Jo Kitawaki

Kyoto Prefectural University of Medicine, Kioto, Kyōto, Japan

Are you Jo Kitawaki?

Claim your profile

Publications (128)307.45 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AF-6/afadin plays an important role in the formation of adherence junctions. In breast and colon cancer, loss of AF-6/afadin induces cell migration and cell invasion. We aimed to elucidate the role of AF-6/afadin in human endometrial cancer. Morphology and AF-6/afadin expression in endometrial cancer cell lines was investigated by 3-dimensional culture. We used Matrigel invasion assay to demonstrate AF-6/afadin knockdown induced invasive capability. Cell proliferation assay was performed to estimate chemoresistance to doxorubicin, paclitaxel and cisplatin induced by AF-6/afadin knockdown. The associations between AF-6/afadin expression and clinicopathological status were determined by immunohistochemical analysis in endometrial cancer tissues. Informed consent was obtained from all patients before the study. The majority of cell clumps in 3-dimensional cultures of Ishikawa cells that strongly expressed AF-6/afadin showed round gland-like structures. In contrast, the cell clumps in 3-dimensional cultures of HEC1A and AN3CA cells-both weakly expressing AF-6/afadin-showed irregular gland-like structures and disorganized colonies with no gland-like structures, respectively. AF-6/afadin knockdown resulted in reduced number of gland-like structures in 3-dimensional cultures and enhancement of cell invasion and phosphorylation of ERK1/2 and Src in the highly AF-6/afadin-expressing endometrial cancer cell line. Inhibitors of MAPK/ERK kinase (MEK) (U0126) and Src (SU6656) suppressed the AF-6/afadin knockdown-induced invasive capability. AF-6/afadin knockdown induced chemoresistance to doxorubicin, paclitaxel and cisplatin in Ishikawa cells, not in HEC1A. Immunohistochemical analysis showed that AF-6/afadin expression was significantly associated with myometrial invasion and high histological grade. AF-6/afadin regulates cell morphology and invasiveness. Invasive capability is partly regulated through the ERK and Src pathway. The inhibitors to these pathways might be molecular-targeted drugs which suppress myometrial invasion in endometrial cancer. AF-6/afadin could be a useful selection marker for fertility-sparing therapy for patients with atypical hyperplasia or grade 1 endometrioid adenocarcinoma with no myometrial invasion. AF-6/afadin knockdown induced chemoresistance especially to cisplatin. Therefore, loss of AF-6/afadin might be a predictive marker of chemoresistance to cisplatin.
    BMC Cancer 04/2015; 15(1):275. DOI:10.1186/s12885-015-1286-x · 3.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endometriosis is an estrogen-dependent disease. Abnormally biosynthesized estrogens in endometriotic tissues induces the growth of the lesion and worsen endometriosis-associated pelvic pain. Dienogest, a selective progesterone receptor agonist, is widely used to treat endometriosis and efficiently relieves the symptoms. However, its pharmacological function remains unknown. Here, we elucidated the effect of dienogest on enzymes involved in local estrogen metabolism in endometriosis. Surgically obtained specimens of 23 ovarian endometrioma (OE) and their homologue endometrium (EE), 10 OE treated with dienogest (OE w/D), and 19 normal endometria without endometriosis (NE) were analyzed. Spheroid cultures of stromal cells (SCs) were treated with dienogest and progesterone. The expression of aromatase, 17β-hydroxysteroid dehydrogenase 1 (HSD17β1), HSD17β2, HSD177, HSD12, steroid sulfatase (STS), and estrogen sulfotransferase (EST) was evaluated by real-time quantitative polymerase chain-reaction. The activity and protein level of HSD17β1 were measured by an enzyme assay by using radiolabeled estrogens and immunohistochemistry, respectively. OESCs showed increased expression of aromatase, HSD17β1, STS, and EST, along with decreased HSD17β2 expression, when compared to NESCs (P < 0.01) or EESCs (P < 0.01). In OESCs, dienogest inhibited HSD17β1 expression and enzyme activity at 10-7 M (P < 0.01). Immunohistochemical analysis showed reduced HSD17β1 staining intensity in OE w/D (P < 0.05). In conclusion, dienogest exerts comprehensive inhibition of abnormal estrogen production through inhibition of aromatase and HSD17β1, contributing to a therapeutic effect of dienogest on endometriosis.
