tbuckley/cabot-search huggingface dataset:
SP0145 HDL as a Pro-Inflammatory Agent
Authors: M. Mcmahon
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Although HDL levels are traditionally inversely related to atherosclerosis, the relationship is complex and involves both HDL quantity and function. HDL has been described as "chameleon-like," <b><i>anti</i></b>-inflammatory in the basal state and <b><i>pro</i></b>-inflammatory (piHDL) during an acute-phase response. In piHDL, levels of anti-inflammatory components of HDL such as apo A-I and HDL-associated paraoxonase activity are reduced. Additionally, acute phase HDL is greatly enriched in acute phase reactants such as serum amyloid A. Dysfunctional piHDL cannot perform many of the anti-atherogenic functions of normal HDL; it cannot prevent oxidation of LDL-C and actually increases it, leading to impairment of reverse cholesterol transport and increased recruitment of monocytes to the cell wall. Oxidatively modified HDL also stimulates an enhanced inflammatory response, including upregulation of the adhesion molecule VCAM-1 on endothelial cells. Chronic inflammatory responses and oxidative stress may be a mechanism for HDL dysfunction in patients with rheumatic diseases. Indeed, our group has found that HDL function is abnormal in many SLE and RA patients; 45% of women with SLE, compared to 20% of rheumatoid arthritis patients and 4% of controls, had pro-inflammatory HDL that was not only unable to prevent oxidation of LDL but caused increased levels of oxidation. Subsequent studies have indicated that 85% of SLE women with plaque on carotid ultrasound have piHDL, indicating that piHDL may be a biomarker of risk for atherosclerosis in SLE. In addition, HDL appear to be dysfunctional in primary antiphospholipid syndrome. Accumulating evidence suggests that dysfunctional pro-inflammatory HDL may not only be a biomarker for increased atherosclerotic risk but may also directly contribute to systemic inflammation and organ manifestations in patients with rheumatic diseases. <h3>Disclosure of Interest</h3> None Declared
Abstract 4306: Lack of TGF-β signaling induces a switch from single to collective cell migration in vivo
Authors: Lauren A. Matise, Trenis D. Palmer, William J. Ashby, Abudi Nashabi, Anna Chytil, Mary Aakre, Agnieszka Gorska, Michael W. Pickup, Andries Zijlstra, Harold L. Moses
Journal: Cancer Research (2012)

Abstract Transforming growth factor-beta (TGF-β) has a dual role during tumorigenesis initially as a suppressor and then as a promoter. In stromal fibroblasts, TGF-β signaling suppresses tumorigenesis in adjacent epithelia, while its ablation potentiates tumor formation. Concurrently, epithelial TGF-β signaling regulates fibroblast recruitment and activation. Yet, the role of TGF-β in stromal-epithelial migration during tumorigenesis is unknown. We hypothesize that TGF-β is a critical regulator of tumor-stromal interactions that promote mammary tumor cell migration and invasion. We are using the chicken embryo chorioallantoic membrane (CAM) model to study this interplay by grafting both breast cancer epithelial cells, isolated from either TGF-β receptor II knockout (TβRII-deficient) or TβRII floxed (control) mice, and fibroblasts onto the CAM. Intravital microscopy revealed fibroblast stimulation of either a single cell/strand migration of control cells or collective migration of TβRII-deficient cells, both along the vasculature. Epithelial clusters at the epithelial-stromal boundaries of TβRII-deficient tumors express E-cadherin, p120, and β-catenin, while control epithelia in these regions express αSMA. TβRII-deficient tumors also exhibit a two-fold greater local CAM metastasis than control tumors. Epithelial tumor RNA isolated by laser capture microdissection was analyzed on a qPCR array. In TβRII-deficient epithelium compared to control epithelium, we found upregulation of Igfbp4 and Tspan13 and downregulation of Col1α2, Bmp7, Wnt11, Gng11, Vcan, Tmeff1, and Dsc2. Western and qPCR analyses validated these targets in vitro. For current and future studies determining the relevance of these targets to migration patterning, we achieved Wnt11 overexpression in TβRII-deficient cells, as well as knockdown of Wnt11 and Tmeff1 in control cells. Our findings about TGF-β signaling in stromal-epithelial interactions are important in identifying migratory mechanisms that can be targeted as recourse for breast cancer treatment. 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 4306. doi:1538-7445.AM2012-4306
SAT0093 Pregnancy in patients with rheumatoid arthritis treated witn biological agents: Results of the 8-year of japanese tbc registry
Authors: H. Ishikawa, Y. Hirano, A. Kaneko, D. Kida, T. Sato, T. Kojima, T. Kanamono, N. Ishiguro
