tbuckley/cabot-search huggingface dataset:
Abstract 299: Targeting epithelial-mesenchymal transition in breast cancer cells using Honokiol, a natural phenolic compound.
Authors: Dimiter B. Avtanski, Arumugam Nagalingam, Panjamurthi Kupusamy, Neeraj K. Saxena, Dipali Sharma
Journal: Cancer Research (2013)

Abstract Introduction: The epithelial-mesenchymal transition (EMT) presents a critical step in the acquisition of metastatic state. Tumor cells undergoing EMT not only exhibit increased migration and invasion potential but also acquire increased resistance to chemotherapy and radiation therapy. Hence, EMT is an attractive target for therapeutic interventions directed against tumor metastasis. Honokiol (HNK) is a natural phenolic compound isolated from an extract of seed cones from Magnolia grandiflora. Recent studies from our lab show that honokiol inhibits breast carcinogenesis. The present study is designed to systematically elucidate if nontoxic lower doses of honokiol can be used to specifically inhibit EMT in breast cancer cells. Results: Our studies show that HNK inhibits EMT in human breast cancer cells. Exposure of estrogen-independent and estrogen-responsive breast cancer cells to nontoxic lower doses of HNK results in significant downregulation of mesenchymal marker proteins (Fibronectin, Vimentin) along with simultaneous upregulation of epithelial markers (E-cadherin, Cytokeratin-18). HNK also inhibits expression and nuclear translocation of transcriptional modulators of EMT-related genes (Snail, ZEB1/2 and Twist). Experimental EMT induced by exposure to TGFβ and TNFα in a spontaneously immortalized nontumorigenic human mammary epithelial cell line (MCF-10A) was also completely reversed by HNK treatment as evidenced by morphological changes (inhibition of fibroblast-like appearance, decreased pseudopodia and actin reorganization to membrane-bound location in TGFβ and TNFα treated MCF10A cells) as well as molecular changes (downregulation of Fibronectin, Vimentin, Snail, Zeb1/2 and upregulation of E-cadherin and Cytokeratin-18). Mechanistically, HNK inhibits MTA1-Wnt1 axis leading to stabilization and nuclear translocation of β-catenin to inhibit EMT. Analysis of breast tumors treated with honokiol show modulation of EMT markers and inhibition of key molecules of MTA1-Wnt1-β-catenin axis corroborating our in vitro findings. Conclusions: Taken together, these data provide the first in vitro and in vivo evidence of the potential of HNK as a novel, non-toxic and non-endocrine therapeutic strategy for breast carcinoma. MTA1, Wnt1 and β-catenin appear to be novel biomarkers associated with HNK treatment. Citation Format: Dimiter B. Avtanski, Arumugam Nagalingam, Panjamurthi Kupusamy, Neeraj K. Saxena, Dipali Sharma. Targeting epithelial-mesenchymal transition in breast cancer cells using Honokiol, a natural phenolic compound. [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 299. doi:10.1158/1538-7445.AM2013-299
THU0259 Periprosthetic Infection after Total Replacement of Largest Joints in Rheumatic Patients
Authors: V. Pavlov, S. Makarov, M. Makarov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> <h3>Objectives</h3> Periprosthetic infection (PI) after total hip and knee replacement (THR, TKR) is an actual and not fully solve problem of joint surgery in RP. We intend to compare a) the frequency of PI after THR versusTKR and b) results of the treatment for this complication <h3>Methods</h3> 1201 THR, n-1069 PTC, F/M – 3,6:1, age -49,6 (16-83), rheumatoid arthritis (RA) -323 PTC, juvenile rheumatoid arthritis (JRA) -124, ankylosing spondylitis (AS) -80, systemic lupus erithematosis (SLE) -79, psoriatic arthritis (PsA) -18, systemic scleroderma (SSD) -11, osteoarthritis (OA) -353, others (O) -81. 234 TKR, n-197 PTC, F/M – 4,9:1, age - 47,7 (19-75), RA -139 PTC, OA -38, JRA -14, one with JRA, SLE and AS PI registered in 7 THR with RA (2,18%), 1 with JRA (0,8%) and 1 with OA (0,28%), in 6 TKR with RA (2,5%). The treatment of PI included revision surgery, influx-drain system with daily constant antibiotics irrigation during two weeks. <h3>Results</h3> THR implants: one had preserved, 8-removed and 7 PTC of them are needing in repeated revision surgery. Implants of TKR: 2 had preserved, 3 – removed with subsequent arthrodeses. One THR patient died from diabetes complications, one TKR –died from infarction <h3>Conclusions</h3> Risk periprosthetic infection in TKR-patients a 1,5 times higher than THR-patients. RA-patients with THR had a 10 times higher risk periprosthetic infection than OA patients and it can assume, that rheumatoid arthritis may be one from some risk factors for this complication. <h3>Disclosure of Interest</h3> None Declared
