tbuckley/cabot-search huggingface dataset:
P17.92 * GLIOBLASTOMA IN ELDERLY PATIENTS: SURVIVAL OUTCOME
Authors: M. Vaz, J. Munoz del Toro, J. Gutierrez, L. Ley Urzaiz, A. Carrrato, A. Madariaga, H. Pian, M. del Alamo
Journal: Neuro-Oncology (2014)

BACKGROUND: The management of glioblastoma (GB) in elderly patients is not well established. The incidence is higher in this population and is expected to increase over the next decades in relation with an aging population in western countries. Otherwise GB is the most life-threatening primary brain tumor especially in elderly patients and survival is significantly less than seen in younger patients. Until recently, this patients have been excluded from randomized trials and the effectiveness of the conventional active treatment has been controversial, since benefit was attenuated in older and there are concerns about mental deterioration. Different treatment approaches have been proposed. Here we review our experience in this population. METHODS: The authors retrospectively reviewed 53 patients at a single institution from February 2005 to March 2013. Patients were 70 years of age and older with histologically confirmed GB. RESULTS: Median age was 75 years (range 70-88). Fifty-six percent were men and 43% women. Most had frontal lobe location (37.7%) followed by temporal lobe (32%). Majority of patients had some kind of morbidity (89%), mainly arterial hypertension (55%) diabetes (13%) and thyroid function alteration (17%). Partial resection was planned in 49% of cases and a complete resection in 45%. After surgery, 71% received radiotherapy, in 45% of cases the dose was 60 Gy and in 26% was 30 Gy. Nearly 40% were treated with concomitant and adjuvant temozolomide. The median umber of cycles was 4,43 (range 1-14). Median survival for the whole cohort was 7,36 m (95% CI 4,8-9,8) and 8,3m for those who received some kind of treatment after surgery. Treatment with temozolomide concomitant and adjuvant (Stupp regimen) was associated with longer overall survival ( 11,16 months vs 4,1m p = 0.008 ). The median overall survival was 8,3 months for those who received radiotherapy and 1,5m for those who did not (p = 0,046). Differences were found between those treated with 30 or 60 Gy in terms of overall survival in favor of 60Gy treatment ( 6,3 vs 11,1 m) but didńt reach the statistical significance level (p = 0.143). Compared with temporal location, patients with tumor located in parietal lobe had a better overall survival. In 10% of cases received a second line treatment after progression and median survival was 4,8 months. CONCLUSION: Elderly patients diagnosed with GB had worst prognosis. In our experience, in patients with newly diagnosed glioblastoma over the age of 70, more intensive treatment was associated with prolonged OS, and results are close to those obtained from younger patients. Nevertheless these are retrospective data and a selection bias may be the explanation. Further randomized trial should be conducted to investigate this topic.
Urinary Diarrhea Detected by Tc-99m DTPA Scintigraphy in a 3-Year-Old Girl
Authors: HANNA BERNSTINE, ADAM P. STEINMETZ, RUTH HARDOFF
Journal: Clinical Nuclear Medicine (2002)

BERNSTINE, HANNA M.D., M.Sc.; STEINMETZ, ADAM P. M.D.; HARDOFF, RUTH M.D., D.Sc. Author Information
Aspirin and the Risk of Colorectal Cancer in Women
Authors: Edward Giovannucci, Kathleen M. Egan, David J. Hunter, Meir J. Stampfer, Graham A. Colditz, Walter C. Willett, Frank E. Speizer
Journal: New England Journal of Medicine (1995)

Most data suggest that the regular use of aspirin reduces the risk of colorectal cancer, but some apparently conflicting evidence exists. The effects of the dose and the duration of aspirin consumption on the risk of colorectal cancer are not well understood.
ES2-3: Patient-Derived Xenograft Models for Preclinical Breast Cancer Research: Not Just "Basal" Anymore.
Authors: MT Lewis
Journal: Cancer Research (2011)

