tbuckley/cabot-search huggingface dataset:
Abstract 2100: Role of pocket proteins in HPV-associated head and neck squamous cell carcinomas
Authors: Myeong Kyun Shin, Henry C. Pitot, Julien Sage, Paul F. Lambert
Journal: Cancer Research (2011)

Abstract High-risk human papillomaviruses(HPVs) are associated with a subset of head and neck squamous cell carcinomas (HNSCC) as well as most of cervical cancers. HPV type 16 (HPV-16), which is found in the vast majority of HPV-positive HNSCC, encodes for three oncogenes: E5, E6, and E7. Previously, we learned that HPV-16 E7 is the dominant oncoprotein in head and neck cancer in mice. More recently, we learned that tissue specific inactivation of the retinoblastoma-susceptibility gene, pRb, a well known cellular target of HPV E7 and a member of the “pocket protein’ family, was not sufficient to account fully for the oncogenic properties of E7 in HNSCC. E7 is known to inactivate not just pRb, but also other related cellular proteins, specifically p107 and p130. This led to our current study in which we have observed that the combined loss of pRb and p130, or pRb and p107 leads to increased susceptibility to head and neck cancers in comparison to mice conditionally disrupted only for pRb, yet are not sufficient to account fully for E7's oncogenic potential in HPV-associated head and neck carcinogenesis. Additionally, combinatorial loss of pRb and p130, or pRb and p107 partially mediates E7-induced acute phenotypes in head and neck epithelia. Taken together, our results indicate that the combined inactivation of two pocket proteins are not sufficient to fully recapitulate E7 oncogenic properties in HNSCC. We conclude that inactivation of all three pocket proteins is necessary to account for E7's carcinogenic properties in HNSCC or that other targets of E7 contribute to its carcinogenic potential in HNSCC. 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 2100. doi:10.1158/1538-7445.AM2011-2100
Commentary: Regulatory Aspects and Research Needs
Authors: Glenn E. Schweitzer
Journal: Environmental Health Perspectives (1975)

This conference has underscored the many gaps in our understanding of the behavior of vinyl chloride and the inadequacies of current research efforts to improve the data base which supports the regulatory decisions that must be made now. In addition to the need for much better information on the human health effects of exposures to low levels of vinyl chloride, we know relatively little about the persistence of vinyl chloride in air and water and the degradation products associated with this chemical, the ecological effects of vinyl chloride, particularly as it interacts with aquatic organisms, and the rates of migration of unreacted vinyl chloride monomer from products containing PVC during their use and disposal. Perhaps, even more importantly the conference has highlighted what many environmentalists are calling the tip of the icebergan iceberg of chemical problems that will continue to float to the surface during the decades ahead. For example, the array of hundreds of chemicals added to plastics that was shown here clearly illustrated the complexity of the task of the researcher in attempting to provide an early warning of future problems. It certainly appears that, except for continuing concern over spills and accidents, government and industry have been rather complacent with regard to the potential environmental threat from the high volume industrial chemicals. This complacency is in large measure attributable to the relative absence of visible and uncontrolled dangers from exposure to the chemicals during their long histories. In addi-
Abstract 4917: CD44 standard form expression in human ovarian carcinoma is correlated with disease progression but not prognosis.
Authors: Jing Zhang, Bin Chang, Jinsong Liu
Journal: Cancer Research (2013)

Abstract Single-chain glycoprotein CD44 is a major cell surface receptor for hyaluronan and mediates epithelial cell adhesion by its involvement in cell-cell and cell-matrix interactions. Recently, CD44 has been identified as a biomarker of cancer stem cells in many malignancies, including ovarian carcinoma. However, its clinical significance in human ovarian carcinoma has been controversial until recently. The aim of our current study was to clarify the clinical role of CD44 expression in ovarian carcinoma. Immunohistochemical staining of 483 human primary ovarian carcinoma, and 27 paired primary and recurrent ovarian carcinoma samples for CD44 standard form (CD44s) was performed using tissue microarray. The associations between CD44s expression and clinical factors (diagnosis, tumor grade, International Federation of Gynecology and Obstetrics stage, and response to chemotherapy) and overall and disease-free survivals were analyzed. We observed CD44s expression in 38.1% of the ovarian carcinoma samples. Results of Fisher's exact test suggested that CD44s expression was associated with high-grade carcinoma (P = 0.013), especially high-grade serous carcinoma (P = 0.037); International Federation of Gynecology and Obstetrics stage (III-IV, P &amp;lt; 0.001); age at diagnosis less than 60 years old (P = 0.011); and transitional cell carcinoma (P = 0.039). However, CD44s expression was not associated with overall survival (P = 0.529) or disease-free survival (P = 0.035) by the log-rank test. Moreover, there was no statistical difference in CD44s expression between the primary and recurrent epithelial ovarian carcinomas. Our results showed that CD44s expression is correlated with tumor progression but not prognosis. Citation Format: Jing Zhang, Bin Chang, Jinsong Liu. CD44 standard form expression in human ovarian carcinoma is correlated with disease progression but not prognosis. [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 4917. doi:10.1158/1538-7445.AM2013-4917
SP0086 Regulatory B cells in healthy and in patients with SLE
Authors: C. Mauri
Journal: Annals of the Rheumatic Diseases (2013)

