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ABSTRACT: Introduction: Metastasis of uterine cervical carcinoma to the heart is uncommon and cases with metastasis to the right atrium are especially rare. This type of metastasis occurs in the epicardium and the myocardium in over 90% of cases with a heart metastatic tumor. Most cases of a metastatic tumor in the heart are found by chance during autopsy. Case report: We present the case of a patient with stage IIa uterine cervical carcinoma who visited our hospital with a chief complaint of arrhythmia 1.9 years after surgical treatment of carcinoma. CT and MRI showed that recurrent metastatic uterine cervical carcinoma had grown from the inferior vena cava upward into the right atrium. Conclusion: Although gynecological malignant tumors rarely metastasize to the heart, it is important to consider this possibility in patients with chest symptoms, and to make an early definite diagnosis and give appropriate treatment.
The Tokai journal of experimental and clinical medicine 01/2013; 38(1):42-5.
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ABSTRACT: Glycolipid and transporter protein gene expression in ovarian serous carcinoma-derived 2008 cells, and their paclitaxel-resistant P×2 and cisplatin-resistant C13 forms was examined to confirm the previous finding, i.e., that it was characteristically altered in anticancer drug-resistant cells established on continuous cultivation of ovarian carcinoma-derived KF28 cells in the different anticancer drug-containing media. Although the concentrations of lipid constituents in 2008 cells were higher than those in KF28 cells, and the glycolipid compositions were different, the following glycolipids and genes were commonly altered in KF28- and 2008-derived resistant cells. Gb(3)Cer was increased in all resistant cells, irrespective of whether the resistance was to paclitaxel or cisplatin, and expression of the MDR1 gene and gangliosides was enhanced in paclitaxel-resistant cells, but gangliosides were absent in cisplatin-resistant cells. In accord with the decreased amounts of gangliosides in cisplatin-resistant cells, the gene expression and specific activity of GM3 synthase were greatly decreased in cisplatin-resistant cells. Furthermore, paclitaxel- and cisplatin-resistant cells were converted to forms more sensitive to the respective anticancer drugs on cultivation with D-PDMP, an inhibitor of GlcCer synthase, and GM3, respectively, prior to the addition of anticancer drugs, indicating the possible involvement of glycolipids in anticancer drug resistance.
Journal of biochemistry 10/2012; · 1.95 Impact Factor
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ABSTRACT: Cell surface glycans change during the process of malignant transformation. To characterize and distinguish endometrial cancer and endometrium, we performed glycan profiling using an emerging modern technology, lectin microarray analysis. The three cell lines, two from endometrial cancers [well-differentiated type (G1) and poorly differentiated type (G3)] and one from normal endometrium, were successfully categorized into three independent groups by 45 lectins. Furthermore, in cancer cells, a clear difference between G1 and G3 type was observed for the glycans recognized with six lectins, Ulex europaeus agglutinin I (UEA-I), Sambucus sieboldiana agglutinin (SSA), Sambucus nigra agglutinin (SNA), Trichosanthes japonica agglutinin I (TJA-I), Amaranthus caudatus agglutinin (ACA), and Bauhinia purpurea lectin (BPL). The lectin microarray analysis using G3 type tissues demonstrated that stage I and stage III or IV were distinguished depending on signal pattern of three lectins, Dolichos biflorus agglutinin (DBA), BPL, and ACA. In addition, the analysis of the glycans on the ovarian cancer cells showed that only anticancer drug-sensitive cell lines had almost no activities to specific three lectins. Glycan profiling by the lectin microarray may be used to assess the characteristics of tumors and potentially to predict the success of chemotherapy treatment.
Genes to Cells 09/2012; 17(10):826-36. · 2.68 Impact Factor
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ABSTRACT: It is well known that a poorly differentiated endometrial adenocarcinoma shows more rapid progression and a worse response to therapy than a well-differentiated endometrial adenocarcinoma. Qualitative and quantitative changes of cell surface glycolipids occur during neoplastic transformation. Sulfatide is one of the sulfated glycolipids in the cell membrane that may have an important role in various functions such as cell adhesion. To examine the molecular background of the morphological and biological features of well-differentiated and poorly differentiated cancer, we measured the levels of lipids, especially glycolipids, in tumor tissues from patients with endometrial carcinoma.
We determined the composition of lipids and glycolipids in tumor tissues, investigated glycosyltransferase messenger RNA expression by the reverse transcription-polymerase chain reaction, and assessed the localization of galactosylceramide sulfotransferase (an enzyme involved in sulfatide biosynthesis) by immunohistochemical staining.
