tbuckley/cabot-search huggingface dataset:
Abstract 2476: The oncogenic role of p63 in altered-FGFR3 bladder tumors
Authors: Macarena Zambrano, Aura I. Moreno-Vega, Florent Dufour, Marianela Sciacca, Yanina V. Langle, François Radvanyi, Ana M. Eiján, Isabelle Bernard-Pierrot, Catalina Lodillinsky
Journal: Cancer Research (2021)

Abstract Recently, a new classification of muscle-invasive bladder cancer (MIBCs) has been proposed (Kamoun, 2020). There are 6 classes of MIBC: the over-expression or activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with luminal subtypes. As typically expected, basal tumors exhibit increased TP63 activity, but interestingly, this is also observed in luminal-papillary (LumP) tumors. LumP are enriched in both, FGFR3 mutations and p63 activation. The regulatory gene pathways and p63 functional role in these tumors remains poorly characterized. Therefore, this is our main objective, together with the study of the link with FGFR3 mutations. We hypothesize that p63 drives a protumoral program in bladder cancer (BC) commanded by the regulation of altered FGFR3. We used human BC cell lines bearing FGFR3 mutations with inducible silencing for p63 in order to identify the functional role of p63 in this context. Loss of p63 led to a decreased 2D and 3D growth (p&amp;lt;0.001). Gelatin degradation and migration ability were significantly lower in p63 depleted cells compared to CRL (p&amp;lt;0,01). In vivo assays showed that tumor volume was significantly lower in p63 depleted tumors compared to CRL (p&amp;lt;0.01), accompanied by a reduction of proliferating cell nuclear antigen (PCNA) expression, indicating that p63 is an essential protein through which the cell mediates its proliferative and migratory mechanism. In order to study the link between both, FGFR3 alterations and p63 activity, we used FGFR3 Knocked down cells and pharmacological inhibitors. FGFR3 inhibition decreased p63 expression associated with a reduction in TP63 activity. It reduced proliferation and cell migration in similar level to those observed by directly silencing p63 in FGFR3 altered cells. Conversely, FGFR3 wt cells were not affected by the inhibitor. Overall, these results show that FGFR3 inhibition blunted the carcinogenic program carried out by p63, suggesting there is a regulation of FGFR3 over p63. Supporting the regulation of p63 by FGFR3, analysis of mRNA levels in human bladder tumors showed that p63 expression was significantly higher in FGFR3 mutated tumors in two different sets of samples. In summary, we experimentally demonstrated the regulation of FGFR3 over the protumoral transcription factor p63 that induces proliferation, migration and tumor growth in bladder cancer. Citation Format: Macarena Zambrano, Aura I. Moreno-Vega, Florent Dufour, Marianela Sciacca, Yanina V. Langle, François Radvanyi, Ana M. Eiján, Isabelle Bernard-Pierrot, Catalina Lodillinsky. The oncogenic role of p63 in altered-FGFR3 bladder tumors [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 2476.
Abstract 2412: Decursin inhibits tumor progression in head and neck squamous cell cancer by down regulating CXCR7 expression
Authors: Mina Joo, Solbi Kim, Nayoung Kim, Myung-Won Lee, Heung Jin Jeon, Hyewon Ryu, Ik-Chan Song, Jin-Man Kim, Hyo Jin Lee
Journal: Cancer Research (2021)