    Journal of Endocrinology 03/2015; 225(2). DOI:10.1530/JOE-15-0052 · 3.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To demonstrate the effects of the selective G protein-coupled estrogen receptor 1 (GPER) agonist G-1 in human ovarian endometriotic stromal cells (ESCs). Experimental in vitro study. University hospital. A total of 33 patients with ovarian endometrioma. Endometriotic stromal cells from ovarian chocolate cysts were treated with the GPER agonist G-1. The primary outcomes were cell proliferation, measured using the WST-8 assay; cell cycle, as analyzed using flow cytometry, fluorescent immunocytochemistry, and cytotoxicity; caspase activity, as measured by fluorescent and luminescent enzyme assays; and protein expression levels, as determined by Western blot analysis. G-1 suppressed ESC proliferation in a concentration-dependent manner. The inhibitory effect was not blocked when GPER signaling pathways, including the GPER itself, were inhibited. G-1 induced cell cycle arrest and accumulation in the sub-G1 phase in ESCs. Immunofluorescence analysis demonstrated that G-1 interrupted microtubule assembly at the mitotic phase. G-1 also induced caspase-3-dependent apoptosis without significant cytotoxicity. G-1 suppressed proliferation and induced apoptosis in ESCs, suggesting the potential use of this compound as a therapeutic drug for the treatment of endometriosis. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    Fertility and Sterility 02/2015; 103(5). DOI:10.1016/j.fertnstert.2015.01.026 · 4.30 Impact Factor
  • 01/2015; 3(1):8-13. DOI:10.9734/ISRR/2015/14352
  • [Show abstract] [Hide abstract]
    ABSTRACT: Peritoneal loose bodies (PLBs) are defined as fibrotic or calcified-free bodies within the peritoneal cavity; they commonly autoamputate from appendices epiploicae that have undergone torsion. Pedunculated, subserosal uterine leiomyomas (PSULs) are subserosal uterine leiomyomas connected to the uterus via a pedicle. In the present report, we describe the case of a PLB that originated from the autoamputation of a PSUL, confirmed based on histological evidence consistent with a uterine leiomyoma and the laparoscopic findings of a broken pedicle. This case clearly demonstrates the potential for a uterine leiomyoma to be the source of a PLB. Our findings contribute to the understanding of the etiological relationship between PLBs and uterine leiomyomas.
    Archives of Gynecology and Obstetrics 12/2014; 291(4). DOI:10.1007/s00404-014-3580-2 · 1.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction. The incidence of endometriosis affecting skin tissue represents only 0.5-1.0% of all endometriosis cases. A malignancy in the abdominal wall arising from endometriosis following cesarean section is even rarer; only 21 cases have previously been reported. The therapeutic strategy has not been determined because of the limited cases. We report a case of clear cell adenocarcinoma arising in the abdominal wall from endometriosis tissues following cesarean section and review previous literature to achieve the optimal treatment and better prognosis. Case Presentation. A 60-year-old woman presented with a growing mass at the left side of a cesarean section scar. Radical resection of the abdominal wall mass was performed. Histopathological examination showed a clear cell adenocarcinoma. Benign endometrium-like tissues were found adjacent to the cancer lesion in the excised specimen, suggesting malignant transformation from endometriosis of the abdominal wall. Discussion. Local resection was performed in 10 cases (47.6%) and total abdominal hysterectomy or oophorectomy was conducted in 11 cases (52.4%). No malignant lesions were observed in either the uterus or adnexa that were resected. These cases may be expected to increase with increasing incidence of cesarean section. The significance of the extensional resection should be further elucidated.
