tbuckley/cabot-search huggingface dataset:
AB1225 Treatment with TNF blockers are effective and safe in BD patients with uveitis
Authors: K. Terauchi, M. Takeno, T. Uehara, A. Ueda, N. Mizuki, E. Shibuya, Y. Ishigatsubo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Infliximab (IFX) is highly effective for uveitis in Behcet’s disease (BD), but the therapy does not completely suppress ocular manifestations. <h3>Objectives</h3> This study determined what factors are associated with ocular attacks during the IFX therapy. <h3>Methods</h3> We retrospectively examined clinical courses of 19 BD patients (female 2+1, male 15+1, age 39.9±12.1 yo patients are only for the analysis of he safety of IFX) who received IFX due to uveitis. In the original regimen, IFX (5mg/kg) was given at 0, 2, 6 week, and thereafter every 8 weeks, but the intervals were shortened after major ocular attacks occurred. Mean duration was 5.7±5.8 years from the disease onset to initiation of infliximab therapy. Before the infiliximab therapy, 16 patients had received colchicines and 7 patients had cyclosporine A. Duration of IFX was 29.9±14.8 months (7 to 60 months, 5 to 51 times). IFX therapy was discontinued in two patients by infusion reaction. The infusions were suspended one or two week in 2 patients because of infection including infectious mononucleosis by cytomegalovirus. <h3>Results</h3> Visual acuity were improved in 18 eyes, unchanged in 7 eyes, and deteriorated in 5 eyes, (except blind eyes.) Frequency of ocular attacks was 2.6±2.1/6 month before and during the IFX therapy, while that was reduced to 0.41 + 0.49/6 months. During the therapy, total 35 ocular attacks occurred at 5.28±1.87 weeks after the last infusion, 1.53±1.59 weeks before the next expected infusion. After ocular attacks, the infusion interval was shortened from 5 to 7 weeks in 8 patients. Treatment with IFX is effective, safety and tolerable in BD patients with uveitis. Ocular attacks were significantly suppressed, resulting in improvement of visual acuity. However, the attacks were accumulated in the last 2 weeks of infusion interval. <h3>Conclusions</h3> It is hard to predict responsiveness to IFX therapy based on the pre-therapeutic clinical features. <h3>Disclosure of Interest</h3> None Declared
THU0368 Risk of herpes viruses infections (HSV,VZV) during anti-tnf therapy in patients with inflammatory rheumatic diseases. Systematic review and meta-analysis
Authors: H. Che, J. Morel, B. Combe, C. Lukas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> TNF blockers have demonstrated their efficacy in inflammatory rheumatic diseases (IRD) and are now widely used. A moderate but indubitable increase in bacterial infectious events is known in patients treated with these drugs but little is known about the potential risk of reactivation of herpes zoster infections. <h3>Objectives</h3> To assess the risk of herpes zoster infections in patients with IRD treated with TNF blockers based on available reported data in the literature. <h3>Methods</h3> A systematic literature search was performed to January 2011, in Medline, Embase, Cochrane library and abstracts from ACR and EULAR congresses 2006-2010. Studies were included for meta-analysis if they reported the respective incidences of herpes infections in anti-TNF and conventional DMARDs-treated patients. The Mantel-Haenszel method was used to provide a pooled odds-ratio (OR) estimate and a 95% confidence interval (CI) in anti-TNF versus conventional DMARDs. Statistical heterogeneity was assessed on the basis of the Q test (Chi2), using a significance level of 0.05. Incidence of severe herpetic infections (multidermatomal lesions, requiring hospitalization or intravenous treatment) was extracted and reported when available. <h3>Results</h3> The literature search identified 655 articles and 134 congress abstracts, and the additional manual search considered 11 national registries and 2 articles. Finally, 22 articles and 28 abstracts met selection criteria and were included in the study. Among these, 3 articles (1,2,3) and 2 abstracts (4,5) allowed a meta-analysis to estimate the relative risk of herpes infections, with a total follow up of 124,966 patient-years (PY) (74,198 PY in biologics group and 50,768 PY in conventional DMARDs group). Based on these 5 registries, the pooled OR was 1.75 [95%CI 1.50–2.04] without significant heterogeneity (I2=52%, p=0.08). Proportions of severe herpes infections, reported in the US and German populations were respectively 4.9% and 20.9% (1,2). In the British registry, the respective rates were 6% and 0.02% with biologics and conventional DMARDs. <h3>Conclusions</h3> This meta-analysis of registries shows a significant increased risk of herpes zoster infections up to 75% in patients with IRD treated with TNF blockers. These data raise the issue of a systematic prophylactic treatment in patients with a known history of herpetic infections, or vaccination in naïve patients. <h3>References</h3> McDonald JR et al, Clin Infect Dis. 2009 ;48(10):1364-71. RABBIT: Strangfeld et al, JAMA. 200918;301(7):737-44. CORRONA: Greenberg JD et al, Ann Rheum Dis. 2010;69(2):380-386. BSRBR: Galloway et al, Abstract 421. ACR 2010. Perez-Zafrillaand al, FRI0129. Ann Rheum Dis 2008;67(Suppl II):327. <h3>Disclosure of Interest</h3> None Declared
Staging an Esophageal Carcinoma by F-18 Fluorodeoxyglucose Whole-Body Positron Emission Tomography
Authors: S Hoegerle, C Altehoefer, E U Nitzsche
Journal: Clinical Nuclear Medicine (2000)

