tbuckley/cabot-search huggingface dataset:
Congress Gives More Attention To Breast Cancer
Authors: Tom Reynolds
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Congress Gives More Attention To Breast Cancer Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 14, 17 July 1991, Page 996, https://doi.org/10.1093/jnci/83.14.996 Published: 17 July 1991
Abstract 2229: Detection of somatic mutations in KRAS gene in Chilean patients with advanced colorectal cancer
Authors: Claudia Hurtado, Alejandro J. Zárate, Udo Kronberg, Jorge Lévican, Luis Contreras, Francisco López-Köstner
Journal: Cancer Research (2011)

Abstract Introduction: At present, the application of tailored oncologic therapies requires previous performance of mutational analysis of certain genes. In patients with advanced colorectal cancer (CRC), it is essential to detect the presence of activating mutations in the KRAS gene to predict the effectiveness of certain treatments. Purpose: To determine the presence of KRAS mutations in Chilean patients with advanced CRC, and correlate the mutational status with clinical-pathological data. Methods: Between October 2009 and August 2010, we prospectively studied the presence of somatic mutations in the KRAS gene in codons 12 and 13 in biopsies of patients with advanced colorectal cancer by allele specific and real time PCR kit. The results were registered in a database, along with the pathology results and clinical data of the patients. Statistical analysis was performed by Student T test and Chi-square test. A p&amp;gt;0.05 was no significant. Results: A total of 123 patients were analyzed, with a mean age of 61 years and male predominance (60%). Mutations were detected in 47 (39%) of them and only in 2 cases the study was inconclusive. The distribution of the different mutations was as follows: 12Asp (32%), 12Val (26%), 13Asp (19%), 12Cys (11%), 12Ala (6%) and 12Ser (6%). Separated by gender, the detection rate was higher in male patients (45% vs 30%) (p=0.59). Analyzing the data by location of tumor, we found that mutations in right colon tumors was present in 26% (6/23), whereas tumors of the left colon and sigmoid were 43% (16/37) (p=0.1). Mutations detected in patients with lymph node metastasis was 42% comparing to node-negative patients (32%) (p=0.3). In patients with poorly differentiated tumors we found 50% mutations compared to well differentiated (18%) (p=0.08). Finally, the mortality was similar when we compared between WT and mutations patients. Conclusions: In Chile, 39% of patients with advanced CRC carry mutations in KRAS gene. This result is similar to that described in other populations. There is a tendency to a higher mutation rate in males, patients with left colon cancer, poorly differentiated tumors and patients with lymph nodal involvement. 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 2229. doi:10.1158/1538-7445.AM2011-2229
A5.2 Paracrine effects of human adipose tissue derived stem cells on osteoarthritic cartilage explants in cocultures<i>in vitro</i>
Authors: E Bernotiene, J Denkovskij, E Bagdonas, I Kusleviciute, I Porvaneckas, A Unguryte, Z Mackiewicz
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) ensures maintenance of healthy cartilage, whereas weighted damaging effects of the enzymes leads to the development of osteoarthritis (OA). To develop the adipose tissue derived stem cell (ASC) therapy in OA, we were seeking to evaluate paracrine and chondroprotective properties of the cells in recovering the homeostasis between MMPs/TIMPs in the joint. <h3>Methods</h3> To determine the effects of ASCs on OA cartilage, we performed short (3 &amp; 7 days) and long (21 day) in vitro ASC cocultures with articular cartilage explants (CE). To further reproduce the OA conditions, cocultures were also stimulated with IL-1β. Production of TIMPs, MMPs, and factors, related to inflammation or chondrogenesis, was analysed in coculture supernatants by ELISA. CE were further processed for RT-qPCR and immunohistochemical analysis. <h3>Results</h3> ASC produced TIMP-1, -2 and -3, as well as gelatinases MMP-2 and -9 at the levels similar to those of CE. Gelatinases MMP-2 and -9 degrade denatured collagens, including type I. Cocultures with ASC resulted in up-regulation of COL1A1 gene. Although the increase in collagen type I production is generally considered as a sign of fibrosis, its enhancement has also been demonstrated during cartilage development, and might reflect early events of the repair. No or low production of MMP-1, MMP-3, and MMP-13 was determined in supernatants of ASC, whereas CE produced them abundantly. Noteworthy, cocultures with the cells resulted in significant suppression of MMP-13 on days 3 &amp; 7, and in particular, day 21, as compared to CE alone at the both, mRNA and protein level. Stimulation with IL-1β differentially modulated production of various MMPs and TIMPs by ASCs and CE, however the effects of ASC seem to further be beneficial. Histological examination showed a tendency to extracellular matrix improvement in the osteoarthritic CE cocultured with ASC, further supporting chondroprotective effects of those cells in the both, presence or absence of IL-1β. <h3>Conclusions</h3> Production of TIMPs and gelatinases, associated with the increase in collagen I production in CE by ASC suggest their active participation in cartilage turnover, encompassing stimulation of remodelling processes. Absence of MMP-1, -3 or -13 production implies safety of the use of ASC for intraarticular clinical applications. Down-regulation of MMP13 in CE indicates possible antihypertrophic effects of ASC. Taken together, results of our study suggest beneficial properties of ASC in prevention of cartilage from degradation during OA, even in the presence of IL-1β.
P524 COMPARISON OF DIFFERENT MODELS IN PREDICTING CLINICALLY SIGNIFICANT PORTAL HYPERTENSION INCLUDING ELF-SCORE AND vWF-Ag
Authors: A. Maieron, S. Hametner, M. Ferlitsch, A. Etschmaier, R. Schoefl, A. Ziachehabi, D. Trubert-Exinger, A. Ferlitsch
Journal: Journal of Hepatology (2014)
Abstract 5105: Genetic alterations of the metastatic lesions in ovarian carcinoma
Authors: Joel Malek, Eliane Mery, Binu George, Alejandra Martinez, Jean-Paul Thiery, Ruby Huang, Denis Querleu, Arash Rafii
Journal: Cancer Research (2012)

