tbuckley/cabot-search huggingface dataset:
EP-01 * HETEROGENEITY OF RELA PROTEIN EXPRESSION IN PAEDIATRIC EPENDYMOMA
Authors: T. Ritzmann, H. Rogers, J. Ward, R. Grundy
Journal: Neuro-Oncology (2015)

INTRODUCTION: Ependymoma is the second commonest central nervous system malignancy in children. 50% of sufferers relapse and 80% of these subsequently die. Few prognostic factors have been identified but improved outcomes are seen in children over 3 years old and those with more complete surgical resection. Intratumour heterogeneity has not been previously described in ependymoma and refers to the diversity within a tumour. It has implications because, if present, single biopsies may ‘miss’ important areas whilst conventional treatments may ‘select’ for more resistant clonal populations. Overexpression of RelA protein has been described in ependymomas with the C11Orf95-RELA fusion gene; previously identified in 70% of supratentorial ependymomas. We aimed to interrogate a cohort of ependymomas for evidence of heterogeneity using RelA protein as a marker. METHODS: Tissue microarrays (TMAs) and whole sections from a group of children with ependymoma underwent immunohistochemistry for RelA protein. Each TMA core was scored as negative, positive or strongly positive (+/− nuclear staining) for RelA protein expression. RESULTS: 746 cores from 283 tumours (Mean = 2.63 cores/tumour) were scored. RelA protein was expressed in posterior fossa (34.2%), supratentorial (46.2%) and spinal (50.0%) tumours. 42 tumours had only 1 core available so were excluded. Of the remaining 241 tumours, 63 (26.1%) had multiple heterogeneous cores. Tumours with more cores were more likely to demonstrate heterogeneity. Heterogeneity was also seen across 23 tumour sections. CONCLUSIONS: Knowledge of ependymoma heterogeneity will facilitate approaches to diagnosis and development of targeted therapies. RelA protein is expressed heterogeneously in ependymoma and work based on protein expression in TMAs should therefore consider the risk of sampling bias. The extent of heterogeneity in ependymoma merits further study; including investigation of the relationship between RelA protein expression and the C11Orf95-RELA fusion genes and assessment of the association between RelA expression and clinical features.
Is the rate of post-ERCP pancreatitis not reduced by guide-wire cannulation?
Authors: D. Park, S. Lee, D.-W. Seo, S.-K. Lee, M.-H. Kim
Journal: Endoscopy (2008)

