tbuckley/cabot-search huggingface dataset:
THU0005 Predictors of END Stage Renal Disease in Patients with Lupus Nephritis: A Nationwide Cohort Study in Taiwan
Authors: C.H. Tung, C.-C. Lee
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Lupus nephritis is a critical manifestation of systemic lupus erythematosus. It would progress to end stage renal disease (ESRD) if no appropriate treatment or refractory to clinical management. <h3>Objectives</h3> The predictors of ESRD progression were rarely been explored in Asian populations. The aim of this study was to investigate the factors affecting outcome in Taiwanese patients with lupus nephritis and to identify groups of patients with a high risk which need aggressive treatment. <h3>Methods</h3> We conducted a nationwide cohort study of the risk factors of ESRD among 2073 patients who had the history of lupus nephritis, using the National Health Insurance database of Taiwan from 1997 to 2009. Hazzard ratios (HRs) of predictors of ESRD development in lupus nephritis were analyzed. <h3>Results</h3> Among the patients with lupus nephritis, 19.3% patients developed ESRD within 10 years follow up, of which 48.6% patients developed within 5 years. The incidence rate of ESRD development decreased from 1997 to 2009 in Taiwan. The 10 year survival rate in patients with and without ESRD was 71.9% and 85.9% respectively. Age of less than 20 years old (HR 1.37, 95% CI 1.09-1.72) and concomitant hypertension (HR 1.33, 95% CI 1.02-1.74) was found to be independent risk factors for the development of ESRD. Patients with the history of receiving renal biopsy had a significantly decreased risk of ESRD (HR 0.708, 95% CI 0.56-0.89). <h3>Conclusions</h3> The lupus nephritis patients with ESRD had a decreased survival rate. The lupus nephritis patients which were younger than 20 years old and have the comorbidity of hypertension have an increased risk of ESRD development. Clinical management should be aggressive to avoid ESRD progression. Anti-hypertension treatment and renal biopsy if necessary should be recommended in those patients with high risks. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1716
Long-lasting potentiation of GABAergic inhibitory synaptic transmission in cerebellar Purkinje cells: Its properties and possible mechanisms
Authors: Masanobu Kano
Journal: Behavioral and Brain Sciences (1996)

The cellular basis of motor learning in the cerebellum has been attributed mostly to long-term depression (LTD) at excitatory parallel fiber (PF)-Purkinje cell (PC) synapses. LTD is induced when PFs are activated in conjunction with a climbing fiber (CF), the other excitatory input to PCs. Recently, by using whole-cell patch-clamp recording from PCs in cerebellar slices, a new form of synaptic plasticity was discovered. Stimulation of excitatory CFs induced a long-lasting (usually longer than 30 min) “rebound potentiation (RP)” of γ-amino-butyric acid A (GABAa)-receptor mediated inhibitory postsynaptic, currents (IPSCs). As in LTD, induction of RP requires transient elevation of intracellular calcium concentration ([Ca2+]1) due to activation of voltage-gated Ca2+ channels. Activity of inhibitory synapses seems also to be necessary for RP to occur. RP is mainly due to up-regulation of postsynaptic GABAa receptor function, since PC response to bath-applied exogenous GABA is also potentiated with a time course similar to RP. The difference in the time scale between the Ca2+ transients (10–30 sec) and the durations of RP (&gt;30 min) strongly suggests that some intracellular biochemical machinery is involved. Pharmacological evidence suggests that protein kinases are involved in RP of inhibitory synapses and LTD of excitatory PF synapses. Besides the well-described LTD, RP could be a cellular mechanism that plays an important role in motor learning.
