tbuckley/cabot-search huggingface dataset:
Abstract 1626: PMC309, a highly selective anti-VISTA antibody enhances T cell activation through blocking the interaction of T cells and myeloid derived suppressor cells (MDSC)
Authors: Cheon Ho Park, Sang Soon Byun, Jin Yong An, Sun Hyung Ha, Hye Rim Han, Nu Ri Kang, Beom Yong Park, Eun Ah Lee, Hyun Sun Park, Jin-San Yoo, Weon Sup Lee
Journal: Cancer Research (2021)

Abstract TME (tumor microenvironment) consists of blood &amp; lymphatic vessels, stromal cells, and immune cells such as lymphocytes, macrophages, and antigen-presenting cells (APC). Cellular interactions among various immune cell types within TME regulate tumor growth, metastasis, and resistance to cancer therapy. V-domain Ig suppressor of T cell activation (VISTA) is a negative checkpoint regulator highly expressed on tumor-infiltrating myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAMs) and VISTA blockade could enhance antitumor immunity in TME. PMC-309 binding to VISTA expressing cells is highly selective and the selectivity is maintained even in the low pH conditions that mimic TME. Binding of PMC-309 on MDSC cells enhances the secretion of IFN-γ, TNF-α, and IL-2 in Mixed Lymphocyte Reaction (MLR) settings. In in vivo study, PMC-309 suppressed tumor growth, which was further attenuated with an anti-PD1 antibody. The anti-tumor activity was associated with enhanced T cell activation, increased secretion of pro-inflammatory cytokines, and increased penetration of tumor-infiltrating leukocytes (TIL) into TME. Patients who became resistant to anti-CTLA-4 and anti-PD(L)1 antibody showed increased expression of VISTA, suggesting that anti-VISTA therapeutics can help to treat the patients who do not respond well to other immuno-oncology drugs. We are developing PMC-309 as a next generation immuno-oncology (IO) agent, which can convert immunologically cold into hot tumors as a mono- or combo- therapy with other IO agent. Citation Format: Cheon Ho Park, Sang Soon Byun, Jin Yong An, Sun Hyung Ha, Hye Rim Han, Nu Ri Kang, Beom Yong Park, Eun Ah Lee, Hyun Sun Park, Jin-San Yoo, Weon Sup Lee. PMC309, a highly selective anti-VISTA antibody enhances T cell activation through blocking the interaction of T cells and myeloid derived suppressor cells (MDSC) [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 1626.
Abstract 1922: Protective tumor neo-epitopes are processed from conformationally stable neo-antigen segments
Authors: Samuel J. Landry
Journal: Cancer Research (2021)

Abstract Immunogenic tumor neo-epitopes are the basis of successful checkpoint immunotherapy for cancer, and they potentially offer a target for personalized cancer vaccines. However, the frequency of immunologically protective neo-epitopes appears to be very low in comparison to the frequency of tumor mutations. Vaccine designers typically select neo-epitopes by demonstrable gene expression and elevated MHC class I binding, anticipating that corresponding CD8+ T cells will be protective; but CD4+ T-cells are more often correlated with therapeutic effects. CD4+ T cells are most well known for helping B cells make antibodies, and B cells also have recently been implicated in protection from tumors. Antigen-presenting cells, including dendritic cells, B cells, and macrophages present epitope peptides in complexes with class II MHC molecules (MHCII) to CD4+ T cells, and CD4+ T cells signal responding cells to eliminate tumor cells. Studies on immunodominant CD4+ T-cell epitopes from foreign antigens suggest that immunogenicity depends on antigen conformational stability. Likewise, the immunogenic CD4+ neo-epitopes of tumors could be associated with mutations affecting residues in conformationally stable protein segments. In order to test this hypothesis, we surveyed existing tumor neo-epitope data to analyze the conformational context of neo-epitopes that are associated with protection from tumors. First, protective neo-epitopes are three-fold more likely to occur in a crystal structure (67%) than other potential neo-epitopes (22%). Second, the protective neo-epitopes are enriched within or adjacent to conformationally stable segments of the neo-antigens, as reported by the Antigen Processing Likelihood algorithm. Third, the distribution of mutations between functionally similar hotspots encoding R248 and R273 in the gene for the p53 tumor suppressor is consistent with increased immunologic selection in tumors subjected to increased immune response. These results suggest that neo-epitope evaluation for cancer prognosis and vaccines should include the analysis of conformational stability in the neo-antigen. Citation Format: Samuel J. Landry. Protective tumor neo-epitopes are processed from conformationally stable neo-antigen segments [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 1922.
Evaluation of clinicopathological profiles and development of a risk model in epithelioid angiomyolipoma patients: A large-scale Chinese retrospective study
Authors: A. Anwaier, W-H. Xu, Y.Y. Qu, X. Tian, H.K. Wang, F.N. Wan, Y.P. Zhu, D.L. Cao, G.H. Shi, H.L. Zhang, D.W. Ye
Journal: European Urology (2021)
Elevated Cardiovascular Risk Factors at Time of Allotransplant Do Not Impact Survivals in Adult Patients: A Retrospective Study of 194 Cases
Authors: Sophie Vantyghem, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Pierre Gallas, Cyrille Touzeau, Thomas Gastinne, Anne Lok, Steven Le Gouill, Philippe Moreau, Marie C Bene, Patrice Chevallier
Journal: Blood (2017)
Abstract 620: Interrogating the molecular profile of lung cancer tumors in Puerto Rican Hispanics
Authors: Hilmaris Centeno-Girona, Ingrid M. Montes-Rodríguez, Camila Rivera-Lynch, Marievelisse Soto-Salgado, Noridza Rivera, Marcia Cruz-Correa
Journal: Cancer Research (2021)

