tbuckley/cabot-search huggingface dataset:
Utility of Tc-99m Human Polyclonal Immunoglobulin G Scintigraphy for Assessing the Efficacy of Yttrium-90 Silicate Therapy in Rheumatoid Knee Synovitis
Authors: ESRA ARZU GENCOGLU, GULSEREN ARAS, OZLEM KUCUK, GULAY ATAY, IBRAHIM TUTAK, SEBNEM ATAMAN, AYFER SOYLU, ERKAN IBIS
Journal: Clinical Nuclear Medicine (2002)

Purpose The aim of this study was to determine the utility of Tc-99m human polyclonal immunoglobulin G (HIG) scintigraphy for evaluating the efficacy of yttrium-90 (Y-90) silicate therapy in rheumatoid knee synovitis. Materials and Methods Fifteen patients (13 women, 2 men; mean age, 53.5 ± 8.4 years) with rheumatoid arthritis had radionuclide synovectomy using 185 MBq (5 mCi) Y-90 silicate to evaluate 24 knee joints with chronic persistent synovitis. Radiologic and clinical evaluations and Tc-99m HIG scans were performed in each patient before radionuclide synovectomy. Each patient was reassessed 3, 6, 9, and 12 months after therapy using clinical examination and Tc-99m HIG scintigraphy. Results In 14 of 24 knee joints (4 Larsen stage I, 10 Larsen stage II) that had excellent or good clinical responses to Y-90 silicate therapy, the Tc-99m HIG index values 3 months after treatment were significantly lower than the pretreatment index values (P < 0.001). In 13 of these 14 joints, these low index values and clinical results remained constant throughout the 1 year of follow-up. One patient (1 of the 14 knee joints) experienced severe pain and swelling as a result of recurrent arthritis at 9 months, and the Tc-99m HIG index value increased at 9 months and remained high 12 months after therapy. In 10 of 24 knee joints (4 Larsen stage II, 6 Larsen stage III) that had a fair or poor clinical response, Tc-99m HIG index values were statistically similar before and after radionuclide therapy. Conclusions Quantitative Tc-99m HIG scintigraphy is a valuable method for assessing the efficacy of Y-90 silicate therapy in rheumatoid knee synovitis.
RT-28 * INSTITUTIONAL REVIEW OF GAMMA KNIFE RADIOSURGERY IN PRIMARY AND RECURRENT HIGH-GRADE GLIOMAS
Authors: R. Planchard, K. Merrell, S. Thalacker, I. Parney, N. Laack
Journal: Neuro-Oncology (2014)

The role of Gamma Knife stereotactic radiosurgery (GK-SRS) as a treatment option for patients with primary or recurrent high grade gliomas (HGG) is not well defined. To better understand clinical outcomes with GK-SRS we reviewed the charts of 94 consecutive patients treated for primary (n = 10) or recurrent (n = 84) WHO grade III/IV astrocytomas (n = 91), oligodendrogliomas (n = 2), or mixed (n = 1) lesions. Treatment prior to GK-SRS included External beam radiotherapy (EBRT) (median dose, 60Gy) in 90% and chemotherapy in 87%. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate and multivariate analyses (MVA) were performed using Cox proportional hazards regression models incorporating age, Karnofsky performance status (KPS) prior to GK-SRS (100 vs. <100), grade at treatment (III vs. IV), interval time from EBRT to GK-SRS (<6 vs. 6-18 vs. >18mos), and tumor volume (≤12,000, >12,000). Median age at treatment was 49.6yrs (range, 18.4-77.2). KPS was ≥ 70 for all patients. Median follow-up was 0.9 years (range, 0.15-21.5). Tumor grade at diagnosis was II (10), III (18), or IV (66), with several progressions of II-to-III (9), II-to-IV (1), and III-to-IV (4) at time of GK-SRS. Median treatment volume was 12,800 mm3 (range, 484-139,000) with a median prescription dose of 15 Gy (50% isodose; range, 8-24). Median survival was 4.8 years for grade III (initial grade III: 3.9yrs; grade II-to-III progression: 5.6yrs) and 1.8 years for grade IV (initial grade IV 1.8yrs; grade II/III-to-IV progression: 4.2yrs). Predictors of OS on MVA include age at GK-SRS treatment per year (p = 0.0014, HR 1.033, 95% CI 1.012-1.053), grade IV at GK-SRS (p = 0.0078, HR 2.218, 95% CI 1.233-3.990), and interval EBRT to GK-SRS >18 months (p = 0.0011, HR 2.909, 95% CI 1.531-5.528). Our results show favorable survival outcomes with the use of GK-SRS compared to historic controls. Further prospective investigation is warranted.
EUS-FNA As a ?First and Single Test? For The Diagnosis and Staging of Lung Cancer - Prospective Comparison of EUS, CT scan and PET scan
Authors: P Singh, B Camazine, Y Jadhav, R Gupta, P Mukhopadhyay, A Khan, R Reddy, R Erickson
Journal: Endoscopy (2006)

