Collaborations are most welcome. Please send your proposals to Dr. John G. Delinasios or Dr. George J. Delinasios.
The following research projects are in progress at the IIAR in cooperation with other Cancer Research Centers.
- Invasion and metastasis: In vitro and in vivo models.
- In vitro and in vivo preclinical evaluation of new anticancer agents.
- Mechanisms of development of resistance to cisplatin in vitro.
- The biochemical pathways of pyrimidine and purine synthesis as targets of combination chemotherapy with new anticancer agents (in the process of organization).
Brief Description of the Projects.
A. INVASION AND METASTASIS: IN VITRO AND IN VIVO MODELS.
Study of the initial development stages of the invasive properties of tumor cells; Heterogeneity of the invasive cells; Interactions between stromal fibroblasts and tumor cells; In vitro and in vivo evaluation of the new antimetastatic agents; In vitro antimetastatic drug assay.
INTERACTIONS BETWEEN STROMAL FIBROBLASTS AND TUMOR CELLS
This is one of the main projects of the IIAR.
Considering recent advances and the current interest in the role of tumor microenvironment on cancer development and progression, this project is a continuation of earlier work:
- Delinassios JG, Hoffman RM. The cancer-inhibitory effects of proliferating tumor-residing fibroblasts. Biochim Biophys Acta Rev Cancer. 2021 Dec 22;1877(1):188673. doi: 10.1016/j.bbcan.2021.188673. Epub ahead of print. PMID: 34953931.
- Lamprecht S, Sigal-Batikoff I, Shany S, Abu-Freha N, Ling E, Delinasios GJ, Moyal-Atias K, Delinasios JG, Fich A. Teaming Up for Trouble: Cancer Cells, Transforming Growth Factor-β1 Signaling and the Epigenetic Corruption of Stromal Naïve Fibroblasts. Cancers (Basel). 2018 Feb 27;10(3):61. doi: 10.3390/cancers10030061. PMID: 29495500; PMCID: PMC5876636.
- Delinasios JG, Angeli F, Koumakis G, Kumar S, Kang WH, Sica G, Iacopino F, Lama G, Lamprecht S, Sigal-Batikoff I, Tsangaris GT, Farfarelos CD, Farfarelos MC, Vairaktaris E, Vassiliou S, Delinasios GJ. Proliferating fibroblasts and HeLa cells co-cultured in vitro reciprocally influence growth patterns, protein expression, chromatin features and cell survival. Anticancer Res. 2015 Apr;35(4):1881-916. PMID: 25862842.
- Delinassios JG. Fibroblasts against cancer cells in vitro. Anticancer Res. 1987 Sep-Oct;7(5B):1005-10. PMID: 3324932.
- Angeli F, Koumakis G, Chen MC, Kumar S, Delinassios JG. Role of stromal fibroblasts in cancer: promoting or impeding? Tumour Biol. 2009;30(3):109-20. doi: 10.1159/000218708. Epub 2009 May 14. PMID: 19440007.
- Delinassios JG. Cytocidal effects of human fibroblasts on HeLa cells in vitro. Biol Cell. 1987;59(1):69-77. doi: 10.1111/j.1768-322x.1987.tb00517.x. PMID: 2955837.
- Delinassios JG, Kottaridis SD. Interactions between human fibroblasts and HeLa cells in vitro. Biol Cell. 1984;50(1):9-16. doi: 10.1111/j.1768-322x.1984.tb00250.x. PMID: 6234042.
- Delinassios JG, Kottaridis SD, Garas J. Uncontrolled growth of tumour stromal fibroblasts in vitro. Exp Cell Biol. 1983;51(4):201-9. doi: 10.1159/000163192. PMID: 6873436.
- Delinassios J, G: Prolonged in vitro Maintenance of Human Diploid Fibroblasts in a New Tissue Culture Medium (PRC-1). Pathobiology 1983;51:315-321. doi: 10.1159/000163210
- Delinassios J, G, Kottaridis S, D: Interactions between Human Lymphoblastoid Cells and Human Fibroblast Feeder Layers in vitro. Pathobiology 1981;49:177-184. doi: 10.1159/000163821
- Delinassios JG, Pandis NB, Margaronis M, Kottaridis SD. Double minutes in fibroblast-like cells isolated from human tumors. Experientia. 1981 Jun;37(6):569-70. doi: 10.1007/BF01990054. PMID: 7262278.
B. IN VITRO AND IN VIVO PRECLINICAL EVALUATION OF NEW ANTICANCER AGENTS.
Phenothiazine derivatives; Compounds of Gallium, Ruthenium and Vanadium; New 5- substituted pyrimidine derivatives; Cell cycle specific targets; New methodologies involving single cell assays, chromosomal aberrations, induction of apoptosis, specific enzyme activity on single cells, in situ hybridization; Methioninase as a tumor selective therapeutic modulator.
C. MECHANISMS OF DEVELOPMENT OF RESISTANCE TO CISPLATIN IN VITRO.
Study of the initial stages of development of resistance to cisplatin in vitro, focusing on specific chromosomal abnormalities, existence of HSR, AgNOR, morphology and SCEs.
This project ia a continuation of earlier work:
- Experientia 39: 1394-1395, 1983
- Medical Oncology & Tumor Pharmacotherapy 2:33-38, 1985
- Experimental Cell Biology 55:69-73, 1987
D. THE BIOCHEMICAL PATHWAYS OF PYRIMIDINE AND PURINE SYNTHESIS AS TARGETS OF COMBINATION CHEMOTHERAPY WITH NEW ANTICANCER AGENTS
Investigation of the possibilities of blocking simultaneously several biochemical pathways leading to the synthesis of pyrimidine and purine nucleotides. Combinations of recently developed compounds, which show remarkable activity against enzymes involved in the de novo synthesis of pyrimidine nucleotides will be used for this purpose. A series of established and primary human cancer cell lines will be used in the in vitro chemosensitivity assays for these combinations. The results are expected to identify new targeting methodologies against cancer, which may then be directly applicable in the chemotherapeutic treatment of cancer patients.