Making CT Dose Monitoring Meaningful: Augmenting Dose with Imaging Quality.

Due to the concerns about radiation dose associated with medical imaging, radiation dose monitoring systems (RDMSs) are now utilized by many radiology providers to collect, process, analyze, and manage radiation dose-related information. Currently, most commercially available RDMSs focus only on radiation dose information and do not track any metrics related to image quality. However, to enable comprehensive patient-based imaging optimization, it is equally important to monitor image quality as well. This article describes how RDMS design can be extended beyond radiation dose to simultaneously monitor image quality. A newly designed interface was evaluated by different groups of radiology professionals (radiologists, technologists, and physicists) on a Likert scale. The results show that the new design is effective in assessing both image quality and safety in clinical practices, with an overall average score of 7.8 out of 10.0 and scores ranging from 5.5 to 10.0. Radiologists rated the interface highest at 8.4 out of 10.0, followed by technologists at 7.6 out of 10.0, and medical physicists at 7.5 out of 10.0. This work demonstrates how the assessment of the radiation dose can be performed in conjunction with the image quality using customizable user interfaces based on the clinical needs associated with different radiology professions.

The lncRNA Tincr Regulates the Abnormal Differentiation of Intestinal Epithelial Stem Cells in the Diabetic State Via the miR-668-3p/Klf3 Axis.

BACKGROUND: Diabetes mellitus (DM) is among the most common chronic diseases, and diabetic enteropathy (DE), which is a complication caused by DM, is a serious health condition. Long noncoding RNAs (lncRNAs) are regulators of DE progression. OBJECTIVE: However, the mechanisms of action of multiple lncRNAs involved in DE remain poorly understood. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) and in situ hybridization were used to analyze terminal differentiation-induced lncRNA (Tincr) expression in intestinal epithelial cells (IECs) in the DM state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays were used to identify the genes targeted by Tincr. The role of miR-668-3p was then explored by up- and down-regulating its expression in vitro and in vivo. RESULTS: In this study, we observed that the level of lncRNA Tincr was increased in IECs in the DM state. More importantly, Tincr was associated with abnormal intestinal epithelial stem cell (IESC) differentiation in DM. Our mechanistic study demonstrated that Tincr is a major marker of Lgr5+ stem cells in DM. In addition, we investigated whether Tincr directly targets miR-668-3p and whether miR-668-3p targets Klf3. Our findings showed that Tincr sponged miR-668-3p, which attenuated abnormal IESC differentiation in DM by regulating Klf3 expression. CONCLUSION: This study presents evidence of an essential role for Tincr in IESC differentiation in DM.

Ferroptosis-related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma.

Ferroptosis is a regulated cell death nexus linking metabolism, redox biology and diseases including cancer. The aim of the present study was to identify a ferroptosis-related gene prognostic signature for stomach adenocarcinoma (STAD) by systematic analysis of transcriptional profiles from The Cancer Genome Atlas (TCGA), GEO and a clinical cohort from our centre. We developed a predictive model based on three ferroptosis-related genes (CHAC1, NOX4 and HIF1A), gene expression data and corresponding clinical outcomes were obtained from the TCGA database, and the reliability of this model was verified with GSE15459 and 51 queues in our centre. ROC curve showed better predictive ability using the risk score. Immune cell enrichment analysis demonstrated that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. The experimental results confirmed that NOX4 was upregulated and CHAC1 was downregulated in the STAD tissues compared with the normal stomach mucosal tissues (p < 0.05). In sum, the ferroptosis-related gene signature can accurately predict the outcomes of patients with STAD, providing valuable insights for personalized treatment. As the signature also has relevance to the immune characteristics, it may help improve the efficacy of personalized immunotherapy.

Key Performance Indicators for Quality Imaging Practice: Why, What, and How.

A common trend across health care organizations is the development of key performance indicators (KPIs) for characterizing quality, identifying areas in need of change, and quantifying the impact of change. This article outlines a list of KPIs that can be used to quantify, target, and optimize value and value delivery in medical imaging practice. Of particular focus here is the aspect of practice that should be overseen and informed by the work of medical physicists, along the trajectory and expectations of a Medical Physics 3.0 model. The authors offer a framework for developing site-specific KPIs and several demonstrative clinical examples.