Background: Multiple tests are required for the management of lung cancer. We evaluated EUS-FNA as a single test for the diagnosis and staging of lung cancer.
Opportunistic testing for urogenital infection with Chlamydia trachomatis in south-western Switzerland, 2012: a feasibility study
Authors: F Bally, A Quach, G Greub, K Jaton, C Petignat, C Ambord, J Fellay, E Masserey, B Spencer
Journal: Eurosurveillance (2015)

The feasibility of opportunistic screening of urogenital infections with Chlamydia trachomatis was assessed in a cross-sectional study in 2012, in two cantons of south-western Switzerland: Vaud and Valais. Sexually active persons younger than 30 years, not tested for C. trachomatis in the last three months, were invited for free C. trachomatis testing by PCR in urine or self-applied vaginal swabs. Of 2,461 consenting participants, 1,899 (77%) were women and all but six (0.3%) submitted a sample. Forty-seven per cent of female and 25% of male participants were younger than 20 years. Overall, 134 (5.5%) of 2,455 tested participants had a positive result and were followed up. Seven per cent of all candidates for screening were not invited, 10% of invited candidates were not eligible, 15% of the eligible candidates declined participation, 5% of tested participants testing positive were not treated, 29% of those treated were not retested after six months and 9% of those retested were positive for C. trachomatis. Opportunistic C. trachomatis testing proved technically feasible and acceptable, at least if free of charge. Men and peripheral rural regions were more difficult to reach. Efforts to increase testing and decrease dropout at all stages of the screening procedure are necessary.
Abstract 1386: Predictive markers of efficacy for an angiopoietin-2 targeting therapeutic in xenograft models
Authors: Gallen B. Triana-Baltzer, Adam Pavlicek, Ariadne Goulart, Hanhua Huang, Gary Woodnutt, Nancy Levin
Journal: Cancer Research (2012)

