tbuckley/cabot-search huggingface dataset:
Abstract 1792: MDM2 promoter variants and mRNA expression in irradiated lymphocytes.
Authors: Liv B. Gansmo, Stian Knappskog, Per E. Lonning
Journal: Cancer Research (2013)

Abstract Background. The ubiquitin ligase protein MDM2 plays an important role in cellular processes like growth arrest, senescence and apoptosis, and one of its main targets is the key cell cycle regulator p53. MDM2 is found overexpressed in several solid tumors, and its dysregulation is caused by gene amplification or by enhanced transcription or translation. The MDM2 gene has two main promoters; promoter P1 is constitutive while P2 is considered to be inducible in response to cellular stress. One polymorphism located in the MDM2 promoter P2 region, SNP309T&amp;gt;G (rs2279744), has been shown to enhance Sp1 transcription factor binding and is associated with increased cancer risk. Recently we reported a second polymorphism SNP285G&amp;gt;C (rs117039649) located 24 bp upstream of rs2279744. SNP285C resides on the SNP309G allele and was found to reduce Sp1 binding and lower the risk of ovarian, endometrial and breast cancer. A third SNP located in the same region, SNP344T&amp;gt;A (rs1196333) has been found not to be associated with cancer risk. In this study we examined the expression levels from the two MDM2 promoters among individuals harboring the different SNP variants (SNP309T/G, SNP285G/C and SNP344T/A) before and after irradiation. Materials and methods. Blood samples were collected from 219 healthy individuals. From this blood the buffy coat fraction was separated, divided into two and cultured. Prior to RNA extraction and subsequent cDNA synthesis, one half of the cells were irradiated with a dose equivalent to 3 Grey. Each sample was investigated for SNP285, SNP309 and SNP44 status by sequencing, and MDM2 expression was determined by qPCR using hydrolysis probes. All statistical analyses were calculated using SPSS and GraphPad Prism 5. Results. After stress (ionizing radiation) we observed, on average, a 8 and 60 fold increase in mRNA levels from promoter P1 and P2, respectively (p&amp;lt;0,0001). Statistical analysis of MDM2 mRNA expression from promoter P1 and P2, showed no significant difference between individuals harboring the different genotypes of SNP309 (TT/TG/GG), SNP285 (GG/GC/CC) or SNP344 (TT/TA/AA) before or after stress. Since the SNP285C allele counteracts the effect of SNP309G (reduces Sp1 binding), we analyzed the impact of SNP309G in the subgroup of individuals harboring SNP285 GG, but found no correlation to higher expression levels in this subgroup either. Conclusions. Despite their association with risk of several major solid tumor forms, we found no correlation between MDM2 promoter SNP285 or SNP309 with mRNA expression levels in WBC. Citation Format: Liv B. Gansmo, Stian Knappskog, Per E. Lonning. MDM2 promoter variants and mRNA expression in irradiated lymphocytes. [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 1792. doi:10.1158/1538-7445.AM2013-1792
PWE-229 Innovations in enterocutaneous fistula management: a systematic review: Abstract PWE-229 Table 1
Authors: JK Dastur, S Nachiappan, Y Maeda, J Warusavitarne, C Vaizey
Journal: Gut (2015)

<h3>Introduction</h3> Enterocutaneous fistulas are defined as abnormal communications between the gastrointestinal tract and the skin which may occur in various disease processes or iatrogenically. Patients who suffer with this condition manifest signs and symptoms of fluid and electrolyte imbalance, malnutrition and pain. Despite improvements in management and treatment modalities, mortality and morbidity rates remain high. This review aims to report on treatment innovations in this specialised field since 1980. <h3>Method</h3> A systematic review of studies reporting on techniques and modalities in ECF treatment was undertaken. Studies reporting on treatment of ECFs in inflammatory bowel disease settings, and negative pressure wound management modalities were excluded in this review. <h3>Results</h3> Thirty-six studies met the inclusion criteria. 32 were case series with small numbers, one was a case controlled study and three were systematic reviews/meta analysis. The newer modalities that have been described fell into the following categories: endoscopic (eight case series), surgical (six case series), percutaneous techniques (six case series and one case controlled study), other therapies (two case series) and pharmacological (10 case series and three systematic reviews/meta-analysis). <h3>Conclusion</h3> These studies describe the newer modalities of ECF management. There is a paucity of randomised controlled trials due to the tenuous and protracted treatment requirements for this condition. The current standard of parenteral nutrition, control of sepsis, fluid and electrolyte homeostasis, wound care and a carefully timed definitive surgical procedure, form the core of its treatment. The described techniques generally attempt to reduce fistula output or mechanically occlude the fistulous tract. The newer modalities are not well-established and in most cases, act as adjuncts to the current standard therapies in ECF management. This review enables clinicians to objectively explore available therapies to treat this difficult condition and may allow for targeted approaches to be utilised in treating these patients. <h3>Disclosure of interest</h3> None Declared.