Patient-based Performance Assessment for Pediatric Abdominal CT: An Automated Monitoring System Based on Lesion Detectability and Radiation Dose.

RATIONALE AND OBJECTIVE: To deploy an automated tool for evaluating pediatric body computed tomography (CT) performance utilizing metrics of radiation dose and image quality for the task of liver lesion detection. MATERIALS AND METHODS: This IRB approved retrospective investigation used 507 IV-contrast-enhanced abdominopelvic CT scans of pediatric patients (<18 years) between June 2014 and November 2017 acquired on three scanner models from two manufacturers. The scans were evaluated in terms of radiation metrics (CTDIvol, DLP, and SSDE) as well as task-based performance based on the clinical task of detecting a 5 mm liver lesion with a 10 HU attenuation difference from background liver. An informatics algorithm extracted a previously-validated quantitative detectability index (d') from each case reflective of the likelihood of detecting a liver lesion. The results were analyzed in terms of the relationship between d' and radiation dose metrics. RESULTS: There was minimal SSDE variability by age. Median SSDE at 100 kV on one scanner model was 5.2 mGy (5.0-5.4 mGy interquartile range). However, when assessing image quality by applying d', the age groups separated such that the younger patients had higher d' values than older patients. Similar trends were seen in all scanners. CONCLUSIONS: An automated method to assess clinical image quality for pediatric CT provided a metric of image quality that varied as expected across ages (i.e., higher quality for younger patients). This tool affords the establishment of a quality reference level that, in addition to dose estimations currently available, would allow for enhanced assessment (e.g., facilitated audit) of CT imaging performance.

Immune checkpoint inhibitor combination therapy for gastric cancer: Research progress.

Gastric cancer is one of the most common types of cancer; notably, gastric cancer is one of the top five malignancies with regards to incidence and mortality rates. The symptoms of early gastric cancer are not typical, exhibiting only slight upper abdominal discomfort. When the symptoms become more obvious, the lesion has usually progressed to an advanced stage. Notably, >90% of inpatients already have locally advanced or metastatic gastric cancer at the time of initial diagnosis, with limited treatment options for advanced gastric cancer. These options include chemotherapy, targeted therapy and immune checkpoint inhibitors (ICIs). With regards to ICIs, the clinical benefit of monotherapy for advanced gastric cancer is limited; however, combinations of ICIs and other therapies may have clinical benefit. Relevant clinical studies have demonstrated that combinations of ICIs with chemotherapy, anti-vascular targeted therapy or other molecular targeted therapies, and the use of two ICIs, improve outcomes for patients with advanced gastric cancer. This article is a review of progress in the use of ICIs in combination with other therapies for the treatment of gastric cancer. The purpose of this article was to advance gastric cancer immunotherapy and to improve the overall therapeutic benefit for patients with advanced gastric cancer.

Expression and function of transmembrane 4 superfamily proteins in digestive system cancers.

BACKGROUND: Although the medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found. In recent years, studies have found that four-transmembrane superfamily proteins are involved in multiple stages of tumorigenesis and development, but their expression and function in tumors have not been systematically studied. METHODS: We used the Oncomine database to analyze the mRNA expression levels of TSPAN family in various cancers. Then differentially expressed genes were screened out and verified by liver cancer, colorectal cancer, and gastric cancer cells by q-PCR and Western blot analysis. CCK8 and EDU analysis are used to detect cell proliferation, Cell wound scrape assay and Cell invasion assay are used to analyze cell invasion and metastasis. Nude tumor formation test used to verify the tumor suppressive effect of TSPAN7 in vivo. RESULTS: Differential analysis of 33 TSPAN proteins revealed that a total of 11 proteins showed differential expression in 10% of independent analyses, namely TSPAN1, TSPAN3, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN13, TSPAN25, TSPAN26, TSPAN29, TSPAN30. TSPAN7 is the only four-transmembrane protein with reduced expression in three types of digestive tract tumors, so we chose TSPAN7 to be selected for cellular and molecular level verification. We found that compared with normal cells, the expression of TSPAN7 in liver cancer cells was significantly reduced, while the expression of gastric and colon cancer was not significantly different from that of normal cells. In addition, we also found that the high expression of Tspan7 not only inhibited the proliferation of HCC-LM3 cells, but also inhibited its invasion and metastasis. CONCLUSIONS: Our study evaluated the expression and function of the TSPANs family in digestive cancers and explored TSPAN7 in hepatoma cells in detail. We found some members of the TSPAN family show significant expression differences between cancer and normal tissues, of which TSPAN7 may be a potential biomarker for liver cancer.

