52 research outputs found
Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha-ras oncogenes and is associated with endonuclease availability.
Oncogenes and oncosuppressors can deregulate cell replication in tumours, and recently have been shown to influence the probability of apoptosis. The effects of human c-myc and mutated (T24) Ha-ras oncogenes on susceptibility to apoptosis were investigated by introducing them into immortalised rat fibroblasts. The resulting family of transfectants showed closely similar measures of proliferation, but widely divergent rates of apoptosis, differing by up to fifteen-fold, that correlated inversely with population expansion rates in vitro. T24-ras transfectants with moderate or high p21ras expression showed reduced apoptosis, and this was reversed by pharmacological inhibition of membrane localisation of p21ras by mevinolin. In contrast, c-myc stimulated apoptosis, and this was further enhanced by serum deprivation. Inducibility of effector proteins represents one possible mechanism of genetic control of the susceptibility to apoptosis, and its investigation showed that c-myc was associated with expression by viable cells of latent calcium/magnesium sensitive endonuclease activity characteristic of apoptosis. In contrast, endonuclease activity was not detected in viable cells of a T24-ras transfectant expressing high levels of p21ras. Thus, there appeared to be differential regulation of susceptibility to apoptosis, positively by c-myc and negatively by activated ras, and this was associated with availability of endonuclease activity. Genetic modulation of apoptosis in human neoplasms is likely to influence net growth rate, retention of cells acquiring new mutations and response to certain chemotherapeutic agents
Drug-target interactions: only the first step in the commitment to a programmed cell death?
The search for novel antitumour drugs has reached a plateau phase. The carcinomas remain almost as intractable as they did 40 years ago and the need for effective therapy is pressing. There is an argument that the current pharmacopoeia is sufficient but, to be effective, the biochemical mechanisms of drug resistance must be circumvented. In tackling the question of why certain cancer cells are resistant, the converse question of why others are sensitive still remains to be answered fully. Asking the fundamental question of why and how a cell dies may provide clues as to what avenues lie open for improved chemotherapy. In this review we survey the recent literature on cell death and we argue that it is possible that the outcome of chemotherapy may be determined by the response of the cell to the formation of the drug-target complex, and/or its sequellae, rather than to the biochemical changes brought about by the drug alone. One of these responses, determined by the phenotype of the cell, may be activation of a genetic programme for cell death
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Long-term Risk Assessment for Medical Application of Cold Atmospheric Pressure Plasma
Despite increasing knowledge gained based on multidisciplinary research, plasma medicine still raises various questions regarding specific effects as well as potential risks. With regard to significant statements about in vivo applicability that cannot be prognosticated exclusively based on in vitro data, there is still a deficit of clinical data. This study included a clinical follow-up of five probands who had participated five years previously in a study on the influence of cold atmospheric pressure plasma (CAP) on the wound healing of CO2 laser-induced skin lesions. The follow-up included a complex imaging diagnostic involving dermatoscopy, confocal laser scanning microscopy (CLSM) and hyperspectral imaging (HSI). Hyperspectral analysis showed no relevant microcirculatory differences between plasma-treated and non-plasma-treated areas. In summary of all the findings, no malignant changes, inflammatory reactions or pathological changes in cell architecture could be detected in the plasma-treated areas. These unique in vivo long-term data contribute to a further increase in knowledge about important safety aspects in regenerative plasma medicine. However, to confirm these findings and secure indication-specific dose recommendations, further clinical studies are required. Β© 2020 by the authors
Long-Term Risk Assessment for Medical Application of Cold Atmospheric Pressure Plasma
Despite increasing knowledge gained based on multidisciplinary research, plasma medicine still raises various questions regarding specific effects as well as potential risks. With regard to significant statements about in vivo applicability that cannot be prognosticated exclusively based on in vitro data, there is still a deficit of clinical data. This study included a clinical follow-up of five probands who had participated five years previously in a study on the influence of cold atmospheric pressure plasma (CAP) on the wound healing of CO2 laser-induced skin lesions. The follow-up included a complex imaging diagnostic involving dermatoscopy, confocal laser scanning microscopy (CLSM) and hyperspectral imaging (HSI). Hyperspectral analysis showed no relevant microcirculatory differences between plasma-treated and non-plasma-treated areas. In summary of all the findings, no malignant changes, inflammatory reactions or pathological changes in cell architecture could be detected in the plasma-treated areas. These unique in vivo long-term data contribute to a further increase in knowledge about important safety aspects in regenerative plasma medicine. However, to confirm these findings and secure indication-specific dose recommendations, further clinical studies are required. Β© 2020 by the authors
In vitro effect of cadmium and copper on separated blood leukocytes of Dicentrarchus labrax.
