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1.
J Agric Food Chem ; 68(1): 213-224, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31861958

RESUMO

Asparanin A (AA), a steroidal saponin from Asparagus officinalis L., has anticancer activity: however, its detailed molecular mechanisms in endometrial cancer (EC) have not been studied so far. We evaluated the anticancer activity and underlying mechanism of AA on EC cell line Ishikawa in vitro and in vivo. AA inhibited the Ishikawa cell proliferation and caused cell morphology alteration and cell cycle arrest in G0/G1 phase. Moreover, it could induce apoptosis through mitochondrial pathway, including the deregulation of Bak/Bcl-xl ratio which led to the generation of ROS, up-regulation of cytochrome c followed by decrease of Δψm, and activation of caspases, besides inhibition of the PI3K/AKT/mTOR pathway. In vivo data showed that administration of AA significantly inhibited the tumor tissue cell proliferation, reduced the tumor growth, and induced the apoptosis occurrence. AA can be a possible functional food ingredient to cure endometrial cancer followed by clinical trials.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Asparagus (Planta)/química , Neoplasias do Endométrio/tratamento farmacológico , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Neoplasias do Endométrio/fisiopatologia , Feminino , Humanos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
2.
Med Sci Monit ; 25: 8248-8259, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31678981

RESUMO

BACKGROUND Novel biomarkers provide clinicians more critical information on tumor genetic features and patients' prognosis. Here, we aimed to establish prognosis-predicting signatures for endometrial carcinoma (EC) patients based on the miRNA information. MATERIAL AND METHODS The Cancer Genome Atlas (TCGA) website was available for dataset extraction. Prognosis-associated miRNAs were generated by univariate Cox regression test. Online websites were used to predict the targeted genes of these enrolled miRNAs. The miRNA-mRNA network was described by Cytoscape software, while the relevant signaling pathways of these targeted genes were enriched by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS The miRNA-based overall survival (OS) and recurrence-free survival (RFS) predicting signatures were constructed by LASSO Cox regression analyses, respectively, by which, the endometrial carcinoma patients were separated into high- and low-risk groups in both the discovery and validation sets. Univariate Cox regression analyses suggested that these high-risk patients had elevated death and recurrence risk compared to low-risk patients. In addition, multivariate Cox regression analysis confirmed that our signatures were independent prognosticate factors with or without clinicopathological features for endometrial carcinoma patients. Moreover, the miRNA-mRNA network was displayed by Cytoscape software, and the pathway enrichment analyses found that the targeted genes of these enrolled miRNAs were enriched in tumor progression and drug resistance-related pathways. CONCLUSIONS The OS and RFS predicting classifiers serve as independent prognosis-associated determiners for EC patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Endométrio/genética , MicroRNAs/genética , Neoplasias do Endométrio/fisiopatologia , Endométrio/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Prognóstico , RNA Mensageiro/metabolismo
3.
Radiol Oncol ; 53(3): 307-315, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31553703

RESUMO

Background Endometrial adenocarcinoma (EAC) is one of the most commonly diagnosed gynaecological malignancies among female population of the developed countries. DUSP6 is a negative regulator of ERK signaling, which is a molecular switch involved in MAPK signaling during the progress of malignancies. DUSP6 was previously found to inhibit tumorigenesis and EMT-associated properties in several cancers, however, its exact role in EAC remains unclear Methods The level of DUSP6, (E-cad) and (N-cad) in EAC cancerous tissues and respective adjacent non-cancerous tissues were examined by western-blot or immunohistochemistry. The cell growth, invasion and migration abilities were measured in Ishikawa 3H12 endometrial cancer cell lines with overexpressed or knock down DUSP6. Protein levels of EMT-associated markers E-cadherin, N-cadherin and Vimentin were also determined. The impacts of DUSP6 on ERK signaling was assessed by detection of ERK and p-ERK. Results Down-regulation of DUSP6 was observed in EAC compared with the normal controls. The overexpression of DUSP6 significantly attenuated tumor cell growth, invasion, migration abilities and inhibited EMT-associated markers, while knock down of DUSP6 showed opposite trends. Overexpression of DUSP6 also down-regulated p-ERK and the knock down of DUSP6 inversely up-regulated p-ERK level. Conclusions DUSP6 inhibited cell growth, invasion and migration abilities in Ishikawa 3H12 cells as well as attenuating EMT-associated properties. This tumor suppressive effect of DUSP6 in EAC is achieved by inhibiting ERK signaling pathway.


