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1.
DNA Cell Biol ; 39(5): 875-889, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32354230

RESUMO

Several studies have revealed that miR-205 plays important roles in the development of gynecological cancers and thus may serve as a potential prognostic biomarker, but the current conclusions remain controversial. Therefore, the goal of this study was to explore the prognostic significance and functional mechanisms of miR-205 based on a meta-analysis and bioinformatics investigation. A total of 14 published studies containing 5835 patients were enrolled by searching the PubMed, EMBASE, and Cochrane library databases, 13 (14 datasets) and 5 (6 datasets) of which evaluated the correlations between the expression level of miR-205 and overall survival (OS) or disease-free survival (DFS)/disease-specific survival (DSS)/progression-free survival (PFS)/distant metastasis-free survival (DMFS), respectively. Furthermore, the use of online Kaplan-Meier plotter database analysis supplemented another seven results for OS. Then, a meta-analysis using these 21 and 6 datasets was performed. As a result, the overall analysis failed to demonstrate any significant associations between miR-205 expression and OS (p = 0.267) or DSS/DFS/DMFS/PFS (p = 0.457), but the subgroup analysis suggested that elevated miR-205 predicted a reduced OS for breast cancer (BC) patients (hazard ratio [HR] = 0.84, 95% confidence interval [CI] = 0.72-0.98; p = 0.022), while higher miR-205 was associated with a poor DSS for endometrial cancer (EC) patients (HR = 2.19, 95% CI = 1.45-3.32; p < 0.001). Function prediction analysis indicated that miR-205 may be involved in BC by negatively influencing hub genes, SMARCA5 and SIAH1, whereas miR-205 may participate in EC by negatively modulating BMPR1B because of the presence of interactions of miR-205 with them at 3'-untranslated region and their opposite prognosis outcomes with miR-205. In conclusion, our findings suggest miR-205 may be a promising prognostic biomarker and therapeutic target for BC and EC patients.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , MicroRNAs/genética , Neoplasias da Mama/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Prognóstico
2.
Aging (Albany NY) ; 12(8): 6518-6535, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32339157

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What's more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.


Assuntos
Betacoronavirus , Carcinoma de Células Renais , Infecções por Coronavirus , Neoplasias do Endométrio , Imunidade Celular , Neoplasias Renais , Pandemias , Peptidil Dipeptidase A/biossíntese , Pneumonia Viral , Biomarcadores Tumorais , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Prognóstico
3.
Yonsei Med J ; 61(4): 317-322, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233174

RESUMO

PURPOSE: To evaluate factors associated with endometrial pathology during tamoxifen use in premenopausal breast cancer (BC) patients. MATERIALS AND METHODS: We reviewed the medical records of premenopausal BC patients treated with tamoxifen who underwent endometrial biopsy with or without hysteroscopy. Clinical characteristics were compared between women with endometrial pathology (endometrial hyperplasia or cancer) and those with normal histology or endometrial polyps. RESULTS: Among 284 endometrial biopsies, endometrial hyperplasia was diagnosed in 7 patients (2.5%), endometrial cancer was diagnosed in 5 patients (1.8%), normal histology was noted in 146 patients (51.4%), and endometrial polyp was present in 114 patients (40.1%). When comparing women with endometrial cancer (n=5) to women with normal histology, abnormal uterine bleeding was more common (p=0.007), and endometrial thickness was greater (p=0.007) in women with endometrial cancer. Chemotherapy for BC was also more common in patients with endometrial cancer (p=0.037). When comparing women with endometrial polyps and those with endometrial hyperplasia or cancer, the presence of abnormal uterine bleeding was more common in patients with endometrial hyperplasia or cancer (p<0.001); however, tamoxifen duration and endometrial thickness did not differ significantly between the two groups. CONCLUSION: In premenopausal BC patients treated with tamoxifen, abnormal uterine bleeding, increased endometrial thickness, and chemotherapy for BC were associated with the occurrence of endometrial cancer. These findings may provide useful information for gynecologic surveillance and counseling during tamoxifen treatment in premenopausal BC patients.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hiperplasia Endometrial/induzido quimicamente , Neoplasias do Endométrio/induzido quimicamente , Endométrio/efeitos dos fármacos , Pólipos/induzido quimicamente , Pré-Menopausa , Tamoxifeno/efeitos adversos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Biópsia , Hiperplasia Endometrial/diagnóstico por imagem , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Endométrio/diagnóstico por imagem , Endométrio/patologia , Feminino , Humanos , Histeroscopia , Pessoa de Meia-Idade , Pólipos/diagnóstico por imagem , Pólipos/patologia , Fatores de Risco , Tamoxifeno/uso terapêutico , Fatores de Tempo , Doenças Uterinas , Neoplasias Uterinas/induzido quimicamente , Neoplasias Uterinas/patologia
4.
Radiat Oncol ; 15(1): 72, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252781

