Dynamic change in the peritoneal cancer index based on CT after chemotherapy in the overall survival prediction of gastric cancer patients with peritoneal metastasis.

PURPOSE: The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy. METHODS: This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression. RESULTS: The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than -15% had significantly longer OS. CONCLUSION: CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.

Fully semantic segmentation for rectal cancer based on post-nCRT MRl modality and deep learning framework.

PURPOSE: Rectal tumor segmentation on post neoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) has great significance for tumor measurement, radiomics analysis, treatment planning, and operative strategy. In this study, we developed and evaluated segmentation potential exclusively on post-chemoradiation T2-weighted MRI using convolutional neural networks, with the aim of reducing the detection workload for radiologists and clinicians. METHODS: A total of 372 consecutive patients with LARC were retrospectively enrolled from October 2015 to December 2017. The standard-of-care neoadjuvant process included 22-fraction intensity-modulated radiation therapy and oral capecitabine. Further, 243 patients (3061 slices) were grouped into training and validation datasets with a random 80:20 split, and 41 patients (408 slices) were used as the test dataset. A symmetric eight-layer deep network was developed using the nnU-Net Framework, which outputs the segmentation result with the same size. The trained deep learning (DL) network was examined using fivefold cross-validation and tumor lesions with different TRGs. RESULTS: At the stage of testing, the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and mean surface distance (MSD) were applied to quantitatively evaluate the performance of generalization. Considering the test dataset (41 patients, 408 slices), the average DSC, HD95, and MSD were 0.700 (95% CI: 0.680-0.720), 17.73 mm (95% CI: 16.08-19.39), and 3.11 mm (95% CI: 2.67-3.56), respectively. Eighty-two percent of the MSD values were less than 5 mm, and fifty-five percent were less than 2 mm (median 1.62 mm, minimum 0.07 mm). CONCLUSIONS: The experimental results indicated that the constructed pipeline could achieve relatively high accuracy. Future work will focus on assessing the performances with multicentre external validation.

Early Contrast-Enhanced MR for Diagnosing Complete Tumor Response of Locally Advanced Esophageal Squamous Cell Carcinoma After Neoadjuvant Therapy: A Retrospective Comparative Study.

BACKGROUND: This study assessed the performance of early contrast-enhanced magnetic resonance (ECE-MR) in the detecting of complete tumor response (ypT0) in patients with esophageal squamous cell carcinoma following neoadjuvant therapy. PATIENTS AND METHODS: Preoperative MR images of consecutive patients who underwent neoadjuvant therapy and surgical resection were reviewed retrospectively. The accuracy of ECE-MR and T2WI+DWI was evaluated by comparing the findings with pathological results. Receiver operating characteristic curve analysis was used to assess the diagnostic performance, and DeLong method was applied to compare the areas under the curves (AUC). Chi-squared analysis was conducted to explore the difference in pathological changes. RESULTS: A total of 198 patients (mean age 62.6 ± 7.8 years, 166 men) with 201 lesions were included. The AUC of ECE-MR was 0.85 (95% CI 0.79-0.90) for diagnosing ypT1-4, which was significantly higher than that of T2WI+DWI (AUC 0.69, 95% CI 0.63-0.76, p < 0.001). The diagnostic performance of both T2WI+DWI and ECE-MR improved with increasing tumor stage. The AUCs of ECE-MRI were higher in ypT1 and ypT2 tumors than T2WI+DWI. Degree 2-3 tumor-infiltrating lymphocytes and neutrophils were commonly seen in ypT0 tumors misdiagnosed by ECE-MR. CONCLUSIONS: Visual evaluation of ECE-MR is a promising diagnostic protocol for the detection of complete tumor response, especially for differentiation with early stage tumors. The accurate diagnosis of complete tumor response after neoadjuvant therapy using imaging modalities is of important significance for clinical decision-making for patients with esophageal squamous cell carcinoma. It is hoped that early contrast-enhanced MR will provide supportive advice for the development of individualized treatment options for patients.