A 49-year-old man was evaluated for dysphagia. Double-contrast examination showed esophageal lumen narrowing, and histologic assessment of the endoscopically obtained biopsy specimen revealed esophageal carcinoma. To plan the therapy strategy and stage tumors, CT and F-18 fluorodeoxyglucose whole-body positron emission tomography (PET) were performed. Surprisingly, the PET scan revealed a bone metastasis in the spine (T3), which showed no morphologic correlate on the CT. To clarify this discrepancy, MRI was performed and confirmed a metastasis of the third thoracic vertebrae. Infiltration of the bone marrow occurred with malignant cells but without any morphologic changes of the osseous structure. This case indicates that PET may be important for tumor staging.
Abstract LB-84: The Importance of Consumer Involvement in Design, Implemenation and Dissemination of Breast Cancer Research
Authors: Kathleen Werner
Journal: Cancer Research (2011)

Abstract There is a growing recognition among researchers and clinicians to include consumers and patients in all stages of cancer research. Various advocacy groups and individuals are designing programs to educate and equip survivors and consumers on various aspects of the cancer research and advocacy processes. It is crucial to make these consumers valued members of the dialogue on developing research that may one day directly impact them. The consumer voice is a valued aspect of research that has been consistently overlooked by many researchers and clinicians in the past. By including consumer perspective, these researchers and clinicians are now finding it can greatly enrich the scope, design, impact and outcomes of their research. This poster follows the path of one such consumer advocate_a young, pre-menopausal breast cancer survivor_and how other such consumers can impact the research process to maximize consumer benefit. Researchers will be able to explore how they may better engage consumers for enrichment of their research impact and stated aims. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-84. doi:10.1158/1538-7445.AM2011-LB-84
A memorable trainer: Dr John Annear
Authors: D. C Riordan
Journal: BMJ (2002)

Dr Annear was a sage-like, enigmatic, paternalistic, “old school” eccentric whose outpatients clinics stretched into the very late evening. Patients would wait to see him for their appointments, often bringing soup or tea and bedding down until it was their turn. This was not some outback post in the Third World, this was inner city London. Although, the length of outpatients clinics and the fluidity in boundaries were frustrating at times, they were a place of great …
AI-06 * NON-CANONICAL NF-kB SIGNALING DRIVES THE AGGRESSIVE INVASIVENESS OF GLIOBLASTOMA
Authors: E. Cherry, D. Lee, J. Jung, R. Sitcheran
Journal: Neuro-Oncology (2014)

