tbuckley/cabot-search huggingface dataset:
Abstract 883: Parsimonious model to predict length of stay following cystectomy
Authors: Rashmi Pathak, Jaileene Perez-Morales, Sephalie Y. Patel, Michael A. Poch, Matthew B. Schabath
Journal: Cancer Research (2021)

Abstract BACKGROUND: The gold standard treatment for urinary bladder cancer is cystectomy, which can result in postoperative complications, patient morbidities, and lengthy hospital visits post-surgery. At present, there are limited models that can predict length of stay for patients post cystectomy. Identifying risk factors associated with increased length of stay could have translational implications in mitigating such risk factors. As such, the goal of this study was to generate parsimonious models to predict length of hospital stay (LOHS) following cystectomy in bladder cancer patients. METHODS: Data from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) was used to analyze patients who underwent cystectomy between 2014 and 2016. Modeling building approaches were used to identify the most informative preoperative and postoperative covariates to predict LOHS. Separate models were identified for preoperative covariates and for postoperative covariates and the most informative pre- and postoperative covariates were combined into a single model. RESULTS: This analysis includes 6,074 patients (mean LOHS = 9.4 days). The preoperative (5 covariates; R squared= 0.245 and Adj R-squared = 0.240) and postoperative models (13 covariates; R squared= 0.237 and Adj R-squared = 0.236) were significantly better predictors compared to the ACS risk calculator model (19 covariates; R-square= 0.026 and Adj R-squared = 0.025). Likewise, the combined model (15 covariates) was a significantly better predictor (R squared= 0.241 &amp; Adj R-squared = 0.239) when compared to the ACS risk calculator model. The combined model was subjected into CART analysis to stratify patients into five risk-groups based on ventilator over 48 hours, organ/space surgical site infection, wound disruption, and pneumonia. Patients in the high-risk group had significantly longer mean LOHS of 26.29 days compared to low-risk group of 8.4 days. CONCLUSIONS: This study identified and validated a clinically important combined model that is to the ACS NSQIP surgical risk calculator to predict LOHS in patients who underwent cystectomy. Patients at high-risk may benefit from allocation of additional follow-up to prevent longer LOHS. Citation Format: Rashmi Pathak, Jaileene Perez-Morales, Sephalie Y. Patel, Michael A. Poch, Matthew B. Schabath. Parsimonious model to predict length of stay following cystectomy [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 883.
Postoperative Skin Lesion After Knee Replacement
Authors: Christopher J. Fang, Brian W. Lester, Brian L. Hollenbeck
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 1176: CHD4 predicts aggressiveness in PTC patients and promotes cancer stemness and EMT in PTC cells
Authors: Pratheeshkumar Poyil, Abdul K. Siraj, Sasidharan Padmaja Divya, Sandeep Kumar Parvathareddy, Roxanne Diaz, Rafia Begum, Khadija Al-Obaisi, Saravanan Thangavel, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya
Journal: Cancer Research (2021)

Abstract Papillary thyroid carcinoma (PTC) is the most common histologic subtype, accounting for nearly 90% of thyroid cancer. Chromodomain-helicase-DNA-binding protein 4 (CHD4), a core subunit of the nucleosome remodeling and deacetylation (NuRD) complex is highly expressed in several cancers. However, its role in the pathogenesis and progression of PTC has not been investigated. Immunohistochemistry was performed to assess CHD4 protein expression in PTC using a tissue microarray. We also performed in vitro analysis to investigate the role of CHD4 in regulating cancer stemness and EMT in PTC cells. CHD4 overexpression was observed in 45.3% (650/1436) of PTCs, and was associated with aggressive clinico-pathological parameters and worse outcome. Functional analysis using PTC cell lines showed that forced expression of CHD4 promoted cell proliferation, spheroid growth, migration, invasion, and progression of epithelial to mesenchymal transition (EMT) in PTC cells whereas its knockdown reversed the effect. Methylation of E-cadherin was associated with loss of expression in CHD4 expressing cells, while CHD4 depletion reactivated E-cadherin expression. Most importantly, knockdown of mesenchymal transcriptional factors, Snail1 or Zeb1, attenuated the spheroid growth in CHD4 expressing PTC cells, showing a potential link between EMT activation and stemness maintenance in PTC. These findings suggest that CHD4 might be a promising therapeutic target in the treatment of patients with an aggressive subtype of PTC. Citation Format: Pratheeshkumar Poyil, Abdul K. Siraj, Sasidharan Padmaja Divya, Sandeep Kumar Parvathareddy, Roxanne Diaz, Rafia Begum, Khadija Al-Obaisi, Saravanan Thangavel, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya. CHD4 predicts aggressiveness in PTC patients and promotes cancer stemness and EMT in PTC 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 1176.
Abstract 2945: Novel engineered B-NDG B2M/KO mice plus and steroid treated B-NDG Mice shows delayed GvHD response when engrafted with hPBMC
Authors: Lan Gao, Shruti Sharma, Eugene Lin, Xiaoen Wang, Chengzhang Shang, Yuting Hu, W. Frank An, Mehma Kaur Chawla, Kaiqi Li, Qingcong Lin, Zhaoxue (Luke) Yu, Yujie Liu
Journal: Cancer Research (2021)

