tbuckley/cabot-search huggingface dataset:
Abstract 377: Organic Anion Transporting Polypeptides (OATPs): A potential new molecular target for imaging/therapy of hormone dependent breast cancers
Authors: Nilasha Banerjee, Christine Allen, Reina Bendayan
Journal: Cancer Research (2012)

Abstract The purpose of this research is to explore the potential of Organic Anion Transporting Polypeptides (OATPs), a family of membrane-associated uptake transporters, as a novel molecular target for imaging and treatment of breast cancers. It has been reported that some of the OATP isoforms (e.g. OATP1A2, OATP2B1) are over expressed (up to ten times) in breast cancer tissues as compared to surrounding normal tissues. Furthermore, estrone-3-sulpahte (E3S), a predominant source for tumour estrogen in post-menopausal patients with hormone dependent breast cancers has been characterized to be a substrate for many of the OATP isoforms. This suggests that the two- three times higher E3S concentration reported in malignant tissues, as compared to the surrounding normal tissues, could be due to higher expression and/or increased functional activity of OATPs in breast tumour tissues. By characterizing the differential expression and function of OATPs in breast epithelial cells and breast cancer cells, their potential as novel molecular targets can be established. In this study, the gene and protein expression of seven OATPs (i.e. OATP1A2, OATP1B1, OATP1B3, OATP1C1, OATP2B1, OATP3A1 and OATP4A1) that are known to recognize E3S as a substrate, were compared in normal breast epithelial cells (MCF10A), hormone dependent breast cancer cells (MCF7) and hormone independent breast cancer cells (MDA/LCC6-435, MDA-MB-231 and MDA-MB-468) by real time qPCR and immunoblotting. OATP mediated E3S uptake was also characterized by transport experiments. Six of the seven OATPs (except SLCO1C1) were found to be expressed in breast cancer cells at the transcript level. Expression of SLCO1A2, 1B1, 1B3, 2B1 and 3A1 was exclusive, similar or significantly higher (p&amp;lt;0.001) in cancer cell lines compared to the normal breast epithelial cells (MCF10A). At the protein level, expression of all the OATP isoforms was observed to be either exclusive or higher in the cancer cell lines as compared to the MCF10A cells. Specificity of OATP mediated E3S uptake was observed only in the cancer cells with significantly higher total uptake in the MCF7 cells. Estimation of the transport kinetics (Km and Vmax) of E3S uptake by the breast cancer cell lines, demonstrated E3S transport efficiency to be 10 times greater in the hormone dependent breast cancer cells than in the hormone independent cells. Taken together, these data suggest that i) OATPs can be a potential molecular target for hormone dependent breast cancers in post menopausal patients and ii) E3S can be used a ligand for actively targeting hormone dependent breast cancers. 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 377. doi:1538-7445.AM2012-377
The Paradox of Osteopathy
Authors: Joel D. Howell
Journal: New England Journal of Medicine (1999)

In the spring of 1864, Andrew Taylor Still, a rural Kansas practitioner, watched helplessly as the best medications then available failed to save his three children from spinal meningitis. Bitterly disappointed, Still set out to devise an alternative healing practice. He eventually based his new system on the idea that manipulation of the spine could improve blood flow and thus improve health by allowing the body to heal itself. His philosophy included a healthy dose of moralism; patients were forbidden to consume any liquor and, as part of the break from existing practices, were also forbidden to take any medicine. . . .
Familial Aggregation of Bronchodilator Response
Authors: TIANHUA NIU, JOHN J. ROGUS, CHANGZHONG CHEN, BINYAN WANG, JIANHUA YANG, ZHIAN FANG, SCOTT T. WEISS, XIPING XU
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We investigated familial aggregation of bronchodilator response (BDR) among 4,946 subjects selected from 1,161 index families with asthma in a rural community in China. Each family unit consisted of both parents and their first and subsequent offspring, aged 8–20. Raw BDR measurements, defined as the percentage change in FEV1 after 180 μ g of albuterol, were adjusted to account for sex, age, height, weight, education, smoking, asthma, wheeze, and allergy status. Using these adjusted BDR values, we found significant correlation for father-first offspring pairs, mother–first offspring pairs, mother–subsequent offspring pairs, and first offspring–subsequent offspring pairs. The overall magnitude of the correlation coefficient (0.088–0.165) suggests a modest degree of familial clustering. The largest odds ratio was seen for subsequent offspring who had mothers and first offspring with adjusted BDR values above the median: 3.10 (95% CI: 1.85–5.20) in these index families with asthma. Thus, our data support a significant familial aggregation of BDR in this Chinese population, which points to a role of genetic factors in BDR.
