tbuckley/cabot-search huggingface dataset:
Risk assessment of anticancer treatments beyond performance status: A prospective study in 277 cancer patients.
Authors: Anne Jouinot, Clara Vazeille, Jean-Philippe Durand, Nathalie Neveux, Anatole Cessot, Pascaline Boudou-Rouquette, Julie Giroux, Ithar Gataa, Sylvie Bellanger, Jerome Alexandre, Luc Cynober, Francois Goldwasser
Journal: Journal of Clinical Oncology (2015)

9620 Background: Alterations of performance status (PS) and of nutritional status are predictors of acute toxicity following anticancer treatment. Resting energy expenditure (REE) is often increased in cancer patients and may be a major determinant for the alteration of nutritional status and the development of precachexia and cachexia. We investigated whether abnormal metabolism could predict early acute toxicity (EAT). Methods: In this prospective observational monocentric study, REE was measured by indirect calorimetry before anticancer treatment initiation. C-Reactive Protein (CRP), albumin, transthyretin and PS were collected. Measured REE was compared with predicted REE as defined by the Harris-Benedict formula. Patients were classified as hypometabolic (REE < 90%), normometabolic (90-110%) or hypermetabolic ( > 110%). Toxicity was assessed after the first cycle of treatment. An EAT was defined as any event leading to unplanned hospital admission, dose reduction, treatment delay ( > 7 days) or discontinuation. Results: A total of 277 patients (pts) with solid tumors (gastro-intestinal 25%, genitourinary 23%, thoracic 22%) were included. Sex ratio: 1.25; median age: 63 years (20-91). Most of the pts (211; 76%) had locally advanced or metastatic disease and were treated with chemotherapy (246; 89%) or tyrosine-kinase inhibitor (30; 11%). Calorimetry revealed pts with either normo- (29%), hyper- (51%) or hypometabolism (20%). A subset of 59 pts (21%) experienced an EAT. The occurrence of EAT was associated with poor PS (2-3 vs 0-1: OR = 2.04 [1.12-3.73], p = 0.029), low albumin ( < 35 vs ≥ 35g/l: OR = 2.39 [1.03-5.54], p = 0.048), inflammation (CRP ≥ 10 vs < 10mg/l: OR = 2.43 [1.35-4.37], p = 0.004) and abnormal metabolism (abnormal vs normal: OR = 2.36 [1.13-4.95], p = 0.023). In multivariate analysis, elevated CRP was an independent predictor of EAT (p = 0.047). The REE was associated with higher sensitivity (83%) than CRP (55%), PS (41%) and albumin (17%) to predict EAT. Conclusions: Pts with abnormal metabolism experience more early acute toxicity. The measurement of resting energy expenditure might improve the detection of patients at risk for toxicity and missed with the standard clinical evaluation.
Combining activatable nanodelivery with immunotherapy in a murine breast cancer model
Authors: Azadeh Kheirolomoom, Matthew T. Silvestrini, Elizabeth S. Ingham, Lisa M. Mahakian, Sarah M. Tam, Spencer K. Tumbale, Josquin Foiret, Neil E. Hubbard, Alexander D. Borowsky, Katherine W. Ferrara
Journal: Journal of Controlled Release (2019)
Degradation of extracellular matrix measured in serum for predicting mortality risk in women diagnosed with cancer: The Prospective Epidemiologic Risk Factor (PERF I) study.
Authors: Nicholas Willumsen, Stephanie Nina Kehlet, Cecilie Liv Bager, Kathrine Dragsbaek, Jesper Neergaard, Henrik Bo Hansen, Anne-Christine Bay-Jensen, Diana Julie Leeming, Claus Christiansen, Morten Asser Karsdal
Journal: Journal of Clinical Oncology (2015)