FRI0216 Does ultrasonography guidance increase the yield of temporal artery biopsy in patients with giant cell arteritis? Results from a single-blinded randomized study
Authors: G. Germanò, N. Possemato, N. Pipitone, L. Cimino, L. Boiardi, G. Bajocchi, P. Macchioni, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Temporal artery biopsy (TAB) is the gold standard to diagnose giant cell arteritis (GCA), but is negative in approximately 20% of patients <h3>Objectives</h3> The study aimed to establish whether Color-doppler-ultrasonography (CDU)-guided TAB might provide a greater yield compared to standard TAB technique in patients with GCA <h3>Methods</h3> We enrolled 100 consecutive patients suspected of having GCA from September 2009 through December 2011. The average age of patients was 74 years. At randomization mean values of ESR were 54 mm/1st hour, mean CRP were 6 mg/dl (n.v. &lt;0.5). Two patients were excluded because biopsy showed no evidence of artery. 44 out of 98 patients were taking mean dose of 17.4 mg of prednisone daily for more than 2 weeks. Patients were randomized to undergoing US-guided TAB (group 1), or to undergoing TAB performed according to conventional technique (group 2). Patients randomized to group 1 were 47; those to group 2 were 51. All patients were evaluated by physical examination of the temporal arteries (PETA), CDU and TAB. CDU was carried out by a physician who was blinded to the clinical data of the patients. CDU was performed using an ESAOTE MyLab 70 device fitted with a LA435 probe set for examination of the temporal arteries. The common trunk and the main branches of the temporal arteries were screened in a longitudinal and transverse plane along the entire vessel course. In patients from group 1 the ultrasonographist marked the segment of the temporal artery which showed the largest halo if present. In patients from group 1 the TAB was performed in the segment marked by the ultrasonographist, while in patients from group 2 was carried in according to standard procedure. PETA was performed before CDU. PETA was considered positive in the presence of tenderness or decreased or absent pulse of the temporal arteries. Chi square test was used for statistical analysis. <h3>Results</h3> TAB was positive in 33/98 (33.7%) patients, including 17/47 (36.2%) in group 1 and 15/51 (29.4%) in group 2. The difference of TAB positivity between group 1 and 2 was not significant. In total, the halo was detected in 42 (42.9%) patients, 25 (53.2%) in group 1 and 15 (29.4%) in group 2.In the group 1, the frequency of positive biopsy in patients with US evidence of halo was 68% (17/25), while in the group 2 the biopsy was positive in 15 of the overall 51 patients (29.4%). The difference was statistically significant (p=0.0489; OR: 2.31; 95% CI: 0.1-5.3). <h3>Conclusions</h3> Halo-guided TAB was associated with a significantly greater probability of being positive. However, the frequency of TAB-positive patients was similar regardless of whether TAB was performed under CDU guidance or not. <h3>Disclosure of Interest</h3> None Declared
AB0721 Magnetic resonance imaging of sacroiliac joints in early polyarthicular peripheral psoriatic and rheumatoid arthritis (remarca investigation)
