Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

A Potential Pitfall and Clinical Solutions in Surface-Guided Deep Inspiration Breath Hold Radiation Therapy for Left-Sided Breast Cancer.

Purpose: Deep inspiration breath hold (DIBH) is an effective technique to spare the heart in treating left-sided breast cancer. Surface-guided radiation therapy (SGRT) is increasingly applied in DIBH setup and motion monitoring. Patient-specific breathing behavior, either thoracically driven or abdominally driven (A-DIBH), should be unaltered, online identified, and monitored accordingly to ensure reproducible heart-sparing treatment. Methods and Materials: Sixty patients with left-sided breast cancer treated with SGRT were analyzed: 20 A-DIBH patients with vertical chest elevation (VCE ≤ 5 mm) were prospectively identified, and 40 control patients were retrospectively and randomly selected for comparison. At simulation, both free-breathing (FB) and DIBH computed tomography (CT) were acquired, guided by a motion surrogate placed around the xiphoid process. For SGRT treatment setups, the region of interest (ROI) was defined on the CT chest surface, and the surrogate-based setup was a backup. For all 60 patients, the VCE was measured as the average of the FB-to-DIBH elevations at the breast and xiphoid process, together with abdominal elevation. In the 40-patient control group, A-DIBH patients (VCE ≤ 5 mm) were identified. Of the 20 A-DIBH patients, 10 were treated with volumetric modulated arc therapy plans, and 10 patients were treated with tangent plans. Clinical DIBH plans were recalculated on FB CT to compare maximum dose (DMax), 5% of the maximum dose (D5%), mean dose (DMean), and V30Gy, V20Gy, and V5Gy of the heart and lungs and their significance. Results: In the 20 A-DIBH patients, VCE = 3 ± 2 mm, surrogate motion (9 ± 6 mm), and abdomen motion of 14 ± 5 mm are found. Heart dose reduction from FB to DIBH is significant (P < .01): ∆DMax = -8.4 ± 9.8 Gy, ∆D5% = -2.4 ± 4.4 Gy, and ∆DMean = -0.6 ± 0.9 Gy. Six out of 40 control patients (15%) are found to have VCE ≤ 5 mm. Conclusions: A-DIBH (VCE ≤ 5 mm) patient population is significant (15%), and they should be identified in the SGRT workflow and monitored accordingly. A new abdominal ROI or an abdominal surrogate should be used instead of the conventional chest-only ROI. Patient-specific DIBH should be preserved for higher reproducibility to ensure heart sparing.

Investigating the causal impact of gut microbiota on glioblastoma: a bidirectional Mendelian randomization study.

BACKGROUND: Currently, the influence of microbiota on the occurrence, progression, and treatment of cancer is a topic of considerable research interest. Therefore, based on the theory of the gut-brain axis proved by previous studies, our objective was to uncover the causal relationship between glioblastoma and the gut microbiome using Mendelian randomization analysis. METHODS: We conducted a bidirectional Mendelian randomization study using summary statistics of gut microbiota derived from the MiBioGen consortium, the largest database of gut microbiota. Summary statistics for glioblastoma were obtained from IEU OpenGWAS project, which included 91 cases and 218,701 controls. We assessed the presence of heterogeneity and horizontal pleiotropy in the analyzed data. We primarily employed the inverse variance weighting method to investigate the causal relationship between gut microbiota and glioblastoma after excluding cases of horizontal pleiotropy. Four other analysis methods were employed as supplementary. Excluding abnormal results based on leave-one-out sensitivity analysis. Finally, reverse Mendelian randomization analysis was performed. RESULTS: Four genus-level taxa and one family-level taxa exhibited causal associations with glioblastoma. And these results of reverse Mendelian randomization analysis shown glioblastoma exhibited causal associations with three genus-level taxa and one family-level taxa. However, the Prevotella7(Forward, P=0.006, OR=0.34, 95%CI:0.158-0.732; Reverse, P=0.004, OR=0.972, 95%CI:0.953-0.991) shown the causal associations with glioblastoma in the bidirectional Mendelian randomization. CONCLUSIONS: In this bidirectional Mendelian randomization study, we identified five gut microbiota species with causal associations to glioblastoma. However, additional randomized controlled trials are required to clarify the impact of gut microbiota on glioblastoma and to reveal its precise mechanisms.

Photothermally sensitive gold nanocage augments the antitumor efficiency of immune checkpoint blockade in immune "cold" tumors.

