tbuckley/cabot-search huggingface dataset:
Abstract 5680: Identification and characterization of a novel class of ATX inhibitors.
Authors: James Fells, Sue Chin Lee, Derek Norman, Yuko Fujiwara, Ryoko Tsukahara, Jianxiong Liu, Jason Kirby, Sandra Nelson, Gabor Tigyi
Journal: Cancer Research (2013)

Abstract The lysophospholipase D (autotaxin, ATX) plays an important role in cancer invasion and metastasis. A High-throughput screen of over 10,000 compounds from the University of Cincinnati Drug Discovery Center, identified several small-molecule inhibitors with IC50 values ranging from nanomolar to low micromolar. The pharmacology of the two most potent compounds, 966791(1) and 918103(2), were further characterized in enzyme, cellular, and whole animal systems. Both of these compounds, significantly reduced cell invasion in melanoma cancer cell lines without any apparent cytotoxicity. Compound (1) was shown to be a competitive inhibitor of ATX for both FS-3 and Pnp-TMP substrates, while compound (2) was competitive only for FS-3. This suggest that compound (2) targets the hydrophobic pocket not the active site of ATX, which was supported by docking of compounds 1 and 2, along with mutagenesis data. The potency of the compounds was comparable to each other in each of the assays. Current ATX inhibitors reported in literature target the active site in the catalytic domain. In our search for ATX inhibitors we identified compounds able to inhibit both the active site and hydrophobic pocket. We conclude that these data suggest compounds solely inhibiting the hydrophobic pocket are sufficient to disrupt the ATX-LPA signaling axis can serve as specific small-molecule modulators for mechanistic studies of ATX as well as a potential leads for the development of anti-cancer drugs. Citation Format: James Fells, Sue Chin Lee, Derek Norman, Yuko Fujiwara, Ryoko Tsukahara, Jianxiong Liu, Jason Kirby, Sandra Nelson, Gabor Tigyi. Identification and characterization of a novel class of ATX inhibitors. [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 5680. doi:10.1158/1538-7445.AM2013-5680
P1119 EARLY VIRAL KINETICS DO NOT PREDICT TREATMENT OUTCOME WITH SOFOSBUVIR + RIBAVIRIN FOR 12 OR 24 WEEKS IN HCV GENOTYPE 2/3 PATIENTS IN THE VALENCE TRIAL
Authors: S. Zeuzem, G.M. Dusheiko, M. Colombo, R. Flisiak, R.H. Hyland, A. Illeperuma, D.M. Brainard, W.T. Symonds, J.G. McHutchison, O. Weiland, H.W. Reesink, A. Brown, S. Pol, C. Hezode, R. Esteban
Journal: Journal of Hepatology (2014)
A Call to Redefine Where Cancer Begins
Authors: J. Randal
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article A Call to Redefine Where Cancer Begins Get access Judith Randal Judith Randal Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 2, 18 January 1995, Pages 78–80, https://doi.org/10.1093/jnci/87.2.78 Published: 18 January 1995
Abstract LB-468: miR-345 downregulation is associated with apoptosis resistance in pancreatic cancer: therapeutic implications
Authors: Sanjeev K. Srivastava, Arun Bhardwaj, Sumit Arora, Seema Singh, Steven McClellan, Bin Wang, William E. Grizzle, Ajay P. Singh
Journal: Cancer Research (2012)

Abstract Resistance to apoptosis is one of the mechanisms underlying the highly metastatic and drug-resistant nature of pancreatic malignancy, which currently stands as the fourth leading cause of cancer-related death. Recent studies have identified several differentially-expressed microRNAs in pancreatic cancer, including miR-345, which is among the top aberrantly-expressed genes exhibiting significant downregulation. In this study, we have investigated the functional consequences of miR-345 downregulation in pancreatic cancer. We observed that miR-345 was significantly downregulated in our set of pancreatic cancer tissues as compared to the normal pancreas. Furthermore, a relative decrease in miR-345 levels was observed in poorly-differentiated pancreatic cancer cell lines as compared to the well-differentiated cell lines. Ectopic expression of miR-345 in two pancreatic cancer cell lines, MiaPaCa and Panc1, led to reduced cell viability and induction of apoptosis. miR-345 overexpressing pancreatic cancer cells exhibited loss of mitochondrial membrane potential, release of cytochrome c, activation of caspases 3/7 and PARP1 cleavage. In addition, we also observed translocation of apoptosis inducing factor (AIF) from mitochondria to nucleus and increased DNA fragmentation in miR-345 overexpressing pancreatic cancer cells. All these effects were reversed upon treatment of miR-345 overexpressing pancreatic cancer cells with anti-miR-345 oligonucleotides, thus confirming the role of miR-345 in apoptosis induction. Based on in silico analysis, we identified BCL2 as a candidate miR-345 target gene and experimentally validated the direct targeting of the 3′ UTR of BCL2 using a luciferase reporter assay. Consistent with this, miR-345 overexpressing pancreatic cancer cells exhibited a downregulated expression of BCL2 at the protein level. When we allowed unopposed exogenous expression of BCL2, it rescued pancreatic cancer cells from miR-345-induced apoptosis. Altogether, our data suggest that miR-345 downregulation is associated with gain of apoptosis resistance, and restoring its expression may have therapeutic effects in pancreatic 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-468. doi:1538-7445.AM2012-LB-468
PTU-151 Predictors For Coeliac Disease In Cases Of Lymphocytic Duodenosis
Authors: I Aziz, T Key, JG Goodwin, DS Sanders
Journal: Gut (2014)

