tbuckley/cabot-search huggingface dataset:
SAT0120 Anti TNF therapy with adalimumab restores the bone metabolism balance through a dual mechanism in rheumatoid arthritis
Authors: A. Krishnamurthy, S. Revu, P. Neregård, A. Hensvold, M. Engström, E.A. Erik af Klint, D. Makrygiannakis, A.I. Catrina
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Large clinical studies have demonstrated that TNF blockade delays radiological progression in rheumatoid arthritis (RA) independent of the clinical response. <h3>Objectives</h3> We aimed to investigate the mechanisms by which adalimumab, a human anti TNF antibody, affects osteoclastogenesis in vivo and in vitro. <h3>Methods</h3> Expression of OPG, RANK and RANKL was evaluated by immunohistochemistry and semi quantitative double blind analysis of serial synovial biopsies obtained from 12 RA patients treated with adalimumab before and 8 weeks after treatment initiation. The in-vitro effect of adalimumab on RANKL and OPG expression in osteoblast-like cells with or without TNF priming was evaluated by RT-PCR and Western blots. Further investigation of the direct effect of adalimumab on osteoclasts formation (TRAP staining) and function was tested in a bone resorption assay using blood derived CD14 positive monocytes. Resorption area and number of pits were analysed by computer assisted image analysis. <h3>Results</h3> Treatment with adalimumab significantly decreased the RANKL/OPG ratio and RANK expression in synovial tissue in parallel with a reduction in the number of synovial macrophages, while no changes were seen in the number of synovial lymphocytes. No significant differences were observed between EULAR responders and non-responders. In-vitro adalimumab mimicked the in-vivo effect inducing a decrease in the RANKL/OPG ratio in osteoblast-like cells (SaOS2). In addition adalimumab was able to inhibit in-vitro osteoclast formation and bone resorption even in the presence of RANKL. <h3>Conclusions</h3> Therapy with adalimumab regulates not only synovial inflammation but also bone metabolism through direct modulation of the RANKL/RANK/OPG pathway and inhibition of osteoclasts formation. These effects might explain the bone sparing effect seen with TNF blockade even in the presence of ongoing inflammation. <h3>Disclosure of Interest</h3> A. Krishnamurthy: None Declared, S. Revu: None Declared, P. Neregård: None Declared, A. Hensvold: None Declared, M. Engström: None Declared, E. Erik af Klint: None Declared, D. Makrygiannakis: None Declared, A. Catrina Grant/Research support from: AI Catrina has received an unrestricted research grant from Abbott.
Prognostic Subgroups among Patients with Stage II Colon Cancer
Authors: C Richard Boland, Ajay Goel
Journal: New England Journal of Medicine (2016)

Colon cancer has traditionally been treated surgically. However, many cases of colon cancer are systemic at the time of diagnosis, and apparently curative surgery is followed at a later date by tumor recurrence as a consequence of circulating tumor cells before the surgery. Adjuvant medical therapies are designed to prevent recurrences after surgical resection. The current standard for clinical prognostication relies principally on pathological staging. In early-stage colon cancers (stages I and II), all the tumor is contained within the wall of the colon. Less than 10% of patients with stage I disease have a recurrence, and adjuvant chemotherapy is . . .
Abstract 5445: Differential roles of E2F1 in melanoma.
Authors: Peng Meng, Rita Ghosh
Journal: Cancer Research (2013)

Abstract Melanoma, the malignant tumor of melanocytes, accounts for 4% of all skin cancer incidence but approximately 78% of skin cancer related deaths. No current treatment significantly enhances disease-free survival once distant metastases have established. The 5 year survival rate drops dramatically from 99.9% to 9% when melanoma progresses. To facilitate the development of effective treatment strategies, it is imperative that we obtain a better understanding of the biology of melanoma cells as they progress through the various stages of disease. Previous studies have shown that E2F1, a transcription factor, is over-expressed in melanoma cells. Interaction between E2Fs and tumor suppressor, Rb is essential for regulation of cell cycle progression. E2F1 is known to be involved in many other important biological processes, including DNA damage, DNA repair, differentiation, development, autophagy and apoptosis. Involvement of E2F1 in so many diverse functions underscores the importance of this protein under normal and pathologic conditions including melanoma. Previously we have found that primary melanoma cells have high level of E2F1 message and protein, and that the acetylation of E2F1 (active form) is higher in late stage melanoma cells. This led us to propose that E2F1 may function differentially in various stages of melanoma progression. Therefore we generated stable E2F1 knockdown cells in early stage primary and advanced metastatic melanoma cells. Our results show that E2F1 reduction works more effectively to inhibit cell growth in primary melanoma cells. Further, we also found differential effects on apoptosis and invasion in early and late stage melanoma cells. There is increased spontaneous cell death in primary melanoma cells after E2F1 knockdown, while there is increased apoptosis resistance in response to UV or valinomycin. These results taken together suggest that E2F1 has pleotropic effects in melanoma. It can switch between oncogenic or tumor suppressive functions during melanoma progression. A better understanding of the mechanism involved in this switch may allow combining gene therapies with other therapies for improved therapeutics for malignant melanoma. Supported by R21 CA125719 (RG). Citation Format: Peng Meng, Rita Ghosh. Differential roles of E2F1 in melanoma. [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 5445. doi:10.1158/1538-7445.AM2013-5445
P5-11-17: Evaluating Tumor Heterogeneity in Immunohistochemistry Stained Breast Cancer Tissue.
Authors: SJ Potts, N Landis, DA Eberhard, SC Schmechel, D Young, H Lange
Journal: Cancer Research (2011)