Abstract Severely immunodeficient mouse strains, such as NOD.Cg-Prkdcscid Il2rg-/-, have been used to study the immune response in humans. These mice lack T, B and natural killer (NK) cells and allow for engraftment of human peripheral blood mononuclear cells (PBMCs). However, hPBMC engraftment may lead to severe acute xenogeneic graft versus host disease (GvHD) which arises due to a response from T cells against human leukocyte antigens (HLA) that are encoded by major histocompatibility complex (MHC) class I and II. GvHD shortens animal life span and results in only a brief window of evaluation of human immune cell functions in such mouse models. Efforts have been undertaken to reduce human PBMC-induced GvHD and to subsequently extend the window of human immunity assessment by eliminating mouse MHC I and MHC II. While these beta-2-microglobulin (B2M) knockout mice which are MHC deficient showed fewer symptoms of GvHD, an unintended result was the shorter half life of the antibodies which lead to its rapid clearance. This occurred because B2M is also associated with neonatal Fc receptor (FcRn) and is important to FcRn-mediated in vivo antibody recycling and retention. This is a pharmacokinetic limitation because it renders antibody efficacy assessment and makes these mice unsuitable for studying immune responses. To overcome this limitation, we engineered B-NDG B2M knockout mice plus (NOD.Cg-Prkdcscid Il2rg-/-/Bcgen) that is deficient in MHC I expression but expresses the B2M gene fused in the FcRn gene. In the present study we demonstrate the phenotypic changes in the immune system of the engineered mice using flow cytometry and validate immune tolerance developed over the several weeks of post engraftment by looking at the homeostatic balance between CD8/Treg ratio in the partially reconstituted humanized immune systems. In a parallel study, we used corticosteroid treatment in hPBMC induced B-NDG mice GvHD model. Corticosteroids are the fine line of therapy for GvHD and the phenotypic response generated in B-NDG mice confirms this finding in our GvHD model. Citation Format: Lan Gao, Shruti Sharma, Eugene Lin, Xiaoen Wang, Chengzhang Shang, Yuting Hu, W. Frank An, Mehma Kaur Chawla, Kaiqi Li, Qingcong Lin, Zhaoxue (Luke) Yu, Yujie Liu. Novel engineered B-NDG B2M/KO mice plus and steroid treated B-NDG Mice shows delayed GvHD response when engrafted with hPBMC [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 2945.
Abstract 743: Altered ER and PR transcription factor activity associated with endocrine therapy resistance in breast cancer
Authors: Rosemary J. Huggins
Journal: Cancer Research (2021)

Abstract Half of estrogen receptor (ERα)-positive breast cancer patients treated with endocrine therapies display intrinsic or acquired therapy resistance. One-third of patients with acquired resistance present with metastatic tumors containing ERα-Y537S mutations. This mutation results in constitutive activity of ERα and altered ERα-associated gene expression. Previous research suggests that ERα and the progesterone receptor (PR) engage in complex interactions involving reciprocal regulation of ERα and PR transcription factor activity known as ERα/PR crosstalk. My central hypothesis is that ERα-Y537S alters the transcription factor activity of ERα and PR, causing dysregulation of gene expression in SERM-resistant breast cancer. While previous research has assessed the impact of the ERα-Y537S mutation on ERα-associated chromatin binding and gene expression, here I assess the effect of the resistance-associated ERα-Y537S mutation on ERα and PR activity and crosstalk. Simultaneous analysis of transcription factor binding activity (ChIP-seq), gene expression (RNA-seq), and proximity-based interaction (NanoBRET) indicates that active PR binding across the genome is increased in the context of ERα-Y537S, suggesting that ERα/PR crosstalk is significantly altered. Importantly, PR chromatin binding in the context of ERα-Y537S appears to be elevated regardless of the stimulation of PR activity with the agonist R5020. These findings, along with identification of candidate genes of potential therapeutic value, will be applied using patient-derived tumor organoids to determine the efficacy of simultaneously targeting ERα and PR to overcome endocrine therapy resistance in breast cancer. Citation Format: Rosemary J. Huggins. Altered ER and PR transcription factor activity associated with endocrine therapy resistance in breast 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 743.
Viewpoint on Comprehensive Medicaid Reform—Reply
Authors: Rebekah E. Gee, David Shulkin, Iyah Romm
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Bench surgery and kidney auto-transplantation in rescue of germ-cell residual mass. 3D models utility in surgical planning
Authors: F.J. Burgos Revilla, V. Hevia-Palacios, I. Rivero-Belenchón, I. Laso-García, G. Gómez-Ciriza, M. Santiago-González, C. González-Gordaliza, A. Saiz-González, R.A. Medina-López, V. Gómez-Dos-Santos
Journal: European Urology (2021)
Abstract 406: Development of a gene signature assessing ER modulation by SERMs and SERDs as a target engagement biomarker for endocrine therapy in breast cancer
Authors: Joon Sang Lee, Maysoun Shomali, Monsif Bouaboula, Emma Wang, Wilson Dos-Santos-Bele, Colette Dib, Eric Boitier, Vasiliki Pelekanou, Nils Ternes, Alice Gosselin, Patrick Cohen, Marina Celanovic, Christopher Soria, Alexei Protopopov, Jack Pollard
Journal: Cancer Research (2021)