SAT0095 Control of Disease Activity is Associated with Improvement in Physical Activity in Patients with Rheumatoid Arthritis: Table 1
Authors: S. Verstappen, J. Anderson, A. Barton, K. Hyrich
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> It is well-known that patients with rheumatoid/undifferentiated arthritis (RA/UA) experience reduced functioning in daily tasks. Less is known about changes in physical activity over time and the association with disease related factors. <h3>Objectives</h3> i) To evaluate changes in physical activity in patients with RA/UA over a 6 month period and ii) to determine the association between clinical/patient reported outcomes (PROs) and physical activity. <h3>Methods</h3> 550 consecutive patients participating in the Rheumatoid Arthritis Medication Study (RAMS), which recruits patients with RA/UA starting MTX for the first time, were included. At baseline and 6 mo., patients were asked to compare, using a 5-point Likert Scale, their current physical activity with others their same age (much more to much less). The 5 categories were grouped into more, the same, or less physical activity. At baseline they were also asked how many days of the week (none to every day) they (i) exercised more than 20 minutes and (ii) performed exercise that made them sweat. Baseline and 6 mo. clinical/PRO variables included: DAS28, VAS physician, VAS general well-being, VAS pain, VAS fatigue and HAQ. Changes in scores over 6-mo. were calculated and EULAR response criteria were determined in a subgroup of patients with available DAS28 scores. Multinominal logistic regression analyses were applied to assess the association between change in clinical/PROs with a change in rating over 6 mo. on physical activity in comparison to others; more activity, less activity and no change. <h3>Results</h3> Mean (SD) age was 60 (13) yrs; 70% were female. At baseline, 38% exercised for more than 20 minutes and 69% reported exercising until sweating on one day or less during the wk. Patients reported that they exercised less (55%), the same (26%) or more (19%) than other people their own age. After 6 mo., 15% reported more activity, 17% less activity and 68% no change compared to their baseline ranking. A good EULAR response was significantly associated with improvement in physical activity. Improvement of all PROs was also associated with an improvement in physical activity, whereas only worsening of VAS well-being, VAS fatigue and HAQ scores were associated with decreased physical activity over 6 mo. <h3>Conclusions</h3> Improved physical activity was associated with better disease control supporting the idea of treat-to-target strategies to encourage healthy ageing in patients with RA/UA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4373
SAT0174 Clinical and Histological Features in Patients with Permanent Visual Los Due to Biopsy-Proven Giant Cell Arteritis
Authors: R. Solans-Laqué, G. Fraile, M. Monteagudo, L. Caminal, M. Abdilla, P. Fanlo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Amaurosis is the most frequent ischemic complication and the main cause of permanent disability among patients with giant cell arteritis (GCA). Some premonitory symptoms of visual loss such as amaurosis fugax, diplopia and blurry vision have been described <h3>Objectives</h3> To determine associated clinical and histological findings in patients with GCA and visual loss due to anterior ischemic optic neuropathy (AION). <h3>Methods</h3> Demographic, clinical and histological features of patients with biopsy-proven GCA recruited at 6 different Hospitals from Spain were analyzed. Statistical analysis was performed using the SPSS vs. 17. <h3>Results</h3> There were 135 patients, 82 (60.7%) females and 53 (39.3) males, with a mean age of 74.9 ± 7 (58-89) at diagnosis. Cardiovascular risk factors were present in 45% of cases (hypertension in 40%, hypercholesterolemia in 20%, diabetes mellitus in 18.5%, and smoking habit in16.2%). The most frequent symptoms at CGA diagnosis were recent-onset headache (83%), jaw claudication (37%), cranial hyperesthesia 55 (40.7%) and constitutional symptoms (48.1%). Polymyalgia rheumatica was present in 50.4% of cases. Sixteen patients had lost vision due to AION, two of them involving both eyes. Sixty-two percent of patients complained of classical GCA cranial symptoms for an average of 7 weeks (range 2 days to 16 weeks). Seven (43.8%) patients had premonitory visual symptoms before visual loss. Six patients had an apparent isolated polymyalgia rheumatica for an average of 14 months (range 6 to 24 months). Mean ESR was 99 (28-163). 