Novel Mutations in a Patient with <i>ALK</i>-Rearranged Lung Cancer
Authors: Smith Giri, Jashmin K Patel, Daruka Mahadevan
Journal: New England Journal of Medicine (2014)

A variety of mechanisms of crizotinib resistance have been defined in patients with ALK-rearranged lung cancer who no longer have a response to the drug. A case is presented in which the tumor lost the rearrangement and mutations developed in several other genes.
FRI0261 Anti-phospholipid antibodies in systemic sclerosis: Prevalence and clinical correlations
Authors: K.B. Morrisroe, W.M. Stevens, J. Byron, V. Thakkar, O. Moore, S. Proudman, M. Nikpour
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-phospholipid antibodies (APLA) are typically associated with thrombosis in systemic lupus erythematosus and anti-phospholipid syndrome. However, little is know about the clinical associations of these antibodies in systemic sclerosis (SSc). <h3>Objectives</h3> We sought to determine the prevalence and correlates of APLA in a large cohort of patients with SSc. <h3>Methods</h3> Patients participating in the Australian Scleroderma Cohort Study who fulfilled the ACR or Medsger criteria for SSc, were tested for APLA (anti-cardiolipin IgM [ACA IgM], anti-cardiolipin IgG [ACA IgG] and anti-beta2 glycoprotein antibodies [Anti-β<sub>2</sub>GP]) using commercial ELISA assays at each annual visit. APLA and various clinical manifestations were defined as present ever from SSc diagnosis. Chi-square and unadjusted logistic regression were used to identify and quantify clinical associations of APLA in SSc. <h3>Results</h3> One or more types of APLA were present in 226 (24.0%) of 940 patients included in the study. There were no patients with lupus anticoagulant. Type and titre of APLA are summarized in Table 1. Moderate to high titre ACA IgG were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH) (odds ratio 1.6, 95% CI: 1.03-2.52, p=0.038). Both ACA IgM (odds ratio 2.04, 95% CI: 1.4-3.0, p&lt;0.0001) and ACA IgG (odds ratio 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). ACA IgG was a marker of coexistent PAH and ILD (odds ratio 2.10, 95% CI: 1.1-4.2, p=0.036). There was no association between APLA and SSc disease subtype (limited v. diffuse), presence of other autoantibodies, or other disease manifestations e.g. renal crisis. <h3>Conclusions</h3> Anti-phospholipid antibodies are found in 24% of patients with SSc, but in most cases the titres are low (&lt;20 U/ml). Moderate to high titre APLA are associated with a 1.6 to 2-fold increased risk of PAH or ILD, and a 2-fold increased risk of coexistent PAH and ILD in SSc. <h3>Disclosure of Interest</h3> None Declared
AB0683 A rare case of progressive pseudo-rheumatoid dysplasia in a young tunisian patient
Authors: H. Hariz, L. Metoui, I. Gharsallah, F. Ajili, N. Boussetta, S. Foughali, B. Louzir, S. Othmani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Progressive pseudorheumatoid dysplasia is an inherited skeletal dysplasia with radiographic changes notably in the spine, similar to spondyloepiphyseal dysplasia tarda. There is also articular cartilage involvement which gives it some clinical resemblance to juvenile rheumatoid arthritis. <h3>Results</h3> We report a case of fifteen year old patient presenting chronic painless swollen joints, accompanied by progressive motion restriction and progressive walking difficulties. Radiologically, there was enlargement of the epimetaphyseal portions of the large joints, metacarpal heads, and phalanges, and platyspondyly with irregular delineation of the endplates of the vertebral bodies. Normal values were found for the erythrocyte sedimentation rate and C-reactive protein level. Rheumatoid factors and antinuclear antibodies were negative. The combination of the dysplastic abnormalities of the joints and the spine, the absence of destructive lesions of rheumatoid arthritis and the negativity of inflammatory and immunologic tests led to the diagnosis of progressive pseudorheumatoid dysplasia. <h3>Conclusions</h3> Progressive pseudorheumatoid dysplasia is an autosomal recessive disease characterized by abnormal cartilage homeostasis. It should be included among the differential diagnoses of juvenile idiopathic arthritis. <h3>Disclosure of Interest</h3> None Declared
Contract With America Creates Flurry of Legislation
Authors: S. Bennett
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Contract With America Creates Flurry of Legislation Get access Sylvia Bennett Sylvia Bennett Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 15, 2 August 1995, Pages 1111–1112, https://doi.org/10.1093/jnci/87.15.1111 Published: 02 August 1995
Abstract 4341: Bortezomib primes neuroblastoma cells for TRAIL- triggered apoptosis by linking the death receptor to the mitochondrial pathway
Authors: Ivonne Naumann, Roland Kappler, Dietrich von Schweinitz, Klaus-Michael Debatin, Simone Fulda
Journal: Cancer Research (2011)

