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Patient derived xenograft PDX

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https://www.readbyqxmd.com/read/29774094/selumetinib-based-therapy-in-uveal-melanoma-patient-derived-xenografts
#1
Didier Decaudin, Rania El Botty, Béré Diallo, Gerald Massonnet, Justine Fleury, Adnan Naguez, Chloé Raymondie, Emma Davies, Aaron Smith, Joanne Wilson, Colin Howes, Paul D Smith, Nathalie Cassoux, Sophie Piperno-Neumann, Sergio Roman-Roman, Fariba Némati
The prognosis of metastatic uveal melanoma (UM) is among the worst of all human cancers. The identification of near-ubiquitous GNAQ/GNA11 mutations and the activation of MAPK signaling in UM have raised hopes of more effective, targeted therapies, based on MEK inhibition, for example. We evaluated the potential of drug combinations to increase the efficacy of the MEK inhibitor selumetinib (AZD6244, ARRY-142886), in UM cell lines and Patient-Derived Xenografts. We first evaluated the combination of selumetinib and DTIC...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29768500/clinically-relevant-inflammatory-breast-cancer-patient-derived-xenograft-derived-ex-vivo-model-for-evaluation-of-tumor-specific-therapies
#2
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/29765518/increasing-aggressiveness-of-patient-derived-xenograft-models-of-cervix-carcinoma-during-serial-transplantation
#3
Catherine S Wegner, Anette Hauge, Lise Mari K Andersen, Ruixia Huang, Trude G Simonsen, Jon-Vidar Gaustad, Einar K Rofstad
Four patient-derived xenograft (PDX) models (BK-12, ED-15, HL-16, LA-19) of carcinoma of the uterine cervix have been developed in our laboratory, and their stability during serial transplantation in vivo was investigated in this study. Two frozen cell stocks were established, one from xenografted tumors in passage 2 (early generation) and the other from xenografted tumors transplanted serially in mice for approximately two years (late generation), and the biology of late generation tumors was compared with that of early generation tumors...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29760161/ctcf-boundary-remodels-chromatin-domain-and-drives-aberrant-hox-gene-transcription-in-acute-myeloid-leukemia
#4
Huacheng Luo, Fei Wang, Jie Zha, Haoli Li, Bowen Yan, Qinghua Du, Fengchun Yang, Amin Sobh, Christopher Vulpe, Leylah Drusbosky, Christopher Cogle, Iouri Chepelev, Bing Xu, Stephen D Nimer, Jonathan Licht, Yi Qiu, Baoan Chen, Mingjiang Xu, Suming Huang
HOX gene dysregulation is a common feature of acute myeloid leukemia (AML). The molecular mechanisms underlying aberrant HOX gene expression and associated AML pathogenesis remain unclear. The nuclear protein CCCTC-binding factor (CTCF), when bound to insulator sequences, constrains temporal HOX gene expression patterns within confined chromatin domains for normal development. Here, we employed targeted pooled CRISPR-Cas9 knockout library screening to interrogate the function of CTCF boundaries in the HOX gene loci...
