tbuckley/cabot-search huggingface dataset:
SP0130 How to Distinguish Normal from Abnormal Findings.
Authors: D. Kane
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Ultrasound is a highly sensitive tool in demonstrating high definition structural changes in soft tissues such as synovium, tendons and muscle and in bone and cartilage. Multiple studies have confirmed that ultrasound is more sensitive than clinical examination in the detection of synovial inflammation and joint effusion in both small and large joints and also in the detection of tendonitis, tenosynovitis and enthesitis. Ultrasound findings have better interobserver reproducibility than clinical examination findings and have been validated by correlation with MRI, CT scintigraphy and histological techniques. These finding have been reproduced in patients with both early and late disease and by researchers of different levels of expertise and using equipment of varying technological standards. However gray scale and power Doppler ultrasound abnormalities of joint and soft tissues have been noted in normal asymptomatic populations and in patients with disease who meet remission criteria, leading to concerns as to how to distinguish normal from abnormal ultrasound findings. This lecture reviews the OMERACT definitions of ultrasound pathology, how they were defined and how effective they are in defining abnormality in clinical practice. The relevance of abnormal ultrasound findings in asymptomatic and remission populations in terms of prognosis and outcome is examined. The effect of ageing on ultrasound findings in joints of normal subjects is presented. <h3>Disclosure of Interest</h3> None Declared
Abstract P2-07-02: Low-LET γ-Radiation Induced Protein S-Nitrosylation Regulates Tumor Invasion and Metastatic Transcriptional Response
Authors: J Veeraraghavan, M Natarajan, TS Herman, N. Aravindan
Journal: Cancer Research (2010)

Abstract Local-regional radiotherapy is one of the major therapeutic means in the management of breast cancer. However, besides the therapeutic effect, studies have shown that irradiation promotes malignant behavior of cancer cells both in vitro and in vivo by activating several tumor invasion and metastatic molecules. In this regard, ascertaining the molecular alterations contributing to this radiation-induced response is imperative. Accordingly, we investigated the role of radiation-induced NO-dependent nitrosylation in the transcription of invasion and metastatic genes in human breast adenocarcinoma cells. Human MCF-7 cells either mock irradiated, exposed to 2Gy (IR), treated with L-NAME (NOS inhibition) or BAY-11-7082 (phosphorylation inhibition) and then exposed to 2Gy, were examined for modulations in the transcriptional response of 93 tumor invasion and metastasis signaling genes. Cells treated with β-estradiol and mock-irradiated MDA-MB-231 cells were used as positive controls. Compared to mock irradiated cells, real time QPCR profiling revealed that 20 of 29 IR-induced genes including Birc3, Casp8, Ctgf, Ctsk, Htatip2, Kras, Map2k7, Mgat5, Mta2, Nme1, Nme2, Nme4, Pax5, Pten, Runx1, Serpinb5, Syk, Timp1, Timp2 and Timp4 were completely suppressed with NOS inhibition. Conversely, as opposed to NOS inhibition, IR-induced phosphorylation inhibition either failed to suppress or further induced the expression of these IR-induced genes. Furthermore, β-estradiol treatment revealed upregulation of 16 of these 20 IR-induced nitrosylation-dependent molecules and serves as a positive control for the study. More importantly, the highly metastatic, MDA-MB-231 cell line showed a robust induction in the expression of 15 of these 20 IR-induced nitrosylation-dependent genes. Taken together, these data imply that IR induces the expression of tumor invasion and metastatic genes and more importantly, may regulate the radiation-activated invasion and metastatic phenotype in breast adenocarcinoma cells. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-07-02.
Condensations of the Carcinogenesis Bioassay Technical Reports.
