RESUMEN
Pancreatic cancer is an aggressive malignancy with poor survival and high mortality rate with 250 000 deaths per year worldwide. The unique pancreatic cancer microenvironment serves as a major obstacle in the effective treatment of this malignancy. The microenvironment consists not only of pancreatic ductal adenocarcinoma cells but also comprises cells of pancreatic cancer stellate, vascular, and immune origin combined with a dense extracellular matrix containing collagen. The aforementioned pathology leads to an increased intratumor pressure combined with an erratic vascular proliferation within the tumor causing hypoxia and decreased drug delivery. This has led both scientists and clinicians to develop and study drugs with unique mechanisms of action to target the pancreatic cancer microenvironment. Herein, we discuss the pancreatic cancer hypoxic microenvironment, development of hypoxia-activated prodrugs, and results of trials utilizing those drugs to target pancreatic cancer.
Asunto(s)
Antineoplásicos/farmacocinética , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Profármacos/farmacocinética , Animales , Hipoxia de la Célula , HumanosRESUMEN
We developed a computational model to explore the hypothesis that regulatory instructions are context dependent and conveyed through specific 'codes' in human genomic DNA. We provide examples of correlation of computational predictions to reported mapped DNase I hypersensitive segments in the HOXA locus in human chromosome 7. The examples show that statistically significant 9-mers from promoter regions may occur in sequences near and upstream of transcription initiation sites, in intronic regions, and within intergenic regions. Additionally, a subset of 9-mers from coding sequences appears frequently, as clusters, in regulatory regions dispersed in noncoding regions in genomic DNA. The results suggest that the computational model has the potential of decoding regulatory instructions to discover candidate transcription factor binding sites and to discover candidate epigenetic signals that appear in both coding and regulatory regions of genes.
Asunto(s)
Biología Computacional/métodos , ADN/química , Secuencias Reguladoras de Ácidos Nucleicos/genética , Sitios de Unión , Cromosomas Humanos Par 7/genética , ADN/metabolismo , Genoma Humano , Proteínas de Homeodominio/genética , Humanos , Regiones Promotoras Genéticas/genéticaRESUMEN
In the current state of interventional cardiology, the ability to offer advanced therapies to patients who historically were not surgical candidates has grown exponentially in the last few decades. As therapies have expanded in complex coronary and structural interventions, the nuances of treating certain populations have emerged. In particular, the role of sex-based anatomic and outcome differences has been increasingly recognized. As guidelines for cardiovascular prevention and treatment for certain conditions may vary by sex, therapeutic interventions in the structural and percutaneous coronary areas may also vary. In this review, we aim to discuss these differences, the current literature available on these topics, and areas of focus for the future.