CT radiomics in the identification of preoperative understaging in patients with clinical stage T1-2N0 esophageal squamous cell carcinoma.

Background: Predicting preoperative understaging in patients with clinical stage T1-2N0 (cT1-2N0) esophageal squamous cell carcinoma (ESCC) is critical to customizing patient treatment. Radiomics analysis can provide additional information that reflects potential biological heterogeneity based on computed tomography (CT) images. However, to the best of our knowledge, no studies have focused on identifying CT radiomics features to predict preoperative understaging in patients with cT1-2N0 ESCC. Thus, we sought to develop a CT-based radiomics model to predict preoperative understaging in patients with cT1-2N0 esophageal cancer, and to explore the value of the model in disease-free survival (DFS) prediction. Methods: A total of 196 patients who underwent radical surgery for cT1-2N0 ESCC were retrospectively recruited from two hospitals. Among the 196 patients, 134 from Peking University Cancer Hospital were included in the training cohort, and 62 from Henan Cancer Hospital were included in the external validation cohort. Radiomics features were extracted from patients' CT images. Least absolute shrinkage and selection operator (LASSO) regression was used for feature selection and model construction. A clinical model was also built based on clinical characteristics, and the tumor size [the length, thickness and the thickness-to-length ratio (TLR)] was evaluated on the CT images. A radiomics nomogram was established based on multivariate logistic regression. The diagnostic performance of the models in predicting preoperative understaging was assessed by the area under the receiver operating characteristic curve (AUC). Kaplan-Meier curves with the log-rank test were employed to analyze the correlation between the nomogram and DFS. Results: Of the patients, 50.0% (67/134) and 51.6% (32/62) were understaged in the training and validation groups, respectively. The radiomics scores and the TLRs of the tumors were included in the nomogram. The AUCs of the nomogram for predicting preoperative understaging were 0.874 [95% confidence interval (CI): 0.815-0.933] in the training cohort and 0.812 (95% CI: 0.703-0.912) in the external validation cohort. The diagnostic performance of the nomogram was superior to that of the clinical model (P<0.05). The nomogram was an independent predictor of DFS in patients with cT1-2N0 ESCC. Conclusions: The proposed CT-based radiomics model could be used to predict preoperative understaging in patients with cT1-2N0 ESCC who have undergone radical surgery.

CT radiomics features of meso-esophageal fat in predicting overall survival of patients with locally advanced esophageal squamous cell carcinoma treated by definitive chemoradiotherapy.

OBJECTIVE: To investigate the value of CT radiomics features of meso-esophageal fat in the overall survival (OS) prediction of patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 166 patients with locally advanced ESCC in two medical centers were retrospectively analyzed. The volume of interest (VOI) of meso-esophageal fat and tumor were manually delineated on enhanced chest CT using ITK-SNAP. Radiomics features were extracted from the VOIs by Pyradiomics and then selected using the t-test, the Cox regression analysis, and the least absolute shrinkage and selection operator. The radiomics scores of meso-esophageal fat and tumors for OS were constructed by a linear combination of the selected radiomic features. The performance of both models was evaluated and compared by the C-index. Time-dependent receiver operating characteristic (ROC) analysis was employed to analyze the prognostic value of the meso-esophageal fat-based model. A combined model for risk evaluation was constructed based on multivariate analysis. RESULTS: The CT radiomic model of meso-esophageal fat showed valuable performance for survival analysis, with C-indexes of 0.688, 0.708, and 0.660 in the training, internal, and external validation cohorts, respectively. The 1-year, 2-year, and 3-year ROC curves showed AUCs of 0.640-0.793 in the cohorts. The model performed equivalently compared to the tumor-based radiomic model and performed better compared to the CT features-based model. Multivariate analysis showed that meso-rad-score was the only factor associated with OS. CONCLUSIONS: A baseline CT radiomic model based on the meso-esophagus provide valuable prognostic information for ESCC patients treated with dCRT.

TL1A induces apoptosis via DR3 in grass carp (Ctenopharyngodon idella).