9582 Background: Extracellular matrix (ECM) turnover mediated by matrix metalloproteinase (MMP) has been speculated to be associated with cancer diagnosis and mortality. No tools have so far been able to quantify this. Degradation of ECM is part of the malignant changes that drives cancer. The most abundant ECM protein is type I collagen. MMP mediated degradation of type I collagen in serum can be quantified by the novel C1M ELISA assay. The aim of the current study was to investigate whether MMP mediated ECM degradation (C1M) was predictive of cancer mortality in a large prospective study. Methods: In the period 1999-2001, 5,856 women aged 60-85 participated in the Prospective Epidemiologic Risk Factor (PERF I) study. Demographics and serum samples were collected at time of enrollment. Cancer diagnoses, cause and time of death were obtained from Danish registries ultimo 2014. Serum C1M levels were assessed by ELISA and divided into quartiles (Q1-Q4). Hazard ratios (HR) for all-cause and cancer-specific mortality were determined by Cox-regression analysis and adjusted for common risk factors: age, smoking, alcohol intake, exercise and BMI. Women deceased >3 years after enrollment was excluded from analysis. Results: Within 3 years from PERF I enrollment subjects with high serum C1M levels at baseline showed significant increased mortality (see Table). The 3-year HR for all-cause mortality and cancer-specific mortality was >2 when comparing Q1 to Q4 for all women. Women diagnosed with cancer (n=1280) had an HR for all-cause mortality of >2.5 compared to cancer survivors. Adjusting for common confounders did not change significance. Conclusions: MMP-mediated degradation of the ECM was predictive of cancer mortality by 2.3 fold, and predicted for mortality for cancer patients with >2.5-fold within 3 years of follow-up. Cohort All With cancer diagnosis Mortality All cause Cancer specific All cause n, total 4408 4333 1280 n, death within 3 years from enrollment 187 112 112 HR (95% CI), C1M Q4 relative to Q1, p-value 2.08 (1.30-3.33), p=0.0024 2.31 (1.27-4.19), p=0.0064 2.59 (1.45-4.63), p=0.0014
Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics
Authors: Carlos G. Santos-Gallego, Juan Antonio Requena-Ibanez, Rodolfo San Antonio, Kiyotake Ishikawa, Shin Watanabe, Belen Picatoste, Eduardo Flores, Alvaro Garcia-Ropero, Javier Sanz, Roger J. Hajjar, Valentin Fuster, Juan J. Badimon
Journal: Journal of the American College of Cardiology (2019)
Acid‐Responsive H<sub>2</sub>‐Releasing 2D MgB<sub>2</sub> Nanosheet for Therapeutic Synergy and Side Effect Attenuation of Gastric Cancer Chemotherapy
Authors: Mingjian Fan, Yanyuan Wen, Dien Ye, Zhaokui Jin, Penghe Zhao, Danyang Chen, Xifeng Lu, Qianjun He
Journal: Advanced Healthcare Materials (2019)

Abstract The hydrogen molecule is recognized as a high potential to attenuate toxic side effects of chemotherapy and also enhance chemotherapeutic efficacy, and the development of a novel hydrogen‐generating prodrug for facile, safe, and efficient hydrogen delivery is vitally important for combined hydrogenochemotherapy but is still challenging. Here, targeting gastric cancer, a 2D magnesium boride nanosheet (MBN) is synthesized as a new type of acid‐responsive hydrogen‐releasing prodrug by an ultrasound‐assisted chemical etching route, which is used to realize hydrogenochemotherapy by combination of facile oral administration of polyvinylpyrrolidone (PVP)‐encapsulating MBN (MBN@PVP) pills with routine intravenous injection of doxorubicin (DOX). The MBN@PVP pill has high stability in normal tissues/blood environments as well as high gastric acid‐responsiveness with sustained release behavior, which matches well with its metabolism rate in the stomach in great favor of continuous and long‐term hydrogen administration. Hydrogenochemotherapy with DOX+MBN@PVP has remarkably prolonged the survival time of gastric tumor‐bearing mice by reducing the toxic side effects of chemotherapy. The mechanism for therapeutic synergy and side effect attenuation of hydrogenochemotherapy is discovered to be derived from the selectivity of hydrogen molecules in inhibiting aerobic respiration of gastric cells but activating aerobic respiration of normal cells including marrow mesenchymal stem cells and cardiac, hepatic, and splenic cells.
Stem cells from human exfoliated deciduous teeth as an alternative cell source in bio-root regeneration
Authors: Xueting Yang, Yue Ma, Weihua Guo, Bo Yang, Weidong Tian
Journal: Theranostics (2019)