Authors: E. Y. Loginova, T. V. Korotaeva, E. L. Luchikhina, O. V. Zhelybina, A. V. Smirnov, D. E. Karateev, E. L. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Active sacroiliitis (SI) by magnetic resonance imaging (MRI) has been proposed as an important symptom of early spondyloarthritis (SpA) and would be helpful for the distinction between perhypheral polyarthicular psoriatic arthritis (PsA) and rheumatoid arthritis (RA) at an early stage. <h3>Objectives</h3> To compare involvement of sacroiliac joints by MRI, frequency of inflammatory back pain (IBP) and HLA-B27 in early perypheral polyarthicular PsA and RA. <h3>Methods</h3> 54 patients (pts) with early inflammatory polyarthritis were included, 29 (M/F – 13/16) with PsA, according to the CASPAR criteria, the mean age 36.5±11.27 yrs, the mean duration of disease 13.0±9.77 mo. and 25(M/F – 7/18) with RA, according to the ACR/EULAR 2010 criteria, the mean age 52.6±14.7 yrs, the mean duration of disease 4.0±1.72 mo. All pts underwent clinical examination (CE) to determine short-term IBP and IBP by ASAS criteria, HLA-B27 antigen test (in 27 PsA pts and in 20 RA pts) MRI of the SI joints by the apparatus "Signa Ovation" (0,35T "GE Medical Systems") according to REMARCA (<b>R</b>ussian Inv<b>E</b>stigation of <b>M</b>ethotrex<b>A</b>te and Biologics in Ea<b>R</b>ly A<b>C</b>tive Inflammatory <b>A</b>rthritis) protocol. Bone marrow oedema (BMO)/osteitis on STIR-images by MRI are believed to be a sign of active sacroiliitis (MRI-ASI). All MRI-scans were checked by blinded readers. Mean±SD, median and quartiles [Me (Q25; Q75)], t-test, χ2-test, Fisher's exact, Yule's coefficient of association (Q-level from -1 to 1) and Phi were performed. All p&lt;0.05 were considered to indicate statistical significance. <h3>Results</h3> Those pts with PsA and RA had an equal level of activity by DAS28 - 4.09±1.26/4.62±0.86 (t-test p&gt;0.24). In comparison a greater number of MRI-ASI was found in PsA than in RA – 12 pts (41.4%)/3pts (12%) accordingly (Fisher's exact, p&lt;0.016). No correlations were found between MRI-ASI and DAS28 in PsA and RA pts. In PsA pts IBP was found in 11 pts (37.9%), 6 out of 11 pts (54.5%) had IBP by ASAS criteria and 5 out of 11 pts (45.5%) had short-term IBP. In RA group 3 pts had only mechanical back pain. In PsA HLA-B27 was found in 9 out of 27 pts (33.3%) and in 3 out of 20 RA pts (15%) (t-test p&lt;0.014). A high level of association was found between IBP and ASI in PsA pts (Q=0.91, Phi=0.56, Fisher's exact p&lt;0,003) (see table 1). A modest association was found between HLA-B27 and ASI in PsA pts (Q=0.75, Phi=0.56, Fisher's exact p&lt;0.039) (see table 2). <h3>Conclusions</h3> MRI-ASI is quite common in early PsA but also can be found in early RA. In PsA pts MRI-ASI is strongly associated with IBP and moderately with HLA-B27 in most cases, so all three tests can be helpful in distinguishing polyarthicular PsA and RA at an early stage. <h3>Disclosure of Interest</h3> None Declared
AB0782 Indirect costs associated with ankylosing spondylitis in turkey
Authors: N. Akkoc, H. Direskeneli, H. Erdem, A. Gul, Y. Kabasakal, S. Kiraz, B. Durguner, O. Başer, V. Hamuryudan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The musculoskeletal symptoms, as well as extra-articular manifestations of ankylosing spondylitis (AS) decrease quality of life and productivity and result in significant direct and indirect costs, with the latter being even higher than the former. However, data on the economic burden of AS in Turkey are scarce. <h3>Objectives</h3> To describe indirect resource utilization for AS patients attending at rheumatology outpatient clinics of tertiary health centers in Turkey over a 1-year period and to identify demographic factors and clinical assessment measures associated with indirect costs. <h3>Methods</h3> Medical records of 650 prevalent AS patients attending rheumatology outpatient clinics in seven tertiary healthcare hospitals nationwide were examined to assess annual indirect healthcare costs. Eligible patients were age ≥18 and diagnosed with AS for at least 12 months. We assessed relevant indirect cost-related variables and activities, and actual costs. Multivariate regression was used to determine the effects of demographic factors and clinical assessment measures on indirect costs. The Pearson correlation matrix and the association between disease assessment measures and indirect costs were assessed. <h3>Results</h3> Mean (±SD) patient age was 40.1± 11.33 years, with 35% of the patients being female. 