tbuckley/cabot-search huggingface dataset:
Abstract 4852: cFLIP-regulated and caspase-8-mediated limited cleavage of RIP1 promotes NF-kB activation and inhibits cell death induced by TRAIL
Authors: Hasem Habelhah, Laiqun Zhang, Siegfried Janz, Lauren Workman, Ken Blackwell
Journal: Cancer Research (2012)

Abstract Although TRAIL is considered a potential anti-cancer agent, many types of cancer cells possess intrinsic or acquired resistance to TRAIL. In addition, TRAIL has been found to activate NF-κB and enhance metastasis in apoptosis-resistant cancer cells. Notably, caspase-8 activity and RIP1 expression have been shown to be essential for TRAIL-induced NF-κB activation. RIP1 is a dual-function molecule that can be either prosurvival or prodeath depending on the cellular context. RIP1 contains an N-terminal kinase domain (KD), a C-terminal death domain (DD) and an intermediate domain (ID) between the KD and DD domains. The ID domain of RIP1 is essential for its activation of the NF-κB pathway, whereas the KD domain is required for its induction of apoptosis and necrosis. We have discovered that, in apoptosis-sensitive cells, caspase-8 cleaves RIP1 in the KD and ID domains in response to TRAIL treatment, resulting in rapid depletion of RIP1 and the induction of apoptosis. In apoptosis-resistant cells, however, cFLIP inhibited caspase-8-mediated RIP1 cleavage in the ID but not in the KD domain, producing a KD domain-deleted C-terminal fragment, p51RIP1c. Stable expression of p51RIP1c in RIP1−/− cells significantly promoted NF-κB activation and inhibited cell death induced by TRAIL. Moreover, stable expression of the cleavage sites-mutated form of RIP1 in RIP1−/− cells, not only sensitized the cells to apoptosis induced by TRAIL, but also to necrosis induced by oxidative stress. Importantly, in Hodgkin's lymphomas that overexpress cFLIP, as well as in tumor tissues derived from iMyc-Bcl-XL double transgenic mice, a portion of RIP1 is constitutively processed to p51RIP1c. Collectively, these data suggest that cFLIP-regulated and caspase-8-mediated limited cleavage of RIP1 promotes NF-κB activation and inhibits cell death, and that such cleavage occurs constitutively in certain types of cancers. Thus, inhibiting cFLIP-regulated RIP1 cleavage could be a new target for maximizing the effectiveness of TRAIL as an anti-cancer agent. 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 4852. doi:1538-7445.AM2012-4852
Delayed Introduction of Food and Effect On Incidence of Food Allergy in a Population At High Risk for Atopy: The Canadian Asthma Primary Prevention Study (CAPPS)
Authors: Tiffany Wong, Moira Chan-Yeung, Roxanne Rousseau, Anne Dybuncio, Anita L. Kozyrskyj, Clare Ramsey, Allan Becker, Edmond S. Chan
Journal: Journal of Allergy and Clinical Immunology (2013)
Abstract P2-09-07: Elevated Pretreatment Serum CA9 (CAIX) (Carbonic Anhydrase 9) Predicts Reduced Progression-Free and Overall Survival in Trastuzumab-Treated Metastatic Breast Cancer
Authors: UI Anyanwu, HY Hou, V Shrinvastava, M Evans, K Leitzel, SM Ali, W Koestler, E-M Fuchs, S Brown-Shimer, J Ramirez, P Hamer, W Carney, R Kalu, K Repich, S Rizvi, A. Lipton
Journal: Cancer Research (2010)

