tbuckley/cabot-search huggingface dataset:
Abstract 3746: Fasting in mice enables abdominal radiation dose escalation in the setting of pancreatic cancer by mitigating small intestinal toxicity
Authors: Marimar de la Cruz Bonilla, Kristina M. Stemler, Sabrina Jeter-Jones, Tara N. Fujimoto, Jessica Molkentine, Gabriela M. Asencio Torres, Cullen M. Taniguchi, Helen Piwnica-Worms
Journal: Cancer Research (2019)

Abstract Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate that a 24 hour fast also protects mice from lethal doses of total-abdominal radiation. Histologic analyses using the Withers-Elkind microcolony assay show that fasting protected small intestinal (SI) stem cells from radiation damage and promoted early regeneration. To show a proof-of-principle for the use of this radioporotective maneuver in cancer therapy, we used an orthotopic model of pancreatic cancer using KPC tumor cells syngeneic to C57BL/6. Here, we show that fasting-mediated intestinal protection enabled dose escalated SBRT for treatment of these orthotopic tumors. RT with fasting-mediated radioprotection delayed tumor growth and improved survival compared to controls. Given this robust phenotype, we developed a 3D culture ex vivo assay using intestinal stem cell-enriched epithelial spheroid cultures. We modified these intestinal spheroids with a bioluminescent reporter and used these cells to develop a modified clonogenic assay for 3D culture that can be used to identify novel radioprotectors, such as a fasting mimetic. Taken together, these results suggest that fasting protects small intestinal stem cells, allowing animals to receive potentially curative doses of abdominal radiation that would otherwise be lethal. Future work will aim to identifying the mechanisms by which fasting confers intestinal protection and drug candidates that can be used to mimic this fasting-mediated protection. Citation Format: Marimar de la Cruz Bonilla, Kristina M. Stemler, Sabrina Jeter-Jones, Tara N. Fujimoto, Jessica Molkentine, Gabriela M. Asencio Torres, Cullen M. Taniguchi, Helen Piwnica-Worms. Fasting in mice enables abdominal radiation dose escalation in the setting of pancreatic cancer by mitigating small intestinal toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3746.
Abstract 3295: GPRASP1:A novel potential biomarker for neuroendocrine carcinoma
Authors: Minggang Xiong, Fuhao Wang, Haiyen E. Zhau, Xin Huang, Leland Chung, Jian Zhang, Yi Lu
Journal: Cancer Research (2019)

