tbuckley/cabot-search huggingface dataset:
OP0289 A Prospective, Randomized, Open-Label, Assessor-Blind, Multicenter Study of Efficacy and Safety of Combined Treatment of Methotrexate + Glucocorticoids versus Glucocorticoids Alone in Patients with Polymyositis and Dermatomyositis (Prometheus Trial)
Authors: J. Tomasova Studynkova, H. Mann, K. Jarosova, S. Blumhardt, B. Maurer, M. Dastmalchi, K. Danko, K. Świerkocka, M. Olesinska, O. Distler, I.E. Lundberg, J. Vencovsky
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Polymyositis (PM) and dermatomyositis (DM) are usually treated with glucocorticoids (GC) and immunosuppressive drugs. Controlled trials are scarce and include low numbers of patients. Early addition of methotrexate (MTX) to GC is often used in clinical practice; however evidence of the benefit for this strategy is lacking. <h3>Objectives</h3> The aim of the trial was to assess the efficacy and safety of the combination therapy with MTX as compared to GC treatment only from the early phases of PM and DM. <h3>Methods</h3> Patients naïve to methotrexate were randomized into 2 groups treated with GC alone (group A) or with added MTX (group B). This was an open label study with the efficacy assessor being unaware of the treatment assignment. Duration of treatment was 48 weeks with monthly assessments. Primary endpoint was the total dose of GC in mg/kg body weight administered between baseline and the end of treatment in the two groups. GC were initially given at 1 mg/kg and tapered according to a pre-defined scheme if definition of improvement (DOI, IMACS) was achieved. Maximal duration of previous GC treatment was 8 weeks. Maximum dose of MTX was 20 mg/week. Secondary endpoints were individual disease activity core set parameters, muscle endurance, functional disability and safety. <h3>Results</h3> Five centers enrolled a total of 31 patients (17 PM, 14 DM). 16 patients were randomized in group A, 15 into group B. Groups A and B showed similar baseline characteristics. There were 4 dropouts during the study (3 in A, 1 in B). 85% (group A) and 86% (group B) of patients fulfilled DOI at week 48. There was no significant difference in the total prednisone dose (124±16 mg/kg in group A vs. 135±14 mg/kg in group B, p=0.6). None of the secondary efficacy parameters differed significantly between the two groups at the end of the study. There were 92 reported adverse events (AE). The overall number of AE in the 2 groups was similar. AE related to GC use were more frequent in the group A (5 cases) than in the group B (2 cases). <h3>Conclusions</h3> Patients with PM and DM do not significantly benefit from upfront methotrexate addition to GC during one year treatment, when the two strategies are commenced in the early stages of the disease. <h3>Acknowledgements</h3> Supported by EULAR and by Institutional Project No. 00023728. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3886
Abstract 3979: Identification of microRNA 885-5p as a novel regulator of tumor metastasis in colorectal cancer
Authors: CSC Lam
Journal: Cancer Research (2011)

Abstract Introduction: MicroRNAs (miRNAs) are a class of small non-coding RNAs that play a crucial role in cellular proliferation, differentiation and apoptosis by regulating gene expression. They are involved in the regulation of human diseases as well as colorectal cancer (CRC). CRC is the third most common cancer in the world and second leading cause of cancer death in the Hong Kong. Liver is the most common site of distant metastasis with poor prognosis for CRC patients. Recent evidences suggested that miRNAs affect the cell invasiveness of various cancers and regulate key steps in metastatic cascade. Moreover, studies also demonstrated that miRNAs play critical roles in the regulation of drug resistance. The study of miRNAs mechanism in liver metastasis may provide some new strategies for cancer treatment. Method: Microarrays were used for screening the expression differences of miRNAs between normal colon, CRC and liver metastasis. Lentiviral transduced colon cell lines were sorted with flow cytometer high-speed sorter by green fluorescent protein signal. Functional assay such as wound healing and invasion chamber were used to study the metastatic property (migration and invasion) in vitro. GeneChip expression was used to study the mRNA expression differences between gain-of-function and control. Orthotopic implantation of mi-885-5p-expressing CRC cells into the cecal wall of nude mice was performed to investigate their tumorigenic and metastatic capacity in vivo. Results: We quantified the expression levels of miRNAs in 14 liver metastasis samples and 12 colorectal cancer tissues, and identified hsa-miR-885-5p whose expression levels were significantly up-regulated in liver metastasis samples compared with the CRC samples. Over-expressed miR-885-5p cell line showed more invasive and migratory when comparing with control. 67% of the mice developed liver metastasis with orthotopic implantation of a CRC cell line overexpressing miR-885-5p, as compared with 33% of metastatic incidence in mice injected with the vector-expressing CRC cell line. GeneChip array showed that VCAM1 may be one of a possible target of miR-885-5p, which was comparable with the online database. Conclusion: We conclude that over expression of miR-885-5p is observed in liver metastasis has an important role in regulating the metastatic capacity of CRC cells vitro and in vivo. 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 3979. doi:10.1158/1538-7445.AM2011-3979
THU0384 Juxtaarticular Osteoporosis Exists in the Wrist Joint from the Early Stage of Rheumatoid Arthritis
Authors: H. Ito, M. Furu, M. Hashimoto, T. Fujii, N. Yamakawa, C. Terao, T. Mimori
Journal: Annals of the Rheumatic Diseases (2013)

