tbuckley/cabot-search huggingface dataset:
Abstract 1349: NSAIDs: Multiple roles in multiple environments
Authors: Gloria M. Calaf, Debasish Roy
Journal: Cancer Research (2017)

Abstract Non steroidal drugs are mainly known for their activities and use as anti-inflammatory, antipyretic compounds. But, in recent observations, they are exposed to use as an effective alternative compounds to prevent or stimulate different metabolic activities and help in preventing various neoplastic progression. They have specific role in controlling estrogen metabolism during breast cancer progression. Sometimes, they are used as an apoptotic induction in various cancers. Their role in hypoxia induced proliferation is also showing promising results. Different NSAIDs will help to induce the activities of various tumor suppressor genes. As chronic inflammation increases the risk for various cancers, therefore, it is important to eliminate inflammation through anti-Inflammatory compounds where NSAIDs are playing a vital role. Most of them are acting to prevent inflammation either via selective or non-selective COX based mechanism. The non-selective COX inhibitor sulindac and the COX-2 selective inhibitor etodolac etc. have been shown to prevent the formation and cause regression of adenomas in patients with familial polyposis. Unfortunately, COX-1 and/or COX-2 inhibition and depletion of physiologically important prostaglandins is associated with gastrointestinal, renal and cardiovascular toxicities that limit the use of NSAIDs and COX-2 inhibitors for cancer chemoprevention In this particular study, we are using various NSAIDs in a radiation-induced estogren treated breast cancer model to establish their role in differential expression of various cancer related genes selected from different cell cycle pathways microarray. Selection of biomarkers from these altered genes will help to develop a valid strategy for cancer prevention through precision based molecular targeted therapy. Supported by Office of Academic Affairs, Honors Program, COBI, Hostos-CUNY, NY, USA (DR) and Tarapacá University, Arica, Chile (GMC). Citation Format: Gloria M. Calaf, Debasish Roy. NSAIDs: Multiple roles in multiple environments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1349. doi:10.1158/1538-7445.AM2017-1349
Abstract 2997: The tetravalent bispecific antibody AFM13 engages and primes innate immune cells for anti-cancer immunity
Authors: Jens Pahl, Joachim Koch, Uwe Reusch, Thorsten Gantke, Adelheid Cerwenka, Martin Treder
Journal: Cancer Research (2017)

Abstract AFM13 is a tetravalent bispecific antibody with bivalent binding to both CD30 and CD16A. It has been shown to engage NK-cells through CD16A with high affinity and specificity, resulting in strong NK-cell cytotoxicity, and is currently being tested in Phase 2 monotherapy and in combination with pembrolizumab in Phase 1b clinical trials. We have previously shown that AFM13-dependent activation of NK-cell cytotoxicity towards CD30+ tumor cells is more pronounced than that of anti-CD30 mAbs. In addition, AFM13 enhances NK-cell sensitivity to low doses of IL-2 and IL-15, leading to an increased NK-cell proliferative potential. Here, we have extended the panel of phenotypic markers on NK-cells that are modulated after exposure to CD30+ tumor cells in the presence of AFM13. Targeting some of these markers may enable the development of novel combination therapies. Moreover, we have analyzed the kinetics of NK-cell responses to AFM13 exposure. Even though short-term exposure to AFM13 significantly enhanced NK-cell cytotoxicity, long-term exposure led to a partial, transient functionally exhausted phenotype in vitro, which could be fully restored by cytokine stimulation for several days in the absence of AFM13. Importantly, these recovered cells displayed high cytotoxicity towards CD30+ target cells in the presence of AFM13. Interestingly, the transient NK-cell exhaustion was not related to the expression of typical exhaustion markers or insufficient levels of perforin and granzyme. These data may warrant the development of novel metronomic application regimens of AFM13. Further studies imply that immune cells other than NK-cells are able to inhibit growth of CD30+ tumor cells in an AFM13-dependent manner. This appears to be strictly dependent on CD16A and a specific cytokine milieu. Taken together, AFM13 specifically enhances the cytotoxic, proliferative and cytokine-producing potential of NK-cells, parameters that can be utilized to monitor NK-cell responses during AFM13 therapy. Moreover, based on our data, engagement of CD16A+ cells to the tumor site might enable several innate immune effector functions within the tumor microenvironment for synergistic anti-tumor activity. Citation Format: Jens Pahl, Joachim Koch, Uwe Reusch, Thorsten Gantke, Adelheid Cerwenka, Martin Treder. The tetravalent bispecific antibody AFM13 engages and primes innate immune cells for anti-cancer immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2997. doi:10.1158/1538-7445.AM2017-2997
Double whammy: the disappearing right atrium
Authors: Aparna Kadambi, Parimal Kumar Chaudhari, Lawrence DeLorenzo, Oleg Epelbaum
Journal: Thorax (2017)