OP0095 Comparison of Interstitial Lung Disease CT Indexes and Pulmonary Function Values in Sistemic Sclerosis Patients: A Multicenter Study
Authors: A. Ariani, E. Bravi, M. Saracco, S. Parisi, F. De Gennaro, L. Idolazzi, M. Silva, F. Lumetti, C. Benini, E. Arrigoni, D. Santilli, E. Fusaro, R. Pellerito, G. Delsante, F.C. Bodini, N. Sverzellati
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Currently, interstitial lung disease (ILD) related to systemic sclerosis (SSc) is assessed with pulmonary function tests (PFTs) and chest Computed Tomography (CT). FVC &lt;70% and DLco &lt;70% were proposed as parameters to define remarkable ILD [1]. Recently, quantitative assessment of ILD extention on chest CT was suggested as reliable parameter for disease assessment [2]. Quantitative score is based on voxel-wise analysis of lung density, summarized in the following quantiatative CT (QCT) parameters: kurtosis (Kurt), skewness (Skew), mean lung attenuation (MLA), standard deviation (Sdev) and fibrosis ratio (FR). <h3>Objectives</h3> To test the correlation between QCT parameter and PFTs and report the most accurate QCT for ILD assessment. Furthermore, to descibe QCT parameters in patients with FVC and DLco above or below the suggested threshold. <h3>Methods</h3> 226 SSc patients fullfilling ACR/EULAR diagnosis criteria undewent chest CT and PFTs in six different hospitals. All CTs were processed with an open-source DICOM-viewer (OsiriX) [3] that provided FR and the other QCT parameters (i.e. Kurt, Skew, MLA, Sdev) both related to normal lung parenchyma (nQCT) and to total lung (tQCT). Spearman rank test was used to verify the correlations between QCT parameters and PFTs data. The Mann-Whitney test was used to assess differences between patients with FVC and DLco above or below the suggested threshold. QCT parameters discriminative performances were verified using ROC analysis. A p-value &lt;0.05 was considered significant. <h3>Results</h3> Among QCT parameters, nKurt showed the best correlation with FVC (r =0,535; p&lt;0,0001) and DLco (r =0,394; p&lt;0,0001). Notably, nKurt was significantly lower in patients with FVC and DLco &lt;70% (p&lt;0.00001). ROC analysis showed that nKurt =1,69 can discriminate very well patients with FVC &lt;70% (sensibility 67,0%, specificity 81,0%). Similarly nKurt =5,25 distiguishes subjects with DLco &lt;70% (sensibility 80,8%, specificity 53,6%). <h3>Conclusions</h3> QCT parameters correlate with PFTs as reported in literature. In particular, nKurt showed the strongest correlation with FVC and DLco. Furthermore, the proposed thresholds of nKurt could be very useful in clinical practice allowing furhter characterization of ILD associated with SSc. <h3>References</h3> Khanna D, et al. Arthritis Rheum 2005;52(2):592–600. Ariani A, et al. Rheumatol Int 2013. Rosset A, et al. J Digit Imaging 2004;17(3):205–216. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3048
IN VIVO OPTICAL MOLECULAR - STRUCTURAL IMAGING OF CORONARY ARTERY STENT INFLAMMATION PREDICTS THE SITE-SPECIFIC RESTENOSIS RISK
Authors: Eric A. Osborn, Giovanni J. Ughi, Adam Mauskapf, Amr El Maghraby, Joerg Oettgen, Guillermo Tearney, Farouc Jaffer
Journal: Journal of the American College of Cardiology (2015)
Accrual Improvements in High Priority Trials
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Accrual Improvements in High Priority Trials Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 9, 3 May 1989, Pages 651–652, https://doi.org/10.1093/jnci/81.9.651 Published: 03 May 1989
Abstract 3286: Interleukin-17 receptor c (IL-17RC) knockout mice developed fewer and smaller prostate tumors compared to the wild-type mice in Pten-deficient context
Authors: Zongbing You, Qiuyang Zhang, Sen Liu, Dongxia Ge, Qingsong Zhang, Yun Xue
Journal: Cancer Research (2012)

Abstract Introduction: Interleukinα17 (ILα17) is a key cytokine in inflammatory and immune diseases. ILα17 may promote or inhibit tumor growth. Several studies have linked ILα17 with prostate cancer. ILα17's role in prostate cancer is unknown. The objective of this study is to investigate ILα17's role in formation and growth of prostate adenocarcinoma. Methods: ILα17 receptor C (ILα17RC) knockout mice were crossed with Pten conditional knockout mice (using ProbasinαCre). Ptenα/β male mice with intact ILα17 signaling (named RC+ mice, including ILα17RC+/+ and ILα17RC+/−) were compared with Ptenα/β male mice without ILα17 signaling (ILα17RCα/α, named RCβ mice). Results: There was no difference between the weight of genitourinary bloc of RC+ mice and that of RCβ mice at 4, 6 and 9 weeks. At 12 and 30 weeks, the GUαbloc weight of RC+ mice was 14% and 47% heavier than that of RCβ mice, respectively (P = 0.005, N = 54, and P = 0.004, N = 32, respectively). We found similar prostatic epithelial hyperplasia at 4 weeks and prostatic intraepithelial neoplasia (PIN) at 6 weeks in both RC+ and RCβ mice, suggesting that ILα17RC knockout did not affect PIN formation. At 9 weeks, invasive cancer was formed in 87% of RC+ prostate lobes, but only in 25% of RCβ prostate lobes (P &amp;lt; 0.001). At 30 weeks, 100% of RC+ prostate lobes formed invasive cancer, whereas only 70% of RCβ prostate lobes showed invasive cancer (P &amp;lt; 0.005). This suggests that ILα17RC knockout decreased progression of PIN to invasive cancer. The RCβ PINs were surrounded with a thick layer of fibromuscular stroma, whereas the stroma layer was