tbuckley/cabot-search huggingface dataset:
Abstract 3006: Alterations of the microRNA genes targeting MYCC are frequent in medulloblastomas with MYCC overexpression
Authors: Sheng-Qing Lv, Young-Ho Kim, Sumihito Nobusawa, Michael Grotzer, Hiroko Ohgaki
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRNAs) regulate a variety of cellular processes (including differentiation, proliferation and apoptosis) via the regulation of multiple target genes, including oncogenes and tumor suppressors. Abnormal miRNA expression may therefore play a significant role in tumor development. Medulloblastoma is a common malignant brain tumor in children. Several studies have shown abnormal miRNA-expression profiles in medulloblastomas, but little is known as to whether such profiles are caused by alterations in miRNA genes. In the present study, we screened 48 medulloblastomas for mutation, deletion, and amplification of nine miRNA genes (miR-33b, miR-135a-1, miR-135a-2, miR-135b, miR-186, miR-200b, miR-512-2, miR-548d-1, and miR-548d-2). These miRNAs were selected on the basis of the presence of potential target sequences within the 3’-untranslated region of the MYCC messenger RNA, since MYCC is frequently overexpressed without MYCC gene amplification in medulloblastoma. Differential PCR revealed deletions in miR-186 (15%), miR-135a-1 (33%), miR-548d-1 (42%), miR-548d-2 (21%) and miR-512-2 (33%) genes, whereas deletion or amplification was detected in miR-135b (23%) and miR-135a-2 (15%). In miR-33b, deletion, amplification or a mutation at the precursor miRNA were detected in 10% of medulloblastomas. Overall, 35 out of 48 (73%) medulloblastomas had at least one alteration in the miRNA genes analyzed. Real-time RT-PCR revealed MYCC overexpression in 11 out of 37 medulloblastomas analyzed (30%), and there was a significant correlation between MYCC overexpression and miR-512-2 gene deletion (P = 0.0084). These results suggest that deletion or amplification in miRNA genes is frequent, and may play a role in the pathogenesis of medulloblastomas. 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 3006.
FRI0070 High Prevalence of Subclinical Cardiovascular Disease and Abnormal Left Ventricular Geometry Detected by CMR in Asymptomatic Rheumatoid Arthritis Patients: Table 1.
Authors: L.-A. Bissell, B. Erhayiem, E.M.A. Hensor, S. Plein, P. Emery, J.P. Greenwood, M.H. Buch, J. Andrews
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Cardiac MRI (CMR) has merit in the assessment of cardiovascular disease (CVD) with increased left ventricular mass/end-diastolic volume (LVmass/EDV) associated (ass.) with greater CV risk.[1] CMR-RA studies are few; unclear if CMR assessments are applicable to RA. <h3>Objectives</h3> To describe and quantify CV risk and sub-clinical CVD in an asymptomatic (CVD perspective) established RA cohort, using gold standard CMR-measured outcomes and a clinically deliverable comprehensive CV assessment. <h3>Methods</h3> 78 RA patients (pts) (1980 ACR criteria) with disease &gt;5yrs, no CVD/diabetes, assessed for traditional CV risk factors (RFs), RA profile, pulse wave velocity (PWV), and a subset of 58; non-contrast 3.0T CMR reported by CMR cardiologists. 10yr JBS CV risk scores calculated (x1.5 if required)[2,3]. Univariable analysis (UVA) variables marked* in Table 1. CMR values (exc. LVEF) adj. for body surface area (BSA); “abnormal” values adj. for age/sex[4]. <h3>Results</h3> 73% were female, mean (SD) age 60 (9.3)yrs, 91% white British (RA profile in Table 1). JBS risk: median (IQR) 13.3 (7.4, 20.8)%; 16 (22%) pts &gt;20% (only 5/16 were on primary prevention therapy). Only age (B0.065, p=0.001) and syst. BP (B0.036, p&lt;0.001) were ass. with higher PWV on multivariable analysis (MVA) (R<sup>2</sup> 0.482). CMR abnormalities were common (Table 1). Greater LV mass/BSA was ass. with male gender, HTN, ever-smoking, waist/hip ratio (WHR); only gender (B13.519, p&lt;0.001) and HTN (B5.658 p=0.003) sig. on MVA (R<sup>2</sup> 0.643). Greater LVmass/EDV was ass. with male gender, age, HTN; only gender (B0.064, p&lt;0.001) and HTN (B0.039, p=0.012) sig. on MVA (R<sup>2</sup> 0.411). 