tbuckley/cabot-search huggingface dataset:
Abstract 4434: Contribution of heterogenous ribonucleoprotein A18 in prostate cancer progression
Authors: Elizabeth Tsuying Chang, Eun Yong Choi, Palak R. Parekh, France Carrier
Journal: Cancer Research (2018)

Abstract Prostate cancer is the third leading cause of cancer deaths among men in the United States, with recurrent metastasis being the predominant cause of mortality. In spite of the significant progress made in the past half century with hormonal therapy for metastatic prostate cancer, a majority eventually progresses to a lethal stage of the disease commonly known as castration-resistant prostate cancer. New treatment strategies are therefore needed. Previous work from our lab has identified the RNA-binding protein heterogenous ribonucleoprotein A18 (hnRNP A18) as a new regulator of protein translation in cancer cells. While its localization is predominantly nuclear, hnRNP A18 translocates out to the cytosol in response to cellular stress like hypoxia. Immunohistochemistry data from tissue microarrays reveals increased expression of hnRNP A18 in prostate hyperplasia, and even greater overexpression in prostate adenocarcinoma as compared to the surrounding normal tissue. Furthermore, a greater percentage of hnRNP A18 is seen to shift from the nucleus to the cytosol as the disease progresses. In the cytosol, hnRNP A18 recognizes and binds to a specific 51 nucleotide RNA motif in the 3' untranslated region of targeted transcripts, stabilizing them and enhancing their translation. Transcripts targeted by hnRNP A18 confer tumor growth advantages. The down-regulation of hnRNP A18 was seen to reduce cancer cell proliferation, migration, and invasion. Moreover, down-regulation of hnRNP A18 significantly reduces prostate cancer growth in a mouse tumor xenograft model. Taken together, our data suggests that hnRNP A18 could be a potentially new target to stop or limit prostate cancer progression. Citation Format: Elizabeth Tsuying Chang, Eun Yong Choi, Palak R. Parekh, France Carrier. Contribution of heterogenous ribonucleoprotein A18 in prostate cancer progression [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 4434.
Abstract 5117: A murine hematogenous bone metastatic cancer to model spontaneous metastasis of triple negative breast cancer
Authors: Hye Jin Lee
Journal: Cancer Research (2018)

Abstract The development of bone metastasis in breast cancer and its pathologic progression are known to be clinically important problem. It is known that immunologic response in microenvironment is important as soil in the bone metastasis process and progression. Thus, immunologic modulation is expected to play a role in the prevention and treatment of the disease in bone metastasis. However, most studies to date; researches in bone metastasis were carried out using human breast cancer cell lines in xenograft model of immuno-deficient mouse or in vitro co-culture system. These approaches have limitations in regard to interaction among immune cells, cancer cells, and other stroma cells. To overcoming these limitation, we used the C3(1)Tag mouse model to establish a spontaneous bone metastasis model. First, a cell line (M6) obtained from a spontaneously occurring tumor in C3(1)Tag mice was infected with lentiviral-luciferase. M6 cells with lentiviral-luciferase were administered using intracardiac injection and C3(1) Tag mice were monitored until tumors are detected under bioluminescence imaging. In 3 weeks, metastatic bone lesions were apparent in 85.7% of mice. To understand biologic characteristics of in vivo selected bone metastatic subpopulation, metastatic cancer cells were harvested and were analyzed using immunohistochemical staing in comparison with parent cells. Tumor cells metastasized to bone showed differential expression in HIF1A, c-MET, and EMT markers. Unexpectedly, bone metastatic cancers showed better sensitivity to paclitaxel and cisplatin than parent cells in cell viability assay. In addition, immune microenvironment in bone metastatic foci was assessed using multiplex immunohistochemical staining and showed an immune suppressive MDSCs infiltration. Taken together, we established a murine hematogenous bone metastatic cancer and characterized biologic characteristics to model human triple negative breast cancer. The potential targets identified in this study might be a future immunologic target in patients with bone metastasis. Citation Format: Hye Jin Lee. A murine hematogenous bone metastatic cancer to model spontaneous metastasis of 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 5117.
Abstract 17333: CHOP Serves as a Positive Feedback Toward Activation of CaMKII in ER Stress Mediated-apoptosis and Cardiac Dysfunction: Novel Signaling Pathway in Cardiac Pressure Overload
Authors: Guangming Cheng, Xing Chen, Lin Zhao, Anweshan Samanta, Magdy Girgis, Sheng Ye, Arash Davani, Anja Browning, Yanjuan Yang, Jianye Yang, Amy Cantilena, Jeryl Hauptman, Robert Vincent, Buddhadeb Dawn
Journal: Circulation (2016)

