tbuckley/cabot-search huggingface dataset:
IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKI
Authors: Guowei Feng, Jimin Zhang, Yang Li, Yan Nie, Dashuai Zhu, Ran Wang, Jianfeng Liu, Jie Gao, Na Liu, Ningning He, Wei Du, Hongyan Tao, Yongzhe Che, Yong Xu, Deling Kong, Qiang Zhao, Zongjin Li
Journal: Journal of the American Society of Nephrology (2016)

Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan–IGF-1C hydrogel increased cell viability through paracrine effects. In vivo , cotransplantation of the chitosan–IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI.
Sugar tax campaigners plea for action ahead of obesity strategy
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Several leading UK public health campaigners have written to the prime minister to urge him to include a “sugar tax” on soft sugary drinks in the government’s long awaited childhood obesity strategy.

The letter to David Cameron, published in the Guardian ,1 cited “unequivocal evidence” from other countries that a tax would reduce sales of sugar sweetened soft drinks, particularly …
Abstract 18676: Anti-miR33 Therapy Induces PGC1a Expression to Regulate Immunometabolic Pathways in Atherosclerosis and Obesity
Authors: Denuja Karunakaran, A. Brianne Thrush, Zongbin Wu, Michele Geoffrion, Eleni Ramphos, Kathryn J Moore, Mary-Ellen Harper, Katey J Rayner
Journal: Circulation (2013)

Atherosclerosis and obesity are epidemic causes of morbidity and mortality, and immunometabolic mechanisms are at the intersection of both diseases. Recently, microRNA 33 (miR33) was identified as a novel and critical regulator of lipid metabolism and a therapeutic target for reducing atherosclerosis. However, the exact mechanism(s) by which anti-miR33 exerts these beneficial effects are unclear. Comprehensive microarray profiling of mRNA from atherosclerotic plaque macrophages of anti-miR33 treated mice identified PPARγ coactivator 1α (PGC1α) as a novel miR33 target gene that is markedly de-repressed. PGC1α is a key regulator of mitochondrial function and energy metabolism, and promoting its activity improves metabolic syndrome (e.g. insulin resistance, obesity, inflammation). Here, we determine if anti-miR33 therapy upregulates PGC1α and affects energy metabolism in atherosclerosis. Results: miR33 overexpression reduced the 3’UTR activity of PGC1α by 40% (p≤0.05), confirming it was a direct and specific target of miR33. Transfection of macrophages with either miR33 mimics or anti-miR33 in vitro resulted in a decrease or increase of Pgc1α mRNA and protein respectively. Using the Seahorse XF Flux Analyzer, we showed that anti-miR33 treatment boosted maximal mitochondrial oxygen consumption rate, confirming that anti-miR33 impacts positively on mitochondrial respiration. Anti-miR33 treated macrophages also increased the expression of known functional mitochondrial genes (e.g. Slc25a25, Nrf1, Bid and Mtch2), implying miR33 controls several genes in the mitochondrial metabolic pathway. Inhibition of miR33 in vivo in Ldlr-/- mice upregulated Pgc1α mRNA expression in adipose tissue, liver and macrophages. Adipose tissue from anti-miR33 treated obese mice also showed upregulation of so-called “browning” genes (e.g. Ucp-1, Elovl3) that contribute to increased energy utilization of white adipose tissue, possibly improving whole-body metabolism. Conclusion: Anti-miR33 therapy specifically targets PGC1α in macrophages and adipose tissue and improves mitochondrial function, all of which can positively regulate inflammatory and energy utilization processes in cardiometabolic diseases (eg. atherosclerosis and obesity).
CASE REPORTS
Authors: ARTHUR S. SAMUELS
Journal: American Journal of Psychiatry (1957)

