tbuckley/cabot-search huggingface dataset:
Abstract PS7-78: Trends in BRCA testing among patients diagnosed with breast cancer -a retrospective analysis of a United States commercial claims database from the PRIOR-1 study
Authors: Shelby Corman, Hrishikesh Kale, Pooja Shah, Gboyega Adeboyeje
Journal: Cancer Research (2021)

Abstract Background The use of BRCA testing to guide the course of breast cancer treatment has evolved in the last 5 years; however, little is known about the use of BRCA testing in a real-world setting. This study assessed the trend in prevalence of BRCA testing and sociodemographic and clinical predictors of receiving a BRCA test among newly diagnosed patients with breast cancer. Methods This was a retrospective study conducted using the Optum Clinformatics Datamart database. Patients newly diagnosed with breast cancer, continuously enrolled in a health plan for ≥6 months before and after diagnosis were included in the study. Claims for BRCA testing were identified after diagnosis using HCPCS, ICD-9/10 procedure, and LOINC codes. The prevalence of BRCA testing was calculated for patients diagnosed in each year from 2012-2017. Multivariable logistic regression was used to assess predictors of BRCA testing controlling for sociodemographic and clinical factors. Results From a total of 81,774 breast cancer patients included, 13,529 (16.5%) received a BRCA test after diagnosis. The prevalence of BRCA testing increased from 1,721 (11.5%) in 2012 to 2,384 (17.1%) in 2013 and remained stable over time until 2017 [2,191, (18.5%)]. Of patients receiving a BRCA test, 11,688 (86%) were tested within 1 year of diagnosis. The median time to receive a BRCA test from diagnosis was 29 days (mean: 172.7 days). Results from logistic regression indicated that diagnosis at a younger age (e.g., 18-44 years versus ≥75 years, odds ratio [OR] = 25.3), diagnosis in recent years (e.g., 2017 versus 2012, OR =1.94), having a point of service versus health maintenance organization plan type (OR = 1.10), presence of metastasis (OR = 1.62), and family history of cancer (OR = 4.98) significantly (P&amp;lt;0.05) increased odds for receiving a BRCA test. Female gender (OR = 0.28), living in regions other than West (e.g. South, OR = 0.86), having commercial insurance versus Medicare Advantage (OR = 0.96), Charlson comorbidity index score of ≥3 vs 0 (OR= 0.83) were significantly (P&amp;lt;0.05) associated with lower odds of receiving a BRCA test. Conclusions Prevalence of BRCA testing among breast cancer patients increased initially in 2013 and remained stable over time until 2017. Several demographic and clinical factors were associated with the use of BRCA testing among breast cancer patients. Citation Format: Shelby Corman, Hrishikesh Kale, Pooja Shah, Gboyega Adeboyeje. Trends in BRCA testing among patients diagnosed with breast cancer -a retrospective analysis of a United States commercial claims database from the PRIOR-1 study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-78.
Abstract 20413: Relationship Between Early Cardiac Catheterization following Cardiac Arrest Resuscitation and Acute Kidney Injury
Authors: Eric L Mutter, Anne V Grossestreuer, Michael G Shashaty, Todd Miano, David F Gaieski, Benjamin S Abella
Journal: Circulation (2016)

Background: A survival benefit has been demonstrated when survivors of cardiac arrest receive bundled post-arrest care, including early cardiac catheterization (ECC). Cardiac arrest and ECC have bo...
Ibrutinib and venetoclax target distinct subpopulations of CLL cells: implication for residual disease eradication
Authors: Pin Lu, Shengchun Wang, Carrie A. Franzen, Girish Venkataraman, Rebecca McClure, Lei Li, Wenjun Wu, Nifang Niu, Madina Sukhanova, Jianming Pei, Donald A. Baldwin, Reza Nejati, Mariusz A. Wasik, Nadia Khan, Yifan Tu, Juehua Gao, Yihua Chen, Shuo Ma, Richard A. Larson, Y. Lynn Wang
Journal: Blood Cancer Journal (2021)