We read with great interest the paper on the role of guide-wire cannulation with regard to post-ERCP pancreatitis (PEP) by Bailey et al. [1]. To date, the results for guide-wire cannulation in the prevention of PEP are conflicting [2] [3] [4]; Bailey et al. carried out a neat prospective randomized trial on this issue. In their study [1], interestingly, guide-wire cannulation improved the primary success rate for biliary cannulation during ERCP but did not reduce the incidence of PEP, compared with conventional contrast cannulation.
SP0196 Delivering an Online Disease-Specific Rehabilitation Intervention: Examples from the SPIN Hand Project
Authors: L. Mouthon
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> People with rare diseases such as systemic sclerosis (SSc) do not typically have access to evidence-based, disease-specific rehabilitation interventions, and many factors complicate the delivery of these types of interventions. Few centers treat enough patients with a given rare disease to sustain a disease-specific intervention program. Additionally, many patients with rare diseases live far from major treatment centers. These individuals often receive care in local settings from health care providers with little or no experience treating their disease and without knowledge about the specific needs of people with the disease. Hand problems, including joint contractures and limits in range of motion are common in SSc, and frequently lead to functional limitations in daily activities. Interventions from physical and occupational therapists may help to reduce disability, but finding a way to feasibly deliver these types of interventions in a cost-effective manner is an important challenge. The objective of this presentation is to illustrate the development of a feasibly-delivered, disease-specific online intervention to improve hand function, based on relevant literature, clinical expertise, and existing programs. The intervention is developed by investigators of the Scleroderma Patient-centered Intervention Network (SPIN), an international collaboration of patient organizations, clinicians, and researchers, who are establishing a clinical research infrastructure to test accessible, low-cost, self-guided online interventions to reduce disability and improve the health-related quality of life for people living with SSc. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6226
FRI0121 Concordance of 6 composite disease activity measures in a peruvian population with rheumatoid arthritis
Authors: M. Ugarte-Gil, A. Garcia-Poma, R. Gamboa-Cardenas, C. Mora, M. Cucho, H. Terrazas, C. Pastor, E. Rhor, E. Acevedo-Vasquez, M.I. Segami
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The management of the Rheumatoid Arthritis using standardized activity measures have probed better outcomes than usual care. There are few studies that evaluated the concordance of the most used activity measures in Hispanic population. <h3>Objectives</h3> To evaluate concordance and agreement of the original DAS28/ESR-4 item composite disease activity status measure with 3 of its derivatives: DAS28/CRP-4 item, DAS28/ESR-3 item, DAS28/CRP 3-item, SDAI and CDAI when classifying patient disease activity by European League of Associations for Rheumatology (EULAR) criteria, using an established rheumatoid arthritis (RA) patient cohort. <h3>Methods</h3> A cross-sectional study was performed at the Rheumatology Departments of the two biggest hospitals of Lima, Peru (since 2005 to 2009). Disease activity was evaluated using DAS28/ESR-4 item, DAS28/CRP-4 item, DAS28/ESR-3 item, DAS28/CRP 3-item, SDAI and CDAI. We analyzed the degree of agreement using kappa (k) index for these cutoff points: DAS28-ESR 4 or 3 item (&lt;2.6: remission, 2.6 to &lt;3.2: mild activity, 3.2 to 5.1: moderate activity and&gt;5.1: severe activity), DAS28-CRP 4 or 3 item (&lt;1.8: remission, 1.8 to &lt;2.5: mild activity, 2.5 to 4.1: moderate activity and&gt;4.1: severe activity), SDAI (&lt;3.3: remission, 3.3 to &lt;11: mild activity, 11 to 26: moderate activity and&gt;26: severe activity) and CDAI (&lt;2.8: remission, 2.8 to &lt;10: mild activity, 10 to 22: moderate activity and&gt;22: severe activity). <h3>Results</h3> We included 615 patients, with an average age of 57.54 years (SD 13.34), and a disease duration of 15.29 years (SD: 11.23); 536 (87.2%) were female. The average DAS28/ESR-4 item was 4.87 (SD 1.44). According to DAS28/ESR-4 item 33 (5.4%) were in remission, 52 (8.5%) showed mild activity, 258 (42.0%) moderate and 272 (44.2%) severe activity. Agreement between the categories using DAS28/ESR-4 item and DAS28/CRP-4 item was 79.3% (k: 0.68); DAS28/ESR-4 item and DAS28/ESR-3 item was 84.4% (k: 0.75), DAS28/ESR-4 item and DAS28/CRP-3 item was 68.8% (k: 0.53), DAS28/ESR-4 item and SDAI was 65.1% (k: 0.47), DAS28/ESR-4 item and CDAI was 69.2% (k: 0.54). <h3>Conclusions</h3> The DAS28/ESR-4 item, and its variants, SDAI, and CDAI are valid tools for disease activity assessment in Peruvian population with RA, and present a moderate or good agreement between its categories. <h3>References</h3> Gamboa RV, Ugarte-Gil MF, Diaz K, Alfaro JL, Cucho M, et al. New cut off points of the DAS28(CRP) to define categories of disease activity in Peruvian patients with rheumatoid arthritis. Ann Rheum Dis 2011; 70 (Suppl3): 592 <h3>Disclosure of Interest</h3> None Declared
The chemoresistant population of luminal subtype human breast cancer cells expresses a basal phenotype.
Authors: P Kabos, WW Dye, A Elias, KB Horwitz, CA Sartorius
Journal: Cancer Research (2009)