The immunotoxic effects of heavy metals on blood leukocytes of sea bass (Dicentrarchus labrax) were examined. The cells, separated by a discontinuous Percoll-gradients, were exposed in vitro to various sublethal concentrations of cadmium and copper (10(-7) M, 10(-5) M, and 10(-3) M) and their immunotoxic effect was then evaluated by measuring neutral red uptake, MU assay, DNA fragmentation and Hsp70 gene expression. First of all, we demonstrated that the cells treated in vitro could incorporate Cd and Cu. A relationship between heavy metal exposure and dose-time-dependent alterations in responses of leukocytes from blood was found for both metals, but copper was more immunotoxic than cadmium in all assays performed. A significant reduction in the cells' ability to uptake neutral red and viability by MU assay was recorded, indicating that both cadmium and copper could change the membrane permeability, inducing cellular apoptosis when the concentration of metals reached 10(-3) M. The apoptotic effect may also explain the high level of cytotoxicity found when the leukocytes were exposed to higher concentration of metals. These results demonstrated that toxic effect of copper and cadmium affect on the mechanisms of cell-mediated immunity reducing the immune defences of the organism. (C) 2014 Elsevier Inc. All rights reserved
ΠΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ Π²Π΅ΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΈ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠΈ Π°ΠΏΠΎΠΏΡΠΎΠ·Π°
In the review the existent methodic approaches to the verification of ACD (apoptotic cell death) based on the dying cell morphology study (routine light and electron microscopy, luminescent microscopic examination, DNA fragmentation reveal in situ and so on) have been observed, the main structural differences between necrosis and apoptosis in connection with the pathophysiology of these processes and the significance of specific morphological changes in differential diagnostics of cell death type have been discussed. It has been demonstrated the relativity of the existing ACD criterions, many of them were classic characteristics of the cell states, the former necrobiosis and coagulation necrosis. The causes of some misunderstandings, connected with this circumstance, in literature devoted to the ACD morphology, have been analyzed.Π ΠΎΠ±Π·ΠΎΡΠ΅ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Ρ ΠΊ Π²Π΅ΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΠ‘Π (Π°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ), ΠΎΡΠ½ΠΎΠ²Π°Π½Π½ΡΠ΅ Π½Π° ΠΈΠ·ΡΡΠ΅Π½ΠΈΠΈ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΠΈ Π³ΠΈΠ±Π½ΡΡΠΈΡ
ΠΊΠ»Π΅ΡΠΎΠΊ: ΡΡΡΠΈΠ½Π½Π°Ρ ΡΠ²Π΅ΡΠΎΠ²Π°Ρ ΠΈ ΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½Π°Ρ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΡ, ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΠΎ-ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅, Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ°ΡΠΈΠΈ ΠΠΠ in situ ΠΈ Ρ.Π΄., ΠΎΠ±ΡΡΠΆΠ΄Π°ΡΡΡΡ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΡΡΡΡΠΊΡΡΡΠ½ΡΠ΅ ΠΎΡΠ»ΠΈΡΠΈΡ Π½Π΅ΠΊΡΠΎΠ·Π° ΠΎΡ Π°ΠΏΠΎΠΏΡΠΎΠ·Π° Π² ΡΠ²ΡΠ·ΠΈ Ρ ΠΏΠ°ΡΠΎΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΠ΅ΠΉ ΡΡΠΈΡ
ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² ΠΈ Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ ΠΊΠΎΠ½ΠΊΡΠ΅ΡΠ½ΡΡ
ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Π² Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΡΠΈΠΏΠ° ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΌΠ΅ΡΡΠΈ. ΠΠΎΠΊΠ°Π·Π°Π½Π° ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΡ
ΠΊΡΠΈΡΠ΅ΡΠΈΠ΅Π² ΠΠ‘Π, ΠΌΠ½ΠΎΠ³ΠΈΠ΅ ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
ΡΠ²Π»ΡΡΡΡΡ ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠΈΠ·Π½Π°ΠΊΠ°ΠΌΠΈ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΉ ΠΊΠ»Π΅ΡΠΎΠΊ, ΡΠ°Π½Π΅Π΅ ΠΎΠ±ΠΎΠ·Π½Π°ΡΠ°Π΅ΠΌΡΡ
ΠΊΠ°ΠΊ Π½Π΅ΠΊΡΠΎΠ±ΠΈΠΎΠ· ΠΈ ΠΊΠΎΠ°Π³ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΠΉ Π½Π΅ΠΊΡΠΎΠ·, ΠΈ ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ ΠΏΡΠΈΡΠΈΠ½Ρ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΡΠ²ΡΠ·Π°Π½Π½ΡΡ
Ρ ΡΡΠΈΠΌ ΠΎΠ±ΡΡΠΎΡΡΠ΅Π»ΡΡΡΠ²ΠΎΠΌ ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠ΅ΡΠΈΠΉ, ΠΈΠΌΠ΅ΡΡΠΈΡ
ΡΡ Π² Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ΅, ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π½ΠΎΠΉ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΠ‘Π
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