76.3 of patients had anemia. No significant relationship was found between visual loss development and cardiovascular risk factors. AION was significantly related to the presence of amaurosis fugax (p=0.002), jaw claudication (p=0.025) and temporal artery abnormalities on physical examination (p = 0.04). In addition, the presence of giant cells in temporal artery biopsy (p = 0.004), inflammatory infiltrate (p=.0.001) and elastic membrane disruption (p= 0.020), were significantly most frequent in patients with AION. <h3>Conclusions</h3> A high proportion of patients with permanent visual loss have a delayed diagnosis and treatment. A wider recognition of the disease would potentially reduce the prevalence of irreversible visual loss among GCA patients. <h3>References</h3> Font C et al. Clinical features in patients with permanent visula loss due to biopsy-proven giant celll arteritis. Br J Rheumatol 1997 Makkuni D. Is intimal hyperplasia a marker of neuro-opthalmic complications of giant cell arteritis?. Rheumatol 2008 <h3>Disclosure of Interest</h3> None Declared
Abstract 4764: The LTbR mediates immune cell-exerted anti-tumor cytotoxicity
Authors: Xiaolin Hu, Kebin Liu
Journal: Cancer Research (2011)

Abstract Lymphotoxin beta Receptor (LTβR) belongs to the Tumor Necrosis factor (TNF) receptor superfamily and was originally identified to be critical for the development and maintenance of secondary lymphoid architectures. However, it is increasingly appreciated that the LTβR signaling pathway is involved in induction of extrinsic apoptotic cell death in tumor cells. Strikingly, it was recently observed that sustained expression of LTβR ligands also promote tumor development via a NF-κB-dependent mechanism. Thus, LTβR could function as two-edged sword. There are two physiological ligands, LTα1LTβ2 and LIGHT, that engage the LTβR to initiate signaling transduction. These two ligands are known to be expressed in immune cells. However, whether immune cells use these two ligands to suppress tumor development is unknown. In this study, we observed that LTβR protein in expressed in all tumor cell lines examined and in human colon carcinoma and sarcoma specimens. Engagement of the LTβR with LTβR-specific agonist mAbs activated both the canonical and alternative NF-κB signaling pathways in tumor cells. However, these agonist mAbs at the same time also effectively suppressed the growth of colon carcinoma, melanoma, mammary carcinoma and sarcoma cells in vitro, suggesting that the LTβR-mediated apoptosis signaling pathway overpowers the LTβR-initiated NF-κB signaling pathways to yield an overall tumor suppressive effect. Furthermore, both LTα1LTβ2 and LIGHT were activated in tumor-infiltrating macrophage, NK and T cells. Chimera mice with LTα-, LIGHT- or both LTβ and LIGHT-deficient immune cells exhibited significantly high incidence of MCA-induced tumor and greater tumor growth than chimera mice with wt immune cells. Furthermore, double-deficiency of LTβ and LIGHT in the immune cells resulted in significantly higher tumor incidence and greater tumor growth than LTα-deficiency alone. Taken together, our data suggest that LTβR mediates an immune cell-exerted anti-tumor effector mechanism 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 4764. doi:10.1158/1538-7445.AM2011-4764
AB0609 Fluorescence Optical Imaging of Inflammation in Systemic Sclerosis – A Pilot Study
Authors: A. Pfeil, K.F. Drummer, J. Boettcher, C. Jung, P. Oelzner, G. Wolf
Journal: Annals of the Rheumatic Diseases (2014)