Abstract The clinical efficacy of anti-angiogenic therapies has been difficult to predict, and in this era of personalized medicine biomarkers that can predict effect are sorely needed. CVX-060 is an angiopoietin-2 (Ang2) targeting therapeutic, consisting of two peptides that bind Ang2 with high affinity and specificity, covalently fused to a scaffold antibody. The resulting therapeutic has shown promising activity in a phase 1 clinical trial, with several phase 2 clinical programs in progress/planning. In order to optimize the use of this compound in the clinic a set of predictive biomarkers are desired. Here we describe the construction of a predictive model based on the efficacy of CVX-060 in 13 conventional xenograft models, focusing on renal and ovarian cancer. Pretreatment size tumors from each of the models were profiled for the levels of ∼25 protein markers of angiogenesis, SNP haplotype in 5 angiogenesis genes, and somatic mutation status for ∼12 genes implicated in tumor growth and/or vascularization. The markers chosen for evaluation were accumulated from angiogenesis literature and a differential gene expression analysis of CVX-060 treatment-induced changes. CVX-060 efficacy was determined as tumor growth inhibition (TGI%) at termination of each study. A predictive statistical model was constructed based on the correlation of these efficacy data with the marker profiles, and the model was subsequently tested via prospective analysis in 7 additional models The results of this work reveal a range of CVX-060 efficacy in xenograft models of diverse tissue types (0-49% TGI, median = 38%). Notably, we define a subset of 5-7 proteins, the levels of which are predictive of TGI by Ang2 blockade. The majority of these proteins are proximal to the target of CVX-060 and the direction of the associations is such that better efficacy correlates with high levels of target and low levels of compensatory/antagonizing molecules. The SNPs and somatic mutations examined here did not correlate with TGI. Our study describes a systematic approach to the problem of identifying predictive markers of anti-angiogenic affect, and demonstrates the significant ground work necessary to reveal treatment-sensitive predictive markers which can be quantitatively defined. This effort has revealed a set of predictive markers for CVX-060 efficacy that will be further evaluated in ongoing clinical trials. 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 1386. doi:1538-7445.AM2012-1386
FRI0126 Evaluation of cervical pain and dysfunction in patients with rheumatoid arthritis
Authors: F. Kaygisiz, P. Borman, M. Okumus, R. Erdem
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cervical spine involvement in (RA) is not uncommon and can lead to deformities and functional disability. <h3>Objectives</h3> The aim of this study was to evaluate cervical pain and function in RA patients and determine the correlation between these variables and disease activity, and quality of life. <h3>Methods</h3> A hundred and one patients with a diagnosis of RA recruited from outpatient clinics in the last two months. Patients with prior trauma, surgery or conditions related with cervical spine, were excluded. The demographic variables and clinical and laboratory disease activity parameters including DAS28 and HAQ were recorded. The patients were assessed according to the presence of neck pain. The intensity of neck pain was determined by VAS, and quality of life by RA-quality of life (RA-QoL). The patients with neck pain were completed neck disability index (NDI). The relationship between intensity of neck pain and functional scores, QoL, and clinical and laboratory variables were analyzed. <h3>Results</h3> A hundred and one patients with a mean age and median disease duration of 53.9±11.3 and 10 years respectively were included. The ratio of patients with moderate, low disease activity and remission according to DAS28, were 50%, 30.7% and 19.3% respectively. 28% of patients had neck pain and they mostly had moderate disease activity. The mean scores of VAS-pain and NDI were 6.3±2.5 and 28.4±17.8. There was a positive correlation between NDI and RA-QoL (p&lt;0.001, r=0.621) and HAQ (p&lt;0.05, r=468) scores. <h3>Conclusions</h3> One third of the RA patients had neck pain and impaired cervical function which is closely related with general functional disability and quality of life. We suggest the detailed evaluation of cervical pain and function in order to enhance general functional status and improve quality of life in RA patients. <h3>Disclosure of Interest</h3> None Declared
Abstract B10: Germline copy number variation in Li-Fraumeni syndrome patients with TP53 mutations
Authors: Amanda G.S. Silva, Maria Isabel W. Achatz, Ricardo Brentani, Ana Cristina V. Krepischi, Carla Rosenberg
Journal: Cancer Research (2011)

Abstract Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited disorder characterized by a remarkably increased risk of early-onset and multiple cancers, including breast, brain tumors and other neoplasms in individuals carrying germline TP53 mutations. The specific presence of constitutional copy number variation of large DNA segments (CNV) in LFS individuals may either represent a cancer susceptibility factor or result from a genetic instability. We used a 180K oligoarray platform from Agilent to estimate the CNV frequencies in 21 unrelated Li-Fraumeni patients carrying TP53 mutations. We compared the resulting frequencies between these individuals (n=21) to a population based control group (n=100), and defined as “rare genomic alterations” those located in coding regions and covered by ≤3 individual CNVs described in DGV (Database of Genomic Variants). Similar frequencies of CNVs were found in both patients and control groups with an average of 7–8 CNVs per genome. Rare CNVs were significantly more frequent among cancer patients (average of 0.8 per individual) than among controls (average of 0.3 per individual) (p&amp;lt;0.0001). Some of the genes encompassed by the rare germline CNVs from Li-Fraumeni patients have been previously reported to be altered in tumors, but are here described for the first time as altered in germline. Funding by Fapesp and CNPq. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B10.
Spectrum of 68Ga-DOTA TATE Uptake in Patients With Neuroendocrine Tumors
Authors: Farshad Moradi, Mehran Jamali, Amir Barkhodari, Bernadette Schneider, Frederick Chin, Andrew Quon, Erik S. Mittra, Andrei Iagaru
Journal: Clinical Nuclear Medicine (2015)