TSPAN9 suppresses the chemosensitivity of gastric cancer to 5-fluorouracil by promoting autophagy.

BACKGROUND: The issue of drug resistance in gastric cancer has attracted global attention. TSPAN9, a 4-transmembrane protein that plays an important role in tumor progression and signal transduction, has been found to be closely related to tumor invasion, metastasis, and autophagy. METHODS: Immunoblotting was used to evaluate TSPAN9 expression in parental and drug-resistant gastric cancer cells. Functional assays, such as the CCK-8 assay, were used to detect the proliferation of gastric cancer cells and the response of TSPAN9 to 5-fluorouracil (5-FU). Western blotting was used to analyze the expression of constituents of the PI3K/AKT/mTOR-mediated autophagy pathway induced by TSPAN9. Coimmunoprecipitation was performed to assess the specific mechanism by which TSPAN9 affects the PI3K pathway. RESULTS: We demonstrated that TSPAN9 is overexpressed in 5-FU-resistant cells compared to parental cells. 5-FU-mediated inhibition of cell proliferation can be significantly restored by increasing TSPAN9 expression, and inhibiting this expression in drug-resistant cells can restore the sensitivity of the cells to 5-FU. In addition, TSPAN9 also significantly promoted autophagy in gastric cancer cells in vitro. Further studies indicated that TSPAN9 downregulates the expression of PI3K and proteins associated with PI3K-mediated autophagy. In addition, TSPAN9 interacts with PI3K and inhibits its catalytic activity. CONCLUSION: The current study reveals the important role of TSPAN9 in drug resistance to 5-FU in gastric cancer. It also provides a new target to clinically address drug-resistant gastric cancer and will contribute to the treatment strategy of this disease.

Acidic stress induces protective autophagy in SGC7901 cells.

Objective To investigate the effect of acidity on gastric cancer SGC7901 cells in terms of autophagy and provide a new strategy for therapeutically targeting gastric cancer autophagy in an acidic environment. Methods Transmission electron microscopy (TEM) and confocal laser scanning microscopy were used to examine the effect of an acidic environment on autophagosome formation. Light chain 3 (LC3) and p62 levels in SGC7901 cells exposed to acidic conditions were measured using Western blot analysis. To explore changes in autophagy flux, the cells were treated with an inhibitor of autophagy bafilomycin A1. The CCK-8 assay was performed to determine if inhibiting acid-induced autophagy affected cell proliferation. Results Increased autophagosome formation was observed by TEM. Punctate LC3 structures were observed in cells cultured under acidic conditions, whereas untreated cells exhibited diffuse and weak staining for punctate LC3 structures. Cytoplasmic LC3-I translocated to the autophagic membrane (LC3-II) levels increased under acidic conditions, whereas p62 levels decreased. The bafilomycin A1-induced inhibition of autophagy caused by the acidic environment inhibited cell proliferation. Conclusion The acidic environment upregulates autophagy in SGC7901 cells. In long-term culture, a stable and high level of autophagy is maintained in an acidic environment, which has a protective effect on cells.

Outcomes of adjuvant epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutant non-small-cell lung cancer: a propensity-score analysis.

