tbuckley/cabot-search huggingface dataset:
LONG-TERM OUTCOME OF THE UNRESTRICTED USE OF EVEROLIMUS-ELUTING STENTS COMPARED TO SIROLIMUS-ELUTING STENTS AND PACLITAXEL-ELUTING STENTS IN DIABETIC PATIENTS: THE BERN-ROTTERDAM DIABETES COHORT STUDY
Authors: Cihan Simsek, Lorenz Raber, Michael Magro, Eric Boersma, Yoshinobu Onuma, Giulio Stefanini, Bindu Kalesan, Peter Wenaweser, Robert Van Geuns, Peter Juni, Ron Van Domburg, Stephan Windecker, Patrick Serruys
Journal: Journal of the American College of Cardiology (2012)
Abstract 5637: Combination of oncolytic vaccinia virus and immune checkpoint blockade overcomes resistance to immunotherapy in renal cell carcinoma
Authors: Hongjae Chon, Chan Kim
Journal: Cancer Research (2018)

Abstract Renal cell carcinoma (RCC) is a hypervascular tumor with variable immunogenic responses, and VEGF-targeted anti-angiogenic agent has become a standard treatment during the past decade. Recently, immune checkpoint inhibitor (ICI) has merged as another standard of care in RCC, but response is limited as a monotherapy. To determine the optimal combination strategy for immunotherapy in RCC, we employed JX594 (Pexa-Vec), an oncolytic vaccinia virus currently in phase 3 clinical trial, as a combination partner for ICI in RCC. Intratumoral injection of JX594 remodeled the tumor microenvironment of Renca tumor model through dynamic changes in immune system, leading to the conversion of an immunuosuppressive, non-inflamed tumor into an inflamed tumor. The JX594 virotherapy increased the intratumoral infiltration of CD8+ T cell by 16-fold, resulting in systemic and tumor-specific anti-cancer immune response against RCC. Moreover, the expression of immune checkpoint molecules such as PD-1 (4.0-fold), CTLA-4 (2.3-fold), and LAG-3 (3.1-fold) were increased. Depletion experiment showed that the therapeutic effect of JX594 is largely dependent on the cooperation of CD8+ and CD4+ T cells. In addition, GM-CSF has been shown to potentiate the immunotherapeutic efficacy of JX594. Combination of JX594 and ICI targeting PD-1 or CTLA-4 further increased the intratumoral infiltration of activated CD8+ T cells and effectively suppressed the growth of RCC. Furthermore, the optimal schedule was rationalized by combination treatment of various administration methods. Finally, based on these combination results, triple combination of JX594, anti-PD-1, and anti-CTLA-4 maximized the anti-cancer immune responses and induced durable responses with improved overall survival. Collectively, we demonstrate that intratumoral injection of JX594 sensitizes non-inflamed RCC to ICI treatment through CD8+ T cell infiltration in tumor and induces anti-cancer immune responses that can overcome immunotherapy resistance. Citation Format: Hongjae Chon, Chan Kim. Combination of oncolytic vaccinia virus and immune checkpoint blockade overcomes resistance to immunotherapy in renal cell carcinoma [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 5637.
Abstract 5188: MDM2 and MDMX promote p53-independent initiation of circulating tumor cells from triple negative breast cancers
Authors: Chong Gao, Gu Xiao, Ale Piersiga, Jiangtao Gou, Olorunseun Ogunwobi, Jill Bargonetti
Journal: Cancer Research (2018)