Abstract Context: Quantitative clinical measurement of heterogeneity in immunohistochemistry staining would be useful in both evaluating patient therapeutic response and identifying underlying issues in histopathology laboratory quality control. Objective: To create a heterogeneity scoring approach (HetMap) that allows the visualization of an individual patient's IHC heterogeneity in the context of a population. Design: We combined HER2 semi-quantitative analysis with the use of ecology diversity statistics to evaluate cell-level heterogeneity (consistency of protein expression within neighboring cells in a tumor nest) and tumor-level heterogeneity (differences of protein expression across a tumor as represented by a tissue section). We evaluated the approach on HER2 immunohistochemistry stained breast cancer samples, using 200 specimens across two different CLIA laboratories, with three pathologists at each laboratory each outlining regions of tumor for scoring by automatic cell-based image analysis. HetMap was evaluated using three different scoring schemes: HER2 scoring according to ASCO/CAP guidelines, H-Score and a new continuous HER2 score (HER2cont). Results: Two definitions of heterogeneity, cell-level and tumor-level, provided useful independent measures of heterogeneity. Cell-level heterogeneity, reported either as an average or the maximum area of heterogeneity across a slide, had low levels of dependency on the pathologist choice of region (coefficient of variation of 15%). Tumor-level heterogeneity measurements had more dependence on the pathologist choice of regions (coefficient of variation of 25%). Results were highly similar between the two laboratories, which is encouraging for HER2 standardization, as the labs involved different pathologists, different specimens, and different standardization procedures, although both complied with CLIA/CAP guidelines for HER2 testing. Conclusions: HetMap is a measure of heterogeneity, by which pathologists, oncologists, and drug development organizations can view cell-level and tumor-level heterogeneity for a patient for a given marker in the context of an entire patient cohort. Heterogeneity analysis can be a useful means to identify tumors with higher degrees of heterogeneity, or to highlight slides that should be rechecked for QC issues. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-17.
Evidence of polyclonality in neurofibromatosis type 2–associated multilobulated vestibular schwannomas
Authors: Ramita Dewan, Alex Pemov, H. Jeffrey Kim, Keaton L. Morgan, Raul A. Vasquez, Prashant Chittiboina, Xiang Wang, Settara C. Chandrasekharappa, Abhik Ray-Chaudhury, John A. Butman, Douglas R. Stewart, Ashok R. Asthagiri
Journal: Neuro-Oncology (2014)

Neurofibromatosis type 2 (NF2) is a tumor syndrome that results from mutation of the NF2 tumor suppressor gene. The hallmark of NF2 is the presence of bilateral vestibular schwannoma (VS). Though NF2-associated and sporadic VS share identical histopathologic findings and cytogenetic alterations, NF2-associated VS often appears multilobulated, is less responsive to radiosurgery, and has worse surgical outcomes. Temporal bone autopsy specimens and MRI of the inner ear performed on NF2 patients suggest that multiple discrete tumors may be present within the labyrinth and cerebellopontine angle. Treatment-naïve ears in patients enrolled in a prospective NF2 natural history study (NIH#08-N-0044) were included for MRI analysis. T2-weighted and postcontrast T1-weighted MRIs were evaluated for the presence of multiple discrete tumors or a multilobulated mass. Peripheral blood (germline) and regional samples of tumor tissue were procured from consecutive patients enrolled in this study undergoing resection of a multilobulated VS (MVS). Histopathologic evaluation and genetic analysis (single nucleotide polymorphism array analysis, NF2 sequencing) were performed on each specimen. Over half of NF2 ears harbored either an MVS (60/139 ears) or multiple discrete masses (19/139 ears). For 4 successive MVSs, genetic analysis revealed an admixture of cell populations, each with its own somatic NF2 mutation or deletion. These findings suggest that the majority of NF2-associated VSs are polyclonal, such that the tumor mass represents a collision of multiple, distinct tumor clones. This explains the characteristic lobulated gross appearance of NF2-associated VS, and may also explain the substantially different treatment outcomes compared with sporadic VS.
Superficial pharyngeal cancer can be diagnosed in the West
Authors: S. Mou, T. Kaltenbach, M. Yao, R. Soetikno
Journal: Endoscopy (2011)

