tbuckley/cabot-search huggingface dataset:
Abstract LB-474: Estrogen receptor regulated long non coding RNA: An evolving paradigm in prostate cancer progression
Authors: Dimple Chakravarty, Andrea Sboner, Eugenia Giannopoulou, Olivier Elemento, Archa Fox, Mark Rubin
Journal: Cancer Research (2012)

Abstract Prostate cancer is the second leading cause of cancer death in men. Anti-androgen therapy has been the preferred modality of treatment for several years, however prostate tumor co-opts alternate molecular mechanisms to overcome need for androgen and thereby become “castrate resistant”. Several prognostic markers have received functional evaluation in clinical setting; unfortunately current biomarkers are not accurate enough to predict disease progression and/or response to anti-androgen therapy. Thus there is an unmet need for novel biomarkers. Several studies have indicated that Estrogen receptor (ER) plays an important role in different types of tumors and while the importance of ER/E2 signaling pathway has been extensively investigated in breast cancer and other gynecological malignancies, the impact of this pathway on malignancies associated with other tissues like prostate warrants further investigation. Here we report a novel ERα- lncRNA signaling axis in prostate cancer progression. Our data provides compelling evidence to demonstrate that expression of ERα can “over-ride” requirement of androgens or androgen receptor during prostate cancer progression. Using a combination of ChIP-seq and RNA-seq approach we successfully identified a compendium of ER regulated lncRNA. We have utilized several biochemical assays and invivo xenograft studies to demonstrate the oncogenic relevance of ERα regulated lncRNA. Expression of lncRNA correlated well with clinicopathological variables in several patient cohorts. Finally we have tested therapeutic efficacy of targeting these oncogenic lncRNA using siRNA encapsulated chitosan based nanoparticles either single or in combination with current treatment modalities. In conclusion we have identified ER-regulated lncRNA as novel biomarkers for prostate cancer progression and therapy resistance in patients with advanced PCa. 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 LB-474. doi:1538-7445.AM2012-LB-474
First Pass Tc-99m MIBI Ventriculography in the Assessment of Left Ventricular Diastolic Function
Authors: MOHSEN SHARIFI, NANDA KHEDKAR, PATRICK PELLER, CHARLES MARTINEZ, RICHARD SORKIN, JEFFREY LAKIER
Journal: Clinical Nuclear Medicine (1996)

Tc-99m MIBI is used for myocardial imaging and firstpass studies. However, little is known about its utility in the assessment of left ventricular diastolic function. The authors retrospectively compared first pass studies of Tc-99m MIBI at rest with Doppler flow velocity measurements to assess left ventricular diastolic performance. Thirty-nine patients who had both studies performed within 48 hours of each other were evaluated. Three indices of diastolic function were measured by first pass Tc-99m MIBI ventriculography and Doppler echocardiography: 1) Time to peak early diastolic velocity; 2) normalized peak filling rate; and 3) half filling fraction. The results demonstrated a correlation of 0.82 (P < 0.001), 0.82 (P < 0.001), and 0.53 (P = 0.001) for the above indices, respectively. This study indicates that the indices of left ventricular diastolic function by first pass Tc-99m MIBI compare favorably with those derived from Doppler flow velocity measurements in which the diagnostic value has been previously established. Both methods accurately reflect diastolic flow and may facilitate clinical evaluation of diastolic function.