Tumor necrosis factor like ligand 1A (TL1A), a member of TNF superfamily, regulates inflammatory response and immune defense. TL1A homologues have recently been discovered in fish, but their functions have not been studied. In this study, a TL1A homologue was identified in grass carp (Ctenopharyngodon idella) and its bioactivities were investigated. The grass carp tl1a (Citl1a) gene was constitutively expressed in tissues, with the highest expression detected in the liver. It was upregulated in response to infection with Aeromonas hydrophila. The recombinant CiTL1A was produced in bacteria and was shown to stimulate the expression of il1ß, tnfα, caspase 8 and ifnγ in the primary head kidney leucocytes. In addition, co-immunoprecipitation assay revealed that CiTL1A interacted with DR3 and induced apoptosis via activation of DR3. The results demonstrate that TL1A regulates inflammation and apoptosis and is involved in the immune defense against bacterial infection in fish.

A CT-Based Radiomics Nomogram Model for Differentiating Primary Malignant Melanoma of the Esophagus from Esophageal Squamous Cell Carcinoma.

Objective: The diagnosis of primary malignant melanoma of the esophagus (PMME) before treatment is essential for clinical decision-making. However, PMME may be misdiagnosed as esophageal squamous cell carcinoma (ESCC) sometimes. This research is aimed at devising a radiomics nomogram model of CT for distinguishing PMME from ESCC. Methods: In this retrospective analysis, 122 individuals with proven pathologically PMME (n = 28) and ESCC (n = 94) were registered from our hospital. PyRadiomics was applied to derive radiomics features from plain and enhanced CT images after resampling image into an isotropic resolution of 0.625 × 0.625 × 0.625 mm3. The diagnostic efficiency of the model was evaluated by an independent validation group. Results: For the purpose of differentiation between PMME and ESCC, a radiomics model was constructed using 5 radiomics features obtained from nonenhanced CT and 4 radiomics features derived from enhanced CT. A radiomics model including multiple radiomics features showed excellent discrimination efficiency with AUCs of 0.975 and 0.906 in the primary and validation cohorts, respectively. Then, a radiomics nomogram model was developed. The decision curve analysis has shown remarkable performance of this nomogram model for distinguishing PMME from ESCC. Conclusions: The proposed radiomics nomogram model based on CT could be used for distinguishing PMME from ESCC. Moreover, this model also contributed to helping clinicians determine an appropriate treatment strategy for esophageal neoplasms.

Histogram array and convolutional neural network of DWI for differentiating pancreatic ductal adenocarcinomas from solid pseudopapillary neoplasms and neuroendocrine neoplasms.

PURPOSE: This study aimed to investigate the diagnostic performance of the histogram array and convolutional neural network (CNN) based on diffusion-weighted imaging (DWI) with multiple b-values under magnetic resonance imaging (MRI) to distinguish pancreatic ductal adenocarcinomas (PDACs) from solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine neoplasms (PNENs). METHODS: This retrospective study consisted of patients diagnosed with PDACs (n = 132), PNENs (n = 45) and SPNs (n = 54). All patients underwent 3.0-T MRI including DWI with 10 b values. The regions of interest (ROIs) of pancreatic tumor were manually drawn using ITK-SNAP software, which included entire tumor at DWI (b = 1500 s/m2). The histogram array was obtained through the ROIs from multiple b-value data. PyTorch (version 1.11) was used to construct a CNN classifier to categorize the histogram array into PDACs, PNENs or SPNs. RESULTS: The area under the curves (AUCs) of the histogram array and the CNN model for differentiating PDACs from PNENs and SPNs were 0.896, 0.846, and 0.839 in the training, validation and testing cohorts, respectively. The accuracy, sensitivity and specificity were 90.22%, 96.23%, and 82.05% in the training cohort, 84.78%, 96.15%, and 70.0% in the validation cohort, and 81.72%, 90.57%, and 70.0% in the testing cohort. The performance of CNN with AUC of 0.865 for this differentiation was significantly higher than that of f with AUC = 0.755 (P = 0.0057) and α with AUC = 0.776 (P = 0.0278) in all patients. CONCLUSION: The histogram array and CNN based on DWI data with multiple b-values using MRI provided an accurate diagnostic performance to differentiate PDACs from PNENs and SPNs.