55% were employees, of which 59% had employer permission to miss work due to AS, costing patients an average €412 annually due to workday loss as calculated based on income level. 2% of the patients had other AS-related consultations not covered by insurance (acupuncture, homeopathic, other), bringing their average annual burden to Є2,482. 10.46% of the AS patients incurred additional AS-related costs (e.g. need for new car, apartment, special equipment), spending an additional Є1,978 per year. 6.92% of the patients required caregivers, costing €546 annually. Multivariate regression showed that age and gender played no significant role related to the increase in indirect costs. Patients needing AS related equipments reported significantly higher Global Disease Activity (GDA), visual analog scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and lower EuroQoL health status (EQ-5D) scores <h3>Conclusions</h3> AS represents a considerable economic burden to Turkish Society. Studies assessing chronic disease costs, especially in developing nations, are important to determine efficient allocation of the limited resources in such regions. <h3>Acknowledgements</h3> This study was sponsored by Pfizer Turkey <h3>Disclosure of Interest</h3> N. Akkoc: None Declared, H. Direskeneli: None Declared, H. Erdem: None Declared, A. Gul: None Declared, Y. Kabasakal: None Declared, S. Kiraz: None Declared, B. Durguner Employee of: Pfizer, O. Başer: None Declared, V. Hamuryudan: None Declared
Bevacizumab in hepatocellular carcinoma (HCC) in patients without metastasis and without invasion of the portal vein
Authors: J. D. Schwartz, M. Schwartz, D. Lehrer, D. Coll, M. Kinkhabwala, M. Sung, S. B. Holloway, S. Wadler
Journal: Journal of Clinical Oncology (2005)

4122 Bevacizumab in hepatocellular carcinoma (HCC) in patients without metastasis and without invasion of the portal vein Background: HCC is a vascular tumor; angiogenesis contributes to pathogenesis. Bevacizumab (anti-VEGF) delays progression in colon cancer and its effect may be dose-dependent. VEGF-inhibition has not been previously attempted in cirrhosis. Methods: We enrolled patients with unresectable HCC to bevacizumab at 5mg/kg or 10mg/kg every 14 days to assess safety and preliminary efficacy. Inclusion criteria were BR < 3.0mg/dl, transaminases 75K and PT within 4 seconds of normal. Additional criteria included no history of gastrointestinal bleed, myocardial infarction, stroke, or condition requiring antiplatelet or antithrombotic therapy. Results: An initial safety assessment indicates that 10 of 11 patients treated for at least 8 weeks tolerated bevacizumab at 5mg/kg with minimal toxicity. Two patients had serious esophageal bleeding which was likely secondary to progression of HCC and liver disease (although contribution of drug to these events cannot be excluded). The protocol has been modified to identify and treat esophageal varices prior to enrollment. Three patients treated at 10mg/kg have undergone at least 8 weeks of therapy with minimal toxicity (grade 1 fatigue, abdominal pain and diarrhea). For the first 13 patients evaluable for efficacy, 11 have had confirmed response or stability. Two patients had disease progression at less than 4 months. Two patients had partial responses, one with eventual progression at 11.3 months. For the 9 patients with stable disease, 6 had eventual progression at 5.5, 6.5, 6.5, 6.7, 7.2, and 7.6 months. Three others have ongoing stability at 3.5+, 3.9+, and 12.7+ months. At least four of the patients with confirmed response/stability had documented rapidly-progressing disease in the months before receiving therapy. Conclusions: Bevacizumab can be given safely at both 5mg/kg and 10mg/kg in HCC patients with localized, unresectable HCC, preserved liver function and no significant esophageal varices. Preliminary results suggest significant disease-modifying effect, including 6+ month stability in patients with prior rapid growth. No significant financial relationships to disclose.
