tbuckley/cabot-search huggingface dataset:
Abstract A2: Oncogenic and drug-sensitive <i>ERBB2</i> mutations in glioblastoma
Authors: Heidi Greulich, Milan Chheda, Tzu-Hsiu Chen, Kumiko Tanaka, Amit Dutt, Kwok-Kin Wong, William Hahn, Matthew Meyerson
Journal: Cancer Research (2009)

Abstract The Cancer Genome Atlas (TCGA) Consortium recently completed a multidimensional analysis of glioblastoma, characterizing somatic alterations across a large sample set, and identifying genetic lesions that likely contribute to tumor fitness (TCGA Network, Nature, 2008). However, functional experiments are required to determine whether significantly altered genes are in fact oncogenes or tumor suppressor genes in glioblastoma. We experimentally analyzed mutations in one of the significantly mutated genes, ERBB2. Unlike ERBB2 mutations in lung adenocarcinoma, ERBB2 mutations in glioblastoma are primarily located in the extracellular region, clustering around the domain that mediates receptor dimerization. We have determined that a subset of the reported mutations are gain-of-function and oncogenic, require kinase activity for oncogenic transformation, and are sensitive to specific small molecule kinase inhibitors. This discovery has therapeutic implications for glioblastoma patients who harbor somatic ERBB2 mutations. Citation Information: Cancer Res 2009;69(23 Suppl):A2.
AB0554 Basdai or asdas in axial spondyloarthritis: which score choose to evaluate response to tnf alpha-blockers, according to c-reactive protein?
Authors: Q. Brehier, T. Lequerre, X. L. Loët, A. Daragon, S. Pouplin, M. Kozyreff-Meurice, O. Vittecoq
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> to compare proprtions of responders to infliximab according to the level of C-reactive protein (CRP) in a population of axial spondyloarthritis (AS) defined with the ASAS 2009 criteria set. <h3>Methods</h3> 106 AS patients, fulfilled the ASAS criteria, were included in this monocentric, observational and retrolective study, conducted between 2001 and 2011, in the rheumatologic department of Rouen University Hospital (France). All patients were treated by infliximab (5 mg/kg at week 0, 2, 6 and every 8 weeks). Their response to infliximab was evaluated at 6 and 12 month with ASDAS and BASDAI calculated retrospectively. The percentages of responders with BASDAI (improvement of 50% or at least 2 points) and ASDAS responders (improvement ≥ 1,1 point) were compared at 6 and 12 month for overall patient and according the CRP level (&gt; 5 mg/l or &lt; 5 mg/l) before treatment. <h3>Results</h3> Among the 106 AS patients (57 women and 49 men), 56 had raised CRP while 50 had normal CRP. Under infliximab, BASDAI decreased from 6 (4-9.4) to 3.6 (0-5.9) at 6-month and to 3.6 (0-5.9) at 1 year. ASDAS decreased from 3.6 (2.1-5.7) to 2.5 (0.83-4.25) at 6-months and to 2.3 (0.7 – 4.4) at 12 months. At 6-month, the percentages of BASDAI and ASDAS responders were respectively 52,8% and 43,4% for overall patient (p=0,012), 60,7% and 57,1% (p=0,41) when CRP is elevated, and, 44% and 28% in the normal CRP group (p=0,0114). At 12-month percentage of BASDAI and ASDAS responders was respectively 49,1% and 46,2% for overall patients (p=0,56); 55,4% and 60,7% in the raised CRP group (p=0,18) and 42% and 30% in the normal CRP group (p=0,014). Moreover, BASDAI and ASDAS scores were better correlated in absence of inflammatory syndrome. <h3>Conclusions</h3> This study have shown for the first time that when CRP is high, ASDAS and BASDAI classify similarly the AS patients while when CRP is normal, BASDAI classify more responders than ASDAS. So, ASDAS criteria could be used when baseline CRP is high but BASDAI criteria seem more appropriate than ASDAS when CRP is normal in this cohort of AS patients treated with infliximab <h3>Disclosure of Interest</h3> None Declared
Abstract 2105: Advanced glycation end products of type I collagen promote cell proliferation and resistance against doxorubicin in HT-1080 cancer cells.
Authors: Charles Saby, Hassan EL Btaouri, Laurence Van Gulick, Marie Guilbert, Pierre Jeannesson, Hamid Morjani
Journal: Cancer Research (2013)

