tbuckley/cabot-search huggingface dataset:
Abstract 2923: A novel cell-penetrating peptide targeting ATF5 (CP-d/n-ATF5) exerts anti-cancer activity in vitro and in vivo against a broad spectrum of human cancers
Authors: Georg Karpel-Massler, Chang Shu, Lily Chau, James M. Angelastro, Lloyd A. Greene, Markus D. Siegelin
Journal: Cancer Research (2015)

Abstract Background The purpose of this study was to validate the anti-neoplastic activity of a novel ATF5-targeted therapeutic approach against various recalcitrant human malignancies. Activating transcription factor 5 (ATF5) is a member of the cAMP response element binding (CREB)/ATF subfamily of basic leucine zipper transcription factors and has been shown to be overexpressed in many human cancers. CP-d/n-ATF5 is a novel peptide specifically designed to contain a cell-penetrating domain and a domain inhibiting the function of ATF5 in a unique and novel targeted therapeutic approach. This therapeutic strategy was tested among a large panel of different therapy refractory human cancers including glioblastoma, melanoma, breast, prostate-, lung- and pancreatic cancer. Methods Cellular viability was assessed by MTT-assays. The induction of apoptosis was examined by staining for annexin V/propidium iodide or JC-1 (loss of mitochondrial membrane potential) prior to flow cytometric analysis. Western blotting was performed for further molecular analysis detecting caspase cleavage and expression of Bcl-2 family members. Subcutaneous xenograft models were used to examine the anti-neoplastic effects of CP-d/n-ATF5 in vivo. Results Our data show that CP-d/n-ATF5 yields a significant increase in apoptosis across a panel of 10 different cancer cell lines when compared to treatment with a mock-mutated control peptide or penetratin. On the molecular level, treatment with CP-d/n-ATF5 resulted in a marked down-regulation of the anti-apoptotic Bcl-2 family members Mcl-1 and Bcl-2. This effect was amplified in a synergistic manner by adding either ABT-263 or TRAIL to a combined targeted therapeutic approach. In vivo, treatment with CP-d/n-ATF5 resulted in a significant reduction of tumor growth in a heterotopic glioblastoma- and an orthotopic melanoma model. Conclusions The novel ATF5-targeting compound CP-d/n-ATF5 provides a broad and pronounced anti-neoplastic activity against human cancers in vitro and in vivo. On the molecular level, this effect is at least in part due to a shift of the cellular homeostasis towards a pro-apoptotic cellular phenotype by inhibiting anti-apoptotic Bcl-2 family proteins. Overall, CP-d/n-ATF5 may represent a promising novel anti-cancer agent. Citation Format: Georg Karpel-Massler, Chang Shu, Lily Chau, James M. Angelastro, Lloyd A. Greene, Markus D. Siegelin. A novel cell-penetrating peptide targeting ATF5 (CP-d/n-ATF5) exerts anti-cancer activity in vitro and in vivo against a broad spectrum of human cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2923. doi:10.1158/1538-7445.AM2015-2923
There is a difference of vitamin D receptor gene (VDR) single-nucleotide polymorphisms (SNPs) frequencies between malignant melanoma patients and healthy volunteers and by sex?