Abstract Background: Approximately one-half of HER2-positive breast cancer patients will respond to first-line trastuzumab-containing therapy. However, in those patients with an initial trastuzumab response, most will progress within a year with acquired resistance. Since trastuzumab treatment is also now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a vexing clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Serum HER2, tissue inhibitor of metalloproteinase-1 (TIMP-1), urokinase-type plasminogen activator (uPA), CA9, Insulin-like growth factor-1 receptor (IGF-1R), VEGF-165, and endoglin were measured using ELISA assays in 60 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. The HER2, TIMP-1, uPA, CA9, IGF-IR, and VEGF-165 ELISAs were from Oncogene Science/Siemens Healthcare Diagnostics, Cambridge, MA; and the endoglin ELISA was from R&amp;D Systems, Minneapolis, MN. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with continuous pretreatment serum biomarker variables. Results: Pretreatment serum HER2 (p= 0.008), TIMP-1 (p&amp;lt; 0.0001), uPA (p= 0.006), endoglin (p= 0.010), and CA9 (p &amp;lt;0.0001) were all significant as univariate continuous biomarkers for predicting PFS to first-line trastuzumab-containing therapy, but VEGF (p=0.94) and IGF-IR (p=0.11) were not. In multivariate analysis for PFS with all 7 biomarkers, only serum CA9 (p= 0.002) was a significant independent covariate. For OS, pretreatment serum HER2 (p= 0.018), TIMP-1 (P&amp;lt;0.0001), uPA (P&amp;lt;0.0001), endoglin (0.006), CA9 (P&amp;lt;0.0001) were all significant as univariate continuous biomarkers for prognosis, but VEGF (p=0.69) and IGF-IR (p=0.098) were not. In multivariate analysis for OS with all 7 biomarkers, only serum CA9 was a significant independent prognostic covariate (p=0.001), and TIMP-1 trended significant (p=0.069). Conclusions: Elevated pretreatment serum CA9 (a marker of hypoxia) predicts reduced progression-free survival and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-07.
IMPACT OF EARLY PALLIATIVE CARE INTERVENTION ON MATERNAL STRESS IN MOTHERS OF INFANTS PRENATALLY DIAGNOSED WITH SINGLE VENTRICLE HEART DISEASE: A RANDOMIZED CLINICAL TRIAL
Authors: Hayley Hancock, Kenneth Pituch, Karen Uzark, Priya Bhat, Carlen Fifer, Maria Silveira, Sunkyung Yu, Janet Donohue, Ray Lowery, Ranjit Aiyagari
Journal: Journal of the American College of Cardiology (2016)
Abstract 43: Using matrix factorization to discover clinically-relevant molecular signatures across cancers
Authors: Christopher W. Szeto, Jingchun Zhu, James Durbin, Stephen Benz, Charles Vaske, Joshua Stuart, David Haussler
Journal: Cancer Research (2011)

Abstract With increasing ubiquity of genome-wide assays it is now common to molecularly subtype cancers to predict patient therapy response. However identifying high-performing, robust molecular signatures for predictions remains difficult. Presented here is work towards a novel machine-learning algorithm that discovers intuitively understood and clinically relevant stratifying molecular signatures. This classification method, as well as many competing methods (SVM, random forests, Bayes nets, etc.), were applied by predicting drug-sensitivity to hundreds of compounds tested on the NCI60 cell lines. This new drug-sensitivity prediction method competes with and in many cases outperforms leading classifiers. The prediction results, as well as the molecular signatures that they are derived from, are publicly available for web-browsing through a new extension to the UCSC Cancer Genomics Browser, hgClassifications (http://genome-cancer.soe.ucsc.edu/hgClassifications). 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 43. doi:10.1158/1538-7445.AM2011-43
Abstract P6-01-05: Long-Term Diagnostic Accuracy of Fine-Needle Aspiration Cytology Performed in a One Stop Clinic for the Diagnosis of Suspect Nodular Breast Lesions
Authors: I Borget, P Vielh, S Canale, C Balleyguier, S Azoulay, J-R Garbay, C Bourgier, M-C Mathieu, S. Delaloge
Journal: Cancer Research (2010)

