tbuckley/cabot-search huggingface dataset:
Abstract 13849: Impact of Statin-Ezetimibe Combination on Coronary Atheroma Progression/Regression in Patients With and Without Prior Statin Therapy - Subanalysis of PRECISE-IVUS Trial
Authors: Kenichi Tsujita, Kenshi Yamanaga, Seigo Sugiyama, Hideki Shimomura, Takuro Yamashita, Kenji Sakamoto, Koichi Nakao, Sunao Nakamura, Masaharu Ishihara, Kunihiko Matsui, Nobuyasu Yamamoto, Shunichi Koide, Toshiyuki Matsumura, Kazuteru Fujimoto, Ryusuke Tsunoda, Yasuhiro Morikami, Koushi Matsuyama, Shuichi Oshima, Koichi Kaikita, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2015)

Introduction: IMPROVE-IT trial showed the clinical benefit of statin-ezetimibe (EZE) combination appeared to be pronounced in patients with prior statin therapy. On the other hand, the PRECISE-IVUS ( P laque RE gression with C holesterol absorption I nhibitor or S ynthesis inhibitor E valuated by I ntra V ascular U ltra S ound) trial was a prospective, randomized, controlled, multicenter study evaluating the effects of EZE addition to atorvastatin (atorva), compared with atorva monotherapy, on coronary atherosclerosis evaluated by IVUS and lipid profile. Hypothesis: We hypothesized that the antiatherosclerotic effect of atorva-EZE combination was pronounced in patients with statin pretreatment. Methods: 246 patients undergoing IVUS-guided percutaneous coronary intervention were randomized to EZE/atorva combination or atorva alone. The dosage of atorva was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol (LDL-C) below 70mg/dL. Serial volumetric IVUS was performed at baseline and 9–12 months follow-up to quantify the coronary plaque response in 202 patients. We compared the IVUS endpoints in all subjects, stratified by the presence of statin pretreatment. Results: The baseline LDL-C level (100.7±23.1mg/dL vs. 116.4±25.9mg/dL, p&lt;0.001) and lathosterol (55 [38 to 87])μg/100mg TC vs. 97 [57 to 149]μg/100mg TC, p&lt;0.001) was significantly lower, and campesterol/lathosterol ratio (3.9 [2.4 to 7.4] vs. 2.6 [1.5 to 4.1], p&lt;0.001) was significantly accelerated in patients with statin pretreatment. Contrary to the patients without statin pretreatment (-1.3 [-3.1 to -0.1]% vs. -0.9 [-2.3 to 0.9]%, p=0.12), the atorva-EZE combination showed the significantly stronger reduction in delta percent atheroma volume, compared with atorva alone, in patients with statin pretreatment (-1.8 [-3.6 to -0.3]% vs. -0.1 [-1.6 to 0.8]%, p=0.002). Conclusions: Compared to atorva alone, atorva-EZE combination demonstrated stronger regression effect in coronary atheroma volume especially in patients with statin pretreatment. Compensatory accelerated cholesterol absorption might be associated with reduced coronary plaque regression. Low-dose statin-EZE combination might be a promising option in statin-hyporesponder.