Abstract Translational breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect the range of patient tumor biology accurately. In an effort to overcome these limitations, several groups have recently succeeded in propagating patient-derived breast cancer xenografts representing multiple breast cancer subtypes, including estrogen and progesterone receptor positive, and HER2 positive tumors. In our laboratory, we have developed a diverse set of human breast tumors grown as xenografts in the mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null (NSG) mice, two relatively new immunocompromised mouse models, under various transplant conditions. In all cases, xenograft lines were established directly from breast cancer patient samples, without intervening culture in vitro, using the epithelium-free mammary fat pad as the transplantation site. Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet without exogenous human fibroblasts. Thirty five stably transplantable xenograft lines representing 27 patients were established, using pre-treatment, mid-treatment, and/or post-treatment samples. Most patients yielding xenografts were “triple-negative” (ER−PR-HER2−) (n=21). However, we were able to establish lines from three ER−PR-HER2+ patients, one ER+PR+HER2−, one ER+PR-HER2−, and one “triple-positive” (ER+PR+HER2+) patients. Serially passaged xenografts show phenotypic consistency with the tumor of origin at the histopathology level, and remarkable stability across multiple transplant generations at both the genomic, transcriptomic, and proteomic levels. Of 27 lines evaluated fully, thirteen xenografts showed metastasis to the mouse lung. These models, in conjunction with others like them, thus serve as renewable, quality-controlled tissue resources, and are proving useful for preclinical evaluation of experimental therapeutics. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES2-3.
Relation between Spondylosis Cervicalis and Injury of the Cervical Spine and Its Contents
Authors: Donald Munro
Journal: New England Journal of Medicine (1960)

SPONDYLOSIS cervicalis has been known to the medical profession for years under the name of "cervical hypertrophic arthritis" or "cervical hyper-trophic osteoarthritis." Although detailed knowledge of its cause and pathology is far from complete, considerable strides in their elucidation have been made during the last several years.Perhaps the most significant and basic contribution in the field has been made by Brain and his co-workers.1 , 2 It was he who coined the term "spondylosis cervicalis" to describe certain changes previously spoken of as osteoarthritis, and who first suggested that, closely linked with it and involving the same anatomic structures as it . . .
Commentary: Environmental Estrogens: Health Implications for Humans and Wildlife
Authors: Theo Colborn
Journal: Environmental Health Perspectives (1995)

Recent efforts to increase communication among specialists from a wide range of disciplines has led to a better understanding of the scope and magnitude of the geographic distribution and effects of synthetic chemicals.Cross-discipline research has improved detection of widely dispersed chemicals that are capable of disrupting the endocrine system and/or interfering with reproduction.Reviewing what is known about the effects of xenobiotics from the molecular, cellular, tissue, and organismal levels in relation to effects reported at the population level provides insight about functional changes that are often not visi- ble and are difficult to determine.By adding a wildlife component to these analyses, a clearer picture of the nature of endocrine disruption has been demon- strated.Parallels among laboratory, human, and wildlife studies provide guidance for further multidisciplinary and interagency research.Movement toward forensic research among federal agencies responsible for human and environmental health will lead to increased knowledge about the role of endocrine disruptors in the environment.
Abstract 1502: Adenoviral-mediated interferon α induces endoplasmic reticulum stress related cytotoxicity in human cancer but not normal cells
Authors: Xinqiao Zhang, William F. Benedict
Journal: Cancer Research (2010)

