tbuckley/cabot-search huggingface dataset:
Abstract 4301: Hypoxia-induced Nur77 activates PI3K-p110a/Akt/mTOR via suppression of Dicer/let-7i-5p to induce epithelial-to-mesenchymal transition in colon cancer cells
Authors: Sally K. Y. To, Shan Deng, Jin-Zhang Zeng, Alice Sze Tsai Wong
Journal: Cancer Research (2019)

Abstract Cancer cells reside in the hypoxic niches of tumors easily undergo epithelial-to-mesenchymal transition (EMT). We have recently shown that hypoxia-induced EMT to enhance colon cancer cell invasive growth is dependent on the orphan nuclear receptor Nur77 and is mediated by Akt signaling. However, its underlying molecular mechanisms remain elusive. Here we found that hypoxia-induced Nur77 reduced Akt phosphorylation and its downstream mediator mTOR by decreasing the mRNA stability of p110α, the catalytic subunit α of phosphatidylinositol 3-kinase. Further analyses revealed that this effect could be mediated by down-regulation of Dicer, an important microRNA (miR) processor, and decreased biogenesis of the miR, let-7i-5p. Luciferase reporter assays confirmed that let-7i-5p could directly target the 3’UTR of p110α mRNA. Knockdown of Dicer or overexpression of let-7i-5p inhibited Nur77-induced EMT phenotypes. These data uncover a novel mechanistic link connecting Nur77, Akt, and invasive properties of colon cancer in the hypoxic microenvironment. Citation Format: Sally K. Y. To, Shan Deng, Jin-Zhang Zeng, Alice Sze Tsai Wong. Hypoxia-induced Nur77 activates PI3K-p110a/Akt/mTOR via suppression of Dicer/let-7i-5p to induce epithelial-to-mesenchymal transition in colon cancer cells [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 4301.
Abstract 1220: High-resolution epitope mapping differentiates monoclonal antibodies in the crowded cancer immunotherapy space
Authors: Sharon Willis
Journal: Cancer Research (2019)

Abstract Epitope mapping provides essential information for differentiating monoclonal antibodies (MAbs) that bind to proteins targeted by many competing drugs. In cancer immunotherapy, for instance, numerous approved or investigational MAbs target the immune checkpoint protein PD-1. Recent high-profile patent law cases have centered on epitope data, highlighting the importance of distinguishing MAb binding sites at amino-acid resolution. Additionally, epitope data can be used to distinguish the mechanisms by which MAbs exert their therapeutic effects, uncovering important differences between competing drugs. To achieve rapid and comprehensive conformational epitope mapping at the amino-acid level, we developed the Shotgun Mutagenesis Epitope Mapping platform. Every residue in a target protein is individually mutated by alanine scanning mutagenesis, expressed in human cells, and assayed by flow cytometry to determine the critical epitope residues. Data from our platform have been used to differentiate MAbs in terms of their binding residues and therapeutic mechanisms of action. We have used our platform to differentiate the unique binding residues and, in some cases, the mechanisms of action of novel MAbs on the crowded surfaces of cancer targets, such as HER-2, from those of benchmark MAbs. Citation Format: Sharon Willis. High-resolution epitope mapping differentiates monoclonal antibodies in the crowded cancer immunotherapy space [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 1220.
Abstract LB-210: An enhanced tumor evolution model for colorectal cancer evolution
Authors: Lixing Yang
Journal: Cancer Research (2019)

Abstract The classical genetic model of colorectal cancer presents somatic APC mutations as the earliest genomic alterations, followed by KRAS and TP53 mutations. However, the timing and relative order of clonal expansion and other types of somatic genome alterations such as genomic rearrangements are still unclear. Here, we performed detailed analysis of somatic genetic alterations, including point mutations, copy number alterations and genomic rearrangements, in 63 whole-genome sequenced colorectal cancers from the Cancer Genome Atlas Research Network. The relative order of these alterations occurring during tumorigenesis was inferred from variant allele fractions. We found that driver point mutations, gene fusions, and arm level copy losses typically arise early. Copy-neutral loss of heterozygosity is often a two-step event: a deletion followed by a duplication. Different mechanisms act in different genomic regions to optimize the DNA dosage. Chromothripsis, clustered genomic rearrangements previously thought to occur as a single catastrophic event, is frequent and may occur multiple times independently in the same tumor through different mechanisms. In contrast to recent studies reporting neutral growth of tumors, selection is often present on subclones. Our results suggest that different evolutionary models can operate in a single tumor at different stages. Combining these results, we present a refined tumor progression model for human colorectal cancer. Our enhanced genetic model significantly expands our understanding of tumorigenesis process. Citation Format: Lixing Yang. An enhanced tumor evolution model for colorectal cancer evolution [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 LB-210.
Abstract 17419: Sex and Race Related Disparities in Care and Outcomes After Hospitalization for Coronary Artery Disease Among Older Adults
Authors: Shanshan Li, Gregg C Fonarow, Kenneth Mukamal, Li Liang, Phillip J Schulte, Eric E Smith, Adam DeVore, Adrian F Hernandez, Eric D Peterson, Deepak L Bhatt
Journal: Circulation (2015)