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> RA is one of the autoimmune disease, often generated in a middle-aged woman and the patient of reproductive age is not few either. We set up the registry of RA patients treated using biologics named Tsurumai Biologics Communication Registry (TBCR) and collected 2072 cases until now. <h3>Objectives</h3> The evidence of treatment with Disease Modifying Anti Rheumatic Drugs (DMARDs) for the pregnant RA patient is limited. It is very difficult to give what kind of medication for them because of a possibility of the pregnancy. The aim of this study is to investigate how the pregnant patients in TBC registry were treated with biologics. <h3>Methods</h3> The usage of biological agents including tumor necrosis factor inhibitors and interleukin-6 inhibitors before or during pregnancy and the outcome of pregnancy in patients with rheumatoid arthritis (RA) were investigated using TBCR until December, 2011. <h3>Results</h3> 30 pregnancies in 26 female patients with RA were identified among 2072 patients during 8-year registry periods (22 with ETN exposure, 2 with INF exposure and 6 with TCZ exposure). Biological agents were prescribed at conception in 19 pregnancies (63.3%) among which etanercept and tocilizumab were used in 15and 4, respectively. Although biological agents were prescribed during pregnancy after conception in no case, oral prednisolone was prescribed more frequently during pregnancy (70.0%) than before planning pregnancy (36.0%). Although 3 premature deliveries and 4 spontaneous abortions occurred, no anomalies of infants were observed. <h3>Conclusions</h3> In this study, we reported how the biologic agents used in young female RA patients and how many pregnancies were occurred in TBC registry. It is difficult to do clinical research about safety of drug for the pregnancy. Although the usage of biological agents, especially etanercept, is one of the choices in the strategy of pregnancy in patients with active RA, firm conclusion on safety of etanercept use during pregnancy is difficult to describe from the results of this retrospective study without control. More information on association between biological agents and pregnancy in RA patients should be collected in the future. <h3>Disclosure of Interest</h3> None Declared
AB0252 Traps syndrome in a three generation greek family with long lasting recurrent fevers
Authors: O. Vougiouka, T. Karpathios, H. Konstantopoulos, C. Bakoula
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tumor necrosis factor receptor associated periodic fever syndrome (TRAPS) is an autosomal dominant inherited periodic fever syndrome caused by mutation of the 55kDa TNF receptor superfamily A1 gene,TNFRSF1A.TRAPS is defined as recurrent attacks of systemic inflammation for which no infectious or auto-immune cause can be identified. To date, over 50 mutations in the gene have been reported. Typical TRAPS features include recurrent long lasting fevers (7-28 days), myalgia, rashes, periorbital edema, conjunctivitis, joint and abdominal pain. <h3>Objectives</h3> We report a 3 generation family, whose members presented with recurerrent fevers, lasting 15-30 days, myalgia, painful skin underlying expanding erythema and abdominal pain. One patient from 1st and 4 from 2nd generation of this family were used to live with their symptoms. In recent years a 10 year old girl from 3rd generation, with symptoms since the age of 7y., was brought to medical attention. <h3>Results</h3> She was undertaken a series of laboratory tests, including gene analysis for FMF and hyper Ig-D syndrome with negative results. 8 years later C73W TRAPS mutation was detected by the scientific team of the Genetic Laboratory, Montpellier University Hospital. The same mutation was also found to the symptomatic mother and sister of the girl. She was initially treated with colchicine, without response, even if she lacked compliancy. Occasionally short courses of NAIDS and steroids were prescribed with partial response. After genetic confirmation of TRAPS Canacinumab was prescribed for her, but we are still waiting her appliance to medical care providers. Genetic confirmation of the disease is anticipated for 5 other symptomatic members, by the same Hospital Centre. <h3>Conclusions</h3> TRAPS, the syndrome originally described as Familial Hibernian Fever, has broadened out its Irish and Scottish borders, so it is considered in cases of recurrent fevers. Besides poor life quality of the patients, amyloidosis can be developed in up to 25% of cases. The role of mutated TNFr-a in TRAPS manifestations is not very well clarified, but it is involved in IL-1 overproduction, as it happens in other inflammasome associated recurrent fever syndromes. So anti-IL-1 targeted therapies for TRAPS appeared in literature which are also justified from the results. This justify the prescription of anti-IL-1 monoclonal antibody for our patient with chronic intractable symptoms. We anticipate her to come back to medical attention. <h3>References</h3> Medicine (Baltimore) 2002, 81 349-368. Arthritis Rheum 2008, 58 1516-1520. <h3>Disclosure of Interest</h3> None Declared
Effects of Desipramine, Amitriptyline, and Fluoxetine on Pain in Diabetic Neuropathy
Authors: Mitchell B. Max, Sue A. Lynch, Joanne Muir, Susan E. Shoaf, Bruce Smoller, Ronald Dubner
Journal: New England Journal of Medicine (1992)

Amitriptyline reduces the pain caused by peripheral-nerve disease, but treatment is often limited by side effects related to the drug's many pharmacologic actions. Selective agents might be safer and more effective.
