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ABSTRACT: A case of a 70-year-old woman with endometrioid adenocarcinoma of the ovary with functioning stroma is presented. The symptom was postmenopausal bleeding. The preoperative level of serum estradiol was as high as 162.4 pg/mL, and serum gonadotropin levels were suppressed. The endometrial tissue showed hyperplastic changes. The surgical specimens consisted of a multilocular cystic ovarian tumor of 95 mm in diameter and an enlarged uterus. Histologically, the tumor was composed of proliferating, atypical, columnar cancer cells resembling early secretory endometrial cells, and condensation of plumed stromal cells resembling theca lutein cells. The diagnosis of endometrial adenocarcinoma of the ovary with functioning stroma was made. After surgery, the serum levels of estradiol decreased and of follicle-stimulating hormone increased. Almost all types of ovarian tumor have been reported to be associated with endocrine abnormalities. Mucinous epithelial ovarian tumors most commonly present with estrogenic stroma, although the frequency of endometrioid adenocarcinoma with functioning stroma is very low. Here, a rare case with the patient's clinical course and histopathologic findings is reported.
Journal of Obstetrics and Gynaecology Research 07/2007; 33(3):381-3. · 0.94 Impact Factor
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Tsuyoshi Ohta,
Masahide Ohmichi, Tadashi Hayasaka,
Seiji Mabuchi,
Maki Saitoh,
Jun Kawagoe,
Kazuhiro Takahashi,
Hideki Igarashi,
Botao Du,
Masakazu Doshida,
Ishida Gabriela Mirei,
Teiichi Motoyama,
Keiichi Tasaka,
Hirohisa Kurachi
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ABSTRACT: The phosphatidylinositol 3-kinase (PI3K)/Akt cascade has an important role in the resistance of ovarian cancer cells to cisplatin in vitro; however, there have been no reports about whether blocking the PI3K/Akt cascade enhances the sensitivity to cisplatin in vivo. We investigated whether inhibition of PI3K increased the efficacy of cisplatin in an in vivo ovarian cancer model. Blocking the PI3K/Akt cascade with a PI3K inhibitor (wortmannin) increased the efficacy of cisplatin-induced inhibition of intraabdominal dissemination and production of ascites in athymic nude mice inoculated ip with the Caov-3 human ovarian cancer cell line. In addition, wortmannin increased the efficacy of cisplatin-induced apoptosis in tumors cells. There were no detectable side effects in mice treated with wortmannin. Moreover, the antitumor effect of cisplatin detected in mice inoculated with Caov-3 cells stably transfected with empty vector was significantly attenuated, compared with mice inoculated with Caov-3 cells stably transfected with a dominant-negative Akt, K179M-Akt. We confirmed that wortmannin blocked Akt phosphorylation and the downstream targets of the PI3K/Akt cascade, such as BAD (Bcl-2-associated death protein) and nuclear factor-kappaB in vivo by immunohistochemical staining and Western blotting. In accordance with the previously reported in vitro results, these in vivo results support the idea that combination therapy with cisplatin and a PI3K inhibitor would increase the therapeutic efficacy of cisplatin.
Endocrinology 05/2006; 147(4):1761-9. · 4.46 Impact Factor
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ABSTRACT: Since ovarian borderline tumor with invasive implant behaves as carcinoma, it should be managed like carcinoma. Since its characteristic features have not been reported, its preoperative diagnosis was thought to be impossible. We evaluated the features of MRI and macroscopic appearance in two cases of ovarian borderline tumor with invasive implant.
Borderline tumor with invasive implant was evaluated in two patients by MRI and macroscopic examination.
In these patients, MRI revealed profuse papillary projections. Although the lesion showed high signal intensity on contrast-enhanced T1-weighted images compared with that on T1-weighted ones, most of the signal intensity on T2-weighted images was high, suggesting that the lesion is an assembly of vesicles and an obvious solid part is absent. The macroscopic appearance of the tumor showed profuse papillary projections consisting of many vesicles perforating and extending far beyond the ovarian capsule, without a solid part. The histological findings indicated serous borderline tumors with invasive implant.
In these two cases, we found the characteristic features of serous borderline tumor with invasive implant by MRI and macroscopic examination. Our findings may be of clinical value since the preoperative information about the possibility of invasive implant may be quite important for the management of borderline tumor with invasive implant, especially for young patients wishing to bear children.