Authors: J Huff
Journal: Environmental Health Perspectives (1982)

Caprolactam (aminocaproic lactam, 2-oxohexamethylenimine, CAS No. 105-60-2), the monomer used in the production of nylon-6, was selected and testing initiated by the Carcinogenesis Testing Program, National Cancer Institute (now part of the National Institute of Environmental Health Sciences/National Toxicology Program) because nearly one billion pounds per year are produced, because of the widespread use in food packaging materials and clothing, and because no carcinogenicity stud- ies had been done (1).Nylon 6 resins/fibers are used extensively in carpets, knit fabrics, hosiery, thread, hairbrushes, replacement parts for automobiles and machinery, flotation devices, and food packaging.Highly solu- ble in water, caprolactam reportedly leaches from clothing made from polyamide fibers when soaked in simulated perspiration (2).Ferguson and Wheeler (3) reported irritation of the skin, eyes, nose, and throat in workers occupationally exposed to capro- lactam dust or vapor at concentrations ranging from 10 to 100 ppm. MethodsMale and female inbred Fischer 344 rats and male and female hybrid B6C3F1 mice, obtained from the Frederick Cancer Research Center, were used in this study.Control and treated groups contained 50 animals of each sex and species.For 103 consecu- tive weeks all groups received Ralston Purina Laboratory Chow.Treated groups were fed this
P745 SEQUENCING OF INITIAL AND RECURRENT HCV INFECTIONS IN HIV-INFECTED MEN WHO HAVE SEX WITH MEN (MSM)
Authors: M. Macartney, A. Ricciardi, A. Rodger, D. Webster, D. Karageorgopoulos, T. Fernandez, F. Ferro, J. Sasadeusz, S. Bhagani
Journal: Journal of Hepatology (2014)
Abstract 3921: Androgens stimulate phosphorylation of ERK and AKT in thyroid cancer cells
Authors: Melanie MacEwan, Ismatun Swati, Suqing Xie, Olena Ardacheva, Codrin Iacob, Edward Shin, Augustine Moscatello, Stimson Schantz, Raj K. Tiwari, Jan Geliebter
Journal: Cancer Research (2012)

Abstract Thyroid cancer is the most common endocrine malignancy with the papillary variety comprising ∼85% of thyroid neoplasms. While the greatest incidence of PTC is in women of childbearing age, the occurrence of PTC in men and postmenopausal women is associated with increased aggressiveness and poorer clinical outcomes. This gender disparity suggests that while the initiation of PTC is driven by estrogens, its progression may be mediated by androgens. Immunohistochemical analysis of PTC specimens from 5 male and 15 female patients indicated that all expressed androgen receptors (AR). AR mRNA was detected in equivalent amounts in three thyroid cell lines, but the PTC cell lines, BCPAP and TPC-1 expressed significantly more AR protein (4.6 fold and 3.9 fold, respectively) than the “normal” T-antigen transformed thyrocyte cell line, Nthy-ori-1. The treatment of the cell lines with the synthetic androgen, R1881 (10nM) resulted in increased phosphorylation of ERK and AKT in all three cell lines. Nthy expressed 2 fold more pERK when treated with R1881 whereas pAKT, which was previously undetected increased to significantly higher levels. R1881 addition increased pERK and pAKT 3 fold and 2 fold, respectively, in the male, RET/PTC cell line, TPC-1. pERK and pAKT were undetectable in the female, BRAFV600E cell line and were significantly induced by R1881.The known role of ERK and AKT in cellular proliferation, migration and invasion, and the activation of these molecules by androgens, may provide the mechanistic basis for the gender disparity in PTC aggressiveness and clinical outcome between young women and men/postmenopausal women. 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 3921. doi:1538-7445.AM2012-3921
EPIGENETIC TARGETING OF HEDGEHOG PATHWAY TRANSCRIPTIONAL OUTPUT
Authors: Y.-J. Cho, Y. Tang, S. Schubert, M. Willardson, P. Bandopadhayay, G. Bergthold, B. Nguyen, S. Masoud, N. Vue, B. Balansay, S. Gholamin, S. H. Cheshier, S. X. Atwood, R. J. Whitson, A. Lee, J. Y. Tang, J. Qi, R. Beroukhim, R. Wechsler-Reya, A. E. Oro, B. Link, J. E. Bradner, Y.-J. Cho
Journal: Neuro-Oncology (2014)

BACKGROUND: (blind field) METHODS: We used ligand and genetic activation of the Hedgehog pathway to study the effects of BET bromodomain inhibition on Hedgehog pathway transcriptional output. Furthermore, we studied the in vitro and in vivo efficacy of BET bromodomain inhibitors using tumor cells generated from genetically engineered mouse (GEM) and patient derived xenograft models of Hedgehog driven tumors, including a panel of tumors resistant to the current FDA-approved Smoothened antagonists. RESULTS: We show that knockdown of BRD4 or treatment with the BET bromodomain inhibitor, JQ1, dramatically inhibits transcription of GLI1, GLI2 and other Hedgehog target genes upon ligand-mediated or genetic activation of the Hedgehog pathway. We confirm the inhibitory effect of JQ1 occurs downstream of SMO and SUFU and verify by chromatin immunoprecipitation that BRD4 directly occupies the GLI1 and GLI2 promoters with a substantial decrease in the engagement of these genomic sites upon treatment with JQ1. We observe a corresponding downregulation of genes associated with medulloblastoma-specific GLI1 binding sites upon exposure to JQ1, confirming the direct regulation of GLI1 by BET bromodomain proteins. Finally, in patient- and GEM-derived cells of Hedgehog-driven cancer (basal cell carcinoma, medulloblastoma and atypical teratoid/rhabdoid tumor), we show that JQ1 decreases Hh pathway output and proliferation, even in cells resistant to Smoothened inhibitors. CONCLUSIONS: These results expand the role of BET bromodomain inhibitors to targeting Hedgehog-driven cancers and highlight a strategy that overcomes the limitation of Hedgehog pathway inhibitors currently in clinical use. SECONDARY CATEGORY: Pediatrics.