The signs and symptoms of acute poisoning with chlorpromazine are similar to those reported for the antihistamines, to which it is chemically related. Poisoning is characterized most prominantly by central nervous system depression. In some cases there is also a phase of central nervous system stimulation with convulsions. Other prominent signs and symptoms may include marked hypotension to shock-like levels, tachycardia, tachypnea, hypothermia, diminished or absent reflexes, hypotonia, pinpoint pupils, stomatitis, blurred vision, and slurred speech. No permanent sequelae have been reported. Treatment is primarily symptomatic. Because of the possibility of convulsions and postictal depression, the use of stimulant drugs is not recommended(2). Noradrenalin may be effectively used to counteract hypotension. Constant vigilance should be maintained to guard against respiratory failure, with artificial respiration the treatment of choice if failure should take place. A broad-spectrum antibiotic may be used to prevent secondary infection and intravenous fluids administered to maintain fluid balance.
Hepatocellular Carcinoma in Children: Does Modified Platinum- and Doxorubicin-Based Chemotherapy Increase Tumor Resectability and Change Outcome? Lessons Learned From the SIOPEL 2 and 3 Studies
Authors: Maciej Murawski, Víola B. Weeda, Rudolf Maibach, Bruce Morland, Derek J. Roebuck, Arthur Zimmerman, Michela Casanova, Giorgio Perilongo, Veronique Laithier, Rejin Kebudi, Marcelo J. Scopinaro, Albert Shun, Benedicte Brichard, Beatriz de Camargo, Margaret Childs, Daniel C. Aronson, Piotr Czauderna
Journal: Journal of Clinical Oncology (2016)

The aim of this article is to present an experience of two prospective studies from the International Childhood Liver Tumor Strategy Group (SIOPEL 2 [S2] and SIOPEL [S3]) trials and to evaluate whether modified platinum- and doxorubicin-based chemotherapy is capable of increasing tumor resectability and changing patient outcomes.Between 1995 and 2006, 20 patients with hepatocellular carcinoma (HCC) were included in the S2 trial and 70 were included in the S3 trial. Eighty-five patients remained evaluable.Response to preoperative chemotherapy was observed in 29 of 72 patients (40%) who did not have primary surgery, whereas 13 patients underwent upfront surgery. Thirty-three patients had a delayed resection. Thirty-nine tumors never became resectable. Complete tumor resection was achieved in 34 patients (40%), including seven of those treated with liver transplantation (LTX). After a median follow-up period of 75 months, 63 patients (74%) had an event (a progression during treatment, a relapse after treatment, or death from any cause). Sixty patients died. Twenty-three of 46 patients (50%) who underwent tumor resection died. Eighteen of 27 patients (63%) with complete tumor resection (without LTX) and 20 of 34 patients (59%) with LTX survived. Only one of seven patients (14%) with microscopically involved margins survived. Overall survival at 5 years was 22%.Survival in pediatric HCC is more likely when complete tumor resection can be achieved. Intensification of platinum agents in the S2 and S3 trials has not resulted in improved survival. New treatment approaches in pediatric HCC should be postulated.
Enhanced Immunogenicity of Line 10 Guinea Pig Hepatocarcinoma Cells After Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Laura L. Correll, M.S., Larry D. Nielsen, Ph.D., Peter J. Kelleher, Ph.D., John W. Harbell, Ph.D., Percy Minden, M.D.
 7
Journal: JNCI Journal of the National Cancer Institute (1983)

Line 10 hepatocarcinoma cells derived from ascites in a strain 2 guinea pig were tumorigenic when transferred intradermally. After they had been cultured in vitro for 20 days or more in medium enriched with 10% fetal bovine serum (FBS), they became immunogenic. Injections of immunogenic cells did not cause lethal tumors, and recipients were resistant to subsequent challenges with tumorigenic line 10 cells. Resistance was specific since growth of line 1 cells, a syngeneic but antigenically distinct tumor, was not affected. Cells cultured in medium enriched with 10% calf bovine serum or 10% normal guinea pig serum or in reduced concentrations of FBS were less effective in inducing resistance. When cultured line 10 cells were injected ip into normal guinea pigs, ascites tumors developed that were tumorigenic. The growth rate of line 10 cells in culture was considerably decreased as determined by reduced [3H]thymidine incorporation and mitotic indices. The mechanism(s) responsible for enhancement of immunogenicity in cultured line 10 cells is discussed but was not determined.
Implementation of a Voice Messaging System is Associated With Improved Time-to-Treatment and Overall Survival in Patients With Hepatocellular Carcinoma
Authors: Ali Mokdad, Travis Browning, John C. Mansour, Hao Zhu, Amit G. Singal, Adam C. Yopp
Journal: Journal of the National Comprehensive Cancer Network (2016)