Abstract Background: In the United States, lung cancer accounted for approximately one-quarter of all cancer deaths; meanwhile, it was reported as the second cause of death in Puerto Rico (PR) for 2018. Worldwide, the development of new technologies such as next-generation sequencing (NGS) has allowed describing the profile of tumors and identifying mutation drivers in oncologic patients. The information on these is limited for Puerto Rican Hispanics (PRH). Methods: Using retrospective data from CARIS Life Sciences from 2015 to 2020, we were able to estimate the prevalence of somatic mutations of 119 PRH with lung cancer. In addition, we compared them with the mutational profiles reported for lung cancer from the TCGA Pan-Lung data available in the cBioPortal for Cancer Genomics. Frequencies and percentages were calculated to describe the data. Results: The results showed that the 10 most mutated genes for lung cancer tumors in PRH were TP53 (53.7%, n=67), EGFR (20.6%, n=73), KRAS (20.6%, n=73), T.M.L. (14.1%, n=64), APC (11.0, n=73), PTEN (10.3%, n=68), ARID1A (13.6%, n=44), PIK3CA (6.9%, n=73), STK11 (6.9%, n=72), and BRAF (5.5%, n=73). Additionally, only one positive mutation was found in MET (1.4%, n=72), and no mutations were identified in ALK and RET. When comparing to the top 10 tumor mutational profiles from the TCGA study, only BRAF was observed with a mutational frequency of 67.7% (n=1,444). Conclusion: Understanding the common molecular pathways that affect the PRH population is necessary to develop new therapeutic modalities. Moreover, this preliminary review of oncogenic drivers in PRH with lung cancer will inform clinicians, scientists, and the health community about actionable mutations to guide research, treatment, and health policy efforts. Citation Format: Hilmaris Centeno-Girona, Ingrid M. Montes-Rodríguez, Camila Rivera-Lynch, Marievelisse Soto-Salgado, Noridza Rivera, Marcia Cruz-Correa. Interrogating the molecular profile of lung cancer tumors in Puerto Rican Hispanics [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 620.
Abstract 852: Index-based dietary patterns and risk of pancreatic ductal adenocarcinoma: Results from the NIH-AARP Diet and Health Study
Authors: Sachelly Julián-Serrano, Jill Reedy, Kim Robien, Rachael Stolzenberg-Solomon
Journal: Cancer Research (2021)

