tbuckley/cabot-search huggingface dataset:
Abstract 160: Novel strategy targeting breast cancer stem cells CD44+/CD24-low responsible for breast cancer progression
Authors: Fatma A. Abouelnazar, Ahmed S. Sultan
Journal: Cancer Research (2018)

Abstract The present study has been designed to isolate the highly tumorigenic sub-population of cells from the breast cancer cell line (T47-D). The effect of Manuka honey (MH), Frankincense essential oil (F), Metformin (M) and combined treatment on eradicating breast cancer stem cells (BCSCs) that are responsible for cancer progression was investigated. The isolated (BCSCs) were subjected to different concentrations of (MH), (F), (M) and combined treatment to visualize their effects on BCSCs viability, morphological changes, caspase-3 activity, apoptosis induction, clonogenic survival, β-catenin, ALDH6A1, Notch-1, Notch-4 and Nonog protein expression, using western blot analysis and protein localization by immunocytochemical technique. Inhibited viability of isolated breast cancer stem cells, which showed apoptotic morphological changes were observed beside increased caspase-3 activity and inhibited clonogenic survival compared to control. At the protein level, our data showed that (MH), (F), (M) and combined synergistic treatment decreased the expression of β-catenin levels, ALDH6A1 and Notch-1 compared to control. In addition, (MH) showed no effect on Notch-4 expression, but significantly decreased the expression level of Nanog. In contrast, (F) treatment enhanced the protein expression of Nanog level in a dose dependent manner compared to control. Furthermore, (MH), (F), (M), and combined treatment showed conspicuously decrease in the nuclear and cytoplasmic level of β-catenin and ALDH6A1 of CD44+/CD24-low (BCSCs) compared to control. Taken together, natural compounds of Manuka honey and Frankincense essential oils and their combination with Metformin have been emerged as a potential strategy to target and eradicate (BCSCs). Citation Format: Fatma A. Abouelnazar, Ahmed S. Sultan. Novel strategy targeting breast cancer stem cells CD44+/CD24-low responsible for breast 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 160.
Abstract IA10: Targeted therapies as molecular probes for comprehensive preclinical evaluation
Authors: Mark A. Dawson
Journal: Clinical Cancer Research (2017)

Abstract Cancer biology is profoundly influenced by changes in the epigenome. Because the dynamic plasticity of the epigenome lends itself well to therapeutic manipulation, the past few years have witnessed an unprecedented investment in the development, characterization, and translation of targeted epigenetic therapies. Several of these epigenetic therapies have now transitioned into the clinical arena, and emerging evidence suggests that these drugs are well tolerated and show single-agent efficacy in a range of hematopoietic cancers. The enduring challenge for clinicians and scientists will be understanding the cellular and molecular mechanisms that may govern sensitivity and resistance to these agents. This information could then be used to design more effective combination regimes. A major limitation to our current knowledge is the fact that we are blinded to the mechanism of action of these agents in a cellular context. In this seminar, I will discuss our strategy to overcome this limitation by converting epigenetic agents into molecular probes that maintain the functional integrity of the compound but now allow the compounds to be used much like antibodies in all routine cell and molecular assays both in vitro and in vivo. Citation Format: Mark A. Dawson. Targeted therapies as molecular probes for comprehensive preclinical evaluation [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr IA10.
Abstract 3730: Structure determination, mode of action and safe delivery of an improved K6L9-type peptide
Authors: Tej B. Shrestha, Jing Yu, Stefan Bossmann, Deryl Troyer
Journal: Cancer Research (2018)