Abstract 800: Inflammatory chemokines mediate immune surveillance of intestinal cancer
Authors: Venkatakrishna R. Jala, Steven P. Mathis, Sobha R. Bodduluri, Paramahamsa Maturu, Elangovan Krishnan, Michelle E. Smith, Paula M. Chilton, Thomas C. Mitchell, Massimo Locati, Alberto Mantovani, Haribabu Bodduluri
Journal: Cancer Research (2011)

Abstract Immune system plays a dual role in cancer development and progression. Under conditions of chronic inflammation the repair response initiated by the immune system strongly promotes tumor growth. Epidemiological evidence of increased cancer incidence in organ transplant recipients and immune compromised individuals suggests a critical role for immune surveillance in keeping cancer under control. The cellular and molecular mechanisms that control tumor promoting chronic inflammation or tumor suppressing immune surveillance are unclear. Chemokines direct the migration of leukocytes to the sites of infection or injury and therefore are likely to play a central role in perpetuating tumor promoting chronic inflammation as well as orchestrating tumor eradicating immune surveillance. D6 is a chemokine decoy receptor and an effective scavenger of inflammatory CC-chemokines. D6-knockout (D6-/-) mice showed enhanced inflammation in different models including carcinogen-induced inflammation-promoted skin cancers. In this study, we show that D6-/- mice when bred onto mice with a heterozygous mutation in the adenomatous polyposis coli (ApcMin/+) gene demonstrated reduced intestinal tumor burden and increased survival. A decrease in tumor promoting inflammation is coincidental with increased mast cells and CD8+ T cell activation profiles in tumors from the D6-/-ApcMin/+ mice compared to ApcMin/+ mice. The D6-/-ApcMin/+ mice in the context of the lymphocyte deficient, Rag2-/-background (Rag2-/-D6-/-ApcMin/+), showed a significant increase in tumor burden that is reversed by the adoptively transferred CD8+ and/or CD4+T-lymphocytes from the D6-/-ApcMin/+ mice. Chemokine levels in serum and chemokine receptor expression patterns on lymphocytes from the ApcMin/+ and D6-/-ApcMin/+ mice and the Rag2-/-D6-/-ApcMin/+ mice undergoing adoptive transfer treatments identified the increased levels of ligand-receptor pairs of LTB4/BLT1, CCL2/CCR2, and CXCL9/CXCR3 being critical in promoting tumor suppressive immune surveillance in this spontaneous tumor model. These results show that inflammatory chemokines play a protective role against progression of intestinal cancers by immune surveillance. 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 800. doi:10.1158/1538-7445.AM2011-800
Abstract 2224: Targeted PI3K/mTOR inhibition impairs tumor cell motility and bone metastatic outgrowth via modulation of p27
Authors: Alexandra H. Besser, Seth A. Wander, Dekuang Zhao, Feng Hong, Jian Qin Wei, Bin Wang, Tan Ince, Clara Milikowski, Mehrdad Nadji, Karoline Briegel, Nanette Bishopric, Joyce M. Slingerland
Journal: Cancer Research (2012)

Abstract The pleiotropic oncogenic effects of PI3K/mTOR have stimulated development of catalytic PI3K and mTOR inhibitors for the treatment of cancer. Present data provide a novel rationale for the use of dual PI3K/mTOR inhibitors to oppose tumor motility, invasion and metastasis. Cytoplasmic mislocalization of p27 is implicated as a key downstream driver of PI3K/mTOR-dependent tumor cell motility in vitro and bone metastatic outgrowth in vivo. Here, we report that PI3K/mTOR-kinase inhibition with PF-04691502 impairs breast cancer metastasis to bone, in part via effects on p27. Low-dose PF-04691502 impaired motility and invasion of highly PI3K/mTOR activated, bone-metastatic MDA-MB-1833 cells in vitro without affecting apoptosis or proliferation. Moreover, drug pre-treatment impaired bone metastasis in vivo. PF-04691502 decreased cytoplasmic p27pT157 and p27pT198, and p27T157D/T198D overexpression conferred resistance to inhibition of motility by PF-04691502. p27 knockdown in MDA-MB-1833 relieved RhoA-ROCK inhibition, decreased cell motility/invasion in vitro, and bone metastasis in vivo. p27 knockdown also reversed EMT phenotypic markers in MDA-MB-1833, as did PI3K/mTOR inhibition, demonstrating that p27 may be critical for maintenance of the EMT cellular program. Indeed, loss of cytoplasmic p27 reversed expression of an EMT gene profile supporting the notion that p27 acts as a key mediator of metastasis downstream of PI3K/mTOR. Cytoplasmic p27 in human cancers may prove to be a useful predictive marker to assess both PI3K/mTOR activation and the potential efficacy of catalytic PI3K/mTOR inhibitors. 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 2224. doi:1538-7445.AM2012-2224
