tbuckley/cabot-search huggingface dataset:
FRI0421 Immune Effects of Human Papilloma Virus (HPV) Immunization in Patients with Systemic Lupus Erythematosus (SLE)
Authors: L. Baranda, C. Alvarez-Quiroga, R. González-Amaro, B. Hernández-Castro, L. Doniz-Padilla, H. Portillo-Salazar, E. Layseca-Espinosa, C. Abud-Mendoza
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Women with SLE show an increased risk for HPV infection and development of precancerous lesions. Although HPV vaccine is safe and effective in healthy females, there are limited data on the immune effects of HPV immunization in females with SLE. In this work we evaluated different laboratory and clinical data in young women with SLE that received the bivalent HPV vaccine cervarix. <h3>Objectives</h3> To evaluate the possible effect of HPV immunization on different immune and clinical parameters in patients with SLE. <h3>Methods</h3> We performed a prospective, open-label study in 34 patients with SLE. In all cases, the following parameters were assessed at 0, 1, 3, 6 and 12 months: Disease activity (SLEDAI),anti-HPV antibody titers, levels of memory B cells, Th17 lymphocytes, and NK cell subsets as well as nTreg lymphocyte function and number, and ILT2 (CD85j) expression and function. <h3>Results</h3> We observed that in most patients diminished their SLEDAI score after HPV immunization. In addition, we detected a significant increase in CD19+CD27+ memory B and Th17 lymphocytes as well as in different NK cell subsets. In contrast, the levels of nTreg cells diminished. However, we also detected an increased function of Treg cells upon HPV immunization as well as an ehnaced expression and function of the immunoregulatory receptor ILT2. No important clinical events were detected, and only 2 out of 17 patients with lupus nephritis showed a mild deterioration in renal function. <h3>Conclusions</h3> Our data suggest that HPV immunization in SLE is safe and that it has different interesting immune effects. <h3>References</h3> Lai-Shan T, Chan YK, Chan PK, Chang AR, Li EK. Increased prevalence of squamous intraepithelial lesions in systemic lupus erythematosus, association with human papillomavirus infection. Arthritis Rheum 2004;50:3619-3625. Colmenares V, Noyola DE, Monsivais-Urenda A, Salgado-Bustamante M, Estrada-capetillo L, González-Amaro R, Baranda L. Human papillomavirus immunization is associated with increased expression of different innate immune regulatory receptors. Clin Vaccine Immunol 2012;19:105-1011. <h3>Acknowledgements</h3> This work was supported by a grant from CONACYT-SEP (CB2012-180094) to Baranda L. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5934
Abstract 2725: Progesterone promotes estrogen induced mammary tumorigenesis through the activation of nodal and notch signaling
Authors: Diego A. Pedroza, Arunkumar Arumugam, Sushmita Nandy, Ramadevi Subramani, Thiyagarajan Boopalan, Rajkumar Lakshmanaswamy
Journal: Cancer Research (2015)

Abstract Nodal and Notch are considered to be important embryonic morphogens, regulating cell - cell communication, determining left - right asymmetry and in formation of the mesoderm. Cellular processes in embryogenesis can be compared to processes occurring during tumorigenesis. Nodal has been shown to re emerge in aggressive triple negative breast carcinomas, and Notch is known to promote breast cancer. The role of Nodal and Notch in breast carcinomas is being studied; however hormonal regulation of theses two cancer-promoting genes is unknown. Ovarian hormones Estrogen (E) and Progesterone (P) play a vital role in the normal development and function of breast tissue, while extensive exposure to these hormones increases the risk of breast cancer. Studies conducted by the Women's Health Initiative (WHI) have demonstrated that combined Hormone Replacement Therapy (HRT) increases breast cancer risk. The objective of this study is to determine whether P promotes E induced mammary tumorigenesis through the activation of Nodal and Notch signaling. To study the molecular mechanism, MCF-7 cells were cultured and treated with hormones: E, P, E+P and E+Mifepristone (MP - a progesterone antagonist). MTS assay for cellular proliferation, PCR array for gene expression, and western blot for protein expression, were performed. MTS assay showed increased cell proliferation of MFC-7 hormone treatment E+P when compared to control. PCR array analysis showed significant alteration of genes associated with Nodal signaling, specifically Lefty in E+MP treatment, protein expression analysis showed activation of Notch and up - regulation of its downstream targets HES1 and HEY1 with E and P individual and combination treatments while it was down regulated in E+MP treatment. Based on our findings, we suggest that P mediates E induced mammary tumorigenesis through the activation of Nodal and Notch signaling, proposing a possible crosstalk between both pathways in the development and progression of breast cancer. Citation Format: Diego A. Pedroza, Arunkumar Arumugam, Sushmita Nandy, Ramadevi Subramani, Thiyagarajan Boopalan, Rajkumar Lakshmanaswamy. Progesterone promotes estrogen induced mammary tumorigenesis through the activation of nodal and notch signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2725. doi:10.1158/1538-7445.AM2015-2725
IMAGING BIOMARKERS OF MALIGNANT PROGRESSION OF DIFFUSE LOW-GRADE GLOMA (LGG)
Authors: S. M. Chang, A. Elkhaled, L. Jalbert, J. J. Phillips, S. Cha, A. Molinaro, S. J. Nelson
Journal: Neuro-Oncology (2014)