Abstract There is a significantly increased interest in using antimicrobial peptides for anticancer therapy. D-K6L9, LKLLKKLLKKLLKLL is an antimicrobial peptide that has been explored. It kills cancer cells by depolarizing their cell membranes, thus inducing apoptosis. Further modification of the peptide for increased toxicity and safe packaging into a delivery vehicle for targeted delivery is highly desired for the in vivo applications. Here, the peptide was modified with two extra amino acids (serine and alanine) at both C and N terminals, resulting in SA-LKLLKKLLKKLLKLL-AS. The sequence and structure of the modified peptide were determined by means of 2D 1H-1H -COSY, NOESY, and TOCSY-NMR spectroscopy. The 3D structure of the peptide in the solution phase was generated by CNS software using a distance constraint generated by NOE spectroscopy. The 3-D structure of SA-D-K6L9-AS is maintained, as well as the amphiphilicity required for insertion into cell membranes. This peptide was tested on the following mouse cancer cell lines: GL 26 (glioma), B16-F10 (melanoma lung metastases) and 4T1 (metastasizing breast cancer). The LC50 values of the modified peptide were found to be 0.707 µM for B16-F10, 6.237 µM for 4T1 and 1.707 µM for GL 26, which is 5- 10 fold more active than the original D-K6L9. To explore the findings using the modified peptide, SA-D-K6L9-AS tagged with a rhodamine dye was incubated with GL 26 cancer cells. Sequential confocal imaging (every 30 seconds) revealed that the peptide gets internalized into the cytoplasm in less than 5 min and then localizes in the mitochondria. This peptide is found to be toxic to neuronal stem cells and monocytes as well. To avoid the non-specific toxicity of the peptide for in vivo applications, highly mesoporous silica nanoparticles (MSN) were synthesized. The peptide was loaded into the MSN. MSN were further coated with a polysilazane as a “gift wrap” after loading the peptide. This gift wrap can hold the contents inside the MSN, showing no toxicity at 24 hours and subsequent slow release of the peptide payload into the cytoplasm within 72 hours. This gift wrapping of the highly toxic peptide into the MSN could be very useful for in vivo cancer therapy by means of targeted delivery to the cancer site with appropriate surface modification of MSN. Citation Format: Tej B. Shrestha, Jing Yu, Stefan Bossmann, Deryl Troyer. Structure determination, mode of action and safe delivery of an improved K6L9-type peptide [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 3730.
Perspectives for Induced Pluripotent Stem Cell Technology
Authors: NaokiNagata, ShinyaYamanaka
Journal: Circulation Research (2014)

Induced pluripotent stem cell technology makes in vitro reprogramming of somatic cells from individuals with various genetic backgrounds possible. By applying this technology, it is possible to produce pluripotent stem cells from biopsy samples of arbitrarily selected individuals with various genetic backgrounds and to subsequently maintain, expand, and stock these cells. From these induced pluripotent stem cells, target cells and tissues can be generated after certain differentiation processes. These target cells/tissues are expected to be useful in regenerative medicine, disease modeling, drug screening, toxicology testing, and proof-of-concept studies in drug development. Therefore, the number of publications concerning induced pluripotent stem cells has recently been increasing rapidly, demonstrating that this technology has begun to infiltrate many aspects of stem cell biology and medical applications. In this review, we discuss the perspectives of induced pluripotent stem cell technology for modelin...
Abstract 12440: Global Longitudinal Strain With 2D-Speckle Tracking Predicts Chemotherapy-related Systolic Dysfunction Independenty of Basal Assessment in Patients With Breast Carcinoma
Authors: FedericoGuerra, MarcoMarchesini, DanieleContadini, AlessioMenditto, MarcoMorelli, ElisaPiccolo, MarcoTagliavento, NicolaBattelli, RossanaBerardi, StefanoCascinu, AlessandroCapucci
Journal: Circulation (2015)

Introduction: Recent developments in anticancer therapies for breast carcinoma allowed an improvement in patient survival, notwithstanding a parallel increase of cardiovascular morbidity. Systolic dysfunction and heart failure represent a relevant problem in these patients due to insidious onset and the potential irreversible nature of cardiac damage. Therefore, strong and early predictors of chemoteraphy-realted systolic dysfunction are been sought. Hypothesis: To investigate global longitudinal strain (GLS) assessed by 2D-speckle tracking as a potential early marker of systolic dysfunction in chemoteraphy-treated breast cancer patients. Methods: Population include sixty-nine patients, referred to our unit for cardiologic assessment prior to neo-adjuvant or adjuvant chemotherapy for breast cancer. Patients with prior heart failure and atrial fibrillation were excluded. The protocol included a baseline echocolorDoppler and 2D-strain evaluation before the beginning of chemotherapy and subsequent serial con...
Thermal Treatment Attenuates Neointimal Thickening With Enhanced Expression of Heat-Shock Protein 72 and Suppression of Oxidative Stress
Authors: MotoiOkada, NaoyukiHasebe, YoshiakiAizawa, KazumaIzawa, Jun-ichiKawabe, KenjiroKikuchi
Journal: Circulation (2004)