Introduction: Immune checkpoint blockade (ICB) has revolutionized the therapy landscape of malignancy melanoma. However, the clinical benefits from this regimen remain limited, especially in tumors lacking infiltrated T cells (known as "cold" tumors). Nanoparticle-mediated photothermal therapy (PTT) has demonstrated improved outcomes in the ablation of solid tumors by inducing immunogenic cell death (ICD) and reshaping the tumor immune microenvironment. Therefore, the combination of PTT and ICB is a promising regimen for patients with "cold" tumors. Methods: A second near-infrared (NIR-II) light-activated gold nanocomposite AuNC@SiO2@HA with AuNC as a kernel, silica as shell, and hyaluronic acid (HA) polymer as a targeting molecule, was synthesized for PTT. The fabricated AuNC@SiO2@HA nanocomposites underwent various in vitro studies to characterize their physicochemical properties, light absorption spectra, photothermal conversion ability, cellular uptake ability, and bioactivities. The synergistic effect of AuNC@SiO2@HA-mediated PTT and anti-PD-1 immunotherapy was evaluated using a mouse model of immune "cold" melanoma. The tumor-infiltrating T cells were assessed by immunofluorescence staining and flow cytometry. Furthermore, the mechanism of AuNC@SiO2@HA-induced T-cell infiltration was investigated through immunochemistry staining of the ICD-related markers, including HSP70, CRT, and HMGB1. Finally, the safety of AuNC@SiO2@HA nanocomposites was evaluated in vivo. Results: The AuNC@SiO2@HA nanocomposite with absorption covering 1064 nm was successfully synthesized. The nano-system can be effectively delivered into tumor cells, transform the optical energy into thermal energy upon laser irradiation, and induce tumor cell apoptosis in vitro. In an in vivo mouse melanoma model, AuNC@SiO2@HA nanocomposites significantly induced ICD and T-cell infiltration. The combination of AuNC@SiO2@HA and anti-PD-1 antibody synergistically inhibited tumor growth via stimulating robust T lymphocyte immune responses. Discussion: The combination of AuNC@SiO2@HA-mediated PTT and anti-PD-1 immunotherapy proposed a neoteric strategy for oncotherapy, which efficiently convert the immune "cold" tumors into "hot" ones.

Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia.

BACKGROUND: There is a mutual hemodynamic and pathophysiological basis between the heart and brain. Glutamate (GLU) signaling plays an important role in the process of myocardial ischemia (MI) and ischemic stroke (IS). To further explore the common protective mechanism after cardiac and cerebral ischemic injuries, the relationship between GLU receptor-related genes and MI and IS were analyzed. RESULTS: A total of 25 crosstalk genes were identified, which were mainly enriched in the Toll-like receptor signaling pathway, Th17 cell differentiation, and other signaling pathways. Protein-protein interaction analysis suggested that the top six genes with the most interactions with shared genes were IL6, TLR4, IL1B, SRC, TLR2, and CCL2. Immune infiltration analysis suggested that immune cells such as myeloid-derived suppressor cells and monocytes were highly expressed in the MI and IS data. Memory B cells and Th17 cells were expressed at low levels in the MI and IS data; molecular interaction network construction suggested that genes such as JUN, FOS, and PPARA were shared genes and transcription factors; FCGR2A was a shared gene of MI and IS as well as an immune gene. Least absolute shrinkage and selection operator logistic regression analysis identified nine hub genes: IL1B, FOS, JUN, FCGR2A, IL6, AKT1, DRD4, GLUD2, and SRC. Receiver operating characteristic analysis revealed that the area under the curve of these hub genes was > 65% in MI and IS for all seven genes except IL6 and DRD4. Furthermore, clinical blood samples and cellular models showed that the expression of relevant hub genes was consistent with the bioinformatics analysis. CONCLUSIONS: In this study, we found that the GLU receptor-related genes IL1B, FOS, JUN, FCGR2A, and SRC were expressed in MI and IS with the same trend, which can be used to predict the occurrence of cardiac and cerebral ischemic diseases and provide reliable biomarkers to further explore the co-protective mechanism after cardiac and cerebral ischemic injury.

Efficacy of radiotherapy in combination with first-line immunotherapy and chemotherapy for advanced lung squamous cell carcinoma: a propensity score analysis.

