Japan