Mirosława Koronkiewicz

Biological investigation of the platinum(II)-[*I]iodohistamine complexes of potential synergistic anti-cancer activity

Cisplatin chemotherapy in combination with external irradiation or with low-dose continuous internal radiotherapy produces significant supra-additive treatment effects towards several tumor cells. The purpose of our research is to develop a new class of platinum-based anticancer drugs containing moieties of synergistic potency such as platinum core and a radiotherapeutic isotope which, delivered directly to the tumorous cells by a specifically designed vectors, should produce a local enhancement of therapeutic dose. Thus, we have synthesized a new platinum-iodohistamine complex and its radioactive analogues labeled with I-125 and I-131. In the present study some biological properties of those compounds have been investigated. The in vitro screening study pointed out that non-radioactive platinum-iodohistamine complex possesses high cytostatic activity against COLO-205 cells, and moderate activity against HL-60 cell line. No cytotoxicity was observed against MOLT-4 and L-1210 cells, as well as against VERO normal cells. The biodistribution of intravenously administered radioactive platinum-[131I]-iodohistamine complex to normal rats revealed the highest accumulation in the liver (c.a. 40%ID). Intraperitoneal injections of the complex to tumor-bearing C3H mice resulted in scattering of the dose in the organs (mainly in GIT, liver, kidney). The retention of radioactive complex in neoplastic tissue was 3-4 times higher than in normal muscular tissue, although exhibited the tendency to decrease with time post injection. The results of the present study show promising features of the newly developed platinum-iodohistamine complexes and justify prospective investigation of in vivo anticancer potency on animal models of solid tumors.

Changes of percentages in immune cells phenotypes and cytokines production during two-year IFN-β-1a treatment in multiple sclerosis patients

Abstract.Objective:The aim of the study was to find out whether INF-β-1a influences the immune profile of peripheral blood (PB) leukocytes in MS patients.Method:We have studied 20 patients with relapsing-remitting form of MS treated with INF-β-1a using twocolor cytometry. We determined immune cells phenotypes and production of some cytokines: IL-4, IL-10, IL-12, IFN-γ, before drug administration and after starting the treatment.Results:In MS patients an increased percentage of CD14+CD86+ cells and CD3+CD25+ cells was noticed after 6, 9 and 12 months of INF-β-1a therapy. Among cytokine-producing cells we noted an increased fraction of CD3+IL-4, CD14+IL-10 and CD14+IL-12 cells after 12 months, which decreased to the level observed before treatment after 24-month therapy.Conclusions:IFN-β-1a treatment was associated with significant changes in immune response. This effect was mostly evident within the first year of treatment.

Radiosensitivity of HCV cells and their v-ras and v-raf transfectants.

In the present work, it was found that transfection of cultivated urothelial cells HCV-29 with v-raf and v-ras oncogenes increased their sensitivity to ionizing radiation, as documented by clonogenic studies. Flow cytometry study showed, that HCV-29 and their v-ras transfectants were arrested around middle S phase, whereas v-raf transfectants randomly at each point of S phase. This unusual reaction of HCV-29 v-raf cells may partially explain studies of P21(WAF1/CIP1) and GADD45 genes, whose transcripts were found only in these cells. Increased radiosensitivity of v-ras transfectants is probably associated with c-JUN protein overexpression. Altogether the obtained results suggested different mechanism of reaction on irradiation of v-raf and v-ras transfected cells.