tbuckley/cabot-search huggingface dataset:
Abstract AP06: SUBCLINICAL SIGNIFICANCE OF CIRCULATING TUMOR CELLS IN EPITHELIAL OVARIAN CANCER AS AN EARLY INDICATEOR OF RECURRENCE
Authors: Carmen Ruiz, Serena Zheng, Bridgette Duggan, James Hicks, Peter Kuhn
Journal: Clinical Cancer Research (2017)

Abstract BACKGROUND: After diagnosis of cancer and subsequent treatment, a fraction of epithelial ovarian cancer (EOC) patients relapse with distant metastatic disease. While the fraction of the treated population that will relapse is predictable, there is not yet a way to determine the specific cases that will become metastatic. This transition between localized and disseminated cancer is clinically identified by the appearance of the patient's original cancer in a new anatomic location by various imaging methodologies or the increase of surrogate serum biomarkers. The actual biologic transition point, however, clearly occurs at some point prior to the time when metastasis becomes clinically evident. This becomes relevant during periods when disease is not clinically evident, where more sensitive identification methods of relapsing cancer may offer opportunities for therapy before tumor burden rises to an incurable level. PURPOSE: With the observation that circulating tumor cells (CTCs) are found in cancer patients with no clinical evidence of disseminated disease prior to clinically evident relapse, we sought to investigate whether the presence of CTCs in the circulatory compartment could possibly indicate tumor dissemination at its earliest time point and whether that could be leveraged to develop predictive models and markers that identify patients prior to clinical evidence of recurrent disease. METHODS: Peripheral blood samples collected after chemotherapy from 18 patients diagnosed with serous EOC were evaluated using the High Definition– Single Cell Assay (HD–SCA) for HD–CTCs enumeration, cytomorphological analysis and DNA copy number variation (CNV) profiling. RESULTS: HD–CTCs (≥1 CTC/mL) were detected in 9 (50%) of these patients, 3 of whom relapsed. Despite the genomic heterogeneity of the CTCs analyzed, single cell CNV profiles from one of these recurrent patients showed clonal cyclin E1 amplification on chromosome 19 and ARID1A tumor suppressor gene deletion on chromosome 1, genomic alterations consistent with EOC. CONCLUSION: The data suggests malignancy of multiple, single CTCs in recurrent patients, and further analysis of CTCs from non–recurrent patients could provide the means to determine the subclinical significance of CTCs in ovarian cancer. Earlier diagnosis of relapse, and subsequent personalized treatment, could eventually lead to more favorable prognoses in EOC patients. Citation Format: Carmen Ruiz, Serena Zheng, Bridgette Duggan, James Hicks and Peter Kuhn. SUBCLINICAL SIGNIFICANCE OF CIRCULATING TUMOR CELLS IN EPITHELIAL OVARIAN CANCER AS AN EARLY INDICATEOR OF RECURRENCE [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP06.
Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study
Authors: D Gray Heppner, Tracy L Kemp, Brian K Martin, William J Ramsey, Richard Nichols, Emily J Dasen, Charles J Link, Rituparna Das, Zhi Jin Xu, Eric A Sheldon, Teresa A Nowak, Thomas P Monath, DG Heppner, TL Kemp, BK Martin, WJ Ramsey, R Nichols, EJ Dasen, J Fusco, J Crowell, C Link, J Creager, TP Monath, R Das, ZJ Xu, R Klein, T Nowak, E Gerstenberger, R Bliss, EA Sheldon, RA Feldman, Brandon J Essink, WB Smith, L Chu, WM Seger, J Saleh, JL Borders, M Adams
Journal: The Lancet Infectious Diseases (2017)
Relationship between the pre-operative background enhancement coefficient under MRI of breast cancer and recurrence of postoperative chest wall.
Authors: Ruimei Ren, Haimin Lin, Tianshu Zhao
Journal: Journal of Clinical Oncology (2017)

