tbuckley/cabot-search huggingface dataset:
THU0461 Evaluation of Various Endothelial Biomarkers and T Helper-17 Cytokines in Patients with Familial Mediterranean Fever
Authors: I. Sari, B. O. Pamuk, S. Selcuk, G. Gokce, D. L. Kozaci
Journal: Annals of the Rheumatic Diseases (2013)

Background Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease that affects the populations with certain ethnic backgrounds. It is characterized by self-limiting febrile attacks of polyserositis. In recent years, some studies reported that FMF patients had increased vascular wall alterations and damage which may be another clinical phenotype of the disease. It is suggested that, because its association of inflammasome, the key cytokine in the pathogenesis of FMF is IL-1. Some of the studies also reported increased concentrations of IL-17 which is a key cytokine related with T-helper (Th-17) axis. However, available data regarding these subjects are still limited and additional information is required. Objectives In the present study, we primary intended to evaluate some of the biomarkers related with vascular injury and cytokines related with Th-17 axis in regularly treated and attack-free FMF patients. Methods Forty (21 males [M] and 19 females [F], 31 [15-58] years) FMF patients and eighteen healthy controls (11 M and 7 F, 35.5 [19-46] years) with no known cardiovascular (CV) risk factors were included. All patients were receiving regular colchicine treatment and examinations were performed during attack-free periods. Serum samples were used for the determination of high sensitive C-reactive protein (hs-CRP), tissue factor (TF), tissue plasminogen activator (t-PA), osteoprotegerin (OPG), interleukin-6 (IL-6), IL-17, and IL-23. Plasma samples were used for the determination of asymmetric dimethylarginine (ADMA) and thrombomodulin (TM). Results Age, sex distribution, waist circumference, body mass index, smoking status and serum lipids were similar between the patients and controls ( P > 0.05). The concentrations of (hs-CRP) and IL-17 were significantly higher in FMF patients compared to controls ( P < 0.05). On the other hand, IL-6 and IL-23 levels were not different between the groups ( P > 0.05). ADMA, OPG and TM concentrations were significantly lower in the patients’ group compared to those of controls ( P < 0.05). However, vWF, TF and t-PA levels were similar between the groups ( P > 0.05). ![Figure][1]</img> Conclusions In this study we showed that IL-17 was significantly higher in FMF patients compared to controls. We also revealed that markers related with endothelial injury including ADMA, OPG and TM were significantly down-regulated in FMF patients who were on regular colchicine treatment during attack-free disease state. Disclosure of Interest None Declared [1]: pending:yes
Abstract 3034: Determining the profiles and parameters for gene amplification testing of growth factor receptors in lung cancer.
Authors: Eva Pros, Sylvie Lantuejoul, Lydia Sanchez-Verde, Sandra D. Castillo, Ana Suarez-Gauthier, Esther Conde, Juan C. Cigudosa, Fernando Lopez-Rios, Juan Torres-Lanzas, Josep Castellví, Santiago Ramon y Cajal, Elisabeth Brambilla, Montse Sanchez-Cespedes
Journal: Cancer Research (2013)

Abstract Growth factor receptors (GFRs) are amenable to therapeutic intervention in cancer and it is important to select patients appropriately. One of the mechanisms for activation of GFRs is gene amplification (GA) but discrepancies arising from the difficulties associated with data interpretation and the lack of agreed parameters confound the comparison of results from different laboratories. Here, we attempt to establish appropriate conditions for standardization of the determination of GA in a panel of GFRs. A NSCLC tissue microarray panel containing 302 samples was screened for alterations at ALK, FGFR1, FGFR2, FGFR3, ERBB2, IGF1R, KIT, MET and PDGFRA by FISH, immunostaining and/or real-time quantitative RT-PCR. Strong amplification was found for FGFR1, ERBB2, KIT/PDFGRA and MET, with frequencies ranging from 1 to 6%. Thresholds for overexpression and GA were established. Strong immunostaining was found in most tumors with ERBB2, MET and KIT amplification, although some tumors underwent strong immunostaining in the absence of GA. KIT and PDFGRA were always co-amplified, but only one tumor showed PDGFRA overexpression, indicating that KIT is the main target. Amplification of FGFR1 predominated in squamous cell carcinomas, although the association with overexpression was inconclusive. Interestingly, alterations at ALK, MET, EGFR, ERBB2 and KRAS correlated with augmented levels of phospho-S6 protein, suggesting activation of the mTOR pathway, which may prove useful to pre-select tumors for testing. Overall, here, we provide with parameters for the determination of GA at ERBB2, MET, KIT, and PDGFRA which could be implemented in the clinic to stratify lung cancer patients for specific treatments. Citation Format: Eva Pros, Sylvie Lantuejoul, Lydia Sanchez-Verde, Sandra D. Castillo, Ana Suarez-Gauthier, Esther Conde, Juan C. Cigudosa, Fernando Lopez-Rios, Juan Torres-Lanzas, Josep Castellví, Santiago Ramon y Cajal, Elisabeth Brambilla, Montse Sanchez-Cespedes. Determining the profiles and parameters for gene amplification testing of growth factor receptors in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3034. doi:10.1158/1538-7445.AM2013-3034
Drive and Performance of the Ventilatory Apparatus in Chronic Obstructive Lung Disease
Authors: Ruy V. Lourenço, Joseph M. Miranda
Journal: New England Journal of Medicine (1968)