Small molecule tyrosine kinase inhibitors (TKIs) have transformed the management of advanced non-small-cell lung cancer (NSCLC) harboring activating epithelial growth factor receptor (EGFR) mutations, while the efficacy of TKIs in the adjuvant setting remains unclear. We collected the data of 209 EGFR-mutant NSCLC patients receiving complete resection from 2010 to 2013. Study end points were disease-free survival (DFS) and overall survival (OS). Among the eligible patients, 41 (19.6%) received EGFR TKIs in the adjuvant treatment. The 3-year DFS of adjuvant EGFR TKIs treatment group (70.5%, 95% CI, 54.6-86.4%) was significantly superior that control group (50.2%, 95% CI, 40-60.4%; log-rank P = 0.014). TKIs treatment (HR, 0.51; 95% CI, 0.29-0.97; P = 0.04) was significantly associated with improved DFS in multivariate Cox analysis. No significant difference was observed in 3-year OS between two groups (73.1% [58.0-88.2%] vs 61.8% [52.2-71.4%], log-rank P = 0.21). Propensity-score matching further confirmed that adjuvant TKIs treatment extended the DFS (log-rank P = 0.024), but did not improve OS (log-rank P = 0.40). Our analysis revealed that adjuvant EGFR TKIs treatment was beneficial for early-stage NSCLC patients harboring activating EGFR mutations after complete resection.

Pixel response-based EPID dosimetry for patient specific QA.

Increasing use of high dose rate, flattening filter free (FFF), and/or small-sized field beams presents a significant challenge to the medical physics community. In this work, we develop a strategy of using a high spatial resolution and high frame rate amorphous silicon flat panel electronic portal imaging device (EPID) for dosimetric measurements of these challenging cases, as well as for conventional external beam therapy. To convert a series of raw EPID-measured radiation field images into water-based dose distribution, a pixel-to-pixel dose-response function of the EPID specific to the linac is essential. The response function was obtained by using a Monte Carlo simulation of the photon transport in the EPID with a comprehensive calibration. After the raw image was converted into the primary incident photon fluence, the fluence was further convolved into a water-based dose distribution of the dynamic field by using a pregenerated pencil-beam kernel. The EPID-based dosimetric measurement technique was validated using beams with and without flattening filter of all energies available in Varian TrueBeam STx™. Both regularly and irregularly shaped fields measured using a PTW 729 ion chamber array in plastic water phantom. The technique was also applied to measure the distribution for a total of 23 treatment plans of different energies to evaluate the accuracy of the proposed approach. The EPID measurements of square fields of 4 × 4 cm2 to 20 × 20 cm2, circular fields of 2-15 cm diameters, rectangular fields of various sizes, and irregular MLC fields were in accordance with measurements using a Farmer chamber and/or ion chamber array. The 2D absolute dose maps generated from EPID raw images agreed with ion chamber measurements to within 1.5% for all fields. For the 23 patient cases examined in this work, the average γ-index passing rate were found to be 99.2 ± 0.6%, 97.4 ± 2.4%, and 72.6 ± 8.4%, respectively, for criterions of 3 mm/3%, 2 mm/2%, and 1 mm/1%. The high spatial resolution and high frame rate EPID provides an accurate and efficient dosimetric tool for QA of modern radiation therapy. Accurate absolute 2D dose maps can be generated from the system for an independent dosimetric verification of treatment delivery.

Association of Mixed Lineage Kinase Domain-Like Protein Expression With Prognosis in Patients With Colon Cancer.