59% had reduced LV mass/BSA, more common in females (69% vs. 38% males, p=0.038). LVmass/EDV was reduced referent to published controls [5]; lower in females (p&lt;0.001). No RA variables were ass. with PWV/CMR measures. <h3>Conclusions</h3> CMR-detected subclinical CVD abnormalities are common in asymptomatic RA pts and ass. with traditional CV RFs. Despite enhanced CV risk in RA, we demonstrate reduced LV mass/BSA and LVmass/EDV, similar to the only other comparably sized CMR-RA study.[5] This suggests usual LV geometry interpretations may not apply to RA and implies complex mechanisms, with perhaps different compensatory remodelling in RA; warranting further study. <h3>References</h3> JACC Card Img 2010; v3i6. Heart 2005:91:S5. ARD 2010; 69v2. www.cmr-guide.com. A&amp;R 2010; 62v4. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4079
Abstract 1165: Image-guided Raman endoscopy for <i>in vivo</i> clinical detection of cancer in the stomach
Authors: Wei Zheng, Seng Khoon Teh, Khek Yu Ho, Ming Teh, Khay Guan Yeoh, Jimmy Bok Yan So, Feng Zhu, Zhiwei Huang
Journal: Cancer Research (2010)

Abstract Objective: Raman spectroscopy is a unique optical vibrational spectroscopic technique that is capable of noninvasively probing biomolecular changes associated with cancerous transformation. The aim of this study was to investigate the feasibility of a novel imaged-guided Raman endoscopy system developed for distinguishing cancer lesions from the non-cancerous tissues in the human stomach in vivo. Materials and Methods: A fiber-optic Raman endoscopy system was utilized for tissue Raman spectroscopic measurements at 785 nm laser excitation. A total of 20 in vivo gastric Raman measurement sites were used in this study, in which 15 sites were from 10 patients who underwent gastroscopic inspection, and 5 were from the suspicious lesion sites of 5 patients who underwent endoscopic ultrasound procedure. The histopathogical examinations on the biopsied tissues from the Raman measurement sites showed that 15 were non-cancerous and 5 were cancers. Multivariate statistical algorithms including principal component analysis (PCA) and linear discriminant analysis (LDA) were employed to determine the diagnostic sensitivity and specificity. Results: High-quality in vivo gastric Raman spectra in the range of 800-1800 cm−1 can be collected in less than 1 second, together with the simultaneous utilization of white-light reflectance imaging modality for guiding the Raman endoscopic probe to the suspicious tissue sites. Raman spectral shapes were significantly different between non-cancerous and cancers, particularly in the spectral ranges of 850-900 cm−1, 1000-1090 cm−1, 1200-1305 cm−1 and 1600-1800 cm−1 which contain signals related to hydroxyproline for collagen, phenylalanine, amide III, amide I and C=C stretching of lipids. The Raman technique together with PCA-LDA-based analytic algorithm yielded diagnostic sensitivity of 96.1% and specificity of 100% for detection of cancer from the non-cancerous gastric tissues in vivo. Conclusion: This study illustrates for the first time that the image-guided Raman endoscopy technique has promising clinical potential for rapid in vivo diagnosis of cancer tissues in the stomach. 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 1165.
Abstract 719: Accumulation of amino acids in metastatic foci of human colon cancer xenografts revealed by newly developed method for imaging mass spectrometry of amino acids.