e12091 Background: With the rapid development of MRI scanning technology , DCE-MRI in breast cancer has been one of the most sensitive examinations for the reason of allowing precise imaging, which can be helpful to demonstrate and evaluate the anatomical structures of breast cancer and its surrounding. What is more,through application of postprocessing technique of MRI,quantitative and half-qualitative data can be obtained for the diagnosis and the differential diagnosis of breast cancer. It is reported that the recurrence of breast cancer after breast conserving surgery is related with elevated BEC of MRI before operation as the result of the difficulty to find the micro-lesions and the margin of infiltrative lesions. Objective: Study on the relationship between the background enhancement coefficient of breast cancer under MRI before operation and recurrence of postoperative chest wall. Material and Methods: 194 cases of breast cancer patients undergoing radical surgery were retrospectively analyzed, all of which were confirmed by pathology and molecular classification.Before surgery all the patients did MRI and the BEC was measured.Aim for study on the relevance of the elevated BEC and chest wall recurrence,we investigate the relationship between the stage, grade,molecular subtype of breast cancer and the elevated BEC statistically. Results: The elevated BEC of the breast before operation is associated with chest wall recurrence after operation (P=0.045), and high expression of HER-2 (P=0.07). Multiple lesions of breast cancer and Ki-67&gt;14% also appeared to be associated with the elevated BEC (P=0.08).While there seem to be no correlation between the size of tumor ,LN metastases, nuclear and pathological grade,molecular typing, PR expression,ER expression, status of the LN capsule and the elevated BEC. Conclusions: The elevated BEC of breast before operation is an independent prognostic factor for chest wall recurrence after operation.Given BEC get a potential to make a brand new biomarker for breast cancer,further relevant research is needed.
Hospitalizations for Endocarditis and Associated Health Care Costs Among Persons with Diagnosed Drug Dependence — North Carolina, 2010–2015
Authors: Aaron T. Fleischauer, Laura Ruhl, Sarah Rhea, Erin Barnes
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Opioid dependence and overdose have increased to epidemic levels in the United States. The 2014 National Survey on Drug Use and Health estimated that 4.3 million persons were nonmedical users of prescription pain relievers (1). These users are 40 times more likely than the general population to use heroin or other injection drugs (2). Furthermore, CDC estimated a near quadrupling of heroin-related overdose deaths during 2002-2014 (3). Although overdose contributes most to drug-associated mortality, infectious complications of intravenous drug use constitute a major cause of morbidity leading to hospitalization (4). In addition to infections from hepatitis C virus (HCV) and human immunodeficiency virus (HIV), injecting drug users are at increased risk for acquiring invasive bacterial infections, including endocarditis (5,6). Evidence that hospitalizations for endocarditis are increasing in association with the current opioid epidemic exists (7-9). To examine trends in hospitalizations for endocarditis among persons in North Carolina with drug dependence during 2010-2015, data from the North Carolina Hospital Discharge database were analyzed. The incidence of hospital discharge diagnoses for drug dependence combined with endocarditis increased more than twelvefold from 0.2 to 2.7 per 100,000 persons per year over this 6-year period. Correspondingly, hospital costs for these patients increased eighteenfold, from $1.1 million in 2010 to $22.2 million in 2015. To reduce the risk for morbidity and mortality related to opioid-associated endocarditis, public health programs and health care systems should consider collaborating to implement syringe service programs, harm reduction strategies, and opioid treatment programs.
Abstract AP04: THE MOLECULAR DETECTION OF CIRCULATING TUMOR CELLS IN THE BLOOD OF OVARIAN CANCER PATIENTS
Authors: Eva Obermayr, Elisabeth Maritschnegg, Paul Speiser, Eva Schuster, Barbara Holzer, Nina Pecha, Robert Zeillinger
Journal: Clinical Cancer Research (2017)

