tbuckley/cabot-search huggingface dataset:
Abstract 1115: Impaired Angiogenic Potential of Cardiac Progenitor Cells in Mice with a Cardiomyocyte-Restricted Knock Out of STAT3
Authors: Philipp Fischer, Ewa Missol-Kolka, Nils-Holger Zschemisch, Christian Templin, Helmut Drexler, Denise Hilfiker-Kleiner
Journal: Circulation (2007)

Mice with a cardiomyocyte-restricted knock out of STAT3 (KO: alpha-MHC-Cre tg/+; STAT3 flox/flox ) show a continuous decrease of the cardiac capillary density and develop heart failure beyond the age of 9 months. We sought to determine the paracrine influence of cardiomyocyte STAT3 on the endothelial differentiation potential of cardiac progenitor cells (CPC) of the adult mouse heart. Sca-1 + CPC were isolated from male mice hearts by MACS separation. STAT3 was entirely deleted in cardiomyocytes of KO mice, while CPC from KO showed normal expression of STAT3 (confirmed by PCR and Western blot). No difference in the total number of CPC per heart was observed between wildtype (WT: STAT3 flox/flox ) and KO mice. FACS analysis revealed a reduced number of endothelial progenitor cells (as defined by coexpression of Sca-1, CD31 and CD38, −25%, P&lt;0.05) among CPC from KO compared to CPC from WT. The differentiation potential of CPC from WT and KO was analyzed during in vitro culture on fibronectin-coated plates. After 4 weeks of culture RT-PCR for CD31 and immunohistochemistry (IHC) for endothelial cell (EC) marker tie2 and isolectin B4 was performed. CPC from WT showed markedly more efficient EC differentiation and tube formation compared to CPC from KO (p&lt;0.01). In contrast, adipocyte differentiation was enhanced in CPC from KO (p&lt;0.05, oil red staining and RT-PCR). Proliferation capacity of CPC from KO was reduced by 33% (p&lt;0.01) as compared to CPC from WT. Microarray results of freshly isolated CPC were consistent with the differences in EC and adipocyte differentiation (i.e. prostaglandin E receptor 3 up 2.3-fold in CPC from WT, Lipocalin-2 up 2.7-fold in CPC from KO). We did not observe cardiomyocyte differentiation (IHC for alpha-sarcomeric actinin; RT-PCR for Nkx 2.5, alpha-MHC, or alpha-skeletal actin) of CPC from both genotypes, neither in vitro by addition of oxytocin, 5-AZA, DMSO, nor following intramyocardial injection of CPC in vivo. Conclusion: STAT3-dependent paracrine mediators released from cardiomyocytes are determinants of differentiation and vasculogenic properties of new EC derived from cardiac progenitor cells. The identification of these factors may offer new approaches to enforce the endogenous vasculogenic repair potential of the adult heart.
Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse
Authors: K. Tobal, J. Newton, M. Macheta, J. Chang, G. Morgenstern, P. A. S. Evans, G. Morgan, G. S. Lucas, J. A. Liu Yin
Journal: Blood (2000)
Serum phosphatidylcholine is lower among breast cancer patients on systemic chemotherapy.
Authors: Xin Li, John Lim, Anand Kolatkar, Lisa Welter, Kathryn Waitman, Eun-Sil Shelley Hwang, Janice M. Lu, Peter Kuhn, Jorge J. Nieva
Journal: Journal of Clinical Oncology (2017)