Introduction: Increased apoptosis accompanies the transition from compensated left ventricular (LV) hypertrophy to failure. CCAAT-enhance-binding protein homologous protein (CHOP) is a key molecule...
A phase II trial of trabectedin (T) in patients with hormone receptor-positive, HER2-negative advanced breast cancer, according to xeroderma pigmentosum gene (XPG) expression.
Authors: Ahmad Awada, Javier Cortes, Miguel Martin, Philippe Aftimos, Mafalda Oliveira, Marc Espie, Pilar Lardelli, Sonia Extremera, Carmen Maria Kahatt, Eva Fernandez-Garcia, Suzette Delaloge
Journal: Journal of Clinical Oncology (2012)

TPS652 Background: Hormone receptor-positive, HER2-negative breast cancer (BC) is currently associated with 3-4 years overall survival in the metastatic setting and, after ≥2 relapses, therapeutic approaches are reduced. XPG expression is frequently modified in BC. T is a cytotoxic agent that forms a complex with the XPG, inducing cell apoptosis. As a single agent, T has shown anti-tumor activity in patients with poor prognosis BC, and a better response to T in BC patients with XPG RNA overexpression has been observed. Methods: This is an open-label, phase II study of T (1.3 mg/m 2 in 3-hour intravenous infusion every 3 weeks) in patients with hormone receptor-positive, HER2-negative advanced BC, according to their primary tumor’s XPG expression. Primary endpoint: to evaluate the efficacy of T in terms of progression free survival rate at 4 months (PFS4) according to the patient’s XPG expression. Secondary endpoints: Comparison of PFS, overall response rate, duration of response, overall survival and safety profile in XPG-high and XPG-low patients. Assignment: BC patients who have previously received anthracyclins and/or taxanes and who progressed after 2-5 chemotherapy lines will be assigned according to their XPG expression from paraffin embedded tumor samples to stratum A (XPG-high [&gt;3]) or to stratum B (XPG-low [≤3]) (threshold was selected from median XPG expression values observed in a previous trial). Statistical methods: A two-stage design was chosen: at a first stage 20 patients will be enrolled in each stratum. A futility analysis (O’Brien Fleming boundary) based on the primary endpoint (PFS4) will be conducted once 40 evaluable patients have been recruited. If ≥ 7 out of 20 patients achieve PFS4, recruitment will continue to a maximum sample size of 50 evaluable patients per stratum. If ≥ 22 out of 50 patients achieve PFS4, T will be considered active in this group (alpha error: 0.025, power: 80%). To date, 35 patients (16 XPG-high and 15 XPG-low) have been enrolled from three countries and five centers. Recruitment is ongoing.
Cardiac Sympathetic Rejuvenation
Authors: KensukeKimura, MasakiIeda, HideakiKanazawa, TakashiYagi, MakotoTsunoda, Shin-ichiNinomiya, HiroyukiKurosawa, KenjiYoshimi, HidekiMochizuki, KazutoYamazaki, SatoshiOgawa, KeiichiFukuda
Journal: Circulation Research (2007)

