tbuckley/cabot-search huggingface dataset:
Abstract 4463: Loss of APC mediates doxorubicin resistance in breast cancer cells
Authors: Casey D. Stefanski, Kaitlyn Keffler, Stephanie McClintock, Jenifer R. Prosperi
Journal: Cancer Research (2018)

Abstract Resistance to chemotherapy is one of the leading causes of breast cancer related deaths. Understanding the molecular basis for chemoresistance is essential for the advancement of novel therapeutic approaches to ultimately improve patient outcomes. The Adenomatous Polyposis Coli (APC) tumor suppressor is either mutated or hypermethylated in up to 70% of sporadic breast cancer; however, little is known about how loss of APC contributes to chemoresistance. Using the ApcMin/+ mouse crossed to the Polyoma middle T antigen (PyMT) transgenic model, we demonstrated that APC loss decreased cisplatin and doxorubicin-induced apoptosis. We previously showed that loss of APC in MMTV-PyMT;ApcMin/+ cells induced STAT3-activation resulting in an enhanced tumor initiating cell (TIC) population and increased multidrug resistance protein 1 (MDR1) expression. Therefore, we hypothesized that APC loss increased MDR1 activity and decreased doxorubicin-mediated DNA damage, ultimately preventing cell death. Using calcein incorporation, we first demonstrated that APC loss increased MDR1 activity which was normalized to WT control levels by the MDR1 inhibitor, Valspodar. We next showed that MDR1 inhibition in MMTV-PyMT;ApcMin/+ cells could restore doxorubicin-mediated apoptosis to that of MMTV-PyMT;Apc+/+ treated cells. Due to STAT3 inducing MDR1 activity and TIC population, MDR1 inhibition in MMTV-PyMT;ApcMin/+ cells was also shown to reduce the TIC population. In addition, we are investigating the effect of APC loss on DNA damage repair pathways. Preliminary studies have shown decreased γH2AX in MMTV-PyMT;ApcMin/+ cells treated with doxorubicin, suggesting a decrease in DNA damage. Downstream signaling of γH2AX, measured by phosphorylation of ATM, also demonstrated decreased DNA damage with ongoing studies measuring phosphorylation of ATR. Due to APC binding to topoisomerase IIα (topo IIα), a target of doxorubicin, the activity of topo IIα was measured to address whether this decreased DNA damage was attributed to impaired topo IIα activity or decreased intracellular doxorubicin due to increased MDR1 efflux. Future studies will investigate whether MDR1 inhibition in combination with doxorubicin will reduce tumor burden in vivo. Taken together, APC loss mediates doxorubicin resistance via enhanced MDR1 activity and altered DNA damage repair pathways demonstrating the potential use of combination therapy to overcome resistance to chemotherapy. Citation Format: Casey D. Stefanski, Kaitlyn Keffler, Stephanie McClintock, Jenifer R. Prosperi. Loss of APC mediates doxorubicin resistance in breast 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 4463.
Abstract 008: Bone Marrow Mesenchymal Stem Cells Prevented Cardiac Arrhythmias Of Infarcted Heart Via Regulating Calcineurin And Potassium Channels Expression
Authors: BenzhiCai, NanChen, GangWang, YanjuLiu, XingdaLi, FanYang, YanjieLu
Journal: Circulation Research (2013)

Bone marrow mesenchymal stem cells (BMSCs) emerge as a new promising approach for treating heart diseases. However, the effects of BMSCs-based therapy on cardiac electrophysiological remodeling following myocardial infarction were largely unclear. This study was aimed to investigate whether BMSCs transplantation prevented cardiac arrhythmias in post-infarcted hearts. Myocardial infarction was established in male SD rats, and BMSCs were then intramyocardially transplanted into the infarcted hearts after 3 days. Cardiac electrophysiological remodeling in the border zone was evaluated by western blotting and whole-cell path clamp technique after 2 weeks. We found that BMSCs transplantation significantly ameliorated the increased heart weight index, the impaired left ventricular functions, and the enhanced cardiac fibrosis in infarcted hearts. The survival ratio of infarcted rats was also improved after BMSCs transplantation. Importantly, electrical stimulation-induced arrhythmias were seldom observed in BMSC...
Abstract 638: Microbubble enrichment of CTCs
Authors: Thomas Jones, Leo J. Ostruszka, Shamileh Fouladdel, Ebrahim Azizi, Jaroslav Slamecka, Brandon H. McNaughton, John Younger, Max Wicha, Steven McClellan
Journal: Cancer Research (2018)

