Intraparenchymal Striatal Transplants Required for Maintenance of Behavioral Recovery in an Animal Model of Huntington's Disease

Rats which receive injections of kainic acid (KA) into the striatum show many of the anatomical, biochemical and behavioral abnormalities seen in patients with Huntington's disease. Recently, it has been reported that fetal striatal transplants into the lesioned striatum could normalize the neurological and behavioral abnormalities produced by the KA lesion. The present study examined the issue of transplant integration in producing behavioral recovery. In one experiment, lesioned animals with transplants located within the lateral ventricle were compared against parenchymally transplanted rats. It was found that unless the ventricular transplant grew into the lesioned striatum there was no recovery. The second experiment demonstrated that electrolytic destruction of a successful fetal striatal transplant could reverse the transplant-induced behavioral recovery. These results suggest that the integrity of the transplant is important in maintaining behavioral recovery. A continuing functional interaction between the host brain and transplanted tissue may be a vital element in the success of the fetal striatal transplant

Radiomics using computed tomography to predict CD73 expression and prognosis of colorectal cancer liver metastases

ABSTRACT: Background Finding a noninvasive radiomic surrogate of tumor immune features could help identify patients more likely to respond to novel immune checkpoint inhibitors. Particularly, CD73 is an ectonucleotidase that cata- lyzes the breakdown of extracellular AMP into immunosuppressive adenosine, which can be blocked by therapeutic antibodies. High CD73 expression in colorectal cancer liver metastasis (CRLM) resected with curative intent is associ- ated with early recurrence and shorter patient survival. The aim of this study was hence to evaluate whether machine learning analysis of preoperative liver CT-scan could estimate high vs low CD73 expression in CRLM and whether such radiomic score would have a prognostic significance. Methods We trained an Attentive Interpretable Tabular Learning (TabNet) model to predict, from preoperative CT images, stratified expression levels of CD73 (CD73High vs. CD73Low ) assessed by immunofluorescence (IF) on tissue microarrays. Radiomic features were extracted from 160 segmented CRLM of 122 patients with matched IF data, preprocessed and used to train the predictive model. We applied a five-fold cross-validation and validated the perfor- mance on a hold-out test set. Results TabNet provided areas under the receiver operating characteristic curve of 0.95 (95% CI 0.87 to 1.0) and 0.79 (0.65 to 0.92) on the training and hold-out test sets respectively, and outperformed other machine learning models. The TabNet-derived score, termed rad-CD73, was positively correlated with CD73 histological expression in matched CRLM (Spearman’s ρ = 0.6004; P < 0.0001). The median time to recurrence (TTR) and disease-specific survival (DSS) after CRLM resection in rad-CD73High vs rad-CD73 Low patients was 13.0 vs 23.6 months (P = 0.0098) and 53.4 vs 126.0 months (P = 0.0222), respectively. The prognostic value of rad-CD73 was independent of the standard clinical risk score, for both TTR (HR = 2.11, 95% CI 1.30 to 3.45, P < 0.005) and DSS (HR = 1.88, 95% CI 1.11 to 3.18, P = 0.020)

Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response

IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcεRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcεRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development

Prediction of CD3 T-cell infiltration status in colorectal liver metastases: a radiomics-based imaging biomarker

Colorectal cancer (CRC) continues to be a leading cause of cancer-related death in the developed world due to metastatic progression of the disease. In an effort to improve the understanding of tumor biology and developing prognostic tools, it was found that CD3+ tumor infiltrating lymphocytes (TIL) had a very strong prognostic value in primary CRC as well as in colorectal liver metastases (CLM). Quantification of TILs remains labor intensive and requires tissue samples, hence being of limited use in the pre-operative period or in the context of non-operable disease. Computed tomography (CT) images however are widely available for patients with CLM. In this study, we propose a pipeline to predict CD3 T-cell infiltration in CLM from pre-operative CT images. Radiomic features were extracted from 58 automatically segmented CLM lesions. Subsequently, dimensionality reduction was performed by training an autoencoder (AE) on the full feature set. We then used AE bottleneck embeddings to predict CD3 T-cell density, stratified into two categories: CD3hi and CD3low. For this, we implemented a 1D convolutional neural network (1D-CNN) and compared its performance against five machine learning models using 5-fold cross-validation. Results showed that the proposed 1D-CNN outperformed the other trained models achieving a mean accuracy of 0.69 (standard deviation [SD], 0.01) and a mean area under the receiver operating curve (AUROC) of 0.75 (SD, 0.02) on the validation set. Our findings demonstrate a relationship between CT radiomic features and CD3 tumor infiltration status with the potential of noninvasively determining CD3 status from preoperative CT images