BACKGROUND: The mixed lineage kinase domain-like protein has recently been identified as a key downstream component of tumor necrosis factor-induced necroptosis, which is an important pathway of cancer cell death. The goal of the current study is to explore the expression of mixed lineage kinase domain-like protein in colon cancer tissues and evaluate the prognostic value in patients with colon cancer. METHODS: We collected normal and cancer colon tissues from 135 patients diagnosed with colon cancer after radical operation during July 2007 to April 2009 at The Affiliated Hospital of Qingdao University. Immunohistochemistry analysis was scored using an established scoring system. Kaplan-Meier survival curves were generated for recurrence-free survival and overall survival for all patients and 2 subsets of patients. The relationship between mixed lineage kinase domain-like protein expression and prognosis parameter (recurrence-free survival, overall survival) was analyzed by univariate and multivariate Cox regression analyses. RESULTS: The median age of all patients was 67 years and 56.3% were male. Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (78.6 vs 81.2 months; P = .011) in all patients. In the subset of 79 patients who received adjuvant chemotherapy, low expression of mixed lineage kinase domain-like protein was associated with decreased recurrence-free survival (60.4 vs 72.8 months; P = .032) and decreased overall survival (66.3 vs 72.9 months; P = .005). Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival (74.9 vs 79.8 months; P = .006) and recurrence-free survival (69.6 vs 78.8 months; P = .005) among patients with Tumor Node Metastasis (TNM) stage II colon cancer. CONCLUSIONS: Low expression of mixed lineage kinase domain-like protein was associated with decreased overall survival in all patient-group with resected colon cancer. It is associated with decreased recurrence-free survival and overall survival in the subset of patients who receive adjuvant chemotherapy and patients who were TNM stage II. Mixed lineage kinase domain-like protein may provide important prognostic information in patients with colon cancer.

Prognostic significance of Tspan9 in gastric cancer.

Tetraspanins are a large superfamily of glycoproteins, which are engaged in a wide range of specific molecular interactions by forming tetraspanin-enriched microdomains. Tetraspanin 9 (Tspan9) is a previously poorly studied tetraspanin gene, which was predominantly identified as an amplified gene in serous Fallopian tube carcinoma. However, the expression and role of Tspan9 in gastric cancer have yet to be fully elucidated. The aim of the present study was to evaluate the expression and clinical significance of Tspan9 in gastric cancer. In the present study, 105 gastric cancer tissue samples and corresponding adjacent normal samples were detected for Tspan9 expression using immunohistochemistry; furthermore, the association between clinical characteristics and Tspan9 expression was also analyzed. Tspan9 expression was determined to be significantly lower in cancer samples compared with those in corresponding adjacent normal samples (P<0.001). However, its increased levels of expression in cancer samples appeared to demonstrate a poorer prognostic tendency, which is associated with deeper tumor depth (P=0.025), more nodal involvement (P=0.01), more advanced tumor/lymph node/metastasis (TNM) stages (P=0.017) and a larger tumor size (P=0.026). Additionally, multivariate analysis demonstrated that high expression of Tspan9 was an independent prognostic factor for poor overall survival (P<0.01). These results suggested that Tspan9 may be used as a potential prognostic factor in gastric cancer.

VirtualDose: a software for reporting organ doses from CT for adult and pediatric patients.

This paper describes the development and testing of VirtualDose--a software for reporting organ doses for adult and pediatric patients who undergo x-ray computed tomography (CT) examinations. The software is based on a comprehensive database of organ doses derived from Monte Carlo (MC) simulations involving a library of 25 anatomically realistic phantoms that represent patients of different ages, body sizes, body masses, and pregnant stages. Models of GE Lightspeed Pro 16 and Siemens SOMATOM Sensation 16 scanners were carefully validated for use in MC dose calculations. The software framework is designed with the 'software as a service (SaaS)' delivery concept under which multiple clients can access the web-based interface simultaneously from any computer without having to install software locally. The RESTful web service API also allows a third-party picture archiving and communication system software package to seamlessly integrate with VirtualDose's functions. Software testing showed that VirtualDose was compatible with numerous operating systems including Windows, Linux, Apple OS X, and mobile and portable devices. The organ doses from VirtualDose were compared against those reported by CT-Expo and ImPACT-two dosimetry tools that were based on the stylized pediatric and adult patient models that were known to be anatomically simple. The organ doses reported by VirtualDose differed from those reported by CT-Expo and ImPACT by as much as 300% in some of the patient models. These results confirm the conclusion from past studies that differences in anatomical realism offered by stylized and voxel phantoms have caused significant discrepancies in CT dose estimations.

Development of an accurate EPID-based output measurement and dosimetric verification tool for electron beam therapy.

