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1.
Diagn Cytopathol ; 49(6): 682-690, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33755339

RESUMO

BACKGROUND: Appropriate surgical treatment of epithelial ovarian tumors is reliant on intraoperative diagnosis. A retrospective study to compare the diagnostic accuracies of imprint cytology (IC) with frozen section histology (FSH) in these tumors was performed. METHODS: About 78 cases of IC-based and FSH-based diagnoses against the final histopathologic diagnoses in terms of both histologic subtype (serous, mucinous, endometrioid, or clear cell tumor) and behavioral type (benign, borderline, or malignant) were compared. The cytomorphologic features of the tumor cells (nuclear atypia, papillary clusters, adenoma cells, and necrosis) in relation to behavioral types were also evaluated. RESULTS: While the diagnostic accuracy of IC and FSH were similar with respect to behavioral type (87% and 88%, respectively), the diagnostic accuracy of IC was superior to that of FSH with respect to histologic subtype (83% and 74%, respectively). Among histopathologically confirmed malignant tumors, the diagnostic accuracy of IC (62/64; 97%) was superior to that of FSH (58/64; 91%). The presence of necrosis and absence of adenoma cells were significantly more prevalent among malignant group than among borderline and benign groups (P < .01, for both). CONCLUSION: Since the presence of necrosis and absence of adenoma cells around the carcinoma cells appear useful in distinguishing malignant and borderline tumors, it was proposed to include IC for further intraoperative assessment of any tumors initially diagnosed as a borderline tumor by FSH.


Assuntos
Algoritmos , Carcinoma Epitelial do Ovário/diagnóstico , Citodiagnóstico/métodos , Secções Congeladas/métodos , Adulto , Idoso , Feminino , Humanos , Período Intraoperatório , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
Tokai J Exp Clin Med ; 45(4): 156-161, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33300584

RESUMO

Diagnosis of malignant uterine tumor with continuous lesions from the uterine body to the cervix, i.e., endometrial or cervical cancer, depends on the main site of the lesions. However, it may be difficult to differentiate advanced cancer that is widespread in the uterus. We experienced a patient who was diagnosed with small cell neuroendocrine carcinoma (SCNEC) based on histopathological characteristics of SCNEC in the endometrium. This tumor frequently coexists with endometrioid carcinoma, but we had difficulty finding the original site of SCNEC in the endometrium. The patient was a 59-year-old, two-parous woman who underwent hysterectomy after diagnosis of malignant uterine tumor. Preoperative cervical and endometrial histology permitted diagnosis of SCNEC. Imaging showed that most of the anterior uterine wall from the uterine body to cervix was replaced by tumors. Histopathologic findings for the resected uterus showed that most of these tumors were SCNEC, but components of endometrioid carcinoma had developed from the endometrium just beneath the fundus to the lower uterine body. The growth pattern of endometrioid carcinoma was endophytic. Based on this finding, the patient was diagnosed with endometrial SCNEC associated with endometrioid carcinoma. The patient initially responded well after postoperative chemotherapy, but early recurrence led to death at three months after the first treatment. This case shows that SCNEC in the uterine body is likely to coexist with endometrioid carcinoma. These findings are useful to determine the original site in postoperative pathological diagnosis of highly advanced tumors. SCNEC is a rapidly progressive and aggressive tumor in clinical practice, but some cases have a relatively good initial response to chemotherapy and it is important to start treatment early.


Assuntos
Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/cirurgia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/cirurgia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/cirurgia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Neoplasias Primárias Múltiplas , Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/sangue , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Terapia Combinada , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Evolução Fatal , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Cuidados Pós-Operatórios
3.
Tokai J Exp Clin Med ; 45(1): 5-9, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32219803

RESUMO

The patient was a 69-year-old multiparous female (gravida/para, 3/3) who had hypertension and arrhythmia. Her history included cerebral infarction treated with conservative therapy. She visited our hospital for atypical genital bleeding. She was diagnosed with atypical glandular cells (AGC) based on cervical cytology, atypical cells in endometrial cytology, and atypical endometrial hyperplasia on preoperative endometrial biopsy, and underwent total laparoscopic hysterectomy. However, in a postoperative pathologic examination, she was diagnosed with stage IB1 cervical adenocarcinoma without endometrial abnormality. AGC appeared in cervical cytology before surgery, but a surgical plan was not made with consideration of cervical adenocarcinoma.