<h3>Introduction</h3> Lymphocytic duodenosis (LD) is an early marker for coeliac disease (CD). However, the majority of cases are due to non-CD related conditions. <h3>Aims</h3> To identify the predictors of CD when presented with LD. <h3>Methods</h3> 215 LD patients had undergone prospective and systematic evaluation for CD and other recognised associations. The gold-standard diagnosis of CD was based upon the presence of HLA-DQ2 and/or DQ8, persistence or progression of LD following a gluten challenge, symptomatic improvement on a gluten-free diet, and no alternate cause found. Binary logistic regression models, adjusting for age and gender, were subsequently performed to compare presenting variables between CD and non-CD cases, and to determine their sensitivity, specificity, positive and negative predictive values (PPV and NPV). <h3>Results</h3> CD was diagnosed in 47 cases (22%) and non-CD in 168 cases (78%). There was no statistical difference in demographics, clinical symptoms (i.e. diarrhoea, weight loss, abdominal pain), anaemia or haematinics between the CD and non-CD group. Patients with CD, in comparison to non-CD, were significantly more likely to have a positive family history of CD (21.3% vs. 3.6%, OR 6.81; PPV 62.5%, NPV 81.4%, specificity 96.4%), positive HLA-DQ status (100% vs. 49.4%; PPV 36.2%, NPV 100%, specificity 50.6%), and presence of endomysial antibody [EMA] (49% vs. 0.6%, OR 159; PPV 96%, NPV 87%, specificity 99.4%); all p ≤ 0.001. A normal tissue transglutaminase antibody (TTG) level was seen in 29.8% CD and 82.7% non-CD cases (OR 0.086, p &lt; 0.001; PPV 9.1%). There was no difference in the prevalence of TTG levels 1–2 x upper limit of normal (ULN) between the groups (29.8% CD vs. 14.3% non-CD; PPV 38%). However, TTG levels between 3–20 x ULN were significantly more prevalent in the CD group (31.9% vs. 3%; PPV 66.6% &gt;87.5%), whilst a TTG &gt; 20 x ULN was exclusive to CD (8.5%, p &lt; 0.001, PPV 100%). <h3>Conclusion</h3> At the outset, only the presence of positive EMA or TTG &gt; 20 x ULN are highly predictive and specific for CD. However, as they have limited sensitivities, most patients with LD require further work-up prior to diagnostic confirmation. <h3>Disclosure of Interest</h3> None Declared.
RESULTADOS DEL ESTUDIO PILOTO DEL CRIBADO DE CÁNCER COLORRECTAL EN EL ÁREA SUR DE GRAN CANARIA
Authors: A Castellot Martín, JM Marrero Monroy, M Lorente Arencibia, L Lopez Lopez, C Sánchez Vilar, A González Almeida, A Cruz Bonilla, V Malo De Molina Zamora, T Barata Gomez, A Sierra Hernández
Journal: Endoscopy (2013)

