tbuckley/cabot-search huggingface dataset:
Abstract 2454: Vitamin D-mediated anti-cancer activity involves iron homeostatic balance disruption and oxidative stress induction in breast cancer
Authors: Khuloud Bajbouj, Jasmin Shafarin, Lina Sahnoon, Abeer Al-Ali, Jibran Sualeh Muhammad, Salman Y. Guraya, Mawieh Hamad
Journal: Cancer Research (2021)

Abstract Background: Vitamin D deficiency has long been associated with increased risk of breast cancer (BC). Moreover, increased cellular iron content is emerging as a biomarker of BC metastasis. Although the connection between vitamin D and cellular iron content in BC remains ambiguous, recent studies have shown that vitamin D exerts some of its anti-cancer effects by modulating the expression of key iron regulatory genes (IRGs). Herein, we addressed the question of whether vitamin D signaling plays a role in cellular iron homeostasis and whether this has a effects on breast cancer cell survival and growth. Experimental Methods: Bioinformatics analysis from publicly available transcriptomic data set has been utilized to profile the expression status of key IRGs in vitamin D-treated breast cancer cells. Additionally, hormonal-responsive (MCF-7) and triple negative (MDA-MB-231) BC cells were treated with 1α,25-dihydroxyvitamin D3 (calcitriol; the vitamin D active form) and evaluated for labile iron content, expression of IR proteins, oxidative stress, and cell survival. Results and Discussions: Bioinformatics analysis revealed that several IRGs including hepcidin, ferroportin, ferritin and transferrin receptor as well as genes related to metabolic cellular stress are differentially expressed in BC cells. Vitamin D treatment resulted in cellular iron depletion and differentially affected the expression of key IR proteins. Moreover, vitamin D induced oxidative stress and altered the redox balance in treated cells by reducing catalase protein levels and increasing the expression of several stress-related markers including γ-H2AX, hypoxia-inducible factor 1 alpha and hemoxygenase 1. Consecutively, BC cell survival was significantly decreased in vitamin D-treated cells. Conclusion: Collectively, data presented here demonstrate that vitamin D disrupts iron homeostasis, augments oxidative damage and reduces BC cell survival and growth. Citation Format: Khuloud Bajbouj, Jasmin Shafarin, Lina Sahnoon, Abeer Al-Ali, Jibran Sualeh Muhammad, Salman Y. Guraya, Mawieh Hamad. Vitamin D-mediated anti-cancer activity involves iron homeostatic balance disruption and oxidative stress induction 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 2454.
PD-1 MOUNTAINEER: Open-label, phase 2 study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress)
Authors: S. Siena, E. Elez, M. Peeters, T. André, M. Van den Eynde, K. Ng, A. Cercek, C. Fountzilas, F. Sanchez, J. Hubbard, C. Wu, J. Tabernero, A. Kardosh, A. Saeed, J. Strickler, T. Bekaii-Saab, M. Stecher, M. Palanca-Wessels, E. Van Cutsem
Journal: Annals of Oncology (2021)
International Observational Analysis of Evolution and Outcomes of Chronic Stable Angina: The Multinational CLARIFY Study
Authors: Jules Mesnier, Gregory Ducrocq, Nicolas Danchin, Roberto Ferrari, Ian Ford, Jean-Claude Tardif, Michal Tendera, Kim M. Fox, Philippe Gabriel Steg
Journal: Circulation (2021)