Abstract Abstract #42 Background: We recently identified rare cells that express cytokeratin 5 (CK5+) and lack estrogen and progesterone receptors (ER– and PR–), in solid tumor xenografts derived from ER+PR+ T47D luminal A subtype human breast cancer cells (Horwitz et al, 2008 PNAS 105: 5774). These rare CK5+ cells have the capacity to re-form the majority of ER+PR+CK18+ cells in luminal tumor xenografts, and recapitulate the original tumor heterogeneity. CK5 is a marker of the poor prognosis basal-like subtype of human breast cancers. Additionally, CK5 is postulated to be a marker of stem/progenitor like cells in the human breast, and we have shown that CK5+ cells co-express the breast cancer stem cell marker CD44. We postulated that these rare basal-like CK5+ cells represent a potential chemoresistant subpopulation within luminal tumors. To test this, we used T47D and MCF7 cells, both of which have been classified by genetic profiling as luminal A (ER+PR+CK18+HER2–).&amp;#x2028; Methods: Cells were plated at subconfluent densities in serum-containing media and treated with either vehicle or cyclophosphamide (1mM), 5-fluorouracil (150μM) or docetaxel (11nM) for 72 hours; these doses were determined to yield a one to two-log kill. Residual chemoresistant cells were fixed: i) immediately following chemotherapy, or ii) after colony repopulation for 7 days. The chemoresistant subpopulation was characterized by immunocytochemistry for markers of basal/stem and luminal phenotypes, including CK5, ER, PR, CK18, and CD44.&amp;#x2028; Results: At baseline, as well as in controls, both cell lines were ER+PR+CK18+ and ER–PR–CK5+ cells were rare or undetectable. In response to treatment with each of the three drugs, the surviving population was enriched in ER–CK5+ cells. PR expression was variable (+/–) in CK5+ cells. These chemoresistant cells were able to repopulate colonies that expressed ER+PR+CK18+ and resembled the original cells by having a predominant luminal phenotype, with only rare/undetectable receptor negative, CK5+ basal-like cells.&amp;#x2028; Conclusion: We conclude that luminal subtype human breast cancer cells contain a rare basal/stem-like chemoresistant subpopulation that is capable of repopulating a luminal tumor after therapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 42.
Abstract 3603: Zidovudine (AZT)-induced aneuploidy, mediated by Stathmin 1 (STMN1), involves a loss of polymerized β-tubulin.
Authors: Andrea V. Rivera, Vanesa C. Sanchez, Miriam C. Poirier, Ofelia A. Olivero
Journal: Cancer Research (2013)

Abstract The nucleoside reverse transcriptase inhibitor AZT induces multiple manifestations of genotoxicity, among which aneuploidy, observed as micronuclei containing whole chromosomes, has been reported (Borojerdi et al., Mut Res, 2009). We have seen a loss of β-tubulin polymerization in about 23% of normal human mammary epithelial cells (NHMECs) exposed for 24 hr to 200 μM AZT, and demonstrated down-regulation of hsa-miR-770-5p, a microRNA known to target STMN1, in the same AZT-exposed cells. STMN1 prevents microtubule polymerization, resulting in destabilization of the mitotic spindle and chromosome misalignment. We therefore hypothesized that, if AZT exposure downregulates hsa-miR-770-5p, there should be increased expression of STMN1, which would result in loss of microtubule polymerization leading to aneuploidy. In this study we exposed cells of the human breast line MCF-10A to 100 μM AZT continuously for 1 to 3 passages (P). By Western Blot we showed that total STMN1 was 3.5-fold increased at P1, in AZT-exposed cells, compared to the unexposed controls. Using the same STMN1 antiserum, by immunohistochemistry (IHC), we observed that some cells stained heavily for STMN1, while others had virtually no staining, and that the overall STMN1 fluorescence was increased in AZT-exposed cells, compared to unexposed controls. When tubulin polymerization was evaluated by IHC, using β-tubulin antiserum, 10.1% of AZT-exposed cells showed a loss of tubulin polymerization, while only 0.7% of unexposed cells showed the same effect (p=0.004). The data suggest that AZT induced aneuploidy may be mediated by inhibition of hsa-miR-770-5p, upregulation of STMN1, impaired polymerization of β-tubulin, aberrant mitotic spindle formation and consequent chromosome misalignment resulting in aneuploidy. If confirmed, this will constitute a novel mechanism of AZT-induced genotoxicity that may or may not be related to AZT-DNA incorporation. Ongoing experiments will explore these relationships further by localizing STMN1 and β-tubulin in specific cells, and examining the same cultures for spindle aberrations at mitosis. Citation Format: Andrea V. Rivera, Vanesa C. Sanchez, Miriam C. Poirier, Ofelia A. Olivero. Zidovudine (AZT)-induced aneuploidy, mediated by Stathmin 1 (STMN1), involves a loss of polymerized β-tubulin. [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 3603. doi:10.1158/1538-7445.AM2013-3603
Abstract LB-331: Polymorphisms in inflammation pathway genes and endometrial cancer
Authors: Ryan J. Delahanty, Yong-Bing Xiang, Amanda Spurdle, Alicia Beeghly-Fadiel, Jirong Long, Deborah Thompson, Ian Tomlinson, Herbert Yu, Diether Lambrechts, Thilo Dörk, Marc T. Goodman, Helga B. Salvesen, Wei Lu, Qiuyin Cai, Wei Zheng, Xiao Ou Shu
Journal: Cancer Research (2012)