Background Systemic sclerosis is a connective tissue disease affecting various organs including the peripheral vessels resulting in Raynaud's phenomenon. For treatment of Raynaud's phenomenon the vasodilator Prostaglandin I2 analogue iloprost is widely used. An anti-inflammatory and immunmodulating effect is also described for iloprost. Fluorescence optical imaging (FOI) is an in vivo technique to visualize inflammation based on the accumulation of fluorescence optical contrast media (indocyanine green) in rheumatoid arthritis. Objectives The aim of this study was to visualize inflammation using FOI in patients with Systemic Sclerosis (SSc) with SSc-related Raynaud's phenomenon depended and to clarify therapeutic response depending on the treatment with iloprost. Methods 16 patients with SSc and Raynaud's phenomenon were prospectively included. The SSc patients were intravenously treated with over seven days. FOI (Xiralite system, Mivenion GmbH, Berlin, Germany) was performed at baseline and after seven days using on intravenous application of indocyanine green (ICG). Both hands were investigated, divided into 19 segments per hand (total 38 segments). Segments of both hands were quantitatively evaluated to determine enhancement of ICG. Results In total 798 hand segments were scored considering all patients with SSc. At baseline 31.5% hand segments showed an ICG enhancement. The highest ICG enhancement was observed at the proximal phalanx of all fingers. After seven days of iloprost therapy a significant reduction of visible ICG enhancement was verified with -40.9% (p<0.001). Conclusions The FOI technique seems to consists a high potential to visualize inflammation in patients with SSc and Raynaud's phenomenon. The anti-inflammatory effects of iloprost were detectable using the FOI based on the reduced enhancement of ICG. FOI offers a promising impact for the diagnosis and therapy monitoring of patients with SSc associated with Raynaud's phenomenon. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3271
SAT0496 Countermeasures Against Methotrexate Intolerance in Juvenile Idiopathic Arthritis Instituted by Parents Show no Effect: Table 1
Authors: A. Scheuern, N. Fischer, J.-P. Haas, B. Hugle
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Methotrexate (MTX) is the mainstay treatment in the therapy of children with juvenile idiopathic arthritis (JIA) and can lead to prolonged remission and improved quality of life. However JIA patients frequently develop intolerance to MTX, with anticipatory and associative gastrointestinal adverse effects before drug intake, arising as a conditioned response. Parents frequently try to alleviate these symptoms with a variety of countermeasures against nausea. <h3>Objectives</h3> The objective of this study was to investigate the course of MTX intolerance in pediatric patients over a period of 6 months, as well as the effect of countermeasures by parents on the severity of MTX intolerance. <h3>Methods</h3> Consecutive patients admitted to the German Center for Pediatric and Adolescent Rheumatology from October 2012 until April 2014 were included in this study. MTX intolerance was measured using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. Inclusion criteria were 1) diagnosis of JIA, 2) treatment with MTX for at least 3 months prior to inclusion, and 3) confirmation of MTX intolerance by a MISS value of ≥6. Exclusion criteria were other diseases leading to nausea and/or abdominal complaints, and concomitant medications possibly inducing nausea (excepting biologics and non-steroidal anti-inflammatory drugs). Methotrexate dose, MISS and countermeasures instituted by the parents were determined at 4 time points (at inclusion, at 6 weeks, 3 months and 6 months). Countermeasures were classified into 4 criteria: antiemetic drugs, covert dosing, taste masking and complementary medicine. Results were analyzed using descriptive statistics and non-parametric testing (Wilcoxon signed rank test). <h3>Results</h3> 38 patients were included (63% female, median age at inclusion 11.7 years, median disease duration 7.1 years). Average MISS at inclusion was 10.8±4.1, and after 6 months 12.2±7.2 (p=0.316). In 6/38 patients (16%), MTX was reduced or discontinued during the study. In 89 time intervals between study visits, 40 countermeasures were introduced by the parents. <h3>Conclusions</h3> If MTX intolerance is present, symptoms will not decrease over the course of 6 months. Various modalities used by the parents as countermeasures against nausea by the parents show no discernible effect. <h3>Acknowledgements</h3> This study was supported by the “Stiftung Hilfe für das rheumakranke Kind e.V.” <h3>Disclosure of Interest</h3> None declared
Abstract 1292: Broad vascular distribution of Neuropilin-1 and its ligands in human tumors
Authors: Judy Mak, Raymond Tong, Alexander Koch, Joe Kowalski, Gretchen Frantz, Franklin Peale, Ryan Watts, Anil Bagri
Journal: Cancer Research (2010)