Introducción: El cáncer colorrectal (CCR) es un importante problema de Salud. Los programas de cribado son eficaces y se están implantando en varias Comunidades Autónomas. Objetivo: Analizar los resultados del estudio piloto del programa de cribado de CCR instaurado por el Servicio Canario de Salud en el Área Sur de Gran Canaria desde 2009. Material y Método: Se invitó mediante carta a la población diana (50 – 74 años) a realizarse un test de sangre oculta en heces (método inmunoquímico cuantitativo: ≥100 mcg Hb/mg), siendo los positivos derivados para colonoscopia. Dos endoscopistas expertos realizaron las exploraciones (indicadores de calidad: Asociación Española de Gastroenterología; clasificación de lesiones: Organización Mundial de la Salud). Se incluyeron las exploraciones realizadas hasta diciembre 2012, recogiendo los resultados en una base de datos diseñada para tal fin. Resultados: Se enviaron 31.261 cartas, con una respuesta del 38% y 5,6% de positividad. Se realizaron 629 colonoscopias (completas: 97,6%, sedación: 98%, tiempo medio de retirada: 11 minutos). El 62% fueron varones con edad media de 60 años. 477 pacientes presentaron pólipos, 38 neoplasias, 118 otras patologías y 90 normales. De las 1292 lesiones extirpadas (95% recuperadas), el 1% eran tumores invasivos (pT1), 38,7% adenomas de alto riesgo, 39% adenomas de bajo riesgo y 20% no adenomatosos. Se diagnosticaron 47 tumores invasivos, 67% en estadio ≤ II y 74% en colon izquierdo. Se registraron 8 complicaciones mayores en colonoscopias terapéuticas: 2 perforaciones que precisaron cirugía y 6 hemorragias post-polipectomía resueltas endoscópicamente. Conclusiones: El programa de cribado poblacional realizado en nuestro medio tuvo una adherencia aceptable. La determinación de sangre oculta en heces es eficaz para disminuir la incidencia de CCR. Las colonoscopias detectaron patología neoplásica en fases precoces.
Effect of Hyperthermia on Vascular Functions of Normal Tissues and Experimental Tumors: Brief Communication2
Authors: Chang W. Song
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Effect of Hyperthermia on Vascular Functions of Normal Tissues and Experimental Tumors: Brief Communication Get access Chang W. Song Chang W. Song Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 3, March 1978, Pages 711–713, https://doi.org/10.1093/jnci/60.3.711 Published: 01 March 1978 Article history Received: 04 August 1977 Accepted: 30 September 1977 Published: 01 March 1978
INTRAVENOUS ADENOSINE INFUSION IS SAFE AND WELL TOLERATED DURING CORONARY FRACTIONAL FLOW RESERVE ASSESSMENT IN SEVERE AORTIC STENOSIS
Authors: Dusan A. Stanojevic, Prasad Gunasekaran, Micah Levine, Mark Reichuber, Randall Genton, Ashwani Mehta, Matthew Earnest, Mark Wiley, Peter Tadros, Buddhadeb Dawn, Kamal Gupta
Journal: Journal of the American College of Cardiology (2015)
PMO-183 Role of IL28B polymorphism in prediction of response to therapy in patients with genotype 1 chronic hepatitis c infection
Authors: Z Mustafa, D Gaffney, E Matthews, S Barclay, M Priest, R Spooner, P R Mills
Journal: Gut (2012)

<h3>Introduction</h3> Patients with chronic hepatitis C virus (HCV) infection have a variable response to antiviral therapy with pegylated interferon and ribavirin. Influences include age, gender, viral genotype, viral load, severity of liver disease and coinfection. Around 45% of patients with viral genotype 1(G1) infection respond compared with 70%–80% with genotype 2/3. Recently a human IL28B polymorphism has been found to predict response in patients with G1 infection. There is little data on this from Europe and a study of IL28B polymorphisms in patients with G1 infection treated in Glasgow was conducted. <h3>Methods</h3> Sequential Caucasian patients with G1 chronic HCV who had been treated with combination antiviral therapy were studied. Responses were classified as sustained viral response (SVR), relapse (R) or non-responder (NR). None had coinfection. Data on age, gender, viral load, duration of therapy and severity of liver disease (Ishak fibrosis stage &lt;4 or ≥4) were collected. Individuals were genotyped for IL28B polymorphism rs12979860 using TaqMan<sup>®</sup>, Drug Metabolism Genotyping Assays and reported as CC, CT or TT. <h3>Results</h3> 63 patients were classified (number, mean age, females, advanced fibrosis) by treatment response as SVR (18, 44, 4, 1), R (20, 46, 8, 8) and NR (25, 46.4, 4, 10). Mean pre-treatment viral load was similar in the three groups (5.2, 5.4, 5.8 log<sub>10</sub> IU/ml) and mean duration of therapy shorter for NR (46.2, 47.2, 8.4 weeks) who often fulfilled an early stopping rule. The IL28B genotype was highly predictive of response (Abstract PMO-183 table 1). CC individuals have a much greater likelihood (p&lt;0.002) of being in the SVR group than CT or TT individuals. Poorer response was also seen in patients with advanced fibrosis. <h3>Conclusion</h3> The IL28B polymorphism is a useful and cheap assay allowing some prediction of response to antiviral therapy in patients with G1 chronic HCV infection. <h3>Competing interests</h3> None declared.
Fertility in Men Exposed Prenatally to Diethylstilbestrol
Authors: Allen J. Wilcox, Donna D. Baird, Clarice R. Weinberg, Paige P. Hornsby, Arthur L. Herbst
Journal: New England Journal of Medicine (1995)

