tbuckley/cabot-search huggingface dataset:
Abstract 3243: Associations of polyomavirus seroreactivity with AIDS-related non-Hodgkin's lymphoma
Authors: Minkyo Song, Noemi Bender, James J. Goedert, Cheryl A. Winkler, Nicole Brenner, Tim Waterboer, Charles S. Rabkin
Journal: Cancer Research (2018)

Abstract Background: Human polyomaviruses have a suspected role in carcinogenesis. In the setting of human immunodeficiency virus (HIV) infection, coinfection with MCV polyomavirus is associated with high risk of Merkel cell carcinoma. A role in lymphomagenesis has also been suggested by studies in the general population, but there are no prior studies in individuals with the acquired immunodeficiency syndrome (AIDS). Methods: We measured antibodies against 11 common polyomaviruses in archived serum and plasma samples from two prospective cohort studies of HIV infection. Patients with incident (n=28) and prevalent (n=38) AIDS-related non-Hodgkin lymphoma (NHL) were matched by age, sex, and CD4 count to 67 HIV-positive AIDS-free controls. Seroreactivity was measured by fluorescent bead-based multiplex serology, quantified as median fluorescence intensity (MFI). Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for NHL risk. Multinomial logistic regression compared incident and prevalent NHL cases to lymphoma-free controls and heterogeneity between case groups was evaluated by Wald tests. Differences in MFI were assessed by Kruskal-Wallis tests. Based on log-transformed MFI values for 15 masked duplicate samples, estimated coefficients of variation (CV) were &amp;lt;20% and intraclass correlation coefficients (ICC) were &amp;gt;90% for all antibodies except LPV (CV 29%, ICC 67%). Results: Cases had significantly lower prevalence of antibodies to WU polyomavirus than lymphoma-free controls (64% vs. 85%), with OR 0.28 (95% CI 0.12-0.68). Cases had non-significantly lower prevalence of antibodies to JC, TSV, MCV and KI polyomaviruses (ORs 0.42-0.71); similar prevalence of antibodies to BK, HPyV6 and HPyV7 polyomaviruses (ORs 0.98-1.18); and non-significantly higher prevalence of antibodies to HPyV10, LPV and HPyV9 polyomaviruses (ORs 1.35-1.77). MFIs for anti-WU antibodies were also lower for cases (median 552.6, interquartile range [IQR] 140.3-1298.3) than controls (median 1096.3, IQR 410.3-2044.3; p-value 0.047). The association of anti-WU antibody with NHL was stronger in samples obtained post-diagnosis (OR 0.18, 95% CI 0.07-0.48) than pre-diagnosis (OR 0.66, 95% CI 0.19-2.31; p-heterogeneity=0.037). Conclusion: Our data do not directly implicate known polyomaviruses as lymphomagenic in the setting of HIV-associated immunodeficiency. Nevertheless, impaired antibody response to WU may be a harbinger of AIDS-related lymphoma. Citation Format: Minkyo Song, Noemi Bender, James J. Goedert, Cheryl A. Winkler, Nicole Brenner, Tim Waterboer, Charles S. Rabkin. Associations of polyomavirus seroreactivity with AIDS-related non-Hodgkin's lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3243.
Abstract 14555: Meta-analysis of Bleeding Risk Prediction Scores in Patients on Dual Antiplatelet Therapy After Percutaneous Coronary Intervention
Authors: Stephanie Q Ko, Yu-Chen Cheng, Atsushi Hirayama, Po-Hong Liu, Naoki Yanagisawa, Hsuan Yen, Jordan B Strom, Changyu Shen, Robert W Yeh
Journal: Circulation (2017)

Introduction: Dual antiplatelet therapy (DAPT) prescribed to patients after percutaneous coronary intervention (PCI) involves a careful balance between ischemia and bleeding. Many risk scores have ...
Abstract 4415: Characterization of tumor-derived exosomes in <i>BRCA</i>-associated breast tumors
Authors: Vivian Y. Shin, Man-Ting Siu, Isabella Cheuk, Ava Kwong
Journal: Cancer Research (2018)