BACKGROUND: Patients with tumors that recur from a prior LGG have quite different outcomes depending on their histological subtype, grade, and molecular/cytogenetic features. Non-invasive biomarkers that accurately reflect the biological properties of the lesion are urgently needed to make informed decisions about patient care. The primary objective of this study was to evaluate the role of noninvasive imaging parameters as biomarkers of malignant progression in diffuse LGG (WHO II) and to use these parameters to select the most metabolically active regions of tumors for characterization of their histological features. METHODS: After obtaining informed consent, 125 patients undergoing surgical resection of tumors that recurred from a prior LGG were prospectively enrolled from 2008-2012 in an institutional review board approved protocol. Preoperative MR metabolic and physiological images were used to select image guided tissue sample targets for histological status, IDH1 mutation and ex vivo metabolic profiles. H&E and immunohistochemistry of the tissue samples provided the following parameters: tumor score, necrosis, CA9 status (measure of hypoxia), MIB-1 status, cellularity, SMI-31 status and vascular status. RESULTS: 44% of the 125 tumors were grade II at recurrence, with 56% having upgraded in histology (44% grade III and 12% grade IV). Significant differences were observed for in vivo measures of maximum choline to N-acetylasparate index (CNI) and lactate, normalized apparent diffusion coefficient <1.5, and normalized cerebral blood volume >2 for patients with upgraded versus non-upgraded lesions. CONCLUSIONS: The results from this study highlight tumor heterogeneity and underline the use of metabolic and physiologic imaging for non-invasively predicting upgrade status for patients with recurrent LGG who are not surgical candidates and also for directing the surgeon to the most malignant region of the lesion to get representative tissue for evaluation. These enhanced parameters will be utilized in a new cohort of 100 patients with recurrent LGG and their tissue will be used to characterize the genomic properties of non-upgraded versus upgraded samples. SECONDARY CATEGORY: n/a.
Rapid Functional Suppression of the Adrenal Cortex Due to Prednisone Therapy
Authors: Leon J. Marks, Richard Chute, Richard L. Sallade
Journal: New England Journal of Medicine (1961)

SINCE Ingle's1 observation that long-term administration of adrenocortical extract results in atrophy of the adrenal cortex in animals, it has been recognized that corticosteroid-induced adrenocortical atrophy is one of the most undesirable side effects of corticosteroid therapy in man.2 In a recent study, Marks and his associates3 demonstrated that patients who have been receiving corticosteroids for a period of four to six months or longer have a markedly diminished adrenocortical capacity to respond to the stimulus either of exogenous ACTH or of a major surgical procedure.3 However, their data did not reveal how rapidly depression of adrenal function can occur . . .
VORAPAXAR AND ACUTE LIMB ISCHEMIA: INSIGHTS FROM THE THROMBIN RECEPTOR ANTAGONIST IN SECONDARY PREVENTION OF ATHEROTHROMBOTIC ISCHEMIC EVENTS-TIMI 50 TRIAL
Authors: Antonio Gutierrez, Marc Bonaca, Benjamin Scirica, Mark Creager, Sabina Murphy, Eugene Braunwald, David Morrow
Journal: Journal of the American College of Cardiology (2015)
Abstract 2798: Tyrosine phosphorylation of LDH-A is important for cancer cell redox homeostasis and tumor growth
Authors: Jun Fan, Taro Hitosugi, Tae-Wook Chung, Xu Wang, Ting-Lei Gu, Johannes L. Roesel, Zhuo (Georgia) Chen, Titus Boggon, Fadlo R. Khuri, Sumin Kang, Jing Chen
Journal: Cancer Research (2011)