Abstract Many human breast cancers overexpress the E3 ubiquitin ligase MDM2 and its homolog MDMX. The Cancer Genome Atlas (TCGA) shows that high MDM2 and MDMX expression correlates with both estrogen receptor positive (ER+) and triple negative breast cancer (TNBC) subtypes. Overexpression of MDM2 and MDMX can drive breast cancer progression through molecular pathways that do not require wild-type p53 degradation. ER positive breast cancers often express wild-type p53 but 80% of TNBC express mutant p53 (mtp53). It has not been determined how MDM2 and MDMX expression in different sub-types of breast cancer, with mutant p53, influence proliferation and metastasis. We compared MDM2 and MDMX-dependent biological outcomes for mtp53 expressing ER+ T47D (mtp53 L194F) and TNBC cell type MDA-MB-231 (mtp53 R280K). In the ER+ cells no change was detected for real time cell migration or E-cadherin protein levels when MDM2 was knocked down by stable shRNA expression but cell proliferation was reduced. In support of this in vitro data, these MDM2 knockdown cells tested in an orthotopic xenograft model in NSG mice demonstrated no MDM2-mediated change in primary tumor invasiveness but did show a reduced tumor volume. Importantly, in the TNBC MDA-MB-231 cells, knocking down either MDM2 or MDMX did not reduce cell proliferation in vitro but greatly blocked cell migration. In support of this in vitro data, these MDA-MB-231 cells with either MDM2 or MDMX knockdown in NSG mice did not show a reduced primary tumor volume but showed a significant inhibition of the production of circulating tumor cells (CTCs). Our data shows that in different subtypes of breast cancers, MDM2 and MDMX can promote alternative p53-independent biological outcomes. The estrogen-activated MDM2 strongly promotes cell proliferation while MDM2 and MDMX overexpression in TNBC promotes circulating tumor cells and potentially metastasis. Understanding the alternative p53-independent roles of MDM2 and MDMX in ER+ and triple negative breast cancers will provide insight for the development of MDMs-targeted theranostics. Citation Format: Chong Gao, Gu Xiao, Ale Piersiga, Jiangtao Gou, Olorunseun Ogunwobi, Jill Bargonetti. MDM2 and MDMX promote p53-independent initiation of circulating tumor cells from triple negative breast cancers [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 5188.
The extent of pseudoxanthoma elasticum skin changes is related to cardiovascular complications and visual loss: a cross‐sectional study
Authors: N. Navasiolava, M. Gnanou, M. Douillard, P. Saulnier, T. Aranyi, J.‐M. Ebran, S. Henni, H. Humeau, G. Lefthériotis, L. Martin
Journal: British Journal of Dermatology (2018)
Unplanned Inpatient and Observation Rehospitalizations After Acute Myocardial Infarction
Authors: Connie N. Hess, Tracy Y. Wang, Lisa A. McCoy, John C. Messenger, Mark B. Effron, Marjorie E. Zettler, Timothy D. Henry, Eric D. Peterson, Gregg C. Fonarow
Journal: Circulation (2016)

Previous studies examining early readmission after acute myocardial infarction have focused exclusively on inpatient readmissions. However, from a patient's perspective, any unplanned inpatient or observation rehospitalization after acute myocardial infarction represents a significant event; these unplanned rehospitalizations have not been well characterized.We examined all patients with acute myocardial infarction treated with percutaneous coronary intervention and discharged alive from 233 hospitals in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Our primary outcome was unplanned rehospitalizations (inpatient or observation status) within 30 days after discharge. We identified factors associated with unplanned rehospitalizations using multivariable logistic regression. Among 12 312 patients, 1326 (10.8%) had 1483 unplanned rehospitalizations within 30 days of the index event: 1028 (69.3%) were inpatient readmissions, and 455 (30.7%) were observation stays. The majority of unplanned rehospitalizations (72%) were for cardiovascular reasons. Variation in hospital rates of 30-day unplanned rehospitalization ranged from 5.4% to 20.0%, with a median of 10.7%. After multivariable modeling, the factors most strongly associated with unplanned rehospitalization were baseline quality of life and depression, followed by index hospital length of stay.Early unplanned rehospitalizations are common after acute myocardial infarction, and close to one third were classified as an observation stay. Predischarge and postdischarge assessments of overall, not just cardiovascular, health and strategies to optimize patient functional status may help to reduce unplanned rehospitalizations.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01088503.
Monitoring asparaginase activity in middle-income countries
Authors: Daiane Keller Cecconello, Isabel Cristina Ribas Werlang, Ana Paula Alegretti, Monique Cabral Hahn, Mariana Rodrigues de Magalhães, Ana Paula Battistel, Priscila Pini Zenatti, Jose Andres Yunes, Caroline Cabreira-Cagliari, Ciliana Rechenmacher, Marcelo Zubaran Goldani, Liane Esteves Daudt, Mariana Bohns Michalowski
Journal: The Lancet Oncology (2018)
Heavier but Healthier — Diabetes and Smoking Cessation
Authors: Steven A. Schroeder
Journal: New England Journal of Medicine (2018)

Two opposing trends provide a point and counterpoint for the health of the public. The good news is that the prevalence of smoking among adults in the United States has dropped to a provisional modern low of 13.9% (although this figure means that there are still 37 million smokers), reflecting a powerful combination of public health and clinical interventions.1 But we are also in the midst of a global obesity epidemic that shows no signs of abating; indeed, 40% of adult Americans are now classified as either obese or overweight.2 A direct result of the obesity epidemic is a surge . . .
Comparative Effects of Castration and Antiandrogen Treatment on the Aortas of Hypertensive and Normotensive Male Rats
Authors: Harveywolinsky
Journal: Circulation Research (1973)