Abstract Hormone or endocrine therapy is the primary treatment for estrogen receptor-positive (ER+) breast cancer. Selective Estrogen Receptor Modulators (SERMs) have been used for women with ER+ invasive cancer in the adjuvant setting. However, they do not fully inhibit ER transcriptional activity. Therefore, selective estrogen receptor degraders (SERDs) such as fulvestrant have been developed to overcome the partial modulation of ER transcriptional activity by SERMs. However, the clinical benefit of fulvestrant is limited by its pharmaceutical properties, and burden of intramuscular administration. We developed amcenestrant (SAR439859), a novel, orally bioavailable SERD to improve drug properties and is under clinical investigation.To assess the relative ER modulating activity, we developed a gene signature by transcriptional profiling of multiple ER+ cell lines. We identified 87 genes that were either up- or down-regulated by estradiol and reversed by SERM and SERD compounds or differentially expressed between a SERM/SERD compound and estradiol. We assessed ER activity scores by applying Gene Set Variation Analysis (GSVA) method to the ER gene signature and evaluated the effect of 6 SERD compounds. Amcenestrant and fulvestrant illuminated a deeper inhibition of ER activity compared to the other compounds. In addition, these ER activity scores could potentially be utilized in clinics as pharmacodynamic (PD) biomarker to assess target engagement. We applied this ER signature to RNA-seq data from paired pre- and post-treatment tumor biopsies from patients of NCT03284957 study (AMEERA-1), an open-label, phase 1/2 study of amcenestrant in postmenopausal women with ER+/HER2- metastatic breast cancer. The results of our analysis showed that ER activity is down-regulated by amcenestrant (oral SERD) for 3 out of 5 patients, in parallel with clinical benefit. Validation in a larger patient cohort is needed. Citation Format: Joon Sang Lee, Maysoun Shomali, Monsif Bouaboula, Emma Wang, Wilson Dos-Santos-Bele, Colette Dib, Eric Boitier, Vasiliki Pelekanou, Nils Ternes, Alice Gosselin, Patrick Cohen, Marina Celanovic, Christopher Soria, Alexei Protopopov, Jack Pollard. Development of a gene signature assessing ER modulation by SERMs and SERDs as a target engagement biomarker for endocrine therapy in breast 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 406.
Prognostic Significance of Nonischemic Myocardial Fibrosis in Patients With Normal LV Volumes and Ejection-Fraction
Authors: Amrit S. Lota, Adam Tsao, Ruth Owen, Brian P. Halliday, Dominique Auger, Vassilios S. Vassiliou, Upasana Tayal, Batool Almogheer, Silvia Vilches, Amer Al-Balah, Akhil Patel, Florence Mouy, Rachel Buchan, Simon Newsome, John Gregson, James S. Ware, Stuart A. Cook, John G.F. Cleland, Dudley J. Pennell, Sanjay K. Prasad
Journal: JACC. Cardiovascular imaging (2021)

This study aims to investigate the prognostic significance of late gadolinium enhancement (LGE) in patients without coronary artery disease and with normal range left ventricular (LV) volumes and ejection fraction.
Abstract 502: <i>In vitro</i> characterization of antibodies targeting the SIRPα-CD47 phagocytosis checkpoint using tumor-associated macrophages from HuGEMM™ mice
Authors: Xuefei Yan, Hongjuan Zhang, Yi Liu, Yahong Zhang, Lei Zheng, Mingfa Zang, Annie Xiaoyu An, kevin Qijin Xu, Davy Ouyang, Henry Li, Yujun Huang
Journal: Cancer Research (2021)