Recent advances have demonstrated the existence of a B cell subset with regulatory function named (Bregs). Bregs have been shown to restrain the severity of several autoimmune disease and contribute to the development of infection and cancer. In human CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup>CD1d<sup>hi</sup>regulatory B cells inhibit the activation of T helper (Th)1 and Th17 responses whilst supporting the differentiation of FoxP3<sup>+</sup> Tregs. We have shown that in addition to regulate CD4+T cells differentiation, Breg are essential for <i>i</i>NKT cell homeostasis in healthy individuals but fail to exert the same effect in SLE patients. CD1d-restricted <i>invariant</i> natural killer T (<i>i</i>NKT) cells play an immune-regulatory role functioning in both innate and adaptive immunity. Defective B cell-mediated stimulation of <i>i</i>NKT cells in SLE, was associated with rapid internalization and reduced surface expression of CD1d on immature B cells from SLE patients compared with B cells from healthy individuals. <i>i</i>NKT cell number and function were restored in SLE patients responding to B cell depletion therapy, upon normalization of CD1d levels in repopulated CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup>CD1d<sup>hi</sup>regulatory B cells. <h3>Disclosure of Interest</h3> None Declared
Abstract 120: Detection of acrolein-derived cyclic DNA adducts in human cells by monoclonal antibodies.
Authors: Jishen Pan, Bisola Awoyemi, Zhuoli Xuan, Priya Vohra, Hsiang-Tsui Wang, Marcin Dyba, Emily Greenspan, Ying Fu, Karen Creswell, Lihua Zhang, Deborah Berry, Moon-Shong Tang, Fung-Lung Chung
Journal: Cancer Research (2013)

Abstract Acrolein (Acr) is a ubiquitous environmental pollutant found in cigarette smoke and automobile exhaust. It can also be produced endogenously by oxidation of polyunsaturated fatty acids. The Acr-derived 1,N2-propanodeoxyguanosine (Acr-dG) adducts in DNA are mutagenic lesions that are potentially involved in human cancers. In this study, monoclonal antibodies were raised against Acr-dG adducts and characterized using ELISA. They showed strong reactivity and specificity towards Acr-dG, weaker reactivity towards crotonaldehyde- and trans-4-hydroxy-2-nonenal-derived 1,N2-propanodeoxyguanosines, and weak or no reactivity towards 1,N6-ethenodeoxyadenosine, 8-oxo-deoxyguanosine, and benzo(a)pyrene- and malondialdehdye-derived adducts. Using these novel antibodies, we developed assays to detect Acr-dG in vivo: First, a simple and quick FACS-based assay for detecting these adducts directly in cells; Second, a highly sensitive direct ELISA assay for measuring Acr-dG in cells and tissues using only one μg DNA; And third, a competitive ELISA for better quantitative measurement of Acr-dG levels in DNA. The assays were validated using Acr-treated HT29 cell DNA samples or calf thymus DNA and the results were confirmed by LC-MS/MS-MRM. An immunohistochemical assay was also developed to detect and visualize Acr-dG in HT29 cells as well as in human oral cells. These antibody-based methods provide useful tools for the studies of Acr-dG as a cancer biomarker and of the molecular mechanisms by which cells respond to Acr-dG as a ubiquitous DNA lesion. (This work was supported by NCI grant CA134892) Citation Format: Jishen Pan, Bisola Awoyemi, Zhuoli Xuan, Priya Vohra, Hsiang-Tsui Wang, Marcin Dyba, Emily Greenspan, Ying Fu, Karen Creswell, Lihua Zhang, Deborah Berry, Moon-Shong Tang, Fung-Lung Chung. Detection of acrolein-derived cyclic DNA adducts in human cells by monoclonal antibodies. [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 120. doi:10.1158/1538-7445.AM2013-120
Abstract 204: p53-induced gene 3 activity is glutathione peroxidase 3 dependent
Authors: Yan P. Yu, Hui Wang, Katherine L. Luo, Jian-Hua Luo
Journal: Cancer Research (2011)

