Multiparametric magnetic resonance imaging (MRI)-based radiomics model explained by the Shapley Additive exPlanations (SHAP) method for predicting complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a multicenter retrospective study.

Background: Predicting the response to neoadjuvant chemoradiotherapy (nCRT) before initiating treatment is essential for tailoring therapeutic strategies and monitoring prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to develop and validate radiomic-based models to predict clinical and pathological complete responses (cCR and pCR, respectively) by incorporating the Shapley Additive exPlanations (SHAP) method for model interpretation. Methods: A total of 285 patients with complete pretreatment clinical characteristics and T1-weighted (T1W) and T2-weighted (T2W) magnetic resonance imaging (MRI) at 3 centers were retrospectively recruited. The features of tumor lesions were extracted by PyRadiomics and selected using least absolute shrinkage and selection operator (LASSO) algorithm. The selected features were used to build multilayer perceptron (MLP) models alone or combined with clinical features. Area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were applied to evaluate performance of models. The SHAP method was adopted to explain the prediction models. Results: The radiomic-based models all showed better performances than clinical models. The clinical-radiomic models showed the best differentiation on cCR and pCR with mean AUCs of 0.718 and 0.810 in the validation set, respectively. The decision curves of the clinical-radiomic models showed its values in clinical application. The SHAP method powerfully interpreted the prediction models both at a holistic and individual levels. Conclusions: Our study highlights that the radiomic-based prediction models have more excellent abilities than clinical models and can effectively predict treatment response and optimize therapeutic strategies for patients with LARCs.

The cardiovascular system at high altitude: A bibliometric and visualization analysis.

BACKGROUND: When exposed to high-altitude environments, the cardiovascular system undergoes various changes, the performance and mechanisms of which remain controversial. AIM: To summarize the latest research advancements and hot research points in the cardiovascular system at high altitude by conducting a bibliometric and visualization analysis. METHODS: The literature was systematically retrieved and filtered using the Web of Science Core Collection of Science Citation Index Expanded. A visualization analysis of the identified publications was conducted employing CiteSpace and VOSviewer. RESULTS: A total of 1674 publications were included in the study, with an observed annual increase in the number of publications spanning from 1990 to 2022. The United States of America emerged as the predominant contributor, while Universidad Peruana Cayetano Heredia stood out as the institution with the highest publication output. Notably, Jean-Paul Richalet demonstrated the highest productivity among researchers focusing on the cardiovascular system at high altitude. Furthermore, Peter Bärtsch emerged as the author with the highest number of cited articles. Keyword analysis identified hypoxia, exercise, acclimatization, acute and chronic mountain sickness, pulmonary hypertension, metabolism, and echocardiography as the primary research hot research points and emerging directions in the study of the cardiovascular system at high altitude. CONCLUSION: Over the past 32 years, research on the cardiovascular system in high-altitude regions has been steadily increasing. Future research in this field may focus on areas such as hypoxia adaptation, metabolism, and cardiopulmonary exercise. Strengthening interdisciplinary and multi-team collaborations will facilitate further exploration of the pathophysiological mechanisms underlying cardiovascular changes in high-altitude environments and provide a theoretical basis for standardized disease diagnosis and treatment.

Does the time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery affect outcomes for locally advanced esophageal squamous cell carcinoma?