PURPOSE: To develop an efficient and robust tool for output measurement and absolute dose verification of electron beam therapy by using a high spatial-resolution and high frame-rate amorphous silicon flat panel electronic portal imaging device (EPID). METHODS: The dosimetric characteristics of the EPID, including saturation, linearity, and ghosting effect, were first investigated on a Varian Clinac 21EX accelerator. The response kernels of the individual pixels of the EPID to all available electron energies (6, 9, 12, 16, and 20 MeV) were calculated by using Monte Carlo (MC) simulations, which formed the basis to deconvolve an EPID raw images to the incident electron fluence map. The two-dimensional (2D) dose distribution at reference depths in water was obtained by using the constructed fluence map with a MC simulated pencil beam kernel with consideration of the geometric and structural information of the EPID. Output factor measurements were carried out with the EPID at a nominal source-surface distance of 100 cm for 2 × 2, 3 × 3, 6 × 6, 10 × 10, and 15 × 15 cm(2) fields for all available electron energies, and the results were compared with that measured in a solid water phantom using film and a Farmer-type ion chamber. The dose distributions at a reference depth specific to each energy and the flatness and symmetry of the 10 × 10 cm(2) electron beam were also measured using EPID, and the results were compared with ion chamber array and water scan measurements. Finally, three patient cases with various field sizes and irregular cutout shapes were also investigated. RESULTS: EPID-measured dose changed linearly with the monitor units and showed little ghosting effect for dose rate up to 600 MU/min. The flatness and symmetry measured with the EPID were found to be consistent with ion chamber array and water scan measurements. The EPID-measured output factors for standard square fields of 2 × 2, 3 × 3, 6 × 6, 10 × 10, 15 × 15 cm(2) agreed with film and ion chamber measurements. The average discrepancy between EPID and ion chamber/film measurements was 0.81% ± 0.60% (SD) and 1.34% ± 0.75%, respectively. For the three clinical cases, the difference in output between the EPID- and ion chamber array measured values was found to be 1.13% ± 0.11%, 0.54% ± 0.10%, and 0.74% ± 0.11%, respectively. Furthermore, the γ-index analysis showed an excellent agreement between the EPID- and ion chamber array measured dose distributions: 100% of the pixels passed the criteria of 3%/3 mm. When the γ-index was set to be 2%/2 mm, the pass rate was found to be 99.0% ± 0.07%, 98.2% ± 0.14%, and 100% for the three cases. CONCLUSIONS: The EPID dosimetry system developed in this work provides an accurate and reliable tool for routine output measurement and dosimetric verification of electron beam therapy. Coupled with its portability and ease of use, the proposed system promises to replace the current film-based approach for fast and reliable assessment of small and irregular electron field dosimetry.

Independent calculation of monitor units for VMAT and SPORT.

PURPOSE: Dose and monitor units (MUs) represent two important facets of a radiation therapy treatment. In current practice, verification of a treatment plan is commonly done in dose domain, in which a phantom measurement or forward dose calculation is performed to examine the dosimetric accuracy and the MU settings of a given treatment plan. While it is desirable to verify directly the MU settings, a computational framework for obtaining the MU values from a known dose distribution has yet to be developed. This work presents a strategy to calculate independently the MUs from a given dose distribution of volumetric modulated arc therapy (VMAT) and station parameter optimized radiation therapy (SPORT). METHODS: The dose at a point can be expressed as a sum of contributions from all the station points (or control points). This relationship forms the basis of the proposed MU verification technique. To proceed, the authors first obtain the matrix elements which characterize the dosimetric contribution of the involved station points by computing the doses at a series of voxels, typically on the prescription surface of the VMAT/SPORT treatment plan, with unit MU setting for all the station points. An in-house Monte Carlo (MC) software is used for the dose matrix calculation. The MUs of the station points are then derived by minimizing the least-squares difference between doses computed by the treatment planning system (TPS) and that of the MC for the selected set of voxels on the prescription surface. The technique is applied to 16 clinical cases with a variety of energies, disease sites, and TPS dose calculation algorithms. RESULTS: For all plans except the lung cases with large tissue density inhomogeneity, the independently computed MUs agree with that of TPS to within 2.7% for all the station points. In the dose domain, no significant difference between the MC and Eclipse Anisotropic Analytical Algorithm (AAA) dose distribution is found in terms of isodose contours, dose profiles, gamma index, and dose volume histogram (DVH) for these cases. For the lung cases, the MC-calculated MUs differ significantly from that of the treatment plan computed using AAA. However, the discrepancies are reduced to within 3% when the TPS dose calculation algorithm is switched to a transport equation-based technique (Acuros™). Comparison in the dose domain between the MC and Eclipse AAA/Acuros calculation yields conclusion consistent with the MU calculation. CONCLUSIONS: A computational framework relating the MU and dose domains has been established. The framework does not only enable them to verify the MU values of the involved station points of a VMAT plan directly in the MU domain but also provide a much needed mechanism to adaptively modify the MU values of the station points in accordance to a specific change in the dose domain.

