tbuckley/cabot-search huggingface dataset:
Abstract 4801: Comprehensive genome methylation analysis in bladder cancer; identification and validation of novel methylated genes and application of these as urinary tumor markers
Authors: Thomas Reinert, Charlotte Modin, Philippe Lamy, Tomasz K. Wojdacz, Lise L. Hansen, Carsten Wiuf, Michael Borre, Lars Dyrskjøt, Torben F. Ørntoft
Journal: Cancer Research (2011)

Abstract Cancer of the urinary bladder is one of the major cancers being the fifth most common neoplasm in the industrialised countries. Urothelial carcinomas account for more than 90% of all bladder cancers. The majority of bladder cancers are non-muscle invasive cancers characterized by frequent recurrences after resection and up to 25% will develop an aggressive phenotype. We investigated the methylation in bladder cancer with respect to location in genome, consistency, variation in metachronous tumors, impact on transcripts, chromosomal location, and usefulness as urinary markers of bladder cancer. In this study, a microarray assay with more than 27.000 CpG sites was utilized to analyze methylation in 56 samples. Independent validations were performed in 63 samples by methylation-sensitive high-resolution melting (MS-HRM) and bisulfite sequencing. Transcript levels were analyzed using expression microarrays, and pathways using dedicated software. DNA from 40 urinary specimens was analyzed by MS-HRM. Our results show that global methylation patterns were established within and outside CpG-islands. Differential methylation (p&amp;lt;0.0001 to p&amp;lt;0.05) was identified in 1588 genes between normals and cancers, in 1019 genes with stage specific methylation, and in 149 genes as progression markers. We validated methylation of eight genes, the tumor markers ZNF154 (p&amp;lt;0.0001), HOXA9 (p&amp;lt;0.0001), and POU4F2 (p&amp;lt;0.0001) and the progression marker TBX4 (p&amp;lt;0.002). The methylation of metachronous tumors was relatively stable and targeted to certain pathways. The correlation to expression was not stringent. Chromosome 21 showed most differential methylation (p&amp;lt;0.0001) and specifically hypomethylation of keratins, which together with keratin like proteins were epigenetically regulated. In DNA from voided urine we detected differential methylation of ZNF154 (p&amp;lt;0.0001), POU4F2 (p&amp;lt;0.0001), and HOXA9 (p&amp;lt;0.0044), achieving 94% sensitivity and 100% specificity. Our results suggest that both hypo- and hyper methylation is stage dependent, over-represented at chromosome 21, and has a restricted influence on transcript levels in general, but clearly on keratins. The methylated genes are highly promising urinary cancer markers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4801. doi:10.1158/1538-7445.AM2011-4801
Abstract 5580: Wnt signaling as chemotherapy sensitivity marker of triple negative breast cancer (TNBC).
Authors: Carolin Huelsewig, Christof Bernemann, Christian Ruckert, Ludwig Kiesel, Lajos Pusztai, Cornelia Liedtke
Journal: Cancer Research (2013)

