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Patients derived xenograft mouse model cancer (PDX)

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https://www.readbyqxmd.com/read/29768500/clinically-relevant-inflammatory-breast-cancer-patient-derived-xenograft-derived-ex-vivo-model-for-evaluation-of-tumor-specific-therapies
#1
Bedrich L Eckhardt, Maria Gagliardi, LaKesla Iles, Kurt Evans, Cristina Ivan, Xiuping Liu, Chang-Gong Liu, Glauco Souza, Arvind Rao, Funda Meric-Bernstam, Naoto T Ueno, Geoffrey A Bartholomeusz
Inflammatory breast cancer (IBC) is a rare and aggressive presentation of invasive breast cancer with a 62% to 68% 5-year survival rate. It is the most lethal form of breast cancer, and early recognition and treatment is important for patient survival. Like non-inflammatory breast cancer, IBC comprises multiple subtypes, with the triple-negative subtype being overrepresented. Although the current multimodality treatment regime of anthracycline- and taxane-based neoadjuvant therapy, surgery, and radiotherapy has improved the outcome of patients with triple-negative IBC, overall survival continues to be worse than in patients with non-inflammatory locally advanced breast cancer...
2018: PloS One
https://www.readbyqxmd.com/read/29755432/murine-endogenous-retroviruses-are-detectable-in-patient-derived-xenografts-but-not-in-patient-individual-cell-lines-of-human-colorectal-cancer
#2
Stephanie Bock, Christina S Mullins, Ernst Klar, Philippe Pérot, Claudia Maletzki, Michael Linnebacher
Endogenous retroviruses are remnants of retroviral infections. In contrast to their human counterparts, murine endogenous retroviruses (mERV) still can synthesize infectious particles and retrotranspose. Xenotransplanted human cells have occasionally been described to be mERV infected. With genetic engineered mice and patient-derived xenografts (PDXs) on the rise as eminent research tools, we here systematically investigated, if different tumor models harbor mERV infections. Relevant mERV candidates were first preselected by next generation sequencing (NGS) analysis of spontaneous lymphomas triggered by colorectal cancer (CRC) PDX tissue...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29748904/androgen-receptor-signaling-in-castration-resistant-prostate-cancer-alters-hyperpolarized-pyruvate-to-lactate-conversion-and-lactate-levels-in-vivo
#3
Niki Zacharias, Jaehyuk Lee, Sumankalai Ramachandran, Sriram Shanmugavelandy, James McHenry, Prasanta Dutta, Steven Millward, Seth Gammon, Eleni Efstathiou, Patricia Troncoso, Daniel E Frigo, David Piwnica-Worms, Christopher J Logothetis, Sankar N Maity, Mark A Titus, Pratip Bhattacharya
PURPOSE: Androgen receptor (AR) signaling affects prostate cancer (PCa) growth, metabolism, and progression. Often, PCa progresses from androgen-sensitive to castration-resistant prostate cancer (CRPC) following androgen-deprivation therapy. Clinicopathologic and genomic characterizations of CRPC tumors lead to subdividing CRPC into two subtypes: (1) AR-dependent CRPC containing dysregulation of AR signaling alterations in AR such as amplification, point mutations, and/or generation of splice variants in the AR gene; and (2) an aggressive variant PCa (AVPC) subtype that is phenotypically similar to small cell prostate cancer and is defined by chemotherapy sensitivity, gain of neuroendocrine or pro-neural marker expression, loss of AR expression, and combined alterations of PTEN, TP53, and RB1 tumor suppressors...