Mechanical performance of the ventilatory apparatus (lungs and chest wall) and drive from the respiratory center were independently assessed in patients with chronic obstructive lung disease and normal subjects. Performance was abnormal in all the patients but more noticeably in those with hypercapnia. Drive, assessed from changes in the electromyogram of the diaphragm during rebreathing, was abnormally low only in patients with hypercapnia (average arterial-blood P CO 2 of 61 mmHg); the integrated electromyographic activity increased an average of 1.7 units/mmHg of arterial-blood P CO 2 whereas in other patients and in normal subjects, it increased 24 and 18 units respectively. These results suggest that mechanical alterations of lungs and chest wall have a fundamental role in the buildup of CO2 retention in chronic obstructive lung disease. However, once hypercapnia appears, decreased respiratory-center drive is also important and becomes predominant with marked CO2 retention. Mechanical and central factors in the treatment of respiratory failure must be distinguished.
AB0756 Application of plantoconturographic examination to the assessment of foot statics disturbances in patients with rheumatoid arthritis
Authors: S. Chwieśko-Minarowska, A. Kuryliszyn-Moskal, Z. Dzięcioł, K. Kaniewska
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic, inflammatory and multiple-system disorder of connective tissue leading to damage, deformation and functional impairment of joints. It frequently affects joints and periarticular structures of feet that constitute a significant supporting element underlying normal gait and motion of the body centre of gravity. <h3>Objectives</h3> The aim of the study was to evaluate foot deformities on the basis of plantoconturographic examination in a group of patients with RA according to the severity of the disease. <h3>Methods</h3> The study was performed on 54 patients (43 women and 11 men). The control group consisted of 34 volunteers free of any disorders of the musculoskeletal system. Plantoconturographic examination was carried out by means of a CQST2K podoscope. The following parameters were applied to the assessment of the disturbances of foot statics: hallux valgus angle (α), Sztriter-Godunow index (KY), Wejsflog's index (Wwp) and Clarke's angle (CL). <h3>Results</h3> Markedly higher values of the alpha angle have been noted in RA patients in comparison with a control group. Moreover, values of the alpha angle were higher in patients in the third stage of radiological changes than those in the second one. On the other hand, values of the Clarke's angle for the right foot were considerably higher in men in the second and third stage of RA compared to the control group. <h3>Conclusions</h3> Plantoconturographic examination can be consider as an to constitute a useful diagnostic tool for assessment and monitoring of foot deformities in RA patients. The most common deformities in RA patients include hallux valgus and transverse flat foot. <h3>References</h3> Kuryliszyn-Moskal A, Kaniewska K, Konarzewski P, Dzięcioł Z. Współczesne metody diagnostyki i terapii zaburzeń wydolności statycznej stóp w przebiegu reumatoidalnego zapalenia stawów. Reumatologia 2012; 50, 6: 507-511 Hills AP, Hennig EM, McDonald M, Bar-Or O. Plantar pressure differences between obese and non-obese adults: a biomechanics analysis. Int J Obes Relat Metab Disord 2011; 25, 11: 1674-1679 Tuna H, Birate M, Tastekin N, et al. Pedobarography and its relation to radiologic erosion scores in rheumatoid arthritis. Rheumatol Int 2005; 26: 42 <h3>Disclosure of Interest</h3> None Declared
Detection of Breast Carcinoma in a Man on Dual-Isotope Tl-201 and Tc-99m Myoview Myocardial Perfusion Imaging
Authors: Farhat S Khairallah, Judith M Joyce, Daniel T Myers, Michele Organist
Journal: Clinical Nuclear Medicine (2002)