Assuntos
Adenocarcinoma/metabolismo , Fosfatase 6 de Especificidade Dupla/metabolismo , Neoplasias do Endométrio/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Sistema de Sinalização das MAP Quinases , Adenocarcinoma/fisiopatologia , Antígenos CD/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Neoplasias do Endométrio/fisiopatologia , MAP Quinases Reguladas por Sinal Extracelular , Feminino , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica
4.
Medicine (Baltimore) ; 98(29): e16433, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335697

RESUMO

RATIONALE: Endometrial neuroendocrine carcinoma is a rare histological subtype of endometrial cancer, divided into low-grade neuroendocrine carcinoma (carcinoid) and high-grade neuroendocrine carcinoma (small cell and large cell neuroendocrine carcinoma). It is characterized by high invasiveness and poor prognosis. L/SCNEC is an extremely rare pathological type of endometrial carcinoma, and the number of reports on this condition is few globally. PATIENT CONCERNS: A 54-year-old Chinese female presented with vaginal bleeding. DIAGNOSES: Outpatient hysteroscopy and endometrial biopsy were performed, and the pathological examination revealed that cervix was invaded by endometrial malignancy. The patient underwent a laparoscopic radical hysterectomy was diagnosed with the mixed large and small cell neuroendocrine carcinoma (L/SCNEC) of the endometrium combined with serous carcinoma III C2 (FIGO2009). INTERVENTIONS: Chemotherapy-radiotherapy-chemotherapy "sandwich" treatment was performed as postoperative therapy. OUTCOMES: After three chemotherapy circles, the patient showed no evidence of further disease progression. LESSONS: L/SCNEC is a rare and invasive disease. Once diagnosed, comprehensive treatments including surgery, radiotherapy, and chemotherapy can prolong the survival of patients and improve the prognosis.


Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Quimioterapia Adjuvante/métodos , Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Endométrio/patologia , Histerectomia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia/métodos , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/fisiopatologia , Carcinoma Neuroendócrino/terapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/fisiopatologia , Carcinoma de Células Pequenas/terapia , Terapia Combinada , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/fisiopatologia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/fisiopatologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Resultado do Tratamento , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/etiologia
5.
Int J Gynecol Cancer ; 29(8): 1311-1316, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31326951

RESUMO

BACKGROUND: There is a paucity of data on whether pre-operative walking and functional capacity has a direct association with post-operative gastrointestinal function in patients who have undergone surgery to treat gynecologic cancers. OBJECTIVE: To explore the relationship between pre-operative walking and post-operative recovery of bowel function. METHODS: This randomized trial was performed from January 1, 2018 to August 31, 2018. All patients had a diagnosis of endometrial or ovarian cancer and were scheduled for comprehensive staging. Group A served as the control group who did not walk regularly on the last night before surgery. Patients in group B walked for 30 min at an average speed of 3 km/h from 20.00 to 20.30 and 21.30. to 22.00 on the last night before surgery under the supervision of a nurse or doctor. The study was registered with clinicaltrials.gov (no: NCT03553121). RESULTS: A total of 85 patients were enrolled: 43 patients were assigned to the walking group and 42 to the control group. There were no significant differences in demographics between the groups. Median age was 57.3±8.5 in the control and 59.9±9.1 in the walking group. In addition, 28 patients had endometrial cancer and 14 had ovarian cancer in the control group. 33 patients and 10 patients in the walking group had endometrial and ovarian cancer, respectively. The mean time to first flatus was shorter in the walking group than in the control group (32.5±10.4 vs 40.6±16.9 hours, respectively; p=0.010). In addition, the time to first defecation was significantly shorter in the walking group (62.8±26.7 vs 91.4±51.8 hours; p=0.002). Patients who walked before surgery were less likely to have post-operative paralytic ileus (25.0% vs 60.7%; p=0.003). Walking before the operative period and laparoscopic surgery independently protected against the development of post-operative paralytic ileus. CONCLUSION: Walking before surgery expedited time to bowel motility and ability to tolerate food. In addition, this method significantly decreased the risk of post-operative paralytic ileus.We consider that walking before surgery may be integrated into the pre-operative management of patients under going surgery for gynecologic cancers. CLINICAL TRIAL REGISTRATION: clinicaltrial.org record number: NCT03553121.


