tbuckley/cabot-search huggingface dataset:
266TiP A multicenter, prospective, longitudinal registry of prostate cancer in Asia
Authors: H. Uemura, D. Ye, T.-L. Wu, J.-Y. Lee, Y.L. Chong, A.H.A. Razack, C. Pripatnanont, E. Chiong, W.K.O. Lau, R. Kanesvaran, C. Li, S. Rawal, H. Tongaonkar, Y.-S. Pu, A. Santingamkun, B. Lojanapiwat, H. Liang, K.W. Mah, M. van Kooten Losio, Y. Liu
Journal: Annals of Oncology (2015)
Abstract LB-204: Neoadjuvant Ezh2 inhibition amplifies an inflammatory program and sensitizes Kras-driven NSCLC to anti-NF-κB inhibition
Authors: Michela Serresi, Bjorn Siteur, Matteo Cesaroni, Natalie Proost, Danielle Hulsman, Maarten van Lohuizen, Gaetano Gargiulo
Journal: Cancer Research (2016)

Abstract Kras mutant non-small cell lung cancer (NSCLC) is a leading cause of death but has limited therapeutic options. We investigated the impact of Polycomb repressive complex 2 (PRC2) inhibitors as single agent or as neoadjuvant treatment for subsequent anti-inflammatory therapy. Using orthotopic grafts, we show that Kras cells highly expressing the PRC2 enzymatic component Ezh2 display sensitivity to its inhibition. Ezh2 inhibition leads to transcriptional amplification of an inflammatory program involving NF-kB. Pharmacological inhibition of Ezh2 rerouted Kras tumor progression towards exploiting PRC2/NF-kB target genes as inferred by in vivo RNAi screen but also enhanced the response of Kras NSCLC to a combination of Nimesulide and Bortezomib. These data suggest that low PRC2 levels in Kras-driven NSCLC promote an epigenetic switch, providing a rationale for exploring a novel therapeutic option in which Ezh2 simultaneously acts as biomarker for therapeutic decision and as a neoadjuvant target for therapy. Citation Format: Michela Serresi, Bjorn Siteur, Matteo Cesaroni, Natalie Proost, Danielle Hulsman, Maarten van Lohuizen, Gaetano Gargiulo. Neoadjuvant Ezh2 inhibition amplifies an inflammatory program and sensitizes Kras-driven NSCLC to anti-NF-κB inhibition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-204.
Abstract 2891: High throughput single cell gene expression profiling by multiplex qPCR
Authors: Steven T. Okino, Michelle Kong, Jason Ma, Joshua Fenrich, Luca Boveri, Yann Jouvenot, Yan Wang
Journal: Cancer Research (2016)

Abstract Single cell gene expression analysis is a powerful technique that provides a unique and insightful perspective on biological pathways and processes. Here we present a robust workflow that enables fast and accurate analysis of up to 100 genes in isolated single cells. Our workflow is highly sensitive, by assessing RNA reference standards we find that a single RNA transcript is detected with about 80% efficiency. We used this workflow to study differentiation in cultured NTera2 cells (NT2), a human embryonic stem cell model system. We analyzed untreated NT2 cells, and NT2 cells treated with low and high doses of retinoic acid (RA) for 10 days to initiate differentiation to a neuronal lineage. The expression levels of 16 genes were quantified in 164 single cells by multiplex real-time qPCR with two technical replicates. The entire experiment, from cultured cells to results, can be completed in 2-3 days and requires four 384-well qPCR plates for gene expression quantification. We find that control cells and cells treated with a high dose of RA (10 uM) are relatively homogeneous in the expression levels of the targeted genes. However cells treated with a low dose of RA (0.25 uM) exhibit significant heterogeneity with respect to gene expression; about half of the cells are similar to the high-dose RA cells, the other cells exhibit a wide range of partial differentiation. Interestingly, we find that LEFTY2 expression is almost exclusive to the low dose RA cells and strongly correlates with partial differentiation. A time-course study analyzing cell populations reveals that LEFTY2 is only transiently expressed in differentiating NT2 cells with peak expression at 3 days of high dose RA treatment. These findings imply that, in NT2 cells, LEFTY2 is a potential biomarker of early differentiation. In summary, we present an accurate, sensitive and robust single cell analysis procedure that uses standard reagents and platforms. We envision that this workflow will enable researchers to investigate cell heterogeneity in biological pathways in a cost-effective way. Citation Format: Steven T. Okino, Michelle Kong, Jason Ma, Joshua Fenrich, Luca Boveri, Yann Jouvenot, Yan Wang. High throughput single cell gene expression profiling by multiplex qPCR. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2891.
Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with metastatic (MET) chemotherapy refractory <i>K-RAS </i>wild-type (WT) colorectal carcinoma (CRC): The NCIC Clinical Trials Group and AGITG CO.20 trial.
Authors: Lillian L. Siu, Jeremy D. Shapiro, Derek J. Jonker, Christos Stelios Karapetis, John Raymond Zalcberg, John Simes, Felix Couture, Malcolm J. Moore, Timothy Jay Price, Jehan Siddiqui, Louise M. Nott, Danielle Charpentier, Winston S. Liauw, Michael B. Sawyer, Michael Jefford, Nadine M Magoski, Andrew Mark Haydon, Ian B. Walters, Dongsheng Tu, Christopher J. O'Callaghan
Journal: Journal of Clinical Oncology (2012)

