Zhongying Dai

Impurity induced spin filtering in graphene nanoribbons

Zigzag-edged graphene nanoribbons (ZGNRs) are used to build devices in which transport with high spin polarization is realized by first-principles simulations. At first, we dope the semiconducting ZGNRs with B atoms on both sides to obtain a metallic ribbon. Then, in one segment of this ribbon which acts as the scattering region, the B atoms at one edge are substituted by C atoms or by N atoms. It is found that such devices show very good spin filtering effect which originates from the interaction between the impurity atoms and the edge states.

Spin-filtering transport and switching effect of MnCu single-molecule magnet

Electron transport of a single-molecule magnet (SMM) device has been investigated using the first-principles calculations. The SMM based device is constructed by a SMM MnCu [MnCuCl(5-Br-sap)2(MeOH)] bridged between semi-infinite Au(100) electrodes with thiol groups connecting the molecule and the gold electrodes. Our results exhibit crucial features of spin filtering and Kondo resonance. The spin filtering remains robust, whereas the Kondo resonance highly depends on the contact geometry. Specifically, this Kondo resonance can be switched on or off by changing the contact distance. The mechanisms of these features are formulated in details.

Carbon ions induce autophagy effectively through stimulating the unfolded protein response and subsequent inhibiting Akt phosphorylation in tumor cells

Heavy ion beams have advantages over conventional radiation in radiotherapy due to their superb biological effectiveness and dose conformity. However, little information is currently available concerning the cellular and molecular basis for heavy ion radiation-induced autophagy. In this study, human glioblastoma SHG44 and cervical cancer HeLa cells were irradiated with carbon ions of different linear energy transfers (LETs) and X-rays. Our results revealed increased LC3-II and decreased p62 levels in SHG44 and HeLa cells post-irradiation, indicating marked induction of autophagy. The autophagic level of tumor cells after irradiation increased in a LET-dependent manner and was inversely correlated with the sensitivity to radiations of various qualities. Furthermore, we demonstrated that high-LET carbon ions stimulated the unfolded protein response (UPR) and mediated autophagy via the UPR-eIF2α-CHOP-Akt signaling axis. High-LET carbon ions more severely inhibited Akt-mTOR through UPR to effectively induce autophagy. Thus, the present data could serve as an important radiobiological basis to further understand the molecular mechanisms by which high-LET radiation induces cell death.

Role of autophagy in high linear energy transfer radiation-induced cytotoxicity to tumor cells

Heavy‐ion radiotherapy has a potential advantage over conventional radiotherapy due to improved dose distribution and a higher biological effectiveness in cancer therapy. However, there is a little information currently available on the cellular and molecular basis for heavy‐ion irradiation‐induced cell death. Autophagy, as a novel important target to improve anticancer therapy, has recently attracted considerable attention. In this study, the effect of autophagy induced by high linear energy transfer (LET) carbon ions was examined in various tumor cell lines. To our knowledge, our study is the first to reveal that high‐LET carbon ions could induce autophagy in various tumor cells effectively, and the autophagic level in the irradiated cells increased in a dose‐ and LET‐dependent manner. The ability of carbon ions to inhibit the activation of the PI3K/Akt pathway rose with increasing their LET. Moreover, modulation of autophagy in tumor cells could modify their sensitivity to high‐LET radiation, and inhibiting autophagy accelerated apoptotic cell death, resulting in an increase in radiosensitivity. Our data imply that targeting autophagy might enhance the effectiveness of heavy‐ion radiotherapy.