Childhood tuberculosis (TB) poses a high risk for morbidity and death. This study describes the characteristics of childhood TB in Israel and examines treatment outcomes. Data sources were the National TB Registry and the National Civil Census. Between 1999 and 2010, 416 children (aged &lt;18 years) had TB, averaging 1.5 per 100 000 children (range 0.6–3.2), demonstrating a declining trend. The average proportion of all TB cases reported annually that were in children was 8.4% (range 5.4–11.8%). Most (n=320, 79%) of the childhood TB cases were pulmonary. TB rates were highest for the 0–4-year age group and lowest for the 10–14-year age group. Of all childhood TB cases, 236 (56.7%) were born in countries with high prevalence of TB: 214 were Israeli citizens who were Ethiopian-born and 22 were non-Israeli citizens. The overall childhood TB incidence in 2010 was 1.05 cases per 100 000 children. The incidence of TB for Israeli-born children, children whose parents were Ethiopian-born and children of migrant workers was 0.55 per 100 000, 7.5 per 100 000 and 50–100 per 100 000, respectively. Cultures were taken from 60% of all childhood TB cases. Most children (97.8%) achieved treatment success, while three children (0.7%) died. Overall, rates of childhood TB rates in Israel are decreasing. However, children of parents born in countries with a high prevalence of TB are still at high risk of developing TB. Bacteriological confirmation should be encouraged to improve control of childhood TB.
P878 MULTIVARIATE ANALYSIS OF FACTORS INFLUENCING SUSTAINED VIROLOGICAL RESPONSE RATE OF PROTEASE INHIBITOR-BASED TREATMENT FOR RECURRENT HCV GENOTYPE 1 AFTER LIVER TRANSPLANTATION: MULTICENTER EXPERIENCE
Authors: S. Pungpapong, B. Aqel, M. Charlton, H. Vargas, A. Keaveny
Journal: Journal of Hepatology (2014)
Abstract 4978: The C/EBPbeta isoform, liver-enriched inhibitory protein (LIP) induces cell death in breast cancer cell lines
Authors: Maria M. Abreu, Linda Sealy
Journal: Cancer Research (2012)

Abstract C/EBPbeta is a member of a family of basic-leucine zipper transcription factors. It has been shown to be a key regulator of growth and differentiation in the mammary gland. There are three different protein isoforms of C/EBPbeta. C/EBPbeta-1 and -2 are transactivators, and differ by just 23 N-terminal amino acids present in beta-1 only. C/EBPbeta-3 (LIP) lacks the transactivation domain and represses transcription. Here, we report that LIP expression stimulates autophagy and induces cell death in breast cancer cell lines. Overexpression of LIP is incompatible with cell growth and when cell cycle analysis was performed in the LIP-MDA-MB-231 breast cancer cell line, a DNA profile of cells undergoing apoptosis was not observed. Instead, LIP expressing cells appeared to have large autophagic vesicles when examined via electron microscopy. Autophagy is an evolutionarily conserved cellular process responsible for self-cannabalization through a lysosomal degradation pathway. Autophagy was further assessed in LIP expressing and control breast cancer cells by monitoring the development of acidic vesicular organelles and conversion of LC3 from the cytoplasmic form to the autophagosome form. LIP expression leads to an increase in acidic vesicles. In addition, activation of LC3 was detected in LIP expressing cells by immunoblot analysis and immunofluorescence studies. Interestingly, we find that LIP expression not only leads to massive and rapid cell death in the MDA-MB-468 breast cancer cell line, but cell cycle profiling reveals a dramatic increase in DNA content in LIP expressing cells. We present data that the induction of autophagy appears to accompany or possibly follow the engulfment of neighboring cells by the LIP expressing cells. Recently, there have been reports of different cell death processes that occur due to cell internalization. LIP overexpression may be one important factor that is driving cell engulfment resulting in cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4978. doi:1538-7445.AM2012-4978
Interactions among Drugs for HIV and Opportunistic Infections
Authors: Stephen C. Piscitelli, Keith D. Gallicano
Journal: New England Journal of Medicine (2001)