Neuronal function and innervation density is regulated by target organ-derived neurotrophic factors. Although cardiac hypertrophy drastically alternates the expression of various growth factors such as endothelin-1, angiotensin II, and leukemia inhibitory factor, little is known about nerve growth factor expression and its effect on the cardiac sympathetic nerves. This study investigated the impact of pressure overload-induced cardiac hypertrophy on the innervation density and cellular function of cardiac sympathetic nerves, including kinetics of norepinephrine synthesis and reuptake, and neuronal gene expression. Right ventricular hypertrophy was induced by monocrotaline treatment in Wistar rats. Newly developed cardiac sympathetic nerves expressing β3-tubulin (axonal marker), GAP43 (growth-associated cone marker), and tyrosine hydroxylase were markedly increased only in the right ventricle, in parallel with nerve growth factor upregulation. However, norepinephrine and dopamine content was paradoxically ...
Abstract B38: Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells
Authors: Uwe Thiel, Sebastian J. Schober, Ingo Einspieler, Andreas Kirschner, David Schirmer, Katja Gall, Oxana Schmidt, Thomas G. P. Grunewald, Poul H. Sorensen, Guenther H. S. Richter, Irene Teichert von Luettichau, Dirk H. Busch, Stefan Burdach
Journal: Clinical Cancer Research (2018)

Abstract Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone-marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1 specific allorestricted T-cell receptor (TCR) wild-type and transgenic cytotoxic (CD8+) T cells against ES. Patients and Methods: Three refractory HLA-A2+ ES patients were treated with HLA-A*02:01/peptide specific allorepertoire-derived (i.e., allorestricted) CD8+ T cells. Patient #1 received up to 4.8 x 105/kg body weight HLA-A*02:0 allorestricted donor-derived wild type CD8+ T cells. Patient #2 received up to 8.2 x 106/kg HLA-A*02:01 donor-derived and patient #3 up to 6 x 106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1 peptide 319 (CHM1319). Findings: HLA-A*02:01/CHM1319 specific allorestricted CD8+ T cells showed specific in vitro lysis of all patient-derived ES cell lines. Therapy was well tolerated and did not cause graft-versus-host disease (GVHD). Patients #1 and #3 showed slow progression, whereas patient #2, while having BM involvement, showed partial metastatic regression associated with T-cell homing to involved lesions. CHM1319 TCR transgenic T cells could be tracked in his BM for weeks. Interpretation: HLA-A*02:01/antigen specific allorestricted T cells proliferate in vivo without causing GVHD. CHM1319 TCR transgenic T cells home to affected BM and are associated with partial disease regression. Funding: Wilhelm Sander-Stiftung (2006.109.1), Else Kröner-Stiftung (GR &amp; SB; P31/08//A123/07), BMBF (GR, UT and SB, TranSarNet 01GM1104B; SB, PROVABES 01KT1311) and Cura Placida Children's Cancer Research Foundation. PHS is funded by the Excellenzinitiative at TUM/CCC Munich. Citation Format: Uwe Thiel, Sebastian J. Schober, Ingo Einspieler, Andreas Kirschner, David Schirmer, Katja Gall, Oxana Schmidt, Thomas G. P. Grunewald, Poul H. Sorensen, Guenther H. S. Richter, Irene Teichert von Luettichau, Dirk H. Busch, Stefan Burdach. Ewing sarcoma regression without GVHD by allo-MHC/CHM1 specific T cells [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B38.
Abstract 13994: Masked Hypertension in Ischemic Stroke Patients
Authors: SahraiSaeed, UlrikeWaje-Andreassen, AnnetteFromm, Halvorøygarden, EvaGerdts
Journal: Circulation (2014)

Background: Masked hypertension (MHT) is characterized by normal clinic blood pressure (BP), but elevated ambulatory BP (ABP) and associated with increased risk for target organ damage. We assessed clinical and metabolic characteristics of MHT in ischemic stroke patients. Methods: Clinic and ABP was recorded in 219 patients (aged 15-60 years) included in the prospective Norwegian Stroke in the Young Study (NORSYS) 3 ± 1 month after the acute stroke to identify normotension (NT), white-coat hypertension (WCHT), MHT and sustained hypertension (HT). Results: MHT was found in 10% of patients. In univariate analyses, patients with MHT had higher systolic ABP and serum triglycerides than those with HT, higher body mass index and waist circumference than those with NT and WTCH and lower serum HDL cholesterol than all other BP categories (all p<0.01) (Table). In multivariate logistic regression analysis, lower HDL cholesterol (OR 7.14[95% CI 1.61-33.33], p<0.01), lower fasting blood glucose (OR 2.44[95% CI 1.15-5...
Lessons From the Canadian Experience With Single-Payer Health Insurance
Authors: Noah Ivers, Adalsteinn D. Brown, Allan S. Detsky
Journal: JAMA Internal Medicine (2018)