IL-27 suppresses spring viremia of carp virus replication in zebrafish.

Interleukin (IL) 27 is a member of the IL-12 family and is a heterodimeric cytokine composed of IL-27A and Epstein-Barr virus-induced 3 (EBI3). It plays an important role in regulating inflammation and cancer progression. IL-27A not only functions by dimerizing with EBI3 but also acts alone. Here, we report that IL-27A and EBI3 suppress spring viremia of carp virus (SVCV) replication in zebrafish. Expression analysis reveals that il-27a and ebi3 were significantly upregulated in the ZF4 cells by SVCV and poly(I:C), and in the zebrafish caudal fin (ZFIN) cells overexpressed with SVCV genes. Interestingly, il-27a and ebi3 were not modulated by IFNφ1, indicating that they are not IFN stimulated genes (ISGs). Furthermore, overexpression of IL-27A and EBI3 alone inhibited SVCV replication in the EPC cells, but less potent than co-expression of IL-27A and EBI3. Intriguingly, IL-27A could not induce the expression of irf3, ifn, isg15 and mx1. Taken together, our results demonstrate that IL-27A and EBI3 activate innate antiviral response in an IFN independent manner in zebrafish.

LncRNA DNAJC3-AS1 promotes the biological functions of papillary thyroid carcinoma via regulating the microRNA-27a-3p/CCBE1 axis.

Long noncoding RNA DNAJC3-AS1 (lncRNA DNAJC3-AS1) has been probed in many studies, while the regulatory mechanism of DNAJC3-AS1 on papillary thyroid carcinoma (PTC) via regulating microRNA (miR)-27a-3p remains inadequate. This research aims to depict the role of DNAJC3-AS1, miR-27a-3p, collagen, and calcium-binding EGF domain-containing protein 1 (CCBE1) on PTC development. DNAJC3-AS1, miR-27a-3p, and CCBE1 expression levels in PTC tissues and adjacent normal tissues were tested. The relation of DNAJC3-AS1, miR-27a-3p, and CCBE1 was analyzed. DNAJC3-AS1 and miR-27a-3p and CCBE1-related oligonucleotides were transfected into IHH-4 cells to investigate their role in PTC development. Cell tumorigenicity was detected by in vivo assay. DNAJC3-AS1 and CCBE1 expressed highly and miR-27a-3p expressed lowly in PTC. Downregulation of DNAJC3-AS1, upregulating miR-27a-3p or downregulating CCBE1 impaired the malignant behaviors of IHH-4 cells. Depletion of miR-27a-3p reversed the DNAJC3-AS1 suppression-induced phenotypic inhibition of IHH-4 cells. DNAJC3-AS1 bound to miR-27a-3p and CCBE1 as a target of miR-27a-3p. Our study highlights that DNAJC3-AS1 inhibits miR-27a-3p to promote CCBE1 expression, thereby facilitating PTC development. This study affords distinguished therapeutic strategies and novel research directions for PTC treatment.

Quantitative CT evaluation after two cycles of induction chemotherapy to predict prognosis of patients with locally advanced oesophageal squamous cell carcinoma before undergoing definitive chemoradiotherapy/radiotherapy.