Abstract 3694: Role of the inflammatory response in pancreatic cancer treatment
Authors: Mary Jo Cantoria, Tomislav Dragovich, Emmanuelle Meuillet
Journal: Cancer Research (2012)

Abstract Pancreatic adenocarcinoma is an aggressive malignancy, often diagnosed late in the course of the disease, and very difficult to diagnose and treat. To date, systemic treatment for pancreatic cancer, either a single agent or combinations of agents, has shown only modest benefits; however, growing understanding of the molecular pathogenesis of pancreatic cancers, and the complex heterogeneous signals associated with them, may help to target these pathways specifically and improve patient outcome. There is evidence for a significant role of cyclooxygenase (COX)-2 and COX-2-generated prostaglandin (PG) E2 (PGE2) during pancreatic tumorigenesis. COX-2 has therefore become a potential chemotherapeutic target for pancreatic cancer. Clinical trials combining Gemcitabine and Celecoxib [1] or Gemcitabine+ Irinotecan and Celecoxib [2] have not shown a significant benefit from celecoxib but there were relatively few patients treated and they were not selected or stratified based on biomarkers. We have measured the levels of 4 cytokines, including Interleukin (IL)-6, IL-1α, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-α in patient blood samples at day 0, day 29 and day 50 following the combination Gemcitabine - Celecoxib treatment. For all samples analyzed and averaged, we show an increase in plasma TNF-α (by 1.37 fold) and IL-1α (by 2 fold) concomitantly with a dramatic increase in IFN-γ (by 7 fold on day 29, by 3 fold on day 50) and stable IL-6 using the Meso Scale Discovery multiplex platform. One patient had a stable profile of all 4 cytokines and was shown to have partial response to the treatment. All others exhibited a strong variation in their cytokines during the treatment and did exhibit progression of the disease. Although the number of patients enrolled in the trial [1] was low, these results showed an interesting trend. These findings provide a basis for investigating further the inflammation-linked pathways along the COX2/mPGE-S1/EP4/IL-6 axis in pancreatic cancer cells and animal models of pancreatic cancers which will be subjected to the comparative treatment. [1]. Dragovich et al., Am. J. Clin. Oncol. 31:157-162 (2008) [2]. Lipton et al., J. Clin. Gastroenterol. 44:286-288 (2010) 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 3694. doi:1538-7445.AM2012-3694
Primary Hepatic Amyloidosis Well Delineated by Tc-99m DTPA Galactosyl HSA Liver SPECT
Authors: K Koizumi, S Monzawa, C Shindo, M Hosaka
Journal: Clinical Nuclear Medicine (1999)

Tc-99m GSA is a hepatic tracer that specifically binds to the asialoglycoprotein receptors on the membrane of hepatocytes. Decreased hepatic uptake indicates liver dysfunction. Heterogeneous uptake of Tc-99m GSA in the liver was observed in a patient with primary hepatic amyloidosis, although the hepatic uptake of Tc-99m HMDP was rather homogeneous. SPECT imaging showed that the distribution of decreased uptake was in an area in the liver analogous to that of a low-density area seen on CT scan. Tc-99m GSA SPECT might be useful to determine the spared area in the liver involved with amyloid deposition.
SPECT/CT of Osteitis Condensans Ilii
Authors: Filip Gemmel, Arwin van Vrijberghe de Coningh, James Collins, Paul Rijk
Journal: Clinical Nuclear Medicine (2010)

A 16-year-old, nonpregnant, healthy, and sportive teenager suffers from intermittent low back pain. Pelvic x-ray complemented by bone-SPECT/CT demonstrated an uncommon benign condition called osteitis condensans ilii. In the early phase, it is of paramount importance to distinguish osteitis condensans ilii from sacroiliitis or ankylosing spondylitis. This case report highlights the incremental value of performing one-stop shop hybrid SPECT/low-dose CT bone imaging in diagnosing and managing this rare benign skeletal condition.
