Immunomodulatory effect of low concentrations of antineoplastic

• Grant number: 11/05258-0
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2012
• Effective date (End): July 31, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ramon Kaneno
• Grantee: Juliana Cristina Longo Frederico
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Our previous studies have shown that the treatment of human colorectal cancer cells HCT-116 with non-toxic concentrations of antineoplastic drugs such as paclitaxel (PAC) or doxorubicin (DOX) induces changes in the transcription of a wide variety of genes. The treatment was also able to make tumor cells more immunogenic and more sensitive to the activity of cytotoxic T cells generated in vitro. Among the genes, which transcription was increased by pre-treatment, we have found the heat shock proteins genes (HSP40 and HSP70). HSPs are chaperones that direct cross-presentation of antigenic peptides associated with class I molecules and can act as activators of immunocompetent cells, playing an important role in the activation of macrophages and lymphocytes, as well as the activation and maturation of dendritic cells (DCs). Therefore, in the present work we will evaluate whether changes of transcription of HSPs genes, previously identified by DNA microarray, translate into increased protein expression. Confirming such a phenomenon, we will test the hypothesis that the increased immunogenicity of colorectal cancer cells is due to increased expression of HSPs. For this purpose, HCT-116 and HT-29 tumor cells will be treated with minimum effective concentrations (cytostatic concentration) and non-toxic concentrations of 5-fluorouracil (5-FU) or PAC. Expression of HSP40 and 70 will be semi-quantitatively analysed by dot-blot method and qualitatively by immunocytochemical assay. Cells treated with these drugs will be used to sensitize human DCs generated from peripheral blood monocytes of normal donors to assess the effect of expression of HSPs on the DCs functions.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE CAMARGO, MARCELA RODRIGUES; GORGULHO, CAROLINA MENDONCA; RODRIGUES, CECILIA PESSOA; PENITENTI, MARCIMARA; LONGO FREDERICO, JULIANA CRISTINA; MARCHESAN RODRIGUES, MARIA APARECIDA; KANENO, RAMON. Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to Activate Murine Dendritic Cells. CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS, v. 32, n. 8, p. 302-308, OCT 2017. (09/18331-8, 10/06013-9, 11/05258-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FREDERICO, Juliana Cristina Longo. Efeito imunomodulador de baixas concentrações de antineoplásicos. 2013. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.