significantly thinner in RC+ prostate glands, suggesting that failure of PIN to invade stroma was a critical deficit in RCβ mice. We found that MMP7 expression was significantly decreased in RCβ prostates compared to RC+ prostates, suggesting that lack of MMP7 expression is likely responsible for the observed phenotype. Furthermore, we found that ILα17 treatment induced MMP7 mRNA and protein expression in exαvivo cultured RC+ prostate tissues but not in RCβ prostate tissues, suggesting that MMP7 is a downstream target gene of ILα17 signaling. Conclusions: ILα17 promotes prostate adenocarcinoma formation and growth through induction of MMP7 expression in mouse prostate. Funding provided by NIH/NCRR COBRE Grant (2P20RR020152α06), DoD (W81XWHα05α1α0567 and W81XWHα10α1α0937), Tulane Cancer Center, Louisiana Cancer Research Consortium, and Tulane Framework for Global Health Seed Grant. 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 3286. doi:1538-7445.AM2012-3286
Abstract 4912: MELK-dependent phosphorylation of FOXM1 is essential for mitotic progression of glioma stem cells.
Authors: Kaushal Joshi, Ichiro Nakano
Journal: Cancer Research (2013)

Abstract Glioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM is essential to achieve cure. The transcription factor FOXM1 has recently gained attention as a master regulator for mitotic progression of cancer cells in various organs. Here, we demonstrate that FOXM1 forms a protein complex with the serine/threonine kinase MELK in GSCs, leading to phosphorylation and activation of FOXM1 in a MELK kinase-dependent manner. The MELK-dependent activation of FOXM1 results in an increase of mitotic regulatory genes in GSCs. MELK-driven FOXM1 activation is regulated by the binding and subsequent trans-phosphorylation of FOXM1 by another kinase PLK1 (Polo-like kinase 1). Using neural progenitor cells (NPCs) derived from mouse brains, we found that transgene expression of FOXM1 enhances, while its siRNA-mediated gene silencing diminishes clonal neurosphere formation, suggesting that FOXM1 is required for NPC growth. During tumorigenesis, FOXM1 expression sequentially increases from NPCs, pre-tumorigenic progenitors, and GSCs. As expected, sensitivity of GSCs to pharmacological inhibition of MELK-mediated FOXM1 signaling via the thiazole antibiotic Siomycin A is substantially higher than NPCs. In addition, treatment with the first-line chemotherapy agent for GBM, Temozolomide, paradoxically enriches for both FOXM1 (+) and MELK (+) cells in GBM cell culture, and addition of Siomycin A to Temozolomide treatment to mice harboring GSC-derived intracranial tumors enhances the effects of the latter. Collectively, our data indicate that FOXM1 signaling through its direct interaction with the kinase domain of MELK regulates mitotic key genes in GSCs in a PLK1-dependent manner and thus, this protein complex is a potential therapeutic target for GBM. Citation Format: Kaushal Joshi, Ichiro Nakano. MELK-dependent phosphorylation of FOXM1 is essential for mitotic progression of glioma stem cells. [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 4912. doi:10.1158/1538-7445.AM2013-4912
Abstract 2675: Characterization of human thioesterase 2 and its potential for breast cancer drug discovery
Authors: Melissa K. Ritchie, Lynnette C. Johnson, Laura A. Watts, Steven J. Kridel, W. Todd Lowther
Journal: Cancer Research (2010)

Abstract Human thioesterase II (TE2) may limit the anti-tumour potential of fatty acid synthase (FASN) inhibitors designed to target endogenous thioesterase (TE1) domain of FASN in breast cancer. Recent studies have firmly established the anti-tumour effects of TE1-targeted FASN inhibition via the drug Orlistat in prostate tumour xenografts, and current studies are revealing similar cytotoxic effects in breast cancer cell lines. Both TE1 and TE2 act on the acyl carrier protein (ACP) domain of FASN to liberate fully saturated, long-chain or medium-chain fatty acids, respectively. Therefore, TE2 may rescue fatty acid synthesis on TE1 inhibited FASN in cancer cells, thus highlighting TE2 as a potential new target for cancer therapy. Encouraged by the developments in TE1 inhibitors and by the expression of TE2 in breast cancers, we are now investigating the biochemical and structural properties of recombinant TE2 in order to define the factors that determine substrate specificity. In addition, the expression profile of endogenous TE2 in several breast cancer cell lines is under investigation. The long-term goal of this project is to determine whether TE2 is a viable target for the development of breast cancer specific anti-tumour therapies and/or whether a combined drug discovery strategy against both thioesterases must be pursued. Here we report the kinetic profiling of human TE1 and TE2 using model substrates and select β-lactone inhibitors. As well, we report immunoblot analyses of endogenous TE2 in MCF 7, SKBr 3, and MDA 231 breast cancer cell lines. Finally, we report the current progress of determining the crystal structure of recombinant TE2. Our results show lower β-lactone inhibitor potency against TE2 compared with TE1, as well as differential expression of endogenous TE2 in breast cancer cell lines. These results suggest that TE2 may need to be specifically targeted in breast cancer in order to fully realize the anti-tumour potential of FASN inhibition. 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 2675.
