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1.
BMC Cancer ; 23(1): 608, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37391693

RESUMO

PURPOSE: To assess the clinical characteristics and the risk factors related to the unfavorable prognosis of endometrioid ovarian carcinoma (EOVC) based on data from the Surveillance, Epidemiology, and End Results (SEER) database and two clinical centers in China. METHODS: Data were extracted from the SEER database and two clinical centers in China (2010 ~ 2021), 884 cases and 87 patients with EOVC were selected, respectively. Overall survival (OS) and progression-free survival (PFS) were compared among the different groups using Kaplan-Meier analysis. The Cox proportional-hazards model was used to identify independent prognostic factors related to EOVC. A nomogram was constructed based on the risk factors of the SEER database affecting prognosis and the discrimination and calibration of the nomogram were evaluated by C-index and calibration curves. RESULTS: The average age at diagnosis of patients with EOVC in the SEER database and two centers in China was 55.77 ± 12.40 years and 47.14 ± 11.50 years, 84.7% and 66.6% of them were diagnosed at FIGO stage I ~ II, respectively. In the SEER database, age over 70 years, advanced FIGO stage, tumor grade 3, only unilateral salpingo-oophorectomy were independent risk factors of unfavorable prognosis. In two clinical centers in China, 27.6% of EOVC patients were diagnosed with synchronous endometriosis. Advanced FIGO stage, HE4 > 179 pmol/L and bilateral ovarian involvement significantly correlated with poor OS and PFS in Kaplan-Meier analysis. Body mass index (BMI) < 19.34 kg/m2 was an independent risk factor relating to OS and PFS. Additionally, C-index of internal and external verification for the nomogram were 0.812 and 0.754 respectively, revealing good accuracy and clinical applicability. CONCLUSIONS: Most patients were diagnosed at early stage, low grade and had better prognosis. Asian/Pacific Islander and Chinese diagnosed with EOVC were more likely to be younger than whites and blacks. Age, tumor grade and FIGO stage (SEER database) and BMI (two centers) are independent prognostic factors. HE4 appears to be more valuable in prognostic assessment compared with CA125. The nomogram had good discrimination and calibration for predicting prognosis, providing a convenient and reliable tool for clinical decision-making for patients with EOVC.


Assuntos
Carcinoma Endometrioide , Neoplasias Ovarianas , Feminino , Humanos , Idoso , Prognóstico , Nomogramas , Carcinoma Epitelial do Ovário , China/epidemiologia , Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/terapia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/terapia
2.
BMC Cancer ; 21(1): 322, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766002

RESUMO

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian carcinoma (EOC). We conducted this research to investigate the clinical characteristics and outcomes of OCCC and to provide additional supporting evidence to aid in the clinical diagnosis and management. METHODS: This was a retrospective study investigating the clinical characteristics and survival outcomes of 86 patients with OCCC treated at our center between January 2010 and March 2020. Survival analysis was also performed on 179 patients with OCCC obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registry database. RESULTS: The median age of participants was 49.21 ± 9.91 years old, and 74.42% of them were diagnosed at early stage. The median CA125 level was 601.48 IU/mL, while 19.77% of the patients had normal CA125 levels. Sixteen patients (18.60%) had co-existing endometriosis and 8 patients (9.3%) developed venous thromboembolism (VTE). There were 5 patients received suboptimal cytoreduction. Sixty-six patients (76.74%) underwent lymphadenectomy, and only 3 (4.55%) patients had positive lymph nodes. Patients diagnosed at an early stage had higher 3-year overall survival (OS) and progression-free survival (PFS) rates than those with advanced stage OCCC. CA19-9 (P = 0.025) and ascites (P = 0.001) were significantly associated with OS, while HE4 (P = 0.027) and ascites (P = 0.001) were significantly associated with PFS. Analysis of data from the SEER database showed that positive lymph nodes is also an independent prognostic factor for OS (P = 0.001). CONCLUSIONS: OCCC often presents at an early stage and young age with a mildly elevated CA125. CA19-9, HE4, massive ascites, and positive lymph node are independent prognostic factors.


