tbuckley/cabot-search huggingface dataset:
Abstract 5584: Disregulation of phosphorelated Amplified In Breast Cancer3 (AIB3) contributes to poor prognosis and mediates trastuzumab efficacy in breast cancer patients
Authors: Hao Zhang, Hongmei Dong, Yuping Chen, Xueyun Zhong
Journal: Cancer Research (2012)

Abstract Trastuzumab (Herceptin) is the first line HER2 (ErbB2)/neu-directed therapy for the treatment of patients with metastatic breast cancer. Although the efficacy of trastuzumab depends on the HER2/neu status of the tumour, the single-agent response rate ranges from 12 to 30% and ew patients respond to trastuzumab monotherapy largely due to various resistance mechanisms. Amplifeid In Breast Cancer3 (AIB3) is a transcriptional coactivator. AIB3 plays an important role in embryonic development, adipocyte differentiation, metabolism. AIB3 was initially found to be amplified in subgroup of breast cancer patients. Our previous data using knockout mouse mode combined cell culture indicate that AIB3 plays important role in breast tumorigenesis. Here we report that AIB3 can be phosphorylated by MAPK at S884 site and phosphorylation at S884 of AIB3 dramatically reduced ligand-dependent AIB3 interactions with estrogen receptors when compared with the wild-type unphosphorylated form, although there was a significant increase of interactions with the unliganded receptor. Misexpression of phosphorylated AIB3 was observed in human breast cancer tissues and disregulation of phosphorylated AIB3 was associated with patients’ poor prognosis. Breast cancer is a heterogeneous disease and intrinsic subtypes play an extremely important role in improve on current standards for breast cancer prognosis and prediction of chemotherapy. Noticeably, phosphorylated AIB3 was highly expressed in Her2-enriched subtype of human breast cancer patients, as well as in the mammary tumor of MMTV-Her2 transgenic mice. Mechanism studies reveal that phosphorylated AIB3 alters trastuzumab efficacy in cultured breast cancer cells. The association between pAIB3 and important clinical outcomes confers pAIB3 a significant prognostic marker in breast cancer. Phosphorylated AIB3 as a modulator in ErbB2-MAPK regulating loop represents a potentially novel mechanism for trastuzumab (herceptin) efficacy. The implied interaction between pAIB3 and Her2 suggests the potential of dual targeting of Her2 and pAIB3 as a promising therapeutic approach for personalized breast cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5584. doi:1538-7445.AM2012-5584
New Options in Anticoagulation for Atrial Fibrillation
Authors: Gregory J. del Zoppo, Misha Eliasziw
Journal: New England Journal of Medicine (2011)

The presence of atrial fibrillation significantly increases the risk and burden of thromboembolic stroke.1 Warfarin is the reference standard treatment for the primary prevention of embolic stroke during atrial fibrillation.2 However, the long-term use of warfarin has its limitations. Although guidelines suggest a target international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0) for this indication,2 only about 60% of patients have an INR within the recommended range at a given time in usual clinical practice. This is the reason that is most often given for the search for other oral antithrombotic agents that could be simpler to manage . . .
SP0091 MRI in spondyloarthritides - update on the current state
Authors: R.G. Lambert
Journal: Annals of the Rheumatic Diseases (2013)

