tbuckley/cabot-search huggingface dataset:
SAT0418 Prediction of rate of adjudication of radiological progression in rheumatoid arthritis (RA) randomized controlled trials (RCTS) in early and established disease:
Authors: V. Navarro-Compán, R. Landewé, H. Ahmad, C. Miller, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> For the evaluation of radiographic progression in RCTs, at least 2 readers should read all films in order to constrain measurement error. If differences in change scores between readers exceed a certain threshold, a third reader (adjudicator) can be used to obtain a more precise result. While the selection of a threshold that triggers this 3rd read is somewhat arbitrary (historically between 7 and 15 points), regulatory authorities suggest a cause for concern if 20% or more of the cases in a given clinical trial results in adjudication. <h3>Objectives</h3> To provide data on which percent of sets of radiographs need adjudication for a predetermined cut-off of difference in change score from baseline between two readers in RCTs in patients with early and established RA. <h3>Methods</h3> Fifteen datasets from radiographic trials in RA were scored by 13 readers as pairs according to the modified Sharp van der Heijde method (SHS). The reader was blinded to chronological sequence. The number of time points per study was 2 in 2 trials, 3 in 10 trials, and 4 in 3 trials. We calculated the theoretical adjudication rates if adjudication thresholds from 3 to 20 units were selected per study plus the weighted mean for all studies. We investigated the influence of the number of time points within the same session, the length of the interval, and mean disease duration (early (≤3 years) versus established RA) on the adjudication rates. Statistical analysis was performed using SPSS software version 18.0. <h3>Results</h3> 20.098 time points from 7.643 patients were included in the analysis. Median (range) sample size of the studies was 517 (103-901) patients, and the number of time points within one reading session was 2 for 1172 patients, 3 for 5296 patients and 4 for 1175 patients. Median (IQR) baseline radiological damage- and progression scores were 32 (18-48) and 1.05 (0.5-2.0) respectively. The percentage of adjudicated cases was inversely related to the threshold. The higher the number of time points within the same reading session, and the longer the time interval, the higher the adjudication rate. The adjudication rate was also higher in RCTs with early vs established RA, especially at lower thresholds. In all cases, the adjudication rate remained below 19%, even with a very conservative threshold selection of 3 units. <h3>Conclusions</h3> With trained and experienced readers, the adjudication rate in RCTs with patients with RA is low even with very conservative adjudication thresholds, which adds to the validity of the SHS scoring method as a precise and reliable outcome measure in RA. The adjudication rate is higher in RCTs with early- vs established RA. <h3>Disclosure of Interest</h3> None Declared
Abstract 4983: Galectin-3 regulates p21 expression through negatively regulating its degradation
Authors: Yi Wang, Pratima Nangia-Makker, Avraham Raz
Journal: Cancer Research (2010)

Abstract Galectin-3 (Gal-3), a carbohydrate-binding protein, has been demonstrated to be involved in multiple biological events such as cell adhesion, cell migration, cell proliferation, apoptosis and so on. p21, originally described as a inhibitor of cyclin-dependent kinases (CDK), has been shown to have anti-apoptotic activity as well as regulation of cell proliferation. Since both of these two proteins play important roles in cancer and some of their functions overlap, we assumed that there may be some relationship between Gal-3 and p21. Here, we first reported that Gal-3 positively regulates p21 expression in cancer cells, and this effect works at protein degradation level. Over-expression of Gal-3 in Gal-3 null human prostate cancer cell line LNCap and breast cancer cell line BT549 inhibited p21 degradation. Moreover, Gal-3 knockdown in Gal-3 expressing prostate cancer cell line DU145 potentiated p21 degradation, suggesting that Gal-3 negatively regulates p21 degradation in cancer cells. Furthermore, our data showed that Gal-3 negatively regulated proteasomal turnover of p21 in an ubiquitin-dependent way. In this study, we also showed for the first time the direct interaction between Gal-3 and p21. This study suggested that p21 may serve as the downstream molecule of Gal-3 signal transduction pathway to mediate some of Gal-3 functions, and it helps to understand further the mechanisms for Gal-3 functions. 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 4983.
Abstract 4370: Network-based signatures for drug repositioning and combination for the breast tumor initiating cells
Authors: Guangxu Jin, Hong Zhao, Yang Cong, Changhe Fu, Jenny Chang, Michael Lewis, Stephen Wong
Journal: Cancer Research (2011)