Abstract Background: BRCA-mutated tumors are usually with higher grade than sporadic tumors and the biology is poorly understood. Exosomes are small membrane-derived vesicles that function to mediate cell-cell communication via the transfer of tumor-promoting microRNAs (miRNAs), RNAs and proteins. Interestingly, different spectrum of miRNAs is released by cancer cells to promote tumor growth and metastasis in breast cancer. However, the selectivity of miRNA released from tumor-derived exosomes and its relevance in cancer treatment has not been widely studied. Hence, this study is sought to characterize the role of exosomal-miRNA (exo-miR) for the development of BRCA-associated tumors. Methods: Plasma samples from patients with BRCA-positive and non-BRCA carriers were recruited and selected from the Hong Kong Hereditary Breast Cancer Family Registry. By using miRCURY LNA array, the exosomal-miRNA expressions in plasma of patient with BRCA-positive (n=4) and non-carriers (n=4), as well as healthy controls (n=4) were profiled. Selected miRNAs were further validated in pre- and post-operative plasma and paired primary tissues (n=40) using real-time RT-PCR. Functional study of miRNA was also carried out in the cell lines. Results: LNA array data showed that differential expressed BRCA-associated exo-miRNAs were identified. Upregulated miRs (miR-106a, miR-20a, miR-23a, miR-451 and miR-486) were validated in BRCA-positive, BRCA-negative and healthy controls by real-time RT-PCR. In addition, the expression levels of miR-106a, miR-451 and miR-486 were significantly lower in post-operative plasma of BRCA-carriers than non-carriers. Importantly, the expression of miR-451 was reduced after tumor resection in BRCA mutation carriers. In parallel, high expression of exo-miR-106a, miR-20a, miR-23a, miR-451 and miR-486 were also seen in breast cancer cell lines (MB-231 and MB-468) relative to normal breast cells (MCF-10A). We found that cells transfected with miR-451 inhibitor significantly reduce cell proliferation. Conclusions: These preliminary results reveal differential exo-miRNA profiles between BRCA carriers and non-carriers with breast cancer, and identify potential targets of dysregulated miRNAs which is crucial in disease progression of BRCA-associated breast cancers. Citation Format: Vivian Y. Shin, Man-Ting Siu, Isabella Cheuk, Ava Kwong. Characterization of tumor-derived exosomes in BRCA-associated breast tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4415.
Blood Lipids and First-Ever Ischemic Stroke/Transient Ischemic Attack in the Bezafibrate Infarction Prevention (BIP) Registry
Authors: DavidTanne, NiraKoren-Morag, EranGraff, UriGoldbourt
Journal: Circulation (2001)

Background— Despite unclear associations between blood lipids, including fractionated cholesterol and triglycerides, and stroke, recent evidence demonstrates that lipid-modifying agents decrease the risk of stroke in patients with coronary heart disease (CHD). Methods and Results— Patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study and had no history of stroke or transient ischemic attack (TIA) (n=11 177) were followed up. At baseline, medical histories were obtained and blood lipids assessed at a central study laboratory. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic cerebrovascular disease, of whom 487 had verified ischemic stroke (per clinical findings and brain CT) or TIA. Patients experiencing an ischemic stroke/TIA had higher mean levels of triglycerides, lower levels of HDL cholesterol, and lower percentages of cholesterol contained in the HDL cholesterol moiety (%HDL; P<0.01 for all). In ...
Augmentation of Postnatal Neovascularization With Autologous Bone Marrow Transplantation
Authors: SatoshiShintani, ToyoakiMurohara, HisaoIkeda, TakafumiUeno, Ken-ichiroSasaki, JunliDuan, TsutomuImaizumi
Journal: Circulation (2001)