May 10, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29743053/pdxliver-a-database-of-liver-cancer-patient-derived-xenograft-mouse-models
#4
Sheng He, Bo Hu, Chao Li, Ping Lin, Wei-Guo Tang, Yun-Fan Sun, Fang-You-Min Feng, Wei Guo, Jia Li, Yang Xu, Qian-Lan Yao, Xin Zhang, Shuang-Jian Qiu, Jian Zhou, Jia Fan, Yi-Xue Li, Hong Li, Xin-Rong Yang
BACKGROUND: Liver cancer is the second leading cause of cancer-related deaths and characterized by heterogeneity and drug resistance. Patient-derived xenograft (PDX) models have been widely used in cancer research because they reproduce the characteristics of original tumors. However, the current studies of liver cancer PDX mice are scattered and the number of available PDX models are too small to represent the heterogeneity of liver cancer patients. To improve this situation and to complement available PDX models related resources, here we constructed a comprehensive database, PDXliver, to integrate and analyze liver cancer PDX models...
May 9, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29706843/nirf-optical-pet-dual-modal-imaging-of-hepatocellular-carcinoma-using-heptamethine-carbocyanine-dye
#5
Caiqin Zhang, Yong Zhao, Ningning Zhao, Dengxu Tan, He Zhang, Xue Chen, Hai Zhang, Jiaze An, Changhong Shi, Mengbin Li
Combining near-infrared fluorescence (NIRF) and nuclear imaging techniques provides a novel approach for hepatocellular carcinoma (HCC) diagnosis. Here, we report the synthesis and characteristics of a dual-modality NIRF optical/positron emission tomography (PET) imaging probe using heptamethine carbocyanine dye and verify its feasibility in both nude mice and rabbits with orthotopic xenograft liver cancer. This dye, MHI-148, is an effective cancer-specific NIRF imaging agent and shows preferential uptake and retention in liver cancer...
2018: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29675102/synergistic-antitumor-effects-of-cmet-inhibitor-in-combination-with-anti-vegf-in-colorectal-cancer-patient-derived-xenograft-models
#6
Xiangheng Chen, Zhonghai Guan, Jun Lu, Haohao Wang, Zhongkun Zuo, Fei Ye, Jiangsheng Huang, Lisong Teng
cMet signaling pathway is involved in the resistance to anti-VEGF therapy and cMet overexpression is associated with tumor progression and poor prognosis. In this study, the expression of cMet in 146 Chinese colorectal cancer (CRC) patients was examined by immunohistochemistry staining. Our data demonstrated that cMet overexpression rate was 42.5% (62/146) and cMet overexpression was closely correlated with distant metastasis of CRC. Using CRC patient-derived xenograft (PDX) mouse models we investigated antitumor activity of a novel selective cMet inhibitor volitinib alone or in combination with anti-VEGF inhibitor apatinib in vivo ...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29622581/targeting-tissue-factor-for-immunotherapy-of-triple-negative-breast-cancer-using-a-second-generation-icon
#7
Zhiwei Hu, Rulong Shen, Amanda Campbell, Elizabeth L McMichael, Lianbo Yu, Bhuvaneswari Ramaswamy, Cheryl A London, Tian Xu, William E Carson
Triple-negative breast cancer (TNBC) is a leading cause of breast cancer death and is often associated with BRCA1 and BRCA2 mutation. Due to the lack of validated target molecules, no targeted therapy for TNBC is approved. Tissue factor (TF) is a common yet specific surface target receptor for cancer cells, tumor vascular endothelial cells and cancer stem cells in several types of solid cancers including breast cancer. Here we report evidence supporting the idea that TF is a surface target in TNBC. We used in vitro cancer lines and in vivo tumor xenografts in mice, all with BRCA1 or BRCA2 mutations, derived from patients' tumors...
April 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29596326/differentiation-therapy-targeting-the-%C3%AE-catenin-cbp-interaction-in-pancreatic-cancer
#8
Philipp Manegold, Keane K Y Lai, Yongfeng Wu, Jia-Ling Teo, Heinz-Josef Lenz, Yuri S Genyk, Stephen J Pandol, Kaijin Wu, David P Lin, Yibu Chen, Cu Nguyen, Yi Zhao, Michael Kahn
BACKGROUND: Although canonical Wnt signaling is known to promote tumorigenesis in pancreatic ductal adenocarcinoma (PDAC), a cancer driven principally by mutant K-Ras , the detailed molecular mechanisms by which the Wnt effector β-catenin regulates such tumorigenesis are largely unknown. We have previously demonstrated that β-catenin's differential usage of the Kat3 transcriptional coactivator cyclic AMP-response element binding protein-binding protein (CBP) over its highly homologous coactivator p300 increases self-renewal and suppresses differentiation in other types of cancer...
