RESUMO
Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.
Assuntos
Antineoplásicos Imunológicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Imunoconjugados/farmacologia , Evasão Tumoral/efeitos dos fármacos , Alfa-Amanitina/farmacologia , Alfa-Amanitina/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Receptores Coestimuladores e Inibidores de Linfócitos T/antagonistas & inibidores , Receptores Coestimuladores e Inibidores de Linfócitos T/imunologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/imunologia , Humanos , Imunoconjugados/uso terapêutico , Imunoterapia/métodos , Instabilidade de Microssatélites/efeitos dos fármacos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , RNA Polimerase II/antagonistas & inibidores , Resultado do Tratamento , Evasão Tumoral/genética , Evasão Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Proteína Supressora de Tumor p53/genéticaRESUMO
AIM: To explore the effects of culture supernatant of bladder tumor cell lines BIU-87 on the development and function of peripheral blood mononuclear cell (PBMC)-derived dendritic cells. METHODS: The culture supernatant of BIU-87 cells was collected and used as the conditional culture medium for PBMC-derived DCs culture in experiment group. Normal cultured DCs were used as control group. The phenotypes of DCs in experiment group and in control group were analyzed by FACS. The capacity and difference to stimulate allogenetic T cells of PBMC-derived DCs from the two groups were evaluated by MTT colourimetry. RESULTS: Phenotypic analysis showed that DCs co-cultured with culture supernatant of BIU-87 cells expressed lower levels of CD1a, CD83 and CD86. Moreover, as compared with control group, the maturation of DCs was inhibited, and the capacity to stimulate allgentic T cell proliferation by DCs descended(P<0.05). CONCLUSION: The culture supernatant of BIU-87 cells can inhibit the development and function of DCs. It is a possible reason for the decrease of the number of DCs and the descent of its functional in the patients with bladder tumor.
Assuntos
Meios de Cultivo Condicionados/farmacologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Antígenos CD/metabolismo , Antígenos de Superfície/imunologia , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/patologia , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologiaRESUMO
cDNA cloning and 1 899 bp sequence of growth hormone receptor (GHR) from guinea pig liver are described. The guinea pig GHR consists of 610 amino acids. The structural feature and homology comparison of guinea pig GHR are also reported.
RESUMO
A cDNA of rice ragged stunt oryzavirus(RRSV) coding for its protein PS9 was prepared and expressed in E.coli as a fusion protein then purified and cleaved by factor-Xa to a 38kD polypeptide. Using the IgG of the antiserum raised against the expressed fusion protein the gold immuno-labelling experiments provided a direct evidence that the 38kD polypeptide is one of the major proteins forming the virus spikes. Virus transmission experiments in brown planthopper fed with PS9 showed the inhibition of transmission of virus by the PS9 protein suggesting that the spike proteins of the virus may be essential for the virus infection.