The aggressive migration and invasion of glioblastoma multiforme (GBM) cells into healthy brain tissue are major factors contributing to the therapy resistance and poor prognosis of this malignancy. Aberrant activation of NF-kB has been shown to play key roles in the invasiveness and pathogenesis of many cancers, including GBM. Most of these studies have focused on canonical NF-kB signaling, which is mediated by RelA and p50. Activation of the canonical NF-kB pathway is induced by IkB kinase-b (IKKb), whose inhibition has been pursued as a therapeutic approach to attenuate NF-kB activation in cancer with limited success to-date. We have recently shown that the alternative, or non-canonical, NF-kB signaling pathway mediated by RelB, predominates in a very aggressive GBM subtype. Here, we investigate this previously unrecognized role for non-canonical NF-kB signaling in CNS tumor initiation and progression. Using both established and primary GBM tumor lines, we show that in high RelB-expressing GBM cells, loss of RelB inhibits invasion to a greater extent than loss of RelA. Furthermore, RelB expression is sufficient to promote invasion in RelA-deficient GBM cells. Stimulation with Tumor Nectosis Factor Weak Inducer of Apoptosis (TWEAK) preferentially activates non-canonical NF-kB signaling and regulation of Matrix Metalloproteinase 9 (MMP9) expression, resulting in strongly increased invasion. Finally, we show that a key upstream regulator of RelB, NF-kB-inducing kinase (NIK), induces dramatic cell shape changes, increases tumor cell invasion and promotes aggressive orthotopic tumor growth in mouse xenografts. These results not only expand on previously described roles for TWEAK in promoting tumor cell survival, but also demonstrate a potent pro-invasion function for NIK in aggressive GBM and, potentially, other RelB-driven tumors. Notably, oncogenic functions of the non-canonical NF-kB pathway remain poorly elucidated in the CNS. Our data highlight the therapeutic potential of targeting NIK in GBM.
Abstract 3050: Transcriptome sequencing identifies oncogenic microRNA signatures related to NF-kB, TP53 and Notch family members in head and neck squamous cell carcinoma.
Authors: Anthony D. Saleh, Han Si, Xingping Yang, Jamie Coupar, Zhong Chen, Carter Van Waes
Journal: Cancer Research (2013)

Abstract MicroRNA dysregulation has been shown to be nearly universal in cancer biology, driving oncogenic signaling networks. However, microRNA mediated global regulatory mechanisms underlying malignant phenotypes of head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we have performed genome-wide small RNA sequencing on a panel of nine HNSCC cell lines and three normal primary oral keratinocyte cell lines, as well as matched primary tumor and normal tissues using the SOLiD parallel sequencing platform. A panel of microRNAs with altered expression was identified, including several novel oncogenic microRNAs which are upregulated in parallel with altered activation of NF-KB c-REL, TP53 family members ΔNp63α and TAp73, and potentially involved in the down-modulation of p53 and Notch1, two genes most often mutated or inactivated in HNSCC. To examine the hypothesis that these microRNAs could potentially be regulated by NF-KB and p53 pathways, NF-KB inducer TNF-α was used to treat an HNSCC cell line with high expression of mtTP53, ΔNp63α and TAp73. Genome-wide small RNA sequencing revealed significant changes in microRNA expression modulated by TNF-α that overlaps with the panel of constitutively dysregulated microRNAs in HNSCC. Furthermore, genome-wide ChIP-sequencing revealed that TNF-α modulated DNA binding activities of c-REL, ΔNp63α and TAp73 aligned within the regulatory regions of several differentially expressed microRNAs. Modulation of these microRNAs with anti-miR repression altered cell cycle and reduced proliferation in HNSCC cell lines, which confirmed the oncogenic activity of the microRNAs and their potential for therapeutic targeting. Citation Format: Anthony D. Saleh, Han Si, Xingping Yang, Jamie Coupar, Zhong Chen, Carter Van Waes. Transcriptome sequencing identifies oncogenic microRNA signatures related to NF-kB, TP53 and Notch family members in head and neck squamous cell carcinoma. [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 3050. doi:10.1158/1538-7445.AM2013-3050 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
P1060 ASSOCIATION BETWEEN GENOTYPE AND BASELINE HBsAg LEVELS AND THE HBsAg LEVELS AT HBeAg SEROCLEARANCE IN HBeAg-POSITIVE CHRONIC HEPATITIS B PATIENTS TREATED WITH ENTECAVIR
Authors: C.-Y. Peng, H.-C. Lai, W.-P. Su, C.-H. Lin, P.-H. Chuang, S.-H. Chen
Journal: Journal of Hepatology (2014)
Abstract 5348: In vivo and in vitro alveolar rhabdomyosarcoma cell growth is affected by TNK2 expression
Authors: Fernanda I. Arnaldez, Choh L. Yeung, Lee J. Helman
Journal: Cancer Research (2011)