Authors: F. Morgese, R. Berardi, S. Pagliaretta, C. Sampaolesi, M. Torniai, A. Campanati, G. Ganzetti, V. Brisigotti, E. Molinelli, G. Ceccarelli, A. Offidani, S. Cascinu
Journal: Annals of Oncology (2015)
Abstract A1-28: Chromosome fusions triggered by noncoding RNA
Authors: John Bracht, Xing Wang, Keerthi Shetty, Xiao Chen, Mariusz Nowacki, Sierra McCloud, Derek Clay, Laura Landweber
Journal: Cancer Research (2015)

Abstract Chromosomal fusion is a frequent occurrence in cancer cells and can promote transformation through the generation of oncogenic gene products. There are two non-exclusive models for how these chromosome fusions may occur: (1) the instability of the cancer genome produces chromosomal fusions randomly and those promoting transformation enjoy a selective advantage, or (2) some non-random mechanism drives chromosome fusion. Evidence for (2) comes from recurrent fusion events and correlative human data linking noncoding RNA expression with chromosome fusion. To help address this important fundamental question, we functionally tested the role of noncoding RNA, specifically piRNAs, in promoting chromosomal fusion in the ciliate, Oxytricha trifallax, a microbial eukaryote. We microinjected custom piRNAs into cells and observed chromosome fusion in four cases (of four tested), including a double fusion event and a chromosome circularization event (self-fusion). Furthermore, these RNA-mediated inter-and-intra-chromosomal fusions are heritable over multiple sexual generations, illustrating the ability of noncoding RNAs to program genome architecture, including chromosome fusion and circularization. Citation Format: John Bracht, Xing Wang, Keerthi Shetty, Xiao Chen, Mariusz Nowacki, Sierra McCloud, Derek Clay, Laura Landweber. Chromosome fusions triggered by noncoding RNA. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-28.
Abstract 1706: Whole exome sequencing of pre and post treatment diffuse large B cell lymphoma reveals the mutation spectrum of the relapse/refractory patient population
Authors: Danielle Greenawalt, Kate Byth, Zhongwu Lai, Justin Johnson, Ambar Ahmed, Brian Dougherty, Kenneth Thress, Michael Zinda, Winnie S. Liang, John Carpten, Stephen Fawell, J. Carl Barrett
Journal: Cancer Research (2015)

Abstract Our current understanding of the mutation spectrum of relapse/refractory patients is limited. Several published studies describing the mutational landscape of Diffuse Large B cell Lymphoma (DLBCL) have focused, by design, on diagnostic (pre-treatment) biopsies alone, while re-biopsy of patients who are refractory to first line therapy or who relapse on treatment is not standard of care in DLBCL. We have performed whole exome sequencing on 47 post treatment DLBCL core needle biopsies, 8 with matched diagnostic biopsies. Samples were obtained during a phase II trial prior to the start of treatment with the BCR targeted agent fostamatinib (1,2). Patients had progressed following therapy with an anthracycline-based regimen such as R-CHOP and had a median of 3 prior therapies (range 1-8). We compared the whole exome somatic variant and copy number calls from the post treatment and matched pairs to 2 cohorts of primary DLBCL (n = 112) analyzed with the same mutation caller (3,4). The average mutation rate between the pre and post treatment samples (n = 250, 282 respectively) and the paired diagnostic and post treatment biopsies were similar. However, we found that the mutation spectrum between the paired biopsies differed. Known DLBCL hotspot mutations such as MYD88 L265P remained consistent between pre and post treatment biopsies, however novel mutations in known DLBCL targets were found to emerge in the post treatment biopsies. 1. Veldman-Jones, M. et al. Reproducible, quantitative and flexible molecular sub-typing of clinical DLBCL samples using the NanoString nCounter system. Clin Cancer Res (2014) 2. Flinn I, B.N., Blum KA, et al. A Phase II Trial to Evaluate the Efficacy of Fostamatinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL). American Society of Hematology (San Francisco, 2014). 3. Zhang, J. et al. Genetic heterogeneity of diffuse large B-cell lymphoma. Proc Natl Acad Sci U S A 110, 1398-403 (2013). 4. Pasqualucci, L. et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet 43, 830-7 (2011). Citation Format: Danielle Greenawalt, Kate Byth, Zhongwu Lai, Justin Johnson, Ambar Ahmed, Brian Dougherty, Kenneth Thress, Michael Zinda, Winnie S. Liang, John Carpten, Stephen Fawell, J. Carl Barrett. Whole exome sequencing of pre and post treatment diffuse large B cell lymphoma reveals the mutation spectrum of the relapse/refractory patient population. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1706. doi:10.1158/1538-7445.AM2015-1706
Need of Reconsideration of Mobilization Strategy in Autologous Stem Cell Transplantation for Multiple Myeloma: Results of the Positive Impact of High Number of CD34+ Infused Cells.
