Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Surg Endosc ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489501

RESUMO

BACKGROUND: Endoscopic surgery for infrarenal para-aortic lymphadenectomy has been widely accepted. Two major approaches, "transperitoneal" and "extraperitoneal", are generally used; however, they have several disadvantages. A "transperitoneal" approach to the left para-aortic region is usually indirect, often performed after wide extension of the right para-aortic region. An "extraperitoneal" approach is unsuitable when a peritoneal tear exists after a prior surgical procedure such as hysterectomy. Here, we propose a modified transperitoneal technique, "Left dome formation (LDF)," which directly provides a surgical field for left infrarenal para-aortic lymphadenectomy even after hysterectomy. METHODS: The LDF procedure comprised three processes: (1) setting, (2) dissection of inframesenteric lymph nodes (step 1), and (3) dissection of infrarenal lymph nodes (step 2). SETTING: two trocars were added 4 cm bilateral to the low-mid abdominal trocar that was used in prior hysterectomy. Step 1: The posterior layer of the renal fascia along with the left ureter and left ovarian vessel were separated from the left common iliac artery and iliopsoas. Left inframesentric nodes were removed from the surgical field. Step 2: The left ureter was isolated from the posterior renal fascia, and the dome was expanded cranially to the left renal vein, with the ovarian vein always visualizable at the dome ceiling. Left infrarenal nodes were removed. RESULTS: We applied LDF to ten endometrial cancer patients, recommended for additional dissection of para-aortic nodes based on intraoperative evaluation using the laparoscopically removed uterus. The operative time and number of removed lymph nodes in Step 1 and Step 2 were 28.8 (20-49) min and 5.3 (2-10) and 54.6 (52-70) min and 6.5 (1-11), respectively. Blood loss was below 50 ml. No serious organ injury occurred during procedures. CONCLUSION: Since the left ureter is always observable, LDF procedure facilitates effective surgery to overcome the anatomical complexity of the left para-aortic region and is potentially useful for sentinel node sampling.

2.
Cancer Sci ; 110(8): 2658-2666, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199029

RESUMO

Although direct adhesion of cancer cells to the mesothelial cell layer is considered to be a key step for peritoneal invasion of ovarian cancer cell masses (OCM), we recently identified a different strategy for the peritoneal invasion of OCM. In 6 out of 20 cases of ovarian carcinoma, extraperitoneal growth of the OCM was observed along with the neovascularization of feeding vessels, which connect the intraperitoneal host stroma and extraperitoneal lesions through the intact mesothelial cell layer. As an early step, the OCMs anchor in the extraperitoneal fibrin networks and then induce the migration of CD34-positive and vascular endothelial growth factor A (VEGF-A)-positive endothelial cells, constructing extraperitoneal vascular networks around the OCM. During the extraperitoneal growth of OCM, podoplanin-positive and α smooth muscle actin (αSMA)-positive cancer-associated fibroblasts (CAF) appears. In more advanced lesions, the boundary line of mesothelial cells disappears around the insertion areas of feeding vessels and then extraperitoneal and intraperitoneal stroma are integrated, enabling the OCM to invade the host stroma, being associated with CAF. In addition, tissue factors (TF) are strongly detected around these peritoneal implantation sites and their levels in ascites were higher than that in blood. These findings demonstrate the presence of neovascularization around fibrin net-anchored OCMs on the outer side of the intact peritoneal surface, suggesting a novel strategy for peritoneal invasion of ovarian cancer and TF-targeted intraperitoneal anti-cancer treatment. We observed and propose a novel strategy for peritoneal implantation of ovarian cancer. The strategy includes the preinvasive growth of fibrin-anchored cancer cells along with neovascularization on the outer side of the intact peritoneal surface.