Assuntos
Neoplasias do Endométrio/fisiopatologia , Neoplasias do Endométrio/cirurgia , Trato Gastrointestinal/fisiopatologia , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/cirurgia , Caminhada/fisiologia , Feminino , Humanos , Histerectomia/métodos , Excisão de Linfonodo , Pessoa de Meia-Idade , Omento/cirurgia , Período Pós-Operatório , Período Pré-Operatório , Salpingo-Ooforectomia/métodos
6.
Int J Gynecol Cancer ; 29(6): 1010-1015, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31203202

RESUMO

OBJECTIVE: To increase discussion about obesity and endometrial cancer and referrals to weight loss clinic in patients with newly diagnosed low-risk endometrial cancer. METHODS: A multidisciplinary team used a quality improvement methodology to increase patient awareness about obesity and endometrial cancer. Target population included patients <80 years old with a body mass index ≥30 kg/m2 who underwent surgery at our institution and had a final diagnosis of complex hyperplasia or stage I, grade 1-2 endometrioid endometrial cancer. A toolkit was developed for the intervention. Clinical characteristics, discussion about obesity, and referrals to a weight loss clinic were abstracted for a historic and intervention cohort. Data for the two cohorts were compared using chi-square, Fisher's exact test, and t-test. RESULTS: 54 patients from the historic cohort and 53 from the intervention cohort met inclusion criteria. Clinical characteristics were balanced between the groups. Discussion about obesity increased from 11.1% (6/54) to 79.2% (42/53) after implementing the toolkit (p<0.001). Referrals to the weight loss clinic also increased from 3.7% (2/54) to 26.4% (14/53) after implementing the toolkit (p=0.001), but in both groups only 50% of those referred actually attended the weight loss clinic. No clinical characteristics were identified as associated with being more likely to have documented conversations or referrals. CONCLUSIONS: A multidisciplinary quality-improvement project can be used to increase discussion about obesity and referral to a weight loss clinic in patients with low-risk endometrial cancer. Increasing patient awareness of the connection between obesity and endometrial cancer may have implications on the long-term health of endometrial cancer survivors.


Assuntos
Neoplasias do Endométrio/fisiopatologia , Neoplasias do Endométrio/psicologia , Obesidade/psicologia , Obesidade/terapia , Perda de Peso , Idoso , Conscientização , Índice de Massa Corporal , Estudos de Coortes , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Educação de Pacientes como Assunto , Melhoria de Qualidade , Encaminhamento e Consulta
7.
J Agric Food Chem ; 67(26): 7378-7389, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31184118

RESUMO

The molecular mechanism of Juglone-induced cell cycle arrest and apoptosis in human endometrial cancer cells was investigated. Juglone was purified from the green husk of Carya cathayensis Sarg and identified by HPLC, LC-MS/MS, and NMR. At an IC50 of 20.81 µM, juglone significantly inhibited Ishikawa cell proliferation, as shown by S phase arrest mediated by inactivation of cyclin A protein ( p < 0.05). The ROS levels increased significantly after exposure to juglone, which paralleled increases in the mRNA and protein expression of p21 and decreases in the levels of CDK2, cdc25A, CHK1, and cyclin A. The expression of Bcl-2 and Bcl-xL was significantly down-regulated, whereas the expression of Bax, Bad and cyto c was up-regulated, and we later confirmed the involvement of the mitochondrial pathway in juglone-induced apoptosis. Our in vitro results stated that juglone can be studied further as an effective natural anticancer agent.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carya/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias do Endométrio/fisiopatologia , Naftoquinonas/farmacologia , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Naftoquinonas/química , Extratos Vegetais/química , Fosfatases cdc25/genética , Fosfatases cdc25/metabolismo
8.
Genet Med ; 21(10): 2167-2180, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31086306