A8.04 The histone methyltransferase dot1l is essential for growth and homeostasis of the articular cartilage
Authors: S Monteagudo, F Cornelis, L Storms, RJ Lories
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> DOT1L is the only known H3K79 histone methyltransferase. Genome-wide association and functional studies identified the <i>DOT1L</i> gene to be associated with cartilage thickness and hip osteoarthritis (OA) and showed an interaction of DOT1L with canonical Wnt signalling. Variations in the <i>DOT1L </i>gene are also associated with human height. These findings and our earlier <i><i>in vitro</i></i> insights prompted us to investigate the impact of DOT1L loss of function <i><i>in vivo</i></i>. <h3>Methods</h3> We generated a conditional cartilage-specific knockout (KO) model of DOT1L by crossing <i>Dot1l<sup>fl/fl</sup></i> mice with <i>Col<sup>2</sup>-Cre<sup>+/-</sup></i>mice. The deletion of exon2 in the <i>Dot1l </i>gene in cartilage was confirmed by PCR. We performed skeletal staining to identify skeletal abnormalities and growth defects, and histology of the growth plate. To study if the absence of DOT1L activity causes the development of early OA, we injected the chemical DOT1L inhibitor EPZ-5676 intra-articularly in the right knee of 8-week-old wild-type C57Bl/6 mice. Severity of disease was determined by histological scores on sections throughout the knee. Both cartilage damage and synovial hyperplasia were assessed based on OARSI guidelines. Based in our <i><i>in vitro</i></i> observations, we analysed the effect of DOT1L loss of function on specific Wnt target genes in either DOT1L cartilage-specific KO mice or in mice injected with EPZ-5676, by immunohistochemistry. <h3>Results</h3> A growth defect resulting in short stature became quickly apparent and resulted in mortality from the age of 4-weeks onwards in <i>Dot1l</i> cartilage-specific KO mice. These DOT1L deficient mice exhibited changes in the growth plates with a reduced and disorganised proliferative and pre-hypertrophic zone. In mice injected with EPZ-5676, histology severity scores were significantly increased over time compared to control treatment groups. We confirmed the regulatory role of DOT1L on canonical Wnt signalling in cartilage, since the absence of DOT1L activity in either cartilage specific KO mice or mice injected with DOT1L inhibitor resulted in increased protein levels of specific Wnt target genes. <h3>Conclusions</h3> Our findings support an essential role for DOT1L in growth and cartilage homeostasis as a key regulator of canonical WNT signalling in the joint.
P112 LIVER DAMAGE DETERMINES THE GENE EXPRESSION PROFILE OF LIVER PROGENITOR CELLS AND THEIR CONTRIBUTION TO HEPATIC REGENERATION
Authors: D. Rodrigo-Torres, S. Affò, M. Coll, O. Morales-Ibanez, C. Millán, D. Blaya, J.J. Lozano, J. Caballería, V. Arroyo, P. Ginès, R. Bataller, P. Sancho-Bru
Journal: Journal of Hepatology (2014)
THU0192 Subclinical Baker's Cysts and Functional Limitation in Patients with Knee Osteoarthritis: Ultrasonographic and Power Doppler Study
Authors: A. Abogamal, A. Kasem, H.S. Nasser, S. Abdulhakim, A.M. Dewedar, T.M. Abd Elghaffar, F.H. Zayed, E.A. Helal, K.F. Elhasanein
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Baker9s cysts have a significant functional impact in patients with knee osteoarthritis (KOA), which in turn made its detection an important issue. Despite the impact of these cysts, clinical diagnosis remains of low sensitivity which raises the possibility of subclinical cysts. <h3>Objectives</h3> Estimate the subclinical presence of popliteal cyst and its impact on functional limitation in patients with KOA. <h3>Methods</h3> Study was carried out on 444 patients with primary KOA, grade III according to kellgren and Lawrence scale with absence of any clinical signs suggesting the presence of Baker9s cyst. Knee functional status was assessed using KOOS scale for Pain, other Symptoms, Activities of Daily Living (ADL), Sport and Recreation Function (Sport/Rec) and knee-related Quality of Life (QOL). All patients were assessed by Ultrasound and power Doppler for detection of Baker9s cyst. <h3>Results</h3> US showed that 396 (89.2%) patients out of 444 had no Bakers cyst and they represent group one, on the other hand bakers cyst detected in 48 (10.8%) patients which represent group two. Comparison of both groups shows that KOOS scale parameters was significantly higher in group one than group two, as t was 9.4 for Pain, 8.2 for Symptom, 10.1 for ADL, 17.9 for Sport/Rec, and 11.3 for QOL and p&lt;0.001. On the other hand a significant negative correlation was found between the cyst size and the KOOS parameters where r was -0.794, -0.702, -0.653, -0.448, -0.607 for Pain, Symptom, ADL, Sport/Rec, and QOL respectively and p&lt;0.001. <h3>Conclusions</h3> According to our results Baker9s cysts appears to be frequently present subclinically and its subclinical presence was associated with highly significant functional limitation of the Knee joint. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1144
