Kaei Nasu

Oita University, Ōita, Ōita, Japan

Are you Kaei Nasu?

Claim your profile

Publications (176)422.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A 33-year-old woman with type 2 diabetes mellitus (DM) was suspected of being primarily infected with Toxoplasma gondii at 12 weeks of gestation (GW). Although acetylspiramycin was started at 17 GW, the T. gondii DNA gene was detected in the amniotic fluid at 18 GW. Chemotherapy was changed to pyrimethamine plus sulfadiazine from 20 GW, but was changed back to acetylspiramycin after 2 weeks because of vomiting. Acetylspiramycin was continued until her delivery. DM was controlled well during the pregnancy. An asymptomatic male baby was born by cesarean section at 37 GW, and was treated with acetylspiramycin for 4 weeks because the polymerase chain reaction results of umbilical cord blood were positive. He has developed normally until the present, that is, 6 months of age. Herein, we describe a case report in which symptomatic congenital toxoplasmosis was avoided in a pregnant woman with an immunosuppressive risk due to prompt chemotherapy.
    Journal of Obstetrics and Gynaecology Research 09/2014; · 0.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    Supportive Care in Cancer 05/2014; · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Grade 3 immature teratoma of the ovary is rare and has a poor prognosis due to early recurrence. This report describes a case of grade 3 immature teratoma of the ovary that recurred 16 years after the last treatment. The patient underwent abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, pelvic-para-aortic lymphadenectomy, and adjuvant chemotherapy under the diagnosis of grade 3 immature teratoma of the ovary when she was 15 years old, and complete remission was achieved. Sixteen years after the initial treatment, the tumor relapsed in her liver and pleura. She was treated by 10 courses of tri-weekly paclitaxel and carboplatin, and was alive with stable disease for 12 months after the disease relapse. After 1 year, the tumor progressed, and she died 16 months after the relapse. This is the first report of grade 3 immature teratoma of the ovary that relapsed more than 5 years after the prior treatment.
    Journal of Obstetrics and Gynaecology Research 05/2014; 40(5). · 0.84 Impact Factor
  • Journal of Obstetrics and Gynaecology 01/2014; · 0.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Accumulating evidence suggests that epigenetic aberrations play definite roles in the pathogenesis of endometriosis. These include aberrations in genomic DNA methylation, microRNA expression, and histone modification. The aberrant histone modification status and the aberrant expression of histone deacetylases, which regulate histone acetylation, in endometriosis are the focus of this review. Herein, we summarize the recent studies in the following areas: (i) hyperacetylation of histones located in the promoter lesions of G-protein-coupled estrogen receptor 1, steroidogenic factor-1, and hypoxia-inducible factor-1 alpha genes and (ii) hypoacetylation of histones located in the promoter lesions of estrogen receptor alpha, homeobox A10, CCAAT/enhancer-binding protein alpha, p16 INK4a , p21 Waf1/Cip1 , p27 Kip1 , checkpoint kinase 2, death receptor 6, and E-cadherin genes. Further research from the viewpoint of epigenetics may lead to the identification of the candidate molecules that are aberrantly expressed in endometriosis and may help elucidate the pathogenesis of this disease. In addition, epigenetic drugs (including histone deacetylase inhibitors) show promise for the treatment of endometriosis by amending the expression of these epigenetically dysregulated genes.
    Frontiers in bioscience (Landmark edition). 01/2014; 19:1202-1214.
  • [Show abstract] [Hide abstract]
    ABSTRACT: While mature cystic teratoma of the ovary is the most common ovarian tumor in young women, immature teratoma is a very rare tumor, representing only 1% of all ovarian cancers. In the three cases presented here, young women who were suspected to have mature cystic teratoma, based on CT scan and MRI, were ultimately diagnosed with immature teratoma Ic (b) G1 after laparoscopic operation. They underwent salpingo-oophorectomy of the affected side only and have shown no sign of recurrence during follow-up. We sometimes encounter patients with immature teratoma who have no findings pointing to malignancy on CT or MRI. Generally, if the components of immature nerve cells that represent immature teratoma are very few, it is difficult to diagnose the entity as immature teratoma with imaging evaluations such as CT or MRI. In many hospitals, laparoscopic surgery is selected for patients with ovarian mature teratoma. Therefore, it is essential to attempt as much as possible not to disseminate the fluid content of the tumor into the intra-abdominal space during laparoscopic operation, because in rare cases the tumor turns out not to be benign mature teratoma.
