Differentiating effect of thalidomide and GM-CSF combination on HL-60 acute promyelocytic leukemia cells

Aim: To investigate whether granulocyte-macrophage colony-stimulating factor (GM-CSF) with or without thalidomide can induce apoptosis and differentiation of HL-60 acute promyelocytic leukemia cell line in vitro. Methods: Effect of GM-CSF and thalidomide on proliferation of HL-60 cells was evaluated by MTT assay, cell cycle analysis was performed by propidium iodide staining approach and flow cytometry, and apoptosis rate was analyzed using FITC-conjugated annexin-V and FACScan flow cytometry. Results: The study revealed that thalidomide alone at high concentrations inhibited HL-60 cell growth and induced apoptosis. Three days treatment of low-dose thalidomide in combination with GM-CSF induced marked terminal differentiation of HL-60 cells, as it was assessed by increased expression of differentiation antigens on cell surface. Conclusion: Treatment of HL-60 cells by low concentration of thalidomide combined with GM-CSF induced terminal differentiation of HL60 cells in vitro, which may be advantageous for the elaboration of novel therapeutic regimens in patients with differentiation-inducible leukemias.Цель: изучить эффект гранулоцитарно-макрофагального колониестимулирующего фактора (ГМ-КСФ) в сочетании с талидомидом на индукцию апоптоза и дифференцировку клеток острого промиелоцитарного лейкоза линии HL-60 in vitro. Методы: для оценки пролиферации и жизнеспособности клеток HL-60 применяли MTT анализ, для изучения клеточного цикла — окраску пропидиум бромидом и проточную цитометрию. Для оценки апоптоза клетки линии HL-60 обрабатывали талидомидом, ГМ-КСФ, и совместно талидомидом и ГМ-КСФ в течении 48 ч, и затем метили анексином, конъюгированным с FITC, и анализировали с помощью проточной цитометрии. Результаты: талидомид в высоких концентрациях ингибирует пролиферацию клеток HL-60 и вызывает апоптоз. В сочетании с ГМ-КСФ в течение 3 дней талидомид в низкой концентрации индуцировал терминальную дифференцировку клеток HL-60, о чем свидетельствовало появление экспрессии дифференцировочных антигенов на поверхности клеток. Выводы: применение талидомида в низкой концентрации в сочетании с ГМ-КСФ вызывает терминальную дифференцировку клеток HL-60

Plasma and erythrocyte lipid peroxidation levels in patients with testis tumor after orchiectomy

Plasma and erythrocyte lipid peroxidation levels of 20 patients with histopathologically confirmed testis cancer and 20 healthy control individuals were studied between November 1995 and June 1997. The group with testis cancer had a mean age of 24.8 +/- 8.2 yr and the control group's mean age was 28.3 +/- 6.9 yr. Stage distribution of the testis cancer cases were 4 of stage A, 10 of stage B, and 6 of stage C. Blood samples of the patients were drawn after orchiectomy and after 12 h fasting before chemotherapy. Mean plasma and erythrocyte lipid peroxidation levels were detected to be 14.51 +/- 5.30 nmol malondialdehide (MDA)/mL and 9.30 +/- 2.06 nmol MDA/g hemoglobin (Hb), respectively, in the testis cancer group, whereas the healthy control group had mean plasma and erythrocyte lipid peroxidation levels of 10.7 +/- 1.82 nmol MDA/mL and 6.18 +/- 1.68 nmol MDA/g Hb, respectively. Plasma and erythrocyte lipid peroxidation values of the testis cancer patients were determined to be statistically significantly higher than that of the health control group (p < 0.001, p < 0.001). No significant correlation was determined between plasma, erythrocyte lipid peroxidation levels and tumor markers. In conclusion, it can be said that an increase in the lipid peroxidation may play a role in the pathogenesis of testis carcinomas in addition to the other causes

Outcome of patients with stage II and III nonseminomatous germ cell tumors: Results of a single center

Background: The prognostic factors in nonseminomatous germ cell tumors have been mainly derived from the analysis of stage I tumors. Aims: The aim of this study was to evaluate some prognostic factors and the outcome of patients with stage II and III nonseminomatous germ cell tumors according to risk groups treated between 1993 and 2002. Settings and Design: Patients were retrospectively classified as good, intermediate and poor risk groups according to International Germ Cell Cancer Consensus Group. Materials and Methods: Biopsy specimens of 58 patients with stage II and III nonseminomatous germ cell tumors were analyzed by means of tumor histopathology, primary localization site of the tumor, relapse sites, initial serum tumor marker levels, the presence of persistent serum tumor marker elevation and the patients' outcome. Statistical Analysis : Kruskall Wallis test and Mann-Whitney U test were used to determine the differences between the groups. Kaplan-Meier method was used for survival analysis and log rank test was used to compare the survival probabilities of groups. Cox proportional hazard analysis was used to determine the prognostic factors in univariate and multivariate analysis. Results: Five-year overall and disease-free survival rates were calculated as 85% and 75% in stage II; 44% and 29% in stage III cases, respectively. Fifty-seven percent of patients were classified in good risk, 9% in intermediate risk and 27% in poor risk groups. Five-year overall survival rates were 97%, 75% and 7% ( P < 0.001) and disease-free survival rates were 83%, 34% and 7% ( P < 0.001) in good, intermediate and poor risk groups, respectively. Analysis of the prognostic factors revealed that the localization site of the primary tumor ( P < 0.001), the initial stage of disease ( P < 0.001), the initial serum AFP level (p: 0.001), the initial β -HCG level (p: 0.0048), the presence of yolk sac and choriocarcinoma components in tumor (p: 0.003 and p: 0.004), relapse sites of tumor (lung versus other than lung) (p: 0.003), persistent elevation of serum tumor markers ( P < 0.001) were significant prognostic factors in univariate analysis. However, in multivariate analysis, only the localization site of tumor (p: 0.049) and the relapse site (p: 0.003) were found statistically significant. Conclusions: This retrospective study revealed that in advanced stage of nonseminomatous germ cell tumors, the outcome is essentially related with the localization site of the tumor and the relapse site