RESUMO

BACKGROUND: The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. METHODS: We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. RESULTS: One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. CONCLUSIONS: Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.


Assuntos
Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos
5.
Anticancer Res ; 40(3): 1563-1570, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132058

RESUMO

BACKGROUND/AIM: This study aimed to determine whether a pelvic and para-aortic lymphadenectomy (PPAL) improves survival compared with a pelvic lymphadenectomy (PL) in patients with endometrial cancer. PATIENTS AND METHODS: Data from all women operated for endometrial cancer between 1998 and 2013 were extracted from the Surveillance, Epidemiology and End Results database. Women treated with PL were matched with those treated with PPAL according to age and risk of recurrence. The primary endpoint was disease-specific survival (DSS). RESULTS: A total of 1015 patients who underwent PL were matched with 1015 patients who underwent PPAL. The 3-year DSS probabilities for patients at intermediate- and high-risk (IHR) of recurrence were similar in the PPAL group and the PL group. Multivariate analysis of prognostic factors indicated that in patients with an IHR of recurrence, PPAL did not reduce the risk of death compared with PL. CONCLUSION: For patients with an IHR of recurrence, the extent of lymphadenectomy does not impact DSS.


Assuntos
Neoplasias do Endométrio/cirurgia , Excisão de Linfonodo/métodos , Estudos de Coortes , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Taxa de Sobrevida
6.
Anticancer Res ; 40(3): 1669-1676, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132073

RESUMO

AIM: To study whether mismatch repair (MMR) status is related to the expression of programmed cell death-ligand 1 (PD-L1) and CD8 counts in a series of grade 3 endometrial carcinomas. MATERIALS AND METHODS: The expression of MMR protein PD-L1 and CD8+ cell count were evaluated by immunohistochemistry and related to several clinicopathological parameters. RESULTS: Among 105 endometrial carcinomas, 40% were of endometrioid and 60% of non-endometrioid histology. MMR deficiency was observed in 28.6% of cases and was related to endometrioid histology (p<0.001), positive PD-L1 expression (p=0.047) and high CD8+ cell count (p=0.022). When examined by histotype, endometrioid MMR-deficient tumors were related only to PD-L1 expression (p=0.032) but not to high CD8+ cell count (p=0.231), whereas non-endometrioid MMR-deficient carcinomas were not related to either of these markers. MMR deficiency was associated with PD-L1+/CD8high status (p=0.006), whilst MMR proficiency was associated with PD-L1-/CD8low status. In MMR-proficient tumors, high CD8+ cell infiltration alone and combined with PD-L1- status was associated with better progression-free survival (p=0.013 and p=0.04, respectively). CONCLUSION: MMR-deficient high-grade endometrioid tumors might be more likely to benefit from immunotherapy compared to other grade 3 endometrial carcinomas.


Assuntos
Biomarcadores Tumorais/metabolismo , Reparo de Erro de Pareamento de DNA/imunologia , Neoplasias do Endométrio/terapia , Imunoterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade
9.
Orv Hetil ; 161(11): 425-433, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32148096

RESUMO

Introduction: Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The best survival rates are expected after surgical removal, thus the aim of a complex treatment is to achieve resecability in locally and locoregionally advanced disease. Aim: The primary purpose of this study was to evaluate if the neoadjuvant systemic treatment leads to better overall survival compared to irradiation solely. Method: From January 2015 to December 2018, we enrolled 28 patients diagnosed with irresecable, locally and locoregionally advanced high-risk endometrial carcinoma. Patients were treated by neoadjuvant paclitaxel-carboplatin, then radical hysterectomy, bilateral oophorectomy and lymphadenectomy were performed. Results: After administration of 6 cycles of carboplatin-paclitaxel, the control MR test showed tumor shrinkage in all patients. Complete resection was achieved in the case of every patient. Tumor residuum in lymph nodes was verified in 4 cases by pathological evaluation. The 2-year survival and the 2-year progression-free survival rates were 65,1% and 66,1%, respectively. The median overall survival was 16,5 months. Conclusion: Neoadjuvant treatment can be an effective approach in providing the conditions for complete tumor resection, which may result in survival advantage. Despite multimodal treatment, prognosis is poor. Orv Hetil. 2020; 161(11): 425-433.