Assuntos
Fibrina/metabolismo , Invasividade Neoplásica/patologia , Neovascularização Patológica/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Ascite/metabolismo , Ascite/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Peritônio/metabolismo , Peritônio/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-30378495

RESUMO

The invasion of an extravillous trophoblast (EVT) into maternal decidual tissues, especially toward maternal spiral arteries, is an essential process in human placental formation and subsequent normal fetal development. However, the precise regulatory mechanisms to induce EVT invasion toward arteries and/or to protect EVT from further invasion are not well understood. We found that a chemokine receptor, CCR1, was specifically expressed on EVT migrating toward maternal arteries. Using EVT isolated from a primary villous explant culture, RANTES, which is one of the ligands for CCR1, was shown to enhance EVT invasion. Furthermore, we observed that the platelets were deposited among intravascular EVT and platelet-derived soluble factors, which contained RANTES, enhanced EVT invasion. On the one hand, dipeptidyl peptidase IV (DPPIV), which can metabolize RANTES on the cell surface, was expressed on non-invading EVT and was demonstrated to suppress EVT invasion. In contrast, laeverin/aminopeptidase Q, which is specifically expressed on EVT, was shown to induce EVT invasion. Also, CD9 which is a cell surface marker of platelets and a regulator of integrin function, was expressed on EVT and gene knockdown of the CD9 molecule enhanced EVT invasion. These findings suggest that the chemokine-chemokine receptor, chemokine-peptidase, and CD9-integrin systems play important roles in the regulation of EVT invasion during early human placental formation.

4.
Am J Clin Pathol ; 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30260388

RESUMO

Objectives: To evaluate the clinical performance of novel detection kits for 14 high-risk human papillomavirus (hrHPV) types with the BD Onclarity HPV Assay (Onclarity; Becton Dickinson, Sparks, MD). Methods: Two cervical specimens from 144 women were obtained and placed in BD SurePath Collection Vials. The first specimen was used for cervical cytology and digene HC2 High-Risk HPV DNA Test (HC2; Qiagen, Germantown, MD), and the second specimen was used for Onclarity and Roche Cobas 4800 HPV (Cobas; Roche Molecular Systems, Pleasanton, CA). Other HPV genotyping kits were used for specimens identified as positive by Onclarity or Cobas. Results: Fifty-three of 144 specimens were positive by Onclarity. Overall agreement rates of Onclarity with HC2 and Cobas were 93.8% and 94.4%, respectively. The sensitivity and specificity for cervical intraepithelial neoplasia type 2 or higher of Onclarity were similar to HC2 and Cobas. Conclusion: The results showed that the clinical performance of Onclarity was equivalent to HC2 and Cobas.

5.
J Obstet Gynaecol Res ; 44(10): 2003-2007, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30043438

RESUMO

Recent reports showed that neoadjuvant chemotherapy (NAC) has been successfully applied to treat advanced uterine cervical cancers during pregnancy. However, its side effects on the fetus remain unclear. Here, we report a 33-year-old primipara who underwent four courses of NAC therapy, paclitaxel and cisplatin, from 17 to 27 weeks of gestation due to uterine cervical cancer stage IB2. At 31 weeks of gestation, cesarean section and radical hysterectomy were performed, and a female baby weighing 1446 g was born. Although pre- and postnatal courses were uneventful, neonatal erythroderma over the entire body was observed just after delivery. The pathological diagnosis was ichthyosiform erythroderma, which was later demonstrated to be keratitis-ichthyosis-deafness syndrome, by exome sequencing analysis. Although her skin disorder was consistent with keratitis-ichthyosis-deafness syndrome, the skin condition gradually improved after delivery. These findings suggest that NAC therapy during pregnancy might cause or exacerbate systemic skin lesions in the fetus/neonate.

6.
Cancer Sci ; 109(1): 231-240, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29151279

RESUMO

Circulating tumor cells (CTC) are newly discovered biomarkers of cancers. Although many systems detect CTC, a gold standard has not yet been established. We analyzed CTC in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (-) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTC were detected in 6 of 23 patients with cervical cancers (26.0%). Expression of CTC did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTC originated from HPV-infected cancer cells. These CTC were all negative for cytokeratins. The CTC detected by our system were genetically confirmed. CTC derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.