The diagnosis and treatment of cancer is a continuum, with multiple steps and interfaces between patients and providers allowing for potential delays in cancer recognition and subsequent treatment. The diagnosis and treatment of hepatocellular carcinoma (HCC) is especially prone to missteps along the continuum, leading to treatment delays due to non-tissue-based diagnosis and multiprovider treatments. The aim of this study was to evaluate outcome measures after implementation of a voice messaging system (VMS) designed to streamline patient referrals to downstream treatment physicians and ultimately reduce delays in HCC treatment, thereby improving outcome measures.A retrospective study of outpatients with HCC was conducted in a safety net hospital between February 2008 and January 2012. In February 2010, VMS notification of HCC to the ordering physician and downstream treating physicians was implemented. Patients were divided into 2 groups: (1) preintervention: diagnosis 2 years before implementation or failure of notification following implementation, and (2) postintervention: diagnosis 2 years after implementation. Demographics, tumor characteristics, treatment, and survival were compared.This study included 96 patients diagnosed with HCC: 51 in the preintervention group and 45 in the postintervention group. The main cause of chronic liver disease was HCV infection, and no differences in symptoms, liver dysfunction, tumor characteristics, or treatment were observed between groups. The time from diagnosis to clinic contact (0.5 vs 2.9 months; P=.003) and time from detection to treatment (2.2 vs 5.5 months; P=.005) was significantly shorter after implementation of the VMS. Barcelona Clinic Liver Cancer stage A status (hazard ratio [HR], 3.1; 95% CI, 2, 6), treatment (HR, 1.9; 95% CI, 1, 4), and VMS (HR, 1.8; 95% CI, 1, 3) were independently associated with overall survival. Patients diagnosed after implementation of the VMS had a median survival of 28.5 versus 15.7 months (P=.02).Implementation of VMS reduces time to treatment and time to clinic visit. Reduction in time to treatment is associated with improved outcome independent of tumor stage, underlying liver function, and treatment.
Relationship between serum vitamin D levels, adipocytes, and bone density in pre-adolescents and teenagers with newly diagnosed acute lymphoblastic leukemia.
Authors: A. Butturini, S. Mittelman, D. R. Freyer, V. Gilsanz, N. Hart, D. Nuno
Journal: Journal of Clinical Oncology (2010)

e20009 Background: Vitamin D regulates several metabolic and hormonal pathways, which may be important in both the biology of acute lymphoblastic leukemia (ALL) and the pathogenesis of therapy-related complications. In normal individuals, there is a linkage between Vitamin D and adipose tissue. In persons with ALL older than 10 years, obesity is associated with increased risk of relapse and therapy-related bone abnormalities, but its relationship with Vitamin D is unknown. Methods: We are conducting a clinical study to assess the relationship between obesity, vitamin D and bone and bone marrow changes in pre-adolescents and teenagers with ALL. At diagnosis, at end of Induction and before starting Maintenance therapy patients are studied for serum levels of vitamin 25[OH]D, PTH, alkaline phosphatase and calcium, and for total body fat and calcium content by DEXA scans. The size and the cortical bone density is assessed by CT; the bone marrow fat content is studied by MRI using a 1.5 T GE MR unit to obtain coronal images of the femur with the Dixon sequence, which allows for the differentiation between fat and water based on different resonant frequency differences. Bone marrow biopsies are performed at diagnosis and at the end of induction to assess the spatial relationship between osteoblasts, adipocytes and hematopoietic cells. We planned to enroll 70 patients divided in two cohorts: in the first cohort patients with low vitamin D are only observed, while those in the second cohort will receive Vitamin D and calcium therapy starting after completing Induction. Our preliminary results of the first cohort indicate that vitamin D deficit is almost universal at diagnosis of ALL: vitamin D levels correlate with the amount of body fat and the initial bone density. By the end of Induction, vitamin D levels and bone density decreased in all the patients, accompanied by an increase in body fat and in serum PTH. Studies correlating these findings with bone marrow changes by histology and radiology are in progress. No significant financial relationships to disclose.
P-272 Phase II study of Regorafenib as single agent for the treatment of patients with metastatic colorectal cancer with any RAS or BRAF mutation and previously treated with FOLFOXIRI plus bevacizumab
Authors: P. García Alfonso, M.J. Ortiz, G. Durán, E. Falcó, A. Muñoz, B. García-Paredes, M. Salgado, A. López-Ladrón, J.M. Vieitez de Prado, M. Valladares, A. Salud, C. Guillén-Ponce, R. Lopez, L. Robles, A. Juárez, S. Serrano, C. Montagut, M. Zanui, M. Gil Raga, A. La Casta, M. Benavides, E. Aranda
Journal: Annals of Oncology (2015)
Reduced ability to clear ultrafilterable platinum with repeated courses of cisplatin.
Authors: P A Reece, I Stafford, J Russell, P G Gill
Journal: Journal of Clinical Oncology (1986)