A 66-year-old man with hepatitis C virus (HCV) infection complicated by liver cirrhosis presented with about 6 months of severe right shoulder pain as well as more recent progressive dyspnoea on exertion and lower extremity oedema. On outpatient evaluation at the onset of shoulder symptoms, they had been ascribed to an orthopaedic aetiology. He had recently completed treatment for HCV with ledipasvir/sofosbuvir after failure to respond to a regimen of interferon/ribavirin. Approximately 2 years earlier, he had been diagnosed with unresectable multifocal stage III hepatocellular carcinoma (HCC) and treated with transarterial chemoembolisation (TACE), radiofrequency ablation and ethanol ablation as a bridge to possible liver transplantation. On presentation, he was hemodynamically stable with no reported pulsus paradoxus. Physical examination revealed an elevated jugular venous pulse, anasarca and decreased breath sounds over the right lower chest. There was no clinically overt ascites. His plain chest radiograph showed a right pleural effusion and a thickened right …
CDC Grand Rounds: Addressing Health Disparities in Early Childhood
Authors: Lara R. Robinson, Rebecca H. Bitsko, Ross A. Thompson, Paul H. Dworkin, Mary Ann McCabe, Georgina Peacock, Phoebe G. Thorpe
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Research suggests that many disparities in overall health and well-being are rooted in early childhood (1,2). Stressors in early childhood can disrupt neurologic, metabolic, and immunologic systems, leading to poorer developmental outcomes (1). However, consistent, responsive caregiving relationships and supportive community and health care environments promote an optimal trajectory (3,4). The first 8 years of a child's life build a foundation for future health and life success (5-7). Thus, the cumulative and lifelong impact of early experiences, both positive and negative, on a child's development can be profound. Although the health, social service, and education systems that serve young children and their families and communities provide opportunities to support responsive relationships and environments, efforts by these systems are often fragmented because of restrictions that limit the age groups they can serve and types of services they can provide. Integrating relationship-based prevention and intervention services for children early in life, when the brain is developing most rapidly, can optimize developmental trajectories (4,7). By promoting collaboration and data-driven intervention activities, public health can play a critical role in both the identification of at-risk children and the integration of systems that can support healthy development. These efforts can address disparities by reducing barriers that might prevent children from reaching their full potential.
Abstract 1965: A novel biocompatible fluorescent nanoparticle enables enhanced live cell tagging and tracking of cancer cells
Authors: Nick Asbrock, Vi Chu, Kevin Su, Ben Zhong Tang, Bin Liu
Journal: Cancer Research (2017)

Abstract Metastasis is the leading cause of cancer mortality. Metastasis is a multi-step process which includes local tumor cell invasion, cell migration into the vasculature, exit of cells from the circulation and colonization at the distal tissue sites. Long-term noninvasive cell tracking by fluorescent probes is of great importance to life science and biomedical engineering. Current methods used to fluorescently tag cancer cells have been limited by short signal duration, high background auto-fluorescence or lengthy cell line generation using GFP. We have developed a biocompatible fluorescent nanoparticle which relies on Aggregation Induced Emission (AIE) technology that are highly resistant to fluorescent signal quenching. These particles enable highly efficient live cell fluorescent tagging while retaining fluorescent signal for up to 10 days in vitro and 21 days in vivo. These nanoparticles will open new avenues in the development of fluorescent probes for following biological processes such as carcinogenesis. Citation Format: Nick Asbrock, Vi Chu, Kevin Su, Ben Zhong Tang, Bin Liu. A novel biocompatible fluorescent nanoparticle enables enhanced live cell tagging and tracking of cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1965. doi:10.1158/1538-7445.AM2017-1965
Abstract LB-064: Cheminformatics studies to analyze the therapeutic potential of alkaloids from Rhazya stricta
Authors: Jamal S. Sabir, Abdullah Obaid Y. Obaid, Sreedhara Voleti, Roop S. Bora, Nahid H. Hajrah, Abdulkader M. Omar, Kulvinder S. Saini
Journal: Cancer Research (2017)

