Targeting TRIM40 signaling reduces esophagus cancer development: A mechanism involving in protection of oroxylin A.

Oroxylin A (OA), a naturally active O-methylated flavone derived from Scutellaria baicalensis, is regarded as a potential drug with strong anticancer effects. Unfortunately, our understanding of the antineoplastic mechanism of oral exposure to such flavonoids is inadequate. Growing evidence has confirmed the important role of OA in the regulation of oxidative stress- and inflammatory-response-induced tissue injury. However, it remains unknown whether OA is capable of mitigating esophagus cancer (EC) progression and its potential molecular mechanism. Furthermore, the tripartite motif containing 40 (TRIM40) is a ubiquitin ligase that mediates the immune response. The potential molecular function of TRIM40 in regulating EC is largely unknown. We confirmed that OA-triggered oxidative stress markedly upregulates TRIM40. During the OA challenge, increased TRIM40 reduced oxidative stress and promoted the ER stress response. Inversely, deletion of TRIM40 facilitated oxidative stress and blocked cancer cell growth in vivo and in vitro. Mechanistically, in response to OA treatment, TRIM40 directly interacts with Keap1 and promotes ubiquitin-proteasome degradation, thus leading to the promotion of Nrf2 nuclear translocation and its downstream cascade activation, which increases antioxidant defense and cell survival. TRIM40 expression was positively correlated with Nrf2 expression and negatively associated with Keap1 expression in EC xenografts and human specimens. In addition, high TRIM40 expression correlates with poor patient survival in EC. The findings suggested that oral exposure to OA significantly mitigates EC development by targeting TRIM40 activity. These findings further elucidated the potential role of TRIM40 in EC progression by mediating Keap1 degradation, which could be considered a therapeutic target for the treatment of such a disease.

Target volumes comparison between postoperative simulation magnetic resonance imaging and preoperative diagnostic magnetic resonance imaging for prone breast radiotherapy after breast-conserving surgery.

BACKGROUND: This study investigated the differences in target volumes between preoperative magnetic resonance imaging (MRIpre) and postoperative MRI (MRIpost) for breast radiotherapy after breast-conserving surgery (BCS) using deformable image registration (DIR). METHODS AND MATERIALS: Seventeen eligible patients who underwent whole-breast irradiation in the prone position after BCS were enrolled. On MRIpre, the gross tumor volume (GTV) was delineated as GTVpre, which was then expanded by 10 mm to represent the preoperative lumpectomy cavity (LC), denoted as LCpre. The LC was expanded to the clinical target volume (CTV) and planning target volume (PTV) on the MRIpre and MRIpost, denoted as CTVpre, CTVpost, PTVpre, and PTVpost, respectively. The MIM software system was used to register the MRIpre and MRIpost using DIR. Differences were evaluated regarding target volume, distance between the centers of mass (dCOM), conformity index (CI), and degree of inclusion (DI). The relationship between CILC /CIPTV and the clinical factors was also assessed. RESULTS: Significant differences were observed in LC and PTV volumes between MRIpre and MRIpost (p < 0.0001). LCpre was 0.85 cm3 larger than LCpost, while PTVpre was 29.38 cm3 smaller than PTVpost. The dCOM between LCpre and LCpost was 1.371 cm, while that between PTVpre and PTVpost reduced to 1.348 cm. There were statistically significant increases in CI and DI for LCpost-LCpre and PTVpost-PTVpre (CI = 0.221, 0.470; DI = 0.472, 0.635). No obvious linear correlations (p > 0.05) were found between CI and GTV, primary tumor volume-to-breast volume ratio, distance from the primary tumor to the nipple and chest wall, and body mass index. CONCLUSIONS: Despite using DIR technology, the spatial correspondence of target volumes between MRIpre and MRIpost was suboptimal. Therefore, relying solely on preoperative diagnostic MRI with DIR for postoperative LC delineation is not recommended.

Impact of different zero valent iron-based particles on anaerobic microbial dechlorination of 2,4-dichlorophenol: Comparison of dechlorination performance and the underlying mechanism.

The integration of iron-based materials and anaerobic microbial consortia has been extensively studied owing to its potential to enhance pollutant degradation. However, few studies have compared how different iron materials enhance the dechlorination of chlorophenols in coupled microbial systems. This study systematically compared the combined performances of microbial community (MC) and iron materials (Fe0/FeS2 +MC, S-nZVI+MC, n-ZVI+MC, and nFe/Ni+MC) for the dechlorination of 2,4-dichlorophenol (DCP) as one representative of chlorophenols. DCP dechlorination rate was significantly higher in Fe0/FeS2 +MC and S-nZVI+MC (1.92 and 1.67 times, with no significant difference between two groups) than in nZVI+MC and nFe/Ni+MC (1.29 and 1.25 times, with no significant difference between two groups). Fe0/FeS2 had better performance for the reductive dechlorination process as compared with other three iron-based materials via the consumption of any trace amount of oxygen in anoxic condition and accelerated electron transfer. On the other hand, nFe/Ni could induce different dechlorinating bacteria as compared to other iron materials. The enhanced microbial dechlorination was mainly due to some putative dechlorinating bacteria (Pseudomonas, Azotobacter, Propionibacterium), and due to improved electron transfer of sulfidated iron particles. Therefore, Fe0/FeS2 as a biocompatible as well as low-cost sulfidated material can be a good alternative for possible engineering applications in groundwater remediation.

