RESUMO
Erythropoietin-producing hepatocellular receptor A2 (EphA2) receptor tyrosine kinase plays an important role in tissue organization and homeostasis in normal organs. EphA2 is overexpressed in a variety of types of solid tumours with oncogenic functions. However, the role of EphA2 in cervical cancer (CC) is still needed to be further explored. Here, we examined the role of EphA2 by establishing a stable EphA2 knock-down CC cell lines or a stable EphA2-overexpressed CC cells lines. Overexpression of EphA2 increased cell proliferation and migration of CC while EphA2 knock-down decreased the CC tumorigenicity. In addition, EphA2 knock-down suppressed CC tumour development in the xenograft mouse model. Inhibition of EphA2 by AWL-II-41-27, EphA2-specific tyrosine kinase inhibitor, or knock-down of EphA2 decreased mRNA and protein expression of cyclin-dependent kinase (CDK) 6 in CC cells, which increased cellular susceptibility to epirubicin (EPI), an anti-cancer chemotherapy drug. A clinicopathological study of EphA2 was conducted on a cohort of 158 human CC patients. EphA2 protein expression was positively correlated with CDK6 protein expression, invasion depth, lymph node metastasis and clinicopathological stage (P < .05). This study demonstrates the oncogenic activity of EphA2 in vitro and in vivo, which provides insights into the relevant mechanisms that might lead to novel treatments for CC.
Assuntos
Transformação Celular Neoplásica/genética , Quinase 6 Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , Receptor EphA2/genética , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Receptor EphA2/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologiaRESUMO
Background: Various trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. Methods: We utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR). Results: Four trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9-36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1-70.2) for dMMR group and 33.1% (95% CI: 25.7-40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3-78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5-97.6) for the dMMR group and 76.3% (95% CI: 66.3-86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5-100.0) and 80.2% (95% CI: 59.9-100.0), respectively. Conclusion: Lenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Recidiva Local de Neoplasia , Compostos de Fenilureia , Quinolinas , Feminino , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/mortalidade , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate optical coherence microscopy (OCM) imaging features and the application value of these high-resolution images for identifying endocervical canal lesions (ECLs), which is a clinical dilemma in cervical cancer screening programs. METHODS: In total, 520 OCM images were obtained by scanning the cervical canal lesions with an ultra-high-resolution OCM system (204 specimens from 73 patients). The OCM morphologic characteristics of ECLs were observed and summarized, and then 3 researchers performed a diagnostic test of OCM images of cervical canal lesions. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, 95% confidence interval of each parameter, and interinvestigator agreement (κ) were calculated. RESULTS: Normal endocervix, cysts, squamous metaplasia, high-grade squamous intraepithelial lesions involving glands, and invasive carcinoma had distinct OCM characteristics, which correlated well with corresponding H&E histologic sections. The accuracy, sensitivity, and specificity of the 3 researchers were 90.6%, 89.3% (95% CI, 86.5%-91.7%) and 91.6% (95% CI, 89.2%-93.5%), respectively. The positive predictive value was 90.1% (95% CI, 87.3%-92.4%), and the negative predictive value was 90.9% (95% CI, 88.5%-92.9%), with almost perfect agreement (κ = 0.874). CONCLUSIONS: The application of the OCM system in cervical canal lesions is feasible and could help improve detection of occult ECLs in cervical cancer screening programs. This study lays the foundation for further research on OCM in cervical canal lesions in vivo, which also has a potential impact on projecting pathologic evaluation beyond what is currently possible, perhaps globally.
RESUMO
MicroRNAs serve a role in the development of ovarian cancer (OC). The present study investigated whether let-7c is able to regulate the proliferation of OC cells by targeting cell division cycle 25A (CDC25a). The reverse transcription-quantitative polymerase chain reaction was performed to detect the expression of let-7c in OC specimens. Let-7c agomir was transfected into OC cells, and the proliferation and apoptosis of OC cells were detected. A dual-luciferase assay and western blotting were performed to analyze whether CDC25a was the target gene of let-7c as well as its interaction site. The results revealed that, in OC tissue, let-7c was downregulated when compared with normal ovarian tissue. A Cell Counting Kit-8 (CCK8) assay, colony formation assay and flow cytometry demonstrated that increased expression of let-7c was able to inhibit the proliferation and increase the apoptosis of OC cells. Western blotting revealed that upregulated let-7c is able to decrease the expression of CDC25a, and a dual-luciferase assay and a recovery assay demonstrated that let-7c was able to regulate the expression of the 3' untranslated region of CDC25a. Therefore, the roles of let-7c in inhibiting the proliferation and promoting the apoptosis of OC cells may be realized through the regulation of the expression of CDC25a. The results of the present study revealed that let-7c may be a novel target in the diagnosis and treatment of OC.
RESUMO
Annexin A2 is a member of the Annexin family that acts as a Ca2+-dependent phospholipid and membrane binding protein, which is associated with the survival and spread of multiple neoplasms. However, the function of Annexin A2 in ovarian cancer progression remains unclear. In this study, we aimed to investigate the role and underlying molecular mechanism of Annexin A2 in cell proliferation and invasion in ovarian cancer. We found that the mRNA expression of Annexin A2 was upregulated in ovarian cancer tissues and cell lines. In the loss-of-function of Annexin A2, ß-catenin was indicated to be significantly suppressed and EMT constrained. Moreover, cell proliferation and invasion were both markedly inhibited by the downregulation of Annexin A2. Additionally, the overexpression of ß-catenin obviously reversed the effect of Annexin A2 on EMT, and cell proliferation and invasion, indicating that Annexin A2 suppression regulated EMT through controlling ß-catenin. Taken together, this study showed that Annexin A2 inhibition suppresses proliferation and invasion in ovarian cancer via ß-catenin/EMT, proposing the potential role of Annexin A2 in the prevention and treatment of ovarian cancer.
Assuntos
Anexina A2/genética , Proliferação de Células/genética , Neoplasias Ovarianas/genética , beta Catenina/genética , Adulto , Anexina A2/antagonistas & inibidores , Linhagem Celular Tumoral , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , RNA Mensageiro/genéticaRESUMO
Recently, several studies have reported associations between fat mass and obesity-associated (FTO) gene mutations and cancer susceptibility. But little is known about their association with risk and survival of breast cancer in Chinese population. The aim of this study is to examine whether cancer-related FTO polymorphisms are associated with risk and survival of breast cancer and BMI levels in controls in a Chinese population. We genotyped six FTO polymorphisms in a case-control study, including 537 breast cancer cases and 537 controls. FTO rs1477196 AA genotype had significant decreased breast cancer risk [odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.34-0.86] compared to GG genotype, and this association was only found in women with BMI < 24 kg/m(2) (OR = 0.41, 95% CI: 0.22-0.76); and rs16953002 AA genotype conferred significant increased breast cancer risk (OR = 1.80, 95% CI: 1.23-2.63) compared to GG genotype. Haplotype analysis showed that FTO TAC haplotype (rs9939609-rs1477196-rs1121980) had significant reduced breast cancer risk (OR = 0.76, 95% CI: 0.62-0.93) compared with TGC haplotype. But we failed to find any association between FTO polymorphisms and breast cancer survival. These findings suggest that variants in FTO gene may influence breast cancer susceptibility.