RESUMEN

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.

Asunto(s)

Antineoplásicos Inmunológicos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Inmunoconjugados/farmacología , Escape del Tumor/efectos de los fármacos , Alfa-Amanitina/farmacología , Alfa-Amanitina/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/mortalidad , Receptores Coestimuladores e Inhibidores de Linfocitos T/antagonistas & inhibidores , Receptores Coestimuladores e Inhibidores de Linfocitos T/inmunología , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/inmunología , Humanos , Inmunoconjugados/uso terapéutico , Inmunoterapia/métodos , Inestabilidad de Microsatélites/efectos de los fármacos , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Inhibidores de la Síntesis del Ácido Nucleico/uso terapéutico , ARN Polimerasa II/antagonistas & inhibidores , Resultado del Tratamiento , Escape del Tumor/genética , Escape del Tumor/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Proteína p53 Supresora de Tumor/genética

RESUMEN

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.

Asunto(s)

Medios de Cultivo Condicionados/farmacología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/metabolismo , Antígenos CD/metabolismo , Antígenos de Superficie/inmunología , Proliferación Celular/efectos de los fármacos , Células Dendríticas/patología , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/patología

RESUMEN

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.

RESUMEN

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.