386 Background: The anti-EGFR monoclonal antibody CET has improved survival in pts with MET, chemotherapy refractory, K-RAS wild type (WT) CRC. The addition of BRIV, a tyrosine kinase inhibitor targeting vascular endothelial and fibroblast growth factor receptors (VEGFR/FGFR), to CET has shown encouraging activity in an early phase clinical trial. Methods: Pts with MET CRC previously treated with combination chemotherapy were randomized 1:1 to receive CET 400 mg/m 2 IV loading dose followed by weekly maintenance of 250 mg/m 2 plus either BRIV 800 mg PO daily (Arm A) or placebo (Arm B). Pts may have had 1 prior anti-VEGF, but no prior anti-EGFR therapy. The trial was amended shortly after opening to enrol K-RAS WT pts. Primary endpoint was overall survival (OS). Results: From 02/2008 to 02/2011, 750 pts were randomized (376 in Arm A and 374 in Arm B). Demographics: median age=64 (range 27-88); male=64%; ECOG 0:1:2 (%)=32:58:10; &gt;3 prior chemotherapy regimens=92%; prior anti-VEGF therapy=41%; K-RAS WT=97%. Median OS in the intent-to-treat population was 8.8 months in Arm A and 8.1 months in Arm B, hazard ratio (HR)=0.88; 95% CI=0.74 to 1.03; p=0.12. Median progression-free survival (PFS) was 5.0 months in Arm A and 3.4 months in Arm B, HR=0.72; 95% CI=0.62 to 0.84; p&lt;0.0001. Both partial responses (13.6% vs 7.2%, p=0.004) and stable disease (50% vs 44%) were higher in Arm A. Incidence of any ≥grade 3 adverse event (AE) was 78% in Arm A and 53% in Arm B. Most frequent ≥grade 3 AEs were fatigue (25%), hypertension (11%) and rash (10%) in Arm A, vs fatigue (11%), rash (5%) and dyspnea (5%) in Arm B. Time to deterioration of physical function was shorter and global quality of life scores were lower in Arm A vs Arm B. Pts received ≥90% dose intensity of CET=57% in Arm A vs 83% in Arm B; of BRIV/placebo=48% in Arm A vs 87% in Arm B. Conclusions: Despite positive effects on PFS and objective response, the combination of CET+BRIV did not significantly improve OS in pts with MET, chemotherapy refractory, K-RAS WT CRC. AEs were consistent with those reported for each drug given as monotherapy.
P1054 : Liver enzymes, adiponectin and vitamin D levels as predictors of diabetes – data from the Heinz Nixdorf Recall study
Authors: J. Kälsch, L.P. Bechmann, D. Heider, P. Manka, H. Kälsch, J.-P. Sowa, S. Moebus, U. Slomiany, K.-H. Jöckel, R. Erbel, G. Gerken, A. Canbay
Journal: Journal of Hepatology (2015)
Abstract 5189: Caloric restriction augments the chemotherapeutic response in a murine triple negative breast cancer model
Authors: Brittany Simone, Tu Dan, Ajay Palagani, Meredith LaRose, Jason E. Savage, Nicole Simone
Journal: Cancer Research (2016)