Abstract Resistance to apoptosis and chemotherapy is a critical factor in cancer recurrence and patient relapse. Extracellular matrix via its receptors, the integrins, has emerged as a major pathway contributing to cancer cell survival and resistance to chemotherapy (Aoudjit and Vuori, Chemother Res Pract. 2012;2012:283181). However, the effects of extracellular matrix advanced glycation end products (AGE) on cell proliferation and sensitivity to chemotherapy is not well established. In this study, we investigated whether type I collagen and particularly its AGE are involved in cell proliferation and resistance to doxorubicin in human fibrosarcoma HT-1080 cancer cells. Type I collagen was extracted from rats tail tendons (10 days, 8 and 96 weeks-old) and prepared as already described (Millerot-Serrurot et al., 2010, Cancer Cell Int, 13: 10-26). First, we characterized the glycation pattern of the different collagens using SDS-PAGE electrophoresis and fluorescence spectroscopy. A significant increase in AGE level has been observed in collagen extracted from 8 and 96 weeks-old rats. AGE level was significantly higher in collagen extracted from 96 weeks-old rats when compared to 8 weeks-old ones. Only collagen extracted from 96 weeks-old rats was able to induce 3-fold increase in proliferation of HT-1080 cells. Western-blot analysis showed that activation of MAPK/ERK, but not PI3K/AKT, was required for collagen AGE mediated cell proliferation. The MAPK/ERK inhibitor U0126 abolished this effect. Both collagens were able to inhibit doxorubicin-induced apoptosis in HT-1080 cells. Moreover, protection against apoptosis was significantly higher in the presence of collagen extracted from 96 weeks-old rats. Our data suggest extracellular matrix AGE signalling as an important promoter of cancer cell proliferation and that this pathway may contribute to a new mechanism of drug resistance. Citation Format: Charles Saby, Hassan EL Btaouri, Laurence Van Gulick, Marie Guilbert, Pierre Jeannesson, Hamid Morjani. Advanced glycation end products of type I collagen promote cell proliferation and resistance against doxorubicin in HT-1080 cancer cells. [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 2105. doi:10.1158/1538-7445.AM2013-2105
AB0056 Hmgb1 regulates hypoxia-inducible factor 1alpha expression and function in synovial fibroblasts from patients with rheumatoid arthritis
Authors: S. Y. Park, H. R. Lee, H. Y. Kim, S. H. Baek, C. D. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> High mobility group box chromosomal protein 1 (HMGB1) is a nuclear DNA binding protein that is secreted into extracellular medium by cellular activation and proinflammatory response, and promotes inflammation. HMGB1 is known as ligand for TLR4 that produces TNF-a and IL-8 (1, 2). Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor which is composed of an alpha and beta subunit. HIF-1 has been reported as regulator of angiogenesis in rheumatoid arthritis (RA) (3, 4). <h3>Objectives</h3> We investigated the role and molecular mechanism of HMGB1 in the expression and function of HIF-1α in synovial fibroblasts from patients with RA. <h3>Methods</h3> HIF-1 activity and VEGF expression were measured by ELISA. Signaling and molecular events were analyzed by immunoblotting. <h3>Results</h3> The expression of extracellular HMGB1 was increased in synovium of RA patients than OA patients. Treatment of RA synovial fibroblasts with HMGB1 increased HIF-1αexpression and HIF-1 activity. HMGB1 mediated production of VEGF was dependent upon HIF-1. When TLR4 was blocked by TLR4 siRNA or anti-TLR4 antibody, HIF-1αdidn't be increased, leading to abolish the increase in VEGF production. <h3>Image/graph</h3> <h3>Conclusions</h3> Our results suggest that HMGB1stimulation of HIF-1α expression and activity results in VEGF expression that is dependent upon TLR4. <h3>References</h3> Bustin M, Reeves R. High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function. Prog Nucleic Acid Res Mol Biol 1996, 54:35-100. Hamada T, Torikai M, Kuwazuru A, et al. Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheum 2008, 58:2675-2685, Imtiyaz HZ, Simon MC. Hypoxia-inducible factors as essential regulators of inflammation. Curr Top Microbiol Immunol 2010, 345:105-120. Giatromanolaki A, Sivridis E, Maltezos E, et al. Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 2003, 5:R193–201. <h3>Disclosure of Interest</h3> None Declared
Abstract 145: Interactions among DNA methyltransferase isoforms and their effects on DNA methylation
Authors: Beth O. Van Emburgh, Keith D. Robertson
Journal: Cancer Research (2010)

