Browsing by Author "Jurisic, V. (6603015144)"

Purpose: Impaired IFNγ production in peripheral blood lymphocytes (PBL) and their subsets reflects immunosuppression and inadequate antitumor immune response in cancer patients. Decreased function of natural killer (NK) cells has not been investigated in breast cancer with respect to altered pSTAT signaling pathways. Methods: PBL of breast cancer patients and healthy controls were analyzed for IFNγ and pSTAT1 expression and NK cell activity using flow cytometry and 51Cr-release assay, respectively. The level of pSTAT1, 3 and 5 was investigated by Western blotting. Results: Our results indicated that PBL and CD3- CD16+ NK cells of patients had significantly lower level of IFNγ. The patients had a significantly decreased NK cell cytotoxicity compared to controls, with the decrease being dependent on the stage of disease. Positive correlation between IFNγ level in PBL and NK cytotoxicity in controls and patients was also shown. The PBL of patients, compared to controls, expressed lower level of pSTAT1, 3 and 5. The patients' T and NK cell subsets had lower pSTAT1 level. Conclusion: This study indicates that pSTAT1 in PBL of breast cancer patients could be a biomarker of decreased NK cell cytotoxicity and IFNγ level that are associated with progression of this disease. © 2011 Zerbinis Medical Publications.

Purpose: Impaired IFNγ production in peripheral blood lymphocytes (PBL) and their subsets reflects immunosuppression and inadequate antitumor immune response in cancer patients. Decreased function of natural killer (NK) cells has not been investigated in breast cancer with respect to altered pSTAT signaling pathways. Methods: PBL of breast cancer patients and healthy controls were analyzed for IFNγ and pSTAT1 expression and NK cell activity using flow cytometry and 51Cr-release assay, respectively. The level of pSTAT1, 3 and 5 was investigated by Western blotting. Results: Our results indicated that PBL and CD3- CD16+ NK cells of patients had significantly lower level of IFNγ. The patients had a significantly decreased NK cell cytotoxicity compared to controls, with the decrease being dependent on the stage of disease. Positive correlation between IFNγ level in PBL and NK cytotoxicity in controls and patients was also shown. The PBL of patients, compared to controls, expressed lower level of pSTAT1, 3 and 5. The patients' T and NK cell subsets had lower pSTAT1 level. Conclusion: This study indicates that pSTAT1 in PBL of breast cancer patients could be a biomarker of decreased NK cell cytotoxicity and IFNγ level that are associated with progression of this disease. © 2011 Zerbinis Medical Publications.

Based on the possibility of tumor necrosis factor (TNF)-α to perform multiple and opposite biologic effects, we simultaneously investigated in vitro its effects on intracellular lactate dehydrogenase (LDH)-H and LDH-M isoenzyme activity and morphological characteristics following induction of apoptosis in peripheral blood mononuclear cells (PBMC) of non-Hodgkin's lymphoma patients (NHL) prior to and after the end of applied chemotherapy. TNF-α showed a significant increase (p<0.05) of LDH-H and LDH-M activity in sonified PBMC of healthy controls after 18 h cultures accompanied with an increase of apoptotic index (AI) from 2.3 to 16.2%. Contrary to this, in PBMC of NHL patients prior to therapy TNF-α induced a significant decrease (p<0.05) of LDH-H isotype activity. In patients after administration of chemotherapy, TNF-α in a dose of 100 U/ml induced a significant increase (p<0.05) of LDH-M isotype activity, but not of LDH-H. In the PBMC of NHL patients prior to chemotherapy, TNF-α in vitro induced an increase of AI from 2.8 up to 6.8%, while in PBMC of NHL patients after applied chemotherapy AI changed from 7.2 to 14.4%. However, there was no significant difference in the increase of apoptosis in PBMC of NHL patients with high-grade malignancy and high rate response among patients who received first-line therapy, high-dose therapy, or third-line therapy regimens after in vitro TNF-α treatment. These results indicated different susceptibilities of PBMC of NHL to TNF-α when effects were analyzed by determination of intracellular LDH isotype profile and induction of apoptosis prior to and after administration of therapy in comparison to effects on healthy controls PBMC.