Radiosensitivity Of Malignant Cells Research Articles

Combined effect of heterogeneous target dose and heterogeneous radiosensitivity on tumor control probability for different fractionation regimens

PurposeTo evaluate the combined effect of heterogeneous target dose and heterogeneous radiosensitivity on tumor control probability (TCP) for different number of fractions (Nf). MethodsThe linear-quadratic (LQ) model is employed to study dependence of TCP on Nf under the condition of fixed nominal biologically effective dose (BEDnom). ResultsFormula for the optimum target dose which maximizes TCP under the condition BEDnom=const is analytically derived. It is shown that the dependence of TCP on Nfis non-monotonic. In addition, the dependence of TCP on Nf for different variances of the target dose and radiosensitivity of malignant cells is demonstrated by using numerical computations. ConclusionsIt is shown that the optimum mean dose in the target is defined by the standard deviations of the target dose (σD) and standard deviations of parameters alpha (σα) and beta (σβ). The findings of this study indicate that hypofractionated regimens for stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) with Nf⩽3 can be radiobiologically inferior to the regimens with five or more fractions.

A New Approach to the Stimulation of the Body’s Defense Systems with Low Radiation Doses

The article considers the effects arising after exposure to low doses of radiation in vitro and in vivo, as well as the mechanisms of their formation. Analysis of the literature shows that the result of the action of low-dose radiation depends on the cell type, radiation sources, assessment methods, etc. This action differs from the effects of high doses and is associated with the activation of defense systems. Stimulation of the endogenous antioxidant system and repair was detected in normal cells after exposure to low doses. At the level of the organism, the response to the effect of low radiation doses is also accompanied by activation of the immune system. This leads to an increase in the resistance of normal cells to the action of genotoxic factors (the radio-adaptive response), which can be used to protect the normal tissues surrounding the tumor from the effects of high radiation doses during radiation therapy. The resistance of most malignant cells after irradiation with low doses did not change. However, the fractionated effect of low-dose radiation on the tumor could induce an increase in radio-sensitivity in malignant cells. The review presents data that show the change in the expression of a number of genes and regulatory RNA after exposure to low-dose radiation. These epigenetic parameters make it possible to explain individual differences in the magnitude of the radio-adaptive response. The paper discusses the prospects of the use of low-dose radiation for the treatment of certain human pathological conditions.

Radiosensitization induced by the anti-epidermal growth factor receptor monoclonal antibodies cetuximab and nimotuzumab in A431 cells

Epidermal growth factor receptors (EGFR) are overexpressed in a wide range of malignancies including head and neck, colon, and breast cancers. It has been identified that carcinomas with high expression levels of EGFR are more resistant to radiotherapy. Therefore, inhibiting nuclear translocation of EGFR to increase the radiosensitivity of malignant cells expressing EGFR offers the potential for increasing the therapeutic index of radiotherapy. The purpose of the present study was to quantify and to compare the radiosensitizing properties of the well-known anti-EGFR antibodies, cetuximab and nimotuzumab in human epidermoid A431 overexpressing EGFR cells. Cells were treated with two concentrations of the antibodies and then irradiated with a single dose of 4 Gy. The results indicated that the two antibodies induced radiosensitization increasing the percentage of dead/dying cells and the yield of γ-H2AX foci 24 h after irradiation. Whereas cetuximab exhibited a significant increase in radiosensitization at the highest concentration, the effects of nimotuzumab were more modest. A correlation between γ-H2AX foci signals and dead/dying cells was observed. The disparity in modulation of radiation-induced DNA damage by the two antibodies could be associated with the level of their respective intrinsic cytotoxic properties. Overall, the findings highlight the potential therapeutic benefit of combination therapy with anti-EGFR antibodies and radiotherapy for relevant carcinomas.

The ubiquitin-proteasome system as a molecular target in solid tumors: an update on bortezomib.

The ubiquitin-proteasome system has become a promising molecular target in cancer therapy due to its critical role in cellular protein degradation, interaction with cell cycle and apoptosis regulation, and unique mechanism of action. Bortezomib (PS-341) is a potent and specific reversible proteasome inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies. In preclinical studies, bortezomib induced apoptosis of malignant cells through the inhibition of NF-|B and stabilization of pro-apoptotic proteins. Bortezomib also promotes chemo- and radiosensitization of malignant cells in vitro and inhibits tumor growth in murine xenograft models. The proteasome has been established as a relevant target in hematologic malignancies and bortezomib has been approved for the treatment of multiple myeloma. This review summarizes recent data from clinical trials in solid tumors.