Authors: Mauricette Michallet, Mohamad Sobh, Benjamin Riche, Franck Emmanuel Nicolini, Nicole Raus, Fiorenza Baracco, Giovanna Cannas, Youcef Chelghoum, Emmanuelle Nicolas-Vierlizier, Gilles Clapisson, Xavier Thomas, Jacques Troncy, Amina Zinai, René Ecochard, Sophie Ducastelle
Journal: Blood (2009)
Delayed management of Staphyloccocus aureus infective endocarditis in a Middle East respiratory syndrome coronavirus possible case hospitalized in 2015 in Paris, France
Authors: A. Bleibtreu, P. Arias, D. Vallois, A. Debit, M. Lermuzeaux, C. Rioux, O. Cabras, J.C. Lucet, C. Choquet, J.F. Timsit, Y. Yazdanpanah, F.X. Lescure
Journal: Clinical Microbiology and Infection (2016)
Graphene quantum dots with nitrogen-doped content dependence for highly efficient dual-modality photodynamic antimicrobial therapy and bioimaging
Authors: Wen-Shuo Kuo, Hua-Han Chen, Shih-Yao Chen, Chia-Yuan Chang, Pei-Chi Chen, Yung-I Hou, Yu-Ting Shao, Hui-Fang Kao, Chih-Li Lilian Hsu, Yi-Chun Chen, Shean-Jen Chen, Shang-Rung Wu, Jiu-Yao Wang
Journal: Biomaterials (2016)
Daunorubicine, Cytarabine and Cladribine (DAC) Vs Daunorubicine and Cytarabine (DA) Induction Treatment in Elderly Acute Myeloid Leukemia (AML) Patients – Results of the Prospective, Multicenter, Randomized Trial of the Polish Adult Leukemia Group (PALG)
Authors: Agnieszka Pluta, Tadeusz Robak, Agata Wrzesien-Kus, Bozena Katarzyna Budziszewska, Kazimierz Sulek, Ewa Wawrzyniak, Magdalena Czemerska, Malgorzata Zwolinska, Aleksandra Golos, Aleksandra Holowiecka-Goral, Slawomira Kyrcz-Krzemien, Jaroslaw Piszcz, Janusz Kloczko, Monika Mordak, Andrzej Lange, Małgorzata Razny, Krzysztof Madry, Wieslaw Wiktor-Jedrzejczak, Sebastian Grosicki, Aleksandra Butrym, Kazimierz Kuliczkowski, Krzysztof Warzocha, Jerzy Holowiecki, Agnieszka Wierzbowska
Journal: Blood (2012)
Comparison of Acalabrutinib, A Selective Bruton Tyrosine Kinase Inhibitor, with Ibrutinib in Chronic Lymphocytic Leukemia Cells
Authors: Viralkumar Patel, Kumudha Balakrishnan, Elena Bibikova, Mary Ayres, Michael J. Keating, William G. Wierda, Varsha Gandhi
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Ibrutinib inhibits Bruton tyrosine kinase (BTK) by irreversibly binding to the Cys-481 residue in the enzyme. However, ibrutinib also inhibits several other enzymes that contain cysteine residues homologous to Cys-481 in BTK. Patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL) demonstrate a high overall response rate to ibrutinib with prolonged survival. Acalabrutinib, a selective BTK inhibitor developed to minimize off-target activity, has shown promising overall response rates in patients with relapsed/refractory CLL. A head-to-head comparison of ibrutinib and acalabrutinib in CLL cell cultures and healthy T cells is needed to understand preclinical biologic and molecular effects. Experimental Design: Using samples from patients with CLL, we compared the effects of both BTK inhibitors on biologic activity, chemokine production, cell migration, BTK phosphorylation, and downstream signaling in primary CLL lymphocytes and on normal T-cell signaling to determine the effects on other kinases. Results: Both BTK inhibitors induced modest cell death accompanied by cleavage of PARP and caspase-3. Production of CCL3 and CCL4 chemokines and pseudoemperipolesis were inhibited by both drugs to a similar degree. These drugs also showed similar inhibitory effects on the phosphorylation of BTK and downstream S6 and ERK kinases. In contrast, off-target effects on SRC-family kinases were more pronounced with ibrutinib than acalabrutinib in healthy T lymphocytes. Conclusions: Both BTK inhibitors show similar biological and molecular profile in primary CLL cells but appear different on their effect on normal T cells. Clin Cancer Res; 23(14); 3734–43. ©2016 AACR.