Abstract Background: There is limited-suggestive evidence for individual dietary components, and few studies have examined whether dietary patterns are associated with pancreatic cancer risk. Objective: We examined the associations between five established index-based dietary quality patterns and pancreatic ductal adenocarcinoma (PDAC) risk in middle aged and older US adults. Methods: The Healthy Eating Index (HEI)-2015, Alternative HEI-2010 (AHEI-2010), alternate Mediterranean diet (aMED), and two Dietary Approaches to Stop Hypertension (DASH) scores (Fung et al. and Mellen et al.) were calculated using responses from a food frequency questionnaire data from 535,398 (315,780 men and 224,044 women) NIH-AARP Diet and Health Study participants aged 51-70 years at baseline (1995-1996). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for PDAC risk according to each dietary pattern quintile. Covariates included in multivariable models were age, sex, smoking, body mass index, diabetes, and energy intake. Results: During follow-up though 2011 (15.5 years median), 3,137 incident PDAC cases were identified. Participants with the highest adherence scores compared to those with the lowest adherence scores for each dietary pattern (Q5 versus Q1), had a significantly lower risk of PDAC, except for AHEI-2010: HRs (95% CIs) for HEI-2015 [0.84 (0.75, 0.94)], aMED [0.82 (0.73, 0.93)], DASH-Fung [0.86 (0.77, 0.96)], DASH-Mellen [0.86 (0.77, 0.99)] and AHEI-2010 [0.93 (0.83, 1.04)]. Sex-stratified analyses showed stronger results in men for the HEI-2015 [0.78 (0.68, 0.90)], DASH-Fung [0.78 (0.67, 0.91)], and DASH-Mellen [0.82 (0.71, 0.95)] indices. Only the aMED score remained statistically significantly associated with PDAC risk in women [0.76 (0.63, 0.92)]. Tests for interaction by sex were not significant (P-values &amp;gt; 0.07). Conclusions: In this analysis of dietary patterns and PDAC, we observed a 14-24% lower cancer risk with greater adherence to index-based dietary quality patterns. Our findings support the hypothesis that adherence to dietary recommendations such as the Dietary Guidelines for Americans, Harvard's Healthy Eating Plate, the Mediterranean Diet and the DASH diet may reduce the risk of developing PDAC Citation Format: Sachelly Julián-Serrano, Jill Reedy, Kim Robien, Rachael Stolzenberg-Solomon. Index-based dietary patterns and risk of pancreatic ductal adenocarcinoma: Results from the NIH-AARP Diet and Health Study [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 852.
Efficacy of intravesical therapies on the prevention of recurrence and progression of non-muscle-invasive bladder cancer: A systematic review and network meta-analysis
Authors: Q-D. Xia, J-L. Lu, J. Hu, H-L. Hu, J-X. Sun, C-Q. Liu, J-Z. Xu, S-G. Wang
Journal: European Urology (2021)
Effect of quitting smoking on health outcomes during treatment for tuberculosis: secondary analysis of the TB &amp; Tobacco Trial
Authors: Kamran Siddiqi, Ada Keding, Anna-Marie Marshall, Omara Dogar, Jinshuo Li, Rumana Huque, Razia Fatima, Amina Khan, Helen Elsey, Rhian Gabe, Daniel Kotz, Aziz Sheikh
Journal: Thorax (2021)

Background Despite treatment, patients with tuberculosis (TB) who smoke have poorer outcomes compared with non-smokers. It is unknown, however, if quitting smoking during the 6 months of TB treatment improves TB outcomes. Methods The TB &amp; Tobacco Trial was a double-blind, placebo-controlled randomised trial of cytisine for smoking cessation in 2472 patients with pulmonary TB in Bangladesh and Pakistan. In a secondary analysis, we investigated the hypothesis that smoking cessation improves health outcomes in patients during the TB treatment course. The outcomes included an eight-point TB clinical score, sputum conversion rates, chest X-ray grades, quality of life (EQ-5D-5L), TB cure plus treatment completion rates and relapse rates. These were compared between those who stopped smoking and those who did not, using regression analysis. Results We analysed the data of 2273 (92%) trial participants. Overall, 25% (577/2273) of participants stopped smoking. Compared with non-quitters, those who quit had better TB cure plus treatment completion rates (91% vs 80%, p&lt;0.001) and lower TB relapse rates (6% vs 14%, p&lt;0.001). Among quitters, a higher sputum conversion rate at week 9 (91% vs 87%, p=0.036), lower mean TB clinical scores (−0.20 points, 95% CI −0.31 to −0.08, p=0.001) and slightly better quality of life (mean EQ-5D-5L 0.86 vs 0.85, p=0.015) at 6 months were also observed. These differences, except quality of life, remained statistically significant after adjusting for baseline values, trial arm and TB treatment adherence rates. Conclusion Patients with TB who stop smoking may have better outcomes than those who don’t. Health professionals should support patients in stopping smoking.
Abstract 1756: The roles of Regnase-1 in pancreatic cancer development and progression
Authors: Junya Okabe, Takahiro Kodama, Tetsuo Takehara
Journal: Cancer Research (2021)

