Patient-Derived Xenografts (PDXs) are, so far, the best preclinical model to validate targets and predictors of response to therapy. While subcutaneous implantation very rarely allows metastatic dissemination, orthotopic implantation (Patient-Derived Orthotopic Xenograft-PDOX) increases metastatic capability. Using a modified tool to analyze model validity, we performed a systematic review of Embase, PubMed, and Web of Science up to December 2018 to identify all original publications describing gastric cancer (GC) PDOXs. We identified ten studies of PDOX model validation from January 1981 to December 2018 that fulfilled the inclusion and exclusion criteria. Most models (70%) were derived from human GC cell lines rather than tissue fragments. In 90% of studies, the implantation was performed in the subserosal layer. Tumour engraftment rate ranged from 0 to 100%, despite the technique. Metastases were observed in 40% of PDOX models implanted into the subserosal layer, employing either cell suspension or cell line-derived tumour fragments. According to our modified model validity tool, half of the studies were defined as unclear because one or more validation criteria were not reported. Available GC PDOX models are not adequate according to our model validity tool. There is no demonstration that the submucosal site is more effective than the subserosal layer, and that tissue fragments are better than cell suspensions for successful engraftment and metastatic spread. Further studies should strictly employ model validity tools and large samples with orthotopic implant sites mirroring as much as possible the donor tumour characteristics.Reactive oxygen species (ROS) are continuously produced as byproducts of aerobic metabolism. Oxidative stress (OS) plays an important role in the occurrence of several neurodegenerative diseases as well as aging because of the accumulation of ROS. Gnaq is a member of G protein α subunits. It has been reported that the expression level of Gnaq in the mouse forebrain cortex was significantly decreased with age in our previous study; therefore, we supposed that Gnaq contributes to attenuate the OS. In this study, we generated a Gnaq-overexpression cell using gene recombinant technique and lentivirus transfection technique in a neuron-like PC12 cell, and investigated whether Gnaq had antioxidant effects in PC12 cells treated with H2O2. The viability of cells, concentration of ROS, Nrf2 nuclear translocation, expression of antioxidant enzymes, activation of NF-κB and apoptosis were compared between Gnaq-PC12 cells and Vector-PC12 cells. Results showed that, compared with Vector-PC12 cells, the antioxidative ability of Gnaq-PC12 cells was significantly improved, while the ROS level in Gnaq-PC12 cells was significantly decreased. Nrf2 nuclear translocation was up-regulated and NF-κB nuclear translocation was down-regulated in Gnaq-PC12 cells after H2O2 treatment. The results suggest that Gnaq plays a crucial role in neuroprotection in PC12 cells. A possible mechanism for this would be that the overexpressed Gnaq enhances the antioxidative effect mediated by Nrf2 signal pathway and inhibits the cellular damaging effect through NF-κB signal pathway.BACKGROUND High F18-fluorodeoxyglucose (FDG) uptake has been reported to be a predictor of poor prognosis in patients with breast cancer. We investigated the relationship between FDG uptake and immunological factors, including the data of programmed cell death-ligand 1 (PD-L1), CD8, and tumor-infiltrating lymphocytes (TILs). METHODS Breast cancer tissues of 97 patients who underwent surgery without preoperative therapy were examined. The grade of stromal TILs was immunohistochemically evaluated using the criteria of the International TILs Working Group in breast cancer. PD-L1 positivity and CD8 positivity were immunohistochemically evaluated. The FDG uptakes were evaluated based on the standardized uptake value max (SUVmax). The relationships between SUVmax and TIL grade and expression of PD-L1 and CD8 were investigated. RESULTS Among the 97 patients, 41 (42.3%) had a high SUVmax in their primary tumor, based on the SUVmax cut-off value 3 yielded by receiver operating characteristic curves. PD-L1 was positive in 17 patients (17.5%). Our analyses revealed that large tumor size, high nuclear grade, high degree of TILs and positive expression of PD-L1 were significantly associated with high SUVmax in the primary tumor. There were significant associations between SUVmax and the degree of TILs (r = 0.428, p  less then  0.001) and between SUVmax and the PD-L1 positivity (r = 0.413, p  less then  0.001). All cases with a high degree of TILs showed high CD8 expression. CONCLUSION Our results indicate that the FDG uptake may be predictive of immunological features including TILs and PD-L1 expression in breast cancer patients. Additional research is necessary to further evaluate FDG-PET as a biomarker of immune checkpoint therapy in breast cancer.BACKGROUND A prognostic model based on the results of molecular analysis of sentinel lymph nodes (SLN) is needed to replace the information that staging the entire axilla provided. The aim of the study is to conduct an external validation of a previously developed model for the prediction of 5-year DFS in a group of breast cancer patients that had undergone SLN biopsy assessed by the One Step Nucleic Acid Amplification (OSNA) method. METHODS We collected retrospective data of 889 patients with breast cancer, who had not received systemic treatment before surgery, and who underwent SLN biopsy and evaluation of all SLN by OSNA. The discrimination ability of the model was assessed by the area under the ROC curve (AUC ROC), and its calibration by comparing 5-years DFS Kaplan-Meier estimates in quartile groups of model predicted probabilities (MPP). RESULTS The AUC ROC ranged from 0.78 (at 2 years) to 0.73 (at 5 years) in the training set, and from 0.78 to 0.71, respectively, in the validation set. The MPP allowed to distinguish four groups of patients with