tbuckley/cabot-search huggingface dataset:
P17.32 * EFFICACY AND TOLERABILITY OF BEVACIZUMAB MONOTHERAPY IN PATIENTS WITH PREVIOUSLY TREATED RECURRENT GLIOBLASTOMA MULTIFORME (GBM)
Authors: E. Francini, S. Mazzaroppi, M. Salvati, S. Caponnetto, L. Laera, C. Migali, V. Bianco
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma Multiforme (GBM) represents the most common and malignant form of brain tumor. GBMs are highly vascularized and their cells frequently express the vascular endothelial growth factor (VEGF) receptor. VEGF has a key role in stimulating angiogenesis and enhancing intratumoral vascular permeability. Bevacizumab is a humanized monoclonal antibody which inhibits VEGF and tumor cell growth. Data from the literature show that this drug has a different toxicity profile, pattern of response, and relapse rate in comparison with alchilant agents. PATIENTS AND METHODS: The aim of this study was to evaluate the efficacy and tolerability of Bevacizumab in patients with GBM progressed after prior treatments (STUPP and FTM protocols) and with adequate bone marrow, renal, and hepatic function and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2. The drug was administered as monotherapy every 14 days as an intravenous infusion at the dose of 10 mg/kg until recurrence and/or clinical-radiological progression. Brain magnetic resonance imaging (MRI) scans were performed every 60 days and treatment response was defined according to the McDonald criteria. Toxicity was assessed using the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. RESULTS: From October 2009 to March 2014, we analyzed 15 patients, 8 males (53.3%) and 7 females (46.7%), with a median age of 54.8 years (range 36-70, 4 were over 65 years old); nine (60%) and six (40%) patients had an ECOG PS of 1 and 2, respectively. The median number of cycles administered was 14.3 (range 2-62). Median progression-free survival (PFS) was 130 days (average PFS was 201.8 days). Six patients showed a survival benefit of 12, 12, 10, 8, 17 and 31 months, a partial response and a stable disease were observed in the last three of them, respectively. Disease control rate (DCR) was 53.3%. Bevacizumab was generally well tolerated. Particularly, hematological toxicity, commonly of grade 1, was observed as leucopenia in 40% of cases, while the most common non-hematological side effects were grade 1 increase of gamma glutamyl transpeptidase (GGT) levels (33.3%), fatigue (20%), and proteinuria (20%). CONCLUSIONS: Although our limited sample size does not permit definitive conclusions, Bevacizumab monotherapy appears to be a safe and effective treatment option for recurrent GBM, with a good clinical-radiological response and an increased PFS in most patients.
A7.22 The ETS1 Transcription Factor May Predispose to Rheumatoid Arthritis Susceptibility
Authors: A Chatzikyriakidou, PV Voulgari, AA Drosos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> ETS1 is the founder member of ETS transcription factors' family which control the transcription of various immune related genes. The aim of this study was to identify if polymorphism ETS1 Rs11221332, described in Caucasian subjects, plays any role in rheumatoid arthritis (RA) susceptibility. <h3>Materials and Methods</h3> We genotyped this polymorphism in 136 unrelated patients with RA and 147 healthy individuals with no history of autoimmune diseases. Genotyping was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and the data were analysed by the SPSS statistical software. <h3>Results</h3> Statistical significant difference was observed in the distribution of Rs11221332 genotypes between RA patients and controls (<i>p</i> = 0.041). Comparing Rs11221332 alleles' distribution between the studied groups the difference was higher [<i>p</i> = 0.039, (OR = 1.504, CI:1.036–2.183)]. <h3>Conclusions</h3> The present study revealed, for first time, the positive association of a polymorphism in the sequence of ETS1 transcription factor with RA susceptibility. Further studies in other ethnic group of patients are needed to confirm the results of the present genetic association study related to ETS1, a widely used transcription factor in the regulation of various genes' expression.