Monitoring of Myocutaneous Flaps by Measuring Capillary Glucose and Lactate Levels

IF : 1.535 (2016)International audienceIntroduction In surgery, certain defects require reconstruction with a microsurgical flap. The free flap failure rate varies between 2% and 5%. Vascular thrombosis is the most frequent complication and represents 15% to 73% of failures. The success rate of salvage therapy is greater when salvage surgery is early. Currently, clinical monitoring is the criterion standard but many noninvasive or minimally invasive techniques have been developed to improve early diagnosis of complications of vascular thrombosis. The aim of our experimental study was to compare clinical assessments with measurements of capillary glycemia and lactatemia during the monitoring of free flaps.Materials and Methods Myocutaneous latissimus dorsi flaps with skin paddles were created in pigs under general anesthesia. For each animal, 2 flaps were created (right and left) using the same technique. Four groups were made: group 1 (no flap ligation: control group), group 2 (flap with permanent ligation of the artery), group 3 (flap with permanent ligation of the two veins), group 4 (flap with transient ligation of the artery and 2 veins for 1 hour). The postoperative monitoring protocol consisted of monitoring the clinical, biological (glucose and lactate), and histological parameters.Results Eight animals were operated on and sixteen flaps were created. Each flap was clinically and biologically tested 25 times. Clinical, biological, and histological monitoring showed significant variations between the groups. The analysis of variance of capillary glycemia and lactatemia showed statistically significant difference between control group and group 2 (P < 0,0001), group 3 (P < 0,0001), or group 4 (P < 0,0001). There were no histological abnormalities after transient ligature at different times contrary to permanent ligature.Discussion-Conclusion Measuring capillary levels of lactate and glucose associated with clinical monitoring may shorten the time to diagnosis of flap failure. Ultimately, this will save lives and achieve better functional and aesthetic results

Monitoring of Myocutaneous Flaps by Measuring Capillary Glucose and Lactate Levels

IF : 1.535 (2016)International audienceIntroduction In surgery, certain defects require reconstruction with a microsurgical flap. The free flap failure rate varies between 2% and 5%. Vascular thrombosis is the most frequent complication and represents 15% to 73% of failures. The success rate of salvage therapy is greater when salvage surgery is early. Currently, clinical monitoring is the criterion standard but many noninvasive or minimally invasive techniques have been developed to improve early diagnosis of complications of vascular thrombosis. The aim of our experimental study was to compare clinical assessments with measurements of capillary glycemia and lactatemia during the monitoring of free flaps.Materials and Methods Myocutaneous latissimus dorsi flaps with skin paddles were created in pigs under general anesthesia. For each animal, 2 flaps were created (right and left) using the same technique. Four groups were made: group 1 (no flap ligation: control group), group 2 (flap with permanent ligation of the artery), group 3 (flap with permanent ligation of the two veins), group 4 (flap with transient ligation of the artery and 2 veins for 1 hour). The postoperative monitoring protocol consisted of monitoring the clinical, biological (glucose and lactate), and histological parameters.Results Eight animals were operated on and sixteen flaps were created. Each flap was clinically and biologically tested 25 times. Clinical, biological, and histological monitoring showed significant variations between the groups. The analysis of variance of capillary glycemia and lactatemia showed statistically significant difference between control group and group 2 (P < 0,0001), group 3 (P < 0,0001), or group 4 (P < 0,0001). There were no histological abnormalities after transient ligature at different times contrary to permanent ligature.Discussion-Conclusion Measuring capillary levels of lactate and glucose associated with clinical monitoring may shorten the time to diagnosis of flap failure. Ultimately, this will save lives and achieve better functional and aesthetic results