The effective static dielectric constant of an electron plasma system in the simultaneous presence of two electromagnetic waves and a strong DC magnetic field is calculated. It is found that as the difference ∆ω of the two electromagnetic wave frequencies matches the plasma frequency ωρ a breakdown in screening occurs thereby increasing the plasma heating rate via the external fields due to inverse Bremmstrahlung. An application is made by considering the typical parameters of a hot plasma.

Telomeres and telomerase are closely linked to uncontrolled cellular proliferation, immortalization and carcinogenesis. Telomerase has been largely studied in the context of cancer, including leukemias. Deregulation of human telomerase gene hTERT is a well-established step in leukemia development. B-acute lymphoblastic leukemia (B-ALL) recovery rates exceed 90% in children; however, the relapse rate is around 20% among treated patients, and 10% of these are still incurable. This review highlights the biological and clinical relevance of telomerase for B-ALL and the implications of its canonical and non-canonical action on signaling pathways in the context of disease and treatment. The physiological role of telomerase in lymphocytes makes the study of its biomarker potential a great challenge. Nevertheless, many works have demonstrated that high telomerase activity or hTERT expression, as well as short telomeres, correlate with poor prognosis in B-ALL. Telomerase and related proteins have been proven to be promising pharmacological targets. Likewise, combined therapy with telomerase inhibitors may turn out to be an alternative strategy for B-ALL.

From the quantum mechanical viewpoint we derive the dielectric function of an electron plasma system in the presence of a radiation field. By using timedependent wavefunctions for plasma electrons under the external ac field, we calculate the charge density fluctuation of the electronic system under a weak probing potential and the spectrum of the collective excitation is calculated and found to be strongly dependent upon the amplitude and frequency of the radiation field. We show, in the classical limit, that the reduction of the collective excitation frequency under the radiation field can be associated with the suppression of the plasma high-frequency reactive electrical conductivity. The result is consistent with the recent experimental observation of increased high-frequency mobility in two-dimensional electron gases under a radiation field.

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BACKGROUND: The inhibition of the enzyme telomerase (TERT) has been widely investigated as a new pharmacological approach for cancer treatment, but its real potential and the biochemical consequences are not totally understood. OBJECTIVE: Here, we investigated the effects of the telomerase inhibitor MST-312 on a human glioma cell line after both short- and long-term (290 days) treatments. METHODS: Effects on cell growth, viability, cell cycle, morphology, cell death and genes expression were assessed. RESULTS: We found that short-term treatment promoted cell cycle arrest followed by apoptosis. Importantly, cells with telomerase knock-down revealed that the toxic effects of MST-312 are partially TERT dependent. In contrast, although the long-term treatment decreased cell proliferation at first, it also caused adaptations potentially related to treatment resistance and tumor aggressiveness after long time of exposition. CONCLUSIONS: Despite the short-term effects of telomerase inhibition not being due to telomere erosion, they are at least partially related to the enzyme inhibition, which may represent an important strategy to pave the way for tumor growth control, especially through modulation of the non-canonical functions of telomerase. On the other hand, long-term exposure to the inhibitor had the potential to induce cell adaptations with possible negative clinical implications.

Telomerase, the enzyme responsible for the length maintenance of telomeres is expressed in about 85% of cancer cells, being a key to tumorigenesis. Telomerase inhibitor drugs have been studied as a promising cancer therapy due to its specificity, with less side effects than conventional approach. However, the effects expected from these therapy require many cell divisions, and the consequences of these long-term therapies are poorly understood. This work evaluated the effects of a long term treatment in cancer cells (HeLa) using BRACO-19, a G-quadruplex-interactive molecule, evaluating the consequences of its use in cell viability and its potential to induce senescence. Telomerase positive HeLa cells were grown in DMEM medium supplemented with 10% fetal bovine serum at pattern conditions. Culture medium was changed every 2 days. For preliminary citotoxicity assay, cells were seeded in 96 wells plate at 3.2x104 cells/cm2, incubated for 24 hours and treated for 24 hours with increasing concentrarions of BRACO-19 and vehicle (0.1% H2O). Cell viability was measured by MTT assay. For the long-term treatment, a subtoxic concentration was chosen. The cells (5.5x102 cells/cm2) were grown under continuous presence of the drug or 0.02% H2O for 11 weeks. During the long-term exposure to BRACO-19, the cells were splitted every 7 - 20 days, depending on its proliferation rate, viable and unviable cells were counted at these points through trypan blue dye exclusion assay. β-Galactosidase (β-gal) activity was used as cell senescence marker to evaluate the senescence after 24 hours treatment and after a long exposure to the telomerase inhibitor. Changes in cell morphology were accessed by phase contrast microscopy. The short-term (24h) treatment with BRACO-19 showed a dose-dependent effect on cell viability. The IC50% for HeLa was 5.25 µM. The subtoxic concentration of 1µM was used for long-term treatment, showing effect on cell proliferation in a way that HeLa cells exposed to the drug showed their proliferative profile decreased when compared to control. Furthemore, no senescent cells were found in control group, even after many passages; on the other hand, 24 hours and long-term exposure to BRACO-19 led to senescence. Long-term treatment was also associated with visual changes on cell morphology. The telomerase inhibitor BRACO-19 showed an expected dose-dependent effect on HeLa cells at short-term exposition, since cytotoxic effect of this compound has been demonstrated in several cell lines, but the impact of the long-term treatment on cell proliferation pattern points BRACO-19 as a potential prototype of a new telomere related drug for cancer therapy. Also, it was demonstrated the senescence inducing action of this drug, perhaps due to erosion of HeLa telomeres. These results show that HeLa is sensitive do BRACO-19 even under subtoxic concentrations. Its effectiveness against other cell lines and tumors is under investigation. Citation Format: Ana Flavia Reis Guimaraes, Diêgo M. de Oliveira. Effect of long term treatment with BRACO 19 on HeLa proliferation and senescence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3476. doi:10.1158/1538-7445.AM2017-3476