Background—Endothelial progenitor cells (EPCs) have been identified in adult human peripheral blood. Because circulating EPCs should originate from bone marrow (BM), we examined whether BM mononuclear cells (BM-MNCs) can give rise to functional EPCs and whether transplantation of autologous BM-MNCs might augment angiogenesis and collateral vessel formation in a rabbit model of hindlimb ischemia. Methods and Results—Rabbit BM-MNCs were isolated by centrifugation through a Histopaque density gradient and cultured on fibronectin. EPCs developed from BM-MNCs in vitro, as assessed by acetylated LDL incorporation, nitric oxide (NO) release, and expression of von Willebrand factor and lectin binding. Unilateral hindlimb ischemia was surgically induced in rabbits (n=8), and fluorescence-labeled autologous BM-MNCs were transplanted into the ischemic tissues. Two weeks after transplantation, fluorescence microscopy revealed that transplanted cells were incorporated into the capillary network among preserved skeleta...
Abstract 14046: Heparin Alone is Not Enough. Gp IIb/IIIa Inhibitors Improve Outcome in Patients With Primary PCI for STEMI Treated With Heparin. Results of the Prospective ALKK-Registry
Authors: UweZeymer, MatthiasHochadel, AnselmGitt, DietrichAndresen, RalfZahn
Journal: Circulation (2014)

Background: There is still debate about the optimal antithrombotic therapy in patients undergoing primary PCI. Earlier randomized trials have shown a benefit of GP IIb/IIIa inhibitors in patients treated with heparin, with the highest benefit in high risk patients. Most recent trials did not support the earlier data. Therefore we evaluated the impact of GP IIb/IIIa inhibitors on outcome in patients with primary PCI for STEMI in real life in a large number of patients. Methods: We used the data of the ongoing prospective ALKK-PCI registry and included patients with PCI for STEMI < 24 h duration treated with heparin in 40 centres. We excluded patients who were treated with bivalirudin. Results: Between 2008 and 2012 a total of 15061 consecutive patients with PCI for STEMI without cardiogenic shock were included. Of these 8864 (58.9 %) received a GP IIb/IIIa inhibitor. Baseline characteristics, procedural features and in-hospital outcomes are given in the table. In a multivariate analysis GP IIb/IIIa inhibit...
Abstract 20082: Feasibility of His Bundle Pacing in Patients Meeting Criteria for Cardiac Resynchronization Therapy and Implantable Cardioverter-defibrillator
Authors: Olujimi A Ajijola, Carlos Macias, Vinisha Garg, Gabriel Vorobiof, Alison H Mally, Kalyanam Shivkumar, Roderick Tung
Journal: Circulation (2015)

Objective: The role of His bundle pacing to physiologically narrow QRS duration in patients meeting criteria for CRT/CRT-D is not well understood. Methods: Patients with CRT/CRT-D indication with failed CS lead placement, suboptimal coronary venous targets, or those who opted for His bundle pacing underwent implantation of a His bundle lead, along with an RV defibrillator lead if indicated. In all patients, the His bundle pacing lead was placed into the LV lead port with CRT pulse generator. The LV-RV offset was programmed at maximum, with RV lead subthreshold to minimize fusion. An atrial lead was implanted if the patient was not in permanent atrial fibrillation. Results: Thirteen patients (65±18 years, 7 males, mean LVEF 27.3±8.9%, QRS duration 180±30ms, and 11 with LBBB) underwent His bundle pacing. The mean PR interval in this cohort was 220±111ms, 3 patients had complete heart block, 3 had permanent atrial fibrillation, and 9 required ICD placement. The His pacing lead (Medtronic 3830 Select Secure) was successfully placed in 12 of 13 patients, with narrowing of the QRS duration to 120±23ms (p&lt;0.0001). No complications or lead dislodgements were seen. At 6-month follow up, LVEF increased by an average of 18.7%, and left ventricular internal dimension in diastole(LVIDd) decreased by 0.9cm. Echocardiographic global longitudinal strain improved from -9.1 to -10.5%. Conclusions: In patients meeting criteria for CRT/CRT-D implantation, QRS narrowing achieved by His bundle pacing is feasible, and is associated with favorable mechanical and clinical outcomes.
Heart Valve Tissue Engineering
Authors: IvanVesely
Journal: Circulation Research (2005)

