tbuckley/cabot-search huggingface dataset:
Abstract 5012: Establishment of a transplantable, NY-BR-1 expressing breast cancer model in HLA-transgenic mice
Authors: Krishna Das, Adriane Gardyan, Mathias Vormehr, Karin Mueller-Decker, Inka Zörnig, Dirk Jäger, Wolfram Osen, Stefan B. Eichmüller
Journal: Cancer Research (2015)

Abstract Introduction: Breast cancer is one of the leading causes of cancer related deaths in women worldwide and current standard therapies show limited efficacy. However, immunotherapeutic approaches like adoptive T cell transfer might represent an attractive option for the treatment of breast carcinoma. The differentiation antigen NY-BR-1 appears as a suitable target for T cell immunotherapy against breast cancer as it is overexpressed in 60% of breast carcinomas compared to healthy breast. Objectives: The aim of this project is to establish a NY-BR-1-expressing, transplantable tumor model in HLA transgenic mice that would allow to investigate the functional role of NY-BR-1-specific HLA-restricted CD4+ T cells in vivo with respect to their capacity to sustain cytotoxic T lymphocytes (CTL)-mediated tumor attack. Furthermore, the capability of NY-BR-1-specific CD4+ T cells to interact with tumor-associated macrophages (TAMs) thereby potentially promoting differentiation of TAMs into immunostimulatory type-1 macrophages (M1) will be investigated. Materials and methods: Stable transfectant clones of the C57BL/6 derived lymphoma cell line EL4 and of the mammary adenocarcinoma cell line EO771 expressing NY-BR-1 were established. Furthermore, an H2Db-restricted, NY-BR-1-specific CTL epitope could be identified which upon peptide immunization of C57BL/6 mice resulted in the generation of NY-BR-1 specific, H2Db-restricted CTL lines, similarly to immunization with a rec. NY-BR-1 encoding adenovirus as observed in parallel experiments. Results and conclusions: Transplanted EL4 and EO771 derived transfectant clones stably expressing NY-BR-1 gave rise to subcutaneous tumors in H2-compatible, HLA-DR4 transgenic mice. In addition, a NY-BR-1-specific CTL line recognizing EL-4/NY-BR-1 expressing transfectants in vitro was successfully generated upon peptide immunization as described above. Studies to investigate the cooperative effect between the aforementioned CTL line and HLA-DR3- and HLA-DR4-restricted NY-BR-1-specifc CD4+ T cell lines, upon joint adoptive transfer into tumor bearing HLA-transgenic mice are currently ongoing. The results presented here demonstrate the first NY-BR-1 expressing mouse tumor model, allowing the investigation of NY-BR-1-specific immune responses in vivo. Citation Format: Krishna Das, Adriane Gardyan, Mathias Vormehr, Karin Mueller-Decker, Inka Zörnig, Dirk Jäger, Wolfram Osen, Stefan B. Eichmüller. Establishment of a transplantable, NY-BR-1 expressing breast cancer model in HLA-transgenic mice. [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 5012. doi:10.1158/1538-7445.AM2015-5012
Activated ERK1/2 increases CD44 in glomerular parietal epithelial cells leading to matrix expansion
Authors: Sebastian S. Roeder, Taylor J. Barnes, Jonathan S. Lee, India Kato, Diana G. Eng, Natalya V. Kaverina, Maria W. Sunseri, Christoph Daniel, Kerstin Amann, Jeffrey W. Pippin, Stuart J. Shankland
Journal: Kidney International (2016)
Abstract 1835: Intraluminal Ultrasonography Depicts Detailed Pathology in Type B Aortic Dissection and Safely Guides Emergency Fenestration