Prenatal exposure to diethylstilbestrol causes infertility in male mice and has been associated with malformations of the genital tract in men. However, little is known about the fertility of men who have been exposed prenatally to diethylstilbestrol.
P1-04-08: Distribution of ALDH1 Positive Stem Cells in Benign Mammary Tissue from Women with and without Breast Cancer.
Authors: BL Isfoss, B Holmqvist, P Alm, H Olsson
Journal: Cancer Research (2011)

Abstract Background and Aims. ALDH1 in female breast tissue has been linked to stem cells, but little is known about the benign cellular organisation in situ. We investigated the distibution of ALDH1 immunoreactive (ALDH1+) cells in histomorphologically benign breast tissue from 28 women with or without breast cancer. Methods and Results. ALDH1+ cells were detected in benign tissue of women age 20 - 72, located most commonly within the luminal and intermediate ductular levels and in the stroma. ALDH1+ cell populations and Ki-67+ cell populations were present in separate ductules, both cell types rarely showing epithelial differentiation. ALDH1 + cells were non-reactive to Ki-67 and oestrogen receptor. Stromal round/oval ALDH1+ non-leukocyte cells in both age groups expressed contractile protein. There was a lower concentration of luminal and intermediate ductular ALDH1+ cells in post-menopausal women than pre-menopausal women, lower in cancer than non-cancer patients, and higher in women on exogenous hormones. Conclusions. The study provides further evidence for the stem cell character of ALDH1+ cells, here in benign breast tissue of cancer and non-cancer women throughout non-lactating adult life, and contributes evidence of benign stromal ALDH1+ cells. The distribution of ductular ALDH1+ stem cells appears to be influenced by hormonal status. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-04-08.
States Aim Laws At Off-Label Reimbursement
Authors: K. Nagy
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article States Aim Laws At Off-Label Reimbursement Get access Kate Nagy Kate Nagy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 9, 5 May 1993, Pages 701–702, https://doi.org/10.1093/jnci/85.9.701 Published: 05 May 1993
RACIAL DISPARITIES IN LEFT VENTRICULAR REMODELING AMONG PATIENTS WITH SYSTOLIC HEART FAILURE
Authors: Yulanka Castro Dominguez, Shashank Jain, Atish Mathur, Adam Raskin, Frank Wang, Carlos Osorio, Monali Patel, Vivek Joseph, Pallavi Solanki, Marc Klapholz
Journal: Journal of the American College of Cardiology (2015)
The impact of a national routine immunisation programme initiated in 1999 on Hepatitis A incidence in Israel, 1993 to 2012
Authors: H Levine, E Kopel, E Anis, N Givon-Lavi, R Dagan
Journal: Eurosurveillance (2015)

Data on long-term impact of universal national vaccination programmes against hepatitis A are lacking. We aimed at evaluating the impact on hepatitis A incidence of the Israeli toddlers-only universal routine two-dose vaccination programme against hepatitis A initiated in 1999. All hepatitis A episodes reported to the national surveillance system from 1993 to 2012 were analysed in relation to the vaccination programme and coverage. Mean vaccine coverage in Israel between 2003 and 2010 was 92% for the first dose, given at 18 months of age, and 88% for the second dose, given at 24 months. The annual hepatitis A incidence declined from a mean of 50.4 per 100,000 in the period between 1993 and 1998 to a mean of?&lt;1.0, during the period from 2008 to 2012, representing a reduction of?&gt;98%. The decline was evident in all ages and ethnicity groups, including unvaccinated populations. Of the 1,247 cases reported nationwide between 2002 and 2012, the vaccination status could be ascertained in 1,108 (89%). Among them, only 20 (2%) were reported be vaccinated with one dose and three (&lt;1%) received two doses. The sustained results of this long-term impact study suggest that a toddlers-only universal routine two-dose vaccination programme is highly effective and practical. These findings underscore the importance of sustainability in both the surveillance systems and vaccination programmes and will aid to determine vaccination policies.
Abstract 4731: Population specific microRNA expression and biological implications
Authors: R. Stephanie Huang, Eric R. Gamazon, Dana Ziliak, Wei Zhang, Hae Kyung Im, Claudia Wing, Shiwei Duan, Wasim K. Bleibel, Nancy J. Cox, M. Eileen Dolan
Journal: Cancer Research (2011)

