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Cetin: Istanbul University Research Fund: Employment, Research Funding. Kuruca:Istanbul University Research Fund: Research Funding.

Abstract 4326 Intensive treatment of acute lymphoblastic leukemia in children has brought an increase of total remissions but also an increase of various complications resulting from toxicity of the treatment itself. One of the side effects of the use of cytostatics is their suppressive effect on the immune system. As an important element of the immune system, NK (Natural Killer) cells have critical roles in many different functions such as infection control, cancer surveillance, fetal implantation and cytokine production that will be affected by the immune suppresion. Dysfunctions of the NK cells by treatment are both of quantitative and qualitative nature. Our aim with this study is to analyze qualitative and quantitative chemotherapy induced changes on NK cells in children with acute lymphoblastic leukemia.Thirty three children aged between 2 and 19 years were included in the patient group. Their immunphenotypes, risk groups, prophylactic cranial radiation status and clinical characteristics were recorded. According to ALL BFM 2000 protocol, patients were classified into three groups: group 1 (patients who finished protocol M), group 2 (patients still on maintenance chemotherapy) and group 3 (patients who finished treatment). Control group (group 4) consisted of eleven healthy children aged between 2 and 13 years. NK cytotoxicity test, flow cytometric analysis of NK subgroups, cytokine analysis were performed in blood samples taken with informed consent from parents of both patients and controls. Clinical characteristics of the patients were evaluated with these results. Analysis was performed with “one way ANOVA” statistical test using SPSS 14.0.In 1:1 E:T ratio, group 2's NK cytotoxicity was significantly higher than any other group (p<0.05) (Figure 1). As the receptor expressions evaluated, group 2 was lower significantly than the control group in CD16+CD56+, CD16+NKG2D+, CD94+NKp46+ subgroups (p<0.05) (Figure 2,3). When the prophylactic cranial radiation status of all cases were considered, irradiated patients' NK cytotoxicity value was significantly higher than non-irradiated cases (p<0.05) (Table 1). As NK cytotoxicity and NK subgroups evaluated according to risk groups and time passed from end of treatment (less than a year or more), no significant differences were found. Only in samples which weren't stimulated by tumor cells, IFNγ and IL-15 was found significantly lower in group 2 and group 3 compared with the control group (p<0.05).NK cells and subgroups in quantity seem to have decreased by the maintenance chemotherapy but not their functions. Group 2's (patients on maintenance therapy) higher NK cytotoxicity value may be due to low dose radiation's augmentation effect on NK cell functions as group 2 mostly consists of patients treated with prophylactic cranial radiation. A better understanding of NK cells changed by chemotherapy and radiotherapy will give us the opportunity of developing treatment that enhance their functions and so will contribute to the life quality of children with acute lymphoblastic leukemia (This project is sponsored by Istanbul University Research Fund, project number: T-889/02062006).Aksu Uzunhan: Istanbul University Istanbul Medical Faculty: Employment; Istanbul University Research Fund: Research Funding.

Abstract 4770

Abstract 4326

1H-Indole-2,3-dione (isatin) is an endogenous compound identified in many organisms, possesses a wide range of biological activities. Biological properties of isatin include a range of actions in brain and offer protection against certain types of infections. This molecule has a versatile moiety that displays diverse biological activities, including anticancer activity. The discovery of numerous biologically active 3-substituted 2-indolinones led in the past decade to extensive synthesis of related compounds and as a result, anticancer agents were developed. In particular, among the 5-substituted analogs tested in the growth inhibitions against several human cancer cell lines, 5-halide, methoxy and trifluoromethoxy groups containing 3-substituted 2-indolinones show high antiproliferative effects. For this purpose, we first synthesized twelve 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones that antituberculosis activities were shown previously by our teamwork and we researched anticancer drug potential in this study. The cytotoxic effects of twelve thiosemicarbazone derivatives were investigated by MTT assay in chronic myeloid leukemia cell lines (K562, HL60), B-lymphoma cell lines (P3HR1) and in vincristine resistant forms. The IC50values (IC50is a concentration that kills 50% of cells) were calculated from dose-response curve according to cytotoxicity index. The effectiveness of thiosemicarbazone derivatives were evaluated by comparing IC50values in leukemic cell lines. All of the compounds were found cytotoxic in B-lymphoma cell lines (P3HR1, P3HR1Vin) in range 0.95–2.41 μM. However, the allyl derivative of thiosemicarbazones has cytotoxic activity in all the cancer cell lines (K562, K562Vin, HL-60, P3HR1, P3HR1Vin) that were tested. As a result, 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones derivates might have chemotherapeutic drug potential in B-lymphoma patients. The allyl derivative of thiosemicarbazones has benefit both B-lymphoma and chronic myeloid leukemia patients in a large spectrum.

1H-Indole-2,3-dione (isatin) is an endogenous compound identified in many organisms, possesses a wide range of biological activities. Biological properties of isatin include a range of actions in brain and offer protection against certain types of infections. This molecule has a versatile moiety that displays diverse biological activities, including anticancer activity. The discovery of numerous biologically active 3-substituted 2-indolinones led in the past decade to extensive synthesis of related compounds and as a result, anticancer agents were developed. In particular, among the 5-substituted analogs tested in the growth inhibitions against several human cancer cell lines, 5-halide, methoxy and trifluoromethoxy groups containing 3-substituted 2-indolinones show high antiproliferative effects. For this purpose, we first synthesized twelve 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones that antituberculosis activities were shown previously by our teamwork and we researched anticancer drug potential in this study. The cytotoxic effects of twelve thiosemicarbazone derivatives were investigated by MTT assay in chronic myeloid leukemia cell lines (K562, HL60), B-lymphoma cell lines (P3HR1) and in vincristine resistant forms. The IC50 values (IC50 is a concentration that kills 50% of cells) were calculated from dose-response curve according to cytotoxicity index. The effectiveness of thiosemicarbazone derivatives were evaluated by comparing IC50 values in leukemic cell lines. All of the compounds were found cytotoxic in B-lymphoma cell lines (P3HR1, P3HR1Vin) in range 0.95–2.41 μM. However, the allyl derivative of thiosemicarbazones has cytotoxic activity in all the cancer cell lines (K562, K562Vin, HL-60, P3HR1, P3HR1Vin) that were tested. As a result, 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones derivates might have chemotherapeutic drug potential in B-lymphoma patients. The allyl derivative of thiosemicarbazones has benefit both B-lymphoma and chronic myeloid leukemia patients in a large spectrum.