P581Genetic spectrum of idiopathic restrictive cardiomyopathy uncovered by new generation sequencing
Authors: A Kostareva, A Gudkova, A Kiselev, A Zlotina, N Smolina, A Klyushina, T Hodyuchenko, G Sjoberg, T Sejersen, E Shlyakhto
Journal: Cardiovascular Research (2014)

Background: cardiomyopathies represent a rare group of disorders often of genetic origin. The genetic spectrum of cardiomyopathies include more then 50 genes. While approximately 50% of genetic causes is known for hypertrophic and arrhythmogenic cardiomyopathy, the genetic spectrum of restrictive cardiomyopathy (RCMP) is widely unknown. Sanger sequencing approach revealed that sarcomeric protein gene mutations and mutations in structural proteins can be associated with idiopathic restrictive cardiomyopathy. The aim of the present study was to identify genetic background of idiopathic RCMP using new generation sequencing. Patients and Methods: we applied new generation sequencing approach (Ion Torrent) to perform a genetic screening for 62 cardiomyopathy-associated genes in 19 patients with idiopathic RCMP after exclusion of infiltratiove and storage discorders. Results: in 70% of patients more then 1 pathogenic variant was identified. Among all identified pathogenic substitutions only 27% represented variants in sarcomeric protein genes being the only pathogenic variant only in 21% of patients. Pathogenic variants in cytoplasmic and intrasarcomeric cytoskeletal protein genes represented 43%, the rest 30% of the variants were detected in membrane-associated cytoskeletal and matrix-interacting proteins. Conclusions: using new generation sequencing we identified more then one pathogenic variant in most of patients with RCMP. Most of the variants were identified not in sarcomeric, but in cytoskeletal and matrix-associated protein genes.
P08.25 * CLINICO-PATHOLOGICAL STUDY IN 156 PATIENTS OPERATED FOR BRAIN METASTASES
Authors: A. Salmaggi, A. Marando, I. Vittimberga, G. Grimod, G. Rossi, A. Vola, M. Parolin, E. Bonoldi
Journal: Neuro-Oncology (2014)

Brain metastases are the most common brain tumors in adulthood. They arise from lung, breast, kidney, gastrointestinal cancer, melanoma and other primary cancers. A recent study (Sperduto, JCO 2012) has provided algorythms for prediction of the expected survival in patients with different histologies of the primary tumor, refining previously available risk stratification classes. Increase in survival in patients with brain metastases may be linked to earlier detection, availability of new treatments for primary tumor and adoption of stereotactic surgery/surgery in fit patients. The data obtained by Sperduto need to be validated in other populations of brain metastases patients. We assessed survival in a cohort of 156 patients with brain metastases (all undergoing neurosurgery) followed in 2 Hospitals (Lecco and Varese) in Lombardia over 12 years (2000 to 2012). 75 cases were from lung cancer, 36 breast, 21 melanoma and 12 colorectal and 12 from other sites. Mean time to metastatic brain disease was 4.6 months for lung, 35.4 for colorectal, 52.2 for breast, 61.2 for melanoma and 78.5 for kidney cancer, respectively. Mean survival after diagnosis of metastatic brain disease was 6.9 months for melanoma, 7.2 for colorectal, 14.5 for lung, 26.6 for kidney and 26.9 months for breast-derived metastases. Our data confirm that time to onset of metastatic brain disease is dependent on the type of primary tumor and - in agreement with those reported in Sperduto's graded prognostic assessment database - show the presence of a non-negligible percentage of patients with prolonged survival after diagnosis and treatment of brain metastatic disease.