A stem cell-mediated bioengineered tooth root (bio-root) has proven to be a prospective tool for the treatment of tooth loss.As shown in our previous studies, dental follicle cells (DFCs) are suitable seeding cells for the construction of bio-roots.However, the DFCs which can only be obtained from unerupted tooth germ are restricted.Stem cells from human exfoliated deciduous teeth (SHEDs), which are harvested much more easily through a minimally invasive procedure, may be used as an alternative seeding cell.In this case, we compared the odontogenic characteristics of DFCs and SHEDs in bio-root regeneration.Methods: The biological characteristics of SHEDs and DFCs were determined in vitro.The cells were then induced to secrete abundant extracellular matrix (ECM) and form macroscopic cell sheets.We combined the cell sheets with treated dentin matrix (TDM) for subcutaneous transplantation into nude mice and orthotopic jaw bone implantation in Sprague-Dawley rats to further verify their regenerative potential.Results: DFCs exhibited a higher proliferation rate and stronger osteogenesis and adipogenesis capacities, while SHEDs displayed increased migration ability and excellent neurogenic potential.Both dental follicle cell sheets (DFCSs) and sheets of stem cells from human exfoliated deciduous teeth (SHEDSs) expressed not only ECM proteins but also osteogenic and odontogenic proteins.Importantly, similar to DFCSs/TDM, SHEDSs/TDM also successfully achieved the in vivo regeneration of the periodontal tissues, which consist of periodontal ligament fibers, blood vessels and new born alveolar bone.Conclusions: Both SHEDs and DFCs possessed a similar odontogenic differentiation capacity in vivo, and SHEDs were regarded as a prospective seeding cell for use in bio-root regeneration in the future.
Abstract 15235: Characterization of Hypoxia-induced Long Non-coding RNAs in Endothelial Cells
Authors: Philipp Neumann, Nicolas Jaé, David John, Shizuka Uchida, Marcus Krüger, Stefanie Dimmeler
Journal: Circulation (2015)

RNA deep sequencing revealed that the majority of the genome is transcribed, however, only 2% of all transcripts encode for proteins. The remaining transcripts are referred to as non-coding RNAs and can be divided into small non-coding RNAs (&lt;200nt) and long non-coding RNAs (lncRNAs; &gt;200nt). Recent studies suggest that lncRNAs can regulate gene expression at various stages, e.g. by acting as scaffolds, by modulating splicing, or by chromatin modification. Regarding endothelial cells (EC), the response to hypoxia and the regulation of angiogenic activity are key events in the context of several diseases, however, the involvement of regulatory lncRNAs and their molecular function is still elusive. To systematically determine the regulation of lncRNAs by hypoxia, we performed RNA-seq in HUVEC after exposure to hypoxia (24h; 0.2% O 2 ) and identified 71 lncRNAs to be significantly up- (p≤0.01) and 78 lncRNAs to be down-regulated in comparison to normoxic conditions. qRT-PCR was used to validate the hypoxia-dependent regulation of 5 selected lncRNAs (Hyp_up_1 to Hyp_up_5). Since hypoxia controls the angiogenic function of EC, we next investigated whether our candidate lncRNAs affect endothelial cell sprouting as an in vitro measurement for angiogenic response. Silencing was achieved by GapmeRs (Hyp_up_1, 3) or siRNAs (Hyp_up_2, 5). Strikingly, only silencing of Hyp_up_1 significantly reduced sprouting under basal conditions and VEGF stimulation. Therefore, we selected Hyp_up_1 for further functional characterization: First, nuclear cytoplasmic fractionation revealed its predominant nuclear localization. Second, RNA immunoprecipitation (RIP) showed that Hyp_up_1 is mainly associated with repressive chromatin marks (3meH3K27) indicating that it may be involved in epigenetic gene regulation. Third, GO term analysis based on exon array data revealed a reduced expression of angiogenesis related genes upon Hyp_up_1 silencing. Finally, using antisense affinity purification and mass spectrometry, we identified several Hyp_up_1 binding proteins and confirmed their interaction by RIP. Hyp_up_1 bound proteins included PTBP1/U2AF65, two splicing regulators, as well as LOXL2, a transcription factor known to mediate angiogenic functions in EC.
A self-assembled, modular nucleic acid-based nanoscaffold for multivalent theranostic medicine
Authors: Veronica Liv Andersen, Mathias Vinther, Rajesh Kumar, Annika Ries, Jesper Wengel, Jesper Sejrup Nielsen, Jørgen Kjems
Journal: Theranostics (2019)