Assuntos
Carboplatina/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapêutico , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Ovariectomia , Taxa de Sobrevida , Resultado do Tratamento
10.
Orv Hetil ; 161(10): 382-388, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32115990

RESUMO

Introduction: Recently published unfavourable results of endoscopic radical surgery for early-stage cervical cancer compared to open surgery raises the need for auditing treatment results of endoscopic staging surgery for endometrial cancer. Aim: Comparison of progression-free and overall survival (PFS and OS) between endometrial cancer patients treated with laparoscopic (LSC) and open surgical techniques. Method: Retrospective analysis was performed to compare clinicopathological and survival data of endometrial cancer patients who had either laparoscopic or open staging surgery between 2013 and 2019 at the Gynaecological Oncology Unit of the University of Debrecen, Hungary. Distribution of the most relevant prognostic factors were compared with χ2 and t-tests. Frequencies of progressive disease and disease-specific deaths were compared in the Cox-model, while progression-free and overall survival curves were compared with the Kaplan-Meier method. Results: The frequency of endometrioid, serous papillary, mixed Müllerian, adenosquamous and other histological types in the laparoscopic and open groups were similar (p = 0.3356). The frequency of grade 1, 2 and 3 tumours in the endoscopic and open groups showed significant differences (p = 0.0036). Pathological stage-distribution (IA, IB, II, IIIA, IIIB, IIIC1, IIIC2) of endoscopic cases and open cases was also statistically different (p = 0.0048). The mean number of removed lymph-nodes was higher in the open surgery group (14.3 vs. 9,3, p<0.0001). The frequency of recurrence did not show significant difference between the two groups, in contrast to the frequency of disease-specific deaths (2/120 vs. 29/345, p = 0.01; 2/120 vs. 17/345, p = 0.12). In the Cox-model, progression-free survival and overall survival showed a hazard ratio favouring laparoscopic surgery, however, the range of 95% confidence intervals showed no statistical significance (PFS LSC vs. open: HR = 0.36, 95% CI = 0.084-1.538; OS LSC vs. open: HR = 0.603, 95% CI = 0.135-2.693). Conclusion: Progression-free and overall survival of endoscopically staged endometrial cancer is not worse than those of patients staged with open surgery. Orv Hetil. 2020; 161(10): 382-388.


Assuntos
Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Histerectomia , Laparoscopia/métodos , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Feminino , Humanos , Hungria/epidemiologia , Excisão de Linfonodo , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
11.
Zhonghua Fu Chan Ke Za Zhi ; 55(2): 112-119, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32146740