    11/2014; 2014:642483. DOI:10.1155/2014/642483
  • [Show abstract] [Hide abstract]
    ABSTRACT: The epithelial ovarian carcinoma (EOC) is an aggressive malignant tumor, and is currently the leading cause of gynecologic cancer death. CA125 is the most commonly used serum marker for EOC, but shows a high-false positive rate for several benign diseases such as endometriosis. The purpose of this study is therefore to identify a useful biochemical tool for detecting qualitative differences between CA125 from patients with endometriosis and EOC, and to facilitate differential diagnosis of these diseases. In this study, using two different CA125-binding molecules, i.e., recombinant mesothelin and an anti-CA125 monoclonal antibody, a novel sandwich ELISA for determining the serum levels of CA125 with mesothelin-binding ability (CA125meso) was developed, and tested for patients with endometriosis (n = 59) and EOC (n = 36). We found that both the serum CA125meso level, and the ratio of the serum CA125meso to CA125 levels (CA125meso/CA125) were significantly higher in patients with EOC than in patients with endometriosis (p < 0.00005 and p < 0.000001, respectively). Furthermore, receiver operating characteristic (ROC) analysis showed that the CA125meso assay was superior to the conventional antibody-based CA125 assay in discriminating endometriosis from EOC. Thus, mesothelin-binding ability may be a useful indicator for qualitatively evaluating CA125 in patients with endometriosis and EOC. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 09/2014; 136(8). DOI:10.1002/ijc.29185 · 5.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fulminant type 1 diabetes is a new subtype of rapid-onset type 1 diabetes, with pancreatic exocrine dysfunction, that usually develops during the third trimester of pregnancy. We describe a patient with fulminant type 1 diabetes onset during her second trimester, resulting in premature delivery. The 34-year-old woman, without any known risk factors for diabetes mellitus, experienced a sudden stillbirth at 24-weeks gestation. Her blood glucose level was 950 mg/dL and she was positive for urine ketone bodies. The condition met all the diagnostic criteria for fulminant type 1 diabetes, and was diagnosed as such. Although this disease is rare, its progression is rapid, and its clinical course is severe and occasionally leads to death; therefore, a full knowledge of the disease is important to facilitate an accurate diagnosis.
    08/2014; 2014:968547. DOI:10.1155/2014/968547
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Endometriosis is defined as the presence of endometrium-like tissues at extrauterine sites, most commonly in the abdominal cavity. Lymph node endometriosis is a rare but clinically important type of endometriosis that can mimic lymph node metastasis of a malignant tumor. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing malignant tumors, although it occasionally shows false positive results in tissues with high metabolic activity caused by severe inflammation. In the present report, we describe a case of lymph node endometriosis that mimicked lymph node metastasis of a malignant tumor and showed a positive result on (18)F-FDG PET/CT. The findings of the present case suggest that lymph node endometriosis could present as swollen lymph nodes with (18)F-FDG PET/CT-positive results and provide important information for determining an appropriate treatment strategy.
    08/2014; 2014:648485. DOI:10.1155/2014/648485
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: •Metastases from extrapelvic organs to the uterine cervix are rare.•Cervical metastases from the stomach are often accompanied by extrauterine metastases.•We report a case of cervical metastasis of gastric cancer, occurring 10 years after the first surgical treatment.
    04/2014; 8:17-20. DOI:10.1016/j.gynor.2014.01.002
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Endometriosis is an estrogen-dependent disease, and estrogen is overproduced by abnormally elevated aromatase in endometriotic tissues. Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) is a transcriptional coactivator-modulating steroid hormone. Objective: To investigate the effect of PGC-1α on aromatase activity in endometriosis. Design: Specimens from ovarian endometrioma (OE), endometrium with endometriosis (EE), and normal endometrium (NE) were analyzed for PGC-1α and aromatase expression. PGC-1α-dependent changes in aromatase expression in primary cultured stromal cells (SCs) were identified using luciferase and enzymatic assays, exon I-specific RT-PCR, and real-time PCR. Environmental stimulus-induced changes in PGC-1α were also examined. Results: PGC-1α was more highly expressed in OE than in EE and NE (P < 0.01). In OE, PGC-1α was coexpressed with aromatase, and their mRNAs expressions were also correlated (r = 0.56, P = 0.02). PGC-1α was recruited to the nuclear receptor half-site between PI.3 and II in the aromatase promoter. PGC-1α overexpression enhanced aromatase promoter activity (P < 0.01), mRNA expression (P < 0.05), and enzymatic activity (P < 0.01) in OESCs, but not in EESCs or NESCs. The levels of PI.3, II, and exon II mRNA increased and transcriptional enhancement was abolished by mutation of the PGC-1α-interacting site. PGC-1α expression was enhanced in OESCs by TNF-α (P < 0.05) but not by hypoxia or estradiol-17β. Conclusions: PGC-1α stimulated by TNF-α regulates aromatase expression and activity to promote local estrogen biosynthesis in OE, suggesting that PGC-1α is a promising candidate for novel targeted therapies in endometriosis treatment.