Abstract 3014: Expression of hypoxia-inducible factors (HIF-1alpha) mediates Matrix Metalloproteinases (MMP) in colorectal carcinomas progression
Authors: Maqbool Ahmed, Azhar R. Hussain, Prashant Bavi, Rong Bu, Sahar M A Al-Janadi, Fouad Al-Dayel, Shahab uddin, Khawla S. Al-Kuraya
Journal: Cancer Research (2012)

Abstract Hypoxia-inducible factors (HIFs) are transcription factors that respond to changes in available oxygen in the cellular environment, specifically, to decreases in oxygen, or hypoxia. Most, if not all, oxygen-breathing species express the highly-conserved transcriptional complex HIF-1, which is a heterodimer, composed of an alpha and a beta subunit. HIF-1 transcription factor has been shown to promote pathogenesis of several malignancies. We have shown previously using a large cohort of CRC samples in a tissue micro array (TMA) format found that HIF-1α was expressed in the majority of CRC samples. HIF-1α over expression was found to be associated with MMP-2, and MMP-9. In the current study we investigated whether down regulation of HIF-1α by YC-1 a pharmacological inhibitor and gene silencing with specific HIF-1α siRNA leads to inhibition of cell proliferation and inhibition of apoptosis using a panel of CRC cell lines. Treatment of CRC cell lines with YC-1, inhibitor of HIF-1α resulted in inhibition of cell viability via induction of apoptosis. This apoptosis was initiated via loss of mitochondrial potential leading to the release of cytochrome c that resulted in sequential activation of caspases-9, and -3 and cleavage of PARP. Interestingly, pharmacological inhibition of HIF-1α also down-regulated expression of MMP-2, and MMP-9 in CRC cell lines. This data was further validated by siRNA knockdown strategy where expression of siRNA against HIF-1α also down-regulated the expression of HIF-1α, MMP-2 and MMP-9. Altogether, these data suggests that HIF-1α and its associated signaling pathway play a critical role in CRC tumorigenesis, therefore targeting of HIF-1α expression may be a viable therapeutic intervention for treatment of these 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 3014. doi:1538-7445.AM2012-3014
A10.09 Safety data of four treatment regimens in early rheumatoid arthritis patients
Authors: EV Fedorenko, GV Lukina, YA Sigidin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To compare safety data in patients (pts) with early (&lt;2 years duration) RA who were randomly assigned to receive 4 different regimens of DMARDs treatment. <h3>Methods</h3> One hundred forty-one pts with RA of less than 2 years duration (122 women, mean age 51 years, mean disease duration 24 weeks, mean DAS 28 5,9; 64% RF-positive,59% ACCP-positive) were randomly allocated to receive one of the following treatment regimens: methotrexate (MTX, up to 20 mg/week, 35 pts); MTX plus prednisolone (P) 10 mg daily (MTX-P, 34 pts); MTX-P plus methylprednisolone (MP) 1000 mg intravenously on the first day of treatment (MTX-P-MP, 35 pts); leflunomide 20 mg daily (LEF, 37 pts). Duration of treatment was one year. Control points were 3, 6 and 12 months from the initiation of therapy. Safety data was assessed at the main control points. <h3>Results</h3> At baseline all groups were comparable in their demographic, clinical and radiographic characteristics. Onehundred twenty-seven pts completed the study. Side effects were registered in the same number of patients in eachgroup (9 patients; 24.3%-26%). Therapy had to bestopped in six patients due to side effects: MTX − 1&nbsp;(depigmentation of the skin), MTX-P − none, MTX-P-MP − 1 (stomatitis) and LEF − 4 (dermatitis-2; pancytopenia