The last decade has seen dramatic advances in the role of MRI in the clinical management of patients with inflammatory arthritis and much research has been done investigating its diagnostic capabilities. MRI is now regarded as the most sensitive imaging modality for the detection of spondyloarthritis (SpA) in early disease which may be detected even when radiographs are completely normal. Proposed classification criteria now include a positive MRI demonstrating sacroiliitis as an imaging criterion indicative of SpA together with at least one clinical feature of SpA. MRI can reliably measure bone marrow inflammation in the axial skeleton and is now widely used in clinical trials as a surrogate outcome to objectively measure response to anti-inflammatory therapy especially biologic agents. Recent research also confirms that the diagnostic utility of MRI is high and, as well as active inflammation, structural lesions can be clearly identified that have important diagnostic relevance. MRI research continues to provide important evidence in support of the link between active inflammation and subsequent bone formation. In addition to improving our understanding of the findings on MRI, research has also highlighted new acquisition techniques that may have important or useful applications in imaging of the spine and bone marrow in SpA. Whole body MRI can quickly image the entire axial skeleton, shoulder, thorax, pelvis and lower extremities and may be very suitable for SpA imaging. New or newly applied techniques, such as the Dixon technique, chemical shift imaging, water excitation, high-resolution 3 dimensional acquisitions and others are being investigated, with mixed success, for potential use in detecting pathology in bone, cartilage or bone marrow. <h3>Disclosure of Interest</h3> R. Lambert Consultant for: Abbott Laboratories
AB0142 Mir-223 Expression Profile as A Biomarker in Rheumatoid Arthritis
Authors: R. Shumnalieva, D. Kachakova, S. Monov, R. Kaneva, Z. Kolarov, R. Rashkov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with altered miRNA expression profile in peripheral blood, synovial fluid and synovial membrane. There are several reports on the role of miR-223 in the disease pathogenesis but data on its use as biomarkers in the clinical practice are lacking. <h3>Objectives</h3> To analyze the expression of miR-223 in peripheral blood (PB) and synovial fluid (SF) from RA patients in regard to its use as biomarker for disease activity and severity. <h3>Methods</h3> Total RNA including miRNAs was isolated from the PB of 57 RA patients and 20 healthy controls (HCs) using PAX gene tubes and from paired SF samples from 44 patients and 11 controls by RNeasy Protect Cell Mini kit (according to manufacturer9s protocol). Reverse transcription was performed in order to synthesize cDNA by using miScript II RT kit. Expression of miR-223 was analyzed by relative quantitation method (2^-(ΔΔCq)) using quantitative real-time polymerase chain reaction (qPCR). RNU6B gene was used as reference control for normalization. Data were analyzed by SPSS. The results were related to the clinical presentation and laboratory data for disease activity. The latter was assessed using disease activity score 28 (DAS28). <h3>Results</h3> MiR-223 was underexpressed in 65.91% of RA SF samples compared to PB samples. We found statistically significant (p&lt;0.05) overexpression of miR-223 in 81.82% of the SF samples and 35.1% of the PB samples from RA patients compared to HCs. Receiver operating characteristic (ROC) curve analysis was constructed in order to evaluate the diagnostic accuracy of miR-223 in SF by using relative expression (RQ) values. Area under the curve (AUC) was 0.841 (95 CI: 0.727-0.956) with 81.4% sensitivity and 72.7% specificity when RQ value is greater than or equal to 2. The result was statistically significant (p=0.001). Levels of miR-223 in SF correlate with laboratory markers for disease activity such as ESR (p&lt;0.01 two tailed) and CRP (p=0.051 two tailed), with the swollen joint count (p=0.029 two tailed), VAS (0.027 two tailed) and DAS28 score (p=0.003 two tailed). The Spearman9s correlation coefficients were 0.463, 0.338, 0.300, 0.303 and 0.402 respectively. No correlations between miR-223 levels in blood and clinical pathological characteristics were observed. Independent T test analysis showed that miR-223 expression in blood is associated with the RA diagnosis. <h3>Conclusions</h3> MiR-223 is a potential biomarker for diagnosis with high sensitivity and specificity and for evaluating the activity of RA as its expression is altered significantly in synovial fluid and correlates with diseases activity measured by DAS28 score. We did not observed correlation between the expression of miR-223 in blood and the disease activity but we found week correlation with the RA diagnosis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5687
Sentinel Lymph Node Mapping for Endometrial Cancer: A Modern Approach to Surgical Staging
Authors: Nadeem R. Abu-Rustum
Journal: Journal of the National Comprehensive Cancer Network (2014)

Most patients with endometrial cancer will present with early-stage disease. Although the rate of metastasis in these patients is low, proffering excellent prognoses, the standard of treatment in many practices still includes a complete or selective pelvic and para-aortic lymphadenectomy for staging; and accurate surgical staging is the most important prognostic factor. Many patients will undergo a comprehensive lymphadenectomy despite having disease confined to the uterus, resulting in prolonged operating time, additional cost, and potential side effects, such as lower extremity lymphedema. However, recent studies show that a complete lymphadenectomy may have no therapeutic benefit in patients with early-stage endometrial cancer. Sentinel lymph node (SLN) mapping, which has been used in other cancer types, may be an acceptable surgical strategy between a complete lymphadenectomy and no nodal evaluation in patients with endometrial cancer. SLN mapping is based on the concept that lymph node metastasis is the result of an orderly process; that is, lymph drains in a specific pattern away from the tumor, and therefore, if the SLN, or first node, is negative for metastasis, then the nodes after the SLN should also be negative. This approach can help patients avoid the side effects associated with a complete lymphadenectomy, although disease must be thoroughly staged for accurate prognosis and determination of appropriate treatment approach. Surgeon experience, adherence to an SLN algorithm, and the use of pathologic “ultrastaging” are key factors for successful SLN mapping.
Allogeneic stem cell transplantation in patients with Hodgkin's-Lymphoma
Authors: H. Pohl, A. Shimoni, N. Kroeger, H. Martin, V. Vucinic, N. Basara, A. Nagler, A. Zander, A. A. Fauser, M. G. Kiehl
Journal: Journal of Clinical Oncology (2004)