Assuntos
Adenocarcinoma/cirurgia , Histerectomia/métodos , Laparoscopia/métodos , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/patologia , Idoso , Endométrio/patologia , Feminino , Humanos , Hiperplasia , Neoplasias do Colo do Útero/patologia
4.
Tokai J Exp Clin Med ; 44(4): 90-93, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31768997

RESUMO

The patient was a 50-year-old multiparous female (gravida/para 4/2) who had divorced. She was followed up for 1 year and 5 months after completion of initial treatment for peritoneal cancer (preoperative chemotherapy + optimal surgery + chemotherapy). A gradual increase in the tumor marker CA125 occurred, and computed tomography and ultrasonography showed bilateral neck, left supraclavicular and right axillary lymphadenopathy. The patient wanted to continue her job. Therefore, she was treated with etoposide (25 mg) daily for 3 weeks and TJ-48 (juzen-taihoto, 7.5 g) daily for 4 weeks, and then followed up. After two weeks, swelling of lymph nodes had been reduced or eliminated and tumor marker CA125 was negative. The only adverse reaction was slight numbness and the patient continued to work while receiving the same drugs orally for 2 years and 8 months without any symptoms or recurrence. This case shows that a combination of etoposide and TJ-48 has an antitumor effect on recurrent progressive peritoneal cancer while allowing a patient to work and have a normal daily life.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Etoposídeo/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Atividades Cotidianas , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno Ca-125/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/patologia , Resultado do Tratamento
5.
Tokai J Exp Clin Med ; 44(3): 40-44, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31448394

RESUMO

Bevacizumab is an effective drug for recurrent/advanced cervical cancer. A 59-year-old patient diagnosed with FIGO stage I B2 squamous cell carcinoma of the cervix at our hospital was treated with concurrent chemoradiotherapy as initial treatment. The outcome was judged as close to CR. Local recurrence in the irradiation field and paraaortic lymph node metastasis were noted 2 months after completion of this treatment. Chemotherapy of bevacizumab combined with paclitaxel plus carboplatin (TC) was initiated for recurrent cervical cancer. At 17 days after the 4th cycle, abdominal pain suddenly developed, and a close examination detected free air on abdominal CT, based on which intestinal perforation was diagnosed. Laparoscopic surgery performed to investigate the intraabdominal cavity showed that the small intestine was perforated at 2 sites. These were treated with laparoscopy-assisted partial resection of the small intestine and functional end-to-end anastomosis. Drug therapy for the recurrent cervical cancer was considered, but the primary disease rapidly aggravated and the patient died of the primary disease 11 months after completion of the initial treatment.


Assuntos
Anastomose Cirúrgica/métodos , Anti-Inflamatórios não Esteroides/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma de Células Escamosas/terapia , Perfuração Intestinal/induzido quimicamente , Perfuração Intestinal/cirurgia , Intestino Delgado/cirurgia , Laparoscopia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias do Colo do Útero/terapia , Anti-Inflamatórios não Esteroides/administração & dosagem , Bevacizumab/uso terapêutico , Quimiorradioterapia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade
6.
Int J Clin Oncol ; 23(2): 201-234, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29159773

RESUMO

BACKGROUND: Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese. OBJECTIVE: The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan. METHODS: The guideline was created according to the basic principles in creating the guidelines of JSGO. RESULTS: The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget's disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions. CONCLUSION: Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.


Assuntos
Neoplasias Vaginais/patologia , Neoplasias Vaginais/terapia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/terapia , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Doença de Paget Extramamária/patologia , Doença de Paget Extramamária/terapia
7.
J Obstet Gynaecol Res ; 43(10): 1613-1620, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28691209

RESUMO

AIM: This study was conducted to evaluate the efficacy and the difference in effects of the oral neurokinin-1(NK-1) receptor antagonist aprepitant for chemotherapy-induced nausea/vomiting (CINV) in Japanese patients with gynecological cancer receiving highly emetogenic (cisplatin) and moderately emetogenic (carboplatin) chemotherapy. METHODS: Aprepitant was added during the second course of chemotherapy in Japanese patients with grade ≥ 2 (Common Terminology Criteria for Adverse Events, version 3.0) nausea and vomiting during the first course despite receiving antiemetic therapy (a first-generation 5-hydroxytryptamine 3 receptor antagonist + dexamethasone), and in patients who requested stronger antiemetic therapy despite only having grade 1 nausea and vomiting. The incidence of nausea and vomiting was compared between the first and second courses in each group. RESULTS: Ninety-six (55.5%) out of 173 patients received add-on therapy with aprepitant. There was a significant increase in the complete response (CR: no vomiting or salvage therapy) rate in the patients receiving aprepitant, with marked improvement being confirmed for delayed CINV. Stratified analysis showed that patients with delayed CINV treated with carboplatin had a significantly higher CR rate, while patients with both acute and delayed CINV treated with cisplatin had significantly higher CR rates. There was a positive correlation between the incidence of nausea and the incidence of vomiting in the patients treated with aprepitant. CONCLUSION: The oral NK-1 receptor antagonist aprepitant could be effective for both acute and delayed CINV with cisplatin and for delayed CINV with carboplatin in Japanese gynecological cancer patients.