Tissue-engineered heart valves have been proposed by physicians and scientists alike to be the ultimate solution for treating valvular heart disease. Rather than replacing a diseased or defective native valve with a mechanical or animal tissue–derived artificial valve, a tissue-engineered valve would be a living organ, able to respond to growth and physiological forces in the same way that the native aortic valve does. Two main approaches have been attempted over the past 10 to 15 years: regeneration and repopulation. Regeneration involves the implantation of a resorbable matrix that is expected to remodel in vivo and yield a functional valve composed of the cells and connective tissue proteins of the patient. Repopulation involves implanting a whole porcine aortic valve that has been previously cleaned of all pig cells, leaving an intact, mechanically sound connective tissue matrix. The cells of the patients are expected to repopulate and revitalize the acellular matrix, creating living tissue that alrea...
Ductular Reaction in Liver Diseases: Pathological Mechanisms and Translational Significances
Authors: Keisaku Sato, Marco Marzioni, Fanyin Meng, Heather Francis, Shannon Glaser, Gianfranco Alpini
Journal: Hepatology (2018)

Ductular reaction (DR) is characterized by the proliferation of reactive bile ducts induced by liver injuries. DR is pathologically recognized as bile duct hyperplasia and is commonly observed in biliary disorders. It can also be identified in various liver disorders including nonalcoholic fatty liver disease. DR is associated with liver fibrosis and damage, and the extent of DR parallels to patient mortality. DR raises scientific interests because it is associated with transdifferentiation of liver cells and may play an important role in hepatic regeneration. The origin of active cells during DR can be cholangiocytes, hepatocytes, or hepatic progenitor cells, and associated signaling pathways could differ depending on the specific liver injury or animal models used in the study. Although further studies are needed to elucidate detailed mechanisms and the functional roles in liver diseases, DR can be a therapeutic target to inhibit liver fibrosis and to promote liver regeneration. This review summarizes previous studies of DR identified in patients and animal models as well as currently understood mechanisms of DR.
Outcomes From a Minority-Based Lung Cancer Screening Program vs the National Lung Screening Trial
Authors: Mary M. Pasquinelli, Kevin L. Kovitz, Matthew Koshy, Martha G. Menchaca, Li Liu, Robert Winn, Lawrence E. Feldman
Journal: JAMA Oncology (2018)

This population-based study assesses demographic characteristics, CT scan findings, and lung cancer detection in minority populations compared with outcomes from the National Lung Screening Trial.
Proposed response assessment and endpoints for meningioma clinical trials: report from the Response Assessment in Neuro-Oncology Working Group
Authors: Raymond Y Huang, Wenya Linda Bi, Michael Weller, Thomas Kaley, Jaishri Blakeley, Ian Dunn, Evanthia Galanis, Matthias Preusser, Michael McDermott, Leland Rogers, Jeffrey Raizer, David Schiff, Riccardo Soffietti, Jörg-Christian Tonn, Michael Vogelbaum, Damien Weber, David A Reardon, Patrick Y Wen
Journal: Neuro-Oncology (2018)

No standard criteria exist for assessing response and progression in clinical trials involving patients with meningioma, and there is no consensus on the optimal endpoints for trials currently under way. As a result, there is substantial variation in the design and response criteria of meningioma trials, making comparison between trials difficult. In addition, future trials should be designed with accepted standardized endpoints. The Response Assessment in Neuro-Oncology Meningioma Working Group is an international effort to develop standardized radiologic criteria for treatment response for meningioma clinical trials. In this proposal, we present the recommendations for response criteria and endpoints for clinical trials involving patients with meningiomas.
Abstract 3878: Drug-loaded microparticles as a treatment approach for pancreatic cancer
Authors: Maria Munoz-Sagastibelza, Oluwafeyikemi Okome, Jenny E. Paredes Sanchez, Albert Palileo, Catherine Burkhart, Laura Martello-Rooney
Journal: Cancer Research (2018)