OP51METABOLIC ACTIVITY OF THE INVASIVE MICROENVIRONMENT OF GLIOBLASTOMAS DETERMINES TIME PROGRESSION: A MULITOMODAL MRI STUDY
Authors: Stephen J. Price, Adam M.H. Young, William Scotton, Natalie R. Boonzaier, Mary A. McLean, Timothy J. Larkin
Journal: Neuro-Oncology (2015)

INTRODUCTION: Virtually all glioblastoma (GBM) patients will die from progressive disease adjacent to the tumour resection cavity. Our previous work has shown that we can identify the invasive margin with diffusion tensor MR (DTI) and that we can use multimodal MRI to study the microenvironment of this region. This study aims to understand how the microenvironment influences progression and response to therapy. METHOD: 50 patients with GBM were recruited prospectively and imaged pre-operatively at 3 Tesla. Imaging involved conventional imaging, DTI, dynamic susceptibility perfusion imaging (to provide rCBV) and multivoxel short echo spectroscopy. Regions of interest from the invasive margin were identified on the DTI and perfusion and metabolite analysis performed. All patients subsequently underwent a 5-ALA guided resection followed by chemoradiotherapy. The progression free survival interval (PFS) was noted for all patients. ROC curves were produced to assess different parameters ability to predict PFS >1 year. Survival was assessed with Kaplan-Meier survival curves and a multivariate Cox regression model used to assess impact of imaging parameters with clinical parameters. RESULTS: 30% of patients had PFS > 1 year. The best predictor of this was the NAA/Cho ratio (AUC 0.73) - a marker of cellular proliferation. A cut-off of 0.6 differentiated between PFS > 1 year and PFS  0.6 PFS = 497 days (P = 0.01). CONCLUSION: Our data suggests that more metabolically active tumour margin is associated with better outcome. One hypothesis is that areas with low Cho/NAA have less proliferative activity and are less likely to respond to cytotoxic therapy.
Monitoring By Chromosome Banding Analysis (CBA) and FISH Of Circulating CD34+ Cells In Low-Risk MDS Patients Treated In The Le-Mon-5 Study With Lenalidomide Monotherapy Reveals 82% Cytogenetic Responders With Different Response – , Evolutionary -, and Remission Patterns and No Increased Karyotype Evolution (KE)
Authors: Katayoon Shirneshan, Uwe Platzbecker, Florian Nolte, Aristoteles Giagounidis, Katharina Götze, Richard F. Schlenk, Michael Lübbert, Gesine Bug, Friederike Braulke, Julie Schanz, Ulrich Germing, Detlef Haase
Journal: Blood (2013)
The follow-up and lifestyle (FUCSAM project). Oncology Network of Piemonte and Valle d'Aosta (ROPVdA): preliminary data
Authors: O. Bertetto, M.G. Pacquola, I. Romaniello, F. Castiglione, P. Bellingeri, N. De Piccoli, A. Fedi, S. Gattino, C. Finocchiaro, M. Mistrangelo, M.P. Mano, C. Monagheddu, M. Viale, G. Ciccone, C. Senore, L. Giordano
Journal: Annals of Oncology (2015)
126. Non-Viral Gene Therapy By Liver-Directed Hydrodynamic Delivery of Sleeping Beauty Transposons to Treat Hemophilia and Mucopolysaccharidoses in Dogs
Authors: Perry B. Hackett, Elena L. Aronovich, Jason B. Bell, Myra Rusten, David W. Hunter, Bryan C. Hall, Erik R. Olson, Kendra A. Hyland, N. Matthew Ellinwood, R. Scott McIvor
Journal: Molecular Therapy (2015)

The goal of gene therapy is to achieve sustained expression of a transgene encoding an enzyme deficient in patients. Others and we have reported effectiveness of the Sleeping Beauty (SB) transposon system for gene therapy of both hemophilia B and mucopolysaccharidoses (MPS) types I and VII in adult mice. Although more than 99% of transgene expression comes from the liver following hydrodynamic delivery, restoration of deficient enzyme activity in other organs can be achieved through metabolic cross-correction whereby IDUA enters the circulation and is distributed to other