RESUMO

Objective: To investigate the surgical complications in the treatment of stage Ⅰ endometrial cancer by robotic-assisted laparoscopy, the risk degree of Clavein-Dindo complications and the main risk factors affecting the occurrence of surgical complications. Methods: A retrospective case-control study was conducted in the First Affiliated Hospital of Zhengzhou University from October 2014 to June 2019. The patients were divided into robotic-assisted laparoscopy group and traditional laparoscopy group according to the operation mode, including 131 cases in robot group and 290 cases in traditional laparoscopy group. To compare the complications during and after operation and the risk degree of complications between the two groups by Clavein-Dindo classification standard, the age, body mass index (BMI), comorbidities, past history of pelvic surgery, American Society of Anesthesiologists (ASA) grade, preoperative anemia, number of pelvic lymph node resection, number of abdominal aortic lymph node resection, the total number of lymph node resection, operation time, surgical methods (robot surgery or traditional laparoscopic surgery) and other clinicopathological data were analyzed by logistic regression analysis. Results: (1) Complications of operation: the incidence of operative complications (including intraoperative and postoperative complications) in robot group was significantly lower than that in traditional laparoscopy group [(20.6%, 27/131) vs (34.8%, 101/290); χ(2)=8.620, P=0.003)]. The incidence of intraoperative complications in robot group was lower than that in traditional laparoscopy group [1.5% (2/131) vs 6.2% (18/290); χ(2)=4.368, P=0.037]. The incidence of intraoperative vascular injury in robot group was significantly lower than that in traditional laparoscopy group [0.8% (1/131) vs 5.2% (15/290); χ(2)=4.798, P=0.022]. The incidence of postoperative complications in robot group was also lower than that in traditional laparoscopy group [19.1% (25/131) vs 28.6% (83/290); χ(2)=4.303, P=0.038], but the incidence of postoperative lymphatic leakage in robot group was higher than that in traditional laparoscopy group [10.7% (14/131) vs 5.2% (15/290); χ(2)=4.279, P=0.039]. (2) Clavein-Dindo classification: the incidence of Clavein-Dindo Ⅰ, Ⅲ, Ⅲ, Ⅳ and Ⅴ grade between two groups were respectively 3.8% (5/131) vs 11.0% (32/290), 13.7% (18/131) vs 14.5% (42/290), 3.1% (4/131) vs 8.6% (25/290), 0 (0/131) vs 0.3% (1/290), 0 (0/131) vs 0.3% (1/290), and the incidence of grade Ⅰ (χ(2)=5.684, P=0.015) and Ⅲ (χ(2)=4.361, P=0.037) complications were statistically significant. The incidence of severe complications in robot group (grade Ⅲ and above) was lower than that in traditional laparoscopy group [3.1% (4/131) vs 9.3% (27/290); χ(2)=5.179, P=0.023]. (3) Analysis of influencing factors of surgical complications: univariate analysis showed that BMI (χ(2)=15.801, P=0.000), preoperative anemia (χ(2)=14.299, P=0.000), total number of lymph node resection (χ(2)=10.425, P=0.001), surgical methods (χ(2)=8.620, P=0.003) were related to the occurrence of surgical complications of endometrial carcinoma. Multivariate analysis showed that BMI (OR=0.289, 95%CI: 0.097-0.864, P=0.026), preoperative anemia (OR=0.309, 95%CI: 0.129-0.740, P=0.008), the total number of lymph node resection (OR=0.624, 95%CI: 0.403-0.966, P=0.034) and surgical methods (OR=3.491, 95%CI: 1.030-11.840, P=0.045) were independent risk factors for surgical complications of endometrial carcinoma. Conclusions: Compared with traditional laparoscopic surgery, robot-assisted laparoscopic surgery has fewer complications and lower incidence of severe complications. BMI, preoperative anemia, the total number of lymph node resection and surgical methods are independent risk factors for the occurrence of surgical complications of stage Ⅰ endometrial cancer.


Assuntos
Neoplasias do Endométrio/cirurgia , Laparoscopia , Excisão de Linfonodo/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos de Casos e Controles , China/epidemiologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
12.
Asian Pac J Cancer Prev ; 21(3): 733-741, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212801

RESUMO

OBJECTIVE: To compare the Ki-67 index of endometrial cancer cells before and after treatment between the metformin and placebo group in women with endometrial cancer (EC). METHODS: This study was a randomized, double-blind, placebo-controlled trial conducting in non-diabetic women who diagnosed with endometrioid EC and had a schedule for elective surgical staging at Rajavithi Hospital between August 2018 and June 2019. Tissue specimens were obtained via endometrial curettage at the time of initial diagnosis (pre-treatment) and hysterectomy (post-treatment) to assess the value of the Ki-67 index by immunochemistry. Patients were randomly assigned into 2 groups: metformin and placebo group. Metformin 850 mg or placebo 1 tab were administered once daily for at least 7 days, starting on the first morning after recruitment until one day before surgery. Baseline characteristics (e.g., age, body mass index, co-morbidities) including surgical and pathological characteristics were recorded. The metabolic effect of metformin was also evaluated by a recording of fasting blood sugar, HbA1C and potential adverse events including nausea, vomiting, dizziness, and hypoglycemic symptom. RESULTS: A total of 49 EC patients were included in this study. Twenty-five patients were assigned to the metformin group and 24 patients were assigned to the placebo group. Baseline demographic, surgical, and pathological characteristics between the 2 groups were similar. Metformin significantly changed the Ki-67 index relative to placebo, with a mean decrease of 23.3% (p=0.001) and a mean proportional decrease of 39.1% (p=0.006) before and after treatment. Additionally, no significant differences were detected in metabolic effects and adverse events between the metformin and the placebo groups. CONCLUSION: Short-term treatment with an oral metformin significantly reduced a proliferative marker Ki-67 index in women with endometrioid EC awaiting surgical staging. This study supports the biological effect of metformin in EC and potential applications in the adjuvant treatment in EC patients.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Metformina/uso terapêutico , Biomarcadores/análise , Proliferação de Células , Método Duplo-Cego , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade
13.
DNA Cell Biol ; 39(4): 615-630, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32105510