Authors: Sakino Toue, Yuki Sugiura, Akiko Kubo, Mitsuyo Ohmura, Sachise Karakawa, Toshimi Mizukoshi, Junya Yoneda, Hiroshi Miyano, Yasushi Noguchi, Tsuyoshi Kobayashi, Yasuaki Kabe, Makoto Suematsu
Journal: Cancer Research (2013)

Abstract MALDI imaging mass spectrometry (IMS) provides information about the spatial distribution of metabolites within thin slices of tissue, and has been used to elucidate complex phenotypes under various physiological conditions. Previously, our group reported distinct spatial distribution of a variety of metabolites in experimental model of hepatic micrometastasis of the solid tumor. However the metabolic properties in tumor and host tissues are not fully characterized, because of difficulty in visualizing most amino acids, due to their lower ionization efficiency. Here, by using of p-N,N,N-trimethylammonioanily N’-hydroxysuccinimidyl carbamate iodide (TAHS) as a derivatizing reagent, we have successfully developed the method for the detection of various amino acids simultaneously by MALDI-MS on tissue section. We prepared liver section from hepatic metastasis model of human colon cancer, and then performed MALDI-IMS. To compare the signal intensities of amino acids among the different sections, we normalized the MALDI-IMS data with the quantified value of each amino acid obtained from capillary electrophoresis-mass spectrometry. The result indicated the amount of glycine, phenylalanine, leucine, glutamate, and glutamine were significantly elevated in metastatic foci compared to liver parenchyma. Other metabolites such as ATP and glutathione also accumulated in metastatic foci, and these results suggested that increased amino acid pool were required to maintain ATP and GSH levels in tumor. In conclusion, we have demonstrated that novel imaging technique by using of IMS combined with on-tissue TAHS derivatization enables the visualization of amino acid distribution in tissue. The current method could be powerful tool to elucidate the mechanism for metabolic changes of cancer disease in vivo. Citation Format: Sakino Toue, Yuki Sugiura, Akiko Kubo, Mitsuyo Ohmura, Sachise Karakawa, Toshimi Mizukoshi, Junya Yoneda, Hiroshi Miyano, Yasushi Noguchi, Tsuyoshi Kobayashi, Yasuaki Kabe, Makoto Suematsu. Accumulation of amino acids in metastatic foci of human colon cancer xenografts revealed by newly developed method for imaging mass spectrometry of amino acids. [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 719. doi:10.1158/1538-7445.AM2013-719
Autodeimination of<i>Porphyromonas gingivalis</i>peptidylarginine deiminase: a novel antigen in rheumatoid arthritis
Authors: Elena Lugli, Anne-Marie Quirke, Jimmy Ytterberg, Natalia Wegner, Bart Hamilton, Peter Charles, Muslima Chowdhury, Geoffrey Thiele, Ted Mikuls, Benjamin A Fisher, Patrick J Venables
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> <i>Porphyromonas gingivalis</i>, a major periodontal pathogen, has been implicated in the pathogenesis of rheumatoid arthritis (RA). It is the only pathogenic prokaryote known to possess a bacterial peptidylarginine deiminase (PPAD), an enzyme that catalyses the post-translational modification of arginine to citrulline. The enzyme is surface expressed and citrullinates c-terminal arginines of human fibrinogen and enolase peptides. Here, the authors show that PPAD is capable of autocitrullination and able to raise an immune response in RA. <h3>Materials and methods</h3> PPAD was expressed as a GST/His-tagged fusion protein using a bacterial expression system. Site-directed mutagenesis using a PCR based method was used to create a PPAD mutant (mPPAD) with a single residue mutation (cysteine 351 to alanine) and with no enzymatic activity. Citrullination was determined by immunoblotting with an antimodified citrullinated antibody kit (AMC, New York, NY, USA). Mass spectrophotometry was carried out to verify PPAD-GST citrullination. ELISAs using recombinant PPAD and recombinant mPPAD were developed to test sera from patients with periodontitis (PD) (n=44), RA (n=82) and healthy controls (C) (n=80). Reactivity was expressed as arbitrary units per ml (AU/ml) using a standard curve. <h3>Results</h3> Sera from patients with RA, PD and healthy controls were tested for IgG antibodies to PPAD and showed that RA sera have a significantly elevated antiPPAD IgG response (mean 182.4 AU/ml) compared to PD (mean 96.4AU/ml; p&lt;0.01) and healthy control sera (mean 99.2AU/ml; p&lt;0.05). An ELISA with the enzymatically non-active, C351A mutated PPAD (mPPAD), showed that the antibody response in the RA group was no longer significantly elevated compared to the antibody responses in the PD and healthy control sera. Antimodified citrulline immunoblotting demonstrated that recombinant PPAD was citrullinated whereas the mPPAD was not. Citrullination of PPAD was confirmed by mass spectrophotometry which showed that 7 of the 18 arginines in PPAD were citrullinated. All citrullines detected were internal and no c-terminal citrullination was observed. <h3>Conclusions</h3> The authors present evidence that PPAD is capable of autocitrullination and its target site is not restricted to c-terminal peptide arginines. The antibody response to autocitrullinated PPAD was significantly elevated in RA patients compared to PD patients and controls. This indicates that PPAD is a potential novel antigen in RA and may form part of the anticitrullinated protein antigen response seen in this disease, thus substantiating a possible link between PD and RA.