Distribution, sources, and health risk of polycyclic aromatic hydrocarbons and their derivatives in the watershed: the case of Yitong River, China.

Polycyclic aromatic hydrocarbons (PAHs) and substituted PAHs (SPAHs) are persistent organic pollutants prevalent globally, and SPAHs have received widespread attention in recent years due to their stronger toxicity and carcinogenicity compared to PAHs. There is a lack of systematic examination of PAHs and their derivatives in watersheds. Thus, to clarify the current status, possible sources, and potential risks of PAHs and their derivatives in watersheds, a study was conducted on Yitong River in China. The results showed that the concentrations of ∑PAHs, ∑OPAHs, and ∑NPAHs ranged from 297.9-1158.3 ng/L, 281.1-587.2 ng/L, and 65.7-269.1 ng/L, respectively. Diagnostic ratio analysis showed that the PAHs were mainly derived from petroleum sources, agricultural waste, and coal combustion. Nitrated PAHs (NPAHs) were mainly derived from liquid combustion sources, and oxygenated PAHs (OPAHs) were derived mainly from petroleum source emissions and atmospheric deposition. The exposure risk model of PAHs revealed that 86% of the studied sites would pose carcinogenic risks after dermal contact. The contaminant causing a major carcinogenic risk was DahA, and none of the sites produced non-carcinogenic risks. The lifetime carcinogenic risk of NPAHs was 8.85 × 10-10-1.44 × 10-4, and some surface waters presented with potential carcinogenic risks.

Notch1 signaling activation alleviates coronary microvascular dysfunction through histone modification of Nrg-1 via the interaction between NICD and GCN5.

The Notch signaling pathway is related to endothelial dysfunction in coronary atherosclerosis. Our objective was to explore the role of Notch signaling in coronary microvascular dysfunction (CMD). CMD models were constructed by sodium laurate injection in vivo and homocysteine (Hcy) stimulation in vitro. The binding ability of Notch Intracellular Domain (NICD)/H3K9Ac/GCN5 (General Control Non-derepressible 5) to Neuregulin-1 (Nrg-1) promoter was examined by chromatin immunoprecipitation. Immunofluorescence staining was conducted to detect CD31 positive cells, NICD localization, and co-localization of NICD and GCN5. Flow cytometry and Tunel staining were conducted to identify the apoptosis. Hematoxylin and eosin staining, quantitative real-time PCR, western blot, immunohistochemical staining, co-immunoprecipitation, and double luciferase report analysis were also conducted. Notch signaling pathway-related protein levels were decreased, levels of Nrg-1 and the phosphorylation of ErbB2 and ErbB4 were enhanced in CMD models. Interference with Nrg-1 further increased the apoptosis in Hcy-induced cardiac microvascular endothelial cells (CMECs). Meanwhile, the activation of the Notch signaling pathway increased the levels of Nrg-1 and the phosphorylation of ErbB2 and ErbB4, as well as inhibited the apoptosis induced by Hcy. Furthermore, NICD and histone acetyltransferase enzyme GCN5 could regulate Nrg-1 promoter activity by affecting the expression of acetylation-modified protein H3K9Ac. In addition, NICD also interacted with GCN5. In vivo results also confirmed that the activation of the Notch signal alleviated CMD. Notch signaling pathway regulates Nrg-1 level through synergistic interaction with GCN5, thereby mitigating CMD.

Pre-operative evaluation and mid-term outcomes of anomalous origin of the left coronary artery from the pulmonary artery based on left ventricular ejection fraction.