Archives of Gynecology and Obstetrics 11/2005; 272(4):278-82. · 1.28 Impact Factor
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ABSTRACT: Primary vaginal adenocarcinomas are rare neoplasms. Herein is reported a case of primary vaginal mucinous adenocarcinoma with an interesting mucin profile, presumably arising from a lesion of adenosis in a patient without in utero exposure to diethylstilbesterol (DES). The patient, a 44-year-old woman, had undergone vaginal total hysterectomy 10 years previously for myoma uteri corporis. The histological features of the vaginal intramural tumor found in this patient resembled those of mucinous adenocarcinoma of the endocervical type. Therefore, it was necessary to determine whether or not the tumor was metastatic from an occult cervical adenocarcinoma. However, the adenocarcinoma cells of the present case did not contain sulfomucin at all, being different from most mucinous adenocarcinoma cells of the endocervical type. Moreover, there were foci of adenosis adjacent to the adenocarcinoma foci, which also did not contain sulfomucin. These findings indicate that the mucinous adenocarcinoma arose from vaginal adenosis. Further studies are necessary to investigate whether lack of sulfomucin expression is a characteristic feature of vaginal adenosis.
Pathology International 07/2005; 55(6):372-5. · 1.62 Impact Factor
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Seiji Mabuchi,
Masahide Ohmichi,
Yukihiro Nishio, Tadashi Hayasaka,
Akiko Kimura,
Tsuyoshi Ohta,
Jun Kawagoe,
Kazuhiro Takahashi,
Namiko Yada-Hashimoto,
Hozumi Seino-Noda,
Masahiro Sakata,
Teiichi Motoyama,
Hirohisa Kurachi,
Joseph R Testa,
Keiichi Tasaka,
Yuji Murata
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ABSTRACT: We investigated whether inhibition of nuclear factor-kappaB (NFkappaB) increases the efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Treatment of paclitaxel-sensitive Caov-3 cells with paclitaxel transiently activated the phosphorylation of Akt, the phosphorylation of IkappaB kinase (IKK), and the phosphorylation of inhibitor of NFkappaB (IkappaBalpha). Paclitaxel also caused a transient increase in NFkappaB activity, followed by a decrease in NFkappaB activity. We show an association between Akt and IKK and show that the phosphorylation of IKK induced by paclitaxel is blocked by treatment with a phosphatidylinositol 3-kinase inhibitor (wortmannin or LY294002). Furthermore, interference of the Akt signaling cascade inhibits the transient induction of IkappaBalpha phosphorylation and NFkappaB activity by paclitaxel. Inhibition of NFkappaB activity by treatment with an IkappaBalpha phosphorylation inhibitor (BAY 11-7085) attenuated both basal and transient induction of IkappaBalpha phosphorylation by paclitaxel. Treatment with BAY 11-7085 also enhanced the inhibition of NFkappaB activity by paclitaxel for up to 24 hours. In addition, treatment with BAY 11-7085 decreased the viability of cells treated with paclitaxel. Moreover, treatment with BAY 11-7085 increased the efficacy of paclitaxel-induced inhibition of intraabdominal dissemination and production of ascites in athymic nude mice inoculated intraperitoneally with Caov-3 cells. These results suggest that paclitaxel transiently induces NFkappaB activity via the phosphatidylinositol 3-kinase/Akt cascade and that combination therapy with paclitaxel and an NFkappaB inhibitor would increase the therapeutic efficacy of paclitaxel.
Clinical Cancer Research 12/2004; 10(22):7645-54. · 7.74 Impact Factor
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ABSTRACT: Small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. Although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. In this study, the authors tentatively defined small cell neuroendocrine carcinoma (SCNEC) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin A immunoreactivity, and synaptophysin immunoreactivity. We found 10 cases fulfilling these requirements. Five of the 10 tumors were composed mainly of small ("oat") cells and 5 of mainly larger "intermediate" cells. The majority of both subtypes showed an insular pattern. Three of the 10 SCNECs were pure, whereas the other seven were mixed with adenocarcinoma and/or squamous cell carcinoma or cervical intraepithelial neoplasia. In addition to the definitional markers noted earlier, the tumors were immunoreactive for serotonin (6 cases), somatostatin, gastrin, glucagon, and pancreatic polypeptide. No tumors were immunoreactive for cytokeratin 20. Human papillomavirus (HPV)-18 was detected in all of the pure tumors and both the SCNEC and adenocarcinomatous components in four of the mixed tumors. No other types of HPV were detected. The tumors showed a relatively low frequency of loss of heterozygosity for representative tumor suppressor gene sites; p53 mutations were found in only one case.