Respiratory motion management using audio‐visual biofeedback for respiratory‐gated radiotherapy of synchrotron‐based pulsed heavy‐ion beam delivery

PURPOSE To efficiently deliver respiratory-gated radiation during synchrotron-based pulsed heavy-ion radiotherapy, a novel respiratory guidance method combining a personalized audio-visual biofeedback (BFB) system, breath hold (BH), and synchrotron-based gating was designed to help patients synchronize their respiratory patterns with synchrotron pulses and to overcome typical limitations such as low efficiency, residual motion, and discomfort. METHODS In-house software was developed to acquire body surface marker positions and display BFB, gating signals, and real-time beam profiles on a LED screen. Patients were prompted to perform short BHs or short deep breath holds (SDBH) with the aid of BFB following a personalized standard BH/SDBH (stBH/stSDBH) guiding curve or their own representative BH/SDBH (reBH/reSDBH) guiding curve. A practical simulation was performed for a group of 15 volunteers to evaluate the feasibility and effectiveness of this method. Effective dose rates (EDRs), mean absolute errors between the guiding curves and the measured curves, and mean absolute deviations of the measured curves were obtained within 10%-50% duty cycles (DCs) that were synchronized with the synchrotrons flat-top phase. RESULTS All maneuvers for an individual volunteer took approximately half an hour, and no one experienced discomfort during the maneuvers. Using the respiratory guidance methods, the magnitude of residual motion was almost ten times less than during nongated irradiation, and increases in the average effective dose rate by factors of 2.39-4.65, 2.39-4.59, 1.73-3.50, and 1.73-3.55 for the stBH, reBH, stSDBH, and reSDBH guiding maneuvers, respectively, were observed in contrast with conventional free breathing-based gated irradiation, depending on the respiratory-gated duty cycle settings. CONCLUSIONS The proposed respiratory guidance method with personalized BFB was confirmed to be feasible in a group of volunteers. Increased effective dose rate and improved overall treatment precision were observed compared to conventional free breathing-based, respiratory-gated irradiation. Because breathing guidance curves could be established based on the respective average respiratory period and amplitude for each patient, it may be easier for patients to cooperate using this technique.

High LET Radiation Enhances Nocodazole Induced Cell Death in HeLa Cells through Mitotic Catastrophe and Apoptosis

To understand how human tumor cells respond to the combined treatment with nocodazole and high LET radiation, alterations in cell cycle, mitotic disturbances and cell death were investigated in the present study. Human cervix carcinoma HeLa cells were exposed to nocodazole for 18 h immediately followed by high LET iron ion irradiation and displayed a sequence of events leading to DNA damages, mitotic aberrations, interphase restitution and endocycle as well as cell death. A prolonged mitotic arrest more than 10 h was observed following nocodazole exposure, no matter the irradiation was present or not. The occurrence of mitotic slippage following the mitotic arrest was only drug-dependent and the irradiation did not accelerate it. The amount of polyploidy cells was increased following mitotic slippage. No detectable G(2) or G(1) arrest was observed in cells upon the combined treatment and the cells reentered the cell cycle still harboring unrepaired cellular damages. This premature entry caused an increase of multipolar mitotic spindles and amplification of centrosomes, which gave rise to lagging chromosomal material, failure of cytokinesis and polyploidization. These mitotic disturbances and their outcomes confirmed the incidence of mitotic catastrophe and delayed apoptotic features displayed by TUNEL method after the combined treatment. These results suggest that the addition of high-LET iron ion irradiation to nocodazole enhanced mitotic catastrophe and delayed apoptosis in HeLa cells. These might be important cell death mechanisms involved in tumor cells in response to the treatment of antimitotic drug combined with high LET radiation.

Effectiveness of respiratory-gated radiotherapy with audio-visual biofeedback for synchrotron-based scanned heavy-ion beam delivery

A synchrotron-based heavy-ion accelerator operates in pulse mode at a low repetition rate that is comparable to a patients breathing rate. To overcome inefficiencies and interplay effects between the residual motion of the target and the scanned heavy-ion beam delivery process for conventional free breathing (FB)-based gating therapy, a novel respiratory guidance method was developed to help patients synchronize their breathing patterns with the synchrotron excitation patterns by performing short breath holds with the aid of personalized audio-visual biofeedback (BFB) system. The purpose of this study was to evaluate the treatment precision, efficiency and reproducibility of the respiratory guidance method in scanned heavy-ion beam delivery mode. Using 96 breathing traces from eight healthy volunteers who were asked to breathe freely and guided to perform short breath holds with the aid of BFB, a series of dedicated four-dimensional dose calculations (4DDC) were performed on a geometric model which was developed assuming a linear relationship between external surrogate and internal tumor motions. The outcome of the 4DDCs was quantified in terms of the treatment time, dose-volume histograms (DVH) and dose homogeneity index. Our results show that with the respiratory guidance method the treatment efficiency increased by a factor of 2.23-3.94 compared with FB gating, depending on the duty cycle settings. The magnitude of dose inhomogeneity for the respiratory guidance methods was 7.5 times less than that of the non-gated irradiation, and good reproducibility of breathing guidance among different fractions was achieved. Thus, our study indicates that the respiratory guidance method not only improved the overall treatment efficiency of respiratory-gated scanned heavy-ion beam delivery, but also had the advantages of lower dose uncertainty and better reproducibility among fractions.