tissues. However, the efficacy of hydrodynamic delivery to treat animals larger than mice has been discouraging. We have tested the use of balloon-catheters for intravascular infusion and expression of SB transposons in the liver of dogs as a large animal model for human therapy. Balloon-catheters were introduced under fluoroscopic guidance through either the jugular or the femoral vein and positioned in the inferior vena cava for occlusion of venous outflow of the and retrograde infusion through the left hepatic vein. Infusions were 10 seconds in duration and delivered volumes of DNA solution equal to about three times the estimated blood volume of the left side of the liver. Using canine secreted alkaline phosphatase (cSEAP) as a reporter we have developed effective protocols for infusion of transposons into canine liver as a scale-up for preclinical gene therapy studies in large animal models of human disease. We tested our protocol on both Factor IX (FIX)-deficient and beta-glucuronidase (GUSB)-deficient young dogs by hydrodynamically infusing two plasmids, one that harbors a T2-SB transposon containing either a canine FIX gene or a canine GUSB gene under transcriptional direction of a CAGGS or liver specific promoter (LSP) and a second carrying either the SB11 or SB100X transposase regulated by the CMV early promoter. Duration of FIX and GUSB expression in the treated dogs was transient, lasting only about 1 – 8 weeks. PCR analysis of plasmids in liver suggest that the efficiency of catheter-mediated delivery to canine livers is approximately 0.1-1% that in the mouse, which accounts for the relatively poor levels of transgene activity in the larger animals. We discuss our hypothesis that the larger vascular net with many more bifurcations in the livers of large animals lowers both impulse and shear forces necessary for effective hydrodynamic delivery in the liver.
Autologous Versus Allogeneic Hematopoietic Stem Cell Transplantation (SCT) for Peripheral T-Cell Lymphomas (PTCLs): Japan and Korea Cooperative Study with 330 Patients.
Authors: Sung-Won Kim, Sung-Soo Yoon, Ritsuro Suzuki, Hyeon Gyu Yi, Hiroatsu Ago, Masahiro Imamura, Atsushi Wake, Takashi Yoshida, Je-Jung Lee, Jin Seok Kim, Yoshinobu Maeda, Koji Izutsu, Hye Jin Kang, Je-Hwan Lee, Hugh Chul Kim, Junji Suzumiya, Yoshihiro Matsuno, Chul Woo Kim, Koji Nagafuji, Yoichi Takaue, Mine Harada, Chul Soo Kim
Journal: Blood (2009)
RIC Allo-SCT with Flu/Bu in Comparison to Flu/Mel for AML Results in Similar Overall Survival: A Report from the ALWP of the EBMT
Authors: Frederic Baron, Myriam Labopin, Andrew Peniket, Pavel Jindra, Boris Afanasyev, Miguel A. Sanz, Eric Deconinck, Arnon Nagler, Mohamad Mohty
Journal: Blood (2014)
Lenalidomide Is Likely To Improve Overall Survival in Patients with del(5q) Myelodysplastic Syndrome with a Complex Karyotype.
Authors: Aristoteles A. Giagounidis, Sabine Haase, Ulrich Germing, Gundula Göhring-Michaelsen, Brigitte Schlegelberger, Carlo Aul
Journal: Blood (2006)
Forced Expression of CC Chemokine Receptor 2 Enhances Anti-Cancer Reactivity Mediated by T Lymphocytes Beforehand Redirected Toward WT1 Inside the Tumor Microenvironment
Authors: Hiroaki Asai, Hiroshi Fujiwara, Toshiki Ochi, Jun An, Toshiaki Shirakata, Kozo Nagai, Yukihiro Miyazaki, Junichi Mineno, Kiyotaka Kuzushima, Hiroshi Shiku, Masaki Yasukawa
Journal: Blood (2011)
Abstract 11924: Plasma 27-hydroxycholesterol/cholesterol Ratio is Increased in Low High Density Lipoprotein-Cholesterol Healthy Subjects
Authors: Valeria S Nunes, Camila C LeanCa, Natalia B Panzoldo, Eliane Parra, Vanessa Zago, Patricia M Cazita, Edna R Nakandakare, Eliana C de Faria, Eder C Quintao
Journal: Circulation (2012)
The Gamma Catenin/CBP Complex Maintains Survivin Transcription In β-Catenin Deficient/Depleted Cancer Cells.