Abstract Cancer cells take up more glucose than normal tissue and favor aerobic glycolysis, generating lactate through a NADH-dependent enzyme, lactate dehydrogenase A (LDH-A). This is the last step of glycolysis that permits the regeneration of NAD+, which is needed as an electron acceptor to maintain cytosolic glucose catabolism. Therefore, most tumor cells are reliant on lactate production for their survival. LDH-A gene expression is believed to be upregulated by both HIF and Myc in cancer cells to achieve increased lactate production, and expression of LDH-A was previously implicated to be involved in tumour initiation and growth. However, how oncogenic signals activate LDH-A to regulate cancer cell metabolism remains unclear. Our phospho-proteomics studies revealed that oncogenic fibroblast growth factor (FGF) receptor type 1 (FGFR1) tyrosine kinase directly phosphorylates LDH-A. Structural and biochemical studies revealed that phosphorylation at Y10 and Y83 activates LDH-A by promoting the formation of active, tetrameric LDH-A and binding of LDH-A substrate NADH, respectively. Moreover, we found that LDH-A is commonly phosphorylated at Y10 in diverse human cancer cells by multiple oncogenic tyrosine kinases including BCR-ABL, FLT3 and JAK2, which represents an acute molecular mechanism underlying increased lactate production in cancer cells. Furthermore, cancer cells with stable knockdown of endogenous LDH-A and rescue expression of a catalytic hypomorph LDH-A mutant, Y10F, show decreased cell proliferation and ATP levels under hypoxia, increased mitochondrial respiration to sustain glycolysis by providing NAD+, and reduced tumor growth in xenograft nude mice. Our findings suggest that tyrosine phosphorylation activates LDH-A to promote the Warburg effect and tumor growth by regulating NADH/NAD+ redox homeostasis in cancer cells. 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 2798. doi:10.1158/1538-7445.AM2011-2798
Diffuse FDG Uptake of the Bilateral Atrial Walls in a Patient With Atrial Fibrillation
Authors: Aisheng Dong, Tiejun Zhao, Jing Gong, Changjing Zuo
Journal: Clinical Nuclear Medicine (2013)

A 59-year-old man, who had a 3-year history of paroxysmal atrial fibrillation, was referred to our hospital because of palpitation for 12 hours. Atrial fibrillation was confirmed by ECG. F-FDG PET/CT scan was performed showing diffuse FDG uptake of the bilateral atrial walls. Enhanced chest CT showed that the bilateral atria and ventricles were normal. This case highlights that atrial fibrillation should be included in the differential diagnosis of abnormal atrial FDG accumulation along with tumor and inflammatory processes.
The puzzle of metabolic effects of obstructive sleep apnoea in children
Authors: Oreste Marrone, Maria R. Bonsignore
Journal: European Respiratory Journal (2016)

In adults, obstructive sleep apnoea (OSA) is often associated with metabolic alterations. Although obesity is a major culprit [1], large epidemiological studies have reported a metabolic risk associated with OSA that is independent of obesity. In particular, meta-analyses have shown that effective treatment of OSA by continuous positive airway pressure (CPAP) improves glycaemic control in both diabetic [2] and nondiabetic patients [3]. In obese children with obstructive sleep apnoea insulin resistance is common while lipids do not show a clear pattern <http://ow.ly/XNR9s>
Paracentesis with Intravenous Infusion of Albumin as Compared with Peritoneovenous Shunting in Cirrhosis with Refractory Ascites
Authors: Pere Ginès, Vicente Arroyo, Victor Vargas, Ramón Planas, Fernando Casafont, Julià Panés, Melchor Hoyos, Lluis Viladomiu, Antoni Rimola, Rosa Morillas, Joan Manuel Salmerón, Angels Ginès, Rafael Esteban, Joan Rodés
Journal: New England Journal of Medicine (1991)

There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits.
Spotlight on HDL biology: new insights in metabolism, function, and translation
Authors: D. J. Rader
Journal: Cardiovascular Research (2014)

