Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mol Biol Rep ; 50(11): 9497-9509, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37731028

RESUMO

Oestrogen, the primary female sex hormone, plays a significant role in tumourigenesis. The major pathway for oestrogen is via binding to its receptor [oestrogen receptor (ERα or ß)], followed by nuclear translocation and transcriptional regulation of target genes. Almost 70% of breast tumours are ER + , and endocrine therapies with selective ER modulators (tamoxifen) have been successfully applied. As many as 25% of tamoxifen-treated patients experience disease relapse within 5 years upon completion of chemotherapy. In such cases, the ER-independent oestrogen actions provide a plausible explanation for the resistance, as well as expands the existing horizon of available drug targets. ER-independent oestrogen signalling occurs via one of the following pathways: signalling through membrane receptors, oxidative catabolism giving rise to genotoxic metabolites, effects on mitochondria and redox balance, and induction of inflammatory cytokines. The current review focuses on the non-classical oestrogen signalling, its role in cancer, and its clinical significance.


Assuntos
Recidiva Local de Neoplasia , Receptores de Estrogênio , Humanos , Feminino , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Estrogênios/metabolismo , Tamoxifeno/farmacologia , Transdução de Sinais
2.
Breast Cancer Res Treat ; 194(2): 207-220, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35597840

RESUMO

BACKGROUND: Therapeutic response predictors like age, nodal status, and tumor grade and markers, like ER/PR, HER2, and Ki67, are not reliable in predicting the response to a specific form of chemotherapy. The current study aims to identify and validate reliable markers that can predict pathological complete response (pCR) in fluorouracil, epirubicin, and cyclophosphamide (FEC)-based neoadjuvant therapy with (NACT/RT) and without concurrent radiation (NACT). MATERIALS AND METHODS: Tandem mass tag (TMT) quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify differentially expressed proteins from core needle breast biopsy between pCR (n = 4) and no-pCR (n = 4). Immunoblotting of shortlisted proteins with the tissue lysates confirmed the differential expression of the markers. Further, immunohistochemistry (IHC) was performed on formalin-fixed paraffin-embedded sections of treatment-naive core needle biopsies. In the NACT, 29 pCR and 130 no-pCR and in NACT/RT, 32 pCR and 71 no-pCR were used. RESULTS: 733 and 807 proteins were identified in NACT and NACT/RT groups, respectively. Ten proteins were shortlisted for validation as potential pCR-predictive markers. THBS1, TNC, and DCN were significantly overexpressed in no-pCR in both the groups. In NACT, CPA3 was significantly upregulated in the no-pCR. In NACT/RT, HnRNPAB was significantly upregulated and HMGB1 significantly downregulated in the no-pCR. HMGB1 was the only marker to show prognostic significance. CONCLUSION: Quantitative proteomics followed by IHC identified and validated potential biomarkers for predicting patient response to therapy. These markers can be used, following larger-scale validation, in combination with routine histological analysis providing vital indications of treatment response.


Assuntos
Neoplasias da Mama , Proteína HMGB1 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Cromatografia Líquida , Feminino , Proteína HMGB1/uso terapêutico , Humanos , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Espectrometria de Massas em Tandem , Resultado do Tratamento
3.
Gene ; 815: 146137, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35007686

RESUMO

The extracellular matrix (ECM) is composed of a mesh of proteins, proteoglycans, growth factors, and other secretory components. It constitutes the tumor microenvironment along with the endothelial cells, cancer-associated fibroblasts, adipocytes, and immune cells. The proteins of ECM can be functionally classified as adhesive proteins and matricellular proteins (MCP). In the tumor milieu, the ECM plays a major role in tumorigenesis and therapeutic resistance. The current review encompasses thrombospondins, osteonectin, osteopontin, tenascin C, periostin, the CCN family, laminin, biglycan, decorin, mimecan, and galectins. The matrix metalloproteinases (MMPs) are also discussed as they are an integral part of the ECM with versatile functions in the tumor stroma. In this review, the role of these proteins in tumor initiation, growth, invasion and metastasis have been highlighted, with emphasis on their contribution to tumor therapeutic resistance. Further, their potential as biomarkers and therapeutic targets based on existing evidence are discussed. Owing to the recent advancements in protein targeting, the possibility of agents to modulate MCPs in cancer as therapeutic options are discussed.


Assuntos
Biomarcadores Tumorais , Proteínas da Matriz Extracelular/fisiologia , Neoplasias/etiologia , Neoplasias/terapia , Moléculas de Adesão Celular/fisiologia , Proteínas da Matriz Extracelular/análise , Humanos , Metaloproteinases da Matriz/fisiologia , Osteonectina/análise , Osteonectina/fisiologia , Osteopontina/fisiologia , Tenascina/fisiologia , Trombospondina 1/fisiologia , Resultado do Tratamento
4.
J Chromatogr Sci ; 56(6): 488-497, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29608650

RESUMO

A combination of 5-fluorouracil (FU), epirubicin (EP) and cyclophosphamide (CP) is routinely employed in the treatment of breast cancer. The objective of this study was to develop a reverse phase high-performance liquid chromatography (HPLC)-UV method for simultaneous quantitative analysis of the triple-drug and their metabolites in plasma. RP-HPLC system with a C18 column and a diode array detector was employed. The plasma samples were precipitated with acetonitrile and the supernatant was dried under a flow of nitrogen gas. The mobile phase comprised of two combinations, water (pH 4.0) and methanol (98:2 v/v), and water (pH 4.0):methanol:acetonitrile (70:13:17 v/v/v). The retention times for the compounds were determined and the parameters of validation established in plasma indicated the robustness and reliability. The corresponding HPLC peaks were confirmed using electron spray ionization mass spectrometry. FU and metabolites had a recovery of >93%; EP, epirubicinol and CP were >78% from plasma. Stability at 28-30°C in water (pH 4.0) of FU, 5,6-dihydro-5-fluorouracil and EP were higher followed by CP, EPol, fluorodeoxyuridine and fluorouridine (FUR). Storage of the drug-spiked plasma at -80°C assessed for 72 h showed a small but significant (P < 0.05) change in the recovery of FUR and EP. The method was validated in patient's plasma samples (n = 6).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Ciclofosfamida/sangue , Ciclofosfamida/química , Ciclofosfamida/metabolismo , Estabilidade de Medicamentos , Epirubicina/sangue , Epirubicina/química , Epirubicina/metabolismo , Fluoruracila/sangue , Fluoruracila/química , Fluoruracila/metabolismo , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...