Assuntos
Infecções por Adenoviridae/genética , Adenoviridae/fisiologia , Células Neoplásicas Circulantes/metabolismo , Telomerase/genética , Neoplasias do Colo do Útero/sangue , Adenoviridae/genética , Linhagem Celular Tumoral , Feminino , Células HeLa , Humanos , Queratinas/metabolismo , Replicação Viral
7.
Mol Clin Oncol ; 7(6): 1057-1060, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29285373

RESUMO

The current report describes a case of extragenital gestational choriocarcinoma in the kidney. A 36-year-old woman with a history of two deliveries of male babies visited the present hospital due to secondary amenorrhea following a positive urinary pregnancy test. Despite a high serum level of human chorionic gonadotropin, at 51,800 mIU/ml, diagnostic imaging methods and pathological examination did not detect any conceptus in the genital tract. Positron emission tomography-computed tomography detected 18F-FDG-positive tumors in the left kidney and right lung. A fine needle biopsy of the renal lesion pathologically revealed the presence of choriocarcinoma and a subsequent polymerase chain reaction analysis verified the presence of a Y-chromosome-specific the sex-determining region Y (SRY) gene, diagnosed as extragenital gestational choriocarcinoma. Clinically, 10 cycles of EMA/CO chemotherapy were administered and an optimal response was obtained. In conclusion, this is the first report of the diagnosis of extragenital gestational choriocarcinoma by the detection of the SRY gene with PCR using biopsy samples.

8.
PLoS One ; 12(11): e0188641, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29190668

RESUMO

Although histological grade and muscular invasion are related to the malignant behaviors of endometrial endometrioid carcinoma, lymphatic and/or distant metastases are unexpectedly encountered, even in patients in the low-risk group. To re-evaluate additional reliable parameters to predict the risk of progression, we examined the immunohistochemical expression profiles of p53 and estrogen receptor (ER) ß proteins. Patients with endometrial endometrioid carcinoma who underwent surgical treatment at our hospital (n = 154) were recruited to this study, and the significance of the relationships between the incidence of regional lymph node metastasis and/or postoperative recurrence and clinical or experimental parameters was evaluated. By multivariate analysis, we found that histological grades, detection of immunoreactive p53 (positive rates more than 10%, p53-stained), and high expression of ERß (high-ERß) were independently associated with metastasis and/or recurrence. Among these parameters, the sensitivity and negative predictive values of high-ERß were very high (up to 100%). In the population with high-ERß, the positive rates of metastasis and/or recurrence were 61.1% in the p53-stained group and 21.9% in the p53-non-stained (negative) group. Furthermore, the positive rate in the group showing myometrial invasion of more than 1/2 and showing both p53-stained and high-ERß was 80%. The disease-free survival of patients who were double-positive for p53-stained and high-ERß was significantly shorter than that in other patients. In summary, our findings showed that increases in ERß and p53 immunoreactivity were significantly correlated with the incidence of metastasis and/or recurrence in endometrial endometrioid carcinoma, suggesting that double-positivity for p53-stained and high-ERß may provide a promising clinical indicator to predict the risk of progression.


Assuntos
Carcinoma Endometrioide/metabolismo , Neoplasias do Endométrio/metabolismo , Receptor beta de Estrogênio/metabolismo , Metástase Linfática , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Período Pós-Operatório , Recidiva , Proteína Supressora de Tumor p53/genética , Adulto Jovem
9.
Mol Clin Oncol ; 7(5): 820-824, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29181171