Abstract Purpose: Triple negative breast cancers (TNBC) are a highly aggressive subtype of breast cancer, linked with a poor prognosis. TNBC tumors have a higher propensity for metastasis and unfortunately have fewer treatment options due to their lack of estrogen, progesterone or Her-2/neu receptors. We sought to determine if caloric restriction (CR) could augment the response of chemotherapy including docetaxel and cisplatin in a TNBC model and improve survival. Methods: An orthotopic mouse model using a highly metastatic, luciferase-tagged TNBC cell line (4T1), was used to generate palpable tumors. Mice were then treated with CR, cisplatin alone, docetaxel alone or a combination of CR and chemotherapy. Three times a week, primary tumors were measured with calipers and in vivo imaging was performed to evaluate the metastatic burden of disease. Molecular evaluation of the tumors was performed, generating a mechanistic hypothesis for increased sensitivity to chemotherapy. Results: Combining either docetaxel or cisplatin with CR, significantly decreased the rate of primary tumor growth (p&amp;lt;0.001). Average time to metastases (19 days in ad lib group) was increased by an average of 10.5 +/- 3 days with the addition of either docetaxel or cisplatin, and increased by an additional 6 days in the CR+cisplatin (35 days until metastases, p&amp;lt;0.01). The addition of CR to chemotherapy decreased the overall number and volume of lung metastases, and increased overall survival as compared with those groups receiving chemotherapy alone. Molecularly, CR was noted to augment the effect of chemotherapy by decreasing inflammation that results from IL-1β mediated acute RT toxicity and molecular effectors in the insulin (insulin, IGF-1, IGF-BP3 and IGF-1R) and adipokine signaling pathways (decreased leptin and increased adiponectin). Conclusions: CR augments the effect of systemic chemotherapy in an aggressive TNBC mouse model, in part by decreasing the inflammatory response. The novel use of CR in combination with systemic chemotherapy has the potential to enhance clinical outcomes for patients with triple negative breast cancer and should be tested in the clinical setting. Citation Format: Brittany Simone, Tu Dan, Ajay Palagani, Meredith LaRose, Jason E. Savage, Nicole Simone. Caloric restriction augments the chemotherapeutic response in a murine triple negative breast cancer model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5189.
Two Cyclin-Dependent Kinase Derived Peptides Are Potential Leukemia-Associated-Antigens Able To Eradicate Acute Myeloid Leukemia Cells after Allogeneic Stem Cell Transplantation.
Authors: Yukio Kondo, Xingmin Feng, Xuzhang Lu, Kanako Mochizuki, Jeffrey J. Molldrem, Shinji Nakao
Journal: Blood (2005)
Response by Peralta et al to Letter Regarding Article, “Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial”
Authors: Carmen A. Peralta, Leslie A. McClure, Rebecca Scherzer, Michelle C. Odden, Carole L. White, Michael Shlipak, Oscar Benavente, Pablo E. Pergola
Journal: Circulation (2016)
Abstract 2226: Anti-human PD-1 antibody BGB-A317 exhibits potent immune cell activation
Authors: Tong Zhang, Jing Song, Yucheng Li, Jie Ma, Yingdi Shi, Xiaoran Wu, Lanlan Xu, Qi Liu, Yanping Cao, Yali Wang, Hao Peng, Hongjia Hou, Xu Zhao, Xiaomin Song, Lai Wang, Min Wei, Lusong Luo, Kang Li
Journal: Cancer Research (2016)

Abstract Background: PD-1 is a “check point” inhibitory receptor, which is primarily expressed in activated and/or exhausted T cells. Engagement of PD-1 receptor by its ligand PD-L1 or PD-L2 (expressed on APCs and some tumor cells), leads to negative regulatory signaling in T-cells, promoting functional exhaustion of tumor-infiltrating T-lymphocytes. BGB-A317 is a novel humanized IgG4 anti-PD-1 antibody under clinical development. The immunomodulatory activity of BGB-A317 was evaluated in in vitro assays and reported here. Materials and methods: BGB-A317 was generated through hybridoma fusion, humanized by CDR grafting and structural simulation. The Fc and hinge regions of BGB-A317 were engineered to remove Fc gamma receptor (FcγR) binding and to stabilize the hinge region. The binding affinity and specificity were studied by ELISA, FACS and SPR (Biacore). The immunomodulatory functions of BGB-A317 were evaluated using both T-cell lines and primary immune cells. Results: BGB-A317 binds to the extracellular domain of human PD-1 with high affinity (KD = 0.15nM) and specificity. In competition assays, BGB-A317 efficiently blocks the interactions between PD-1 and its ligands. In vitro cell-based assays, BGB-A317 significantly enhances cytokine (IL-2 and IFN-γ) production using T-cell line or primary T cells cocultured with signal-sending cells in a dose-dependent manner. BGB-A317 also potently increases NK cell-mediated IFN-γ production and cytotoxicity against PD-L1+ tumor cells. As an important functional attribute, BGB-A317 exhibits no binding to any of FcγRs, including FcγRI, FcγRIIA, FcγRIIB and FcγRIIIA. Therefore, no antibody-dependent cell-mediated (ADCC) or complement-dependent cytotoxicity (CDC) has been observed in activated T cells treated with high concentration of BGB-A317 up to 100 μg/ml. BGB-A317 is stable as bivalent antibody unlike the wild type human IgG4 going through dynamic conformational change, forming bispecific antibody by Fab-arm exchange. Conclusions: BGB-A317 demonstrated potent immune cell activation in in vitro assays, supporting its clinical development for the treatment of human cancers. Keywords: Anti-PD-1, immunotherapy, functional assays Citation Format: Tong Zhang, Jing Song, Yucheng Li, Jie Ma, Yingdi Shi, Xiaoran Wu, Lanlan Xu, Qi Liu, Yanping Cao, Yali Wang, Hao Peng, Hongjia Hou, Xu Zhao, Xiaomin Song, Lai Wang, Min Wei, Lusong Luo, Kang Li. Anti-human PD-1 antibody BGB-A317 exhibits potent immune cell activation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2226.
Abstract 2625A: Damnacanthal and its nanoformulation suppress cyclin D1 expression
Authors: Pakin Sukamporn, Pleumchitt Rojanapanthu, Seung Joon Baek
Journal: Cancer Research (2016)