Abstract Understanding the signaling mechanisms of breast tumor initiating cells (TIC) is important to design efficient therapeutic and management strategies of breast cancer. We present a network-based signature and a comprehensive signaling map for identification of candidates of drug repositioning and combinations for breast TIC. The network-based signature is based on an extended concept of network motifs, known as cancer-signaling bridges (CSBs), which can be used to expand the cancer drug-targets of known signaling pathways. We use the profiles of TIC derived from CD44+/CD24-/low breast cancer cells and mammospheres (MS) cells to establish network-based signatures. Facilitated by the signaling pathways that are highly connected with CSBs, e.g., MAPK, NOTCH, ECM-receptor, Jak-STAT, and Wnt, we first identify the high-confidence signaling paths automatically chosen out of CSBs by two scoring systems, namely, Differential Expression Score (DES) and Signaling Pathway Score (SPS). The high-confidence signaling paths are used to build the network-based signature that characterizes the breast TIC. The network-based signature for CD44+/CD24-/low cells is composed by 140 proteins and 132 protein-protein interactions and that for mammospheres contains 153 proteins and 119 protein-protein interactions. The FDA-approved drugs whose targets are included in the network-based signatures are repositioned to breast TIC as the candidates for the repositioning. Furthermore, we curate a comprehensive signaling map for breast TIC by using the available signaling transductions in BioCarta, KEGG, and IPA and include seven signaling pathways, PI3K/AKT, JAK/STAT, Notch, HH, Wnt, P53, and ECM. The signaling map enables us to further refine the repositioning candidates and eventually propose combination candidates by using the cross-talks of signaling pathways in the map. Using this mapping approach, the drugs targeting on TNF, KDR, and IKBKB, such as sunitinib, Arsenic trioxide, and Atorvastatin, are repositioned for treating breast TIC, while the crosstalks between pathways such as Notch+hedgehog and Hedgehog+wnt+PI3K are used to identify drug combination candidates from the target combinations, TNF+KDR, and TNF+IKBKB. Acknowledgements: This research is partially funded by NIH ICBP U54CA149169. The authors would also appreciate the discussion and advice of Jeff Rosen and David Tweardy from Baylor College of Medicine during the generation of comprehensive signaling map for breast TICs. Guangxu Jin and Hong Zhao contribute to this work equally. 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 4370. doi:10.1158/1538-7445.AM2011-4370
1085 PEG-INTERFERON AND RIBAVIRIN IN HCV-RELATED CIRRHOTIC PATIENTS WITH PROFOUND THROMBOCYTOPENIA
Authors: A. Andriulli, A. Iacobellis, C. Iannacone, G. Angarano, A. Adinolfi, M. Persico, A. Mangia, G. Fattovich, F. Capra, M. Rizzetto, C. Golotta
Journal: Journal of Hepatology (2012)
Abstract 289: Inhibition of Trk receptor leads to mesenchymal-epithelial transition in human hepatocellular carcinoma cell lines.
Authors: Mitsuhiko Abe, Hironori Koga, Takafumi Yoshida, Hiroshi Masuda, Masahiro Sakata, Yu Ikezono, Toru Nakamura, Eitaro Taniguchi, Takumi Kawaguchi, Hirohisa Yano, Takuji Torimura, Michio Sata
Journal: Cancer Research (2013)

