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Further, the inhibition of phospho-AKTThr308 and phospho-AKTSer473 reversed PTPN3 induced-silencing in tumor cell migration. Our work revealed that the overexpression of PTPN3 could suppress kidney cancer progression by negatively regulating the AKT signaling pathway, and served as a favorable prognostic factor in ccRCC patients. Our findings provided insight that PTPN3 could be a potential target for therapy aiming to inhibit the malignant behaviors of ccRCC. Implications PTPN3 is an independent favorable prognostic factor for ccRCC patients and could be a potential target for therapy aiming to inhibit the malignant behaviors of ccRCC. Copyright ©2020, American Association for Cancer Research.Tumor-host interactions play a major role in malignancies' initiation and progression. We have reported in the past that tumor cells attenuate genotoxic stress-induced p53 activation in neighboring stromal cells. Herein we aim to further elucidate cancer cells' impact on signaling within lung cancer stroma. Primary cancer-associated fibroblasts were grown from resected human lung tumors. https://www.selleckchem.com/products/arv-110.html Lung cancer lines as well as fresh cultures of resected human lung cancers were used to produce conditioned medium (CM) or co-cultured with stromal cells. Invasiveness of cancer cells was evaluated by transwell assays, and in vivo tumor growth was tested in Athymic nude mice. We found CM of a large variety of cancer cell lines as well as ex-vivo cultured lung cancers to rapidly induce protein levels of stromal-MDM2. CM of non-trasnformed cells had no such effect. Mdm2 induction occurred through enhanced translation, was mTORC1-dependent, and correlated with activation of AKT and p70 S6 Kinase. AKT or MDM2 knockdown in fibroblasts reduced the invasion of neighboring cancer cells, independently of stromal-p53. MDM2 overexpression in fibroblasts enhanced cancer cells' invasion and growth of inoculated tumors in mice. Our results indicate that stromal-MDM2 participates in a p53-independent cancer-host feedback mechanism. Soluble cancer-originated signals induce enhanced translation of stromal-MDM2 through AKT/mTORC1 signaling, which in turn enhances the neighboring cancer cells' invasion ability. link2 The role of these tumor-host interactions needs to be further explored. Implications We uncovered a novel tumor-stroma signaling loop, which is a potentially new therapeutic target in lung cancer and possibly in additional types of cancer. Copyright ©2020, American Association for Cancer Research.Glioblastoma multiforme (GBM) tumors are highly metabolic and vascularized, yet little has been reported regarding the spatial localization of metabolic activity within these tumors. A mass spectrometry imaging (MSI) study by Randall and colleagues in this issue provides provocative observations of metabolic gradients in xenograft GBM models. The intensity of acylcarnitines is dramatically increased at tumor margins, which interface with normal tissue, but not in tumor margins at the edge of the brain. A secondary examination of drug metabolites suggests that the observed metabolic gradients are pharmacologically relevant. These findings underscore previously undescribed spatial metabolic heterogeneity in GBM biology and opportunities for MSI investigations.See related article by Randall et al., p. 1258. ©2020 American Association for Cancer Research.Advanced glycation end-products (AGEs) are implicated in the pathogenesis of several chronic diseases including cancer. AGEs are produced endogenously but can also be consumed from foods. AGE formation in food is accelerated during cooking at high temperatures. Certain high fat or highly processed foods have high AGE values. The objective of the study was to assign and quantify NƐ-carboxymethyl-lysine (CML)-AGE content in food and investigate the association between dietary AGE intake and breast cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). The study included women enrolled in the intervention arm who were cancer-free at baseline and completed a baseline questionnaire and food frequency questionnaire (DQX). CML-AGE values were assigned and quantified to foods in the DQX using a published AGE database. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs of breast cancer among all women, and stratified by race/ethnicity, invasiveness of disease, and hormone receptor status. After a median 11.5 years of follow-up, 1,592 women were diagnosed with breast cancer. Higher CML-AGE intake was associated with increased risk of breast cancer among all women (HRQ5 VS Q11.30, 95% CI 1.04-1.62; P-trend 0.04) and in non-Hispanic white women (HRT3 VS T1 1.21, 95% CI 1.02-1.44). Increased CML-AGE intake was associated with increased risk of in situ (HRT3 VS T1 1.49, 95% CI 1.11-2.01) and hormone receptor positive (HRT3 VS T1 1.24, 95% CI 1.01-1.53) breast cancers. In conclusion, high intake of dietary AGE may contribute to increased breast cancer. Copyright ©2020, American Association for Cancer Research.Songbirds are a powerful model to study vocal learning given that aspects of the underlying behavioral and neurobiological mechanisms are analogous in many ways to mechanisms involved in speech learning. Perineuronal nets (PNN) represent one of the mechanisms controlling the closing of sensitive periods for vocal learning in the songbird brain. In zebra finches, PNN develop around parvalbumin-expressing interneurons in selected song control nuclei during ontogeny and their development is delayed if juveniles are deprived of a tutor. However, song