6690 Background: Due to intensified standard radio-chemotherapy a substantial proportion of patients will be cured of Hodgkin's Lymphoma. In patients with relapse after standard therapy, the therapy of choice is an autologous stem cell transplantation with high remission rates. Despite therapeutic progress some patients suffer from refractory or relapsing disease. As graft versus Hodgkin's lymphoma effects have been described allready, allogeneic stem cell transplantation might be an therapeutic effort in these high risk patients. Methods: We analysed the course of 14 patients receiving an allogeneic transplant between 07/99 and 11/03. Results: Median age was 23 years (range 19 to 41) and patients received a median of 4.5 chemotherapies (range 2 to 8) before transplant. All but one received previously an autologous transplant. Disease status at transplant was CR in 2, PR in 1, SD in 5, and PD in 6 patients. Eight patients received a transplant from a related HLA-identical donor and 6 from an unrelated donor (4 matched, 2 DRB1 mismatch). All but one received peripheral blood stem cell grafts. Different conditioning regimens were used (Fludarabine (Flu)/busulfan (Bu) “b ATG n=6, Flu/Melphalan (Mel) “b Campath n=5, Bu/Cy n=1, TBI/Cy n=1, Mel/Thiotepa/ATG n=1). Four patients received donor lymphocyte infusions in escalating dosage for SD (n=2), PD (n=1), or mixed chimerism (n=1), respectively. OS is 43% and DFS 28.6% after a median FU of 25 months (1 to 52 months). TRM is 14.3 %. Five patients died due to disease progression and one due to refractory GVHD. Conclusions: Taking into account that all patients were heavily pre-treated and that only two patients were transplanted in CR these data argue for a strong graft versus Hodgkin effect. Especially a melphalan/fludarabin “b ATG reduced conditioning seems to be very effective in this setting. Furthermore, it's speculative but very likely that the results of allogeneic stem cell transplantation will improve significantly if patients receive the allo transplant earlier during their disease. Thus, risk factors should be defined and those patients with a high risk feature should be scheduled for allo transplant within a controlled clinical trial. No significant financial relationships to disclose.
Octreotide Scans Are Positive in a Subset of Patients with Hepatocellular Carcinoma
Authors: Ian Rabinowitz, Robert Telepak, Fa-Chyi Lee
Journal: Clinical Nuclear Medicine (2002)

In vitro data suggest that a proportion of hepatocellular carcinomas express the somatostatin receptor. However, in vivo data are lacking. There has been little reported use of octreotide scans in hepatocellular carcinomas. This study was performed to determine the percentage of positive results of octreotide scanning in patients with hepatocellular carcinoma.In-111 octreotide scans were performed in the standard manner in eight patients with unresectable hepatocellular carcinoma. Computer fusion imaging of the nuclear medicine and computed tomographic scans was performed in selected patients.Five of eight (63%) patients tested had hepatocellular carcinomas that displayed focal tracer uptake.This is the first report of positive uptake of octreotide scans in patients with hepatocellular carcinoma. These findings may have implications for the treatment of hepatocellular carcinoma with octreotide. Furthermore, these results may broaden the differential diagnosis in patients with positive results of octreotide scanning.
Abstract 3669: Chemoprevention of mammary and prostate cancer by phenethyl isothiocyanate <i>in vivo</i> is associated with suppression of vimentin protein expression.
Authors: Kozue Sakao, Eun-Ryeong Hahm, Shivendra V. Singh
Journal: Cancer Research (2013)