With single-payer public health insurance again on the political radar in the United States at both the state (California) and federal (Democrat party) levels, the performance of the Canadian health care system during the last 50 years and the lessons it may offer should be considered. Canadians are proud of their universal approach to health insurance based on need rather than income. The system has many strengths, such as the ease of obtaining care, relatively low costs, and low administrative costs, with effectiveness and safety roughly on par with other countries, including those, such as the United States, that spend considerably more per capita. There are increasing frustrations, however, with system performance, especially with issues related to access and coordination of care. Medicine has changed dramatically since the introduction of Canadian Medicare in the late 1960s, which primarily covered acute care physician and hospital services-the needs of the time. Meaningful reforms that match coverage and services to changing needs, especially those of community-based patients with multiple chronic conditions, have been difficult to implement. The status quo represents a compromise struck decades ago between payers and physicians and organizations that provide health care, and the current system works just well enough for those who both need it and vote. Enacting substantial change simply carries too much risk. Perhaps the most important lesson that the United States can learn from Canada's experience during the last 50 years is that a single-payer health care system solves a lot of problems, but it does not equate to an integrated, well-managed system that can readily meet the changing health care needs of a population.
Abstract 3333: Detection of IDH1 R132H mutation in situ in human astrocytoma and glioma FFPE samples
Authors: Na Li, Mindy Wang, Hongzhe Sun, Zhifu Zhang, Xin Wang, Emily Park, Xiao-Jun Ma, Robert Monroe
Journal: Cancer Research (2018)

Abstract IDH1 and IDH2 mutations have been shown to be early events in gliomagenesis. IDH1 mutations are present in ~33% of gliomas and constitute ~90% of all IDH mutations. Approximately 88% of IDH1 mutations involve the substitution c.395G&amp;gt;A leading to the R132H amino acid change. IDH1 mutations, including R132H, are important to recognize clinically as they are more frequent in younger patients and confer a survival advantage. Patients with IDH1 mutations show lower expression of the prognostic markers p53 and Ki-67 and achieve greater benefit from maximal tumor resection. In addition to their prognostic utility, IDH mutations including IDH1 R132H can be useful as diagnostic markers for low-grade gliomas. In difficult to diagnose glial lesions, the presence of IDH mutations strongly favors a diagnosis of glioma versus reactive gliosis. Although PCR and DNA sequencing-based approaches can detect the IDH1 R132H mutation, these techniques require destruction of tissue for nucleic acid isolation and destroy the morphologic context, highlighting the need for a methodology that can be performed on formalin-fixed, paraffin-embedded (FFPE) tissues. In this study, we developed an assay to specifically detect the IDH1 R132H mutation in FFPE samples in expressed IDH1 mRNA transcripts using the novel BasescopeTM technology. IDH1 wild-type (WT) and IDH1 mutation (MT) probes were tested in 6 astrocytoma and 3 glioma FFPE specimens from unique clinical cases. All samples exhibited positivity with the IDH1 WT probe. Two of six astrocytomas and one of three gliomas showed positivity with the IDH1 R132H mutation probe. Among the three positive samples, one astrocytoma exhibited positive signals for the IDH1 R132H mutation in almost all tumor cells, whereas one astrocytoma and one glioma showed only scattered positive signals with the IDH1 R132H mutation probe in a subset of tumor cells. Our findings indicate that the BasescopeTM assay is a novel RNA in situ hybridization assay to visualize point mutations in a highly specific and sensitive manner within the morphologic tissue context. In this study, we demonstrate that the BasescopeTM IDH1 R132H assay is capable of detecting the IDH1 R132H mutation in routine FFPE clinical specimens for the purpose of assisting in the diagnosis of gliomas and providing prognostic information. The BasescopeTM technology also allows for correlation of the frequency and distribution of IDH1 R132H mutations in glial tumors with patient outcomes and overall survival. Citation Format: Na Li, Mindy Wang, Hongzhe Sun, Zhifu Zhang, Xin Wang, Emily Park, Xiao-Jun Ma, Robert Monroe. Detection of IDH1 R132H mutation in situ in human astrocytoma and glioma FFPE samples [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 3333.
Overview of Late Outcome of Medical and Surgical Treatment for Takayasu Arteritis
Authors: HitoshiOgino, HitoshiMatsuda, KenjiMinatoya, HiroakiSasaki, HiroshiTanaka, YuMatsumura, HatsueIshibashi-Ueda, JunjiroKobayashi, ToshikatsuYagihara, SoichiroKitamura
Journal: Circulation (2008)
Abstract LB-009: Intracellular delivery with SOCS3 suppresses angiogenesis in tumors
Authors: Yukdong Jung, Kuysook Lee, Youngsil Choi, Daewoong Jo
Journal: Cancer Research (2018)