RESUMO

PURPOSE: Endometrial cancer (EC) is often the sentinel cancer in women with Lynch syndrome (LS). However, efforts to implement universal LS screening in EC patients have been hampered by a lack of evidence detailing the proportion of EC patients that would be expected to screen positive for LS. METHODS: Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I2 score was used to assess heterogeneity across studies. RESULTS: Fifty-three studies, including 12,633 EC patients, met the inclusion criteria. The overall proportion of endometrial tumors with microsatellite instability or mismatch repair (MMR) deficiency by immunohistochemistry (IHC) was 0.27 (95% confidence interval [CI] 0.25-0.28, I2: 71%) and 0.26 (95% CI 0.25-0.27, I2: 88%), respectively. Of those women with abnormal tumor testing, 0.29 (95% CI 0.25-0.33, I2: 83%) had LS-associated pathogenic variants on germline testing; therefore around 3% of ECs can be attributed to LS. Preselection of EC cases did increase the proportion of germline LS diagnoses. CONCLUSION: The current study suggests that prevalence of LS in EC patients is approximately 3%, similar to that of colorectal cancer patients; therefore our data support the implementation of universal EC screening for LS.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/fisiopatologia , Neoplasias do Endométrio/fisiopatologia , Adulto , Neoplasias Encefálicas/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Comorbidade , Reparo de Erro de Pareamento de DNA/genética , Detecção Precoce de Câncer , Neoplasias do Endométrio/genética , Feminino , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/genética
9.
Turk J Med Sci ; 49(2): 653-660, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30997980

RESUMO

Background/aim: This study compared TRPM2 and TRPM7 ion channel gene expression and immunohistochemical staining in endometrial hyperplasia and endometrium adenocarcinoma. Materials and methods: Sections were taken from paraffin blocks of 120 patients who were divided into 6 groups as follows: G1 (n = 20), proliferative endometrium (PE); G2 (n = 20), EH without atypia; G3 (n = 20), EH with atypia; G4 (n = 20), stage 1A, grade 1 EC; G5 (n = 20), stage 1A, grade 2 EC; and G6 (n = 20), stage 1A, grade 3 EC. TRPM2 and TRPM7 genes were analyzed with qRT-PCR in paraffin-embedded tissue samples. Under light microscopy, TRPM2 and TRPM7 immunostaining scores of the samples taken from polylysine slides were evaluated. Results: Compared to G1, TRPM2 mRNA gene expression was significantly downregulated in G3 and G5. TRPM2 immunoreactivity scores were similar in all groups. TRPM7 mRNA gene expression was significantly downregulated in G2, G3, and G6 when compared to G1. TRPM7 immunoreactivity scores were similar in G1, G2, and G3, but significantly decreased in G4, G5, and G6 Conclusion: Reduction in TRPM7 ion channel activity may be a progression marker for endometrial hyperplasia regardless of the atypical criteria.


Assuntos
Hiperplasia Endometrial/metabolismo , Neoplasias do Endométrio/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Canais de Cátion TRPM/metabolismo , Biomarcadores/metabolismo , Hiperplasia Endometrial/fisiopatologia , Neoplasias do Endométrio/fisiopatologia , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas Serina-Treonina Quinases/genética , Estudos Retrospectivos , Canais de Cátion TRPM/genética
10.
Gynecol Oncol ; 153(2): 399-404, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30879878