RESUMO

Uterine corpus endometrial carcinoma (UCEC) is one of the leading causes of death from gynecological cancer due to the high recurrence rate. A recent study indicated that molecular biomarkers can enhance the recurrence prediction power if they were integrated with clinical information. In this study, we attempted to identify a new multi-RNA-type-based molecular biomarker for predicting the recurrence risk and recurrence-free survival (RFS). Matched mRNA (including lncRNA) and miRNA RNA-sequencing data from 463 UCEC patients (n = 75, recurrent; n = 388, non-recurrent) were downloaded from The Cancer Genome Atlas database. LASSO (least absolute shrinkage and selection operator) analysis was used to screen the optimal combination of prognostic RNAs and then the risk score model was constructed. Moreover, the molecular mechanisms of prognostic RNAs were explored by establishing various interaction networks based on corresponding predictive databases. A multi-RNA-type-based signature (including three miRNAs: hsa-miR-6511b, hsa-miR-184, hsa-miR-4461; three lncRNAs: ENO1-IT1, MCCC1-AS1, AATBC; and 7 mRNAs: EPPK1, ASB9, BDNF, CYP11A1, ECEL1, EN2, F13A1) was developed for the prediction of RFS. The risk scoring system established by these signature genes was effective for the discrimination of the 5-year RFS in the high-risk from low-risk patients in the training [an area under the receiver operating characteristic curve (AUC) = 0.960], validation (AUC = 0.863), and entire datasets (AUC = 0.873). This risk score model was also proved to be a more excellent, independent prognostic discriminator than the single-RNA-type (overall AUC: 0.947 vs. 0.677, lncRNAs; 0.709, miRNAs; 0.899, mRNAs) and clinical staging (overall AUC: 0.947 vs. 0.517). Furthermore, the downstream mechanisms for some prognostic miRNAs or lncRNAs (HAND2-AS1-hsa-miR-6511b-APC2, PAX8-AS1-hsa-miR-4461-TNIK and MCCC1-AS1/ENO1-IT1-TNIK) were newly predicted based on the coexpression or competitive endogenous RNA theories. In conclusion, our findings may provide novel biomarkers for recurrence prediction and targets for treatment of UCEC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Sequência de Bases , Colo do Útero/patologia , Intervalo Livre de Doença , Neoplasias do Endométrio/diagnóstico , Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Análise de Sequência de RNA
14.
Nat Med ; 26(2): 252-258, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32042192

RESUMO

Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate that the genetic determinants of testosterone levels are substantially different between sexes and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1 s.d. higher testosterone increases the risks of type 2 diabetes (odds ratio (OR) = 1.37 (95% confidence interval (95% CI): 1.22-1.53)) and polycystic ovary syndrome (OR = 1.51 (95% CI: 1.33-1.72)) in women, but reduces type 2 diabetes risk in men (OR = 0.86 (95% CI: 0.76-0.98)). We also show adverse effects of higher testosterone on breast and endometrial cancers in women and prostate cancer in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific genetic analyses.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Síndrome do Ovário Policístico/sangue , Testosterona/sangue , Testosterona/farmacologia , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Composição Corporal , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Análise por Conglomerados , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/genética , Estradiol/sangue , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Masculino , Análise da Randomização Mendeliana , Razão de Chances , Fenótipo , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Fatores Sexuais , Software , Reino Unido
15.
Medicine (Baltimore) ; 99(8): e19281, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080141