Background— The beneficial effects of thermal therapy have been reported in several cardiovascular diseases. However, it is unknown whether the thermal treatment has some beneficial roles against the development of atherosclerosis. Methods and Results— The inflammatory arterial lesion was introduced by placement of a polyethylene cuff on femoral arteries of male Sprague-Dawley rats for 4 weeks. Thermal-treated group underwent daily bathing in 41°C hot water for 15 minutes. Neointimal thickening along with immunohistochemical expression of heat-shock proteins (HSPs), monocyte chemoattractant protein-1 (MCP-1), and NADPH oxidase were compared with those of a thermally untreated (Control) group. Morphometric analysis demonstrated a significant suppression of neointimal thickening in thermal-treated group compared with the Control group (intimal/medial area ratios, 0.01±0.01 versus 0.31±0.04, P<0.01). Expression of MCP-1 and infiltration of ED-positive cells were enhanced in the adventitial layer of Control. ...
Managment of choledocholithiasis in patients post Roux-En-Y gastric bypass with Laparoscopic Transgastric Endoscopic Retrograde Pancreatocholangiography (LTERCP)
Authors: S.N. Rupasinghe, H. Barrow, V.P. Lekharaju, O. Noorullah, M.S. Javed, A. Menon
Journal: International Journal of Surgery (2018)
Synthetic Lethal and Convergent Biological Effects of Cancer-Associated Spliceosomal Gene Mutations
Authors: Stanley Chun-Wei Lee, Khrystyna North, Eunhee Kim, Eunjung Jang, Esther Obeng, Sydney X. Lu, Bo Liu, Daichi Inoue, Akihide Yoshimi, Michelle Ki, Mirae Yeo, Xiao Jing Zhang, Min Kyung Kim, Hana Cho, Young Rock Chung, Justin Taylor, Benjamin H. Durham, Young Joon Kim, Alessandro Pastore, Sebastien Monette, James Palacino, Michael Seiler, Silvia Buonamici, Peter G. Smith, Benjamin L. Ebert, Robert K. Bradley, Omar Abdel-Wahab
Journal: Cancer Cell (2018)
Abstract 1424: Elucidating the microRNA-203 specific biological processes in glioblastoma cells from high-throughput RNA-sequencing
Authors: Bhavesh K. Ahir, Herbert H. Engelhard, Sajani S. Lakka
Journal: Cancer Research (2018)

Abstract Glioblastoma (GBM) is the most common primary malignant intracranial adult brain tumor. Allelic deletion on chromosome 14q play an essential role in GBM pathogenesis, and this chromosome 14q site was thought to harbor multiple tumor suppressor gene associated with GBM, a region that also encodes microRNA-203 (miR-203). This study was conducted to identify gene expression profile changes associated with mir-203 expression by high-throughput RNA sequencing. Enrichment analyses for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that mir-203 expression had a strong, negative effect on a number of fundamental and interconnected biological processes involved in cell growth and proliferation. The biological processes mostly influenced were p53 signaling pathway, FoxO signaling pathway, DNA replication, cell cycle, MAPK signaling pathway and Apoptosis. In total, 847 upregulated and 345 downregulated differentially expressed genes (DEGs) were identified in control versus miR203 expressing glioma cells. After GO enrichment, the downregulated DEGs and miR-203 predicted target genes such as BCL-2, SPARC, PDGFA, CREB were found to be mainly enriched in cell cycle regulation and apoptosis processes, whereas the upregulated DEGs, such as CCND1, E2F1 were involved in the DNA replication and cell cycle regulation of gene expression. We also demonstrate that mir-203 expression suppressed BCL-2 protein and mRNA by western blotting and qRT-PCR analysis. Moreover, co-transfection experiments using a luciferase-based reporter assay demonstrated that mir-203 directly regulated BCL-2 expression and BCL-2 overexpression suppressed mir-203 mediated cell death. Knowledge gained through this profiling study can facilitate targeted therapeutic interventions. Citation Format: Bhavesh K. Ahir, Herbert H. Engelhard, Sajani S. Lakka. Elucidating the microRNA-203 specific biological processes in glioblastoma cells from high-throughput RNA-sequencing [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 1424.
Differential Regulation of Proteasome Function in Isoproterenol-Induced Cardiac Hypertrophy
Authors: OliverDrews, OsamuTsukamoto, DavidLiem, JohnStreicher, YibinWang, PeipeiPing
Journal: Circulation Research (2010)

