Propofol inhibits proliferation, migration, and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells

Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/β-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/β-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice

PURPOSE: To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. METHODS: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. RESULTS: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. CONCLUSION: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

Major clinical research advances in gynecologic cancer in 2014 / 부인종양

In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

Long-term survival of patients with recurrent endometrial stromal sarcoma: a multicenter, observational study / 부인종양

OBJECTIVE: The aim of this study was to evaluate the clinical behavior and management outcome of recurrent endometrial stromal sarcoma (ESS). METHODS: A retrospective review of charts of 10 patients with recurrent ESS was performed and relapse-free interval, relapse site, treatment, response to treatment, duration of follow-up and clinical outcome extracted. Survival outcome measures used were post-relapse survival which was defined as the time from first evidence of relapse to death from any cause. Living patients were censored at the date of last follow-up. RESULTS: The median age and median relapse-free interval at the time of initial relapse were 51.5 years and 66.5 months, respectively. The number of relapses ranged from one to five. Sixteen surgical procedures for recurrent disease included nine (56.0%) complete resections. There was no statistically significant difference between initial recurrent tumors and second/subsequent recurrent tumors in the rate of complete surgery (44.4% vs. 71.4%, respectively, p=0.36). Of the eleven evaluable occasions when hormonal therapy was used for recurrent disease, disease control was achieved in eight (72.7%). There was no difference between initial recurrent tumors and second/subsequent recurrent tumors in disease control rate by hormonal therapy (85.7% vs. 50.0%, respectively, p=0.49). The 10-year post-relapse survival rate was 90.0% and the overall median post-relapse survival 119 months (range, 7 to 216 months). CONCLUSION: Post-relapse survival of patients with ESS can be expected to be >10 years when treated by repeated surgical resection and hormonal therapy or both.

Treatment outcome and prognostic factors in intermediate risk stage I endometrial carcinoma.

Introducton: The aim of this study was to evaluate the clinical characteristics, post-surgery adjuvant treatment approach and posttreatment disease course in patients with intermediate risk stage I endometrium cancer and also to assess the effects of known prognostic factors on this group of patients. Patients and Methods: A total of 148 patients followed up postoperatively or after adjuvant treatment between 1996 and 2007 were evaluated retrospectively. Median follow-up duration was 67 months (range: 7-166). Among the study population 14.9% had Ib and 83.1% had stage Ic disease. 72 were treated by external beam radiotherapy (EBRT), 7 by intracavitary radiotherapy (ICRT), 65 by external + intracavitary radiotherapy (EBRT + ICRT), and one by chemoradiotherapy (CRT). Results: Vaginal vault is found to be the most common site of recurrences. Five and 10-year local control (LC) rates were 96.6% and 95.9%, respectively, while 5 and 10-year distant control (DC) rates were 94.6% and 91.9%, respectively. One, 5 and 10-year overall survival rates (OS) were 99.3%, 87.6% and 71.2%, respectively, while 1, 5 and 10-year progression-free survival rates (PFS) were 97.3%, 87.6% and 71.2%, respectively. Univariate analysis has revealed that prognostic factors as age (P = 0.0001), menopausal status (P = 0.049) and EBRT duration (P = 0.003) statistically significantly affected OS; while age (P = 0.0001) and EBRT duration (P = 0.006) affected PFS. Multivariate analysis has revealed that only age (P = 0.001) (P = 0.0001) and ERT duration (P = 0.021) (P = 0.027) affected both OS and PFS. Conclusion: LC and OS rates are high in the intermediate risk group. Age over 60 years and EBRT duration of 35 days and over both have negative effects on outcome in this group.

Collision of Three Histologically Distinct Endometrial Cancers of the Uterus

A collision tumor is defined by the presence of two separate masses in one organ, which are pathologically distinct. We described a 70-yr-old patient who complained of abnormal vaginal bleeding with a collision tumor of the uterine corpus. The patient received total hysterectomy, bilateral salphingo-oophorectomy, bilateral pelvic-paraaortic lymphadenectomy, omentectomy, and intraperitoneal chemotherapy. The uterine corpus revealed three separate masses, which were located at the fundus, anterior and posterior wall. Each tumor revealed three pathologically different components, which were malignant mixed mullerian tumor, papillary serous carcinoma, and endometrioid adenocarcinoma. Among these components, only the papillary serous carcinoma component invaded the underlying myometrium and metastasized to the regional lymph node. Adjuvant chemotherapy and radiation therapy were performed. The patient is still alive and has been healthy for the last 8 yr. We have reviewed previously reported cases of collision tumors which have occurred in the uterine corpus.