A 51-year-old man with a history of heavy alcohol and tobacco use presented with globus sensation. Esophagogastroduodenoscopy demonstrated a 6-mm patch of reddish mucosa in the left pyriform sinus ([Fig. 1]). The lesion was visualized most clearly using narrow-band imaging (NBI) ([Fig. 2]). Biopsy revealed squamous cell carcinoma in situ. The patient therefore underwent an endoscopic mucosal resection using cap (EMR-C) under general anesthesia ([Video 1]). The procedure was well tolerated. The en-bloc resection specimen was pinned and examined using white light and Lugol's solution to assess the resection margin ([Fig. 3]). The histopathology of the oriented resection specimen confirmed squamous cell carcinoma in situ ([Fig. 4]). Because carcinoma in situ in the hypopharynx can metastasize, the patient had a positron emission tomography (PET) scan, which revealed a hypermetabolic lung lesion ([Fig. 5]). He underwent video-assisted thorascopic surgery, left upper lobectomy, and removal of a 1.5-cm adenocarcinoma.
Abstract 2782: Genetic susceptibility to prostate cancer progression and relationship with PSA level: Case-case study
Authors: Nora Pashayan, David Neal, Freddie Hamdy, Jenny Donovan, Richard Martin, Stephen Duffy, Paul Pharoah
Journal: Cancer Research (2011)

Abstract Purpose: Prostate cancer is a mixture of progressive and non-progressive cancers. To date, genome-wide association studies have identified more than 30 common susceptibility variants associated with the risk of prostate cancer. However, case-control study designs have failed to identify variants consistently associated with aggressive cancer. The aim of this study is to investigate whether prostate cancer susceptibility variants distinguish between progressive and non-progressive cancers, using case-case study design. Methods: We genotyped 85 prostate cancer susceptibility variants in 4,856 men with prostate cancer identified from the Prostate Testing for Cancer and Treatment (ProtecT), Prostate Cancer Mechanisms of Progression and Treatment (ProMPT), and Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) studies. Men with advanced stage (T3-T4) (n=624), or Gleason score ≥ 7 (n=1,792) prostate cancer were compared to those with localised stage (T1-T2) (n=3,805), or Gleason score &amp;lt;7 (n=2,090) cancer, respectively, using logistic regression to estimate the odds ratio (OR) associated with risk allele and genotype, after controlling for age at diagnosis, PSA level at diagnosis, stage and / or Gleason score. Results: On univariate analysis, three variants (rs16901979, rs10896449, rs2735839) were associated with stage, and six (rs1447295, rs16901979, rs10896449, rs2735839 rs17181356 rs3760511) with Gleason score. In multivariate analysis, the variant rs2735839 at 19q13 in KLK2/3 region was associated with 42% increase in the odds for advanced stage cancer (adjusted OR per allele =1.42; 95% CI 1.08-1.87; ptrend =0.01). However, there was evidence of interaction with PSA level (p&amp;lt;0.001). The adjusted OR for rs2735839 for advanced compared to localised cancers among those with PSA ≥10ng/ml was 1.79 (95% CI 1.26-2.54; p=0.001), whereas among those with PSA&amp;lt;10ng/ml, the OR was 0.96 (95% CI 0.60-1.56; p=0.88). Whereas the variant rs3760511 at 17q12 was associated with reduced risk for high Gleason score cancer (adjusted OR per allele=0.85 95% CI 0.75-0.96; ptrend =0.01). Conclusion: The interaction between PSA level and stage may inform the underlying biological mechanism for cancer progression in stage. These findings may also have clinical utility in identifying tumours with and without the potential for progression to advanced stage or higher Gleason score. Further validation in larger studies would be needed. 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 2782. doi:10.1158/1538-7445.AM2011-2782
Abstract LB-180: Epigenetic portraits of human breast cancers
Authors: Sarah Dedeurwaerder, Christine Desmedt, Emilie Calonne, Sandeep K. Singhal, Benjamin Haibe-Kains, Matthieu Defrance, Stefan Michiels, Michael Volkmar, Rachel Deplus, Judith Luciani, Françoise Lallemand, Denis Larsimont, Jérôme Toussaint, Sandy Haussy, Françoise Rothé, Ghizlane Rouas, Otto Metzger, Samira Majjaj, Kamal Saini, Pascale Putmans, Gérald Hames, Nicolas van Baren, Pierre G. Coulie, Martine Piccart, Christos Sotiriou, François Fuks
Journal: Cancer Research (2011)