Background: It is unclear to what extent following a standard performance protocol will help reduce gaps in cardiovascular health among sexes, racial/ethnic groups, and geographic regions in United States hospitals. Method: Based on the Get With The Guidelines Coronary Artery Disease (GWTG-CAD) registry linked with Medicare inpatient data, we included 49,358 patients, age 65 years or older, from 366 US hospitals from 2003 to 2009. Our primary outcome was 3-year all-cause mortality. Exposures included sex, race/ethnicity, and geographic region. Our mediator was a composite score of quality of care, defined as the total number of performance measures the patient received divided by total number of performance measures the patient was eligible for. Logistic regression with generalized estimating equations and mediation analysis were used. Results: During 3 years of follow-up, 16,130 deaths were identified. Compared with men, women were less likely to receive optimal care at discharge (adjusted odds ratio (aOR)=0.92, 95% Confidence Interval (CI): 0.88-0.95, p&lt;0.0001). We identified a significant interaction between sex and quality of care measures (p for interaction=0.04). Compared with men, women had higher odds of mortality (aOR=1.23, 95%CI: 0.99-1.54, p=0.06) if they received sub-optimal care, though the sex disparity disappeared with optimal care (aOR=0.97, 95%CI: 0.92-1.01, p=0.13). There was no difference in terms of quality of care across racial/ethnic groups or geographic regions. Compared with whites, blacks had higher mortality (aOR=1.36, 95%CI: 1.24-1.50, p&lt;0.0001), and the disparity persisted regardless of the quality of care received. We did not identify a significant mortality difference based on geographic region. Conclusion: Compared with men, women were less likely to receive optimal care at discharge which was associated with higher mortality. The observed sex disparity in mortality could potentially be reduced or even eliminated by providing equitable and optimal care. In contrast, the higher mortality observed in black patients could not be accounted for by differences in the quality of care measured in this study. We did not observe differences in care or outcomes by geographic region.
Clinical characteristics of primary cutaneous lymphoma: analysis from two centres in China
Authors: H.‐Z. Shi, Y.‐X. Liu, Y.‐Q. Jiang, S.‐L. Chen, X.‐L. Xu, X.‐M. Lu, W. Zhang, X.‐S. Zeng, G.‐Z. Zhou, J.‐F. Sun, H. Chen
Journal: British Journal of Dermatology (2019)
Retinal microvascular dysfunction in patients with coronary artery disease with and without heart failure: a <i>continuum</i>?
Authors: Jens Barthelmes, Matthias P. Nägele, Silviya Cantatore, Etibar Novruzov, Valeria Ludovici, Arnold von Eckardstein, Michelle Frank, Frank Ruschitzka, Isabella Sudano, Andreas J. Flammer
Journal: European Journal of Heart Failure (2019)
Abstract 153: Automated Angiographic Assessment Of Coronary Artery Vasomotion In Kawasaki Disease Patients
Authors: Mitchel Benovoy, Farida Cheriet, Roch L Maurice, Nagib Dahdah
Journal: Circulation (2015)

