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Patients derived xenograft mouse model cancer (PDX)

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https://www.readbyqxmd.com/read/28672195/combination-treatment-with-the-gsk-3-inhibitor-9-ing-41-and-ccnu-cures-orthotopic-chemoresistant-glioblastoma-in-patient-derived-xenograft-models
#1
Andrey Ugolkov, Wenan Qiang, Gennadiy Bondarenko, Daniel Procissi, Irina Gaisina, C David James, James Chandler, Alan Kozikowski, Hendra Gunosewoyo, Thomas O'Halloran, Jeffrey Raizer, Andrew P Mazar
Resistance to chemotherapy remains a major challenge in the treatment of human glioblastoma (GBM). Glycogen synthase kinase-3β (GSK-3β), a positive regulator of NF-κB-mediated survival and chemoresistance of cancer cells, has been identified as a potential therapeutic target in human GBM. Our objective was to determine the antitumor effect of GSK-3 inhibitor 9-ING-41 in combination with chemotherapy in patient-derived xenograft (PDX) models of human GBM. We utilized chemoresistant PDX models of GBM, GBM6 and GBM12, to study the effect of 9-ING-41 used alone and in combination with chemotherapy on tumor progression and survival...
June 30, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28668828/patient-derived-xenografts-from-colorectal-carcinoma-a-temporal-and-hierarchical-study-of-murine-stromal-cell-replacement
#2
Celia Chao, Steve G Widen, Thomas G Wood, John R Zatarain, Paul Johnson, Aakash Gajjar, Guillermo Gomez, Suimin Qiu, Jill Thompson, Heidi Spratt, Mark R Hellmich
BACKGROUND/AIM: Patient-derived xenografting (PDX) of human colorectal cancer (CRC) is the preferred experimental model to study tumor response to therapeutic agents. Gradually, human stromal cells are replaced by mouse stromal cells; however, the exact timing of the replacement of human with murine stromal cells in human CRC xenograft has not been fully elucidated. We hypothesize that orthologous murine transcripts functionally substitutes for the loss due to replacement of human stromal genes...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28654908/apio-ee-9-is-a-novel-aurora-a-and-b-antagonist-that-suppresses-esophageal-cancer-growth-in-a-pdx-mouse-model
#3
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...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635650/the-application-of-heptamethine-cyanine-dye-dz-1-and-indocyanine-green-for-imaging-and-targeting-in-xenograft-models-of-hepatocellular-carcinoma
#4
Caiqin Zhang, Yong Zhao, He Zhang, Xue Chen, Ningning Zhao, Dengxu Tan, Hai Zhang, Changhong Shi
Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28611205/mouse-pdx-trial-suggests-synergy-of-concurrent-inhibition-of-raf-and-egfr-in-colorectal-cancer-with-braf-or-kras-mutations
#5
Yung-Mae M Yao, Gregory P Donoho, Philip Iversen, Youyan Zhang, Robert D Van Horn, Amelie Forest, Ruslan Novosiadly, Yue Webster, Ebert J Philip, Steven M Bray, Jason C Ting, Amit Aggarwal, James R Henry, Ramon V Tiu, Gregory D Plowman, Sheng-Bin Peng
Purpose: It is to evaluate the anti-tumor efficacy of cetuximab in combination with LSN3074753, an analogue of LY3009120 and pan-RAF inhibitor in 79 colorectal cancer (CRC) patient derived xenograft (PDX) models.<br />Experimental Design: 79 well characterized CRC PDX models were employed to conduct a single mouse per treatment group (n=1) trial.<br />Results: Consistent with clinical results, cetuximab was efficacious in wild type KRAS and BRAF PDX models, with an overall response rate (ORR) of 6...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28534338/-application-and-development-of-patient-derived-tumor-xenograft-model-in-translational-medicine-of-tumor
#6
Zhenqiang Wang, Zhenggang Zhu
Development of novel drugs is an integral part of the translational medicine in the field of cancer research, and the construction and application of preclinical animal models play vital roles in drugs development. Patient-derived tumor xenograft models (PDX) have been shown to be more accurate in prediction of clinical outcomes of novel drugs and are being used for preclinical drug evaluation based on the fact that PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28450563/sstr-mediated-breast-cancer-imaging-is-there-a-role-for-radiolabeled-sstr-antagonists
#7
Simone U Dalm, Joost Haeck, Gabriela N Doeswijk, Erik de Blois, Marion de Jong, Carolien van Deurzen
INTRODUCTION: Recent studies showed enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared to clinically widely used agonists. However, these results have mostly been obtained in neuroendocrine tumors and only limited data is available for cancer types with lower SSTR expression, including breast cancer (BC). To date, only two studies reported higher binding of the antagonist versus the agonist in BC, but in both studies a limited number of cases were evaluated. In this pre-clinical study, we further investigated whether the application of a SSTR antagonist could improve SSTR-mediated BC imaging in a large panel of BC specimens...