OP0139 A distinct subset of CD19-negative plasma cells resides in the human bone marrow
Authors: H.E. Mei, I. Wirries, C. Giesecke, D. Frölich, M. Brisslert, S. Schmidt, R. Engelmann, C. Perka, A. Radbruch, T. Dörner
Journal: Annals of the Rheumatic Diseases (2013)

Background Plasma cells (PC) are the unique source of protective and autoreactive immunoglobulin. Mature PC are resting and have downregulated CD20, rendering them refractory to almost all conventional and modern antirheumatic therapies including rituximab. Consequently, the failure to eridacte autoantibody production by plasma cells appears as a therapeutical hurdle in patients with autoimmune diseases. We have identified two distinct subsets of plasma cells based on differing expression of CD19 in the human BM which are comparatively characterised here against the background of the development of anti-CD19 directed immunotherapies. Objectives To characterise CD19+ vs. CD19-negative PC subsets in normal human bone marrow. Methods BM samples from iliac crest, femural heads and sternum as well as blood, spleen and tonsil specimen were analyzed for CD38hi plasma cells by FACS and the expression of CD19, CD138, Ki-67, HLA-DR, CD95, CD28 and CD56 wa studied. Transcriptional analyses of sort-purified plasma cell subsets were performed on an Affymetrix platform. The antibodies expressed by individual plasma cells were characterized using Elispot, cytoplasmic Ig staining and single cell RT-PCR. Results CD19+ and CD19-negative plasma cells were readily detectable in all human BM samples irrespective of the anatomic site analyzed and co-expressed CD138. At average, 60-70% of the plasma cells expressed CD19 in the BM, while 85% were CD19+ in spleen and tonsils and 95-100% in the blood, respectively. Transcriptional and phenotypical analyses of CD19-negative BMPC suggest their advanced maturity, inasmuch they express CD56 and CD28 while HLA-DR, CD95 and Ki-67 are downregulated compared to CD19+ BMPC. CD19-negative BMPC were enriched for IgG-secreting cells which showed suprisingly low mutational load within their VH gene rearrangements. Treatment of RA patients with rituximab significantly reduced numbers of CD19+ BMPC but not CD19-negative BMPC. Conclusions Our data indicate an unexpected heterogeneity within the mature plasma cell compartment in the human bone marrow. Detailled characterisation according to CD19 expression suggests that CD19-negative plasma cells aquired a more mature differentiation state and represents a rather static population as compared to CD19+ BMPC. A potential anti-CD19 directed B cell depletion approach for therapy of autoimmunity will likely target many but not all plasma cells, while the relationship betwen CD19 expression by plasma cells and autoantibody production remains to be analysed in order to estimate targeting of autoantibody production. Our data provides new insight into the homeostasis of normal mature plasma cells which opens new perspectives for studies on plasma cells as sources of auto-antibodies in patients with autoimmune diseases. Disclosure of Interest None Declared
Genetic Contribution of GADD45A to Susceptibility to Sporadic and Non-BRCA1/2 Familial Breast Cancers: A Systemic Evaluation in Chinese Populations.
Authors: K. Yu, G. Di, Z. Shao
Journal: Cancer Research (2009)

Abstract GADD45A is a candidate breast cancer susceptibility gene because its product participates in DNA repair and it is a downstream gene of p53 and BRCA1, both of which are breast cancer susceptibility genes. The genetic contribution of GADD45A to sporadic and familial breast cancer is still ambiguous. We screened germline mutation of GADD45A in 185 non-BRCA1/2 familial breast cancer patients, but no deleterious mutation was found. Seven single-nucleotide-polymorphisms were identified in a sub-sample. Five common variants (minor allele frequency (MAF)&amp;gt;10%) were genotyped for association analyses to scrutinize the relationship between breast cancer and polymorphisms in GADD45A in two independent population sets. In the first case-control study, a comparison of genotype frequencies between sporadic breast cancer patients and controls indicated the CT/TT-genotypes of +1506C&amp;gt;T and CG/CC-genotypes of +3204G&amp;gt;C were associated with decreased breast cancer risk (adjusted odds ratio (OR), 0.77; 95% confidence interval (CI), 0.62-0.96; and adjusted OR, 0.71; 95%CI, 0.57-0.88, respectively) compared with their wild-type homozygotes. A common hyplotype CGTCC was also associated with reduced risk (P=1.0×10-4). In a second familial breast cancer patient-based case-control study, although +1506C&amp;gt;T and +3204G&amp;gt;C failed to be validated, the haplotype CGTCC showed a borderline significance. Notably, the combined P-values were robust for +3204G&amp;gt;C (P=3.1×10-4) and CGTCC (P=1.6×10-5). Moreover, CGTCC was correlated with a higher GADD45A expression in normal breast tissues. In conclusion, although germline mutation of GADD45A is not common in familial breast cancer patients, polymorphisms/haplotypes in GADD45A contribute to breast cancer risk, at least to sporadic breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5163.