FRI0180 The musashi study: Comparison of subcutaneous tocilizumab monotherapy versus intravenous tocilizumab monotherapy: Results from a double-blind, parallel-group, comparative phase III non-inferiority study in japanese patients with rheumatoid arthritis:
Authors: A. Ogata
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Efficacy and safety of intravenous (IV) tocilizumab (TCZ) has been established in rheumatoid arthritis (RA). Subcutaneous (SC) TCZ injection has been developed as an additional important treatment option to enhance user-friendliness for patients and healthcare professionals. <h3>Objectives</h3> To compare the efficacy and safety of SC and IV TCZ monotherapy in Japanese RA patients. <h3>Methods</h3> Patients with RA who had responded inadequately to any synthetic or biologic DMARDs were randomized to receive SC TCZ 162 mg Q2W (TCZ-SC) or IV TCZ 8 mg/kg Q4W (TCZ-IV) without any DMARDs. The primary endpoint was to assess the non-inferiority of TCZ-SC to TCZ-IV by the ACR20 response rate at Week 24 in per protocol patients.The non-inferiority margin was predefined at 18%. <h3>Results</h3> A total of 346 patients received at least 1 dose of TCZ: 159/173 in TCZ-SC and 156/173 in TCZ-IV were eligible for the per protocol analysis. Baseline demographics were comparable between TCZ-SC and TCZ-IV: body weight (kg, mean ± SD), 53.8±8.7 vs. 54.4±10.1; proportion of patients who previously used TNF- α inhibitor, 19.5% vs. 23.1%; and RA duration (years, mean ± SD), 7.3±7.5 vs. 8.0±7.3. At Week 24, 79.2% (95% CI: 72.9, 85.5) of TCZ-SC patients and 88.5% (95% CI: 83.4, 93.5) of TCZ-IV patients had achieved an ACR20 response: the difference (95% CI) was -9.4% (-17.6, -1.2), confirming the non-inferiority of TCZ-SC to TCZ-IV. ACR50 and 70 response rates, change of DAS28 and rates of Boolean remission were also similar between TCZ-SC and TCZ-IV. The serum trough concentrations of TCZ in TCZ-SC and TCZ-IV were similar over time. In both, serum CRP was normalized while serum TCZ concentration remained above 1 μg/mL. Serum TCZ concentrations remained above 1 μg/mL at Week 24 in 85.9% of TCZ-SC patients and in 89.4% of TCZ-IV patients. The incidence of adverse events (AEs) over 24 weeks was 89.0% in TCZ-SC and 90.8% in TCZ-IV. There was no death in this study. Safety profiles were comparable between TCZ-SC and TCZ-IV: serious AEs, 7.5% vs. 5.8%; serious adverse drug reactions, 3.5% vs. 5.8%; serious infections, 1.2% vs. 2.9%; and injection site reactions (ISR), 12.1% vs. 5.2%. All ISRs were mild and manageable. Anti-TCZ antibodies were detected more frequently in MRA-SC than in MRA-IV. No case of serious ISR and anaphylactoid reaction were seen in patients with positive anti-TCZ antibodies. <h3>Conclusions</h3> TCZ-SC was non-inferior to TCZ-IV for ACR20 response rates. Other efficacy variables were also comparable between TCZ-SC and TCZ-IV. Serum trough concentration of TCZ in TCZ-SC was comparable to TCZ-IV. The clinical safety profile of TCZ-SC was consistent with that of TCZ-IV, and TCZ-SC was as well-tolerated as TCZ-IV. <h3>Disclosure of Interest</h3> A. Ogata Consultant for: Chugai Pharmaceutical CO., LTD
Localized Intracoronary Gamma-Radiation Therapy to Inhibit the Recurrence of Restenosis after Stenting
Authors: Martin B. Leon, Paul S. Teirstein, Jeffrey W. Moses, Prabhakar Tripuraneni, Alexandra J. Lansky, Shirish Jani, S. Chiu Wong, David Fish, Stephen Ellis, David R. Holmes, Dean Kerieakes, Richard E. Kuntz
Journal: New England Journal of Medicine (2001)

Although the frequency of restenosis after coronary angioplasty is reduced by stenting, when restenosis develops within a stent, the risk of subsequent restenosis is greater than 50 percent. We report on a multicenter, double-blind, randomized trial of intracoronary radiation therapy for the treatment of in-stent restenosis.