Outcome of patients with stage II and III nonseminomatous germ cell tumors: Results of a single center

Background: The prognostic factors in nonseminomatous germ cell tumors have been mainly derived from the analysis of stage I tumors. Aims: The aim of this study was to evaluate some prognostic factors and the outcome of patients with stage II and III nonseminomatous germ cell tumors according to risk groups treated between 1993 and 2002. Settings and Design: Patients were retrospectively classified as good, intermediate and poor risk groups according to International Germ Cell Cancer Consensus Group. Materials and Methods: Biopsy specimens of 58 patients with stage II and III nonseminomatous germ cell tumors were analyzed by means of tumor histopathology, primary localization site of the tumor, relapse sites, initial serum tumor marker levels, the presence of persistent serum tumor marker elevation and the patients' outcome. Statistical Analysis : Kruskall Wallis test and Mann-Whitney U test were used to determine the differences between the groups. Kaplan-Meier method was used for survival analysis and log rank test was used to compare the survival probabilities of groups. Cox proportional hazard analysis was used to determine the prognostic factors in univariate and multivariate analysis. Results: Five-year overall and disease-free survival rates were calculated as 85% and 75% in stage II; 44% and 29% in stage III cases, respectively. Fifty-seven percent of patients were classified in good risk, 9% in intermediate risk and 27% in poor risk groups. Five-year overall survival rates were 97%, 75% and 7% ( P &lt; 0.001) and disease-free survival rates were 83%, 34% and 7% ( P &lt; 0.001) in good, intermediate and poor risk groups, respectively. Analysis of the prognostic factors revealed that the localization site of the primary tumor ( P &lt; 0.001), the initial stage of disease ( P &lt; 0.001), the initial serum AFP level (p: 0.001), the initial \u3b2 -HCG level (p: 0.0048), the presence of yolk sac and choriocarcinoma components in tumor (p: 0.003 and p: 0.004), relapse sites of tumor (lung versus other than lung) (p: 0.003), persistent elevation of serum tumor markers ( P &lt; 0.001) were significant prognostic factors in univariate analysis. However, in multivariate analysis, only the localization site of tumor (p: 0.049) and the relapse site (p: 0.003) were found statistically significant. Conclusions: This retrospective study revealed that in advanced stage of nonseminomatous germ cell tumors, the outcome is essentially related with the localization site of the tumor and the relapse site

Outcome of patients with stage II and III nonseminomatous germ cell tumors: Results of a single center

Background: The prognostic factors in nonseminomatous germ cell tumors have been mainly derived from the analysis of stage I tumors. Aims: The aim of this study was to evaluate some prognostic factors and the outcome of patients with stage II and III nonseminomatous germ cell tumors according to risk groups treated between 1993 and 2002. Settings and Design: Patients were retrospectively classified as good, intermediate and poor risk groups according to International Germ Cell Cancer Consensus Group. Materials and Methods: Biopsy specimens of 58 patients with stage II and III nonseminomatous germ cell tumors were analyzed by means of tumor histopathology, primary localization site of the tumor, relapse sites, initial serum tumor marker levels, the presence of persistent serum tumor marker elevation and the patients' outcome. Statistical Analysis : Kruskall Wallis test and Mann-Whitney U test were used to determine the differences between the groups. Kaplan-Meier method was used for survival analysis and log rank test was used to compare the survival probabilities of groups. Cox proportional hazard analysis was used to determine the prognostic factors in univariate and multivariate analysis. Results: Five-year overall and disease-free survival rates were calculated as 85% and 75% in stage II; 44% and 29% in stage III cases, respectively. Fifty-seven percent of patients were classified in good risk, 9% in intermediate risk and 27% in poor risk groups. Five-year overall survival rates were 97%, 75% and 7% ( P < 0.001) and disease-free survival rates were 83%, 34% and 7% ( P < 0.001) in good, intermediate and poor risk groups, respectively. Analysis of the prognostic factors revealed that the localization site of the primary tumor ( P < 0.001), the initial stage of disease ( P < 0.001), the initial serum AFP level (p: 0.001), the initial β -HCG level (p: 0.0048), the presence of yolk sac and choriocarcinoma components in tumor (p: 0.003 and p: 0.004), relapse sites of tumor (lung versus other than lung) (p: 0.003), persistent elevation of serum tumor markers ( P < 0.001) were significant prognostic factors in univariate analysis. However, in multivariate analysis, only the localization site of tumor (p: 0.049) and the relapse site (p: 0.003) were found statistically significant. Conclusions: This retrospective study revealed that in advanced stage of nonseminomatous germ cell tumors, the outcome is essentially related with the localization site of the tumor and the relapse site