Abstract Neuroendocrine differentiation has been observed to correlate with the progression and prognosis of prostate cancer (PCa), gastric cancer and pancreatic cancer, but the mechanisms remain unclear. GPRASP-1, a G protein coupled receptor-associated sorting protein 1, is known as a significant modulator of lysosomal sorting, and functional down-regulation of G- protein coupled receptors by interacting with Beclin2. The GPRASP-1 was originally considered as a serum tumor biomarker for breast cancer and later it was confirmed as a ubiquitous tumor marker among lung, liver and brain cancers. Based on its function as a tumor biomarker, we conducted serum ELISA analysis of GPRASP-1, and correlated results with RNAseq and gene copy numbers among a large cohort of PCa patients. We found overexpression and gene amplification of GPRASP-1 in 24 of 77 patients (31%) with neuroendocrine PCa (NEPCa). The patients with elevated serum GPRASP-1 level had a higher risk of metastasis to liver, lung and lymph nodes. Furthermore, immunohistochemical analysis for GPRASP-1 showed a strong staining of the pathological section from pancreatic neuroendocrine carcinoma patients and their liver metastases. Knocking down of the GPRASP-1 in a NEPCa PC3 cell line showed dramatic downregulation of TACR family, Tachykinin Receptor, which is known to be involved in the neuroinflammation and neurotransmitter transport and cancer proliferation. Our results offer a novel link among GPRASP-1, neuroendocrine differentiation and castration resistance in human PCa. We proposed serum GPRASP-1 can serve as a novel biomarker differentiating cancers with and without neuroendocrine differentiation. (Supported by NSFC projects 81773146; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, 2017B030301018); JCYJ20170412152943794, JCYJ20170412154619484, JCYJ20170307105128101, JCYJ2017030711041760) Note: This abstract was not presented at the meeting. Citation Format: Minggang Xiong, Fuhao Wang, Haiyen E. Zhau, Xin Huang, Leland Chung, Jian Zhang, Yi Lu. GPRASP1:A novel potential biomarker for neuroendocrine carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3295.
SETD2 Non-Genomic Loss of Function and p53 Functional Inactivation in Advanced Systemic Mastocytosis (SM): Pathogenetic and Therapeutic Implications
Authors: Manuela Mancini, Cecilia Monaldi, Sara De Santis, Cristina Papayannidis, Michela Rondoni, Maria Chiara Abbenante, Luana Bavaro, Margherita Martelli, Elisa Ficarra, Giulia Paciello, Viviana Guadagnuolo, Maria Chiara Fontana, Marco Manfrini, Roberta Zanotti, Livio Pagano, Francesco Albano, Fabio Ciceri, Chiara Elena, Patrizia Tosi, Massimo Delledonne, Peter Valent, Michele Cavo, Giovanni Martinelli, Simona Soverini
Journal: Blood (2017)
Abstract 1627: Using internet-platform technology to train community-based researchers in developing countries: Lessons learned from a Caribbean study
Authors: Kamilah B. Thomas-Purcell, Marva Primus Primus-Jospeh, Christine Richards, Lydia S. Atkins, Julie Blaze, Patsy Wylie, Ann Marie Burnie James, Kimlin Ashing
Journal: Cancer Research (2019)

Abstract Cancer is increasing as a health crisis in the Caribbean region. In the U.S. advocate engagement and Community Based Participatory Research (CBPR) have been used successfully to partner with community members in each stage of the research process thereby utilizing the knowledge and experience of those individuals for improved community responsive research and greater societal benefit. We utilized advocate engagement and CBPR towards building a cancer prevention program of research between U.S. and Caribbean researchers. In 2016-2017, a two-phased CBPR research study was initiated to address breast and cervical cancer screening in the four countries of the English-speaking Windward Islands of the Caribbean. The aims were to determine 1) community member’s perceptions of breast and cervical cancer screening and 2) gatekeepers’ perceptions of the quality and availability of breast and cervical cancer screening and treatment services. Mobile communication and internet-platform technologies were used to successfully train Caribbean community researchers on qualitative data collection and analysis methods. Our results showed that the incorporation of internet-based technology facilitated training, communication, social interactions, and alleviated transportation challenges. In particular, mobile platforms including GoToTraining, WhatsApp, Dedoose, Google Drive, and email were to used to deliver interactive training modules to community researchers and facilitate the collaborative development of recruitment materials, data collection instruments, data management, reports, manuscripts and results dissemination. Participatory research studies of this nature not only shed light on the cancer burden in developing nations but also builds community trust and capacity to engage in future international research. Citation Format: Kamilah B. Thomas-Purcell, Marva Primus Primus-Jospeh, Christine Richards, Lydia S. Atkins, Julie Blaze, Patsy Wylie, Ann Marie Burnie James, Kimlin Ashing. Using internet-platform technology to train community-based researchers in developing countries: Lessons learned from a Caribbean study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1627.
Abstract 2637: Novel targeted therapy-resistant <i>FGFR3</i> splice variant increases oncogenic phenotype in African American prostate cancer
Authors: Jacqueline Moy, Bi-Dar Wang, Norman H. Lee
Journal: Cancer Research (2019)