Aim: To compare the efficacy and safety of radiotherapy in combination with immunotherapy after achieving disease control from the first-line combination therapy of platinum-based chemotherapy and immunotherapy for advanced lung squamous cell carcinoma (LUSC). Methods: This study retrospectively evaluated the patients with advanced LUSC treated with the combination of radiotherapy with immunotherapy and chemotherapy (ICRT group, n = 52) or immunotherapy and chemotherapy (ICT group, n = 63) as the first-line treatment from April 2018 to April 2022. Using propensity score matching (PSM), 50 pairs were created, while the confounders and bias were controlled. The objective response rate (ORR), duration of overall response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed in the two groups. The PFS and OS were re-analyzed separately for patients treated with thoracic radiotherapy. Results: After PSM, the median PFS (12.23 vs. 7.43 months; P <0.001) and median OS (19.7 vs. 12.9 months; P <0.001) were significantly longer in the ICRT group than those in the ICT group. Both the PFS and OS rates were also significantly higher in the ICRT group than those in the ICT group, except for the OS rates in the 6th and 12th months. The mDOR of the ICRT group patients (17.10 vs. 8.27 months; P <0.001) was significantly higher than that of the ICT group patients. The median PFS, median OS, and local control rate were significantly longer in the thoracic radiotherapy group than in the control group. Radiation pneumonia was the most common adverse effect after radiotherapy; however, no treatment-related deaths occurred. The Cox regression analysis showed that ECOG scores 0-1, presence of necrosis in the tumor, radiotherapy, and optimal efficacy better than the stable disease (SD) were independent factors, affecting the PFS, while the patients with recurrent post-operative, pre-treatment NLR, radiotherapy, and optimal efficacy better than SD were the independent factors, affecting the OS. Conclusions: The combination of radiotherapy with systematic immunotherapy and chemotherapy for the advanced LUSC was effective with tolerable adverse effects.

Evidence-based region of interest (ROI) definition for surface-guided radiotherapy (SGRT) of abdominal cancers using deep-inspiration breath-hold (DIBH).

To define and evaluate the appropriate abdominal region of interest (ROI) as a surrogate of diaphragm positioning in deep-inspiration breath-hold (DIBH) for surface-guided radiotherapy (SGRT) of abdominal cancers using 3D optical surface imaging (OSI). Six potential abdominal ROIs were evaluated to calculate their correlations with the diaphragm position using 4DCT images of 20 abdominal patients. Twelve points of interest (POIs) were defined (six on the central soft tissue and six on the bilateral ribs) at three superior-inferior levels, and different sub-groups represented different ROIs. ROI-1 was the largest, containing all 12 POIs from the xiphoid to the umbilicus and between the lateral body midlines while ROI-2 had only eight inferior POIs, ROI-3 had six lateral POIs, and ROI-4 had four superior-lateral POIs over the ribs, ROI-5 contained six central and two most inferior-lateral POIs and ROI-6 contained six central and four inferior-lateral POIs. Internally, the right diaphragm dome was used to represent its positions in 4DCT (0% and 50% within the cycle). The Pearson correlation coefficients were calculated between the diaphragm dome and all 12 external POIs individually or grouped as six ROIs. The quality of the abdominal ROIs was evaluated as potential internal surrogates and, therefore, potential ROIs for SGRT DIBH setup. The four most inferior POIs show the highest mean correlation (r = 0.75) with diaphragmatic motion, and the correlation decreases as POIs move superiorly. The mean correlations are the highest for ROIs with little or no rib support: r = 0.67 for ROI-2, r = 0.64 for ROI-5, and r = 0.63 for ROI-6, while lower for ROIs with rib support: ROI-1 has r = 0.60, ROI-3 has r = 0.50, and ROI-4 has only r = 0.28. This study demonstrates that the rectangular/triangular soft-tissue ROI (with little rib support) is an optimal surrogate for body positioning and diaphragmatic motion, even when treating tumors under the rib cage. This evidence-based ROI definition should be utilized when treating abdominal cancers with free-breathing (FB) and/or DIBH setup.

Intrafractional accuracy and efficiency of a surface imaging system for deep inspiration breath hold during ablative gastrointestinal cancer treatment.