RESUMO

OBJECTIVE: The primary aim of this study was to pilot the use of an objective measurement technique to prospectively evaluate the incidence of lower extremity lymphedema (LEL) after minimally invasive staging surgery for endometrial cancer. Secondary objectives included observation of changes in lower extremity function and quality of life in this patient population. METHODS: A prospective evaluation of LEL was performed in 97 women who underwent minimally invasive staging surgery for endometrial cancer using comparative circumferential volume measurements. Postoperative changes in lower extremity function and global quality of life were also assessed using patient-reported outcome measures. RESULTS: Ninety-seven patients were included for lymphedema analysis. The rate of LEL was 25% at 4-6 weeks, 19% at 6-9 months, and 27% at 12-18 months postoperatively. The presence of LEL was associated with a significant worsening from baseline Lower Extremity Functional Scale (LEFS) scores at 4-6 weeks (-27.0% vs -3.7%, p = 0.02) and 6-9 months (-13.0% vs 0%, p = 0.01). LEL was not associated with a change in patient-reported global quality of life. CONCLUSIONS: Up to one in four women experience lymphedema following surgical staging for endometrial cancer, and its presence is associated with diminished lower extremity function. Larger, prospective trials using the objective methodology piloted in this study should better clarify risk factors and long-term outcomes of this morbidity.


Assuntos
Neoplasias do Endométrio/cirurgia , Perna (Membro)/fisiopatologia , Linfedema/etnologia , Linfedema/fisiopatologia , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Linfedema/etiologia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Estadiamento de Neoplasias , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida
11.
Semin Oncol Nurs ; 35(2): 157-165, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30867105

RESUMO

OBJECTIVE: To provide an overview of the etiology, diagnosis, treatment, and survivorship concerns surrounding endometrial cancer. DATA SOURCES: A review of articles dated 2006-2018 from PubMed and NCCN guidelines. CONCLUSION: Endometrial cancer is the most common gynecologic malignancy. Staging and treatment are primarily surgical, with adjuvant radiation and chemotherapy administered as indicated by grade and stage. IMPLICATIONS FOR NURSING PRACTICE: Cancer prevention, response to treatment, and quality of life can be affected by lifestyle factors, including nutrition, exercise, and tobacco use. Nurses in diverse roles and practice settings can educate patients about lifestyle choices that can affect individuals across the cancer trajectory.


Assuntos
Neoplasias do Endométrio/fisiopatologia , Neoplasias do Endométrio/terapia , Antineoplásicos/uso terapêutico , Feminino , Humanos , Radioterapia Adjuvante
12.
Proc Natl Acad Sci U S A ; 116(10): 4528-4537, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30782821

RESUMO

Endometrioid endometrial carcinomas (EECs) carry multiple driver mutations even when they are low grade. However, the biological significance of these concurrent mutations is unknown. We explored the interactions among three signature EEC mutations: loss-of-function (LOF) mutations in PTEN, gain-of-function (GOF) mutations of phosphoinositide 3-kinase (PI3K), and CTNNB1 exon 3 mutations, utilizing in vivo mutagenesis of the mouse uterine epithelium. While epithelial cells with a monoallelic mutation in any one of three genes failed to propagate in the endometrium, any combination of two or more mutant alleles promoted the growth of epithelium, causing simple hyperplasia, in a dose-dependent manner. Notably, Ctnnb1 exon 3 deletion significantly increased the size of hyperplastic lesions by promoting the growth of PTEN LOF and/or PI3K GOF mutant cells through the activation of neoadenogenesis pathways. Although these three mutations were insufficient to cause EEC in intact female mice, castration triggered malignant transformation, leading to myometrial invasion and serosal metastasis. Treatment of castrated mice with progesterone or estradiol attenuated the neoplastic transformation. This study demonstrates that multiple driver mutations are required for premalignant cells to break the growth-repressing field effect of normal endometrium maintained by ovarian steroids and that CTNNB1 exon 3 mutations play critical roles in the growth of preneoplastic cells within the endometrium of premenopausal women and in the myometrial invasion of EECs in menopausal women.


Assuntos
Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/fisiopatologia , Ovário/fisiopatologia , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , beta Catenina/genética , Alelos , Transformação Celular Neoplásica , Progressão da Doença , Hiperplasia Endometrial/enzimologia , Hiperplasia Endometrial/metabolismo , Neoplasias do Endométrio/enzimologia , Feminino , Humanos , Mutação
13.
Cell Cycle ; 18(3): 320-332, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30636489