Rationale:Proteasomal degradation is altered in many disease phenotypes including cardiac hypertrophy, a prevalent condition leading to heart failure. Our recent investigations identified heterogeneous subpopulations of proteasome complexes in the heart and implicated multiple mechanisms for their regulation. Objective:The study aimed at identification of molecular mechanisms changing proteasome function in the hypertrophic heart. Method and Results:Proteasome function, expression, and assembly were analyzed during the development of cardiac hypertrophy induced by β-adrenergic stimulation. The analysis revealed, for the first time, divergent regulation of proteasome function in cardiac hypertrophy. Proteasome complexes have 3 different proteolytic activities, which are ATP-dependent for 26S complexes (19S assembled with 20S) and ATP-independent for 20S core particles. The 26S activities were enhanced in hypertrophic hearts, partially because of increased expression and assembly of 19S subunits with 20S co...
Abstract 11329: Superiority of Assessing Endocardial Strain to Whole Wall Thickness Strain by Dobutamine Stress Echocardiography in the Dectection of Coronary Artery Disease
Authors: Jing PingSun, ZhiqingQiao, YitingFan, XuedongShen, HangZhao, JunPu, Alex Pui-waiLee, BenHe, Cheuk-ManYu
Journal: Circulation (2014)

Background: Myocardial ischemia typically extends from the endocardium to the epicardium. Therefore methods of assessment myocardial functional abnormality at the endocardial layer may permit a more accurate detection of coronary artery disease (CAD) this was testified in the current study with the use of dobutamine stress echocardiography. Methods: After baseline echocardiographic scans obtained, 40 patients with suspected CAD underwent dobutamine stress echocardiography (peak dose, 40μg/kg/min). Coronary angiography was performed within 3 days after test. Echocardiographic images were post-processed by a layer-specific speckle tracking software (EchoPac Version 113, GE) to measure the peak longitudinal strain (STE-L) at the endocardium, midlayer, and epicardium as well as total wall thickness (STE-W). Results: Forty patients were enrolled into the study. Among them 22 (mean age of 56 ± 15 years) had significant coronary artery disease (stenosis >70%). This included single-vessel disease at left anterior...
Abstract 2905: Deciphering and blocking the mechanisms of cadmium induction of TCTP in prostate cancer cells
Authors: Rama Saad, Gnanasekar Munirathinam, Theresa Kucynda, Marta Ribeiro, Paul Lindholm, Andre Balla
Journal: Cancer Research (2018)

Abstract While cadmium is a well-known lung carcinogen, its role in prostate cancer is yet to be understood. Recently, a meta-analysis study showed that cadmium did not increase the risk of prostate cancer. It is not known whether cadmium exposure at environmentally relevant concentrations increases aggressiveness of already existing prostate cancer. Although our lab previously showed that the 75th percentile of cadmium concentration in prostate cancer was associated with biochemical recurrence, more evidence is needed to substantiate this finding. We also showed evidence that cadmium promotes prostate cancer cells migration and invasion via inducing the expression of translationally controlled tumor protein (TCTP). Furthermore, it was demonstrated that cadmium induces the phosphorylation of p38, and that the p38 inhibitor SB203580 (SB) blocks the effects of cadmium on migration and invasion. In this study, we aimed to delineate the signaling events upon cadmium treatment; whether p38 or TCTP is upstream. We addressed this via inhibition of p38 using SB203580 and by inducing TCTP degradation via dihydroartemisinin (DHA) followed by measurement of TCTP expression and phosphorylation of p38 respectively. p38 inhibition led to the increased expression of TCTP on both mRNA and protein levels. Pretreatment with DHA led to less TCTP expression and less phosphorylation of p38. We also aimed to understand the effect of cadmium on cell proliferation, survival and migration. While DHA lowered the colony count and EdU incorporation, cadmium did not alter these functions. In addition, DHA abrogated the cadmium-mediated migration of PC3-Inv prostate cancer cell line. Furthermore, we aimed to determine the effect of nanomolar cadmium concentrations on the phosphorylation of PlK1, which is well established to be upstream of TCTP. Our results demonstrated that nanomolar concentrations of cadmium resulted in increased phosphorylation of PlK1 in both PC3 and LNCaP cells. Altogether, our results suggest that environmentally relevant exposures of cadmium induce TCTP expression through several pathways, and that there is a feedback mechanism between p38 and TCTP. Citation Format: Rama Saad, Gnanasekar Munirathinam, Theresa Kucynda, Marta Ribeiro, Paul Lindholm, Andre Balla. Deciphering and blocking the mechanisms of cadmium induction of TCTP in prostate cancer cells [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 2905.
18F-FDG PET-defined therapy response to predict acute hematologic toxicity for anal cancer patients treated with chemoradiation.
Authors: John David, Yong Yue, Kevin Blas, Benedick Fraass, Andrew Eugene Hendifar, Peyman Kabolizadeh, Richard Tuli
Journal: Journal of Clinical Oncology (2018)