Objective: The purpose of this study was to evaluate the prognosis of patients with anomalous left coronary artery originating from pulmonary artery with varying cardiac function after surgical correction. Methods: This was a single-center retrospective cohort study including 51 patients with anomalous left coronary artery originating from pulmonary artery, all of whom underwent surgery at our center. Results: All 5 deaths occurred in the pre-operative low cardiac function group (n = 39). After corrected by body surface area, parameters such as left coronary artery, right coronary artery, left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and main pulmonary artery diameter, were lower in patients in the normal cardiac function group than in the low cardiac function group. The rate of collateral circulation formation was higher in the normal cardiac function group. The proportion of changes of T wave was higher in the low cardiac function group (P = 0.005), and the duration of vasoactive drugs (dopamine, milrinone, epinephrine, nitroglycerin.) was longer in the low cardiac function group. Left ventricular end-diastolic diameter, left ventricular end-systolic diameter, main pulmonary artery diameter, and left atrial diameter were smaller than those pre-operatively (P < 0.05). Left ventricular ejection fraction was higher than that pre-operatively (P = 0.003). The degree of mitral regurgitation in the low cardiac function group was reduced post-operatively (P < 0.001). Conclusion: There was a significant difference between the pre-operative baseline data of the low cardiac function group and the normal cardiac function group. After surgical repair, cardiac function gradually returned to normal in the low cardiac function group. The low cardiac function group required vasoactive drugs for a longer period of time. The left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, and main pulmonary artery diameter decreased and gradually returned to normal after surgery. The degree of mitral regurgitation in the low cardiac function group was reduced after surgery.

Inter-Observer and Intra-Observer Variability in Gross Tumor Volume Delineation of Primary Esophageal Carcinomas Based on Different Combinations of Diagnostic Multimodal Images.

Background and Purpose: This study aimed to investigate inter-/intra-observer delineation variability in GTVs of primary esophageal carcinomas (ECs) based on planning CT with reference to different combinations of diagnostic multimodal images from endoscopy/EUS, esophagography and FDG-PET/CT. Materials and Methods: Fifty patients with pathologically proven thoracic EC who underwent diagnostic multimodal images before concurrent chemoradiotherapy were enrolled. Five radiation oncologist independently delineated the GTVs based on planning CT only (GTVC), CT combined with endoscopy/EUS (GTVCE), CT combined with endoscopy/EUS and esophagography (X-ray) (GTVCEX), and CT combined with endoscopy/EUS, esophagography, and FDG-PET/CT (GTVCEXP). The intra-/inter-observer variability in the volume, longitudinal length, generalized CI (CIgen), and position of the GTVs were assessed. Results: The intra-/inter-observer variability in the volume and longitudinal length of the GTVs showed no significant differences (p>0.05). The mean intra-observer CIgen values for all observers was 0.73 ± 0.15. The mean inter-observer CIgen values for the four multimodal image combinations was 0.67 ± 0.11. The inter-observer CIgen for the four combined images was the largest, showing significant differences with those for the other three combinations. The intra-observer CIgen among different observers and inter-observer CIgen among different combinations of multimodal images showed significant differences (p<0.001). The intra-observer CIgen for the senior radiotherapists was larger than that for the junior radiotherapists (p<0.001). Conclusion: For radiation oncologists with advanced medical imaging training and clinical experience, using diagnostic multimodal images from endoscopy/EUS, esophagography, and FDG-PET/CT could reduce the intra-/inter-observer variability and increase the accuracy of target delineation in primary esophageal carcinomas.

[Effect of iron death inhibitor on hypoxia/reoxygenation injury of cardiomyocytes and its mechanism].

OBJECTIVE: To investigate the effects of ferrostatin-1 (Fer-1) on cardiomyocyte hypoxia/reoxygenation injury and its mechanisms. METHODS: The original generation of myocardial cells were extracted from 1～3 d newborn SD rats, which were randomly divided into normal control group (control), hypoxia reoxygenation (H/R) group and hypoxia reoxygenation + iron death inhibitors group (H/R + Fer-1). After 52 h of culture, cells in H/R group were added with 4 mmol/L Na2S2O4 solution. After 1 h of hypoxia, cells were reoxygenated with DMEM medium containing 10% calf serum for 3 h.The H/R+ Fer-1 group was pretreated with Fer-1 (2 µmol/L) for 24 h and then subjected to hypoxia and reoxygenation. The release rate of lactate dehydrogenase (LDH) was measured by UV spectrophotometry, the cell survival rate was measured by CCK-8 method, SOD was measured by xanthine oxidase method, MDA was measured by chemical coloration, and the changes of mitochondrial membrane potential and reactive oxygen species (ROS) were observed by immunofluorescence. Western blot was used to detect the expressions of ACSL4 and GPX4. RESULTS: Compared with the control group, the cell activity, SOD release and MMP level were decreased (P＜0.05), the levels of LDH, MDA and ROS were increased (P＜0.05), the protein expression of ACSL4 was increased (P＜0.05), and the protein expression of GPX4 was decreased (P＜0.05) in H/R group. Compared with the H/R group, the cell activity, SOD release and MMP level were increased (P＜0.05), the level of LDH, MDA and ROS were decreased (P＜0.05), the protein expression of ACSL4 was decreased (P＜0.05), and the protein expression of GPX4 was increased (P＜0.05) in H/R+Fer-1 group. CONCLUSION: Fer-1 can inhibit the production of intracellular reactive oxygen species by regulating ACSL4 and GPX4, thereby alleviating the hypoxia and reoxygenation injury of primary cardiomyocytes caused by iron death.

