title: Immodin and its immune system supportive role in paclitaxel therapy of 4T1 mouse breast cancer.
abstract: It is evident that standard chemotherapy agents may have an impact on both tumor and host immune system. Paclitaxel (PTX), a very potent anticancer drug from a taxane family, has achieved prominence in clinical oncology for its efficacy against a wide range of tumors including breast cancer. However, significant toxicity, such as myelosuppression, limit the effectiveness of Paclitaxel-based treatment regimens. Immodin (IM) is low molecular dialysate fraction of homogenate made from human leukocytes. It contains a mixture of substances from which so far have been described e.g. Imreg 1 and Imreg 2 formed by the dipeptide tyrosine-glycine and the tripeptide tyrosine-glycine-glycine, respectively. The aim of this study was to explore immunopharmacological activities of IM, using the strongly immunogenic 4T1 mouse breast cancer model, and evaluate its effect on the reactivity and the efficiency of PTX cancer therapy. The results highlight a potentially beneficial role for IM in alleviating PTX-induced toxicity, especially on the nonspecific immunity, during breast cancer therapy. Co-treatment exhibited an antitumor effect including reduced tumor growth, prolonged survival of tumor bearing mice, increased number of monocytes and lymphocytes in peripheral blood. In spleens, IM+PTX therapy elevated proportion of whole lymphocytes in the account of myelo-monocytic cells characteristic with low expression of CD11c+ and bearing Fc receptor (CD16/32) as well as T-lymphocytes, NK cells and dendritic cells. Accumulation of tumor-associated granulocytes in stroma of PTX-treated group and intensive 4T1-necrosis/apoptosis in tumors after co-treatment were also recorded. These findings suggest the possibility of using IM alongside PTX treatment for maintaining the immune system functions and increasing patient survival.
authors.affiliation: Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, 040 01, Košice, Slovak Republic.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Demečková
authors.affiliation: Department of Cell Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, 040 01, Košice, Slovak Republic. Electronic address: peter.solar@upjs.sk.
authors.forename: Peter
authors.initials: P
authors.lastname: Solár
authors.affiliation: Parasitological Institute of the Slovak Academy of Sciences, 040 01, Košice, Slovak Republic.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hrčková
authors.affiliation: Department of Microbiology and Immunology, University of Veterinary Medicine and Pharmacy, 041 81, Košice, Slovak Republic.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Mudroňová
authors.affiliation: Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, 040 01, Košice, Slovak Republic.
authors.forename: Bianka
authors.initials: B
authors.lastname: Bojková
authors.affiliation: Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, 040 01, Košice, Slovak Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Kassayová
authors.affiliation: Department of Microbiology and Immunology, University of Veterinary Medicine and Pharmacy, 041 81, Košice, Slovak Republic.
authors.forename: Soňa
authors.initials: S
authors.lastname: Gancarčiková
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D007107:Immune System / Q000187:drug effects* / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008222:Lymphokines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D017239:Paclitaxel / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C049120:IMREG-1; D008222:Lymphokines; D017239:Paclitaxel
keywords: 4T1 derived mouse breast cancer; Immodin; Paclitaxel