Abstract PURPOSE OF THE STUDY: The detection of circulating tumor cells (CTCs) in the blood of cancer patients has raised considerable interest over the last decade as a promising biomarker of minimal residual disease in various solid tumors. Although hematogenous spread has not been deemed a major issue for ovarian cancer, there are several studies demonstrating the presence and prognostic impact of CTCs in ovarian cancer patients. Recently, we developed a protocol for the enrichment of CTCs from ovarian cancer blood samples, achieving a high purity of the target cells and enabling high specificity. EXPERIMENTAL PROCEDURES: Blood samples were enriched using a density gradient centrifugation (OncoQuick, Greiner Bio–One) followed by a micro–fluidic based isolation of the target cells using the Parsortix™ system (Angle plc.). The captured target cells were lysed, RNA was extracted (RNeasy Micro Kit, Qiagen) and transcribed into cDNA (ssVILO, Life Technologies). After a pre–amplification step (PreAmp Master Mix, Life Technologies), the transcript levels of selected genes (EpCAM, PPIC, TUSC3, EMP2, LAMB1, MAL2, FN1) were measured using RT–qPCR. Additionally, density gradient enriched cells were immuno–fluorescently stained targeting CK8/18/19, PPIC, TP53 and CD45. SUMMARY: By combining a density gradient based pre–enrichment and the micro–fluidic Parsortix™ technology we achieved an up to 106–fold depletion of blood cell contamination. The analysis of CTC–related transcripts in the enriched samples indicated the presence of CTCs in 78% of the ovarian cancer blood samples taken at primary diagnosis (N=15) and in 80% of the samples taken at relapse (N=9). Concordant results of immuno–fluorescent staining and RT–qPCR were obtained in just 30% of ovarian cancer samples. By adding further 22 RT–qPCR markers, 92% of all cancer patients (n=13) and 100% of the ovarian cancer patients (n=7) were classified as being CTC–positive by RT–qPCR. CONCLUSIONS: In conclusion, we developed a protocol which enabled the detection of CTC–related transcripts in the majority of ovarian cancer blood samples, which is a clear improvement in sensitivity as compared to earlier studies employing density gradient centrifugation as the only enrichment step. Our results are currently validated in the large cohort of platinum resistant ovarian cancer patients provided by a multi–center Gannet53 study. Citation Format: Eva Obermayr, Elisabeth Maritschnegg, Paul Speiser, Eva Schuster, Barbara Holzer, Nina Pecha, Robert Zeillinger. THE MOLECULAR DETECTION OF CIRCULATING TUMOR CELLS IN THE BLOOD OF OVARIAN CANCER PATIENTS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP04.
Unique Cardiac Purkinje Fiber Transient Outward Current β-Subunit Composition
Authors: Ling Xiao, Tamara T. Koopmann, Balázs Ördög, Pieter G. Postema, Arie O. Verkerk, Vivek Iyer, Kevin J. Sampson, Gerard J.J. Boink, Maya A. Mamarbachi, Andras Varro, Luc Jordaens, Jan Res, Robert S. Kass, Arthur A. Wilde, C.R. Bezzina, Stanley Nattel
Journal: Circulation Research (2013)

A chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis of transient outward current (I(to)) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF I(to) and that its overexpression might specifically alter PF I(to) properties and repolarization.To assess the potential role of DPP6 in PF I(to).Clinical data in 5 idiopathic ventricular fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF and ventricular muscle I(to) had similar density, but PF I(to) differed from ventricular muscle in having tetraethylammonium sensitivity and slower recovery. DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced, I(to) density and tetraethylammonium sensitivity in canine PF but not in ventricular muscle cells. The K(+)-channel interacting β-subunit K(+)-channel interacting protein type-2, essential for normal expression of I(to) in ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary cells produced small I(to); I(to) amplitude was greatly enhanced by coexpression with K(+)-channel interacting protein type-2 or DPP6. Coexpression of DPP6 with Kv4.3 and K(+)-channel interacting protein type-2 failed to alter I(to) compared with Kv4.3/K(+)-channel interacting protein type-2 alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF I(to) composition) greatly enhanced I(to) compared with Kv4.3/neuronal calcium sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that I(to) enhancement can greatly accelerate PF repolarization.These results point to a previously unknown central role of DPP6 in PF I(to), with DPP6 gain of function selectively enhancing PF current, and suggest that a DPP6-mediated PF early-repolarization syndrome might be a novel molecular paradigm for some forms of idiopathic ventricular fibrillation.
Pharmacokinetics (PK) and pharmacodynamics (PD) of rituximab administered by faster infusion in patients with previously untreated diffuse large B-cell (DLBCL) or follicular lymphoma (FL).
Authors: Michael Brewster, Deborah Hurst, Akiko Chai, Edward James Lee, Gargi H. Upadhyaya, Shaker R. Dakhil
Journal: Journal of Clinical Oncology (2012)

