Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

Humans ; HIV Infections ; HIV-1 ; Integrases ; China ; Drug Resistance, Viral ; Mutation

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Humans ; Radiotherapy, Intensity-Modulated ; Immune Tolerance ; Nasopharyngeal Carcinoma ; ROC Curve ; Nasopharyngeal Neoplasms/radiotherapy*

Objective: To report an implementation method and results of an independent brachytherapy dose verification software (DVS). Methods: The DVS was developed based on Visual C+ + and the modular structure design was adopted. The DICOM RT files exported from the treatment planning system (TPS) were automatically loaded into the DVS. The TG-43 formalism was employed for dose calculation. Six cervical cancer patients who underwent brachytherapy were retrospectively selected to test the DVS. Different applicators were utilized for each patient. Dosimetric parameters and γ analysis (0.1cm, 5%) were used to evaluate the dose difference between the DVS and the TPS. Results: Compared with the TPS dose, the γ pass rates of the doses calculated by the DVS were higher than 98%. For CTV, the dosimetric differences were less than 0.29% and 0.53% for D_100% and D_90%. For bladder, rectum and sigmoid, the agreement of D_0.1cm³, D_1cm³ and D_2cm³ within a 0.5% level. Conclusion With minimal human-computer interactions, the DVS can verify the accuracy of dose calculated by TPS for brachytherapy.

In the present work, Monte Carlo simulations were employed to study the characteristics of the dose distribution of high energy electron beam in the presence of uniform transverse magnetic field. The simulations carried out the transport processes of the 30 MeV electron beam in the homogeneous water phantom with different magnetic field. It was found that the dose distribution of the 30 MeV electron beam had changed significantly because of the magnetic field. The result showed that the range of the electron beam was decreased obviously and it formed a very high dose peak at the end of the range, and the ratio of maximum dose to the dose of the surface was greatly increased. The results of this study demonstrated that we could change the depth dose distribution of electron beam which is analogous to the heavy ion by modulating the energy of the electron and magnetic field. It means that using magnetic fields in conjunction with electron radiation therapy has great application prospect, but it also has brought new challenges for the research of dose algorithm.
Algorithms ; Electrons ; Humans ; Magnetic Fields ; Monte Carlo Method ; Phantoms, Imaging ; Radiation Dosage

The hybrid pencil beam model (HPBM) is an effective algorithm for calculating electron dose distribution in radiotherapy. The mean energy distribution of incident electron beam in phantom is one of the factors that affect the calculation accuracy of HPBM, especially in field edge areas near the end of the electron range. A new fitted formula based on Monte Carlo (MC) simulation data for electron beams with energy range of 6-20 MeV in the homogeneous water phantom is proposed in this paper. The precision of the fitted formula within the scope of the energy was evaluated by comparing the electron dose distribution of ECWG measured data with that obtained from HPBM which took the mean electron energy that calculated by the fitted formula and the existed empirical formula, respectively. The results showed that the accuracy of dose distribution that obtained by the mean electron energy calculated with the fitted formula increased about 1%.
Algorithms ; Electrons ; Humans ; Monte Carlo Method ; Phantoms, Imaging ; Radiotherapy Planning, Computer-Assisted ; Water

As a method of dosimetric verification in radiotherapy, gamma index has been widely used for evaluating dose distribution in research and clinical cases. However, for three-dimensional dose distributions, gamma index calculation is very time consuming for the computers. In this paper, based on a pre-sorting technique, we implement a parallel computing algorithm of gamma index on graphic processing unit (GPU). Dose comparisons are performed for seven cases to test our new implementation. It was shown that the GPU-based gamma index calculations achieved a speedup of ten-folds in comparison with corresponding CPU implementation without losing accuracy. The result showed that utilizing GPU parallel computing to speed up gamma index calculations could be reliable and efficient in the implementation.
Algorithms ; Computer Graphics ; Humans ; Radiometry ; methods ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; methods ; Software

Digitally reconstructed radiographs (DRR) which greatly contribute to the quality control of radiotherapy are critical element in the process of virtual simulation in radiotherapy. In this paper, an algorithm based on ray tracing has been used to generate the DRR. By applying an exponential transformation to the electronic density determined by CT value, the generated DRR can be enhanced by adjusting the attenuation and the transformation parameter.
Computer Simulation ; Phantoms, Imaging ; Radiographic Image Enhancement ; methods ; Radiographic Image Interpretation, Computer-Assisted ; Radiotherapy Planning, Computer-Assisted ; Tomography, X-Ray Computed

Aim To investigate the differential expression of apoptosis-associated genes in human gastric cancer MGC803 cells induced by diallyl trisulfide(DATS).Methods Growth inhibition against MGC803 cells was assayed by MTT assay;The apoptosis induced by DATS was assessed by Flow cytometry and fluorescent microscope.The apoptosis-associated gene expression of MGC803 cell treated with DATS was determided by Human Apoptosis Gene Array.Apaf-1 and SODD genes were confirmed by RT-PCR.Results DATS had significant growth inhibitory activity against MGC803 cells,inhibition ratio increased from 11% to 78% at 4,8,12,16 and 24 mg?L-1 for 72 h(P