PURPOSE: Beam gating with deep inspiration breath hold (DIBH) usually depends on some external surrogate to infer internal target movement, and the exact internal movement is unknown. In this study, we tracked internal targets and characterized residual motion during DIBH treatment, guided by a surface imaging system, for gastrointestinal cancer. We also report statistics on treatment time. METHODS AND MATERIALS: We included 14 gastrointestinal cancer patients treated with surface imaging-guided DIBH volumetrically modulated arc therapy, each with at least one radiopaque marker implanted near or within the target. They were treated in 25, 15, or 10 fractions. Thirteen patients received treatment for pancreatic cancer, and one underwent separate treatments for two liver metastases. The surface imaging system monitored a three-dimensional surface with ± 3 mm translation and ± 3° rotation threshold. During delivery, a kilovolt image was automatically taken every 20° or 40° gantry rotation, and the internal marker was identified from the image. The displacement and residual motion of the markers were calculated. To analyze the treatment efficiency, the treatment time of each fraction was obtained from the imaging and treatment timestamps in the record and verify system. RESULTS: Although the external surface was monitored and limited to ± 3 mm and ± 3°, significant residual internal target movement was observed in some patients. The range of residual motion was 3-21 mm. The average displacement for this cohort was 0-3 mm. In 19% of the analyzed images, the magnitude of the instantaneous displacement was > 5 mm. The mean treatment time was 17 min with a standard deviation of 4 min. CONCLUSIONS: Precaution is needed when applying surface image guidance for gastrointestinal cancer treatment. Using it as a solo DIBH technique is discouraged when the correlation between internal anatomy and patient surface is limited. Real-time radiographic verification is critical for safe treatments.

Gut microbiome dysbiosis in patients with hepatitis B virus-related hepatocellular carcinoma after extended hepatectomy liver failure.

Background: Hepatitis B virus-related hepatocellular carcinoma (B-HCC) negatively affects the gut microbiome. This study aimed to investigate the gut microbiome profiles and functions post-hepatectomy liver failure (PHLF) after extended hepatectomy (e-PHLF) to obtain valuable insights, identify potential diagnostic biomarkers, and assist in the treatment of this disease. Methods: B-HCC patients who underwent extended hepatectomy were consecutively recruited and divided into Group A (n=15) and Group B (n=15) based on the presence and absence of e-PHLF, respectively. The relationships between gut microbiota and extended hepatectomy liver failure were explored using 16S ribosomal RNA (16S rRNA) gene sequencing data. Results: Following extended hepatectomy, the α-diversity of Group A was significantly higher than that of Group B (Shannon P=0.034 or Simpson P=0.031), and the ß-diversity differed significantly between Groups A and B (P=0.004, R=0.100). At the genus level, 10 bacterial genera (Bacteroides, Pantoea, Methylobacterium-Methylorubrum, Inquilinus, Mycobacterium, Allisonella, Helicobacter, GCA-900066575, IS-44, and Faecalibacterium) were significantly enriched in Group A, whereas five genera (Papillibacter, Scardovia, Turicibacter, Catabacter, and Senegalimassilia) were significantly enriched in Group B. The highly abundant genera Bacteroides, Pantoea, Faecalibacterium, and Turicibacter participated in multiple amino acid metabolism pathways, organic acid metabolism pathways, pyrimidine metabolism pathways, palmitate biosynthesis, and stearate biosynthesis. Redundancy analysis showed that four environmental factors (total bilirubin, international normalized ratio, prealbumin, and albumin) were significantly correlated with intestinal microorganisms. The formation of interaction networks between different gut microbiomes revealed important correlations between the gut microbiome, and there was a significant correlation between the highly abundant gut microbiome and main functions. Conclusions: The gut microbiota characteristics in B-HCC patients after extended hepatectomy liver failure might allow for the use of non-invasive biomarkers for disease diagnosis and treatment.

Operable hepatitis B virus-related hepatocellular carcinoma: gut microbiota profile of patients at different ages.