OBJECTIVE: To investigate the performance of quantitative CT analysis in predicting the prognosis of patients with locally advanced oesophageal squamous cell carcinoma (ESCC) after two cycles of induction chemotherapy before definitive chemoradiotherapy/radiotherapy. METHODS: A total of 110 patients with locally advanced ESCC were retrospectively analysed. Baseline chest CT and CT after two cycles of induction chemotherapy were analysed. A multivariate Cox proportional-hazard regression model was used to identify independent prognostic markers for survival analysis. Then, a CT scoring system was established. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method were employed for analysing the prognostic value of the CT scoring system. RESULTS: Body mass index, treatment strategy, change ratios of thickness (ΔTHmax), CT value of the primary tumour (ΔCTVaxial) and the short diameter (ΔSD-LN), and the presence of an enlarged small lymph node (ESLN) after two cycles of chemotherapy were noted as independent factors for predicting overall survival (OS). The specificity of the presence of ESLN for death after 12 months was up to 100%. Areas under the curve value of the CT scoring system for predicting OS and progression-free survival (PFS) were higher than that of the RECIST (p < 0.05). Responders had significantly longer OS and PFS than non-responders. CONCLUSION: Quantitative CT analysis after two cycles of induction chemotherapy could predict the outcome of locally advanced ESCC patients treated with definitive chemoradiotherapy/radiotherapy. The CT scoring system could contribute to the development of an appropriate strategy for patients with locally advanced ESCC. KEY POINTS: • Quantitative CT evaluation after two cycles of induction chemotherapy can predict the long-term outcome of locally advanced oesophageal cancer treated with definitive chemoradiotherapy/radiotherapy. • A CT scoring system provides valuable imaging support for indicating the prognosis at the early stage of therapy. • Quantitative CT evaluation can assist clinicians in personalising treatment plans.

Quantitative CT analysis to predict esophageal fistula in patients with advanced esophageal cancer treated by chemotherapy or chemoradiotherapy.

BACKGROUND: Esophageal fistula is one of the most serious complications of chemotherapy or chemoradiotherapy (CRT) for advanced esophageal cancer. This study aimed to evaluate the performance of quantitative computed tomography (CT) analysis and to establish a practical imaging model for predicting esophageal fistula in esophageal cancer patients treated with chemotherapy or chemoradiotherapy. METHODS: This study retrospectively enrolled 204 esophageal cancer patients (54 patients with fistula, 150 patients without fistula) and all patients were allocated to the primary and validation cohorts according to the time of inclusion in a 1:1 ratio. Ulcer depth, tumor thickness and length, and minimum and maximum enhanced CT values of esophageal cancer were measured in pretreatment CT imaging. Logistic regression analysis was used to evaluate the associations of CT quantitative measurements with esophageal fistula. Receiver operating characteristic curve (ROC) analysis was also used. RESULTS: Logistic regression analysis showed that independent predictors of esophageal fistula included tumor thickness [odds ratio (OR) = 1.167; p = 0.037], the ratio of ulcer depth to adjacent tumor thickness (OR = 164.947; p < 0.001), and the ratio of minimum to maximum enhanced CT value (OR = 0.006; p = 0.039) in the primary cohort at baseline CT imaging. These predictors were used to establish a predictive model for predicting esophageal fistula, with areas under the receiver operating characteristic curves (AUCs) of 0.946 and 0.841 in the primary and validation cohorts, respectively. The quantitative analysis combined with T stage for predicting esophageal fistula had AUCs of 0.953 and 0.917 in primary and validation cohorts, respectively. CONCLUSION: Quantitative pretreatment CT analysis has excellent performance for predicting fistula formation in esophageal cancer patients who treated by chemotherapy or chemoradiotherapy.

PLAAT1 inhibits type I interferon response via degradation of IRF3 and IRF7 in Zebrafish.

PLAAT1 is a member of the PLAAT protein family and plays important roles in tumor suppression, transglutaminase activation and peroxisomal biogenesis. Recently, PLAAT1 has been shown to promote degradation of p53 protein and cellular organelles such as mitochondria, endoplasmic reticulum and lysosome. In this study, we show that PLAAT1 inhibits the production of type I interferon and promotes virus replication in zebrafish. Overexpression of Plaat1 in zebrafish cells suppresses antiviral responses and promotes virus replication. Mechanistically, PLAAT1 interacts with IRF3 and IRF7 to initiate degradation of IRF3 and IRF7, which can be attenuated by 3-methyladenine, an inhibitor of autophagosome. Our study provides novel insights into the functions of PLAAT1 in host immune response to viral infection.

Primary malignant melanoma of the esophagus: differentiation from esophageal squamous cell carcinoma and leiomyoma using dynamic contrast-enhanced CT findings.