Assuntos
Adenocarcinoma de Células Claras/diagnóstico , Carcinoma Epitelial do Ovário/diagnóstico , Neoplasias Ovarianas/diagnóstico , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/cirurgia , Adulto , Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Feminino , Humanos , Histerectomia/estatística & dados numéricos , Excisão de Linfonodo/estatística & dados numéricos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Ovariectomia/estatística & dados numéricos , Ovário/patologia , Ovário/cirurgia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Salpingectomia/estatística & dados numéricos
3.
BMC Pregnancy Childbirth ; 20(1): 349, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513127

RESUMO

BACKGROUND: Severe obstetric haemorrhage caused by placenta accreta spectrum (PAS) results in significant maternal morbidity and mortality. The effectiveness of prophylactic balloon occlusion of the internal iliac artery in PAS patients remains controversial. Therefore, we conducted a retrospective case-control study to investigate the clinical effectiveness of this treatment. METHODS: The clinical data of 104 patients with PAS complicated with placenta previa who delivered by caesarean section between January 2016 and January 2019 were collected, and the patients were divided into two groups. The study group (48 cases) underwent internal iliac artery preset balloon occlusion before caesarean section and uterine artery embolisation according to the bleeding status after surgery, while the control group (56 cases) did not undergo internal iliac artery preset balloon occlusion before caesarean section. RESULTS: The operation and hospitalisation times in the study group were longer than those in the control group. Additionally, the hysterectomy rate in the study group was significantly higher than that in the control group. No significant differences in blood loss, blood transfusion volume, urinary system injury, postoperative ICU transfer rate, or neonatal scores were identified between the groups. Among the patients without invasive placenta (placenta increta and percreta), blood loss was lower in the study group, and the caesarean hysterectomy rate did not significantly differ between the groups. Among the patients with invasive placenta, blood loss and the caesarean hysterectomy rate did not significantly differ between the groups. The risk of hysterectomy in the study group was related to invasive placenta penetration, a large area of placental invasion, or abnormal vascular filling. One patient in the study group had a thrombus in the left lower extremity artery. CONCLUSIONS: Balloon occlusion of the internal iliac artery is effective for haemostasis of placenta previa in the absence of invasive placenta. For patients with invasive placenta, especially placenta percreta, a large area of placental invasion or abnormal vascular filling suggests the need for hysterectomy. The risks of the prophylactic use of internal iliac artery balloon occlusion include vascular injury and thrombus formation.


Assuntos
Oclusão com Balão , Artéria Ilíaca , Placenta Acreta/terapia , Placenta Prévia/terapia , Adulto , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Estudos de Casos e Controles , Cesárea , Feminino , Humanos , Histerectomia/estatística & dados numéricos , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Estudos Retrospectivos , Embolização da Artéria Uterina , Adulto Jovem
4.
Cytokine ; 120: 165-175, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31085454

RESUMO

This study explored the effect of LncRNA Lnc-LIF-AS on cell proliferation, migration and invasion in the human cervical cancer (HCC) cell line SiHa. SiHa cells had the lowest expression of Lnc-LIF-AS in the 4 human cervical cancer cell lines (SiHa, ME-180, C-33A and HeLa) and were transfected and divided into the SiHa/con (transfected with pMIGRI) cell group, SiHa/Lnc-LIF-AS (transfected with pMIGRI-Lnc-LIF-AS) cell group, and SiHa/Lnc-LIF-AS-DN (transfected with pMIGRI-Lnc-LIF-AS-DN, in which the sequences overlapping with LIF mRNA was deleted) cell group. Overexpression of Lnc-LIF-AS could promote the proliferation, colony formation, invasion and migration in SiHa and ME-180 cells. And the low expression of Lnc-LIF-AS suppress the proliferation, colony formation invasion and migration in HeLa cells when the Lnc-LIF-AS expression has been suppressed. In the SiHa/Lnc-LIF-AS cells group, the cell cycle was mainly halted in the S phase and overexpression of Lnc-LIF-AS had no effect on the apoptosis of SiHa cells. Overexpression of Lnc-LIF-AS could promote the secretion of LIF in SiHa cells, and the supernatant from SiHa/Lnc-LIF-AS cells could promote cell proliferation in the SiHa/con cells. The STAT3 inhibitor could inhibit cell proliferation in the SiHa/Lnc-LIF-AS cells. The expression level of Lnc-LIF-AS in cervical cancer tissues was higher than that in normal tissues and the expression level of Lnc-LIF-AS was positively correlated with the level of LIF. In the SiHa/con and SiHa/Lnc-LIF-AS-DN cell groups, there were no significant differences in cell proliferation, cell migration and cell invasion. The overexpression of Lnc-LIF-AS can promote cell proliferation, migration and invasion in cervical cancer cells, and the core function domain of this lncRNA was located in the overlapping a 3'-UTR base sequence of LIF mRNA.


