tbuckley/cabot-search huggingface dataset:
Advances in Understanding the Association Between Pediatric Traumatic Brain Injury and Attention-Deficit/Hyperactivity Disorder
Authors: Keith Owen Yeates, Jeffrey E. Max, Megan E. Narad
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Sensitive markers to detect progression of lung disease in children with cystic fibrosis
Authors: Mirjam Stahl
Journal: European Respiratory Journal (2021)

<b>LCI detects progression of lung disease in children with CF. Preschool LCI is a strong predictor of lung disease in older children with CF. However, factors influencing progression remain diverse and are not comparable between different patient cohorts.</b>https://bit.ly/2MCeJTW
Abstract NG02: Identification of high priority genes for basic and translational pancreatic cancer research
Authors: Zeribe Chike Nwosu, Heather C. Giza, Verodia Charlestin, Maya Nassif, Daeho Kim, Samantha Kemp, Nina G. Steele, Costas A. Lyssiotis, Marina Pasca di Magliano
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is highly metastatic and drug resistant and is one of the most lethal solid malignancies. Genomic profiling studies have defined the molecular subtypes and mutational landscape of PDAC and extensive gene expression profiling dataset have been accumulated to date. However, there is a knowledge gap on the consistency of gene expression across profiled PDAC samples and this limits the prospects of clinical translation. To facilitate novel drug target prioritization and biomarker discovery, we have extensively analyzed over 20 publicly accessible datasets. We report the most consistently expressed genes in PDAC tissues compared to non-tumors. Specifically, we identified 3,938 consistent genes, including 2,010 consistently upregulated genes, topmost of which included LAMC2, TMPRSS4, S100P, SLC6A14, COL10A1, CTSE, LAMB3, CEACAM5/6, and glucose transporter SLC2A1, and 1,928 consistently downregulated genes top among which include AOX1, IAPP, albumin (ALB), SERPINI2, PDK4 and PNLIPRP1/2 (adjusted P&amp;lt;0.05). Over 50% of the genes are unknown. In addition, these genes largely reflected the same expression pattern in bulk and single cell RNA sequencing analysis, showed tumors-specificity, and correlated with several cancer indices including proliferation, metastasis, mutation and tumor grade. Pathway enrichment analyses revealed ‘pathways in cancer', ‘focal adhesion', ‘p53', ‘cell cycle', ‘transcription factor binding', “glycolysis” among upregulated processes. These pathway alterations were accompanied by profound metabolic alterations and signatures of disrupted pancreatic homeostasis. Interactome and disease ontology analyses further linked the consistent genes with precancerous conditions, PDAC, and malignancy. We found that ~41% of the genes predicted patients' overall survival in at least two datasets while clustering analyses and receiver operating characteristic analysis uncovered highly probable biomarkers. Subsequent analysis of gene silencing datasets identified 185 ‘high-priority' genes (notably candidates in cell cycle and glycolysis) whose knockdown suppress PDAC viability. Our multi-dimensional analysis is an important milestone in the quest for mechanisms, drug targets and biomarkers in PDAC, and outlines an adaptable analytical approach that can aid biomarker or therapeutic target discovery in other cancers. Citation Format: Zeribe Chike Nwosu, Heather C. Giza, Verodia Charlestin, Maya Nassif, Daeho Kim, Samantha Kemp, Nina G. Steele, Costas A. Lyssiotis, Marina Pasca di Magliano. Identification of high priority genes for basic and translational pancreatic cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr NG02.