Rationale: Within the field of personalized medicine there is an increasing focus on designing flexible, multifunctional drug delivery systems that combine high efficacy with minimal side effects, by tailoring treatment to the individual.Methods: We synthesized a chemically stabilized ~4 nm nucleic acid nanoscaffold, and characterized its assembly, stability and functional properties in vitro and in vivo.We tested its flexibility towards multifunctionalization by conjugating various biomolecules to the four modules of the system.The pharmacokinetics, targeting capability and bioimaging properties of the structure were investigated in mice.The role of avidity in targeted liver cell internalization was investigated by flow cytometry, confocal microscopy and in vivo by fluorescent scanning of the blood and organs of the animals. Results:We have developed a nanoscaffold that rapidly and with high efficiency can self-assemble four chemically conjugated functionalities into a stable, in vivo-applicable system with complete control of stoichiometry and site specificity.The circulation time of the nanoscaffold could be tuned by functionalization with various numbers of polyethylene glycol polymers or with albumin-binding fatty acids.Highly effective hepatocyte-specific internalization was achieved with increasing valencies of tri-antennary galactosamine (triGalNAc) in vitro and in vivo.Conclusion: With its facile functionalization, stoichiometric control, small size and high serum-and thermostability, the nanoscaffold presented here constitutes a novel and flexible platform technology for theranostics.
Abstract 463: Elevated Oxidative Stress and Reduction of Hydrogen Sulfide (H <sub>2</sub> S) and Nitric Oxide (NO) in HIV Patients: Possible Role in Cardiovascular (CV) Disease
Authors: Kazi N Islam, Erinn Donnelly, Christopher Parsons, David J Lefer
Journal: Circulation Research (2016)

Background: HIV attacks the immune system and weakens the ability to fight infections/disease. HIV infection confers approximately two-fold higher risk of cardiac events compared with the general population. ADMA, high-sensitivity CRP (hs-CRP) and IL-6 are well-characterized biomarkers of cardiac events. H 2 S and NO exert potent antioxidant properties and are cardioprotective. The present study was undertaken to determine the levels of H 2 S, NO, and CV disease biomarkers in HIV patients. Methods: Plasma from both HIV patients and normal subjects were used for all assays. Oxidative stress was determined by analyzing the levels of advanced oxidation protein products and H 2 O 2 . Antioxidant levels were determined by measuring the levels of trolox equivalent capacity. ADMA, hs-CRP, and IL-6 were determined by using ELISA. The levels of H 2 S/sulfane sulfur and nitrite were determined in plasma by using gas chromatography and HPLC, respectively. Results: We observed a marked induction in the levels of oxidative stress and decreased antioxidant status in the plasma of HIV patients as compared with the controls. CV risk factors levels such as ADMA, hs-CRP, and IL-6 were significantly increased in the plasma of HIV patients. Significant reduction in the levels of both nitrite and H 2 S/sulfane sulfur were observed in the plasma of HIV patients as compared with controls. Conclusion: Our data demonstrate significant increases in oxidative stress and CV disease biomarkers in conjunction with decreased bioavailability of H 2 S and NO in HIV patients. Diminished levels of these two cardioprotective gaseous signaling molecules may be involved in the pathogenesis of CV disease in the setting of HIV.
Response by Mueller et al to Letter Regarding Article, “Deletion of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Accelerates Atherosclerosis Regression and Increases C-C Chemokine Receptor Type 7 (CCR7) Expression in Plaque Macrophages”
Authors: Paul A. Mueller, Lin Zhu, Hagai Tavori, Katherine T. Huynh, Ilaria Giunzioni, John M. Stafford, MacRae F. Linton, Sergio Fazio
Journal: Circulation (2019)
THU-216-Rapid turnover of HBV cccDNA in nucleoside-treated chronic hepatitis B patients during drug resistance emergence and breakthrough
Authors: Qi Huang, Bin Zhou, Dawei Cai, Yuhua Zong, Yaobo Wu, Shi Liu, Haitao Guo, Jian Sun, Jinlin Hou, Richard Colonno
Journal: Journal of Hepatology (2019)
Stage dependent increase of CCL2 and CCL5 in peripheral blood of colorectal cancer patients.
Authors: Heinz Philipp Laubli, Katharina-Susanne Spanaus, Alfred Zippelius, Lubor Borsig
Journal: Journal of Clinical Oncology (2015)