E3 ubiquitin ligase mind bomb 1 overexpression reduces apoptosis and inflammation of cardiac microvascular endothelial cells in coronary microvascular dysfunction.

BACKGROUND: The apoptosis and inflammation in cardiac microvascular endothelial cells (CMECs) promote the development of coronary microvascular dysfunction (CMD). The present study aimed to explore the role of E3 ubiquitin ligase mind bomb 1 (MIB1) in the apoptosis and inflammation in CMECs during CMD. METHODS: In vivo, CMD in rats was induced by sodium laurate injection. In vitro, rat primary CMECs were stimulated by homocysteine (Hcy). The apoptosis of CMECs was measured using flow cytometry. The inflammation of CMECs was evaluated by the level of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß). The interplay between MIB1 and mitogen-activated protein kinase kinase kinase 5 (map3k5, also called ASK1) was measured using Co-immunoprecipitation. RESULTS: MIB1 expression was decreased and ASK1 expression was increased in the heart tissues of CMD rats and Hcy-treated CMECs. MIB1 overexpression decreased fibrinogen-like protein 2 (FGL2) secretion, inflammation, and apoptosis induced by Hcy in CMECs. Meanwhile, MIB1 overexpression decreased the protein levels of ASK1 and p38, while not affected ASK1 mRNA levels. The following mechanism experiments revealed that MIB1 downregulated ASK1 expression by increasing its ubiquitination. ASK1 overexpression reversed the inhibitory effect of MIB1 on FGL2 secretion, apoptosis, inflammation, and p38 activation in Hcy-treated CMECs. In CMD rats, MIB1 overexpression partly retarded CMD progression, manifesting as increased coronary capillary density and decreased microthrombi formation. CONCLUSION: MIB1 overexpression relieved apoptosis and inflammation of CMECs during CMD by targeting the ASK1/p38 pathway.

Effect of abdominal compression on target movement and extension of the external boundary of peripheral lung tumours treated with stereotactic radiotherapy based on four-dimensional computed tomography.

BACKGROUND: This study aimed to investigate the effect of abdominal compression on tumour motion and target volume and to determine suitable planning target volume (PTV) margins for patients treated with lung stereotactic body radiotherapy (SBRT) based on four-dimensional computed tomography (4DCT). METHODS: Twenty-three patients diagnosed to have a peripheral pulmonary tumour were selected and divided into an all lesions group (group A), an upper middle lobe lesions group (group B), and a lower lobe lesions group (group C). Two 4DCT scans were performed in each patient, one with and one without abdominal compression. Cone beam computed tomography (CBCT) was performed before starting treatment. The gross target volumes (GTVs) were delineated and internal gross target volumes (IGTVs) were defined. IGTVs were generated using two methods: (1) the maximum intensity projections (MIPs) based on the 4DCT were reconstructed to form a single volume and defined as the IGTVMIP and (2) GTVs from all 10 phases were combined to form a single volume and defined as the IGTV10. A 5-mm, 4-mm, and 3-mm margin was added in all directions on the IGTVMIP and the volume was constructed as PTVMIP5mm, PTVMIP4mm, and PTVMIP3mm. RESULTS: There was no significant difference in the amplitude of tumour motion in the left-right, anterior-posterior, or superior-inferior direction according to whether or not abdominal compression was applied (group A, p = 0.43, 0.27, and 0.29, respectively; group B, p = 0.46, 0.15, and 0.45; group C, p = 0.79, 0.86, and 0.37; Wilcoxon test). However, the median IGTVMIP without abdominal compression was 33.67% higher than that with compression (p = 0.00), and the median IGTV10 without compression was 16.08% higher than that with compression (p = 0.00). The median proportion of the degree of inclusion of the IGTVCBCT in PTVMIP5mm, PTVMIP4mm, and PTVMIP3mm ≥ 95% was 100%, 100%, and 83.33%, respectively. CONCLUSIONS: Abdominal compression was useful for reducing the size of the IGTVMIP and IGTV10 and for decreasing the PTV margins based on 4DCT. In IGTVMIP with abdominal compression, adding a 4-mm margin to account for respiration is feasible in SBRT based on 4DCT.

Evaluation of lung tumor motion in a large sample: Target-related and clinical factors influencing tumor motion based on four-dimensional CT.