BACKGROUND: There is currently no consensus on the optimal interval time between neoadjuvant therapy and surgery, and whether prolonged time interval from neoadjuvant therapy to surgery results in bad outcomes for locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we aim to evaluate outcomes of time intervals ≤ 8 weeks and > 8 weeks in locally advanced ESCC. METHODS: This retrospective study consecutively included ESCC patients who received esophagectomy after neoadjuvant camrelizumab combined with chemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine. The primary endpoints were disease-free survival (DFS) and overall survival (OS), while the secondary endpoints were pathological response, surgical outcomes, and postoperative complications. RESULTS: From 2019 to 2021, a total of 80 patients were included in our study and were divided into two groups according to the time interval from neoadjuvant immunochemotherapy to surgery: ≤ 8 weeks group (n = 44) and > 8 weeks group (n = 36). The rate of MPR in the ≤ 8 weeks group was 25.0% and 27.8% in the > 8 weeks group (P = 0.779). The rate of pCR in the ≤ 8 weeks group was 11.4%, with 16.7% in the > 8 weeks group (P = 0.493). The incidence of postoperative complications in the ≤ 8 weeks group was 27.3% and 19.4% in the > 8 weeks group (P = 0.413). The median DFS in the two groups had not yet reached (hazard ratio [HR], 3.153; 95% confidence interval [CI] 1.383 to 6.851; P = 0.004). The median OS of ≤ 8 weeks group was not achieved (HR, 3.703; 95% CI 1.584 to 8.657; P = 0.0012), with the > 8 weeks group 31.6 months (95% CI 21.1 to 42.1). In multivariable analysis, inferior DFS and OS were observed in patients with interval time > 8 weeks (HR, 2.992; 95% CI 1.306 to 6.851; and HR, 3.478; 95% CI 1.481 to 8.170, respectively). CONCLUSIONS: Locally advanced ESCC patients with time interval from neoadjuvant camrelizumab combined with chemotherapy to surgery > 8 weeks were associated with worse long-term survival.

A Convenient and Effective Preoxygenation Technique for Prolonging Deep Inspiration Breath-Hold Duration With a Venturi Mask With a 50% Oxygen Concentration.

PURPOSE: Voluntary deep inspiration breath-hold (DIBH) is commonly used in radiation therapy (RT), but the short duration of a single breath-hold, estimated to be around 20 to 40 seconds, is a limitation. This prospective study aimed to assess the feasibility and safety of using a simple preoxygenation technique with a Venturi mask to prolong voluntary DIBH. METHODS AND MATERIALS: The study included 33 healthy volunteers and 21 RT patients. Preoxygenation was performed using a Venturi mask with a 50% oxygen concentration. Paired t tests compared the duration of a single DIBH in room air and after 5, 15, and 30 minutes of preoxygenation in healthy volunteers. Sustainability of breath-hold and tolerability of heart rate and blood pressure were assessed for multiple DIBH durations in both volunteers and patients. RESULTS: In healthy volunteers, a 15-minute preoxygenation significantly prolonged the duration of a single DIBH by 24.95 seconds compared with 5-minute preoxygenation (89 ± 27.76 vs 113.95 ± 30.63 seconds; P < .001); although there was a statistically significant increase in DIBH duration after 30-minute preoxygenation, it was only extended by 4.95 seconds compared with 15-minute preoxygenation (113.95 ± 30.63 vs 118.9 ± 29.77 seconds; P < .01). After 15-minute preoxygenation, a single DIBH lasted over 100 seconds in healthy volunteers and over 80 seconds in RT patients, with no significant differences among 6 consecutive cycles of DIBH. Furthermore, there were no significant differences in heart rate or blood pressure after DIBHs, including DIBH in room air and 6 consecutive DIBHs after 15-minute preoxygenation (all P > .05). CONCLUSIONS: Preoxygenation with a 50% oxygen concentration for 15 minutes effectively prolongs the duration of 6 cycles of DIBH both in healthy volunteers and RT patients. The utilization of a Venturi mask to deliver 50% oxygen concentration provides a solution characterized by its convenience, good tolerability, and effectiveness.

Suicide rates among patients with first and second primary cancer.

