tbuckley/cabot-search huggingface dataset:
Abstract 1015: Head and neck cancer expression of YAP65: A novel oncogene
Authors: Lin Ge, Lin Ge, Wenxia Meng, Hongmei Zhou, Neil Bhowmick
Journal: Cancer Research (2010)

Abstract Yes-associated protein (YAP), a transcription coactivator associated with maintaining tissue size, is reported as an oncogene in many types of cancer including ovarian, liver, lung, colon and prostate. However, the role of YAP in head and neck carcinomas is not known. Our objective was to explore the role of YAP in head and neck carcinomas. We found YAP overexpressed in the epithelial and stromal compartments of head and neck carcinomas compared to benign tissues in 140 samples. Interestingly, the squamous cell carcinomas, had elevated YAP expression in the epithelial cytoplasm in 36% of the patients. However, we observed both cytoplasmic and prominently nuclear localization of YAP in the adenocarcinomas. The tumor microenvironment is widely accepted as a promoter of tumor progression, where carcinoma-associated fibroblasts (CAFs) constitute the majority of cells. In the stroma, YAP was found to be expressed in endothelial cells and some heterogenously within the CAF population. As reported for prostate cancer, we found the transforming growth factor-beta (TGF-ß) receptor type II expression to be lost in the head and neck cancer-associated stromal cells. Since YAP has never been reported to be associated with CAFs, we performed in vitro experiment to determine the relationship of YAP and TGF-ß signaling in primary stromal cells associated with benign and head and neck cancer cells. We found TGF-ß1 can promote YAP expression and nuclear localization in normal fibroblasts. The oral human CAFs have differential expression of YAP and α-smooth muscle actin (α-SMA). Although CAFs are commonly characterized by their expression of α-SMA, YAP-expressing CAFs expressed less α-SMA and α-SMA-expressing CAFs expressed less YAP in seven independent CAF lines developed. However, all of these heterougenous head and neck CAF lines had the loss of TGF-ß receptor type II expression and concomitant upregulation of Wnt5a. Interestingly, those CAFs expressing YAP had 2-fold greater Wnt5a expression. In conclusion YAP expression is differentially expressed in adeno- and squamous cell carcinomas of head and neck carcinomas, and is heterogenously expressed in the associated CAF. YAP may regulate Wnt5a as a paracrine factor, reported to promote the progression of oral carcinomas, in a TGF-ß dependent and independent manner. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1015.
Abstract 2465: Gene expression, phenotypic and karyotypic analyses of stepwise prostate carcinogenesis <i>in vitro</i>
Authors: Xi-Song Ke, Wen-Cheng Li, Yi Qu, Randi Hovland, Run-hui Liu, Varda Rotter, Lars A. Akslen, Anne Margrete Oyan, Karl-Henning Kalland
Journal: Cancer Research (2010)

Abstract The loss of epithelial characteristics and the acquisition of a migratory phenotype, referred to as epithelial to mesenchymal transition (EMT), is a crucial event in tumor metastasis. Our previous work reported an EMT model based on primary prostate epithelial cells (EP156T) which gave rise to mesenchymal cells (EPT1) without malignant transformation. To achieve transformed prostate cells, EPT1 cells were kept growing in extended saturation density cultures to select for cells overriding quiescence. Following about 30 subconfluent passages and thereafter, foci appeared repeatedly in EPT1 monolayers following three to four weeks in confluent cultures. For comparison, in parallel experiments foci appeared neither in confluent cultures of EPT1 cells of early passage nor in confluent EP156T cells of either low or late passages. Cells from the foci of EPT1 monolayers formed robust colonies in soft agar suggesting full malignant transformation. The transformed cells were named EPT2. In this stepwise transformation model, EPT2 cells showed much higher abilities to proliferate at confluence, migrated better, were less dependent on exogenous growth factors and were more resistant to staurosporine induced apoptosis than EP156T and EPT1 cells. Also, while EP156T cells and EPT1 cells remained diploid, chromosomal instability and aneuploidy were evident in EPT2 cells. Gene expression profiling and western blots showed progressive down-regulation of CDH1 from EP156T, through EPT1 to EPT2 together with a number of additional changes. Our findings provide a novel stepwise transformation model according to which EMT can occur independently of transformation, but is associated with subsequent malignant transformation in prostate carcinogenesis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2465.