Assuntos
Movimento Celular/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
5.
Cytokine ; 96: 114-122, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28391028

RESUMO

We aim to determine the lncRNA targets of ΔNp63α in cervical cancer and molecular programs in cancerous differentiation. Different profiles of the lncRNAs were assayed and validated in overexpressing p63 SiHa cells (SiHa/ΔNp63α) and the control cell lines (SiHa/pCon). ENST00000422259, ENST00000447565 (Lnc-LIF-AS) and ENST00000469965, together with their related antisense mRNA DPYD (dihydropyrimidine dehydrogenase, a pyrimidine catabolic pathway gene), LIF (leukemia inhibitor factor) and FLNC (filamin C) were all notably differentially expressed in both ΔNp63α overexpression cells and knockdown cells. Here, we illustrated that ΔNp63α can inhibit the levels of LIF mRNA by direct transcription regulation and decrease LIF mRNA stability by suppressing the expression of Lnc-LIF-AS. An inverse interaction of LIF and ΔNp63α expression was as well validated in clinical samples of cervical cancer, and high level of LIF in cervical cancers was related with poor patient survival. The decrease of ΔNp63α also attenuated the differentiation of cervical cancerous cells. Suggesting that ΔNp63α may be form a complex network in regulation cervical cancerous differentiation.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Fator Inibidor de Leucemia/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias do Colo do Útero/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Di-Hidrouracila Desidrogenase (NADP)/genética , Regulação para Baixo , Feminino , Filaminas/genética , Humanos , Fator Inibidor de Leucemia/metabolismo , Ligação Proteica , Análise Serial de Tecidos , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Regulação para Cima
6.
Mol Ther Oncolytics ; 28: 293-306, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36911068

RESUMO

Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide. Receptor tyrosine kinases (RTKs) have long been sought as therapeutic targets for EOC, as they are frequently hyperactivated in primary tumors and drive disease relapse, progression, and metastasis. More recently, these oncogenic drivers have been implicated in EOC response to poly(ADP-ribose) polymerase (PARP) inhibitors and epigenome-interfering agents. This evidence revives RTKs as promising targets for therapeutic intervention of EOC. This review summarizes recent studies on the role of RTKs in EOC malignancy and the use of their inhibitors for clinical treatment. Our focus is on the ERBB family, c-Met, and VEGFR, as they are linked to drug resistance and targetable using commercially available drugs. The importance of these RTKs and their inhibitors is highlighted by their impact on signal transduction and intratumoral heterogeneity in EOC and successful use as maintenance therapy in the clinic through suppression of the VEGF/VEGFR axis. Finally, the therapeutic potential of RTK inhibitors is discussed in the context of combinatorial targeting via co-inhibiting proliferative and anti-apoptotic pathways, epigenomic/transcriptional programs, and harnessing the efficacy of PARP inhibitors and programmed cell death 1/ligand 1 immune checkpoint therapies.

7.
Int Urogynecol J ; 23(7): 887-91, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22249281

RESUMO

INTRODUCTION AND HYPOTHESIS: To report the outcomes of modified laparoscopic extraperitoneal uterine suspension to anterior abdominal wall for uterine prolapse using mesh. METHODS: Twenty-two patients with uterovaginal prolapse, stage 2 or greater according to pelvic organ prolapse quantification (POP-Q), and with desire for uterine preservation, underwent modified laparoscopic extraperitoneal uterine suspension to the anterior abdominal wall bilaterally using mesh. The outcomes were measured by POP-Q and quality-of-life questionnaires. Intraoperative or postoperative complications were also observed. RESULTS: Patient age was 61.4 ± 12 years, and parity was 3.3 ± 1.8. After surgery, there was significant improvement in POP-Q measurements of Ba, Bp, and C (P < 0.001). The objective cure rate at 1 year was 100%. A significant improvement in quality-of-life scores was observed (P < 0.001). There were no major intraoperative or postoperative complications. However, all patients reported postoperative dragging pain at the points of puncture ports where the mesh was fixed to the abdominal wall. The visual analog scale decreased from a mean 3-day score of 2.9-0 at 1-month follow-up. CONCLUSIONS: Modified laparoscopic extraperitoneal uterine suspension to the anterior abdominal wall using mesh is a feasible and effective method for treating uterine prolapse and is easy to perform.