KHAIRALLAH, FARHAT S. M.D.*; JOYCE, JUDITH M. M.D.†; MYERS, DANIEL T. M.D.†; ORGANIST, MICHELE M.D.‡ Author Information
Stage-specific regulation of the WNT/β-catenin pathway enhances differentiation of hESCs into hepatocytes
Authors: Thomas Touboul, Shujuan Chen, Cuong C. To, Sergio Mora-Castilla, Karen Sabatini, Robert H. Tukey, Louise C. Laurent
Journal: Journal of Hepatology (2016)

Hepatocytes differentiated from human embryonic stem cells (hESCs) have the potential to overcome the shortage of primary hepatocytes for clinical use and drug development. Many strategies for this process have been reported, but the functionality of the resulting cells is incomplete. We hypothesize that the functionality of hPSC-derived hepatocytes might be improved by making the differentiation method more similar to normal in vivo hepatic development.We tested combinations of growth factors and small molecules targeting candidate signaling pathways culled from the literature to identify optimal conditions for differentiation of hESCs to hepatocytes, using qRT-PCR for stage-specific markers to identify the best conditions. Immunocytochemistry was then used to validate the selected conditions. Finally, induction of expression of metabolic enzymes in terminally differentiated cells was used to assess the functionality of the hESC-derived hepatocytes.Optimal differentiation of hESCs was attained using a 5-stage protocol. After initial induction of definitive endoderm (stage 1), we showed that inhibition of the WNT/β-catenin pathway during the 2nd and 3rd stages of differentiation was required to specify first posterior foregut, and then hepatic gut cells. In contrast, during the 4th stage of differentiation, we found that activation of the WNT/β-catenin pathway allowed generation of proliferative bipotent hepatoblasts, which then were efficiently differentiated into hepatocytes in the 5th stage by dual inhibition of TGF-β and NOTCH signaling.Here, we show that stage-specific regulation of the WNT/β-catenin pathway results in improved differentiation of hESCs to functional hepatocytes.
The response to neoadjuvant chemotherapy and prognosis of triple-negative breast cancer patients.
Authors: E Nakano, T Hojo, K Masumura, M Kikuyama, S Akashi, T Kinoshita
Journal: Cancer Research (2009)

Abstract Abstract #5121 Purpose: It is said that triple negative breast cancer (TNBC) has poor prognosis. However, many study shows TNBC has better response to chemotherapy. Since neoadjuvant chemotherapy plays an important role to TNBC, we compared clinical and pathological response rate and prognosis between TNBC and non-TNBC.&amp;#x2028; Patients and methods: This analysis retrospectively collected 2563 breast cancer patients for StageI-III who underwent surgery between January 2000 and September 2004 (median: 3.9 years) at National Cancer Center, Tokyo, Japan. We defined TNBC as Estorpgen and progesterone receptor negative and HER2 score 0-2+ by immnohistological report. There were 91 TNBC patients (23.1%) out of 400 patients (15.6%) who underwent neoadjuvant chemotherapy. Clinical and pathological response rate and Four-year progression free survival were compared between TNBC and non-TNBC.&amp;#x2028; Results: There were 91 TNBC patients (23.1%). TNBC patients compared with non-TNBC had tendency to achieve cCR (91% vs 78%; p=.058) although TNBC had higher rate for cPD (6.6% vs 1.7%; p &amp;lt;.0001). Also TNBC tended to have higher pathological CR rate of which we classified pCR only for grade 3 cases, compared to non-TNBC (13.1% vs 7.2%; p= .042 ). Interestingly HER2 overexpression type also had higher rate for pCR. As for pPD rate, TNBC had similar rate compared to non-TNBC (5.5% v 4.3%). Four-year progression free- survival rate was higher for non-TNBC. However, TNBC had higher Four-year survival free rate only when pCR were achieved after neoadjuvant chemotherapy (99% vs 82%; p=.02).&amp;#x2028; Conclusion: Patients with TNBC tend to have clinical and pathological response of either CR or PD. Although non-TNBC had better prognosis by four-year survival free rate, TNBC could have better prognosis if neoadjuvant chemotherapy resulted in pCR. There may be some way to predict the efficacy of neoadjuvant chemotherapy and prognosis by analyzing the shrink pattern. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5121.
Abstract LB-412: Urinary polyphenols, <i>GST copy</i> number variation, and breast cancer risk: Results from the Shanghai Women's Health Study (SWHS)
Authors: Jianfeng Luo, Yu-Tang Gao, Wong-Ho Chow, Xiao-ou Shu, Honglan Li, Gong Yang, Qiuyin Cai, Guoliang Li, Nathaniel Rothman, Hui Cai, Martha J. Shrubsole, Adrian A. Franke, Wei Zheng, Qi Dai
Journal: Cancer Research (2010)