Abstract P3-03-03: A tri-modality imaging assessment algorithm to evaluate neoadjuvant therapy response in patients with operable breast cancer
Authors: H Umphrey, W Bernreuter, K Bland, J Carpenter, C Falkson, A Forero, K Keene, H Krontiras, R Meredith, M Urist, J De Los Santos
Journal: Cancer Research (2012)

Abstract Background: To determine the negative predictive value (NPV), positive predictive value (PPV), accuracy, sensitivity and specificity of a pre-surgical tri-modality imaging assessment algorithm to determine complete pathologic response (pCR) post neoadjuvant therapy in patients with operable breast cancer. Methods: A retrospective analysis was performed on data collected from patients receiving neoadjuvant therapy and pre-surgical breast magnetic resonance imaging (MRI), ultrasound (US) and mammography between 2004 and 2010 at our institution. Tri-modality imaging was reviewed by a single blinded breast radiologist and evaluated for predetermined modality specific parameters as defined in Table 1. The NPV, PPV, accuracy, sensitivity, and specificity were calculated on the basis of the final surgical pathology report with a complete pathologic response in the breast defined as no residual invasive disease or in situ disease. Results. Eighty-three tumors in 83 patients with a mean age of 50 (range 27–70) were evaluated. Twenty-three patients had a pCR. The NPV, PPV, sensitivity, specificity, and accuracy of tri-modality imaging algorithm for pCR were 0.87, 0.95, 0.95, 0.87 and 0.93 utilizing a cut-point of ≤ 5 for complete response by imaging. The mean score for patients with pCR was 4.61 (range 3–10) with 3 patients scoring above 5. The mean score for patients with residual disease was 7.73 (range 5–11). Conclusions: A tri-modality imaging scoring algorithm is predictive of complete pathologic response. This algorithm will be tested in a developing prospective trial that will also assess the additive value of tumor bed biopsy in patients who achieve a score of 5 or less. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-03-03.
FRI0076 Ra patients with the highest scores for the 2010 ra classification criteria are less prone to achieve remission after 2 years of follow-up in a very early arthritis clinic
Authors: M. D. Mjaavatten, A. J. Haugen, H. Nygaard, O. Bjørneboe, H. C. Gulseth, T. K. Kvien
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Early treatment to achieve remission is the current paradigm in early RA (ERA). Accordingly, the ACR/EULAR recently published both new classification and remission criteria. Presumably, patients with a high score according the classification criteria could have a worse prognosis, but this has not been investigated in a real life setting. <h3>Objectives</h3> To determine the proportion of ERA patients achieving remission after two years according to the new remission criteria, and to describe factors associated with remission. <h3>Methods</h3> Patients with arthritis of &lt;16 weeks’ duration were included in an early arthritis cohort from 2004-2010 and followed for 2 years with a comprehensive data collection. Patients were treated according to current clinical practice and not with a structured treat-to-target approach. Patients with 2010 ACR/EULAR RA and 2-year data on the 2010ACR/EULAR remission criteria (Boolean version) were included in this analysis. Frequency of 2-year remission was calculated, and baseline factors were compared in patients achieving vs. not achieving remission by univariate analyses. <h3>Results</h3> Of 1086 very early arthritis patients, 239 (22.0 %) could be classified as RA at inclusion. Of these, 185 (77.4 %) had completed 2-year follow-up and had data on ACR/EULAR Boolean remission. None of these patients were in remission at inclusion. At 2 years, 41/185 (22.2 %) were in remission. Comparisons of selected baseline factors between patients in vs. not in remission are shown in the table. <h3>Conclusions</h3> Only 22 % of patients with ERA were in remission after 2 years. High scores for the classification criteria (9 or 10 points) were associated with lower frequency of remission. Our findings confirm the need for a treat-to-target approach with careful monitoring in this patient population. <h3>Disclosure of Interest</h3> None Declared
Abstract 3094: MiRNAs 484 and 210 control Pax-5 expression and function in breast cancer.