Assuntos
Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Morfolinas/farmacologia , Náusea/tratamento farmacológico , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Vômito/tratamento farmacológico , Adulto , Idoso , Aprepitanto , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Náusea/induzido quimicamente , Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Vômito/induzido quimicamente
8.
Oncol Lett ; 12(5): 3215-3223, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27899985

RESUMO

Thymidine phosphorylase (TP) is structurally similar to platelet-derived endothelial cell growth factor, and it activates 5-fluorouracil (5-FU) prodrugs and also promotes angiogenesis. In the present study, the possibility of using TP expression as a biomarker for 5-FU prodrugs, and the significance of TP as an angiogenic factor, were investigated in patients with gynecological tumors. The subjects enrolled in the study were 188 patients with gynecological tumors who provided informed consent and underwent tumor resection at the Department of Obstetrics and Gynecology of Tokai University Hospital between February 2002 and January 2010. Measurement of the enzymatic activity of TP and dihydropyrimidine dehydrogenase (DPD) was performed by enzyme-linked immunosorbent assay. In addition, immunohistochemistry (IHC) analysis of microvessels by monochrome imaging, western blotting and reverse transcription-polymerase chain reaction were performed. The mean TP activity and the TP/DPD ratio were increased in squamous cell carcinoma of the cervix (306.9 and 2.2 U/mg protein, respectively) and adenosquamous carcinoma (317.6 and 1.4 U/mg protein, respectively) compared with benign tumors and other malignancies, including endometrial (uterine) carcinoma, ovarian serous adenocarcinoma and ovarian mucinous adenocarcinoma. However, these parameters were also elevated in other histological types of cancer such as clear cell adenocarcinoma of the ovary (115.2 and 2.1 U/mg protein, respectively), in which the microvessel area was the largest of all the histological types analyzed. Since high TP expression and a high TP/DPD ratio were identified in other tumors besides cervical cancer, it is possible that patients for whom 5-FU prodrugs are indicated could be selected appropriately if their TP activity is determined and their TP expression is analyzed by IHC prior to initiation of the treatment.

9.
PLoS One ; 9(2): e89206, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24586595

RESUMO

OBJECTIVE: To develop a convenient screening method that can predict perioperative venous thromboembolism (VTE) and identify patients at risk of fatal perioperative pulmonary embolism (PE). METHODS: Patients hospitalized for gynecological abdominal surgery (n = 183) underwent hematology tests and multidetector computed tomography (MDCT) to detect VTE. All statistical analyses were carried out using the SPSS software program (PASWV19.0J). RESULTS: The following risk factors for VTE were identified by univariate analysis: plasmin-alpha2-plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and prolonged immobility (all p<0.001); age, neoadjuvant chemotherapy (NAC), malignancy, hypertension, past history of VTE, and hormone therapy (all p<0.01); and hemoglobin, transverse tumor diameter, ovarian disease, and menopause (all p<0.05). Multivariate analysis using these factors revealed that PIC, age, and transverse tumor diameter were significant independent determinants of the risk of VTE. We then calculated the incidence rate of perioperative VTE using PIC and transverse tumor diameter in patient groups stratified by age. In patients aged ≤40 years, PIC ≥1.3 µg/mL and a transverse tumor diameter ≥10 cm identified the high-risk group for VTE with an accuracy of 93.6%. For patients in their 50 s, PIC ≥1.3 µg/mL identified a high risk of VTE with an accuracy of 78.2%. In patients aged ≥60 years, a transverse tumor diameter ≥15 cm (irrespective of PIC) or PIC ≥1.3 µg/mL identified the high-risk group with an accuracy of 82.4%. CONCLUSIONS: We propose new screening criteria for VTE risk that are based on PIC, transverse tumor diameter, and age. Our findings suggest the usefulness of these criteria for predicting the risk of perioperative VTE and for identifying patients with a high risk of fatal perioperative PE.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Tromboembolia Venosa/epidemiologia , Adulto , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Período Perioperatório , Fatores de Risco
10.
Int J Gynecol Cancer ; 23(7): 1210-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23899586