Abstract Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2. Both drugs are highly effective as monotherapy against chronic lymphocytic leukemia (CLL), and clinical trials using the combination therapy have produced remarkable results in terms of rate of complete remission and frequency of undetectable minimal residual disease. However, the laboratory rationale behind the success of the drug combination is still lacking. A better understanding of how these two drugs synergize would eventually help develop other rational combination strategies. Using an ex vivo model that promotes CLL proliferation, we show that modeled ibrutinib proliferative responses, but not viability responses, correlate well with patients’ actual clinical responses. Importantly, we demonstrate for the first time that ibrutinib and venetoclax act on distinct CLL subpopulations that have different proliferative capacities. While the dividing subpopulation of CLL responds to ibrutinib, the resting subpopulation preferentially responds to venetoclax. The combination of these targeted therapies effectively reduced both the resting and dividing subpopulations in most cases. Our laboratory findings help explain several clinical observations and contribute to the understanding of tumor dynamics. Additionally, our proliferation model may be used to identify novel drug combinations with the potential of eradicating residual disease.
250P FDG-PET/CT in high-risk primary breast cancer: A prospective study of stage migration and clinical impact
Authors: M. Vogsen, J.D. Jensen, I.Y. Christensen, O. Gerke, A.M.B. Jylling, L.B. Larsen, P-E. Braad, K.L. Søe, C. Bille, M. Ewertz, M.G. Hildebrandt
Journal: Annals of Oncology (2020)
Novel Risk Factors for Epstein-Barr Virus (EBV) Reactivation and Post-Transplant Lymphoproliferative Disorder (PTLD) after Allogeneic Hematopoietic Stem Cell Transplant
Authors: Lizamarie Bachier Rodriguez, Tsiporah B. Shore, Usama Gergis, Jingmei Hsu, Adrienne A. Phillips, Sebastian A. Mayer, Hanna Rennert, Koen Van Besien
Journal: Blood (2017)
Tumor-Derived Pericytes Driven by EGFR Mutations Govern the Vascular and Immune Microenvironment of Gliomas
Authors: Berta Segura-Collar, María Garranzo-Asensio, Beatriz Herranz, Esther Hernández-SanMiguel, Teresa Cejalvo, Bárbara S. Casas, Ander Matheu, Ángel Pérez-Núñez, Juan Manuel Sepúlveda-Sánchez, Aurelio Hernández-Laín, Verónica Palma, Ricardo Gargini, Pilar Sánchez-Gómez
Journal: Cancer Research (2021)

Abstract The extraordinary plasticity of glioma cells allows them to contribute to different cellular compartments in tumor vessels, reinforcing the vascular architecture. It was recently revealed that targeting glioma-derived pericytes, which represent a big percentage of the mural cell population in aggressive tumors, increases the permeability of the vessels and improves the efficiency of chemotherapy. However, the molecular determinants of this transdifferentiation process have not been elucidated. Here we show that mutations in EGFR stimulate the capacity of glioma cells to function as pericytes in a BMX- (bone marrow and X-linked) and SOX9-dependent manner. Subsequent activation of platelet-derived growth factor receptor beta in the vessel walls of EGFR-mutant gliomas stabilized the vasculature and facilitated the recruitment of immune cells. These changes in the tumor microenvironment conferred a growth advantage to the tumors but also rendered them sensitive to pericyte-targeting molecules such as ibrutinib or sunitinib. In the absence of EGFR mutations, high-grade gliomas were enriched in blood vessels, but showed a highly disrupted blood–brain barrier due to the decreased BMX/SOX9 activation and pericyte coverage, which led to poor oxygenation, necrosis, and hypoxia. Overall, these findings identify EGFR mutations as key regulators of the glioma-to-pericyte transdifferentiation, highlighting the intricate relationship between the tumor cells and their vascular and immune milieu. Our results lay the foundations for a vascular-dependent stratification of gliomas and suggest different therapeutic vulnerabilities determined by the genetic status of EGFR. Significance: This study identifies the EGFR-related mechanisms that govern the capacity of glioma cells to transdifferentiate into pericytes, regulating the vascular and immune phenotypes of the tumors.
You Talking to Me? Cadherin and Integrin Crosstalk in Biomaterial Design
Authors: Eva Barcelona‐Estaje, Matthew J. Dalby, Marco Cantini, Manuel Salmeron‐Sanchez
Journal: Advanced Healthcare Materials (2021)

