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Patients derived xenograft mouse model cancer (PDX)

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https://www.readbyqxmd.com/read/29338446/the-latest-animal-models-of-ovarian-cancer-for-novel-drug-discovery
#1
Elizabeth Magnotti, Wayne A Marasco
Epithelial ovarian cancer is a heterogeneous disease classified into five subtypes, each with a different molecular profile. Most cases of ovarian cancer are diagnosed after metastasis of the primary tumor and are resistant to traditional platinum-based chemotherapeutics. Mouse models of ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the tumor's response to therapeutics. Areas covered: The authors provide a review of mouse models currently employed to understand ovarian cancer...
January 17, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29301832/pharmacological-inhibition-of-nos-activates-ask1-jnk-pathway-augmenting-docetaxel-mediated-apoptosis-in-triple-negative-breast-cancer
#2
Daniel Dávila-González, Dong Soon Choi, Roberto R Rosato, Sergio Granados-Principal, John G Kuhn, Wen-Feng Li, Wei Qian, Wen Chen, Anthony J Kozielski, Helen H Wong, Bhuvanesh Dave, Jenny C Chang
PURPOSE: Chemoresistance in triple negative breast cancer (TNBC) is associated with the activation of a survival mechanism orchestrated by the endoplasmic reticulum (EnR) stress response and by inducible nitric oxide synthase (iNOS). Our aim was to determine the effects of pharmacological NOS-inhibition on TNBC. EXPERIMENTAL DESIGN: TNBC cell lines, SUM-159PT, MDA-MB-436, and MDA-MB-468, were treated with docetaxel and NOS-inibitor (L-NMMA) for 24, 48 and 72 hours...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29290814/dual-targeting-of-acute-leukemia-and-supporting-niche-by-cxcr4-directed-theranostics
#3
Stefan Habringer, Constantin Lapa, Peter Herhaus, Margret Schottelius, Rouzanna Istvanffy, Katja Steiger, Julia Slotta-Huspenina, Andreas Schirbel, Heribert Hänscheid, Stefan Kircher, Andreas K Buck, Katharina Götze, Binje Vick, Irmela Jeremias, Markus Schwaiger, Christian Peschel, Robert Oostendorp, Hans-Jürgen Wester, Götz-Ulrich Grigoleit, Ulrich Keller
C-X-C chemokine receptor 4 (CXCR4) is a transmembrane receptor with pivotal roles in cell homing and hematopoiesis. CXCR4 is also involved in survival, proliferation and dissemination of cancer, including acute lymphoblastic and myeloid leukemia (ALL, AML). Relapsed/refractory ALL and AML are frequently resistant to conventional therapy and novel highly active strategies are urgently needed to overcome resistance. Methods: We used patient-derived (PDX) and cell line-based xenograft mouse models of ALL and AML to evaluate the efficacy and toxicity of a CXCR4-targeted endoradiotherapy (ERT) theranostic approach...
2018: Theranostics
https://www.readbyqxmd.com/read/29284644/cox-2-seh-dual-inhibitor-ptupb-potentiates-the-anti-tumor-efficacy-of-cisplatin
#4
Fuli Wang, Hongyong Zhang, Ai-Hong Ma, Weimin Yu, Maike Zimmermann, Jun Yang, Sung Hee Hwang, Daniel Zhu, Tzu-Yin Lin, Michael Malfatti, Kenneth W Turteltaub, Paul T Henderson, Susan Airhart, Bruce D Hammock, Jianlin Yuan, Ralph W de Vere White, Chong-Xian Pan
Cisplatin-based therapy is highly toxic, but moderately effective in most cancers. Concurrent inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) results in anti-tumor activity, and has organ protective effects. The goal of this study was to determine the anti-tumor activity of PTUPB, an orally bioavailable COX-2/sEH dual inhibitor, in combination with cisplatin and gemcitabine (GC) therapy. NSG mice bearing bladder cancer patient-derived xenografts were treated with vehicle, PTUPB, cisplatin, GC or combinations thereof...