Authors: Jason M. Harquail, Gilles A. Robichaud
Journal: Cancer Research (2013)

Abstract Every hour, approximately 21 people are diagnosed with cancer where 9 will succumb to their disease. Recent studies have enabled the identification of important factors regulating cancer progression, one of these being the Pax-5 gene. Pax-5, an essential developmental factor, is aberrantly expressed in various B cell cancer lesions and solid tumors such as carcinoma. Although Pax-5 downstream activity is well characterized, the regulation of aberrant Pax-5 expression in a cancer specific context is poorly understood. To investigate the regulation of Pax-5 expression, we turned our attention to micro-RNAs (miRNAs). MiRNAs are highly conserved, small non-coding RNA molecules that regulate key biological processes. Extensive studies also show their deregulation in multiple cancer lesions. This study aims to elucidate a correlation between differentially expressed miRNAs in cancer cells and deregulated Pax-5 expression levels. Using bioinformatics platforms we observe that miRNAs 484, and 210 are aberrantly expressed in breast cancer cells and cross-reference with their capacity to target the Pax-5 mRNA 3’ untranslated region (UTR 3’). Using anti-miRNAs transfected into Pax-5 expressing breast cancer cell lines (MCF-7 and MB231), we demonstrate that miRNAs 484 and 210 are capable of regulating Pax-5 expression. In addition, miRNA-regulated Pax-5 expression resulted in a concomitant alteration in Pax-5-dependant phenotype and cancer processes. This is the first study demonstrating the regulation of Pax-5 expression and function by non-coding RNAs in cancer cells. We believe that the aberrant expression of Pax-5 in cancer cells is in part due to deregulated miRNA expression profiles. This study will bring insight in regards to cancer regulating processes associated with miRNA and Pax-5 deregulations, thus helping us to better understand the aberrant Pax-5 expression levels within cancerous states. This study can therefore provide the eventual possibility of earlier, more efficient diagnostics as well as more targeted treatments for cancer patients. Citation Format: Jason M. Harquail, Gilles A. Robichaud. MiRNAs 484 and 210 control Pax-5 expression and function in breast cancer. [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 3094. doi:10.1158/1538-7445.AM2013-3094
Abstract 3036: The dependence receptor TrkC is a putative colon cancer tumor suppressor.
Authors: Anne-Laure Genevois, Gabriel Ichim, Marie-May Coissieux, Marie-Pierre Lambert, Florian Lepinasse, Zdenko Herceg, Jean-Yves Scoazec, Servane Tauszig-Delamasure, Patrick Mehlen
Journal: Cancer Research (2013)

Abstract Backgrounds &amp; Aims: The TrkC neurotrophin receptor belongs to the functional dependence receptors family, members of which share the ability to induce apoptosis in the absence of their ligands. Such a trait has been hypothesized to confer tumor-suppressor activity. Indeed, cells that express these receptors are thought to be dependent on ligand availability for their survival, a mechanism that inhibits uncontrolled tumor cell proliferation and migration. TrkC is yet a relatively classic tyrosine kinase receptor and therefore generally rather considered as a proto-oncogene. We investigated here whether, because of its dependence receptor activity, TrkC is a putative tumor suppressor in colorectal malignancies. Methods: The level of TrkC was analyzed in a panel of 45 primary sporadic colorectal carcinomas. Loss of heterozygosity and epigenetic alterations in the TrkC promoter were also analyzed. The level of TrkC was also analyzed in a panel of colorectal cancer cell lines. The TrkC tumor suppressive activity was investigated by expressing TrkC and related TrkC variants in colorectal cancer cell lines and by measuring apoptosis, anchorage-independent growth, migration and tumor growth in a chicken model. Results: We show here that TrkC expression is down-regulated in a large fraction of human colorectal cancers, mainly through promoter methylation. Moreover, we show that TrkC silencing by promoter methylation is a selective advantage for colorectal cell lines to limit tumor cell death. Consequently, we show that reestablished TrkC expression in colorectal cancer cell lines is associated with tumor cell death and inhibition of in vitro characteristics of cell transformation and in vivo tumor growth. Conclusions: The loss of TrkC expression observed in human colorectal cancer is a selective advantage for tumor cell survival. Thus, TrkC appears to be a putative new colon cancer tumor suppressor. Citation Format: Anne-Laure Genevois, Gabriel Ichim, Marie-May Coissieux, Marie-Pierre Lambert, Florian Lepinasse, Zdenko Herceg, Jean-Yves Scoazec, Servane Tauszig-Delamasure, Patrick Mehlen. The dependence receptor TrkC is a putative colon cancer tumor suppressor. [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 3036. doi:10.1158/1538-7445.AM2013-3036