Authors: Thomas Bartel, Holger Eggebrecht, Silvana Muller, Achim Gutersohn, Johannes Bonatti, Otmar Pachinger, Raimund Erbel
Journal: Circulation (2006)
696. TLR9 Signaling Mediates Transgene Antibody Formation
Authors: Scott Ashley, Deirdre McMenamin, Christine Draper, James M. Wilson
Journal: Molecular Therapy (2016)

Recent success in gene therapy clinical trials have shown great promise towards developing efficacious treatments, however antibody formation to the therapeutic protein resulting in treatment attenuation still remains a concern. Driven by the immunologic stimuli of vector administration, transgene expression can elicit a humoral response against "non-self" protein, as these antigens were not presented during the process of central tolerance induction. Previously, we have shown that TLR9 signaling is necessary to mount a CD8+ T cell response that reduces expression of non-secreted transgene product. Here, we show that TLR9 signaling is also involved in driving the activation of B cells to secrete transgene-specific neutralizing antibody. Delivery of the viral vector and the effect of TRL9, route of administration, and promoter on the immune response to transgene expression was studied using the human IDUA gene, which is mutated in the lysosomal storage disorder, mucopolysaccharidosis type I (MPS I). IV administration of C57Bl/6 mice with AAV9.hIDUA under the control of a universal CMV promoter resulted in the production of neutralizing IgG antibodies and loss of transgene activity measured in serum. Surprisingly, when administered to TLR9 knockout mice, antibody formation was very modest to not detectable and IDUA activity maintained at a steady state. Next, we administered AAV9 vectors with expression driven by different promoters, including the universal promoters, CMV and CB7, and the liver-restricted promoter, TBG. Mice that received vectors containing universal promoters demonstrated elevated IgG to hIDUA, while those with liver-specific expression did not. Co-administration of the TBG- and CMV-containing vectors did not inhibit IgG formation, demonstrating that expression in non-liver tissue drives the immune system to a humoral response, and overcomes the potential tolerogenic effect of liver-specific expression. In ongoing experiments, hIDUA constructs containing CpG motifs that are known to bind efficiently to TLR9 will be used to assess the impact of TLR9 signaling on transgene-specific neutralizing antibody production. Overall, our results suggest that TLR9 signaling is important for the development of anti-transgene antibodies.
Phase I/II Study of Subcutaneous Injections of Low-Dose Anti-CD20 Veltuzumab in Relapsed Immune Thrombocytopenia,
Authors: Howard A Liebman, Mansoor N Saleh, James B Bussel, Zale P Bernstein, O George Negrea, Anthony C Onyegbula, Charles M Farber, Heather Horne, William A Wegener, David M Goldenberg
Journal: Blood (2011)
Non-Myeloablative Allogeneic Transplantation for Hodgkin’s and Non-Hodgkin’s Lymphoma: Evidence for a Graft-Versus-Lymphoma Effect and Relevance of Chimerism.
Authors: Philippe Armand, Haesook T. Kim, Ann S. LaCasce, Corey S. Cutler, Vincent T. Ho, John Koreth, Eric D. Jacobsen, David C. Fisher, Jennifer R. Brown, George P. Canellos, Joseph H. Antin, Arnold S. Freedman, Robert J. Soiffer, Edwin P. Alyea
Journal: Blood (2007)
Activity and Safety of Lenalidomide and Dexamethasone in Multiple Myeloma Patients with Advanced Renal Failure: a Spanish Multicenter Retrospective Study.