Abstract Despite numerous new cell analysis technologies, contaminating red- and white blood cells remain a central barrier to the efficient characterization of circulating tumor cells. Microbubbles, which capture and separate cells by flotation, recently have been described as an alternative or adjunct to magnetic beads or microfluidic methods for CTC sample preparation. This technology may find particular value in applications where mechanical force needs to be minimized or magnetization of cells needs to be avoided. Here, we evaluate novel RBC-targeting microbubbles for buoyancy-based enrichment of CTCs. Cultured human pancreatic cancer cells (line CFPAC-1, ATCC CRL 1918) were spiked into standardized samples representative of common CTC workflows (106 RBC : 5x104 WBC : 1.5x102 tumor cells). Microbubbles bearing antibodies to human erythrocytes were added at various Bubble:RBC ratios and mixed via trituration for 1 minute. Samples were then centrifuged, the microbubble-captured RBCs removed, and the remaining pelleted cells analyzed for the fraction of RBCs removed and the extent of off-target depletion of tumor cells. Cells were quantified with an automated cell counter, and all experimental conditions were performed in at least triplicate. RBC removal rose with increasing Bubble:RBC ratio ( p &amp;lt; 0.001 ). At a ratio of 1:1, 92 +/- 1% of RBCs were removed with one minute of mixing; at a ratio of 1.5:1, 97 +/- 1% of RBCs were removed. Off-target binding of CFPAC-1 cells was minimal at a Bubble:RBC ratio of 1:1, with 0 +/- 6% of tumor cells captured. Off-target capture increased at a Bubble:RBC ratio of 2:1, with 12 +/- 9% tumor cell loss from the experimental samples. Using a standardized blood sample with a clinically relevant low concentration of cultured tumor cells, microbubbles targeting RBCs and dosed at a ratio of one bubble per target erythrocyte were able to achieve &amp;gt; 90% removal without statistically detectable loss of a cultured cancer line. Higher bubble concentrations resulted in more exhaustive RBC removal, but with some loss of cultured cells. Microbubble-based cell separation may have a useful role in CTC purification protocols. Citation Format: Thomas Jones, Leo J. Ostruszka, Shamileh Fouladdel, Ebrahim Azizi, Jaroslav Slamecka, Brandon H. McNaughton, John Younger, Max Wicha, Steven McClellan. Microbubble enrichment of CTCs [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 638.
Abstract 4220: Heterogeneous distribution of prognostic protein markers in glioblastoma
Authors: Lindsay C. Stetson, Quinn T. Ostrom, Peter Liao, Andrew E. Sloan, Mark R. Chance, Jill S. Barnholtz-Sloan
Journal: Cancer Research (2018)