Exploiting off-target effects of estrogen deprivation to sensitize estrogen receptor negative breast cancer to immune killing
Authors: Benjamin Wolfson, Michelle R Padget, Jeffrey Schlom, James W Hodge
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background There are highly effective treatment strategies for estrogen receptor (ER)+, progesterone receptor (PR)+, and HER2+ breast cancers; however, there are limited targeted therapeutic strategies for the 10%–15% of women who are diagnosed with triple-negative breast cancer. Here, we hypothesize that ER targeting drugs induce phenotypic changes to sensitize breast tumor cells to immune-mediated killing regardless of their ER status. Methods Real-time cell analysis, flow cytometry, qRT-PCR, western blotting, and multiplexed RNA profiling were performed to characterize ER+ and ER− breast cancer cells and to interrogate the phenotypic effects of ER targeting drugs. Sensitization of breast cancer cells to immune cell killing by the tamoxifen metabolite 4-hydroxytamoxifen (4-OHT) and fulvestrant was determined through in vitro health-donor natural killer cell 111 IN-release killing assays. A syngeneic tumor study was performed to validate these findings in vivo. Results Pretreatment with tamoxifen metabolite 4-OHT or fulvestrant resulted in increased natural killer (NK)–mediated cell lysis of both ER+ and ER− breast cancer cells. Through multiplexed RNA profiling analysis of 4-OHT-treated ER+ and ER− cells, we identified increased activation of apoptotic and death receptor signaling pathways and identified G protein-coupled receptor for estrogen (GPR30) engagement as a putative mechanism for immunogenic modulation. Using the specific GPR30 agonist G-1, we demonstrate that targeted activation of GPR30 signaling resulted in increased NK cell killing. Furthermore, we show that knockdown of GPR30 inhibited 4-OHT and fulvestrant mediated increases to NK cell killing, demonstrating this is dependent on GPR30 expression. Moreover, we demonstrate that this mechanism remains active in a 4-OHT-resistant MCF7 cell line, showing that even in patient populations with ER+ tumors that are resistant to the cytotoxic effects of tamoxifen, 4-OHT treatment sensitizes them to immune-mediated killing. Moreover, we find that fulvestrant pretreatment of tumor cells synergizes with the IL-15 superagonist N-803 treatment of NK cells and sensitizes tumor cells to killing by programmed death-ligand 1 (PD-L1) targeting high-affinity natural killer (t-haNK) cells. Finally, we demonstrate that the combination of fulvestrant and N-803 is effective in triple-negative breast cancer in vivo. Conclusion Together, these findings demonstrate a novel effect of ER targeting drugs on the interaction of ER+ and, surprisingly, ER− tumors cells with the immune system. This study is the first to demonstrate the potential use of ER targeting drugs as immunomodulatory agents in an ER agnostic manner and may inform novel immunotherapy strategies in breast cancer.
Abstract 786: Geography and adolescent and young adult cancer stage and survival
Authors: Kimberly J. Johnson, Xiaoyan Wang, Justin Barnes, Arash Delavar
Journal: Cancer Research (2021)

Abstract Background. Survival improvement in adolescents and young adults (AYA) diagnosed with cancer has lagged behind other age groups. Few studies have focused on geographic factors and outcomes in AYA. Our objective was to evaluate evidence for geographic disparities in cancer diagnosis stage and overall survival in AYAs. We also examined whether stage mediated survival associations. Methods. National Cancer Database data on AYA 15-39 years diagnosed from 2010-2014 were obtained. Rural/metro residence at diagnosis was defined using Rural Urban Continuum Codes. Distance between the case's residence and the reporting hospital was classified as short (&amp;lt;12.5 miles), intermediate (&amp;gt;12.5 and &amp;lt;50 miles), and long (&amp;gt;50 miles). Logistic and Cox proportional hazards regression models were used for analyses. Results. The stage and survival analyses included 146,418 and 178,688 AYA. The odds of a late vs. early stage diagnosis (stages 3 and 4 vs. 1 and 2) were 1.22 (95% CI 1.10 to1.35) times higher for AYA living in rural vs. metro counties and 1.23 (1.19 to1.28) times higher for AYA living at long vs. short distances. The hazard of death was 1.18 (1.04 to 1.34) and 1.37 (1.31 to 1.43) times higher for those living in rural vs. metro counties and for long vs. short distances. Stage mediated 41% and 27% of the associations between survival and rural/metro residence and residential distance. Conclusions. Rural residence and living long distances from the reporting hospital were associated with later-stage diagnoses and lower survival in AYA cancer patients. Further research is needed to understand mechanisms. Citation Format: Kimberly J. Johnson, Xiaoyan Wang, Justin Barnes, Arash Delavar. Geography and adolescent and young adult cancer stage and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 786.
