tbuckley/cabot-search huggingface dataset:
Abstract 3071: MicroRNA-486 (miR-486) promotes invasion by targeting RECK in nasopharyngeal carcinoma cells
Authors: Chin-Tarng Lin, Cheng-Der Wu
Journal: Cancer Research (2015)

Abstract Nasopharyngeal carcinoma (NPC) is a common cancer in Taiwanese and people living in the southeastern region of China. In order to investigate NPC pathogenesis, our laboratory has previously established NPC-TW01 cell line, which was derived from a Taiwanese NPC patient. We also established a NPC-TW01N1 cell line, which was derived from the NPC xenograft in SCID mouse. Both NPC-TW01 and NPC-TW01N1 cell lines have an identical DNA profile (STR). NPC-TW01N1 cell line has higher malignant potency than NPC-TW01 line. For example, the proliferation and invasion capabilities of NPC-TW01N1 line were higher than that of NPC-TW01 line. When we used microRNA microarray to compare the endogenous microRNA expression profiles between NPC-TW01 and NPC-TW01N1 lines, the miR-486, miR-200a and other miRNAs showed higher expression in NPC-TW01N1 cell. Transfection of exogenous miR-486 or anti-miR-486 into NPC-TW01 cells or NPC-TW01N1 cells revealed that miR-486 involves in the regulation of NPC cell progression and invasion. To determine whether miR-486 targeted gene involves in progression and invasion, we analyzed microRNA targeted gene database, Ingenuity pathway databases, and cDNA expression microarrays from miR-486 transfected cells. We found that the RECK gene is one of miR-486 candidate targeted genes that involves in NPC cell progression and invasion. We used pmirGLO luciferase reporter vector assays to demonstrate that miR-486 directly targets RECK 3′ UTR. When we transfected miR-486 or RECK siRNA into NPC cells, we found that they can accelerate tumor progression and invasion. It is concluded that miR-486 and RECK genes maybe potential targets for NPC therapy. Citation Format: Chin-Tarng Lin, Cheng-Der Wu. MicroRNA-486 (miR-486) promotes invasion by targeting RECK in nasopharyngeal carcinoma cells. [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 3071. doi:10.1158/1538-7445.AM2015-3071
OA11.03 A Randomized, Multi-Center, Double-Blind Phase II Study of Fruquintinib in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Shun Lu, Jianhua Chang, Xiaoqing Liu, Jianhua Shi, You Lu, Wei Li, Jinji Yang, Jianying Zhou, Jie Wang, Lei Yang, Zhiwei Chen, Xiangdong Zhou, Zhe Liu, Ye Hua, Weiguo Su
Journal: Journal of Thoracic Oncology (2017)
Aven and Survivin Expression in Egyptian Acute Leukemia and Their Relation to Apoptosis.