AB0655 Relationship between synaptosomal-associated protein 25 (snap-25) gene polymorphism and fibromyalgia syndrome
Authors: A. Balkarli, E. Tepeli, H. Balkarlı, V. Cobankara
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> SNAP-25 protein is a protein contributory to plasma membrane and synaptic vesicle fusions which is a critical point in neurotransmission. SNAP-25 gene is associated with personality disorders, behavioral symptoms and psychological disorders that can develop later in life. In addition, SNAP-25 protein can be related to different neurotransmitter functions because it is associated with vesicle membrane transition and fusion. This is important because neurologic, cognitive, psychologic disorders in fibromyalgia syndrome (FMS) can be related to this. Such relation will be enlightening for etiopathogenesis of FMS and treatment approaches. <h3>Objectives</h3> We aimed to investigate SNAP-25 gene polymorphism and FMS relation in this prospective study. <h3>Methods</h3> We included 71 patients who were diagnosed according to new criteria and 57 matched healthy women in this study. Both groups were evaluated in age, height, weight, BMI, education level, marital status and working conditions. FMS new diagnosis criteria scoring, sleep symptom scale, SF-36, Beck depression scale, BASDAI, VAS, revised fibromyalgia impact (FIQR) questionnaires were done to the patient group. SNAP-25 gene polymorphism and disease activity score correlations were compared. <h3>Results</h3> Mean age was 38±5,196 and 38.12±4.939 in patient and control groups, respectively (p=0.542). No significant difference was found between groups in age, height, weight, BMI, education level, marital status and working condition (p&gt;0,05). We determined MnlI T/G genotype in 34 (47.9%), MnlI G/G genotype in 7 (9.9%), Ddel T/C genotype in 40 (56.3%), and Ddel C/C genotype in 2 (2.8%) patients. 19 (33.3%) MnlI T/G genotype, 11 (19.3%) MnlI G/G genotype, 17 (29.8%) Ddel T/C genotype and 4 (7%) Ddel C/C genotypes were found in the control group. Ddel T/C genotype was significantly higher in the patient group (p=0,009). MnlI gene polymorphism did not show any correlation with any score whereas significant correlation was found between Ddel T/C genotype and lethargy score (p=0.042). <h3>Conclusions</h3> FMS etiopathogenesis is not clearly known. Numerous neurologic, cognitive and psychological disorders were found during cause intended studies. Our study showed increased SNAP-25 Ddel T/C genotype which is related with personality disorders, behavioral symptoms and psychological disorders that can develop later in life in FMS patients when compared with the control group. However larger population is needed with temperament and character inventory in order to explain this relationship. <h3>Disclosure of Interest</h3> None Declared
DECREASED FLUOROSCOPY TIME AND CONTRAST USE WHEN UTILIZING OPTICAL COHERENCE TOMOGRAPHY (OCT) GUIDED SUPERFICIAL FEMORAL ARTERY CHRONIC TOTAL OCCLUSION INTERVENTION
Authors: Perwaiz M. Meraj, Rajkumar Doshi, Pavitra Vijayaraghavan, Krishna Patel, Daniel Helfgott, Avneet Singh
Journal: Journal of the American College of Cardiology (2016)
AB0112 Anisomeles indica and its active principles modulate IL-1BETA
Authors: Y.-C. Shih, K.-K. Huang, Y.-F. Tsai, N.-Y. Hu, M.-N. Lin, Y.-L. Hsu, J.-M. Lo, L.-T. Lee
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Gout is a chronic disease induced by the deposition of monosodium urate. It consists with four stages, hyperuricemia, asymptoms, gout flare and tophaceous gout. Current therapies mainly prevent the flare by using the xanthine oxidase inhibitors, low dose colchicine or uretic agents to keep the level of serum uric acid lower than 6mg/dl. For the flare, the treatment is using steroid or colchicine to control the inflammation and pain. The efficacy of xanthine oxidase inhibitors is very good. But patients have difficulty to go through in the initial stage when the