Background: Mechanical properties of coronary arteries (CA) hold clues to vascular health and viability. Traditionally assessed with intracoronary imaging, we present an angiography-based system to assess CA vasomotion using automatic vessel segmentation and spatio-temporal tracking. Elastic moduli computed from dynamic CA calibers are compared between non-KD patients (CTL), KD patients with no CA aneurysms (KDAN-), and those with aneurysms (KDAN+). Methods: Proximal CA angiograms are automatically segmented and tracked over a cardiac cycle. CA centerline is extracted and the mean caliber is computed from diameters along its length. The resulting caliber variation reflects the CA vasomotion (Figure 1a). We then calculated the Vasomotion Standard Deviation (VSD) and CA recoil with the mean constriction velocity (MCV). Finally, Elastic Pressure moduli were computed using trans-myocardium pressure gradients. Results: We analyzed 51 left CA segments from 23 patients (5 CTL, 5 KDAN-, 13 KDAN+). Data are mean ± SD normalized pixels (npx). VSD was significantly reduced ( p &lt;0.01) in KDAN+ (0.25±0.05) and KDAN- (0.27±0.04) vs CTL (0.38±0.07 npx). Coronary recoil was significantly reduced (p&lt;0.05) in KDAN+ vs CTL, with MCV 3.50±0.67 vs 4.59±1.94 npx/sec. Pressure-dependent stiffness characteristics were equally atypical (Figure 1b). Conclusion: The proposed angiography-based stiffness assessment system shows abnormal CA vascular physiology in our cohort of KD patients. These results concur with previous invasive studies. The potential usability of this system for vascular health assessment could be applied to previously recorded CA angiograms for risk stratification.
Efficacy and safety of intermittent dosing schedule of apatinib for advanced gastric cancer in second-line setting
Authors: Y. He, Y. Yan, G. Wang, Y. Sun, T. Xu, S. Wu, J. Niu, H. Li, H. Xu, H. Luo, L. Ke, W. Chen, L. Cao, X. Hu, C. Ji, B. Hu
Journal: Annals of Oncology (2019)
Randomized phase II clinical trial to evaluate the efficacy of second-line FOLFIRI-panitumumab in patients with RAS wild-type metastatic colorectal cancer who have received FOLFOX-panitumumab in first-line (BEYOND)
Authors: J. Aparicio, A. Virgili, J. Capdevila, F. Muñoz Boza, R. Álvarez, C. Bosch, J. Cámara, C. Fernandez-Martos, J. Fernandez-Plana, J. Gallego, R. Gallego, X. Hernández-Yagüe, I. Macías Declara, N. Rodríguez-Salas, R. Vera, M. Taberner, J. Maurel
Journal: Annals of Oncology (2019)
Abstract 1195: Stochastic co-evolution of the adaptive immune system and an evading cancer population
Authors: Jason Thomas George, Jeffrey J. Molldrem, Herbert Levine
Journal: Cancer Research (2019)