Abstract Rhazya stricta is a unique medicinal plant source for many indole alkaloids, non- alkaloids, flavonoids, triterpenes and other unknown molecules with tremendous potential for therapeutic applications against many diseases. In the present article, we generated computational data on predictive properties and activity across two key therapeutic areas of cancer and obesity, and corresponding cheminformatics studies were carried out to examine drugable properties of these alkaloids. Computed physiochemical properties of the 78 indole alkaloids from Rhazya stricta plant using industry-standard scientific molecular modeling software and their predictive anti-cancer activities from reliable web-source technologies indicate their plausible therapeutic applications. Their predictive ADME properties are further indicative of their drug-like-ness. We believe that the top-ranked molecules with anti-cancer activity are clearly amenable to chemical modifications for creating potent, safe and efficacious compounds with the feasibility of generating new chemical entities (NCEs) after pre-clinical and clinical studies. Keywords: Rhazya stricta, Alkaloids, Physiochemical properties, Druggability, Anticancer molecules, Anti-obesity molecules. Citation Format: Jamal S. Sabir, Abdullah Obaid Y. Obaid, Sreedhara Voleti, Roop S. Bora, Nahid H. Hajrah, Abdulkader M. Omar, Kulvinder S. Saini. Cheminformatics studies to analyze the therapeutic potential of alkaloids from Rhazya stricta [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-064. doi:10.1158/1538-7445.AM2017-LB-064
Abstract 1421: Evaluation of DDR-targeting strategy using ATR inhibitor in biliary tract cancer
Authors: Ah Rong Nam, Ji Eun Park, Ju Hee Bang, Mei Hua Jin, Do Youn Oh, Yung Jue Bang
Journal: Cancer Research (2017)

Abstract Background: The DNA damage response (DDR) is a multicomplex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints and apoptosis. The ataxia telangiectasia and Rad3-related (ATR) protein kinase is a key enzyme in the DDR that activates checkpoint kinase 1 (Chk1), resulting in cell cycle arrest. Tumor types with loss of ATM function and/or high replication stress are expected to be more susceptible to DDR targeting. In biliary tract cancer (BTC), DNA repair pathway, which includes BAP1, MSH6, BRCA1, ATM, MLH1, MSH2, is altered in about 20 % of cases. TP53 module is observed in 33.9% of BTC cases (Nat Genet 2015). The purpose of this study is to test DDR targeting strategy using ATR inhibitor in biliary tract cancer. Methods: Using 9 kinds of BTC cells, MTT assay and colony formation assay were done for determining growth inhibitory effect of AZD6738, an ATR inhibitor. Cell cycle analysis was done by FACS Calibur flow cytometer and the methods described by Chou and Talalay were used to determine whether a synergistic effect existed between AZD6738 and cytotoxic chemotherapeutic agents (cisplatin, 5-FU, gemcitabine). The alkaline comet assay was done to measure of DNA damage in individual cells. Tumor xenografts model was used for in vivo test of AZD6738. Results: Among 9 BTC cells, SNU478 and SNU869 were most sensitive to AZD6738, which showed low expression of both ATM and p53. AZD6738 blocked ATR-mediated Chk1 phosphorylation and increased rH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis (cleavage of PARP and caspase-7) and G2/M arrest, increased level of p21, and decreased cdc2. In addition, combination of AZD6738 and cytotoxic chemotherapeutic agents demonstrated synergistic effects in colony formation assay, cell cycle analysis and comet assay. In xenograft model of SNU478, AZD6738 monotherapy decreased tumor growth. The combination of AZD6738 and cisplatin showed more potent growth inhibitory effects, decreased Ki67, increased Tunel than monotherapy of each drug. Conclusion: In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC. Citation Format: Ah Rong Nam, Ji Eun Park, Ju Hee Bang, Mei Hua Jin, Do Youn Oh, Yung Jue Bang. Evaluation of DDR-targeting strategy using ATR inhibitor in biliary tract cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1421. doi:10.1158/1538-7445.AM2017-1421
Early prediction of clinical outcomes in resected stage II and III colorectal cancer (CRC) through deep sequencing of circulating tumor DNA (ctDNA).
Authors: Maximilian Diehn, Ash A. Alizadeh, Hans-Peter Adams, John J. Lee, Susanne Klassen, John F. Palma, Bernd Hinzman, Alexander F. Lovejoy, Aaron M. Newman, Lijing Yao, Stephanie Yaung, Aarthi Balasubramanyam, Ulrich Peter Rohr, Andre Rosenthal, Rainer Kube, Thomas Steinmüller, Frank Marusch, Rene Mantke, Michael Heise, Matthias Pross
Journal: Journal of Clinical Oncology (2017)