treatment usually causes more flare. The prevention treatment is not benefit for the long term disease outcome and side effects. Recently, the drug development turns to decrease the flare frequency and release the pain at flare-up. The clinical trials showed that the use of IL-1β trap or monoclonal antibody can reduce the number of flares and fast response on pain relief. They are all biologics and inconvenient for long term use and very costly. <h3>Objectives</h3> Our goal was to discover candidates for gout flare treatment by screening the herbal extracts with inhibitory activity of IL-1β secretion in cell and further evaluating in the gout animal model. <h3>Methods</h3> IL-1β secretion from macrophage cells was stimulated by the monosodium urate crystal and the amount of IL-1β was measured with ELISA. The gout animal model was created by the injection of filtered air to form a pseudosynovial air pouch. The exudates induced by the monosodium urate in the air pouch were analyzed for the cytokines and cells. <h3>Results</h3> <i>Anisomeles indica (</i>AG-02) was selected from more than 1000 herbal extracts screening against IL-1β secretion from macrophage cells. The active ingredients of AG-02 were isolated and identified as AG02-RA1 and AG02-RA2. AG-02 ethanol extract and active ingredients AG02-RA1 and AG02-RA2 showed IL-1β inhibitory activity with IC50s of 37±6μg/ml, 4.5±4.6 and 2.2±1.6, respectively. Oral administration of 500mg/kg AG-02 ethanol extract or 6 to 50 mg/kg AG02-RA1 showed both samples could decrease IL-1βsecretion and inflammatory cells infiltration in the air pouch. <h3>Conclusions</h3> The results indicate that AG02 and AG02-RA1 confer anti-inflammatory effects by modulation pro-inflammatory cytokines IL-1β production. Both AG-02 and its active principles may be potential candidates for the treatment of gouty arthritis. <h3>Disclosure of Interest</h3> None Declared
The clinical usefulness of Carotid Ultrasonography in Patients with an Inconclusive Exercise Treadmill Stress Test Result
Authors: Can Yucel Karabay, Gonenc Kocabay, Ahmet Guler, Vecih Oduncu, Taylan Akgun, Arzu Kalayci, Alev Kılıcgedik, Cetin Gecmen, Ayhan Erkol, Akin Izgi, Cevat Kirma
Journal: Journal of the American College of Cardiology (2013)
Screening Tests Pick Up Too Many Indolent Cancers
Authors: D. Holzman
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Screening Tests Pick Up Too Many Indolent Cancers Get access David Holzman David Holzman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 20, 18 October 1995, Pages 1506–1507, https://doi.org/10.1093/jnci/87.20.1506 Published: 18 October 1995
364 DOWNREGULATION OF METHYLTHIOADENOSINE PHOSPHORYLASE (MTAP) EXPRESSION IN CHRONIC LIVER DISEASE PROMOTES HEPATIC INFLAMMATION AND FIBROSIS
Authors: B. Czech, M. Saugspier, K. Dettmer, A. Stevens, C. Dorn, D. Valletta, A. Bosserhoff, P.J. Oefner, C. Hellerbrand
Journal: Journal of Hepatology (2012)
Head Trauma and Exposure to Prolactin-Elevating Drugs as Risk Factors for Male Breast Cancer
Authors: H. Olsson, J. Ranstam
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Head Trauma and Exposure to Prolactin-Elevating Drugs as Risk Factors for Male Breast Cancer Get access Hakan Olsson, Hakan Olsson 3Department of Oncology, University HospitalS-221 85 Lund, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jonas Ranstam Jonas Ranstam 4Department of Community Health Sciences, Malmö General HospitalMalmö, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 9, 6 July 1988, Pages 679–683, https://doi.org/10.1093/jnci/80.9.679 Published: 06 July 1988 Article history Received: 23 February 1988 Revision received: 21 April 1988 Accepted: 28 April 1988 Published: 06 July 1988
DISECCIÓN SUBMUCOSA ENDOSCÓPICA COLORRECTAL AL INICIO DE LA CURVA DE APRENDIZAJE: FACTORES IMPLICADOS EN LA DURACIÓN DEL PROCEDIMIENTO Y LA APARICIÓN DE COMPLICACIONES