Abstract Pancreatic cancer is the fourth leading cause of cancer death in the United States with only 7% of diagnosed patients surviving 5 years. Most pancreatic cancer patients are not surgical candidates due to advanced stage at diagnosis. Also, current systemic chemotherapies have not been very effective at decreasing tumor burden. Poly(lactic-co-glycolic acid)-based (PLGA) microparticles (MPs) are a promising tool for localized drug delivery within the tumor due to their biocompatibility, flexibility in drug encapsulation and extended drug release. The present study investigated whether gemcitabine-loaded microparticles (GMPs), paclitaxel-loaded microparticles (PMPs) or sequential treatment of both, in comparison with blank (no drug) MPs, systemic treatments and no treatment control, are able to promote cancer cell killing effects and modulate drug resistance in vitro and in vivo. We previously showed in vitro studies with PANC-1 cells and we were able to complete the MPs studies with a second human pancreatic cancer cell line, MIAPaCa-2. In both cases, we tested the effect of single and combination treatments on two well-known resistance markers for gemcitabine, ribonucleotide reductase catalytic subunit M1 and cytidine deaminase, as well as on the promotion of cell death measuring cleaved caspase-3 (CC3). When treated with GMPs alone, both markers went up suggesting an increase in resistance against gemcitabine. Interestingly, both cell lines treated with PMPs alone showed an increase in CC3 expression and a significant decrease in the expression of both markers. Subsequently, we tested the in vivo efficacy of MPs by direct injection into established subcutaneous MIAPaCa-2 tumors in nude mice. Following four weeks of treatment, the tumors were excised, biopsied for protein analysis and frozen in OCT to allow visualization of fluorescent MPs and detect apoptosis by immunofluorescence. We also want to evaluate reactive oxygen species production; where we expect to see an increase in the MPs treated groups. This analysis is in progress. In conclusion, we observed a decrease in cell viability and drug resistance proteins in vitro using the drug-loaded microparticles in two grade 3 (or high grade) pancreatic cancer cell lines. The described drug delivery method has the potential to be a more efficient treatment modality than systemic gemcitabine and paclitaxel against early stage and locally advanced pancreatic cancer. Citation Format: Maria Munoz-Sagastibelza, Oluwafeyikemi Okome, Jenny E. Paredes Sanchez, Albert Palileo, Catherine Burkhart, Laura Martello-Rooney. Drug-loaded microparticles as a treatment approach for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3878.
Abstract 2181: Functionalizing intratumoral signaling heterogeneity in triple negative breast cancer
Authors: Amanda L. Rinkenbaugh, Vidya C. Sinha, Xiaomei Zhang, Helen Piwnica-Worms
Journal: Cancer Research (2018)

Tumors are highly heterogeneous populations of cells, and measures of intratumoral heterogeneity (ITH) and diversity correlate with worse prognosis in many cancers, including breast cancer. Emerging studies are highlighting functional interactions between subclones, as well as among subclones and components of the tumor microenvironment. However, these studies have largely focused on soluble factors without interrogating the spatial distribution of subclones defined by activated signaling pathways. Previous work in this area has been severely limited by technical restrictions – existing techniques allowing measurement of many biomarkers simultaneously lose all information about the tissue architecture, while those that do retain spatial information can only assay a handful of markers at once. We will circumvent these limitations by undertaking imaging mass cytometry (IMC), which allows for simultaneous measurement of 30-40 antigens while retaining the spatial organization of the sample. Our objective is to dissect the signaling heterogeneity in tumors from patients and patient-derived xenograft (PDX) models of triple negative breast cancer (TNBC), through two main approaches: (1) characterization of signaling heterogeneity in human tumors and PDX models of TNBC through the use of imaging mass cytometry (IMC) and (2) modeling cell signaling heterogeneity in cell line-based models to determine mechanisms of cell-cell interaction and communication. We have constructed an IMC panel of antibodies that combines markers for tissue architecture, cell phenotyping, and signaling pathway activation. Profiling of a panel of TNBC PDX models, including matched sets of pre- and post-chemotherapy treatment, indicates emerging patterns of pathway activation. We will utilize these results to inform functional studies in our isogenic cell line models. As it is becoming more clear that tumors are composed of heterogeneous subclones, it is crucial that we understand the communication between subclones and with components of the microenvironment. Ultimately, we plan to use these results to identify novel vulnerabilities in subclonal interactions that can be targeted therapeutically in TNBC.Citation Format: Amanda L. Rinkenbaugh, Vidya C. Sinha, Xiaomei Zhang, Helen Piwnica-Worms. Functionalizing intratumoral signaling heterogeneity in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2181.
Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancreatic malignancy
Authors: Erhao Zhang, Peiwei Yang, Jieyi Gu, Heming Wu, Xiaowei Chi, Chen Liu, Ying Wang, Jianpeng Xue, Weiyan Qi, Qingbo Sun, Shengnan Zhang, Jialiang Hu, Hanmei Xu
Journal: Journal of Hematology & Oncology (2018)