Abstract Alterations in DNA methylation patterns are a hallmark of cancer development demonstrated as both global hypomethylation and gene specific hypermethylation. This results in genomic instability as well as tumor suppressor gene silencing. Methylation is catalyzed by the DNA methyltransferases (DNMTs) DNMT1, DNMT3A, and DNMT3B and is assisted by DNMT3L. In order to understand the role of the DNMTs in aberrant methylation and cancer, a better understanding of how they function and interact with one another is essential. All of the DNMTs, but especially DNMT3B, are alternatively spliced generating many isoforms of unknown function. Immunodeficiency, centromere instability, and facial anomalies syndrome (ICF), which is caused by mutations in the de novo methyltransferase DNMT3B and results in altered DNA methylation patterns, is a model disease that can be studied to better understand the function of DNMT3B. We have successfully expressed each of the DNMTs using baculovirus and E. coli expression systems along with several of their common splice variants, mutations associated with ICF syndrome, and deletion constructs of Dnmt3b. A novel system was developed for these recombinant enzymes using a plasmid containing a satellite 2 sequence as a template in order to analyze both the amount of methylation and site specific methylation with bisulfite genomic sequencing and pyrosequencing. The effects of common splice variants and mutations/deletions on protein-protein interactions are being ascertained using GST pull downs and effects on their interaction with DNA examined using electrophoretic mobility shift assays. Preliminary analyses suggest that the splice variants and mutations/deletions significantly affect DNA methylation and also alter their interaction with DNMT3L and DNA. For example, Dnmt3b2 demonstrates less DNA methylation activity than Dnmt3b1, but both are enhanced by the addition of DNMT3L. Both Dnmt3b1 and Dnmt3b2 bind DNMT3L in pull down assays, but unlike Dnmt3b1 the interaction between Dnmt3b2 and DNMT3L is lost at higher salt concentrations suggesting a weaker association. Ongoing studies will provide additional insights into how interaction between Dnmt3a and Dnmt3b splice variants influences methylation and what impact mutations or deletions can have on this. We anticipate that our results will allow for an improved understanding of the functional interactions of DNMTs which will, in turn, enhance our understanding of how and why methylation patterns go awry in cancer. (Supported by NCI grants F32CA132327 and R01CA114229) 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 145.
A systematic review on skin complications of bone anchored hearing aids in relation to surgical techniques
Authors: S. Mohamad, I. Khan, S. Hey, M. Hussain
Journal: International Journal of Surgery (2015)

A systematic review to study the skin complications associated with the bone-anchored hearing aid in relation to surgical techniques. The following databases have been searched: MEDLINE, EMBASE, the Cochrane Library , Google scholar and the PubMed. The literature search date was from January 1977 until November 2013. Randomised controlled trials and retrospective studies were included. Initial search identified 420 publications. Thirty articles met the inclusion criteria of this review. The most common surgical techniques identified were full-thickness skin graft, Dermatome and linear incision techniques. The result shows that dermatome technique is associated with higher rate of skin complications when compared to linear incision and skin graft techniques. Based on the available literature, the use of a linear incision technique appears to be associated with lower skin complications; however, there is limited data available supporting this. Higher quality studies would allow a more reliable comparison between the surgical techniques.
Late Cardiovascular Toxicity Following Chemotherapy for Germ Cell Tumors
Authors: Darren R. Feldman, Wendy L. Schaffer, Richard M. Steingart
Journal: Journal of the National Comprehensive Cancer Network (2012)