e12571 Background: Chemotherapy-induced cognitive impairment, also known as 'chemobrain', is widely recognized as a frequent adverse effect of chemotherapy, occurs in 10-40% of all cancer patients. Those cancer survivors suffer from poor concentration, memory, abstract reasoning, and motor dysfunction. The etiology is unclear. In our study, we analyzed the metabolite panels in breast cancer patients with vs. without chemotherapy trying to identify metabolic mediators of neurologic injury. Methods: We obtained plasma sample from 18 breast cancer patients, 9 received chemotherapy prior to blood drawn; while the other 9 had no systemic therapy. The plasma samples were sent for mass spectroscopy. Each metabolites level was normalized, and the two groups were compared in each metabolite by t-test with statistical significance corrected for multiple comparisons using the Holm-Sidak method. Results: We identified 57 amines and their metabolites; 106 carbohydrate related metabolites, and 228 lipid molecules. While amino acid, and carbohydrate did not show significant difference, phosphatidylcholine level in the chemotherapy treated group demonstrated lower level in the patients received chemotherapy. Among 59 phosphatidylcholine identified, 6 variants were significantly lower in the chemo group compare with non chemo group. Additionally the sum of all phosphatidylcholine variants was diminished in the chemotherapy treated patients compared with untreated controls. No other differences in plasma lipid levels were identified. Conclusions: Phosphatidylcholine is a major component of cell membranes and lipid rafts which are critical elements in nerve conduction. It also plays a role as the precursor to the neurotransmitter acetylcholine. The finding that phosphatidylcholine is significantly different between chemotherapy treated vs. the no chemotherapy group raises the possibility that lipid metabolism contributes to chemotherapy-induced cognitive impairment and further experiments are planned to explore this hypothesis.
Serum Peptidome Based Biomarkers Searching for Monitoring Minimal Residual Disease in Adult Acute Monocytic Leukemia
Authors: Ju Bai, Yun Yang, Jianli Wang, Wanggang Zhang, Lei Zhang, Fangxia Wang, Xiaman Wang, Hongli Chen, Ying Shen, Yuandong Feng, Wei Li, Aili He
Journal: Blood (2016)
Social cognition interventions for people with schizophrenia: a systematic review focussing on methodological quality and intervention modality
Authors: Nina Grant, Megan Lawrence, Antonio Preti, Til Wykes, Matteo Cella
Journal: Clinical Psychology Review (2017)

People with a diagnosis of schizophrenia have significant social and functional difficulties. Social cognition was found to influences these outcomes and in recent years interventions targeting this domain were developed. This paper reviews the existing literature on social cognition interventions for people with a diagnosis of schizophrenia focussing on: i) comparing focussed (i.e. targeting only one social cognitive domain) and global interventions and ii) studies methodological quality.Systematic search was conducted on PubMed and PsycInfo. Studies were included if they were randomised control trials, participants had a diagnosis of schizophrenia or schizoaffective disorder, and the intervention targeted at least one out of four social cognition domains (i.e. theory of mind, affect recognition, social perception and attribution bias). All papers were assessed for methodological quality. Information on the intervention, control condition, study methodology and the main findings from each study were extracted and critically summarised.Data from 32 studies fulfilled the inclusion criteria, considering a total of 1440 participants. Taking part in social cognition interventions produced significant improvements in theory of mind and affect recognition compared to both passive and active control conditions. Results were less clear for social perception and attributional bias. Focussed and global interventions had similar results on outcomes. Overall study methodological quality was modest. There was very limited evidence showing that social cognitive intervention result in functional outcome improvement.The evidence considered suggests that social cognition interventions may be a valuable approach for people with a diagnosis of schizophrenia. However, evidence quality is limited by measure heterogeneity, modest study methodology and short follow-up periods. The findings point to a number of recommendations for future research, including measurement standardisation, appropriately powered studies and investigation of the impact of social cognition improvements on functioning problems.
Pazopanib vs pazopanib + gemcitabine in refractory soft tissue sarcoma: A randomized phase II trial of the AIO.
Authors: Hans-Joachim Schmoll, Jörn Rüssel, Peter Reichardt, Lars Lindner, Hans-Georg Kopp, Alexander Stein, Franziska Cygon, Klaus Heissner
Journal: Journal of Clinical Oncology (2016)

