RESUMO
Despite decades of basic and clinical research and trials of promising new therapies, cancer remains a major cause of morbidity and mortality due to the emergence of drug resistance to anticancer drugs. These resistance events have a very well-understood underlying mechanism, and their therapeutic relevance has long been recognized. Thus, drug resistance continues to be a major obstacle to providing cancer patients with the intended "cure". PAQR4 (Progestin and AdipoQ Receptor Family Member 4) gene is a recently identified novel protein-coding gene associated with various human cancers and acts through different signaling pathways. PAQR4 has a significant influence on multiple proteins that may regulate various gene expressions and may develop chemoresistance. This review discusses the roles of PAQR4 in tumor immunity, carcinogenesis, and chemoresistance. This paper is the first review, discussing PAQR4 in the pathogenesis of cancer. The review further explores the PAQR4 as a potential target in various malignancies.
Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Oncogenes/genética , Terapia de Alvo Molecular/métodos , Antineoplásicos/uso terapêutico , Proteínas de Membrana/genética , Animais , Transdução de Sinais/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
Traditional therapies often struggle with specificity and resistance in case of cancer treatments. It is therefore important to investigate new approaches for cancer treatment based on nanotechnology. Zinc oxide nanoparticles (ZnONPs) are known to exhibit anti-cancer properties by inducing oxidative stress, apoptosis, and cell cycle arrest. Methotrexate (MTX) a known anti-folate shows specificity to folate receptors and interrupts healthy functioning of cells. This study proposes the use of previously characterized biocompatible Methotrexate loaded Zinc oxide nanoparticles (MTX-ZnONPs) as a dual action therapeutic strategy against breast cancer cell lines, MCF-7 (MTX-sensitive) and MDA-MB-231 (MTX-resistant). To elucidate the cytotoxicity mechanism of MTX-ZnONPs an in depthIn vitrostudy was carried out.In vitroassays, including cell cycle analysis, apoptosis assay, and western blot analysis to study the protein expression were performed. Results of these assays, further supported the anti-cancer activity of MTX-ZnONPs showing apoptotic and necrotic activity in MCF-7 and MDA-MB-231 cell line respectively.In vivoacute oral toxicity study to identify the LD50in animals revealed no signs of toxicity and mortality up to 550 mg kg-1body weight of animal, significantly higher LD50values than anticipated therapeutic levels and safety of the synthesized nanosystem. The study concludes that MTX-ZnONPs exhibit anti-cancer potential against breast cancer cells offering a promising strategy for overcoming resistance.
Assuntos
Apoptose , Neoplasias da Mama , Metotrexato , Óxido de Zinco , Metotrexato/farmacologia , Metotrexato/química , Metotrexato/administração & dosagem , Humanos , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Células MCF-7 , Apoptose/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacosRESUMO
OBJECTIVES: To explore the extent to which doctor-rating websites are known and used among a sample of respondents from London. To understand the main predictors of what makes people willing to use doctor-rating websites. DESIGN: A cross-sectional study. SETTING: The Borough of Hammersmith and Fulham, London, England. PARTICIPANTS: 200 individuals from the borough. MAIN OUTCOME MEASURES: The likelihood of being aware of doctor-rating websites and the intention to use doctor-rating websites. RESULTS: The use and awareness of doctor-rating websites are still quite limited. White British subjects, as well as respondents with higher income are less likely to use doctor-rating websites. Aspects of the doctor-patient relationship also play a key role in explaining intention to use the websites. The doctor has both a 'complementary' and 'substitute' role with respect to Internet information. CONCLUSIONS: Online rating websites can play a major role in supporting patients' informed decisions on which healthcare providers to seek advice from, thus potentially fostering patients' choice in healthcare. Subjects who seek and provide feedback on doctor-ranking websites, though, are unlikely to be representative of the overall patients' pool. In particular, they tend to over-represent opinions from non-White British, medium-low-income patients who are not satisfied with their choice of the healthcare treatments and the level of information provided by their GP. Accounting for differences in the users' characteristics is important when interpreting results from doctor-rating sites.