BACKGROUND AND PURPOSE: We aimed to analyze the influence of target-related and clinical factors on lung tumor motion based on four-dimensional CT (4DCT), and clarify the motion based on subgroups in lung stereotactic body radiation therapy. MATERIALS AND METHODS: 4DCT image data of 267 tumors from 246 patients were analyzed. The coordinates in the left-right (LR), anterior-posterior (AP), and cranial-caudal (CC) directions of the center of mass (COM) of the gross tumor volumes in 10 phases of 4DCT were measured. The peak-to-peak COM displacement in the LR, AP, CC, and 3D directions was calculated. The influence of target-related and clinical factors on tumor motion was evaluated using multivariate analysis. RESULTS: The tumor segment location correlated with the tumor motion in each direction. Tumor size was predictive of tumor motion in the 3D (p = 0.023) and AP directions (p = 0.049). The tumor motion for metastatic tumors was smaller than that for primary tumors in the LR (p = 0.019) and AP directions (p = 0.008). The CC motion for pulmonary surgery recipients (3.8 ± 4.5 mm) was less than that for patients who had not undergone surgery (5.6 ± 5.4 mm), and no significant clinical factor was observed. BSA and BMI were positively correlated with the motion in the CC (p = 0.02) and LR directions (p = 0.002). CONCLUSION: The tumor segment location was a good predictor of tumor motion. A larger tumor tends to have a smaller motion. Patients with metastatic tumors or those who have undergone pulmonary surgery exhibited smaller and more unpredictable tumor motions, which required individual assessments. Thus, clinical factors can potentially predict tumor motion.

DE-MR simulation imaging for prone radiotherapy after breast-conserving surgery: assessing its application in lumpectomy cavity delineation based on deformable image registration.

BACKGROUND: The application of delayed-enhancement magnetic resonance (DE-MR) simulation imaging in lumpectomy cavity (LC) delineation for prone radiotherapy in patients with an invisible seroma or a low seroma clarity score (SCS) after breast-conserving surgery (BCS) based on deformable image registration (DIR) was assessed. METHODS: Twenty-six patients who were suitable for radiotherapy in prone positions after BCS were enrolled, and both computed tomography (CT) and DE-MR simulation scans were acquired. The LC delineated based on titanium surgical clips on CT images was denoted as LCCT. The LC delineated based on the signal of cavity boundaries on fat-suppressed T2-weighted imaging (T2WI) and multiphase delayed-enhancement T1-weighted imaging (DE-T1WI), which was performed at 2 min, 5 min and 10 min postinjection, were denoted as LCT2, LC2T1, LC5T1 and LC10T1, respectively. Afterwards, DIR was performed to compare the volumes and locations of the LCs with MIM software. The generalized conformity index (CIgen) of inter (intra) observer (Inter-CIgen and Intra-CIgen) was also used to explore the inter(intra) observer variation for LC delineation on each image modality. RESULTS: LCCT-LC10T1 provided the best conformal index (CI) and degree of inclusion (DI), increasing by 2.08% and 4.48% compared to LCCT-LCT2, 11.36% and 2.94% for LCCT-LC2T1, and 8.89% and 7.69% for LC5T1-LCCT, respectively. The center of mass (COM) of LCCT-LC10T1 decreased by 17.86%, 6.12% and 13.21% compared with that of LCCT-LCT2, LCCT-LC2T1 and LCCT-LC5T1, respectively. The agreement of LC delineation was strongest for 10th min DE-TIWI (coefficient of variation, COV = 2.30%, Inter-CIgen = 87.06%, Intra-CIgen = 92.64%). CONCLUSION: For patients with a low SCS (SCS ≤ 2) after BCS, it is feasible to contour the LC based on prone DE-MR simulation images. Furthermore, the LC derived from prone DE-T1WI at 10 min was found to be most similar to that derived from prone CT simulation scans using titanium surgical clips regardless of the volume and location of the LC. Inter (intra) variability was minimal for the delineation of the LC based on 10th min DE-TIWI.

Comparison of the Gross Target Volumes Based on Diagnostic PET/CT for Primary Esophageal Cancer.

BACKGROUND: Clinically, many esophageal cancer patients who planned for radiation therapy have already undergone diagnostic Positron-emission tomography/computed tomography (PET/CT) imaging, but it remains unclear whether these imaging results can be used to delineate the gross target volume (GTV) of the primary tumor for thoracic esophageal cancer (EC). METHODS: Seventy-two patients diagnosed with thoracic EC had undergone prior PET/CT for diagnosis and three-dimensional CT (3DCT) for simulation. The GTV3D was contoured on the 3DCT image without referencing the PET/CT image. The GTVPET-ref was contoured on the 3DCT image referencing the PET/CT image. The GTVPET-reg was contoured on the deformed registration image derived from 3DCT and PET/CT. Differences in the position, volume, length, conformity index (CI), and degree of inclusion (DI) among the target volumes were determined. RESULTS: The centroid distance in the three directions between two different GTVs showed no significant difference (P > 0.05). No significant difference was found among the groups in the tumor volume (P > 0.05). The median DI values of the GTVPET-reg and GTVPET-ref in the GTV3D were 0.82 and 0.86, respectively (P = 0.006). The median CI values of the GTV3D in the GTVPET-reg and GTVPET-ref were 0.68 and 0.72, respectively (P = 0.006). CONCLUSIONS: PET/CT can be used to optimize the definition of the target volume in EC. However, no significant difference was found between the GTVs delineated based on visual referencing or deformable registration whether using the volume or position. So, in the absence of planning PET-CT images, it is also feasible to delineate the GTV of primary thoracic EC with reference to the diagnostic PET-CT image.