Abstract Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. To investigate this hypothesis, we carried out a two-stage study to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 830 endometrial cancer cases and 2,322 controls using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (P&amp;lt;0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. We then selected one SNP from each of the 24 loci for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in the stage 2 sample, which consisted of eight additional studies including 4,890 endometrial cancer cases and 5,403 controls. Four of the 21 SNPs in or near the FABP1, CXCL3, MSR1, and MMP9 genes were significantly associated with endometrial cancer in the combined data sets. The allelic odds ratios were 0.90 (0.82-0.97) for FABP1, 1.17 (1.05-1.31) for CXCL3, 0.86 (0.78-0.96) for MSR1, and 0.90 (0.85-0.95) for MMP9. The SNPs in CXCL3 and MMP9 were significantly associated with endometrial cancer in both the discovery and replication samples. Of these findings, the association for the MMP9 promoter polymorphism rs3918249 (P=0.00047) remained significant after adjustment for the total number of comparisons. These findings suggest that genetic polymorphisms in the MMP9 gene and possibly in or near the FABP1, CXCL3, and MSR1 genes may contribute to genetic susceptibility to endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-331. doi:1538-7445.AM2012-LB-331
Abstract 557: Fluorescence <i>in situ</i> hybridization versus qPCR as means to detect Merkel cell polyomavirus in Merkel cell carcinoma
Authors: Anke M. Haugg, Dorit Rennspiess, Axel zur Hausen, Ernst-Jan M. Speel, Gieri Cathomas, Jürgen C. Becker, David Schrama
Journal: Cancer Research (2012)

Abstract Background: Merkel cell polyoma virus (MCPyV) is detected in 80% of Merkel cell carcinomas (MCC). The clonal integration and tumor specific mutations in the large T Antigen (LTAg) gene strongly implicate an oncogenic impact of the virus. To date the relationship between the viral presence and cancer induction, development or clinical prognosis is discussed controversial. Yet almost all studies are based on quantitative virus detection e.g. PCR or qPCR. Material and Method: In order to gain additional information about the quality of the viral presence on the single cell level we performed FISH analysis of formalin fixed and paraffin embedded (FFPE) MCCs (n= 62) on tissue micro arrays (TMA), determined the FISH pattern and correlated the results of the FISH analysis with the qPCR data. We grouped the MCCs according to different FISH evaluations and correlated them with the respective qPCR data on the basis of a determined cut-off. MCPyV FISH was established using the MKL-1 cell line which harbors integrated copies of MCPyV DNA. For MCPyV-qPCR the LT3 primer pair was used on whole tissue sections. Results: MCPyV-FISH on FFPE MKL-1 cells revealed punctate signals compatible with viral integration. The MCPyV FISH positive MCC cores (76%) mainly revealed two different signal patterns: a punctate pattern (85%) which correlated with a moderate relative viral presence and in some areas the punctate pattern was combined with a diffuse pattern (15%) indicating the episomal presence of the virus which is linked to viral replication. If a pattern mixture was seen this was associated with very high qPCR values. Comparing MCPyV FISH and qPCR data the results correlated highly with 83 % in the MCPyV positive evaluated group, whereas the negative group showed a concordance of 93 %. The mean of the qPCR values of all MCPyV positive cores differed significantly from the negative cores (p= 0.0076). The FISH signals were in some tumor areas from the same patient heterogenic in intensity, pattern and localization. Conclusion: While the qPCR using the LT3 primer pair was highly sensitive to detect MCPyV sequences in the respective MCC cases, the MCPyV FISH analysis highly concordantly revealed the quality of the viral presence, i.e. viral integration or episomal presence and morphological sublocalization in the tissues. 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 557. doi:1538-7445.AM2012-557
Abstract 4884: Involvement of autophagy in penta-1,2,3,4,6-O-galloyl-beta-D-glucose-induced senescence-like growth arrest in human cancer cells.
Authors: Yinhui Dong, Junxuan Lü, Hongbo Hu
Journal: Cancer Research (2013)