Authors: Magda Assem, Thoraya Mohamed Abdel Hamid, Gihan Abedel Basset, Amany Hilal, Mahmoud Kamel, Iman Khalil, Nahla Alsharkaway, Aymen Metwally
Journal: Blood (2009)
Abstract 3925: Production and biochemical characterization of farnesylated and methylated KRAS4b using engineered baculovirus
Authors: Andrew G. Stephen, William K. Gillette, Carissa Grose, Dominic Esposito
Journal: Cancer Research (2015)

Abstract KRAS4b, which is frequently mutated in pancreatic, colon and lung cancers, is processed in several steps including farnesylation by farnesyl-transferase (FNT); proteolytic cleavage at the C-terminus by ras converting enzyme 1 (RCE1) and carboxymethylation by isoprenylcysteine carboxymethyl transferase (ICMT). Plasma membrane localization of KRAS4b requires this processing as does KRAS4b-dependent RAF kinase activation. Previous attempts to produce modified KRAS have relied on protein engineering approaches or in vitro farnesylation of bacterially expressed KRAS protein. The proteins produced by these methods do not completely replicate the final KRAS protein found in mammalian cells and the yield and quality of the protein are typically low. Using an engineered baculovirus containing the two subunits of farnesyl-transferase (FNTA/B) and a maltose-binding protein (MBP)-KRAS4b fusion we are able to produce highly purified, farnesylated, and methylated KRAS4b (FMe-KRAS4b) in insect cells at yields of approximately 10mg/L. This protein has been extensively characterized by electrospray-ionization mass spectrometry, analytical ultracentrifugation, and circular dichroism. In addition, we demonstrate that FMe-KRAS4b is fully active in hydrolyzing GTP, binding to RAF-RBD, and interacting with lipid nanodiscs. Citation Format: Andrew G. Stephen, William K. Gillette, Carissa Grose, Dominic Esposito. Production and biochemical characterization of farnesylated and methylated KRAS4b using engineered baculovirus. [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 3925. doi:10.1158/1538-7445.AM2015-3925
Recommendations for the Treatment of Patients With Parkinson Disease During Ramadan
Authors: Philippe Damier, Jasem Al-Hashel
Journal: JAMA Neurology (2016)

Every year, Ramadan fasting is practiced by many Muslim individuals. In cases of chronic disease, religious texts allow fasting to be broken. However, many believers still want to fast even at the risk of damaging their health. To our knowledge, there are no published recommendations on the medical management of Parkinson disease (PD) during Ramadan. Effective treatments exist in PD and usually require several daily drug intakes. Apart from worsening symptoms, interrupting PD treatment might lead to a severe withdrawal syndrome.Although no specific studies on this topic have led to formal recommendations, we suggest some options for adapting the treatment for patients who fast during Ramadan. The general principle is based on switching the patient's treatment to an equivalent dosage of a dopamine agonist that can be administered once daily or by transdermal patch. However, such an option is only feasible for patients who require a moderate amount of PD treatment and can tolerate dopamine agonist therapy.Because many patients with PD require regular multiple daily administration of dopamine-replacement medication, the management of Ramadan fasting is not easy. Switching the patient's treatment to an equivalent dosage of a dopamine agonist that can be administered once daily or by transdermal patch seems to be a reasonable option to consider for patients treated with a low-to-moderate amount of PD medication.
524. Immune-Monitoring of Mature Human T Cell Reconstitution in Humanized NRG Mice After Cord Blood Stem Cell Transplantation and Engineered Dendritic Cell Prime/Boost: TCR Polyclonality and No GvHD
Authors: Renata Stripecke, Andreas Schneider, Valery Volk, Deves-Roth Candida, Sundarasetty Bala Sai, Eliana Ruggiero, Manfred Schmidt, Carlos A. Guzman, Constanca Figueiredo, Arnold Ganser
Journal: Molecular Therapy (2015)

Cord blood (CB) is a major and convenient "off the shelf" source of stem cells for hematopoietic stem cell transplantation (HSCT) when a matched donor is not available. Although relatively lower incidence of graft versus host disease is observed after CB-HSCT than PB-HSCT, delayed T cell immune reconstitution, relapse and viral infections harmfully impact survival after CB-HSCT. We validated genetically reprogrammed CB-derived monocytes capable to differentiate into dendritic cells in vivo as means to improve human immune reconstitution in lymphopenic hosts and protect them against cytomegalovirus (CMV). Monocytes were isolated from the CB CD34− fraction, transduced with an integrase-defective lentiviral vector (co-expressing GM-CSF, IFN-α and the CMV antigen pp65) and administered after CB-HSCT or cryopreserved. Prime/boost administrations of the engineered "SmyleDCpp65" cell vaccine into NOD.Rag1–/–.IL2rγ–/– mice 6-11 weeks after CB-HSCT resulted into higher levels of human T cell development in the thymus and evidence of maturation of memory and effector T cells in peripheral blood and secondary lymphatic tissues. This model allows mechanistic characterization of human CTL, Th and Treg cell reconstitution (by multicolor flow cytometry), homing (bone marrow, thymus, spleen, lymph nodes, liver; by flow cytometry), immune functions (pp65-specific responses by ELISPOT and cytotoxic assays), T cell receptor polyclonality analyses (by deep sequencing), inflammatory responses (array analyses of plasma cytokines and immune globulins). Despite the de novo activation of human T cells, GVHD was not observed. This model demonstrates the prof-of-concept of an adjuvant cell vaccine to be used in conjunction with CB-HSCT in the clinics and offers a practical experimental system to study adaptive human T cell immune reconstitution and antigen-specific responses in vivo. We are currently evaluating further approaches to maximize lentiviral transduction of CB monocytes and co-stimulation of human antibody responses against the cytomegalovirus gB antigen in the CB-HSCT model.