775 Background: Hematologic toxicities (HT) induced during chemoradiotherapy (CRT) for anal cancer can lead to increased infection rates, bleeding, asthenia, and unplanned breaks compromising treatment efficacy. We hypothesize that HT in anal cancer patients treated with CRT correlate with change in active bone marrow (ABM) characterized by pre- and post-CRT 18F-FDG PET/CT (PET). Methods: Twenty-eight locally advanced anal cancer patients treated with definitive CRT from 2011-2016 were identified. PET scans were obtained 0-2 weeks pre- and 6-8 weeks post-CRT. HT was evaluated by weekly white blood cell count, absolute neutrophil count (ANC), hemoglobin (Hg) and platelet nadirs. Total bone marrow (TBM) was defined on CT images, and segmented into three subregions: lumbosacral (LS), left and right iliac pelvis. PET images were normalized to bone outside of the TBM uptakes. ABM was characterized in all PET images as the volume having standard uptake value SUV &gt; 40% of SUVmax in the TBM. Image variables (global, subregional SUVmean, SUVmax, ABMs) of pre- and post-CRT and their differential changes were evaluated as predictors of HT. Locoregional radiomics features were calculated using a 3D kernel-based approach. HT prediction was modeled by logistic regression with the Lasso algorithm with 10-fold cross-validation. HT endpoints were defined as change between baseline blood nadir and the lowest nadir values during and up to 2 weeks after CRT. Results: The lasso regression identified 5 predictors of HT (pre-SUVmax, post-LS-ABM, LS-ABM change, homogeneity texture change, and variance). Ratios of LS-ABMs to TBM were reduced from 18.9% (pre-CRT) to 16.3% (post-CRT). This reduction of LS-ABM significantly correlated with acute HT measured by ANC (p &lt; 0.001) and Hg (p &lt; 0.001) nadirs. Conclusions: PET-derived active BM changes between pre- and post-CRT significantly associated with HT in anal cancer patients undergoing definitive CRT. LS-ABM is a robust surrogate for evaluation of HT and can be used to develop BM-sparing radiotherapy for reduction of potential HT.
Nitric Oxide Synthesis by Cultured Endothelial Cells Is Modulated by Flow Conditions
Authors: MarinaNoris, MarinaMorigi, RobertaDonadelli, SistianaAiello, MarcoFoppolo, MartaTodeschini, SilviaOrisio, GiuseppeRemuzzi, AndreaRemuzzi
Journal: Circulation Research (1995)

Abstract In the present study, we examined the hypothesis that dynamic characteristics of flow modulate the production of vasoactive mediators, namely nitric oxide (NO) and endothelin-1 (ET-1), by human umbilical vein endothelial cells (HUVECs). Cells were exposed for 6 hours in a cone-and-plate apparatus to different types of flow: steady laminar, with shear stresses of 2, 8, and 12 dyne/cm2; pulsatile laminar, with shear stress from 8.2 to 16.6 dyne/cm2 and a frequency of 2 Hz; periodic laminar, with square wave cycles of 15 minutes and shear stress from 2 to 8 dyne/cm2; and turbulent, with shear stress of 8 dyne/cm2 on average. A second culture dish was kept in a normal incubator as a static control for each experiment. Laminar flow induced synthesis of NO by HUVECs that was dependent on shear-stress magnitude. Laminar shear stress at 8 dyne/cm2 also upregulated the level of NO synthase mRNA. As observed with steady laminar flow, pulsatile flow also induced an increase in NO release by endothelial cell...