Abstract Background: Ovarian cancer is the most deadly gynecological cancer. The high rate of mortality is due to the large tumor burden with extensive metastatic lesion of the abdominal cavity. There are few studies on genetic alterations and their consequences in peritoneal metastatic tumors when compared to their matched ovarian primary tumors. Our hypothesis is that differences between the metastatic and primary lesions might be the cause of residual disease and, most importantly may have a role in post-chemotherapeutic recurrences. Methods: We conducted integrated genomics analysis on matched primary and metastatic tumors from 9 patients. In the papers presented here we analyze genome-wide Copy Number Variations (CNVs) using SNP Arrays targeting peritoneal metastasis differences, Gene expression differences using Microarrays also targeting peritoneal metastasis differences, and for some patients, Single Nucleotide Polymorphisms (SNPs) in genes through Exome sequencing. Results: Here we show that CNVs vary significantly between primary and metastatic tumors and include genes that have been considered potential chemotherapeutic targets based on primary tumor only data. Gene expression differences, while minor, showed highly statistically significant enrichment of genes in ovarian cancer critical pathways. In agreement with findings in other cancers, exome sequencing data revealed very few SNP differences of which most metastasis enriched SNPs were present at very low levels in the primary tumor. The results presented here should allow better design of therapies to target residual ovarian cancer disease. 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 5105. doi:1538-7445.AM2012-5105
Abstract P2-04-05: Prolonged targeted overexpression of Aurora-A in mammary epithelium promotes mammary adenocarcinoma with genomic instability
Authors: W Treekitkarnmongkol, H Katayama, S Sen
Journal: Cancer Research (2012)