heterogeneous DFS (log-rank test p  less then  0.0001). In the highest risk group, the HR were 6.04 [95% CI 2.70, 13.48] in the training set and 4.79 [2.310, 9.93] in the validation set. CONCLUSIONS The model for the prediction of 5-year DFS was successfully validated using the most stringent form of validation, in centers different from those involved in the development of the model. The external validation of the model confirms its utility for the prediction of 5-year DFS and the usefulness of the TTL value as a prognostic variable.BACKGROUND Advances in breast cancer research are making treatment options increasingly effective and reducing mortality. Body composition is an example of a prognostic tool that can help personalize breast cancer treatments and further increase their effectiveness. In this study, we examine the association of several body composition measures with comorbidities, physical function, and quality of life. METHODS This study is a cross-sectional analysis of 99 women with early breast cancer scheduled for chemotherapy. Univariate regression models were used to identify significant associations of body composition metrics with patient demographics, clinical characteristics, measures of physical function, and patient-reported outcomes (PRO)s. Multivariable modeling was used to evaluate associations adjusted for age. RESULTS Median age was 58 (range 24-83), 27% were non-white, and, 47% were obese (≥ 30 kg/m2). Increasing age was associated with lower Skeletal Muscle Density (SMD) (p = 0.0001), lower Skeletal Muscle Gauge (SMG) (p = 0.0005), and higher Visceral Adipose Tissue (VAT) (p  14 with higher VAT remained significant (p = 0.02). CONCLUSIONS Suboptimal body composition prior to treatment is associated poor physical function and may be an indicator of clinical importance.PURPOSE To describe the experience with radioiodine-resistant differentiated thyroid cancer (RR-DTC) patients treated with lenvatinib in two university hospitals from Argentina. METHODS Adult patients with a diagnosis of RR-DTC treated with lenvatinib from April 2017 to February 2020 were registered into a retrospective database. Primary objectives were assessment of progression-free survival (PFS) and tumor response evaluated according to RECIST v 1.1. Adverse events (AEs) were evaluated by using Common Terminology Criteria for Adverse Events v5.0. RESULTS Twenty-two patients were treated with lenvatinib, 13 of whom had previously received one or more multikinase inhibitors. Median duration of treatment was 7.1 months (2.2-24). Best overall response was complete response in one patient (4.5%), partial response in seven (31.8%), stable disease in seven (31.8%), and progressive disease in six (27.3%). Median PFS was 13.7 months (95% CI 3.2-24.2). All patients experienced at least one AE. Grade ≥3 AEs were observed in eight (36.4%) patients. Hypertension was the most frequent AE (63.6%) and the most common grade ≥3 AE (22.7%). Definitive withdrawal was necessary in two patients due to recurrent proteinuria (9%). CONCLUSIONS Tumor responses and PFS in our study were in line with other real-life clinical data and they seem to be inferior to the reported in the SELECT trial, probably related to the higher number of patients with prior MKI therapy, comorbidities, and poor performance status. Although virtually all patients experienced AEs, most of them were manageable and rarely a definitive withdrawal was necessary.PURPOSE Evidences have shown that elevated lipoprotein(a) [Lp(a)] levels were associated with a lower risk of type 2 diabetes, but a higher risk of cardiovascular events in general populations. We aim to demonstrate the effect of Lp(a) concentrations on type 2 diabetes and cardiovascular events in a Chinese population with very high cardiovascular risk. METHODS Seven hundred ninety-eight participants who underwent coronary angiography between March and November 2013 with normal glucose metabolism were followed up from July to December 2018. RESULTS Five hundred thirty-five participants completed follow-up, and 395 of them had blood glucose data. Among 395 participants with blood glucose data, a total of 28 incident type 2 diabetes were identified during a median follow-up period of 4.42 years. Compared with the patients in the lowest tertile of Lp(a), the multifactorial adjusted HR for type 2 diabetes was 0.29 in the highest tertile (95% confidence intervals (CI) 0.10-0.89; P for trend = 0.03). Among 535 patients who completed follow-up, a total of 80 cases of major adverse cardiovascular events (MACE) were identified during a median follow-up period of 5.08 years. Compared with the patients in the lowest tertile of Lp(a), the multifactorial adjusted HR for MACE was 1.95 in the highest tertile (95% CI 1.05-3.65; P for trend = 0.03). CONCLUSIONS Elevated Lp(a) levels were associated with a lower risk of type 2 diabetes, but a higher risk of cardiovascular events in a Chinese population with very high cardiovascular risk.PURPOSE Previous studies have demonstrated handwriting changes in patients with overt hyperthyroidism due to Graves’ disease. The aim of the present study was to investigate handwriting features in patients affected by overt autoimmune hypothyroidism. METHODS Thirty subjects – 24 females and 6 males, mean and median age of 50.15 ± 16.8 years and 52.5 years, respectively – with overt hypothyroidism (OH) related to Hashimoto’s thyroiditis (Group 1), and 30 age- and sex-matched euthyroid individuals (Group 2) were recruited to write a „standard text”. Group 1 patients repeated the text once the euthyroid state was reached on L-T4 substitution therapy. Group 2 subjects wrote the text again 1 to 4 weeks thereafter. The letters underwent a detailed analysis by a handwriting expert, through inspection, a stereoscopic microscope and a magnifying glass. Furthermore, the time that both Groups took to go through with the text was clocked. RESULTS None of the handwriting variables differed significantly within each Group and between the two Groups.