Abstract Background: In vitro studies found that the flavanol epigallocatechin (EGC) and flavonols, but not the flavanol epicatechin (EC), activated glutathione s-transferases (GST), a family of phase II enzymes which detoxify reactive oxygen species, such as catechol estrogen metabolites. Objective: To investigate whether urinary excretion of tea polyphenols interacted with GST polymorphism in relation to breast cancer risk. Design: We conducted a study of 353 incident breast cancer cases and 701 individually-matched controls nested within the Shanghai Women's Health Study cohort of women aged 40-70 years at baseline. Liquid chromatography tandem mass spectrometry was used to measure urinary excretion of flavanols and flavonols. Real-time multiplex PCR were used to quantify the copy number variation for the GSTM1 and GSTT1 genes. Results: Urinary excretion of flavonols and flavanols, particularly, EGC(p=0.02), were significantly higher among those null for GSTM1 than those positive for GSTM1. Furthermore, urinary excretion of flavanol EGC significantly interacted with GSTM1 polymorphism (p=0.04), while flavonols, particularly kaempferol, may interact with both GSTM1 and GSTT1 genotype in relation to breast cancer. As a result, flavanols (primarily EGC) and flavonols significantly interacted with the joint genotypes of GSTM1 and GSTT1 in relation to breast cancer risk. Flavonols and flavanols (EGC in particular) were associated with a reduced risk of breast cancer among those null for GSTM1 and GSTT1, whereas flavonols, particularly kaempferol, were significantly associated with an increased risk of breast cancer for those possessing both GSTM1 and GSTT1. Conclusion: These results, if confirmed, may provide a new avenue for the personalized prevention of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-412.
GC-02 * CNS GERMINOMAS ARE CHARACTERIZED BY GLOBAL DEMETHYLATION, CHROMOSOMAL INSTABILITY AND MUTATIONAL ACTIVATION OF THE KIT-, RAS/RAF/ERK- AND AKT-PATHWAYS
Authors: T. Pietsch, B. Steiger, D. Denkhaus, C. Vokuhl, I. Leuschner
Journal: Neuro-Oncology (2015)