New Database Allows Researchers To Evaluate Cancer Care Costs
Authors: J. Ziegler
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article New Database Allows Researchers To Evaluate Cancer Care Costs 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 85, Issue 5, 3 March 1993, Pages 351–352, https://doi.org/10.1093/jnci/85.5.351 Published: 03 March 1993
Interferon Therapy for Condylomata Acuminata
Authors: Lawrence J. Eron, Franklin Judson, Steven Tucker, Steven Prawer, John Mills, Kevin Murphy, Mary Hickey, Mari Rogers, Steven Flannigan, Ngo Hien, Harry I. Katz, Sandy Goldman, Alan Gottlieb, Katherine Adams, Patricia Burton, Daniel Tanner, Eugene Taylor, Edwin Peets
Journal: New England Journal of Medicine (1986)

Current therapy for condylomata acuminata (genital warts) is not consistently effective. Therefore, we conducted a randomized, double-blind trial to compare interferon alpha-2b with placebo in the treatment of this disorder. Our rationale was that interferon has both antiproliferative and antiviral properties. The placebo or interferon (1 X 10(6) IU) was injected directly into one to three warts three times weekly for three weeks. The injections were well tolerated by both groups of patients. The side effects of fever, chills, myalgia, headache, fatigue, and leukopenia occurred more commonly in the interferon group than in the placebo group, but such effects rarely disrupted daily routines. Only 13 of 296 patients (4 percent) discontinued therapy because of side effects (11 in the interferon group and 2 in the placebo group). Twenty-six other patients were excluded from analysis because of a loss to follow-up or other deviations from protocol, thus leaving 257 patients in the final evaluation. At one week after the completion of therapy, interferon had produced a large and significantly greater reduction in mean wart area (a 62.4 percent decrease), as compared with placebo (a 1.2 percent increase in mean area) (P less than 0.001). At the conclusion of the study (13 weeks after the completion of therapy), the mean wart area was still decreased 39.9 percent below the initial size in the interferon group, whereas it had increased by 46 percent over base-line measurements in the placebo group (P less than 0.001). At the same time, all treated warts had completely cleared in 36 percent of the interferon recipients and in 17 percent of the placebo recipients (P less than 0.001), whereas treated warts progressed in 13 percent of the interferon recipients and in 50 percent of the placebo recipients (P less than 0.001). We conclude that injection of interferon alpha-2b directly into genital warts appears to be an effective and fairly well-tolerated form of therapy.