3591 Background: Adjuvant chemotherapy is offered to most pts with Stage III CRC, and to a subset with Stage II disease deemed at high-risk for recurrence. Nevertheless, risk stratification strategies remain suboptimal. Detection of minimal residual disease (MRD) through ctDNA analysis has been shown to identify pts at high recurrence risk in Stage II CRC, but not Stage III disease. Methods: The next-generation sequencing based AVENIO ctDNA Surveillance Kit (Research Use Only) was used to identify single nucleotide variants (SNVs) in tumor tissue within a cohort of 145 Stage II and III CRC pts following R0 surgical resection (n = 86 and 59 respectively; median follow-up = 32.1 mo). The same assay was used to monitor ctDNA with a single post-operative blood sample (mean surgery-to-phlebotomy time: 10 days). Regions from 197 genes recurrently mutated in CRC were interrogated, and pts were classified as ctDNA positive (+) or negative (-) in plasma based on the detection of SNVs previously identified in tumor tissue. Results: Variants were identified in 99% of tumors (n = 144) with a median of 4 SNVs/sample (range 1-24) and all post-operative plasma samples were successfully profiled. Pts with detectable ctDNA (n = 12) displayed a significantly shorter 2-year relapse-free survival (RFS; 17% vs 88%; HR 10.3; 95% CI 2.3-46.9; p &lt; 0.00001), time to recurrence (TTR; HR 20.6; 95% CI 3.1-139.0; p &lt; 0.00001) and overall survival (OS; HR 3.4; 95% CI 0.5-25.8; p = 0.041) than ctDNA- pts (n = 132). 11 (92%) of ctDNA+ pts developed recurrence compared to 9 (7%) of ctDNA- pts. Monitoring multiple variants doubled sensitivity of MRD detection compared to tracking a single driver mutation. TTR was shorter in ctDNA+ vs ctDNA- Stage II (HR 23.1, 95% CI 0.28-1900.4; p &lt; 0.00001) and stage III pts (HR 17.9; 95% CI 2.7-117.3, p &lt; 0.00001). TTR of Stage II and III ctDNA- pts was similar (p = 0.7). Conclusions: Our results indicate that ctDNA analysis can detect MRD within days after complete resection of CRC and accurately identifies pts at high risk of recurrence in both Stage II and III CRC. MRD detection via ctDNA sequencing may allow personalization of adjuvant treatment strategies.
Abstract 1303: A genome-wide association study of prostate cancer in Latinos
Authors: Hannah Hopp, Sue Ingles, Chad Huff, Xin Sheng, Brandi Weaver, Mariana Stern, Sara Strom, Ian Thompson, David Conti, Christopher A. Haiman
Journal: Cancer Research (2017)