learning in zebra finches takes place during a relatively short period of development and it is difficult to determine whether PNN development correlates with the end of the sensory or the sensorimotor learning period. Canaries have a longer period of sensorimotor vocal learning, spanning over their first year of life so that it should be easier to test whether PNN development correlates with the end of sensory or sensorimotor vocal learning. link3 Here we quantified PNN aarning process they control has not been formally identified. We demonstrate here that during ontogeny in male canaries, PNN develop essentially during the sensorimotor phase of song learning, which suggests that they represent part of the neuronal mechanisms underlying song crystallization. Copyright © 2020 Cornez et al.Human observers perceptually discriminate the dynamic deformation of materials in the real world. However, the psychophysical and neural mechanisms responsible for the perception of dynamic deformation have not been fully elucidated. By using a deforming bar as the stimulus, we showed that the spatial frequency of deformation was a critical determinant of deformation perception. Simulating the response of direction-selective units (i.e., MT pattern motion cells) to stimuli, we found that the perception of dynamic deformation was well explained by assuming a higher-order mechanism monitoring the spatial pattern of direction responses. Our model with the higher-order mechanism also successfully explained the appearance of a visual illusion wherein a static bar apparently deforms against a tilted drifting grating. In particular, it was the lower spatial frequencies in this pattern that strongly contributed to the deformation perception. Finally, by manipulating the luminance of the static bar, we observed that the mechanism for the illusory deformation was more sensitive to luminance than contrast cues.Significance Statement From the psychophysical and computational points of view, the present study tried to answer the question, "how do human observers see deformation?". In the psychophysical experiment, we used a clip wherein a bar dynamically deformed. We also tested the illusory deformation of a bar, which was caused by tilted drifting grating, because it was unclear whether the illusory deformation could be described by our model. In the computational analysis, in order to explain psychophysical data for deformation perception, it was necessary to assume an additional unit monitoring the spatial pattern of direction responses of MT cells that were sensitive to local image motion. Copyright © 2020 Kawabe and Sawayama.BACKGROUND Outbreaks of hepatitis A are being reported more commonly among men who have sex with men (MSM) globally. Australia has also reported a sharp increase in the number of cases of hepatitis A in 2017. This study aimed to determine the level of immunity to hepatitis A among MSM attending a large urban sexual health clinic in Victoria in the lead up to recent outbreak. METHODS This was a retrospective audit of serological testing data from first-time MSM attendees at Melbourne Sexual Health Centre (MSHC) in Australia from 1 January 2012 to 31 December 2018. We determined the proportion of MSM who were tested and who had serological detection of hepatitis A IgG, stratified by age and calendar year. We used univariable and multivariable logistic regression to investigate factors associated with testing for and detection of hepatitis A IgG. RESULTS There were 16 609 first-time MSM attendees at MSHC over the 7-year period, of which 9718 (59%, 95% CI 58% to 60%) were tested for hepatitis A IgG. There was a 2% annual increase in the proportion of men tested (from 60% in 2012 to 69% in 2018; OR=1.02, 95% CI 1.00 to 1.03, p=0.025). Men born outside of Australia/New Zealand, and younger men less then 30 years had higher odds of being tested. Of those tested, 44% (n=4304, 95% CI 43% to 45%) had hepatitis A IgG detected at their first visit, with no change over time (OR=1.01, 95% CI 0.99 to 1.03, p=0.210). Detection of hepatitis A IgG was associated with being aged 30 years or older (adjusted OR=2.06, 95% CI 1.89 to 2.24, p less then 0.001) or being born overseas versus Australia/New Zealand (AOR=1.21, 95% CI 1.11 to 1.31, p less then 0.001). CONCLUSION Hepatitis A immunity among MSM remains below the estimated 70% required to prevent outbreaks. Measures including increased testing and higher vaccination coverage are needed to prevent outbreaks and to limit the number of cases and deaths. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The pks + E. coli metabolite colibactin caused a unique mutational signature in intestinal organoids. ©2020 American Association for Cancer Research.A new method called MicroMapping can identify nanoscale protein-protein interactions on live cells. ©2020 American Association for Cancer Research.A chemotherapy-induced shift to ICOSL+ B cells in breast tumors correlated with better survival. ©2020 American Association for Cancer Research.A large international study found that the composition of the intestinal microbiome can predict clinical outcomes in patients undergoing allogenic hematopoietic-cell transplant (HCT) for blood cancers. The findings may help assess patients' transplantation-related mortality risk and aid in developing interventions to prevent or mitigate microbiome changes that affect HCT outcomes. ©2020 American Association for Cancer Research.Symmetric division of stem cells positive for gastrin receptor CCK2R is linked to gastric cancer. ©2020 American Association for Cancer Research.