Abstract Background: Understanding the diversity of breast cancer is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Our goal was to explore the DNA methylation landscapes of phenotypically heterogeneous tumours, to relate this diversity to landscape features, and extract biological and clinical meaningful information. Methods: We performed comprehensive DNA methylation profiling to assess the methylomes of two independent sets of frozen breast tissue samples: a “main set” of 123 samples (4 normal and 119 infiltrating ductal carcinomas, IDCs), and a “validation set” of 125 samples (8 normal and 117 IDCs). We used the recently developed Illumina's Infinium Methylation Assay, that allows to assess the methylation status of more than 27,000 CpGs corresponding to over 14,000 genes. Results: Firstly, it emerged that the two major phenotypes of breast cancers determined by ER status are widely epigenetically controlled. Secondly, we have distinguished, and validated in an independent set of tumours, 6 methylation-profile-based tumour groups, some coinciding with known “expression subtypes” but also new entities that may provide a meaningful basis for refining breast tumour taxonomy. Thirdly, we showed that DNA methylation profiling can reflect the cell type composition of the tumour microenvironment. Lastly, we highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, revealing a set of immune genes having high prognostic value in specific tumour categories. Conclusions: In this study, we have generated the largest and most comprehensive DNA methylation data set for human breast tumor tissues. Several novel findings and original concepts for breast cancer emerge, that previous RNA expression profiling has not highlighted. By laying the ground for better understanding of breast cancer heterogeneity and improved tumor taxonomy, the precise epigenetic portraits drawn in our work should contribute to better management of breast cancer patients. 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 LB-180. doi:10.1158/1538-7445.AM2011-LB-180
229 THE ASSESSMENT OF GFR AFTER ORTHOTOPIC LIVER TRANSPLANTATION USING CYSTATIN C AND CREATININE-BASED EQUATIONS
Authors: D. Wagner, D. Kniepeiss, P. Stiegler, S. Zitta, H. Müller, A. Meinitzer, A. Fahrleitner-Pammer, A.R. Rosenkranz
Journal: Journal of Hepatology (2012)
ASSOCIATION OF REQUIREMENT FOR TRANSFUSION TO COST OF CARE, LENGTH OF STAY AND INCIDENCE OF ADVERSE EVENTS IN PERCUTANEOUS LEFT ATRIAL APPENDAGE CLOSURE
Authors: Ronak Bhimani, Badal Thakkar, Ronak G. Soni, Dipen Khanapara, Nileshkumar Patel, Parth Bhatt, Achint Patel, Apurva Badheka
Journal: Journal of the American College of Cardiology (2016)
O110 AN INTERNATIONAL COLLABORATIVE STUDY ASSESSING THE ROLE OF AETIOLOGY AND STAGE IN SURVIVAL IN HCC – IMPLICATIONS FOR SCREENING
Authors: P. Johnson, S. Berhane, S. Satomura, T. Tada, T. Kumada, M. Teng, A. Skowronska, T. Cox, D. Palmer, W. Yeo, F. Mo, P. Lai, M. Iñarrairaegui, F. Pardo, J. Bilbao, S. Chan, B. Sangro, H. Toyoda
Journal: Journal of Hepatology (2014)
Follicle center lymphoma is associated with significantly elevated levels of BCL-6 expression among lymphoma subtypes, independent of chromosome 3q27 rearrangements
Authors: F Jardin, G Buchonnet, F Parmentier, N Contentin, S Leprêtre, P Lenain, JM Picquenot, S Laberge, P Bertrand, A Stamatoullas, J d'Anjou, H Tilly, C Bastard
Journal: Leukemia (2002)
S155 The role of ST2 in a model of pulmonary hypertension
Authors: A. Mahmood, C. McSharry, D. Xu, A. J. Peacock, D. J. Welsh
Journal: Thorax (2010)