AIMS: With advancements in cancer treatments, the survival rates of patients with their first primary cancer (FPC) have increased, resulting in a rise in the number of patients with second primary cancer (SPC). However, there has been no assessment on the incidence of suicide among patients with SPC. This study assessed the occurrence of suicide among patients with SPC and compared them with that in patients with FPC. METHODS: This was a retrospective, population-based cohort study that followed patients with FPC and SPC diagnosed from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 17 registries database between 1 January 2000 and 31 December 2019. RESULTS: For patients with SPC, an age of 85+ years at diagnosis was associated with a higher incidence of suicide death (HR, 1.727; 95% CI, 1.075-2.774), while the suicide death was not considerably different in the chemotherapy group (P > 0.05). Female genital system cancers (HR, 3.042; 95% CI, 1.819-6.361) accounted for the highest suicide death among patients with SPC. The suicide death distribution of patients with SPC over time indicated that suicide events mainly occurred within 5 to 15 years of diagnosis. Compared with patients with FPC, patients with SPC in general had a lower risk of suicide, but increased year by year. CONCLUSION: The risk of suicide was reduced in patients with SPC compared with patients with FPC, but increased year by year. Therefore, oncologists and related health professionals need to provide continuous psychological support to reduce the incidence of suicide. The highest suicide death was found among patients with female genital system cancer.

Early Enteral Nutrition and Sepsis-Associated Acute Kidney Injury: A Propensity Score Matched Cohort Study Based on the MIMIC-III Database.

PURPOSE: We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.). MATERIALS AND METHODS: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. RESULTS: 2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245-0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0-48 hours vs. 48-53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. CONCLUSION: EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

Genome-wide analysis and identification of microRNAs in Medicago truncatula under aluminum stress.

Numerous studies have shown that plant microRNAs (miRNAs) play key roles in plant growth and development, as well as in response to biotic and abiotic stresses; however, the role of miRNA in legumes under aluminum (Al) stress have rarely been reported. Therefore, here, we aimed to investigate the role of miRNAs in and their mechanism of Al tolerance in legumes. To this end, we sequenced a 12-strand-specific library of Medicago truncatula under Al stress. A total of 195.80 M clean reads were obtained, and 876 miRNAs were identified, of which, 673 were known miRNAs and 203 were unknown. A total of 55 miRNAs and their corresponding 2,502 target genes were differentially expressed at various time points during Al stress. Further analysis revealed that mtr-miR156g-3p was the only miRNA that was significantly upregulated at all time points under Al stress and could directly regulate the expression of genes associated with root cell growth. Three miRNAs, novel_miR_135, novel_miR_182, and novel_miR_36, simultaneously regulated the expression of four Al-tolerant transcription factors, GRAS, MYB, WRKY, and bHLH, at an early stage of Al stress, indicating a response to Al stress. In addition, legume-specific miR2119 and miR5213 were involved in the tolerance mechanism to Al stress by regulating F-box proteins that have protective effects against stress. Our results contribute to an improved understanding of the role of miRNAs in Al stress in legumes and provide a basis for studying the molecular mechanisms of Al stress regulation.

Alternating Expiration and Inspiration Breath-Hold Spares the Chest Wall During Stereotactic Body Radiation Therapy for Peripheral Lung Malignancies.

PURPOSE: The proximity of tumors to the chest wall brings additional risks of chest wall pain during stereotactic body radiation therapy. Herein, we dosimetrically compared alternated breath-hold (ABH) plans with single BH plans and determined the common characteristics of eligible patients who may obtain better chest wall sparing using this technique. METHODS AND MATERIALS: Twenty patients with lung lesions adjacent to the chest wall were enrolled and received respiratory training. Their half-fraction end expiration BH and deep inspiration BH plans were summed to generate the ABH plans. Dosimetric parameters of the chest wall were compared between single and alternated BH plans, and the correlation between tumor location and the outcome of chest wall sparing was quantitatively evaluated. Pretreatment cone beam computed tomography variations in eligible patients were recorded as well. RESULTS: Compared with the end expiration BH and deep inspiration BH plans, the ABH plans reduced chest wall dosimetric results with median reductions of 2.0% and 3.9% (Dmax: maximum point dose), 15.4% and 14.8% (D1cc: dose to a volume of 1 cm3), and 48.8% and 63% (V30: volume receiving 30 Gy or more), respectively. Relative tumor displacements (ratio of tumor displacement in the superior-inferior direction to planning target volume diameter) were greater in the lower lobe than in the upper and middle lobes (1.17 vs 0.18). Meanwhile, better median reductions of 44% (Dmax), 46% (D1cc), and 98% (V30) were obtained in the lower lobe cohort using the ABH technique. Pretreatment variations for all BHs met the 5-mm threshold. CONCLUSIONS: The ABH technique can significantly spare the adjacent chest wall without compromising planning target volume coverage in comparison with the single BH, and patients with tumors in the lower lobes can obtain better chest wall sparing than in the upper and middle lobes. Further investigation is warranted to validate these findings.