Abstract Sorafenib, the first molecular targeted agent for HCC, has been shown to be clinically effective in global clinical trials. Although overall survival of HCC patients has been extended by a few months, these results are not satisfactory. Clinical studies involving other molecular targeted therapies and combination therapies are ongoing, but no clearly effective therapy has yet emerged. While we were exploring new targets related to epithelial-mesenchymal transition (EMT), which is involved in metastasis and ivasion of advanced cancers, we found the EMT-inducing potential of the tropo-myosine-related kinase B (TrkB) receptor, whose ligands include brain-derived neurotrophic factor (BDNF). We observed by phase contrast microscopy that K252a, a Trk inhibitor, induced alterations in cell shape of several HCC cell lines (HAK-1A, HAK-1B, KYN-2, Huh7, and HLF). The morphological change was most obvious in HAK-1B cells, which have been proven to have mesenchymal features: the K252a-treated HAK-1B turned to polygonal epithelial-like cells. In Western blot analysis, the E-cadherin expression level was increased in the K252a-treated HAK-1B cells. Similar findings were demonstrated also in HAK-1A, which is a sister cell line of HAK-1B. The mechanistic basis for the “mesenchymal-epithelial transition (MET)” was down-regulation of E2A, an EMT-regulating transcriptional factor. Although the down-regulation of E2A was universally found in other cell lines, such as KYN-2, Huh7, and HLF, their expression levels of E-cadherin were not apparently increased. Our findings suggest that inhibition of TrkB signaling may be a new therapeutic approach for advanced HCC, since the inhibition may give rise to “MET” in aggressive tumors. In addition, the present data are impressive insofar as they imply a relationship between the liver and neurosystem. Citation Format: Mitsuhiko Abe, Hironori Koga, Takafumi Yoshida, Hiroshi Masuda, Masahiro Sakata, Yu Ikezono, Toru Nakamura, Eitaro Taniguchi, Takumi Kawaguchi, Hirohisa Yano, Takuji Torimura, Michio Sata. Inhibition of Trk receptor leads to mesenchymal-epithelial transition in human hepatocellular carcinoma cell lines. [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 289. doi:10.1158/1538-7445.AM2013-289
Treatment of Antibiotic-Resistant<i>Helicobacter pylori</i>Infection
Authors: Francesco Perri, Virginia Festa, Angelo Andriulli
Journal: New England Journal of Medicine (1998)

To the Editor: In 1996, several European gastroenterologists recommended that first-line treatment of Helicobacter pylori infection should consist of a proton-pump inhibitor combined with two of th...
Family Outbreaks of Infectious Hepatitis
Authors: Benjy F. Brooks, David Yi-Yung Hsia, Sydney S. Gellis
Journal: New England Journal of Medicine (1953)

ALTHOUGH the epidemiology of infectious hepatitis has been extensively studied in institutional outbreaks,1 2 3 4 5 6 7 the incidence and mode of transmission of the disease in families in civilian life has received scant attention. Pickles,8 Propert,9 Newman10 and Kunkel11 have reported outbreaks among members of single families and their immediate contacts. Ford,12 in a study involving 300 cases in a civilian epidemic, found that 17 per cent of the households had multiple cases of infectious hepatitis.Stokes and Neefe13 first demonstrated the value of gamma globulin prepared from pooled human plasma in the prevention or modification of infectious hepatitis in a group of . . .
Dopa Decarboxylase in Medullary Carcinoma of the Thyroid
Authors: Floyd L. Atkins, Michael A. Beaven, Harry R. Keiser
Journal: New England Journal of Medicine (1973)

Aromatic amino acid decarboxylase (dopa decarboxylase) is thought to be a constituent of the thyroid C-cell. Thyroid tumors from members of a family with a strong history of medullary thyroid carcinoma were found to have 30 to 90 times higher activity of dopa decarboxylase than in the surrounding normal thyroid tissue. The dopa decarboxylase activity in the tumor resembled that in pheochromocytoma in its behavior to various substrates and inhibitors. Other decarboxylase enzymes, histidine and ornithine decarboxylase, were not detectable in either tumor or normal thyroid. Tyrosine hydroxylase and tryptophan hydroxylase activities, although present, were not markedly elevated. Histaminase activity, which has previously been shown to be present in this tumor, was high in all samples of tumor. These results demonstrate that dopa decarboxylase may occur in a C-cell tumor as well as in thyroid C-cells. (N Engl J Med 289:545–548, 1973)
Bone Infarction Resulting from Parosteal Soft Tissue Angiosarcoma
Authors: SATORU YOSHIDA, KENJI FUJIMORI, MIKI TAKEDA, MITSUHARU TAMAKAWA, HIDENARI AKIBA, MASATO HAREYAMA
Journal: Clinical Nuclear Medicine (2002)

YOSHIDA, SATORU M.D.; FUJIMORI, KENJI M.D.; TAKEDA, MIKI M.D.; TAMAKAWA, MITSUHARU M.D.; AKIBA, HIDENARI M.D.; HAREYAMA, MASATO M.D. Author Information
Response of Thyrotropin-Secreting Pituitary Adenomas to a Long-Acting Somatostatin Analogue
Authors: R.J. Comi, N. Gesundheit, L. Murray, P. Gorden, B.D. Weintraub
Journal: New England Journal of Medicine (1987)