Abstract Background: Regnase-1 is a RNA-degrading enzyme that plays an important role in the regulation of inflammation by degrading mRNA of inflammation-related genes. Although inflammation is known to promote pancreatic carcinogenesis, involvement of Regnase-1 in this process has never been studied. In this study, we thus investigated the role of Regnase-1 in pancreatic cancer development and progression. Methods: We examined the expression levels of Regnase-1 in the pancreas of chronic pancreatitis by repeated administration of caerullein in mice. We sought for a regulator of the Regnase-1 expression in Panc-1 pancreatic cancer cell line. We assessed the biological phenotypes caused by siRNA-mediated Regnase-1 inhibition in multiple pancreatic cancer cell lines, including cell proliferation, migration, apoptosis and cytokine expressions. We generated pancreas-specific Kras-activated and Regnase-1-deficient (PDX1-Cre; Kras G12D KI Regnase-1 fl/fl) mice (PKR mice) and examined these phenotypes. We assessed the relationship between the expression levels of Regnase-1 in pancreatic tumor tissue and prognosis in 39 pancreatic cancer patients who underwent curative surgical resection. Results: The expression levels of Regnase-1 significantly decreased in the murine pancreas of chronic pancreatitis together with the increase in IL-1β. The expression levels of Regnase-1 was downregulated by IL-1β administration in Panc-1 cells. siRNA-mediated Rengase-1 Inhibition significantly promoted cell proliferation, migration and inhibited apoptosis with Bcl-xL upregulation in Panc-1 cells. Rengase-1 Inhibition also upregulated a variety of chemokines involved in the recruitment and activation of myeloid-derived suppressor cells (MDSCs) including CXCL1, CXCL2, CXCL8, CSF2 and CSF3 in Panc1cells. All PKR mice developed pancreatic tumors and became moribund by 3 months of age. We observed massive infiltration of CD11b+Ly6g+Ly6c- PMN-MDSCs and significant upregulation of Arg1, Nos2, Nox2, and S100a8/9 mRNA levels, which are suppressors of anti-tumor immunity known to be secreted from MDSCs. Surgically-resected pancreatic cancer patients with low levels of intra-tumor Regnase-1 expression had significantly shorter recurrence-free and overall survival than those with high levels of Regnase-1. Intratumor Regnase-1 expression levels were negatively correlated with the number of CD11b+ cell infiltration. Conclusion: Inflammation-mediated downregulation of Regnase-1 may contribute to pancreatic cancer development and progression in cell-autonomous and -heteronomous manners. Citation Format: Junya Okabe, Takahiro Kodama, Tetsuo Takehara. The roles of Regnase-1 in pancreatic cancer development and 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 1756.
The role of simulation in endourology training: development and validation of a 3D-printed model
Authors: S. Chiva, R. Polo Gay, C. Muñoz Bastidas, J. Colombas Vives, C. Gutierrez Castañé, P. Domenech, F.J. Diez-Caballero Alonso, M. Llorente Ortega, F.J. Ancizu Marckert, M. Torres Roca, L. Labairu Huerta, D. Rosell Costa, J.E. Robles García, F. Ramón De Fata Chillón, F. Villacampa Aubá, G. Barbas Bernardos, G. Andrés Boville, B. Miñana López, J.I. Pascual Piédrola
Journal: European Urology (2021)
Abstract 11708: Contemporary Etiology, Prevalence and Outcome of Severe Right Ventricular Dysfunction
Authors: Ratnasari Padang, Nikhitha Chandrashekar, Manasawee Indrabhinduwat, Christopher Scott, Sushil A Luis, Krishnaswamy Chandrasekaran, Hector I Michelena, Vuyisile T Nkomo, Sorin Pislaru, Patricia A Pellikka, Garvan Kane
Journal: Circulation (2019)