Abstract 2346: Contribution of VLA-4 to ovarian cancer metastasis and platinum resistance
Authors: Jennifer M. Scalici, Christine Harrer, Karen McLachlan, Jill Slack-Davis
Journal: Cancer Research (2010)

Abstract Ovarian cancer is the fourth leading cause of cancer-related death among women. The relatively poor prognosis for ovarian cancer (5-year survival of 30-40%) reflects 1) the advanced stage of disease at diagnosis and 2) the frequent development of recurrent disease refractory to front line therapy. Ovarian cancers metastasize by attaching to and invading through the mesothelium, a single cell layer of mesothelial cells lining the peritoneal cavity. The presence of invasive peritoneal metastases is associated with a poor prognosis for ovarian cancer (5 yr survival &amp;lt;25%). We identified the integrin VLA-4 and its ligand VCAM-1 as regulators of mesothelial invasion. VLA-4 expression correlates with the ability of ovarian cancer cells to invade mesothelial monolayers. Additionally, VLA-4 is expressed on primary ovarian cancer cells obtained from patient tumors or ascites. The contribution of VLA-4 to ovarian cancer peritoneal metastasis was evaluated using a mouse xenograft model and function-blocking antibodies directed against VLA-4. Mice were injected intraperitoneally with platinum-resistant human ovarian cancer cells; one week later the mice were randomized into four groups and treated with 1) anti-VLA-4 antibodies, 2) carboplatin, 3) anti-VLA-4 and carboplatin, or 4) control IgG. Treatment with either anti-VLA-4 therapy or carboplatin alone had no effect on tumor burden compared to the IgG control group. However, the combined treatment of anti-VLA-4 and carboplatin significantly reduced tumor burden compared to the control or either treatment alone. This study supports a role for the active involvement of VLA-4 expressed by tumor cells in the regulation of ovarian cancer chemoresponsiveness. 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 2346.
SAT0354 Usefulness of Imaging Techniques in Mixed Crystal Deposition (Pilot Study).
Authors: F. Kudaeva, S. Vladimirov, L. Bozhieva, A. Smirnov, A. Volkov, V. Barskova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The coexistence of both urate and calcium pyrophosphate (CPP) crystals in the same synovial fluid has been reported by many authors. The evaluation of crystal deposits in mixed microcrystallic arthropathy by imaging is essential for the diagnosis and management of both diseases. It is especially important for the diagnosis of calcium pyrophosphate deposition disease (CPPD) that is paid a little attention. <h3>Objectives</h3> To evaluate to usefulness of plain radiography (Rg), computed tomography (CT) and Doppler ultrasonography (US) in presenting specific images of monosodium urate (MSU) and CPP deposits in patients with gout and CPP crystals in synovial fluid. <h3>Methods</h3> 15 pts (14m/1f), mean age 59 years, mean disease duration 12 years, with crystal-proven gout and the presence of CPP crystals in synovial fluid (SF) were enrolled. All patients had arthritis and underwent aspiration of SF from inflamed joint (11 knees, 4 I MTPs). 6 patients had acute, 9 – chronic arthritis. Mean number of joints involved – 4, intradermal tophi were recorded in 10 patients (elbows, helix). Crystal identification was performed using polarised light microscopy with compensator (Olympus). Rg, CT and US of the knee joints were made in all patients. CT was obtained using a lightspeed VCT Select (GE), US – with Volusion-I (GE). Rg and CT evidence of cartilage calcification (CC) included thick linear linear deposits in hyaline cartilage, parallel to and separated from subchondral bone. Rg feature of tophi was erosion with sclerotic rim. CT identification of tophi included round and oval opacities with density about 170 HU. US