Abstract 4280: Utilizing a selective agonist of the intermediate-affinity IL-2 receptor with an improved pharmacokinetic profile leads to an enhanced immunostimulatory response With reduced toxicity in mice
Authors: Heather C. Losey, Jared E. Lopes, Reginald L. Dean, Heather Flick, Madison Gomes, Michael R. Huff, Rosemarie A. Moroso, Lei Sun, Chunhua Wang, Julie F. Waters, Juan C. Alvarez
Journal: Cancer Research (2015)

Abstract RDB 1450 is an engineered fusion protein which selectively activates the intermediate-affinity IL-2 receptor present on NK cells and memory CD8 T cells. In rodents, RDB 1450 has a half-life of 6-8 hours, compared to a half-life of minutes for recombinant human IL-2 (rhIL-2). Repeat daily dosing (QD) of RDB 1450 in mice results in marked expansion of NK cells and CD8+CD44high T cells, with minimal expansion of CD4+ regulatory T cells (Tregs). Higher QD doses elicit more pronounced effector cell expansion with modest pulmonary edema. TID delivery of the same total daily dose of RDB 1450 enhances the immunological responses in the absence of pulmonary edema. These results suggest that prolonged delivery of reduced concentrations of RDB 1450 drive the desired immune responses with improved tolerability. In contrast, high circulating concentrations of rhIL-2 are required to stimulate effector cells due to its preferential activation of Tregs at lower concentrations. The selectivity profile and favorable pharmacokinetics of RDB 1450 highlight its potential as a novel, differentiated immunotherapeutic agent for the treatment of cancer. Citation Format: Heather C. Losey, Jared E. Lopes, Reginald L. Dean, Heather Flick, Madison Gomes, Michael R. Huff, Rosemarie A. Moroso, Lei Sun, Chunhua Wang, Julie F. Waters, Juan C. Alvarez. Utilizing a selective agonist of the intermediate-affinity IL-2 receptor with an improved pharmacokinetic profile leads to an enhanced immunostimulatory response With reduced toxicity 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 4280. doi:10.1158/1538-7445.AM2015-4280
HER2 FISH ratio cut-points and pathologic complete response (pCR), residual tumor (RT), HER2 status, and survival prediction in HER2-positive breast cancer (BC)
Authors: R. S. Mehta, D. Jackson, T. Schubbert, D. Hsiang
Journal: Journal of Clinical Oncology (2009)

e22033 Background: We demonstrated that pCR is correlated with increasing HER2-FISH ratio, while disease-free survival (DFS) with pCR and ER-positivity in HER2-positive breast cancer treated with trastuzumab (SABCS 2008). It is known that quantitative HER2-FISH ratio correlates with ER levels and HER2-positivity imparts a higher grade in ER-positive BC. Collectively, we hypothesized that combined ER (≥10) and a HER2 ratio cut-point may subdivide HER2-positive BC into pCR predictive subtypes.Methods: Of the 80 HER2-positive (IHC3+/FISH+) BC, quantitative HER2 FISH ratio (widely spread over 1–18.3) and ER correlation was noted (r=0.34, p=0.002). Moreover, HER2 ratio (&gt;4) correlated with higher Ki-67 (r= 0.5, p=0.01) and grade (p trend=0.05) in ER-positive subtype, inferring a biologic cut-point. Results: Of patients with stage I-IV BC treated neoadjuvantly (92% trastuzumab-based), pCR was 0% (0/13) in ER-positive-low-HER2 compared to 77% (10/13, p=0.0001), 75% (24/32, p&lt;0.0001) and 37.5% (3/8, p=0.043) in ER-positive-high-HER2, ER-negative-high-HER2 and ER-negative-low-HER2, respectively. DFS was 100, 90, 80% and 60% (logrank-trend p&lt;0.05) in these 4 subtypes (excluding stage IV), respectively, at a median follow-up of 38 months (range 6–72). In ER-negative subtypes, DFS was 97% and 29% (logrank p=0.0001) in patients with or without pCR; of the six