TNF-? induces changes in LDH isotype profile following triggering of apoptosis in PBL of non-Hodgkin?s lymphomas

Abstract

Based on the possibility of tumor necrosis factor (TNF)-alpha 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-alpha 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-alpha induced a significant decrease ( p<0.05) of LDH-H isotype activity. In patients after administration of chemotherapy, TNF-alpha 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-alpha 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-alpha treatment. These results indicated different susceptibilities of PBMC of NHL to TNF-alpha 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.

F1FOATP Synthase Is Expressed at the Surface of Embryonic Rat Heart-Derived H9c2 Cells and Is Affected by Cardiac-Like Differentiation

“…The overall description of the differentiating treatments was outlined in Figure , together with some characteristics acquired by the cells and relevant for the discussion of the results (i.e., growth rate, cardiac markers, mitochondrial mass, and mitochondrial F 1 F O ATP synthase assembly). During the treatment, cytotoxicity was verified by a sensitive LDH‐release assay, as widely reported for several cell systems [Jurisic, ; Jurisic et al, ]. Very low treatment cytotoxicity was observed (Fig.…”

Clinical stage-depending decrease of NK cell activity in multiple myeloma patients

“…We previously reported that patients with multiple myeloma have stage dependent increase of serum TNF-a that strongly correlated with tumor burden, percentage of plasma cell infiltration in bone marrow and presence of osteolyses [16]. TNF-a can modulate NK cell activity by inducing disturbance in cell metabolic activity following induction of apoptosis and necrosis, depending on TNF receptor system expression [17][18][19][20]. We show here, like in other patients with solid tumors (breast cancer and malignant melanoma) as well as in hematological diseases (Hodgkin's and non-Hodgkin's lymphoma) that multiple myeloma patient's show impairment of NK cell activity [3,4].…”

Irreversible pan-ErbB tyrosine kinase inhibitor CI-1033 induces caspase-independent apoptosis in colorectal cancer DiFi cell line

“…45 In tumor cells the rate of apoptosis is accompanied by the increase in LDH-B and correlates with cisplatin 46 and TNF-alpha sensitivity. 47 Although the physiological role of annexins is still unclear, they have been shown to be involved in membrane trafficking, fusion and permeabilization. 48 CLIC1 expression in cultured CHO-K1 cells stimulates chloride channel activity in plasma and nuclear membranes.…”