Abstract 2790: Prospective study of urinary prostaglandin E2 metabolite and lung cancer risk
Authors: Qiuyin Cai, Yu-Tang Gao, Wanqing Wen, Ginger L. Milne, Gong Yang, Bu-Tian Ji, Nathaniel Rothman, Hong-Lan Li, Xiao-Ou Shu, Wong-Ho Chow, Wei Zheng
Journal: Cancer Research (2010)

Abstract Cumulative evidence from both in vitro and animal studies suggests that cyclooxygenase-2 (COX-2) may be involved in the development and progression of lung cancer. Overproduction of prostaglandin E synthase and prostaglandin E2 (PGE2), one of the end products of the COX-2 pathway, has been implicated in the pathogenesis of non-small cell lung cancer. It is believed that the pro-inflammation effects of COX-2 pathway are largely mediated through PGE2. PGE2 is quickly converted to 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), a major PGE2 metabolite and excreted from urine. In this study, we evaluated the association of urinary PGE-M levels and lung cancer risk. A nested case-control study was conducted within the Shanghai Women's Health Study, in which 74,942 Chinese women aged 40-70 years were recruited from 1997 to 2000 and followed up for up to 10 years. Urinary PGE-M in 192 incident lung cancer patients were compared to 192 matched controls. The baseline level of urinary PGE-M was comparable between cases and controls. Excluding 20 case-control pairs who were diagnosed with lung cancer within one year of follow-up or excluding 22 case-control pairs who ever smoked did not change the null association. No interaction was found between PGE-M and smoking or passive smoking in relation to lung cancer risk. Our data suggest that the PGE2 pathway may not play a major role in lung cancer development in non-smoking women. Further studies are being conducted to evaluate whether genetic variations in the PGE2 pathway will modify the urinary PGE-M and lung cancer association. Given the substantial laboratory evidence, further evaluation of the COX-2 pathway in lung cancer pathogenesis, including other urinary biomarkers and genetic variations, may be warranted. 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 2790.
Abstract 5257: Manipulating the Noxa/Bim axis undermines the multicellular resistance of 3D tumor spheroids
Authors: Dario Barbone, Priscilla Cheung, Tsung-Ming Yang, David M. Jablons, David J. Sugarbaker, Raphael Bueno, Dean A. Fennell, Anthony G. Letai, Courtney V. Broaddus
Journal: Cancer Research (2012)

Abstract When grown in 3D cultures as spheroids, cancer cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found in lung cancer and mesothelioma that multicellular resistance lies at the level of mitochondria and can be reduced by manipulating the Bcl-2 repertoire with BH3-mimetics. One mechanism for the multicellular resistance to apoptosis is the lack of up-regulation of the pro-apoptotic sensitizer Noxa upon treatment; Noxa displaces pro-apoptotic Bim from its anti-apoptotic buffering proteins allowing the Bim to induce apoptosis. Interestingly, we have found that, at the same time that cells acquire apoptotic resistance in 3D, they also acquire a pro-apoptotic potential that has been termed “apoptotic priming,” due to an elevated Bim that is sequestered by the anti-apoptotic Bcl-2 proteins. We found that multicellular resistance could be abolished either by restoring Noxa levels using a permeable Noxa peptide or by releasing Bim via inhibition of the anti-apoptotic Bcl-2 proteins using the small molecule inhibitor, ABT-737. Moreover, multicellular resistance was also abolished by the histone deacetylase inhibitor SAHA which upregulated both Noxa and Bim expression. Knockdown of Bim blocked the effect of the Noxa peptide, ABT-737 or SAHA showing the importance of Bim in the chemotherapeutic response. Our results using a clinically-relevant 3D model show that manipulation of the core apoptotic repertoire in order to release Bim may improve chemosensitivity of lung cancer and mesothelioma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5257. doi:1538-7445.AM2012-5257
Abstract 2189: ΔN-ASPP2 is a novel isoform of the ASPP2 tumor suppressor and a regulator of ASPP2 function
Authors: Kathryn Van Hook, Zhiping Wang, Dexi Chen, Hun Joo Lee, Zhiyi Zhu, Charles Lopez
Journal: Cancer Research (2011)