Authors: Yong-Mi Kim, Hong Ma, Vivian Oehler, Enzi Jiang, Cu Nguyen, David P. Masiello, Han Liu, Yi Zhao, Jerald P. Radich, Michael Kahn
Journal: Blood (2010)
Antibiotic Prophylaxis Revisited: The Impact of Fluoroquinolones on Epidemiology and on the Emergence of Resistant Strains in Acute Leukemia Patients. Results of a Prospective Study By the Rete Ematologia Lombarda (REL)
Authors: Chiara Cattaneo, Patrizia Zappasodi, Silvia Ferrari, Francesca Pavesi, Claudio Annaloro, Cristina Skert, Luisa Verga, Elisabetta Todisco, Andrea Ferrario, Vittoria Saccà, Angela Passi, Erika Borlenghi, Matteo C Da Vià, Valentina Mancini, Gabriella Mometto, Claudia Basilico, Roberto Cairoli, Annamaria Nosari, Giuseppe Rossi
Journal: Blood (2014)
Expression of insulin-like growth factor-1 receptor (IGF-1R) as a marker of response to erlotinib in pancreatic ductal adenocarcinoma (PDA).
Authors: A. Witkiewicz, M. E. Valsecchi, J. R. Brody, L. R. Simon, C. Yeo, B. I. Carr, C. Solomides, S. Peiper
Journal: Journal of Clinical Oncology (2011)

e14628 Background: Erlotinib proved to be active in unselected patients with metastatic PDA. Hence, there is an unmet need to select patients likely to respond to anti-EGFR therapy. IGF-1R was reported to be over-expressed in 38-64% of patients with PDA and in-vitro studies showed that it modulates response to EGFR inhibitors. In this study, we evaluated the relationship between IGF-1R and EGFR expression and response to erlotinib. Methods: Patients with stage I-IV PDA, who received erlotinib either in the adjuvant or neo-adjuvant or metastatic setting, were studied. IGF-1R and EGFR membrane expression in neoplastic cells and IGF-1R in tumoral stroma was measured using automatic image analysis (Aperio, Vista, CA). Protein expression in tumor cells was scored using membranous Aperio algorithm developed for HER-2 scoring. EGFR and IGF-1R scores were dichotomized as low vs. high. Clinical and pathological information was also recollected. Cox-Proportional hazard ratio was used to explore the association with overall survival (OS) or time to recurrence (TTR). Results: A total of 54 patients were included; 37 (68.5%) stage I-II, 7 (13%) stage III and 10 (18.5%) stage IV. The median follow up was 17 months (min 4; max 64). Approximately 63% (34/54) showed high EGFR membrane expression, 42.5% (23/54) showed high IGF-1R expression and 54% (29/54) showed high IGF-1R stromal expression. After adjusting for TNM stage, time and setting when patients received erlotinib, high expression of membrane IGF-1R was significantly associated with better OS (HR=.28; 95% CI: 0.12-0.67; P=0.004) and TTR (HR=.30; 95% CI: 0.14-0.65; P=0.002). However, high levels of stromal IGF-1R were related with poor OS (HR=2.2; 95% CI: 0.96-5.14; P=0.062) and TTR (HR=3.32; 95% CI: 1.53-7.24; P=0.003). No significant relationship was found in regards to EGFR expression. Conclusions: We found a statistically significant association between high expression of IGF-1R in neoplastic cells and erlotinib response. Moreover, the stromal expression of IGF-1R and its potential significance merits further investigation. Combination of these markers should help to select PDA patients for EGFR-targeted therapies in future trials.