Assuntos
Parede Abdominal/cirurgia , Laparoscopia , Telas Cirúrgicas , Prolapso Uterino/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória , Qualidade de Vida , Técnicas de Sutura , Resultado do Tratamento
8.
Oncol Lett ; 23(5): 155, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35836483

RESUMO

The present study aimed to evaluate the postoperative complications and the impact of an enhanced recovery programme in patients who underwent primary surgery (including extensive upper abdominal surgery) for epithelial ovarian carcinoma (EOC). All patients with stage I-IV ovarian carcinoma who underwent primary surgery were identified, and postoperative complications were evaluated and graded according to the Clavien-Dindo classification. Of 161 patients, 46 (28.57%) underwent surgical staging, 27 (16.77%) standard cytoreduction, 12 (7.45%) en bloc debulking and 76 (47.20%) extraradical debulking. A total of 157 patients (97.52%) achieved optimal tumor reduction (<1 cm). The mean postoperative hospitalization time was 17.33±11.29 days after completion of the initial postoperative chemotherapy (IPC), and the IPC interval was 16.22±10.09 days. A total of 13 patients (8.07%) had grade 3 complications (9 with wound dehiscence, 3 with digestive tract leakage and 1 with a bladder fistula). A total of 2 patients (1.24%) had grade 4-5 complications [1 patient with severe pneumonia returned to the intensive care unit (ICU) for tracheotomy and respiration rehabilitation; the other patient died of septicemia on day 19]. The multivariate analysis of the preoperative factors revealed that a human epididymis protein 4 (HE4) level of ≥717 pM (P=0.015) and Federation International of Gynecology and Obstetrics (FIGO) stage IV (P=0.004; compared with stage IIIC) were associated with grade 3-5 complications. The bootstrap analysis revealed that a cancer antigen 125 (CA125) level of ≥1,012 U/ml (P=0.034), a HE4 level of ≥717 pM (P=0.007) and FIGO stage IV (P=0.002; compared with stage IIIC) were significantly associated with grade 3-5 complications. Meanwhile, the multivariate analysis of the postoperative factors did not reveal any risk factors associated with grade 3-5 complications; the bootstrap analysis revealed that only transfer to the ICU after surgery (P=0.026) was significantly associated with grade 3-5 complications. In conclusion, the study found that application of enhanced recovery after surgery protocols is feasible in patients with EOC, especially in those undergoing advanced extensive upper abdominal surgery, and CA125, HE4 and FIGO stage IV were related with the occurrence of adverse perioperative outcomes.

9.
Cell Death Dis ; 12(1): 57, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431827

RESUMO

Cytosolic inflammasomes are supramolecular complexes that are formed in response to intracellular pathogens and danger signals. However, as to date, the detailed description of a homotypic caspase recruitment domain (CARD) interaction between NLRP1 and ASC has not been presented. We found the CARD-CARD interaction between purified NLRP1CARD and ASCCARD experimentally and the filamentous supramolecular complex formation in an in vitro proteins solution. Moreover, we determined a high-resolution crystal structure of the death domain fold of the human ASCCARD. Mutational and structural analysis revealed three conserved interfaces of the death domain superfamily (Type I, II, and III), which mediate the assembly of the NLRP1CARD/ASCCARD complex. In addition, we validated the role of the three major interfaces of CARDs in assembly and activation of NLRP1 inflammasome in vitro. Our findings suggest a Mosaic model of homotypic CARD interactions for the activation of NLRP1 inflammasome. The Mosaic model provides insights into the mechanisms of inflammasome assembly and signal transduction amplification.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Inflamassomos/metabolismo , Proteínas NLR/metabolismo , Humanos , Modelos Moleculares
10.
J Int Med Res ; 49(2): 300060520987725, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33530802

RESUMO

Choriocarcinoma is a highly malignant gynaecological tumour. This disease becomes life-threatening once brain haemorrhage or brain herniation occurs. Timely and accurate brain surgery can gain treatment time for patients that have a large number of cerebral haemorrhages and/or brain herniation. This current report describes a case of choriocarcinoma secondary to a hydatidiform mole in a 55-year-old woman that presented with neurological symptoms. Following admission to hospital, computed tomography examination found that lung and brain metastases were accompanied by cerebral haemorrhage. Cerebral hernia occurred during induction chemotherapy treatment and emergency surgery was performed. The patient recovered after individual chemotherapy and rehabilitation treatment. Patients with a very high risk of choriocarcinoma with brain metastasis should be referred to a comprehensive medical centre. Necessary surgical treatment and individualized chemotherapy can reduce the mortality of patients with choriocarcinoma brain metastasis.