with RT, 0% DFS was noted in four with HER2-negative/HER2-reduced (HER2-R) RT, compared to 100% in the two with unchanged HER2 (p=&lt;0.05, logrank test). In ER-positive subtypes, DFS is 95% overall, and 100% in patients with RT; 7 of 10 tested RT were HER2- R. Conclusions: pCR is crucial and high in ER-negative-high-HER2 and is crucial (but low) in ER-negative-low-HER2-positive BC for improved outcome. Improved DFS is associated with high pCR in ER-positive-high-HER2 BC, but is independent of the low pCR in ER-positive-low-HER2-subtype. Thus, combined HER2 and ER offer improved prediction. In hypothesis generating analysis, HER2-R may underlie relapse in ER-negative subtypes (HER2-basal-transitional-residual), while it may be beneficial in ER-positive subtypes (luminal-B- A-transitional) by reducing HER2-pathway mediated endocrine resistance. [Table: see text]
Glyoxalase-I Inhibition Eliminates Hypoxia-Adapted CML Cells Resistant to Imatinib, Dasatinib, and INNO-406
Authors: Miki Takeuchi, Shinya Kimura, Junya Kuroda, Takashi Ushiki, Makoto Kawatani, Hiroyuki Osada, Kazuo Umezawa, Eiko Yasui, Masaya Imoto, Takashi Tsuruo, Keiko Hodohara, Tatsutoshi Nakahata, Yoshihide Fujiyama, Taira Maekawa
Journal: Blood (2008)
Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML
Authors: Bob Löwenberg, Thomas Pabst, Johan Maertens, Yvette van Norden, Bart J. Biemond, Harry C. Schouten, Olivier Spertini, Edo Vellenga, Carlos Graux, Violaine Havelange, Georgine E. de Greef, Okke de Weerdt, Marie-Cecile J. C. Legdeur, Juergen Kuball, Marinus van Marwijk Kooy, Bjorn T. Gjertsen, Mojca Jongen-Lavrencic, Arjan A. van de Loosdrecht, Daniëlle van Lammeren-Venema, Beata Hodossy, Dimitri A. Breems, Yves Chalandon, Jakob Passweg, Peter J. M. Valk, Markus G. Manz, Gert J. Ossenkoppele
Journal: Blood (2017)
Abstract 4199: Developing therapies for rare tumors: Using mouse models of malignant peripheral nerve sheath tumors to complement rare human samples in drug screens
Authors: Karlyne M. Reilly, Robert G. Tuskan, Brigitte C. Widemann
Journal: Cancer Research (2015)

Abstract Rare cancers are defined by the US Orphan Drug Act as affecting &amp;lt;200,000 patients in the US. For patients with these cancers, there may be an urgent need for new therapies; however, these rare cancers present challenges to drug development. Because of the small number of patients, the cancers are not well characterized, the molecular mechanisms may not be well-understood, and there may not be adequate model systems available for research and drug development. The Rare Tumors Initiative in the Intramural Research Program at the National Cancer Institute is focusing on overcoming hurdles in rare tumor research by developing new approaches to treat malignant peripheral nerve sheath tumors (MPNST). MPNSTs occur in younger adults with an incidence of 1 in 100,000, with a higher incidence in patients with Neurofibromatosis type 1. Due to a limited number of high quality human MPNST tumor lines, drug testing has been challenging both in vitro and in vivo. A genetically engineered mouse model carrying mutations in Nf1 and Trp53 develops MPNST spontaneously starting around 3 months of age. We have generated tumor lines from over 30 independent mouse MPNSTs, from different sexes and genetic backgrounds that we are using to test drugs in combination with available human MPNST lines. We find good concordance between the mouse and human MPNST lines in response to drugs. Furthermore, although the MPNST lines show good dose response and high maximum response to many targeted compounds, the concentrations of drug required to achieve inhibition is often high, suggesting that one of the