Abstract Background: Fine-needle aspiration cytology (FNAC) has been used extensively in the diagnosis of breast lesions, but false-negative rates are a matter of concern. Immediate onsite evaluation of breast lesions, combining FNAC results with clinical and radiological data allows improving its diagnostic accuracy. The objective of this study was to evaluate the diagnostic accuracy of a large series of FNAC of breast lesions during the first 3-year period of a dedicated one-stop clinic, by comparing the FNAC results with the corresponding definitive histological examination outcome or the results of the radiological follow-up at 18 months. Method: Data of all consecutive patients (pts) whose lesions were prospectively characterized by ultrasonography (US) and diagnosed by FNAC in the one stop clinic of the Institute Gustave Roussy between May 2004 and March 2007. Histological verification by core-needle biopsy or surgery was systematically performed for lesions classified malignant or suspicious by cytopathology, and for benign lesions, when no perfect concordance between clinico-radiologic features and FNAC results (such as benign FNAC but BI-RAD 5) was found. For non-operated patients, follow-up consisted on biannual US and/or mammography; the results at 18 months were considered. Pts characteristics, radiological findings, cytopathological and histological results were extracted from the hospital computerized prospectively registered medical records. Complete sensitivity (number of carcinomas that were malignant or suspicious by cytopathology) and full specificity (benign lesions at cytology of the total number of benign lesions) were calculated by comparing the cytopathological results to the histological or the long-term follow-up status. Results: A total of 1822 nodular breast lesions (mean size: 20 mm, BI-RAD ACR 1/2/3/4/5/unknown: 10/96/471/459/777/9) in 1739 pts (mean age: 56 years) were studied. FNAC was US-guided in 1115 lesions (61 %). Lesions were classified by FNAC as malignant in 842 (46%), benign in 771 (42%), suspicious in 154 (9%), and unsatisfactory in 55 (3%) cases. Complete sensitivity (number of carcinomas that were malignant or suspicious by cytopathology) was estimated at 98.5%, whereas full specificity (benign lesions at cytology of the total number of benign lesions) was equal to 94.4%. There were 4 false-positive lesions and 32 false-negative lesions, but all these lesions except one were operated as radiological results were suspicious of malignity. Conclusions: Breast FNAC performed in a dedicated one-stop clinic with immediate on-site diagnosis presented a low rate of unsatisfactory specimens and a very efficient tool for triaging patients candidates for histological evaluation conversely for follow-up by imaging. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-05.
Preventive Care for Women -- Does the Sex of the Physician Matter?
Authors: Nicole Lurie, Jonathan Slater, Paul McGovern, Jacqueline Ekstrum, Lois Quam, Karen Margolis
Journal: New England Journal of Medicine (1993)

Emphasis on ensuring women's access to preventive health services has increased over the past decade. Relatively little attention has been paid to whether the sex of the physician affects the rates of cancer screening among women. We examined differences between male and female physicians in the frequency of screening mammograms and Pap smears among women patients enrolled in a large Midwestern health plan.
CORRELACIÓN ENTRE LA CÁPSULA ENDOSCÓPICA (CE) Y LA RESONANCIA MAGNÉTICA NUCLEAR (RMN) EN EL DIAGNÓSTICO DE LESIONES DE INTESTINO DELGADO EN LA ENFERMEDAD DE CROHN
Authors: L Ferrer, A Díaz Sánchez, S Rodríguez, C Rodríguez de Miguel, I Ordás, A Jáuregui, E Ricart, A Ramirez, M Gallego, J Rimola, M Pellisé, G Fernández-Esparrach, A Ginès, J Llach, J Panés, B González-Suárez
Journal: Endoscopy (2012)

Introducción: La capacidad diagnóstica de la CE comparada con la RMN en el estudio del intestino delgado no está bien establecida. La Cápsula endoscópica colónica (CCE) es un avance tecnológico con un ángulo de visión superior y una mejor calidad de imágenes en comparación con la cápsula de intestino delgado (SBCE). Estudios anteriores comparan la SBCE y la RMN, pero no hay estudios actuales que comparen esta técnica radiológica con la CCE. Objetivo: Evaluar y comparar el rendimiento diagnóstico de la RM y la CCE en la detección de la enfermedad de Crohn del intestino delgado. Pacientes y métodos: Se incluyeron treinta y cuatro pacientes (13 hombres y 21 mujeres) con enfermedad inflamatoria intestinal (28 pacientes con enfermedad de Crohn establecida, 3 pacientes con colitis indeterminada y 3 paciente con sospecha de enfermedad de Crohn). A 23 pacientes se les realizó CCE y a 11 SBCE. Todos los pacientes fueron sometidos con anterioridad a una resonancia magnética para descartar una estenosis intestinal y luego a la CE. Cuatro pacientes con sospecha de estenosis fueron sometidos previamente a una Cápsula Agile Patency para asegurar la permeabilidad del intestino. Los pacientes realizaron una preparación estándar para CE el día antes y el día del procedimiento. Resultados: Se encontraron lesiones en 28 pacientes con CE (82%) y en 22 pacientes con RM (64%). Seis pacientes no tenían ninguna lesión en la CE (4CCE y 2 SBCE) y cinco de ellos tenían RM normal. Para la presencia o ausencia de patología, CE y la RM coincidieron en 23/34 pacientes (65%). La resonancia magnética detectó hipertrofia de válvulas conniventes a nivel del yeyuno en 4 pacientes en los que la CE diagnosticó úlceras yeyuno-ileales. Cuatro pacientes con sospecha de estenosis en la RM fueron sometidos a la cápsula Agile Patency y posteriormente a CE que reveló úlceras ileales y estenosis permeables a este nivel. De los tres pacientes con colitis indeterminada, dos de ellos tenían lesiones en el reservorio ileo-anal (después de la colectomía) que fueron diagnosticadas porla CE y RM. Los resultados se observan en la siguiente tabla comparativa:
Abstract 4199: A transgenic mouse for imaging caspase-dependent apoptosis within the skin
Authors: Chritin A. Hamilton, Divya Khanna, Mahaveer S. Bhojani, Kuei C. Lee, Andrej Dludosz, Brian D. Ross, Alnawaz Rehemtulla
Journal: Cancer Research (2010)