AB0672 Articular hyper mobility in chronic lumbar pain : touching 10% of the patients
Authors: M. Norberg, C. Schindler
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chronic lumbar pain is a relative frequent pain problem, with different etiologies: a great part is of no specific origin. Another part of the problem, is the presence of increased flexibility (named hypermobility), it can have a role in the chronic pain patient. <h3>Objectives</h3> The aim of this study is to analyze the prevalence of hypermobility in a low back pain patient group starting a multidisciplinary rehabilitation program, and the first results of a multidimensional treatment program <h3>Methods</h3> We have studied the inclusion results of 550 of our patients that have accomplished a multi-disciplinary program and that have been followed over 24 months. The program contained physical training, occupational work hardening the hole in a cogntivo-comportemental approach. We have analyzed the clinical signs for hypermobility in these patients according to the Beighton criteria, and also the evolution over 2 years comparing with the other low back pain patients. <h3>Results</h3> The prevalence of hypermobility(HMP) –according to the Beighton criteria- among our chronic lumbar pain population (CLP)was 9.8 %, with a ratio of 3 men for 8 women. They have an increase in physical parameters similar as the global lumbar patients, but they started at a higher base level (see for example the Shirado test) <h3>Conclusions</h3> Hypermobility represents almost 10% of the patients in a rehabilitation program for chronic low back pain. They have physical base values that are quite better than the global population, but the clinical outcome doesn’t really differ according work ability. <h3>Disclosure of Interest</h3> None Declared
Guillain-Barré syndrome associated with Zika virus infection
Authors: Patrícia Brasil, Patricia Carvalho Sequeira, Andrea D'Avila Freitas, Heruza Einsfeld Zogbi, Guilherme Amaral Calvet, Rogerio Valls de Souza, André Machado Siqueira, Marcos Cesar Lima de Mendonca, Rita Maria Ribeiro Nogueira, Ana Maria Bispo de Filippis, Tom Solomon
Journal: The Lancet (2016)
AB0276 Methotrexate therapy monitoring by MTOR, autophagy-related ULK1, caspase 3, CDK-inhibitor p21, TNF alpha, and osteoclast-specific cathepsin K and gelatinase MMP-9 gene expression in the peripheral blood of early rheumatoid arthritis patients
Authors: E.V. Tchetina, N.V. Demidova, D.E. Karateev, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Altered rates of cell proliferation and apoptosis were also observed in RA. We hypothesized that expression of the genes responsible for cell growth and proliferation (mTOR, p21), autophagy (ULK1), apoptosis (caspase 3), inflammation (TNFalpha), and bone resorption (cathepsin K and gelatinase MMP-9) measured in the peripheral blood could serve important biomarkers for anti-rheumatic therapy monitoring. <h3>Objectives</h3> To find peripheral blood gene expression indicators pointing to treatment efficacy of methotrexate (MTX) in early RA patients. <h3>Methods</h3> 14 early-stage seropositive RA females aged 44±16.0 years old, disease duration 9.0±6.5 weeks treated with MTX (17.5 mg) during two years and 47 healthy age-matched control females were examined in this study. Clinical response was assessed by disease activity score (DAS) 28, serum levels of anti-CCP antibodies, C-reactive protein (CRP), and rheumatoid factor (RF). Bone erosion and joint space narrowing scores were monitored by X-ray analysis. Total RNA isolated from the peripheral blood was used in gene expression studies performed with quantitative Real-time RT-PCR. p70-S6K, p21, and caspase 3 protein levels were quantified by ELISA. <h3>Results</h3> Expression of all the examined genes measured in the peripheral blood was significantly upregulated (p&lt;0.05) in RA patients compared to control at baseline. DAS 28 and CRP values have significantly decreased (p&lt;0.05) at the end of follow up period. This was associated with significant downregulation of mTOR, p21, caspase 3, and cathepsin K gene expression, which attained the levels observed in healthy subjects. TNFalpha gene expression has also decreased (p&lt;0.05) versus the baseline values. However it remained significantly higher than that in control subjects. In contrast, MMP-9 and ULK1 gene expression was significantly (p&lt;0.05) upregulated in early RA patients compared to control in response to MTX therapy. This was accompanied by an increase in bone erosion numbers and joint space narrowing. <h3>Conclusions</h3> Our results show that the examined gene expression measured in the peripheral blood could provide essential information for disease monitoring in RA in response to treatment. Moreover, blood levels of gelatinase MMP-9 and autophagy protein ULK1 gene expression might serve an important biomarker of treatment efficacy in respect to bone and joint integrity. <b>Acknowledgments:</b> This study was funded by Russian Foundation for Basic Research (project no. 09-04-01158-a and no. 12-04-00038-a). <h3>Disclosure of Interest</h3> None Declared
Autologous blood transfusions and prognosis in colorectal cancer surgery.