Protective Role of Shenmai Injection on Radiation-Induced Heart Injury.

Radiation-induced heart injury (RIHI) limits the dose delivery of radiotherapy for thoracic cancer. Shenmai injection (SMI) is reported to have potential cytoprotective properties and is commonly used in cardiovascular diseases. So, we aimed to investigate the potential protective effects of SMI treatment on RIHI. In this study, we established the RIHI model using Sprague-Dawley rats and H9c2 cell line. In vivo, the biochemical assay was used to measure serum cardiac injury-related biomarkers and echocardiography to evaluate heart function. The pathological analysis was also applied to observe the myocardial structural changes. In vitro, we further measured the cell viability and reactive oxygen species (ROS) levels after irradiation with or without SMI treatment. Our data showed the administration of SMI reduced the level of serum cardiac injury biomarkers and ameliorated cardiac dysfunction after irradiation in rats. Pathological analysis revealed that SMI mitigated cardiac structural damage, fibrosis, and macrophage infiltration. Besides, treatment with SMI increased cell viability and decreased excess ROS production after irradiation in vitro. Taken together, our study demonstrated the protective role of SMI treatment on RIHI by inhibiting oxidative stress and decreasing structural remodeling.

A comparative transcriptomic analysis reveals a coordinated mechanism activated in response to cold acclimation in common vetch (Vicia sativa L.).

BACKGROUND: Due to its strong abiotic stress tolerance, common vetch is widely cultivated as a green manure and forage crop in grass and crop rotation systems. The comprehensive molecular mechanisms activated in common vetch during cold adaptation remain unknown. RESULTS: We investigated physiological responses and transcriptome profiles of cold-sensitive (Lanjian No. 1) and cold-tolerant (Lanjian No. 3) cultivars during cold acclimation to explore the molecular mechanisms of cold acclimation. In total, 2681 and 2352 differentially expressed genes (DEGs) were identified in Lanjian No. 1 and Lanjian No. 3, respectively; 7532 DEGs were identified in both lines. DEGs involved in "plant hormone signal transduction" were significantly enriched during cold treatment, and 115 DEGs involved in cold-processed hormone signal transduction were identified. Common vetch increased the level of indoleacetic acid (IAA) by upregulating the transcriptional regulator Aux/IAA and downregulating GH3, endowing it with stronger cold tolerance. An auxin-related DEG was overexpressed in yeast and shown to possess a biological function conferring cold tolerance. CONCLUSION: This study identifies specific genes involved in Ca2+ signaling, redox regulation, circadian clock, plant hormones, and transcription factors whose transcriptional differentiation during cold acclimation may improve cold tolerance and contributes to the understanding of common and unique molecular mechanisms of cold acclimation in common vetch. The candidate genes identified here also provide valuable resources for further functional genomic and breeding studies.

Comprehensive and clinically accurate head and neck cancer organs-at-risk delineation on a multi-institutional study.

Accurate organ-at-risk (OAR) segmentation is critical to reduce radiotherapy complications. Consensus guidelines recommend delineating over 40 OARs in the head-and-neck (H&N). However, prohibitive labor costs cause most institutions to delineate a substantially smaller subset of OARs, neglecting the dose distributions of other OARs. Here, we present an automated and highly effective stratified OAR segmentation (SOARS) system using deep learning that precisely delineates a comprehensive set of 42 H&N OARs. We train SOARS using 176 patients from an internal institution and independently evaluate it on 1327 external patients across six different institutions. It consistently outperforms other state-of-the-art methods by at least 3-5% in Dice score for each institutional evaluation (up to 36% relative distance error reduction). Crucially, multi-user studies demonstrate that 98% of SOARS predictions need only minor or no revisions to achieve clinical acceptance (reducing workloads by 90%). Moreover, segmentation and dosimetric accuracy are within or smaller than the inter-user variation.