Although angina is common in patients with stable coronary artery disease, limited data are available on its prevalence, natural evolution, and outcomes in the era of effective cardiovascular drugs and widespread use of coronary revascularization.Using data from 32 691 patients with stable coronary artery disease from the prospective observational CLARIFY registry (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease), anginal status was mapped each year in patients without new coronary revascularization or new myocardial infarction. The use of medical interventions in the year preceding angina resolution was explored. The effect of 1-year changes in angina status on 5-year outcomes was analyzed using multivariable analysis.Among 7212 (22.1%) patients who reported angina at baseline, angina disappeared (without coronary revascularization) in 39.6% at 1 year, with further annual decreases. In patients without angina at baseline, 2.0% to 4.8% developed angina each year. During 5-year follow-up, angina was controlled in 7773 patients, in whom resolution of angina was obtained with increased use of antianginal treatment in 11.1%, with coronary revascularization in 4.5%, and without any changes in medication or revascularization in 84.4%. Compared to patients without angina at baseline and 1 year, persistence of angina and occurrence of angina at 1 year with conservative management were each independently associated with higher rates of cardiovascular death or myocardial infarction (adjusted hazard ratio, 1.32 [95% CI, 1.12-1.55] for persistence of angina; adjusted hazard ratio, 1.37 [95% CI, 1.11-1.70] for occurrence of angina) at 5 years. Patients whose angina had resolved at 1 year with conservative management were not at higher risk of cardiovascular death or myocardial infarction than those who never experienced angina (adjusted hazard ratio, 0.97 [95% CI, 0.82-1.15]).Angina affects almost one-quarter of patients with stable coronary artery disease but resolves without events or coronary revascularization in most patients. Resolution of angina within 1 year with conservative management predicted outcomes similar to lack of angina, whereas persistence or occurrence was associated with worse outcomes. Because most patients with angina are likely to experience resolution of symptoms, and because there is no demonstrated outcome benefit to routine revascularization, this study emphasizes the value of conservative management of stable coronary artery disease. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN43070564.
Biliary rendezvous through the gallbladder using a lumen-apposing metal stent
Authors: Margarida Flor de Lima, Nuno Nunes, Diogo Bernardo Moura, Carolina Chálim Rebelo, Vera Costa Santos, José Renato Pereira, Maria Antónia Duarte
Journal: Endoscopy (2021)

Endoscopic ultrasound (EUS)-guided rendezvous is a feasible and safe technique to provide biliary access when endoscopic retrograde cholangiopancreatography (ERCP) fails [1] [2]. Recently, EUS-guided gallbladder stent deployment has been used as an alternative drainage method [3]. Local treatment of biliary perforations aims to divert bile and allow spontaneous wound healing [4]. We describe a modified biliary rendezvous technique using a transmural gallbladder stent.
Abstract 17400: Charge-Stabilized Nanostructures Reduce Ischemia-Reperfusion Injury in A Pig Model in vivo
Authors: Andreas Kalmes, Supruna Ghosh, Richard Watson
Journal: Circulation (2011)

Background: Inflammation contributes to reperfusion injury, and experimental studies employing anti-inflammatory treatments have shown beneficial effects. RNS60 is a 0.9% NaCl solution containing charged-stabilized nanostructures as a result of mechanical processing in the presence of oxygen. Preclinical in-vitro and in-vivo studies in multiple disease models have demonstrated that RNS60 modulates ion channels and has broad anti-inflammatory and cytoprotective effects. Objective: To test the hypothesis that RNS60 will positively influence survival and physiological parameters after myocardial infarction, we conducted a study in the balloon-induced myocardial ischemia/reperfusion (I/R) model in pigs. Methods: Male and female domestic pigs (45-50 kg) were subjected to myocardial ischemia by occlusion of the left anterior descending coronary artery for 40 minutes. Groups of males or females (n = 4/group) were treated with RNS60 or normal saline (NS) as control by single intracoronary injection (0.065 mL/kg) at time of reperfusion and by subsequent intravenous injections (100 mL/kg) every 4 hours for 7 days. ECGs were analyzed for T-wave abnormalities including T-elevation, biphasic T-waves and flipped T-waves. Myocardial damage was assessed by measuring circulating levels of troponin and by histologic analysis of the left ventricle for signs of tissue necrosis and inflammatory cell infiltration. Results: RNS60 treatment reduced mortality in male pigs (0/4 in RNS60 group vs. 2/4 in NS group) and caused a normalization of ECG tracings both in males and in females. In addition, RNS60 treatment completely prevented the infarct-induced elevation of circulating levels of cardiac troponin in male pigs at 6 (RNS60 1.12±0.36 vs. NS 6.00±3.39 ng/mL), 12 (RNS60 0.71±0.16 vs. NS 16.96±11.05 ng/mL), and 24 hours (RNS60 0.46±0.17 vs. NS 16.41±12.75 ng/mL). Consistent with these findings, the hearts of RNS60-treated male pigs were free of signs of necrosis or mononuclear infiltration at 7 days post I/R. Conclusion: Treatment with a saline solution containing CSNs has the potential to reduce I/R injury in vivo.
Abstract 1831: Affinity tuned XmAb®2+1 GPC3 x CD3 bispecific antibodies demonstrate selective activity in liver cancer models
Authors: Alex Nisthal, Nargess Hassanzadeh-Kiabi, Kendra N. Avery, Rumana Rashid, Juan E. Diaz, Umesh S. Muchhal, Seung Y. Chu, Gregory L. Moore, Katrina Bykova, John R. Desjarlais
Journal: Cancer Research (2021)