Abstract Aurora kinase-A (referred to as Aurora-A) identified as a sereine/threonine kinase induces mitotic progression process including centrosome amplification, bipolar spindle formation and chromosome segregation through modulation of activity and localization of its interacting proteins during cell division. Beside its essential roles in mitosis, cancer profiling studies have revealed that Aurora-A function is implicated in tumor relevant signaling pathways and overexpressed in many human tumors. The findings showed highly frequent overexpression of Aurora-A in human breast ductal carcinoma in situ and primary invasive ductal breast carcinoma. Moreover, the Aurora-A overexpression correlates with poor prognosis in breast carcinoma, deregulated overexpression of Aurora-A associates with centrosome anomalies and chromosome instability in rodent models of mammary caricinogenesis. However, published studies in several transgenic mouse models attempting to address the role of Aurora-A in tumorigenesis and genomic instability have raised conflicting results. In this report we targeted expression of Aurora-A transgene in an inducible mouse model in which expression of Aurora-A was restricted to mammary epithelium during multiple pregnancy and lactation cycles under the activity of β-lactoglobulin promotor. The results demonstrate that overexpression of Aurora-A could induce tumorigenesis in mouse mammary epithelium. The tumor incidence was 70% of Aurora-A transgenic mice at 16 months of age. Of note, overexpression of Aurora-A led to genomic instability. Comparative genomic hybridization (CGH) array analyses revealed loss of Trim12a, Trim12c, Trim30b, Trim30d, Trim30e, Cdkn2d, Pten, Cep55 and gain of Adam6. Notably, Aurora-A overexpression caused nuclear accumulation of cyclin D1, activation of AKT, overexpression of TPX2 and PLK1and loss of ERα expression in tumors. Our findings indicated that prolonged Aurora-A expression in mammary epithelium leads to mammary adenocarcinomas with genomic instability. Aurora-A driven adenocarcinoma reveals deregulation of critical tumor relevant genetic pathways involving both oncogenes and tumor suppressor genes. These transgenic mouse model findings indicate that Aurora-A may be an important therapeutic target for mammary cancer. Keywords: Aurora-A, carcinogenesis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-05.
FRI0417 Long term influence of nsaids on radiographic progression in patients with ankylosing spondylitis.
Authors: R. Schiotis, P. Font, A. Escudero, A. Buzoianu, P. Zarco, R. Almodovar, J. Gratacos, J. Mulero, X. Juanola, C. Montilla, M. Moreno, R. Ariza Ariza, E. Collantes Estevez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The inhibitory effect of the treatment on styructural damage in AS is not completely understood and it is sill a matter under debate. Recent data indicated that NSAIDs could retard radiographic progression in certain subgroups of patients<sup>[1],[2]</sup> <h3>Objectives</h3> To investigate the long term influence of NSAIDs on the rate of radiographic progression administrated as continuous vs.on-demand therapy. <h3>Methods</h3> Patients included in REGISPONSER with the diagnosis of AS were selected and ought to be administrated only NSAIDs for a period of 3 years. Patients were divided in 2 groups according to NSAIDs intake (continuously vs on-demand). BASRI-spine was applied at baseline and after 3 years. Patients who had the maximum BASRI value of 12 at baseline were excluded form the study. X<sup>2</sup> test, student T test and ANCOVA were applied to compare differences between groups. A logistic regression was performed to analyze the influence of NSAIDs treatment and other factors on the rate of radiographic progression. <h3>Results</h3> One hundred eighteen patients were included. No significant differences were found in the two treatment groups at baseline, with exception of disease activity(table 1). Significant radiographic progression was identified in the 2 treatment groups after 3 years follow up( p&lt;0.001). The mean BASRI change was 0.66 ± 1.04 in on-demand treatment group vs.0.64 ± 1.22 in continuous treatment group (p-NS after adjustment for symptoms duration). Although in the logistic regression the type of NSAID treatment was not identified as independent predictive factor of increased radiographic damage as were male sex (p= 0.025) and baseline damage (p&lt;0.001), a significant interaction was found between NSAIDs treatment and time-average (ta) CRP (&gt;6 vs. ≤6 mg/L) (OR: 0.04, CI95 %( 0.003-0.524) <h3>Conclusions</h3> NSAIDs treatment could not stop radiographic damage in AS. Patients with high CRP level who received NSAIDs on–demand showed the highest progression risk. <h3>References</h3> Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Märker-Hermann E, Zeidler H, et al. Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis. 2012, 71:1616-22. Kroon F, Landewé R, Dougados M, van der Heijde D. Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis. Ann Rheum Dis. 2012;71:1623-9. <h3>Disclosure of Interest</h3> None Declared
Abstract 4332: Development of AGS15E, a novel antibody drug conjugate targeting SLITRK6 for the treatment of bladder cancer.
Authors: Kendall Morrison
Journal: Cancer Research (2013)