Long-term survival of a patient with multiple abdominal metastasis from endometrial carcinoma treated with multi-portal conformal re-irradiation and chemotherapy

A patient with recurrent endometrial cancer with multiple abdominal and pelvic tumoral masses was treated with re-irradiation combined with liposomal doxorubicin and oxaliplatin. A multiple field conformal technique was used to deliver a highly accelerated and hypo fractionated scheme [15 fractions of 3.5 Gy, within 19 days]. Complete response was confirmed four months after therapy. Four years later a lung metastasis appeared and was again treated with a similar course of therapy, once again resulting in a complete response. It is suggested that in the era of modern image-guided radiotherapy patients with endometrial cancer who have relapsed within or outside the loco-regional area, should be carefully assessed for an eventual gross tumor eradication using high-dose localized radiotherapy, leaving as the only target of chemotherapy the microscopic undetectable disease

Tratamento do câncer de endométrio / Treatment of endometrial cancer

O carcinoma de endométrio é o câncer ginecológico mais comum domundo desenvolvido. A maioria das mulheres apresenta-se no estádio I da doença, com bom prognóstico e taxade sobrevida global superior a 90%. O tratamento definitivo para o carcinoma endometrial é a histerectomiatotal abdominal e salpingo-ooforectomia bilateral associada ou não à linfadenectomia pélvica e para-aórtica,omentectomia e, eventualmente, seguida de terapias adjuvantes. Dentre elas, a radioterapia pélvica, a braquiterapiavaginal e a quimioterapia têm sido utilizadas como tratamentos complementares à cirurgia. Porém, a relevânciada dissecção linfonodal e da adjuvância permanece controversa particularmente na doença inicial, dada aexcelente taxa de sobrevida global dessas pacientes. O presente artigo discute algumas evidências em relaçãoa cada tipo de tratamento.

Endometrial carcinoma is the most common gynecological cancer inthe developed world. Most women are diagnosed with stage I disease, has good prognostic and an overallsurvival of up to 90%. The definitive treatment for endometrial carcinoma is total abdominal hysterectomyand bilateral salpingo-oophorectomy with or without pelvic and para-aortic lymphadenectomy, omentectomyand, eventually, adjuvant therapies. Among these therapies, the pelvic external beam radiotherapy, the vaginalbrachytherapy and the chemotherapy have been used as complementary treatment. However, the relevanceof lymphadenectomy and adjuvant therapies remains controversial, particularly in the initial disease, given theexcellent overall survival of this group of patients. The article brings a discussion on some evidences with regardto each of these adjuvant treatments

Condutas preconizadas pela FIGO, a partir de 2003, em relação aos cânceres ginecológicos C) Corpo do útero / Guidelines of gynecologic cancers by FIGO. C) Corpus uteri

Em 2003 a FIGO (Federação Internacional de Ginecologia e Obstetrícia); juntamente com a IGCS (International Gynecological Cancer Society) sugeriram e publicaram as condutas de tratamento frente aos diversos cânceres em ginecologia, baseados em trabalhos científicos e na experiência dos mais respeitados serviços do mundo. Em relação ao câncer de endométrio, o estadiamento é cirúrgico. A cirurgia preconizada no estádio I é a histerectomia total abdominal associada à anexectomia bilateral (HTA + AB). A linfadenectomia pélvica e para-aórtica é sugerida para os estádios I e tipos histológicos não endometrióides; quanto à radioterapia não há consenso sobre sua aplicabilidade nos estádios I. A braquiterapia pode ser útil, diminuindo a recidiva vaginal em casos de impossibilidade cirúrgica. Nos estádios II, pressupostos pré-operatoriamente, pode-se indicar a cirurgia de Whertheim-Meigs com linfadenectomia pré-aórtica; caso contrário, se a constatação foi intra-operatória, agir como nos estádios I, com linfadenectomia. Nos prováveis estádios III, a radioterapia pode ser indicada inicialmente e, se possível, seguida da cirurgia básica HTA + AB. Por outro lado, é de interesse a cito-redução. Nos estádios IV, assim como nas recidivas, devem ser avaliadas a quimioterapia ou a hormonioterapia com progestágenos ou eventualmente exenteração

Cáncer del endometrio: breves consideraciones / Brief considerations on endometrium cancer

Actualmente el cáncer del endometrio es la malignidad genital más frecuente en Estados Unidos. Esta neoplasia es susceptible de curación si se identifica con oportunidad mediante evaluación apropiada del sangrado vaginal postmenopáusico. Para establecer el diagnóstico dependemos del estudio del tejido recogido por dilatación cervical y legrado uterino fraccionado. Están en estudio otros recursos diagnósticos novedosos y prometedores. La hiperplasia adenomatosa compleja atípica es lesión precursora de cáncer endometrial. No disponemos de métodos de pesquisa o marcadores tumorales para identificar cáncer asintomático. La clasificación quirúrgica representa un adelanto significativo y orienta mejor el pronóstico y la terapéutica. El tratamiento es quirúrgico, individualizado y multidisciplinario. Recursos terapéuticos adicionales incluyen: radiaciones, quimio y hormonoterapia. El tratamiento de los tumores genitales malignos deben ser atendidos responsablemente por gineco-oncólogos certificados.