Introduction: Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. However, data are sparse on the epidemiology and outcome ...
Abstract CT129: ARC-3: Updated results of etrumadenant (AB928) + modified FOLFOX-6 (mFOLFOX-6) in metastatic colorectal cancer (mCRC) patients
Authors: Michael Cecchini, Cheng Quah, Shiyao Liu, Rachel Woloski, Akshata Udyavar, Marios Giannakis
Journal: Cancer Research (2021)

Abstract Background: The release of ATP from dying cancer cells in response to platinum-based chemotherapy increases immunosuppressive extracellular adenosine, which can bind and activate the A2a and A2b receptors on immune cells, diminishing the effectiveness of the anti-tumor immune response. Concomitant dual adenosine receptor blockade may therefore enhance the therapeutic efficacy of some chemotherapeutic agents. Etrumadenant (etruma, AB928) is the first clinical-stage small-molecule, selective dual antagonist of A2aR and A2bR for which combination data with mFOLFOX-6 in mCRC were previously presented1,2. Here we present updated results for safety in all patients (pts) and efficacy in 3L+ pts. Methods: ARC-3 (NCT03720678) was a phase 1/1b, multicenter, open-label study to evaluate etruma + mFOLFOX-6 in pts with mCRC. Eligible pts had histologically confirmed mCRC with ≥1 measurable lesion. Pts received 75 mg (phase 1 only) or 150 mg etruma orally once daily (QD) + mFOLFOX-6. The primary objective was to assess the safety of the combination; secondary objectives included evaluation of clinical activity. Results: As of 20Nov2020, 44 pts were enrolled and received etruma (75mg: n=4; 150mg: n=40) + mFOLFOX-6. Etruma-related AEs were reported in 34 pts and were mostly Grade 1 or 2; those reported in &amp;gt;30% of pts were fatigue and nausea. One pt had an etruma-related Grade 3 acute kidney injury and there were no Grade 4-5 etruma-related SAEs. There were 22 efficacy-evaluable 3L+ subjects, all of which had received prior FOLFOX and/or FOLFIRI. In this subgroup, the ORR was 9.1% and the median PFS and OS were 3.9 and 15.7 mos respectively. Conclusions: Updated results confirm etruma + mFOLFOX-6 was well tolerated in pts with mCRC without significant additive toxicity and was associated with disease control in heavily pretreated pts. Based on these encouraging data, a platform study (ARC-9) has been initiated to further explore this and other combinations in mCRC pts. References 1. Cecchini M, et.al. AACR Annual Meeting 2020, Abstract# 99532. Udyavar A, et.al. SITC Annual Meeting 2020, Abstract# 338 Citation Format: Michael Cecchini, Cheng Quah, Shiyao Liu, Rachel Woloski, Akshata Udyavar, Marios Giannakis. ARC-3: Updated results of etrumadenant (AB928) + modified FOLFOX-6 (mFOLFOX-6) in metastatic colorectal cancer (mCRC) patients [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 CT129.
Decreased infectivity following BNT162b2 vaccination: A prospective cohort study in Israel
Authors: Gili Regev-Yochay, Sharon Amit, Moriah Bergwerk, Marc Lipsitch, Eyal Leshem, Rebecca Kahn, Yaniv Lustig, Carmit Cohen, Ram Doolman, Arnona Ziv, Ilya Novikov, Carmit Rubin, Irena Gimpelevich, Amit Huppert, Galia Rahav, Arnon Afek, Yitshak Kreiss
Journal: The Lancet Regional Health - Europe (2021)

BNT162b2 was shown to be 92% effective in preventing COVID-19. Prioritizing vaccine rollout, and achievement of herd immunity depend on SARS-CoV-2 transmission reduction. The vaccine's effect on infectivity is thus a critical priority.
Maternity services are not improving fast enough, say MPs
Authors: Adrian O’Dowd
Journal: BMJ (2021)

The government’s plans to improve maternity services in England and take action to make progress on their safety ratings are moving far too slowly, according to MPs.

The parliamentary health and social care committee published two reports on 6 July which called for boosts to midwifery staffing levels, increased investment of at least £200-350m (€234-409m; $277-485m) per year, and a new target by which to end disparities in maternal and neonatal outcomes.

The first report, which focused on the safety of maternity services in England,1 found that improvements in maternity services had been too slow. The Care Quality Commission’s (CQC) chief inspector of hospitals, Ted Baker, who gave evidence to the inquiry, reported a “defensive culture,” “dysfunctional teams,” and …