Authors: JC Marín-Gabriel, J Díaz Tasende, P Hernán-Ocaña, A González-Blanco, S Rodríguez Muñoz, AJ Del Pozo García, M Alonso-Riaño, F Colina-Ruizdelgado, M Pérez Carreras, A Domínguez-Rodríguez, G Castellano Tortajada
Journal: Endoscopy (2013)

Introducción: La disección submucosa endoscópica es una técnica de reciente introducción en nuestro país. Objetivo: Identificar los factores relacionados con la duración de la misma y la aparición de complicaciones. Material y Método: Se recogieron de forma prospectiva los datos de 31 lesiones resecadas en el Hospital Universitario 12 de Octubre de Madrid (88,6%) y 4 del Hospital Sanitas La Moraleja (11,4%). Resultados: Se llevaron a cabo 35 D.S.E.s entre septiembre de 2008 y junio de 2013. Se detectaron 4 perforaciones (11,4%) y 5 casos de hemorragia digestiva (14,3%). La mediana de duración de la técnica fue de 185 min. No se detectó asociación estadísticamente significativa entre el tiempo (minutos) empleado para la DSE (mediana; rango intercuartílico) y los siguientes factores: lesión proximal vs. rectal (267,5; 95 vs. 159; 133; p= 0,07), ausencia o desarrollo de complicaciones (190; 146 vs. 148; 150; p= 0,65), diámetro < 20 vs. ≥20 mm (150; 113 vs. 200; 150; p= 0,19), técnica DSE pura vs. híbrida (175; 151 vs. 217; 132; p= 0,31) o resección fragmentada vs. en bloc (215; 162 vs. 157,5; 149; p= 0,12). La duración del procedimiento resultó inferior, de manera estadísticamente significativa (129; 75 vs. 252,5; 109; p= 0,001) cuando se empleaba 1 único bisturí vs. ≥2 knives. No se detectaron diferencias estadísticamente significativas entre el porcentaje de complicaciones y los factores evaluados: lesión proximal vs. rectal (25% vs. 28%; p= 1,00), diámetro < 20 vs. ≥20 mm (50% vs. 26,9%; p= 0,56), técnica DSE pura vs. híbrida (29,4% vs. 25%; p= 1,00), resección fragmentada vs. en bloc (33,3% vs. 16,7%; p= 0,43) o empleo de 1 único bisturí vs. ≥2 knives (33,3% vs. 22,2%; p= 0,69). Conclusión: La duración del procedimiento resultó superior, de manera estadísticamente significativa, cuando fue necesario usar al menos 2 endoknives.
Treatment of consecutive episodes of major depression in the elderly
Authors: C F Reynolds, E Frank, J M Perel, M D Miller, C Cornes, A H Rifai, B G Pollock, S Mazumdar, C J George, P R Houck
Journal: American Journal of Psychiatry (1994)

The purpose of this study was to determine treatment outcome in elderly patients with consecutively treated episodes of recurrent unipolar major depression.Subjects were 32 "young" elderly patients with recurrent unipolar depression (mean age = 66.8 years, SD = 5.1) and with two consecutively treated episodes of major depression. Both index and subsequent episodes of major depression were treated in open trial with combined nortriptyline and interpersonal psychotherapy. Rates of remission in index and subsequent episodes were compared by using nonparametric statistics and survival analysis with proportional hazards modeling.Of 30 patients who completed treatment of the subsequent episode, 27 (90%) achieved stable remission of symptoms in both consecutively treated episodes, whereas three patients (10%) did not. Twenty-two (81%) of 27 patients who responded to treatment had a shorter time to remission in treatment of the subsequent episode than in the index episode. Survival analysis with proportional hazards modeling detected a significant difference in time to remission of the index and subsequent episodes (32 paired observations).In this research study group, recurrent episodes of unipolar major depression in the young elderly were successfully treated to remission in over 80% of patients by using combined pharmacotherapy and psychotherapy similar to that employed in treatment of the index episode. Remission rate and time to remission in consecutively treated episodes were comparable to those in a group of midlife patients with recurrent depression reported by Kupfer et al. in 1989. Thus, recurrent depressive disorder appears to be as treatable in the young elderly as it is in midlife patients.