Abstract Neuropilin-1 (NRP1) is a multi-domain transmembrane receptor that is important for the development of the nervous and vascular systems and has been implicated in modulating various aspects of tumor biology. We have previously shown that an antibody directed against NRP1 inhibits tumor growth and reduces tumor angiogenesis, as a single agent and more potently in combination with anti-VEGF. Currently, anti-NRP1 is in evaluation in early clinical studies. Therefore, understanding the expression pattern of Nrp1 and its relevant ligands in human tumor samples is of critical importance. To this end, we first evaluated the binding of a number of putative ligands that have been suggested to interact with NRP1 in the literature, and furthermore to understand which of these are biochemically or functionally inhibited by our anti-NRP1. We found that members of the semaphorin and VEGF families, but not HGF bind to NRP1. However, only binding and function of specific ligands from the VEGF family are inhibited by anti-NRP1. Additionally, we evaluated the expression pattern of NRP1 in human tumor samples from a number of different tumor types, including breast, colorectal, lung, ovarian, pancreatic, prostate and renal cancer. NRP1 is broadly expressed in the vasculature of most cases of all these tumor types. Additionally, NRP1 is also variably expressed by tumor cells and other stromal elements in a more variable manner that is tumor type dependent. These results suggest that NRP1 is a potentially important therapeutic target in many different tumor types. 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 1292.
FRI0507 Dual Energy Computed Tomography for the Evaluation of Calcinosis in Systemic Sclerosis: Table 1.
Authors: V.M. Hsu, M. Bramwit, N. Schlesinger
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Calcinosis, the deposition of calcified material in the skin and subcutaneous soft tissues, is frequently seen in up to 40% patients with SSc (1, 2). Calcium hydroxyapatite (3) is the major constituent of SSc-calcinosis. We used a new imaging modality, the dual-energy computer tomography (DECT) to study SSc-calcinosis. DECT is useful for assessing monosodium urate (MSU) crystal deposition in gout (4). Differences in attenuation enable differentiation between calcium hydroxyapetite and MSU crystals. <h3>Objectives</h3> To examine clinical characteristics and patterns of systemic sclerosis (SSc) – related calcinosis of the hands using dual-energy computer tomography (DECT). <h3>Methods</h3> 10 SSc patients with hand calcinosis had DECT of hands and wrists and their clinical information obtained. <h3>Results</h3> Nine were females and 8 were Caucasians. Five had diffuse SSc. The mean age was 57 and mean disease duration was 19.4 years. DECT showed calcinosis most commonly in the subcutaneous fat pad of fingertips, along tendon sheaths, within the carpal tunnel, and adjacent to muscle groups. Two patients had extension (in sheets) into their forearms. Eight patients with bulky deposits also had advanced SSc- related organ complications, including ischemic digital ulcers, esophageal reflux and pulmonary fibrosis. Half of our cohort was disabled by SSc-calcinosis due to painful ulcers (100%), soft tissue swelling (80%), contractures (80%) new joint swelling (50%), or subsequent infections (40%). All had acro-osteolysis and 4 had bony destruction adjacent to the calcinosis. <h3>Conclusions</h3> Calcinosis affects both diffuse and limited SSc and can be destructive in a subset of patients with bulky deposits, who typically have ischemic digital ulcers and advanced SSc organ complications. More studies are needed to better define calcinosis risk factors and the role of DECT in assessing SSc-calcinosis. <h3>References</h3> Steen VD, Ziegler GL, Rodnan G et al, Clinical and Laboratory associations of anti-centromere antibody in patients with progressive systemic sclerosis. Arthritis &amp; Rheum 1984;27 (2): 125-131 Elhai M, Guerini H, Bazeli R, et al. Ultrasonographic hand features in systemic sclerosis and correlates with clinical, biologic and radiographic findings. Arthritis Care Res 2012;64 (8):1244-1249 Freire V, Becde F, Feydy A, et al. MDCT imaging of calcinosis in systemic sclerosis. Clin Radiol 2013; 68(3): 302-309. Choi K, Al-Arfaj AM, Eftekhari A, et al. Dual Energy computed tomography in tophaceous gout. Ann Rheum Dis.2009 68 (10): 1609-1612. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1049