Abstract While much work has been done in the design of biomaterials to control integrin‐mediated adhesion, less emphasis has been put on functionalization of materials with cadherin ligands. Yet, cell–cell contacts in combination with cell–matrix interactions are key in driving embryonic development, collective cell migration, epithelial to mesenchymal transition, and cancer metastatic processes, among others. This review focuses on the incorporation of both cadherin and integrin ligands in biomaterial design, to promote what is called the “adhesive crosstalk.” First, the structure and function of cadherins and their role in eliciting mechanotransductive processes, by themselves or in combination with integrin mechanosensing, are introduced. Then, biomaterials that mimic cell–cell interactions, and recent applications to get insights in fundamental biology and tissue engineering, are critically discussed.
Dendritic cells induce TH2 responses in the airways by interacting with the TH2-selective molecule T1/ST2
Authors: B.n. Lambrecht, A.j. Coyle, J.c. Guttierez-Ramos, Marijke De Veerman, Kris Thielemans, R.a. Pauwels
Journal: American Journal of Respiratory and Critical Care Medicine (1999)
Findings and Resolution of Melanoma Perineural Spread Along the Greater Auricular Nerve on FDG PET/CT and MRI
Authors: Jennifer Nguyen, Thomas W. Barber, Rhoda Cameron, Andrew Haydon, Victoria Mar
Journal: Clinical Nuclear Medicine (2021)

Abstract We report an unusual case of a 59-year-old man with recurrent right ear melanoma resulting in perineural spread to the right greater auricular nerve. Direct perineural spread to the greater auricular nerve is not commonly reported in melanoma. Our case demonstrates perineural spread along the greater auricular nerve on 18 F-FDG PET/CT and MRI. This finding was supported by intraneural invasion noted at the surgical margin of the wide local excision of the right helix melanoma. Resolution of FDG activity and improved MRI appearances of the right greater auricular nerve were seen after immunotherapy treatment.
Intratumoral heterogeneity as a predictive biomarker in anti-PD-(L)1 therapies for non-small cell lung cancer
Authors: Wenfeng Fang, Haoxuan Jin, Huaqiang Zhou, Shaodong Hong, Yuxiang Ma, Yaxiong Zhang, Xiaofan Su, Longyun Chen, Yunpeng Yang, Shengqiang Xu, Yuwei Liao, Yuming He, Hongyun Zhao, Yan Huang, Zhibo Gao, Li Zhang
Journal: Molecular Cancer (2021)
Carfilzomib-induced endothelial dysfunction, recovery of proteasome activity, and prediction of cardiovascular complications: a prospective study
Authors: Efstathios Kastritis, Ageliki Laina, Georgios Georgiopoulos, Maria Gavriatopoulou, Eleni-Dimitra Papanagnou, Evangelos Eleutherakis-Papaiakovou, Despina Fotiou, Nikolaos Kanellias, Ioanna Dialoupi, Nikolaos Makris, Efstathios Manios, Magdalini Migkou, Maria Roussou, Maria Kotsopoulou, Konstantinos Stellos, Evangelos Terpos, Ioannis P. Trougakos, Kimon Stamatelopoulos, Meletios A. Dimopoulos
Journal: Leukemia (2021)
Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study
Authors: Fiona Blackhall, Kevin Jao, Laurent Greillier, Byoung Chul Cho, Konstantin Penkov, Noemi Reguart, Margarita Majem, Kristiaan Nackaerts, Konstantinos Syrigos, Karin Hansen, Wolfgang Schuette, Jeremy Cetnar, Federico Cappuzzo, Isamu Okamoto, Mustafa Erman, Seppo W. Langer, Terufumi Kato, Harry Groen, Zhaowen Sun, Yan Luo, Poonam Tanwani, Laura Caffrey, Philip Komarnitsky, Niels Reinmuth
Journal: Journal of Thoracic Oncology (2021)

IntroductionDLL3, an atypical Notch ligand, is expressed in SCLC tumors but is not detectable in normal adult tissues. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate containing a DLL3-targeting antibody tethered to a cytotoxic agent pyrrolobenzodiazepine by means of a protease-cleavable linker. The efficacy and safety of Rova-T compared with topotecan as second-line therapy in patients with SCLC expressing high levels of DLL3 (DLL3-high) was evaluated.MethodsThe TAHOE study was an open-label, two-to-one randomized, phase 3 study comparing Rova-T with topotecan as second-line therapy in DLL3-high advanced or metastatic SCLC. Rova-T (0.3 mg/kg) was administered intravenously on day 1 of a 42-day cycle for two cycles, with two additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1.5 mg/m2) was administered intravenously on days 1 to 5 of a 21-day cycle. The primary end point was overall survival (OS).ResultsPatients randomized to Rova-T (n = 296) and topotecan (n = 148) were included in the efficacy analyses. The median age was 64 years, and 77% had the extensive disease at initial diagnosis. The median OS (95% confidence interval) was 6.3 months (5.6–7.3) in the Rova-T arm and 8.6 months (7.7–10.1) in the topotecan arm (hazard ratio, 1.46 [95% confidence interval: 1.17–1.82]). An independent data monitoring committee recommended that enrollment be discontinued because of the shorter OS observed with Rova-T compared with topotecan. Safety profiles for both drugs were consistent with previous reports.ConclusionsCompared with topotecan, which is the current standard second-line chemotherapy, Rova-T exhibited an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. A considerable unmet therapeutic need remains in this population.
Mevalonate Pathway Inhibition Slows Breast Cancer Metastasis via Reduced <i>N</i>-glycosylation Abundance and Branching
Authors: Rosemary Yu, Joseph Longo, Jenna E. van Leeuwen, Cunjie Zhang, Emily Branchard, Mohamad Elbaz, David W. Cescon, Richard R. Drake, James W. Dennis, Linda Z. Penn
Journal: Cancer Research (2021)