Abstract Background: CX chemokine receptor 7 (CXCR7) is frequently overexpressed in a variety of tumors and plays a significant role in tumor growth and metastasis. Thus, inhibition of CXCR7 is an important potential anticancer treatment strategy. Decursin, a derivative from Angelica gigas Nakai has been reported to have anti-tumor activity in various cancers. However, little is known about its anti-tumor activity and underlying mechanisms of action in head and neck squamous cell cancer (HNSCC). Methods: CXCR7-overexpressing HNSCC cell lines were established in vitro. The effects of decursin on cell growth, motility, migration, and invasion were investigated using CCK-8, wound healing, and transwell assays. In addition, the mechanism by which decusin shows antitumor activity was investigated. Results: Overexpression of CXCR7 significantly increased cell proliferation, migration, invasion, and cell motility compared with control cells. Treatment with decursin decreased membrane expression of CXCR7 in a concentration dependent manner and significantly inhibited tumor progression by suppressing cell growth, migration, invasion, and motility. Decursin was found to induce G0/G1 cell cycle arrest and regulate cell cycle-related proteins such as Cyclin A and CDK2 in HNSCC cells. In addition, decursin inhibited CXCR7-induced STAT3/c-MYC activation. Conclusion: These results demonstrate that CXCR7 promotes cancer progression through the STAT3/c-Myc pathway in HNSCC and that decursin is a natural product that may target CXCR7 for HNSCC treatment. Citation Format: Mina Joo, Solbi Kim, Nayoung Kim, Myung-Won Lee, Heung Jin Jeon, Hyewon Ryu, Ik-Chan Song, Jin-Man Kim, Hyo Jin Lee. Decursin inhibits tumor progression in head and neck squamous cell cancer by down regulating CXCR7 expression [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 2412.
Health Insurance Deductibles and Health Care–Seeking Behaviors in a Consumer-Driven Health Care System With Universal Coverage
Authors: José Luis Sandoval, Dusan Petrovic, Idris Guessous, Silvia Stringhini
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Characteristics of a health care system can facilitate forgoing of health care owing to economic reasons and can influence population health. Whether health insurance deductibles are associated with forgoing of health care in a consumer-driven health care system with universal coverage, such as the Swiss health system, remains to be determined. <h3>Objective</h3> To assess the association between insurance plan deductibles and forgoing of health care with consideration of socioeconomic factors. <h3>Design, Setting, and Participants</h3> This cross-sectional study was conducted in Geneva, Switzerland, using data collected from January 1, 2007, to December 31, 2019. Population-based samples were obtained yearly through random stratified sampling by age and sex of the general population aged 20 to 74 years. Participants were invited to an appointment at 1 of the 3 study sites in Geneva, where they completed a sociodemographic and health questionnaire. <h3>Exposures</h3> Insurance plan deductible level. <h3>Main Outcomes and Measures</h3> The main outcome was forgoing of health care owing to economic reasons. Unadjusted and multivariable Poisson models were used to assess the association between deductible level and forgoing of health care. Differences in forgoing health care across the range of health insurance deductibles or household income levels were quantified using the relative index of inequality (RII). <h3>Results</h3> The study group included 11 872 participants (5974 [50.3%] male; median age, 48.1 years [interquartile range, 38.7-59.1 years]); 1146 (9.7%) reported forgoing health care. Participants with high-deductible plans reported forgoing health care more frequently than those with low-deductible plans (331 [13.5%] vs 591 [8.7%]). In adjusted analysis, higher-deductible plans were associated with a greater likelihood of forgoing health care (RII, 2.2; 95% CI, 1.7-3.0;<i>P</i> &lt; .001) independently of socioeconomic status, known comorbidities, and cardiovascular risk factors. Deductible level was associated with forgoing of health care among participants younger than 40 years (RII, 2.5; 95% CI, 1.6-4.0;<i>P</i> &lt; .001) and those aged 40 to 64 years (RII, 1.9; 95% CI, 1.3-2.9;<i>P</i> = .002) but not among those older than 65 years (RII, 2.9; 95% CI, 0.8-10.4;<i>P</i> = .11). <h3>Conclusions and Relevance</h3> In this cross-sectional study, high insurance plan deductibles were associated with forgoing of health care independent of socioeconomic status and preexisting conditions in a universal consumer-driven health care system with good population outcomes in Switzerland. Uncovering health care system design features that could lead to suboptimal population care may help decision makers improve their current health care system design to achieve better outcomes.
John Arthur Lunn
Authors: Joanna Lunn
Journal: BMJ (2021)

John Arthur Lunn left school in 1948 to start medical studies at St Mary’s Hospital, Paddington. His first house job, a surgical one, was at Edgware General Hospital in the Almroth Wright ward, a specialist unit for treating tuberculosis meningitis. For the first time, with the arrival of streptomycin, this previously 100% fatal illness was starting to have a survival rate. It was here that John was to meet his future wife, charge nurse Maureen Marshall.