Abstract We have previously shown that adenoviral-mediated interferon α (Ad-IFNα) treatment is specifically cytotoxic to various cancer cells, not only to the cancer cells sensitive to the interferon protein (IFNα), but also to the cells which are resistant to IFNα. We also found that there is very little cytotoxic effect of Ad-IFNα on non-cancer cells. The cancer cell specific toxic effects of Ad-IFNα can be classified into three different mechanisms: 1. Expression and secretion of interferon α protein that results in kill of IFNα sensitive cancer cells; 2. Direct kill of IFNα resistant cancer cells by Ad-IFNα and 3. Cancer cell kill by Ad-IFNα produced bystander factors. After Ad-IFNα infection, the host cells produce a large amount of IFN protein. We hypothesized that this protein over-load is cytotoxic to cancer cells and may be a major reason for Ad-IFNα direct effect. We now report that Ad-IFNα infection induces ER stress and ER stress related apoptosis in human cancer but not normal urothelial cells. In addition we found that the Ad-IFNα produced bystander cytotoxicity was not related to ER stress. To investigate whether Ad-IFNα induced cancer specific cytotoxicity was correlated with the activation of ER stress pathways, the expression of several markers of ER stress was studied. Experiments utilized the interferon resistant human bladder cancer cell line, KU7, and the normal human urothelial cell line, TERT-NHU, for the studies. We found that three ER stress response pathways examined were activated in KU7 cells. In contrast, the ER stress response pathways remained silent in the normal TERT-NHU cells or in KU7 cells treated with conditioned medium from Ad-IFNα treated KU7 cells (to test the effect of bystander factor produced cytotoxicity) the ER stress response pathways remained silent. After 24hr of Ad-IFNα exposure, KU7 cancer cells produced spliced X-box binding protein 1 (sXBP1), activating transcription factor 4 (ATF4) and activating transcription factor (ATF6) protein, and evoked an ER stress response that contribute to Ad-IFNα induced apoptosis in cancer cells. In addition, we found GADD153/CHOP and GADD34 were also upregulated following the activation of the three ER stress pathways, thereby signaling downstream effectors in a pro-apoptotic manner. Ad-IFNα recently has been used in Phase I clinical trial for patient with superficial bladder cancer. The results presented here could provide a mechanistic basis for Ad-IFNα action and support the positive clinical results obtained to date. 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 1502.
AB0284 The Diagnostic Utility of Anti-Mutated Citrullinated Vimentin Antibodies, Anti-Cyclic Citrullinated Peptide Antibodies and Rheumatoid Factor in Rheumatoid Arthritis
Authors: A. Badr Eldin, S.A. Mobasher, G. Hegazy
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Antibodies against citrullinated peptides have gained special importance in the diagnosis of rheumatoid arthritis (RA) (1,2). <h3>Objectives</h3> This study aims to investigate the diagnostic sensitivity and specificity of anti-mutated citrullinated vimentin (anti-MCV) antibodies for rheumatoid arthritis (RA) in comparison to IgM RF and anti-CCP and to assess their clinical significance particularly as a marker of RA activity. <h3>Methods</h3> 60 patients with different rheumatic diseases 40 patients with RA and 20 patients with other rheumatic diseases (disease controls) were recruited from Ain Shams University Hospitals, and 20 persons (healthy controls) All participants underwent history taking, clinical examination, laboratory and radiological investigations, and calculation of disease activity score DAS-28 for each RA patient. Enzyme-linked immunosorbent assay (ELISA) techniques were used to detect RF-IgM, anti-CCP antibodies, and anti-MCV antibodies <h3>Results</h3> The sensitivity of anti-MCV antibodies was 95% with 97.1% specificity. For anti-CCP antibodies the sensitivity was 95% and the specificity was 100%. The sensitivity of RF was 72.5% with 97.1% specificity. Anti-CCP antibodies have higher diagnostic specificity and positive predictive value than RF and anti-MCV antibodies. The best cut-off value for the anti-MCV test was found at 22.7 U/L, while that for Anti-CCP antibodies and RF were 20 u/l and 44 IU/ml respectively. Of RA patients with positive RF, 86.2% were anti-MCV antibodies positive, including only 6.8% with negative Anti-CCP. Of patients with negative RF, 81.8% were positive for anti-MCV, including 9% who tested negative for anti-CCP. <h3>Conclusions</h3> Our results suggest that anti-MCV antibodies may be valuable for diagnosing RA and that, it may be better to assay both anti-MCV and anti-CCP in RF -negative RA patients without replacing them. Long-term study is required to find out whether anti-MCV antibodies can be used as predictive test for incidence of RA. <h3>References</h3> Klareskog L, Rönnelid J, Lundberg K, Padyukov L, Alfredsson L: Immunity to citrullinated proteins in rheumatoid arthritis. Annu Rev Immunol 2008, 26: 651-675. Shmerling RH, Delbanco TL: How useful is the rheumatoid factor? An analysis of sensitivity, specificity and predictive value. Arch Intern Med. 1992,152: 2417–2420. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5120
BI-26 * HOW MUCH INSIGHT CAN A STEREOTACTIC BIOPSY DELIVER?
Authors: M. Timmer, M. Perrech, G. Rohn, D. Ruess, T. Blau, N. Breuer, N. Galldiks, R. Goldbrunner, M. Ruge
Journal: Neuro-Oncology (2014)