Abstract Aberrant N-glycan Golgi remodeling and metabolism are associated with epithelial–mesenchymal transition (EMT) and metastasis in patients with breast cancer. Despite this association, the N-glycosylation pathway has not been successfully targeted in cancer. Here, we show that inhibition of the mevalonate pathway with fluvastatin, a clinically approved drug, reduces both N-glycosylation and N-glycan-branching, essential components of the EMT program and tumor metastasis. This indicates novel cross-talk between N-glycosylation at the endoplasmic reticulum (ER) and N-glycan remodeling at the Golgi. Consistent with this cooperative model between the two spatially separated levels of protein N-glycosylation, fluvastatin-induced tumor cell death was enhanced by loss of Golgi-associated N-acetylglucosaminyltransferases MGAT1 or MGAT5. In a mouse model of postsurgical metastatic breast cancer, adjuvant fluvastatin treatment reduced metastatic burden and improved overall survival. Collectively, these data support the immediate repurposing of fluvastatin as an adjuvant therapeutic to combat metastatic recurrence in breast cancer by targeting protein N-glycosylation at both the ER and Golgi. Significance: These findings show that metastatic breast cancer cells depend on the fluvastatin-sensitive mevalonate pathway to support protein N-glycosylation, warranting immediate clinical testing of fluvastatin as an adjuvant therapy for breast cancer.
Діагностична значущість лабораторних досліджень при захворюваннях біліарної системи
Authors: K.V. Paramonovа, O.V. Zakrevska, V.M. Gladun, I.Yu. Skyrda
Journal: GASTROENTEROLOGY (2013)

Вивчено світовий та вітчизняний досвід з питання оцінки ефективності застосування гематологічних досліджень при жовчнокам’яній хворобі (ЖКХ) і визначений необхідний обсяг лабораторних тестів при асимптомній ЖКХ, жовчній кольці та тих ускладненнях ЖКХ, що зустрічаються найчастіше: гострий холецистит, холедохолітіаз, холангіт, біліарний панкреатит.Діагноз встановлюється за допомогою методів візуалізації: ультразвукового дослідження, сцинтиграфії, комп’ютерної, магнітно-резонансної томографії, ретроградної холецистохолангіопанкреатографії та в деяких тяжких випадках — інтраопераційно.Лабораторна діагностика, що є невід’ємною частиною сучасної медицини, не втрачає своєї значущості для ведення пацієнтів із ЖКХ. Гематологічні дослідження використовуються з метою встановлення діагнозу, етіології, стратифікації ризику тяжкого перебігу, виявлення органної недостатності, визначення адекватності терапії. Зміни лабораторних показників дозволяють своєчасно запідозрити розвиток ускладнень та проводити моніторинг стану хворого. Лабораторні тести зазвичай є більш чутливими показниками стану пацієнта, ніж його самопочуття. Сукупність клінічних проявів, лабораторних даних та методів візуалізації покращує результати діагностики ЖКХ.
Abstract PS16-23: Elucidating the role of APC resulting in doxorubicin resistance in breast cancer
Authors: Jeni Prosperi, Casey Stefanski
Journal: Cancer Research (2021)