6591 Background: Faster infusion of rituximab (R) can improve patient (pt) convenience and reduce strain on oncology unit resources. To assess the safety, PK and PD of a 90-min infusion rate for R in NHL pts, a prospective, open-label, phase III, multicenter, single-arm trial (RATE) was conducted. Safety results have been previously presented (ASH 2011). Methods: Pts (≥18 yrs old) with untreated DLBCL or FL, without clinically significant cardiovascular disease, received R-chemotherapy. R (375 mg/m 2 ) was given at the standard infusion rate (4–6 h) in Cycle 1. Pts who did not experience Grade 3/4 infusion-related reactions (IRRs) and who had circulating lymphocyte counts ≤ 5000/µl before Cycle 2, received subsequent R (375 mg/m 2 ) infusions at a 90-min rate: 20% over 30 min then 80% over the next 60 min. Pts (n=14) who completed all cycles at the 90-min infusion rate gave further serum samples up to 16 wks after the last cycle for determination of PK parameters, including R terminal half-life (t ½ ), maximum serum concentration (C max ), systemic clearance (CL) and volume of distribution (V). Results: For pts (n=365) that received the 90-min infusion rate at Cycle 2, serum R concentrations increased over the course of the study. Estimated median values were: CL, 107 ml/d; V at steady state, 3830 ml; t ½ , 24.6 d. At Cycle 2, 50.5% of pts had undetectable CD19+ levels; this percentage increased during the study (68.3% Cycle 6, 87.5% Cycle 8). Conclusions: Peak R levels were higher than seen in published data of q3w R regimens but comparable with levels seen for q1w R regimens. The estimated median values for CL, V, t ½ and B cell (CD19+) depletion with the 90-min infusion rate were similar to previously reported estimates for infusions at the standard rate. These results, in combination with the safety profile previously reported, show that a faster infusion of R can be an acceptable option for selected NHL pts who tolerated the standard infusion rate at Cycle 1 without a severe IRR. [Table: see text]
Novel therapeutic clues in thyroid carcinomas: The role of targeting cancer stem cells
Authors: Alessandro Antonelli, Concettina La Motta
Journal: Medicinal Research Reviews (2017)

Abstract Thyroid carcinomas (TCs), the most common endocrine tumors, represent the eighth most common cancer diagnosed worldwide in both women and men. To treat these malignancies, several drugs are now available and a number of novel ones have been enrolling in clinical trials, addressing both oncogenic pathways in cancer cells and angiogenic pathways in tumor endothelial cells. However, their use is not devoid of serious toxicities and their efficacy is limited, being dependent on carcinoma typology and the occurrence of acquired resistance. Accordingly, it is time to recast therapeutic strategies against these types of tumors to get to newer and fully effective drugs. In this perspective, latest findings demonstrate that cancer stem cells (CSCs) represent a challenging target to strike. They possess core traits of self‐renewal and differentiation, being resistant to the effects of chemotherapy and radiation and playing a key role in mediating metastasis. Therefore, basic molecular elements sustaining both development of thyroid cancer stem cells and their residence in the stemness condition represent a set of innovative and still unexplored targets to address. In this review, a thorough literature survey has been accomplished, to take stock of mechanisms governing thyroid carcinomas and to point out both their currently available treatments and the novel forthcoming ones. Pubmed, Scifinder and ClinicalTrials.gov were exploited as research applications and registry database, respectively. Original articles, reviews, and editorials published within the last ten years, as well as open clinical investigations in the field, were analyzed to suggest new exciting therapeutic opportunities for people affected by TCs.
TREATMENT OF PRURITUS ANI AND ANAL FISSURE: THE USE OF ANAESTHETIC SOLUTIONS IN OIL
Authors: W. B. Gabriel
Journal: BMJ (1929)

ONE of the most striking facts about the world-wide and extraordinarily fatal epidemic of " influenza " in, 1918 was that in the bad cases one of the symptoms was a peeuliar blne or violet form of cyanosis.At the time this cvanosis was attributed to bronchi-puenmonia; bTut aga;inst thi.s explanIiationi was the fact that administration of oxygen failed to abolish or diminish the cyanosis, whereas in the cyanosis which sometimes accompanies ordiniar-y lobar pteu- moiia, or the lung iniflanmmation of poisoning by irritant g:as, the eyallosis cani usually be abolished easily by adding s6nme oxygen to the inspired air.In a paper puiblished in the British, Medical Joirnal of August 1st, 1925 (p.187), on the presence pest mortem of
The AMP-Related Kinase (AMPK) Induces Ca <sup>2+</sup> -Independent Dilation of Resistance Arteries by Interfering With Actin Filament Formation
Authors: Kai Michael Schubert, Jiehua Qiu, Stephanie Blodow, Margarethe Wiedenmann, Lubomir T. Lubomirov, Gabriele Pfitzer, Ulrich Pohl, Holger Schneider
Journal: Circulation Research (2017)