AB0270 Outcomes after discontinuation of TNF blockers in rheumatoid arthritis
Authors: C.-B. Choi, S.-K. Cho, C.-N. Son, J.J. Kim, Y.-K. Sung, T.-H. Kim, J.-B. Jun, D.-H. Yoo, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although there have been reports of sustained remission, especially in early diseases, after discontinuation of anti-TNF agent after achieving remission, outcomes after discontinuation of anti-TNF agents are not well known. But in real practice there are always unexpected circumstances where anti-TNF agents are discontinued. <h3>Objectives</h3> We investigated the patients who had received anti-TNF agent for treatment of RA and then discontinued for reasons other than ineffectiveness to assess the outcome after discontinuation of anti-TNF agents. <h3>Methods</h3> Retrospective medical record review was conducted of 291 patients with RA treated with biologics from December 2000 to November 2009 at Hanyang University Hospital for Rheumatic Diseases to assess for flare after anti-TNF discontinuation. Flare was defined, in accordance with the OMERACT working definition of RA flare, as any worsening of disease activity leading to modification in therapy. <h3>Results</h3> Twenty-one patients were included in the analysis after excluding 110 patients who were being maintained on anti-TNF agents, 23 patients treated with biologics other than anti-TNF agents, 9 who had received anti-TNF agents for less than 3 months, and 128 patients who had discontinued for other reasons (88 after completion of clinical trials, 22 due to ineffectiveness, 18 due to lost to follow-up). Of the 21 patients, 17 patients (81%) had flared and 4 patients (19%) showed no flare. <h3>Conclusions</h3> Majority (81%) showed flare after discontinuation of anti-TNF agents within a median of 6 months in a cohort of RA patients. <h3>Disclosure of Interest</h3> None Declared
Abstract 2168: Molecular pathway analysis of esophageal squamous cell differentiation versus carcinoma formation
Authors: Wusheng Yan, Liang Zhu, Joanna Shih, Jaime Rodriguez-Canales, Jason Hipp, Audrey Player, Nan Hu, Alisa M. Goldstein, Philip R. Taylor, Michael R. Emmert-Buck, Heidi S. Erickson
Journal: Cancer Research (2010)

Abstract Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer and is characterized by high mortality. Our previous work analyzing candidate tumor associated genes in ESCC highlighted the important differences in mRNA expression between the normal esophageal and tumor epithelial compartments. However, to date there are limited studies examining expression changes that occur during esophageal squamous cell differentiation versus those associated with ESCC tumorigenesis. To address this issue, we microdissected the basal cell layer and differentiated cell layer from normal epithelium and compared these expression profiles with matched tumor samples in twelve patients using gene expression microarrays (Hu133A 2.0, Affymetrix, Inc.) and qRT-PCR for selected miRNAs. Genes and pathways of interest were determined using class comparison and pathway analyses. Pathway expression of BRCA1 in the DNA damage response pathway presented the most significant difference (P &amp;lt;0.00001) in normal differentiated cells compared to tumor differentiated cells, but no difference was present between normal basal cells and tumor peripheral cells. PDGF signaling was significant only in the normal basal vs. tumor comparison. Taken together, BRCA1 and PDGF expression suggest oncogenetic process differences in esophageal epithelial compartments. Basal cells presented with CCND1 and CDKN2A high expression and p53 low expression, implying that basal cells gene expression is closer to a pattern of tumorigenesis than that of differentiated cells. A typical “stem cell” pattern of CD44high/CD24low expression in normal basal cells vs. normal differentiated cells and tumor vs. normal comparisons indicated that the basal cell compartment may house progenitor or stem-like cells and tumor cells expression is indicative of this stem-like origin. Converse to our expectations, tumor peripheral vs. tumor center comparison revealed that the ESCC tumor clusters were essentially homogenous on the transcriptomic level. Overall, the preliminary results indicate that tumor profiles were closer to basal cells than differentiated cells, consistent with their rapid growth rate and less well differentiated morphology. Investigation of gene expression patterns in normal cell types and ESCC provides novel insight into the transcript profiles associated with normal development versus carcinogenesis. 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 2168.