    The Journal of Clinical Endocrinology and Metabolism 03/2014; 99(7):jc20132525. DOI:10.1210/jc.2013-2525 · 6.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Monocyte adhesion to endothelial cells is an important initial event in atherosclerosis and is partially mediated by adhesion molecule expression on the cell surface. While estrogens inhibit atherosclerosis development, effects of co-administered progestogen remain controversial. Objective: We examined effects of progestogen on cytokine-stimulated human umbilical venous endothelial cell (HUVEC) expression of adhesion molecules. Design: In HUVECs, adhesion molecule mRNA levels were measured by real-time PCR. Protein expression was quantified by immunocytochemistry and enzyme-linked immunosorbent assays. To mimic monocyte adherence to endothelial cells, we used a flow chamber system to assess progestogen effects on U937 monocytoid cell adherence to HUVEC monolayers. We also examined suppression effects of adhesion molecules with small interference RNAs. Results: mRNA levels of adhesion molecules in HUVECs treated with medroxyprogesterone acetate (MPA) or 17β-estradiol (E2) + MPA were 1.7- to 2.5-fold higher than those in the control. MPA increased protein expression of E-selectin, P-selectin, and ICAM-1 compared to that for the control (83.0 ± 0.7, 34.8 ± 1.2, and 5.4 ± 0.0 ng/mL, respectively), whereas other progestogens or E2 additive to progestogens did not significantly change expression. MPA significantly increased U937 monocytoid cell adherence compared with the control (56.0 ± 1.5 vs. 46.5 ± 3.5 adherent cells/10 fields), but did not increase adherence to HUVECs with knocked down ICAM-1. Conclusions: MPA increases cell adhesion molecule expression on HUVECs, causing increased numbers of monocytoid cells to adhere to HUVECs. These MPA effects may be a risk factor for atherogenesis on endothelial cells in postmenopausal women receiving HRT.
    The Journal of Clinical Endocrinology and Metabolism 02/2014; 99(6):jc20132925. DOI:10.1210/jc.2013-2925 · 6.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Japan Society of Obstetrics and Gynecology Reproductive Endocrinology Committee summarizes the activities of each subcommittee below from April 2011 to March 2013. Survey for clinical outcomes of infertility treatment for women with adenomyosis and complications of pregnant women with adenomyosis. Survey for multiple pregnancies after controlled ovarian stimulation in non-assisted-reproductive-technology infertility treatment cycles: population-based study in Japan. Study on the effect of endometriosis management on ovarian reserve.
    Journal of Obstetrics and Gynaecology Research 02/2014; 40(2):349-52. DOI:10.1111/jog.12355 · 0.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Seprafilm is an ideal synthetic adhesion barrier, but its insertion into the abdomen in laparoscopic surgery is difficult because of its stiff and brittle nature. We tested the usefulness of a novel technique of moistening Seprafilm before use to increase its flexibility before insertion through a trocar during laparoscopic surgery. Laparoscopic pelvic surgeries that were followed by insertion of Seprafilm were evaluated in 67 women. A piece of Seprafilm (1/6 or 1/4 the size of a full sheet) was placed on gauze moistened with saline solution to soften it. The prepared piece was then rolled, inserted with forceps through a 12-mm trocar port, and placed at the intended site. A total of 245 pieces of Seprafilm sheets were pretreated and inserted using a 12-mm trocar port with a success rate of 100% and placed correctly with a success rate of 80.0% (196 of the 245 pieces). The mean total time required for placement of all pieces per surgery was 601±248 seconds. This is a simple and effective technique that enables the film to be applied securely without breaking and without the need for special equipment.