At the end of 1954 John had to start his national service and was posted to the British Military Hospital at Fayid, Egypt, in the Suez Canal Zone. At the beginning of 1956 he was posted to Cyprus and completed …
Abstract 2133: Systematic mapping of genetic interactions in human cancer cells reveals context dependent cancer signaling pathways
Authors: Samson H. Fong, Brent M. Kuenzi, John Lee, Kyle Sanchez, Ana Bojorquez-Gomez, Kyle Ford, Brenton P. Munson, Katherine Licon, Jeff Hager, John Paul Shen, Jason F. Kreisberg, Prashant Mali, Trey Ideker
Journal: Cancer Research (2021)

Abstract Genetic interaction screens have long been used to map gene functions and cellular pathways in model organisms and more recently in human cells. However, due to the technical challenges of these maps, most studies in human cells have focused on a single cell line, limiting the ability to determine how different genetic and cellular contexts influence genetic interactions. Here, we engineered a 110,728-element combinatorial CRISPR-Cas9 library to systematically map 12,282 genetic interactions among tumor suppressor genes and druggable targets. We mapped the landscape of genetic interactions in cell lines from breast cancer, head and neck squamous carcinoma, and non-small cell lung cancer as well as in non-cancerous, epithelial cells. The resulting genetic interaction maps emphasize the context dependency of these interactions. Of the interactions that are conserved across multiple cell lines, many include frequently essential genes, suggesting that these interactions may be critical for fundamental cellular functions. We found that genetic interaction maps from cancer cell lines are more similar to one another than non-cancer interaction maps, even between cancer and normal cells from the same tissue. Subsequent targeted chemogenetic screens confirmed interaction hubs across multiple cell lines while highlighting the robustness of some of the strongest interactions. Many of the identified genetic interactions suggest therapeutic interventions, such as the combination of CDK4 and MAPK inhibitors. Using the tissue-specific genetic interaction networks, we also built a deep learning model that accurately predicts patient outcomes, outperforming models that use accepted biomarkers such as MammaPrint. In summary, these genetic interaction maps provide a broad resource to investigate context dependency in cancer signaling pathways and in cancer drug response. Citation Format: Samson H. Fong, Brent M. Kuenzi, John Lee, Kyle Sanchez, Ana Bojorquez-Gomez, Kyle Ford, Brenton P. Munson, Katherine Licon, Jeff Hager, John Paul Shen, Jason F. Kreisberg, Prashant Mali, Trey Ideker. Systematic mapping of genetic interactions in human cancer cells reveals context dependent cancer signaling pathways [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 2133.
Semi-closed-circuit vacuum-assisted Mini-PCNL system for renal stones in pediatric patients: The experience by a tertiary referral center
Authors: G. Sampogna, A. Berrettini, S.P. Zanetti, A. Gallioli, M. Gnech, E.A. De Marco, D.G. Minoli, F. Longo, G. Manzoni, E. Montanari
Journal: European Urology (2021)
Chitinase-3-like 1 protein complexes modulate macrophage-mediated immune suppression in glioblastoma
Authors: Apeng Chen, Yinan Jiang, Zhengwei Li, Lingxiang Wu, Ulises Santiago, Han Zou, Chunhui Cai, Vaibhav Sharma, Yongchang Guan, Lauren H. McCarl, Jie Ma, Yijen L. Wu, Joshua Michel, Yi Shi, Liza Konnikova, Nduka M. Amankulor, Pascal O. Zinn, Gary Kohanbash, Sameer Agnihotri, Songjian Lu, Xinghua Lu, Dandan Sun, George K. Gittes, Qianghu Wang, Xiangwei Xiao, Dean Yimlamai, Ian F. Pollack, Carlos J. Camacho, Baoli Hu
Journal: Journal of Clinical Investigation (2021)