Abstract Bispecific T cell engagers simultaneously bind CD3 on T cells and tumor-associated antigens to promote T cell-mediated killing of tumor cells. These agents provide synthetic immunity by expanding, activating, and redirecting T cells against a target of interest. While targeting lineage-restricted antigens such as CD19 or CD20 have found clinical success in hematopoietic cancers, targeting solid tumors requires high expressing tumor associated antigens (TAAs) with minimal normal tissue expression. Glypican 3 (GPC3), a lipid-anchored cell surface protein, is over-expressed in the majority of hepatocellular carcinoma (HCC) and a smaller subset of lung squamous cell carcinoma. It is considered an ideal target because its expression is not detected in adult tissues, and its function can promote tumor growth through the Wnt/beta-catenin pathway. Although GPC3 demonstrates good differential expression, bispecific T cell engagers are powerful immunomodulatory agents and careful tuning can improve the therapeutic window on all targets. Building upon the XmAb® heterodimeric Fc platform, we generated bispecific antibodies in an XmAb 2+1 Fab2-scFv-Fc format that are bivalent for GPC3 and monovalent for CD3. Reducing the affinity of GPC3 encouraged avid binding and strong killing activity only on high GPC3 expressing cell lines while minimizing reactivity on low expressing cell lines. We found modulating the CD3 affinity, either directly through mutation or indirectly by the molecular format, contributes to the selectivity of the bispecific antibodies. To ensure biologically valid antigen densities were being considered, IHC was conducted on paraffin embedded arrays of tumor tissue, normal tissue, and cell lines. Upon matching the staining intensity between the three sample types, we identified cell lines with corresponding GPC3 antigen density that could serve as proxies of tumor and normal tissue. In vitro T cell-dependent cellular cytotoxicity (TDCC) assays on the relevant cell lines confirmed selective potency on high versus low expressing cells. Citation Format: Alex Nisthal, Nargess Hassanzadeh-Kiabi, Kendra N. Avery, Rumana Rashid, Juan E. Diaz, Umesh S. Muchhal, Seung Y. Chu, Gregory L. Moore, Katrina Bykova, John R. Desjarlais. Affinity tuned XmAb®2+1 GPC3 x CD3 bispecific antibodies demonstrate selective activity in liver cancer models [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 1831.
Clinically insignificant residual fragment perception among endourologists after percutaneous nephrolithotomy: A world-wide survey by EAU-YAU Endourology and Urolithiasis Working Group
Authors: S. Tonyali, E. Emiliani, T.E. Sener, A. Pietropaolo, M. Ozsoy, O. Aboumarzouk, B. Somani, P. Kallidonis, V.M. De Coninck, M. Talso, T. Tailly
Journal: European Urology (2021)
Implications of 3-Year Follow-up Data From the Childhood and Adolescent Migraine Prevention Medication Trial
Authors: Sinifunanya E. Nwaobi, Joshua Kamins
Journal: JAMA Network Open (2021)

Scott W. Powers, PhD; Christopher S. Coffey, PhD; Leigh A. Chamberlin, RD, MEd; Dixie J. Ecklund, RN, MSN; Elizabeth A. Klingner, MS; Jon W. Yankey, MS; James L. Peugh, PhD; Leslie L. Korbee, BS; Kerry Simmons, BS; Stephanie M. Sullivan, BS; Marielle A. Kabbouche, MD; Joanne Kacperski, MD; Linda L. Porter, PhD; Brooke L. Reidy, PhD; Andrew D. Hershey, MD, PhD
Beneficial Effect of Microrna-155 in Vincristine Response and Clinical Outcome in Especially GCB Diffuse Large B-Cell Lymphoma
Authors: Hanne Due, Anna Amanda Schönherz, Laura Barett Ryø, Anne Stidsholt Roug, Hans Erik Johnsen, Martin Bøgsted, Jacob Giehm Mikkelsen, Karen Dybkær
Journal: Blood (2017)
Alternative Diagnostic Models of the Psychotic Disorders: Evidence-Based Choices
Authors: Bruce M. Cohen, Dost Öngür, Suzann M. Babb
Journal: Psychotherapy and Psychosomatics (2021)