Lowering androgen levels by gonadectomy or inhibiting circulating androgen by administration of the antiandrogen, BOMT, did not affect morphological or compositional changes induced by hypertension in the thoracic aorta of male rats. However, treatment with cyproterone acetate, another antiandrogenic drug, did result in the maintenance of total elastin and collagen at levels the same as those for the normotensive group and significantly lower than those for other treated and untreated hypertensive groups. In rapidly growing normotensive rats, neither castration nor administration of an antiandrogenic drug had any detectable effect on aortic wall morphology or composition regardless of whether the latter was expressed in absolute or relative terms. These findings suggest that growth and hypertension result in the accumulation of connective tissue proteins, elastin, and collagen in the blood vessel wall by different, independent mechanisms.
Abstract 3399: Comparative genomic analyses of osteosarcoma etiology reveal a chromosomal structural rationale for the increased incidence of osteosarcoma in dogs
Authors: Aaron L. Sarver, Lauren Mills, Nuri Temiz, MIlcah Scott, Anne Sarver, Logan Spector, Jinhua Wang, Mathew Breen, Subbaya Subramanian, Branden Moriarity, Jaime Modiano, David Largaespada
Journal: Cancer Research (2018)

Abstract Risk of osteosarcoma is significantly higher in large and giant breed dogs than in any other animal, including humans. To identify the reason for this observation, we used a comparative genomic approach to identify aberrations responsible for osteosarcoma etiology in a Sleeping Beauty transposon-accelerated mouse model, in human patients, and in naturally occurring canine tumors, using RNA-Seq and exome paired tumor normal analyses. Fusions identified in Sleeping Beauty-mutagenized tumors revealed a role for Cdkn2a disruption in Trp53 signaling, and for numerous genes which cooperate with disrupted TrpP53 signaling, indicating the existence of many diverse routes to osteosarcoma tumor formation. Similarly, human tumors showed TP53 pathway disruption associated with a high level of diversity of additional driver mechanisms, supporting multiple independent routes to tumor formation. However, in the majority of canine tumors, observed TP53 pathway aberrations co-occurred with loss of both copies of the region containing the PTEN tumor suppressor. In human osteosarcoma, only heterozygous PTEN loss was observed, and in both humans and mice, PTEN aberration was observed in a much smaller percentage of the tumor population. We hypothesize that increased osteosarcoma incidence in dogs is partly due to a syntenic rearrangement of the peri-PTEN locus in the canine genome. The PTEN gene is part of a small synteny block that localized in the distal end of canine chromosome 26 (CFA 26) during evolution. We hypothesize that this location change creates a high risk of loss in the context of cytogenetic instability caused by disruption of TP53, thereby providing a structural genetic rational for the higher incidence of osteosarcoma in dogs. Consistent with these results and with the powerful nature of PTEN as a tumor suppressor, canine osteosarcomas with homozygous loss of PTEN are associated with worse outcomes than canine osteosarcomas with intact PTEN. These results suggest that engineering genomes to minimize cancer risk may be a realistic approach to the prevention of cancer. Citation Format: Aaron L. Sarver, Lauren Mills, Nuri Temiz, MIlcah Scott, Anne Sarver, Logan Spector, Jinhua Wang, Mathew Breen, Subbaya Subramanian, Branden Moriarity, Jaime Modiano, David Largaespada. Comparative genomic analyses of osteosarcoma etiology reveal a chromosomal structural rationale for the increased incidence of osteosarcoma in dogs [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 3399.
Abstract PR04: Tumor-derived indoleamine 2,3-dioxygenase regulates density of tumor-infiltrating CD8+ T cells and myeloid-derived suppressor cells in a murine model of ovarian cancer
Authors: Adaobi E. Amobi, Takemasa Tsuji, Robert McGray, Kunle Odunsi
Journal: Clinical Cancer Research (2018)

Abstract The catabolism of the essential amino-acid tryptophan by indoleamine 2,3-dioxygenase (IDO1) is a central pathway that contributes to an immunosuppressive microenvironment in many types of cancer. Our lab has previously shown that IDO1 expression in human ovarian tumor correlates with poor prognosis and poor tumor infiltration by CD8+ T cells, and that improved survival is associated with increased tumor-infiltrating lymphocytes. Thus, IDO1 inhibition represents an attractive target for cancer immunotherapy. To establish the mechanism by which IDO1 inhibition augments immune responses in a murine model of metastatic ovarian cancer, we generated a stable IDO1-overexpressing cell line (IE9mp1-mIDO1) and confirmed functional IDO1 enzyme activity. C57BL/6 mice were challenged intraperitoneally with IE9mp1-mIDO1 or IE9mp1-Empty Vector as a control. IE9mp1-mIDO1 tumor-bearing mice displayed earlier onset of tumor burden and decreased overall survival. To delineate the role of host- and tumor-derived IDO1 on immune cell infiltration in the tumor, IDO1 genetic knockout and C57BL/6 mice were challenged with IE9mp1-EV or -mIDO1 tumor cells. All mice challenged with IE9mp1-mIDO1 demonstrate decreased CD8+ T cells in the tumor compared to IDO1KO mice challenged with IE9mp1-EV tumor cells. Moreover, tumor-derived IDO1 mediates increased CD11b+Gr1+ myeloid derived suppressor cells (MDSC) in tumor ascites. From these data, we conclude that abrogation of IDO1 enzyme function will promote antitumor immune responses by permitting increased effector T cells decrease MDSCs in the tumor microenvironment. Ongoing experiments will characterize the mechanism by which IDO1 inhibition may augment vaccine-induced immune responses in ovarian cancer. This abstract is also being presented as Poster A19. Citation Format: Adaobi E. Amobi, Takemasa Tsuji, Robert McGray, Kunle Odunsi. Tumor-derived indoleamine 2,3-dioxygenase regulates density of tumor-infiltrating CD8+ T cells and myeloid-derived suppressor cells in a murine model of ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr PR04.
Abstract LB-356: Maintenance of breast cancer stem-like cells by cancer associated fibroblast-derived soluble factors
Authors: Takahiko Murayama, Tatsunori Nishimura, Arinobu Tojo, Noriko Gotoh
Journal: Cancer Research (2018)