<h3>Background</h3> Pulmonary arterial hypertension (PAH) is a fatal condition involving remodelling of the pulmonary vessel wall leading to elevated pulmonary arterial pressure and eventually right heart failure. ST2 is a transmembrane receptor with ligand interleukin-33 (IL-33). p38 MAP kinase is an intracellular signalling molecule shown to be involved in the vascular remodelling associated with PAH; and is also involved in ST2/IL-33 signalling. ST2/IL-33 signalling has been shown to reduce fibrosis in the heart following pressure overload in animal models. <h3>Aims</h3> To determine whether ST2/IL-33 signalling was involved in the proliferation of mouse pulmonary artery fibroblasts and if p38 MAP kinase was involved. <h3>Methods</h3> Two cell types were used—wild type (WT) and ST2 knockout (ST2−/−) mouse pulmonary artery fibroblasts. Proliferation was assessed by [<sup>3</sup>H] Thymidine incorporation. Expression of p38 MAP kinase was detected by Western blotting. Cells were cultured at various serum concentrations in normoxia and hypoxia. A p38 MAP kinase inhibitor (SB203580) was used to assess its role in cell proliferation. The effect of IL-33 on cell proliferation and expression of p38 MAP kinase was studied. <h3>Results</h3> WT and ST2−/− cells proliferated in response to increasing serum concentration. WT cells hyperproliferated in response to hypoxia. ST2−/− cells hyperproliferated in normoxia and hypoxia compared to WT cells. The hyperproliferation of ST2−/− cells in normoxia and hypoxia could be reduced by p38 MAP kinase inhibition (p38) (see Abstract S155 Figure 1). Phosphorylated p38 MAP kinase was detected in all ST2−/− cells and in WT cells in hypoxia with 10% serum, demonstrating p38 MAP kinase is involved in the hyperproliferation observed. Hyperproliferation in response to hypoxia in WT cells could be blocked by addition of IL-33. IL-33 stimulation also decreased the phosphorylation of p38 MAP kinase. There was no effect of IL-33 on ST2−/− cells. <h3>Conclusions</h3> Mouse pulmonary artery fibroblasts hyperproliferate in response to hypoxia and in the absence of the ST2 receptor. This hyperproliferation involves phosphorylation of p38 MAP kinase. This phosphorylation and excessive cell proliferation can be blocked by ST2/IL-33 signalling. ST2 may be a potentially novel therapeutic target in the PAH.
LONG-TERM CLINICAL OUTCOME OF ROTATIONAL ATHERECTOMY FOLLOWED BY EVEROLIMUS-ELUTING STENT IMPLANTATION FOR SEVERELY CALCIFIED DE NOVO CORONARY LESIONS: RESULTS FROM TOKYO-MD PCI STUDY
Authors: Yoichi Otaki, Takashi Ashikaga, Taro Sasaoka, Shunji Yoshikawa, Mitsuaki Isobe
Journal: Journal of the American College of Cardiology (2015)
18F-Sodium Fluoride PET/CT in Oncology
Authors: Nathanael Sabbah, Tatianie Jackson, Camila Mosci, Mehran Jamali, Ryogo Minamimoto, Andrew Quon, Erik S Mittra, Andrei Iagaru
Journal: Clinical Nuclear Medicine (2014)

The purpose of this study was to analyze the distribution of 18F Sodium Fluoride (18F-NaF) uptake in the normal skeleton, benign and malignant bone lesions, and extraskeletal tissues, using semiquantitative SUV measurements.We retrospectively analyzed data from 129 patients who had 18F-NaF PET/CT at our institution for an oncological diagnosis between 2007 and 2014. There were 99 men and 30 women, 19 to 90 years old (mean [SD], 61.5 [15.5]). The range, average, and SD of SUV were measured for normal bone and extraskeletal tissues uptake for the entire patient population. A separate statistical analysis was performed to compare group A, which corresponds to the population of patient with no 18F-NaF-avid metastatic lesions, and group B, which corresponds to the population of patient with 18F-NaF-avid metastatic lesions. We also measured SUV max and SUV mean for bony metastases and degenerative changesThe PET/CT images were acquired at 30 to 169 minutes (mean [SD], 76.5 [22.8]) after injection of 3.9 to 13.6 mCi (mean [SD], 7.3 [2.4]) of 18F-NaF. The range and mean (SD) of SUV max for 18F-NaF-avid metastasis were 4.5 to 103.3 and 25.9 (16.6) and for 18F-NaF-avid degenerative changes were 3.3 to 52.1 and 16.5 (7.9), respectively.Various skeletal sites have different normal SUVs. Skeletal metastases have different SUVs when compared with benign findings such as degenerative changes.