Standard diagnostic systems, the predominantly categorical DSM-5 and ICD-11, have limitations in validity, utility, and predictive and descriptive power. For psychotic disorders, these issues were partly addressed in current versions, but additional modifications are thought to be needed. Changes should be evidence based. We reviewed categorical, modified-categorical, and continuum-based models versus factor-based models of psychosis. Factors are clusters of symptoms or single prominent aspects of illness. Consistent evidence from studies of the genetics, pathobiology, and clinical presentation of psychotic disorders all support an underlying structure of factors, not categories, as best characterizing psychoses. Factors are not only the best fit but also comprehensive, as they can encompass any key feature of illness, including symptoms and course, as well as determinants of risk or response. Factors are inherently dimensional, even multidimensional, as are the psychoses themselves, and they provide the detail needed for either grouping or distinguishing patients for treatment decisions. The tools for making factor-based diagnoses are available, reliable, and concordant with actual practices used for clinical assessments. If needed, factors can be employed to create categories similar to those in current use. In addition, they can be used to define unique groupings of patients relevant to specific treatments or studies of the psychoses. Lastly, factor-based classifications are concordant with other comprehensive approaches to psychiatric nosology, including personalized (precision treatment) models and hierarchical models, both of which are currently being explored. Factors might be considered as the right primary structural choice for future versions of standard diagnostic systems, both DSM and ICD.
Abstract 1874: MDX-124, a novel annexin-A1 antibody, induces an anti-tumor immune response and wide-ranging anti-cancer activity in multiple preclinical models
Authors: Fiona C. Dempsey, Hussein Al-Ali, Scott J. Crichton, Chris Pepper, Christopher N. Parris
Journal: Cancer Research (2021)

Abstract Major recent advances have increased the understanding of both the molecular mechanisms and the immune response in cancer. This has led to the discovery of new agents that regulate the tumor immune microenvironment. Annexin-A1 (ANXA1) is a phospholipid binding protein that has been shown to have immunomodulatory effects on T-cells, macrophages and dendritic cells. Although normally localized in the cytoplasm, ANXA1 is secreted in response to a number of different stimuli and can modulate cellular functions through interactions with formyl peptide receptors (FPR1/2). Overexpression of ANXA1 has been observed in several cancer types including triple-negative breast (TNBC), lung, pancreatic and ovarian, and correlates with poor prognosis and decreased overall survival. Furthermore, ANXA1 has also been shown to influence cancer cell proliferation, angiogenesis, migration and drug resistance. Hence, we explored the role of MDX-124, a novel humanized antibody targeting ANXA1, and here present data from several pre-clinical cancer models. Results: Incubation of a panel of cell lines representing several histological cancer subtypes with MDX-124 for 72h resulted in a statistically significant dose-dependent reduction in cell viability compared to control. ANXA1 expression in the subcellular compartments (nucleus, cytoplasm and membrane) was quantified in a panel of cancer cell lines via imaging flow cytometry and the anti-proliferative effect of MDX-124 was shown to correlate with membrane ANXA1 expression. Using a transwell assay, TNBC and acute myeloid leukemia cell lines exposed to MDX-124 exhibited a statistically significant reduction in migration compared to untreated controls. We also observed that MDX-124 induced antibody dependent cellular cytotoxicity (ADCC) activity in a dose-dependent manner using a reporter bioassay (EC50 = 0.38 nM). MDX-124 was further evaluated in an additional panel of in-vitro assays and shown to exert consistent anti-cancer activity. In conclusion, our data indicate that targeting ANXA1 with MDX-124 inhibits tumorigenic processes and induces an immune response in tumors overexpressing ANXA1. MDX-124 therefore provides an innovative approach to cancer therapy. Investigations are continuing to explore the efficacy of MDX-124 in syngeneic mouse models as both a single agent and in combination with standard of care agents. Citation Format: Fiona C. Dempsey, Hussein Al-Ali, Scott J. Crichton, Chris Pepper, Christopher N. Parris. MDX-124, a novel annexin-A1 antibody, induces an anti-tumor immune response and wide-ranging anti-cancer activity in multiple preclinical models [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 1874.
Cancer control outcomes following focal therapy using HIFU in 1,829 men with non-metastatic prostate cancer treated over 15 years
Authors: D.T. Reddy, M. Peters, T. Shah, M. Van Son, P. Huber, D. Lomas, A. Rakauskas, S. Miah, S. Guillaumier, T. Dudderidge, R. Hindley, A. Emara, R. Nigam, M. Valerio, N. Afzal, H. Lewi, C. Orczyk, C. Ogden, R. Persad, J. Virdi, C. Moore, M. Arya, M. Winkler, M. Emberton, H. Ahmed
Journal: European Urology (2021)
Knowledge and attitude of Palestinian women to contraceptives: a cross-sectional study
Authors: Beesan Warasna, Naeema Rajabi, Balqees Mustafa, Anas Najjar, Sojod Daraghmeh, Anwar Ma’ali, Maryam Sawalha, Abrar Ali, Aya Ateeq, Bara’a Ghannam, Belal Ashhab, Georgette Kharoufeh, Muhannad Qiq, Salam Abu Sharar, Samaa Al-atrash, Ahmad Amro
Journal: The Lancet (2021)
Abstract 13769: Correlation of Measures of Cardiovascular Risk to Novel Proteomic Measure of HDL Function
Authors: Marc S Penn, Nicolas Chronos, David DeSantis, Timothy Collier, Michael J McPhaul
Journal: Circulation (2019)