Electrochemical performance and response of bacterial community during phenanthrene degradation in single-chamber air-cathode microbial fuel cells.

Polycyclic aromatic hydrocarbons have attracted considerable attention for their carcinogenic, teratogenic, and mutagenic properties in humans. Phenanthrene is one of the most abundant polycyclic aromatic hydrocarbons in aquatic environments. In this study, different concentrations of phenanthrene were degraded by single-chamber air-cathode microbial fuel cells. The electrochemical parameter of microbial fuel cells and biofilm changes on the anode were observed. The results showed that the addition of phenanthrene reduced the power output of the microbial fuel cell which affected the process of microbial electricity generation. Meanwhile, microorganisms destroyed the original structure of phenanthrene through anaerobic metabolism, and achieved good average degradation of 94.9-98.4%. Observation of the anodic biofilm found that the microbes had tolerance to phenanthrene and the biofilm exhibited to be well-constructed. Bacterial community distribution showed a decrease in the relative abundance of Acidovorax and Aquamicrobium, whereas the relative content of the main electroactive organism, Geobacter, increased by a factor of three. The results show that it is feasible for microbial fuel cells to biodegrade phenanthrene, and provide some references for the changes of microbial community during degradation process.

Geometrical Comparison and Quantitative Evaluation of 18F-FDG PET/CT- and DW-MRI-Based Target Delineation Before and During Radiotherapy for Esophageal Squamous Carcinoma.

BACKGROUND AND PURPOSE: This study aimed to evaluate the geometrical differences in and metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) performed before and during radiotherapy (RT) for patients with esophageal cancer based on the three-dimensional CT (3DCT) medium and explore whether the high signal area derived from DW-MRI can be used as a tool for an individualized definition of the volume in need of dose escalation for esophageal squamous cancer. MATERIALS AND METHODS: Thirty-two patients with esophageal squamous cancer sequentially underwent repeated 3DCT, 18F-FDG PET-CT, and enhanced MRI before the initiation of RT and after the 15th fraction. All images were fused with 3DCT images through deformable registration. The gross tumor volume (GTV) was delineated based on PET Edge on the first and second PET-CT images and defined as GTVPETpre and GTVPETdur, respectively. GTVDWIpre and GTVDWIdur were delineated on the first and second DWI and corresponding T2-weighted MRI (T2W-MRI)-fused images. The maximum, mean, and peak standardized uptake values (SUVs; SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis(TLG) and its relative changes were calculated automatically on PET. Similarly, the minimum and mean apparent diffusion coefficient (ADC; ADCmin and ADCmean) and its relative changes were measured manually using ADC maps. RESULTS: The volume of GTVCT exhibited a significant positive correlation with that of GTVPET and GTVDWI (both p < 0.001). Significant differences were observed in both ADCs and 18F-FDG PET metabolic parameters before and during RT (both p < 0.001). No significant correlation was observed between SUVs and ADCs before and during RT (p = 0.072-0.944) and between ∆ADCs and ∆SUVs (p = 0.238-0.854). The conformity index and degree of inclusion of GTVPETpre to GTVDWIpre were significantly higher than those of GTVPETdur to GTVDWIdur (both p < 0.001). The maximum diameter shrinkage rate (∆LDDWI) (24%) and the tumor volume shrinkage rate (VRRDWI) (60%) based on DW-MRI during RT were significantly greater than the corresponding PET-based ∆LDPET (14%) and VRRPET (41%) rates (p = 0.017 and 0.000, respectively). CONCLUSION: Based on the medium of CT images, there are significant differences in spatial position, biometabolic characteristics, and the tumor shrinkage rate for GTVs derived from 18F-FDG PET-CT and DW-MRI before and during RT for esophageal squamous cancer. Further studies are needed to determine if DW-MRI will be used as tool for an individualized definition of the volume in need of dose escalation.

Evaluation of Lung Tumor Target Volume in a Large Sample: Target and Clinical Factors Influencing the Volume Derived From Four-Dimensional CT and Cone Beam CT.