A3.15 Reconstituted High Density Lipoprotein (rHDL) Modulates T Effector Cell Function in a Murine Model of Rheumatoid Arthritis
Authors: I Tiniakou, VI Zannis, D Boumpas, P Verginis, D Kardassis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> High density lipoprotein (HDL) has a variety of functions which confer protection from cardiovascular and other human diseases. Increased cardiovascular risk is observed in humans with autoimmune disorders such as rheumatoid arthritis (RA), which is associated with either low levels or dysfunctional HDL. Recent evidence suggests a role of HDL in modulating both innate and adaptive immune responses. We sought to investigate the role of rHDL during the development of an autoimmune response in the antigen-induced arthritis (AIA) mouse model. <h3>Materials and Methods</h3> C57BL/6 mice were subcutaneously immunised with ovalbumin (OVA) in complete Freund's adjuvant (CFA) and the inguinal lymph nodes (LN) were excised 9 days after the antigenic challenge. The LN cells were cultured in vitro in the presence of varying concentrations of reconstituted HDL (rHDL) in the presence or absence of OVA and OVA-specific immune responses were measured. To assess the effect of HDL on dendritic cell activation and maturation, mouse bone marrow was cultured with GM-CSF to generate dendritic cells (BM-DCs), which were collected, cultured and treated with LPS in the presence or absence of rHDL. <h3>Results</h3> OVA-primed LN cells secreted increased levels of IFN-γ and IL-17 that were significantly suppressed in the presence of rHDL in a dose-dependent manner. rHDL was also found to exert a suppressive effect on T cell proliferation as indicated by IL-2 measur- ement. Finally, rHDL-treated LPS-stimulated BM-DCs did not demonstrate any significant phenotypic differences as assessed by FACS analysis on CD86, CD40 and PDL-1 molecules as compared to control LPS-stimulated BM-DCs. <h3>Conclusions</h3> rHDL exerts a direct immunomodulatory function on T cells in vitro by suppressing their proliferation and the expression of inflammatory cytokines. Ongoing work is focused on the delineation of the mechanism involved in the rHDL-mediated suppression of the immune response both in vitro and in vivo<i>.</i> These data identify rHDL as an important player in the homeostatic regulation of the inflammatory response and a potential therapeutic target for chronic inflammatory diseases.
Abstract 1263: Induction of nonsteroidal anti-inflammatory drug-activated gene-1 (Nag-1) by NSAIDs: role of p75NTR
Authors: Shehla Wynne, Daniel Djakiew
Journal: Cancer Research (2010)

Abstract Epidemiologic studies have shown that patients with long term consumption of certain nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit a reduced incidence of prostate cancer. Treatment of prostrate cancer cell lines with NSAIDs leads to caspase mediated apoptosis. Previously, our laboratory has demonstrated that R-flurbiprofen and Ibuprofen induce the expression of the pro-apoptotic protein p75NTR in PC-3, DU-145 and LNCaP prostate cancer cell lines, with a subsequent decrease in cell survival. The p75NTR is a member of the Tumor Necrosis Factor Receptor superfamily of death receptors. It acts as a tumor suppressor in the normal prostate. The expression of p75NTR is lost as prostate cancer progresses and is minimal in established metastatic prostate cancer cell lines such as PC-3, DU-145, and LNCaP. The observed increase in p75NTR protein due to R-flurbiprofen and Ibuprofen treatment occurs as a result of activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Here we show that the upregulation of p75NTR following treatment with NSAIDs corresponds to a concomitant upregulation of the NSAID activated gene-1 (Nag-1) protein, a pro-apoptotic member of the TGF beta family, in PC-3 cells. Nag-1 has been linked to decreased cell proliferation in many studies, and has been shown to play a pro-apoptotic role in breast, colorectal, gastric and prostate cancer cells. Nag-1 is also known by the names GDF −15, MIC-1, PDF, PLAB and PTGFB. This study also shows that Nag-1 protein induction following NSAID treatment is mediated by the p38 MAPK pathway, and is downstream of the p75NTR induction. This is the first report of a relationship between p75NTR and Nag-1. 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 1263.