The profound effects of patient arm positioning on organ doses from CT procedures calculated using Monte Carlo simulations and deformable phantoms.

The purpose of this study was to evaluate the organ dose differences caused by the arms-raised and arms-lowered postures for multidetector computed tomography procedures. Organ doses were calculated using computational phantoms and Monte Carlo simulations. The arm position in two previously developed adult male and female human phantoms was adjusted to represent 'raised' and 'lowered' postures using advanced BREP-based mesh surface geometries. Organ doses from routine computed tomography (CT) scan protocols, including the chest, abdomen-pelvis, and chest-abdomen-pelvis scans, were simulated at various tube voltages and reported in the unit of mGy per 100 mAs. The CT scanner model was based on previously tested work. The differences in organ dose per unit tube current between raised and lowered arm postures were studied. Furthermore, the differences due to the tube current modulation (TCM) for these two different postures and their impact on organ doses were also investigated. For a given scan parameter, a patient having lowered arms received smaller doses to organs located within the chest, abdomen or pelvis when compared with the patient having raised arms. As expected, this is caused by the attenuation of the primary X rays by the arms. However, the skin doses and bone surface doses in the patient having lowered arms were found to be 3.97-32.12% larger than those in a patient having raised arms due to the fact that more skin and spongiosa were covered in the scan range when the arms are lowered. This study also found that dose differences become smaller with the increase in tube voltage for most of organs or tissues except the skin. For example, the liver dose differences decreased from -15.01 to -11.33% whereas the skin dose differences increased from 21.53 to 25.24% with tube voltage increased from 80 to 140 kVp. With TCM applied, the organ doses of all the listed organs in patient having lowered arms are larger due to the additional tube current necessary to overcome the presence of the arms while maintaining sufficient image quality Arm position affects the dose to internal organs from CT scans by as much as 25.3%. The presence of arms in the scan range results in a dose increase for the skin and bone surface, but a dose decrease for organs located in the torso. Considering the use of TCM, which is common in many clinics, the patient having lowered arms may receive 50% higher radiation dose to most of the organs because of the increased tube current. The use of higher tube voltage might narrow such dose differences between patients of these two postures due to the greater penetration of higher-energy X rays. Therefore, when calculating or reporting patient doses from CT scans, it is prudent to select an appropriate phantom that accurately represents the patient posture.

A dose-reconstruction study of the 1997 Sarov criticality accident using animated dosimetry techniques.