May 14, 2018: Blood
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#5
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
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
#6
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
#7
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/29748182/a-pdx-organoid-biobank-of-advanced-prostate-cancers-captures-genomic-and-phenotypic-heterogeneity-for-disease-modeling-and-therapeutic-screening
#8
Michael L Beshiri, Caitlin M Tice, Crystal Tran, Holly M Nguyen, Adam G Sowalsky, Supreet Agarwal, Keith H Jansson, Qi Yang, Kerry A McGowen, Juan Juan Yin, Aian Neil Alilin, Fatima H Karzai, William Dahut, Eva Corey, Kathleen Kelly
PURPOSE: Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models   that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29743053/pdxliver-a-database-of-liver-cancer-patient-derived-xenograft-mouse-models
#9
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/29735551/novel-richter-s-syndrome-xenograft-models-to-study-genetic-architecture-biology-and-therapy-responses
#10
Tiziana Vaisitti, Esteban Braggio, John N Allan, Francesca Arruga, Sara Serra, Alberto Zamò, Wayne Tam, Amy Chadburn, Richard R Furman, Silvia Deaglio
Richter's syndrome (RS) represents the evolution of chronic lymphocytic leukemia into an aggressive tumor, most commonly diffuse large B cell lymphoma. The lack of in vitro and in vivo models has severely hampered drug testing in a disease that is poorly responsive to common chemo-immunotherapeutic combinations as well as to novel kinase inhibitors. Here we report for the first time the establishment and genomic characterization of two patient-derived tumor xenograft models of RS, RS9737 and RS1316. RS xenografts were genetically, morphologically and phenotypically stable and similar to the corresponding primary tumor...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29734434/molecular-and-pathological-evaluation-of-cryopreserved-colorectal-cancerous-tissues-effects-of-freezing-method-and-cryoprotection
#11
W Liang, F Ding, M X Wang, B L Liu, M Sun
BACKGROUND: Snap freezing and RNAlater stabilization are methods that were wildly used in biospecimen depositories to preserve cancer tissues. Both methods have its own limitations. An ideal method for preservation of diseased tissues should permit the broader uses of stored tissue samples, including not just for molecular diagnostic analysis, histopathological evaluation, but also for the recovery of functional live cells and tissues as well as the regeneration of patient-derived xenograft (PDX) models for the drug screening study...
July 2017: Cryo Letters
https://www.readbyqxmd.com/read/29721203/patient-derived-xenografts-pdx-predict-an-effective-heparanase-based-therapy-for-lung-cancer
#12
Amit Katz, Uri Barash, Ilanit Boyango, Sari Feld, Yaniv Zohar, Edward Hammond, Neta Ilan, Ran Kremer, Israel Vlodavsky
Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. HS mimicking compounds that inhibit heparanase enzymatic activity were examined in numerous preclinical cancer models. While these studies utilized established tumor cell lines, the current study utilized, for the first time, patient-derived xenografts (PDX) which better resemble the behavior and drug responsiveness of a given cancer patient...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721063/photoacoustic-imaging-as-an-early-biomarker-of-radio-therapeutic-efficacy-in-head-and-neck-cancer
#13
Laurie J Rich, Austin Miller, Anurag K Singh, Mukund Seshadri
The negative impact of tumor hypoxia on radiotherapeutic efficacy is well recognized. However, an easy to use, reliable imaging method for assessment of tumor oxygenation in routine clinical practice remains elusive. Photoacoustic imaging (PAI) is a relatively new imaging technique that utilizes a combination of light and ultrasound (US) to enable functional imaging of tumor hemodynamic characteristics in vivo . Several clinical trials are currently evaluating the utility of PAI in cancer detection for breast, thyroid, and prostate cancer...
2018: Theranostics
https://www.readbyqxmd.com/read/29720672/fty720-decreases-tumorigenesis-in-group-3-medulloblastoma-patient-derived-xenografts
#14
Evan F Garner, Adele P Williams, Laura L Stafman, Jamie M Aye, Elizabeth Mroczek-Musulman, Blake P Moore, Jerry E Stewart, Gregory K Friedman, Elizabeth A Beierle
Group 3 tumors account for 28% of medulloblastomas and have the worst prognosis. FTY720, an immunosuppressant currently approved for treatment of multiple sclerosis, has shown antitumor effects in several human cancer cell lines. We hypothesized that treatment with FTY720 (fingolimod) would decrease tumorigenicity in medulloblastoma patient-derived xenografts (PDXs). Three Group 3 medulloblastoma PDXs (D341, D384 and D425) were utilized. Expression of PP2A and its endogenous inhibitors I2PP2A and CIP2A was detected by immunohistochemistry and immunoblotting...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29720484/ubiquitin-dependent-degradation-of-cdk2-drives-the-therapeutic-differentiation-of-aml-by-targeting-prdx2
#15
Meidan Ying, Xuejing Shao, Hui Jing, Yujia Liu, Xiaotian Qi, Ji Cao, Yingqian Chen, Senfeng Xiang, Hua Song, Ronggui Hu, Guoqing Wei, Bo Yang, Qiaojun He
A distinct hallmark of acute myeloid leukemia (AML) is the arrest of leukemic myeloblasts at an immature stage of development. Therapies that overcome differentiation arrest have emerged as a powerful strategy for treating AML, but targeting leukemia differentiation remains challenging, mainly because of an incomplete mechanistic understanding of the process. Here, we unveil a new role for cyclin-dependent kinase 2 (CDK2) in blocking myeloid differentiation in AMLs. We show that among several interphase CDKs, only CDK2 undergoes ubiquitin-dependent proteasome degradation, which is accompanied by AML cell differentiation...