Substance P/Heparin‐Conjugated PLCL Mitigate Acute Gliosis on Neural Implants and Improve Neuronal Regeneration via Recruitment of Neural Stem Cells
Authors: Donghak Kim, DoYeun Park, Tae Hee Kim, Justin J. Chung, Youngmee Jung, Soo Hyun Kim
Journal: Advanced Healthcare Materials (2021)

Abstract The inflammatory host tissue response, characterized by gliosis and neuronal death at the neural interface, limits signal transmission and longevity of the neural probe. Substance P induces an anti‐inflammatory response and neuronal regeneration and recruits endogenous stem cells. Heparin prevents nonspecific protein adsorption, suppresses the inflammatory response, and is beneficial to neuronal behavior. Poly(l‐lactide‐co‐ ε ‐caprolactone) (PLCL) is a soft and flexible polymer, and PLCL covalently conjugated with biomolecules has been widely used in tissue engineering. Coatings of heparin‐conjugated PLCL (Hep‐PLCL), substance P‐conjugated PLCL (SP‐PLCL), and heparin/substance P‐conjugated PLCL (Hep/SP‐PLCL) reduced the adhesion of astrocytes and fibroblasts and improved neuronal adhesion and neurite development compared to bare glass. The effects of these coatings are evaluated using immunohistochemistry analysis after implantation of coated stainless steel probes in rat brain for 1 week. In particular, Hep/SP‐PLCL coating reduced the activation of microglia and astrocytes, the neuronal degeneration caused by inflammation, and indicated a potential for neuronal regeneration at the tissue–device interface. Suppression of the acute host tissue response by coating Hep/SP‐PLCL could lead to improved functionality of the neural prosthesis.
Abstract 2468: The role of autophagy in lymphangiosarcoma development
Authors: Fuchun Yang, Michael Haas, Jun-Lin Guan
Journal: Cancer Research (2021)

Abstract Lymphangiosarcoma is a rare malignant vascular tumor which is formed from aberrant proliferation of endothelial cells (ECs). We previously established an endogenous mouse model of lymphangiosarcoma by conditional knockout of Tsc1 gene in ECs and revealed that hyper-activated mTORC1 is required for the vascular tumor development and progression through increased VEGF autocrine signaling. Using this model, we investigated the role of an essential autophagy gene FIP200 (FAK family interacting protein of 200 kDa) and its canonical autophagy function in lymphangiosarcoma development and progression by generating a FIP200 knockout (designated as Tsc1/Fip200 2cKO mice) or introducing a knockin allele that specifically blocks its canonical autophagy function (designated as Tsc1/Fip200 cKI mice) in combination with Tsc1 cKO in this study. We found that while both Tsc1/Fip200 cKO and Tsc1/Fip200 cKI mice exhibited lymph edema phenotype as Tsc1 cKO mice, they did not develop lymphangiosarcoma, suggesting that autophagy is required for lymphangiosarcom formation. Consistent with the above results, we also found that CRISPR-Cas9 mediated Fip200 KO in an immortalized vascular tumor cell line Tsc1ΔEC from Tsc1 cKO mice blocked their ability to grow tumors in xenograft transplants. Mechanistically, we found that autophagy was required for maintaining mTORC1 hyper-activation under nutrient stress condition. Moreover, the impaired lipophagy by Fip200 knockout affected lipid catabolism under glucose free condition and thus reduced the substrate for fatty acid oxidation (FAO). Our data showed that Fip200, Atg5 or Atg7 ablation in Tsc1ΔEC inhibited mitochondria respiration and decreased ATP contents as measured by Seahorse assays. Either lipase inhibitor Orlistat or carnitine palmitoyltransferase-1 (Cpt1) inhibitor Etomoxir treatment decreased Tsc1ΔEC mitochondria respiration and ATP production. Collectively, our data suggested that autophagy is required for lymphangiosarcoma initiation and progression by modulating FAO to supply cellular energy under stress for sustaining mTORC1 hyper-activation for tumor growth. Citation Format: Fuchun Yang, Michael Haas, Jun-Lin Guan. The role of autophagy in lymphangiosarcoma development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2468.