Authors: O R Busch, W C Hop, R L Marquet, J Jeekel
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.5.1280 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7738632 Autologous blood transfusions and prognosis in colorectal cancer surgery. O R BuschxO R BuschSearch for articles by this author , W C HopxW C HopSearch for articles by this author , R L MarquetxR L MarquetSearch for articles by this author , J JeekelxJ JeekelSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.5.1280 PDF "Autologous blood transfusions and prognosis in colorectal cancer surgery.." Journal of Clinical Oncology, 13(5), pp. 1280–1281© 1995 by American Society of Clinical Oncology
MULTIPLE OFFICE BLOOD PRESSURE MEASUREMENT WITH AN AUTOMATED DEVICE IS SUPERIOR TO BLOOD PRESSURE MEASURED BY THE DOCTOR IN THE DIAGNOSIS OF HYPERTENSION: A PROSPECTIVE MULTICENTER STUDY
Authors: Tae-Young Choi, Mooyong Rhee, Ji-Hyun Kim, June Namgung, Sung Yun Lee, Deok-Kyu Cho, Seok-Yeon Kim, Jang-Young Kim, Jin-Sun Park, Sang-Min Park
Journal: Journal of the American College of Cardiology (2015)
Neurocutaneous Melanosis
Authors: Maria Mathew D'Souza, Akhila Prasad, Namrita Sachdev, Smita Manchanda, Ajay Choudhary, Rajnish Sharma, Abhinav Jaimini, Madhavi Tripathi, Anupam Mondal
Journal: Clinical Nuclear Medicine (2011)

Neurocutaneous melanosis is an extremely rare, nonfamilial neurocutaneous syndrome characterized by large cutaneous melanocytic nevi and excessive proliferation of melanocytic cells in the leptomeninges. We present the F-18 FDG and [11C]-methionine PET/CT findings in a 16-year-old boy with neurocutaneous melanosis. Diffuse uptake was noted in the leptomeninges extending into the brain parenchyma with both tracers, which corresponded to hyperintensities on MRI. Histopathology revealed extensive melanocytic infiltration with no evidence of malignancy. The increased radiotracer accumulation may thus reflect overall increased cell glucose and amino acid metabolism of this rare disorder.
AB0272 Bsmi and Foki VDR Gene Polymorphisms Influence Disease Activity in Established Rheumatoid Arthritis Patients
Authors: M. Bernardes, J.C. Machado, D. Gonçalves, J. Abelha-Aleixo, R. Fonseca, P. Madureira, R. Vieira, A. Bernardo, M.J. Martins, L. Costa, F. Simões-Ventura
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Vitamin D has been shown to have significant immunomodulatory effects. Its actions are mediated by the ubiquitous vitamin D receptor (VDR). In one study, BsmI VDR gene polymorphism was associated with an early onset of rheumatoid arthritis (RA). Additionally, TT genotype of the FokI VDR gene polymorphism was established as a genetic susceptibility marker for RA in French and Tunisian populations. <h3>Objectives</h3> To determine the degree of association of BsmI and FokI VDR gene polymorphisms with disease activity in patients with established RA. <h3>Methods</h3> Clinical features and peripheral blood samples were collected from a monitoring visit. The Portuguese version of HAQ and the disease activity scores (DAS28 (4v; ESR), DAS28 (3v; ESR), DAS 28 (4v; CRP), DAS28 (3v; CRP)) were obtained. We measured the following acute phase reactants: ESR and CRP. Genomic DNA was extracted from blood and genotyped for the BsmI (A/G) (rs1544410) and FokI (T/C) (rs 2228570) SNPs by PCR-RFLPs analysis. A multivariate analysis model was used for statistical analysis (IBM SPSS Statistics 21). <h3>Results</h3> We evaluated 208 RA patients, 166 (80%) women, 65 (31%) premenopausal women, age 54±12 years, disease duration 14±10 years, mean DAS28 (4v) of 4.25±1.33 and a mean HAQ of 1.254±0.709. In our sample, 107 (51%) were under biologics, 87 (42%) under anti-TNFalpha agents and 42 (20%) under vitamin D supplements. Genotype frequencies were determined for the two distinct VDR polymorphisms: BsmI (GG 37%, 44% AG, AA 19%) and FoKI (CC 42%, TC 46%, TT 12%). GG genotype of the BsmI VDR gene polymorphism was associated with higher DAS28 (4v; ESR), DAS28 (3v; ESR), DAS 28 (4v; CRP) and DAS28 (3v; CRP) scores (p&lt;0.001). Additionally, TT genotype of the FokI VDR gene polymorphism was associated with higher DAS28 (4v; ESR), DAS28 (3v; ESR), DAS 28 (4v; CRP) and DAS28 (3v; CRP) scores (p&lt;0.001). In the subgroup of patients without vitamin D supplements, the previously observed associations remained significant (p&lt;0.001). All these associations were found after adjusting for age, disease duration, current HAQ, time under DMARDs therapy, current average daily dose of prednisone and years of corticosteroid use. <h3>Conclusions</h3> In our RA population, the BsmI GG and the FokI TT genotypes of the VDR gene were related with disease severity. In the future, VDR gene polymorphisms could be useful in establishing RA prognosis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3913