Abstract Introduction: Suppressor of cytokine signaling 3 (SOCS3) is a negative feedback regulator in the Janus kinase/signal transducer and activator of transduction (JAK/STAT) signaling pathway, in which it suppresses inflammation and cancer. The JAK/STAT pathway is activated in some tumors thus enhancing the expression of genes involved in proliferation and angiogenesis, notably, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin-1 and phospoinositide 3-kinase (PI3K)-protein kinase B (AKT). Objective: The aim of this study is to develop an improved cell-permeable (iCP)-SOCS3 and determine its applicability as an anti-angiogenic agent to treat cancer. Methods: The iCP-SOCS3 was expressed in E. coli as a 37 kDa recombinant protein fused to an advanced macromolecule transduction domain (aMTD) and humanized solubilization domain (SD). Uptake of a fluorescently tagged iCP-SOCS3 by cells and tissues was monitored by flow cytometry and confocal microscopy. Biological and biochemical activities of iCP-SOCS3 were determined by in vitro angiogenesis assays and changes in biomarker expression and anti-tumor activities were analyzed in mice bearing human tumor xenografts. Results: The iCP-SOCS3 improved on an earlier generation of CP-SOCS3 fused to FGF4-derived membrane translocating motif (MTM) with regard to solubility, yield, delivery into cells and tissues and biological activity. The iCP-SOCS3 suppressed proliferation of human umbilical vein endothelial cells (HUVECs) by 60% and migration by 54% via inhibition of AKT/mTOR signaling pathway. Moreover, iCP-SOCS3 inhibited invasion of EC cells in PANC-1 and U87MG conditioned medium by 38% and 95%, respectively. In tube formation assay, iCP-SOCS3 reduced the number of branch points by 79% and tube length by 60% compared to the vehicle. In chick chorioallantoic membrane (CAM) assay, iCP-SOCS3 significantly inhibited angiogenesis by 83% in dose dependent manner compared to the reference drug, retinoic acid. The anti-angiogenic activity of iCP-SOCS3 was also shown in matrigel plug assay. The new vessel formation induced by U87-MG glioblastoma cells was significantly reduced by the treatment of iCP-SOCS3. In PANC-1, U87-MG and HepG2 cell-derived xenograft models, iCP-SOCS3 suppressed expression of pro-angiogenic factors including VEGF, ERK and angiopoietin 1. Conclusion: These results validate iCP-SOCS3 targets in promoting angiogenesis and suggest ways to reduce angiogenesis in various types of tumors. Citation Format: Yukdong Jung, Kuysook Lee, Youngsil Choi, Daewoong Jo. Intracellular delivery with SOCS3 suppresses angiogenesis in 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 LB-009.