Authors: Monica Roig, Angela Ibañez, Inmaculada García, Juan A. Vera,, Carlos Aguilar, Raquel del Campo, Nicolas Gonzalez, Rafael Martínez, Luis Palomera, Isabel Picon, José N. Rodríguez, Miguel A. Sanz,, Javier de la Rubia
Journal: Blood (2009)
21. Non-CD3-Based Chimeric Antigen Receptor (CARs) with Enhanced Anti-Tumor Activity in Solid Tumors
Authors: Enxiu Wang, Liang-Chuan Wang, Ching-Yi Tsai, Vijay Bhoj, Steven Albelda, Edmund Moon, Michael Milone
Journal: Molecular Therapy (2015)

Chimeric antigen receptors (CARs) based upon a single chimeric molecule bearing an antigen binding domain linked in cis to the cytoplasmic domains of CD3ζ and costimulatory receptors CD28 or 4-1BB provide a potent method for engineering T cell cytotoxicity towards tumors. We describe a simple chimeric receptor based upon a killer immunoglobulin-like receptors (KIRs) normally expressed by natural killer (NK) cells and T cells. Constructed by fusing a single chain variable fragment (scFv) to the transmembrane and cytoplasmic domain of a KIR, we show that a KIR-based CAR targeting multiple tumor-related antigens triggers antigen-specific cytotoxic activity and cytokine production that is comparable to CD3ζ-based CARs with antigen-induced proliferation that is independent of additional costimulation. Using a solid tumor xenograft model that is highly resistant to CD3ζ-based CAR-targeted T cells, we further demonstrate that KIR-based CAR-targeted T cells can induce tumor regression despite in vivo persistence of CD3ζ-based CAR-modified T cells with CD28 and 4-1BB costimulatory domains. We show that the enhanced activity of the KIR-based CAR is associated with less tumor-induced T cell hypofunction that has previously been demonstrated with CD3ζ-based CARs. These data support the future clinical evaluation of a KIR-based CARs especially within solid tumors.
The Distinctive Morphogenesis of Infantile Megakaryopoiesis Is Associated with Altered P-TEFb Regulation By the Oncofetal Factor IGF2BP3
Authors: Kamaleldin E Elagib, Chih-Huan Lu, Ewelina Zasadzińska, Daniel R Foltz, Peter Balogh, Adam N Goldfarb
Journal: Blood (2014)
Drug resistance induced by plasmatic concentrations of paclitaxel and carboplatin.
Authors: R. Luque, E. González Flores, J. R. Delgado, J. C. Prados, C. Melguizo, V. Conde, B. Gonzalez Astorga, R. Ortiz, A. Rama
Journal: Journal of Clinical Oncology (2011)

e13036 Background: Multidrug resistance (MDR) phenotype is the major cause of chemotherapy failure. The relationship between the expression of these markers and chemotherapy resistance is clear. We study the resistance pattern induced after treatment with paclitaxel, carboplatin in non small cell lung cancer (NSCLC). Methods: We used 5 different cell lines. A549 and A427 cell lines were derived from lung epithelial carcinoma. The NODO line was obtained from lung carcinoma , and 3 cell lines derived from other tumours . The cell lines were exposed to paclitaxel, carboplatin, and the combination of both drugs. The concentrations we used were similar to the plasma concentrations observed in patients treated previously. Results: A549 cell line did not show basal expression of MDR1, but a weak basal expression of MRP3 was observed. After chemotherapy, we observed that paclitaxel induced MDR1and carboplatin induced MRP3. The combination of both drugs induced the expression of both cell lines, however, when paclitaxel is associated to carboplatin, MRP3 expression did not increase significantly. A427 cell line did not show basal expression of MDR1 and MRP3. Paclitaxel induced MDR1 and carboplatin induced MRP3. As previously occurred, the association of both drugs increased significantly the expression of MDR1, and very few the expression of MRP3. NODO cell line did not show any basal expression. Paclitaxel induced MDR1 and carboplatin induced MRP3. Cell lines derived from other tumours not show any basal expression. Paclitaxel induced MDR1 in all cell lines. Carboplatin did not induce MDR1 as previously, nor MRP3 in GAS cell line. Conclusions:The combination of both drugs at plasma concentrations was not able to activate a new resistance mechanism in the studied cell lines, but surprisingly it was able to improve the resistance mechanism induced by each one of the drugs individually. This fact resulted in an increase of MDR1 expression with paclitaxel and MRP3 expression with carboplatin.
DLEU2, Located within the CLL 13q14 Deletion Locus, Encodes an Antisense RNA for the Putative Bicistronic RFP2/LEU5 Gene in Humans and Mouse.