Abstract Introduction: In this study, we investigate the role of alternative splicing in the receptor tyrosine kinase family on prostate cancer health disparities in African American men. Background: Prostate cancer (PCa) is the most diagnosed cancer in men and the second leading cause of male-cancer related deaths in the U.S. Dramatic ethnic disparities have been observed in PCa patients, as African American (AA) men are 60% more likely to be diagnosed with PCa and have a 2.4 fold higher mortality rate compared to European American (EA) men. Increasing evidence suggests that, after accounting for epidemiological factors, a remaining component of this disparity is due to intrinsic genetic and biological factors. Interestingly, exon array data from our lab suggest that differential alternative splicing (dAS) may be occurring in AA PCa. We hypothesize that dAS involving exon 14 of FGFR3 is generating a shorter, more oncogenic variant in AA PCa, which is absent or weakly expressed in EA PCa. Differential splicing of FGFR3 in AA patients may be mechanisms contributing to AA PCa health disparities. Results: Cloning confirmed the presence of the FGFR3-L variant (containing exon 14) and the FGFR3-S variant (without exon 14) from EA and AA PCa cell lines, respectively. RNA-seq data analysis suggests decreased survival of PCa patients with high FGFR3-S/-L expression ratios. EA cell lines overexpressing FGFR3-S show increased small molecule inhibitor (SMI) TKI258-mediated resistance to proliferation, invasion, and apoptosis in vitro. Additionally, mice injected with cells overexpressing FGFR3-S have increased tumor growth, metastasis, and resistance to TKI258 treatment. Conclusions: We have identified an oncogene of interest, FGFR3, which undergoes exon skipping specific to AA PCa. We have successfully cloned this novel FGFR3 variant in cell lines and created stable cell lines overexpressing both short and long variants. In vitro and in vivo studies suggest FGFR3-S is more resistant to SMIs. Thus, dAS in FGFR3 may be one mechanism contributing to the increased aggressiveness of PCa in AA patients. Citation Format: Jacqueline Moy, Bi-Dar Wang, Norman H. Lee. Novel targeted therapy-resistant FGFR3 splice variant increases oncogenic phenotype in African American prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2637.
Survival Benefit of Novel Drug Combinations Using Hypomethylating Agents for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia: A Systemic Review
Authors: Pavan Tenneti, Keri R Maher, Mohamed Mokhtar Bakr, Umar Zahid, Saad Ullah Malik, Warda Faridi, Faiz Anwer
Journal: Blood (2018)
Smoking and Cognitive Performance: The Chicken and Egg Problem
Authors: Peter Hajek, Dunja Pruzlj, Katie Myers Smith
Journal: American Journal of Psychiatry (2019)

offset the influence of the (much stronger) negative selection effects in those with schizophrenia, and that therefore overall, there is no reproductive advantage conferred by common variant liability.Neither our new analyses nor those of Lawn and colleagues challenge that conclusion.We believe alternative explanations are required for the persistence of common alleles that increase susceptibility to schizophrenia.Based on work we have published elsewhere (2), we suggest this may occur through the effects of purifying (negative) selection on genetic diversity at particular loci, which in turn allows mildly deleterious alleles to drift to higher frequencies than otherwise expected.
Abstract 1848: The role of PDK1 in metabolic reprogramming of mesenchymal glioblastoma
Authors: Neha Jain, Maheedhara Guda, Collin Labak, Chase Smith, Simon Park, Andrew Tsung, Kiran Velpula
Journal: Cancer Research (2019)