No significant differences were observed between well-differentiated and poorly differentiated cancer with respect to the levels of cholesterol ester, cholesterol, phospholipids, cholesterol sulfate, ceramides, neutral glycolipids of the globo series, and GM3 ganglioside. However, the amount of sulfatides in well-differentiated tumors was significantly greater than that in poorly differentiated tumors, which was confirmed by thin-layer chromatography and immunostaining with a monoclonal antisulfatide antibody. Altered expression of sulfatide was found to be secondary to a change of galactosylceramide sulfotransferase messenger RNA expression. Immunohistochemical staining revealed that galactosylceramide sulfotransferase expression was characteristically observed in glandular areas but not in solid areas.
These findings suggest that sulfatide contributes to the well-differentiated phenotype of endometrial adenocarcinoma and that it is being expressed in normal uterine endometrium at sites of gland formation during the luteal phase, as we have previously reported.
International Journal of Gynecological Cancer 07/2012; 22(7):1192-7. · 1.65 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 06/2012; 70 Suppl 4:236-41.
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Nippon rinsho. Japanese journal of clinical medicine 06/2012; 70 Suppl 4:789-94.
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Hitomi Tsukada,
Toshinari Muramatsu,
Masaki Miyazawa,
Tetsuji Iida,
Masae Ikeda,
Masako Shida,
Takeshi Hirasawa,
Hiroshi Kajiwara,
Masaru Murakami,
Masanori Yasuda, Mikio Mikami
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ABSTRACT: Many malignant epithelial tumors show increased expression of glucose transporter-1 (GLUT-1) and hexokinase II (HK-II), both of which are involved in glucose metabolism. GLUT-1 levels are often correlated with prognosis in these tumors. The current retrospective study was conducted to evaluate the importance of GLUT-1 and HK-II expression in leiomyosarcoma (LMS), a malignant uterine non-epithelial tumor with a poor prognosis. The subjects were 23 patients with stage I LMS. Expression of GLUT-1 and HK-II was evaluated immunohistochemically in samples removed surgically, and the MIB-1 index was evaluated as a measure of cell proliferation. The association of these results with prognosis was examined. Twenty samples of leiomyoma (LOM), a benign non-epithelial tumor, were used as controls. Immunohistochemical expression was defined as negative staining (-), weak to sporadic staining (1+), and strong staining (2+) per microscopic field, respectively. Malignancy was evaluated in 2000 cells and the MIB-1 index was calculated. Overall survival for LMS was estimated using the Kaplan-Meier method. Of the LMS cases, 12 were GLUT-1-positive (52.2%; 2+: 2, 1+: 10) and 15 were HK-II-positive (65.2%; 2+: 1, 1+: 14). GLUT-1 expression in LMS was significantly correlated with the MIB1 index. The 10-year survival rates were 90.9% and 58.3% in GLUT-1-negative and GLUT-1-positive cases, respectively, and 75.0% and 73.3% in HK-II-positive and HK-II-negative cases, respectively. GLUT-1 expression was significantly correlated with prognosis. Cases of stage I LMS showed a significant correlation between the expression level of GLUT-1 and the MIB-1 index, an indicator of malignancy. GLUT-1-negative cases had a better prognosis than GLUT-1-positive cases, suggesting that GLUT-1 expression is an effective prognostic marker.
ACTA HISTOCHEMICA ET CYTOCHEMICA 04/2012; 45(2):147-54. · 1.68 Impact Factor
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ABSTRACT: Material and methods We analyzed the expression of hypoxia inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) by immunohistochemistry
in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy.
A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous
13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18).
Results The overall positive ratios were as follows: HIF-1α, 74% of
adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and
100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive
ratios of HIF-1α and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly
expressed in serous adenocarcinomas (HIF-1α, 3 + 100%; GLUT-1, 3+76%) than in mucinous adenocarcinomas (HIF-1α, 3+61%;
GLUT-1, 3+28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical
expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than
in mucinous adenocarcinomas.
Conclusion HIF-1α and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association
with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared
with mucinous tumors is related to the difference in their histological characteristics.