Ultrafilterable plasma and urinary levels of platinum were quantitated for 24 hours after the first- and fourth-course infusion of cisplatin (CDDP) to seven patients. Four patients received 80 mg/m2 and three patients received 100 mg/m2 CDDP as a 2-hour infusion. The area under the curve (AUC) of ultrafilterable platinum, average renal clearance (CIR) of ultrafilterable platinum, and percentage of the platinum dose excreted in urine (% E) were determined for each infusion over the 26-hour period of the study. The AUC was higher in all patients after the fourth-course infusion, with a median increase of 74%. The median CLR was 494 mL/min (range, 214 to 996 mL/min) for the first course and decreased to 156 mL/min (range, 108 to 271 mL/min) for the fourth-course infusion (P less than .02). The median % E was 29.2% (range, 19.6% to 37.7%) for the first course and decreased to 19.9% (range, 12.4% to 25.9%) for the fourth-course infusion (P less than .02). There was no difference in creatinine clearance for the two infusions (median, 94 mL/min; P greater than .05). Urinary excretion of B2-microglobulin (B2-MG) and N-acetyl-B-glucosaminidase (NAG) was highly variable between patients and did not provide a useful predictor of changes in renal function. Four courses of CDDP therapy resulted in significantly reduced renal elimination of platinum in patients, probably through a reduction in the secretion of the drug in the proximal tubule of the kidney. The results suggest that increased antitumor effect and toxicity could occur in patients receiving sequential courses of cisplatin.
Defining the Percentage of T Helper 17 Cells in Patients with Eczema and Allergic Disease
Authors: Ranjeet Minocha, John M. Routes, Mary Hintermeyer, Trivikram Dasu, Erin Hammelev, Tucker Keuter, Aniko Szabo, James W. Verbsky
Journal: Journal of Allergy and Clinical Immunology (2016)
Serum resistin levels in children with habitual snoring
Authors: Maria Palma Carbone, Anna Maria Zicari, Azzurra Cesoni Marcelli, Flaminia Bardanzellu, Francesca Occasi, Annalisa di Coste, Marzia Duse
Journal: European Respiratory Journal (2013)

Introduction : Intermittent episodes of hypoxia, and reoxygenation in patients with habitual snoring(HS) might predispose to cell stress trough the activation of a proinflammatory response. Resistin, an adipokine produced by adipocytes, circulating monocytes and macrophages is known to be involved in the inflammatory response regulation.

Objectives: To investigate the association between HS severity and serum levels of resistin.

Methods: Fifty-three children (35 males; 66%) with HS aged between 4 and 16 years of life (mean age 8 ± 3 years) were selected by a SDB validate questionnaire and underwent nocturnal pulse-oximetry recording at home. Moreover 33 healthy non snorers children with similar age, sex and BMI, were included in the study as a control group.

Results: Children with HS had serum resistin levels higher than the control group (4,67 ± 1,91 ng/ml vs 3,80 ± 1,50 ng/ml; p<0.04). Notably the highest resistin levels were found in children with not conclusive and positive pulse-oximetry (5,29 ± 1,91 ng/ml vs 4,20 ± 1,93 ng/ml; p<0.008).

Conclusions: Our findings support the evidence of an increased production of pro-inflammatory mediators, such as resistin, in children with HS. These results might be probably due to the intermittent hypoxia and reoxygenation often occurring during sleep in children with Sleep disordered breathing. The presence of HS should be always investigated by pediatricians in order to identify children at risk of the early development of complications.
PTU-102 Development Of A Food Related Quality Of Life Questionnaire For People With Ibd
Authors: L Hughes, JO Lindsay, MC Lomer, S Ayis, L King, M Morgan, K Whelan
Journal: Gut (2014)