Abstract The expression of glutathione peroxidase 3 (GPx3) was found widely altered in a variety of human malignancies. Methylation and deletion of GPx3 were reported in several types of human cancers. Recently, GPx3 characterized as a tumor suppressor gene. However, the mechanism of the tumor suppressor activity of GPx3 is not clear. In this report, we demonstrated that GPx3 interacts with p53-induced gene 3 (PIG3) in both prostate cancer cells and immortalized prostate epithelial cells. The PIG3 binding motif is located in amino acid 2-114 of GPx3. Expression of GPx3 resulted in apopotosis and necrotic cell death. Interaction of GPx3 and PIG3 led to dramatic increase of reactive oxygene species (ROS) inside the cells and activation of caspase-3. Knocking down of PIG3 or mutation of PIG3 binding motif in GPx3 abrogated ROS generation activity induced by GPx3. These results suggest that PIG3 activity is GPx3-dependent, and reveal a novel signaling pathway that leads to GPx3 mediated tumor suppression. 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 204. doi:10.1158/1538-7445.AM2011-204
Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta‐omics‐based approach
Authors: Federica Del Chierico, Valerio Nobili, Pamela Vernocchi, Alessandra Russo, Cristiano De Stefanis, Daniela Gnani, Cesare Furlanello, Alessandro Zandonà, Paola Paci, Giorgio Capuani, Bruno Dallapiccola, Alfredo Miccheli, Anna Alisi, Lorenza Putignani
Journal: Hepatology (2016)

There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by gut microbiota. Therefore, we investigated its modifications in pediatric NAFLD patients using targeted metagenomics and metabolomics. Stools were collected from 61 consecutive patients diagnosed with nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), or obesity and 54 healthy controls (CTRLs), matched in a case‐control fashion. Operational taxonomic units were pyrosequenced targeting 16S ribosomal RNA and volatile organic compounds determined by solid‐phase microextraction gas chromatography‐mass spectrometry. The α‐diversity was highest in CTRLs, followed by obese, NASH, and NAFL patients; and β‐diversity distinguished between patients and CTRLs but not NAFL and NASH. Compared to CTRLs, in NAFLD patients Actinobacteria were significantly increased and Bacteroidetes reduced. There were no significant differences among the NAFL, NASH, and obese groups. Overall NAFLD patients had increased levels of Bradyrhizobium , Anaerococcus , Peptoniphilus , Propionibacterium acnes, Dorea , and Ruminococcus and reduced proportions of Oscillospira and Rikenellaceae compared to CTRLs. After reducing metagenomics and metabolomics data dimensionality, multivariate analyses indicated a decrease of Oscillospira in NAFL and NASH groups and increases of Ruminococcus , Blautia, and Dorea in NASH patients compared to CTRLs. Of the 292 volatile organic compounds, 26 were up‐regulated and 2 down‐regulated in NAFLD patients. Multivariate analyses found that combination of Oscillospira , Rickenellaceae, Parabacteroides , Bacteroides fragilis , Sutterella , Lachnospiraceae, 4‐methyl‐2‐pentanone, 1‐butanol, and 2‐butanone could discriminate NAFLD patients from CTRLs. Univariate analyses found significantly lower levels of Oscillospira and higher levels of 1‐pentanol and 2‐butanone in NAFL patients compared to CTRLs. In NASH, lower levels of Oscillospira were associated with higher abundance of Dorea and Ruminococcus and higher levels of 2‐butanone and 4‐methyl‐2‐pentanone compared to CTRLs. Conclusion: An Oscillospira decrease coupled to a 2‐butanone up‐regulation and increases in Ruminococcus and Dorea were identified as gut microbiota signatures of NAFL onset and NAFL‐NASH progression, respectively. (H epatology 2017;65:451‐464)
1336 NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) INDEPENDENTLY PREDICTS TYPE-2 DIABETES AND PRE-DIABETES DURING A SEVEN-YEAR PROSPECTIVE FOLLOW-UP
Authors: S. Zelber-Sagi, R. Lotan, O. Shibolet, M. Webb, A. Buch, Z. Halpern, E. Santo, R. Oren
Journal: Journal of Hepatology (2012)
Hepatic Hydrothorax
Authors: Antonio Giacobbe, Domenico Facciorusso, Filippo Barbano, Angelo Andriulli, Vincenzo Frusciante
Journal: Clinical Nuclear Medicine (1996)