International Journal of Gynecological Pathology 11/2004; 23(4):366-72. · 1.45 Impact Factor
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Seiji Mabuchi,
Masahide Ohmichi,
Yukihiro Nishio, Tadashi Hayasaka,
Akiko Kimura,
Tsuyoshi Ohta,
Maki Saito,
Jun Kawagoe,
Kazuhiro Takahashi,
Namiko Yada-Hashimoto,
Masahiro Sakata,
Teiichi Motoyama,
Hirohisa Kurachi,
Keiichi Tasaka,
Yuji Murata
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ABSTRACT: Whether or not inhibition of NFkappaB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models was investigated. We compared the basal levels of phosphorylation of IkappaBalpha and activity of NFkappaB between cisplatin-sensitive A2780 cells and cisplatin-resistant Caov-3 cells. The basal levels of phosphorylation of IkappaBalpha and activity of NFkappaB in Caov-3 cells were significantly higher than those in A2780 cells. Cisplatin caused a more marked decrease in the phosphorylation of IkappaBalpha and activity of NFkappaB in A2780 cells than in Caov-3 cells. Thus, high basal levels of phosphorylation of IkappaBalpha and activation of NFkappaB and less marked inhibition of the phosphorylation of IkappaBalpha and activation of NFkappaB by cisplatin seem to reduce the sensitivity of cells to cisplatin. Inhibition of NFkappaB activity either by treatment with the IkappaBalpha phosphorylation inhibitor (BAY 11-7085) or a specific NFkappaB nuclear translocation inhibitor (SN-50) or by transfection of p50DeltaNLS (which lacks the nuclear localization signal domain) increased the efficacy of both the cisplatin-induced attenuation of IkappaBalpha phosphorylation and NFkappaB activity and the cisplatin-induced apoptosis. In addition, treatment with BAY 11-7085 increased the efficacy of the cisplatin-induced attenuation of both the expression of X-linked inhibitor of apoptosis protein (XIAP) and cell invasion through Matrigel. Moreover, treatment with BAY 11-7085 increased the efficacy of the cisplatin-induced inhibition of the intra-abdominal dissemination and production of ascites using athymic nude mice inoculated intraperitoneally with Caov-3 cells. These results suggest that combination therapy of cisplatin with the NFkappaB inhibitor should increase the therapeutic efficacy of cisplatin.
Journal of Biological Chemistry 06/2004; 279(22):23477-85. · 4.77 Impact Factor
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Seiji Mabuchi,
Masahide Ohmichi,
Yukihiro Nishio, Tadashi Hayasaka,
Akiko Kimura,
Tsuyoshi Ohta,
Maki Saito,
Jun Kawagoe,
Kazuhiro Takahashi,
Namiko Yada-Hashimoto,
Masahiro Sakata,
Teiichi Motoyama,
Hirohisa Kurachi,
Keiichi Tasaka,
Yuji Murata
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ABSTRACT: Whether or not inhibition of NFκB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models was investigated. We compared the basal levels of phosphorylation of IκBα and activity of NFκB between
cisplatin-sensitive A2780 cells and cisplatin-resistant Caov-3 cells. The basal levels of phosphorylation of IκBα and activity
of NFκB in Caov-3 cells were significantly higher than those in A2780 cells. Cisplatin caused a more marked decrease in the
phosphorylation of IκBα and activity of NFκB in A2780 cells than in Caov-3 cells. Thus, high basal levels of phosphorylation
of IκBα and activation of NFκB and less marked inhibition of the phosphorylation of IκBα and activation of NFκB by cisplatin
seem to reduce the sensitivity of cells to cisplatin. Inhibition of NFκB activity either by treatment with the IκBα phosphorylation
inhibitor (BAY 11-7085) or a specific NFκB nuclear translocation inhibitor (SN-50) or by transfection of p50ΔNLS (which lacks
the nuclear localization signal domain) increased the efficacy of both the cisplatin-induced attenuation of IκBα phosphorylation
and NFκB activity and the cisplatin-induced apoptosis. In addition, treatment with BAY 11-7085 increased the efficacy of the
cisplatin-induced attenuation of both the expression of X-linked inhibitor of apoptosis protein (XIAP) and cell invasion through
Matrigel. Moreover, treatment with BAY 11-7085 increased the efficacy of the cisplatin-induced inhibition of the intra-abdominal
dissemination and production of ascites using athymic nude mice inoculated intraperitoneally with Caov-3 cells. These results
suggest that combination therapy of cisplatin with the NFκB inhibitor should increase the therapeutic efficacy of cisplatin.