Abstract Phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables (eg, watercress), exhibits in vivo preventive efficacy against cancer in rodents induced by structurally diverse chemical carcinogens. We have also shown recently that dietary administration of PEITC (3 μmol PEITC/g diet) confers significant protection against breast and prostate cancer development in MMTV-neu and TRAMP model, respectively. Prevention of prostate cancer by PEITC administration in TRAMP mice was associated with induction of E-cadherin protein expression. Because suppression of E-cadherin protein level concomitant with induction of mesenchymal markers (eg, vimentin) is a biochemical hallmark of epithelial-mesenchymal transition, a process implicated in cancer metastasis, we hypothesized that PEITC treatment was likely to suppress vimentin protein expression. Contrary to this prediction, exposure of cultured human breast (MDA-MB-231) and prostate cancer cells (PC-3 and DU145) to PEITC resulted in a dose-dependent increase in vimentin protein level, which was observed as early as 6 hours post-treatment and persisted for the duration of the experiment (24 hours). RNA interference of vimentin resulted in a modest augmentation of PEITC-mediated inhibition of MDA-MB-231 and PC-3 cell migration as well as cell viability. Furthermore, the PEITC-induced apoptosis was moderately increased upon siRNA knockdown of vimentin protein level in MDA-MB-231 and PC-3 cells. To our surprise, PEITC administration caused a marked decrease in vimentin protein expression in vivo in tumors of MMTV-neu (breast) and TRAMP mice (prostate). The results of the present study indicate that cancer chemoprevention by PEITC in vivo is associated with suppression of vimentin protein expression. The present study was supported by the grant CA101753-09 awarded by the National Cancer Institute. Citation Format: Kozue Sakao, Eun-Ryeong Hahm, Shivendra V. Singh. Chemoprevention of mammary and prostate cancer by phenethyl isothiocyanate in vivo is associated with suppression of vimentin protein expression. [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 3669. doi:10.1158/1538-7445.AM2013-3669
Obstruction of the Left Pulmonary Artery by Aortic Arch Aneurysm
Authors: LAURENT MIROULT, BRIAN McCANDLESS, MITCH TUBLIN, JEFFREY COOPER
Journal: Clinical Nuclear Medicine (1996)

A 75-year-old man had exertional dyspnea for 6 months and hoarseness for 3 weeks. Arterial blood gases on room air showed pO2 53 mmHg and pCO2 33 mmHg. A ventilation-perfusion scan showed normal ventilation to both lungs and absent perfusion to the left lung. A chest radiograph showed a mediastinal mass displacing the trachea to the right and the left main bronchus inferiorly. CT and MRI showed a 12-cm aneurysm that involved the entire aortic arch. Loss of perfusion to one lung with preserved ventilation is a rare complication of aortic arch aneurysm and in only one reported case has involved the left pulmonary artery.
AB0214 TLR2 ligation induces the production of IL-23/IL-17 via IL-6, STAT3 and NF-KB pathway in patients with primary sjÖgren’s syndrome
Authors: S.M. Jung, J.H. Lee, J. Lee, E.-J. Kim, S.-K. Kwok, M.-L. Cho, K.S. Park, H.-Y. Kim, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sjögren's syndrome is a chronic, slowly progressive autoimmune disease characterized by lymphocytic infiltration of the exocrine glands resulting in dry mouth and dry eyes. Recent studies have suggested that T helper 17 cell (Th17) plays a key role in the pathogenesis of autoimmune diseases, and activation of toll-like receptor (TLR) is thought to be linked with autoimmune inflammation. <h3>Objectives</h3> The study was undertaken to investigate the interrelation of TLR and IL-17 in the salivary glands of patients with primary Sjögren's syndrome (pSS) and to determine the role of TLR and IL-17 in the pathophysiology of pSS. <h3>Methods</h3> The expressions of various TLRs, IL-17 and the cytokines involved in Th17 cell differentiation including IL-6, IL-23, TNF-αand IL-1βwere examined by immunohistochemistry and confocal staining in salivary glands of pSS patients. After peripheral blood mononuclear cells (PBMCs) were treated with TLR specific ligands, the induction of IL-17 and IL-23 was determined using real-time PCR and ELISA. The signaling pathway that mediates the TLR2 stimulated production of IL-17 and IL-23 was investigated by using treatment with specific signaling inhibitors. <h3>Results</h3> TLR2, TLR4, TLR6, IL-17 and the cytokines associated with Th17 were highly expressed in salivary glands of pSS patients but not in controls. The expressions of TLR2, TLR4 and TLR6 were observed in the infiltrating mononuclear cells and ductal epithelial cells, whereas IL-17 and related cytokines were mainly observed in infiltrating CD4+ T cells. The stimulation of TLR2, TLR4 and TLR6 synergistically induced the production of IL-17 and IL-23 from the PBMCs of pSS patients especially in the presence of TLR2 stimulation. IL-6, STAT3 and NF-kB pathways were implicated in the TLR2 stimulated IL-17 and IL-23. <h3>Conclusions</h3> Our data demonstrate that TLR2 ligation induces the production of IL-23/IL-17 via IL-6, STAT3 and NF-kB pathway in pSS. Therefore, therapeutic strategies that target TLR/IL-17 pathway might be strong cadidates for treatment modalities of pSS. <h3>Disclosure of Interest</h3> None Declared
HALLAZGOS EN LAS COLONOSCOPIAS REALIZADAS AL AÑO TRAS LA EXTIRPACIÓN PREVIA DE ADENOMAS DE ALTO RIESGO EN EL PROGRAMA DE CRIBADO DE CCR. ¿SE PUEDE ALARGAR ESTE INTERVALO?
Authors: M Gomez, J Carrascosa, M Basterra, MDR Calderon
Journal: Endoscopy (2014)

