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1.
Int J Mol Sci ; 24(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37762545

RESUMO

The asymptomatic nature, high rate of disease recurrence, and resistance to platinum-based chemotherapy highlight the need to identify and characterize novel target molecules for ovarian cancer. Fibroblast growth factor 8 (FGF8) aids in the development and metastasis of ovarian cancer; however, its definite role is not clear. We employed ELISA and IHC to examine the expression of FGF8 in the saliva and tissue samples of epithelial ovarian cancer (EOC) patients and controls. Furthermore, various cell assays were conducted to determine how FGF8 silencing influences ovarian cancer cell survival, adhesion, migration, and invasion to learn more about the functions of FGF8. In saliva samples, from controls through low-grade to high-grade EOC, a stepped overexpression of FGF8 was observed. Similar expression trends were seen in tissue samples, both at protein and mRNA levels. FGF8 gene silencing in SKOV3 cells adversely affected various cell properties essential for cancer cell survival and metastasis. A substantial reduction was observed in the cell survival, cell adhesion to the extracellular matrix, migration, and adhesion properties of SKOV3 cells, suggesting that FGF8 plays a crucial role in the development of EOC. Conclusively, this study suggests a pro-metastatic function of FGF8 in EOC.


Assuntos
Recidiva Local de Neoplasia , Neoplasias Ovarianas , Humanos , Feminino , Fator 8 de Crescimento de Fibroblasto/genética , Fator 8 de Crescimento de Fibroblasto/metabolismo , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proliferação de Células
2.
Reprod Sci ; 30(12): 3456-3468, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37378824

RESUMO

Recurrent pregnancy loss (RPL) is a pervasive health issue affecting a large number of couples globally, which leads to increased emotional and financial strain on the affected families. While female factors have been extensively studied and are well known, the contribution of male factors to RPL remains largely unknown. As high as 40% of RPL cases are unexplained, which are termed as idiopathic RPL (iRPL), necessitating the investigation of male factors. The role of spermatozoa in early embryonic development is now well established, and recent research studies have shown that oxidative stress and DNA fragmentation in sperm cells are linked to RPL. The aim of this study was to identify proteomic markers of iRPL in human spermatozoa using tandem mass spectrometry. A label-free method quantified a total of 1820 proteins, and statistical analysis identified 359 differentially expressed proteins, the majority of which were downregulated in iRPL samples (344). Bioinformatics analysis revealed that proteomic alterations were mainly associated with biological processes such as response to stress, protein folding, chromatin organization, DNA conformation change, oxidative phosphorylation, and electron transport chain. In coherence with past studies, we determined fatty acid synthase (FASN) and clusterin (CLU) to be the most potential sperm markers for iRPL and confirmed their expression changes in iRPL by western blotting. Conclusively, we believe that FASN and CLU might serve as potential markers of iRPL and suggest exploratory functional studies to identify their specific role in pregnancy loss.


Assuntos
Aborto Habitual , Sêmen , Gravidez , Humanos , Masculino , Feminino , Sêmen/metabolismo , Clusterina/metabolismo , Proteômica/métodos , Espermatozoides/metabolismo , Aborto Habitual/genética , Ácido Graxo Sintases/metabolismo
3.
Mol Biol Rep ; 47(12): 9459-9468, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33263168

RESUMO

Ovarian cancer, the most lethal gynecological cancer, is the fifth most common cause of cancer-related deaths in women. A cost-effective and non-invasive early screening method for ovarian cancer is required to reduce the high mortality rate. Saliva is a clinically informative unique fluid, which is useful for novel approaches to prognosis, clinical diagnosis, and monitoring for non-invasive detection of disease. Multimerin1 (MMRN1) is a di-sulfide linked homo-polymeric glycoprotein from EMILIN family. Altered expression of MMRN1 has been reported in hepatocellular carcinoma, cervical cancer, and ovarian cancer. But, its role in epithelial ovarian cancer (EOC) is not clear and well documented. In this study, expression of Multimerin 1 was validated in saliva and tissues of EOC patients and age-matched controls by western blotting, ELISA, RT-PCR, and immunohistochemistry. Significant over expression of MMRN1 was observed by western blot and ELISA in saliva samples of EOC patients. The average concentration of MMRN1 in the saliva of healthy controls was 28.7 pg/ml (SE ± 1.76), 42.53 pg/ml (SE ± 4.06) in low grade and 52.91 pg/ml (SE ± 4.24) with p < 0.01 in high-grade EOC. Upregulated cytoplasmic expression of MMRN1 was observed in EOC tissue by immunohistochemistry. Our results suggest that MMRN1 expression is associated with EOC progression and MMRN1 may be potential biomarker candidates for early-stage EOC detection however further experiments are required in a large cohort to establish this proposition. Also, saliva can be explored as a novel medium for ovarian cancer diagnosis.


Assuntos
Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Progressão da Doença , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/patologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Saliva/metabolismo , Transdução de Sinais/imunologia , Adulto Jovem
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