Abstract Apoptosis is an essential process for the maintenance of normal physiology. The ability to non-invasively image apoptosis in living animals would provide unique insights into its role in normal and disease processes. Herein, a recombinant reporter consisting of LacZ gene flanked by two ER regulatory domains and intervening DEVD sequences was constructed to serve as a tool for invivo assessment of apoptotic activity. The results demonstrate that when expressed in its intact form, the hybrid reporter had undetectable β-galactosidase activity. Caspase-3 activation in response to an apoptotic stimulus resulted in cleavage of the reporter, and thereby reconstitution of β-galactosidase activity. Enzymatic activation of the reporter during an apoptotic event enabled non-invasive measurement of β-galactosidase activity in living cells, which correlated with traditional measures of apoptosis in a dose and time dependent manner. Furthermore, using a near-infrared fluorescent substrate of β-galactosidase (DDAOG), non-invasive in vivo imaging of apoptosis was achieved using a xenograft tumor model in response to pro-apoptotic therapy. Lastly, a transgenic mouse model was developed expressing the ER-LacZ-ER reporter within the skin. This reporter and transgenic mouse could serve as a unique tool for the study of apoptosis in living cells and animals especially in context of skin biology. 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 4199.
Low adhesion receptor levels on circulating platelets in patients with lymphoproliferative diseases before receiving Navitoclax (ABT-263)
Authors: Jianlin Qiao, Simone M. Schoenwaelder, Kylie D. Mason, Huy Tran, Amanda K. Davis, Zane S. Kaplan, Shaun P. Jackson, Benjamin T. Kile, Robert K. Andrews, Andrew W. Roberts, Elizabeth E. Gardiner
Journal: Blood (2013)
AB0318 Abatacept (abt) equivalent to anti-tumor necrosis factor a (tnfa) in terms of joint destruction inhibition: multicenter study of 107 patients treated for 52 weeks
Authors: K. Ayabe, K. Takeuchi, M. Matsushita, Y. Tamura, T. Sakurai, H. Inoue
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although two years have passed since the launch of abatacept (ABT) in Japan, little data are available on its efficacy in reducing structural joint damage. We performed a clinical assessment of disease activityand and a radiographic assessment of structural joint damage in 107 patients who had received ABT for 52 weeks. <h3>Objectives</h3> Evaluation of results of 52-week multicenter clinical study of ABT for RA <h3>Methods</h3> One hundred and seven RA patients who received ABT at a facility participating in a study conducted by the Academy of Clinical Rheumatoid Arthritis Gunma Institute (ACAGI) for at least 52 weeks were included in the efficacy analysis. Efficacy was assessed based on the SDAI scores stratified by MTX treatment and prior treatment with biologics using the LOCF method. Structural analysis was performed at Week 52 in 49 patients who underwent joint radiography and the annual progression rate was assessed using the modified Total Sharp Score (mTSS). <h3>Results</h3> Mean SDAI scores decreased from 20.18 at Week 0 to 6.12 at Week 52 in biologics-naive patients (n = 37). Fourteen (37.8%) and 15 patients (40.05%) had remission and low disease activity, respectively. The mean SDAI scores decreased from 24.2 at Week 0 to 11.15 at Week 52 in patients who switched treatments (n = 70). Twelve (17.1%) and 30 patients (42.8%) had remission and low disease activity, respectively. The mean SDAI scores decreased from 21.44 at Week 0 to 9.13 at Week 52 in patients who received a combination of ABT and MTX (n = 63). Seventeen (27.0%) and 25 patients (39.7%) had remission and low disease activity, respectively. The mean SDAI scores decreased from 24.78 at Week 0 to 9.82 at Week 52 in patients who received ABT only (n = 44). Nine (20.5%) and 20 patients (45.4%) had remission and low disease activity, respectively. The retention rate at Week 52 was 68.8%. The annual progression rate at Week 52 was 0.1, showing a significant suppression of joint destruction compared to the estimated annual progression rate at baseline of 8.4. Structural remission (mTSS/year ≤0.5) was achieved in 83.7%. <h3>Conclusions</h3> Based on the clinical evaluation and structural analysis at Week 52, more significant effects and better retention can be expected in ABT-treated patients. ABT could be an effective option in RA treatment. <h3>Disclosure of Interest</h3> None Declared
Abstract 2039: Human Stn1 protects telomere integrity by promoting efficient lagging strand synthesis at telomeres
Authors: Chenhui Huang, Xueyu Dai, Weihang Chai
Journal: Cancer Research (2012)