Abstract Rhabdomyosarcoma is the most common pediatric soft tissue tumor. The two major histologic subtypes are embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS); which have different genetic alterations: 11p15 LOH in ERMS and PAX3 (or PAX7)-FOXO1 translocation in ARMS. Despite utilization of aggressive multimodal therapy, patients with recurrent or metastatic disease remain essentially incurable. This is particularly true in patients with alveolar rhabdomyosarcoma. New therapies are needed to improve outcomes in this disease. To detect genes that are critical for rhabdomyosarcoma cell growth and survival, we performed a loss-of-function shRNA screen in ARMS and ERMS cell lines using a regulated shRNA library that was delivered to RMS cells using retrovirus. We hypothesized that genes whose loss of function significantly influence the growth and survival of ARMS cells with relatively no impact on ERMS cells represent a critical vulnerability or “Achilles’ heel” for ARMS. We sorted our gene list using this approach. In this study, we identified TNK2 (tyrosine kinase, non-receptor 2; also known as ACK1) as a critical gene is ARMS cell survival and as a potential therapeutic target. TNK2 is a non-receptor tyrosine kinase that integrates signals from different membrane receptors, including integrins, EGFR and IGFR. Reported downstream targets include CDC42 and AKT. The TNK2 gene is located at 3q29. TNK2 amplification has been described in prostate, lung and breast cancer and its role in invasion and metastasis has recently been suggested. However, its role in rhabdomyosarcoma has not been previously explored. We initially confirmed that TNK2 is uniformly expressed RMS. In addition, analysis of TNK2 expression in primary tumor samples of RMS using a publicly available database indicated that rhabdomyosarcomas with higher TNK2 expression show lower overall survival. We used a tetracycline-inducible shRNA construct to knock down TNK2 expression in rhabdomyosarcoma cells. TNK2 knock down resulted in significant decrease in cell growth in ARMS. We characterized the specificity of our findings using 5 different shRNA sequences targeting this gene delivered via lentivirus. In addition, we have been able to rescue the effect of an shRNA targeting the 3’UTR of this gene using TNK2 cDNA. We validated our in vitro data in an in vivo model using tumor xenografts. Downstream pathways under investigation include but are not limited to AKT, MAPK and CDC42. These data suggest that TNK2 could represent a therapeutic target in ARMS and highlight the role of loss of function shRNA screens to improve the understanding of tumor biology. 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 5348. doi:10.1158/1538-7445.AM2011-5348
Abstract 4249: Landscape of DNA methylation status of human hepatocellular carcinoma revealed by Human Methylation BeadChip 450K.
Authors: Takafumi Nishimura, Yukiko Mori, Naoshi Nishida
Journal: Cancer Research (2013)