RESUMO

Recent reports indicate that mesenchymal stem cells (MSCs) can fuse with cancer cells to promote cancer progression. Omental adipose-derived stromal cells (O-ASCs) are similar to MSCs, which could be recruited to the stroma in endometrial cancer. The aim of our study was to investigate whether O-ASCs can fuse with endometrial cancer cells to influence cancer cells biological characteristics. We isolated O-ASCs from patients with endometrial cancer. O-ASCs and endometrial cancer cells were labeled with different fluorescent tags and directly co-cultured in an Opera high-throughput spinning-disk confocal microscopy system to observe the processes involved in the fusion, division and migration of hybrid cells. Immunofluorescence and high-throughput imaging analyzes were performed to evaluate proteins related to epithelial-mesenchymal transition (EMT).We found O-ASCs could spontaneously fuse with endometrial cancer cells, including cytomembrane and nuclear fusion. After fusion, endometrial cancer cells assume an elongated and fibroblast-like appearance that exhibit mesenchymal phenotypes. The hybrid cells proliferated through bipolar and multipolar divisions and exhibited more rapid migratory speeds than were observed in the parental cells (P < 0.01), potentially because of their EMT-associated changes, including the down-regulation of E-cadherin and up-regulation of Vimentin. Our results collectively suggest that tumorigenic hybrids spontaneously formed between human O-ASCs and endometrial cancer cells, and that the resulting cells enhanced cancer mobility and heterogeneity by accelerated migration and undergoing multipolar divisions. These data provide a new avenue for investigating the roles of O-ASCs in endometrial cancer.


Assuntos
Tecido Adiposo/citologia , Movimento Celular , Neoplasias do Endométrio/fisiopatologia , Aneuploidia , Carcinogênese , Fusão Celular , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Transição Epitelial-Mesenquimal , Feminino , Humanos , Células Híbridas , Omento/citologia , Células Estromais/fisiologia
14.
Prim Care ; 45(4): 625-641, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30401346

RESUMO

The menopausal transition is a time when many physical and psychological changes are occurring for women. Women may experience irregular menses, vasomotor symptoms, sleep disruption, mood disorders as well as genitourinary symptoms. Despite irregular menstrual cycles, some women can still conceive. It is important to understand what is within normal physiologic changes and what may represent pathologic changes and how to further evaluate this. There are many options available to manage menopausal symptoms when they are impacting quality of life.


Assuntos
Menopausa/fisiologia , Atenção Primária à Saúde/organização & administração , Saúde da Mulher , Anticoncepção/métodos , Neoplasias do Endométrio/fisiopatologia , Terapia de Reposição de Estrogênios/métodos , Feminino , Gabapentina/uso terapêutico , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Transtornos do Humor/tratamento farmacológico , Gravidez , Gravidez não Planejada , Qualidade de Vida , Fatores de Risco , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/terapia
15.
Int J Gynecol Cancer ; 28(9): 1737-1742, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30358703

RESUMO

OBJECTIVE: Sexual health is important to quality of life; however, the sexual health of gynecologic cancer patients is infrequently and inadequately addressed. We sought to understand patient experiences and preferences for sexual health care to help inform strategies for improvement. METHODS/MATERIALS: An anonymous, cross-sectional survey of outpatient gynecologic cancer patients at a large academic medical center was performed as part of a larger study examining patient and caregiver needs. The survey explored patient-provider discussions about sexuality across 3 domains (experiences, preferences, barriers) and 4 phases of cancer care (diagnosis, treatment, treatment completion, follow-up). Age, relationship status, sexual activity, and cancer type were recorded. RESULTS: Mean age was 63 years. Most patients had ovarian cancer (38%) or endometrial cancer (32%). Thirty-seven percent received treatment within the last month, 55% were in a relationship, and 35% were sexuality active. Thirty-four percent reported sexuality as somewhat or very important, whereas 27% felt that it was somewhat or very important to discuss. Importance of sexuality was associated with age, relationship status, and sexual activity but not cancer type. Fifty-seven percent reported never discussing sexuality. Age was associated with sexuality discussions, whereas relationship status, sexual activity, and cancer type were not. The most common barrier to discussion was patient discomfort. Follow-up was identified as the best time for discussion. Sexuality was most often discussed with a physician or advanced practice provider and usually brought up by the provider. CONCLUSIONS: Demographic predictors of importance of sexuality to the patient are age, relationship status, and sexual activity. Providers primarily use age as a proxy for importance of sexuality; however, relationship status and sexual activity may represent additional ways to screen for patients interested in discussing sexual health. Patient discomfort with discussing sexuality is the primary barrier to sexual health discussions, and awareness of this is key to developing effective approaches to providing sexual health care.