Abstract Background: Triple negative breast cancer is characterized by an unfavorable prognosis. While patients do not benefit from endocrine or Her2 targeted therapies except chemotherapy, there is an increased response (pCR) to taxane-/anthracycline-containing therapy compared to other breast cancers. However, molecular determinants of chemotherapy specifically in TNBC remain largely unknown. Current research suggests an increased Wnt Pathway activity in TNBC while Wnt pathway activity has been shown to play an important role in breast cancer pathogenesis. Material and Methods: Differentially expressed genes in TN vs. non-TN breast cancers of patients treated with neoadjuvant taxane-/anthracycline-containing chemotherapy were identified and validated in an independent AffymetrixU133A gene chip dataset (Hess et al. 2006). Genes were tested for correlation with relapse-free survival, response to neoadjuvant chemotherapy and Ki67 expression. The effects of siRNA mediated knockdown of SFRP1 and treatment with small molecule XAV939 (specific inhibitor of Wnt signaling) were analyzed in TNBC cell lines MDA-MB 468, MDA-MB 231, HCC 1806 and luminal cell line MCF7 on chemo sensitivity. Results: Our list of over expressed genes in TNBC vs. non-TNBC contains several genes which are already discussed as potential markers for TNBC like αB-crystallin and transcription factor FOXC1. Furthermore, a few Wnt pathway associated genes (i.e. SFRP1, TCF7L1, TCF7L2, SOX10) occur in this list, which was validated in an independent dataset. While SFRP1 expression was not associated with relapse-free survival in TNBC, it was significantly correlated with a pCR. Importantly, no correlation to Ki67 expression could be demonstrated. mRNA knockdown of Wnt pathway inhibitor SFRP1 in two different TNBC cell lines (MDA-MB 468 and HCC 1806) resulted in an increased resistance to paclitaxel, doxorubicin and cisplatin. Treatment with Wnt inhibitor XAV939 resulted in TNBC cell lines MDA-MB 231, MDA-MB 468 and in luminal cell line MCF7 increased chemo sensitivity to paclitaxel and doxorubicin. Conclusion: We suggest Wnt Signaling and/or SFRP1 expression as a novel maker of chemotherapy sensitivity to taxane-, anthracycline and/or platinum-containing chemotherapy in TNBC in vitro that is independent of Ki67 expression. Citation Format: Carolin Huelsewig, Christof Bernemann, Christian Ruckert, Ludwig Kiesel, Lajos Pusztai, Cornelia Liedtke. Wnt signaling as chemotherapy sensitivity marker of triple negative breast cancer (TNBC). [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 5580. doi:10.1158/1538-7445.AM2013-5580
Use of Tc-99m DTPA Galactosyl Human Serum Albumin to Predict Postoperative Residual Liver Function
Authors: MASAKI UETAKE, KIYOSHI KOIZUMI, AKIHARU YAGAWA, HISASHI NOGATA, TORU TEZUKA, HIROSHI KONO, TOSHIFUSA OZAWA, TASUKU KUSANO, MASAYUKI MIYABUKURO, MASARU HOSAKA
Journal: Clinical Nuclear Medicine (1999)

Purpose: Residual liver uptake at 15 minutes (RLU15), a new index for predicting residual liver function after excision of hepatocellular carcinoma, was evaluated using dynamic liver images and SPECT by Tc-99m DTPA galactosyl human serum albumin. Materials and Methods: In 13 cases of hepatectomy, RLU15 was compared with postoperative serum prothrombin levels, serum bilirubin levels, and ascites. Results: RLU15 showed good correlation with both the prothrombin activity and the serum bilirubin, with correlation coefficients of r = 0.829 and r = −0.757. Conclusion: This new index appears useful for predicting residual liver function after hepatectomy.
Abstract 341: <i>In vivo</i> model of non-small cell lung cancer metastasis to the brain.
Authors: Su I. Chung, Lisa A. Tobin, Yili Xie, John R. Wunderlich, King F. Kwong
Journal: Cancer Research (2013)

Abstract Background: Non-small cell lung cancer (NSCLC) has a high rate of metastasis to distant sites such as the brain. Previous reports have suggested that exogenously expressed EMT transcription factors lead to EMT-induced migration, invasion, and anchorage-independent growth of cancer cells in vitro. In other cancer types, increased EMT transcription factors leads to promotion of metastatic tumor cell dissemination but simultaneously can also inhibit distant colonization by circulating metastatic cells. Methods: To investigate the role of EMT in brain metastasis in NSCLC, we established an in vivo model of brain metastasis through the isolation of brain metastatic clones from iterative rounds of systemic cancer cell inoculation in immunodeficient mice. Results: With each round, an increasing frequency of brain metastasis characterized the metastatic pattern and earlier onset of brain tumor formation was seen in select animals. In the metastatic cell lines established from the explanted brain metastases, we observed elevation of EMT markers such as TWIST, vimentin, and fibronectin compared to the parental cells. In addition, metastatic clones to the brain demonstrated markedly increased migration and EGFR expression. Conclusion: Iterative in vivo passaging of cancer cells facilitated isolation of subclones demonstrating increased brain metastasis. Also, these data suggests that the increased expression of EMT markers does not inhibit the formation of brain metastasis in NSCLC. Citation Format: Su I. Chung, Lisa A. Tobin, Yili Xie, John R. Wunderlich, King F. Kwong. In vivo model of non-small cell lung cancer metastasis to the brain. [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 341. doi:10.1158/1538-7445.AM2013-341
PTPS-09HISTONE DEMETHYLASE INHIBITION IN COMBINATION WITH RADIATION FOR DIFFUSE INTRINSIC PONTINE GLIOMAS
Authors: Quanhong Ma, Liang Mu, Amanda Saratsis, Rishi Lulla, Jason Fangusaro, Stewart Goldman, David James, Rintaro Hashizume
Journal: Neuro-Oncology (2015)