Drug interactions are an important factor in the treatment of patients with human immunodeficiency virus (HIV) infection. The complexity of current drug regimens for such patients requires that clinicians recognize and manage drug interactions. Antiretroviral drug regimens typically consist of three or four antiretroviral drugs but may include even more. In addition, patients may receive other drugs for supportive care, treatment of opportunistic infections, and immunomodulation, as well as alternative drugs obtained from health care providers other than their primary provider. Drug interactions are often unavoidable in HIV-infected patients because of the drug classes involved and the number of drugs . . .
Impaired Glycosylation Due To Autosomal Recessive PGM3 Mutations Results In Atopy, Immune Deficiency, Autoimmunity, and Neurocognitive Impairment
Authors: Joshua D. Milner, Jonathan J. Lyons, Yu Zhang, Xiaomin Yu, Shrimati Datta, Ian T. Lamborn, Matthew R. Biancalana, Lynne A. Wolfe, Thomas DiMaggio, Helen F. Matthews, Sarah M. Kranick, Kelly D. Stone, Steven M. Holland, Daniel S. Reich, Jason D. Hughes, Huseyin Mehmet, Joshua McElwee, Hudson H. Freeze, Alexandra F.F. Freeman, Helen C. Su
Journal: Journal of Allergy and Clinical Immunology (2014)
p53 Tumor Suppressor Gene Status and the Degree of Genomic Instability in Sporadic Colorectal Cancers
Authors: M. S. Kahlenberg, D. L. Stoler, M. Basik, N. J. Petrelli, M. Rodriguez-Bigas, G. R. Anderson
Journal: JNCI Journal of the National Cancer Institute (1996)

Genomic instability reflects the propensity and the susceptibility of the genome to acquire multiple alterations and, in turn, is believed to be a driving force behind multistep carcinogenesis. Although the molecular basis of genomic instability in sporadic colorectal cancers remains largely a mystery, mutation of the p53 tumor suppressor gene (also known as TP53) has been proposed to play an integral role in this process. However, a dilemma exists in that p53 mutation appears to be a late event in the progression of sporadic colorectal tumors, whereas genomic instability, serving as a facilitator of tumor progression, is envisioned as occurring early in this process. We evaluated the relationship between p53 mutation and the major form of genomic instability in sporadic colorectal tumors, namely, that involving DNA breakage, which leads to chromosomal translocations, insertions, deletions, and gene amplification. Fifty-eight sporadic colorectal tumors that had been previously evaluated for genomic instability were analyzed for p53 mutations. These tumors were from consecutively diagnosed patients. Genomic instability was quantified by use of inter-simple sequence repeat polymerase chain reaction analysis that employed (CA) 8 RG and (CA) 8 RY primers (R = purine [A or G]; Y = pyrimidine [C or T]); a genomic instability index (a measure of the number of alterations in tumor DNA in comparison with normal DNA, expressed as a percent) was calculated for each tumor. Mutation of the p53 gene in exons 5–9 was determined by use of single-strand conformational polymorphism-polymerase chain reaction analysis and DNA sequencing. Chi-squared analysis was used to determine the statistical significance of differences between groups of tumors. Reported P values are two-sided. p53 mutations were identified in 29 (50%) of the 58 tumors. The median genomic instability index value was 3.3%. Nineteen (65.5%) of the 29 tumors with p53 mutations had genomic instability indices that were less than the median value (range, 0%–2.6%); the remaining 10 (34.5%) tumors had genomic instability indices that were greater than the median (range, 3.9%–13.0%). Eleven (37.9%) of the 29 tumors with wild-type p53 genes had genomic instability indices that were less than the median value (range, 0%–2.6%), whereas the remaining 18 tumors had genomic instability indices above the median (range, 3.9%–11.7%). There was a statistically significant association between a lesser degree of genomic instability and the presence of p53 mutations ( P = .032). Tumors with no or minimal evidence of genomic instability are more likely to harbor p53 mutations than tumors with evidence of substantial genomic instability. p53 mutations play an important role in the development of cancers but do not appear to initiate or promote genomic instability in sporadic colorectal tumors.
Adhesion Molecules — Blood Vessels and Blood Cells
Authors: Paul S. Frenette, Denisa D. Wagner
Journal: New England Journal of Medicine (1996)