PWE-155 The safety and efficiency of laparoscopic liver resection for benign and malignant liver diseases
Authors: Y S Khaled, D J Malde, R Deshpande, N de' Liguori Carino, B J Ammori
Journal: Gut (2012)

<h3>Introduction</h3> Advances in technology and techniques facilitated the development of laparoscopic liver resection (LLR). The study is aimed at the evaluation of the feasibility and effectiveness of LLR for benign and malignant pathology. <h3>Methods</h3> This is a retrospective study of 61 patients (27 female) aged 63 (25–83) years who underwent LLR for benign (n=9) and malignant (n=52) between 2003 and 2011 in a single UK tertiary centre. The results shown represent median (range). <h3>Results</h3> Surgery was completed laparoscopically in 60 patients (98.3%) and converted to open due to extensive abdominal adhesions in one patient. The procedures performed included the resection of one segment (<i>n</i>=16), two segments (n=36) and three segments (n=9). The overall operative morbidity was 8.5% and there was no mortality. The operating time was 162 (50–300) min. The estimated blood loss was 110 (25–1100) ml and two patients received blood transfusion. The postoperative hospital stay was 3.6 (1–14) days. The resected malignancy in 52 patients included metastases in 47 patients (44 colorectal adenocarcinoma, three others) and hepatocellular carcinoma (n=5), and the R0 resection rate was 86.6% (n=45). At 42 (6–108) months follow-up, 77% were disease-free, 19% showed recurrent metastasis (1 hepatic, 4 hepatic and elsewhere, 5 extra-hepatic) and 4% failed to attend the follow-up. <h3>Conclusion</h3> Our results support the expanding evidence that LLR is safe and efficient for the treatment of benign and malignant liver lesions in carefully selected patients. <h3>Competing interests</h3> None declared.
P4-19-01: Male Breast Cancer According to Tumor Subtype and Race: A California Cancer Registry (CCR)-Population Based Study.
Authors: M Chavez-MacGregor, CA Clarke, DY Lichtensztajn, GN Hortobagyi, SH Giordano
Journal: Cancer Research (2011)

Abstract Background Breast cancer in men is a rare disease and accounts for 0.6% of all breast cancer cases. Prior reports suggest that male breast cancer typically has a ductal histology and is more likely than cancers of the female breast to express estrogen and progesterone receptors (ER and PR). To our knowledge, there are no population-based estimates of the rates of Her-2 positive breast cancer or of the distribution of breast cancer subtypes in male patients. The categorization of breast cancers according to tumor subtype has important implications in the prognosis and in the management of breast cancer patients. We explored the tumor subtype distribution by race/ethnicity in the large, ethnically diverse population of California. Methods: Retrospective study using the CCR. Participants included all male breast cancer patients diagnosed with invasive breast cancer between 2005–2009 with known ER, PR and Her2neu status. Among the patients with hormone receptor positive (HR+) tumors, survival analysis using Kaplan-Meier method was used. Differences in probability of survival between groups were compared using logrank test. Results: Six-hundred and seven patients were included. Median age at diagnosis was 68 years. Ductal histology was present in 84.7% (n=514) of the cases, 51.6% (n=313) of all the tumors were classified as grade II. Four hundred and ninety four (81.4%) patients had HR+ tumors, defined as ER+ and/or PR+ and Her2neu negative. Ninety (14.8%) had Her2neu positive, and 23 (3.8%) had triple receptor negative tumors (TN). The majority of patients were white (71%), 11% were Hispanic, 7.6% black and 10.4% were Asian/Pacific Islander/other. The breast cancer tumor subtype varied significantly across races/ethnicities (p&amp;lt;.0001). Among non-Hispanic Whites, 82.6% had HR+, 14.6% had Her-2+, and 2.8% had TN breast cancer. For Blacks and Hispanics the distributions were 73.9% HR+, 17.4% Her-2+, 8.7% TN and 77.6%, 16.4%, 6.0% respectively. Among HR+ patients, blacks and Hispanics were less likely to have PR+ tumors compared to whites. The rate of ER+PR- was 6.3% among whites, 19.6% among blacks and 16.4% among Hispanics (p&amp;lt;0.001). A survival analysis among HR+ patients showed significant differences according to race (p=0.018) and stage (p&amp;lt;0.001), with Black patients and patients with higher stage disease having poorer outcomes. Conclusions: In this large cohort of male breast cancer patients, the distribution of tumor subtype was different than what has been reported in females. Among males, differences in tumor subtype exist among different racial/ethnic groups. Blacks were more likely to have triple receptor negative tumors and more likely to have ER+/PR- tumors than white patients. Among HR+ patients, blacks experience the worse survival. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-19-01.