Abstract Chemoresistance is a leading cause of breast cancer related deaths. Therefore, understanding the molecularbasis for chemoresistance is essential for novel therapeutic advancement improving patient outcome. TheAdenomatous Polyposis Coli (APC) tumor suppressor is lost in up to 70% of sporadic breast cancer; however,little is known about how APC loss contributes to chemoresistance. Using mammary tumor cells isolated fromthe Apc Min/+ mouse crossed to the Polyoma middle T antigen (PyMT) transgenic model, we werethe first to show that APC loss decreased doxorubicin (DOX) induced apoptosis. Therefore, we investigatedthe mechanisms contributing to DOX resistance with APC loss to identify combination therapy options. DOX, acommonly used chemotherapeutic in breast cancer, inhibits topoisomerase IIa (Topo IIa), causing doublestranded breaks (DSBs), the most lethal form of DNA damage, and APC has been shown to affect Topo IIaactivity. DSB repair is mediated through HRR (homologous recombination repair) or NHEJ (nonhomologousend joining), which are regulated by the repair serine/threonine kinases: ataxia telangiectasia mutated (ATM)or ataxia telangiectasia and Rad3 related (ATR), but only NHEJ activates DNA-dependent protein kinase(DNA-PK). We hypothesized that APC loss prevents DOX-mediated apoptosis through alterations in HRR andNHEJ. To investigate the effect of APC loss on DNA damage repair pathways, we monitored damagerecognition pathways after 24-hour DOX treatment. The MMTV-PyMT;Apc Min/+ cells exhibited decreaseddamage as measured by γH2AX expression and comet assay. We also observed decreased ATMphosphorylation in MMTV-PyMT;Apc Min/+ following DOX treatment compared to control. Decreasedphosphorylation of Chk1 and Chk2 was also observed in DOX-treated MMTV-PyMT;Apc Min/+ cells. Using theATM inhibitor (KU55933) or the DNA-PK inhibitor (NU7441), we observed increased DOX-induced apoptosis inMMTV-PyMT;Apc Min/+ cells. These data suggest enhanced DNA repair in MMTV-PyMT;Apc Min/+ cells and will beconfirmed by measuring repair efficiency via reporter plasmids. In addition, knowing that APC affects activitiesby Topo IIa, we measured the amount of Topo IIa: DNA cleavage complexes following DOX treatment.Taken together, APC loss mediates DOX resistance via increasing DNA repair demonstrating the potential useof combination therapy to overcome chemoresistance. Citation Format: Jeni Prosperi, Casey Stefanski. Elucidating the role of APC resulting in doxorubicin resistance in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-23.
Abstract PS19-08: Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction
Authors: Edward Brown, Danielle Desa, Wencheng Wu, Robert Hill, John Martens, Robert Strawderman, Bradley Turner
Journal: Cancer Research (2021)

Abstract Second harmonic generation (SHG) is an intrinsic optical signal that can be generated from fibrillar collagen. The directionality of SHG emission is influenced by the diameter and spacing of collagen fibrils, and the disorder in their packing within collagen fibers. One measure of SHG directionality is the ratio of forward- to backward-scattered SHG, or “F/B”. F/B has been used to assess healthy vs diseased tissue in breast, ovarian, and lung cancer, and is an independent prognostic indicator of metastasis free survival time in ER+, lymph node-negative (N0), invasive ductal carcinoma (IDC). Here we assess the heterogeneity in F/B within tumor sections from ER+ N0 IDC, and its effect on the use of F/B for metastatic risk prediction. We find that F/B of tumor collagen varies between the tumor/host interface and the more cellular tumor bulk (p&amp;lt;0.0001, Student’s t-test), and that F/B from the tumor/host interface, but not tumor bulk, is prognostic of metastasis free survival in 95 IDC ER+ N0 patients (p=0.0020 and 0.10, respectively, log rank test for trend). This result was repeated with two additional image analysis procedures to generate F/B with reduced user input and hence reduced possibility of bias. Using Random Survival Forests to generate a data-driven predictive model, we find that F/B from the tumor/host interface, but not bulk, as well as a 21-gene prognostic score inferred from Affymetrix data, both contribute to predicting metastasis-free survival in this cohort. Any tool to help predict metastasis and assist with treatment decisions is likely to be applied in combination with the now well-established genomic scores. To understand how F/B can support genomic methods for guiding treatment decisions we divided our patient samples into two cohorts based upon the value of their 21-gene score relative to the TAILORx cutoff of 26 (separating low-intermediate and high-risk groups). The F/B value from tumor-host interface identifies a subgroup of patients in the low-intermediate risk group with poor clinical outcome (p=0.045, log rank test for trend). Overall, this data reveals that intratumor heterogeneity can impact the ability of F/B to predict patient outcome, and that F/B specifically from the tumor-host interface may provide a tool to better identify patients in need of adjuvant treatment or enrollment in clinical trials. Citation Format: Edward Brown, Danielle Desa, Wencheng Wu, Robert Hill, John Martens, Robert Strawderman, Bradley Turner. Intratumoral heterogeneity of second-harmonic generation scattering from tumor collagen and its effects on metastatic risk prediction [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-08.