Abstract In contrast to remarkable improvements in the survival and cure rates that have been encountered for many childhood malignancies, the prognosis of children with advanced stage neuroblastoma remains poor. Searching for novel strategies to modulate apoptosis in neuroblastoma we investigated the potential of the proteasome inhibitor Bortezomib to modulate TRAIL-induced apoptosis in neuroblastoma cell lines, primary neuroblastoma cultures and in an in vivo model of neuroblastoma. Here, we provide first evidence that Bortezomib at subtoxic concentrations synergistically cooperates with TRAIL to induce apoptosis (combination index 0.5). In addition, Bortezomib acts in concert with TRAIL to reduce colony formation of neuroblastoma cells, demonstrating an effect also on longterm survival. Mechanistic studies reveal that Bortezomib profoundly enhances TRAIL-induced cleavage of Bid into tBid, accumulation of tBid in the cytosol and its insertion into mitochondrial membranes, pointing to a concerted effect on Bid cleavage (TRAIL) and stabilization of tBid (Bortezomib), which links the death receptor to the mitochondrial pathway. Additionally, Bortezomib increases expression of p53 and Noxa. All these changes lead to increased activation of Bax and Bak, loss of the mitochondrial membrane potential, cytochrome c release, caspase activation and caspase-dependent apoptosis upon treatment with Bortezomib and TRAIL. Knockdown of either Bid, Noxa or p53 significantly delays the kinetic of Bortezomib- and TRAIL-induced apoptosis, whereas it does not confer longterm protection. By comparison, overexpression of Bcl-2, which simultaneously antagonizes tBid, Noxa and p53, significantly inhibits Bortezomib- and TRAIL-induced apoptosis and even rescues clonogenic survival. Of note, Bortezomib and TRAIL act in concert to trigger apoptosis in several patients’ derived primary neuroblastoma cultures, underscoring the clinical relevance. Importantly, Bortezomib cooperates with TRAIL to suppress tumor growth in an in vivo model of neuroblastoma. In conclusion, these findings demonstrate for the first time that Bortezomib at subtoxic concentrations represents a promising new approach to prime neuroblastoma cells towards TRAIL-induced apoptosis by linking the death receptor to the mitochondrial pathway. Thus, this study provides the rational for future (pre)clinical evaluation of the combination strategy with Bortezomib and TRAIL in neuroblastoma. 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 4341. doi:10.1158/1538-7445.AM2011-4341
Abstract B47: Exploring the mechanism of cancer stem cell-specific action by salinomycin in yeast as a model
Authors: Wolfram Siede
Journal: Cancer Research (2011)

Abstract The antibiotic salinomycin represents a selective potassium ionophore. It has recently attracted considerable attention due to its stem-cell specific mode of action as elucidated in a breast cancer stem cell model [1]. Further studies revealed additional benefits, e.g. the triggering of apoptosis in resistant cancer cell lines and reversal of multidrug resistance [2,3]. In budding yeast, we discovered that this agent is active and, similar to nigericin, prominently causes mitochondrial damage as revealed by the emergence of respiration-defective cells. We also noted the frequent occurrence of salinomycin-resistant clones which may prove to be an obstacle in chemotherapy. We used the collection of systematic gene deletions in haploid yeast to characterize genes whose deletion confers sensitivity or resistance to salinomycin if a carbon source is provided (glycerol) that requires active respiration for growth. With this toxicogenomics approach in a model organism, we attempt to elucidate cancer stem cell-specific therapy targets and suggest strategies to avoid the development of salinomycin resistance. Among salinomycin-sensitive deletion mutants, significant overlap was found with known mutants sensitive to the ionophore monensin. Within this group, mutants that compromise vacuole/Golgi function and autophagy dominate. Novel genes were also uncovered which confer salinomycin sensitivity if deleted, such as CAJ1, encoding a heat shock protein of the dnaJ family, and certain arginine synthesis genes. On the other hand, deletions of TOR pathway components as well as deletions of the E2-ubiquitin conjugating enzymes UBC13 and MMS2 were among the most salinomycin-resistant mutants we found. In almost all cases, a strong correlation between salinomycin and nigericin sensitivity was observed. Since salinomycin appears to be the more efficient anti-cancer stem cell agent [1], the few cases of differential sensitivity will be discussed. [1] Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, et al. (2009) Cell 138:645–659. [2] Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C (2009) Biochem Biophys Res Commun 390:743–749. [3]Fuchs D, Daniel V, Sadeghi M, Opelz G, Naujokat C (2010) Biochem Biophys Res Commun 394:1098–1104. Supported by Cancer Prevention and Research Institute of Texas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B47.