Most computational human phantoms are static, representing a standing individual. There are, however, cases when these phantoms fail to represent accurately the detailed effects on dose that result from considering varying human posture and even whole sequences of motion. In this study, the feasibility of a dynamic and deformable phantom is demonstrated with the development of the Computational Human for Animated Dosimetry (CHAD) phantom. Based on modifications to the limb structure of the previously developed RPI Adult Male, CHAD's posture is adjustable using an optical motion capture system that records real-life human movement. To demonstrate its ability to produce dose results that reflect the changes brought about by posture-deformation, CHAD is employed to perform a dose-reconstruction analysis of the 1997 Sarov criticality accident, and a simulated total body dose of 13.3 Gy is observed, with the total body dose rate dropping from 1.4 Gy s to 0.25 Gy s over the first 4 s of retreat time. Additionally, dose measurements are calculated for individual organs and body regions, including a 36.8-Gy dose to the breast tissue, a 3.8-Gy dose to the bladder, and a 31.1-Gy dose to the thyroid, as well as the changes in dose rates for the individual organs over the course of the accident sequence. Comparison of results obtained using CHAD in an animated dosimetry simulation with reported information on dose and the medical outcome of the case shows that the consideration of posture and movement in dosimetry simulation allows for more detailed and precise analysis of dosimetry information, consideration of the evolution of the dose profile over time in the course of a given scenario, and a better understanding of the physiological impacts of radiation exposure for a given set of circumstances.

Inhibition of ErbB-2 induces TFF3 downregulation in breast cancer cell lines.

ErbB-2 gene plays an important role in carcinoma formation whose overexpression was observed in many types of tumors, including breast cancer. Dysregulation of Trefoil factor 3 (TFF3), which is thought to function in the development and progression of breast cancer, was found to be upregulated in ErbB2-overexpressing breast cancers and cells. However, a putative interaction between ErbB-2 and TFF3 in breast cancer remains unknown. To determine whether TFF3 has an important role in breast tumor, its levels were measured by immunohistochemistry in 130 cases of breast infiltrating duct carcinoma and 30 cases of normal breast tissue with a specific monoclonal antibody raised against human TFF3. Patients who were positive for ErbB-2 also had high expression levels of TFF3 (p < 0.05). Also, after infecting the SK-BR-3 cells with lentivirus-mediated ErbB2-specific shRNA (Lenti-ShERBB2), we detected the expressions of ErbB-2 and TFF3 by real-time polymerase chain reaction and Western blotting, respectively. Compared with the control groups, ErbB-2 mRNA expression was decreased in the Lenti-ShERBB2 infection group, and Western blotting indicated a concordant ErbB-2 protein reduction. On the other hand, TFF3 expression at both mRNA and protein levels was significantly downregulated by ErbB-2 silencing in SK-BR-3. These findings are a proof of the foundation for a certain relationships of ErbB-2 and TFF3, which may serve as novel therapeutic markers of ErbB2-overexpressing breast cancers in the future.

Impact of NPM, TFF3 and TACC1 on the prognosis of patients with primary gastric cancer.

BACKGROUND: NPM, TFF3 and TACC1 are molecular markers that play important roles in cell differentiation. Herein, we investigated their prognostic impact in patients with primary gastric cancer (GC) and determined whether they could be used as markers of more aggressive gastric carcinomas by detecting the extent of expression in human gastric carcinoma samples. METHODOLOGY/PRINCIPAL FINDINGS: Tumor tissue specimens from 142 GC patients were retrospectively retrieved and immunohistochemically evaluated. Correlations between NPM, TFF3 and TACC1 over-expression and clinicopathologic parameters, and their prognostic values were investigated with χ(2), Kaplan-Meier method, and Cox uni- and multivariate survival models. NPM, TFF3 and TACC1 expression was significantly higher in GC patients with poorly differentiated histologic type than that in patients with well differentiated histologic type. NPM expression was significantly higher in patients with hepatic metastasis or recurrence than that in patients without metastasis. TFF3 expression was significantly higher in patients with positive lymph node metastasis than that in patients with negative lymph node metastasis. Age, lymph node metastasis, and TFF3 and TACC1 over-expression were significantly correlated with low survival (P<0.05, P<0.05, P = 0.005 and P = 0.009, respectively). Multivariate analysis showed that lymph node metastasis and TFF3 and TACC1 over-expression were independent prognostic factors. CONCLUSIONS: TFF3 and TACC1 over-expression in epithelial cells of surgically resected GC tissues was an independent predictor of short survival in GC patients. The prognosis was poorer in patients with positive expression of both TFF3 and TACC1 than that in patients with positive expression of TFF3 or TACC1 alone, or with negative expression of TFF3 and TACC1.