PURPOSE: This study aimed to summarize the computed tomography (CT) findings of PMME and differentiate it from esophageal SCC and leiomyoma using CT analysis. METHODS: This was a retrospective study including 23 patients with PMME, 69 patients with SCC, and 21 patients with leiomyoma in our hospital. Qualitative CT morphological characteristics of each lesion included the location, tumor range, ulcer, enhanced pattern, and so on. For quantitative CT analysis, thickness, length and area of tumor, size of largest lymph node, number of metastatic lymph node, and CT value of tumor in plain, arterial, and delayed phases were measured. The associated factors for differentiating PMME from SCC and leiomyoma were examined with univariate and multivariate analysis. Receive operating characteristic curve (ROC) was used to determine the performance of CT models in discriminating PMME from SCC and leiomyoma. RESULTS: The thickness, mean CT value in arterial phase, and range of tumor were the independent factors for diagnosing PMME from SCC. These parameters were used to establish a diagnostic CT model with area under the ROC (AUC) of 0.969, and accuracy of 90.2%. In pathology, interstitial vessels in PMME were more abundant than that of SCC, and the stromal fibrosis was more obvious in SCC. PMME commonly exhibited intraluminal expansively growth pattern and SCC often showed infiltrative pattern. The postcontrast attenuation difference in maximum CT attenuation value between plain and arterial phases was the independent factor for diagnosing PMME from leiomyoma. This parameter was applied to differentiate PMME from leiomyoma with AUC of 0.929 and accuracy of 86.4%. CONCLUSION: The qualitative and quantitative CT analysis had excellent performance for differentiating PMME from SCC and esophageal leiomyoma.

Radiomics analysis based on multiple parameters MR imaging in the spine: Predicting treatment response of osteolytic bone metastases to chemotherapy in breast cancer patients.

PURPOSE: To assess the value of radiomics, apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) and stretched-exponential (SE) MR imaging in prediction of therapeutic response in patients with spinal metastases before chemotherapy. METHODS: Thirty-six patients with 190 osteolytic metastatic lesions from breast cancer were prospectively enrolled and underwent MR imaging before and after 6 months' treatment on a 1.5 T MRI. According to MDA criteria, 68 lesions were categorized as progressive disease (PD) and 122 lesions were categorized as stable or improvement (non-PD). The regions of interest (ROIs) were manually drawn on DWI, T1WI, T2WI and FS-T2WI by two radiologists with ITK-SNAP. The ADCall (multiple b-values method), IVIM parameters (D, D* and f) and SE parameters (DDC and α) were generated. The radiomics features were extracted from the ROIs. RESULTS: The mean values of ADC, DDC, and D before treatment were significantly higher in non-PD group than those in PD group (P = 0.001). The radiomics based on ADCall had the highest AUC value (0.852), followed by that of the T2WI (0.829) and FS-T2WI (0.798). The radiomics model using ADCall and FS-T2WI showed excellent efficiency in predicting treatment response with AUCs of 0.905 and 0.873 in training and validation cohorts. The radiomics model had better performance than that of ADCall, D, and DDC for predicting treatment response of bone metastases. CONCLUSION: Radiomics model based on ADCall and FS-T2WI could predict the treatment response and contribute to assisting clinicians in accurately choosing appropriate management.

PLAAT1 promotes p53 degradation via autophagy-lysosome pathway in zebrafish.

PLAAT1 belongs to the PLAAT family and plays regulatory roles in cell growth, tumor suppression and phospholipid metabolism. However, whether PLAAT1 is involved in p53 mediated signaling has not been investigated. Here, we report that PLAAT1 promotes degradation of p53 in zebrafish. We found that the plaat1 gene was constitutively expressed in tissues including liver, kidney, spleen, intestine, eye and brain, with relative higher expression levels detected in the brain and eye. Overexpression of plaat1 led to inhibition of p53 and tnfα mRNA expression. Furthermore, it was shown that PLAAT1 interacted with p53 to facilitate p53 degradation via autophagy-lysosome dependent pathway. Our work indicates that PLAAT1 is involved in the interplay between p53 mediated cellular responses and autophagy.