    Clinical medicine insights. Case reports. 01/2014; 7:91-4.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ovarian cancer is the second most common gynecological malignancy, yet it has the highest case-fatality ratio of all gynecologic malignancies. Surgery followed by combination platinum-taxane chemotherapy is the standard approach to the management of primary epithelial ovarian cancer. However, standard treatment of patients with recurrent ovarian cancer remains poorly defined. Secondary cytoreductive surgery (SDS) at the time of relapse has been proposed as a means of improving the prognosis of recurrent ovarian cancer patients with a treatment-free interval of at least 6 months. In the present study, we retrospectively collected 16 patients with recurrent epithelial ovarian cancer who might benefit most from SDS and evaluated the impact of SDS on the outcomes for this highly select patient group. We found that SDS led to excellent outcomes, with a 73.1% 8-year overall survival rate after initial treatment, a 67.9% 5-year overall survival rate after prior SDS, and a 31.3% 5-year progression-free survival rate after prior SDS. Although the findings were not significant, these results suggest that repeated SDS might improve outcomes for this patient group. The present study may provide a platform for discussion of the impact of aggressive or repeated SDS on the survival of patients with recurrent epithelial ovarian cancer and favorable prognostic factors. Further multi-institutional studies with larger number of patients are mandatory to confirm the present findings.
    Journal of Obstetrics and Gynaecology Research 11/2013; · 0.84 Impact Factor
  • Journal of Obstetrics and Gynaecology 11/2013; 33(8):914-5. · 0.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study is to evaluate the involvement of death receptor (DR) 6 in the pathogenesis of endometriosis. Endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues and the eutopic endometrial tissues, respectively. The effect of valproic acid (VPA) on the DR6 expression in ECSCs was examined. The roles of DR6 in NESC proliferation and apoptosis were investigated with DR6 siRNA transfection. The distribution of DR6 protein in ovarian endometriotic tissues and normal proliferative-phase endometrium was examined by immunohistochemistry. The expression of DR6 mRNA and protein in ECSCs and NESCs was also examined. Death receptor 6 expression was attenuated in ECSCs and in endometriotic tissues, and its expression was upregulated by VPA stimulation. VPA treatment resulted in an accumulation of acetylated histone H4 in the promoter region of the DR6 gene. DR6 knockdown directed the stimulation of cell proliferation and the resistance to apoptosis in NESCs. The present findings suggested that DR6 is involved in the pathogenesis of endometriosis by creating the proliferative and anti-apoptotic characteristics of endometriosis. The results also suggest that histone deacetylase inhibitors are promising agents for the treatment of endometriosis.
    American Journal Of Reproductive Immunology 09/2013; · 3.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context:Accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis.Objective:The objective of the study was to determine the epigenetically silenced genes by histone deacetylation in endometriosis.Design:Histone deacetylase (HDAC) 1-target mRNAs that were upregulated by valproic acid (VPA) treatment in endometriotic cyst stromal cells (ECSCs) were identified by a global mRNA microarray technique.Results:We identified five candidate genes and chose CCAAT/enhancer-binding protein α (C/EBPα) for further functional experiments. C/EBPα mRNA and protein expression is attenuated in ECSCs, and the expression was upregulated by VPA stimulation. Immunohistochemical stainings also confirmed the decreased staining for C/EBPα protein in endometriotic tissues. VPA treatment resulted in an accumulation of acetylated histones H3 and H4 in the promoter region of the C/EBPα gene in ECSCs. The compulsory expression of C/EBPα in ECSCs directed the inhibition of cell proliferation and the induction of apoptosis. C/EBPα knockdown by siRNA directed the stimulation of cell proliferation and the resistance to apoptosis in normal eutopic endometrial stromal cells. The expressions of peroxisome proliferator-activated receptor (PPAR) γ, period homolog 2 (PER2), p53, apoptosis-inducing factor, mitochondrion-associated 1 (AIFM1), Bax, caspase-8, caspase-10, p16(INK4a), p21(Waf1/Cip1), cyclin dependent kinase (cdk) 2, and cdk4 were downregulated by C/EBPα knockdown.Conclusions:Our findings suggest that an epigenetically suppressed tumor suppressor gene is involved in the pathogenesis of endometriosis by creating the proliferative, anti-apoptotic, and other disease-specific characteristics of endometriosis. The results also suggest that HDAC inhibitors are promising agents for the treatment of endometriosis.
