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Patient derived xenograft PDX

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https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#1
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211314/procedure-for-horizontal-transfer-of-patient-derived-xenograft-tumors-to-eliminate-corynebacterium-bovis
#2
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/28193196/rapid-eradication-of-colon-carcinoma-by-clostridium-perfringens-enterotoxin-suicidal-gene-therapy
#3
Jessica Pahle, Lutz Menzel, Nicole Niesler, Dennis Kobelt, Jutta Aumann, Maria Rivera, Wolfgang Walther
BACKGROUND: Bacterial toxins have evolved to an effective therapeutic option for cancer therapy. The Clostridium perfringens enterotoxin (CPE) is a pore-forming toxin with selective cytotoxicity. The transmembrane tight junction proteins claudin-3 and -4 are known high affinity CPE receptors. Their expression is highly upregulated in human cancers, including breast, ovarian and colon carcinoma. CPE binding to claudins triggers membrane pore complex formation, which leads to rapid cell death...
February 13, 2017: BMC Cancer
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
#4
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...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184379/establishment-of-patient-derived-xenografts-in-mice
#5
Dongkyoo Park, Dongsheng Wang, Guo Chen, Xingming Deng
Patient-derived xenograft (PDX) models for cancer research have recently attracted considerable attention in both the academy and industry (Hidalgo et al., 2014; Wilding and Bodmer, 2014). PDX models have been developed from different tumor types including lung cancer to improve the drug development process. These models are used for pre-clinical drug evaluation and can be used for the predictive results of clinical outcomes because they conserve original tumor characteristics such as heterogeneity, complexity and molecular diversity (Kopetz et al...
November 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28183348/optimized-creation-of-glioblastoma-patient-derived-xenografts-for-use-in-preclinical-studies
#6
Doreen William, Christina Susanne Mullins, Björn Schneider, Andrea Orthmann, Nora Lamp, Mathias Krohn, Annika Hoffmann, Carl-Friedrich Classen, Michael Linnebacher
BACKGROUND: Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults, highlighting the need for novel treatment strategies. Patient derived xenografts (PDX) represent a valuable tool to accomplish this task. METHODS: PDX were established by implanting GBM tissue subcutaneously. Engraftment success was compared between NMRI Foxn1(nu) and NOD/SCID as well as between fresh and cryopreserved tissue. Established PDX were analyzed histologically and molecularly...
February 9, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28174092/pancreatic-cancer-models-for-translational-research
#7
REVIEW
Diana Behrens, Wolfgang Walther, Iduna Fichtner
No abstract text is available yet for this article.
February 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28156002/lucap-prostate-cancer-patient-derived-xenografts-reflect-the-molecular-heterogeneity-of-advanced-disease-an-d-serve-as-models-for-evaluating-cancer-therapeutics
#8
Holly M Nguyen, Robert L Vessella, Colm Morrissey, Lisha G Brown, Ilsa M Coleman, Celestia S Higano, Elahe A Mostaghel, Xiaotun Zhang, Lawrence D True, Hung-Ming Lam, Martine Roudier, Paul H Lange, Peter S Nelson, Eva Corey
BACKGROUND: Metastatic prostate cancer is a common and lethal disease for which there are no therapies that produce cures or long-term durable remissions. Clinically relevant preclinical models are needed to increase our understanding of biology of this malignancy and to evaluate new agents that might provide effective treatment. Our objective was to establish and characterize patient-derived xenografts (PDXs) from advanced prostate cancer (PC) for investigation of biology and evaluation of new treatment modalities...
February 3, 2017: Prostate
https://www.readbyqxmd.com/read/28154808/patient-derived-xenograft-models-of-non-small-cell-lung-cancer-and-their-potential-utility-in-personalized-medicine
#9
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/28146140/tumor-and-normal-thyroid-spheroids-from-tissues-to-zebrafish
#10
Valentina Cirello, Germano Gaudenzi, Elisa S Grassi, Carla Colombo, Leonardo Vicentini, Stefano Ferrero, Luca Persani, Giovanni Vitale, Laura Fugazzola
BACKGROUND: Multicellular spheroids represent an interesting experimental model with promising applications in the pre-clinical studies on anticancer drugs. We recently demonstrated that thyroid spheroids recapitulate the features of the original tissues, in either the differentiated and "stem-like" components. Here we were aimed to characterize thyroid spheroids and to investigate in vivo the proangiogenic potential of patient-derived xenografts (PDX) of spheroids obtained from papillary thyroid cancer (PTC) and the matched normal tissues...
January 31, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/28140525/nanobodies-against-surface-biomarkers-enable-the-analysis-of-tumor-genetic-heterogeneity-in-uveal-melanoma-patient-derived-xenografts
#11
Ronan Crépin, David Gentien, Angeline Duché, Audrey Rapinat, Cecile Reyes, Fariba Némati, Gérald Massonnet, Didier Decaudin, Selma Djender, Sandrine Moutel, Klervi Desrumeaux, Nathalie Cassoux, Sophie Piperno-Neumann, Sebastian Amigorena, Franck Perez, Sergio Roman Roman, Ario de Marco
Monoclonal antibodies specific for biomarkers expressed on the surface of uveal melanoma (UM) cells would simplify the immune-capture and genomic characterization of heterogeneous tumor cells originated from patient derived xenografts (PDXs). Antibodies against four independent tumor antigens were isolated by panning a nanobody synthetic library. Such antibodies enabled flow-cytometry-based sorting of distinct cell sub-populations from UM PDXs and to analyze their genomic features. The complexity and specificity of the biochemical and genomic biomarker combinations mirrored the UM tumor polyclonality...