NPSR1-AS1 activates the MAPK pathway to facilitate thyroid cancer cell malignant behaviors via recruiting ELAVL1 to stabilize NPSR1 mRNA.

Thyroid cancer (TC) is a prevailing malignant disease in endocrine system. Recent reports have demonstrated that long non-coding RNAs (lncRNAs) are crucial participators in TC progression. In our study, we majorly investigated the molecular mechanism of neuropeptide S receptor 1 antisense RNA 1 (NPSR1-AS1) in TC. Western blot and qPCR analyses were applied for the measurement of protein and RNA expressions in TC cells. Colony formation, EdU, and transwell assays, supported by western blot analyses, were implemented for probing NPSR1-AS1 impacts on TC cell malignant phenotype. Moreover, bioinformatics prediction, RIP and Actinomycin D assays detected the downstream mechanism of NPSR1-AS1 in TC cells. In short, NPSR1-AS1 displayed high expression TC cells, and NPSR1-AS1 silence inhibited TC cell malignant behaviors. Additionally, NPSR1-AS1 positively regulated its nearby gene neuropeptide S receptor 1 (NPSR1). ELAV like RNA binding protein 1 (ELAVL1) served as the RNA-binding protein (RBP) to combine with NPSR1-AS1 and NPSR1. Silencing of ELAVL1 reduced the stability of NPSR1 mRNA. Moreover, NPSR1 could activate the mitogen-activated protein kinases (MAPK) pathway in TC cells. Collectively, our study elucidated the aspect of lncRNA-RBP-mRNA interaction which might be a novel sight for TC treatment.[Figure: see text].

Correlation Between the Distance to Mesorectal Fascia and Prognosis of cT3 Rectal Cancer: Results of a Multicenter Study From China.

