RESUMO
The stimulatory and inhibitory coreceptors expressed by T lymphocytes are known to play critical roles in regulating cancer immunity. An array of inhibitory coreceptors involved in the inhibition of T-cell functions and the blockade of immune activation have been discovered in recent years, the most important of which are cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmmed death-1 (PD-1), and B7 homolog 1 (B7-H1). Immunotherapies targeting T-cell coinhibitory molecules have proved to be effective in cancer treatment. Several kinds of monoclonal antibodies have been tested in preclinical studies, with better outcomes than conventional therapies in many malignancies. Common urological malignancies including renal cell carcinoma, bladder cancer and prostate cancer are supposed to be immunogenic cancer types and not so sensitive to conventional therapies as other malignancies. This review will focus on B7-H1/PD-1 blockade therapy in urological malignancies, summarizing the results of clinical trials as well as the challenges and prospects of this emerging immunotherapy.
Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/imunologia , Antineoplásicos/imunologia , Antineoplásicos/uso terapêutico , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Antígeno CTLA-4/antagonistas & inibidores , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Receptor de Morte Celular Programada 1/análise , Neoplasias da Próstata/tratamento farmacológico , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
A rice CDPK gene, OsCDPK14 (AY144497), was cloned from developing caryopses of rice (Oryza sativa cv. Zhonghua 15). Its cDNA sequence (1922 bp) contains an ORF encoding a 514 amino acids protein (56.7kD, pl 5.18). OsCDPK14 shows the typical structural features of the CDPK family, including a conserved catalytic Ser/Thr kinase domain, an autoinhibitory domain and a CaM-like domain with four putative Ca2+-binding EF hands. Subcellular targeting indicated that OsCDPK14 was located in the cytoplasm, probably due to the absence of myristoylation and palmitoylation motifs. OsCDPK14 was expressed in Escherichia coli and purified from bacterial extracts. The recombinant protein was shown to be a functional protein kinase using Syntide-2, a synthetic peptide. Kinase activity was shown to be Ca2+-dependent, and this activation was strongly enhanced by Mn2+ and inhibited by W7 in vitro. These results provide significant insights into the regulation and biochemical properties of OsCDPK14, suggesting OsCDPK14 may be a signal factor of cytoplasm in rice plant.