March 29, 2018: Cancers
https://www.readbyqxmd.com/read/29589317/patient-derived-xenograft-models-of-colorectal-cancer-procedures-for-engraftment-and-propagation
#9
Danielle M Burgenske, David J Monsma, Jeffrey P MacKeigan
Preclinical compounds tested in animal models often demonstrate limited efficacy when transitioned into patients. As a result, individuals are assigned to treatment regimens that may be ineffective at treating their disease. The development of more clinically relevant models, such as patient-derived xenografts (PDXs), will (1) more completely mimic the human condition and (2) more accurately predict tumor responses to previously untested therapeutics.PDX models are clinically relevant as tumor tissue is implanted directly from human donor to the mouse recipient...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29541240/antitumor-activity-of-kinetochore-associated-protein-2-sirna-against-lung-cancer-patient-derived-tumor-xenografts
#10
Yukimasa Makita, Mika Teratani, Shumpei Murata, Yasutaka Hoashi, Satoru Matsumoto, Yuji Kawamata
It has been widely reported that patient-derived tumor xenografts (PDXs) are more similar to tumor tissues than conventional cancer cell lines. Kinetochore-associated protein 2 (KNTC2) is known to be upregulated specifically in tumor tissues of cancer patients and is recognized as a potential target for cancer therapy. Previously, in vivo antitumor activities of KNTC2 short interfering RNA encapsulated into a lipid nanoparticle (KNTC2-LNP) were reported in orthotopic hepatocellular carcinoma mouse models. However, it remains unclear whether KNTC2-LNP exhibits antitumor activities against lung cancer PDXs...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29534550/identification-of-differentially-expressed-genes-between-original-breast-cancer-and-xenograft-using-machine-learning-algorithms
#11
Deling Wang, Jia-Rui Li, Yu-Hang Zhang, Lei Chen, Tao Huang, Yu-Dong Cai
Breast cancer is one of the most common malignancies in women. Patient-derived tumor xenograft (PDX) model is a cutting-edge approach for drug research on breast cancer. However, PDX still exhibits differences from original human tumors, thereby challenging the molecular understanding of tumorigenesis. In particular, gene expression changes after tissues are transplanted from human to mouse model. In this study, we propose a novel computational method by incorporating several machine learning algorithms, including Monte Carlo feature selection (MCFS), random forest (RF), and rough set-based rule learning, to identify genes with significant expression differences between PDX and original human tumors...
March 12, 2018: Genes
https://www.readbyqxmd.com/read/29504396/addressing-drug-resistance-in-cancer-with-macromolecular-chemotherapeutic-agents
#12
Nathaniel H Park, Wei Cheng, Fritz Lai, Chuan Yang, Paola Florez de Sessions, Balamurugan Periaswamy, Collins Wenhan Chu, Simone Bianco, Shaoqiong Liu, Shrinivas Venkataraman, Qingfeng Chen, Yi Yan Yang, James L Hedrick
Drug resistance to chemotherapeutics is a recurrent issue plaguing many cancer treatment regimens. To circumvent resistance issues, we have designed a new class of macromolecules as self-contained chemotherapeutic agents. The macromolecular chemotherapeutic agents readily self-assemble into well-defined nanoparticles and show excellent activity in vitro against multiple cancer cell lines. These cationic polymers function by selectively binding and lysing cancer cell membranes. As a consequence of this mechanism, they exhibit significant potency against drug-resistant cancer cells and cancer stem cells, prevent cancer cell migration, and do not induce resistance onset following multiple treatment passages...