Efficient dose-volume histogram-based pretreatment patient-specific quality assurance methodology with combined deep learning and machine learning models for volumetric modulated arc radiotherapy.

BACKGROUND: Weak correlation between gamma passing rates and dose differences in target volumes and organs at risk (OARs) has been reported in several studies. Evaluation on the differences between planned dose-volume histogram (DVH) and reconstructed DVH from measurement was adopted and incorporated into patient-specific quality assurance (PSQA). However, it is difficult to develop a methodology allowing the evaluation of errors on DVHs accurately and quickly. PURPOSE: To develop a DVH-based pretreatment PSQA for volumetric modulated arc therapy (VMAT) with combined deep learning (DL) and machine learning models to overcome the limitation of conventional gamma index (GI) and improve the efficiency of DVH-based PSQA. METHODS: A DL model with a three-dimensional squeeze-and-excitation residual blocks incorporated into a modified U-net was developed to predict the measured PSQA DVHs of 208 head-and-neck (H&N) cancer patients underwent VMAT between 2018 and 2021 from two hospitals, in which 162 cases was randomly selected for training, 18 for validation, and 28 for testing. After evaluating the differences between treatment planning system (TPS) and PSQA DVHs predicted by DL model with multiple metrics, a pass or fail (PoF) classification model was developed using XGBoost algorithm. Evaluation of domain experts on dose errors between TPS and reconstructed PSQA DVHs was taken as ground truth for PoF classification model training. RESULTS: The prediction model was able to achieve a good agreement between predicted, measured, and TPS doses. Quantitative evaluation demonstrated no significant difference between predicted PSQA dose and measured dose for target and OARs, except for Dmean of PTV6900 (p = 0.001), D50 of PTV6000 (p = 0.014), D2 of PTV5400 (p = 0.009), D50 of left parotid (p = 0.015), and Dmax of left inner ear (p = 0.007). The XGBoost model achieved an area under curves, accuracy, sensitivity, and specificity of 0.89 versus 0.88, 0.89 versus 0.86, 0. 71 versus 0.71, and 0.95 versus 0.91 with measured and predicted PSQA doses, respectively. The agreement between domain experts and the classification model was 86% for 28 test cases. CONCLUSIONS: The successful prediction of PSQA doses and classification of PoF for H&N VMAT PSQA indicating that this DVH-based PSQA method is promising to overcome the limitations of GI and to improve the efficiency and accuracy of VMAT delivery.

mTORC2 Facilitates Liver Regeneration Through Sphingolipid-Induced PPAR-α-Fatty Acid Oxidation.

BACKGROUND & AIMS: During liver regeneration after partial hepatectomy, the function and metabolic pathways governing transient lipid droplet accumulation in hepatocytes remain obscure. Mammalian target of rapamycin 2 (mTORC2) facilitates de novo synthesis of hepatic lipids. Under normal conditions and in tumorigenesis, decreased levels of triglyceride (TG) and fatty acids (FAs) are observed in the mTORC2-deficient liver. However, during liver regeneration, their levels increase in the absence of mTORC2. METHODS: Rictor liver-specific knockout and control mice underwent partial hepatectomy, followed by measurement of TG and FA contents during liver regeneration. FA metabolism was evaluated by analyzing the expression of FA metabolism-related genes and proteins. Intraperitoneal injection of the peroxisome proliferator-activated receptor α (PPAR-α) agonist, p53 inhibitor, and protein kinase B (AKT) activator was performed to verify the regulatory pathways involved. Lipid mass spectrometry was performed to identify the potential PPAR-α activators. RESULTS: The expression of FA metabolism-related genes and proteins suggested that FAs are mainly transported into hepatocytes during liver regeneration. The PPAR-α pathway is down-regulated significantly in the mTORC2-deficient liver, resulting in the accumulation of TGs. The PPAR-α agonist WY-14643 rescued deficient liver regeneration and survival in mTORC2-deficient mice. Furthermore, lipidomic analysis suggested that mTORC2 deficiency substantially reduced glucosylceramide (GluCer) content. GluCer activated PPAR-α. GluCer treatment in vivo restored the regenerative ability and survival rates in the mTORC2-deficient group. CONCLUSIONS: Our data suggest that FAs are mainly transported into hepatocytes during liver regeneration, and their metabolism is facilitated by mTORC2 through the GluCer-PPAR-α pathway, thereby establishing a novel role for mTORC2 in lipid metabolism.