Abstract Agensys (an affiliate of Astellas Pharma), Santa Monica, CA Abstract: SLITRK6 is a member of the SLITRK family of neuronal transmembrane proteins involved in neurite outgrowth. It was discovered by Agensys using suppressive subtractive hybridization on biopsies from bladder cancer patients. Expression in bladder cancer was confirmed by RNA and immunohistochemical analysis. These studies showed SLITRK6 to be highly expressed in bladder carcinoma in situ as well as in invasive and metastatic bladder cancer. In addition, SLITRK6 was shown to be expressed in a subset of lung cancer, breast cancer and glioblastoma specimens. Agensys has generated a novel antibody drug conjugate (ADC), targeting SLITRK6, which is being developed for the treatment of advanced bladder cancer. This Monomethyl Auristatin E based ADC binds to cell surface SLITRK6 with high affinity and cross reacts with the cynomolgus monkey orthologue. Selection and development of this ADC will be discussed including antibody choice, drug platform choice, conjugation development and other aspects of pre-clinical evaluation. Citation Format: Kendall Morrison. Development of AGS15E, a novel antibody drug conjugate targeting SLITRK6 for the treatment of bladder 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 4332. doi:10.1158/1538-7445.AM2013-4332
Volunteers will help diagnose dementia earlier and support patients in the community
Authors: N. Hawkes
Journal: BMJ (2012)

The government has called on a million people to act as “Dementia Friends” in a new initiative to improve the diagnosis and care of dementia in England.

The volunteers will be trained to recognise the signs of dementia and to provide support for those with the condition in their community. The volunteer army would also boost early diagnosis of dementia, the Department of Health says, and help the public to a better understanding of the condition. Once trained, they will be rewarded with a “forget me not” badge to identify them as being able to assist people with dementia.

The department also announced that all health professionals are to be required to ask all patients between the ages of 65 and 74 about their memory; the UK Biobank is to be given £9.6m (€12m; $15.3m) to …
Differences in phenotype, homing properties and suppressive activities of regulatory T cells induced by epicutaneous, oral or sublingual immunotherapy in mice sensitized to peanut
Authors: Vincent Dioszeghy, Lucie Mondoulet, Emilie Puteaux, Véronique Dhelft, Mélanie Ligouis, Camille Plaquet, Christophe Dupont, Pierre-Henri Benhamou
Journal: Cellular and Molecular Immunology (2016)

Allergen-specific immunotherapy has been proposed as an attractive strategy to actively treat food allergy using the following three different immunotherapy routes: oral (OIT), sublingual (SLIT) and epicutaneous (EPIT) immunotherapy. Regulatory T cells (Tregs) have been shown to have a pivotal role in the mechanisms of immunotherapy. The aim of this study was to compare the phenotype and function of Tregs induced in peanut-sensitized BALB/c mice using these three routes of treatment. We show that although EPIT, OIT and SLIT were all able to effectively desensitize peanut-sensitized mice, they induced different subsets of Tregs. Foxp3+ Tregs were induced by the three treatment routes but with greater numbers induced by EPIT. EPIT and OIT also increased the level of LAP+ Tregs, whereas SLIT induced IL-10+ cells. The suppressive activity of EPIT-induced Tregs did not depend on IL-10 but required CTLA-4, whereas OIT acted through both mechanisms and SLIT was strictly dependent on IL-10. Moreover, the three routes influenced the homing properties of induced Tregs differently, with a larger repertoire of chemokine receptors expressed by EPIT-induced Tregs compared with OIT- and SLIT- induced cells, resulting in different protective consequences against allergen exposure. Furthermore, whereas OIT- or SLIT-induced Tregs lost their suppressive activities after treatment was discontinued, the suppressive activities of EPIT-induced Tregs were still effective 8 weeks after the end of treatment, suggesting the induction of a more long-lasting tolerance. In summary, EPIT, OIT and SLIT mediated desensitization through the induction of different subsets of Tregs, leading to important differences in the subsequent protection against allergen exposure and the possible induction of tolerance.
UTILIDAD DE LA PUNCIÓN ASPIRACION CON AGUJA FINA GUIADA POR ECOENDOSCOPIA (USE-PAAF) EN EL ESTUDIO DE ADENOPATIAS. EXPERIENCIA EN NUESTRO CENTRO
Authors: MI Castro Novo, E Sánchez Hernández, P Quintas Lorenzo, MC Penin Corderi, P Vega Villaamil, F Valentín Gomez, MT Alves Perez, JJ Fernández Seara
Journal: Endoscopy (2012)

