RESUMO
The phosphatidylinositol 3-kinase-Akt signaling pathway plays an essential role in regulating cell proliferation and apoptosis. Akt kinase is at the center of this signaling pathway and interacts with a variety of proteins. Akt is overexpressed in almost 80% of tumors. However, inhibiting Akt has serious clinical side effects so is not a suitable treatment for cancer. During recent years, Akt scaffold proteins have received increasing attention for their ability to regulate Akt signaling and have emerged as potential targets for cancer therapy. In this paper, we categorize Akt kinase scaffold proteins into four groups based on their cellular location: membrane-bound activator and inhibitor, cytoplasm, and endosome. We describe how these scaffolds interact with Akt kinase, how they affect Akt activity, and how they regulate the specificity of Akt signaling. We also discuss the clinical application of Akt scaffold proteins as targets for cancer therapy.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Terapia de Alvo Molecular , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismoRESUMO
In recent years, there have been increased incidences of metastatic renal cell carcinoma (RCC), which is refractory to conventional chemotherapy. Owing to the insensitivity to traditional therapy, targeted therapy becomes a possible alternative strategy. Over the past decade, the development of targeted treatments for metastatic RCC has advanced considerably. Several studies have shown that the vascular endothelial growth factor pathway is an important mediator for the occurrence and development of RCC, and tyrosine kinase inhibitors (TKIs) that target vascular endothelial growth factor receptors (VEGFRs) have been considered optimal therapeutic options for RCC. Six small molecules that inhibit VEGFR1/2/3, namely, sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib, have been approved by the Food and Drug Administration (FDA) for the treatment of RCC. Additionally, clinical trials assessing seven TKIs that target VEGFRs are currently in progress. To some extent, these drugs improve quality of life and prolong the survival of patients. This paper presents a review of the systemic targeted therapies against VEGFRs that have been approved so far or are undergoing trials as treatments for RCC.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Carcinoma de Células Renais/metabolismo , Desenvolvimento de Medicamentos , Humanos , Neoplasias Renais/metabolismo , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Earthworms are macro invertebrate and have been widely used as therapeutic drugs for thousands of years. In the current research, experiments viz., the antibacterial, antifungal and antioxidant activity of mucus and solvent extracts of Eisenia foetida were conducted to investigate for the first time in Pakistan against human infectious pathogens. Antimicrobial activity of E. foetida against human pathogens underwent investigation through an agar disc diffusion method while an ABTS(â¢+) free radical scavenging method assessed the antioxidant activity. The percentage of bacterial and fungal growth was analyzed statistically with One-Way Analysis of Variance (ANOVA). Results showed that the mucus IV of E. foetida produced a strong potent antibacterial and antifungal activity. Pseudomonas aeruginosa exhibited the highest inhibition zone (33.67±1.53 mm), followed by Klebsiella pneumonia (30.33±1.53mm), Penicillium notatum (30±0.051), Escherichia coli (29±1 mm), Candida albicans (28.33±0.54 mm), Staphylococcus aureus (27±1mm), Serratia marcescens (25.33±0.58 mm), Aspergillus flavus (25.33±0.58 mm), Staphylococcus epidermidis (24.33±0.58 mm), Streptococcus pyogenes (21.67±1.53 mm), and Aspergillus niger (20.67±0.53 mm). Mucus IV of E. foetida also showed the highest antioxidant activity (99%). The results clearly indicate that the mucus and solvent extracts contain effective antimicrobial properties and bioactive compounds to inhibit the growth of infectious pathogens. We conclude that mucus extracts of earthworm have significant level of antimicrobial and antioxidant activities and in future could be potentially used against various infectious pathogens.