RESUMO

A 65-year-old woman received chemotherapy using taxane and carboplatin prior and following optimal debulking surgery for ovarian cancer stage IV. Five months later, intra-abdominal recurrence was diagnosed, and second-line chemotherapy using nogitecan and bevacizumab was administered. After five courses, the patient presented with a symptom of subileus and subsequent intestinal perforation occurred. An emergent surgery revealed two perforation sites and longitudinally extended ulcerative lesions in the ileum. Pathologically, although metastatic sites were not observed in the submucus layer just beneath the ulcers, there were a number of vascular endothelial growth factor (VEGF)-C-positive cancer cell invasion sites along with marked edema and an increase of the lymphatic endothelial cell marker 'podoplanin'-positive cells in subserous regions. Since bevacizumab is able to inhibit VEGF-A, but not VEGF-C, and induce compensatory increase in VEGF-C production, these findings suggest that the local disturbance of lymphatic circulation in the subserous regions by VEGF-C-producing cancer cells is a possible risk factor for the development of intestinal ulceration and perforation during bevacizumab therapy.

10.
Am J Reprod Immunol ; 77(4)2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28168784

RESUMO

PROBLEM: We previously proposed that platelets promote re-epithelialization during menstruation. As cell movement is one of the important cell behaviors in the process of tissue remodeling, we examined the effects of platelets on endometrial epithelial cell invasion. METHOD OF STUDY: The platelets were isolated from healthy women. Using a human endometrial epithelial cell-derived immortalized cell line, EM-E6/E7/hTERT cells, we examined the effects of platelets and platelet-derived condition media with or without microparticles on the morphological and invasive properties of EM-E6/E7/hTERT cells. RESULTS: Platelets and microparticle-containing conditioned media inhibited Matrigel invasion by EM-E6/E7/hTERT cells along with an increase in cortical ring formation, whereas microparticle-depleted conditioned media promoted their invasion without any significant changes of cortical ring formation. CONCLUSION: These results support our previous proposal and newly suggest the dual roles of platelets: platelet-derived soluble factors that promote cell movement in the distant area, and microparticles that induce re-epithelialization by endometrial epithelial cells in the proximal area.


Assuntos
Plaquetas/metabolismo , Movimento Celular/fisiologia , Micropartículas Derivadas de Células/metabolismo , Endométrio/citologia , Células Epiteliais/citologia , Células Cultivadas , Feminino , Citometria de Fluxo , Humanos
11.
J Obstet Gynaecol Res ; 43(3): 599-603, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27987341

RESUMO

Positron emission tomography (PET) with fluorodeoxyglucose F18 (18 F-FDG) is useful for detecting malignancies, but benign lesions occasionally have false-positive 18 F-FDG uptake. Here, we report the cases of five postmenopausal women with solid ovarian tumors suspected to be ovarian cancer on magnetic resonance imaging and 18 F-FDG uptake. Mean age of the five patients was 57 years (range, 53-65 years). Average early standardized uptake value (SUV) of 18 F-FDG was 5.76 (range, 2.2-12.0) and delayed SUV was 6.56 (range, 2.4-13.8). In all five patients, frozen section diagnosis at surgery was thecoma, and bilateral salpingo-oophorectomy was performed. On immunohistochemistry, immunoreactive glucose transporter 5 (GLUT5) expression was detected in thecoma tissues. This case shows that thecoma sometimes has positive 18 F-FDG uptake on positron emission tomography-computed tomography (PET-CT), indicating the need for caution regarding false-positive PET-CT in patients with benign solid ovarian tumor.


Assuntos
Transportador de Glucose Tipo 5/metabolismo , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tecoma (Neoplasia)/diagnóstico por imagem , Tecoma (Neoplasia)/metabolismo , Idoso , Reações Falso-Positivas , Feminino , Fluordesoxiglucose F18 , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Pós-Menopausa , Tecoma (Neoplasia)/patologia
12.
J Obstet Gynaecol Res ; 42(10): 1390-1394, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27354119