INTRODUCTION: Besides standard evaluation of histology, immunology and molecular markers as MGNT, IDH etc. an additional screening for biomarkers, genetic alterations and epigenetic features deriving from tissue from primary or recurrent brain tumors may harbor potential as prognostic and predictive information. With this pilot study we intended to examine in how far tissue obtained by stereotactic biopsy can be utilized for extended evaluation. METHODS: Stereotactically guided serial tissue samples (1mm diameter) from 16 patients were analyzed. Besides clinically obligatory routine histo-pathological, immunological and molecular evaluation (e.g. GFAP, S100, Vimentin, MAP2, EGFR, IDH1, p53 and MIB-1) probes were also utilized for analysis for further immunohistochemistry, for genomic DNA extraction, for RNA and protein extraction: The biochemical analysis was done by Western blot using various antibodies (e.g. ALDH1, AHR, GFAP, beta-actin). Furthermore, molecular techniques were applied including the methylation status of the MGMT promoter by bi-sulfit conversion of the DNA and following PCR and the IDH1/2 mutation status verification by pyro-sequencing. RESULTS: In most of the 16 patients the clinical routine diagnostic could be evaluated including MGMT promotor- and IDH1/2 mutation status (two diffuse astrocytomas, two anaplastic astrocytomas, nine glioblastomas, three other tumors). Genomic DNA could be extracted from stereotactic probes. RNA extraction was also possible, but the amount of cDNA obtained from the RNA from stereotactic samples was significant lower in 14/16 patient samples than the amount of cDNA normally used for quantitative RT-PCR from open resection. Besides, there was no biopsy-related morbidity. CONCLUSION: Tissue provided by stereotactically guided serial biopsies in patients with primary and recurrent brain tumors is safe and feasible. Besides clinical routine diagnostic the tissue can also sufficiently be used for of a variety of additional immunohistochemical, biochemical, and molecular analyses. This information may provide valuable and potential treatment relevant factors.
Efficacy of<i>Haemophilus Iinfluenzae</i>Type b Polysaccharide–Diphtheria Toxoid Conjugate Vaccine in Infancy
Authors: Juhani Eskola, Heikki Peltola, Aino Kaarina Takala, Helena Käyhty, Maija Hakulinen, Viena Karanko, Eija Kela, Panu Rekola, Pirjo-Riitta Rönnberg, Joel S. Samuelson, Lance K. Gordon, P. Helena Mäkelä
Journal: New England Journal of Medicine (1987)

Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine has recently been shown to be capable of inducing antibodies to H. influenzae in infants. In an evaluation of its clinical efficacy, 60,000 children were enrolled in an open trial in Finland. Children born on odd-numbered days between October 1, 1985, and September 30, 1986, received the vaccine at 3, 4, 6, and 14 months; those born on even-numbered days served as controls. The geometric mean antibody titer measured in a cohort of 99 children rose from a prevaccination level of 0.08 microgram per milliliter at three months of age to 0.42 microgram per milliliter at seven months. Only minor adverse reactions were reported. Up to February 1987, two cases of invasive H. influenzae infection had occurred among the children who had received three doses of vaccine, whereas 12 cases had occurred among the controls (P = 0.0005 by Poisson one-tailed test). The rate of short-term (average follow-up time, five months) protection provided by this conjugate vaccine in infancy was thus 83 percent.
Abstract 4404: Post-transcriptional regulation of dihydropyrimidine dehydrogenase (DPD) by the microRNAs mir27a and mir27b
Authors: Steven M. Offer, Natalie J. Wegner, Robert B. Diasio
Journal: Cancer Research (2011)

