tbuckley/cabot-search huggingface dataset:
Abstract 1083: A novel role of SRC in mediating bypass resistance to MEK inhibition in colorectal cancer stem cells
Authors: Mingli Yang, Thomas B. Davis B. Davis, Michael V. Nebozhyn, Andrey Loboda, Heiman Wang, Michael J. Schell, Lance Pflieger, Ramya Thota, W. Jack Pledger, Timothy J. Yeatman
Journal: Cancer Research (2021)

Abstract Colorectal cancers (CRCs) are hard-wired to RAS/RAF/MEK/ERK pathway oncogenic signaling. However, the promise of targeted therapeutic inhibitors (KRASi/BRAFi/MEKi/ERKi), has been tempered by disappointing clinical activity, likely due to complex resistance mechanisms including intrinsic and adaptive resistance. Here we report a central role of SRC in mediating intrinsic and adaptive “bypass”-resistance to MEK inhibition in cancer stem cells (CSCs). The SRC oncogene is a well-studied non-receptor tyrosine kinase that can regulate multiple signaling pathways involved in the control of cell proliferation, survival, differentiation, adhesion, invasion and motility. Previously, our laboratory was the first to document that human CRC truncating mutations in the negative regulatory domain of SRC result in SRC activation (Nat Genet 1999). Now our integrated and expansive gene expression signature analyses in &amp;gt;2000 human CRCs reveal that MEKi bypass-resistance is strikingly-correlated with SRC activation, which is associated clinically with regional metastasis, disease recurrence and poor overall survival, and associated biologically with EMT and “stemness”. In support of this, SRC-associated MEKi resistance is strongly related to the CMS4 subtype that has a mesenchymal CSC phenotype. The finding is further supported by in vitro analyses demonstrating that CSCs vs. non-CSCs display greater levels of MEKi-resistance, which is attenuated by a SRC inhibitor. These results support a novel notion that SRC may serve as a common targetable node in MEKi resistance mechanisms, permitting effective cancer stem cell targeting. These pre-clinical data, based on strikingly-correlated pathway analyses of thousands of human tumors, support the “fast-track” development of a biomarker-driven (MEKi + SRCi) drug combination targeting problematic SRC-mediated, mesenchymal CSCs. Citation Format: Mingli Yang, Thomas B. Davis B. Davis, Michael V. Nebozhyn, Andrey Loboda, Heiman Wang, Michael J. Schell, Lance Pflieger, Ramya Thota, W. Jack Pledger, Timothy J. Yeatman. A novel role of SRC in mediating bypass resistance to MEK inhibition in colorectal cancer stem cells [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 1083.
A multi-surgeon learning curve analysis of overall and site-specific positive surgical margins after RARP
Authors: C. Gandi, A. Totaro, R. Bientinesi, L. Di Gianfrancesco, F. Pierconti, M. Martini, A. Russo, M. Racioppi, PF. Bassi, E. Sacco
Journal: European Urology (2021)
Successful Treatment of AL Amyloidosis Patients over Age 65 with High-Dose Melphalan and Autologous Stem Cell Transplantation (HDM/SCT).
Authors: David Cary Seldin, Jennifer J. Anderson, Martha Skinner, Karim Malek, Daniel G. Wright, Karen Quillen, Vaishali Sanchorawala
Journal: Blood (2004)
The change of pressure-flow study parameters in patients before and after robot-assisted laparoscopic radical prostatectomy
Authors: P-H. Yu, C-C. Lin, H-J. Chung, T-P. Lin, E.Y-H. Huang, T-H. Huang, I-S. Huang, A.T.I. Lin, W.J.S. Huang
Journal: European Urology (2021)
Abstract LB205: The IRF8-MEF2D transcription factor circuit regulated by a druggable multiple post-translational modification (PTM) reader ZMYND8 in acute myeloid leukemia
Authors: Zhendong Cao, Krista A. Budinich, Hua Huang, Bin Lu, Zhen Zhang, Diqiu Ren, Yeqiao Zhou, Yuhan Huang, Bianca Pingul, Molly C. Kingsley, Alexandra K. Lenard, Jun Qi, Martin P. Carroll, Gerd A. Blobel, Robert B. Faryabi, Kathrin M. Bernt, Shelley L. Berger, Junwei Shi
Journal: Cancer Research (2021)