CPP crystal deposition features were taken as linear hyperechoic deposits in the hyaline cartilage. US feature of urate deposition double-contour sign included hyperechoic bright contour following the contour of the bone surface – double contour sign. <h3>Results</h3> Rg and CT evidence of cartilage CC were disclosed in 60% and 87% of pts, correspondingly. Rg showed intraosseus tophi in 27% of pts. CT revealed intraosseous tophi in 47%, tophi in soft tissues around the knees– in 27% of pts. US appeared to provide CC features and double-contour sign in 100% of pts and revealed tophi in soft tissues around the knees in 30% of pts. <h3>Conclusions</h3> US demonstrated features of both diseases - chondrocalcinosis and double-contour sign – in all patients with MSU and CPP crystals in SF. Besides, US enabled us to see tophi in soft tissues in 30% of pts. CT discloses intraosseous tophi two times more often than Rg. Usefulness of CT in the revealing of CC is 2 times higher than Rg, mostly because of detailed visualization of patello-femoral CC. Moreover, CT, not Rg, has the possibility of revealing tophi in soft tissue that is almost identical to US. <h3>Disclosure of Interest</h3> None Declared
1074 IMPACT OF THE INFLAMMATION ON DIAGNOSING THE LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C BY VIRTUAL TOUCH TISSUE QUANTIFICATION
Authors: H. Tanaka, H. Iijima, M. Yoshida, R. Takata, T. Iwai, T. Takashima, Y. Sakai, N. Aizawa, K. Iwata, N. Ikeda, Y. Iwata, H. Enomoto, M. Saito, H. Imanishi, S. Hirota, J. Fujimoto, S. Nishiguchi
Journal: Journal of Hepatology (2012)
PET/CTA IMAGE FUSION FOR NONINVASIVE ABSOLUTE MYOCARDIAL FLOW QUANTIFICATION ACROSS SPECIFIC CORONARY LESIONS
Authors: Hee-Seung Bom, Marina Piccinelli, Ernest Garcia, John Votaw, C. David Cooke, Russell Folks, Daya Manatunga, Habib Samady
Journal: Journal of the American College of Cardiology (2015)
Genomic and transcriptomic differences between lobular and luminal ductal invasive carcinoma.
Authors: N Gruel, V Raynal, C Lucchesi, G Pierron, V Fourchotte, P Cottu, X Sastre-Garau, A Fourquet, O Delattre, A Vincent-Salomon
Journal: Cancer Research (2009)

Abstract Abstract #2039 Background: Invasive lobular carcinomas (ILCs) of the breast are characterized by morphological and phenotypical features such as small, non cohesive, estrogens receptors positive cells, low proliferation rates with a metastatic spreading in numerous and different unusual metastatic sites as compared to invasive ductal carcinomas (IDCs) (Ferlicot et al, 2004). We have previously shown that ILCs presented the same outcome than IDCs (Sastre-Garau et al, 1996). Beyond E-cadherin genomic inactivation, little is known about the underlying genomic and transcriptomic alterations that may discriminate both subtypes.&amp;#x2028; Aims of the study: To get an insight into ILC biological specificities, we performed a combined genomic (aCGH), transcriptomic (Affymetrix U133A+B) and phenotypic analysis of a series of 24 lobular carcinomas and compared it to a series of 41 ER-positive IDCs.&amp;#x2028; Results: Analysis of genomic copy number showed that ILCs and IDCs shared gains of the 1q11-q43 region and losses of 16q12.1-q24.2 and 17pter-p13.1 regions. ILCs presented the 22q12-q13 loss but not the 16pter-p11.2 gain and 11q23-q24 loss as observed in IDCs. Eight different regions of high level amplifications were found in 29% of ILC cases (7/24 cases). Only one region of amplification was recurrent and observed in 5 out of 24 tumors (21% of the cases). This recurrent region of amplification was localized on the 11q13.2 region and encompassed the Cyclin D1 (CCND1) and Cortactin (CTTN) genes. ILCs and IDCs had comparable overall survival rates, however, unsupervised hierarchical clustering of transcriptomic data showed that ILCs and IDCs clustered apart. Genes involved in cell adhesion and motility, lipid/fatty transport and metabolism and electron transport were differentially expressed between the two groups.&amp;#x2028; Conclusions: This integrated analysis emphasized the biological differences between ILC and IDC and highlighted genes of interest that could be useful for diagnosis, and could be new putative therapeutical targets. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2039.