Abstract C34: Amplified <i>loci</i> on chromosomes 8 and 17 predict Tamoxifen resistance in ER+ breast tumors
Authors: Erhan Bilal, Shridar Ganesan, Gyan Bhanot
Journal: Cancer Research (2009)

Abstract Most ER+ breast cancers are treated with anti-estrogens like Tamoxifen which disrupt the Estrogen growth pathway. However, not all ER+ cases respond to this therapy. This study aims to identify genetic markers associated with increased sensitivity or resistance to Tamoxifen using outlier analysis. We collected 268 ER+ samples of gene expression data from three separate published studies on Tamoxifen treated patients with follow-up information on distant metastasis-free survival time. Genes were associated with Kaplan-Meyer survival curves based on their outlier profile and filtered, using the long-rank test, for differential survival distributions at p-value&amp;lt;0.05. Additional correlation analysis and PCA clustering were used to identify pathways and chromosomal regions enriched with gene markers correlated with Tamoxifen response. We find significantly over-expressed cell cycle genes correlated with poor survival together with an enrichment of chromosomal regions 17q21.33–q25.1, 17q12, 8p11.2 and 8q24.3. These amplicons were previously documented in breast cancer and contain known oncogenes ERBB2, LSM1, WHSC1L1 and HSF1 associated with more aggressive forms of the disease. Since the majority of samples enriched in the cell cycle pathway also have at least one of the amplicons, this suggests the amplifications on chromosomes 8 and 17 are associated with increased proliferation. In addition to this, a relative Oncotype DX™ score was calculated for samples using normalized expression levels and published weights. This analysis showed that high Oncotype DX™ scores are generated by tumors having either the HER2 amplicon (highest Oncotype DX™ scores), or one of the other amplicons on chromosomes 17 and 8. In contrast, low Oncotype DX™ scores were found only for tumors that do not exhibit any of the identified chromosomal aberrations. This implies that amplicons 17q21.33–q25.1, 8p11.2 and 8q24.3 may be responsible for higher proliferation and poor outcome in the setting of Tamoxifen treatment clinically observed in a subset of ER+, HER2− breast cancers. These results have significant implications for the development of targeted treatments for Tamoxifen-resistent ER+ breast cancers as well as in improving current methods of drug response prediction. Citation Information: Cancer Res 2009;69(23 Suppl):C34.
Abstract 3614: Multi-targeted kinase inhibitor E7080 showed anti-tumor activity against medullary thyroid carcinoma and squamous thyroid carcinoma cell line based on RET and VEGFR2 tyrosine kinase inhibition
Authors: Junji Matsui, Yukinori Minoshima, Akihiko Tsuruoka, Yasuhiro Funahashi
Journal: Cancer Research (2010)

Abstract There are about 37,000 and 8,000 new cases of thyroid cancer each year in the US and JP respectively, according to reports of the National Cancer Institute and National Cancer Center in Japan. Thyroid cancer is one of most common cancers after age 30, and its aggressiveness increases significantly in older patients. VEGFR tyrosine kinase inhibitors showed anti-tumor activity against thyroid carcinoma in early clinical study and some of inhibitors have been tested in late stage of clinical trial. E7080, a multi-targeted kinase inhibitor, potently inhibits VEGFR1-3, FGFR1-4 and RET tyrosine kinases and has been tested in several PhII trials including thyroid carcinoma trial. In this study, we report the efficacy of E7080 as an anti-cancer agent for thyroid carcinoma, based on both anti-tumorigenic activity and anti-angiogenic activity. E7080 inhibit RET kinase and VEGFR2 kinase with Ki values of 1.5 and 0.74 nmol/L, respectively, in cell free kinase assays. E7080 inhibited proliferation and phosphorylation of RET as well that of downstream Erk1/2 in medullary thyroid carcinoma (MTC) cell lines, TT and MTC-M, which expressed RET kinase in a dose dependent manner. E7080 showed significantly anti-tumor activity at the dose of 10-100 mg/kg in TT xenograft and 1-100 mg/kg in MTC xenograft without affecting microvessel density, suggesting that anti-tumor activity was caused by anti-tumorigenic activity based on RET kinase inhibition. On the other hand, E7080 did not show anti-proliferative activity against thyroid squamous carcinoma cell line, SW579, which did not expressed RET kinase, even at 10 µmol/L of E7080. While E7080 significantly inhibited in vivo growth of SW579 tumor in nude mice, accompanied by decreased of microvessel density within xenografted tumors at 3 - 100 mg/kg. These results demonstrated that the blockage of RET and VEGFR2 was a promising therapeutic strategy against several types of thyroid carcinoma and E7080, a dual inhibitor of both VEGFR2 and RET tyrosine kinase, is warranted to be examined for thyroid cancer patients. 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 3614.