    The Journal of clinical endocrinology and metabolism 07/2013; · 6.50 Impact Factor
  • Source
    Gynecologic Oncology. 04/2013; 129(1):268.
  • Source
    Gynecologic Oncology. 04/2013; 129(1):269.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endometriosis of the perineum and vulva is extremely rare, with the most common site being episiotomy scars. We report here a case of spontaneously developing perineal endometriosis successfully treated with local excision. A 39-year-old woman was admitted complaining of a painful vulvar lump with cyclic swelling. She had first noticed the mass 7 years before, and it had gradually increased in size. Gynecological examination showed a walnut-size, painful, subcutaneous mass in the left perineum. Magnetic resonance imaging revealed a multilobular cystic mass with inner hemorrhage, suggesting vulvar endometriosis. The patient was treated by local excision of the vulvar mass, and complete excision was achieved. The pathological diagnosis of the excised tissue was endometriosis. The patient is well without evidence of disease 5 months following the local excision. Spontaneous perineal and vulvar endometriosis is extremely rare. However, any lesion that evolves in response to the menstrual cycle should be considered endometriosis.
    Journal of Obstetrics and Gynaecology Research 03/2013; · 0.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: STUDY QUESTION: What is the global expression pattern of microRNAs (miRNAs) in endometriotic stromal cells and is miR-196b involved in the pathogenesis of endometriosis? SUMMARY ANSWER: Several miRNAs are aberrantly expressed in endometriotic cyst stromal cells (ECSCs), including miR-196b whose expression is repressed in endometriotic stromal cells. WHAT IS KNOWN ALREADY: Although, histologically, endometriotic tissues and normal proliferative endometrium are similar, a number of distinct molecular differences have been reported to date. The anti-apoptotic and excessive proliferative properties of endometriotic cells are considered to be involved in the development and progression of endometriosis. STUDY DESIGN AND SIZE DURATION: ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues and eutopic endometrial tissues, respectively and compared. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Aberrantly expressed miRNAs in ECSCs were identified by a global miRNA microarray technique. The roles of miR-196b in ECSC proliferation, apoptosis, and c-myc and B-cell lymphoma/leukemia (Bcl)-2 mRNA expression were investigated with precursor hsa-miR-196b transfection. The methylation status of the miR-196b gene in ECSCs and the effect of a DNA demethylating agent on miR-196b expression were also examined. MAIN RESULTS AND THE ROLE OF CHANCE: miRNA microarray analysis identified eight down-regulated miRNAs (including miR-196b) and four up-regulated miRNAs in ECSCs. Compulsory expression of miR-196b directed the inhibition of proliferation and the induction of apoptosis in ECSCs. miR-196b was found to suppress c-myc and Bcl-2 mRNA expression in ECSCs, and there was a significant correlation between miR-196b and HOXA10 expression in ECSCs and NESCs. The miR-196b gene was hypermethylated in ECSCs when compared with NESCs, and the treatment with a DNA demethylating agent restored the expression of miR-196b in ECSCs. LIMITATIONS AND REASONS FOR CAUTION: miRNA expression profiles were investigated only in the stromal component of ectopic and eutopic endometrium samples. In addition to miR-196b, the roles of other miRNAs aberrantly expressed in ECSCs should be examined. WIDER IMPLICATIONS OF THE FINDINGS: The present findings suggest that aberrant miRNA expression plays an important role in the pathogenesis of endometriosis as a part of epigenetic mechanisms, that expression of miR-196b in ECSCs is repressed by DNA hypermethylation of the miR-196b gene and this repression may be involved in the development of proliferative and anti-apoptotic characteristics of endometriosis. STUDY FUNDING: This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 20591920 to K.N. and no. 23592407 to H.N.) and The Uehara Memorial Foundation (to K.N.).
    Human Reproduction 01/2013; · 4.67 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: Although brain metastases from gynecologic malignancies are rare, such cases have been gradually increasing in number. The aim of the present study was to evaluate the clinicopathologic features and prognostic factors of brain metastases from gynecologic malignancies. METHODS: Retrospective analysis of 139 patients with brain metastases from gynecologic malignancies was carried out as a multi-institutional study. The clinicophathological data of the patients were collected from medical records. RESULTS: Median survival time of the patients with brain metastases was 12.5months for the ovarian cancer group, 6.2months for the corpus cancer group, and 5.0months for the cervical cancer group; two-year overall survival rates were 19.7%, 6.1%, and 4.8%, respectively. Multivariate analysis revealed ovarian/tubal/peritoneal origin, KPS >70, single brain metastasis, absence of extracranial disease, cranial surgery, cranial radiotherapy, and chemotherapy to be independent favorable prognostic factors associated with overall survival. CONCLUSION: It is considered that aggressive multimodal therapy is warranted in the treatment of brain metastases from gynecologic malignancies in carefully selected patients. The present study may provide a platform for the discussion of management strategies in these rare clinical scenarios.