Assuntos
Neoplasias Encefálicas , Coriocarcinoma , Neoplasias Uterinas , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Coriocarcinoma/cirurgia , Craniotomia , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Tomografia Computadorizada por Raios X , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/cirurgia
11.
Cancer Manag Res ; 12: 1221-1227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110096

RESUMO

INTRODUCTION: The functions of DCST1-AS1 have been investigated in liver cancer, while its role in endometrial carcinoma (EC) remains hardly known. This study aimed to analyze the role of DCST1-AS1 in EC. METHODS: Paired EC and non-tumor tissue samples were obtained from 62 EC patients. These patients were followed up for 5 years since their admission to record their survival conditions. HEC-1 cells were transfected with DCST1-AS1, Notch1 vectors, miRNA negative control or miR-92a-3p mimic. Luciferase activity was measured. QPCR and Western blot were applied to determine the RNA level and protein expression, respectively. The invasion and migration of HEC-1 cells were analyzed by Transwell assay. RESULTS: We in this study found that DCST1-AS1 was upregulated in EC. Survival analysis revealed that high levels of DCST1-AS1 expression predicted poor survival of EC patients. Bioinformatics analysis revealed that miR-92a-3p may bind DCST1-AS1 and the interaction between them was further confirmed by dual-luciferase activity assay. However, overexpression of miR-92a-3p and DCST1-AS1 failed to affect the expression of each other. Moreover, DCST1-AS1 overexpression led to upregulated Notch1 and increased cancer cell invasion and migration rates. Overexpression of miR-92a-3p played an opposite role and attenuated the effects of DCST1-AS1 overexpression. DISCUSSION: DCST1-AS1 is downregulated in EC and may sponge miR-92a-3p, thereby promoting cancer cell invasion and migration.

12.
J Int Med Res ; 48(11): 300060520966807, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33131363

RESUMO

This case report describes a 43-year-old female initially diagnosed with gestational trophoblastic neoplasia that then experienced metastasis to the liver and then subsequently to the pancreas nearly 4 years after the primary diagnosis. After resection of the body and tail of the pancreas, the postoperative histopathological examination confirmed a placental site trophoblastic tumour that had developed after several cycles of chemotherapy for the original primary tumour and the liver metastases. This type of sequential recurrence of gestational trophoblastic neoplasia in the primary site or metastatic sites, such as the liver or pancreas, can be cured by a comprehensive treatment strategy involving surgery and/or salvage chemotherapy and continuous follow-up over a long period, especially for patients with a high-risk status.


Assuntos
Doença Trofoblástica Gestacional , Neoplasias Uterinas , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Doença Trofoblástica Gestacional/diagnóstico por imagem , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/cirurgia , Humanos , Fígado , Recidiva Local de Neoplasia , Pâncreas , Gravidez , Estudos Retrospectivos
13.
Oncogene ; 39(4): 905-921, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31576015

RESUMO

The molecular basis underlying the aggressive nature and excessive proliferation of cervical squamous cancer cell remains unclear. ΔNp63α is the predominant isotype of p63 expressed in the epithelia and regulates epithelial cell differentiation. The pro-/anti-tumor role of ΔNp63α in different kinds of solid tumors remains controversial and the precise molecular mechanisms are still elusive. In this study, we uncovered the molecular functions of ΔNp63α in cervical squamous cell carcinoma to clarify its roles as a tumor suppressor. We demonstrated that ΔNp63α suppressed cell migration, invasiveness, and tumor growth in SiHa and ME-180 cells with both in vivo and in vitro assays. Mechanistic investigation via RNA-sequencing and chromatin immunoprecipitation-sequencing revealed that ΔNp63α exerted its antitumor capacity via regulating the expression of a cohort of cell junction genes. Further, we showed that ZNF385B and CLDN1 were two direct ΔNp63α targets with significant relevance to cervical squamous cell carcinoma examined in cell cultures, tumor xenografts, and clinic tumors. We also demonstrated that ΔNp63α downregulated NFATC1 to reduce cisplatin resistance. These findings shed new lights on functions of ΔNp63α in tumors and providing novel insights in targeted therapy of cervical cancers.