December 28, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29277771/effects-of-sirna-silencing-of-tug1-and-lcal6-long-non-coding-rnas-on-patient-derived-xenograft-of-non-small-cell-lung-cancer
#5
Tian Fang, Hairong Huang, Xiaoyou Li, Jing Liao, Zhijian Yang, Robert M Hoffman, X I Cheng, Lei Liang, Wenjuan Hu, Shifeng Yun
BACKGROUND/AIM: The aim of the present study was to establish a patient-derived xenograft (PDX) mouse model of non-small cell lung cancer (NSCLC) and investigate the anti-tumor efficacy of silencing of TUG1 and LCAL6 long non-coding RNA in the PDX model. MATERIALS AND METHODS: PDXs were established by subcutaneously implanting NSCLC surgical tumor fragments into immunodeficient mice. PDX characterization was performed by histopathological, immunohistochemical and real-time polymerase chain reaction (RT-PCR) analyses for NSCLC subtype-specific markers and expression of LCAL6 and TUG1...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29248719/usp9x-promotes-survival-in-human-pancreatic-cancer-and-its-inhibition-suppresses-pancreatic-ductal-adenocarcinoma-in-vivo-tumor-growth
#6
Anupama Pal, Michele Dziubinski, Marina Pasca Di Magliano, Diane M Simeone, Scott Owens, Dafydd Thomas, Luke Peterson, Harish Potu, Moshe Talpaz, Nicholas J Donato
Usp9x has emerged as a potential therapeutic target in some hematologic malignancies and a broad range of solid tumors including brain, breast, and prostate. To examine Usp9x tumorigenicity and consequence of Usp9x inhibition in human pancreatic tumor models, we carried out gain- and loss-of-function studies using established human pancreatic tumor cell lines (PANC1 and MIAPACA2) and four spontaneously immortalized human pancreatic patient-derived tumor (PDX) cell lines. The effect of Usp9x activity inhibition by small molecule deubiquitinase inhibitor G9 was assessed in 2D and 3D culture, and its efficacy was tested in human tumor xenografts...
December 14, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29167314/wnt-%C3%AE-catenin-pathway-activation-mediates-adaptive-resistance-to-braf-inhibition-in-colorectal-cancer
#7
Guangming Chen, Chenxi Gao, Xuan Gao, Dennis Han Zhang, Shih-Fan Kuan, Timothy F Burns, Jing Hu
One of the most encouraging developments in oncology has been the success of BRAF inhibitors in BRAF-mutant melanoma. However, in contrast to its striking efficacy in BRAF-mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF-mutant colorectal cancer (CRC). While many studies on BRAF inhibitor resistance in CRC have focused on mechanisms underlying the reactivation of the EGFR/RAS/RAF/MEK/ERK pathway, the current study focuses on identifying novel adaptive signaling mechanisms, a fresh angle on CRC resistance to BRAF inhibition...