Thyrotropin-secreting pituitary adenomas are aggressive, invasive tumors that respond poorly to available surgical and medical treatments. Inappropriate release of thyrotropin by these tumors can result in hyperthyroidism. We treated five patients who had thyrotropin-secreting pituitary adenomas with the long-acting somatostatin analogue SMS 201-995, which was administered by subcutaneous injection in doses of 50 to 100 micrograms every 8 to 12 hours. Serum levels of thyrotropin were dramatically reduced by treatment in four of the five patients, and levels of another tumor marker, the alpha-subunit of thyrotropin, were reduced in all five. In two patients with hyperthyroidism due to production of excess thyrotropin by the tumor, treatment with the somatostatin analogue resulted in a sustained euthyroid state. One patient who was treated for more than 16 months had a persistent reduction in serum levels of thyrotropin and iodothyronines. We conclude that SMS 201-995 is an effective means of controlling hypersecretion of thyrotropin and the associated hyperthyroidism due to thyrotropin-secreting pituitary tumors.
Abstract B22: Oncogene activation of K-ras in resident myofibroblasts leads to development of spontaneous bronchioalveolar carcinoma in mice
Authors: Sylvia Vong, Hikaru Sugimoto, Yingqi Teng, Liang Xie, Rajan Dewar, Raghu Kalluri
Journal: Cancer Research (2009)

Abstract Stromal myofibroblasts, also known as carcinoma-associated fibroblasts, are recruited to neoplastic lesions and act as accomplices in promoting tumor progression. By secreting various growth factors, cytokines, extracellular matrix molecules, and matrix remodeling proteins, stromal myofibroblasts enhance tumor cell proliferation, angiogenesis, and tumor cell invasion. In contrast, the role of resident myofibroblasts in tumorigenesis is largely unknown. Our preliminary results strongly suggest that resident myofibroblasts may act as contributors to tumorigenesis. Selective expression of the oncogenic mutant of K-ras (K-rasG12D) in alpha smooth muscle actin-positive (αSMA+) stromal myofibroblasts is achieved by crossing αSMA-Cre+ transgenic mice to the LSL-KrasG12D f/+ mouse model (hereafter αSMAKrasG12D). While αSMAKrasG12D mice were phenotypically normal at birth, these mice developed spontaneous bronchioalveolar carcinoma by 5 weeks of age at 100% tumor penetrance. We speculate that genetic mutations in stromal myofibroblasts can disrupt stromal-epithelial homeostasis, driving hyperproliferation of epithelial cells. This fosters further accumulation of genetic mutations in the epithelial compartment, and thus, result in carcinogenesis. Citation Information: Cancer Res 2009;69(23 Suppl):B22.
Abstract 3100: Identifying novel chromosomal fusions out of RNAseq data from oropharyngeal cancers
Authors: Vivian W. Wang, Rebecca R. Laborde, Yan W. Asmann, Yang Li, Jian Ma, Bruce W. Eckloff, Nicole M. Tombers, Steven M. Olsen, Eric J. Moore, Kerry D. Olsen, David I. Smith
Journal: Cancer Research (2012)