Background: Age was important prognostic factors for operable hepatocellular carcinoma patients. The aim of the present study was to assess the difference in gut microbiota in patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) at different ages ; to investigate the features of the microbiota and its function associated with different ages; to provide a preliminary look at effects of the gut microbiota dimension on prognostic. Methods: From September 2020 to May 2021, patients with HBV-HCC were able to undergo liver resection and were recruited consecutively and divided into the younger age group (age <45 years) (Y.AG) (n=20), middle age group (age from 45 to 65 years) (M.AG) (n=13) 45-65 years, and older age group (age >65 years) (O.AG) (n=20). The relationships between gut microbiota and different ages were explored using 16S rRNA gene sequencing data. PICRUST2 was used to examine the metagenomic data in PHLF patients. Fisher's exact and Mann-Whitney U-test were used for the data analysis. Results: Pairwise comparison between the three groups showed that the α-diversity of Y.AG was significantly higher than that of O.AG (ACE Index, P=0.017; chao1 Index, P=0.031; observed_species Index, P=0.011; and goods_coverage Index, P=0.041). The ß-diversity in the 3 groups differed significantly (stress =0.100), while the composition (ß-diversity) differed significantly between the Y.AG and the M.AG (stress =0.090), the M.AG and the O.AG (stress =0.095), and the Y.AG and the O.AG (stress =0.099). At the genus level, 7 bacterial genera were significantly enriched in the O.AG compared with the Y.AG, of which Streptococcus, Blautia, Erysipelotrichaceae_UCG-003, and Fusicatenibacter represented the major variances in O.AG microbiomes. Eleven genera were significantly increased in the O.AG, of which Prevotella, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Ruminiclostridium, and Phascolarctobacterium represented the major variances in the O.AG. The Y.AG and the O.AG were predicted by PICRUSt2 analysis, which found 72 pathways related to differential gut microbiome at the genus level. Redundancy analysis showed that 7 environmental factors were significantly correlated with intestinal microorganisms, especially in the Y.AG compared with the O.AG. Conclusions: Analysis of gut microbiota characteristics in patients of different ages could ultimately contribute to the development of novel avenues for the treatment of HCC at different ages.

Integrated omics analysis: the relationship between significantly increased Klebsiella post-hepatectomy and decreased hub-metabolite 3-methyl-2-oxobutanoic acid is associated with induced liver failure.

Background: This study sought to evaluate the association between intestinal Klebsiella and post-hepatectomy liver failure (PHLF) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (B-HCC), and identify the inner relationship. Methods: Patients with B-HCC were divided into Groups A and B based on the presence or absence of PHLF. 16S ribosomal ribonucleic acid surveys were used to identify gut microbiome alterations. PICRUST2 was used to examine the metagenomic data in PHLF patients. Fecal and serum samples were processed by chromatography-mass spectrometry based non-targeted metabonomics, then comprehensively analyzed to obtain hub metabolites. A Spearman correlation analysis was then conducted to find any associations between fecal differential metabolites and the relative abundance of differential microbes. Results: Hepatectomies were significantly associated with a gut microbial imbalance in B-HCC patients, and a significant elevation of Klebsiella abundance was observed in PHLF patients. Klebsiella appears to act on 13 amino acid-related pathways, especially significantly observed in branched-chain amino acid (BCAA) metabolic pathways. Additionally, Klebsiella was found to be highly correlated with 3-methyl-2-oxobutanoic acid shared by feces and serum in the BCAA metabolic pathway. Conclusions: Hepatectomy can lead to an imbalance of intestinal microflora in B-HCC patients. Due to its potential connections with 3-methyl-2-oxobutanoic acid in the BCAA pathway, significantly increased Klebsiella has the potential to be an evaluation indicator of PHLF in B-HCC patients. Moreover, 3-methyl-2-oxobutanoic acid has research value in PHLF-targeted treatments.

Accuracy and efficiency of respiratory gating comparable to deep inspiration breath hold for pancreatic cancer treatment.

PURPOSE: Deep inspiration breath hold (DIBH) and respiratory gating (RG) are widely used to reduce movement of target and healthy organs caused by breathing during irradiation. We hypothesized that accuracy and efficiency comparable to DIBH can be achieved with RG for pancreas treatment. METHODS AND MATERIALS: Twenty consecutive patients with pancreatic cancer treated with DIBH (eight) or RG (twelve) volumetric modulated arc therapy during 2017-2019 were included in this study, with radiopaque markers implanted near or in the targets. Seventeen patients received 25 fractions, while the other three received 15 fractions. Only patients who could not tolerate DIBH received RG treatment. While both techniques relied on respiratory signals from external markers, internal target motions were monitored with kV X-ray imaging during treatment. A 3-mm external gating window was used for DIBH treatment; RG treatment was centered on end-expiration with a duty cycle of 40%, corresponding to an external gating window of 2-3 mm. During dose delivery, kV images were automatically taken every 20◦ or 40◦ gantry rotation, from which internal markers were identified. The marker displacement from their initial positions and the residual motion amplitudes were calculated. For the analysis of treatment efficiency, the treatment time of every session was calculated from the motion management waveform files recorded at the treatment console. RESULTS: Within one fraction, the displacement was 0-5 mm for DIBH and 0-6 mm for RG. The average magnitude of displacement for each patient during the entire course of treatment ranged 0-3 mm for both techniques. No statistically significant difference in displacement or residual motion was observed between the two techniques. The average treatment time was 15 min for DIBH and 17 min for RG, with no statistical significance. CONCLUSIONS: The accuracy and efficiency were comparable between RG and DIBH treatment for pancreas irradiation. RG is a feasible alternative strategy to DIBH.

