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1.
Med Oncol ; 40(5): 149, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37060468

RESUMO

Cervical cancer (CC) is the fourth leading cause of cancer death (~ 324,000 deaths annually) among women internationally, with 85% of these deaths reported in developing regions, particularly sub-Saharan Africa and Southeast Asia. Human papillomavirus (HPV) is considered the major driver of CC, and with the availability of the prophylactic vaccine, HPV-associated CC is expected to be eliminated soon. However, female patients with advanced-stage cervical cancer demonstrated a high recurrence rate (50-70%) within two years of completing radiochemotherapy. Currently, 90% of failures in chemotherapy are during the invasion and metastasis of cancers related to drug resistance. Although molecular target therapies have shown promising results in the lab, they have had little success in patients due to the tumor heterogeneity fueling resistance to these therapies and bypass the targeted signaling pathway. The last two decades have seen the emergence of immunotherapy, especially immune checkpoint blockade (ICB) therapies, as an effective treatment against metastatic tumors. Unfortunately, only a small subgroup of patients (< 20%) have benefited from this approach, reflecting disease heterogeneity and manifestation with primary or acquired resistance over time. Thus, understanding the mechanisms driving drug resistance in CC could significantly improve the quality of medical care for cancer patients and steer them to accurate, individualized treatment. The rise of artificial intelligence and machine learning has also been a pivotal factor in cancer drug discovery. With the advancement in such technology, cervical cancer screening and diagnosis are expected to become easier. This review will systematically discuss the different tumor-intrinsic and extrinsic mechanisms CC cells to adapt to resist current treatments and scheme novel strategies to overcome cancer drug resistance.


Assuntos
Antineoplásicos , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Detecção Precoce de Câncer , Inteligência Artificial , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/terapia
2.
Adv Protein Chem Struct Biol ; 131: 235-259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35871892

RESUMO

Multiple Sclerosis (MS) is a neurodegenerative autoimmune and organ-specific demyelinating disorder, known to affect the central nervous system (CNS). While genetic studies have revealed several critical genes and diagnostic biomarkers associated with MS, the etiology of the disease remains poorly understood. This study is aimed at screening and identifying the key genes and canonical pathways associated with MS. Gene expression profiling of the microarray dataset GSE38010 was used to analyze two control brain samples (control 1; GSM931812, control 2; GSM931813), active inflammation stage samples (CAP1; GSM931815, CAP2; GSM931816) and late subsided stage samples (CP1; GSM931817, CP2; GSM931818) collected from patients ranging between 23 and 54years and both genders. This analysis yielded a list of 58,866 DEGs (29,433 for active-inflammation stage and 29,433 for late-subsided Stage). The interactions between the DEGs were then studied using STRING, Cytoscape software, and MCODE was employed to find the genes that form clusters. Functional enrichment and integrative analysis were performed using ClueGO/CluePedia and MetaCore™. Our data revealed dysregulated key canonical pathways in MS patients. In addition, we identified three hub genes (SCN2A, HTR2A, and HCN1) that may serve as potential biomarkers for the prognosis of MS. Furthermore, the expression patterns of HPCA and PLCB1 provide insights into the progressive stages of MS, indicating that these genes could be used in predicting MS progression. We were able to map potential biomarkers that could be used for the prognosis and diagnosis of MS.


Assuntos
Esclerose Múltipla , Biomarcadores/metabolismo , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Inflamação/genética , Masculino , Análise em Microsséries , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Mapas de Interação de Proteínas/genética
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