Abstract The transformed state in acute leukemia requires gene regulatory programs involving transcription factors (TFs) and chromatin modulators. Here, we uncover an IRF8-MEF2D TF regulatory circuit as an acute myeloid leukemia (AML)-specific dependency. We discover and characterize the mechanism by which the chromatin ‘reader' ZMYND8 directly activates IRF8 in parallel with the MYC proto-oncogene through their AML-specific enhancers. ZMYND8 is essential for AML proliferation in vitro and in vivo and associates with MYC and IRF8 enhancer elements that we define in cell lines and in patient samples. ZMYND8 occupancy at IRF8 and MYC enhancers requires BRD4, a transcriptional coactivator essential for AML proliferation. We show that ZMYND8 binds to the ET domain of BRD4 via its chromatin reader cassette, which in turn is required for proper chromatin occupancy and maintenance of leukemic growth in vivo. Our results rationalize ZMYND8 as a potential selective therapeutic target for modulating essential transcriptional programs in AML. Citation Format: Zhendong Cao, Krista A. Budinich, Hua Huang, Bin Lu, Zhen Zhang, Diqiu Ren, Yeqiao Zhou, Yuhan Huang, Bianca Pingul, Molly C. Kingsley, Alexandra K. Lenard, Jun Qi, Martin P. Carroll, Gerd A. Blobel, Robert B. Faryabi, Kathrin M. Bernt, Shelley L. Berger, Junwei Shi. The IRF8-MEF2D transcription factor circuit regulated by a druggable multiple post-translational modification (PTM) reader ZMYND8 in acute myeloid leukemia [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 LB205.
Abstract 1906: Relationship between neuroendocrine and immune gene expression in small cell lung cancer
Authors: Ling Cai, Hongyu Liu, Fang Huang, Junya Fujimoto, Luc Girard, Yang Xie, John Minna, Adi Gazdar
Journal: Cancer Research (2021)

Abstract Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings provide a new framework to guide design of treatment regimens in SCLC. Citation Format: Ling Cai, Hongyu Liu, Fang Huang, Junya Fujimoto, Luc Girard, Yang Xie, John Minna, Adi Gazdar. Relationship between neuroendocrine and immune gene expression in small cell lung cancer [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 1906.
Future scenarios of risk of Vibrio infections in a warming planet: a global mapping study
Authors: Joaquin Trinanes, Jaime Martinez-Urtaza
Journal: The Lancet Planetary Health (2021)

BackgroundInfections caused by non-cholera Vibrio species have undergone a global expansion over the past few decades reaching new areas of the world that were previously considered adverse for these organisms. The geographical extent of the expansion has not been uniform, and some areas have shown a rapid increase in infections.MethodsWe applied a new generation of models combining climate, population, and socioeconomic projections to map future scenarios of distribution and season suitability for pathogenic Vibrio. We used the Coupled Model Intercomparison Project 6 framework. Three datasets were used: Geophysical Fluid Dynamics Laboratory's CM4.0 sea surface temperature and sea surface salinity; the coastline length dataset from the World Resources Institute; and Inter-Sectoral Impact Model Intercomparison Project 2b annual global population data. Future projections were used up to the year 2100 and historical simulations from 1850 to 2014. We also project human population at risk under different shared socioeconomic pathways worldwide.FindingsProjections showed that coastal areas suitable for Vibrio could cover 38 000 km of new coastal areas by 2100 under the most unfavourable scenario with an expansion rate of season suitability in these regions of around 1 month every 30 years. Population at risk in suitable regions almost doubled from 1980 to 2020 (from 610 million to 1100 million under the scenario of medium challenges to mitigation and adaptation, shared socioeconomic pathway 2-4.5), although the increment will be more moderate in the future and stabilises after 2050 at 1300 million. Finally, we provide the first global estimate for Vibrio infections, with values around half a million of cases worldwide in 2020.InterpretationOur projections anticipated an expansion of both the temporal and spatial disease burden for Vibrio infections, in particular at high latitudes of the northern hemisphere. However, the largest extent occurred from 1980 to 2020 and a more moderate increase is expected for the future. The most positive outcome is that the projections showed that Vibrio morbidity will remain relatively stable over the coming decades.FundingNOAA Atlantic Oceanographic and Meteorological Laboratory and NOAA OceanWatch, and by the University of Miami's Cooperative Institute for Marine and Atmospheric Studies.
Abstract 2010: Pancreatic cancer stem cell exosomes drive a hierarchical intratumor communication network that fuels disease progression through hippo pathway inhibition
Authors: Carolina F. Ruivo, Nuno Bastos, Ines Batista, Barbara Adem, Cecilia Duraes, Carlos A. Melo, Francisco J. Campos-Laborie, Pedro Moutinho-Ribeiro, Barbara Mourão, Marília Cravo, Guilherme Macedo, Fátima Carneiro, Tony Kouzarides, Raghu Kalluri, Jose C. Machado, Sonia Melo
Journal: Cancer Research (2021)