BACKGROUND AND PURPOSE: This study aimed to systematically evaluate the influence of target-related and clinical factors on volume differences and the similarity of targets derived from four-dimensional computed tomography (4DCT) and cone beam computed tomography (CBCT) images in lung stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: 4DCT and CBCT image data of 210 tumors from 195 patients were analyzed. The internal gross target volume (IGTV) derived from the maximum intensity projection (MIP) of 4DCT (IGTV-MIP) and the IGTV from CBCT (IGTV-CBCT) were compared with the reference IGTV from 10 phases of 4DCT (IGTV-10). The target size, tumor motion, and the similarity between IGTVs were measured. The influence of target-related and clinical factors on the adequacy of IGTVs derived from 4DCT MIP and CBCT images was evaluated. RESULTS: The mean tumor motion amplitude in the 3D direction was 6.5 ± 5 mm. The mean size ratio of IGTV-CBCT and IGTV-MIP compared to IGTV-10 in all patients was 0.71 ± 0.21 and 0.8 ± 0.14, respectively. Female sex, greater BSA, and larger target size were protective factors, while the Karnofsky Performance Status, body mass index, and motion were risk factors for the similarity between IGTV-MIP and IGTV-10. Older age and larger target size were protective factors, while adhesion to the heart, coexistence with cardiopathy, and tumor motion were risk factors for the similarity between IGTV-CBCT and IGTV-10. CONCLUSION: Clinical factors should be considered when using MIP images for defining ITV, and when using CBCT images for verifying treatment targets.

Comparison of gross target volumes based on four-dimensional CT, positron emission tomography-computed tomography, and magnetic resonance imaging in thoracic esophageal cancer.

PURPOSE: The application value of 18 F-FDG PET-CT combined with MRI in the radiotherapy of esophageal carcinoma was discussed by comparing the differences in position, volume, and the length of GTVs delineated on the end-expiration (EE) phase of 4DCT, 18 F-FDG PET-CT, and T2 W-MRI. METHODS: A total of 26 patients with thoracic esophageal cancer sequentially performed 3DCT, 4DCT, 18 F-FDG PET-CT, and MRI simulation for thoracic localization. All images were fused with the 3DCT images by deformable registration. GTVCT and GTV50% were delineated on 3DCT and the EE phase of 4DCT images, respectively. The GTV based on PET-CT images was determined by thresholds of SUV ≥ 2.5 and designated as GTVPET2.5 . The images of T2 -weighted sequence and diffusion-weighted sequence were referred as GTVMRI and GTVDWI , respectively. The length of the abnormality seen on the 4DCT, PET-CT, and DWI was compared. RESULTS: GTVPET2.5 was significantly larger than GTV50% and GTVMRI (P = .000 and 0.008, respectively), and the volume of GTVMRI was similar to that of GTV50% (P = .439). Significant differences were observed between the CI of GTVMRI to GTV50% and GTVPET2.5 to GTV50% (P = .004). The CI of GTVMRI to GTVCT and GTVPET2.5 to GTVCT were statistically significant (P = .039). The CI of GTVMRI to GTVPET2.5 was significantly lower than that of GTVMRI to GTV50% , GTVMRI to GTVCT , GTVPET2.5 to GTV50% , and GTVPET2.5 to GTVCT (P = .000-0.021). Tumor length measurements by endoscopy were similar to the tumor length as measured by PET and DWI scan (P > .05), and there was no significant difference between the longitudinal length of GTVPET2.5 and GTVDWI (P = .072). CONCLUSION: The volumes of GTVMRI and GTV50% were similar. However, GTVMRI has different volumes and poor spatial matching compared with GTVPET2.5 .The MRI imaging could not include entire respiration. It may be a good choice to guide target delineation and construction of esophageal carcinoma by combining 4DCT with MRI imaging. Utilization of DWI in treatment planning for esophageal cancer may provide further information to assist with target delineation. Further studies are needed to determine if this technology will translate into meaningful differences in clinical outcome.

Interobserver Variability of Target Volumes Delineated in the Supine and Prone Positions Based on Computed Tomography Images for External-Beam Partial Breast Irradiation After Breast-Conserving Surgery: A Comparative Study.