    Gynecologic Oncology 11/2012; · 3.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The potential anticancer agent 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein ligand (initially described as a ligand for the peripheral benzodiazepine receptor), induces apoptosis in some lines of human tumor cells. We investigated the effect of PK11195 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of PK11195, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of PK11195. In contrast, the nonsite selective ligand diazepam has a little effect on these cells. Cell cycle analysis indicated that exposure to PK11195 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that PK11195 may serve as a therapeutic agent for the treatment of choriocarcinoma.
    Tumor Biology 04/2012; 33(5):1505-10. · 2.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Meningeal metastasis is rare in the clinical course of ovarian carcinoma and its prognosis is extremely poor. We experienced a case of carcinomatous meningitis from metastatic ovarian small cell carcinoma. A 33-year-old woman with atypical genital bleeding, was diagnosed with a right ovarian tumor and referred to our department. She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy. It was an optimal debulking surgery. She was diagnosed with ovarian carcinoma classified as Stage IIIc according to the Féderation Internationale de Gynécologie et d'Obstétrique classification system. Histological findings showed small cell carcinoma of the pulmonary type. The tumor was bilateral with paraaortic lymph node involvement. The patient was treated with irinotecan and cisplatin (CPT-P therapy). After 4 courses of CPT-P therapy, multiple liver metastases and Virchow's lymph node metastases were found. She was treated with amrubicin as a second-line chemotherapy, but the treatment was ineffective. Five months after surgery, the patient complained of severe headache and nausea. Lumbar puncture was performed and cytology was positive. Magnetic resonance brain imaging indicated meningeal thickening. The patient was diagnosed with meningeal metastasis and received 19-Gy whole cranial irradiation. In spite of these treatments, her disease progressed rapidly and she was often drowsy. She died of aspiration pneumonia 6 months after surgery.
    Rare tumors 04/2012; 4(2):e26.
  • [Show abstract] [Hide abstract]
    ABSTRACT: KN-93, a membrane-permeant calcium/calmodulin- dependent kinase-selective inhibitor, induces apoptosis in some lines of human tumor cells. We investigated the effect of KN-93 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of KN-93, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of KN-93. Cell cycle analysis indicated that exposure to KN-93 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that KN-93 may serve as a therapeutic agent for the treatment of choriocarcinoma.
    Tumor Biology 01/2012; 33(4):1053-8. · 2.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To report a case of a pregnant woman with traumatic spinal cord injury complicated with a psychiatric disorder. A 24-year-old woman at 18 weeks of gestation was transferred to our hospital with a history of having jumped from a third-floor apartment patio. A trauma survey showed no life-threatening hemorrhage, and fetal wellbeing was confirmed. Neurological examination showed complete loss of motor and sensory function in her lower extremities. Termination of pregnancy was advised and was achieved medically. Surgical intervention was performed to achieve stabilization of the spine and decompression of neural elements. After the operation, she was referred to a psychiatrist, and the administration of paroxetine, etizolam and flunitrazepam was begun. Four months after undergoing the abortion, she choked herself to death on her ward bed. Although it is rare, we should pay special attention to the substantial suicide risk of women who face severe spinal cord injury.
    Clinical and experimental obstetrics & gynecology 01/2012; 39(4):532-4. · 0.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bufalin is a traditional oriental medicines which induces apoptosis in some lines of human tumor cells. It constitutes the major digoxin-like immunoreactive component of Chan Su, obtained from the skin and parotid venom glands of toads. Bufalin is cardioactive C-24 steroids that exhibits a variety of biological activities, such as cardiotonic, anaesthetic, blood pressure stimulatory, respiratory and antineoplastic effects. In terms of its anti-tumor activity, bufalin has been demonstrated to inhibit the growth of tumors, such as endometrial and ovarian cancers. This commentary introduces biologic and therapeutic effects of bufalin in treating some cancers. The compound is able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in human cancer cells.
    Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(1):399-402. · 1.50 Impact Factor