Abstract Intra-tumor heterogeneity represents a major challenge for cancer treatment. Resistance to therapy and tumorigenic ability varies greatly between distinct subpopulations of cancer cells. Intercellular communication is critical to establish a cooperative environment that maintains tumor heterogeneity and potentiates disease progression. However, how subpopulations of cancer cells interact to support tumor progression is not fully understood. Exosomes have the potential to re-educate recipient cells through the delivery of their cargo, emerging as the main mediators of intercellular communication. Here we demonstrate that subpopulations of pancreatic cancer cells use exosomes to establish a hierarchical and dynamic communication network, the ExoNet. Exosomes from cancer stem cells (CSC) are preferentially taken up by non-CSC (NCSC). Targeted inhibition of CSC exosomes in PDAC orthotopic, genetically engineered and patient-derived xenograft mouse models is sufficient to impair tumor growth and metastasis establishment. A comprehensive comparative proteomic analysis of exosomes derived from distinct subpopulations of pancreatic ductal adenocarcinoma (PDAC) human cell lines identified a significant enrichment of Agrin in CSC exosomes. Blocking exosomes secretion and downregulating Agrin in CSCs significantly diminishes YAP nuclear localization in receiving cells, indicating that CSC exosomes contribute for Hippo pathway inactivation. Agrin+ circulating exosomes correlate with tumor burden in PDAC patients, and most importantly correlate with CD133+ circulating exosomes, indicating that circulating Agrin+ exosomes are from CSC origin. Longitudinal analysis of circulating Agrin+ exosomes in PDAC patients predicts disease progression and response to therapy. Our study describes a novel role of cancer exosomes in the interplay between subpopulations of cancer cells promoting tumor progression. We identified Agrin as a potential non-invasive biomarker to monitor disease progression and predict treatment response. Citation Format: Carolina F. Ruivo, Nuno Bastos, Ines Batista, Barbara Adem, Cecilia Duraes, Carlos A. Melo, Francisco J. Campos-Laborie, Pedro Moutinho-Ribeiro, Barbara Mourão, Marília Cravo, Guilherme Macedo, Fátima Carneiro, Tony Kouzarides, Raghu Kalluri, Jose C. Machado, Sonia Melo. Pancreatic cancer stem cell exosomes drive a hierarchical intratumor communication network that fuels disease progression through hippo pathway inhibition [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 2010.
The potential clinical utility of measuring severe acute respiratory syndrome coronavirus 2-specific T-cell responses
Authors: Delia Goletti, Linda Petrone, Davide Manissero, Antonio Bertoletti, Sonia Rao, Nduku Ndunda, Alessandro Sette, Vladyslav Nikolayevskyy
Journal: Clinical Microbiology and Infection (2021)

Both humoral and cell-mediated responses are associated with immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although our understanding of the potential role of T-cell responses in the context of coronavirus disease 2019 (COVID-19) is rapidly increasing, more information is still needed.
Outcomes Among Patients Referred to Outpatient Rehabilitation Clinics After COVID-19 diagnosis — United States, January 2020–March 2021
Authors: Jessica S. Rogers-Brown, Valentine Wanga, Catherine Okoro, Diane Brozowsky, Alan Evans, David Hopwood, Jennifer R. Cope, Brendan R. Jackson, Dena Bushman, Alfonso C. Hernandez-Romieu, Robert A. Bonacci, Tim McLeod, Jennifer R. Chevinsky, Alyson B. Goodman, Meredith G. Dixson, Caitlyn Lufty, Julie Rushmore, Emily Koumans, Sapna Bamrah Morris, William Thompson
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

As of June 30, 2021, 33.5 million persons in the United States had received a diagnosis of COVID-19 (1). Although most patients infected with SARS-CoV-2, the virus that causes COVID-19, recover within a few weeks, some experience post-COVID-19 conditions. These range from new or returning to ongoing health problems that can continue beyond 4 weeks. Persons who were asymptomatic at the time of infection can also experience post-COVID-19 conditions. Data on post-COVID-19 conditions are emerging and information on rehabilitation needs among persons recovering from COVID-19 is limited. Using data acquired during January 2020-March 2021 from Select Medical* outpatient rehabilitation clinics, CDC compared patient-reported measures of health, physical endurance, and health care use between patients who had recovered from COVID-19 (post-COVID-19 patients) and patients needing rehabilitation because of a current or previous diagnosis of a neoplasm (cancer) who had not experienced COVID-19 (control patients). All patients had been referred to outpatient rehabilitation. Compared with control patients, post-COVID-19 patients had higher age- and sex-adjusted odds of reporting worse physical health (adjusted odds ratio [aOR] = 1.8), pain (aOR = 2.3), and difficulty with physical activities (aOR = 1.6). Post-COVID-19 patients also had worse physical endurance, measured by the 6-minute walk test† (6MWT) (p<0.001) compared with control patients. Among patients referred to outpatient rehabilitation, those recovering from COVID-19 had poorer physical health and functional status than those who had cancer, or were recovering from cancer but not COVID-19. Patients recovering from COVID-19 might need additional clinical support, including tailored physical and mental health rehabilitation services.
Abstract 778: CD24 mutant p53 contribute to racial disparities in prostate cancer
Authors: Xuelian Cui, Shuaibin Wang, Lizhong Wang
Journal: Cancer Research (2021)