Assuntos
Carcinoma de Células Escamosas/prevenção & controle , Movimento Celular , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias do Colo do Útero/prevenção & controle , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Claudina-1/genética , Claudina-1/metabolismo , Bases de Dados Genéticas , Feminino , Humanos , Camundongos , Camundongos Nus , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , Regiões Promotoras Genéticas , Taxa de Sobrevida , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Eur J Surg Oncol ; 46(5): 855-861, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32001042

RESUMO

OBJECTIVE: To assess the incidence and the risk factors of venous thromboembolism (VTE) in patients with epithelial ovarian carcinoma (EOC) during the perioperative period. METHODS: A retrospective analysis was conducted on the patients with epithelial ovarian cancer treated in our hospital, between January 2017 and July 2019, and a comprehensive review of the medical documentation was performed to collect relevant data. We then analyzed the related factors of the thrombosis in the EOC patients, using univariate and multivariate analysis to identify significant risk factors for VTE, and bootstrap resampling method was used to verify the multivariate analysis results. The ROC curve methods were conducted to evaluate the diagnostic value for the prediction of VTE. RESULTS: We analyzed 233 cases of patients with EOC, of whom the incidence of VTE was 11.16%. According to multivariate and 5000 bootstrap samples analysis, preoperative D-dimer levels (>4.215 µg/ml, p = 0.041 and p = 0.032) and comorbid of cerebral infarction (p < 0.001 and p < 0.001) had statistical significance in predicting VTE events; bootstrap analysis also found the Alb, CA125, OCCC had statistical significance. While According to multivariate and 5000 bootstrap samples analysis, age (>50.5 years old, p = 0.019 and p = 0.002) and nonoptimal debulking surgery (p = 0.007 and p = 0.002) showed significance in predicting VTE after surgery; bootstrap analysis also found the D-dimer levels (>4.215 µg/ml) and tuberculosis had statistical significance. CONCLUSION: More effective thromboprophylaxis and pre-test assessment is necessary for EOC patients. For prediction VTE events, D-dimer levels (>4.215 µg/ml) were the independent predictors before operation. Age and debulking surgery were the independent predictors post operation.


Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Neoplasias Ovarianas/cirurgia , Período Perioperatório , Complicações Pós-Operatórias/epidemiologia , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologia , Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Antígeno Ca-125/metabolismo , Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Infarto Cerebral/epidemiologia , Comorbidade , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Hipertensão/epidemiologia , Incidência , Tempo de Internação , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Císticas, Mucinosas e Serosas/epidemiologia , Neoplasias Císticas, Mucinosas e Serosas/metabolismo , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Embolia Pulmonar/metabolismo , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo , Tuberculose/epidemiologia , Tromboembolia Venosa/metabolismo , Trombose Venosa/metabolismo , Adulto Jovem
15.
Am J Reprod Immunol ; 82(5): e13177, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31373128

RESUMO

PROBLEM: The aim of this prospective study was to investigate the prevalence of chronic endometritis (CE) in repeated implantation failure (RIF) patients and to determine whether intrauterine delivery of the combined administration of antibiotic and dexamethasone improves the clinical pregnancy outcome. METHOD OF STUDY: The combination of hysteroscopy and histology was used to diagnose CE in the patients with RIF, and the diagnosed patients were treated with the intrauterine delivery of the combined antibiotic and dexamethasone therapy. The prevalence of CE in the RIF patients was recorded, and the therapeutic effect was also evaluated in the first IVF-ET cycle. RESULTS: In a total number of 298 patients with RIF, 109 cases (36.58%) were diagnosed as CE. Intrauterine infusion treatment resulted in CE resolution in 77.98% of patients. After the treatment, 85 cases with no signs of CE (Group 2) had a significantly higher implantation rate (31.33%) and clinical pregnancy rate (51.76%) as compared with both 126 cases without CE diagnosis (Group 1; 16.30% and 30.15%, respectively) and 24 cases with persistence of CE (Group 3; 14.89% and 25.00%, respectively). The live birth rate in the first IVF-ET cycle following treatment in Group 2 was significantly higher than that of both Group 1 and Group 3 (all P < .05). CONCLUSION: Chronic endometritis is highly prevalent in patients with RIF. To the best of our knowledge, we for the first time reported that intrauterine delivery of the combined administration of antibiotic and dexamethasone as a treatment option of CE could achieve expected therapeutic effects and successful pregnancy outcomes.