RESUMO

It is frequently difficult to distinguish multiple primary carcinomas from single primary carcinoma with metastasis. Here, we report a case of synchronous endometrioid adenocarcinomas that independently occurred in the uterine cervix and corpus. A 47-year-old woman complaining of genital bleeding was preoperatively diagnosed with cervical adenocarcinoma with an endometrial lesion. On surgical treatment, two separate malignant lesions bearing endometrioid adenocarcinoma were identified in the uterine cervix and cavity. Although both lesions expressed the same type of human papillomavirus (HPV) gene, type 16, microscopic continuity was not observed. Furthermore, we detected a critical difference in PTEN mutation between the tumors and finally diagnosed this case as multiple primary cancers. This is the first report to show multiple primary endometrioid adenocarcinomas simultaneously arising in the uterine cervix and corpus. Considering the rarity of this case, the coexistence of HPV suggests its possible involvement in the carcinogenesis of the endometrioid adenocarcinomas.


Assuntos
Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/patologia , Colo do Útero/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Útero/patologia , Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Feminino , Papillomavirus Humano 16/genética , Humanos , Pessoa de Meia-Idade , Mutação , PTEN Fosfo-Hidrolase/genética
13.
Springerplus ; 4: 425, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26290804

RESUMO

PURPOSE: Tamoxifen is an anti-estrogenic drug that is widely used for endocrine-dependent breast cancer as adjuvant hormonal therapy, and its use has been reported to be frequently associated with high levels of serum estradiol. Since the population of premenopausal women receiving tamoxifen therapy is growing in Japan, we retrospectively analyzed the incidence of ovarian hyperstimulation by tamoxifen therapy in Japanese women. METHODS: Eleven patients who received surgical therapy for endocrine-dependent breast cancer and showed high values of serum estradiol during post-operative tamoxifen therapy were recruited in this study and evaluated by examining the serum concentration of follicular stimulating hormone (FSH) and follicular development. RESULTS: The mean age, serum concentrations of estradiol and FSH, and follicular diameter were 41.3 years old, 1015.8 pg/mL, 11.8 mIU/mL, and 3.47 cm, respectively. In 6 cases, multiple follicular development was observed, while the other cases showed single follicular development with a mean serum estradiol level of 848.6 pg/mL and follicular diameter of 4.46 cm. There was no significant difference in age or FSH concentration between the two groups. The mean periods from the start of the single administration of tamoxifen to the initial detection of a high estradiol concentration was 716.5 days. CONCLUSIONS: These findings indicate that tamoxifen could stimulate the ovarian function even after 2-year treatment. Since single and multiple follicular developments with large sizes were observed, dual mechanisms through the inhibition of both negative and positive feedback to the hypothalamic-pituitary-axis can be proposed to explain the adverse effects of tamoxifen on ovarian function.

14.
Artigo em Inglês | MEDLINE | ID: mdl-26196656

RESUMO

OBJECTIVES: Nerve-sparing techniques to avoid bladder dysfunction in abdominal radical hysterectomy have been established during the past two decades, and they have been applied to radical trachelectomy. Although trachelectomy retains the uterine corpus, no report mentions the preservation of uterine branches of pelvic nerves. The aim of the present study was to introduce and discuss our unique concept for preserving them. STUDY DESIGN AND RESULTS: Four cases with FIGO stage Ia2-Ib1 cervical cancer, in which preservation of uterine branches of the pelvic nerves was attempted, are presented. Operative procedures basically followed the previously reported standard approaches for nerve-sparing radical hysterectomy or trachelectomy, except for some points. Before resection of the sacrouterine ligament, the hypogastric nerve was first identified and translocated laterally. Subsequently, the uterine branches of the pelvic nerve were identified as a continuation of the hypogastric nerve and could be scooped with forceps by detachment of the surrounding connective tissues. Further detachment toward the uterine corpus enabled them to be completely separated from the cervix. This separation was extended up to the level of the junction of the upper and lower branches of the uterine artery. Thereafter, standard resection of the parametrium and paracolpium was performed, followed by cervical resection when it was confirmed that the isolated uterine branches of the pelvic nerves were safely translocated and preserved. There were no recurrences of cancer in these patients. CONCLUSIONS: Uterine branches of autonomic nerves can be safely preserved, and the procedure may be considered one of the nerve-sparing techniques for radical abdominal trachelectomy, which may hopefully improve the reproductive outcomes of this operation, although it needs to be evaluated with more patients.