Abstract The pyrimidine analog 5-fluorouracil (5-FU) and its prodrug capecitabine are prescribed widely for the management of several common cancers, including colorectal, breast, and pancreatic cancers. 5-FU is activated by conversion to cytotoxic metabolites via the pyrimidine anabolic pathway. In the opposing catabolic pathway, dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) initiates rapid and irreversible conversion of greater than 80% of administered 5-FU to inactive metabolites and limits the pool of 5-FU available for anabolism. Deficiency of DPD has been associated with adverse effects to 5-FU treatment, including mucositis, severe diarrhea, neurotoxicity, and life-threatening hematological toxicity, making DPD activity a potentially important predictor of 5-FU toxicity. Despite considerable study of the DPYD gene and its promoter, little is known about the post-transcriptional regulation of DPD expression at the molecular level. The objective of this study was to determine if DPD expression undergoes microRNA-mediated regulation. Computational analysis of the DPYD 3’ untranslated region (UTR) revealed an evolutionarily conserved seed-binding region for the microRNAs mir27a and mir27b. This finding prompted the hypothesis that both mir27a and mir27b are capable of modulating DPD expression. To determine if mir27a and/or mir27b bind to the DPYD 3’ UTR, HCT116 cells lines were engineered to stably express luciferase reporter constructs wherein the luciferase gene was modified to contain the 3’ UTR sequence from DPYD. As controls, stable cells lines containing mutations in the putative microRNA-binding region were generated concurrently. Two colon cancer cell lines (HT29 and HCT15) were also utilized to determine if mir27a and/or mir27b could modulate endogenous DPD expression. In cell lines expressing the luciferase gene juxtaposed to the DPYD 3’UTR, mimics of mir27a or mir27b resulted in significantly reduced luciferase activity relative to scramble control microRNA. Luciferase levels in mir27a or mir27b transfected lines were also significantly reduced compared to stable luciferase-expressing cells harboring the mutant UTR construct. Over-expression of small RNA inhibitors directed toward mir27a or mir27b led to increased luciferase activity in cells containing the wildtype UTR construct. Finally, over-expression of mir27a or mir27b significantly reduced endogenous DPD expression in both HT29 and HCT15 cells. Based on these findings, we conclude that mir27a and mir27b are capable of post-transcriptional regulation of DPD. To our knowledge this is the first report to show microRNA-mediated modulation of DPD expression. 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 4404. doi:10.1158/1538-7445.AM2011-4404
AB0070 Galectin-3 inhibition attenuates interleukin-6 secretion induced by toll-like receptor-stimulation in fibroblast-like synoviocytes
Authors: U. Arad, N. Madar, A. Angel-Korman, S. Amir, O. Elkayam, D. Caspi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Galectin-3 is a β-galactoside-binding lectin that plays an important role in the modulation of immune responses. Galectin-3 levels are increased in rheumatoid arthritis (RA) synovial tissue, synovial fluid and peripheral blood<sup>1</sup>. Recombinant exogenous galectin-3 stimulates pro-inflammatory cytokine secretion by fibroblast-like synoviocytes (FLS)<sup>2</sup>. In a murine, antigen-induced arthritis model, Gal-3-/- mice displayed significantly reduced synovitis and joint erosion compared to WT mice<sup>3</sup>. <h3>Objectives</h3> To examine the effect of galectin-3 inhibition on toll-like receptor (TLR)-induced secretion of interleukin-6 (IL-6) in FLS from RA and osteoarthritis (OA) patients. <h3>Methods</h3> FLS from RA and OA patients were harvested from synovial fluid aspirates or directly from synovial tissue obtained during orthopedic surgery. Galectin-3 was inhibited either by siRNA mediated gene-knockdown, or by the galectin ligands thiodigalactoside and modified citrus pectin (MCP). The cells were then stimulated with ligands for TLR-2, 3 and 4; peptidoglycan (PGN), poly(I:C) and lipopolysaccharide (LPS), respectively, and the levels of IL-6 secretion were measured by ELISA. <h3>Results</h3> Galectin-3 gene knockdown inhibited TLR-2, 3 and 4 induced IL-6 secretion in FLS. Treatment with thiodigalactoside, a galectin oligosaccharide ligand, also decreased TLR-meditated IL-6 secretion. Treatment with MCP, a polysaccharide galectin-3 ligand, attenuated IL-6 secretion due to stimulation with PGN and poly(I:C), but augmented IL-6 secretion following LPS-stimulation, in a dose dependent manner. <h3>Conclusions</h3> Galectin-3 modulates TLR-induced IL-6 secretion in FLS. Knockdown of galectin-3 inhibits PGN, poly(I:C) and LPS-induced IL-6 secretion. Galectin-3 saccharide ligands can also inhibit TLR-induced IL-6 secretion. Understanding the role of galectin-3 in TLR-induced cytokine secretion may add new insights into the pathological mechanisms of autoimmunity and perhaps aid in the design of galectin-3 inhibitors as potential therapeutics. <h3>References</h3> Ohshima S, Kuchen S, Seemayer CA, et al. Galectin 3 and its binding protein in rheumatoid arthritis. Arthritis Rheum. 2003; 48(10): 2788-95. Filer A, Bik M, Parsonage GN, et al. Galectin 3 induces a distinctive pattern of cytokine and chemokine production in rheumatoid synovial fibroblasts via selective signaling pathways. Arthritis Rheum. 2009; 60(6): 1604-14. Forsman H, Islander U, Andreasson E, et al. Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis. Arthritis Rheum. 2011; 63(2): 445-54. <h3>Disclosure of Interest</h3> None Declared