RESUMO
Cisplatin is one of the most effective chemotherapy drugs for ovarian cancer, but resistance is common. The initial response to platinumbased chemotherapy is as high as 80%, but in most advanced patients, final relapse and death are caused by acquired drug resistance. The development of resistance to therapy in ovarian cancer is a significant hindrance to therapeutic efficacy. The resistance of ovarian cancer cells to chemotherapeutic mechanisms is rather complex and includes multidrug resistance, DNA damage repair, cell metabolism, oxidative stress, cell cycle regulation, cancer stem cells, immunity, apoptotic pathways, autophagy and abnormal signaling pathways. The present review provided an update of recent developments in our understanding of the mechanisms of ovarian cancer platinumbased chemotherapy resistance, discussed current and emerging approaches for targeting these patients and presented challenges associated with these approaches, with a focus on development and overcoming resistance.
Assuntos
Antineoplásicos , Neoplasias Ovarianas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismoRESUMO
Alkylation of one of the imidazole rings of hexahistidine with Baylis-Hillman esters tethered to nitrilotriacetate residue was achieved in aqueous solutions at neutral pH and at micromolar concentrations in the presence of Ni(2+), Cu(2+), or Zn(2+) cations. The utility of the approach for selective functionalization of His-tagged recombinant proteins was demonstrated by attachment of a fluorescent label to recombinant protein A with an alkynyl group followed by a "click" 1,3-dipolar cycloaddition reaction.
Assuntos
Histidina/química , Oligopeptídeos/química , Alquilação , Cobre/química , Reação de Cicloadição , Ésteres , Corantes Fluorescentes/química , Concentração de Íons de Hidrogênio , Imidazóis/química , Íons/química , Níquel/química , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteína Estafilocócica A/química , Proteína Estafilocócica A/genética , Proteína Estafilocócica A/metabolismo , Água/química , Zinco/químicaRESUMO
Tridentate chelate ligands of 2,6-bis[hydroxy(methyl)amino]-1,3,5-triazine family rapidly release iron from human recombinant ferritin in the presence of oxygen. The reaction is inhibited by superoxide dismutase, catalase, mannitol and urea. Suggested reaction mechanism involves reduction of the ferritin iron core by superoxide anion, diffusion of iron(II) cations outside the ferritin shell, and regeneration of superoxide anions through oxidation of iron(II) chelate complexes with molecular oxygen.
Assuntos
Ferritinas/química , Quelantes de Ferro/química , Ferro/química , Oxigênio/química , Catalase/metabolismo , Catálise , Ferritinas/genética , Ferritinas/metabolismo , Humanos , Cinética , Ligantes , Oxirredução , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Superóxido Dismutase/metabolismo , Superóxidos/químicaRESUMO
Copper(I) oxide can effectively co-catalyze the Suzuki type cross-coupling reactions of arylboronic acids with ethyl bromoacetate. As an alternative protocol for introducing the methylenecarboxy group into functionalized molecules, this reaction occurs in the absence of highly toxic thallium compounds or special ligands and should be convenient and practical.