Assuntos
Plexo Hipogástrico , Tratamentos com Preservação do Órgão/métodos , Traquelectomia/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Útero/inervação , Feminino , Humanos , Estadiamento de Neoplasias
15.
Fertil Steril ; 101(5): 1337-43, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24656887

RESUMO

OBJECTIVE: To investigate the impact of estrogen contained in oral contraceptives (OCs) on the action of progestin on ovarian endometrioma epithelial cells. DESIGN: Experimental in vitro study and immunohistochemical analysis. SETTING: University hospital. PATIENT(S): Patients who underwent surgery due to ovarian endometrioma. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Telomerase-immortalized epithelial cells derived from ovarian endometrioma were treated with norethindorone (NET; 80 nmol/L) or levonorgestrel (LNG; 20 nmol/L) with or without 17ß-ethynylestradiol (EE; 0.6 nmol/L) for 96 hours, and the cell growth was monitored. Estrogen receptor (ER) α, progesterone receptor (PR) A, and PRB expressions in clinical samples of ovarian endometrioma epithelial cells were analyzed with the use of immunohistochemistry. RESULT(S): NET or LNG effectively suppressed cell growth, and addition of EE significantly enhanced the growth suppression. This EE-mediated enhancement of cell growth suppression was observed only in cells that expressed ERα and therefore was ERα dependent. Western blot analysis revealed that expression of PRB was significantly induced by the addition of EE. Immunohistochemical analysis confirmed that ERα expression and PRB expression are significantly correlated, indicating that progestin-sensitive cells with PRB expression are predisposed to react with estrogen stimulation. CONCLUSION(S): These findings suggest that EE contained in OCs plays a supportive role in progestin-induced growth inhibition of ovarian endometrioma epithelial cells. In the absence of estrogen priming, concurrent estrogen action was essential for rapid induction of PR to achieve maximal progestin effect.


Assuntos
Anticoncepcionais Orais/administração & dosagem , Endometriose , Estrogênios/administração & dosagem , Progestinas/administração & dosagem , Linhagem Celular Transformada , Combinação de Medicamentos , Endometriose/tratamento farmacológico , Endometriose/metabolismo , Feminino , Humanos , Resultado do Tratamento
16.
Int J Oncol ; 44(3): 669-77, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24366104

RESUMO

A small subset of cells with CD133 expression is thought to have increased chemoresistance and tumorigenicity, features of cancer stem cells (CSCs); the molecular mechanisms by which these properties arise remain unclear. We characterized CD133+ endometrial cancer cells based on microarray analyses of Ishikawa cells. Of the genes upregulated in CD133+ cells compared with CD133- cells, we noted several key factors involved in the aggressive behavior of cells, including ABCG2 and matrix metalloproteinase (MMP). Flow cytometric analyses identified a side-cell population (SP) with CSC features in Ishikawa cells, and they were found to be more enriched in CD133+ cells than CD133- cells. In particular, CD133+/SP cells exhibited higher proliferative and colony­forming activity than CD133+/non-SP cells. Matrigel invasion assay revealed that CD133+ cells have enhanced invasive capacity with elevated MT1-MMP expression. siRNA­based knockdown of MT1-MMP largely abolished the invasive capacity of CD133+ cells, but not CD133- cells due to low levels of constitutive MT1-MMP1 expression. These findings demonstrate that increased chemoresistance and tumorigenic potential of CD133+ cells are at least partly attributed to an enriched SP fraction as well as increased MMP-1 expression. These results will be of assistance in the establishment of molecular target therapy to CSCs in endometrial cancer.