The introduction of cisplatin-based chemotherapy has transformed germ cell tumors (GCTs), the most common malignancy to affect young adult men, into a highly curable cancer, even in the setting of advanced disease. However, over the past decade, the success of these chemotherapy regimens in curing GCTs has been temporized by an increasing recognition of their important late toxicities, such as cardiovascular disease. The relative risk of coronary artery disease in this population is particularly elevated within the first 10 years of follow-up, when patients are still in their 30s and 40s, which are age groups often considered too young to experience cardiovascular events. Two hypotheses have been proposed to explain the association between chemotherapy and cardiovascular disease in this population. The direct hypothesis asserts that chemotherapy causes diffuse endothelial damage, including in the coronary arteries, gradually leading to cardiovascular disease. In contrast, the indirect hypothesis proposes that chemotherapy leads to an increased incidence of cardiovascular disease risk factors, such as hypertension, hyperlipidemia, and the metabolic syndrome, which in turn enhance the risk of cardiovascular disease. This article summarizes the data on the association between chemotherapy (predominantly cisplatin-based) and the development of cardiovascular disease among GCT survivors, and reviews the evidence supporting both mechanistic hypotheses. In addition, recommendations are provided for the management of GCT survivors who received cisplatin-based chemotherapy and are therefore at risk for cardiovascular toxicity.
Abstract ES9-3: Balancing Risks of Deconditioning vs. Weight-Lifting for Breast Cancer Survivors
Authors: KH Schmitz, A Cheville, RL Ahmed, A Troxel
Journal: Cancer Research (2010)

Abstract Background: Clinical guidelines for breast cancer survivors with and at-risk for lymphedema have advised against upper body exercise, preventing them from obtaining established health benefits of weight-lifting. The primary hypotheses of the Physical Activity and Lymphedema Trial were that lymphedema onset and worsening would not differ after a one-year weightlifting intervention compared to no exercise among survivors at risk for and with breast cancer-related lymphedema. Methods: We performed a randomized controlled trial of a twice-weekly progressive weight-lifting intervention involving 141 breast cancer survivors with stable arm lymphedema at study entry and 154 survivors at-risk for lymphedema at study entry. Treatment group participants were provided a gym membership and 13 weeks of supervised instruction; the remaining nine months were unsupervised. Control group participants were provided the intervention after study completion. The primary outcome was the change in arm swelling at one year, as measured by water volumetry of the affected and unaffected arms. Secondary outcomes included the clinician defined incidence of onset and exacerbations of lymphedema, lymphedema symptoms, and muscle strength. Participants with lymphedema were required to wear a well-fitted compression garment while weight-lifting. Results: Among the women who entered the study with lymphedema, the proportion who experienced a 5% or greater increase in arm swelling (interlimb difference) was similar in the treatment and control groups (11% versus 12%; cumulative incidence ratio [95% confidence interval], 1.00 (0.88 to 1.13) As compared with the control group, the women in the intervention group with lymphedema had greater improvements in self-reported lymphedema symptom severity (p=0.03), and a lower incidence of lymphedema exacerbations as assessed by a certified lymphedema specialist (14% versus 29% in the control group, p= 0.04). Among the women who entered the study without lymphedema, more control than treatment group women experienced lymphedema onset defined by 5% increase in interlimb difference (17 versus 11%, p = 0.35). Among higher risk women (5+ lymph nodes removed), this comparison was statistically significant (22 versus 7%, p=0.04). Clinician-defined BCRL onset occurred in 1 treatment and 3 control group women (p=0.62). Conclusions: Slowly progressive weight-lifting had no significant impact on arm swelling among breast cancer survivors with lymphedema, and resulted in a reduced incidence of lymphedema flares and improvement in symptoms. In breast cancer survivors at risk for lymphedema, a program of slowly progressive weight-lifting, compared with no intervention, did not result in increased incidence of lymphedema. In secondary analyses, women with 5+ nodes removed who did weight-lifting were less likely to experience increases in arm swelling. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES9-3.
Single-session fluoroless endoscopic ultrasound-guided fine-needle aspiration and choledochoduodenostomy with a biliary lumen-apposing stent
Authors: Joan Gornals, Claudia Consiglieri, Victoria Gallarreta, Juli Busquets, Isabel Catala, Berta Laquente
Journal: Endoscopy (2015)

A 56-year-old woman with unresectable pancreatic cancer causing obstructive jaundice and anorexia was referred to our unit for tissue diagnosis and biliary drainage before undergoing evaluation by a medical oncologist. Previous endoscopic retrograde cholangiopancreatography (ERCP) to attempt biliary cannulation because of signs of severe tumoral invasion in the papilla area had failed, and biopsy specimens were negative for malignancy.
Mechanisms of Edema Formation in Myxedema — Increased Protein Extravasation and Relatively Slow Lymphatic Drainage
Authors: Hans-Henrik Parving, Jens M. Hansen, Steen L. Nielsen, Niels Rossing, Ole Munck, Niels A. Lassen
Journal: New England Journal of Medicine (1979)