Assuntos
Antibacterianos/administração & dosagem , Coeficiente de Natalidade , Dexametasona/administração & dosagem , Endometrite/tratamento farmacológico , Fertilização in vitro , Adulto , Doença Crônica , Endometrite/epidemiologia , Endometrite/metabolismo , Endometrite/patologia , Endométrio/patologia , Feminino , Humanos , Histeroscopia , Gravidez , Estudos Prospectivos
16.
Taiwan J Obstet Gynecol ; 58(3): 332-337, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31122520

RESUMO

OBJECTIVE: To evaluate the efficacy and toxicity of VMP regimen applied to the patients with low-risk gestational trophoblastic neoplasia (LR-GTN) treated in Anhui provincial hospital. MATERIALS AND METHODS: Between 2005 and 2017, 87 patients with low-risk gestational trophoblastic neoplasia received VMP regimen, consisted of vincristine (VCR), methotrexate (MTX) and platinum (cisplatin, carboplatin or nedaplatin), 68 of whom received VMP as their first-line chemotherapy, and 19 methotrexate-failed patients received VMP regimen as their second-line chemotherapy. The staging and scoring system was based on International Federation of Gynecology and Obstetrics (FIGO 2000) criteria. We describe and analyze their baseline characteristics, remission/resistance/recurrence rates, adverse reactions and prognosis. RESULTS: The first-line VMP protocol can achieve an 83.8% remission rate and it tended to develop resistance when the pretreatment ß-hCG reaches 7503.5 IU/L, and can achieve complete remission with FAV and EMA-CO as the salvage regimen. Among the 19 methotrexate-failed patients, 2 of whom were yet resistant to VMP regimen, followed by several courses of salvage chemotherapy such as FAV and EMP, and achieved 89.5% remission rate in second-line VMP group. Resistance to this regimen was obviously related with higher pre-treatment HCG whether used as primary or salvage treatment. Severe myelosuppression (grade 3 or 4) was shown in 4 (5.9%) of 68 cases, of which none was grade 4. CONCLUSION: For patients diagnosed with LR-GTN VMP regimen was a safe and effective treatment with a high rate of remission.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença Trofoblástica Gestacional/tratamento farmacológico , Indução de Remissão/métodos , Adulto , Gonadotropina Coriônica Humana Subunidade beta/sangue , Cisplatino/administração & dosagem , Feminino , Humanos , Metotrexato/administração & dosagem , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/administração & dosagem
17.
J Pediatr Adolesc Gynecol ; 31(4): 426-431, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29317258

RESUMO

BACKGROUND: Uterine adenosarcoma with sarcomatous overgrowth (ASSO) is a rare and aggressive disease. A case of a 16-year-old girl with uterine ASSO is reported herein. The patient received surgical resection and chemotherapy and remained alive without disease 11 months after the surgery. CASE: A 16-year-old girl was diagnosed with uterine ASSO, International Federation of Gynecology and Obstetrics (2009) stage I c. She underwent total abdominal hysterectomy, bilateral salpingectomy, and chemotherapy. She remains alive and there was no evidence of tumor recurrence on follow-up physical, laboratory, and ultrasound scan examinations. SUMMARY AND CONCLUSION: Surgery is the primary treatment for uterine ASSO, total abdominal or laparoscopic-assisted vaginal hysterectomy with or without bilateral salpingo-oophorectomy are recommended. Early surgical resection might increase survival of uterine adenosarcoma. Long-term follow-up of the patients is recommended because of the high chance of recurrence.


Assuntos
Adenossarcoma/diagnóstico , Neoplasias Uterinas/diagnóstico , Adenossarcoma/tratamento farmacológico , Adenossarcoma/cirurgia , Adolescente , Antineoplásicos/uso terapêutico , Feminino , Humanos , Histerectomia/métodos , Imageamento por Ressonância Magnética , Salpingectomia/métodos , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/cirurgia , Útero/patologia
18.
Mol Clin Oncol ; 8(2): 352-355, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29435302