11004 Background: There is a need for active chemotherapy combinations in anthracycline-refractory soft tissue sarcoma. Pazopanib, a TK-inhibitor of VEGF, PDGF and c-kit, significantly improves PFS (PALETTE-Trial, v. d. Graaf, Proc. ASCO 2011). Gemcitabine has shown single agent activity in anthracycline refractory patients (pts), and pazopanib/gemcitabine has shown to be (Plummer R., Cancer Chemother and Pharmacol 2013). This combination (arm A) was investigated against single agent pazopanib (arm B) in anthracycline refractory patients. Methods: From 9/11 - 7/14 90 patients with relapsed or refractory soft tissue sarcoma after at least 1 anthracycline based chemotherapy have been randomize, with life expectancy > 3 months, ECOG-PS 0-2, adequate organ function and at least 1 measurable lesion (RECIST). Primary endpoint (PE): rate of progression @ 3 months (PFS-R), with an anticipated PFS-R of 40 % (arm B) (PALETTE-trial) vs. =/> 60% (arm A), with 90 pts to demonstrate a significant difference (p < 0.05, 1-sided). Randomization was stratified by liposarcoma (lipo-sa)-histology and center. Results: 86 pts (A: 42 / B: 44; 2 pts in each arm not eligible) are evaluable (ITT), with a median follow up of 39 (21-54) months. The primary endpoint was met with 73.2% vs. 45.5% without progression after 3 months , HR 1.62 (CI: 1,16-2,27), p=0,005. For all histology excluding lipo-sa the difference was not significant: HR 1,24 (CI 0,89-1,74), p=0,28, but in lipo-sa with 9/9 (arm A) vs. 1/8 (arm B): HR 8 (CI 1.72-37.27), p<0,001. Response-rates: all pts 12% (A) vs. 5% (B), w/o lipo-sa 15% vs. 6%, lipo-sa. 0 vs. 0. PFS for all pts, adjusted for lipo-sa, was significantly improved with 5,6 (A) vs. 1,9 (B) months (median), HR 0,54 (CI 0,34-0,87), p=0,01. For the lipo-sa subgroup the PFS-difference was striking with 8,6 (A) vs. 1,5 months (B), but not significant. OS was not different for all pts, very likely due to cross over to gemcitabine after progression in arm B; however lipo-sa showed a numerical, non-significant difference: 25,4 vs. 11,1 months, HR 0,42 (CI 0,14-1,28). Toxicity was different, as expected, but tolerable, with mainly °3/4 hematological, and cardiovascular, GI, renal; SAE N=37 (A) vs 9 (B) with 2 fatal events in arm A (ARDS 1; unclear). Conclusion: Gemcitabine in addition to pazopanib significantly improves the PFS-rate at 3 months and overall PFS, with strongest effect in lipo-sa. Although OS was not increased, very likely due to post study crossover (data not shown), and despite higher toxicity, these data support the 2 drug combination for post-anthracycline treatment and evaluation in 1.line of lipo-sa. Clinical trial information: 2009-017261-32.
Study to determine whether SNPs in CYP17A1, ESR1, and TNRC9 loci correlate with increased breast cancer risk and serum 25-OH vitamin D levels.
Authors: Nobuyasu Yoshimoto, Yu Dong, Hiroshi Sugiura, Mitsuo Terada, Naoto Kondo, Yumi Endo, Hiroko Yamashita, Tatsuya Toyama
Journal: Journal of Clinical Oncology (2017)

e13086 Background: Low serum 25-OH vitamin D (25-OH Vit.D) level is associated with a higher risk of breast cancer. Many single nucleotide polymorphisms (SNP) are associated with breast cancer risk, although the mechanisms underlying this association in most cases remain unclear. We attempted to address this issue by determining whether specific SNPs were correlated with breast cancer-associated biomarkers (BM). Methods: We analyzed estrogen receptor (ER)-positive breast cancer patients treated between Jan 2011 and Dec 2014. We measured serum testosterone and 25-OH Vit.D in pre- and post-menopausal women, and also measured estradiol in the latter group. We genotyped 7 individual SNPs both in premenopausal and postmenopausal women. We then looked for correlations between BMs and SNPs in all three genotypes (homozygotes of major alleles, heterozygotes and homozygotes of minor alleles) using the Kruskal-Wallis test. For each SNP locus associated with a trend or significant effect with regard to BM levels, a t-test was then applied to determine which of the two genotypes was responsible for the effect. Results: Four hundred thirteen women were enrolled (163 premenopausal patients, and 250 postmenopausal patients). There was a trend difference between CYP17A1 rs743572 and 25-OH Vit.D (p = 0.0888), ESR1 rs204210 and 25-OH Vit.D (p = 0.0534) in premenopausal women, and a significant difference between TNRC9 rs3803662 and 25-OH Vit.D (p = 0.026) in postmenopausal women. Among premenopausal women, 25-OH Vit.D levels were significantly lower in those with the high-risk rs743572 genotype TC when compared with TT individuals (19.2 +/- 6.7 ng/ml vs 22.9 +/- 8.7 ng/ml; p = 0.0125). Similarly, 25-OH Vit.D was significantly lower in women with the high-risk rs204210 genotype AG when compared with GG individuals (19.1 +/- 6.9 ng/ml vs 21.7 +/- 6.4 ng/ml; p = 0.0219). In postmenopausal women, 25-OH Vit.D was significantly lower in women with the high-risk rs3803662 genotype GG than those with the AA genotype (20.5 +/- 9.2 ng/ml vs 24.4 +/- 8.0 ng/ml; p = 0.0104). Conclusions: Specific SNPs in CYP17A1, ESR1, and TNRC9 genes may modulate breast cancer risk due to their influence on serum 25-OH Vit.D levels.
Distinct Patterns of PD-L1 and PD-L2 Expression By Tumor and Non-Tumor Cells in Patients with MM, MDS and AML
Authors: Monique Dail, Long Yang, Cherie Green, Connie Ma, Alberto Robert, Edward E. Kadel, Harmut Koeppen, Joanne Adamkewicz, John Byon, Joseph Woodard, Scott J Rodig, Jeffrey M Venstrom
Journal: Blood (2016)
Expérience européenne de l'entéroscopie double-ballon: faisabilité, indications et résultats
Authors: B Landi, A May, A Gasbarrini, C Mulder, A de Leusse, B Boboc, S Di Caro, G Heine, C Ell, C Cellier
Journal: Endoscopy (2005)