Authors: Martin M. Corcoran, Marianne Hammarsund, Chaoyong Zhu, Mikael Lerner, Bagrat Kapanadze, Catharina Larsson, Lars Forsberg, Rachel E. Ibbotson, Stefan Einhorn, David G. Oscier, Dan Grander, Olle Sangfelt
Journal: Blood (2004)
P133 Safety and effectiveness of influenza vaccines in people with asthma: a systematic review and meta-analysis
Authors: E Vasileiou, A Sheikh, C Butler, K El Ferkh, CR Simpson
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Influenza vaccination is offered annually in the UK to high-risk individuals such as those with asthma as a preventive measure against influenza infection and influenza-related complications. However, the effectiveness and safety of influenza vaccination in people with asthma is not well established.<sup>1</sup> <h3>Methods</h3> We conducted a systematic review and meta-analysis assessing the overall quality of evidence using the GRADE methodology. Published literature was searched through 13 electronic databases from Jan 1970 to Jan 2016 for clinical trials and epidemiological studies. Unpublished or ongoing literature was searched through references and citations of key publications, and by contacting influenza vaccine manufacturers. The screening for eligible studies, data extraction and quality appraisal was conducted by two reviewers independently. Separate meta-analyses were undertaken for observational and experimental evidence using random-effects models. <h3>Results</h3> We identified 35 eligible studies, and four contributed to the meta-analyses. Risk of bias was high for one randomised controlled trial (RCT), unclear for 11 RCTs, and low for eight RCTs. The quality of five non-RCTs, four cohorts, and two case-control studies was strong. Moderate quality was found for one non-RCT, and three cohort studies. In people with asthma, pooled vaccine effectiveness (VE) was 45% (OR: 0.55; 95% CI: 0.44 to 0.69; I2 = 0%) for laboratory confirmed influenza. Pooled effectiveness of live vaccines was 81% (RR: 0.19; 95% CI: 0.06 to 0.67; I2 = 0%) for influenza infection (confirmed by cell culture or rise in antibody titre) and 72% (RR: 0.28; 95%: 0.10 to 0.80; I2 = 0%) for influenza-like illness. VE was also observed against asthma attacks. No increased risk of vaccine-induced asthma symptoms and attacks was identified. The quality of the body of evidence was considered very low for all outcomes. <h3>Conclusions</h3> Evidence on VE in people with asthma against influenza, asthma exacerbations, and other clinical outcomes is limited and of very low quality. Thus, better quality evidence is required, especially in adults with asthma. Vaccination with inactivated or live vaccines was found to be safe and well tolerated in patients with asthma. <h3>Reference</h3> Cates CJ, Rowe BH. Vaccines for preventing influenza in people with asthma. <i>Cochrane Database Sys Rev</i> 2013;<b>2</b>:Cd000364.
Abstract 265: Robust anti-tumor effects of combined anti-CD4 depleting antibody and anti-PD-1/PD-L1 immune checkpoint antibody treatment in mice
Authors: Satoru Ito, Kouji Matsushima, Satoshi Ueha, Shoji Yokochi, Yoshiro Ishiwata, Kosuke Hachiga, Haru Ogiwara, Krishant Chand, Takumi Nakajima
Journal: Cancer Research (2015)

Abstract Depletion of CD4+ cells in tumor-bearing mice has strong anti-tumor effects. However, the mechanisms underlying these effects and the therapeutic benefits of CD4+ cell depletion relative to other immunotherapies have not been fully evaluated. Here, we investigated the anti-tumor effects of an anti-CD4 depleting monoclonal antibody (mAb) as a monotherapy or in combination with immune checkpoint mAbs. In B16F10, Colon 26 or LLC subcutaneous tumor models, administration of the anti-CD4 mAb alone had strong anti-tumor effects that were superior to those elicited by CD25+ Treg depletion or other immune checkpoint mAbs, and which were completely reversed by CD8+ cell depletion. CD4+ cell depletion led to the proliferation of tumor-specific CD8+ T cells in the draining lymph node and increased infiltration of PD-1+CD8+ T cells into the tumor, with a shift towards type I immunity within the tumor. Combination treatment with the anti-CD4 mAb and immune checkpoint mAbs, particularly anti-PD-1 or anti-PD-L1 mAbs, synergistically suppressed tumor growth and greatly prolonged survival. To our knowledge, this work represents the first report of robust synergy between anti-CD4 and anti-PD-1 or anti-PD-L1 mAb therapies. Citation Format: Satoru Ito, Kouji Matsushima, Satoshi Ueha, Shoji Yokochi, Yoshiro Ishiwata, Kosuke Hachiga, Haru Ogiwara, Krishant Chand, Takumi Nakajima. Robust anti-tumor effects of combined anti-CD4 depleting antibody and anti-PD-1/PD-L1 immune checkpoint antibody treatment in mice. [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 265. doi:10.1158/1538-7445.AM2015-265
Relapsed Follicular Lymphoma Treatment - with or without Hematopoietic Stem Cell Transplant?