Tratamiento conservador en el carcinoma de endometrio estadio inicial en pacientes estériles / Conservative treatment of endometrial carcinoma in sterile patients

Se presentan 5 casos de mujeres que presentaban un adenocarcinoma de endometrio, estadio inicial y que fueron tratadas con acetato de medroxiprogesterona con el fin adicional de preservar su potencial de fertilidad. Habían consultado todas por esterilidad y, durante su estudio, se les diagnosticó un adenocarcinoma de endometrio por biopsia endometral. Se completó la evaluación del resto del endometrio con histeroscopias en 4 casos y con raspado uterino el restante. Clínicamente eran estadios iniciales: en cuatro casos se trataba de un adenocarcinoma bien diferenciado G1 y en un caso semidiferenciado G2. Cuatro pacientes fueron tratadas con acetato de medroxiprogesterona en dosis de 500 mgs por día y con 200 mgs por día la restante. Se realizaron controles histológicos cada dos meses y el tiempo de duración del tratamiento fue de 3 meses en dos casos, de 4 meses en otros dos y de 9 meses en el restante. En 4 mujeres se obtuvo remisión completa del adenocarcinoma. Tres de éstas continuaron con sus estudios y tratamiento de la esterilidad y lograron embarazos que llegaron a término, una paciente en dos oportunidades. Hasta la actualidad ninguna tuvo una recurrencia y el tiempo de seguimiento mínimo es de 30 meses. La cuarta paciente debió abandonar el tratamiento por esterilidad y a los dos años tuvo una recidiva del adenocarcinoma por lo que se le realizó una anexohisterectomía total, comprobándose en la pieza operatoria que se trataba de un adenocarcinoma moderadamente diferenciado G2 y que infiltraba hasta el tercio medio del miometrio. Mantiene curación clínica luego de 42 meses de seguimiento. El tratamiento conservador con progestágenos como primera línea en pacientes que padecen un adenocarcinoma bien diferenciado G1 estadio inicial ofrece la posibilidad de preservar la fertilidad sin disminuir la gran tasa de curación, de estos tumores, alcanzada con la terapia quirúrgica convencional

Influência de corticóide, na Doença de Chagas crônica, administrado em virtude de afecçöes associadas / Corticosteroid influence on chronic Trypanosoma cruzi infected patients, administered by virtue of associated diseases

Individuos acometidos de doença de Chagas em fase crônica foram tratados com corticóide, em virtude de afecçöes concomitantes. A fim de avaliar repercussöes sobre a infecçäo devida ao Trypanosoma cruzi, houve adoçäo de procedimentos de várias ordens, representados por métodos referentes à parasitose, exames inespecíficos e subsídios clínico, eletrocardiográfico e radiológico, tendo também sido mantido, para comparaçäo, grupo controle. Através do xenodiagnóstico ficou constatada a acentuaçäo da parasitemia, diretamente relacionada com a dose de corticóide, sem influência na evoluçäo da enfermidade parasitária, pelo menos durante o período no qual ocorreu a investigaçäo

Tratamento do câncer do endométrio com braquiterapia de alta taxa de dose / Treatment of endometrium neoplasm with high dose rate brachytherapy

Cento e quatro pacientes com histologia comprovada de carcinoma do endométrio foram tratadas desde a instalaçao da BATD no Departamento, em 1991. A idade mediana foi de 65,5 anos e o seguimento mediano de 38 meses. Noventa e cinco eram pós-menopausadas, sete peri-menopausadas e duas estavam na pré-menopausa. Dezesseis pacientes eram do estádio clínico (pós-cirúrgico) EC IA, sendo cinco com grau de diferenciaçao Gl, oito G2 e três G3. Trinta e quatro pacientes eram do EC IB, dez com grau de diferenciaçao Gl, 18 G2 e seis G3. Vinte e cinco eram do EC IC, sendo nove Gl, nove G2 e sete G3. Seis eram do EC IIA, duas Gl, três G2 e uma G3. Oito eram do EC IIB, uma Gl, três G2 e quatro G3. Nove eram do EC IIIA, duas Gl, cinco G2 e duas G3. Três eram do EC IIIB, sendo duas Gl e uma G2. Uma era EC IIIC G3 e duas eram IVA G3. Dependendo da extensao da doença, a cirurgia consistiu de pan-histerectomia (Histerectomia total mais salpingooforectomia bilateral), pan-histerectomia mais omentectomia ou Wertheim-Meigs. Todas as pacientes dos estádios clínicos IA e IB apresentam-se sem evidência de doença (SED). As do EC IC 24 estao SED e uma apresentou metástases (MAD). As do EC IIA, cinco estao SED e uma MAD. As do EC IIB, seis estao SED, uma com progressao de doença local (PDL) e uma foi a óbito (OPD). As do EC IIIA, sete estao SED, uma MAD e uma apresentou progressao de doença. As do EC IIIB l está SED e duas apresentam progressao de doença. A paciente IIIC está SED, dois meses após o tratamento, e as IVA se apresentam SED, três e quatro meses após o término do tratamento. Oito pacientes apresentaram complicaçoes leves de tratamento Os resultados sao semelhantes aos dos tratamentos com braquiterapia de baixa taxa de dose, tanto em sobrevida como em complicaçao, com a vantagem de ser realizado em regime ambulatorial , sem os inconvenientes de uma internaçao hospitalar.