Archives of Gynecology and Obstetrics 04/2012; 277(6):539-546. · 1.28 Impact Factor
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ABSTRACT: IntroductionAdvanced clear cell adenocarcinoma of the ovary is a histologic type with an extremely poor prognosis. No reports have been
published concerning useful drugs for salvage chemotherapy for this type of cancer. We performed salvage therapy with gemcitabine
in a patient with multiple-drug- resistant, unresectable recurrent clear cell adenocarcinoma of the ovary and succeeded in
stabilizing recurrent lesions and controlling carcinomatous peritonitis.
Case reportA 55-year-old woman was in Stage IIIc of clear cell adenocarcinoma of the ovary. She had recurrent tumors after primary cytoreductive
surgery, which were unresectable and also resistant to paclitaxel, carboplatin, irinotecan, and oral etoposide. After three
courses of fourth-line chemotherapy with gemcitabine for the treatment of carcinomatous peritonitis and hepatic and splenic
metastatic lesions, serum CA-125 and the severity of ascites showed marked decreases, and its efficacy for the hepatic and
splenic metastatic lesions was classified as 5-month stable disease. The toxicity of this drug was in the acceptable range.
ConclusionGemcitabine is also useful for heavily pretreated clear cell adenocarcinoma of the ovary. It is necessary to consider the
use of drugs without cross resistance to platinum and taxanes in the selection of drugs for this cancer.
Archives of Gynecology and Obstetrics 04/2012; 278(6):565-568. · 1.28 Impact Factor
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Makiko Harasawa,
Masanori Yasuda,
Takeshi Hirasawa,
Masaki Miyazawa,
Masako Shida,
Toshinari Muramatsu,
Kensho Douguchi,
Naruaki Matsui,
Susumu Takekoshi,
Hiroshi Kajiwara,
R Yoshiyuki Osamura, Mikio Mikami
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ABSTRACT: This study was designed to clarify the mechanism of the mammalian target of rapamycin (mTOR)-hypoxia inducible factor-1 (HIF-1) pathway using the cultured cell strain derived from human ovarian clear cell adenocarcinoma (CCA). Everolimus (a derivative of rapamycin)-treated cells and non-treated cells did not show any difference in mTOR expression. But, phosphorylated-mTOR (p-mTOR) expression significantly decreased in the treated cells, and mTOR-related factors such as phosphorylated-4E-BP1 (p-4E-BP1), HIF-1α, and vascular endothelial growth factor (VEGF) in the downstream region of mTOR revealed a marked decrease in expression. The analysis of influences of the drug on the HIF-1α degradation system showed an increase in von-Hippel Lindau (VHL) expression in the treated cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, was also shown in the treated cells. In the next step, using nude mice implanted with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice which were orally administered with everolimus. As a result, it was suggested that everolimus administration would be helpful as an anti-tumor therapy for CCA not only via down-regulation of p-mTOR but also degradation of HIF-1α by VHL and induction of apoptosis by cleaved caspase-3.
ACTA HISTOCHEMICA ET CYTOCHEMICA 04/2011; 44(2):113-8. · 1.68 Impact Factor
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ABSTRACT: To evaluate the efficacy of major labiaectomy as a surgical management of vulvar lymphangioma circumscriptum, we report two cases of this rare clinical entity.
Two female patients, aged 56 and 68 years, presented with persistent edema of the lower limbs, papule-like condyloma of the labia majora, and lymph oozing from these papules of the vulva, which had developed 24 and 10 years, respectively, after radical hysterectomy with adjuvant pelvic radiation therapy for cervical cancer. After major labiaectomy was performed, symptoms in the first case, of extensive resected skin margin, improved clearly, in the second case, vulvar lymphangioma circumscriptum was more severe than in the first case, and a small amount of lymph oozing occurred from residual papules of the labia majora. In both cases, histology revealed lymphangioma circumscriptum of the vulva.
Major labiaectomy is an effective therapy for vulvar lymphangioma circumscriptum. Particularly, in the case which was extensive and deep resected skin margin, symptoms such as papules of the labia majora and lymph oozing from these papules of the vulva associated with lymphangioma seemed to be clearly improved.
The Tokai journal of experimental and clinical medicine 04/2011; 36(1):17-20.
