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1.
Iran J Vet Res ; 22(3): 222-229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777523

RESUMO

BACKGROUND: Feline mammary gland tumors (FMGTs) are the third most diagnosed tumors in cats. Feline mammary gland tumors have aggressive biological behavior and poor response to both surgical and medical treatments, thus, new therapeutic approaches are essential to improve. Curcumin (CUR) is a polyphenol component exhibiting anti-cancer effects and induces apoptosis through different mechanisms especially in human breast cancer. However, there is no study investigating the effects of CUR on FMGTs. AIMS: The aim of this study was to determine the anti-proliferative and apoptotic effects of CUR on primary cell lines from FMGT tissue samples of two cases classified as carcinoma-simple, tubular type (grade III). METHODS: The cytotoxic effect of CUR was determined by water-soluble tetrazolium salt-1 (WST-1) assay. Annexin V, cell cycle, and acridine orange (AO) analyses were performed to determine the apoptotic effect of CUR. RESULTS: Our results showed that CUR had an anti-proliferative and apoptotic effect through induction of apoptosis and cell cycle arrest (G0/G1) on FMGT cells. CONCLUSION: Therefore, this is the first study that shows the effects of CUR on FMGTs. However, further molecular studies are required to compare the effects of CUR on different histopathological phenotypes and to determine the further molecular mechanisms including the potential apoptotic and cellular pathways affected by CUR.

2.
Drugs Today (Barc) ; 55(7): 459-467, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31347614

RESUMO

Talazoparib tosylate (BMN-673, Talzenna; Pfizer) is an oral poly [ADP-ribose] polymerase (PARP) inhibitor (PARPi) that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of germline BRCA-mutated locally advanced or metastatic breast cancer (BC). In preclinical and clinical studies, talazoparib exerted superior efficacy and offered a significant clinical benefit in advanced or metastatic BC patients harboring germline BRCA mutations compared with other PARPi and standard chemotherapy regimens through the concept of synthetic lethality. Thus, this review provides insight into the results of preclinical and clinical studies, highlights the current challenges of talazoparib and suggests innovative approaches to further improve its clinical efficacy and expand the use of talazoparib in advanced BC and/or triple-negative BC treatments beyond BRCA mutations.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ftalazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteína BRCA1/genética , Neoplasias da Mama/genética , Humanos , Mutação
3.
J Microencapsul ; 33(6): 575-584, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27575255

RESUMO

Manganese (Mn)-based complexes have been drawing attention due to the fact that they are more effective than other metal complexes. However, the use of Mn(II)-based complexes in medicine remains limited because of certain side effects. The aim of this study was to investigate the cytotoxic and apoptotic effects of a novel Mn(II) complex [Mn2(µ-(C6H5)2CHCOO)2(bipy)4](bipy)(ClO4)2 and Mn(II) complex loaded solid lipid nanoparticles (SLNs) on MCF-7 and HUVEC control cells. The average diameter of Mn(II) complex was about 1120 ± 2.43 nm, while the average particle size of Mn(II) complex-SLNs was ∼340 ± 2.27 nm. The cytotoxic effects of Mn(II) complex and Mn(II)-SLNs were 86.8 and 66.4%, respectively (p < .05). Additionally, both Mn(II) complex (39.25%) and Mn(II)-SLNs (38.05%) induced apoptosis and increased the arrest of G0/G1 phase. However, Mn(II) complex exerted toxic effects on the HUVEC control cell (63.4%), whereas no toxic effects was observed when treated with Mn(II)-SLNs at 150 µM. As a consequence, SLNs might be potentially used for metal-based complexes in the treatment of cancer due to reducing size and toxic effects of metal-based complexes.


Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Citotoxinas , Lipídeos , Manganês , Nanopartículas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacocinética , Citotoxinas/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipídeos/química , Lipídeos/farmacocinética , Lipídeos/farmacologia , Células MCF-7 , Manganês/química , Manganês/farmacocinética , Manganês/farmacologia , Tamanho da Partícula
4.
Mol Biol Rep ; 43(11): 1273-1284, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27573125

RESUMO

The PALB2 gene, has been accepted as a moderate-penetrance gene associated with breast cancer susceptibility and this gene product is involved in the DNA damage repair pathway via co-localization with BRCA2. Germline PALB2 mutations are associated with an increased breast cancer risk. However, the prevalence of the diverse types of PALB2 variants depend on the population. Thus, the aim of the present study was to determine, for the first time, the prevalence of PALB2 variants in a Turkish population of BRCA1/BRCA2-negative early-onset patients with breast cancer. In total, 223 Turkish patients with BRCA1/BRCA2 negative early-onset breast cancer and 60 unaffected women were included in the study. All the coding exons and intron/exon boundaries of PALB2 were subjected to mutational analysis by heteroduplex analysis (HDA)and DNA sequencing. Eighteen PALB2 variants were found in breast cancer patients within the Turkish population. Three variants (c.271G>A, c.404C>A and c.2981T>A) have not been previously reported. In addition, nine intronic variants were described, and this study is the first to describe the c.1685-44T>A intronic variant. The prevalence of possible pathogenic PALB2 variants was found to be 4.03 % in BRCA1/2-negative Turkish patients with early-onset breast cancer. Different variants of PALB2 have been reported in the literature, and the prevalence of these variants could different for each population. This is the first study to investigate the prevalence of PALB2 variants in Turkish patients with early-onset breast cancer.


Assuntos
Neoplasias da Mama/genética , Estudos de Associação Genética/métodos , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Proteínas Supressoras de Tumor/genética , População Branca/genética , Adulto , Idade de Início , Proteína BRCA1/genética , Proteína BRCA2/genética , Análise Mutacional de DNA/métodos , Proteína do Grupo de Complementação N da Anemia de Fanconi , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Análise de Sequência de DNA/métodos , Turquia , Adulto Jovem
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