RESUMO

BACKGROUND: The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. METHODS: The PubMed, Web of Science, the data of China National Knowledge Infrastructure, and Wan fang Medical Network were systematically searched for relevant articles without a cut-off date. The keywords for the search were "endometrial cancer," "endometrial carcinoma," "EC," "POLE mutations," "POLE exonuclease domain mutations," "POLE-mutant," "clinical characteristics" "prognostic." Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using Review manager 5.3 and Stata 14.0 statistical software. RESULTS: Six cohort studies assessing 179 EC patients with POLE EDMs were included. The results indicated a favorable progression-free survival in POLE-mutant patients (HR = 0.32; 95% CI: = [0.09-1.18]). Furthermore, the overall survival was great in patients with POLE-mutant (HR = 0.68; 95% CI = [0.41-1.13]). It was shown that a significantly higher incidence of POLE mutations with Federation of International of Gynecologists and Obstetricians (FIGO) I group compared to FIGO II-IV group (pooled ORs: 0.34, 95% CI: [0.12-0.94], P = .04), POLE-mutant EC was not significantly associated with histology (OR = 0.56,95% CI: 0.29-1.23), tumor grade (OR = 1.22,95% CI:0.85-1.74), lymph-vascular space invasion (OR = 0.40,95% 0.06-2.42), depth of myometrial invasion (OR = 0.70,95% CI: 0.41-1.18), lymph node status (OR = 0.41, 95% 0.04-4.50), and European Society for Medical Oncology risk groups (OR = 0.68,95% CI: 0.37-1.26). CONCLUSION: This meta-analysis has confirmed POLE EDMs may serve as a predictive biomarker of favorable prognosis. Further studies are needed to explore the appropriate clinical utility of POLE EDMs in EC.


Assuntos
DNA Polimerase II/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Mutação , Proteínas de Ligação a Poli-ADP-Ribose/genética , Biomarcadores Tumorais/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Linfonodos/patologia , Miométrio/patologia , Invasividade Neoplásica , Prognóstico , Intervalo Livre de Progressão
16.
Zhonghua Fu Chan Ke Za Zhi ; 55(1): 21-28, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32074769

RESUMO

Objective: To analyze the clinical efficacy and pregnancy outcomes of fertility- preserving re-treatment in patients with recurrent atypical endometrial hyperplasia (AEH) and early stage endometrial carcinoma (EEC) after achieved complete remission (CR) of primary fertility-preserving therapy. Methods: There were 104 cases of AEH and EEC collected from 9 hospitals in the multi-center research network platform of fertility-preserving therapy of endometrial carcinoma in China from January 2005 to May 2019. Thirth-one cases of them relapsed from four hospitals mentioned above,who achieved CR after primary fertility-preserving therapy,was analyzed retrospectively. Of the 31 cases, 27 cases chose fertility-preserving re-treatment. The demographic characteristics, re-treatment effect, clinical factors and pregnancy outcomes were observed. Results: (1) There were 16 AEH cases and 11 ECC cases among 27 recurrent patients who chose fertility-preserving therapy again. After re-treatment, CR was found in 13 out of 16 cases of AEH and 9 out of 11 cases of EEC. The overall CR rate was 81% (22/27). (2) After CR of recurrence, 5 cases (23%, 5/22) of re-recurrence were found after with a median time of 33 months (range 21-80 months). There were 4 cases underwent comprehensive surgical staging, and 1 patient chose the third round of fertility preservation therapy with fully informed consent, and CR was reached after 15 months. (3) There were 16 cases with pregnancy intention, with a total of 12 pregnancies, including 5 cases were natural pregnancy and 7 cases were assisted reproductive technology pregnancy. There were 5 live births. The follow-up time was up to May 2019, and the median follow-up time was 73 months (range 0-123 months). All 27 patients had disease free survival. Conclusions: Recurrent patients with AEH and EEC after achieving successful fertility-preserving therapy could choose fertility-preserving therapy again with comprehensive assessment and fully informed consent. After re-treatment, there is a certain tumor CR rate and pregnancy rate, while the close follow-up is required during treatment.