Glioblastoma is a highly malignant and incurable brain tumor characterized by intrinsic and adaptive resistance to immunotherapies. However, how glioma cells induce tumor immunosuppression and escape immunosurveillance remains poorly understood. Here, we find upregulation of cancer-intrinsic Chitinase-3-like-1 (CHI3L1) signaling modulating an immunosuppressive microenvironment by reprogramming tumor-associated macrophages (TAMs). Mechanistically, CHI3L1 binding with Galectin-3 (Gal3) selectively promotes TAM migration and infiltration with a protumor M2-like but not an antitumor M1-like phenotype in vitro and in vivo, governed by a transcriptional program of NFκB/CEBPβ in the CHI3L1/Gal3-PI3K/AKT/mTOR axis. Conversely, Galectin-3-binding protein (Gal3BP) negatively regulates this process by competing with Gal3 to bind CHI3L1. Administration of a Gal3BP mimetic peptide in syngeneic glioblastoma mouse models reverses immune suppression and attenuates tumor progression. These results shed light on the role of CHI3L1 protein complexes in immune evasion by glioblastoma and as a potential immunotherapeutic target for this devastating disease.
Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis
Authors: Nicholas A. Vitanza, Adam J. Johnson, Ashley L. Wilson, Christopher Brown, Jason K. Yokoyama, Annette Künkele, Cindy A. Chang, Stephanie Rawlings-Rhea, Wenjun Huang, Kristy Seidel, Catherine M. Albert, Navin Pinto, Juliane Gust, Laura S. Finn, Jeffrey G. Ojemann, Jason Wright, Rimas J. Orentas, Michael Baldwin, Rebecca A. Gardner, Michael C. Jensen, Julie R. Park
Journal: Nature Medicine (2021)
Abstract LB175: APX601, a Potent TNFR2 Antagonist as a Novel and Promising Approach to Reverse Tumor Immune Suppression
Authors: Sushma Krishnan, Ryan Alvarado, George Huang, Xiaodong Yang, Erin L. Filbert
Journal: Cancer Research (2021)

Abstract A key barrier to effective immunotherapy for cancer is the immunosuppressive tumor microenvironment (TME) characterized by infiltrating regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). While depletion of immune-suppressive cells is a promising cancer immunotherapy strategy, current approaches are ineffective due to lack of specificity and safety concerns. Tumor Necrosis Factor Receptor 2 (TNFR2) is emerging as a novel, selective target to overcome immunosuppression in the TME. Here we present APX601 as a potent Treg and myeloid suppressive cell inhibitor. APX601 is a humanized IgG1 antibody to TNFR2 generated using APXiMAB™, Apexigen's proprietary antibody platform. APX601 selectively binds human and monkey TNFR2, blocks the binding of TNFR2 to TNF-α and depletes TNFR2-expressing Treg and tumor cells in vitro. In addition to depleting suppressive cells, APX601 can also reverse MDSC and Tregs mediated immune suppression. In human TNFR2 knock-in syngeneic mouse tumor models CT26 and MC38, treatment with APX601 results in significant tumor growth inhibition both as a single agent and in combination with anti-PD-1. Thus, APX601 is a potent antagonist antibody against TNFR2 with the ability to reverse immune suppression in TME and inhibit tumor growth. APX601 was evaluated in a repeat dose range finding toxicology study in monkeys and demonstrated a good safety profile when administered up to 100mg/kg. These data strongly support the development of APX601 as a novel therapeutic approach for reversing tumor immune suppression and for the treatment solid tumors. Citation Format: Sushma Krishnan, Ryan Alvarado, George Huang, Xiaodong Yang, Erin L. Filbert. APX601, a Potent TNFR2 Antagonist as a Novel and Promising Approach to Reverse Tumor Immune Suppression [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 LB175.
The cancer immunohistogram, a functional status of tumor-infiltrating cells evaluated by immunohistochemistry, predicts the efficacy of immune checkpoint inhibitors in urological cancer patients
Authors: T. Kijima, T. Kubo, D. Nishihara, A. Nukui, H. Betsunoh, M. Yashi, T. Torigoe, T. Kamai
Journal: European Urology (2021)
Abstract LB238: Multiplex immunohistochemistry profiling with UltraPlex IHC on FFPE lung cancer provides a fast and robust staining platform compatible with clinical laboratory workflows
Authors: Helen Tighe-Snyder, Matt Levin, Zohreh Akhananaghdam, Yanfei Jiang, David Schwartz
Journal: Cancer Research (2021)