Objetivo: Evaluar la utilidad diagnóstica de la USE-PAAF en el estudio de adenopatías en nuestro centro. Material y método: Revisión retrospectiva de pacientes sometidos a USE-PAAF de adenopatías entre enero 2007 y diciembre 2011 en el Complejo Hospitalario de Orense. Las exploraciones se realizaron con el ecoendoscopio lineal Olympus GF-UE160-AL5, puncionándose las adenopatías con aguja de 22G. Criterios de inclusión: pacientes remitidos a nuestra unidad y sometidos a USE-PAAF para estudio de adenopatías supra e infradiafragmáticas. El patrón de referencia empleado para definir si la lesión era benigna o maligna al realizar las pruebas de exactitud diagnóstica fue la anatomía patológica de la pieza quirúrgica o la evolución clínica y respuesta a tratamiento. Se compararon los resultados de la USE-PAAF con el diagnóstico final para calcular la sensibilidad y especificidad. Resultados: Se realizaron 64 USE-PAAF de adenopatías, 76% varones, con una edad media de 65,17 (37–84) años El 65.6% de la adenopatías fueron supradiafragmáticas y el 34.4% infradiafragmáticas, con un tamaño medio de 26.52±14.29mm. Los diagnósticos citológicos obtenidos mediante la punción fueron: 11 adenocarcinoma; 2 carcinoma anaplásico; 1 carcinoma anillo de sello; 1 carcinoma célula grande; 1 carcinoma célula pequeña; 2 carcinoma epidermoide; 2 carcinoma escamosos, 1 carcinoma oat-cell; 1 carcinoma poco diferenciado; 1 carcinoma medular tiroides; 1 colangiocarcinoma; 1 hepatocarcinoma; 7 linfomas; 1 mieloma; 3 linfadenitis granulomatosa no necrotizante; 4 linfadenitis reactivas y 7 sin datos de malignidad. 17 (26.6%) de las muestras citológicas no fueron concluyentes. Se obtuvo una sensibilidad 96.97%, especificidad 92.85%, valor predictivo positivo (VPP) 96.97% y valor predictivo negativo (VPN) 92.85%. No se produjeron complicaciones. Conclusión: La USE-PAAF es un procedimiento seguro, mínimamente invasivo y con un alto rendimiento diagnóstico para el estudio de adenopatías. Por lo que debería se considerada como técnica de elección cuando la PAAF percutánea no sea viable.
Abstract 2838: p53-R72P single nucleotide polymorphism is not associated with cancer risk, histopathologic features or clinical outcome in renal cell carcinoma in Caucasians
Authors: Christine G. Hammerschmied, Robert Stoehr, Bernhard Walter, Kerstin Junker, Holger Moch, Raoul Hinze, Ferdinand Hofstaedter, Arndt Hartmann
Journal: Cancer Research (2010)

Abstract Aims: At codon 72, the human p53 gene contains a single nucleotide polymorphism (SNP), where the sequence can either read CGC, which encodes the amino acid arginine (R), or CCC which codes for proline (P). This SNP, p53-R72P, was found to affect numerous carcinogenesis related cell functions, like apoptosis, cell cycle progression, DNA repair, growth arrest and transcriptional activation. P53-R72 was found to be more effective at protecting stressed cells from neoplastic development. Significant associations of this variant to cancer development were found in various cell types, e.g. breast, gastric and lung cancer. No data are available for renal cell carcinoma (RCC). Methods: DNA extracted from formalin-fixed, paraffin-embedded normal tissue of 334 caucasian renal tumor patients (among them 157 affected by clear cell, 54 by papillary, 70 by chromophobe carcinoma and 41 by benign oncocytoma) and 196 controls was examined by restriction fragment length polymorphism (RFLP) using primers for PCR and the restriction enzyme BSTUI. After digestion, the length of the resulting bands was estimated by gel electrophoresis. Genotype distribution of both groups was compared by two sided exact Chi2 test. We also tested for associations of any genotype to histologic subtype, stage, nuclear grade, age at diagnosis, tumor-related survival and gender. Survival analysis was performed using log rank statistics. For examination of the potential influence of the presence or absence of the C allele, analyses were repeated with a combined C/C+CG group vs. G/G. Results: Genotype distribution of RCC or benign oncocytoma carriers and controls did not differ significantly, and there was no correlation of genotype and age of onset. We did not observe a significant acceleration of a certain genotype relative to gender, age group, subtype, stage or nuclear grade. Both tumor-related survival and progression free survival were not affected by genotype. Similar results were obtained when the two C allele carrying groups were pooled for analysis. Conclusions: The p53 R72P polymorphism does not seem to affect the risk of developing RCC or benign oncocytoma, the course of the disease, or histopathologic features in Caucasians. 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 2838.