April 27, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28446504/feasibility-of-ultra-high-throughput-functional-screening-of-melanoma-biopsies-for-discovery-of-novel-cancer-drug-combinations
#8
Adam A Friedman, Yun Xia, Lorenzo Trippa, Long P Le, Vivien Igras, Dennie T Frederick, Jennifer A Wargo, Kenneth K Tanabe, Donald P Lawrence, Donna S Neuberg, Keith T Flaherty, David Fisher
Purpose: Successful development of targeted therapy combinations for cancer patients depends on first discovering such combinations in predictive preclinical models. Stable cell lines and mouse xenograft models can have genetic and phenotypic drift and may take too long to generate to be useful as a personalized medicine tool. <p>Experimental Design: To overcome these limitations, we have used a platform of ultra-high-throughput functional screening of primary biopsies preserving both cancer and stroma cell populations from melanoma patients to nominate such novel combinations from a library of  thousands of drug combinations in a patient-specific manner within days of biopsy...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28405515/psca-and-muc1-in-non-small-cell-lung-cancer-as-targets-of-chimeric-antigen-receptor-t-cells
#9
Xinru Wei, Yunxin Lai, Jin Li, Le Qin, Youdi Xu, Ruocong Zhao, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Muyun Peng, Fenglei Yu, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Duanqing Pei, Yao Yao, Peng Li
In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA- and MUC1-targeting CAR T cells against NSCLC cell lines in vitro...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28315646/procedure-for-horizontal-transfer-of-patient-derived-xenograft-tumors-to-eliminate-corynebacterium-bovis
#10
Christopher A Manuel, Stacey M Bagby, Julie A Reisinger, Umarani Pugazhenthi, Todd M Pitts, Stephen B Keysar, John J Arcaroli, Jori K Leszczynski
Human patient-derived xenograft (PDX) tumors, propagated in immunodeficient mice, are rapidly growing in use as a model for cancer research. Horizontal transfer between mice, without in vitro cell culture, allows these tumors to retain many of their unique characteristics from their individual patient of origin. However, the immunodeficient mouse strains used to grow these tumors are susceptible to numerous opportunistic pathogens, including Corynebacterium bovis. At our institution, 2 in vivo tumor banks of PDX tumors had been maintained within nude mouse colonies enzootically infected with C...
March 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28249646/chromosomal-abnormalities-and-molecular-landscape-of-metastasizing-mucinous-salivary-adenocarcinoma
#11
Alex Panaccione, Yi Zhang, Yanfang Mi, Yoshitsugu Mitani, Guo Yan, Manju L Prasad, W Hayes McDonald, Adel K El-Naggar, Wendell G Yarbrough, Sergey V Ivanov
BACKGROUND: Mucinous adenocarcinoma of the salivary gland (MAC) is a lethal cancer with unknown molecular etiology and a high propensity to lymph node metastasis. Mostly due to its orphan status, MAC remains one of the least explored cancers that lacks cell lines and mouse models that could help translational and pre-clinical studies. Surgery with or without radiation remains the only treatment modality but poor overall survival (10-year, 44%) underscores the urgent need for mechanism-based therapies...