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ABSTRACT: It has been suggested that expression of TGFß1 and its receptors [TGFß receptor type I (TßRI) and TGFß receptor type II (TßRII)] may play a key role in the proliferation and progression of epithelial ovarian cancer. We investigated the biological significance of TGFß1 and its receptors, as well as their association with the tumor response to paclitaxel (PTX) and carboplatin (CBDCA). We studied 24 patients with ovarian cancer, primary peritoneal cancer, or fallopian tube cancer who had undergone surgery and chemotherapy with PTX and CBDCA. Tissues from the primary tumor were examined and the expression of TGFß1, TßRI, and TßRII mRNA was assessed by the RNase protection assay. It was found that TGFß1 mRNA expression was significantly lower in the tumors of patients who had optimal surgery than in the tumors of patients with suboptimal surgery. TGFß1 mRNA expression was also significantly lower in tumors with high sensitivity to PTX and CBDCA than in those with low sensitivity. TßRI mRNA expression was not associated with any clinicopathological factors. Expression of TßRII mRNA was significantly higher in clear cell adenocarcinoma and mucinous adenocarcinoma, while it was lower in serous adenocarcinoma and endometrioid adenocarcinoma. Moreover, it tended to be higher in early-stage tumors compared with advanced tumors. Among TGFß1, TßRI, and TßRII, expression of TGFß1 mRNA was most strongly associated with progression-free survival. When the prognosis of the patients with advanced cancer was compared on the basis of TGFß1 mRNA expression, those whose tumors showed low expression tended to have a better prognosis than those whose tumors showed high expression. It is suggested that TGFß1 mRNA expression is an indicator of tumor sensitivity to standard therapy with PTX and CBDCA, that it can identify biologically aggressive and highly malignant tumors and that it can predict the prognosis of patients with ovarian cancer.
Oncology Reports 01/2011; 25(4):1131-8. · 1.84 Impact Factor
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Satoru Nagase,
Hidetaka Katabuchi,
Masamichi Hiura,
Noriaki Sakuragi,
Yoichi Aoki,
Junzo Kigawa,
Tsuyoshi Saito,
Toru Hachisuga,
Kiyoshi Ito,
Takashi Uno, [......],
Toru Sugiyama,
Makio Mukai,
Satoru Sagae,
Hiroshi Hoshiai,
Daisuke Aoki,
Masahide Ohmichi,
Hiroyuki Yoshikawa,
Tsuyoshi Iwasaka,
Yasuhiro Udagawa,
Nobuo Yaegashi
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ABSTRACT: Endometrial carcinoma is one of the most common gynecologic malignancies in Japan and its incidence has increased recently. Although surgery is the cornerstone of the management of patients with endometrial cancer, there is significant variation in Japan with regard to the type of hysterectomy employed. Additionally, it remains controversial whether full nodal staging is required in all patients. Furthermore, adjuvant therapy differs between Japan and Western countries. To delineate clearly the standard of care for endometrial cancer treatment in Japan, the guidelines for the treatment of endometrial cancer were published in 2006 and revised in 2009. The 2009 edition included topics not addressed in the previous edition including the treatment of mesenchymal tumors, for example leiomyosarcoma, and sections covering the treatment of serous and clear-cell adenocarcinoma. These guidelines are composed of nine chapters and include nine algorithms. The guidelines also contain fifty-one clinical questions (CQs) and each CQ consists of recommendations, background, explanations, and references. The treatment recommendations herein are tailored to reflect current Japanese clinical practice and ensure equitable care for all Japanese women diagnosed with endometrial cancer.
International Journal of Clinical Oncology 11/2010; 15(6):531-42. · 1.41 Impact Factor
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ABSTRACT: To identify glycolipid antigens associated with histologically defined types of ovarian carcinomas, we determined the amounts of α2,6-sialyl and Lewis-active glycolipids, the specific activities of the α2,3- and α2,6-sialyltransferases, and the gene expression of sugar transferases in mucinous and serous cystadenocarcinoma, clear cell adenocarcinoma and endometrioid carcinoma tissues and cell lines derived from them. α2,6-sialyl glycolipid IV(6)NeuAcα-nLc(4)Cer detected with a newly developed monoclonal antibody, Y916, was present in 5/7 serous cystadenocarcinoma cases in relatively higher amounts than those in the other carcinoma tissues. On the other hand, the amounts of Lewis-active glycolipids in serous cystadenocarcinoma tissues were lower than those in the other carcinoma tissues. No correlation was observed between the structures of Lewis glycolipids and the histological classification. The gene expression of α2,3- and α2,6-sialyltransferases and α1,3/4-fucosyltransferase for the synthesis of Lewis-active glycolipids was not positively correlated with the amounts of the respective glycolipids, probably due to the epigenetic regulation of transferases in the overall metabolic pathways for lacto-series glycolipids. However, the amounts of GM3 and GD3 with short carbohydrate chains correlated with the relative intensities of GM3 and GD3 synthase gene expression, respectively. Among ovarian carcinoma-derived cell lines, the serous cystadenocarcinoma-derived ones exhibited a lower frequency of Lewis-active glycolipid expression than the other carcinoma-derived ones, which was similar to that in the respective tissues. Thus, malignancy-related Lewis-active glycolipids were shown to be regulated in different modes in ovarian serous cystadenocarcinomas and the other carcinomas.
