Synonymous point mutation of gtfB gene caused by therapeutic X-rays exposure reduced the biofilm formation and cariogenic abilities of Streptococcus mutans.

BACKGROUND: The shift of oral microbiota is a critical factor of radiation caries in head and neck cancer patients after the radiotherapy. However, the direct effects of irradiation on the genome and virulence of cariogenic bacteria are poorly described. Here we investigated the genomic mutations and virulence change of Streptococcus mutans (S. mutans), the major cariogenic bacteria, exposed to the therapeutic doses of X-rays. RESULTS: X-ray reduced the survival fraction of S. mutans and impacted its biofilm formation. We isolated a biofilm formation-deficient mutant #858 whose genome only possessed three synonymous mutations (c.2043 T > C, c.2100C > T, c.2109A > G) in gtfB gene. The "silent mutation" of c.2043 T > C in gtfB gene can cause the down-regulation of all of the gtfs genes' expression and decrease the GtfB enzyme secretion without the effect on the growth due to the codon bias. #858 and synonymous point mutation strain gtfB 2043 T>C, similar to the gtfB gene null mutant Δ gtfB, can significantly decrease the extracellular polysaccharide production, biofilm formation and cariogenic capabilities both in vitro and in vivo compared with wild type. CONCLUSION: The direct exposure of X-ray radiation can affect the genome and virulence of oral bacteria even at therapeutic doses. The synonymous mutations of genome are negligent factors for gene expression and related protein translation due to the codon usage frequency.

Error analysis of applicator position for combined internal/external radiation therapy in cervical cancer.

The aim of this study was to analyze the error variation in the applicator placement during the first and second radiotherapy session for cervical cancer. We recruited 22 patients with cervical cancer treated with radiotherapy. According to the image output in the first and second CT-Sim inspection, we conducted comparative analysis of image fusion to accurately measure the errors in applicator position in the horizontal (X-), longitudinal (Y-) and vertical (Z)-axes. The calibration processing was implemented in accordance with the data error measured and the location parameters, such as the angle and depth of the applicator. Electronic portal imaging technology (EPID) was used to calibrate posture change amplitude for the extracorporeal irradiation of patients, and dynamic measurement with applicator position was used to describe the error of the parameters. Finally, the data from two measurements in CT-Sim, digital reconstruction radiography (DRR) and EPID were compared. After calibration, the mean value of error of the applicator were significantly smaller. Image registration planning for error parameter calibration of applicator position can effectively reduce the applied horizontal spatial position error in radiotherapy treatment, and improve the accuracy and effectiveness during treatment.

Preliminary clinical study on brass compensator-based intensity-modulated radiation therapy.

OBJECTIVE: The objective of this study is to preliminarily evaluate the feasibility of brass compensator-based intensity-modulated radiation therapy (CB-IMRT). MATERIALS AND METHODS: Ten patients (three cases of nasopharyngeal cancer, four of esophageal cancer, and three of rectal cancer) who underwent an IMRT treatment planning were selected for this study. The transmission coefficient of brass plates with different thicknesses was measured under a 6 MV photon beam used in the treatment planning system, and the equation for thickness computation was fitted out. The plan file RTPLAN file of each patient was exported from the planning system and transformed to a compensator thickness matrix; therefore, it was input into a numerical control machine for the manufacturing and cutting of the compensators. The CB-IMRT plans obtained were verified on a homogeneous phantom with commercial software. Planar doses were measured by films, and the computed ones were compared using gamma evaluation with 3-mm distance to agreement and 3% dose difference criteria adopting a pass rate of Pγ >90%. The monitor units (MUs) of the multileaf collimator IMRT plan (MLC-IMRT) and the CB-IMRT plans were compared. Depth of cut was computed through the equation fitted from real measurements. The planned RTPLAN files were used to transform the cutting files needed by the numerical control machine. RESULTS: Plan validations show that the minimum and maximum of gamma pass rate among the 10 patients are 90.2% and 98.2%, respectively, which both satisfy the requirements of clinical planning. The MUs of CB-IMRT are significantly smaller compared with MLC-IMRT. CONCLUSION: CB-IMRT satisfies the requirements of clinical therapy and can be used in a radiotherapy routine.

A clinical study of lung cancer dose calculation accuracy with Monte Carlo simulation.

BACKGROUND: The accuracy of dose calculation is crucial to the quality of treatment planning and, consequently, to the dose delivered to patients undergoing radiation therapy. Current general calculation algorithms such as Pencil Beam Convolution (PBC) and Collapsed Cone Convolution (CCC) have shortcomings in regard to severe inhomogeneities, particularly in those regions where charged particle equilibrium does not hold. The aim of this study was to evaluate the accuracy of the PBC and CCC algorithms in lung cancer radiotherapy using Monte Carlo (MC) technology. METHODS AND MATERIALS: Four treatment plans were designed using Oncentra Masterplan TPS for each patient. Two intensity-modulated radiation therapy (IMRT) plans were developed using the PBC and CCC algorithms, and two three-dimensional conformal therapy (3DCRT) plans were developed using the PBC and CCC algorithms. The DICOM-RT files of the treatment plans were exported to the Monte Carlo system to recalculate. The dose distributions of GTV, PTV and ipsilateral lung calculated by the TPS and MC were compared. RESULT: For 3DCRT and IMRT plans, the mean dose differences for GTV between the CCC and MC increased with decreasing of the GTV volume. For IMRT, the mean dose differences were found to be higher than that of 3DCRT. The CCC algorithm overestimated the GTV mean dose by approximately 3% for IMRT. For 3DCRT plans, when the volume of the GTV was greater than 100 cm(3), the mean doses calculated by CCC and MC almost have no difference. PBC shows large deviations from the MC algorithm. For the dose to the ipsilateral lung, the CCC algorithm overestimated the dose to the entire lung, and the PBC algorithm overestimated V20 but underestimated V5; the difference in V10 was not statistically significant. CONCLUSIONS: PBC substantially overestimates the dose to the tumour, but the CCC is similar to the MC simulation. It is recommended that the treatment plans for lung cancer be developed using an advanced dose calculation algorithm other than PBC. MC can accurately calculate the dose distribution in lung cancer and can provide a notably effective tool for benchmarking the performance of other dose calculation algorithms within patients.

Effects of lysophosphatidic acid and its receptors LPA⠓ on radiation pneumonitis.

Radiation pneumonitis (RP) is a serious complication of radiation therapy for thoracic tumors. Lysophosphatidic acid (LPA) and its receptors LPA⅓ were reported to participate in the processes of inflammation. We tested the hypothesis that LPA and its receptors LPA⅓, take part in the pathogenesis of RP. In our study, irradiation increased LPA levels in the lung and expression of LPA⅓. To further determine the role of LPA⅓, we performed pharmacological knockout of LPA⅓ by a specific antagonist, VPC-12249. On day 60 post-irradiation, RP was significantly alleviated in a dose-dependent manner in mice treated with VPC-12249, as shown by H&E staining, malondialdehyde (MDA, an indicator of oxidative damage) assay in lung, and concentrations of proinflammatory and profibrotic cytokines in plasma, including IL-1ß, TNF-α, and TGF-ß1. Additionally, VPC-12249 administration decreased the phosphorylation of IκB-α (the initial event that activates the NF-κB signal way), and expression of TGF-ß1, CTGF, and α-SMA mRNA. Our findings suggest that LPA and LPA⅓ may play a pivotal role in RP, and LPA-LPA⅓ may serve as novel therapeutic targets for the treatment of RP.