Background: Although the supine position remains the dominant position for external-beam partial breast irradiation (EB-PBI), the advantages of administering EB-PBI in the prone position have been recognized. The interobserver variability between target volumes delineated in the different positions for EB-PBI after breast-conserving surgery needs to be investigated. Methods: Twenty-seven patients suitable for EB-PBI were enrolled from July 2016 to April 2017. Supine and prone simulation CT images were sequentially acquired for all enrolled patients during free breathing. Five experienced radiotherapists delineated the target volumes for all patients on supine and prone simulation CT images. The selected parameters, including target volumes, the coefficient of variation (COV), the matching degree (MD), and so on, were calculated to analyze the interobserver variability. Results: Regardless of the patient position, the interobserver variability between tumor bed (TB) and clinical target volume (CTV) measurements in supine and prone positions were statistically significant (F = 31.34, 19.467; 44.000, 41.985; P = 0.000, 0.001; 0.000, 0.001). The interobserver variability of COVCTV was significantly greater in the supine position than in the prone position (T = 2.64, P = 0.014). Furthermore, the interobserver variabilities of MDTB and MDCTV were statistically lower in the supine position than in the prone position (Z = -3.460, -3.195, P = 0.000, 0.001). Conclusion: When delineating the target volume for EB-PBI, the interobserver variability in the prone position was lower than that in the supine position. Hence, the administration of EB-PBI in the prone position during free breathing is a reasonable option.

Definition of Internal Mammary Node Target Volume Based on the Position of the Internal Mammary Sentinel Lymph Nodes Presented on SPECT/CT Fusion Images.

Purpose: Mapping the distribution of internal mammary sentinel lymph nodes (IM-SLNs) presented on single photon emission computed tomography in conjunction with computed tomography (SPECT/CT) images to explore the value of IM-SLN to guide tailored clinical target volume (CTV) delineation of postoperative prophylactic IMNI. Materials and methods: Ninety-seven patients who underwent preoperative lymphoscintigraphy by SPECT/CT and had imaging of IM-SLN were selected in this study. The imaging IM-SLNs on SPECT/CT of eligible patients were projected onto corresponding anatomical positions of a representative axial CT image. The IMN CTVs were delineated on the representative axial CT images according to the Radiation Therapy Oncology Group (RTOG) and Danish Breast Cancer Cooperative Group (DBCG) guideline, and defined as CTVRTOG and CTVDBCG. The location of the IM-SLNs was compared with the RTOG and DBCG guidelines of IMN target volume delineations, respectively. The intercostal space distribution of IM-SLNs was recorded. The distances from the CTVRTOG and CTVDBCG to the IM-SLNs were measured, respectively. Results: The total number of imaging IM-SLNs was 136. IM-SLNs were mostly found in the first intercostal space (40.4%), with 30.2, 24.3, 4.4, and 0.7% of IM-SLNs in the second, third, fourth, and fifth intercostal space, respectively. The average distance from the edge of the CTVRTOG and the edge of CTVDBCG to the central points of the IM-SLNs was 4.10 mm (SD, 3.3 mm) and 1.60 mm (SD, 2.6 mm), respectively (t = 16.640, P = 0.000). The average distance from the edge of CTVRTOG and the edge of CTVDBCG to the lateral border IM-SLN was 6.40 mm (SD, 3.5 mm) and 3.34 mm (SD, 3.3 mm), respectively (t = 19.815, P = 0.000). Only 18.4% of IM-SLN central points were included in the CTVRTOG, and 60.3% of IM-SLN central points were included in the CTVDBCG. When covering 90 and 100% of the IM-SLN center points, the CTVRTOG needs to expand 8 and 15 mm, respectively, and the CTVDBCG needs to expand 5 and 13 mm, respectively. Conclusion: Neither the RTOG nor DBCG consensus guideline about the delineation of IMN CTV was sufficient to cover 90% of IM-SLNs. For 90% coverage of IM-SLN central points, CTVRTOG needed to be expanded by 8 mm, and CTVDBCG needed to be expanded by 5 mm.

External-beam partial breast irradiation in a supine versus prone position after breast-conserving surgery for Chinese breast cancer patients.

To investigate the differences in target volumes and dosimetric parameters between the supine and prone positions for external-beam partial breast irradiation (EB-PBI) after breast-conserving surgery (BCS) for Chinese breast cancer patients, thirty breast cancer patients who underwent three-dimensional conformal radiation therapy (3DCRT) EB-PBI after BCS were enrolled. Supine and prone scan sets were acquired during free breathing for all patients. Target volumes and organs at risk (OARs) including the heart, ipsilateral lung and bilateral breast were contoured by the same radiation oncologist. For each patient, supine and prone EB-PBI plans were generated based on the same planning criteria. The clinical target volume (CTV) and planning target volume (PTV) in the prone position were significantly greater than those in the supine position (P = 0.003, 0.004, respectively). A 0.95 Gy reduction in the mean dose (Dmean) to the heart (P = 0.000) was apparent in the supine position compared to the prone position. The Dmean to the ipsilateral lung was significantly lower in the prone position than in the supine position (1.59 Gy vs. 1.72 Gy, P = 0.029). Therefore, for Chinese breast cancer patients, carrying out 3DCRT EB-PBI in the prone position during free breathing is feasible.