Abstract Despite multimodal therapy and ever-improving surgical technique, glioblastoma (GBM) maintains its poor prognosis due to the chemotherapeutic resistance it builds over time, eventually rendering existing agents ineffective. A well-characterized phenomenon that takes place particularly in mesenchymal GBM tissue is the Warburg Effect, characterized by a shift from oxidative phosphorylation to glycolysis as a primary means to derive energy. Pyruvate Dehydrogenase Kinase 1 (PDK1) is one upregulated molecule in this shift toward anaerobic metabolism that is known for phosphorylating pyruvate dehydrogenase, the “gate keeper” of the TCA cycle. We sought to characterize further the role of PDK1 in terms of its metabolic role and any extra-metabolic functions it may serve. By silencing PDK1 and considering changes in downstream expression, we hope to understand what other factors serve as contributors to metabolic alterations seen in GBM. Elucidating the mechanism of this crucial shift more thoroughly, especially without the prominently cited role of PDK1, can begin to expose new targets for interrupting tumor maintenance and proliferation by affecting its metabolism. In this study we used differential expression of two vectors in which PDK1 was silenced, shPDK1 and SCBT-PDK1. GSEA analysis was done and analyzed to identify classes of genes or proteins that are over-represented and to identify significantly enriched or depleted groups of targets whose expression was vastly changed by silencing of PDK1. Using GSEA heat map data, gene targets whose expression was noted to be consistently changed with silencing of PKD1 targets were identified. Datamining and immunoblot analyses were then conducted to evaluate for expression of these genes in correlating GBM specimens. Ultimately, we further characterize PDK1’s global role in GBM and evaluate non-metabolic effects of PDK1 that may still affect survival and proliferation of GBM tumors. Citation Format: Neha Jain, Maheedhara Guda, Collin Labak, Chase Smith, Simon Park, Andrew Tsung, Kiran Velpula. The role of PDK1 in metabolic reprogramming of mesenchymal glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1848.
Abstract 4910: Neurocognitive effects of central nervous system directed chemotherapy in Non Hodgkin Lymphoma diseased children
Authors: Abeer Abd Elmoneim, Ahlam Eladawy, Mona Abu Elkasem, Soumaya Hadhood
Journal: Cancer Research (2019)

Abstract Background and Purpose. Because the blood-brain barrier serves as a pharmacological barrier, malignant cells can remain in the central nervous system (CNS) despite systemic chemotherapy. Consequently, CNS-directed treatment is an essential part of therapy for Non-Hodgkin lymphoma (NHL). We aimed in this analysis to determine the neurocognitive effects of CNS-directed chemotherapy in children with NHL. Methods. In a cross-sectional study 20 NHL diseased children and 10 healthy controls were tested for neurocognitive functions. The selection criteria were: 3 years or more after the end of NHL chemotherapy only regimen, no anaemia, no CNS or systemic diseases. Both patients and healthy controls were examined for global intelligence quotient (IQ), verbal IQ, performance IQ, attention measures, auditory tests, long and short memory, math skills and academic achievement. Results. No decline in global IQ in NHL children compared to healthy controls but there was a significant decline of attention, verbal comprehension and performance IQ. Among 20 NHL diseased children 18 had poor recent and immediate memories while remote memory was normal in 16 children. Young age at diagnosis and treatment intensity were the commonest risk factors. Conclusion. In absence of cranial irradiation, childhood survivors of NHL experience long-term neurocognitive deficits after chemotherapy treatment. Global IQ is not a sufficiently sensitive measure to detect specific CNS deficits in NHL diseased children. The deficits are mainly present in basic neurophysiologic processes of attention and executive functioning. Note: This abstract was not presented at the meeting. Citation Format: Abeer Abd Elmoneim, Ahlam Eladawy, Mona Abu Elkasem, Soumaya Hadhood. Neurocognitive effects of central nervous system directed chemotherapy in Non Hodgkin Lymphoma diseased children [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4910.
Association of Prognostic Nutritional Index as a predictive factor of survival in patients with colorectal cancer in a Mexican population
Authors: C. Diaz, G. Calderillo-Ruiz, M. Ramos-Ramirez, M. Herrera, F. Manuel, L. Horacio, E. Ruiz-Garcia, V. Itzel, J. Ruan, G. Miranda, A. Gomez, A. Meneses
Journal: Annals of Oncology (2019)
Using Collaborative Cross Mouse Population to Fill Data Gaps in Risk Assessment: A Case Study of Population-Based Analysis of Toxicokinetics and Kidney Toxicodynamics of Tetrachloroethylene
Authors: Yu-Syuan Luo, Joseph A. Cichocki, Nan-Hung Hsieh, Lauren Lewis, Fred A. Wright, David W. Threadgill, Weihsueh A. Chiu, Ivan Rusyn
Journal: Environmental Health Perspectives (2019)

