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1.
Cancer Metastasis Rev ; 43(1): 363-377, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38012357

RESUMO

This comprehensive review explores vimentin as a pivotal therapeutic target in cancer treatment, with a primary focus on mitigating metastasis and overcoming drug resistance. Vimentin, a key player in cancer progression, is intricately involved in processes such as epithelial-to-mesenchymal transition (EMT) and resistance mechanisms to standard cancer therapies. The review delves into diverse vimentin inhibition strategies. Precision tools, including antibodies and nanobodies, selectively neutralize vimentin's pro-tumorigenic effects. DNA and RNA aptamers disrupt vimentin-associated signaling pathways through their adaptable binding properties. Innovative approaches, such as vimentin-targeted vaccines and microRNAs (miRNAs), harness the immune system and post-transcriptional regulation to combat vimentin-expressing cancer cells. By dissecting vimentin inhibition strategies across these categories, this review provides a comprehensive overview of anti-vimentin therapeutics in cancer treatment. It underscores the growing recognition of vimentin as a pivotal therapeutic target in cancer and presents a diverse array of inhibitors, including antibodies, nanobodies, DNA and RNA aptamers, vaccines, and miRNAs. These multifaceted approaches hold substantial promise for tackling metastasis and overcoming drug resistance, collectively presenting new avenues for enhanced cancer therapy.


Assuntos
Aptâmeros de Nucleotídeos , MicroRNAs , Anticorpos de Domínio Único , Vacinas , Humanos , Aptâmeros de Nucleotídeos/farmacologia , Aptâmeros de Nucleotídeos/uso terapêutico , Resistência a Medicamentos , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Metástase Neoplásica , Anticorpos de Domínio Único/farmacologia , Anticorpos de Domínio Único/uso terapêutico , Vacinas/farmacologia , Vacinas/uso terapêutico , Vimentina/antagonistas & inibidores , Vimentina/genética , Vimentina/metabolismo
2.
Eur J Cell Biol ; 102(2): 151299, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36809688

RESUMO

BACKGROUND: Drug resistance is a serious challenge in cancer treatment that can render chemotherapy a failure. Understanding the mechanisms behind drug resistance and developing novel therapeutic approaches are cardinal steps in overcoming this issue. Clustered regularly interspaced short palindrome repeats (CRISPR) gene-editing technology has proven to be a useful tool to study cancer drug resistance mechanisms and target the responsible genes. In this review, we evaluated original research studies that used the CRISPR tool in three areas related to drug resistance, namely screening resistance-related genes, generating modified models of resistant cells and animals, and removing resistance by genetic manipulation. We reported the targeted genes, study models, and drug groups in these studies. In addition to discussing different applications of CRISPR technology in cancer drug resistance, we analyzed drug resistance mechanisms and provided examples of CRISPR's role in studying them. Although CRISPR is a powerful tool for examining drug resistance and sensitizing resistant cells to chemotherapy, more studies are required to overcome its disadvantages, such as off-target effects, immunotoxicity, and inefficient delivery of CRISPR/cas9 into the cells.


Assuntos
Edição de Genes , Neoplasias , Animais , Resistência a Medicamentos , Neoplasias/tratamento farmacológico , Neoplasias/genética
3.
Cancers (Basel) ; 14(6)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35326729

RESUMO

Cancer is the leading cause of death and a major problem to increasing life expectancy worldwide. In recent years, various approaches such as surgery, chemotherapy, radiation, targeted therapies, and the newest pillar, immunotherapy, have been developed to treat cancer. Among key factors impacting the effectiveness of treatment, the administration of drugs based on the circadian rhythm in a person and within individuals can significantly elevate drug efficacy, reduce adverse effects, and prevent drug resistance. Circadian clocks also affect various physiological processes such as the sleep cycle, body temperature cycle, digestive and cardiovascular processes, and endocrine and immune systems. In recent years, to achieve precision patterns for drug administration using computational methods, the interaction of the effects of drugs and their cellular pathways has been considered more seriously. Integrated data-derived pathological images and genomics, transcriptomics, and proteomics analyses have provided an understanding of the molecular basis of cancer and dramatically revealed interactions between circadian and immunity cycles. Here, we describe crosstalk between the circadian cycle signaling pathway and immunity cycle in cancer and discuss how tumor microenvironment affects the influence on treatment process based on individuals' genetic differences. Moreover, we highlight recent advances in computational modeling that pave the way for personalized immune chronotherapy.

4.
Comput Biol Chem ; 86: 107269, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32413830

RESUMO

Protein kinases are enzymes acting as a source of phosphate through ATP to regulate protein biological activities by phosphorylating groups of specific amino acids. For that reason, inhibiting protein kinases with an active small molecule plays a significant role in cancer treatment. To achieve this aim, computational drug design, especially QSAR model, is one of the best economical approaches to reduce time and save in costs. In this respect, active inhibitors are attempted to be distinguished from inactive ones using hybrid QSAR model. Therefore, genetic algorithm and K-Nearest Neighbor method were suggested as a dimensional reduction and classification model, respectively. Finally, to evaluate the proposed model's performance, support vector machine and Naïve Bayesian algorithm were examined. The outputs of the proposed model demonstrated significant superiority to other QSAR models.


Assuntos
Antineoplásicos/classificação , Inibidores de Proteínas Quinases/classificação , Algoritmos , Antineoplásicos/química , Teorema de Bayes , Inibidores de Proteínas Quinases/química , Relação Quantitativa Estrutura-Atividade
5.
Mult Scler Relat Disord ; 37: 101429, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31675638

RESUMO

BACKGROUND: Rituximab is a B-cell-depleting unconjugated monoclonal IgG1 antibody that targets the transmembrane protein CD20. This article reports on a case with the rare complication known as Rituximab-associated mucosal necrosis. CASE PRESENTATION: The present case report addresses, for the first time, a patient affected by Devic's syndrome presenting with oral manifestations of palatal necrosis after rituximab treatment. CONCLUSION: The present case raises the possibility of anti-CD20 antibody contributing to the development of palatal mucosal necrosis in some patients. Given the increasing administration of rituximab as a result of its efficacy against several diseases, a report on the potential iatrogenic effects of this drug is essential.


Assuntos
Antineoplásicos/efeitos adversos , Necrose/induzido quimicamente , Neuromielite Óptica/tratamento farmacológico , Rituximab/efeitos adversos , Anticorpos Monoclonais Murinos/efeitos adversos , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Feminino , Humanos
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