RESUMO

OBJECTIVES: Before setting into the clinical trial using a combination of mammalian target of rapamycin (mTOR) inhibitors (rapamycin and everolimus) and other anticancer drugs, this study was conducted to confirm the efficacy of the new therapeutic strategy for ovarian clear cell adenocarcinoma (CCA), which targeted mTOR-hypoxia-induced factor (HIF) signal transduction system. MATERIALS AND METHODS: Using the cultured cells of CCA and animal models, alteration of mTOR-HIF cofactors and cell proliferation under the mTOR inhibitor-treated condition were analyzed. RESULTS: Mammalian target of rapamycin-HIF cofactors were inhibited dependent on concentration by mTOR inhibitor, resulting in suppression of the cultured CCA proliferation. However, von Hippel-Lindau was up-regulated at the messenger RNA level. In the nude mice with subcutaneously implanted CCA cells, apoptosis and necrosis were detected especially around the center of the tumors in the mTOR inhibitor-treated group more conspicuously than in the nontreated group. In the assessment of combination therapy with other antitumor agents, a combined treatment with mTOR inhibitor and chemotherapeutic agents caused a significant decrease in tumor size compared to the chemotherapeutic agents-only group. CONCLUSIONS: Treatment by mTOR inhibitor is expected to down-regulate the cell proliferation of the CCA as a new therapeutic strategy.


Assuntos
Adenocarcinoma de Células Claras/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Ovarianas/patologia , Transdução de Sinais/efeitos dos fármacos , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidade , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Everolimo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Técnicas Imunoenzimáticas , Imunossupressores/farmacologia , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Oncogênica v-akt/genética , Proteína Oncogênica v-akt/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Tokai J Exp Clin Med ; 38(1): 42-5, 2013 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-23564576

RESUMO

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.


Assuntos
Neoplasias Cardíacas/secundário , Neoplasias de Células Escamosas/secundário , Neoplasias do Colo do Útero/patologia , Adulto , Povo Asiático , Evolução Fatal , Feminino , Átrios do Coração , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/patologia , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia , Neoplasias de Células Escamosas/diagnóstico , Neoplasias de Células Escamosas/patologia , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/diagnóstico , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/patologia , Neoplasias Vasculares/secundário , Veia Cava Inferior
14.
Genes Cells ; 17(10): 826-36, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22957961

RESUMO

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.


Assuntos
Neoplasias do Endométrio/metabolismo , Lectinas/metabolismo , Polissacarídeos/metabolismo , Análise Serial de Proteínas , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Análise por Conglomerados , Neoplasias do Endométrio/patologia , Endométrio/metabolismo , Feminino , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo
15.
Int J Gynecol Cancer ; 22(7): 1192-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22801032

RESUMO

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Diferenciação Celular , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Sulfoglicoesfingolipídeos/metabolismo , Cromatografia em Camada Fina , Feminino , Humanos , Técnicas Imunoenzimáticas , Gradação de Tumores , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sulfotransferases/genética , Sulfotransferases/metabolismo
16.
Acta Histochem Cytochem ; 45(2): 147-54, 2012 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-22685357

RESUMO

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.

17.
Acta Histochem Cytochem ; 44(2): 113-8, 2011 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-21614172

RESUMO

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.

18.
Tokai J Exp Clin Med ; 36(1): 17-20, 2011 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-21547888

RESUMO

OBJECTIVE: To evaluate the efficacy of major labiaectomy as a surgical management of vulvar lymphangioma circumscriptum, we report two cases of this rare clinical entity. CASE REPORTS: 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. CONCLUSION: 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.


Assuntos
Linfangioma/cirurgia , Neoplasias Vulvares/cirurgia , Idoso , Feminino , Humanos , Histerectomia/efeitos adversos , Linfangioma/etiologia , Linfangioma/patologia , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/cirurgia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Neoplasias Vulvares/etiologia , Neoplasias Vulvares/patologia
19.
J Obstet Gynaecol Res ; 36(2): 448-53, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20492406

RESUMO

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.


Assuntos
Tumor de Células da Granulosa/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Western Blotting , Linhagem Celular Tumoral , Feminino , Tumor de Células da Granulosa/cirurgia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR
20.
Oncol Lett ; 1(1): 113-117, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22966267

RESUMO

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.

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