Abstract Damnacanthal is an anthraquinone isolated from the root of Morinda citrifolia L. (Noni) and exhibits many pharmacological properties including anti-cancer activity. It has been reported that Damnacanthal targets several signal transduction proteins related to cell growth inhibition or apoptosis. However, the molecular mechanisms by which Damnacanthal affects anti-cancer activity has not been elucidated in details. Cyclin D1 is the important regulatory protein in cell cycle progression and overexpressed in many cancer cells. In this study, we investigated the molecular mechanism of damnacanthal on cyclin D1 expression. We found that damnacanthal inhibited growth of several cancer cells (HCT-116, HT-29, MCF-7 and PC-3) in a dose- and time- dependent manner with decreasing in cyclinD1 protein expression. Damnacanthal did not change mRNA of cyclin D1, rather it suppressed cyclin D1 expression at the post-translational level. Subsequent experiments with dominant negative mutant cyclin D1 suggest that cyclin D1 at the lysine sites plays a pivotal role in damnacanthal-mediated cyclin D1 suppression. Furthermore, damnacanthal was encapsulated in self-assembled chitosan nanoparticle to improve both physicochemical and biological activities. Our results suggest that encapsulated damnacanthal exhibits better activity in cell growth inhibition, compared to non-encapsulated damnacanthal. Damnacanthal nanoformulation has potential to be a candidate for development of chemoprevention or therapeutic agent for cancers. Grant support: This work was supported by grant from the University of Tennessee Center of Excellence in Livestock Diseases and Human Health and The Thailand Research Fund (TRF) and Faculty of Pharmacy, Mahidol University (IRG5780007). Citation Format: Pakin Sukamporn, Pleumchitt Rojanapanthu, Seung Joon Baek. Damnacanthal and its nanoformulation suppress cyclin D1 expression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2625A.
Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Acute Lymphoblastic Leukemia: Better Outcome in Transplantation during First Complete Remission and with Myeloablative Conditioning
Authors: Avichai Shimoni, Avital Rand, Izhar Hardan, Noga Shem-Tov, Anfisa Stanevsky, Ronit Yerushalmi, Arnon Nagler
Journal: Blood (2008)
Prognostic Performance of the Cytogenetic Risk Classification Defined by the German-Austrian Myelodysplastic Syndromes (MDS) Study Group and Its Contribution to the International Prognostic Scoring System (IPSS) and the World Health Organization-Based Prognostic Scoring System (WPSS)
Authors: Benet Nomdedeu, Meritxell Nomdedeu, Arturo Pereira, Dolors Costa, Anna Carrió, Xavier Calvo, Mohamed Belkaid, Francesc Cobo, Alvaro Urbano-Ispizua
Journal: Blood (2010)
Abstract 2261: PKR and Jagged1 associated with lymph node metastasis in lung cancer
Authors: Apar Pataer, Chuncheng Hao, Arlene M. Correa, Annikka Weissferdt, Carmen Behrens, Ignacio I. Wistuba, Stephen G. Swisher
Journal: Cancer Research (2016)