Oncology letters 11/2010; 1(6):1061-1066. · 0.11 Impact Factor
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Masaki Miyazawa,
Masanori Yasuda,
Mariko Fujita,
Kenichi Hirabayashi,
Takeshi Hirasawa,
Hiroshi Kajiwara,
Toshinari Muramatsu,
Sayuri Miyazaki,
Makiko Harasawa,
Naruaki Matsui,
Naoki Ogane,
Masaru Murakami, Mikio Mikami,
Toshihiko Yanase,
R Yoshiyuki Osamura
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ABSTRACT: The DNA-binding activity of hypoxia-inducible factor-1 alpha (HIF-1alpha) has been analyzed for various gynecological tumors. Among the tumors that were studied, there was a finding of a high level of DNA-binding HIF-1alpha activity, although it was limited to one case of adult type granulosa cell tumor (GCT). In this case a 60-year-old female had marked immunohistochemical expression of HIF-1alpha. The expressions of the mammalian target of rapamycin (mTOR) and phosphorylated-mTOR (p-mTOR) were also marked, and vascular endothelial growth factor (VEGF) was moderately expressed. To compare the expression profiles, 11 consecutive cases with adult type GCT were used. All cases showed marked expressions of HIF-1alpha and mTOR, but p-mTOR expression was moderately to markedly observed in four of the 12 cases. VEGF was expressed in all cases in varying degrees. Based on the evidence that downregulation of the mTOR pathway due to treatment with rapamycin (everolimus) would suppress tumor cell growth, an experimental study using the GCT cell line was designed to clarify whether HIF-1alpha and VEGF expressions decline. As a result, the expressions of p-mTOR, HIF-1alpha and VEGF were suppressed, but those of mTOR were not. It was concluded that mTOR-targeted therapy may represent a promising strategy for some GCT with an activated mTOR-HIF-1alpha-VEGF pathway.
Journal of Obstetrics and Gynaecology Research 04/2010; 36(2):448-53. · 0.94 Impact Factor
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ABSTRACT: This study aimed to promote gland formation in cells derived from endometrial cancer, and assess the relevance of sulfolipids by performing culture with type I collagen. Tumors were developed in nude mice using cultured cell lines, gland formation was induced by culture with type I collagen and the composition of tumor cell sulfolipids was analyzed. Results showed that after culturing the cells on type I collagen gel, the gel was floated. Another layer of gel was placed on top so that the cells were sandwiched between two layers. Using this method, it was possible to induce gland formation in cells that formed only poorly differentiated tumors in nude mice. Mucous staining and electron microscopy demonstrated polarity of the glands. The cell lines that showed gland formation expressed sulfolipids, but not cholesterol sulfate. In conclusion, type I collagen and sulfolipids are involved in the process of gland formation in endometrioid adenocarcinoma.