Evaluation of mesh- and binary-based contour propagation methods in 4D thoracic radiotherapy treatments using patient 4D CT images

Based on four dimensional (4D) computed tomography (CT) images, mesh- and binary-based contour propagation algorithms for 4D thoracic radiotherapy treatments were evaluated. Gross tumor volumes (GTVs), lungs, hearts and spinal cords on the CT images at the end-exhale and end-inhale phases for six patients were delineated by the physician. All volumes of interest (VOIs) were automatically propagated from the end-exhale phase to the end-inhale phase using two propagation methods. The propagated VOIs were quantitatively compared with the VOIs contoured at the end-inhale phase by the physician using Dice Similarity Coefficient (DSC), Mean Slicewise Hausdorff Distance (MSHD), Center Of Mass (COM) displacement and volume difference. A two-sided Students t test was implemented to examine the significance of the differences between the results obtained from the two algorithms. For GTVs, statistically significant differences between the two algorithms were not observed. For all the other VOIs, the mesh-based method showed higher mean DSCs for the heart, left lung, right lung and spinal cord, lower mean MSHD for the spinal cord, lower mean COM displacement for the heart, and lower mean volume differences for the left lung, right lung and spinal cord with statistically significant differences than the binary-based method. The running time for propagation was approximately 3s and 3min for the mesh- and binary-based methods, respectively. Collectively, the mesh-based algorithm provides superiorities in running time and reliability for contour propagation in 4D radiotherapy.

Progress in heavy ion cancer therapy at IMP

After basic research of almost two decades on heavy ion therapy at the Institute of Modern Physics (IMP), Chinese Academy of Sciences, techniques of heavy ion beam delivery and treatment planning have been established. Clinical trial of heavy ion therapy has gotten started since 2006 at IMP. Due to the encouraging clinical results, two dedicated heavy-ion therapy facilities are now under construction in Lanzhou and Wuwei, China, through the efforts of the IMP researchers. The progress of the project of heavy ion cancer therapy at IMP is introduced concisely in this paper.

A novel pencil beam model for carbon-ion dose calculation derived from Monte Carlo simulations

An accurate kernel model is of vital importance for pencil-beam dose algorithm in charged particle therapy using precise spot-scanning beam delivery, in which an accurate depiction of the low dose envelope is especially crucial. Based on the Monte Carlo method, we investigated the dose contribution of secondary particles to the total dose and proposed a novel beam model to depict the lateral dose distribution of carbon-ion pencil beam in water. We demonstrated that the low dose envelope in single-spot profiles in water could be adequately modelled with the addition of a logistic distribution to a double Gaussian one, which was verified in both single carbon-ion pencil beam and superposed fields of different sizes with multiple pencil beams. Its superiority was mainly manifested at medium depths especially for high-energy beams with small fields compared with single, double and triple Gaussian models, where the secondary particles influenced the total dose considerably. The double Gaussian-logistic model could reduce the deviations from 4.1%, 1.7% to 0.3% in the plateau and peak regions, and from 19.2%, 4.9% to 1.2% in the tail region compared for the field size factor (FSF) calculations of 344 MeV/u carbon-ion pencil beam with the single and double Gaussian models. Compared with the triple Gaussian one, our newly-proposed model was on a par with it, even better than it in the plateau and peak regions. Thus our work will be helpful for improving the dose calculation accuracy for carbon-ion therapy.