L'entéroscopie double-ballon (EDB) est une nouvelle technique qui permet en théorie une exploration complète de l'intestin grêle, et contrairement à la capsule de réaliser des biopsies et des gestes thérapeutiques. Le but de cette étude réalisée dans 4 centres européens était d'évaluer sa faisabilité, sa tolérance et ses résultats dans un groupe de patients atteints ou suspects de pathologie du grêle.
Duplicate genetic testing in families: The need for a health identifier solution.
Authors: David James Gallagher, Emily O'Donovan
Journal: Journal of Clinical Oncology (2016)

e13013 Background: The genetics service in SJH was started in 1992 and has reviewed 2200 family pedigrees to date. A new pedigree is prepared with the information received from each referral and completed with the patient during the initial consultation. This is stored on a system which only allows searching by pedigree number. We investigated for the presence of duplication of pedigrees which are stored as unique, independent entrees. Methods: A paper record of 2200 family pedigrees was created and 500 pedigrees were reviewed. Data collected included the proband forename and surname, date of birth, gene mutation status, cancer diagnosis of the proband and of family members. Cancer types were categorised as per the National Cancer Registry of Ireland (2015). The patient correspondence and medical records were accessed to determine the information missing from the pedigree. Missing information included dates of birth, identification of proband and surnames of family members. Results: Seventy-seven of 500 pedigrees were incomplete: 21 were still active waiting for patients to return to clinic, 52 patients did not attend their appointments or cancelled them and a further 4 patients had passed away. Thirty pedigrees were present twice in the database; nineteen duplicates had occurred because two members of the same family had attended for consultation and not informed the genetics service of their relatedness. On 7 occasions two pedigrees were created for the same patient, and it is unclear why the remaining 4 pedigrees were present twice. Conclusions: Six percent of pedigrees in this database were identified as duplicates. The actual number of families attending twice under different names is likely to be higher, and data on all 2200 pedigrees will be presented. A national cancer genetics registry with accurate health identifiers would prevent unnecessary and costly repeat clinical assessment and genetic testing of the same kindred.
Clinical characteristics of adult alveolar rhabdomyosarcoma (ARMS) patients (Pts) on front-line therapies: An MD Anderson Cancer Center (MDACC) series.
Authors: Anthony Paul Conley, Winston W. Huh, Jason Roszik, Douglas James Harrison, Andrea Anita Hayes-Jordan, Kathleen A Kehr, Ravin Ratan, Neeta Somaiah, Vinod Ravi, Dejka M. Araujo, Maria Alejandra Zarzour, Joseph A. Ludwig, Wei-Lien Wang, Robert S. Benjamin, Shreyaskumar Patel
Journal: Journal of Clinical Oncology (2016)