March 2017: Oral Oncology
https://www.readbyqxmd.com/read/28211314/procedure-for-horizontal-transfer-of-patient-derived-xenograft-tumors-to-eliminate-corynebacterium-bovis
#12
Christopher A Manuel Stacey M Bagby Julie A Reisinger Umarani Pugazhenthi Todd M Pitts Stephen B Keysar John J Arcaroli And Jori K Leszczynski
Human patient-derived xenograft (PDX) tumors, propagated in immunodeficient mice, are rapidly growing in use as amodelfor cancer research. Horizontal transfer between mice, without in vitro cell culture, allows these tumors to retainmany of their unique characteristics from their individual patient of origin. However, the immunodeficient mouse strainsused to grow these tumors are susceptible to numerous opportunistic pathogens, including Corynebacterium bovis. At ourinstitution, 2 in vivo tumor banks of PDX tumors had been maintained within nude mouse colonies enzootically infectedwith C...
February 16, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28186974/a-notch-sensitive-upar-regulated-oncolytic-adenovirus-effectively-suppresses-pancreatic-tumor-growth-and-triggers-synergistic-anticancer-effects-with-gemcitabine-and-nab-paclitaxel
#13
Ana Mato-Berciano, Giulia Raimondi, Maria Victoria Maliandi, Ramon Alemany, Lluis Montoliu, Cristina Fillat
Notch signaling pathway is an embryonic program that becomes reactivated in pancreatic cancer and contributes to cancer stem cell (CSC) maintenance. We explored the concept of oncolytic adenoviral activity in response to Notch activation signaling, in the context of a chimeric promoter with uPAR regulatory sequences, as a strategy to drive its activity in neoplastic and CSC. We explored the advantages of a chemo-virotherapy approach based on synergistic combinations. Regulatory sequences recognized by the transcriptional factor CSL upstream a minimal uPAR promoter were engineered in adenoviral vectors and in the oncolytic adenovirus AdNuPARmE1A...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28154808/patient-derived-xenograft-models-of-non-small-cell-lung-cancer-and-their-potential-utility-in-personalized-medicine
#14
Katherine M Morgan, Gregory M Riedlinger, Jeffrey Rosenfeld, Shridar Ganesan, Sharon R Pine
Traditional preclinical studies of cancer therapeutics have relied on the use of established human cell lines that have been adapted to grow in the laboratory and, therefore, may deviate from the cancer they were meant to represent. With the emphasis of cancer drug development shifting from non-specific cytotoxic agents to rationally designed molecularly targeted therapies or immunotherapy comes the need for better models with predictive value regarding therapeutic activity and response in clinical trials. Recently, the diversity and accessibility of immunodeficient mouse strains has greatly enhanced the production and utility of patient-derived xenograft (PDX) models for many tumor types, including non-small cell lung cancer (NSCLC)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28120979/novel-iodinated-gold-nanoclusters-for-precise-diagnosis-of-thyroid-cancer
#15
Xin Chen, Huanhuan Zhu, Xin Huang, Peisong Wang, Fulei Zhang, Wei Li, Guang Chen, Bingdi Chen
As the most common endocrine malignancy with a high incidence, thyroid cancer lacks a dual-modal imaging method for precise diagnosis. An accurate and multimodal imaging system is pivotal to solve this problem. Herein, dual-modality fluorescence/Computed Tomography (CT) iodinated gold nanoclusters for malignant thyroid cancer visualization have been recently fabricated. In this study, innovative iodinated gold nanoclusters (AuNCs@BSA-I) were synthesized via Bovine serum albumin (BSA) and chloramine-T. AuNCs@BSA-I not only possess an ultra-small size and brilliant biocompatibility but also exhibit excellent fluorescence/CT imaging properties...
January 25, 2017: Nanoscale
https://www.readbyqxmd.com/read/28104906/interrogating-open-issues-in-cancer-precision-medicine-with-patient-derived-xenografts
#16
REVIEW
Annette T Byrne, Denis G Alférez, Frédéric Amant, Daniela Annibali, Joaquín Arribas, Andrew V Biankin, Alejandra Bruna, Eva Budinská, Carlos Caldas, David K Chang, Robert B Clarke, Hans Clevers, George Coukos, Virginie Dangles-Marie, S Gail Eckhardt, Eva Gonzalez-Suarez, Els Hermans, Manuel Hidalgo, Monika A Jarzabek, Steven de Jong, Jos Jonkers, Kristel Kemper, Luisa Lanfrancone, Gunhild Mari Mælandsmo, Elisabetta Marangoni, Jean-Christophe Marine, Enzo Medico, Jens Henrik Norum, Héctor G Palmer, Daniel S Peeper, Pier Giuseppe Pelicci, Alejandro Piris-Gimenez, Sergio Roman-Roman, Oscar M Rueda, Joan Seoane, Violeta Serra, Laura Soucek, Dominique Vanhecke, Alberto Villanueva, Emilie Vinolo, Andrea Bertotti, Livio Trusolino
Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and the implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions...