Abstract &amp;lt;Background and aim&amp;gt; Global DNA hypomethylation and regional hypermethylation in CpG island has been recognized as common feature of cancer DNA, including that of hepatocellular carcinoma (HCC). However, precise mechanism underlying the alteration of methylation is still unclear. We conducted a genome-wide methylation analysis to elucidate distribution and characteristics of genes that subject to cancer-related DNA methylation in human HCC. &amp;lt;Materials and methods&amp;gt; With written informed consent, 20 HCC and 3 corresponding matched non-cancerous liver tissues were obtained at the time of hepatectomy (2 tumors) or orthotopic living-donor liver transplantation (17 tumors and 3 non-tumors). After bisulfite modification, the converted DNA was subject to hybridization on Infinium Human Methylation BeadChip 450K (Illumina, Inc., San Diego, CA) that contained 485,577 CpGs of the human genome including gene promoters and repetitive DNA elements. The methylation level for each CpG was represented as a beta value according to the fluorescent intensity ratio. In order to identify alteration of methylation profile between HCC and non-tumor liver, difference of average beta values between tumor and non-tumor was calculated. &amp;lt;Results&amp;gt; Of 485,577 CpG loci, differences of average beta values of 460,036 loci (94.7%) were within 30%. These were considered as constitutively methylated or unmethylated. Tumor-specific hypomethylation was found at 18,807 loci. Of these, 65.1% were located outside CpG islands, shore or shelf (so-called ‘open sea’). Tumor-specific demethylation rarely occurred within CpG islands (6.5%). On the other hand, tumor-specific DNA methylation was found at 6734 loci. Of these, 77.6% were located within CpG islands. Interestingly, normally methylated CpGs (average beta value &amp;lt; 0.20) were mainly located in CpG islands (95,943 of 138,081, 69.0%), and many of normally unmethylated or variably methylated CpGs were located in the open sea (165,209 of 347,496, 47.5%). &amp;lt;Conclusion&amp;gt; Tumor-specific methylation occurring at CpG islands, may simply be dependent on the distribution of normally unmethylated CpGs. This finding may help us target epigenetically silenced tumor suppressor genes. Citation Format: Takafumi Nishimura, Yukiko Mori, Naoshi Nishida. Landscape of DNA methylation status of human hepatocellular carcinoma revealed by Human Methylation BeadChip 450K. [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 4249. doi:10.1158/1538-7445.AM2013-4249
AB0861 Relationship between disease duration and treatment response in patients with ankylosing spondylitis (AS):
Authors: X. Baraliakos, A. Koenig, H. Jones, A. Szumski, D. Collier, E. Bananis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A published report concluded AS patients with a disease duration (DisDur) &lt;10 yrs had a better response to anti-TNF treatment than those with DisDur &gt;10 yrs. [1] <h3>Objectives</h3> To investigate the relationship between DisDur, baseline (BL) characteristics, and treatment responses in patients with AS. <h3>Methods</h3> Data pooled from 4 clinical trials (placebo [PBO] or sulfasalazine [SSZ] versus etanercept [ETN]) were analyzed in 4 DisDur categories* and analyzed by age at diagnosis (≤40 or &gt;40 yrs). Analyses conducted using Chi-Square tests and ANCOVA models. <h3>Results</h3> 1281 patients analyzed; BL increasing age, decreasing age at diagnosis, and BL increasing BASFI significantly correlated with increasing DisDur categories (P&lt;0.05). A higher % of patients responded to ETN compared to SSZ and PBO in all outcome measures and all DisDur categories. At Wk 12, patients with shorter DisDur had a tendency toward better response with ETN for most dichotomous outcomes, but not SSZ or PBO. This trend was significant for ETN when analyzing patients ≤40 yrs old at diagnosis. No significant differences were observed across DisDur for Wk 12 continuous outcomes (ASDAS, BASDAI, BASFI, etc.). <h3>Conclusions</h3> Regardless of the time from diagnosis, and thus treatment initiation, ETN is more effective in patients with active AS compared to SSZ and PBO. Patients treated with ETN with DisDur ≤2 appeared to have the highest treatment response. Additional analyses are needed to further investigate the benefits of early treatment in AS. *DisDur categories analyzed as non-ordered, nominal using CMH test of general association and as ordered (trend) using CMH test of non-zero correlation. <h3>References</h3> Rudwaleit et al. Ann Rheum Dis 2004;63:665–670. <h3>Disclosure of Interest</h3> X. Baraliakos: None Declared, A. Koenig Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Jones Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Szumski Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Collier Shareholder of: Amgen Inc, Employee of: Amgen Inc, E. Bananis Shareholder of: Pfizer Inc, Employee of: Pfizer Inc
Freedom To Puff Goes Up in Smoke
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Freedom To Puff Goes Up in Smoke Get access Francis X. Mahaney, Jr Francis X. Mahaney, Jr Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 7, 7 April 1993, Pages 526–527, https://doi.org/10.1093/jnci/85.7.526 Published: 07 April 1993
ZOTAROLIMUS ELUTING STENT VERSUS EVEROLIMUS ELUTING STENT IN PERCUTANEOUS CORONARY INTERVENTION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Alok Saurav, Ajay Kumar Kaja, Manu Kaushik, Saurabh Aggarwal, Michael White, Mark Woodruff, Aryan Mooss, Michael DelCore
Journal: Journal of the American College of Cardiology (2015)
Extra 1000 medical school places by 2005
Authors: J. Warden
Journal: BMJ (1998)

An annual increase of almost 20% in the number of places at medical schools in Britain, to provide the NHS with the doctors it needs in the new century, was announced last week by the health secretary, Frank Dobson.

A phased expansion programme will admit an extra 20% of medical students every year. This meansthat the present intake of just …
RESIDUAL RISK AND ON-STATIN REDUCTIONS IN TRIGLYCERIDES, REMNANT CHOLESTEROL, AND VLDL LIPOPROTEINS: AN ANALYSIS FROM THE JUPITER TRIAL
Authors: Patrick R. Lawler, Akintunde O. Akinkuolie, Paulo Harada, Robert Glynn, Paul Ridker, Samia Mora
Journal: Journal of the American College of Cardiology (2016)
Serum Insulin Measurements in Children with Idiopathic Spontaneous Hypoglycemia and in Normal Infants, Children and Adults
Authors: Dennis Slone, J. Stuart Soeldner, Jurgen Steinke, John F. Crigler
Journal: New England Journal of Medicine (1966)

THE role of insulin in the pathogenesis of idiopathic spontaneous hypoglycemia is obscure. This paper reports levels of serum immunoreactive insulin and levels of serum insulin-like activity in patients with idiopathic spontaneous hypoglycemia as well as in normal infants, children and adults. Immunoreactive insulin refers to the portion of the circulating insulin that is able to combine with a specific anti-insulin antibody and is thus measurable by radioimmunoassay. It is generally agreed that whereas it may not account for the total circulating biologically active insulin, it is highly specific and reproducible. In contrast, insulin-like activity is measured by an in . . .