Effect of Glut-1 and HIF-1α double knockout by CRISPR/CAS9 on radiosensitivity in laryngeal carcinoma via the PI3K/Akt/mTOR pathway.

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (Glut-1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of 18 F-fluorodeoxyglucose radioactivity. A tumour xenograft model was established by subcutaneous injection of Tu212 cells. Tumour histopathology was determined by haematoxylin and eosin staining, immunohistochemical staining, and TUNEL assays. Signalling transduction was evaluated by Western blotting. We found that hypoxia induced radioresistance in Tu212 cells accompanied by increased glucose uptake capability and activation of the PI3K/Akt/mTOR pathway. Inhibition of PI3K/Akt/mTOR activity abolished hypoxia-induced radioresistance and glucose absorption. Mechanistic analysis revealed that hypoxia promoted higher expressions of HIF-1α and Glut-1. Moreover, the PI3K/Akt/mTOR pathway was a positive mediator of HIF-1α and/or Glut-1 in the presence of irradiation. HIF-1α and/or Glut-1 knockout significantly reduced cell viability, glucose uptake and PI3K/Akt/mTOR activity, all of which were induced by hypoxia in the presence of irradiation. In vivo analysis showed that knockout of HIF-1α and/or Glut-1 also inhibited tumour growth by promoting cell apoptosis, more robustly compared with the PI3K inhibitor wortmannin, particularly in tumours with knockout of both HIF-1α and Glut-1. HIF-1α and/or Glut-1 knockout also abrogated PI3K/Akt/mTOR signalling transduction in tumour tissues, in a manner similar to wortmannin. HIF-1α and/or Glut-1 knockout facilitated radiosensitivity in laryngeal carcinoma Tu212 cells by regulation of the PI3K/Akt/mTOR pathway.

Targeted Inhibition of HK-II Reversed the Warburg Effect to Improve the Radiosensitivity of Laryngeal Carcinoma.

PURPOSE: Hexokinase-II (HK-II) is the key enzyme in the first rate-limiting step of glycolysis that catalyzes the conversion of glucose to glucose-6-phosphate. Here, we examined the association between HK-II expression and radioresistance in laryngeal carcinoma and whether the inhibition of HK-II expression can enhance the radiosensitivity of these tumors. METHODS: The effects of HK-II small interfering RNA (siRNA) on the radiosensitivity of Tu212 cells were examined in vitro and in vivo in a mouse model. Cells were irradiated using a 6-MV linear accelerator. The cell viability, cell survival, proliferation, apoptosis, and cell cycle of Tu212 cells were evaluated using trypan blue staining, colony formation assays, CCK-8 assays, and flow cytometry, respectively. Oxygen consumption, lactic acid production, glucose consumption, and the ATP level of Tu212 cells were also examined. The expression of glycolytic and regulatory enzymes involved in the tricarboxylic acid cycle was assessed using Western blotting. RESULTS: The HK-II siRNA and X-ray combination treatment led to a significantly greater reduction of cell viability, inhibition of cell survival and proliferation, increased apoptosis, and increased G2 phase arrest compared to either treatment alone (all, P<0.01). HK-II siRNA increased the oxygen consumption rate of cells, significantly inhibited lactic acid production and glucose consumption, and significantly suppressed the upregulation of HK-II, pyruvate kinase M2 (PKM2), pyruvate dehydrogenase (PDH), phosphofructokinase platelet (PFKP), lactate dehydrogenase (LD), and citrate synthase (CS) (all, P<0.01). CONCLUSION: The inhibition of HK-II by siRNA enhances the radiosensitivity of laryngeal carcinoma Tu212 cells by inhibiting glycolysis and partially inhibiting oxidative phosphorylation.