Assuntos
Neoplasias dos Genitais Femininos/terapia , Cuidados Paliativos/métodos , Disfunções Sexuais Psicogênicas/terapia , Saúde Sexual , Sexualidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/fisiopatologia , Neoplasias do Endométrio/psicologia , Neoplasias do Endométrio/terapia , Feminino , Neoplasias dos Genitais Femininos/fisiopatologia , Neoplasias dos Genitais Femininos/psicologia , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/terapia , Preferência do Paciente , Qualidade de Vida , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/fisiopatologia , Disfunções Sexuais Psicogênicas/psicologia
16.
Mol Biol Rep ; 45(6): 2257-2262, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30225581

RESUMO

Substance P (SP), a neuropeptide belonging to the tachykinin family, exerts different biological activities mainly through neurokinin-1 receptor (NK1R). The role of SP/NK1R system in tumoral growth and spread is reported in several cancers. We aimed to evaluate the serum SP concentration and NK1R tissue distribution in endometrial cancer, and to study the relationship between these factors with tumor size, lymph node involvement, disease stage and cancer grade. Recruiting 22 patients with endometrial cancer and 21 patients with leiomyoma as the control group, serum SP concentration was measured using an ELISA method, and NK1R tissue distributions were immunohistochemically analyzed. Serum SP concentration in patients was significantly higher than the control group (p-value = 0.005). The expression level of NK1R in tumoral tissue was more than normal tissue (p-value < 0.001). The NK1R expression had a significant relationship with lymph node involvement (p-value = 0.005) and disease stage (p-value = 0.017). The NK1R expression was higher in more advanced and less-differentiated tumors. SP/NK1R system seems to play a role in tumor growth and development in endometrial cancer. As well, the NK1R expression increased in endometrial cancer, and may be considered as a prognostic factor; but further studies are needed in this field.


Assuntos
Neoplasias do Endométrio/metabolismo , Receptores da Neurocinina-1/análise , Substância P/análise , Adulto , Neoplasias do Endométrio/fisiopatologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Irã (Geográfico) , Substância P/sangue , Taquicininas/metabolismo , Distribuição Tecidual/genética
17.
Biosci Trends ; 12(4): 342-353, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30146551

RESUMO

Gynecologic cancer is a vital global healthcare issue with high rates of mortality and morbidity. Tumor metastasis attributes to most of the death suffering from solid tumors. The epithelial-mesenchymal transition (EMT) plays a pivotal role in initiating metastasis. Long non-coding RNAs (lncRNAs), a well-known group of non-coding RNAs, and a prominent topic in life science research, are misregulated in many malignancies and some are EMT-associated. In the case of gynecologic cancers, several EMT-associated lncRNAs have been identified and found to be implicated in cancer aggressiveness and progression. Mechanically, these lncRNAs participate in the EMT-related metastatic process in multiple ways including interaction with polycomb repressive complex 2 (PRC2), regulation of EMT signaling networks, mediation of EMT-transcription factors (EMT-TFs) and EMT markers, and cooperation with microRNAs (miRNAs). Further studies on these EMT-associated lncRNAs and identification of more relevant lncRNAs are imperative for the lncRNAs-based clinical management of high rate of metastasis in patients with gynecologic cancers.