January 31, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28139732/intravenous-formulation-of-het0016-decreased-human-glioblastoma-growth-and-implicated-survival-benefit-in-rat-xenograft-models
#12
Meenu Jain, Nipuni-Dhanesha H Gamage, Meshal Alsulami, Adarsh Shankar, Bhagelu R Achyut, Kartik Angara, Mohammad H Rashid, Asm Iskander, Thaiz F Borin, Zhi Wenbo, Roxan Ara, Meser M Ali, Iryna Lebedyeva, Wilson B Chwang, Austin Guo, Hassan Bagher-Ebadian, Ali S Arbab
Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28135251/effective-personalized-therapy-for-breast-cancer-based-on-predictions-of-cell-signaling-pathway-activation-from-gene-expression-analysis
#13
J-R Jhan, E R Andrechek
Current therapeutic outcomes for breast cancer underscore the complexity of treating a heterogeneous disease. Indeed, studies have shown that differences in gene expression among patients with the same subtype of breast cancer are correlated with the response to treatment. This strongly suggests that there is an urgent need to treat breast cancer with a personalized approach. Here we employed cell signaling pathway signatures to predict pathway activity in subtypes of MMTV-Myc mammary tumors. We then split tumors into subsets and developed individualized combinatorial treatments for two subtypes with distinct pathway activation patterns...
January 30, 2017: Oncogene
https://www.readbyqxmd.com/read/28120979/novel-iodinated-gold-nanoclusters-for-precise-diagnosis-of-thyroid-cancer
#14
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/28119432/exploiting-ar-regulated-drug-transport-to-induce-sensitivity-to-the-survivin-inhibitor-ym155
#15
Michael D Nyquist, Alexandra Corella, John Burns, Ilsa Coleman, Shuai Gao, Robin Tharakan, Luke Riggan, Changmeng Cai, Eva Corey, Peter S Nelson, Elahe A Mostaghel
: Androgen receptor (AR) signaling is fundamental to prostate cancer and is the dominant therapeutic target in metastatic disease. However, stringent androgen deprivation therapy (ADT) regimens decrease quality of life and have been largely unsuccessful in curtailing mortality. Recent clinical and pre-clinical studies have taken advantage of the dichotomous ability of AR signaling to elicit growth-suppressive and differentiating effects by administering hyper-physiological levels of testosterone...
January 24, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28119366/bioluminescence-imaging-enhances-analysis-of-drug-responses-in-a-patient-derived-xenograft-model-of-pediatric-all
#16
Luke Jones, Jennifer Richmond, Kathryn Evans, Hernan Carol, Duohui Jing, Raushan T Kurmasheva, Catherine A Billups, Peter J Houghton, Malcolm A Smith, Richard B Lock
PURPOSE: Robust preclinical models of pediatric acute lymphoblastic leukemia (ALL) are essential in prioritizing promising therapies for clinical assessment in high-risk patients. Patient-derived xenograft (PDX) models of ALL provide a clinically relevant platform for assessing novel drugs, with efficacy generally assessed by enumerating circulating human lymphoblasts in mouse peripheral blood (PB) as an indicator of disease burden. While allowing indirect measurement of disease burden in real-time, this technique cannot assess treatment effects on internal reservoirs of disease...
January 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28112582/the-allosteric-akt-inhibitor-mk2206-decreases-tumor-growth-and-invasion-in-patient-derived-xenografts-of-endometrial-cancer
#17
Abigail Winder, Kenji Unno, Yanni Yu, John Lurain, J Julie Kim
The purpose of this study was to test the effect of MK2206, an allosteric inhibitor of AKT, on the growth and invasion of patient-derived xenografts (PDX) of endometrial cancer. Three PDX lines, USC1 (uterine serous), EEC2 (endometrioid grade 2) and EEC4 (endometrioid grade 3) of endometrial cancer were grafted under the renal capsule of NSG mice. After 2 weeks of tumor growth the mice were treated with vehicle or 120mg/kg MK2206 twice a week for three weeks. Growth of all three PDX lines of different type and grade was significantly inhibited in response to MK2206 compared to vehicle control...
January 23, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28104906/interrogating-open-issues-in-cancer-precision-medicine-with-patient-derived-xenografts
#18
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...
January 20, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28097235/a-patient-derived-xenograft-platform-to-study-brca-deficient-ovarian-cancers
#19
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/28073890/pancreatic-cancer-cell-lines-as-patient-derived-avatars-genetic-characterisation-and-functional-utility
#20
Erik S Knudsen, Uthra Balaji, Brian Mannakee, Paris Vail, Cody Eslinger, Christopher Moxom, John Mansour, Agnieszka K Witkiewicz
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities. DESIGN: 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines...
January 10, 2017: Gut
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