AB0228 Gas6/tam-system in systemic sclerosis and sjÖgren syndrome: SMER as an indicator of pulmonary hypertension
Authors: D. Sola, P.P. Sainaghi, A. Coccetta, M. Bellan, R. Molinari, A. Nerviani, M. Pirisi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Impaired phagocytosis of apoptotic bodies, inflammation and fibrosis are common features of Systemic Sclerosis (SSc) [1] and Sjögren Syndrome (SS) [2]. The Gas6/TAM-system is involved in all these processes [3, 4]. <h3>Objectives</h3> To evaluate plasma Gas6 and sTAM receptors concentrations as putative biomarkers in SSc and SS. <h3>Methods</h3> Forty-one consecutive patients with SSc (n.=23) or SS (n.=18) were recruited at a tertiary level rheumatology unit from December 2010 to May 2011; age-matched patients (n.=46) with degenerative joint disease served as controls. Relevant clinical data, including those on immunosuppressive therapies, comorbidities, physical examination, systolic pulmonary artery pressure (PAPs), ESR, CRP, C3, C4, modified Rodnan-skin-score, Valentini-score, Kazerooni-score, anti-centromere and/or anti-scl70 antibody positivity were recorded in a database. Plasma Gas6, sMer, and sAxl concentrations were measured by an ELISA method developed and validated at our laboratory [5] and by commercially available kits (R&amp;D, USA), respectively. Non parametric, Pearson's chi-square and multiple linear regression analyses were performed. <h3>Results</h3> Subjects with SSc, SS and controls were similar for age, sex and comorbidities (autoimmune thyroid disease and hypertension) (Kruskaal-Wallis variance p&gt;0.31). Median plasma Gas6 and sAxl were not different between groups (Kruskal-Wallis variance, p&gt;0.05), while median plasma sMer was higher in SSc (3.5 ng/ml, 2.9-4.3 IQR) versus SS (3.3, 2.7-4.8) or controls (2.6, 2.4-3.2); post-hoc analysis p&lt;0.009. At multiple linear regression analysis, plasma sMer correlated with PAPs (β=0.86, p=0.02) and ESR (β=0.18, p=0.05) but not with any other variables. <h3>Conclusions</h3> Plasma sMer concentration is higher in SSc patients and associates with pulmonary arterial hypertension, but not with indexes of pulmonary fibrosis or scleroderma disease activity scores. The Gas6/Mer system may be relevant in the pathophysiology of pulmonary hypertension, possibly via the control of endothelial apoptosis. <h3>References</h3> N Hunzelmann and J Brinckmann. What are the new milestones in the pathogenesis of systemic sclerosis? Ann Rheum Dis 2010 69: i52-i56 Rehman HU. Sjögren's syndrome. Yonsei Med J 2003 Dec 30;44(6):947-54. Review. Lemke G, Burstyn-Cohen T.TAM receptors and the clearance of apoptotic cells. Ann N Y Acad Sci 2010 Oct;1209:23-9. doi: 10.1111/j.1749-6632.2010.05744.x. Alciato F, Sainaghi PP, Sola D, Castello L, Avanzi GC. Tnf-alpha, IL-6 and IL-1 expression is inhibited by Gas6 in monocytes/macrophages. J Leuk Biol 2010. Sainaghi PP, Alciato F, Carnieletto S, Castello L, Bergamasco L, Sola D, Bongo AS, Inglese E, Polosa R, Avanzi GC. Gas6 evaluation in patients with acute dyspnea due to suspected pulmonary embolism. Respir Med 2009;103:589-94. <h3>Disclosure of Interest</h3> None Declared
P1115 IMPAIRED IL28B GENE INDUCTION AND EXPRESSION OF IFN-LAMBDA4 ARE CLOSELY ASSOCIATED WITH A NON-RESPONSE TO INTERFERON-BASED THERAPY IN CHRONIC HEPATITIS C PATIENTS
Authors: Y. Asahina, M. Murakawa, F. Kawai, F. Goto, S. Otani, M. Taniguchi, S. Nitta, Y. Nishimura-Sakurai, T. Watanabe, Y. Itsui, M. Nakagawa, S. Azuma, S. Kakinuma, M. Watanabe
Journal: Journal of Hepatology (2014)
Transfer of Symptomatic Peanut Allergy to the Recipient of a Combined Liver-And-Kidney Transplant
Authors: Christophe Legendre, Sophie Caillat-Zucman, Didier Samuel, Sophie Morelon, Henri Bismuth, Jean-François Bach, Henri Kreis
Journal: New England Journal of Medicine (1997)

Peanuts are one of the commonest causes of food allergy in the United States and Europe.1–3 They are also a leading cause of food-induced anaphylaxis and death, which usually follow inadvertent exposures.4,5 Allergy to peanuts is an IgE-mediated, mast-cell–dependent, immediate-hypersensitivity reaction. There are several reports of the transfer of allergen-specific IgE-mediated hypersensitivity by bone marrow transplantation.6–9 We report a case of peanut allergy transmitted through combined liver-and-kidney transplantation. Case Report A 22-year-old man with a history of allergic reactions to peanuts was admitted to our hospital in a coma. After inadvertently ingesting satay sauce, which contains peanuts, . . .