Intrafraction tumor motion during deep inspiration breath hold pancreatic cancer treatment.

PURPOSE: Beam gating with deep inspiration breath hold (DIBH) has been widely used for motion management in radiotherapy. Normally it relies on some external surrogate for estimating the internal target motion, while the exact internal motion is unknown. In this study, we used the intrafraction motion review (IMR) application to directly track an internal target and characterized the residual motion during DIBH treatment for pancreatic cancer patients through their full treatment courses. METHODS AND MATERIALS: Eight patients with pancreatic cancer treated with DIBH volumetric modulated arc therapy in 2017 and 2018 were selected for this study, each with some radiopaque markers (fiducial or surgical clips) implanted near or inside the target. The Varian Real-time Position Management (RPM) system was used to monitor the breath hold, represented by the anterior-posterior displacement of an external surrogate, namely reflective markers mounted on a plastic block placed on the patient's abdomen. Before each treatment, a cone beam computed tomography (CBCT) scan under DIBH was acquired for patient setup. For scan and treatment, the breath hold reported by RPM had to lie within a 3 mm window. IMR kV images were taken every 20° or 40° gantry rotation during dose delivery, resulting in over 5000 images for the cohort. The internal markers were manually identified in the IMR images. The residual motion amplitudes of the markers as well as the displacement from their initial positions located in the setup CBCT images were analyzed. RESULTS: Even though the external markers indicated that the respiratory motion was within 3 mm in DIBH treatment, significant residual internal target motion was observed for some patients. The range of average motion was from 3.4 to 7.9 mm, with standard deviation ranging from 1.2 to 3.5 mm. For all patients, the target residual motions seemed to be random with mean positions around their initial setup positions. Therefore, the absolute target displacement relative to the initial position was small during DIBH treatment, with the mean and the standard deviation 0.6 and 2.9 mm, respectively. CONCLUSIONS: Internal target motion may differ from external surrogate motion in DIBH treatment. Radiographic verification of target position at the beginning and during each fraction is necessary for precise RT delivery. IMR can serve as a useful tool to directly monitor the internal target motion.

Assessing the Validity of Clinician Advice That Patients Avoid Use of Topical Agents Before Daily Radiotherapy Treatments.