Generalized methodology for radiomic feature selection and modeling in predicting clinical outcomes.

Background.Quantitative radiomic features of medical images could provide clinical significance in assisting decision-making, but the existing feature selection and modeling methods are usually parameter-dependent. We aim to develop and validate a generalized radiomic method applicable to a variety of clinical outcomes.Methods and materials.A generalized methodology for radiomic feature selection and modeling ('GRFM' for short), including two-step feature selection and logistic regression, was proposed for studying clinical outcomes correlations. The two-step feature selection consists of Pearson correlation analysis followed by a sequential forward floating selection algorithm to identify robust feature subsets. We also applied an adaptive searching strategy to systematically determine globally optimal parameters, rather than relying on preset parameters. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of three outcomes: lymph node metastasis of gastric cancer (GC), the five-year survival status of high-grade osteosarcoma (HOS), and the pathological grade of pancreatic neuroendocrine tumors (pNETs).Results.The optimal Pearson thresholds were 0.85, 0.80 and 0.75, and the optimal feature numbers were 11, 14 and 8 in GC, HOS and pNETs, respectively. The AUC values of the three predictive models combined with the corresponding parameters were 0.9017 versus 0.9026, 0.7652 versus 0.7113, and 0.8438 versus 0.8212 for the training and validation cohorts, showing promissing generality and classifier performance .Conclusion.The proposed method was helpful in predicting different clinical outcomes, and has potential application as a general and noninvasive prediction tool to guide clinical decision-making in various cancer sites.

Radiosensitizing effects of curcumin alone or combined with GLUT1 siRNA on laryngeal carcinoma cells through AMPK pathway-induced autophagy.

In this study, we investigated the ability of curcumin alone or in combination with GLUT1 siRNA to radiosensitize laryngeal carcinoma (LC) through the induction of autophagy. Protein levels in tumour tissues and LC cells were measured by immunohistochemistry and Western blotting. In vitro, cell proliferation, colony formation assays, cell death and autophagy were detected. A nude mouse xenograft model was established through the injection of Tu212 cells. We found that GLUT1 was highly expressed and negatively associated with autophagy-related proteins in LC and that curcumin suppressed radiation-mediated GLUT1 overexpression in Tu212 cells. Treatment with curcumin, GLUT1 siRNA, or the combination of the two promoted autophagy. Inhibition of autophagy using 6-amino-3-methypourine (3-MA) promoted apoptosis after irradiation or treatment of cells with curcumin and GLUT1 siRNA. 3-MA inhibited curcumin and GLUT1 siRNA-mediated non-apoptotic programmed cell death. The combination of curcumin, GLUT1 siRNA and 3-MA provided the strongest sensitization in vivo. We also found that autophagy induction after curcumin or GLUT1 siRNA treatment implicated in the AMP-activated protein kinase-mTOR-serine/threonine-protein kinase-Beclin1 signalling pathway. Irradiation primarily caused apoptosis, and when combined with curcumin and GLUT1 siRNA treatment, the increased radiosensitivity of LC occurred through the concurrent induction of apoptosis and autophagy.

Comparison of computed tomography- and magnetic resonance imaging-based target delineation for cervical cancer brachytherapy.