Maintaining vascular integrity and defending against invasive pathogens require the rapid regulation of adhesive interactions among blood cells and between blood cells and the vessel wall. Control of these mechanisms depends on the activation of adhesion receptors that are already present on resting blood cells and endothelium, or the expression of new receptors on the cell surface. Some functional overlap of adhesion receptors and their ligands adds a measure of safety to the repair and defense systems, but defective adhesion can occur and cause tissue injury or disrupt homeostasis of the vascular system.The process that allows the extravasation of . . .
PMO-259 Predicting failure of medical management in IBD patients- data from the 3rd round UK IBD audit: Abstract PMO-259 Table 1
Authors: G Walker, R Greenwood, I Arnott, C Probert
Journal: Gut (2012)

<h3>Introduction</h3> The value of admission clinical parameters and therapies to predict inpatient treatment failure is poorly defined. We used data collected in the 3rd Round UK Inflammatory Bowel Disease (IBD) Audit to determine whether number of previous hospital admissions with IBD and outpatient drug therapy predicted surgery after a failure of medical treatment. <h3>Methods</h3> Retrospective patient data from 198 UK sites were collected using an online form with up to 40 patients per site. Inclusion criteria were age &gt;17 years, admission date from September 2010–August 2011 and a discharge diagnosis of IBD. Relevant ICD10 and OPCS codes were provided. Data items collected included number of admissions to hospital with IBD in the previous 2 years and outpatient drug therapy on admission. Our outcome was surgery due to treatment failure and a logistic regression model was fitted using both forward and backwards stepwise modelling to find independent predictors. <h3>Results</h3> There were two statistically valid models which could be used to predict surgery. In both models the number of admissions in the last 2 years was a statistically significant predictor of surgery. Two admissions doubled the risk (OR 1.97, 95% CI 1.17 to 3.32) and three or more admissions increased it further (OR 2.62, 95% CI 1.61 to 4.26). In one model the number of different drugs being taken (corticosteroids (CS), immunosuppressives (IS), anti-TNF (aTNF)) was a predictor and in the other the use of CS and the use of aTNF were both significant independent predictors instead of number of drugs. Other treatments were looked at but were not independent predictors. Taking one drug on admission was associated with a doubling of risk (OR 1.93 95% CI 1.15 to 3.24), two drugs trebled (OR 3.01 95% CI 1.78 to 5.10) and three or more quadrupled (OR 4.10 95% CI 2.08 to 8.05) the risk. Alternatively CS doubled the risk and aTNF trebled the risk with OR 1.73 and 2.96 respectively. <h3>Conclusion</h3> This data shows that the number of previous admissions to hospital can be used as an easy prognostic indicator to better inform patients of their risk of requiring surgery for a failure of medical management after admission to hospital. In addition there is relationship between the risk of surgery and taking CS and aTNF, this probably reflects disease severity, but might also be used to guide patient management. Further analysis is being carried out to find other predictors. <h3>Competing interests</h3> None declared.
Abstract 2605: Identification and development of NVP-HSP990, a potent and orally active Hsp90 inhibitor for cancer treatment
Authors: Zhenhai Gao, Timothy Machajewski, Daniel Menezes, Michael Rugaard Jensen, Karen Yu, Chantale Guy
Journal: Cancer Research (2011)