High-density lipoproteins (HDLs) have captured the imagination of scientists and physicians from virtually the time they were originally described, but especially after the cholesterol carried in HDL (HDL-C) was shown to be strongly and inversely associated with risk of coronary heart disease (CHD).1 This observation, replicated in many populations around the world, has led to the popular view of HDL-C as the ‘good cholesterol’ and to the belief that intervention to raise plasma levels of HDL-C would lead to reduction in risk of CHD (the ‘HDL hypothesis’). Because of its obvious clinical relevance, the structure, function, metabolism, and regulation of HDL has been studied in great detail by hundreds of laboratories around the world. The science and biology of HDL is a mature field that has been informed by structural biology, lipid and protein biochemistry, model systems, human genetics and physiology, and pharmacology. Although much has been learned, there remain major questions surrounding HDL, not the least of which includes recent scepticism about the fundamental HDL hypothesis.

Two major developments over the last few years, in human genetics and clinical trials with pharmacological agents, have led to doubts about the HDL hypothesis. Human genetics have taught us a great deal about HDL metabolism. Mendelian disorders of extreme low and high HDL-C levels have been extremely informative regarding the key roles of specific proteins.2 More recently, unbiased genome-wide studies have led to scores of additional loci associated with HDL-C levels.3 A focus of intense interest has been the relationship between genetic factors that influence HDL-C levels and risk of CHD. It is interesting that despite decades of study, the three Mendelian causes of extremely low HDL-C — apoA-I structural mutations, …
S90 Nurse specialist input is independently associated with anti-cancer treatment in lung cancer
Authors: P. Beckett, I. Woolhouse, R. Stanley, L. J. Tata, M. D. Peake, L. Darlinson
Journal: Thorax (2011)

<h3>Introduction</h3> Lung cancer nurse specialists (LCNS) provide an extremely important service to patients. Their skill and expertise are valued very highly by both patients and colleagues, but it has proven difficult to measure their input objectively, leading to a lack of expansion (and in some areas contraction) of the workforce. Earlier this year the National Lung Cancer Audit (NLCA) reported that for 2009, patients who saw an LCNS were more than twice as likely to receive active anti-cancer treatment, but the relevance of this observation is obscured by a lack of case-mix adjustment and a high proportion of unrecorded data. We have sought to examine this finding more closely on the 2010 dataset (with less unrecorded data) by performing case-mix adjustment. <h3>Methods</h3> Details of all patients from English trusts that were submitted to the NLCA database in 2010 were obtained. We then performed logistic regression analysis based on sex, age, stage and performance status to calculate mutually-adjusted ORs for overall and specific treatments. Since a patient would have reduced opportunity to access an LCNS if their survival were short, a second model was created excluding those patients who had survival of &lt;28 days. <h3>Results</h3> Of 30 334 in the dataset, 42 were removed due to missing sex (4), in situ disease (2) and occult stage (36). 74.8% were recorded as having been seen by a LCNS, 7.8% were not seen, and in 17.4% the outcome was not recorded. The latter two groups were combined for the remainder of the analysis. ORs for treatment if seen by a nurse in both models are shown below. <h3>Conclusions</h3> Contact with a LCNS was associated with increased rates of active treatment, particularly chemotherapy or radiotherapy, but not surgery, and this effect was independent of sex, age, disease stage and performance status. While the LUCADA dataset does not contain detailed information on individual reasons for LCNS assessments, this should be investigated further as there may be important additions to the known benefits LCNS provide to patients. However, regardless of the explanation, all lung cancer patients should have the opportunity to benefit from the expertise of a LCNS.
Abstract 5091: Potent anti-tumor activity of blocking stromal Dll4 in ovarian xenograft models.
Authors: Frank Kuhnert, Guoying Chen, Gavin Thurston
Journal: Cancer Research (2013)