difficulties in developing MPNST therapy is the inherent resistance of MPNST cells to drug inhibition. We will present results of ongoing drug screens in panels of mouse and human MPNST cell lines, using drugs that are in different phases of clinical trials or approved for other diseases. Citation Format: Karlyne M. Reilly, Robert G. Tuskan, Brigitte C. Widemann. Developing therapies for rare tumors: Using mouse models of malignant peripheral nerve sheath tumors to complement rare human samples in drug screens. [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 4199. doi:10.1158/1538-7445.AM2015-4199
Abstract LB-024: Inhibition of bone morphogenetic protein (BMP) type I receptors in lung cancer cells activates the TGFβ signaling cascades which increases Id1 expression by TAK1
Authors: John E. Langenfeld, Elaine Langenfeld, Monica Castle
Journal: Cancer Research (2015)

Abstract Bone morphogenetic protein (BMP) signaling increases Id1 expression while the transforming growth factor (TGF) signaling typically decreases Id1 expression. BMP antagonists decrease growth of cancer through the inhibition of Id1. Both the BMP and TGF signaling pathways activate TGF activated kinase1 (TAK1). TAK1 has been shown to phosphorylate and activate the BMP transcription factor Smad1/5. The purpose of this study was to understand the cross regulation between the BMP and TGFβ signaling pathways in lung cancer cell lines that occurs following the inhibition of BMP signaling. Antagonists targeting the BMP (DMH2, DMH1), TGFβ (SB-505124), and TAK1 ((5Z)-7-Oxozeaenol) signaling cascades were used to examine the cross regulation between these pathways. Here, we show using siRNA and BMP antagonists targeting the type I receptors that upon inhibition of BMP signaling in lung cancer cells, the TGFβ signaling cascade is activated. SB-505124 alone increases Id1 expression in H1299 cells. However, when BMP signaling was inhibited, SB-505124 decreases Id1 expression, which is associated with a decrease expression in pTAK1. When BMP signaling is inhibited, the TGFβ constitutively active alk5 receptor activates TAK1 and increases Id1 expression, which is attenuated with (5Z)-7-Oxozeaenol. A BMP antagonist together with a TGFβ antagonist further enhanced growth suppression. This study reveals that TGFβ signaling can increase the expression of Id1 when BMP signaling is inhibited in lung cancer cells, which is mediated by TAK1. The data suggests that the inhibition of both the BMP and TGF signaling pathways enhances growth suppression of lung cancer cells that involves the downregulation of Id1. Citation Format: John E. Langenfeld, Elaine Langenfeld, Monica Castle. Inhibition of bone morphogenetic protein (BMP) type I receptors in lung cancer cells activates the TGFβ signaling cascades which increases Id1 expression by TAK1. [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 LB-024. doi:10.1158/1538-7445.AM2015-LB-024
Three cases of the HER2-positive advanced gastric cancer with elevated serum alpha-fetoprotein (AFP)
Authors: Hiroki Oka, Masanori Taniguchi, Hideki Nomura, Mikiya Ishihara, Hiroyasu Oda, Yoshiki Yamashita, Kentaro Yamamura, Satoshi Tamaru, Toshiro Mizuno, Naoyuki Katayama
Journal: Annals of Oncology (2015)
Phase II Study with R-FND Followed by 90-Y Ibritumomab Tiuxetan Radioimmunotherapy and Rituximab Maintenance for Untreated High-Risk Follicular Lymphoma
Authors: Nathan H. Fowler, Sattva S. Neelapu, Michelle A. Fanale, Maria A. Rodriguez, Barbara Pro, F.B. Hagemeister, Anas Younes, Jatin J Shah, Larry W Kwak, Diana Rodriguez, Peter McLaughlin
Journal: Blood (2011)
Low Dose Rituximab in Adult Patients with Idiopathic Thrombocytopenic Purpura.