Abstract Hsp90 is recognized as a potential target for the treatment of cancer, due to its chaperone functions that are required for maintaining the stability and/or active conformation of signalling molecules essential for tumorigenesis. The development of small molecule Hsp90 inhibitors has become an extremely competitive field of research. Here for the first time we present biological and pharmacological properties of NVP-HSP990, a potent oral Hsp90 inhibitor discovered by Novartis. In vitro, NVP-HSP990 potently inhibits all 4 isoforms of Hsp90 (Hsp90α, Hsp90β, TRAP-1 and GRP94) and has no major activities in a safety pharmacology panel of kinases, receptors and enzymes evaluated. NVP-HSP990 demonstrates broad-spectrum anti-tumor activities in tumor cell lines (IC 50s ranging from 4-35 nM) and primary patient samples (mean IC50 =49 nM). In vivo, NVP-HSP990 is highly bioavailable across species and a single oral administration of 15 mg/kg induces sustained target inhibition up to 7 days as indicated by downregulation of client protein (c-Met) and upregulation of Hsp70 in a cMet overexpressing gastric GTL16 xenograft tumor model. Weekly administration of NVP-HSP990 was efficacious in a broad range of mouse and rat human tumor xenograft models driven by well defined oncogenic Hsp90 client proteins. In summary, NVP-HSP990 represents a novel class of oral Hsp90 inhibitors with unique and superior pharmacological and drug-like properties. NVP-HSP990 is currently being evaluated in Phase I clinical trial in advanced solid tumors. In addition, we will present multiple secreted biomarkers for Hsp90 that were identified through a novel in-silico data mining approach. Several of these biomarkers have been validated both in vitro and in vivo, and have the potential to be utilized as clinical pharmaco-dynamic markers in the development of Hsp90 inhibitors. 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 2605. doi:10.1158/1538-7445.AM2011-2605
Classic Biphasic Pulmonary Blastoma Demonstrated by 18F-FDG PET/CT
Authors: Khun Visith Keu, Gerald J. Berry, Andrew Quon
Journal: Clinical Nuclear Medicine (2013)

A 75-year-old nonsmoker woman was referred for the evaluation of a nonsecretory left adrenal lesion. An abdominal contrast-enhanced CT showed an incidental left lower lobe mass, which was confirmed on a chest contrast-enhanced CT. A 18F-FDG PET/CT showed a hypermetabolic tumor without nodal or distant metastasis. She underwent a lobectomy, and the final pathology reported a classic biphasic pulmonary blastoma, which is an uncommon histological form of malignant lung neoplasm. This case highlighted the glucose avidity of this rare and aggressive cancer.
Suppression of bone resorption from odanacatib, a cathepsin K inhibitor, in women with bone metastases from breast cancer, and the effect of concomitant anti-neoplastic treatment on efficacy: a 4-week, double-blind, randomized controlled trial.
Authors: AB Jensen, C Wynne, G Ramirez, L Antje, O Nina, A Mehta, H Wang, W He, Y Song, Y Berd, A Lombardi
Journal: Cancer Research (2009)

Abstract Abstract #1157 Background: In breast cancer patients with metastatic bone disease (MBD), an osteolytic process releases factors that sustain tumor cell survival and proliferation. Cathepsin (Cat) K inhibition suppresses osteolysis in preclinical models of MBD. This study assessed the efficacy and safety of odanacatib, a potent and reversible selective Cat K inhibitor, in reducing markers of bone resorption in women with breast cancer and MBD depending on concomitant anti-neoplastic treatment.&amp;#x2028; Materials and Methods: Women with breast cancer and MBD were randomized (double-blind) to oral odanacatib 5 mg daily for 4 weeks or IV zoledronic acid (ZA) 4 mg given once at study initiation. Bone resorption was assessed by urinary N-telopeptide of type I collagen corrected for creatinine (uNTx). A post-hoc analysis of the influence of concomitant therapy (chemotherapy vs hormone therapy) on study medication effects on uNTx was also conducted. Adverse events (AE) were monitored throughout the 4-week study and up to 14 days after last dose.&amp;#x2028; Results: 43 patients (mean age 60 yrs) received odanacatib (n=29) or ZA (n=14); 40 patients completed all 4 weeks of treatment. 12 (41%) and 17 (59%) patients on odanacatib and 6 (46%) and 7 (54%) patients on ZA received chemotherapy or hormone therapy, respectively; one patient was on both co-therapies and one patient on ZA was not on concomitant therapy. Results for the effect of study medication on uNTx as well as the effects of concomitant therapy on each treatment group are shown in the table; results for the full analysis set were similar. The most common reported AEs were nausea, vomiting, headache, and bone pain, and generally not attributed to study drug.&amp;#x2028; Conclusions: In women with breast cancer and MBD, the Cat K inhibitor, odanacatib, suppressed markers of bone resorption after 4 weeks of treatment. Mean uNTx was decreased in both treatment groups. The effect on biomarkers observed in this study was seen irrespective of concomitant anti-neoplastic treatment. Odanacatib was generally safe and well tolerated. These results suggest that Cat K inhibition is a potentially important, novel therapeutic approach for treating MBD.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1157.