To analyze the biodistribution of Ga-DOTA-TATE in the normal tissues and uptake in benign, indeterminate, and malignant lesions in a population of patients with known neuroendocrine tumors (NET) using semiquantitative standardized uptake values (SUV) measurements.One hundred four consecutively scanned patients (51 men and 53 women; mean age, 56.4 years) with confirmed diagnosis of NET underwent PET/CT 1 hour after administration of Ga-DOTA-TATE. SUVmean, and SUVmax were measured in 37 normal anatomical structures for each patient. Abnormal uptake was divided into benign, indeterminate, and malignant categories based on imaging characteristic, clinical follow-up, and pathology.High physiologic uptake (SUVmax > 7) was observed in spleen, renal parenchyma, adrenal glands, pituitary gland, stomach, and liver (in decreasing order). Moderate uptake (3.5-7) was present in the prostate, jejunum, pancreas, ileum, and salivary glands. Mild uptake (2-3.5) was present in the uterus, colon, thyroid, rectum, and skeleton. A total of 678 lesions (limited to 5 lesions with highest uptake per organ) were included in the analysis, including 127 benign and 54 indeterminate lesions. Uptake was significantly higher in malignant lesions than in benign lesions, but an overlap was noted between the groups.Ga-DOTA TATE uptake in normal and abnormal structures is highly variable in patients with NET. SUV is a useful measure for characterizing benign versus malignant lesions. Anatomical and clinical correlation may be necessary to characterize foci of intermediate uptake.
P5-04-01: BP1, a Homeotic Transcription Factor, Indirectly Upregulates ER-alpha in ER Positive Cell Lines.
Authors: PE Berg, S Awate, SP Kirolikar
Journal: Cancer Research (2011)

Abstract Background: BP1 is a member of the homeobox gene family of transcription factors. Our recent studies have shown that BP1 may play a role in breast cancer cell survival, aggressiveness and metastasis. BP1 protein (pBP1) is expressed in 80% of invasive ductal breast tumors, including in 57% of ER positive and 89% of ER negative tumors. BP1 overexpression results in a more aggressive phenotype in breast cancer cells and larger tumors in women with breast cancer. We also observed the presence of mammary tumors in mice without estrogen supplementation after injection of MCF7 cells overexpressing BP1 compared with unsupplemented mice receiving MCF7 cells containing an empty vector. Our goal was to determine the pathway by which BP1 might cause this decrease in estrogen dependence of MCF7 cells. ER-alpha is a nuclear hormone receptor activated by estradiol and is a major target of anti-estrogen therapy. It is tightly regulated at the genomic and the non-genomic levels. Increased stability of ER-alpha is one mechanism by which cells can become ER-alpha independent. One way of altering ER-alpha stability is via p300 and BRCA1 since p300 acetylates and stabilizes ER-alpha, while BRCA1 destabilizes ER-alpha. We have previously shown that BP1 transcriptionally down-regulates BRCA1, suggesting that pBP1 may participate in this pathway. Materials and methods: Protein levels of BRCA1, p300, pS2, pBP1 and ER-alpha were determined by Western Blot analysis. RNA levels were measured by real-time PCR. A ChIP assay was performed to confirm binding of pBP1 to the EP300 gene and binding of ER-alpha to BP1. MCF7 parental cell lines were treated with 10nM E2 to induce the expression of pBP1. Experiments involving effects of siBP1 on p300 expression are underway. Results: Our data demonstrate that MCF7 ER+ cells engineered to overexpress BP1 exhibit increased ER-alpha protein, increased p300 and decreased BRCA1 protein as compared with control cells containing an empty vector and grown under the same conditions. Increased ER-alpha levels correlated with increased pS2 expression, a known downstream target of ER, demonstrating that there is more functional ER-alpha protein in cells overexpressing BP1. ChIP assays showed that pBP1 binds in the first intron of EP300-Histone acetyltransferase (p300). ChIP assays also showed that ER-alpha binds to an estrogen response element (ERE) upstream of the BP1 gene. MCF7 parental cell lines, when serum starved and treated with E2, showed increased BP1 expression compared with cells grown in charcoal stripped serum. Thus, BP1 may increase the stability of ER-alpha by decreasing BRCA1 and increasing p300. Conclusions: pBP1 binds and transcriptionally activates p300, leading to increased ER-alpha stability, while also partially repressing BRCA1. Moreover, ER-alpha, via a feed-forward mechanism, binds to the BP1 gene and increases its expression. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-04-01.
AB0615 Elevated Erythrocyte Sedimentation Rate is Associated with Pulmonary Impairment and Poor Outcome in Patients with Dermatomyositis
Authors: D.J. Go, H.M. Kwon, E.H. Kang, Y.J. Lee, K.C. Shin, E.Y. Lee, E.B. Lee, Y.W. Song, J.K. Park
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Interstitial lung disease (ILD) is a common cause of death in patients with dermatomyositis (DM). Especially, patients with clinically amyopathic DM (CADM) have a worse outcome due to ILD which is often refractory to corticosteroids. Lung involvement as an additional target of inflammation increases the total inflammatory burden in patients with DM. <h3>Objectives</h3> To investigate whether erythrocyte sedimentation rate (ESR) elevation is associated with ILD and a worse prognosis in patients with DM. <h3>Methods</h3> All patients with DM including CADM receiving clinical care in our institution from January 2004 through June 2013 were enrolled. Patients who had shortness of breath or abnormal finding on chest radiograph underwent a high resolution computed tomography (HRCT) and pulmonary function test (PFT). ILD was diagnosed when HRCT showed typical findings compatible with ILD. <h3>Results</h3> A total of 114 DM patients were enrolled in this study. The mean age of patients at diagnosis was 49.4±12.3 years. 69.3% were female. The mean follow-up duration was 32.3±29.3 months. ILD was present in 53 (46.5%) patients. Among 28 patients with CADM, 14 (50%) had ILD. The levels of ESR were significantly higher in patients with ILD than those without ILD (49.9±23.3 vs. 34.4±24.1 mm/hr, p=0.001). The difference was more profound between the CADM patients with ILD and those without ILD (56.3±23.8 vs. 25.4±22.9 mm/hr, p=0.002). The ESR levels were inversely correlated with the forced vital capacity (r=−0.238, p=0.036) and diffusing capacity of carbon monoxide (r=−0.334, p=0.004). Further, the patents with baseline ESR ≥30mm/hr had a worse survival as compared to those with ESR &lt;30mm/hr (p=0.002, by log rank test). <h3>Conclusions</h3> The ESR elevation at the time of DM diagnosis is associated with pulmonary impairment and a poor outcome in patients with DM. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3276
Abstract 4995: Tumor-dervied gammadelta regulatory T cells suppress innate and adaptive immunity through the induction of immunosenescence.
Authors: Jian Ye, Chunling Ma, Eddy C. Hsueh, Yanping Zhang, Mark A. Varvares, Daniel F. Hoft, Guangyong Peng
Journal: Cancer Research (2013)