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, and often harbors oncogenic H3F3A gene mutations, resulting in replacement of lysine 27 by methionine (K27M) in the encoded histone H3.3 protein. Despite being just one of 32 genes that encode histone H3 peptides in a diploid cell, this mutation causes substantial reduction in histone H3K27 methylation in cellular chromatin, and we have recently shown that inhibition of the histone H3K27 demethylase JMJD3 acts to restore H3K27 methylation in DIPG cells, while demonstrating potent anti-tumor activity, both in cell culture and in xenograft models of DIPG. Our expression profiling of K27M DIPG treated with GSKJ4 histone H3K27 demethylase inhibitor revealed decreased transcripts from several genes whose encoded proteins are known to be involved with DNA double-strand break (DSB) repair. These results provide a basis for considering the possibility of GSKJ4 acting as a radiation enhancer, and we investigate this possibility, in association with analysis of therapeutic combination of GSKJ4 and radiation. METHOD: We examine cell growth, colony formation, and DNA DSB repair in association with GSKJ4 monotherapy and combined with radiotherapy (RT) in vitro. We use bioluminescence imaging (BLI), immunohistochemical analysis of tumors, and evaluation of survival benefit from the monotherapies and combination therapies in DIPG xenograft models. RESULTS: Mice received brainstem injection of K27M DIPG cells and are treated with vehicle, GSKJ4 (100mg/kg), RT (1Gy x 10 times), and combination of GSKJ4 + RT. BLI shows that brainstem tumor growth is inhibited by either GSKJ4 or RT monotherapy. Although this study is still ongoing, combination therapy with GSKJ4 + RT shows further reduction of tumor growth rate relative to either monotherapy. We are currently examining the effect of GSKJ4 on radiation-induced DNA DSB repair that will be reported at the meeting.
Abstract P2-08-01: <i>XPD</i> Single Nucleotide Polymorphisms and Copy Number Variation in Puerto Rican Women and Breast Cancer Risk
Authors: AL Pacheco-Torres, C Colon, J Matta, J. Dutil
Journal: Cancer Research (2010)

Abstract Background: The nucleotide excision repair (NER) pathway is the primary mechanism for the repair of bulky and helical distorting adducts. Previous studies suggest that polymorphisms in the XPD gene may contribute to the susceptibility of an individual to develop cancer. However, this data have not been validated in the population of Puerto Rico and most studies were limited to assessing the role of single nucleotide polymorphisms (SNPs). Copy number variations (CNVs) are segments of DNA that have a variable copy number compared to a reference genome. Our objective was to characterize the role of the SNPs and CNVs in the XPD gene and the susceptibility for breast cancer in Puerto Rican women. Material and Methods: Extracted DNA from healthy controls (n=252) and breast cancer patients (n=152) was used to perform TaqMan allelic discrimination for Single Nucleotide Polymorphisms (SNPs) rs13181, rs1799793 and rs238407 of the XPD gene. The XPD genomic region was screened for the presence of copy number variations using a Taqman CNV genotyping assay in exon 10 of the gene. Results: Interestingly, the control population was in Hardy-Weinberg disequilibrium for the SNPs rs1799793 and rs238407, suggesting the presence of copy number variation (CNV) in the XPD genomic region. In our study population, we found that the copy number around XPD ranges from one copy to more of 10 copies. The distribution of the CNV genotypes between controls and cases was statistically significant (p=0.021). Individuals carrying zero copy of the gene were more likely to develop breast cancer than individuals with more than two copies (Odds ratio: 2.6, 95% confidence interval 5.134 — 1.336, P&amp;lt;0.005). Significance: This study is expected to contribute to the identification of individuals that are at higher risk of breast cancer, prior to the development of the disease. This will aid in prevention and treatment decisions in an individual's breast cancer management strategies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-08-01.
Abstract 2220: Analyzing cancer with single cell resolution using droplet technology
Authors: Michael L. Samuels, Scott Kennedy
Journal: Cancer Research (2010)

Abstract Cancers develop and grow in the complex environments present in normal tissue, and tumor cells are composed of heterogeneous mixtures of both clonal transformed cells and other cell types. We demonstrate the use of microfluidic-generated single cell microdroplets in workflows that capture both phenotypic and genomic information from individual cells, enabling analysis of tumors with single cell resolution. This transformative new tool will allow for more thorough examinations of the variations that influence the predisposition and composition of cancers, and the cellular responses to therapeutic and prevention agents. Uniform picoliter-nanoliter volume aqueous droplets suspended in an immiscible oil provide unique opportunities for fluorescence-based analytical techniques, including sorting relevant sub-populations at rates of several hundred cells per second, coupled directly to single cell genomic characterization. We use a defined set of control samples to perform low-bias single cell whole genome amplification (WGA) within the sorted microdroplets, and show how following this with droplet PCR-based targeted amplification (of many thousands of selected genomic loci using a cancer-focused droplet primer library) provides an automated sample preparation method for any Next Gen sequencing platform. Single cell microdroplet technology results in a cost-effective method to gain sequence information from phenotypically selected individual cells, addressing cancer gene discovery and validation by powering the larger studies required to classify driver or passenger mutations and analyzing how epigenomic features (such as cytosine methylation) regulate transcriptional changes that can underlie cancer development. 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 2220.
“Half-Half” Blisters
Authors: Michael O'Connell, Victoria Goulden
Journal: New England Journal of Medicine (2012)

A 66-year-old man presented with an acute pustular eruption. On examination, an annular rash with multiple blisters was seen on the patient's trunk; the blisters contained both clear and yellow fluid. He had no associated cutaneous or systemic symptoms, and there was no facial or mucosal involvement. Examination of a biopsy sample taken from a representative blister revealed a subcorneal vesicle and other features characteristic of a subcorneal pustular dermatosis. Direct immunofluorescent staining showed IgA deposition in the superficial epidermis. Subcorneal pustular dermatosis is a chronic pustular dermatosis that frequently affects the flexures of the trunk and limbs. The face . . .
A Controlled Trial of Sustained-Release Bupropion, a Nicotine Patch, or Both for Smoking Cessation
Authors: Douglas E. Jorenby, Scott J. Leischow, Mitchell A. Nides, Stephen I. Rennard, J. Andrew Johnston, Arlene R. Hughes, Stevens S. Smith, Myra L. Muramoto, David M. Daughton, Kimberli Doan, Michael C. Fiore, Timothy B. Baker
Journal: New England Journal of Medicine (1999)

Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8.
SAT0153 Anxiety and Depression in Rheumatoid Arthritis: Which is More Frequent?
Authors: I. Ben Slama, F. Allali, S. El Kabbaj, T. Lakhdar, L. Medrare, A. Ngeuleu, H. Rkain, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The psychological aspect of rheumatoid arthritis (RA) is often overlooked in the clinical monitoring of the disease. The aim of our study was to determine the prevalence of depression and anxiety in rheumatoid arthritis (RA) and to identify factors that influence them. <h3>Methods</h3> Patients with RA were included in a cross-sectional study. We have collected the demographic characteristics and the characteristics of the RA: duration of evolution, morning stiffness in minutes, functional impact of the disease assessed by the HAQ (Health Assessment Questionnaire) and disease activity estimated by the DAS28-ESR. The psychiatric assessment was made by the DASS -21 (Depression, Anxiety and Stress Scale). Factors influencing depression and anxiety were tested by univariate and multivariate logistic regression. <h3>Results</h3> 103 patients were included with a mean age of 49.7±11.4 years and a female predominance (n=90 (87.4%)). the median of disease progression duration was 8.16 years [3.25-14.16]. The diagnosis of depression was found in 23.3% of patients and the anxiety in 30.1% of them. In the univariate analysis, depression and anxiety were associated with a high disease activity, a significant pain intensity and a significant functional impairment (p&lt;0.001). After multivariate analysis, only the higher HAQ remained significantly associated with depression (OR=3.24, p=0.005, 95% CI [1.22 to 5.38]) and anxiety (OR =2.56, p=0.013, 95% CI [1.44 to 7.33]). <h3>Conclusions</h3> Our study shows a high frequency of both anxiety and depression in the RA. It seems that anxiety is more frequent than depression. Both events would be more marked in patients with significant functional impairment. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5817
DIFFERENCE IN THE IMPACT OF BNP AND PEAK VO2 ON FUTURE HEART FAILURE EVENTS BETWEEN ATRIAL FIBRILLATION AND SINUS RHYTHM
Authors: Yuko Kato, Shinya Suzuki, Hiroaki Semba, Tokuhisa Uejima, Hiroto Kano, Shunsuke Matsuno, Hideaki Takai, Takayuki Otsuka, Yuji Oikawa, Kazuyuki Nagashima, Hajima Kirigaya, Koichi Sagara, Takashi Kunihara, Junji Yajima, Hitoshi Sawada, Tadanori Aizawa, Takeshi Yamashita
Journal: Journal of the American College of Cardiology (2016)
TIMP-1 Status Measured by Immunohistochemistry in 268 ER Positive Postmenopausal High-Risk Breast Cancer Patients Treated with Adjuvant Tamoxifen: Association to Recurrence Free Survival.
Authors: C. Bjerre, A. Knoop, M. Lyng, H. Ditzel, N. Brünner, A. Bartels, A. Laenkholm
Journal: Cancer Research (2009)

Abstract Background: A proportion of ER positive breast cancer patients do not benefit from adjuvant tamoxifen treatment. Tamoxifen has been shown to induce apoptosis in human breast cancer cells in vitro and Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) protects cancer cells against apoptosis. We therefore raised the hypothesis that ER positive breast cancer cells with high TIMP-1 immunoreactivity would show reduced benefit to tamoxifen treatment.Material and methods: Tumor tissue from 268 high-risk postmenopausal ER positive breast cancer patients was used for this study. All patients underwent surgery for primary invasive breast cancer. The majority of the patients were lymph node positive: 92% (246/268). Patients were allocated to 1, 2 or 5 years of adjuvant tamoxifen as mono-therapy. Recurrent disease was diagnosed in 33% (89/268) of the patients. Median time to recurrence was 3.1 years and the median time of follow-up was 12.4 years. Archival formalin-fixed and paraffin-embedded primary tumor tissue was used to generate tissue microarrays comprising two, 2 mm cores from each tumor. TIMP-1 immunoreactivity was evaluated using the mouse monoclonal antibody (clone VT7) raised against recombinant human TIMP-1. This antibody exclusively reacts with TIMP-1. A central assessment of TIMP-1 status was performed. Tumors were analysed by bright field microscopy and scored semi-quantitatively as 0 - 3 with regard to the number of stained tumour cells and intensity of the staining. An index combining the number of positive tumor cells and staining intensity was created: low (0-2), median (3-4) and high expression (5-6).Results: IHC was successfully performed in 266 cases. TIMP-1 IHC negative cases were observed in 39% (105/266) of the tumors and 61% (161/266) were TIMP-1 IHC positive. The index combining the number of positive tumor cells and staining intensity showed low expression in 59% (157/266), median expression in 24% (65/266) and high expression in 17% (44/266) of the tumors. TIMP-1 negativity and low TIMP-1 index showed no significant association with tumor grade, tumor size or lymph node status. When performing Kaplan-Meier plots, TIMP-1 expression was not significantly associated with recurrence free survival in univariate analyses (p = 0.1).Conclusion: This study did not confirm our hypothesis that TIMP-1 immunoreactivity in ER positive breast cancer cells are associated with reduced benefit from adjuvant tamoxifen treatment. This is partly in contrast with prior studies on endocrine therapy of metastatic breast cancer (Lipton et al 2008) where high serum TIMP-1 was associated with reduced response to endocrine therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2025.
Rapidly Growing Chest Wall Mass in a Case of Sporadic Metastatic Paraganglioma
Authors: Ingo Janssen, Paraskevi Xekouki, Joan Nambuba, Clara C. Chen, Peter Herscovitch, Corina M. Millo, David S. Schrump, Karel Pacak
Journal: Clinical Nuclear Medicine (2016)

Pheochromocytomas/paragangliomas (PGLs) are rare tumors and mostly benign. We report on a 32-year-old woman with metastatic PGL who was first diagnosed with an abdominal PGL at the age of 12 years. She soon developed metastatic disease and received several treatments including external beam radiation and chemotherapy. When she was referred to our institution in 2014, her major complaint was a rapidly growing chest wall mass on the left side. The patient was imaged at our institution with 4 different PET radiopharmaceuticals.