Assuntos
Antígenos CD/genética , Neoplasias do Endométrio/genética , Glicoproteínas/genética , Análise em Microsséries , Células-Tronco Neoplásicas/metabolismo , Peptídeos/genética , Antígeno AC133 , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/biossíntese , Antígenos CD/metabolismo , Linhagem Celular Tumoral , Neoplasias do Endométrio/patologia , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Metaloproteinase 14 da Matriz/biossíntese , Proteínas de Neoplasias/biossíntese , Células-Tronco Neoplásicas/patologia , Peptídeos/metabolismo , RNA Interferente Pequeno
17.
Cancer Lett ; 345(1): 106-14, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24333732

RESUMO

The use of molecular target therapy has not been established for endometrial cancer. The present study investigated the potential therapeutic strategy of targeting CD117-positive cancer cells as a novel molecular target therapy. FACS-sorted CD117(+) cells isolated from endometrial cancer cell lines (Ishikawa or MFE280 cells) exhibited higher proliferative capacity in vitro and colony forming activity on soft agar, and decreased sensitivity to cisplatin, compared to CD117(-) cells. Immunohistochemical analyses with surgical specimens of endometrial cancers showed that high CD117 expression was tightly linked to advanced FIGO stages, myometrial invasion and histological grade, and was significantly associated with poor overall survival and relapse-free survival (Kaplan-Meier analysis; p<0.001, log-rank test). The Cox-regression hazard model identified high CD117 expression to be an independent prognostic factor for survival (p<0.05). In vitro assay confirmed that stem cell factor (SCF), a ligand of CD117, was produced specifically in CD117(+) cells of endometrial cancer, and the colony-forming activity were abrogated by adding anti-SCF antibody, indicating an SCF-dependent growth property. Imatinib was confirmed to selectively target CD117(+) cells in vitro, and synergistically enhanced the anti-tumor effect of low dose cisplatin in vivo, which showed only modest effects when used as a single use. These findings suggest that CD117 can be a marker of aggressive behavior of cells as well as an independent prognostic marker in endometrial cancer. Targeting of the SCF/CD117 axis by imatinib sensitized endometrial cancer cells to cisplatin, proposing a novel therapeutic strategy for this tumor type.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzamidas/farmacologia , Biomarcadores Tumorais/metabolismo , Cisplatino/farmacologia , Neoplasias do Endométrio/tratamento farmacológico , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Pirimidinas/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Sinergismo Farmacológico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Mesilato de Imatinib , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Cancer Lett ; 336(1): 68-75, 2013 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-23603247

RESUMO

Progestin inhibits the growth of normal and cancerous endometria via the progesterone receptor (PR), but the distinct functions and signalings of PR subtypes have not been fully understood. The aim of the present study was to dissect the key pathways of progestin to inhibit endometrial epithelial growth. Immortalized endometrial epithelial cells (EM-E6/E7/TERT) with stable PRA or PRB expression were established and used for the experiments. In vitro growth inhibition by progestin was mainly observed in EM-E6/E7/TERT cells with PRB rather than those with PRA. RT-PCR assay confirmed that FOXO1, a key gene for progestin action, was up-regulated by progestin in a PRB-dependent manner. cDNA microarray analysis identified IGFBP-1, which contains FOXO1 binding sites on its promoter, to be induced by medroxyprogesterone acetate (MPA) in EM-E6/E7/TERT cells with PRB but not with PRA. siRNA knockdown of FOXO1 disturbed the induction of IGFBP-1 by MPA, while IGFBP-1 knockdown showed no effect on MPA-induced FOXO1 expression, indicating that FOXO1 is an upstream regulator of IGFBP-1. Luciferase reporter assays showed that MPA activated the IGFBP-1 promoter, which was cancelled by FOXO1 knockdown. Chromatin immunoprecipitation assay confirmed the in vivo binding of FOXO1 to the core promoter of IGFBP-1. IGFBP-1 knockdown significantly attenuated the growth inhibitory effects of MPA. The FOXO1/IGFBP-1 axis is essential for PRB-dependent growth inhibition of endometrial epithelial cells, offering a potential therapeutic clue to enhance the progestin effect.