Abstract In the current study, we analyzed the association between lymph node metastasis and over 50 biomarkers in 319 NSCLC patients. We observed that tumor location and the protein expressions of Jagged1 and RNA-dependent protein kinase (PKR) have significantly association with the lymph node metastasis. We further investigated the mechanism of interaction between Jagged1 and PKR, and demonstrated that induction of PKR promotes Jagged1 protein degradation through proteasome system in lung cancer cells. We also found that combination of Jagged1 with PKR improved prognostic value in all stages NSCLC patients. However, combination of Jagged1 with PKR did not improve lymph node metastatic value. Taken together, our data suggest that PKR and Jagged1 are independent markers for predicting lymph node metastasis, and PKR may reduce lymph node metastasis partly by promote Jagged1 proteins degradation in NSCLC patients. Citation Format: Apar Pataer, Chuncheng Hao, Arlene M. Correa, Annikka Weissferdt, Carmen Behrens, Ignacio I. Wistuba, Stephen G. Swisher. PKR and Jagged1 associated with lymph node metastasis in lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2261.
Interruption de la transmission de la rougeole autochtone confirmée en Catalogne (Espagne)
Authors: L Salleras, A Domínguez, N Torner
Journal: Eurosurveillance (2001)

De novembre 1998 a decembre 2000, 84 cas suspects de rougeole ont ete declares en Catalogne (6 090 040 habitants). Sur les 73 (87%) cas analyses en laboratoire, 20 presentaient des IgM specifiques et 3 avaient un lien epidemiologique avec un cas confirme. Parmi ces 23 cas confirmes, 13 etaient des cas autochtones, les deux derniers cas autochtones datant de juin 1999 et juillet 2000. Ces resultats illustrent le succes du programme d’elimination de la rougeole mis en place en 1998 en Catalogne.
Pan‐genotypic cell culture system for propagation of hepatitis C virus clinical isolates
Authors: Hiromi Abe‐Chayama, C. Nelson Hayes, Kazuaki Chayama
Journal: Hepatology (2016)

Abe‐Chayama, Hiromi Ph.D.; Hayes, C. Nelson Ph.D.; Chayama, Kazuaki M.D., Ph.D. Author Information
Formation en épidémiologie des maladies transmissibles en Europe du Nord
Authors: Preben Aavitsland, Stein Andresen
Journal: Eurosurveillance (2001)

Les cinq pays nordiques (Danemark, Finlande, Islande, Norvege et Suede) jouissent d’une collaboration de longue date dans le domaine de l’epidemiologie et du controle des maladies transmissibles. Les epidemiologistes nationaux et les directeurs des programmes de vaccination se reunissent regulierement pour discuter des defis communs et echanger leurs experiences en matiere de surveillance et de controle des maladies transmissibles.
Abstract 1308: Enhanced antitumor activity of rapamycin and genipin, a UCP-2 inhibitor, in lung cancer
Authors: Wen-Pin Su, Jang-Yang Chang, Ching-Chuan Kuo, Wu-Chou Su
Journal: Cancer Research (2016)

Abstract mTOR is constitutively activated in lung cancer. Deletion of TOR1 increases expression of OXPHOS proteins, and mitochondrial uncoupling proteins 2 (UCP-2) expression promotes chemoresistance. Therefore, we evaluated whether adding genipin, a UCP-2 inhibitor, to rapamycin has better antitumor effect in lung cancer. Combined with genipin and rapamycin have a synergistic effect with more cellular apoptosis in A549, H460 and CL1-0 cells. The similar phenomenon was found in the combination treatment with genipin and everolimus or BGT226 (a dual PI3K/mTOR inhibitor) in this three lung cancer cells. It is said that NrF2 may affect UCP-2 expression, and we found NrF2 was activated in lung cancer A549, H460 and CL1-0 cells treated with rapamycin. Everolimus and dual PI3K/mTOR inhibitor, BGT226, also induced NrF2 nuclear translocation in these lung cancer cells. It is said that under oxidant stress, p62 activates NrF2 through P62 Ser351-phosphorylation. We found that rapamycin induced ROS generation, p62 serine phosphorylation and NrF2 downstream mRNA and protein expression, including UCP-2. ROS inhibitor, NAC, and down-regulation of p62 by siRNA suppressed rapamycin-induced UCP-2 expression. Overexpression of p62 by cDNA transfection enhanced NrF2 activation and then UCP-2 expression in lung cancer cells. Moreover, rapamycin-induced increased UCP-2 expression, leading decreased mitochondrial membrane potential and mild increased oxygen consumption rate. Finally in A549 subcutaneous tumor mode in SCID mice, combined genipin and everolimus also demonstrated the greatest antitumor activity. Therefore, inhibition UCP-2 by genipin enhances anticancer effect of rapamycin in lung cancer. Citation Format: Wen-Pin Su, Jang-Yang Chang, Ching-Chuan Kuo, Wu-Chou Su. Enhanced antitumor activity of rapamycin and genipin, a UCP-2 inhibitor, in lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1308.