AB0278 The effect of rheumatoid factor titer on the response to TNF antagonists:
Authors: E. Salgado, J. Campos, V. Moreira-Navarrete, J. Mulero, F. Navarro, E. Perez-Pampin, L. Carmona, J.J. Gomez-Reino
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Different mechanisms have been proposed to explain the lack of response to TNF antagonists in Rheumatoid Arthritis (RA). These included the potential binding of Rheumatoid Factor (RF) to the Fc region of the drug, causing conformational changes or immune complex formation. (1,2) <h3>Objectives</h3> To examine whether rheumatoid factor (RF) is a predictor of response to TNF antagonists in rheumatoid arthritis (RA) <h3>Methods</h3> All patients with RA treated with TNF antagonists for at least 6 months at three different centers were included in this longitudinal study. Response at 24 weeks was assessed as EULAR good/moderate categories pooled together, and change in DAS28-ESR from baseline (DDAS28). The predictive value of baseline titer of IgM RF was analyzed. <h3>Results</h3> 374 patients were included; 271 (73%) had elevated IgM RF at baseline. At sixth month, 303 (81%) patients were responders. Baseline characteristics of patients and concomitant treatment of both groups are shown in table. There were no statistical differences in baseline IgM RF titer in responders and non-responders (Mann-Whitney, p&gt;0, 05). Also, baseline IgM RF status (positive/negative) and EULAR response were not related (Chi-squared, p&gt;0, 05). DDAS28-ESR did not correlate with IgM RF titer (rho -0, 02, p&gt;0,05) or RF status (t test, p&gt;0,05). A multivariate logistic regression model adjusted for glucocorticoids, methotrexate, and number of prior DMARDs, did not modify the association between RF titer and response. <h3>Conclusions</h3> This large observational study in RA fails to demonstrate association of baseline IgM RF and response to TNF antagonists. <h3>References</h3> Marotte H, Miossec P. Biomarkers for prediction of TNFα blockers response in rheumatoid arthritis. Joint Bone Spine 2010; 77(4):297-305. Bozsoky S, Franklin EC. The effects of chemical modifications of human gamma-globulins on their interaction with rheumatoid factors and antibodies. Arthritis Rheum 1966; 9(3):405-413. <h3>Disclosure of Interest</h3> None Declared
P3-13-09: Impact of Estrogen Receptor Negativity on Clinical Outcomes Following Accelerated Partial Breast Irradiation.
Authors: JB Wilkinson, A Baschnagel, C Shah, M Amin, L Nadeau, CK Mitchell, MF Wallace, PY Chen, IS Grills, AA Martinez, FA Vicini
Journal: Cancer Research (2011)

Abstract Purpose: To determine the impact of estrogen receptor (ER) negativity on clinical outcomes for patients treated with Accelerated Partial Breast Irradiation (APBI). Materials/Methods(s): We evaluated 506 consecutive patients treated with interstitial brachytherapy (n= 199), balloon-based brachytherapy (n=203), and 3D-CRT (n=104). ER negative (ERN) status was assigned using the traditional definition of an ER nuclear IHC stain &amp;lt; 10%, which corresponds to an Allred/NSABP staining score of &amp;lt; 2. 63 patients (12.5%) were ER negative and 443 (87.5%) were ER positive (ERP). Patient demographics and clinical outcomes (IBTR, RNF, DM, DFS, CSS, OS) were analyzed for each group. Results: The two groups had similar patient characteristics. Tumor sizes were slightly larger for the ERN group at 11.9mm vs. 10.7mm, although this was not statistically significant (p=0.14). No differences were seen in median age (63 vs. 64 years, p=0.36), rate of HER-2/neu overexpression (83% vs. 91%, p=0.11), or lymph node positivity (6% vs. 9%, p=0.55) between the ERN vs. ERP groups, respectively. There were an equal distribution of invasive ductal carcinoma (ERN n=55, 87%; ERP n=387, 87%) and DCIS (ERN n=8, 13%; ERP n=56, 13%) patients within each group. The use of chemotherapy (55% vs. 15%, p&amp;lt;0.001) and nuclear grade (71% vs. 12%, p&amp;lt;0.001) were higher in the ERN vs. ERP cohort. With a mean follow up of 6.1 years, the 5-year actuarial rates of ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the entire cohort were 1.8%, 0.6%, and 3.2%. Although this was not statistically significant, ERN patients appear to have an increased rate of local failure than patients with ERP histology (4.0% vs. 1.5%, p=0.13). Rates of RNF and DM were, however, significantly higher for the ERN group (RNF: 4.9% ERN vs. 0% ERP, p&amp;lt;0.001; DM: 12.1% ERN vs. 2.0% ERP, p&amp;lt;0.001). Although there was no difference in overall survival at six years (86% vs. 90%, p=0.67), we observed a shorter disease-free survival (86.4% vs. 96.5%, p= 0.01) and cause-specific survival (90% vs. 98%, p=0.01) for the ERN vs. ERP groups. Conclusion: The ER negative phenotype of early-stage breast cancer may have a decreased rate of locoregional control. We observed a higher rate of DM with reduced disease-free and cause-specific survival in ER negative cases, emphasizing the importance of systemic therapy and careful, long-term follow up for these patients. Prospective study of this histologic subtype with a larger cohort of patients is needed to substantiate these findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-09.