Incidental Thyroid Carcinoma on Parathyroid Imaging
Authors: MICHAEL E. SPIETH, GERALD M. MULLIGAN, THANHCUONG NGUYEN, DARCY L. KASNER
Journal: Clinical Nuclear Medicine (2002)

SPIETH, MICHAEL E. M.D.; MULLIGAN, GERALD M. M.D.; NGUYEN, THANHCUONG M.D.; KASNER, DARCY L. Author Information
Supradiaphragmatic Thoracic-Duct Cyst
Authors: Eli B. Cohen, Eugene Kompaniez
Journal: New England Journal of Medicine (1962)

EMERSON1 documented the first ante-mortem surgically diagnosed case of supradiaphragmatic thoracic-duct cyst (1950), and called attention to 3 previously discovered cases at post-mortem examination. His patient was a twenty-year-old college student who was discovered to have a mediastinal mass on x-ray study of the chest. She had had symptoms for two and a half years, more in the recent five months, of repeated attacks of substernal soreness, with some exertional dyspnea and a nonproductive cough. At surgery a mass, 4.0 by 5.5 cm., was found; it was smooth, with a yellowish hue, and contained a milky solution that took Sudan . . .
Too Many Breast Biopsies? Watching vs. Cutting
Authors: Elaine Blume, David Ariz
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Too Many Breast Biopsies? Watching vs. Cutting Get access Elaine Blume, Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar David Ariz David Ariz Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 17, 4 September 1991, Pages 1207–1209, https://doi.org/10.1093/jnci/83.17.1207 Published: 04 September 1991
Abstract 2371: Arid4b is a potential breast cancer progression modifier gene
Authors: Scott F. Winter, Luanne Lukes, Kent W. Hunter
Journal: Cancer Research (2010)

Abstract Our laboratory's research focuses on the role of host genetics in breast cancer metastasis. The MMTV-PyMT mouse model exhibits varying metastatic efficiency to the lungs when transgenic mice in an FVB background are bred to other strains such as DBA and AKR. Combining quantitative measurement of metastasis with genetic mapping studies of the AKXD recombinant inbred panel of mice has allowed us to determine quantitative trait loci (QTLs) that affect metastatic efficiency. My work has focused on the potential role of Arid4b in breast cancer tumorigenesis and metastasis. Arid4b is a component of the mSin3a histone deacetylase complex that has a known role in breast cancer progression and is a candidate gene underlying a metastasis QTL peak we have identified on mouse chromosome 13. In two independent mouse breast cancer cell lines, Met-1 and PyMT-luc, stable expression of the AKR (high metastatic strain) allele caused significantly larger primary tumor growth than the DBA (low metastatic strain) allele following orthotopic implantation into the mammary fat pads of syngeneic hosts. In Met-1 cells we detected lung surface metastases in the AKR cohort but not in the DBA cohort. We are in the process of performing functional analyses to determine a mechanism of action whereby Arid4b polymorphisms influence tumorigenesis and metastasis. Sequencing has revealed a high density of non-synonymous SNPs between the AKR and DBA alleles in exon 22, which encodes a C-terminal region of the Arid4b protein that is known to mediate interaction with the mSin3a HDAC complex. We are currently using co-IPs and proteomics strategies, such as tandem affinity purification, to identify proteins that bind differentially to the AKR or DBA Arid4b proteins. Arid4b is also alternately spliced and cells ectopically expressing the shorter isoform 2 formed significantly larger tumors in our orthotopic model compared to cells expressing the full-length isoform 1. Interestingly, the alternately spliced exon encodes part of a conserved Chromodomain, which is known to mediate binding of other Chromodomain containing proteins such as HP1 to modified histone tails. Western blots using an Ab specific for dimethylated histone H3 lysine 27 suggest a potential role of Arid4b in modifying chromatin structure. It is likely that both the alternate splicing of the Chromo domain and the allelic variation in the C-terminal domain modulate the epigenetic influence of Arid4b on tumorigenesis and metastasis. 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 2371.