Importance: Radiation dermatitis is common and often treated with topical therapy. Patients are typically advised to avoid topical agents for several hours before daily radiotherapy (RT) out of concern that topical agents might increase the radiation dose to the skin. With modern RT's improved skin-sparing properties, this recommendation may be irrelevant. Objective: To assess whether applying either metallic or nonmetallic topical agents before radiation treatment alters the skin dose. Design, Setting, and Participants: A 24-question online survey of patients and clinicians was conducted from January 15, 2015, to March 15, 2017, to determine current practices regarding topical therapy use. In preclinical studies, dosimetric effect of the topical agents was evaluated by delivering 200 monitor units and measuring the dose at the surface and at 2-cm depth in a tissue-equivalent phantom with or without 2 common topical agents: a petroleum-based ointment (Aquaphor, petrolatum 41%) and silver sulfadiazine cream, 1%. Skin doses associated with various photon and electron energies, topical agent thicknesses, and beam incidence were assessed. Whether topical agents altered the skin dose was also evaluated in 24 C57BL/6 mice by using phosphorylated histone (γ-H2AX) immunofluorescent staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Preclinical studies took place at the University of Pennsylvania. Main Outcomes and Measures: Patient and clinician survey responses; surface radiation dose readings in tissue-equivalent phantom; and γ-H2AX and TUNEL intensity measured in mice. Results: The 133 patients surveyed received RT for cancer and had a median (range) age of 60 (18-86) years; 117 (87.9%) were women. One hundred eight clinicians completed the survey with 105 reporting that they were involved in managing patient skin care during RT. One hundred eleven (83.4%) of the patients and 96 (91.4%) of the 105 clinicians received or gave the advice to avoid applying topical agents before RT treatments. Dosimetric measurements showed no difference in the delivered dose at either the surface or a 2-cm depth with or without a 1- to 2-mm application of either topical agent when using en face 6- or 15-megavoltage (MV) photons. The same application of topicals did not alter the surface dose as a function of beam incident angle from 15° to 60°, except for a 6% increase at 60° with the silver sulfadiazine cream. Surface dose for 6- and 15-MV beams were significantly increased with a thicker (≥3-mm) topical application. For 6 MV, the surface dose was 1.05 Gy with a thick layer of petroleum-based ointment and 1.02 Gy for silver sulfadiazine cream vs 0.88 Gy without topical agents. For 15 MV, the doses were 0.70 Gy for a thick layer of petroleum-based ointment and 0.60 Gy for silver sulfadiazine cream vs 0.52 Gy for the controls. With 6- and 9-MeV electrons, there was a 2% to 5% increase in surface dose with the use of the topical agents. There were no dose differences at 2-cm depth. Irradiated skin in mice showed no differences in γ-H2AX-positive foci or in TUNEL staining with or without topical agents of varying thickness. Conclusions and Relevance: Thin or moderately applied topical agents, even if applied just before RT, may have minimal influence on skin dose regardless of beam energy or beam incidence. The findings of this study suggest that applying very thick amounts of a topical agent before RT may increase the surface dose and should be avoided.

Contour-based lung dose prediction for breast proton therapy.

PURPOSE: This study evaluates the feasibility of lung dose prediction based on target contour and patient anatomy for breast patients treated with proton therapy. METHODS: Fifty-two randomly selected patients were included in the cohort, who were treated to 50.4-66.4 Gy(RBE) to the left (36), right (15), or bilateral (1) breast with uniform scanning (32) or pencil beam scanning (20). Anterior-oblique beams were used for each patient. The prescription doses were all scaled to 50.4 Gy(RBE) for the current analysis. Isotropic expansions of the planning target volume of various margins m were retrospectively generated and compared with isodose volumes in the ipsilateral lung. The fractional volume V of each expansion contour within the ipsilateral lung was compared with dose-volume data of clinical plans to establish the relationship between the margin m and dose D for the ipsilateral lung such that VD  = V(m). This relationship enables prediction of dose-volume VD from V(m), which could be derived from contours before any plan is generated, providing a goal of plan quality. Lung V20 Gy( RBE ) and V5 Gy( RBE ) were considered for this pilot study, while the results could be generalized to other dose levels and/or other organs. RESULTS: The actual V20 Gy( RBE ) ranged from 6% to 23%. No statistically significant difference in V20 Gy( RBE ) was found between breast irradiation and chest wall irradiation (P = 0.8) or between left-side and right-side treatment (P = 0.9). It was found that V(1.1 cm) predicted V20 Gy( RBE ) to within 5% root-mean-square deviation (RMSD) and V(2.2 cm) predicted V5 Gy( RBE ) to within 6% RMSD. CONCLUSION: A contour-based model was established to predict dose to ipsilateral lung in breast treatment. Clinically relevant accuracy was demonstrated. This model facilitates dose prediction before treatment planning. It could serve as a guide toward realistic clinical goals in the planning stage.

A new three-dimensional bis(benzimidazole)-based cadmium(II) coordination polymer.

A new coordination polymer (CP), formulated as [Cd(L)(DCTP)]n (1) (L=1,1'-(1,4-butanediyl)bis(2-methylbenzimidazole), H2DCTP=2,5-dichloroterephthalic acid), was synthesized under hydrothermal conditions and the performance as luminescent probe was also investigated. Single-crystal X-ray diffraction reveals CP 1 is a 3D 3-fold interpenetrated dia network with large well-defined pores. It is found that CP 1 revealed highly sensitive luminescence sensing for Fe3+ ions in acetonitrile solution with a high quenching efficiency of KSV=2541.238L·mol-1 and a low detection limit of 3.2µM (S/N=3). Moreover, the photocatalytic efficiency of 1 for degradation of methylene blue could reach 82.8% after 135min. Therefore, this coordination polymer could be viewed as multifunctional material for selectively sensing Fe3+ ions and effectively degrading dyes.