Introduction: We have described a novel proteomic-based measure of HDL function (HDLfx) that is related to cholesterol efflux capacity (CEC). In the development of HDLfx, a proteomic analysis ident...
Abstract 1686: Host intrinsic STING is a promising biomarkerfor predicting clinical efficacy of anti-PD-1 inhibitors in lung cancer
Authors: Li Zhou, Qiuli Xu, Litang Huang, Ping Zhan, mingxiang ye, Tangfeng Lv, Yong Song
Journal: Cancer Research (2021)

Abstract Background: The stimulator of IFN genes (STING) signaling pathway plays an important role in anti-tumor immune responses. However, the mechanistic contribution of host and tumor STING signaling to the therapeutic efficacy of anti-PD-1 inhibitors in lung cancer remains unknown. Methods: We analyzed the association of STING with immune makers in TCGA datasets; we evaluated the efficacy of anti-PD-1 inhibitors by coculturing spleen cells with LLC cells in vitro, and inoculating wild type/STING knockdown LLC cells into the flank of wild-type/STING knockout mice in vivo. Furthermore, we measured the expression of STING by multiple immunohistochemistry and immunohistochemistry in lung cancer patients, and analyzed the relationship between expression level of STING in different cells and treatment efficacy of DCB(Durable clinical benefit : CR or PR or SD lasting longer than 6 months) and NDB(No durable clinical benefit : PD or SD that lasted ≤ 6 months) patients receiving immunotherapy. Results: Here we first demonstrated that STING signaling pathway activation was associated with better immunotherapy efficacy in lung cancer patients. Next, we identified two distinct STING expression pattern and found that STING in host cells not in tumor cells was positively correlated with infiltration of CD8+ T cells. More importantly, we demonstrated a loss of therapeutic efficacy of anti-PD-1 inhibitor in STING KO spleen cells and STING KO mice. In contrast, knock down of STING expression in tumor cells had no effect. Furthermore, expression of STING on host cells not in tumor cells was correlated with the efficacy of Anti-PD-1 inhibitors in lung cancer patients. Conclusion: Together, these findings demonstrate that STING expressed in host cells, rather than on tumor cells, plays an essential role in anti-PD-1 inhibitor therapy, suggesting that host intrinsic STING could be predictive of sensitivity to anti-PD-1 inhibitors. Citation Format: Li Zhou, Qiuli Xu, Litang Huang, Ping Zhan, mingxiang ye, Tangfeng Lv, Yong Song. Host intrinsic STING is a promising biomarkerfor predicting clinical efficacy of anti-PD-1 inhibitors in 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 1686.
Abstract 3051: On the origin of pediatric leukemia: studying somatic mutations in human blood
Authors: Arianne Brandsma
Journal: Cancer Research (2021)

Abstract The acquisition of oncogenic mutations with age is believed to be rate limiting for carcinogenesis and aging is the biggest risk factor for cancer. However, children can also develop cancers even though their cells are less damaged by age. Here, we studied the cellular origin and time of onset during development of pediatric acute myeloid leukemia (pAML) to increase our understanding of why children can get cancer. We compared by whole genome sequencing individual hematopoietic stem and progenitor cells (HSPCs) and pAML blasts of the same leukemic bone marrow as well as nonmatching healthy HSPCs. We found that the number of clonal mutations in the majority of pAML cases was increased and mutational process contribution altered as compared to normal HSPCs, showing activity of specific processes that are either unique to fetal development or normally not observed in healthy HSPCs. These observations could be explained by altered selection dynamics early in life. Surprisingly, pAML cases with an overall mutation burden comparable to age matched healthy HSPCs showed worse overall and event-free survival. Identifying shared somatic mutations between individual HSPC clones and pAML using single-cell genotyping allowed us to pinpoint the developmental lineage that gave rise to the pAML. Our study provides new insights into the etiology of pAML and underscores the clinical potential of whole genome sequencing in pediatric leukemia. Citation Format: Arianne Brandsma. On the origin of pediatric leukemia: studying somatic mutations in human blood [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 3051.