Abstract Background: Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults. The heterogeneity of the disease leads to significant variability in response to standard therapy (surgery plus concurrent radiation and temozolomide). An accurate and reliable predictor of patient prognosis represents an unmet need to improve the care of GBM patients. While protein markers are an effective readout of cellular function, proteomics has rarely been utilized in GBM prognostic marker discovery. Experimental Procedures: GBM patients were prospectively recruited (Ohio Brain Tumor Study) and proteomics discovery using liquid chromatography mass spectrometry analysis (LC MS/MS) was performed in a discovery set of 27 patients including 13 short-term survivors (&amp;lt; 9 months, STS) and 14 long-term survivors (&amp;gt;= 18 months, LTS). Statistically significant proteins were evaluated in two independent datasets, including in18 samples micro-dissected from multiple tumor areas of 6 GBM patients. Results: Proteomics discovery identified 11,941 peptides in 2,495 unique proteins, with 172 proteins exhibiting significant dysregulation when comparing STS and LTS. Proteins involved in glycolysis/TCA cycle were up-regulated in STS compared to LTS by examination of individual targets as well as upon application of a novel protein and peptide pathway enrichment analysis. Validation of these dysregulated proteins and other protein markers from the literature in our first validation set (18 samples micro-dissected from n=6 patients) demonstrated that they were very unevenly distributed throughout individual patients' tumors. Several proteins overcame the heterogeneous nature of the tumors and were both prognostic markers differentially expressed between LTS and STS, as well as potential drug targets owing to their even distribution throughout the tumor. Protein abundance of significant marker proteins were verified in a second independent validation set using Western immunoblots. Conclusion: The current study verified the importance of metabolism in GBM pathology and demonstrated the heterogeneous nature of GBMs at the protein level. Citation Format: Lindsay C. Stetson, Quinn T. Ostrom, Peter Liao, Andrew E. Sloan, Mark R. Chance, Jill S. Barnholtz-Sloan. Heterogeneous distribution of prognostic protein markers in glioblastoma [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 4220.
Abstract P072: Low-Carbohydrate-Diets and Cardiovascular and Total Mortality in Japanese. A 29-year Follow-up of NIPPON DATA80
Authors: YasuyukiNakamura, NagakoOkuda, TomonoriOkamura, AyaKadota, NaokoMiyagawa, TakehitoHayakawa, YoshikuniKita, AkiraFujiyoshi, MasatoNagai, NaoyukiTakashima, TakayoshiOhkubo, KatsuyukiMiura, AkiraOkayama, HirotsuguUeshima
Journal: Circulation (2014)

Background: Long-term safety of low-carbohydrate-diets in Asian populations, whose carbohydrate intake is relatively high, is not known. Methods: We examined the association of low-carbohydrate-diets with CVD and total mortality using the National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged, (NIPPON DATA80) database with a 29-year follow-up. At the baseline in 1980, data were collected on study participants ages≥30 years from randomly selected areas in Japan. We calculated low-carbohydrate-diet scores based on the percentage of energy as carbohydrate, fat, and protein, estimated by 3-day weighed food records. We followed 9,200 participants (56% women, mean age 51 y). Results: During the follow-up, there were 1,171 CVD deaths (52% in women), and 3,443 total deaths (48% in women). The multivariate-adjusted hazard ratio (HR) for CVD mortality using the Cox model comparing highest versus lowest deciles for a low-carbohydrate-diet score was 0.59 (95% con...
Abstract 1518: Gene expression of trefoil proteins, gastrokines and mucins in Indian gastric cancer patients
Authors: Dipjit Basak, Pronoy Kanti Mondal, Brishti Mondal, Ranajoy Ghosh, Aniket Halder, Gopal Krishna Dhali, Abhijit Chowdhury, Indranil Mukhopadhyay, Shalini Datta
Journal: Cancer Research (2018)