CNS germinomas represent a unique germ cell tumor entity characterized by uniform undifferentiated tumor cells and a high response rate to current treatment protocols. However, only limited information is available on their underlying genomic, epigenetic and biological alterations. In this study we perfomed a genome-wide analysis of genomic copy number alteration and allelic disbalances in 37 cases of CNS germinomas by molecular inversion profiling. In addition, CpG dinucleotide methylation was studied by immunohistochemistry with a specific antibody against methylated cytosine residues. Mutational analysis was performed by resequencing of candidate genes including KIT and RAS family members using FFPE derived DNA. Ras/Erk and Akt pathway activation was analysed by immunostaining with specific antibodies against phospho-Erk and phospho-Akt. All germinomas coexpressed Oct4 and Kit but showed an extensive global demethylation of nuclear DNA compared to other germ cell tumors and normal tissues. Molecular inversion profiling showed predominant genomic instability in 32/37 tumors with a high frequency of regional gains and losses including high level amplifications. Activating mutations of KIT exons 11, 13, 17 as well as a case with genomic KIT amplification and activating mutations or amplifications of RAS gene family members including KRAS, NRAS, RRAS2 and RHOH as well as mutation of BRAF indicated mutational activation of crucial signalling pathways. Activation of both, Ras/Erk and Akt pathways was demonstrated by immunohistochemistry of phospho-Erk and phospho-Akt in germinomas. These data suggest that CNS germinoma cells display a demethylated nuclear DNA similar to primordial germ cells in early development. This finding is associated with extensive genomic instability in the majority of germinomas. In addition, mutational activation of KIT, Ras/Raf/Erk- and Akt- pathways is characteristic indicating the biological importance of these pathways and potential targets for therapy.
THU0503 Hip Bone Marrow Lesions in Asymptomatic and Osteoarthritic Adults: Prevalence, Risk Factors and Significance
Authors: L. Dawson, Y. Wang, A. Wluka, K. Bennell, F. Cicuttini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Bone marrow lesions (BMLs) at the knee have an important role in the pathogenesis of osteoarthritis (OA), being associated with increased pain, accelerated cartilage loss, and increased risk of total knee replacement. However, data is limited for the role of BMLs at the hip. <h3>Objectives</h3> The aim of this study was to determine the prevalence and associations of BMLs at the hip in an asymptomatic and an osteoarthritic population. <h3>Methods</h3> 142 asymptomatic and 19 participants with hip OA were recruited from existing cohorts. Hip magnetic resonance imaging was performed and used to assess femoral head BMLs, cartilage volume and bone area. <h3>Results</h3> The demographic characteristics of the asymptomatic versus the OA population were as follows: age 66.8 +/- 7.4 vs. 59.5 +/- 7.6 years (p&lt;0.001), female 55.6% vs. 57.9% (p=0.85), body mass index 27.6 +/- 4.8 vs. 27.2.+/-.4.8 kg/m<sup>2</sup> (p=0.73). The prevalence of BMLs was 17.6% in the asymptomatic population and 63.2% in the OA population (p&lt;0.001). BMLs were strongly associated with OA after adjusting for age, gender and body mass index (odds ratio 5.32, 95% CI 1.78, 15.9, p=0.003). BMLs were associated with lower femoral head cartilage volume in the whole population (regression coefficient -245.7 mm<sup>3</sup>, 95% CI -455.5, -36.0, p=0.02). In the OA population, BMLs were also associated with lower femoral head cartilage volume (regression coefficient -426.6 mm<sup>3</sup>, 95% CI -855.2, 2.14, p=0.05) after adjusting for age, gender, body mass index, femoral head bone area and hip OA (for analysis of the total population). <h3>Conclusions</h3> Femoral head BMLs are common in those with OA, but are also present in asymptomatic individuals with no clinical hip OA. They are associated with reduced hip cartilage volume. These findings suggest that BMLs at the hip may provide a novel target for the treatment and prevention of hip OA. <h3>Disclosure of Interest</h3> None Declared
ASSOCIATION BETWEEN LEFT VENTRICULAR DIASTOLIC WALL STRAIN AND RECURRENCE OF ATRIAL FIBRILLATION IN PATIENTS UNDERGOING CATHETER ABLATION OF PAROXYSMAL ATRIAL FIBRILLATION
Authors: Takashi Kanda, Masaharu Masuda, Akihiro Sunaga, Masashi Fujita, Osamu Iida, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Tatsuya Shiraki, Takuya Tsujimura, Yasuhiro Matsuda, Shota Okuno, Koji Yanaka, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2015)
Abstract 4438: A membrane modulating strategy improves doxorubicin therapy in spontaneous mouse breast carcinoma
Authors: Albert J. van Hell, Gerben Koning, Jos Jonkers, Wim van Blitterswijk, Marcel Verheij
Journal: Cancer Research (2011)

Abstract BACKGROUND: Frequently, clinical anti-cancer therapy is suboptimal because of the inability to deliver high levels of cytostatics into tumor cells. We identified a class of short-chain sphingolipids that facilitate the translocation of amphiphilic drugs over the plasma membrane, including various cytostatics. RESULTS: The sphingolipid analogue N-octanoyl-GlucosylCeramide (GC) elevates intracellular doxorubicin levels four- to eight-fold, both in vitro and in xenografted B16 melanoma tumor tissue. In order to examine enhanced anti-tumor efficacy by GC preclinically, we used a spontaneous mouse breast cancer model that closely mimics human Invasive Lobular Carcinoma (ILC), and we applied a two-step experimental set-up with mouse cohorts of increasing tumor heterogeneity. In both populations, GC co-administration significantly increased tumor growth delay by doxorubicin, when compared to the conventional free or liposomal doxorubicin formulations. In contrast, the GC co-administration did not add upon bone marrow suppression, the main doxorubicin toxicity as revealed by pathological examination. Overall, mice treated with the GC-doxorubicin co-formulation better endured therapy and showed extended overall survival. CONCLUSION: Concomitant in vivo membrane modulation by short-chain sphingolipids widens the therapeutic window of the anti-cancer agent doxorubicin in a preclinical model for human ILC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4438. doi:10.1158/1538-7445.AM2011-4438