Surgical reperfusion using blood cardioplegia supplemented with the Na+/H+ exchange inhibitor cariporide (HOE 642) attenuates infarction and coronary endothelial dysfunction after severe regional ischemia
Authors: Muraki S, Abe T, Morris Cd, Budde Jm, Zhao Zc, Guyton Ra, Vinten-Johansen J
Journal: Circulation (2001)
Abstract 665: Cannabinoid receptor 2 tumor tissue gene expression positively affects lung cancer survival following radical surgery
Authors: Josef Srovnal, Monika Vidlarova, Emil Berta, Petr Prasil, Pavla Kourilova, Josef Chudacek, Marian Hajduch
Journal: Cancer Research (2021)

Abstract Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival rate of 21%. New treatment options are thus required, and the endogenous cannabinoid system is a potential new therapeutic target. We therefore analysed the expression of cannabinoid 1 and 2 receptor (CB1 and CB2) genes in NSCLC tissue and its influence on survival following radical surgery. Method: CB1 and CB2 gene expression in tumor tissue samples collected from 100 NSCLC patients was analysed using the quantitative real-time polymerase chain reaction. Since gene expression may not correlate with protein production, the presence of the CB2 protein was validated by immunohistochemistry. CB2 gene expression was correlated with disease stage, the presence of lymph node and distant metastases, tumor size, tumor grade, and survival. Result: Patients with tumors expressing CB2 gene had significantly longer overall survival (OS) (p&amp;lt;0.001), cancer-specific survival (CSS) (p=0.002), and disease-free survival (DFS) (p&amp;lt;0.001). They also had less advanced disease stage (p=0.047) and fewer lymph node metastases (p=0.011) at the time of surgery. A multivariate analysis showed that CB2 tumor tissue gene expression was a positive prognostic factor for OS (Hazard ratio (HR) = 0.402, p=0.013), CSS (HR=0.344, p=0.025), and DFS (HR=0.274, p=0.003). CB1 gene expression had no effect on survival. CB1 and CB2 gene expression was detected in 50% and 79.6% of the tumor tissue samples, respectively, and immunohistochemistry confirmed a correlation between CB2 gene expression and the presence of the CB2 protein in tumor tissues. Conclusion: In NSCLC patients undergoing radical surgery, CB2 gene expression in tumor tissue is associated with less advanced disease stage, fewer lymph node metastases, and longer survival (OS, CSS, DFS). Acknowledgement: This study was supported by Ministry of Health of the Czech Republic (NV18-03-00470), Ministry of Education, Youth and Sport of the Czech Republic (LM2018132), Palacky University Olomouc (LF 2020_007), Technological Agency of the Czech Republic (TN01000013), European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868) and Cancer Research Czech Republic. Citation Format: Josef Srovnal, Monika Vidlarova, Emil Berta, Petr Prasil, Pavla Kourilova, Josef Chudacek, Marian Hajduch. Cannabinoid receptor 2 tumor tissue gene expression positively affects lung cancer survival following radical surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 665.