Twelve cases of right hepatic hydrothorax are reported. Tc-99m SC that was injected intraperitoneally and intrapleurally provided evidence of a one-way flow of fluid from the peritoneal to the pleural cavity. Eight patients, whose hydrothorax was refractory to sodium restriction, diuretics and repeated thoracenteses, were treated by endopleural tetracycline instillation. The pathogenetic role of the diaphragmatic defect and the diagnostic usefulness of radionuclide imaging are stressed.
430 KEY GENETIC SIGNATURES IN THE WHOLE pre-S1/Pre-S2/S GENE CORRELATE WITH HBV-INDUCED CARCINOGENESIS BY AFFECTING HBsAg SECRETION AND RELEASE
Authors: V. Svicher, M. Neumann-Fraune, C. Mirabelli, R. Salpini, V. Cento, V.-C. Di Maio, A. Bertoli, C. Alteri, M. Aragri, C. Gori, V. Micheli, G. Gubertini, P. Trimoulet, H. Fleury, J. Vecchiet, N. Iapadre, A. Barlattani, T. Mari, C. Pasquazzi, C. Sarrecchia, F. Ceccherini-Silberstein, M. Andreoni, M. Angelico, J. Verheyen, C.-F. Perno
Journal: Journal of Hepatology (2013)
Successful Treatment of Severe Diabetic Coma Complicated by Chronic Laryngeal Obstruction
Authors: Rosemary V. Gorman, Reed Harwood, Paul D. White
Journal: New England Journal of Medicine (1946)