November 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29137269/local-blockage-of-self-sustainable-erythropoietin-signaling-suppresses-tumor-progression-in-non-small-cell-lung-cancer
#8
Lei He, Shouzhen Wu, Qiang Hao, Elhadji M Dioum, Kuo Zhang, Cun Zhang, Weina Li, Wei Zhang, Yingqi Zhang, Jiming Zhou, Zhijun Pang, Lijuan Zhao, Xiaowen Ma, Meng Li, Qiuyang Zhang
Functional significance of co-expressed erythropoietin (EPO) and its receptor (EPOR) in non-small cell lung cancer (NSCLC) had been under debate. In this study, co-overexpression of EPO/EPOR was confirmed to be positively associated with poor survival in NSCLC. The serum EPO in 14 of 35 enrolled NSCLC patients were found elevated significantly and decreased to normal level after tumor resection. With primary tumor cell culture and patient-derived tumor xenograft (PDX) mouse model, the EPO secretion from the tumors of these 14 patients was verified...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29125731/imaging-pd-l1-expression-with-immunopet
#9
Charles Truillet, Hsueh Ling J Oh, Siok Ping Yeo, Chia-Yin Lee, Loc T Huynh, Junnian Wei, Matthew F L Parker, Collin Blakely, Natalia Sevillano, Yung-Hua Wang, Yuqin S Shen, Victor Olivas, Khaled M Jami, Anna Moroz, Benoit Jego, Emilie Jaumain, Lawrence Fong, Charles S Craik, Albert J Chang, Trever G Bivona, Cheng-I Wang, Michael J Evans
High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG1 (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET/CT studies showed that (89)Zr-C4 detected antigen levels on a patient derived xenograft (PDX) established from a non-small-cell lung cancer (NSCLC) patient before an 8-month response to anti-PD-1 and anti-CTLA4 therapy...
November 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29092942/pdx-mi-minimal-information-for-patient-derived-tumor-xenograft-models
#10
Terrence F Meehan, Nathalie Conte, Theodore Goldstein, Giorgio Inghirami, Mark A Murakami, Sebastian Brabetz, Zhiping Gu, Jeffrey A Wiser, Patrick Dunn, Dale A Begley, Debra M Krupke, Andrea Bertotti, Alejandra Bruna, Matthew H Brush, Annette T Byrne, Carlos Caldas, Amanda L Christie, Dominic A Clark, Heidi Dowst, Jonathan R Dry, James H Doroshow, Olivier Duchamp, Yvonne A Evrard, Stephane Ferretti, Kristopher K Frese, Neal C Goodwin, Danielle Greenawalt, Melissa A Haendel, Els Hermans, Peter J Houghton, Jos Jonkers, Kristel Kemper, Tin O Khor, Michael T Lewis, K C Kent Lloyd, Jeremy Mason, Enzo Medico, Steven B Neuhauser, James M Olson, Daniel S Peeper, Oscar M Rueda, Je Kyung Seong, Livio Trusolino, Emilie Vinolo, Robert J Wechsler-Reya, David M Weinstock, Alana Welm, S John Weroha, Frédéric Amant, Stefan M Pfister, Marcel Kool, Helen Parkinson, Atul J Butte, Carol J Bult
Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29091939/evaluation-of-the-efficacy-of-dasatinib-a-src-abl-inhibitor-in-colorectal-cancer-cell-lines-and-explant-mouse-model
#11
Aaron J Scott, Eun-Kee Song, Stacey Bagby, Alicia Purkey, Martin McCarter, Csaba Gajdos, Kevin S Quackenbush, Benjamin Cross, Todd M Pitts, Aik Choon Tan, S Gail Eckhardt, Hubert Fenton, John Arcaroli, Wells A Messersmith
BACKGROUND: Dysregulation of the Src pathway has been shown to be important at various stages of cancer. Dasatinib is a potent Src/Abl inhibitor and has demonstrated to have anti-proliferative and anti-invasive activity in many preclinical models. The objective of this study was to determine the anti-tumor activity of dasatinib using in vitro and in vivo preclinical colorectal (CRC) models. METHODS: CRC cell lines and patient-derived tumor explant (PDX) models were used to investigate the efficacy of dasatinib...
2017: PloS One
https://www.readbyqxmd.com/read/29039610/establishment-of-a-human-primary-pancreatic-cancer-mouse-model-to-examine-and-investigate-gemcitabine-resistance
#12
Ya-Jing Zhang, Chen-Lei Wen, Yu-Xin Qin, Xiao-Mei Tang, Min-Min Shi, Bo-Yong Shen, Yuan Fang
Pancreatic cancer is one of the most fatal types of cancer and is associated with a dismal prognosis. Gemcitabine-based chemotherapy is clinically used for the treatment of advanced pancreatic cancer. However, many forms of pancreatic cancer have acquired resistance to gemcitabine. In order to prevent patients from suffering from the side effects of chemotherapy and to have the chance to receive more effective intervention, assessment of whether the patient pancreatic cancer cells are resistant to gemcitabine before clinical practice is crucial...