March 28, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29491256/establishment-of-a-patient-derived-tumor-xenograft-model-and-application-for-precision-cancer-medicine
#13
REVIEW
Seiji Okada, Kulthida Vaeteewoottacharn, Ryusho Kariya
Patient-derived xenograft (PDX) models can be created with the transplantation of cancerous cells or tissues from patients' primary tumors into immunodeficient mice. PDXs are now in the spotlight as more accurate human cancer models compared with mouse tumor and human cancer cell lines transplanted into mice. PDX technology leads to breakthroughs with the introduction of novel, highly immunodeficient mice such as NOG (NOD/Scid/IL2Rγnull ), NSG (NOD/Scid/IL2Rγnull ), and NOJ (NOD/Scid/Jak3null ) mice. Xenograft efficiency differs by type of tumor, site of implantation, and tumor aggressiveness...
2018: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29487201/heterochromatin-protein-1%C3%AE-mediates-development-and-aggressiveness-of-neuroendocrine-prostate-cancer
#14
Xinpei Ci, Jun Hao, Xin Dong, Stephen Y Choi, Hui Xue, Rebecca Wu, Sifeng Qu, Peter W Gout, Fang Zhang, Anne M Haegert, Ladan Fazli, Francesco Crea, Christopher J Ong, Amina Zoubeidi, Housheng H He, Martin E Gleave, Colin C Collins, Dong Lin, Yuzhuo Wang
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer arising mostly from adenocarcinoma via neuroendocrine transdifferentiation following androgen deprivation therapy. Mechanisms contributing to both NEPC development and its aggressiveness remain elusive. In light of the fact that hyperchromatic nuclei are a distinguishing histopathologic feature of NEPC, we utilized transcriptomic analyses of our patient-derived xenograft (PDX) models, multiple clinical cohorts, and genetically engineered mouse models to identify 36 heterochromatin-related genes that are significantly enriched in NEPC...
February 27, 2018: Cancer Research
https://www.readbyqxmd.com/read/29398601/losmapimod-overcomes-gefitinib-resistance-in-non-small-cell-lung-cancer-by-preventing-tetraploidization
#15
Yiu To Yeung, Shuying Yin, Bingbing Lu, Suyu Fan, Ran Yang, Ruihua Bai, Chengjuan Zhang, Ann M Bode, Kangdong Liu, Zigang Dong
The epidermal growth factor receptor (EGFR) is known to play a critical role in non-small cell lung cancer (NSCLC). Constitutively active EGFR mutations, including in-frame deletion in exon 19 and L858R point mutation in exon 21, contribute about 90% of all EGFR-activating mutations in NSCLC. Although oral EGFR-tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, show dramatic clinical efficacy with significantly prolonged progression-free survival in patients harboring these EGFR-activating mutations, most of these patients will eventually develop acquired resistance...
February 2018: EBioMedicine
https://www.readbyqxmd.com/read/29338446/the-latest-animal-models-of-ovarian-cancer-for-novel-drug-discovery
#16
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...
March 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
#17
Daniel Dávila-González, Dong Soon Choi, Roberto R Rosato, Sergio M Granados-Principal, John G Kuhn, Wen-Feng Li, Wei Qian, Wen Chen, Anthony J Kozielski, Helen 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 pharmacologic NOS inhibition on TNBC. Experimental Design: TNBC cell lines, SUM-159PT, MDA-MB-436, and MDA-MB-468, were treated with docetaxel and NOS inhibitor (L-NMMA) for 24, 48, and 72 hours. Apoptosis was assessed by flow cytometry using Annexin-V and propidium iodide...
March 1, 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
#18
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-antitumor-efficacy-of-cisplatin
#19
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 antitumor activity and has organ-protective effects. The goal of this study was to determine the antitumor 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...
February 2018: 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
#20
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
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