Abstract Recent advances in immunotherapy have revolutionized modern cancer treatment. While encouraging, robust therapies that lead to durable remission outcomes still remain a challenge in curing many malignancies as cancer cells may acquire clones that effectively evade the immune system. Cancer immunotherapeutic treatment strategies are quite complex. In extreme cases, hematopoietic stem cell recipients enlist an entire allogeneic T-cell repertoire to fight against a growing malignancy. Perhaps most importantly, the adaptive nature of the immune system uniquely enables this treatment approach to co-evolve alongside an evasive threat. However, this process is poorly quantified and thus merits further study in order to maximally benefit cancer patients. Here, we develop a theoretical framework to quantify the dynamics between a growing collection of cancer cells capable of acquiring multiple evasive clones and a T-cell repertoire that may eventually recognize the evading populations. We create the first mathematical model of stochastic tumor-immune co-evolution by applying principles of stochastic process theory. We demonstrate that our model agrees with experimental time-course data in solid and liquid cancers and relate differences in branched vs. clonal evolution to the stringency of immunosurveillance present during early cancer progression. We argue that the clonal dynamics observed in leukemia patients treated with T-cell transplant therapy likely arise from the selection of pre-existent immune-evasive clones. In conclusion, our co-evolutionary model recapitulates empirical observations and offers a framework for quantifiable predictions to further improve cancer immunotherapy. Citation Format: Jason Thomas George, Jeffrey J. Molldrem, Herbert Levine. Stochastic co-evolution of the adaptive immune system and an evading cancer population [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 1195.
Abstract B06: Repositioning the FDA-approved antiviral drug ribavirin as targeted therapy for nasopharyngeal carcinoma
Authors: Sakibul Huq, Joshua Casaos, Michael Peters, Yuanxuan Xia, Andy Ding, Manuel Morales, Noah Gorelick, Riccardo Serra, Tianna Zhao, Wataru Ishida, Alexander Perdomo-Pantoja, Arba Cecia, Chenchen Ji, Ian Suk, David Sidransky, Mariana Brait, Henry Brem, Nicolas Skuli, Betty Tyler
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma that is often diagnosed at an advanced stage, leading to poor disease-free and overall survival. Accumulating literature suggests that elevated protein expression of enhancer of zeste homolog 2 (EZH2), eukaryotic initiation factor 4E (eIF4E), and inosine-5’-monophosphate dehydrogenase (IMPDH)—proteins implicated in myriad cancers—correlates with poor prognosis in NPC. These three proteins are modulated by the Food and Drug Administration-approved antiviral drug ribavirin, which has recently been repositioned by our laboratory and others as a promising anticancer agent. Based on this intersection of molecular signature and drug targets, we investigated the potential of ribavirin as a therapeutic agent for NPC. Experimental Design: We assessed antineoplastic efficacy of ribavirin on six human NPC cell lines in vitro using cellular growth assays, flow cytometry, and scratch wound assays. Mechanistic pathways involved were investigated using genomic expression datasets, Western blots, and enzymatic activity assays. The effects of combining ribavirin with radiation were assessed using clonogenic assays and flow cytometry. Finally, we evaluated the effects of ribavirin on tumor growth in vivo using two human cell line-derived xenograft models. Results: Ribavirin significantly decreased NPC cellular proliferation and migratory capacity in addition to promoting cell cycle arrest and cell death. Modulation of the EZH2, Snail, eIF4E, and IMPDH pathways was observed in response to ribavirin treatment. Ribavirin significantly enhanced the cytotoxic effects of radiation therapy in NPC. Most importantly, ribavirin significantly reduced flank tumor growth in two NPC xenograft models. Conclusions: Our work suggests that ribavirin has potent anticancer effects in NPC and could represent a safe and promising addition to current NPC treatment regimens. Citation Format: Sakibul Huq, Joshua Casaos, Michael Peters, Yuanxuan Xia, Andy Ding, Manuel Morales, Noah Gorelick, Riccardo Serra, Tianna Zhao, Wataru Ishida, Alexander Perdomo-Pantoja, Arba Cecia, Chenchen Ji, Ian Suk, David Sidransky, Mariana Brait, Henry Brem, Nicolas Skuli, Betty Tyler. Repositioning the FDA-approved antiviral drug ribavirin as targeted therapy for nasopharyngeal carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B06.
Abstract 652: Racial/ethnic differences in BRCA testing and test results among adult women
Authors: Fangjian Guo, Erika L. Fuchs, Abbey B. Berenson, Yong-Fang Kuo
Journal: Cancer Research (2019)

Abstract Introduction: BRCA mutation testing has been recommended for targeted, individualized cancer prevention and treatment among women whose family histories or ethnic backgrounds are associated with increased risks for BRCA mutations. This study was to assess BRCA testing in different racial/ethnic groups in the US. Methods: We used data from ClinformaticsTM Data Mart (CDM) Electronic Health Records. We included 134,827 women 18-65 years old with BRCA testing results from 1/1/2015-9/1/2017. BRCA testing rates and test result positive rates were calculated by race/ethnicity. Women with positive test results had a high risk for developing susceptible cancers - breast or ovarian cancer. As we only had data through 9/1/2017, we calculated annual test rates based on data in 2016. Results: The BRCA mutation test rate in 2016 was highest among non-Hispanic Whites (582 per 100,000), while it was 313 per 100,000 in non-Hispanic Black women, 310 per 100,000 in Hispanic Women, and 281 per 100,000 in women of other races/ethnicities. Percentage of positive results was lowest among non-Hispanic White women tested (75.7%), and highest among non-Hispanic Black test takes (85.1%). After adjusting for age, region of residence, education, income, and family history of breast or ovarian cancer, adjusted odds ratio for having a positive test among non-Hispanic Black women tested vs. non-Hispanic White women tested was 1.71, 95% confidence interval 1.61-1.82, and adjusted odds ratio for Hispanics vs non-Hispanic Whites was 1.21, 95% confidence interval 1.13-1.31. Conclusions: There are significant differences in test utilization and test results. Test utilization was highest in non-Hispanic Whites, who were also less likely to have a positive test result. Non-Hispanic Black women tested were more likely to have a positive test result, suggesting a more stringent test selection criteria for this underserved population. Citation Format: Fangjian Guo, Erika L. Fuchs, Abbey B. Berenson, Yong-Fang Kuo. Racial/ethnic differences in BRCA testing and test results among adult women [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 652.
Abstract 2005: Optimized range of osmotic pressure and viscosity for a lymphatic drug delivery system
Authors: Tetsuya Kodama, Shiro Mori
Journal: Cancer Research (2019)