THE association of severe diabetic coma and chronic laryngeal obstruction is rare. The case reported herein presented these two problems, and in addition a third, a severe mental depression following tracheotomy that induced the patient to neglect the treatment of his diabetes. Although his immediate survival depended on recovery from the coma, his return to life as a useful citizen awaited the repair of the tracheotomy. In the treatment of the coma, the largest amount of insulin ever reported to have been given in twenty hours was administered. Three delicate plastic operations were performed to repair the tracheotomy. Our experience . . .
FRI0413 Listening to patients – how to improve a rheumatology service
Authors: C. Mercieca, S.J. Cassar, A.A. Borg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Several studies have shown that involving patients in their medical care results in a better outcome and greater satisfaction with care (1,2). However, few studies focus on the patients' perspective of the actual health service delivery. The patient experience starts from the time of the appointment letter followed by the outpatient clinic, consultation and follow up. An efficient and effective service depends on the whole team including doctors, nurses, pharmacists, therapists, receptionists, secretaries as well as the facilities and clinical pathways. A successful service is only as strong as the weakest link in its chain. <h3>Objectives</h3> To assess the healthcare, information needs and expectations of patients attending a rheumatology outpatient clinic <h3>Methods</h3> Cross sectional survey using a questionnaire of 70 consecutive patients attending rheumatology outpatients. Questionnaire addressed aspects of the structure, process and outcome of a rheumatology consultation and overall satisfaction. <h3>Results</h3> 94% were highly satisfied with the overall service. 87.1% were highly satisfied with the efficiency and service offered at the reception desk. 98.5% agreed that they had adequate time during the consultation to discuss their condition. 75.7% strongly believed that written information helps them understand their illness better. Areas of dissatisfaction reported were waiting longer than 30 minutes from registration at the reception until review by the healthcare professionals (55.7%), interruptions during a consultation (38.6%) and an inadequate waiting area to accommodate their needs and disabilities (24.7%). When asked to rank different aspects of service delivery according to importance, punctuality was ranked first by the majority followed by availability of more frequent appointments and being informed beforehand specifically who will be performing the consultation. 80% agreed that a prompt clinic letter sent to their GP would facilitate clinical care. <h3>Conclusions</h3> Health service research is important for patients, clinicians and policy makers alike. A successful service in the eyes of patients is not only the consultation with the specialist but the holistic experience including structure, process and outcomes. An easily accessible user friendly health care delivery is key in a patient centred care system. This study highlights areas in healthcare delivery which are not meeting patients' expectations. Clinicians are vital in setting a vision, managing and improving the services that they provide. Obtaining patients' perspective of the health service is a key element in ensuring that services are built around the needs of our patients. <h3>References</h3> Wressle E, et al. J Rehabil Med 2002;34:5–11. Brekke M, et al. Arthritis Rheum 2001;45:8–15. <h3>Disclosure of Interest</h3> None Declared
COMPARISON OF LATE GADOLINIUM ENHANCEMENT PATTERNS IN DIFFERENT FORMS OF CARDIAC AMYLOIDOSIS
Authors: Arnt Kristen, Rebekka Kammerer, Fabian aus dem Siepen, Katrin Scherer, Sebastian Buss, Evangelos Giannitsis, Hugo A. Katus, Henning Steen
Journal: Journal of the American College of Cardiology (2013)
OP0296 Hypoxia-Inducible Factor 2A Regulates Macrophage Function in Rheumatoid Arthritis
Authors: W. Hardy, F. Wright, S. Hawtree, U. Fearon, D. Veale, M. Perretti, A. Wilson, M. Muthana
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In rheumatoid arthritis (RA), the influx of inflammatory cells as well as the aggressive proliferation of fibroblast-like synovial cells (FLS) outstrips the oxygen supply from blood vessels leading to joint hypoxia. Macrophages accumulate in these hypoxic sites where they possess broad pro-inflammatory, destructive and remodelling potential leading to inflammation and joint destruction. Macrophages respond to such hypoxia by up regulating the hypoxia inducible transcription factors – HIF-1a and -2a, which leads to the up-regulation of genes involved in proliferation, angiogenesis, and glucose metabolism. <h3>Objectives</h3> To characterise the HIF-2a expressing macrophage populations in response to joint hypoxia, and in particular to dissect out the effects of HIF-2 in a murine model of arthritis. <h3>Methods</h3> Tissue from RA patients was assessed for oxygen levels using an oxygen/temperature probe then sections were immunostained with anti-HIF-2a and co-localised with the pan-macrophage markers CD68 as well as other M1 and M2 macrophage markers. Cell-specific RNA was purified from CD68+ macrophages in RA tissue by laser capture microdissection and differential gene expression was determined using the RT<sup>2</sup> Profiler PCR inflammatory arrays. The significance of HIF-2a was also evaluated in the K/BxN serum transfer model in mice bearing a targeted deletion of HIF-2a in myeloid cells including macrophages (HIF2fl/fl; LysM-Cre+9 mice). Arthritis was assessed clinically and histologically. <h3>Results</h3> In patients with severely hypoxic tissue (pO<sub>2</sub>&lt;20 mmHg), CD68+ macrophages predominately expressed HIF-2a compared to macrophages from mildly hypoxic (pO<sub>2</sub>&gt;20 mmHg) tissue (58%±10.2 vs. 15±9.3 <i>p</i>=0.01, respectively). This reduced in vivo oxygen tension (pO<sub>2</sub>&lt;20 mmHg) also positively correlated with macrophages expressing GLUT 1 and receptors for VEGF (Flt1), angiopoietin "Tie2" and mannose "CD206", all markers associated with M2-skewed macrophages. In addition, these hypoxic macrophages expressed increased mRNA for CXCL-2, -4, -5, IL-1a, IL-6, IL-8 &amp; TNFa compared to macrophages from mildly hypoxic joints. <i>In vivo,</i> macrophages lacking HIF-2a significantly suppressed disease development indicating an indispensable role for HIF-2 in supporting macrophages in K/BxN serum-transfer arthritis. <h3>Conclusions</h3> HIF-2a expressing macrophages have an M2-like phenotype in patients with severely hypoxic joints and loss of HIF-2a in macrophages suppressed arthritis in mice. Collectively, our data identify HIF-2a as an important regulator of macrophage function, suggesting it may be a useful therapeutic target for treating RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4257
INTRACORONARY ADMINISTRATION OF MICROENCAPSULATED INSULIN-LIKE GROWTH FACTOR 1 IMPROVES CARDIAC FUNCTION IN A SWINE MODEL OF ACUTE MYOCARDIAL INFARCTION
Authors: Veronica Crisostomo, Claudia Baez-Diaz, Virginia Blanco, Juan Maestre, Teresa Mangas, Itziar Palacios, Rob Steendam, Christine Hiemstra, Okke Franssen, Francisco Sanchez
Journal: Journal of the American College of Cardiology (2016)