489 AN ALLELIC VARIANT IN THE IRF3 GENE IS ASSOCIATED WITH LIVER CIRRHOSIS IN HEPATITIS C VIRUS CARRIERS
Authors: L.M. Real, A. Caruz, K. Neukam, A. Rivero, A. Rivero-Juárez, D. Merino, M. Márquez, M.J. Gomez, E. Pérez, J. Macias, J.A. Pineda
Journal: Journal of Hepatology (2013)
Quantitative HER2 homodimer levels correlate with time to first recurrence in HER2-positive breast cancer patients who did not receive trastuzumab in the adjuvant setting.
Authors: M Bates, W Koestler, E Fuchs, J Sperinde, K Leitzel, S Ali, J Weidler, Y Wu, C Chappey, W Huang, A Lipton
Journal: Cancer Research (2009)

Abstract Abstract #1074 BACKGROUND: HER2-positive breast cancer patients are currently treated with trastuzumab in the adjuvant setting, but prior to 2005 these patients were not routinely offered trastuzumab, creating an opportunity to examine the relationship between HER2 expression and disease progression. The VeraTag technology is a proximity-based assay system that permits quantitative measurements of total HER2 protein expression (H2T) as well as HER2 homodimers (H2D) in formalin-fixed paraffin-embedded (FFPE) tissues. We measured H2T and H2D in a cohort of patients who were HER2-positive but did not receive trastuzumab in the adjuvant setting, and correlated those measurements with time to first recurrence of disease.&amp;#x2028; METHODS: Patients were selected for study because they were treated with a trastuzumab-containing regimen for HER2+ metastatic breast cancer. HER2-positivity was defined as IHC (Herceptest) 3+ or 2+, FISH+ (Vysis). 96 HER2+ patients who had been treated (but not with trastuzumab) in the adjuvant setting were identified. The VeraTag assay was used to quantitate H2T and H2D. Kaplan-Meier and Cox proportional hazards analyses were employed.&amp;#x2028; RESULTS: The distribution of H2T ranged over approximately 135-fold, and H2D varied over approximately 100-fold. In univariate Cox proportional hazards regression analysis, H2T trended toward significance (HR=1.44, p= 0.088) while both H2D (HR=1.39, p=0.022) and the ratio H2D/H2T (HR=2.01, p=0.03) were significantly correlated with time to first recurrence. Kaplan-Meier analysis of the H2T distribution divided into tertiles showed no significant difference in time to first recurrence among the tertiles (HR=0.7, p=0.16 for low vs. high comparison) and no trend was observed (Log Rank test for trend p=0.2). However, the same analyses performed using H2D (HR=0.59, p=0.03) or H2D/H2T (HR=0.56, p=0.01) demonstrated significantly longer time to first recurrence for the lowest tertile compared with the highest tertile respectively. A trend was observed in both cases (H2D: Log Rank p=0.048; H2D/H2T: Log Rank p=0.026)&amp;#x2028; CONCLUSION: In a population of HER2+ patients who did not receive trastuzumab in the adjuvant setting, and who subsequently developed metastatic disease, higher levels of HER2 homodimers and the ratio of homodimers to HER2 total expression correlated with time to first recurrence while total HER2 expression levels did not. These data suggest that measures of the activated forms of HER2 (dimers) may be better predictors of disease progression than simple quantitation of HER2 alone. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1074.