Assuntos
Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias dos Genitais Femininos/fisiopatologia , RNA Longo não Codificante/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/fisiopatologia , Feminino , Neoplasias dos Genitais Femininos/genética , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/fisiopatologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/fisiopatologia
18.
Int J Mol Sci ; 19(8)2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30061539

RESUMO

Cell contacts exhibit a considerable influence on tissue physiology and homeostasis by controlling paracellular and intercellular transport processes, as well as by affecting signaling pathways. Since they maintain cell polarity, they play an important role in cell plasticity. The knowledge about the junctional protein families and their interactions has increased considerably during recent years. In contrast to most other tissues, the endometrium undergoes extensive physiological changes and reveals an extraordinary plasticity due to its crucial role in the establishment and maintenance of pregnancy. These complex changes are accompanied by changes in direct cell⁻cell contacts to meet the various requirements in the respective developmental stage. Impairment of this sophisticated differentiation process may lead to failure of implantation and embryo development and may be involved in the pathogenesis of endometrial diseases. In this article, we focus on the knowledge about the distribution and regulation of the different junctional proteins in the endometrium during cycling and pregnancy, as well as in pathologic conditions such as endometriosis and cancer. Decoding these sophisticated interactions should improve our understanding of endometrial physiology as well as of the mechanisms involved in pathological conditions.


Assuntos
Comunicação Celular , Neoplasias do Endométrio/fisiopatologia , Endometriose/fisiopatologia , Endométrio/fisiopatologia , Junções Aderentes/metabolismo , Junções Aderentes/patologia , Animais , Implantação do Embrião , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Endometriose/metabolismo , Endometriose/patologia , Endométrio/citologia , Endométrio/metabolismo , Endométrio/patologia , Feminino , Hormônios/metabolismo , Humanos , Junções Íntimas/metabolismo , Junções Íntimas/patologia
19.
Int J Mol Sci ; 19(7)2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30037059

RESUMO

The Human Genome Project led to the discovery that about 80% of our DNA is transcribed in RNA molecules. Only 2% of the human genome is translated into proteins, the rest mostly produces molecules called non-coding RNAs, which are a heterogeneous class of RNAs involved in different steps of gene regulation. They have been classified, according to their length, into small non-coding RNAs and long non-coding RNAs, or to their function, into housekeeping non-coding RNAs and regulatory non-coding RNAs. Their involvement has been widely demonstrated in all cellular processes, as well as their dysregulation in human pathologies. In this review, we discuss the function of non-coding RNAs in endometrial physiology, analysing their involvement in embryo implantation. Moreover, we explore their role in endometrial pathologies such as endometrial cancer, endometriosis and chronic endometritis.


Assuntos
Endométrio/metabolismo , Endométrio/fisiopatologia , RNA Longo não Codificante/genética , Animais , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/fisiopatologia , Endometriose/metabolismo , Endometriose/fisiopatologia , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/fisiologia , RNA Longo não Codificante/fisiologia
20.
J Int Med Res ; 46(9): 3709-3716, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29998764

RESUMO

Objectives Endometrial cancer is the most frequent tumor of the female genital tract. Ubiquitin is a small protein (8.5 kDa) found in all eukaryotic cells, binds to substrate proteins via a three-phase enzymatic pathway referred to as ubiquitination and plays an important role in cellular stability. Neural precursor cell-expressed developmentally down-regulated 4-like (NEDD4L) functions in the last phase of this enzymatic process. In this study, we investigated NEDD4L protein expression in endometrial cancer. Methods The study participants were divided into patients with benign endometrial pathologies (Group 1, n = 23), patients with endometrial hyperplasia (Group 2, n = 21) and patients with endometrial cancer (Group 3, n = 20). NEDD4L expression was detected by immunohistochemical staining and H scores were calculated to standardize staining intensity. Statistical analysis was performed using SPSS 16.0. Results NEDD4L expression levels according to H scores were significantly lower in patients diagnosed with endometrial cancer compared with those with benign endometrial pathologies. Conclusion NEDD4L is involved in maintaining cell stability, and reduced NEDD4L expression as a result of gene mutation may disrupt this balance in favor of tumorigenesis.


Assuntos
Adenocarcinoma/fisiopatologia , Neoplasias do Endométrio/fisiopatologia , Ubiquitina-Proteína Ligases Nedd4/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/fisiopatologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Ubiquitina-Proteína Ligases Nedd4/biossíntese , Pólipos/genética , Pólipos/metabolismo , Pólipos/patologia , Pólipos/fisiopatologia , Estudos Retrospectivos , Doenças Uterinas/genética , Doenças Uterinas/metabolismo , Doenças Uterinas/patologia , Doenças Uterinas/fisiopatologia
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