October 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29025772/impaired-hla-class-i-antigen-processing-and-presentation-as-a-mechanism-of-acquired-resistance-to-immune-checkpoint-inhibitors-in-lung-cancer
#13
Scott Gettinger, Jungmin Choi, Katherine Hastings, Anna Truini, Ila Datar, Ryan Sowell, Anna Wurtz, Weilai Dong, Guoping Cai, Mary Ann Melnick, Victor Y Du, Joseph Schlessinger, Sarah B Goldberg, Anne Chiang, Miguel F Sanmamed, Ignacio Melero, Jackeline Agorreta, Luis M Montuenga, Richard Lifton, Soldano Ferrone, Paula Kavathas, David L Rimm, Susan M Kaech, Kurt Schalper, Roy S Herbst, Katerina Politi
Mechanisms of acquired resistance to immune checkpoint inhibitors (ICI) are poorly understood. We leveraged a collection of 14 ICI-resistant lung cancer samples to investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies. Recurrent mutations or copy-number changes were not detected in our cohort. In one case, we found acquired homozygous loss of B2M that caused lack of cell-surface HLA Class I expression in the tumor and a matched patient-derived xenograft (PDX)...
December 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28991255/patient-derived-xenografts-undergo-mouse-specific-tumor-evolution
#14
Uri Ben-David, Gavin Ha, Yuen-Yi Tseng, Noah F Greenwald, Coyin Oh, Juliann Shih, James M McFarland, Bang Wong, Jesse S Boehm, Rameen Beroukhim, Todd R Golub
Patient-derived xenografts (PDXs) have become a prominent cancer model system, as they are presumed to faithfully represent the genomic features of primary tumors. Here we monitored the dynamics of copy number alterations (CNAs) in 1,110 PDX samples across 24 cancer types. We observed rapid accumulation of CNAs during PDX passaging, often due to selection of preexisting minor clones. CNA acquisition in PDXs was correlated with the tissue-specific levels of aneuploidy and genetic heterogeneity observed in primary tumors...
November 2017: Nature Genetics
https://www.readbyqxmd.com/read/28904884/circulating-tumor-cells-and-cdx-models-as-a-tool-for-preclinical-drug-development
#15
REVIEW
Alice Lallo, Maximilian W Schenk, Kristopher K Frese, Fiona Blackhall, Caroline Dive
Lung cancers are the main cause of cancer-related deaths worldwide. Efforts placed to improve the survival of lung cancer patients and untangle the complexity of this disease, have resulted in the generation of hundreds of lung cancer cell lines and several genetically engineered mouse models (GEMMs). Although these research tools have extended our knowledge of lung cancer, improvement in the clinical care of lung cancer patients have been limited overall, with measured optimism regarding initial responses to targeted therapies in stratified subgroups of patients...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28903551/the-generation-and-application-of-patient-derived-xenograft-pdx-model-for-cancer-research
#16
Jaeyun Jung, Hyang Sook Seol, Suhwan Chang
Establishing an appropriate preclinical model is crucial for translational cancer research. The most common way that has been adopted by far is grafting cancer cell lines, derived from patients. Although this xenograft model is easy to generate, but has several limitations because this cancer model could not represent the unique features of each cancer patient sufficiently. Moreover, accumulating evidences demonstrate cancer is a highly heterogeneous disease so that a tumor is comprised of cancer cells with diverse characteristics...