Authors: Dulcineia Pereira, Carolina Teixeira, Sofia Ramalheira, Patricia Rocha, Claudia Moreira, Alina Rosinha, Duarte Domingues, Natasha Amaral, Edgar Mesquita, Ana Brito, Luisa Viterbo, Isabel Oliveira, Nelson Domingues, Ilidia Moreira, Ana Espirito-Santo, Sergio Chacim, Luis Leite, Isabel Cristina Ferreira, Rui Henrique, Angelo Martins, Jose Mario Mariz
Journal: Blood (2014)
Induction Chemotherapy plus Radiation Compared with Surgery plus Radiation in Patients with Advanced Laryngeal Cancer
Authors: Gregory T Wolf, Susan Gross Fisher, Waun Ki Hong, Robert Hillman, Monica Spaulding, George E Laramore, James W Endicott, Kenneth McClatchey, William G Henderson
Journal: New England Journal of Medicine (1991)

We performed a prospective, randomized study in patients with previously untreated advanced (Stage III or IV) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation.
Clinical Utility of Comprehensive Profiling of Genomic Alterations in Hematologic Malignancies
Authors: Jie He, Jose A. Bufill, Michelle K. Nahas, Kai Wang, Lauren E Young, Kristina M. Knapp, Kristina W. Brennan, Amy L Donahue, Geneva Young, Jeffrey S Ross, Deborah Morosini, Marcel R. M. van den Brink, Omar Abdel-Wahab, Raajit K. Rampal, Andrew M. Intlekofer, Ahmet Dogan, Scott Armstrong, Roman Yelensky, Geoff Otto, Doron Lipson, Philip J. Stephens, Vincent A. Miller, Ross L. Levine
Journal: Blood (2014)
499. Intravenous Delivery of a Novel Micro-Dystrophin Vector Prevented Muscle Deterioration in Young Adult Canine Duchenne Muscular Dystrophy Dogs
Authors: Chady Hakim, Xiufang Pan, Kasun Kodippili, Thais Blessa, Hsiao T. Yang, Gary Yao, Stacey Leach, Craig Emter, Yongping Yue, Keqing Zhang, Sean X. Duan, Nalinda Wasala, Gregory Jenkins, Charles R. Legg, Joel S. Schneider, Jeffrey S. Chamberlain, Dongsheng Duan
Journal: Molecular Therapy (2016)

Duchenne muscular dystrophy (DMD) is a progressive, muscle wasting disorder that affects all muscles in the body. An effective gene therapy for DMD will require efficient whole body muscle transduction. It was recently demonstrated that a single intravenous injection of adeno-associated virus (AAV) can lead to safe, bodywide muscle gene transfer in adolescent dogs affected by the canine model of DMD (cDMD) (Yue et al. 2015 Hum Mol Genet). Here we evaluated systemic gene therapy in three 3.5-m-old cDMD dogs using a novel canine codon-optimized micro-dystrophin vector. Transcriptional regulation is controlled by the muscle-specific CK8 promoter and a synthetic polyadenylation signal. All experimental subjects received transient immune suppression. One dog was administrated with 5×1013 viral genome (vg) particles/kg of the vector. Two dogs received 1×1014 vg particles/kg of the vector. All dogs tolerated injection well. Blood biochemistry (weekly in the first four weeks and biweekly thereafter) was unremarkable. Growth curve was nominally disturbed during the immunosuppression regimen, but recovered thereafter. Biopsy at 1,3 and 6 months after injection revealed widespread micro-dystrophin expression in 50-80% myofibers. The dystrophin-associated glycoprotein complex, including neuronal nitric oxide synthase (nNOS), was restored. While limited in sample size, muscle damage usually seen in young adult untreated dogs (inflammation, fibrosis, calcification) were rarely observed. CD4+, CD8+, and regulatory T cells were minimally detected. Night activity monitoring showed a trend of improvement. Limb muscle force (both forelimb and hind limb) was significantly enhanced compared to that of pre-injection. Our data suggest that systemic AAV micro-dystrophin therapy may translate to large mammals afflicted by DMD (Supported by Solid GT, NIH, DOD, Jesse's Journey).