e22111 Background: Tumor associated inflammation leads to the recruitment of immune cells that contribute to cancer progression. Recruitment of monocytes and their polarization to tumor promoting M2 macrophages is facilitated by chemokines. The two main monocytic chemokines CCL2 and CCL5 were previously associated with cancer progression. Although systemic levels of CCL2 and CCL5 were previously analyzed, their concentration and function during disease progression in colorectal cancer patients remains largely unknown. Methods: We retrospectively measured serum concentrations of CCL2 and CCL5 of patients with colorectal cancer and healthy controls by a cytometric bead array (BD Biosciences). Sera were obtained at the University Hospital in Zurich from 61 patients with histologically diagnosed colorectal cancer and from 21 healthy volunteers. Statistical analysis between loco-regional (stage I-III), disseminated (stage IV) groups and healthy volunteers were performed by one-way ANOVA. Results: CCL2 measurements of sera from patients with systemic disease were not significantly elevated compared to measurements of sera from patients with loco-regional disease (p = 0.21, mean concentrations stage I-III: 187.2 pg/mL, CI 95% 136.3-238.1, stage IV: 241.9 pg/mL, CI 95% 171.3-312.6). Both groups had significantly increased serum concentration of CCL2 when compared to serum samples from healthy controls (63.0 pg/mL, CI 95% 43.9-82.2). CCL5 concentrations were significantly higher in patients with stage IV disease when compared to patients with stage I-III disease (p < 0.01, stage I-III: 36.61 ng/mL CI 95% 29.9-43.32, stage IV: 57.51 CI 95% 45.96-69.05). Patients with metastatic disease had significantly increased concentrations in comparison with healthy controls (p < 0.05) but not patient with stage I-III disease (healthy controls: 40.24 ng/mL, CI 95% 33.89-46.58). Conclusions: CCL2 and CCL5 concentrations are elevated in the peripheral blood of patients with colorectal cancer. These observations and recent experimental findings suggest that inhibition of chemokine-mediated monocyte recruitment might be a strategy to interfere with cancer progression.
A guide to medical etiquette: article finding
Authors: David McAllister
Journal: BMJ (1999)

I'm sure that you've been told, on more than one occasion, how to find relevant articles for course work. First decide what you want to know, work out the synonyms, and broaden or narrow your searches using Medline or some simi-lar database. Then simply take your pick of the wonderful articles you've discovered and retrieve them from the library.