Decreasing Ca2+ sensitivity of vascular smooth muscle (VSM) allows for vasodilation without lowering of cytosolic Ca2+. This may be particularly important in states requiring maintained dilation, such as hypoxia. AMP-related kinase (AMPK) is an important cellular energy sensor in VSM. Regulation of Ca2+ sensitivity usually is attributed to myosin light chain phosphatase activity, but findings in non-VSM identified changes in the actin cytoskeleton. The potential role of AMPK in this setting is widely unknown.To assess the influence of AMPK on the actin cytoskeleton in VSM of resistance arteries with regard to potential Ca2+ desensitization of VSM contractile apparatus.AMPK induced a slowly developing dilation at unchanged cytosolic Ca2+ levels in potassium chloride-constricted intact arteries isolated from mouse mesenteric tissue. This dilation was not associated with changes in phosphorylation of myosin light chain or of myosin light chain phosphatase regulatory subunit. Using ultracentrifugation and confocal microscopy, we found that AMPK induced depolymerization of F-actin (filamentous actin). Imaging of arteries from LifeAct mice showed F-actin rarefaction in the midcellular portion of VSM. Immunoblotting revealed that this was associated with activation of the actin severing factor cofilin. Coimmunoprecipitation experiments indicated that AMPK leads to the liberation of cofilin from 14-3-3 protein.AMPK induces actin depolymerization, which reduces vascular tone and the response to vasoconstrictors. Our findings demonstrate a new role of AMPK in the control of actin cytoskeletal dynamics, potentially allowing for long-term dilation of microvessels without substantial changes in cytosolic Ca2+.
Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer
Authors: Gunter von Minckwitz, Marion Procter, Evandro de Azambuja, Dimitrios Zardavas, Mark Benyunes, Giuseppe Viale, Thomas Suter, Amal Arahmani, Nathalie Rouchet, Emma Clark, Adam Knott, Istvan Lang, Christelle Levy, Denise A. Yardley, Jose Bines, Richard D. Gelber, Martine Piccart, Jose Baselga
Journal: New England Journal of Medicine (2017)

Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer.
Comparison of enhanced liver fibrosis test with procollagen-3 N-terminal peptide (P3NP) as a marker for liver fibrosis
Authors: P. Arzpayma, J. Callander, A. Macfarlane
Journal: British Journal of Dermatology (2017)

Linked Article: van der Voort et al. Br J Dermatol 2017; 176:1599–1606.
Abstract 328: Med13 regulates cardiac metabolism
Authors: Kedryn K Baskin, Chad E Grueter, Christine M Kusminski, Philipp E Scherer, Rhonda Bassel-Duby, Eric N Olson
Journal: Circulation Research (2013)

Background: The heart is a metabolic organ that primarily utilizes fatty acids as energy substrate. While it is well established that the heart is metabolically flexible, the transcriptional network regulating cardiac metabolism is only partially understood. We have previously demonstrated that cardiac overexpression of Med13, a component of the Mediator Complex that regulates transcription, results in a lean phenotype with enhanced basal metabolic rates. We now investigate the mechanisms contributing to metabolic changes in mice with cardiac over-expression of Med13(Med13cTg). Methods and Results: Cardiac fludeoxyglucose (18F-FDG)-PET imaging analysis revealed that Med13cTg hearts take up more glucose than wild type littermates. To determine pathways responsible for enhanced glucose uptake, ventricles from Med13cTg mice were subjected to RNA-seq and metabolomic analysis. The expression of fatty acid oxidation genes was decreased in Med13cTg hearts, accompanied by an increase in acyl CoA and a decrease in acetyl CoA. These data suggest that beta oxidation is decreased in Med13cTg hearts. Mitochondria function was therefore determined in Med13cTg hearts by performing electron-flow analyses and assessing oxygen consumption rates. Indeed, oxygen consumption rates were decreased in mitochondria isolated from Med13cTg hearts. Expression of Krebs Cycle genes and corresponding intermediary metabolites were also decreased in Med13cTg hearts, suggesting decreased flux through this pathway as well. Conclusions: Overexpression of Med13 in the heart increases glucose uptake and decreases fatty acid oxidation in the heart. We speculate that Med13 transcriptionally regulates key mediators of cardiac metabolism. The mechanisms by which this occurs are currently under investigation.