<h3>Introduction</h3> The role of diet as a therapy for Inflammatory Bowel Disease (IBD) is well established and has improved treatment and prognosis for patients. However, little is understood about how IBD impacts on food-related quality of life. A qualitative study indicated a wide range of food related issues across a broad spectrum of IBD experiences which include, amongst others; identifying and avoiding trigger foods, uncertainty about eating and drinking, problems eating out and frustration around eating. This study aimed to develop a food-related quality of life (FRQoL) questionnaire for people with IBD. <h3>Methods</h3> Semi-structured interviews with 28 IBD patients were coded and 150 FRQoL questionnaire items were generated. One hundred IBD patients ranked each item on i) if it had been relevant to them in the past two weeks and; 2) how important it was to them (regardless of whether it had been relevant). Items were removed based on ceiling/floor effects and high inter-item correlations. The 41 highest ranking items were retained with a 5 point Likert (disagree-agree) response scale. Subsequently, 287 IBD patients, 100 asthma patients (chronic disease control) and 117 healthy volunteers completed the FRQoL questionnaire alongside clinical measures, MUST nutritional screening, food satisfaction and generic and disease-specific quality of life questionnaires. Psychometric testing of the FRQoL questionnaire has been carried out including principle components analysis, construct and discriminant validity and test-retest reliability. <h3>Results</h3> Initial principle components analysis identified seven components explaining 68.35% of variance with high internal reliability (Cronbach’s alpha = 0.96). The FRQoL sumscore (higher scores indicate worse quality of life) correlated with younger age (r = -0.12), higher MUST score (r = 0.17) and lower BMI (r = -0.13). Worse FRQoL was associated with female gender (p &lt; 0.001), a diagnosis of Crohn’s Disease (p &lt; 0.05), surgery (p &lt; 0.05) and high MUST score (p &lt; 0.05). <h3>Conclusion</h3> An FRQoL questionnaire has been developed to identify issues around food, eating and nutrition for people with IBD at all stages of the disease process. Preliminary psychometric testing indicates that the questionnaire sumscore is related to clinical characteristics indicative of poor FRQoL. Further testing will determine the validity and reliability of the questionnaire for clinical use to identify IBD patients who may require further support with eating and drinking. <h3>Disclosure of Interest</h3> None Declared.
Tp53 Signature Predicts the Efficacy of Neoadjuvant Chemotherapy (Nac) of Breast Cancers
Authors: Shin Takahashi, Takafumi Fukui, Nobuhisa Gondo, Takanori Ishida, Noriaki Ouchi, Tadashi Nomizu, Yoichiro Kakugawa, Chikashi Ishioka
Journal: Annals of Oncology (2014)
Molecular classes in CRC: Characterization of MSI by expression profiling in the translational study of the PETACC 3-EORTC 40993- SAKK 60-00 trial.
Authors: M. Delorenzi, E. Budinska, V. Popovici, H. Estrella, A. Pavlicek, P. Yan, S. Weinrich, F. Bosman, S. Tejpar, A. Roth
Journal: Journal of Clinical Oncology (2010)

3597 Background: Microsatellite instability (MSI) is the hallmark of a deficient mismatch repair system (MMR) in about 15% of colorectal cancers (CRC). Other studies and our own confirm MSI as an independent prognostic marker associated with a better outcome in stage II and III CRC (ASCO 2009, abstr. #4002). As MSI can be caused by different mechanisms, and dMMR leads to secondary oncogenic alterations, heterogeneity in the clinical and molecular features of MSI CRC is likely but not well understood. In this transcriptome expression study, we explore which genes differentiates MSI from Microsatellite stable (MSS) tumors and look for evidence of additional subclasses. Methods: RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue blocks was used for expression profiling on the ALMAC platform Colorectal Cancer DSA. Classifiers were constructed using AdaBoost and DLDA algorithms and assessed with area under the curve (AUC) by cross-validation. Survival analysis was based on Cox regression. Results: 240 chips passed data quality control (42 MSI, 17.5%). Unsupervised methods allowed only weak separation of MSI and MSS specimen, despite 494 genes with significantly different expression (≤ 1% FDR), due to high variation in both groups. Gene expression differences were in agreement with results from reanalysis of three public datasets. Classifiers discriminated MSI and MSS with AUC of 0.96 [95% CI: 0.95-0.97], using 40-80 selected genes. Prominent discriminatory genes include various pathways: Wnt (f.ex. Axin2), MAPK (DUSP4); inflammation-immunity (REGs, STAT1), differentiation (TNNC2, mucins), metallothioneins. Association of these genes with RFS is heterogeneous. Conclusions: Efficient discrimination of MSS and MSI in gene expression profiles can be obtained, with good quality FFPE material, using a multigene classifier. Inside both classes there is high residual heterogeneity. More samples will be profiled in order to further define molecular subgroups and to search for prognostic genes. The ability to obtain reliable profiles form FFPE material implies that relevant information can be obtained from archival material stored in many biobanks. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer