tbuckley/cabot-search huggingface dataset:
Abstract 3144: A role for DOK2 methylation in platinum resistance and tumor suppression in ovarian cancer
Authors: Elena Lum, Michele Vigliotti, Noelle Cutter, Sohail Khan, Nevenka Dimitrov, Douglas Levine, Robert Lucito
Journal: Cancer Research (2012)

Abstract Ovarian cancer is the 5th leading cause of cancer in women, affecting close to 22,000 women in the year 2011, of which nearly 15,500 will die. It is difficult to detect until it reaches advanced stages and becomes malignant. Currently, the standard treatment for ovarian cancer is platinum-based therapeutics, such as Carboplatin or Cisplatin, combined with Taxol. Unfortunately, approximately 25% of patients are inherently platinum-resistant and all patients who suffer from recurrence will have developed acquired platinum resistance. The genetic/epigenetic causes of this resistance are poorly understood. Epigenetic events are reversible and the identification of genes altered by this mechanism may lead to studies on how to reprogram the process leading up to resistance. To examine the ovarian epigenome, we utilized an array based method, Methylation Oligonucleotide Microarray Analysis (MOMA), to analyze a set of 50 primary ovarian tumors and 12 ovarian normal samples. We identified epigenetic differences that segregated with platinum response and then associated this with expression data to identify gene candidates transcriptionally repressed and methylated in patients resistant to platinum. Next, a pooled shRNA screen was performed on candidate genes to identify those that were functionally relevant to platinum resistance. One of the validated candidate genes identified through the pooled shRNA screen was DOK2, an adapter protein downstream of tyrosine kinase, which has been shown by others to be a lung cancer tumor suppressor. We show that suppression of DOK2 by short hairpin RNAs in ovarian cell lines conferred resistance to platinum treatment. To elucidate the mechanism for resistance, we measured the influx of platinum into the cells using C-14 tagged carboplatin. As a result, uptake of carboplatin was found to be decreased with DOK2 suppression. Consistent with DOK2 having tumor suppressor activity, knockdowns in ovarian cell lines increases growth and migration. Furthermore, loss of DOK2 induces invasive and tumorigenic phenotypes in ovarian cell lines. DOK2 is already a proven tumor suppressor in lung cancer, and our experiments indicate DOK2 has tumor suppressor features in ovarian cancer as well. We show that DOK2 is a tumor suppressor in ovarian cancer and that the loss of DOK2 also contributes to platinum resistance. Understanding DOK2 function will help us understand ovarian cancer development, progression as well as therapy resistance. 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 3144. doi:1538-7445.AM2012-3144
Usefulness of the European Epidemic Intelligence Information System in the management of an outbreak of listeriosis, Belgium, 2011
Authors: M Yde, M Naranjo, W Mattheus, P Stragier, B Pochet, K Beulens, K De Schrijver, D Van den Branden, V Laisnez, W Flipse, A Leclercq, M Lecuit, K Dierick, S Bertrand
Journal: Eurosurveillance (2012)

A cluster of time-linked cases and the identification of a clonal strain suggest the occurrence of an outbreak of listeriosis in Belgium in 2011, presumably due to the consumption of hard cheese made with pasteurised milk and produced by a Belgium manufacturer. The outbreak clone was identified as Listeria monocytogenes serovar 1/2a, sensitive to arsenic and cadmium and of multilocus sequence typing MLST-type 37. Food investigation of this outbreak was facilitated by the European Epidemic Intelligence Information System and data exchanged between French and Belgium listeriosis surveillance systems.
Postchemoembolization Liver Abscess
Authors: SCOTT T. WILLIAMS, SHERIF I. HEIBA, BRIAN P. WHOOLEY, GINA A. CIAVARRA, HUSSEIN M. ABDEL-DAYEM
Journal: Clinical Nuclear Medicine (2002)

We describe a 41-year-old man with a 1-week history of nausea and vomiting 1 month after chemoembolization of a liver metastasis. The patient subsequently became febrile and developed right upper quadrant abdominal and midback pain. Findings of initial laboratory and imaging studies (a noncontrast computed tomographic [CT] scan and ultrasound) were not remarkable. Hepatobiliary scintigraphy, performed to rule out cholecystitis, revealed an abnormal area in the right lobe of the liver consistent with a focal bile leak into an abscess cavity. The patient was subsequently treated for liver abscess. In conclusion, hepatobiliary scintigraphy should be considered as a first-line test in the work-up of patients whenever a postchemoembolization complication is considered likely.
Triple negative status as a risk factor for the development of brain metastases in African American breast cancer patients.
Authors: AM Khan, I Sabnani, E Rogers-Phillips, P Tsang, R Voora, E Pinera, AJ Cohen
Journal: Cancer Research (2009)

Abstract Abstract #2093 Background: Previous studies have described triple negative (TN) breast cancer (ER/PR/ HER2/neu negative) as an aggressive and poor prognostic phenotype with higher relapse rate (RR), distant RR, and shorter survival. The incidence of TN breast cancer has reportedly been higher (30-35%) in African American (AA) women compared to the general population (15%) but the clinical outcomes of TN patients (pts) who develop brain metastases compared to the non-triple negative (NTN) group has not been well described.&amp;#x2028; Methods: We retrospectively reviewed tumor registry data from a large academic medical center serving an inner city population. A total of 282 AA women with invasive breast cancer were identified from 1994-2006 and 248 were determined to be in stages I-III. Characteristics evaluated include age, TNM stage at diagnosis, ER, PR, Her2/neu status, and grade. The RR, distant RR, rate of brain metastases, time from diagnosis to brain metastases, and overall survival were determined.&amp;#x2028; Results: The incidence of TN disease in AA women was 30% (82/282). Median age (57 yrs) was similar in both TN and NTN groups. With a median follow-up of 5.5 years, the RR (30% vs. 14%; p=0.02) and distant RR (22% vs. 10%; p=0.02) were higher for the TN vs. NTN group. Six of 72 (9%) TN pts developed brain metastases compare to 6/178 (3%) in NTN group. There was a shorter time to development of brain metastases (1.7 vs. 6.1; p=0.01) and a lower survival time after brain metastases (0.6 yrs vs. 1.6 yrs) in the TN vs. NTN group.&amp;#x2028; &amp;#x2028; Conclusion: This study represents one of the largest reported series of AA women with breast cancer. TN pts are at higher risk of developing brain metastases. Not only the time to develop brain metastases was shorter but overall survival after development of brain metastases remained poor in TN group compared to NTN group. TN status should be considered as an independent risk factor for the development of brain metastases. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2093.
Abstract 4176: MicroRNA-193b is growth-inhibitory in Ewing sarcoma, and represses ErbB4.
Authors: Colin Moore, Paul Jedlicka
Journal: Cancer Research (2013)

Abstract Ewing sarcoma, the second most common cancer of bone and soft tissue in adolescents and young adults, is an aggressive malignancy with poor long-term outcome. Ewing sarcoma is driven primarily by the EWS/Fli-1 fusion oncoprotein, which arises from the recurrent t(11,22) translocation. Our laboratory has been interested in identifying microRNAs (miRs) with growth-modulating properties in Ewing sarcoma, manipulation of which could potentially be used for novel therapies, as shown in preclinical studies for other cancers. We have previously shown that replacement of select miRs, normally repressed by EWS/Fli1, can inhibit the growth of Ewing sarcoma cells. To identify additional, and more potent, miRs with growth-suppressive properties in EWS, we have performed a phenotype-based, secondary miniscreen in Ewing sarcoma cell lines. This screen, using transfection of miR mimics into the EWS cell lines A673 and SK-ES-1, followed by growth assays as read-out, identified miR-193b as a strong candidate growth suppressive miR in Ewing sarcoma. Subsequent cloning and stable overexpression of endogenous miR-193b verified the growth suppressive phenotype. Examination of candidate targets further identified ErbB4 as potently repressed upon miR-193b overexpression. ErbB4 has recently been shown to play a key role in Ewing sarcoma, specifically as a driver of metastasis and as a mediator of resistance to cytotoxic chemotherapy, key biological parameters that define high-risk disease. With the need for therapy expansion in pediatric EWS, miR-193b replacement, through ErbB4 inhibition, may be a way to help control high-risk disease. Citation Format: Colin Moore, Paul Jedlicka. MicroRNA-193b is growth-inhibitory in Ewing sarcoma, and represses ErbB4. [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 4176. doi:10.1158/1538-7445.AM2013-4176
FRI0387 Long-Term Efficacy of Rituximab in Patients with Refractory Sle: Table 1.
Authors: M. Tsanyan, S. Soloviev, A. Torgashina, E. Aleksandrova, S. Radenska-Lopovok, E. Nikolaeva, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To assess the long-term efficacy and safety of rituximab (RTM) in patients with systemic lupus erythematosus (SLE) resistant to standard therapy. <h3>Methods</h3> 97 patients with relapsing/refractory systemic lupus erythematosus received rituximab. The mean time of follow-up was 24months (6-72months). The most common clinical manifestations of SLE were lupus nephritis (LN) (62%), skin involvement (33%) and neurological symptoms (22,7%). SLE activity was assessed by SLEDAI2K. The following terms such as partial response (PR), complete response (CR) and exacerbation were used. Exacerbation was classified as moderate and severe using the SFI index. <h3>Results</h3> 78% of 97 patients had depleted peripheral B-cells. 84% of patients achieved a clinical response (CR-56%, PR-28%) after repeated courses of RTM during the long-term follow-up. The exacerbation was occurred in 24 (24,7%) patients, the median time of exacerbation was 12[12-24]months after therapy with RTM: 17,5% with LN (the median time of exacerbation was 12[12-24]months), 7,2% with extrarenal SLE (the median time of exacerbation was 18[6-48]months). In 24 patients with exacerbation B-cells recovered after 6[3-12]months. CR was observed more frequently in patients with complete depletion of B-cell (n=35) than in group of patients (n=20) with B-cell recovery (65,7% and 30% respectively, p=0,03). CR was observed significantly more frequently in patients after repeated courses of rituximab, compared with a group of patients who received only one course of therapy (p=0,05) (table 1). Clinical improvement was reflected by reduction of disease activity index SLEDAI2K, normalization of laboratory parameters and decreasing the daily dose of prednisolone during the long-term follow-up. In most of the patients the first and repeated courses of RTM therapy was well tolerated. <h3>Conclusions</h3> RTM had a high rate of efficacy in relapsing and refractory SLE. There was no evidence of an increased risk of infections or increased reporting rates of any types of adverse effects during the 6 years of observation. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1196
Abstract P4-04-03: Transcriptome Analyses of Mouse and Human Mammary Cell Subpopulations Reveals Multiple Conserved Genes and Pathways
Authors: E Lim, D Wu, B Pal, T Bouras, M-L Asselin-Labat, F Vaillant, H Yagita, GJ Lindeman, GK Smyth, JE. Visvader
Journal: Cancer Research (2010)

Abstract INTRODUCTION: Molecular characterization of the normal epithelial cell types that reside in the mammary gland is an important step toward understanding pathways that regulate self-renewal, lineage commitment, and differentiation along the hierarchy. We previously reported distinct stages in human mammary epithelial cell development and linked them to breast tumor subtypes previously defined by gene expression profiling. Here we determined the gene expression signatures of four distinct subpopulations isolated from the mouse mammary gland. The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks. METHODS: RNA was prepared from freshly sorted mouse mammary cell subpopulations (mammary stem cell (MaSC)-enriched, committed luminal progenitor, mature luminal and stromal cell) and used for gene expression profiling analysis on the Illumina platform. Gene signatures were derived and compared with those previously reported for the analogous normal human mammary cell subpopulations. The mouse and human epithelial subset signatures were then subjected to Ingenuity Pathway Analysis (IPA) to identify conserved pathways. RESULTS: The four mouse mammary cell subpopulations exhibited distinct gene signatures. Comparison of these signatures with the molecular profiles of different mouse models of mammary tumorigenesis revealed that tumors arising in MMTV-Wnt-1 and p53-/- mice were enriched for MaSC-subset genes, whereas the gene profiles of MMTV-Neu and MMTV-PyMT tumors were most concordant with the luminal progenitor cell signature. Comparison of the mouse mammary epithelial cell signatures with their human counterparts revealed substantial conservation of genes, whereas IPA highlighted a number of conserved pathways in the three epithelial subsets. CONCLUSIONS: The conservation of genes and pathways across species further validates the use of the mouse as a model to study mammary gland development and highlights pathways that are likely to govern cell-fate decisions and differentiation. It is noteworthy that many of the conserved genes in the MaSC population have been considered as epithelialmesenchymal transition (EMT) signature genes. Therefore, the expression of these genes in tumor cells may reflect basal epithelial cell characteristics and not necessarily cells that have undergone an EMT. Comparative analyses of normal mouse epithelial subsets with murine tumor models have implicated distinct cell types in contributing to tumorigenesis in the different models. Figures available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-04-03.
A Comparison of Active and Simulated Chiropractic Manipulation as Adjunctive Treatment for Childhood Asthma
Authors: Jeffrey Balon, Peter D. Aker, Edward R. Crowther, Clark Danielson, P. Gerard Cox, Denise O'Shaughnessy, Corinne Walker, Charles H. Goldsmith, Eric Duku, Malcolm R. Sears
Journal: New England Journal of Medicine (1998)

Chiropractic spinal manipulation has been reported to be of benefit in nonmusculoskeletal conditions, including asthma.
Abstract 109: DNA methylation profiling associated with recurrence of prostate cancer
Authors: Krishna Vanaja Donkena, Eric W. Klee, Charles Y.F. Young, George G. Klee, Donald J. Tindall, Michael L. Blute
Journal: Cancer Research (2011)

Abstract DNA methylation profiles could signify the risk of prostate cancer and predict the progression of cancer before the appearance of clinical symptoms. Specific CpG sites methylation of genes identified in our study could be used to improve the sensitivity and specificity for early diagnosis and to predict the risk of prostate cancer recurrence. To identify methylation changes associated with prostate cancer, we measured gene methylation using the Infinium Human Methylation27 bead chips. Tissue DNA isolation and bisulfite conversion was done using ZR Genomic DNA kit and EZ methylation kit. The methylation27 microarrays was used to analyze methylation of 27,578 CpG sites of 14,495 genes in 198 tumor tissues and 40 matched normal tissues. Methylation data was processed using the Genome Studio software, differentially methylated genes identified using one-way analysis of variance, and correction for multiple testing done using the false discovery rate q-value. To identify putative diagnostic and prognostic biomarkers we performed four subgroup comparisons: tumor vs. matched normal, recurrent tumors vs. non-recurrent tumors, clinical recurrence vs. biochemical recurrence, and systemic recurrence vs. local recurrence. Clinicopathological and molecular features including patient preoperative PSA levels, Gelason score, TNM stage, GPSM, recurrence type, were also evaluated for subgroup discrimination. Discriminative subgroup candidate methlyation markers were selected using a p value &amp;lt;0.05 and a mean difference between two contrast groups &amp;gt;0.05. Between the tumor and matched normal tissue samples, 164 CpG sites representing 147 genes were identified as significantly differentially methylated (p&amp;lt;9.99E-25, fold change&amp;gt;2.0). Between recurrent tumor and non-recurrent tumor tissues there were 78 CpG sites representing 75 genes that were significantly differentially methylated (p &amp;lt;0.002, fold change &amp;gt;1.5). Between clinically recurrent and biochemically recurrent tumors, 16 CpG sites representing 16 genes were significantly differentially methylated (p &amp;lt;0.05, fold change &amp;gt;1.5). Between systemic recurrent and local recurrent tumors there were 73 CpG sites representing 68 genes that were significantly differentially methylated (p &amp;lt;0.01, fold change &amp;gt;1.5) Our analysis revealed differential methylation of the genes, implicating their role in prostate cancer development and progression. We demonstrated that the hypermethylation of genes could be used as a sensitive molecular tool in detection of prostate tumorigenesis and prediction of tumor progression. 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 109. doi:10.1158/1538-7445.AM2011-109
WAIST CIRCUMFERENCE IS A STRONG PREDICTOR OF REGIONAL LEFT VENTRICULAR DYSFUNCTION IN ASYMPTOMATIC DIABETIC PATIENTS: THE FACTOR- 64 STUDY
Authors: Boaz D. Rosen, Ravi Sharma, Kenneth D. Horton, Heidi May, Yitzhak Rosen, Jeffrey Anderson, Donald Lappe, Joao Lima, J. Muhlestein
Journal: Journal of the American College of Cardiology (2016)
AB0604 Heat Shock Protein Gene-60 (HSP 60) Polymorphism in Behcet's Disease
Authors: Z. Ozbalkan, I. Ertenli, S. Kiraz, M.A. Ozturk, M. Mısırlıoglu, S. Tuncer, Y. Karaaslan, M. Calguneri
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Behcet9s Disease (BD) has the hallmarks of complex genetic disorder. The most established genetic marker-HLA B51 does not account for more than 20% of the relative risk in siblings of affected individuals. Heat shock proteins (HSP) might stimulate both innate and adaptive immune mechanisms in BD. They might be linked to the chemoattraction of inflammatory cells. HSP gene polymorphisms could explain the clinical diversity of the BD. <h3>Methods</h3> Case patients were 110 consecutive Turkish patients with BD, 100 healthy controls and 93 connective tissue disease patients rather then BD (rheumatoid arthritis, n: 29; primer systemic vasculiitis, n:18; ankylosing spondiliitis, n:15; systemic sclerosis, n:11; systemic lupus erythematosus, n:8; primary Raynoud9s syndrome, n:7; Sjögren9s syndrome, n:3; dermatomyositis, n:1; recurrent oral ulceration, n: 1) were involved in this study. All BD patients and controls were genotyped by polymerase chain reaction for HSP60 polymorphism at codon 136-1 and 2, 178, 244, and 336. <h3>Results</h3> The frequency of GAT/GAA single nucleotide polymorphism in codon 136-2 was found in three BD patients with vascular clinical manifestation, but none of the any subject in control groups (p&lt;0.001). <h3>Conclusions</h3> Our findings show that GAT/GAA 136-2 polymorphism of HSP60 might be associated the severity of the BD mainly with vascular manifestations susceptibility. But this association is difficult to be accepted as SNP that causes the disease susceptibility or severity. <h3>References</h3> Ghasemi Y. Comput Biol Med.2012 Nov; 42(1):1079-85. Kaneko F. Clin Dev Immunol 2011; 2011: 681956. Deniz E. Oral Surg Oral Med Oral Pathol Oral Radiol Endo 2010 Aug; 110(2):196-200. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3623
Researchers Struggle To Get Fetal Tissue For Cancer Research
Authors: Cori Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Researchers Struggle To Get Fetal Tissue For Cancer Research 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 84, Issue 6, 18 March 1992, Pages 382–384, https://doi.org/10.1093/jnci/84.6.382-a Published: 18 March 1992
Abnormal Regulation of Ventilation in Infants at Risk for Sudden-Infant-Death Syndrome
Authors: Daniel C. Shannon, Dorothy H. Kelly, Kathleen O'Connell
Journal: New England Journal of Medicine (1977)

To test whether alveolar hypoventilation and an abnormal ventilatory response to inhaled carbon dioxide explains some episodes of sudden-infant-death syndrome, we assessed ventilatory control during quiet sleep in 12 normal infants and 11 infants who had required at least two resuscitations because of prolonged apnea (greater than 20 seconds) during sleep (aborted form of the syndrome). Infants with the aborted syndrome hypoventilated during quiet sleep (alveolar partial pressure of carbon dioxide, 38.9+/-3.5 mm Hg) as compared to normal infants (35.1+/-1.9, P less than 0.01). In addition, the ventilatory response to carbon dioxide breathing during quiet sleep was impaired (mean change in minute ventilation per change in partial pressure of carbon dioxide 22.1+/-8.9, as compared to 63.1+/-19.1 ml per kilogram per minute per millimeter of mercury in controls [p less than 0.001]). Three infants with the "aborted syndrome" subsequently died during sleep at home; autopsy, done in two, revealed no apparent cause of death. We conclude that infants who have had an episode consistent with sudden-infant-death syndrome have a defect in the regulation of alveolar ventilation.