Abstract Fundamentally understanding the suppressive mechanisms utilized by different subsets of tumor-infiltrating regulatory T (Treg) cells is critical for the development of effective strategies for anti-tumor immunotherapy. Gammadelta Treg cells have recently been identified in human diseases including in cancer patients. However, the suppressive mechanisms and functional regulations of this new subset of unconventional Treg cells are largely unknown. In the current studies, we explored the suppressive mechanism(s) utilized by human breast tumor-derived gammadelta Treg cells on innate and adaptive immunity. We found that gammadelta Treg cells induced immunosenescence in targeted naïve and effector T cells, as well as dendritic cells (DCs). Furthermore, senescent T cells and DCs induced by gammadelta Treg cells had altered phenotypes and developed potent suppressive activities, further amplifying the immunosuppression mediated by gammadelta Treg cells. In addition, we demonstrated that manipulation of TLR8 signaling in gammadelta Treg cells can block gammadelta Treg-induced conversion of T cells and DCs into senescent cells in vitro and in vivo. Our studies identify the novel suppressive mechanism mediated by human tumor-derived gammadelta Treg cells on innate and adaptive immunity, which should be critical for development of strong and innovative approaches to reverse the tumor suppressive microenvironment and improve effects of immunotherapy. This work was supported by the grant from the American Cancer Society (RSG-10-160-01-LIB). Key words: gammadelta T cells; Regulatory T cells; Dendritic cells; Senescence; Immune suppression Citation Format: Jian Ye, Chunling Ma, Eddy C. Hsueh, Yanping Zhang, Mark A. Varvares, Daniel F. Hoft, Guangyong Peng. Tumor-dervied gammadelta regulatory T cells suppress innate and adaptive immunity through the induction of immunosenescence. [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 4995. doi:10.1158/1538-7445.AM2013-4995