RESUMO

Cervical stump cancer is a rare type of disease as total hysterectomies are performed infrequently. The purpose of this retrospective study was to assess the diagnosis, treatment, follow-up methods and complications of 10 patients with cervical stump carcinoma treated with surgery in Anhui Provincial Hospital affiliated to Anhui Medical University (Hefei, China). From January 2006 to October 2016 a total of 10 patients underwent surgery for carcinoma of the cervical stump. The pathological reports revealed 80% of cases were squamous cell carcinoma and 20% of cases were adenocarcinoma. The FIGO stage distribution was as follows: Carcinoma in situ (10%); IB1 (70%); IIA (20%). The patients received a transvaginal trachelectomy or a radical trachelectomy and pelvic lymphadenectomy (either laparoscopic or laparotomic abdominal); four of the patients were treated with adjuvant chemotherapy, and two with concurrent chemoradiotherapy. The parametrial and resection margin infiltration, lymph node metastasis and lymph vascular space invasion (LVSI) were negative in all patients, and the deep stromal invasion rate was 66.7% (6/9). No incidences of recurrence or mortality were recorded during the follow-up interval of 6-120 months. Compared with the four patients who received laparotomic abdominal surgery, significantly less blood loss was recorded for the five patients who underwent laparoscopic surgery (P<0.01). There was no significant difference observed in the surgery time (P>0.01) or in the hospital stay duration (P>0.01) for the patients treated with laparotomic abdominal surgery and laparoscopic surgery. One patient experienced bladder fistula due to bladder over-dilation, but recovered quickly after the catheter was reinserted. Surgery for cervical stump cancer at an early-stage is a viable and safer procedure, particularly the laparoscopic approach.

19.
Oncol Lett ; 16(4): 4577-4585, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30214592

RESUMO

Prostaglandin E2 (PGE2) is the most common prostaglandin in the human body, meaning that its malfunction impacts on the development of numerous diseases. Prostaglandin E synthase 2 (PTGES2) is involved in the synthesis of PGE2. In the present study, immunohistochemistry of PTGES2 was performed in 152 patients with endometrial cancer and in 66 patients with normal endometria. The results indicate a notable association among increased expression of PTGES2 and age (P=0.0092) and the depth of myometrial invasion (P<0.0001). Reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that cytochrome P450 17α hydroxylase (CYP17), an enzyme for androgen synthesis, is overexpressed following PGE2 stimulation via signal transducer and activator of transcription 3 (STAT3) phosphorylation. ELISA also detected increased androgen (testosterone) secretion. Further invasion of endometrial cancer cells was induced at high androgen levels and when CYP17 was overexpressed. Furthermore, the present study observed that CYP17 is overexpressed via STAT3 phosphorylation in endometrial cancer cells, which grow at a high concentration of PGE2, resulting in increased androgen secretion. Concentrations of estrogen and progesterone were not elevated, while the concentration of androgens was. Overall, a high concentration of androgens caused increased invasion of endometrial cancer cells. A high concentration of androgens, which is initiated by a high expression of PTGES2 and a high concentration of PGE2, is an important promoter of myometrial invasion in endometrial cancer.

20.
Braz J Med Biol Res ; 51(8): e7334, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29846432

RESUMO

Pregnancy-induced hypertension (PIH) causes significant maternal and fetal morbidity and mortality. A decreased number of regulatory T (Treg) cells is associated with the pathogenesis of PIH. The programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) pathway is critical to normal pregnancy (NP) by promoting Treg cell development. However, the relationship between PD-1/PD-L1 and Treg differentiation in PIH has not been fully elucidated. In this study, venous blood was obtained from 20 NP and 58 PIH patients. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood. The levels of Treg-related cytokines (TGF-ß, IL-10, and IL-35) in serum and PBMCs were measured by ELISA. The percentage of Treg cells in PBMCs was assessed by flow cytometry. The mRNA levels of Treg-specific transcription factor Foxp3 in PBMCs, and PD-1 and PD-L1 in Treg cells were detected by qRT-PCR. The protein levels of PD-1 and PD-L1 in Treg cells were evaluated by western blot. The serum levels of TGF-ß, IL-10, IL-35, and Foxp3 mRNA expression and CD4+CD25+ Treg cell percentage in PBMCs were decreased in PIH. Furthermore, a significant increase of PD-1 in Treg cells was found in PIH compared with NP. In addition, PD-L1 Fc, an activator of PD-1/PD-L1 pathway, increased Treg cell percentage, enhanced Foxp3 mRNA expression, and elevated levels of TGF-ß, IL-10, and IL-35 in PBMCs. However, anti-PD-L1 mAb exerted a reverse effect. These findings revealed that PD-L1 Fc had a favorable effect on Treg cell differentiation, indicating a potential therapeutic value of PD-1/PD-L1 pathway for PIH treatment.


Assuntos
Apoptose , Antígeno B7-H1/metabolismo , Hipertensão Induzida pela Gravidez/metabolismo , Interleucina-10/metabolismo , Interleucinas/metabolismo , Leucócitos Mononucleares/química , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Western Blotting , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Gravidez , Reação em Cadeia da Polimerase em Tempo Real
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