Abstract Potent anti-tumor activity of blocking stromal Dll4 in ovarian xenograft models Delta-like ligand 4 (Dll4) is an emerging anticancer target given its predominant tumor vasculature expression and its role in regulating angiogenic sprouting. We have previously demonstrated that pharmacological blockade of the Dll4-Notch axis results in an excessive production of aberrant non-functional tumor vessels, and these changes were associated with reduced tumor growth. Using VelocImmune® mice, we identified a fully human IgG1 monoclonal antibody, termed REGN421/SAR153192, which binds human Dll4 and potently neutralizes Notch signaling. REGN421 treatment caused potent and dose-dependent inhibition of a number of human tumor xenografts grown in immunodeficient mice engineered to express human Dll4. In the current study, we found that REGN421 treatment of ovarian xenograft models produces potent anti-tumor effects that are dependent on targeting Dll4 in the tumor stroma as opposed to tumor cell-expressed Dll4. In particular, REGN421 treatment (2.5 mg/kg, once weekly) of humanized Dll4 mice bearing established subcutaneous TOV-112D or intraperitoneal A2780 human tumor xenografts resulted in growth inhibition of 86% and 83%, respectively. The inhibition of ovarian tumor growth by REGN421 was associated with a marked increase in tumor vascular structures but reduced vascular perfusion, consistent with the function of Dll4 as a regulator of angiogenic sprouting. Similar anti-tumor effects were observed by strictly targeting stromal Dll4 with a mouse Dll4-specific surrogate antibody REGN1035 in SCID mice bearing OVCAR3 tumors. In contrast, the specific blockade of tumor cell-expressed human Dll4 did not exhibit any appreciable anti-tumor activity, indicating the lack of tumor growth-promoting autocrine Dll4-Notch tumor cell signaling in these models. Finally, the combined treatment of Dll4 antibody with the anti-VEGF agent ziv-aflibercept (VEGF Trap) resulted in enhanced anti-tumor effects and virtually the complete suppression of intraperitoneal A2780 tumor growth, suggesting clinical benefit for the combined blockade of VEGF and Dll4 in ovarian cancer. These studies lend further support for the therapeutic targeting of Dll4 as a promising new angiogenesis-based anticancer strategy in ovarian cancer, both as a single agent and in combination with anti-VEGF agents. Citation Format: Frank Kuhnert, Guoying Chen, Gavin Thurston. Potent anti-tumor activity of blocking stromal Dll4 in ovarian xenograft models. [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 5091. doi:10.1158/1538-7445.AM2013-5091
279 SIDE POPULATION IN HUMAN HEPATIC CARCINOMAS REFLECTS A POPULATION WITH PROGENITOR CELL FEATURES
Authors: O. Govaere, M. Komuta, K. Van den Eynde, J. Wouters, A. Van den Broeck, C. Empsen, L. Gremeaux, R. Aerts, L. van Grunsven, B. Topal, H. Vankelecom, T. Roskams
Journal: Journal of Hepatology (2012)
Terminal Transferase as a Predictor of Initial Responsiveness to Vincristine and Prednisone in Blastic Chronic Myelogenous Leukemia
Authors: Stanley M. Marks, David Baltimore, Ronald McCaffrey
Journal: New England Journal of Medicine (1978)

We undertook a prospective trial to evaluate terminal deoxynucleotidyl transferase activity as a predictor of responsiveness to vincristine and prednisone in 22 Philadelphia-chromosome-positive patients with blastic chronic myelogenous leukemia. Thirteen patients were transferase positive, and nine negative. None of the nine negative patients responded, whereas eight of the 13 positive (P = 0.004) responded with complete clearing of peripheral blood blast cells and a return of normal marrow cellularity with less than 5 per cent blast cells. Among transferase-positive patients under 50 years of age the response rate was 78 per cent. Blast-cell morphology (i.e., lymphoblastic versus myeloblastic) had no significant correlation with either responsiveness or terminal transferase activity. The results of this study suggest that responsiveness to vincristine and prednisone in blastic chronic myelogenous leukemia is confined to patients whose leukemic cells are transferase positive.
Accessory Findings on F-18 FDG Positron Emission Tomography in Bronchogenic Carcinoma
Authors: Gerarda J M  Herder, Alle Welling, Grischa V De Winter, Emile F I Comans, Otto S Hoekstra
Journal: Clinical Nuclear Medicine (2003)

M. HERDER, GERARDA J. M.D.*†; WELLING, ALLE M.D.‡; DE WINTER, GRISCHA V. M.D.‡; COMANS, EMILE F. I. M.D., Ph.D*; HOEKSTRA, OTTO S. M.D. Ph.D.* Author Information
273 PROPERTIES AND LIMITATIONS OF MONOCYTES AND CANCER CELLS AS CARRIERS FOR REPLICATION-COMPETENT ADENOVIRAL VECTORS IN LIVER METASTASES OF PANCREATIC CANCER
Authors: E. Garcia-Aragoncillo, M. Bunuales, R. Casado, S. Bortolanza, J. Prieto, R. Hernandez-Alcoceba
Journal: Journal of Hepatology (2012)