Assuntos
Endométrio/citologia , Células Epiteliais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Progestinas/metabolismo , Receptores de Progesterona/metabolismo , Sítios de Ligação , Linhagem Celular , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Proteína Forkhead Box O1 , Humanos , Acetato de Medroxiprogesterona/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas , Ligação Proteica , RNA Interferente Pequeno/metabolismo , Regulação para Cima
19.
Clin Cancer Res ; 17(6): 1341-50, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21411444

RESUMO

PURPOSE: Although the KRAS mutation is one of critical genetic alterations in endometrial carcinogenesis, the downstream targets are not known. EXPERIMENTAL DESIGN: In this study, we investigated the molecular targets of KRAS signals, using tumorigenic cells with oncogenic KRAS mutation established from telomerase reverse transcriptase (TERT)-immortalized endometrial epithelial cells. RESULTS: We first confirmed that the RAF-ERK pathway, but not the PI3K-Akt pathway, was activated in KRAS tumorigenic cells. However, the introduction of constitutively active MAP/ERK kinase into immortalized cells to mimic RAF-ERK activation failed to obtain tumorigenic phenotypes, indicating the existence of other carcinogenic pathways triggered by KRAS. Recent evidence suggestive of linkage with KRAS signals prompted us to examine the involvement of NF-κB in endometrial carcinogenesis. We found that the DNA-binding activity of NF-κB was markedly elevated in KRAS tumorigenic cells compared with TERT-immortalized cells. Furthermore, the ability of NF-κB to activate the target gene promoters significantly increased in KRAS tumorigenic cells. Introduction of a mutant IκB that is resistant to degradation and thereby enhances the inhibitory effect on NF-κB largely abrogated the transformed phenotypes of KRAS tumorigenic cells. Thus, oncogenic KRAS signals contributed to the tumorigenic phenotypes of endometrial cells by activating the transcription function of NF-κB. CONCLUSIONS: These findings clearly show that NF-κB activation is a novel target of oncogenic KRAS in endometrial carcinogenesis, implying the potential utility of NF-κB inhibitors for endometrial cancer chemoprevention, especially with KRAS mutation.


Assuntos
Carcinoma/genética , Neoplasias do Endométrio/genética , Ativação Enzimática , Genes ras , NF-kappa B/metabolismo , Animais , Carcinoma/metabolismo , Proliferação de Células , Neoplasias do Endométrio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Mutação , Invasividade Neoplásica , Transplante de Neoplasias , Telomerase/metabolismo
20.
Surg Innov ; 18(2): 114-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21307011

RESUMO

When transvaginal removal of ovarian cysts is performed successfully, the procedure compares favorably with laparoscopy in terms of invasiveness. However, the approach into peritoneal cavity has been laborious. The objective was to evaluate feasibility of an ultrasound-guided culdotomy using a newly developed umbrella needle. New culdotomy was performed on 36 patients with ovarian cysts. Each cyst was directly punctured by the needle from vagina under ultrasound guidance. The vaginal walls on both sides of the needle were incised with an electric scalpel. Through the wound, cyst was exteriorized and enucleated. Preoperative characteristics of patients, outcome, operating time, blood loss, complications, and cyst histology were analyzed. Culdotomy was performed successfully in all cases. Operating time was less than 10 minutes and blood loss was less than 10 mL. There were no culdotomy-associated complications. Culdotomy assisted by ultrasound imaging and an umbrella needle is a simple, safe, and reliable method for vaginal ovarian cystectomy.


Assuntos
Culdoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Agulhas , Cistos Ovarianos/cirurgia , Ultrassonografia de Intervenção , Adulto , Estudos de Coortes , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Cistos Ovarianos/diagnóstico por imagem , Ovariectomia/instrumentação , Ovariectomia/métodos , Instrumentos Cirúrgicos , Resultado do Tratamento , Vagina/cirurgia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA