• Progress in Medical Physics
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• v.30 no.1
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• pp.7-13
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• 2019

Purpose: To compare the dosimetrical and radiobiological parameters among various volumetric modulated arc therapy (VMAT) techniques using restricted and continuous arc beams for left-sided breast cancer. Materials and Methods: Ten patients with left-sided breast cancer without regional nodes were retrospectively selected and prescribed the dose of 42.6 Gy in 16 fractions on the planning target volume (PTV). For each patient, three plans were generated using the $Eclipse^{TM}$ system (Varian Medical System, Palo Alto, CA) with one partial arc 1pVMAT, two partial arcs 2pVMAT, and two tangential arcs 2tVMAT. All plans were calculated through anisotropic analytic algorithm and photon optimizer with 6 MV photon beam of $VitalBEAM^{TM}$. The same dose objectives for each plan were used to achieve a fair comparison during optimization. Results: For PTV, dosimetrical parameters such as Homogeneity index, conformity index, and conformal number were superior in 2pVMAT than those in both techniques. $V_{95%}$, which indicates PTV coverage, was 91.86%, 96.60%, and 96.65% for 1pVMAT, 2pVMAT, and 2tVMAT, respectively. In most organs at risk (OARs), 2pVMAT significantly reduced the delivered doses compared with the other techniques, excluding the doses to contralateral lung. For the analysis of radiobiological parameters, a significant difference in normal tissue complication probability was observed in ipsilateral lung while no difference was observed in the other OARs. Conclusions: Our study showed that 2pVMAT had better plan quality and normal tissue sparing than 1pVMAT and 2tVMAT but not for all parameters. Therefore, 2pVMAT could be considered the priority choice for the treatment planning for left breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8431-8438
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• 2016

Doxorubicin (DOX) was introduced as an effective chemotherapeutic for a wide range of cancers but with some severe side effects especially on myocardia. 2-Deoxy-D-glucose (2DG) enhances the damage caused by chemotherapeutics and ionizing radiation (IR) selectively in cancer cells. We have studied the effects of $1{\mu}M$ DOX and $500{\mu}M$ 2DG on radiation induced cell death, apoptosis and also on the expression levels of p53 and PTEN genes in T47D and SKBR3 breast cancer cells irradiated with 100, 150 and 200 cGy x-rays. DOX and 2DG treatments resulted in altered radiation-induced expression levels of p53 and PTEN genes in T47D as well as SKBR3 cells. In addition, the combination along with IR decreased the viability of both cell lines. The radiobiological parameter (D0) of T47D cells treated with 2DG/DOX and IR was 140 cGy compared to 160 cGy obtained with IR alone. The same parameters for SKBR3 cell lines were calculated as 120 and 140 cGy, respectively. The sensitivity enhancement ratios (SERs) for the combined chemo-radiotherapy on T47D and SKBR3 cell lines were 1.14 and 1.16, respectively. According to the obtained results, the combination treatment may use as an effective targeted treatment of breast cancer either by reducing the single modality treatment side effects.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.795-799
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• 2013

Ku70/80 heterodimer is a central element in the nonhomologous end joining (NHEJ) DNA repair pathway, Ku80 playing a key role in regulating the multiple functions of Ku proteins. It has been found that the Ku80 protein located at telomeres is a major contributor to radiosensitivity in some telomerase positive human cancer cells. However, in ALT human osteosarcoma cells, the precise function in radiosensitivity and telomere maintenance is still unknown. The aim of this study was to investigate the effects of Ku80 depletion in the U2OS ALT cell line cell line. Suppression of Ku80 expression was performed using a vector-based shRNA and stable Ku80 knockdown in cells was verified by Western blotting. U2OS cells treated with shRNA-Ku80 showed lower radiobiological parameters (D0, Dq and SF2) in clonogenic assays. Furthermore, shRNA-Ku80 vector transfected cells displayed shortening of the telomere length and showed less expression of TRF2 protein. These results demonstrated that down-regulation of Ku80 can sensitize ALT cells U2OS to radiation, and this radiosensitization is related to telomere length shortening.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.219-225
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• 1993

The evaluation of radiation-induced DNA double strand breaks (DSB) was made following irradiation of human lymphocytes, murine lymphocytes and EL-4 leukemia cells over a wide dose range of $^{60}Co\;{gamma}-rays.$ In lipopolysaccharide (LPS) or phytohemagglutinin (PHA)-stimulated murine lymphocytes, the slopes of the stand scission factor (SSF) revealed that lymphocytes with LPS increased DNA DSB formation by a factor of 1.432 (p<0.005). Furthermore, strand break production was relatively inefficient in the T lymphocytes compared to the B lymuhocytes. And EL-4 leukemia cells were found to form significantly more DNA DSB to a greater extent than normal lymphocytes (p<0.005). The in vitro studies of the intrinsic radiosensitivity between human lymphocytes and murine lymphocytes showed similar phasic kinetics. However, murine lymphocytes were lower in DNA DSB formation and higher in the relative radiation dose of 10 percent DNA strand breaks at 3.5 hours following ${gamma}-irradiation$ than human lymphocytes. Though it is difficult to interpret these results, these differences may be result from environmental and genetic factors. From our data, if complementary explanations for this difference will be proposed, the differences in the dose-effect relationship for the induction of DSB between humans and mice must be related to interspecies variations in the physiological condition of the peripheral blood in vitro and not to differences in the intrinsic radiation sensitivity of the lymphocytes. These results can be estimated on the basis of dose-effect correlation enabling the interpretation of clinical response and the radiobiological parameters of cytometrical assessment.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.99-106
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• 1998

Purpose : We conducted clonogenic assay using human cancer cell lines (MKN-45, PC-14, Y-79, HeLa) to investigate a correlation between the parameters of radiosensitivity. Materials and Methods : Human cancer cell lines were irradiated with single doses of 1, 2, 3, 5, 7 and 10Gy for the study of radiosensitivity and subrethal damage repair capacity was assessed with two fractions of 5Gy separated with a time interval of 0, 1, 2, 3, 4, 6 and 24 hours. Surviving fraction was assessed with clonogenic assay using $Sperman-H\"{a}rbor$ method and mathematical analysis of survival curves was done with linear-quadratic (LQ) , multitarget-single hit(MS) model and mean inactivation dose$(\v{D})$. Results : Surviving fractions at 2Gy(SF2) were variable among the cell lines, ranged from 0.174 to 0.85 The SF2 of Y-79 was lowest and that of PC-14 was highest(p<0.05, t-test). LQ model analysis showed that the values of $\alpha$ for Y-79, MKN-45, HeLa and PC-14 were 0.603, 0.356, 0.275 and 0.102 respectively, and those of $\beta$ were 0.005, 0.016, 0.025 and 0.027 respectively. Fitting to MS model showed that the values of Do for Y-79. MKN-45, HeLa and PC-14 were 1.59. 1.84. 1.88 and 2.52 respectively, and those of n were 0.97, 1.46, 1.52 and 1 69 respectively. The $\v{D}s$ calculated by Gauss-Laguerre method were 1.62, 2.37, 2,01 and 3.95 respectively So the SF2 was significantly correlated with $\alpha$, Do and $\v{D}$. Their Pearson correlation coefficiencics were -0.953 and 0,993. 0.999 respectively(p<0.05). Sublethal damage repair was saturated around 4 hours and recovery ratios (RR) at plateau phase ranged from 2 to 3.79. But RR was not correlated with SF2, ${\alpha}$, ${\beta}$, Do, $\v{D}$. Conclusion : The intrinsic radiosensitivity was very different among the tested human cell lines. Y-79 was the most sensitive and PC-l4 was the least sensitive. SF2 was well correlated with ${\alpha}$, Do, and $\v{D}$. RR was high for MKN-45 and HeLa but had nothing to do with radiosensitivity parameters. These basic parameters can be used as baseline data for various in vitro radiobiological experiments.