with platelet count&nbsp;43 ×10<sup>9</sup>/L, erythrocyte 2.9×10<sup>12</sup> /L, WBC 2×10<sup>9</sup> /L-1; angioedema,&nbsp;periorbital oedema and dermatitis with itching-1). Other side effects were mild: MTX − 8 pts (dyspepsia-1,elevation of transaminases-6, hair loss-1), MTX-P − 9 pts (Cushing<sup>,</sup>s syndrome-1, hair loss-1,anaemia-1, elevation of transaminases-4,&nbsp;arterial hypertension-2), MTX-P-MP − 8 pts (hair loss-1,&nbsp;dermatitis-1,&nbsp;elevation of transaminases-5, Cushing9s syndrome-1) and LEF − 5 pts (elevation of transaminases-5). <h3>Conclusion</h3> Safety profile was the same in all groups. In most cases side effects were moderate or minimal. The most serious side effects, leading to the discontinuation of the therapy, were registered in LEF group. There was no withdrawal of treatment in MTX-P group.
Lung Herniation after Minimally Invasive Cardiothoracic Surgery
Authors: Alexander Weymann, Gabor Szabo
Journal: New England Journal of Medicine (2011)

One year after undergoing minimally invasive direct coronary-artery bypass surgery, a 67-year-old man was admitted to hospital with a well-demarcated deformity overlying the third intercostal space of the left anterior hemithorax. On examination, the lesion had a positive cough impulse and spontaneous reduction with inhalation. Breath sounds could be clearly heard within the mass. Computed tomographic images of the chest confirmed that a large portion of the lung had herniated through an intercostal defect in the chest wall (Panel A, arrow, axial view; Panel B, arrow, sagittal view). Lung herniation is a rare complication of minimally invasive cardiothoracic surgery. In . . .
A relationship between extracapsular involvement and response to steroid treatment in polymyalgia rheumatica: too soon to conclude?
Authors: Li Yang, Hao Zhou, Haiyun Tang, Ashley M Lee, Harrison X Bai
Journal: Annals of the Rheumatic Diseases (2015)

A relationship between extracapsular involvement and response to steroid treatment in polymyalgia rheumatica: too soon to conclude?We read with great interest a recent paper by Mackie et al. 1 The authors found that an extracapsular pattern of inflammatory involvement on whole-body, multiple-joint MRI was associated with complete glucocorticoid response, higher pretreatment C-reactive protein and serum interleukin-6.We commend the authors for studying such a challenging disease with advanced imaging and linking it to treatment response.However, we have several concerns.First, it is unclear what criteria were used to distinguish an MRI of 'extracapsular pattern' from that of 'non-extracapsular pattern'.Since at least eight large joints were evaluated bilaterally, are there patients with an extracapsular pattern in certain joints but not in others?How many joints with an extracapsular pattern of inflammation are needed in order to classify a patient as 'extracapsular'?In addition, it is uncertain if the scoring for the degree of inflammation refers to the extracapsular inflammation, intracapsular inflammation or both.Previous studies have shown that bursitis and glenohumeral joint effusions on MRI were seen in almost all patients with polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA) without any difference in frequency between these two groups. 2If the degree of extracapsular inflammation was taken into account during the scoring process (as it seems to be the case according to figure 1 of the paper), it is unsurprising that patients with PMR with extracapsular pattern had higher scores than patients with PMR with non-extracapsular pattern and patients with RA.