Introducción: Las guías actuales (AGA, ESGE, European Guidelines for Quality Assurance in CCR) indican recomendaciones diferentes sobre el intervalo adecuado para realizar el control tras la extirpación de adenomas de alto riesgo (AAR), variando entre 1 – 3 años.
1204 PHARMACOKINETICS OF MIRAVIRSEN, A MIR-122 INHIBITOR, PREDICT THE PROLONGED VIRAL LOAD REDUCTION IN TREATMENT NAIVE GENOTYPE 1 HCV INFECTED PATIENTS
Authors: R. Persson, M. Hodges, B.D. King, A. Chen, K. Zeh, A.A. Levine
Journal: Journal of Hepatology (2012)
The Treatment of Acute Low Back Pain — Bed Rest, Exercises, or Ordinary Activity?
Authors: Antti Malmivaara, Unto Häkkinen, Timo Aro, Maj-Len Heinrichs, Liisa Koskenniemi, Eeva Kuosma, Seppo Lappi, Raili Paloheimo, Carita Servo, Vesa Vaaranen, Sven Hernberg
Journal: New England Journal of Medicine (1995)

Bed rest and back-extension exercises are often prescribed for patients with acute low back pain, but the effectiveness of these two competing treatments remains controversial.
Abstract 3298: Arsenic induces human bronchial epithelial cell transformation featured with tumor-initiating cells
Authors: Qingshan Chang, Fei Chen, Yongju Lu
Journal: Cancer Research (2012)

Abstract Arsenic is a well-known human carcinogen. Chronic exposure to arsenic is associated with cancers in various tissues, including skin, urinary bladder, lung, liver, kidney and prostate. However, the mechanism underlying arsenic-induced carcinogenesis remains elusive. Here, we demonstrate that long-term (six month) exposure to low levels of sodium arsenite (0.25 µ M) in human bronchial epithelial cell line (BEAS-2B) results in altered morphology, increased cell proliferation and anchorage-independent colony formation in soft agar, indicative of malignant transformation of these cells. Moreover, tumorigenesis analysis revealed that s.c. inoculation of the arsenic-transformed cells can induce tumors in nude mice. The tumors can be observed after 2-3 weeks even only 500 arsenic-transformed cells were injected, suggesting that these transformed cells induced by long-term and low-dose arsenic treatment are highly tumorigenic. Additional studies indicated that some of these arsenic-transformed cells exhibit characteristics of tunor-initiating cells (TICs) or cancer stem cells (CSCs), such as overexpression of Oct3/4, Nanog, Sox2, Klf4, and C-myc. Tumor sphere formation assay, a general procedure in defining TICs or CSCs, suggested that about 5% of these arsenic-transformed cells can form tumor spheres in non-adherent plates. The tumor sphere forming cells were enriched through serial passage of the cells collected from tumor spheres. Flow cytometry sorting showed that 90% of these sphere cells are CD49f positive, whereas CD133, CD44, EpCAM, and c-kit were not detected. Overexpression of CD49f was confirmed by immunoblotting, which indicated an increased CD49f level in the arsenic-transformed cells relative to the non-transformed BEAS-2B cells. Finally, the ability of sphere formation and colony formation in soft agar was compared between the cells showed the strongest and the weakest CD49f expression and suggested that the cells with the strongest CD49f expression are more capable of forming tumor spheres and colonies. In conclusion, our data suggested that the transformed cells induced by arsenic have features of TICs or CSCs. 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 3298. doi:1538-7445.AM2012-3298