Abstract Population differences are commonly observed for many complex traits including response to chemotherapy. These differences may be attributed to the combined effect of socioeconomic, environmental, genetic and epigenetic factors. Indeed, genome-wide genetic and gene expression differences have been reported among different ethnic populations. Furthermore, we have previously reported population differences in cellular sensitivity to carboplatin, daunorubicin and ara-C and have established that both genetic variants and gene expression contribute to these observed population differences. Here we set out to evaluate to what extent population differences may be explained by an epigenetic factor, namely microRNA (miRNA) expression. We characterized genome-wide miRNA expression in unrelated 54 CEU (Utah residents with northern and western European ancestry) and 55 YRI (African from Ibadan, Nigeria) HapMap lymphoblastoid cell lines (LCLs) using the Exiqon miRCURYTM LNA arrays and evaluated baseline mRNA expression using Affymetrix GeneChip® Human Exon 1.0 ST array. Forty-one miRNA expression traits were found to differ significantly between these 2 ethnic groups (pBonferroni corrected&amp;lt;0.05). The potential biological function of these observed differentially expressed miRNAs was explored by examining their relationship with mRNA expression and cellular sensitivity to carboplatin, daunorubicin and cytaribin. After multiple testing adjustment (false discovery rate (FDR)&amp;lt;0.1), we identified 25 and 32 of the 41 differentially expressed miRNAs that were significantly correlated with 530 and 729 mRNA expression levels in the CEU and YRI samples, respectively. Among them, six differentially expressed miRNAs showed significant levels of correlation with 6 differentially expressed mRNAs (FDR&amp;lt;0.1). A substantial proportion (63%) of these miRNAs correlated with cellular sensitivity to chemotherapeutic agents (FDR&amp;lt;0.05). Lastly, upon performing a genome-wide association study between SNPs and miRNA expression, we identified a large number of SNPs showing high levels of population differentiation that affected the expression of these differentially expressed miRNAs, suggesting the role of genetic variants in mediating the observed population differences. In conclusion, the differentially expressed miRNAs we catalog in this study may explain observed population differences in mRNA expression and cellular sensitivity to chemotherapeutic drugs. 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 4731. doi:10.1158/1538-7445.AM2011-4731
Utility of Breast CT in the Management of Breast Cancer – Results from a Prospective Multi-Institutional Study.
Authors: S. Akashi-Tanaka, N. Sato, S. Ohsumi, I. Kimijima, H. Inaji, S. Teramoto, F. Akiyama
Journal: Cancer Research (2009)

Abstract Background:In order to obtain negative margins after breast conserving surgery (BCS), even repeated surgery is widely accepted. Before surgery, it is important to conduct a precise assessment of the extent of the breast cancer so that each patient can receive individualized surgery. To evaluate the utility of breast computed tomography (CT) as a tool to manage BCS, a multi-institutional prospective study was conducted in Japan.Patients and Methods:Patients were eligible to participate in this study if they had histologically proven breast cancer and were determined to be BCS candidates based on palpation, mammography (MMG) and ultrasonography (US). Written informed consent was obtained from each patient. First, the surgeon marked the line of planned excision on the skin using information from the MMG and US. Next, an expired angiographic catheter was placed on the mark to show the original surgical margin on the CT image. Breast CT was scanned 60 seconds after the bolus injection of the contrast material in the supine surgical position. The surgeon determined the extent of surgery based on the breast CT results. Surgical specimens were serially sectioned in 5-mm slices.Results:Three hundred and two patients were enrolled in this study. The CT scanners used in this study varied from a single helical CT to a 64-row multidetector CT. The results of the breast CT changed the extent of resection in 14.7% of patients. Among the 5 patients who were recommended to undergo a mastectomy, 4 patients had multicentric tumors pathologically and 1 patient had a widely spread intraductal component. The other patients were recommended to have a quadrantectomy based on the extent of breast cancer that was visualized by CT. Three patients (1%) who required conversion from a lumpectomy to quadrantectomy resulted in overexcision. In short, breast CT correctly changed the extent of surgery in 13.7% of the examined patients.Conclusion:This prospective study suggested that breast CT is useful for hospitals equipped with any type of CT and can be used to provide patients with individualized surgery. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5021.