Journal of Biological Chemistry 05/2004; 279(22):23477-23485. · 4.77 Impact Factor
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ABSTRACT: Intravenous leiomyomatosis with cardiac extension is an extremely rare uterine tumor. We report here a case of a patient with a uterine leiomyoma which extended into the right atrium through the left ovarian vein, progressing into the left renal vein along the inferior vena cava. Complete one-stage removal of the tumor was performed using cardiopulmonary bypass, and the patient has shown a favorable outcome. Successful therapy for intravenous leiomyomatosis is dependent on total surgical excision of the tumor, cessation of ovarian function and avoidance of postoperative estrogen replacement therapy.
Gynecologic and Obstetric Investigation 02/2004; 58(3):168-70. · 1.28 Impact Factor
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ABSTRACT: Although it is well known that the uterine cervix contains mucin-producing glandular epithelium, only a few studies have described the changes in mucin that accompany malignant transformation. In this study the authors evaluated the characteristics of mucin expression in the normal endocervical epithelium and mucinous and endometrioid adenocarcinomas of the uterine cervix. The normal endocervical epithelium was characterized by predominant sulfomucin and MUC1 expression in all sites and MUC5AC expression in the surface epithelium, while MUC2 was not detected at all and pyloric gland type mucin (using antibody HIK1083) was detected in less than 1% of cases. Cervical adenocarcinomas, especially mucinous adenocarcinomas, showed marked variability in mucin expression that included mucins of pyloric gland and intestinal type.
International Journal of Gynecological Pathology 11/2003; 22(4):393-7. · 1.45 Impact Factor
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ABSTRACT: Although it is well known that the uterine cervix contains mucin-producing glandular epithelium, only a few studies have described the changes in mucin that accompany malignant transformation. In this study the authors evaluated the characteristics of mucin expression in the normal endocervical epithelium and mucinous and endometrioid adenocarcinomas of the uterine cervix. The normal endocervical epithelium was characterized by predominant sulfomucin and MUC1 expression in all sites and MUC5AC expression in the surface epithelium, while MUC2 was not detected at all and pyloric gland type mucin (using antibody HIK1083) was detected in less than 1% of cases. Cervical adenocarcinomas, especially mucinous adenocarcinomas, showed marked variability in mucin expression that included mucins of pyloric gland and intestinal type.
The endocervix is lined by a single layer of mucinous epithelium. Cervical mucus plays a critical role in human reproductive physiology (1). Mucins, the major components of mucus, are high-molecular-weight glycoproteins with oligosaccharides attached to the apomucin protein by O-glycosidic linkages. At least 12 different human mucin genes have been identified (2,3). The expression of mucin genes is relatively specific to the tissue type. For example, MUC1 is expressed by many breast carcinomas (4), MUC2 predominates in colorectal goblet cells (5), and MUC5AC predominates in gastric foveolar epithelium (6). There have been some studies on mucin genes expressed by nonneoplastic human endocervical epithelium (7,8) as well as on the mucin alterations that accompany malignant transformation (9–12). However, there is scanty information about mucin alterations in cervical adenocarcinomas. In the present study, the characteristics of mucins produced by normal endocervical epithelium and cervical adenocarcinomas were investigated.
International Journal of Gynecological Pathology 09/2003; 22(4):393-397. · 1.45 Impact Factor
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ABSTRACT: A case of a 58-year-old woman with ovarian carcinoid exhibiting double function is reported. She had suffered from constipation and hirsutism before surgery. Pathological examination revealed that many carcinoid tumor cells were immunohistochemically positive for peptide YY, which inhibits intestinal motility and many peripheral steroid cells. After surgery the patient recovered from constipation immediately. Although the serum level of testosterone also immediately decreased, hirsutism remained for about 2 years. These clinical manifestations are considered to be due to peptide hormone-producing tumor parenchymal cells and testosterone-producing functioning stromal cells. This is the first report of clinically manifested double-functioning ovarian carcinoid; one function is due to tumor cells themselves and another function is due to stromal cells.
Pathology International 04/2003; 53(3):191-4. · 1.62 Impact Factor
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ABSTRACT: Small cell carcinoma of the ovary is a rare type of ovarian carcinoma with a very poor prognosis.
We report here a case of a 55-year-old woman with small cell carcinoma of the left ovary. The patient underwent cytoreductive surgery with residual tumors of 6 cm at the cul-de-sac and was found to have stage IIIc disease. After six courses of irinotecan (CPT-11) and cisplatin (CDDP) combination therapy, secondary cytoreductive surgery was performed. The patient showed no evidence of residual tumors. After an additional three courses of chemotherapy, the patient is still alive and well without evidence of disease.
CPT-11 and CDDP combination chemotherapy may be effective and safe for patients with small cell carcinoma of the ovary.
Anticancer research 27(4C):2685-7. · 1.73 Impact Factor