Abstract 3166: The role of CD4 T cells in murine model of NASH-promoted HCC
Authors: Chi Ma, Dean Felsher, Tim Greten
Journal: Cancer Research (2015)

Abstract Aim: Non-alcoholic steatohepatitis (NASH), a common condition in obese patients, is an important risk factor for hepatocellular carcinoma (HCC). However, only little information exists about the immunological mechanisms of how NASH promotes HCC. This study was designed to better understand the role of adaptive immunity during the process of NASH-promoted hepatocarcinogenesis. Experimental procedure: Methionine choline deficient (MCD) diet is widely used to induce NASH. In this study we fed Lap-tTA-myc mice, which develop HCC, with MCD diet. Choline-deficient and amino acid-defined (CDAA) diet and high fat (HF) diet was also used to induce NASH in B6 mice. GK1.5 antibody was used to deplete CD4 T cells. Gas chromatography-mass spectrometry was performed to identify free fatty acids. Difference immune cell subsets were identified by flow cytometry. Cell death was measured by 7AAD/Annexin V staining. Results: MCD diet accelerated tumor development in MYC-on mice. A robust selective decrease of hepatic CD4 but not CD8 T cells was observed in NASH mice, which was exacerbated by MYC transgene expression. The selective decrease of hepatic CD4 T cells was also observed in B6 mice treated with CDAA or HF diet suggesting it's a general phenomena in NASH. As expected higher level of cell death was detected in hepatic CD4 T cells after NASH. Phenotypic analysis demonstrated that these CD4 T cells had a CD44highCD62Llow effector memory phenotype and produced more IFNγ. Selective CD4 T cell depletion further accelerated HCC development suggesting an important role of these cells for tumor development. Next, we studied the cause of CD4 T cell death. In co-culture experiments we demonstrated that lipid-laden hepatocytes from mice on MCD diet induced selective CD4 but not CD8 T cells death through a contact-independent mechanism. FFAs were found from hepatocyte culture medium to be responsible for T cell cytotoxicity, and linoleic acid recapitulates the selective toxicity to CD4 T cells. Blocking ROS abolished linoleic acid-induced CD4 T cell death. In vivo study showed that N-acetyl cysteine reversed the NASH-induced hepatic CD4 T cell decrease and delayed NASH-promoted tumor development. Conclusion: Our results suggest the critical role of CD4 T cells in the disease progression of NASH to HCC, and provide a new link between lipid metabolism dysfunction with impaired anti-tumor surveillance. Citation Format: Chi Ma, Dean Felsher, Tim Greten. The role of CD4 T cells in murine model of NASH-promoted HCC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3166. doi:10.1158/1538-7445.AM2015-3166
SAT0492 Risedronate for Prevention of Steroid Induced Osteoporosis in Rheumatoid Arthritis Pacients
Authors: S. Stoica, G. Zugravu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Corticosteroids are widely used to suppress hyperactive inflammation in rheumatoid arthritis (RA). Bone loss is a serious side effect of this therapy. Risedronate is frequently used fo prevention and treatment for corticosteroid induced osteoporosis. <h3>Objectives</h3> The objective of this study is to assess the effects of risedronate for the prevention and treatment of corticosteroid induced osteoporosis. <h3>Methods</h3> The study includes 42 RA postmenopausal women aged between 54-62 years which require long-term corticosteroid therapy at &gt;5 mg/day prednisolone daily. All RA patients fulfilled the 1987 American College of Rheumatology (ACR) revised criteria for RA. All patients were interviewed and examined for the gathering of information on disease and treatment history. All patients received risedronate (35 mg/week),elemental calcium (1000mg/day) and vitamin D (800 U/day) for 12 months. Bone mineral density (BMD) (lumbar spine, hip and whole body) and bone turnover markers (urine deoxypyridinoline, serum osteocalcin) were assessed at baseline, month 6 and month 12. Plain radiographs of the thoracic and lumbar spine for fractures were taken at baseline and month 12. Pacients with gastrointestinal disease and neoplasms were excluded. <h3>Results</h3> The duration and dose of prednisolone received by the participants was 18.4±20 months. Osteopenia or osteoporosis (T scores &lt;-1.0) of the lumbar spine and the hip occurred in 74% at baseline. The body mass index (BMI) of the participants was 21.9±2.3kg/m<sup>2</sup> . At month 12, a significant gain in BMD at the lumbar spine (+1.3±2.4%; p=0.005) and the hip (+1.1±2.6%; p=0.01) was observed. No new fracture was reported. 4 patients were withdrawn from the study because non-compliance to treatment (N=3) and adverse events – dyspepsia (N=1). <h3>Conclusions</h3> Risedronate is effective for preventing and treating bone loss at the lumbar spine and femoral neck after 12 months treatment in RA postmenopausal women receiving long-term glucocorticoids. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5917