April 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28097235/a-patient-derived-xenograft-platform-to-study-brca-deficient-ovarian-cancers
#17
Erin George, Hyoung Kim, Clemens Krepler, Brandon Wenz, Mehran Makvandi, Janos L Tanyi, Eric Brown, Rugang Zhang, Patricia Brafford, Stephanie Jean, Robert H Mach, Yiling Lu, Gordon B Mills, Meenhard Herlyn, Mark Morgan, Xiaochen Zhang, Robert Soslow, Ronny Drapkin, Neil Johnson, Ying Zheng, George Cotsarelis, Katherine L Nathanson, Fiona Simpkins
Approximately 50% of high-grade serous ovarian cancers (HGSOCs) have defects in genes involved in homologous recombination (HR) (i.e., BRCA1/2). Preclinical models to optimize therapeutic strategies for HR-deficient (HRD) HGSOC are lacking. We developed a preclinical platform for HRD HGSOCs that includes primary tumor cultures, patient-derived xenografts (PDXs), and molecular imaging. Models were characterized by immunohistochemistry, targeted sequencing, and reverse-phase protein array analysis. We also tested PDX tumor response to PARP, CHK1, and ATR inhibitors...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/27941872/er-stress-protein-agr2-precedes-and-is-involved-in-the-regulation-of-pancreatic-cancer-initiation
#18
L Dumartin, W Alrawashdeh, S M Trabulo, T P Radon, K Steiger, R M Feakins, M P di Magliano, C Heeschen, I Esposito, N R Lemoine, T Crnogorac-Jurcevic
The mechanisms of initiation of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. In the present study, we analysed the role of anterior gradient-2 (AGR2) in the earliest stages of pancreatic neoplasia. Immunohistochemical analysis of chronic pancreatitis (CP) and peritumoral areas in PDAC tissues showed that AGR2 was present in tubular complexes (TC) and early pancreatic intraepithelial neoplasia (PanINs). Moreover, AGR2 was also found in discrete subpopulations of non-transformed cells neighbouring these pre-neoplastic lesions...
June 1, 2017: Oncogene
https://www.readbyqxmd.com/read/27935045/patient-derived-xenografts-of-gastrointestinal-cancers-are-susceptible-to-rapid-and-delayed-b-lymphoproliferation
#19
Sebastian M Dieter, Klara M Giessler, Mark Kriegsmann, Taronish D Dubash, Lino Möhrmann, Erik R Schulz, Christine Siegl, Sarah Weber, Hendrik Strakerjahn, Ava Oberlack, Ulrike Heger, Jianpeng Gao, Eva-Maria Hartinger, Felix Oppel, Christopher M Hoffmann, Nati Ha, Benedikt Brors, Felix Lasitschka, Alexis Ulrich, Oliver Strobel, Manfred Schmidt, Christof von Kalle, Martin Schneider, Wilko Weichert, K Roland Ehrenberg, Hanno Glimm, Claudia R Ball
Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro...
March 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27929464/labeling-of-breast-cancer-patient-derived-xenografts-with-traceable-reporters-for-tumor-growth-and-metastasis-studies
#20
Colton Hanna, Letty Kwok, Jessica Finlay-Schultz, Carol A Sartorius, Diana M Cittelly
The use of preclinical models to study tumor biology and response to treatment is central to cancer research. Long-established human cell lines, and many transgenic mouse models, often fail to recapitulate the key aspects of human malignancies. Thus, alternative models that better represent the heterogeneity of patients' tumors and their metastases are being developed. Patient-derived xenograft (PDX) models in which surgically resected tumor samples are engrafted into immunocompromised mice have become an attractive alternative as they can be transplanted through multiple generations,and more efficiently reflect tumor heterogeneity than xenografts derived from human cancer cell lines...
November 30, 2016: Journal of Visualized Experiments: JoVE
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