PURPOSE: The objective of this study was to compare and assess the accuracy of computed tomography (CT)-based target delineation with that of magnetic resonance imaging (MRI)-based on high-dose-rate brachytherapy (HDR-BT) for patients with cervical cancer. MATERIAL AND METHODS: Data of 20 patients with locally advanced cervical cancer were collected and evaluated. Dimensions, conformity, and dose parameters of high-risk clinical target volume (CTVHR) as well as D0.1cc, D1cc, and D2cc of organs at risk (OARs) based on MRI were compared with those based on CT. RESULTS: Average age of 20 patients included was 57.8 years. Width, thickness, and volumes of CT-based CTVHR (CTVHR-CT) were significantly overestimated compared with those of MRI-based CTVHR (CTVHR-MR). Mean values of dice similarity coefficient (DSC), Hausdorff distance (HD), and centroid distance (ΔV) of CTVHR were 0.82 cm, 0.96 cm, and 0.35 cm, respectively. Dose values of CTVHR-CT were significantly lower compared with those of CTVHR-MR. Concerning OARs, geometrical and dosimetric values on CT were comparable to those on MRI. CONCLUSIONS: The delineated ranges of CTVHR were significantly over-estimated on CT compared with MRI. D98 and D90 of CTVHR-CT were lower than CTVHR-MR. DSC and ΔV of CTVHR and CTVIR were similar to each other; however, there was a difference in terms of HD. CT images regarding pre-BT MR images for delineating were not enough and MRI fusion is still required.

The benefits evaluation of abdominal deep inspiration breath hold based on knowledge-based radiotherapy treatment planning for left-sided breast cancer.

PURPOSE: To study the impact of abdominal deep inspiration breath hold (DIBH) technique on knowledge-based radiotherapy treatment planning for left-sided breast cancer to guide the application of DIBH technology. MATERIALS AND METHODS: Two kernel density estimation (KDE) models were developed based on 40 left-sided breast cancer patients with two CT acquisitions of free breathing (FB-CT) and DIBH (DIBH-CT). Each KDE model was used to predict dose volume histograms (DVHs) based on DIBH-CT and FB-CT for another 10 new patients similar to our training datasets. The predicted DVHs were taken as a substitute for dose constraints and objective functions in the Eclipse treatment planning system, with the same requirements for the planning target volume (PTV). The mean doses to the heart, the left anterior descending coronary artery (LADCA) and the ipsilateral lung were evaluated and compared using the T-test among clinical plans, KDE predictions, and KDE plans. RESULTS: Our study demonstrated that the KDE model can generate deliverable simulations equivalent to clinically applicable plans. The T-test was applied to test the consistency hypothesis on another ten left-sided breast cancer patients. In cases of the same breathing status, there was no statistically significant difference between the predicted and the clinical plans for all clinically relevant DVH indices (P > 0.05), and all predicted DVHs can be transferred into deliverable plans. For DIBH-CT images, significant differences were observed between FB model predictions and clinical plans (P < 0.05). DIBH model prediction cannot be optimized to a deliverable plan based on FB-CT, with a counsel of perfection. CONCLUSION: KDE models can predict DVHs well for the same breathing conditions but degrade with different breathing conditions. The benefits of DIBH for a given patient can be evaluated with a quick comparison of prediction results of the two models before treatment planning.

Effect of combination of curcumin and GLUT-1 AS-ODN on radiosensitivity of laryngeal carcinoma through regulating autophagy.

BACKGROUND: This study is to explore the role of curcumin and GLUT-1 antisense oligodeoxynucleotides (AS-ODN) on autophagy modulation-initiated radiosensitivity. METHODS: BALB/c mice were employed to establish xenograft model using Tu212 cell. The expression of autophagy- and apoptosis-related proteins was determined by WB. Autophagosome was observed under transmission electron microscope. Apoptosis of tumor tissue were detected by TUNEL staining. RESULTS: Combinations of curcumin and GLUT-1 AS-ODN with 10 Gy inhibited the tumor growth by inducing apoptosis of laryngeal cancer cells followed with the enhancement of autophagy. 3-MA also had a promotion effect on irradiation-mediated growth inhibition possibly by depressing PI3K and on curcumin/GLUT-1 AS-ODN-mediated growth inhibition potentially by regulating autophagic events. Of note, a de-escalation of radiotherapy dose (5 Gy) along with curcumin, GLUT-1 AS-ODN or 3-MA produced a stronger effect than high dosage of radiotherapy (10 Gy) alone. CONCLUSIONS: Curcumin and GLUT-1 AS-ODN improve the radiosensitivity of laryngeal carcinoma through regulating autophagy and inducing apoptosis.