    Surgical laparoscopy, endoscopy & percutaneous techniques 02/2014; 24(1):e13-5. DOI:10.1097/SLE.0b013e31828f6ec1 · 0.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Primary prophylaxis with G-CSF has been used to minimize myelosuppression caused by anticancer agents and to avoid severe neutropenia. The authors retrospectively examined the value of primary prophylaxis using granulocyte colony-stimulating factor (G-CSF) for epithelial ovarian cancer. From 2001 to 2010, 105 patients with ovarian cancer receiving chemotherapy in the present hospital were divided into two groups: one received primary prophylaxis with G-CSF and the other did not receive it in compliance with the guidelines for G-CSF usage. The incidence of febrile neutropenia (FN), degree of neutropenia, frequency of G-CSF administration, number of days of hospitalization, progression-free survival (PFS), and overall survival (OS) were evaluated. Neutrophils decreased almost equally and the length of hospitalization was not significantly lower between the groups. Five-year PFS or OS showed no significant difference either. Primary prophylaxis with G-CSF in chemotherapy for epithelial ovarian cancer could be of low significance.
    European journal of gynaecological oncology 01/2014; 35(1):48-51. · 0.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To review the outcome in patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) who received MPA treatment in the present hospital. Patients with AEH or EC were administered MPA for 12 weeks followed by endometrial curettage. The rates of effect, recurrence, pregnancy, and complications were evaluated. The changes in progesterone receptors and FOXO-1, known as a target of MPA treatment, were examined by immunostaining. Four of seven patients with endometrial cancer and three of three patients with AH had complete response. Four of seven patients had recurred within one year after the treatment and had to undergo hysterectomy. None of the patients showed changes in progesterone receptors. Although six of seven patients were negative for FOXO-1 before and after treatment, all the patients showed increased developments of FOXO-1 during MPA treatment. Progestin as a fertility-preserving treatment is expected to be effective for endometrial cancer, but judicious use might be required because it shows high rate of recurrence. Further studies regarding the mechanism may be necessary to achieve high efficacy.
    European journal of gynaecological oncology 01/2014; 35(1):11-5. · 0.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The authors report a rare case of peritoneal adenomatoid mesothelioma in a woman with no history of asbestos exposure. A 61-year-old woman was originally suspected of having a bilateral ovarian tumor based on chest radiography and magnetic resonance imaging (MRI). Upon referral to our hospital, the presence of two solid masses was confirmed by enhanced MRI and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG-PET/CT). Physical examination was normal, as were serum concentrations of the tumor markers CA 19-9, CA 125, and CEA. Laparoscopic surgery showed a right ovarian tumor and laparoscopic right salpingo-oophorectomy and adhesiotomy were performed. Two months later, the patient underwent laparoscopic segmental resection of the sigmoid colon, with histological analysis identifying an adenomatoid-like tumor. The final diagnosis was peritoneal adenomatoid-like mesothelioma with invasion of the right ovary. This case report demonstrates that imaging techniques must be coupled with laparoscopic surgery for an accurate diagnosis of peritoneal mesothelioma.
    European journal of gynaecological oncology 01/2014; 35(1):91-4. · 0.60 Impact Factor
  • Japanese Journal of Clinical Oncology 12/2013; 43(12):1286. DOI:10.1093/jjco/hyt178 · 1.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: •Preoperative diagnosis of sarcoid reactions is important to avoid overtreatments.•Sarcoid reactions could act as a favorable prognostic factor in ovarian cancer.
    08/2013; 5:43-5. DOI:10.1016/j.gynor.2013.04.001
  • Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 08/2013; 32(8):1522-4. DOI:10.7863/ultra.32.8.1522 · 1.53 Impact Factor