This is, of course, a lie. Input your search term, and the PC will produce 1000 citations. Limit the …
FRI-318-Effects of fatty acids and polyphenols from extra virgin olive oil in a murine animal dietary model knockout for the LDL receptor
Authors: Álvarez Amor Leticia, Amparo Luque-Sierra, Lourdes María Varela, Javier López-Beas, Rocío Gallego-Durán, Manuel Romero Gomez, Karim Hmadcha, Bernat Soria Escoms, Franz Martin
Journal: Journal of Hepatology (2019)
SAT-229-Risk of hepatocellular carcinoma in patients with chronic hepatitis C and stage-3 liver fibrosis after sustained virological response with direct acting antivirals
Authors: Maria Sanchez-Azofra, Inmaculada Fernández Vázquez, Maria Luisa Garcia, Lourdes Dominguez, Conrado Fernández-Rodríguez, Lucia Bonet, Marisa Montes, Pablo Ryan, Francisco Gea, Antonio Diaz Sanchez, Marian Garcia-Mayor, María Luisa Manzano, Leticia Gonzalez Moreno, Otilia Bisbal, Luz Martín Carbonero, Maria Luisa Gutierrez, Antonio Guerrero García, Miguel Rivero, Maria Elena Portales, Antonio Olveira Martin, Pilar Castillo
Journal: Journal of Hepatology (2019)
Novel p.K374E variant of <i>CPA1</i> causes misfolding-induced hereditary pancreatitis with autosomal dominant inheritance
Authors: Balázs Csaba Németh, Anna Orekhova, Wenying Zhang, Shannon A Nortman, Tyler Thompson, Péter Hegyi, Maisam Abu-El-Haija
Journal: Gut (2019)

We read the publication written by Lin et al 1 with great interest. The authors suggest that the majority of functionally defective carboxypeptidase A1 ( CPA1) mutations can elicit reduced expression due to nonsense-mediated decay (NMD) and therefore, only a small subset of the earlier reported CPA1 variants2 will predispose to chronic pancreatitis (CP) via the misfolding-dependent pathway.3 This paper seemingly offered an explanation for the earlier finding of Wu et al 4 where the authors reported no association with CP of rare functionally defective CPA1 variants in a large Chinese cohort.

However, it was earlier reported that functionally impaired variants of the CPA1 gene were strongly associated with sporadic cases of non-alcoholic, early-onset CP in European, Indian and Japanese populations.5 In addition, members of two Polish families carrying the p.S282P variant of the CPA1 gene developed hereditary CP.6 Protein misfolding and consequent endoplasmic reticulum (ER) stress were described as a potential disease mechanism of hereditary pancreatitis caused by loss-of-function variants of CPA1 and PRSS1 genes.3 6 7 Recently, the finding that a knock-in mouse model carrying the misfolding-causing p.N256K CPA1 variant developed CP confirmed the significance of the misfolding-dependent pathway in the disease mechanism8 and revealed a novel opportunity for in vivo …
Colloids, nanoparticles, and materials for imaging, delivery, ablation, and theranostics by focused ultrasound (FUS)
Authors: Adem Yildirim, Nicholas T. Blum, Andrew P. Goodwin
Journal: Theranostics (2019)

This review focuses on different materials and contrast agents that sensitize imaging and therapy with Focused Ultrasound (FUS).At high intensities, FUS is capable of selectively ablating tissue with focus on the millimeter scale, presenting an alternative to surgical intervention or management of malignant growth.At low intensities, FUS can be also used for other medical applications such as local delivery of drugs and blood brain barrier opening (BBBO).Contrast agents offer an opportunity to increase selective acoustic absorption or facilitate destructive cavitation processes by converting incident acoustic energy into thermal and mechanical energy.First, we review the history of FUS and its effects on living tissue.Next, we present different colloidal or nanoparticulate approaches to sensitizing FUS, for example using microbubbles, phase-shift emulsions, hollow-shelled nanoparticles, or hydrophobic silica surfaces.Exploring the science behind these interactions, we also discuss ways to make stimulus-responsive, or "turn-on" contrast agents for improved selectivity.Finally, we discuss acoustically-active hydrogels and membranes.This review will be of interest to those working in materials who wish to explore new applications in acoustics and those in acoustics who are seeking new agents to improve the efficacy of their approaches.