Abstract Autophagy and senescence are two important cellular processes that have been shown to play critical roles in the regulation of carcinogenesis. Our previous studies have demonstrated that cellular features of both autophagy and senescence were induced in response to penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG), a polyphenolic anti-cancer compound, in multiple types of cancer cells. In this follow-up study, we further investigated the cross-talk among these PGG-induced phenotypes and signal transduction mechanisms. In cell culture models, we show that inhibition of autophagy by either chemical inhibitors or genetic approaches (RNA interference) led to a near abolishment of PGG-induced senescence, followed by induction of apoptosis, indicating autophagy is required for the senescent phenotype induced by PGG and antagonistic of apoptosis execution. In addition, we identify unfolded protein responses (UPR) in the endoplasmic reticulum (ER) to play a pivotal role in autophagy-mediated senescence phenotype. Furthermore, our data show that c-Jun NH(2)-terminal kinase (JNK) could be a critical mediator for PGG-induced autophagy. In a subcutaneous xenograft mouse model of human HepG2 liver cancer, we detected biochemical markers of modulations of autophagy, ER stress and senescence induced by PGG intra-peritoneal administration for 16 days. Our findings provided novel insights into cellular processes and signaling mechanisms involved in PGG-induced senescence-like growth arrest in human cancer cells. Citation Format: Yinhui Dong, Junxuan Lü, Hongbo Hu. Involvement of autophagy in penta-1,2,3,4,6-O-galloyl-beta-D-glucose-induced senescence-like growth arrest in human cancer 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 4884. doi:10.1158/1538-7445.AM2013-4884
Pseudohyperkalemia Caused by Fist Clenching during Phlebotomy
Authors: B R Don, A Sebastian, M Cheitlin, M Christiansen, M Schambelan
Journal: New England Journal of Medicine (1990)

CLINICIANS are occasionally confronted with the finding of an elevated serum or plasma potassium level in an otherwise healthy person. Such an abnormality may herald the presence of occult mineralocorticoid deficiency or a defect in renal tubular transport.1 Alternatively, it may represent so-called pseudohyperkalemia, caused by the release of potassium from formed elements in the blood in patients with leukocytosis or thrombocytosis.2 , 3 We report here on a patient in whom pseudohyperkalemia resulted from the common practice of repeatedly clenching and unclenching a fist during venipuncture. This maneuver, which has been passed on from generation to generation of house staff, medical . . .
Abstract 1687: Frequent inactivation of the Mieap-regulated mitochondrial quality control in colorectal cancer.
Authors: Hiroki Kamino, Yasuyuki Nakamura, Noriaki Kitamura, Manabu Futamura, Masaki Yoshida, Ryuya Murai, Yuri Saito, Hitoya Sano, Yae Kanai, Yoshihiro Moriya, Hirofumi Arakawa
Journal: Cancer Research (2013)

Abstract Recently, we discovered a novel mechanism for mitochondrial quality control (MQC), in which Mieap, a p53-inducible protein, controls MQC by repairing or eliminating unhealthy mitochondria in a process known as MALM (Mieap-induced Accumulation of Lysosome-like organelles within Mitochondria) or MIV (Mieap-Induced Vacuole), respectively (1, 2). We also reported that two mitochondrial outer membrane proteins, BNIP3 and NIX, are essential mediators of the MALM (2, 3). To examine the role of Mieap-regulated MQC pathway in tumorigenesis, we analyzed the status of p53, Mieap, BNIP3, and NIX in 57 cases of primary colorectal cancer. Of the 57 patients, Mieap and BNIP3 promoter methylation was observed in 5 (8.8%) and 26 (45.6%) patients, respectively. A p53 mutation was detected in 4 (18%) of the 22 patients with either Mieap or BNIP3 promoter methylation whereas it was found in 9 (52%) of the 17 patients with neither Mieap nor BNIP3 promoter methylation, implying that the p53/Mieap/BNIP3 pathway in the Mieap-regulated MQC is inactivated in at least 80% of colorectal cancer cases. Hypoxia induced MALM in the colorectal cancer cell line LS174T (wild-type p53, Mieap-positive, BNIP3-positive). In vitro knockdown of p53, Mieap, or BNIP3 in the LS174T cells severely inhibited hypoxia-induced MALM, leading to the accumulation of unhealthy mitochondria and increased mitochondrial reactive oxygen species (mtROS) generation. Furthermore, the mtROS dramatically enhanced cancer migration and invasion under hypoxic conditions. These results suggest that the Mieap-regulated MQC function plays a critical role in tumor suppression in colorectal cancer. 1. Miyamoto Y et al. PLoS ONE 6: e16054, 2011 2. Kitamura N et al. PLoS ONE 6: e16060, 2011 3. Nakamura Y et al. PLoS ONE 7: e30767, 2012 Citation Format: Hiroki Kamino, Yasuyuki Nakamura, Noriaki Kitamura, Manabu Futamura, Masaki Yoshida, Ryuya Murai, Yuri Saito, Hitoya Sano, Yae Kanai, Yoshihiro Moriya, Hirofumi Arakawa. Frequent inactivation of the Mieap-regulated mitochondrial quality control in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1687. doi:10.1158/1538-7445.AM2013-1687