Abstract 5273: Role of methylation of Wnt target genes in tumorigenesis and effect of re-expression with demethylating agent decitabine in colon cancer
Authors: Janneke Linnekamp, Raju Kandimalla, Louis Vermeulen, Hanneke van Laarhoven, Jan Paul Medema
Journal: Cancer Research (2015)

Abstract Colon cancer is the fourth leading cause of cancer-related death worldwide. Extensive studies of the Wnt signal cascade have determined its role in colon cancer development and progress. Several targets of the Wnt-cascade like APCDD1, ASCL2, AXIN2 or DKK1 are thought to reduce Wnt activity by negative feedback. As a result, expression of these genes prevents pathway activation and silencing of these targets can cause proliferation of the tumor. Recently, we have shown that silencing of Wnt target genes by DNA-methylation predicts poor prognosis in colon cancer patients. Moreover, demethylation of those genes results in reexpression and is associated with reduced tumor growth in mice. Hence, treatment with demethylating agents can be beneficial for a subgroup of colon cancer patients with high methylation of Wnt target genes. The aim of this study is to clarify whether Wnt target gene methylation is an important driver in development of colon cancer and can be an effective target in colon cancer. To determine the role of Wnt target genes in colon cancer more extensively, we study the effect of selective expression of these genes via an inducible vector system in established colorectal cell lines and in patient derived cultures that display CpG island methylation on these genes. In that way, we can monitor the effect of induced overexpression on tumor growth, tumor invasion and sensitivity towards chemotherapeutic agents. As a control, baseline expression in the same cell population, but in an uninduced state will be used. Furthermore, we are also studying the effect of the demethylating agent decitabine on Wnt target gene methylation in a clinical trial in stage II/III colon cancer patients. Patients are pre-operatively treated with decitabine. Tumor material prior to decitabine treatment obtained during endoscopy is compared to resection material after treatment. Differences in methylation and expression of Wnt target genes are determined by respectively pyrosequencing and q-PCR. We hypothesize that reexpression of Wnt target genes via an inducible vector results in lower Wnt pathway activity through negative feedback. As a result, tumor growth and invasion will be reduced and might be more sensitive towards chemotherapeutics. To translate this into the clinic, demethylation of Wnt target genes by decitabine will hopefully give a similar effect in patients. Citation Format: Janneke Linnekamp, Raju Kandimalla, Louis Vermeulen, Hanneke van Laarhoven, Jan Paul Medema. Role of methylation of Wnt target genes in tumorigenesis and effect of re-expression with demethylating agent decitabine in colon cancer. [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 5273. doi:10.1158/1538-7445.AM2015-5273
A Comparison of the Effectiveness of First-Line Chemoimmunotherapy Regimens for Follicular Lymphoma (FL) Used in the United States
Authors: Loretta Nastoupil, Rajni Sinha, Michelle Byrtek, Michael Taylor, James R Cerhan, Jonathan Friedberg, Brian K Link, Ryan M Ziemiecki, Jamie H. Hirata, Christopher R Flowers
Journal: Blood (2011)