Abstract Accumulating evidence indicates the presence of cancer stem cells (CSCs) or tumor initiating cells in many types of tumors, which would be the leading cause of poor prognosis of tumor patients. They are defined as cell populations which have self-renewal ability and multi-differentiation capacity, and have been thought to greatly contribute to tumor initiation, recurrence and metastasis. CSCs are also known to be highly resistant to conventional therapies. Therefore, developing CSC targeting therapy is in urgent need to eradicate cancer cells efficiently. Stem cell properties of CSCs are thought to be maintained by the interaction with the tumor microenvironment, suggesting that it is important to identify factors which mediate such an interaction between cancer cells and the microenvironment. In this study, we focused on cancer-associated fibroblasts (CAFs) that forms the great part of breast tumor microenvironment and investigated how CAFs influence the functions of CSCs. By sphere forming assay, we found that some soluble factors secreted by CAFs induced growth of CSC-like populations. Then, to identify which factors are upregulated when fibroblasts get CAF-like properties, we compared transcriptomes of fibroblasts which were cultured with or without clinical sample-derived breast cancer cells by RNA-seq analysis. We found two genes in the same gene family were highly upregulated in co-cultured cells and they could induce sphere forming ability of CSCs. We are advancing our research based on a hypothesis that these two factors contribute to maintenance of stem cell functions of CSCs. Here, we will introduce results obtained by recent experiments. Citation Format: Takahiko Murayama, Tatsunori Nishimura, Arinobu Tojo, Noriko Gotoh. Maintenance of breast cancer stem-like cells by cancer associated fibroblast-derived soluble factors [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 LB-356.
Abstract 1311: Integrating network biology and polypharmacology to reveal TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer metastasis
Authors: Neng Wang, Zhiyu Wang, Yifeng Zheng, Shengqi Wang, Fengxue Zhang, Yi Lin
Journal: Cancer Research (2018)

Abstract Purpose: Network pharmacology has become a powerful means of understanding the mechanisms underlying the action of Chinese herbs in cancer treatment. This study aims to validate the preventive effects and molecular mechanisms of a clinical prescription XIAOPI formula against breast cancer. Experimental Design: The anti-metastasis ability of XIAOPI was validated by MMTV-PyMT mice and in vitro cell models. A network pharmacology-based method, which combined large-scale text-mining, drug-likeness filtering, target prediction and network analysis, was conducted to predict TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer metastasis, further supported by cytokine array analysis in vitro and in vivo. Results: In vivo breast cancer xenograft data showed that XIAOPI delayed breast cancer development and efficiently inhibited lung metastasis, accompanied by prolonged survival benefits and decreased cancer stem cell subpopulations. However, similar phenomenon were not observed in a cell model. The herb-ingredient-target network analysis further identified a total of 81 genes closely correlated with the breast cancer chemoprevention effects of XIAOPI. Cytokine array analysis further validated CXCL-1 as the key target of XIAOPI both in vitro and in vivo. Evaluation of the mechanism demonstrated that CXCL-1 administration significantly abrogated the metastatic inhibition effects of XIAOPI on breast cancer migration, invasion, stem cells subpopulations, epithelial-mesenchymal transition(EMT), or mammosphere formation abilities. Conclusions: Overall, our study not only provides experimental evidence and molecular mechanisms that may facilitate the safe and effective use of herbal medicine for the prevention of breast cancer growth or metastasis, and may lead to CXCL-1-based therapeutic strategies for mammary malignancies. Citation Format: Neng Wang, Zhiyu Wang, Yifeng Zheng, Shengqi Wang, Fengxue Zhang, Yi Lin. Integrating network biology and polypharmacology to reveal TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer metastasis [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 1311.
Screening for Atrial Fibrillation Comes With Many Snags
Authors: John Mandrola, Andrew Foy, Gerald Naccarelli
Journal: JAMA Internal Medicine (2018)

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