Background: Interindividual variability in susceptibility remains poorly characterized for environmental chemicals such as tetrachloroethylene (PERC). Development of population-based experimental models provide a potential approach to fill this critical need in human health risk assessment. Objectives: In this study, we aimed to better characterize the contribution of glutathione (GSH) conjugation to kidney toxicity of PERC and the degree of associated interindividual toxicokinetic (TK) and toxicodynamic (TD) variability by using the Collaborative Cross (CC) mouse population. Methods: Male mice from 45 strains were intragastrically dosed with PERC (1,000mg/kg) or vehicle (5% Alkamuls EL-620 in saline), and time-course samples were collected for up to 24 h. Population variability in TK of S-(1,2,2-trichlorovinyl)GSH (TCVG), S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC), and N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine (NAcTCVC) was quantified in serum, liver, and kidney, and analyzed using a toxicokinetic model. Effects of PERC on kidney weight, fatty acid metabolism–associated genes [Acot1 (Acyl-CoA thioesterase 1), Fabp1 (fatty acid-binding protein 1), and Ehhadh (enoyl-coenzyme A, hydratase/3-hydroxyacyl coenzyme A dehydrogenase)], and a marker of proximal tubular injury [KIM-1 (kidney injury molecule-1)/Hepatitis A virus cellular receptor 1 (Havcr1)] were evaluated. Finally, quantitative data on interstrain variability in both formation of GSH conjugation metabolites of PERC and its kidney effects was used to calculate adjustment factors for the interindividual variability in both TK and TD. Results: Mice treated with PERC had significantly lower kidney weight, higher kidney-to-body weight (BW) ratio, and higher expression of fatty acid metabolism–associated genes (Acot1, Fabp1, and Ehhadh) and a marker of proximal tubular injury (KIM-1/Havcr1). Liver levels of TCVG were significantly correlated with KIM-1/Havcr1 in kidney, consistent with kidney injury being associated with GSH conjugation. We found that the default uncertainty factor for human variability may be marginally adequate to protect 95%, but not more, of the population for kidney toxicity mediated by PERC. Discussion: Overall, this study demonstrates the utility of the CC mouse population in characterizing metabolism–toxicity interactions and quantifying interindividual variability. Further refinement of the characterization of interindividual variability can be accomplished by incorporating these data into in silico population models both for TK (such as a physiologically based pharmacokinetic model), as well as for toxicodynamic responses. https://doi.org/10.1289/EHP5105
Abstract 18395: Familial Combined Hyperlipidaemia is Characterized by Increased Vascular Inflammation and Haematopoietic Tissue Metabolic Activation
Authors: Georgios Benetos, Konstantinos Toutouzas, Iosif Koutagiar, John Skoumas, Nikoleta Pianou, Alexis Antonopoulos, Alexandros Georgakopoulos, Pavlos Kafouris, George Spyrou, Georgios Oikonomou, Constantinos Anagnostopoulos, Dimitris Tousoulis
Journal: Circulation (2017)

Introduction: Recent studies have shown increased haematopoietic activity in patients with clinical atherosclerosis, known as cardiosplenic axis. Adults with genetic dyslipidaemias are characterize...
Simple, reliable detection of amyloid in fat aspirates using the fluorescent dye FSB: prospective study in 206 patients
Authors: Masayoshi Tasaki, Paolo Milani, Andrea Foli, Laura Verga, Laura Obici, Marco Basset, Margherita Bozzola, Giovanni Ferraro, Mario Nuvolone, Patrizia Morbini, Gianluca Capello, Mitsuharu Ueda, Konen Obayashi, Marco Paulli, Yukio Ando, Giampaolo Merlini, Giovanni Palladini, Francesca Lavatelli
Journal: Blood (2019)
British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma
Authors: Matthew Banks, David Graham, Marnix Jansen, Takuji Gotoda, Sergio Coda, Massimiliano di Pietro, Noriya Uedo, Pradeep Bhandari, D Mark Pritchard, Ernst J Kuipers, Manuel Rodriguez-Justo, Marco R Novelli, Krish Ragunath, Neil Shepherd, Mario Dinis-Ribeiro
Journal: Gut (2019)

Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer—in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met.