We assessed extravascular accumulation of albumin and fluid in primary myxedema by measuring metabolic turnover and transcapillary escape of 131I-labeled human albumin in seven patients. In the hypothyroid state, we found a low plasma volume (P less than 0.05), a reduced rate of albumin synthesis and catabolism (P less than 0.01), an increased transcapillary escape rate of albumin (P less than 0.01), a remarkable increase in the extravascular mass of albumin (1500 micronmol; P less than 0.01) and a longer mean transit time through the extravascular spaces in primary myxedema than in other states of generalized edema (P less than 0.05). All variables returned to normal during l-thyroxine treatment. The extravascular accumulation of albumin, and presumably of all other plasma proteins, is important in the generalized edema typically found in myxedema. Inadequate lymphatic drainage may also explain the formation of exudates in the serous cavities that are well known in myxedema.
Case 21-1995
Authors: M.J. Barza, J.B. Brennick
Journal: New England Journal of Medicine (1995)

Presentation of CaseA 33-year-old man was admitted to the hospital because of fever and increasing pain in the right leg.The patient had been well until 11 days earlier, when a sore throat developed while he was attending a meeting in Texas. No other symptoms occurred, and he was aware of only low-grade fever. During the next week the sore throat gradually improved. Three days before admission the sore throat was barely noticeable, although fatigue was present. Late in the afternoon he had a shaking chill that lasted more than an hour. The temperature was 38.3 °C and rose . . .
Urgent Colonoscopy for the Diagnosis and Treatment of Severe Diverticular Hemorrhage
Authors: D M Jensen, G A Machicado, R Jutabha, T O Kovacs
Journal: New England Journal of Medicine (2000)

Although endoscopy is often used to diagnose and treat acute upper gastrointestinal bleeding, its role in the management of diverticulosis and lower gastrointestinal bleeding is uncertain.
Abstract 5342: Role of microRNAs in the development of prostate cancer.
Authors: Parameet Kumar, Albert Dobi, George Petrovics, Ahmed Mohamed, Shiv Srivastava, Roopa Biswas
Journal: Cancer Research (2013)

Abstract Prostate Cancer (CaP) is the most common non-cutaneous form of cancer in men. It is also the second leading cause of cancer mortality in men in the USA. Oncogenic activation of the ETS Related Gene (ERG) as a result of gene fusions is the most common genomic alteration in prostate cancer reported to date. ERG has a milieu of transcriptional targets that regulate genes involved in various cellular processes including oncogenesis, inflammation, cell invasion, and DNA damage. Moreover, knockdown (KD) of ERG in TMPRSS2-ERG expressing CaP cells (VCaP) suppresses the growth and invasiveness of VCaP cells and in xenograft models. ERG protein has been implicated as a key player in the progression from pre-invasive to invasive disease status of CaP. Therefore, understanding mechanisms by which ERG promotes CaP progression is essential for developing novel prognostic/therapeutic targets for CaP. Our analyses of miRNA expressions in the human TMPRSS2-ERG fusion harboring VCaP cells compared to ERG-suppressed (with siRNA against ERG) VCaP controls indicate altered expression of miRNAs. Interestingly, we find that ERG suppresses the expression of miR-449a, which has been shown to regulate proliferation of CaP cells. In silico analyses (IPA and Genomatix) of cellular pathways targeted by these miRs focus on regulatory networks that are indicative of EMT and include molecules like DES (desmin), PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) and TGFBR1 (transforming growth factor beta receptor 1). These pathways are potential candidate therapeutic targets. These data form the basis of new insights into the miRNA alterations in the context of major oncogenic activation in prostate cancer. Moreover, these miRNAs will provide novel prognostic marker and therapeutic targets for prostate cancer and will ultimately define CaP associated miRNAs in the context of ERG positive and ERG negative prostate cancers. Supported by: United States Military Cancer Institute [RB] and [SS]. Citation Format: Parameet Kumar, Albert Dobi, George Petrovics, Ahmed Mohamed, Shiv Srivastava, Roopa Biswas. Role of microRNAs in the development of prostate cancer. [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 5342. doi:10.1158/1538-7445.AM2013-5342
Many Italian Researchers Say They Can't Go Home Again
Authors: J. Ziegler
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Many Italian Researchers Say They Can't Go Home Again Get access Jan Ziegler Jan Ziegler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 11, 7 June 1995, Pages 791–792, https://doi.org/10.1093/jnci/87.11.791 Published: 07 June 1995