Mechanisms of Sensitivity of Soft Tissue Sarcoma Cells to Temozolomide.

We studied the mechanisms of sensitivity of soft tissue sarcoma cells to alkylating agent temozolomide. The mechanisms of tumor cell sensitivity to temozolomide are complex and are determined by not only the level of O6-methylguanine-DNA-methyltransferase (MGTM) expression, but also activity of oncosuppressor protein p53. A-673 Ewing's sarcoma cells were found to be the most sensitive to temozolomide, whereas temozolomide-treated SK-LMS-1 leiomyosarcoma cells exhibited signs of cell aging.

Comparative Assessment of Cytokine Pattern in Early and Late Onset of Neonatal Sepsis.

Neonatal sepsis is a significant health issue associated with high mortality. Immune responses associated with neonatal sepsis, such as proinflammatory cytokine production, are believed to play a central role in the pathogenesis of this disease. In the present study, serum levels of the proinflammatory cytokines TNF-α, IL1-ß, and IL-6 and the anti-inflammatory cytokines IL-4 and IL-10 were evaluated for 25 subjects with neonatal sepsis. We observed that subjects with late onset of sepsis (LOS), as well as those with early onset of sepsis (EOS), had a substantial increase in serum TNF-α. In contrast to EOS, subjects with LOS demonstrated a significant increase in serum levels IL-6 and IL-10. Additionally, we observed a significant difference in cytokine profiles between acute and postacute cases of neonatal sepsis. For instance, the level of proinflammatory cytokines, such as TNF-α and IL-6, was elevated in the acute phase, whereas the production of anti-inflammatory cytokines, such as IL-10, became substantially upregulated during the postacute phase. Additionally, no correlation was observed between cytokine levels and CRP levels or lymphocyte counts. Thus, in contrast to CRP levels and lymphocyte counts, examination of the cytokine profile can provide valuable information when determining the most effective therapy for treating neonatal sepsis. This information may be useful to physicians when determining if anti-inflammatory or immune stimulatory therapy is warranted.

[3-Hydroxy-1,5-diaryl-4-pivaloyl-2,5-dihydro-2-pyrrolones induce the mitotic exit failure and cell death in tumor cells in vitro].

Some compound refering to the 3-hydroxy-1,5-diaryl-4-pivaloyl-2,5-dihydro-2-pyrrolones have been found to cause an increase in the number of mitotic cells and their subsequent death in vitro. This increased in the number of mitotic cells was not associated with increased cellular proliferative activity and was likely due to mitotic exit failure. Of note, the effect was more pronounced in the tumor cells when compared to human fibroblasts. Further studies are needed to investigate the molecular mechanisms of action of the compounds belonging to the class of 3-hydroxy-1,5-diaryl-4-pivaloyl-2,5-dihydro-2-pyrrolones.

[A comparative study of lymphocytic apoptosis and ventilation disorders in patients with pulmonary tuberculosis]. / Sravnitel'noe issledovanie apoptoza limfotsitov i ventiliatsionnykh narushenii u bol'nykh tuberkulezom legkikh.

Due to the increasing interest in studies of apoptosis (programmed cell death) in the pathogenesis of many diseases and to the emergence of data on the direct impact of apoptotic disorders on the course of bronchial asthma and the magnitude of the obstructive syndrome, this study was undertaken to investigate apoptosis in patients with new-onset pulmonary tuberculosis who had varying bronchial obstructive syndrome. Twenty-eight patients with new-onset tuberculosis, including 25 (89.3%), 2(7.1%), 1(3.6%) patients with infiltrative, disseminated, and fibrocavernous pulmonary tuberculosis, respectively, were examined. The study of external respiratory function included spirometry, determination of the flow-volume of forced expiration, body plethysmography, examination of lung elasticity by esophageal probing. The mechanisms of spontaneous apoptosis of peripheral lymphocytes from donors and patients with pulmonary tuberculosis were studied. The apoptosis was evaluated in dynamics by some parameters: the change of the mitochondrial potential (MP), the level of phosphatidyl serine, as well as DNA fragmentation by flow cytofluorometry. The results have indicated that there are significant signs of impaired peripheral lymphocytic apoptosis. Examining external respiratory function indicated that the bronchial obstruction syndrome was mild in 7 (25%) patients, moderate in 11 (39.3%), and severe in 5 (17.9%), absent in 5 (17.9%). Mild restrictive disorders were detected in 11 (39.3%) patients. The factor associating the degree of obstruction, with the count of MC540(+)- and MC540-DiOC6(+)-lymphocytes, i.e., with the count of lymphocytes with cellular membranous changes and with the decreased MP, which are one of the most significant signs of apoptosis. Thus, there is a negative correlation of the parameters of apoptosis of peripheral lymphocytes from patients with tuberculosis with those of ventilation obstruction disorders, which suggests that impaired apoptosis might be involved in the development of bronchial obstruction.

Key role of mitochondria in apoptosis of lymphocytes.

Changes in the mitochondrial potential, expression of phosphatidylserine, parameters of direct and lateral light scattering, and DNA fragmentation during spontaneous and induced apoptosis in peripheral blood lymphocytes were studied by flow cytofluorometry. Dexamethasone and Ca2+ ionophore A23187 served as inductors of apoptosis. A decrease in the mitochondrial potential is an early sign of spontaneous and induced apoptosis. Phosphatidylserine expression on the outer plasma membrane occurred later and inversely depended on the mitochondrial potential. Our results indicate that the involvement of mitochondria in spontaneous and induced apoptosis accompanied by a decrease in the mitochondrial potential is an early and key event of programmed lymphocyte death. The decrease in the mitochondrial potential of lymphocytes induced degradation of their nuclei (DNA fragmentation) and promoted elimination of apoptotic cells (phosphatidylserine expression).