What are the different diagnostic tests for female Bladder Outlet Obstruction (fBOO)? A systematic review from the European Association of Urology non-neurogenic female LUTS Guidelines Panel
Authors: K.H. Pang, R. Campi, M.I. Omar, C. Yuan, M. Karavitakis, M. Manso, S.M. Arteaga, A. Nic An Riogh, E. O’Connor, V.I. Sakalis, N. Sihra, L. Tzelves, S. Arlandis, K. Bo, E. Costantini, F. Farag, J. Groen, M.C. Lapitan, A. Nambiar, B. Peyronnet, V. Phé, C.H. Van Der Vaart, C.K. Harding
Journal: European Urology (2021)
Abstract 85: Metastasizing melanoma cells exhibit increased dependence on the pentose phosphate pathway to manage oxidative stress
Authors: Arin B. Aurora, VIshal Khivansara, Ashley Leach, Misty Martin-Sandoval, Thomas Mathews, Sean J. Morrison
Journal: Cancer Research (2021)

Abstract To study distant metastasis we developed a patient-derived xenograft (PDX) assay in which melanoma cells from patients spontaneously metastasize in NOD/SCID IL2Rγnull (NSG) mice in a manner that correlates with metastatic behavior in patients (Sci Transl Med 4:159). Using this assay, we discovered that distant melanoma metastasis is limited by oxidative stress (Nature 527:186). Reactive Oxygen Species (ROS) increase dramatically in melanoma cells as they metastasize through the blood. The rare cells that survive undergo reversible metabolic changes that confer oxidative stress resistance. We found that metastatic melanomas had significant increases in metabolites from the pentose phosphate pathway as compared to primary cutaneous melanomas. Metabolites in the oxidative branch of the pentose phosphate pathway, downstream of the NADPH-regenerating enzyme Glucose-6-Phosphate Dehydrogenase (G6PD), were the most dramatically increased in metastatic nodules. We hypothesized that metastasizing melanoma cells increase their dependence on the pentose phosphate pathway in order to manage oxidative stress. We used CRISPR gene editing to create loss-of-function mutations in G6PD in patient-derived melanomas. When transplanted into NSG mice, the tumors formed by G6PD mutant melanomas showed significantly reduced oxidative pentose phosphate pathway activity, increased ROS levels, decreased NADPH/NADP ratios, and reduced metastatic potential as compared to parental control melanomas. Our results demonstrate that metastasizing melanoma cells exhibit increased dependence upon the pentose phosphate pathway as compared to primary cutaneous tumors. Untargeted metabolomics revealed that G6PD mutant melanomas exhibit increased glutamine utilization, perhaps to compensate for increased oxidative stress. Citation Format: Arin B. Aurora, VIshal Khivansara, Ashley Leach, Misty Martin-Sandoval, Thomas Mathews, Sean J. Morrison. Metastasizing melanoma cells exhibit increased dependence on the pentose phosphate pathway to manage oxidative stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 85.
Abstract 2297: Regulatory role of MRCK gamma in ovarian cancer metastasis
Authors: Leslie Toledo-Jacobo
Journal: Cancer Research (2021)

Abstract In ovarian cancer, compacted cell aggregates known as spheroids detach from the primary tumor and enable metastasis within the peritoneum. Targeting this ovarian metastatic cascade motivates a delineation of the morphogenetic pathways governing spheroid shedding and invasion. Here we analyze the role of one of three related Myotonic Dystrophy Kinase-Related CDC42-Binding Kinases (MRCKγ) in ovarian cancer metastasis, and test its potential as a therapeutic target. MRCKs are downstream effectors of Cdc42 and Rac1 GTPases and through activation of myosin-II could produce the mechanical force required during cell invasion. MRCKγ is amplified or mutant in 12.5% of 1680 serous ovarian cancer patient samples in TCGA. Analyses of ovarian cancer SKOV3ip cells with 4-fold overexpression of GFP-Rac1 and increased GTPase activation showed a 1.5-fold increase in MRCKγ protein and a concomitant increase in the phosphorylation of myosin required for contractile force generation. A similar increase in myosin phosphorylation was observed in two OVCAR8 cell lines with overexpression of GFP-Rac1 and GFP-Cdc42, respectively. Analyses of the effects MRCKγ knockdown on ovarian spheroid formation and in mesothelial clearance are in progress. To evaluate the therapeutic potential of MRCK/Cdc42BPs we are also testing their pharmacological inhibition with BDP9066 and SD208 during spheroid formation and mesothelial clearance. Our findings are supported by a recent report showing that inhibition of the related MRCKα kinase blocks ovarian cancer cell spheroid formation in vitro. By the end of these studies we will have a better understanding of the role of MRCK/Cdc42BPs in ovarian cancer metastatic pathway, and a potential therapeutic target for ovarian cancer treatment. Citation Format: Leslie Toledo-Jacobo. Regulatory role of MRCK gamma in ovarian cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2297.