Avoiding antiperspirants during breast radiation therapy: Myth or sound advice?

Breast cancer patients are typically advised to avoid antiperspirants for fear of increasing radiation dermatitis in the axilla. We hypothesized that antiperspirants would have minimal effect on skin dose. We found no difference in surface dose±antiperspirants using 6MV photons at gantry angles of 0°/30°/60°/90° regardless of aluminum concentration.

Isoliquiritigenin Induces Cytotoxicity in PC-12 Cells In Vitro.

Isoliquiritigenin (ISL) has been reported to have a wide range of biological activities. This study evaluated the cytotoxic effect of ISL on norvegicus pheochromocytoma cell line (PC-12 cells) and its possible molecular mechanism. The cytotoxicity in vitro of ISL against PC-12 cells was investigated by MTT assay. The migration and invasion of PC-12 cells were performed by scratch test and transwell assay. Apoptosis was evaluated by microscopy and flow cytometry. The reactive oxygen species (ROS) and mitochondrial membrane potential were studied by fluorescent microscopy. DNA damage of PC-12 cells was analyzed by comet assay. The protein expression of caspase, Bcl-2 family member, autophagy-associated protein Beclin-1, and LC3 was detected by western blot. The autophagy of PC-12 cells was investigated by acridine orange (AO) and monodansylcadaverine (MDC) staining. The IC50 value of ISL against PC-12 cell is 17.8 ± 1.8 µM. ISL could suppress PC-12 cell migration and invasion. AO/ethidium bromide staining and flow cytometry suggested that ISL caused apoptosis of PC-12 cells. Significant DNA damages of PC-12 cells treated with ISL were observed in a comet assay. ISL inhibited the cell growth of PC-12 cells at S phase. Exposure of PC-12 cells to ISL increased the levels of cellular reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Additionally, ISL trigged the release of cytochrome c from the mitochondria to the cytoplasm. The expression levels of caspase-9, caspase-3, caspase-7, Bax, and Bim were upregulated, whereas the expression levels of Bcl-2 and Bcl-x were downregulated. AO and monodansylcadaverine (MDC) staining assay showed that ISL caused autophagy of PC-12 cells. The upregulation of protein Beclin-1 and LC3 was observed in PC-12 cells. Therefore, the results show that ISL induces apoptosis of PC-12 cells through ROS-mediated activation of the intrinsic mitochondria-cytochrome c-caspase protease mechanism and causes the autophagy of PC-12 cells. Graphical Abstract The in vitro cytotoxicity, apoptosis, comet assay, ROS, mitochondrial membrane potential, cell cycle arrest, autophagy, and western blot induced by ISL were investigated.

Ruthenium(II) polypyridyl complexes: Synthesis, characterization and anticancer activity studies on BEL-7402 cells.

Two new ligand PTTP (2-phenoxy-1,4,8,9-tetraazatriphenylene) and FTTP (2-(3-fluoronaphthalen-2-yloxy)-1,4,8,9-tetraazatriphenylene) and their six ruthenium(II) polypyridyl complexes [Ru(N-N)2(PTTP)](ClO4)2 and [Ru(N-N)2(FTTP)](ClO4)2 (N-N=dmb: 4,4'-dimethyl-2,2'-bipiridine; dmp: 2,9-dimethyl-1,10-phenanthroline; ttbpy: 4,4'-ditertiarybutyl-2,2'-bipyridine) were synthesized and characterized. The cytotoxic activity of the complexes against cancer cells HeLa, BEL-7402, A549, HepG-2, HOS and normal cell LO2 was evaluated by MTT method. The IC50 values range from 1.5±0.1 to 55.9±7.5µM. Complex 3 shows the highest cytotoxic activity toward BEL-7402 cells (IC50=1.5±0.1µM). Complex 5 displays most effective inhibition of the cell growth in A549 and HOS cells with low IC50 values of 2.5±0.6 and 2.6±0.1µM, respectively. The apoptosis, reactive oxygen species, mitochondrial membrane potential, DNA damage, autophagy and anti-metastasis assay were investigated under a fluorescent microscope. The cell cycle arrest was assayed by flow cytometry, and the expression of caspases and Bcl-2 family proteins was studied by western blot. The results obtained show that the complexes induce apoptosis in BEL-7402 cells through a ROS-mediated mitochondrial dysfunction pathway.