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1.
Virchows Arch ; 482(6): 1021-1034, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36580137

RESUMO

We found some clear cell glands appeared in the endometrioid cysts (ECs) of the ovary (EC-CCG). To explore the clinicopathological features, molecular biological changes, and prognosis in EC-CCG and analyze the association with ovarian clear cell borderline tumors (CCBT) and clear cell carcinoma (CCC). We retrospectively examined 35 cases of EC-CCG, compared them to 13 cases of clear cell cystadenomas, 14 cases of CCBT, and 49 cases of CCC. We analyzed the differences in clinicopathological features and prognosis between the four groups. Data on clinicopathology and survival were gathered. Immunohistochemistry (IHC) was performed in all cases, and we analyzed the molecular changes of 2 cases of EC-CCG and 1 case of CCC by whole-exome sequencing (WES). EC-CCG shared some common clinicopathological features with CCBT: they occurred before menopause, had an elevated serum CA125 level in some cases, had an ovarian cystic mass on B-ultrasound, and had a risk of recurrence. Microscopically, both diseases were based on typical EC, and clear cell glands in the EC cyst wall were seen in varying numbers. Some cases of EC-CCG had IHC results similar to those of CCBT and CCC, with positive expression of HNF1ß and NapsinA; decreased expression of ER, PR, and ARID1A; and increased expression of Ki67 (> 5%). WES results revealed that EC-CCG had mutations in TP53BP1, ZNF462, FN1, and FTL (which was also mutated in CCC). In summary, we found that clear cell glands appearing around EC in the ovary have an association with CCC.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Cistos , Neoplasias Ovarianas , Feminino , Humanos , Estudos Retrospectivos , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/patologia , Carcinoma Endometrioide/patologia , Biomarcadores Tumorais , Proteínas de Ligação a DNA , Proteínas do Tecido Nervoso , Fatores de Transcrição
2.
Biomed Pharmacother ; 116: 108984, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31129512

RESUMO

Although the Epstein-Barr virus (EBV) is a well-known human oncogenic virus, its molecular mechanisms involved in the transformation of healthy human cells remain poorly understood. In this study, human lymphocytes were isolated from the peripheral blood of healthy adults, and lymphocytes were transformed in vitro by EBV. Agilent human whole genome microarrays were used to detect the differential gene expression profiles of EBV-transformed lymphoblasts and healthy peripheral blood lymphocytes (PBLs). By constructing the gene functional network of EBV-induced lymphocyte transformation, we screened out candidate key genes in this process and verified their expression levels by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In the EBV-transformed lymphoblasts, 2335 differentially expressed genes, including 1328 up-regulated and 1007 down-regulated, were screened out. Five candidate key genes, namely, PLK1, E2F1, PTPN11, BIRC5 and FYN were mainly screened out according to the results of LIMMA, String, Cytoscape software analysis. RT-qPCR and Western blot showed that PLK1, E2F1, PTPN11, BIRC5 genes had increased expression levels, and FYN gene was down-regulated in EBV-transformed lymphoblasts. Silencing of PLK1 gene in Raji cells could inhibit cell proliferation and invasion, and induce cell cycle arrest and apoptosis. In conclusion, PLK1, E2F1, PTPN11, BIRC5 and FYN are the candidate key molecules of EBV-transformed lymphocytes.


Assuntos
Transformação Celular Viral/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Herpesvirus Humano 4/fisiologia , Linfócitos/metabolismo , Linfócitos/virologia , Apoptose , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Proliferação de Células , Regulação da Expressão Gênica , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Interferente Pequeno/metabolismo , Quinase 1 Polo-Like
3.
Med Microbiol Immunol ; 208(5): 573-583, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30386928

RESUMO

The early stage of oncogenesis is linked to the disorder of the cell cycle. Abnormal gene expression often leads to cell cycle disorders, resulting in malignant transformation of human cells. Epstein-Barr virus (EBV) is associated with a diverse range of human neoplasms, such as malignant lymphoma, nasopharyngeal carcinoma and gastric cancer. EBV mainly infects human lymphocytes and oropharyngeal epithelial cells. EBV is latent in lymphocytes for a long period of time, is detached from the cytoplasm by circular DNA, and can integrate into the chromosome of cells. EBV expresses a variety of latent genes during latent infection. The interaction between EBV latent genes and oncogenes leads to host cell cycle disturbances, including the promotion of G1/S phase transition and inhibition of cell apoptosis, thereby promoting the development of EBV-associated neoplasms. Molecular mechanisms of EBV-driven cell cycle progression and oncogenesis involve diverse genes and signal pathways. Here, we review the molecular mechanisms of EBV-driven cell cycle progression and promoting oncogenesis.


Assuntos
Carcinogênese , Proliferação de Células , Transformação Celular Neoplásica , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno , Células Epiteliais/virologia , Humanos , Linfócitos/virologia
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