Abstract Introduction: The signal-regulatory protein SIRPα-CD47 pathway is a phagocytosis checkpoint for macrophages and other innate immune cells. Tumor cells ubiquitously express CD47, and blocking SIRPα-CD47 interactions has been shown to promote cancer cell elimination by macrophage phagocytosis. The impact of SIRPα-CD47 blockade may be further improved by targeting prophagocytic receptors (Fc receptors) to enhance phagocytosis for anti-CD47 antibodies. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in late-stage tumors. Currently, drug development targeting CD47-SIRPα is rapidly growing, requiring robust in vitro macrophage/tumor cell co-culture assays to evaluate new agents targeting this pathway. Here, we report on the use of macrophages from an engineered mouse model expressing human SIRPα, which may serve as a good tool to test drug candidates. Methods: We have developed and characterized the human CD47 and SIRPα double knock-in mouse model (CD47/SIRPα HuGEMM) via CRISPR/Cas9 targeting. To characterize the effects of anti-human CD47 antibodies on phagocytosis and tumor cell killing, TAMs were isolated from tumor-bearing HuGEMM mice for in vitro macrophage/tumor cell co-culture. Results: Human CD47 expressing tumor cells, such as murine MC38-hCD47 and human Jurkat cells, were labeled with CFSE and used as target cells for antibody-dependent cellular phagocytosis (ADCP) and tumor cell death. The percentage of CFSE-positive among macrophages, and the percentage of dead cells among CFSE-positive tumor cell death, were measured by flow cytometry. We observed significant ADCP effects by TAM and killing of tumor cells after in vitro anti-CD47 antibody treatment. The contribution to ADCP by SIRPα-CD47 blockade and/or Fc effector function of antibodies was further investigated. We also evaluated the effect of SIRPα-CD47 blockade on the modulation of TAM phenotypes. Conclusion: Our data show that the CD47/SIRPα HuGEMM system provides an excellent tool for in vitro functional assays for drug candidates targeting the SIRPα-CD47 pathway, to evaluate the effect on ADCP by macrophages, activation of macrophages, and overall tumor cell death. Citation Format: Xuefei Yan, Hongjuan Zhang, Yi Liu, Yahong Zhang, Lei Zheng, Mingfa Zang, Annie Xiaoyu An, kevin Qijin Xu, Davy Ouyang, Henry Li, Yujun Huang. In vitro characterization of antibodies targeting the SIRPα-CD47 phagocytosis checkpoint using tumor-associated macrophages from HuGEMM™ mice [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 502.
Abstract 1528: Discovery and preclinical characterization of fratricide-resistant TRuC T-cells targeting CD70
Authors: Jian Ding, Amy Watt, Erica Liu, Zieba Adam, Derrick McCarthy, Jessica Gierut, Brett Schrand, Michael Lofgren, Jason Lajoie, Vania Kenanova, Philippe Kiefer-Kwon, Holly Horton, Dario A. Gutierrez, Robert Hofmeister, Robert Tighe
Journal: Cancer Research (2021)

Abstract Previously we have described the design and antitumor activity of T cell receptor fusion constructs (TRuC™) that tether an antibody-derived binder to one of the TCR subunits to achieve redirected T cell killing of tumor cells independent of HLA. Different from CAR-T cells, TRuCs are integrated into the full TCR complex and thus harness its full signaling capacity. The cell surface antigen CD70 represents a promising target for cancer immunotherapy for its selective overexpression in various hematological and solid tumor indications. Because the normal tissue expression of CD70 occurs on activated lymphocytes, including activated T cells, fratricide (self-killing) has been recognized as a significant challenge for CD70-targeted T cell therapies. To address this challenge, we discovered a diverse pool of fully human anti-CD70 scFv binders that were used to make TRuC-T cells and then functionally screened for fratricide-resistance in vitro. We successfully identified a CD70-targeted TRuC-T cell candidate that exhibits normal T cell expansion and an improved memory phenotype, clearly differentiating from fratricide-prone candidates, all while maintaining potent cytotoxicity and cytokine production against tumor cells expressing both low and high levels of CD70. In addition, our CD70-targeted TRuC-T cells showed significant anti-tumor efficacy in multiple xenograft mouse models with no evidence of in vivo fratricide. In summary, we have engineered a fratricide-resistant CD70-directed TRuC-T cell therapy that has the potential to treat a wide range of both hematologic and solid cancers. Citation Format: Jian Ding, Amy Watt, Erica Liu, Zieba Adam, Derrick McCarthy, Jessica Gierut, Brett Schrand, Michael Lofgren, Jason Lajoie, Vania Kenanova, Philippe Kiefer-Kwon, Holly Horton, Dario A. Gutierrez, Robert Hofmeister, Robert Tighe. Discovery and preclinical characterization of fratricide-resistant TRuC T-cells targeting CD70 [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 1528.