Assuntos
Carcinoma/terapia , Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , Preservação da Fertilidade , China , Feminino , Humanos , Recidiva Local de Neoplasia , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Resultado do Tratamento
17.
Life Sci ; 247: 117435, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32081661

RESUMO

Toll-like receptors (TLRs) are critical sensors related to inflammation and tumorigenesis. Among all subtypes, the TLR4 is a highly described transmembrane protein involved in the inflammatory process. The TLR4/myeloid differentiation factor 88 (MyD88) signaling pathway has been implicated in oncogenic events in several tissues and is associated with survival of patients. Through activation, TLR4 recruits adaptor proteins, i.e., MyD88 or TRIF, to triggers canonical and non-canonical signaling pathways that result in distinct immune responses. In most cancer cells, uncontrolled TLR4 signaling modifies the tumor microenvironment to proliferate and evade immune surveillance. By contrast, TLR4 activation can produce antitumor activities, thereby inhibiting tumor growth and enhancing the proper immune response. We review herein recent approaches on the role of the TLR4 signaling pathway and discuss potential candidates for gynecological cancer therapies; among these agents, natural and synthetic compounds have been tested both in vitro and in vivo. Since TLR4 ligands have been investigated as effective immune-adjuvants in the context of these aggressive malignancies, we described how TLR4 signaling controls part of the tumor-related inflammatory process and which are the new targeting molecules implicated in the regulation of tumorigenicity in ovarian, cervical, and endometrial cancers.


Assuntos
Antineoplásicos/química , Neoplasias do Endométrio/metabolismo , Neoplasias Ovarianas/metabolismo , Receptor 4 Toll-Like/metabolismo , Neoplasias do Colo do Útero/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Citocinas/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Terapia de Alvo Molecular/métodos , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais , Microambiente Tumoral/efeitos dos fármacos
18.
Oncology ; 98(4): 195-201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32036368

RESUMO

PURPOSE: The objective of this study was to evaluate the impact of hormone replacement therapy (HRT) on the prognosis in endometrial cancer (EC) survivors. METHODS: The research was conducted using the following electronic databases: MEDLINE (PubMed), Web of Science, ClinicalTrial.gov, and Cochrane Library. We performed a review of studies published from January 1986 to January 2019. We selected studies that included EC patients submitted to surgery with curative intent and postoperative use of HRT. RESULT: Seven of 1,332 abstracts considered were eligible: 4 retrospective series, 1 prospective study, 1 randomized controlled trial, and 1 population study. Globally in the observed studies there was not a significant increase in the recurrence rate, measured by the relative risk, in the EC survivors using HRT compared with the controls in tumour stages I and II. The bias was that HRT was prescribed only to low-risk patients, who were young and had a low stage of disease. CONCLUSION: This systematic review shows that HRT use had no negative effect on prognosis in EC survivors in tumour stages I and II.


Assuntos
Sobreviventes de Câncer , Neoplasias do Endométrio/mortalidade , Terapia de Reposição Hormonal , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Prognóstico
19.
Anticancer Res ; 40(2): 789-794, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014921

RESUMO

BACKGROUND/AIM: To investigate tumor suppression as an indicator of malignization potential within endometrial polyps in asymptomatic postmenopausal women. MATERIALS AND METHODS: Immunohistochemical studies of the phosphatase and tensin homolog (PTEN) were performed. Cases included 52 benign postmenopausal polyps, 19 endometrioid carcinomas with coexisting benign polyps, and 12 polyps with foci of carcinoma. Controls included 31 atrophic endometria and 32 benign premenopausal polyps. PTEN was scored by quantitative methods according to staining intensity. RESULTS: The mean epithelial and stromal PTEN H-score in postmenopausal benign endometrial polyps (193.8 and 123.2, respectively) was significantly higher than that in the atrophic endometrium (135.5 and 90.2, p=0.008), and premenopausal benign endometrial polyps (100.7 and 198.7, p<0.001). Significant difference between postmenopausal endometrial polyps and endometrial carcinoma was noticed in the epithelial compartment (193.8 vs. 65.7, respectively, p<0.001). CONCLUSION: Asymptomatic benign postmenopausal polyps have a distinctively high tumor suppression compared with endometrial cancer, suggesting low malignization potential.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Pólipos/tratamento farmacológico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pólipos/patologia , Pós-Menopausa , Estudos Retrospectivos
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