OC-015 The Influence of Gender and Haemoglobin on TPMT Activity
Authors: P A Blaker, V C Kariyawasam, K V Patel, R M Goel, M G Ward, P M Irving, A M Marinaki, J D Sanderson
Journal: Gut (2013)

<h3>Introduction</h3> Pre-treatment measurement of red blood cell (RBC) thiopurine-<i>S-</i>methyltransferase (TPMT) activity is recommended to guide initial dosing of azathioprine (AZA) and mercaptopurine (MP). TPMT exhibits a trimodal distribution, with low and intermediate activities predicting myelotoxicity at standard drug doses. There is a high concordance between TPMT genotype and normal or low enzyme activity (93–100%); however the relationship is poor in the intermediate range (53–100%) <sup>[1]</sup>. Furthermore, there are few explanations for the wide variation in inter-individual TPMT activities in the wild-type range. Bioavailability of the cofactor <i>S</i>-adenosylmethionine (SAM) and RBC age may play a role. The aim of this study was to determine if gender or anaemia influences RBC TPMT activity. <h3>Methods</h3> We analysed a retrospective cohort of 6,496 RBC TPMT samples (n = 3804 females, n = 2692 males) measured in the PRL since 2004 and correlated enzyme activity with gender and haemoglobin concentrations. <h3>Results</h3> A greater portion of females exhibited intermediate TPMT activity (13.46%) as compared to males (11.07%). The mean TPMT activity was also significantly lower in females (32.94 pmol/mg Hb/h) versus males (34.13 pmol/mg Hb/h; p = &lt; 0.0001, 95% CI 0.7950–1.589). When separated by low, intermediate or normal TPMT activity, this relationship only remained in patients with normal TPMT activity. TPMT activity was significantly higher in female patients with an Hb &lt; 10g/dl (n = 250, mean TPMT 38.06 pmol/mg Hb/h) versus females with an Hb &gt; 12g/dl (n = 2192, mean TPMT 32.46 pmol/mg Hb/h; p = &lt; 0.0001). Similarly TPMT activity was significantly higher in male patients with an Hb &lt; 10g/dl (n = 123, mean TPMT 38.14) versus males with an Hb &gt; 12g/dl (n = 1901, mean TPMT 33.76; p = &lt; 0.0001). <h3>Conclusion</h3> TPMT activity in the wild-type range is lower in females than males, suggesting a post-translational influence on TPMT activity related to gender. Lower levels of SAM have been reported in females, which may explain this observation[2]. Re-appraisal of the concordance between TPMT genotype and phenotype, adjusting for gender is therefore indicated. The finding of higher TPMT activity with anaemia may be due to a younger red cell population in this group. The difference in TPMT activities between patients with or without anaemia is clinically relevant, particularly where the TPMT activity is around the cut-off between intermediate (10–25 pmol/mg Hb/h) and normal (≥26 pmol/mg Hb/h) ranges. TPMT genotyping should be considered in such patients. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> Karas-Kuzelicki, <i>et al.</i> Pharmacogenomics 2009. 10:1309–22. Poirier, <i>et al.</i> Cancer epidemiology, biomarkers &amp; prevention 2001. 10:649–655.