Abstract Background: Gastric cancer is the (GC) third most cause of cancer related mortality worldwide. Histopathologically, GC is sub classified into two major histopathological subtypes- diffuse and intestinal. The trefoil factor family - TFF1, TFF2 and TFF3 is known to play a pivotal role in gastrointestinal mucosal defence and repair. Gastrokines (GKN1, GKN2) are stomach specific secretary proteins which play fundamental roles in regulating gastric epithelial homeostasis. Similarly, secreted mucins are large O-glycosylated proteins that participate in the protection/defence of underlying mucosa in normal adults. The loss of expression of trefoil proteins, gastrokines and several mucins in retinoblastoma and colorectal cancer are reported in recent studies. Aims: The molecular underpinnings and gene expression of Indian GC patients are largely unknown. In this study, we evaluated the gene expression of TFF1, TFF2, TFF3, GKN1, GKN2, MUC3A, MUC5AC, MUC13 in gastric cancer patients from India. Additionally, we wanted to see whether these gene expressions are different in two histopathological groups. Materials and Methods: Endoscopic biopsy tissue from gastric tumour and adjacent normal regions were collected with ethical approval and informed consent from 42 patients . After histopathological confirmation by two pathologists, total RNA were isolated from tumour and corresponding normal tissue and gene expression was measured by qRT-PCR. Statistical analysis was performed by R package. Result and Discussion: We identified that TFF1, TFF2, TFF3, GKN1, GKN2 are significantly differentially expressed in gastric tumour tissue with respect to adjacent normal tissue whereas mucins had no significant deregulation. TFF1, TFF2, GKN1 and GKN2 are found to be down regulated in most tumour tissues compared to adjacent normal. Only GKN2 expression is significantly different among diffuse and intestinal subtypes . Our statistical analysis also revealed that gene expression of TFF1, TFF2, GKN1 and GKN2 are highly correlated with the gene expression of MUC5AC. Further study with larger patient sample is required to fully understand the complex interplay of trefoil, gastrokines and mucins in GC. Citation Format: Dipjit Basak, Pronoy Kanti Mondal, Brishti Mondal, Ranajoy Ghosh, Aniket Halder, Gopal Krishna Dhali, Abhijit Chowdhury, Indranil Mukhopadhyay, Shalini Datta. Gene expression of trefoil proteins, gastrokines and mucins in Indian gastric cancer patients [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 1518.
In situ self-spray coating system that can uniformly disperse a poorly water-soluble H2S donor on the colorectal surface to treat inflammatory bowel diseases
Authors: Wei-Chih Lin, Wen-Yu Pan, Chen-Kao Liu, Wu-Xuan Huang, Hsiang-Lin Song, Kai-Sheng Chang, Meng-Ju Li, Hsing-Wen Sung
Journal: Biomaterials (2018)
Polyphenol–Poloxamer Self‐Assembled Supramolecular Nanoparticles for Tumor NIRF/PET Imaging
Authors: Xinyu Wang, Junjie Yan, Donghui Pan, Runlin Yang, Lizhen Wang, Yuping Xu, Jie Sheng, Yuanyuan Yue, Qianhuan Huang, Yanting Wang, Rongrong Wang, Min Yang
Journal: Advanced Healthcare Materials (2018)

Abstract Self‐assembled supramolecular nanoparticles have remarkable benefits in bioimaging and drug delivery. Here it is first reported that polyphenol and poloxamer self‐assemble supramolecular nanoparticles (PPNPs). PPNPs are fabricated by multivalent hydrogen bonding between tannic acid and Pluronic F‐127 together with hydrophobic interactions of poly(propylene oxide) chains, to be applied in tumor near‐infrared fluorescence (NIRF) imaging and positron emission tomography (PET) imaging. With near‐infrared fluorescent dyes such as IR780 encapsulated via hydrophobic interactions, PPNPs are used in NIRF imaging. PPNPs with excess phenolic hydroxyl groups chelating positron emitting radionuclide 89 Zr function as a PET contrast agent. The in vivo results show surprisingly higher fluorescence intensity in tumors than in other tissues. In addition, PPNPs exhibit good biocompatibility in various cell lines and do not induce hemolysis in vitro. In this study, it is demonstrated that biodegradable and biocompatible PPNPs are an excellent bimodal contrast agent for in vivo tumor imaging.
Transcatheter Aortic Valve Implantation in the United Kingdom
Authors: Peter F. Ludman, Neil Moat, Mark A. de Belder, Daniel J. Blackman, Alison Duncan, Winston Banya, Philip A. MacCarthy, David Cunningham, Olaf Wendler, Damian Marlee, David Hildick-Smith, Christopher P. Young, Jan Kovac, Neal G. Uren, Tomasz Spyt, Uday Trivedi, Jonathan Howell, Huon Gray
Journal: Circulation (2015)

We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality.Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007-2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 μmol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P<0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome.We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors.
Are eosinophilic pustular folliculitis of infancy and infantile acropustulosis the same entity?
Authors: J. VICENTE, A. ESPAÑA, M. IDOATE, M.E. IGLESIAS, E. QUINTANILLA
Journal: British Journal of Dermatology (1996)