Abstract Chromosome rearrangements that result in gene fusions have important roles in the initial steps of tumorigenesis especially in leukemias and lymphomas, but the biological and clinical impact of gene fusions in the common solid tumor has been less appreciated. We previously generated RNAseq data from 12 oropharyngeal tumors along with matched normal tissue from the same patients. We utilized and compared two bioinformatic pipelines, SnowShoes-FTD and FusionHunter to identify two novel fusion events involving of MGST3-ZMAT5 and MS4A7-DKFZp586P0123. These fusions were validated utilizing. Reverse transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing validated. In the first translocation the 5′ UTR of MGST3 was fused with exon 1 of ZMAT5, and in the second translocation the exon 2 of MS4A7 was fused with 3′ UTR of DKFZp586P0123. These precise fusions were not present in the matched normal tissue, however, they were only found in the single tumor in which they were identified. Given a growing and powerful set of high-throughput massively parallel sequencing technologies, the future for genome-wide analysis of chromosome rearrangement appears open in many directions. Ultimately, we hope that this integrative methodology will elucidate key aspects of tumor biology as well as generate novel targets for cancer diagnostics and therapy. 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 3100. doi:1538-7445.AM2012-3100
AB0806 Rituximab in clinical practice for the treatment of interstitial lung disease refractory to cyclophosphamide in patients with diffuse systemic sclerosis:
Authors: I. Castellví, C.P. Simeon, M. Sarmiento, A. Guillen, C. Diaz-Torné, C. Geli, J. Casademont, V. Fonollosa, J.M. de Llobet
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis or scleroderma (SSc) is a connective tissue disease which frequently presents lung affectation, being the principal cause of death in these patients. Currently, only cyclophosphamide (CyC) has shown efficiency to treat this complication. However, this efficiency is modest and not kept through the time. Several medicines have been tested for the treatment of this complication with controversial results. Rituximab (RTX) seems to show improvement in patients with SSc and Interstitial Lung Disease (ILD) refractory to others treatments, but there are not pivotal assays in this regard and the experience is limited. <h3>Objectives</h3> To study the evolution of Pulmonary Function Test (PFT) in patients with SSc affected by ILD refractory to usual treatment and have made at least one cycle of Rituximab. <h3>Methods</h3> Multicenter observational prospective study in patients with ILD-SSc was performed. These patients had one cycle of two Rituximab infusions for ILD and previously had realized CyC, azathioprine or mycophenolic acid with treatment failure. We evaluated the following data: gender, age, onset age of Raynaud’s phenomenon, age at diagnosis of SSc, age at diagnosis of ILD, ILD type, total dose of CYC, use of concomitants steroids, and other immunosuppressive agents. PFT outcome after each therapy and after 4 months of treatment with RTX was included. <h3>Results</h3> We collected the data of four patients who realized one complete cycle of treatment with RTX. Patients were women and presented diffuse cutaneous shape with antitopoisomerase I antibodies. The radiologic affectation was Non-Specific Interstitial Pneumonia (NSIP) in all cases. Patient’s characteristics are showed in table 1. The patient who presented the best response to RTX (Patient 4) had the highest dose of CyC accumulated previously. As a whole, patients presented a worsening of the predicted value of FVC and DLCO after treatment with CyC. Four months later of RTX infusion, we did not observe any worsening in the values of FVC beside of a trend to improve the values of DLCO. The best response in concern to respiratory function parameters was not related with taking concomitant or accumulated dose of other drugs different to CYC. <h3>Conclusions</h3> Rituximab could be an alternative to the treatment and stabilization for interstitial lung disease in patients with SSc, however experience remains limited. <h3>Disclosure of Interest</h3> None Declared
Complete biopsy resection of diminutive polyps
Authors: Yoon Jung, Jung Park, Hong Kim, Yong Cho, Chong Sohn, Woo Jeon, Byung Kim, Jin Sohn, Dong Park
Journal: Endoscopy (2013)

<b>Background and study aims:</b> Cold biopsy forceps polypectomy (CBP) is commonly used for the removal of diminutive polyps; however, evidence for the efficacy of CBP is lacking. The aim of this study was to evaluate the adequacy of resection of diminutive polyps and to identify predictors for complete resection using CBP. <b>Patients and methods:</b> This was a prospective study from a tertiary referral hospital in Korea. A total of 196 patients were screened, and 65 patients with diminutive polyps were enrolled. CBP was used to resect diminutive polyps until no polyp was visible by chromoendoscopy using indigo carmine spray. Each polyp base was then resected using endoscopic mucosal resection (EMR) with a 1 – 3-mm free margin. CBP and EMR specimens were sent to the histopathology department for the evaluation of the completeness of the resection. Cross sections of the EMR specimens made at 1-mm intervals were examined by a pathologist. <b>Results: </b>A total of 86 diminutive polyps were available for assessment. Overall, 90.7 % (78/86) of the diminutive polyps were completely resected using CBP (95%CI 84.6 – 96.8 %). The complete resection rate for all diminutive adenomas was 92.3 % (60/65; 95%CI 85.8 – 98.8 %) and for 1 – 3-mm adenomas 100 % (95%CI 81.5 – 100 %). Polyp size, histology, and location, and number of biopsies were not different between the complete and incomplete resection groups. <b>Conclusions: </b>In this small study approximately 90 % of all diminutive polyps and 100 % of 1 – 3-mm adenomatous polyps were completely resected using CBP and chromoendoscopy. CBP appears to be adequate for the resection of the majority of diminutive polyps, especially small sized adenomas (≤ 3 mm) if no residual tissue is visible by chromoendoscopy.