Authors: Francesco Zaja, Marta L. Battista, Maria T. Pirrota, Salvatore Palmieri, Michela Montagna, Nicola Vianelli, Margherita Cavallin, Monica Bocchia, Marzia Defina, Micaela Ippoliti, Felicetto Ferrara, Francesca Patriarca, Maria A. Avanzini, Mario Regazzi, Miriam Isola, Franca Soldano, Michele Baccarani, Renato Fanin
Journal: Blood (2007)
Impact of Minimal Residual Disease at Unrelated Cord Blood Transplantation In Children with Acute Lymphoblastic Leukemia In Remission: a Study on Behalf of Eurocord-EBMT and EBMT-PDWP
Authors: Annalisa Ruggeri, Gerard Michel, Jean-Hugues Dalle, Maurizio Caniglia, Antonio Campos, Cristina Diaz de Heredia, Mohamad Mohty, Jose Maria Perez Hurtado, Marc Bierings, Henrique Bittencourt, Marcos Mauad, Duncan Purtill, Nabil Kabbara, Christina Peters, Eliane Gluckman, Myriam Labopin, Franco Locatelli, Vanderson Rocha
Journal: Blood (2010)
Effect of FLT3 and RAS Mutations on Protein Expression Patterns In Cases of Acute Myelogenous Leukemia (AML) with NPM1 Mutations
Authors: Steven M. Kornblau, Yujia Huo, Mark Brandt, Nianxiang Zhang, Yi Hua Qiu, Farhad Ravandi, Tapan Kadia, Pierce Sherry, Kevin R Coombes, Hagop M. Kantarjian
Journal: Blood (2010)
Abstract 359: STAT3-axis activated snail expression and promoted drug resistance in pediatric brain tumor
Authors: Tsai Chi-Chang
Journal: Cancer Research (2015)

Abstract Atypical teratoid/rhabdoid tumor (ATRT) is a malignant pediatric brain tumor with great recurrence after complete surgery and chemotherapy. Here, we demonstrate that cisplatin treatment select not only for resistance but also for a more oncogenic phenotype characterized by high self-renewal and invasive capabilities. These phenomena are likely due to STAT3 upregulation which occurred simultaneously with higher expression of Snail, an activator of epithelial-mesenchymal transition (EMT), in ATRT-CisR cells. STAT3 knockdown effectively suppressed Snail expression and blocked motility and invasion in ATRT-CisR cells, while overexpressing Snail reversed these effects. Chromatin immunoprecipitation assay indicated that STAT3 directly bound to Snail promoter. Moreover, STAT3 knockdown effectively suppressed cancer stem-like properties, synergistically enhanced the chemotherapeutic effect, and significantly improved survival rate in ATRT-CisR-transplanted immunocompromised mice. Finally, immunohistochemistrical analysis showed that STAT3 and Snail were coexpressed at high levels in recurrent ATRT tissues. Thus, the STAT3/Snail pathway plays an important role in oncogenic resistance, rendering cells not only drug-resistant but also increasingly invasion and recurrence. Therefore, the STAT3/Snail could be a target for ATRT treatment. Note: This abstract was not presented at the meeting. Citation Format: Tsai Chi-Chang. STAT3-axis activated snail expression and promoted drug resistance in pediatric brain tumor. [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 359. doi:10.1158/1538-7445.AM2015-359