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1.
Cancer Sci ; 113(9): 3244-3254, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35365934

RESUMO

Laryngeal squamous cell carcinoma (LSCC), although one of the most common head and neck cancers, has a static or slightly decreased survival rate because of difficulties in early diagnosis, lack of effective molecular targeting therapy, and severe dysfunction after radical surgical treatments. Therefore, a novel therapeutic target is crucial to increase treatment efficacy and survival rates in these patients. Glycoprotein NMB (GPNMB), whose role in LSCC remains elusive, is a type 1 transmembrane protein involved in malignant progression of various cancers, and its high expression is thought to be a poor prognostic factor. In this study, we showed that GPNMB expression levels in LSCC samples are significantly higher than those in normal tissues, and GPNMB expression is observed mostly in growth-arrested cancer cells. Furthermore, knockdown of GPNMB reduces monolayer cellular proliferation, cellular migration, and tumorigenic growth, while GPNMB protein displays an inverse relationship with Ki-67 levels. Therefore, we conclude that GPNMB may be an attractive target for future LSCC therapy.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Regiões Promotoras Genéticas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Transcrição/metabolismo
2.
Antibodies (Basel) ; 10(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440681

RESUMO

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus for which no known effective antiviral drugs are available. In the present study, to accelerate the discovery of potential drug candidates, bioinformatics-based in silico drug discovery approaches are utilized. We performed multiple sequence alignments of the Spike (S) protein with 75 sequences of different viruses from the Orthocoronavirinae subfamily. This provided us with insights into the evolutionarily conserved domains that can be targeted using drugs or specific antibodies. Further, we analyzed the mechanism of SARS-CoV-2 core proteins, i.e., S and RdRp (RNA-dependent RNA polymerase), to elucidate how the virus infection can utilize hemoglobin to decrease the blood oxygen level. Moreover, after a comprehensive literature survey, more than 60 antiviral drugs were chosen. The candidate drugs were then ranked based on their potential to interact with the Spike and RdRp proteins of SARS-CoV-2. The present multidimensional study further advances our understanding of the novel viral molecular targets and potential of computational approaches for therapeutic assessments. The present study can be a steppingstone in the selection of potential drug candidates to be used either as a treatment or as a reference point when designing a new drug/antibody/inhibitory peptide/vaccine against SARS-CoV-2.

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