Abstract African-American (AA) men have the highest rate of prostate cancer among racial or ethnic groups. CD24, a cell-surface protein anchored by glycosyl-phosphatidyl-inositol (GPI), often is over-expressed in cancers and serves as a marker for poor prognosis of human cancer, including prostate cancer. Using a functional analysis of prostate cancer cells, we found a CD24-dependent inactivation of mutant p53, but the clinical significance of this observation remained uncertain. Here, we validated these results with samples of human prostate cancer and explored the role of a CD24-p53 axis in racial disparities of prostate cancer. Our bioinformatics analysis of public datasets, including TCGA data, confirmed higher levels of CD24 mRNA expression in late-stage and metastatic prostate cancer. In the present study, we addressed the association of CD24 with mutant p53 and their differential expression between AA and European-American (EA) prostate cancers and assessed whether cells with CD24 and mutant p53 contribute to health disparities in prostate cancer. CD24, mutant p53, MDM2, and ARF proteins were expressed in 55%, 24%, 39%, and 68% of prostate cancer samples, respectively. CD24 and mutant p53 were present more frequently in late-stage and metastatic prostate cancer. The presence of CD24 was associated with a &amp;gt; 4-fold risk of metastasis, which included lymph node and distant metastases. H-score analysis showed positive correlations of CD24 expression with mutant p53 and MDM2. A racial disparity was evident for CD24 but not for mutant p53. In 32 CD24+/mutant p53+ cases, a TP53R273H mutation was found in five cases, but no TP53R175H mutation was found. The CD24-p53 axis may contribute to aggressive and metastatic prostate cancers, especially those of AAs. Citation Format: Xuelian Cui, Shuaibin Wang, Lizhong Wang. CD24 mutant p53 contribute to racial disparities in prostate cancer [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 778.
Stress-Induced Progression of Atrioventricular Block in a Patient with Breathlessness
Authors: Ameer Hamid A. Khan, Sagar Kulkarni, Han B. Xiao
Journal: JAMA Internal Medicine (2021)

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Abstract 3069: Radiation exposure of the base of the heart accelerates coronary atherosclerosis
Authors: Prerna R. Nepali, Mickael Mathieu, Sarah Kitz, Chiharuko Nakauchi, James Russell, Sebastien Monette, Andreas Rimner, Fiona A. Stewart, Edgar A. Jaimes, Adriana Haimovitz-Friedman
Journal: Cancer Research (2021)

Abstract Purpose: To determine the mechanisms associated with the development of atherosclerotic lesions in different areas of the heart exposed to radiation therapy (RT). We hypothesize that accelerated development of cardiovascular disease (CVD) post-RT is dependent upon the differential sensitivity of regions of the heart to radiation. Experimental procedures: Male Apolipoprotein E knockout (ApoE-/-) mice on a high fat diet received 16Gy cardiac irradiation targeted to the whole or partial (apical or basal) region of the heart at 9 weeks or 16 weeks of age. Atherosclerotic lesions and inflammatory changes in the hearts as compared to control unirradiated mice were assessed eight weeks following radiation. Results: Our studies demonstrate that atherosclerotic lesion formation is accelerated by cardiac RT. Our results show that (1) Subendocardial atherosclerotic lesions at the base of heart of 9 weeks old mice after basal irradiation are comparable to those formed post whole heart irradiation. (2) A greater number of atherosclerotic lesions were present in the basal coronary arteries and basal subendocardial vasculature after irradiating the cardiac base as compared to unirradiated controls in older mice at 8 weeks post-RT. (3) Apical or whole heart irradiation had no impact on the development or acceleration of lesions in the basal region of the hearts of 16 week old mice, thus demonstrating the adverse impact of basal irradiation. (4) Infiltration of inflammatory cells (CD45 and CD3) and enhanced expression of endothelial adhesion molecules (CD31) were differentially and locally regulated based upon the site of irradiation. This also demonstrates a long-term inflammatory response to RT which may be crucial in the development of RT-related CVD. Conclusion: Our results indicate that the base of the heart is more prone to development of RT-induced atherosclerotic lesions that could lead to CVD and thus omitting this area from RT direct exposure may improve the quality of life for cancer patients receiving thoracic RT. Citation Format: Prerna R. Nepali, Mickael Mathieu, Sarah Kitz, Chiharuko Nakauchi, James Russell, Sebastien Monette, Andreas Rimner, Fiona A. Stewart, Edgar A. Jaimes, Adriana Haimovitz-Friedman. Radiation exposure of the base of the heart accelerates coronary atherosclerosis [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 3069.