Abstract The lymphatic drug delivery system (LDDS) is a method that allows the injection of drugs into sentinel lymph nodes (SLNs) to facilitate their delivery to downstream lymph nodes (LNs) via the lymphatic network to treat or prevent cancer cell development in both LNs. A high concentration of drug is effectively maintained in both LNs. Here we show that therapeutic effects in metastatic LNs depend on the osmotic pressure and viscosity of the administered drug in a metastatic mouse (MXH10/Mo-lpr/lpr) model. We found using an in vivo bioluminescence imaging system that indocyanine (ICG) solutions were retained in the proper axillary lymph node (PALN) at an osmotic pressure &amp;gt; 1,700 kPa and 6 mPa·s viscosity, when ICG solution was injected into the SiLN to deliver it to the (PALN). Edematous swelling was detected near the SiLN at &amp;gt; 3,500 kPa osmotic pressure and 400 mPa·s viscosity. Furthermore, we established that the therapeutic effects of drugs on metastatic PALN were observed in the osmotic pressure range 1000 - 2400 kPa and viscosity range 2 - 30 mPa·s, after tumor cells were injected into the SiLN to induce metastasis in the PALN. Cisplatin solution was injected into the accessory axillary lymph node to deliver cisplatin to the metastatic PALN. Our results demonstrate the optimized values of osmotic pressure and viscosity for LDDS. We anticipate our results to be a starting point for more sophisticated drug administration by a LDDS. Citation Format: Tetsuya Kodama, Shiro Mori. Optimized range of osmotic pressure and viscosity for a lymphatic drug delivery system [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 2005.
Abstract 200: The MCP-1/CCR2 axis enhances VEGF-A-dependent angiogenesis by directly downregulating miR-29c expression in oral squamous cell carcinoma
Authors: Ming-Yu Lien, Chih-Hsin Tang
Journal: Cancer Research (2019)

Abstract Oral squamous cell carcinoma (OSCC), the sixth most common malignancy worldwide, has a poor prognosis due to its aggressiveness and potential for metastasis. Activation of monocyte chemoattractant protein-1 (MCP-1) and its receptor, CC chemokine receptor 2 (CCR2), induces angiogenic activation of endothelial cells, inflammatory responses and aberrant MCP-1/CCR2 expression in malignant tissues. However, the effect of MCP-1 and CCR2 in OSCC angiogenesis is unclear. Our study sought to determine how the MCP-1/CCR2 axis mediates VEGF-A expression in OSCC and results in angiogenesis. Immunohistochemistry (IHC) analysis identified higher concentrations of VEGF-A protein expression in tissue obtained from patients with OSCC compared with tissue from healthy controls; the degree of VEGF-A tumor expression was significantly associated with the clinical disease stage. Our in vitro investigations found that MCP-1 dose-dependently regulated VEGF-A expression through the CCR2, ILK and MEK signal transduction pathways. Following MCP-1 application, conditioned medium from the human OSCC cell line SCC4 significantly promoted endothelial progenitor cell (EPC) migration and tube formation; these events were attenuated and VEGF-A production was suppressed when we stimulated the OSCC cells with the pathway inhibitors RS102895, KP392, and PD98059. We also showed that microRNA (miR)-29c expression was negatively regulated by MCP-1 via the CCR2/ILK/MEK cascade, tying in with an analysis of the cancer genome atlas (TCGA) database showing lower levels of miR-29c expression in tissues from patients with oral cancer compared with samples from healthy controls. According to our results, the MCP-1/CCR2 axis promotes VEGF-A expression in OSCC via the ILK and MEK signal transduction pathways and downregulates miR-29c expression. Thus, MCP-1/CCR2 mediation of VEGF-A mobilizes EPCs required for OSCC and is important for tumor angiogenesis. MCP-1/CCR2 may be an appropriate target in the treatment of OSCC angiogenesis. Citation Format: Ming-Yu Lien, Chih-Hsin Tang. The MCP-1/CCR2 axis enhances VEGF-A-dependent angiogenesis by directly downregulating miR-29c expression in oral squamous cell 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 200.