September 13, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28881819/apio-ee-9-is-a-novel-aurora-a-and-b-antagonist-that-suppresses-esophageal-cancer-growth-in-a-pdx-mouse-model
#17
Guoguo Jin, Ke Yao, Zhiping Guo, Zhenjiang Zhao, Kangdong Liu, Fangfang Liu, Hanyong Chen, Dhilli Rao Gorja, Kanamata Reddy, Ann M Bode, Ziming Dong, Zigang Dong
Esophageal cancer (EC) is one of the most aggressive malignancies of the upper aerodigestive tract. Over the past three decades, with advances in surgical techniques and treatment, the prognosis of esophageal cancer has only slowly improved. Thus identifying novel molecular targets and developing therapeutic agents are critical. Aurora kinases play a crucial role in mitosis and selective inhibitors might provide an effective therapeutic treatment for cancer. However, the role of Aurora kinases in EC is still inadequately studied...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28858862/pancreas-cancer-precision-treatment-using-avatar-mice-from-a-bioinformatics-perspective
#18
Javier Perales-Patón, Elena Piñeiro-Yañez, Héctor Tejero, Pedro P López-Casas, Manuel Hidalgo, Gonzalo Gómez-López, Fátima Al-Shahrour
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death among solid malignancies. Unfortunately, PDAC lethality has not substantially decreased over the past 20 years. This aggressiveness is related to the genomic complexity and heterogeneity of PDAC, but also to the absence of an effective screening for the detection of early-stage tumors and a lack of efficient therapeutic options. Therefore, there is an urgent need to improve the arsenal of anti-PDAC drugs for an effective treatment of these patients...
2017: Public Health Genomics
https://www.readbyqxmd.com/read/28851812/a-first-in-class-twist1-inhibitor-with-activity-in-oncogene-driven-lung-cancer
#19
Zachary A Yochum, Jessica Cades, Lucia Mazzacurati, Neil M Neumann, Susheel K Khetarpal, Suman Chatterjee, Hailun Wang, Myriam A Attar, Eric H-B Huang, Sarah N Chatley, Katriana Nugent, Ashwin Somasundaram, Johnathan A Engh, Andrew J Ewald, Yoon-Jae Cho, Charles M Rudin, Phuoc T Tran, Timothy F Burns
TWIST1, an epithelial-mesenchymal transition (EMT) transcription factor, is critical for oncogene-driven non-small cell lung cancer (NSCLC) tumorigenesis. Given the potential of TWIST1 as a therapeutic target, a chemical-bioinformatic approach using connectivity mapping (CMAP) analysis was used to identify TWIST1 inhibitors. Characterization of the top ranked candidates from the unbiased screen revealed that harmine, a harmala alkaloid, inhibited multiple TWIST1 functions, including single-cell dissemination, suppression of normal branching in 3D epithelial culture, and proliferation of oncogene driver-defined NSCLC cells...
August 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28804556/anti-tumor-efficacy-evaluation-of-a-novel-monoclonal-antibody-targeting-neutral-amino-acid-transporter-asct2-using-patient-derived-xenograft-mouse-models-of-gastric-cancer
#20
Noriyuki Kasai, Aya Sasakawa, Kenta Hosomi, Tze Wei Poh, Bernadette Lynn Chua, Wei Peng Yong, Jimmy So, Shing Leng Chan, Richie Soong, Koji Kono, Toshihiko Ishii, Kazuya Yamano
ASC amino acid transporter 2 (ASCT2), also known as solute linked carrier family 1 member A5 (SLC1A5) is a Na+-dependent glutamine/neutral amino acid transporter. ASCT2 acts as a high-affinity transporter of L-glutamine (Gln) and has been reported to be up-regulated in a variety of cancerous tissues including stomach, liver, and kidney. In this study, we evaluated anti-tumor efficacy of a novel anti-ASCT2 humanized monoclonal antibody, KM8094, which has a neutralizing activity against glutamine uptake, as a therapeutic antibody against gastric cancer and explored clinical predictive biomarker candidates by utilizing patient-derived xenograft (PDX) mouse models...
2017: American Journal of Translational Research
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