11069 Background: ARMS is considered to be one of the most aggressive pediatric malignancies. Adults with ARMS notoriously experience inferior outcomes. Our goal was to define our adult population with ARMS and review their outcomes on front-line systemic therapies. Methods: Adult ARMS pts over the age of 18 years (y) treated at MDACC from 2004 to 2015 were identified from our registry. Descriptive statistics and survival analysis were performed via multivariate analysis. Results: 43 pts were identified. Median age at diagnosis was 31 y (range (R) 18 to 69 y). 51% were male. 26 pts (60%) were Caucasian, 10 pts (23%) were Latino, 5 pts (12%) were Asian and 2 pts (5%) were African-American. The most common primary site was the parameningeal space (25 pts; 58%). The majority were classified with IRSG stage IV (37%) or III disease (47%). The majority were classified with group IV (37%) or III (56%). By COG clinical risk, 27 pts (63%) and 16 pts (37%) were intermediate and high, respectively. N1 disease was noted in 31 pts (72%). M1 disease was observed in 16 pts (37%). 36 pts (84%) had an unfavorable primary site. 60% of pts had primary tumors > 5 cm. FOXO1 fusions were present in 30 pts (70%), negative in 4 pts (9%), and not evaluated in 9 (21%). Most common chemotherapy regimens employed doxorubicin (26 pts; 49%), actinomycin-D (12 pts; 28%), both (3 pts; 7%), or other (2 pts; 5%). A median of 8 cycles (R: 1 – 20 cycles) were received. RECIST Responses included CR (21%), PR (26%), and SD (7%). 30 pts (70%) received radiation therapy for local control. Median OS was 32 months (R: 2 to 97 months). By multivariate analysis, m status (P = 0.007) and clinical risk (P = 0.007) were associated with statistically significant differences in survival. An inferior OS was noted in pts receiving doxorubicin-based chemotherapy (P = 0.037), though an associated increase in absolute tumor size was noted in this group (P = 0.057). Only 21% of pts were disease free at last follow up or death.Conclusions: Adults with ARMS represent a poorly defined group with an unmet need for improved treatment. Clinical trials are needed to improve the outcomes for this rare population of patients.
Résultats de la coloscopie virtuelle (coloscanner) dans la détection des polypes colorectaux comparé à la coloscopie classique
Authors: M Cadi, R Chollet, T Mansourbach, O Lucidarme, T Poyanard, P Grenier
Journal: Endoscopy (2006)

Déterminer la sensibilité et le temps d'analyse du coloscanner dans la détection des polypes coliques.
01.14 Novel mechanism mediated by the IL23/TH17 axis contributing to auto-immune arthritis
Authors: René Pfeifle, Tobias Rothe, Natacha Ipseiz, Hans U Scherer, Stephan Culemann, Ulrike Harre, Axel J Hueber, Martin Herrmann, Stephan Blüml, Falk Nimmerjahn, Georg Schett, Gerhard Krönke
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Checkpoints and mechanisms regulating the onset of rheumatoid arthritis (RA) remain largely elusive. Apart from B cells and auto-antibodies, Th17 cells were shown to critically contribute to disease development. Mice lacking IL-23, a cytokine controlling the pathogenicity of Th17 cells, are completely protected against arthritis. Yet, the exact role of the IL-23/Th17 axis during this autoantibody-driven disease remain incompletely understood. <h3>Material and methods</h3> IL23A<sup>-/-</sup> mice and mice receiving an IL23 blocking antibody were analysed during active and passive arthritis models including collagen-induced arthritis (CIA), the K/BxN arthritis model, collagen-antibody induced arthritis (CAIA) and K/BxN-serum transfer arthritis. Both clinical, histological and immunological parameters of arthritis were assessed. IgG glycosylation was analysed using the MALDI-TOF technique. IgG activity was determined by measuring the cytokine release of immune-complex-stimulated myeloid cells. To study the crosstalk between B cells and Th17 cells, co-culture experiments were performed. <h3>Results</h3> Here we report, that the IL-23/Th17 axis did not directly contribute to auto-antibody induced inflammation within inflamed joints, but controlled the glycosylation profile and inflammatory activity of auto-antibodies during the prodromal phase of disease. Th17 cells were found to accumulate in germinal centres auf secondary lymphatic organs prior to onset of experimental arthritis, where they suppressed the expression of β-glactoside α2,6-sialyltransferase 1 (St6gal1) in differentiating plasmablasts. The consecutive change in the immunoglobulin G (IgG) glycosylation profile provoked a shift towards a pro-inflammatory autoantibody repertoire and triggered the inflammatory phase of arthritis. Plasmablasts of RA patients similarly displayed a decreased St6gal1 activity, while IgG from these individuals showed corresponding changes in its glycosylation profile as well as an increased inflammatory activity, suggesting that related pathways might contribute to onset and progression of autoantibody-mediated diseases in humans. <h3>Conclusion</h3> Our current findings identify a novel IL-23/Th17-dependent checkpoint that controls autoantibody activity, unmasks a preexisting breach in humoral tolerance, and initiates the transition from a stage of asymptomatic autoimmunity into inflammatory autoimmune disease.
Systems immunology: just getting started
Authors: Mark M Davis, Cristina M Tato, David Furman
Journal: Nature Immunology (2017)

Systems-biology approaches in immunology take various forms, but here we review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. This approach has rejuvenated the field of vaccine development and has fostered hope that new ways will be found to combat infectious diseases that have proven refractory to classical approaches. Systems immunology also presents an important new strategy for understanding human immunity directly, taking advantage of the many ways the immune system of humans can be manipulated.