Abstract ASPP2 (Ankyrin-repeats, SH3 domain, Poly-proline domain-2) is a pro-apoptotic member of a family of p53 binding proteins that share homology in the C-terminus. ASPP2 expression is frequently suppressed in human cancers, and mouse models targeting the ASPP2 allele have shown that ASPP2 is a bonafide tumor suppressor. Although ASPP2 is a damage-inducible protein that stimulates apoptosis at least in part through a p53-mediated mechanism, ASPP2 also modulates p53-independent pathways to inhibit the tumorigenic phenotype. However, the complex mechanisms that control ASPP2 regulation and function remain unclear. Using 5’RACE and RT-PCR, we have discovered a new ASPP2 isoform (that we have named ΔN-ASPP2) that is generated from an internal transcription start site in mouse, rat, and human libraries. ΔN-ASPP2 is a predicted 880 amino acid protein that is missing the highly structured N-terminus important for apoptotic function. Western blotting with epitope specific antibodies, and immunoprecipitation followed by LC-MC, confirmed a 95 kD ASPP2 protein. Moreover as predicted, MEFs derived from our ASPP2+/- mouse targeted at exons 10-17, demonstrated decreased levels of ΔN-ASPP2 mRNA and 95 kD ASPP2 immunoreactive protein. Since the N-terminus of ASPP2 is important for pro-apoptotic and tumor suppressor function, we hypothesized that N-terminal truncated ΔN-ASPP2 could inhibit apoptosis and promote tumorigenesis. Indeed, overexpression of ΔN-ASPP2 inhibited UV-induced apoptosis, as well as promoted RasV12-induced 3T3 colony formation in cell culture. Interestingly, we found complex binding dynamics between ΔN-ASPP2, p53, and full-length ASPP2, suggesting that ΔN-ASPP2 could function as a dominant-negative. Importantly, and consistent with a role in promoting tumorigenesis, we found that ΔN-ASPP2 was highly overexpressed in a panel of 20 human breast tumor samples compared to matched adjacent normal tissue. In stark contrast, full-length ASPP2 expression was suppressed in these breast tumors. Together these data suggest that the novel ΔN-ASPP2 isoform may play a role in antagonizing ASPP2 and/or p53 function, and promoting resistance to therapy. These findings open new areas for investigation into a potential new target for therapy in human cancer. 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 2189. doi:10.1158/1538-7445.AM2011-2189
Myocardial-Infarct Extension Detected by Precordial ST-Segment Mapping
Authors: Philip R. Reid, Dean R. Taylor, David T. Kelly, Myron L. Weisfeldt, J. O'Neal Humphries, Richard S. Ross, Bertram Pitt
Journal: New England Journal of Medicine (1974)

Daily precordial ST-segment mapping was performed with the millimeter sum of ST-segment deviation (ΣST) in a 48-lead system (1 mv = 20 mm) to evaluate 26 normal subjects and 19 patients with acute myocardial infarction. At the time of admission, ΣST (± S.D.)for transmural infarction (men + 140 ± 84.8, and women + 95.7 ± 8.8) and nontransmural infarction (-67 ± 32) was significantly different (p<0.001) from controls (men + 30.1 ± 18.1, and women + 17 ± 11.7). ΣST approached normal values by 10.6 and 13 hospital days, respectively. Twelve of 14 patients (86 per cent) with transmural infarction had re-elevation of ΣST ( + 76 ± 49.7) 5.8 days (mean) after admission. This finding was associated with abnormal creatine phosphokinase in eight (57 per cent), suggesting infarct extension. Standard six precordial leads did not reflect re-elevation of ΣST in four of the 12 patients with infarct extension. The 86 per cent incidence of infarct extension indicates that measures designed to decrease myocardial ischemia may be effective for many days after the onset of acute myocardial infarction. (N Engl J Med 290:123–128, 1974)
Advanced Glycosylation End Products in Patients with Diabetic Nephropathy
Authors: Zenji Makita, Steven Radoff, Elliot J. Rayfield, Zhi Yang, Edward Skolnik, Vera Delaney, Eli A. Friedman, Anthony Cerami, Helen Vlassara
Journal: New England Journal of Medicine (1991)

Glucose reacts nonenzymatically with proteins in vivo, chemically forming covalently attached glucose-addition products and cross-links between proteins. The excessive accumulation of rearranged late-glucose-addition products, or advanced glycosylation end products (AGEs), is believed to contribute to the chronic complications of diabetes mellitus.