Abstract Recent studies estimate that individuals of African or Latin American ancestry represent less than 4% of samples analyzed to date in genome-wide association studies. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts in these populations. Here, we performed a genome-wide association study (GWAS) meta-analysis of prostate cancer in Latino men to search for risk loci that may be important in this population. We combined GWAS data for 1034 cases and 1046 controls genotyped with the Illumina 660 Beadarray with GWAS data for 1235 cases and 1053 controls genotyped with the Illumina Oncoarray as part of the ELLIPSE U19 GAME-ON Consortium. A total of ~11 million genotyped and imputed SNPs of ≥1% frequency were tested for association with prostate cancer risk in logistic regression models controlling for age, study and genetic ancestry. Genome-wide significant associations were observed with 24 variants all located at 8q24 (128.484-128.548), and which capture the first reported prostate cancer susceptibility locus in ‘region 1’ of 8q24. The most significant association genome-wide was with SNP rs7824776 (risk allele frequency, 0.35; OR=1.69, p=3.4x10-11). No novel genome-wide significant associations were noted outside of 8q24. We observed a high degree of generalizability of known prostate cancer risk loci, with 78 (76%) of the 103 known risk variants having effects that were directionally consistent in their association with prostate cancer risk as previously reported, of which 31 (30%) were statistically significant with p &amp;lt; 0.05. In addition to these findings from the largest GWAS of prostate cancer in Latinos conducted to date, we will also present the results investigating effect heterogeneity by local ancestry (i.e. proportion Native American vs. European). In addition, we will present a comparison of polygenic risk models between Latinos, African Africans and men of European ancestry that incorporate the known risk loci to better understand how genetic risk tracks with population differences in prostate cancer incidence. Citation Format: Hannah Hopp, Sue Ingles, Chad Huff, Xin Sheng, Brandi Weaver, Mariana Stern, Sara Strom, Ian Thompson, David Conti, Christopher A. Haiman. A genome-wide association study of prostate cancer in Latinos [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1303. doi:10.1158/1538-7445.AM2017-1303
Abstract 2496: Targeting brain tumor stem cells by interfering with choline metabolism: Evidence for an EMT-choline oncometabolic network
Authors: Katharina Koch, Rudolf Hartmann, Abigail K. Suwala, Dayana Herrera Rios, Ulf D. Kahlert, Jaroslaw Maciaczyk
Journal: Cancer Research (2017)

Abstract Glioblastoma (GBM) is the most lethal primary malignant brain tumor with a median survival of less than two years. High levels of therapy resistance, strong cellular invasiveness and rapid cell growth demand aggressive multimodal therapies involving resection as well as radio-chemotherapy. Recent evidence has pointed to the existence of brain tumor stem cells (BTSCs), a subpopulation of human brain tumors which is thought to be responsible for tumor dissemination, relapse and chemo resistance. BTSCs have been associated with the expression of mesenchymal features as a result of epithelial-mesenchymal transition (EMT). Using high resolution proton nuclear magnetic resonance spectroscopy (1H NMR) we compared the intracellular metabolic composition of GBM cells after induction vs. inhibition of EMT as well as under stem cell or differentiated conditions. We identified that both EMT and enrichment for stemness induces the cholinic phenotype which is characterized by high intracellular levels of phosphocholine and total choline derivatives. Furthermore, interference with choline metabolism by targeting choline kinase alpha (CHKα) reversed EMT in GBM cells as we observed reduced invasiveness, clonogenicity, and expression of EMT associated genes. Taken together, interfering with choline metabolism is a powerful strategy to suppress EMT and thus target BTSCs. Moreover, the newly identified BTSC-oncometabolic network could be used to non-invasively monitor the invasive properties of glioblastomas and the success of anti-BTSC therapy. Citation Format: Katharina Koch, Rudolf Hartmann, Abigail K. Suwala, Dayana Herrera Rios, Ulf D. Kahlert, Jaroslaw Maciaczyk. Targeting brain tumor stem cells by interfering with choline metabolism: Evidence for an EMT-choline oncometabolic network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2496. doi:10.1158/1538-7445.AM2017-2496
Why try saving the ANS? An alternative proposal
Authors: Titia Gebuis, Roi Cohen Kadosh, Wim Gevers
Journal: Behavioral and Brain Sciences (2017)

Abstract Leibovich et al. propose that continuous magnitudes and a number sense are used holistically to judge numerosity. We point out that their proposal is incomplete and implausible: incomplete, as it does not explain how continuous magnitudes are calculated; implausible, as it cannot explain performance in estimation tasks. We propose that we do not possess a number sense. Instead, we assume that numerosity judgments are accomplished by weighing the different continuous magnitudes constituting numerosity.