Abstract A wide range of technologies are now available to perform multiplex immunofluorescence(mxIF) to examine the tumor immune microenvironment in FFPE tissue sections, offering the potentialto reveal signatures of anti-tumor immune response. However, mxIF assay performance is often limitedby autofluorescence and other artifacts, particularly in lung and prostate cancer samples. These artifactscan frustrate detection even using dedicated instrumentation to obtain images and advanced softwareto identify and measure the different biomarkers. Compared to immunofluorescence,immunohistochemistry (IHC) displays far less background and uses tools readily available in anypathology lab, but IHC has been traditionally difficult to multiplex especially regarding co-localization oncells. Recently, Cell IDx has overcome this barrier by developing UltraPlex™ multiplex IHC (mxIHC),where we leverage Cell IDx's antibody hapten-tagging technology to enable independent detection of 3-4 primary antibodies from any species on a single tissue section, using different chromogen colors todistinguish each biomarker. In this study of various NSCLC tumors, we display how mxIHC can define theTME while maintaining staining integrity. Using UltraPlex™ mxIHC, we demonstrate a useful clinicalchromogenic triple stain of CD8, PD-L1, and panCK with the ability to produce accurate quantitation forphenotype subsets. Our result show that UltraPlex™ mxIHC on FFPE tissue sections can provideincreased confidence for multiplexing on challenging tissues while requiring only conventionallaboratory methods and apparatus. Citation Format: Helen Tighe-Snyder, Matt Levin, Zohreh Akhananaghdam, Yanfei Jiang, David Schwartz. Multiplex immunohistochemistry profiling with UltraPlex IHC on FFPE lung cancer provides a fast and robust staining platform compatible with clinical laboratory workflows [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 LB238.
Diagnosis and Management of Myocarditis in Children
Authors: Yuk M. Law, Ashwin K. Lal, Sharon Chen, Daniela Čiháková, Leslie T. Cooper, Shriprasad Deshpande, Justin Godown, Lars Grosse-Wortmann, Joshua D. Robinson, Jeffrey A. Towbin
Journal: Circulation (2021)

Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.
Normothermic machine perfusion of porcine kidneys with whole blood - Evaluation of an assistance system for donor kidneys in transplant medicine
Authors: J. Putz, A.E. Yakac, C. Steinhauser, S. Füssel, S. Kromnik, W. Markgraf, R. Mühle, P. Talhofer, C. Thiele, H. Malberg, C. Thomas
Journal: European Urology (2021)
Abstract 2897: The metastatic potential of high-grade serous ovarian cancer cells along disease progression
Authors: Sabrina J. Ritch, Alicia A. Goyeneche, Abu S. Noman, Carlos M. Telleria
Journal: Cancer Research (2021)

Abstract Epithelial ovarian cancer (EOC) represents 90% of all ovarian tumors and is considered to be the deadliest gynecological disease. High grade serous ovarian cancer (HGSOC) is the most aggressive form of EOC and represents 70% of all deaths from the disease. Due to a lack of early symptoms and valid screening methods, HGSOC is often diagnosed at late stages, when metastasis has already occurred. HGSOC disseminates from the primary tumor as single cells or clusters that typically adheres to the peritoneal organs and wall. The purpose of this study was to characterize the migratory, invasive, and adhesive abilities of HGSOC cells representing different stages of disease evolution. Both wound healing (WH) and Boyden chamber (BC) assays were performed to study the migratory capacity of five HGSOC cell lines; PEO1, PEO4 and PEO6, from a first patient, and PEO14 and PEO23, from a second patient. The cell lines were generated along different stages of the disease (e.g. at presentation, recurrence, and before death), thus representing disease evolution. To study the invasive capacity of each cell line, a layer of extracellular matrix was added to the BC assays. Adhesion assays were performed on fibronectin coated plates. It was found that the migratory and invasive capacities of the HGSOC cell lines decreased along disease evolution in both cellular series. PEO1 and PEO14, two chemo-sensitive cell lines, were found to have the highest migratory and invasive capacities, while their chemoresistant counterparts, PEO4, PEO6 and PEO23, showed a decrease in migration and invasion. Moreover, a distinct migration pattern was found to be conserved in both WH and BC assays. Cell lines representing an early stage disease had a tendency to migrate as individual cells, while cells representing a late stage disease were observed migrating in clusters. Adhesion rates were found to be similar between all cells lines. The results suggest that HGSOC disease progression seems to be associated with reduced migratory and invasive capacities, contradicting the idea that advanced stage EOC cancers have higher metastatic potential. Citation Format: Sabrina J. Ritch, Alicia A. Goyeneche, Abu S. Noman, Carlos M. Telleria. The metastatic potential of high-grade serous ovarian cancer cells along disease progression [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 2897.