Abstract Telomeres, the chromosomal termini, are critical for maintaining genome stability. The length of telomere is regulated by multiple genes including telomere-specific shelterin proteins and telomere non-specific proteins such as DNA replication proteins. Stn1, a component of the newly identified Ctc1/Stn1/Ten1 complex, is also known as (DNA polymerase) α-accessory factor AAF44 and plays an unclear role in telomere maintenance. In our studies, Stn1 depletion causes elongated G-overhang and persistent ssDNA at G-rich strand in both telomerase-positive and negative cells. Furthermore, Stn1 depletion shows an increase of fragile telomeres in strands replicated by lagging strand synthesis, implicating that Stn1 is important in efficient replication of lagging strand telomeres. Consistently, BrdU incorporation into lagging telomeres is reduced when Stn1 is depleted. In addition, Stn1 depletion leads to rapid telomere shortening. Examination of the cell cycle-regulated G-overhang dynamics showed that deficiency of hStn1 delays and compromises C-strand synthesis that occurs in the late S/G2 phase, leading to persistent lengthening of G-overhangs at lagging daughter telomeres. We also found that Stn1 interacts with Polα throughout the cycle. ChIP experiments showed that Stn1 depletion results in increased and prolonged Polα association with telomeres, but does not affect the association of Pot1 with telomeres. Our data indicate a key role of Stn1 in telomere replication and maintenance. 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 2039. doi:1538-7445.AM2012-2039
Abstract 994: Role of Akt isoforms in regulating intermediate filaments expression in cancer progression
Authors: Anne-Marie Fortier, Monique Cadrin, Eric Asselin
Journal: Cancer Research (2010)

Abstract Keratins are epithelial-specific intermediate filament (IF) proteins, which are expressed in a tissue-specific manner. As part of the cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, a number of keratins are involved in intracellular signalling pathways which regulate the response to injuries and nonmechanical stresses, cell growth, cell death and cancer progression. Expression of keratins is maintained during malignant transformation of simple epithelial cells. However, vimentin, a mesenchymal-specific IF, is often co-expressed with keratins in late-stage cancer cells presenting a dedifferentiated phenotype. This is associated with an increased metastatic potential. Metastasis, the foremost cause of mortality in cancer patients, is a coordinated biological process involving multiple intracellular signalling pathways. PI3K/Akt pathway has been shown to play a role in invasion/metastasis. Moreover, the three Akt isoforms would play differential roles in this process. In the present study, we investigate the role of Akt isoforms in regulating the expression of keratins and vimentin in different epithelial carcinoma cell lines and the implication of IF in Akt-regulated cell invasion. Our results show that overexpression of constitutively active Akt isoforms up-regulates IF protein and mRNA levels, by increasing IF mRNA stability. On the contrary, down-regulation of Akt isoforms by shRNA decreases IF protein levels. To examine the regulation of IF expression under a more physiological condition, we treated cells with TGF-b1, which is known to induce Akt activation. We demonstrated that IF are up-regulated by TGF-b1 in PI3K-dependent manner. To our knowledge, these results represent the first indication that Akt activity is regulating IF expression. Overexpression of Akt isoforms also increases in vitro cell invasion. Interestingly, we showed that down-regulation of vimentin by siRNA decreases Akt2-induced cell invasion. These results support the hypothesis that modulation of IF expression plays an active role in cancer progression. 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 994.