BACKGROUND: The cT3 substage criteria based on extramural depth of tumor invasion in rectal cancer have several limitations. OBJECTIVE: This study proposed that the distance between the deepest tumor invasion and mesorectal fascia on pretherapy MRI can distinguish the prognosis of patients with cT3 rectal cancer. DESIGN: This is a cohort study. SETTING: This study included a prospective, single-center, observational cohort and a retrospective, multicenter, independent validation cohort. PATIENT: Patients who had cT3 rectal cancer with negative mesorectal fascia undergoing neoadjuvant chemoradiotherapy followed by radical surgery were included in 4 centers in China from January 2013 to September 2014. INTERVENTION: Baseline MRI with the distance between the deepest tumor invasion and mesorectal fascia, extramural depth of tumor invasion, and mesorectum thickness were measured. MAIN OUTCOME MEASURES: The cutoff of the distance between the deepest tumor invasion and mesorectal fascia was determined by time-dependent receiver operating characteristic curves, supported by a 5-year progression rate from the prospective cohort, and was then validated in a retrospective cohort. RESULTS: There were 124 and 274 patients included in the prospective and independent validation cohorts. The distance between the deepest tumor invasion and mesorectal fascia was the only predictor for cancer-specific death (HR, 0.1; 95% CI, 0.0-0.7) and was also a significant predictor for distant recurrence (HR, 0.4; 95% CI, 0.2-0.9). No statistically significant difference was observed in prognosis between patients classified as T3a/b and T3c/d. LIMITATIONS: The sample size is relatively small, and the study focused on cT3 rectal cancers with a negative mesorectal fascia. CONCLUSIONS: A cutoff of 7 mm of the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI can distinguish cT3 rectal cancer from a different prognosis. We recommend using the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI for local and systemic risk assessment and providing a tailored schedule of neoadjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B682.CORRELACIÓN ENTRE LA DISTANCIA DE LA FASCIA MESORRECTAL Y EL PRONÓSTICO DEL CÁNCER DE RECTO cT3: RESULTADOS DE UN ESTUDIO MULTICÉNTRICO DE CHINAANTECEDENTES:Los criterios de subestadificación cT3 basados en la profundidad extramural de invasión tumoral en el cáncer de recto tienen varias limitaciones.OBJETIVO:Este estudio propuso que la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética preterapia puede distinguir el pronóstico de los pacientes con cT3.DISEÑO:Estudio de cohorte.ENTORNO CLINICO:El estudio incluyó una cohorte observacional, prospectiva, unicéntrica, y una cohorte de validación retrospectiva, multicéntrica e independiente.PACIENTE:Se incluyeron pacientes con cáncer de recto cT3 con fascia mesorrectal negativa sometidos a quimio-radioterapia neoadyuvante seguida de cirugía radical en cuatro centros de China desde enero de 2013 hasta septiembre de 2014.INTERVENCIÓN:Imágenes de resonancia magnética de referencia fueron medidas con la distancia entre la invasión tumoral más profunda y la fascia mesorrectal; la profundidad extramural de la invasión tumoral y el grosor del mesorrecto.PRINCIPALES MEDIDAS DE VALORACION:El límite de la distancia entre la invasión tumoral más profunda y la fascia mesorrectal se determinó mediante curvas características operativas del receptor dependientes del tiempo y se apoyó en la tasa de progresión a 5 años de la cohorte prospectiva, y luego se validó en una cohorte retrospectiva.RESULTADOS:Se incluyeron 124 y 274 pacientes en la cohorte de validación prospectiva e independiente, respectivamente. La distancia entre la invasión tumoral más profunda de la fascia mesorrectal fue el único predictor de muerte específica por cáncer (Hazard ratio: 0.1, 95% CI, 0,0-0,7); y también fue un predictor significativo de recurrencia distante Hazard ratio: 0,4, 95% CI, 0,2-0,9). No se observaron diferencias estadísticamente significativas en el pronóstico entre los pacientes clasificados como T3a/b y T3c/d.LIMITACIONES:El tamaño de la muestra es relativamente pequeño y el estudio se centró en los cánceres de recto cT3 con fascia mesorrectal negativa.CONCLUSIONES:Un límite de 7 mm de distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia puede distinguir el cáncer de recto cT3 de diferentes pronósticos. Recomendamos la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia para la evaluación del riesgo local y sistémico, proporcionando un programa personalizado de tratamiento neoadyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B682. (Traducción- Dr. Francisco M. Abarca-Rendon).

Establishment of a multi-parameters MRI model for predicting small lymph nodes metastases (<10 mm) in patients with resected pancreatic ductal adenocarcinoma.

PURPOSE: To evaluate the potential role of MR findings and DWI parameters in predicting small regional lymph nodes metastases (with short-axis diameter < 10 mm) in pancreatic ductal adenocarcinomas (PDACs). METHODS: A total of 127 patients, 82 in training group and 45 in testing group, with histopathologically diagnosed PDACs who underwent pancreatectomy were retrospectively analyzed. PDACs were divided into two groups of positive and negative lymph node metastases (LNM) based on the pathological results. Pancreatic cancer characteristics, short axis of largest lymph node, and DWI parameters of PDACs were evaluated. RESULTS: Univariate and multivariate analyses showed that extrapancreatic distance of tumor invasion, short-axis diameter of the largest lymph node, and mean diffusivity of tumor were independently associated with small LNM in patients with PDACs. The combining MRI diagnostic model yielded AUCs of 0.836 and 0.873, and accuracies of 81.7% and 80% in the training and testing groups. The AUC of the MRI model for predicting LNM was higher than that of subjective MRI diagnosis in the training group (rater 1, P = 0.01; rater 2, 0.008) and in a testing group (rater 1, P = 0.036; rater 2, 0.024). Comparing the subjective diagnosis, the error rate of the MRI model was decreased. The defined LNM-positive group by the MRI model showed significantly inferior overall survival compared to the negative group (P = 0.006). CONCLUSIONS: The MRI model showed excellent performance for individualized and noninvasive prediction of small regional LNM in PDACs. It may be used to identify PDACs with small LNM and contribute to determining an appropriate treatment strategy for PDACs.