Eosinopholic pustular folliculitis(EPF) fantile acropustulosis (IA) are pustular diseases affecting children in the first few months of life. They are characterized by eosinophilic infiltrates which have similar clinical and histological features. We present 6-month-old child with clinical and histological features of both entities.
Some Properties of Ionic and Nonionic Semipermeable Membranes
Authors: Alexandermauro
Journal: Circulation (1960)

Some fundamental properties of barriers are reviewed. The barrier of biologic significance is the plasma membrane. The role of the barrier in the transport of solvent and neutral solute species is discussed; 2 fundamental transport processes, namely, diffusion and mass flow are emphasized. The latter is shown to arise as the barrier offers increasing impedance to the movement of a given solute species; the barrier is then referred to as a semipermeable membrane, and the transport of the solvent as osmosis. The osmotic movement, undoubtedly one of the most important transport mechanisms in physiologic systems, is shown to arise from a gradient of hydrostatic pressure in the barrier. The need for the consideration of profiles of thermodynamic quantities is stressed. Finally, the third thermodynamic quantity, electrical potential, is introduced when ionic species are considered in the analysis of the fixed charge membrane.
The Sympathetic Nervous System Alterations in Human Hypertension
Authors: GuidoGrassi, AllynMark, MurrayEsler
Journal: Circulation Research (2015)

Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphas...
The Coexistence of Acute Rheumatic Fever and Sickle Cell-Hemoglobin C Disease
Authors: Sheldoniisker, Davidfinkelstein, Stanleyschwartz, Kerimanmarulyali, Antoniovaldes-Dapena
Journal: Circulation (1965)

The clinical and postmortem findings in a case of sickle cell-hemaglobin C disease complicated by acute rheumatic fever with accompanying carditis, and rheumatic pneumonitis are presented and discussed. This is believed to be the first such case reported. The recent literature pertaining to the cardiac manifestations of SS and SC hemoglobinopathies is briefly reviewed. A possible explanation for the failure of the rheumatic process to respond to conventional therapy in our patient is given.
Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall
Authors: ChristianWerner, TobiasFürster, ThomasWidmann, JaninePöss, CristianaRoggia, MiladHanhoun, JürgenScharhag, NicoleBüchner, TimMeyer, WilfriedKindermann, JudithHaendeler, MichaelBöhm, UlrichLaufs
Journal: Circulation (2009)

Background— The underlying molecular mechanisms of the vasculoprotective effects of physical exercise are incompletely understood. Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. This study examines the effects of exercising on vascular telomere biology and endothelial apoptosis in mice and the effects of long-term endurance training on telomere biology in humans. Methods and Results— C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks. Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle–checkpoint kinase 2, p16, and p53. Mice preconditioned by voluntary running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transg...
C-Reactive Protein Enhances LOX-1 Expression in Human Aortic Endothelial Cells
Authors: LingLi, NadiaRoumeliotis, TatsuyaSawamura, GenevièveRenier
Journal: Circulation Research (2004)

C-reactive protein (CRP), a characteristic inflammatory marker, is a powerful predictor of cardiovascular events. Recent data suggest that CRP may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a newly identified endothelial receptor for oxLDL that plays a pivotal role in oxLDL-induced endothelial dysfunction. Whether CRP may regulate endothelial LOX-1 and induce endothelial dysfunction through this receptor is unknown. In the present study, we studied the in vitro effect of CRP on LOX-1 expression in human aortic endothelial cells (HAECs) and the role of LOX-1 in CRP-induced human monocyte adhesion to endothelium and oxLDL uptake by endothelial cells. Incubation of HAECs with CRP enhanced, in a dose- and time-dependent manner, LOX-1 mRNA and protein levels. Induction of LOX-1 protein was already present at 5 μg/mL CRP and reached a maximum at 25 μg/mL. This effect was reduced by antibodies against CD32/CD64, ...