Oncology letters 01/2010; 1(1):113-117. · 0.11 Impact Factor
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ABSTRACT: A 73-year-old postmenopausal Japanese woman presented with a complaint of slight fever and weight loss. An elevated level of CA125 in the blood favored a diagnosis of malignant uterine body tumor, but was not confirmed by endometrial cytology and biopsy. Resection of the uterus revealed a solid whitish tumor in the myometrium that was diagnosed as clear cell adenocarcinoma (CCA) arising from adenomyosis. There were transitions between endometrial epithelium of adenomyosis, noninvasive CCA, and invasive CCA. Immunohistochemical expression of hepatocyte nuclear factor-1beta supported the diagnosis of CCA. Only one other English language document pertaining to CCA arising from adenomyosis exists. Malignant tumor arising from adenomyosis should be considered as a differential diagnosis when the serum level of tumor markers such as CA125 is high and when the tumor is intramyometrial.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 06/2009; 28(3):262-6. · 2.07 Impact Factor
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Masaki Miyazawa,
Masanori Yasuda,
Mariko Fujita,
Hiroshi Kajiwara,
Kenichi Hirabayashi,
Susumu Takekoshi,
Takeshi Hirasawa,
Masaru Murakami,
Naoki Ogane,
Kazushige Kiguchi,
Isamu Ishiwata, Mikio Mikami,
R Yoshiyuki Osamura
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ABSTRACT: Malignant tumors usually involve a relatively hypoxic state, which induces overexpression of hypoxia-inducible factor-1alpha (HIF-1alpha) to satisfactorily enable the tumor to survive. Thus, inhibition of the mammalian target of rapamycin (mTOR) pathway including HIF-1alpha is expected to play a major role in suppression of tumor cell growth, having recently drawn much attention as an anti-cancer therapeutic strategy for various malignant tumors. In the present study, which compared clear cell adenocarcinoma (CLA) of the ovary with serous adenocarcinoma (SEA), the immunohistochemical expression of mTOR, phosphorylated-mTOR (p-mTOR), HIF-1alpha, and vascular endothelial growth factor (VEGF) was examined in surgically resected specimens of 29 SEA and 47 CLA. There were no significant differences in expression of mTOR, HIF-1alpha and VEGF between SEA and CLA, but it was noted that p-mTOR expression was more prominent in CLA than SEA. Then, using the cell lines of CLA (RMG-1 and W3uF), an experimental study was designed to clarify whether tumor suppression due to downregulation of mTOR activity could represent a promising therapeutic strategy for CLA. After treatment of an analogue of rapamycin (everolimus), expression of mTOR, p-mTOR, HIF-1alpha and VEGF was examined on western blot. As a result, although mTOR expression remained unchangeable, expression of p-mTOR, HIF-1alpha and VEGF was shown to be sharply depressed. The same expression alterations were demonstrated in the xenograft model treated with everolimus. In conclusion, mTOR-targeted therapy through usage of drugs such as everolimus may be more effective for CLA of the ovary because of its significant expression of p-mTOR.
Pathology International 02/2009; 59(1):19-27. · 1.62 Impact Factor
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Archives of Gynecology 01/2009; · 0.91 Impact Factor
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Masaki Miyazawa,
Masanori Yasuda,
Mariko Fujita,
Takeshi Hirasawa,
Hiroshi Kajiwara,
Kenichi Hirabayashi,
Naoki Ogane,
Michio Shimizu,
Hideki Asanuma,
Masaru Murakami,
Susumu Takekoshi, Mikio Mikami,
R Yoshiyuki Osamura
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ABSTRACT: Hypoxia-inducible factor-1 (HIF-1) is an essential transcription factor that mediates cellular and systemic homeostatic responses to reduced oxygen availability in mammals. So far, using immunohistochemistry we have analyzed the association of HIF-1alpha expression with histological type among epithelial ovarian tumors. In the present study, quantitative analyses of activated HIF-1 level in the nucleus and of accumulated HIF-1alpha level in the cytoplasm were performed to clarify whether or not the hypoxic state would be correlated to histology, malignancy, and tumor size in epithelial ovarian tumors.
HIF-1 level in the nucleus was analyzed using DNA binding assay, and HIF-1alpha level in the cytoplasm was measured by ELISA for a total of 36 epithelial ovarian tumors as follows: 5 serous adenocarcinomas (SEAs), 7 clear cell adenocarcinomas (CLAs), 7 endometrioid adenocarcinomas (ENAs), 4 mucinous adenocarcinomas (MUAs), 2 mucinous borderline tumors (MBTs), and 11 mucinous adenomas.
HIF-1 level (mg/ml) in the nucleus and HIF-1alpha level (mg/ml) in the cytoplasm were on average 0.116 and 0.178 for SEAs, 0.328 and 0.306 for CLAs, 0.171 and 0.305 for ENAs, 0.097 and 0.176 for MUAs, 0.224 and 0.180 for mucinous borderline tumors, 0.152 and 0.154 for mucinous adenomas. CLAs showed the highest levels for both of HIF-1 and HIF-1alpha, while MUAs showed the lowest levels of both. Mucinous adenomas were higher in HIF-1 than MUAs.
Hypoxic state was considered to be closely related to histological type of epithelial ovarian tumors, suggesting that CLAs may be most hypoxic. In the comparison of mucinous tumors, malignancies would not always become most hypoxic. Tumor size may not be strongly associated with hypoxic state.
Archives of Gynecology 11/2008; 279(6):789-96. · 0.91 Impact Factor