May 2, 2018: Blood
https://www.readbyqxmd.com/read/29719259/the-receptor-tyrosine-kinase-axl-is-required-at-multiple-steps-of-the-metastatic-cascade-during-her2-positive-breast-cancer-progression
#16
Marie-Anne Goyette, Stéphanie Duhamel, Léo Aubert, Ariane Pelletier, Paul Savage, Marie-Pier Thibault, Radia Marie Johnson, Peter Carmeliet, Mark Basik, Louis Gaboury, William J Muller, Morag Park, Philippe P Roux, Jean-Philippe Gratton, Jean-François Côté
AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. In the current study, we report AXL expression in HER2-positive (HER2+ ) breast cancers where it correlates with poor patient survival. Using murine models of HER2+ breast cancer, Axl, but not its ligand Gas6, was found to be essential for metastasis. We determined that AXL is required for intravasation, extravasation, and growth at the metastatic site. We found that AXL is expressed in HER2+ cancers displaying epithelial-to-mesenchymal transition (EMT) signatures where it contributes to sustain EMT...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29715275/hedgehog-inhibition-mediates-radiation-sensitivity-in-mouse-xenograft-models-of-human-esophageal-adenocarcinoma
#17
Jennifer Teichman, Lorin Dodbiba, Henry Thai, Andrew Fleet, Trevor Morey, Lucy Liu, Madison McGregor, Dangxiao Cheng, Zhuo Chen, Gail Darling, Yonathan Brhane, Yuyao Song, Osvaldo Espin-Garcia, Wei Xu, Hala Girgis, Joerg Schwock, Helen MacKay, Robert Bristow, Laurie Ailles, Geoffrey Liu
BACKGROUND: The Hedgehog (Hh) signaling pathway is active in esophageal adenocarcinoma (EAC). We used a patient-derived murine xenograft (PDX) model of EAC to evaluate tumour response to conventional treatment with radiation/chemoradiation with or without Hh inhibition. Our goal was to determine the potential radioresistance effects of Hh signaling and radiosensitization by Hh inhibitors. METHODS: PDX models were treated with radiation, chemotherapy or combined chemoradiation...
2018: PloS One
https://www.readbyqxmd.com/read/29715102/pharmacokinetics-biodistribution-and-toxicity-evaluation-of-anti-sema3a-f11-in-in-vivo-models
#18
Jaehyun Lee, Donggeon Kim, Eunju Son, Su-Ji Yoo, Jason K Sa, Yong Jae Shin, Yeup Yoon, DO-Hyun Nam
BACKGROUND/AIM: The aim of our study was to investigate the pharmacokinetics (PK), tissue distribution and toxicity of F11 antibody to semaphorin 3A in mouse models and explore its anti-angiogenic and tumor-inhibitory effect. MATERIALS AND METHODS: Patient-derived xenograft (PDX) models were established via subcutaneous implantation of glioblastoma multiforme (GBM) cells and treated with F11. RESULTS: F11 significantly attenuated tumor growth and angiogenesis in the GBM PDX model...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29708513/dna-methyltransferase-expression-in-triple-negative-breast-cancer-predicts-sensitivity-to-decitabine
#19
Jia Yu, Bo Qin, Ann M Moyer, Somaira Nowsheen, Tongzheng Liu, Sisi Qin, Yongxian Zhuang, Duan Liu, Shijia W Lu, Krishna R Kalari, Daniel W Visscher, John A Copland, Sarah A McLaughlin, Alvaro Moreno-Aspitia, Donald W Northfelt, Richard J Gray, Zhenkun Lou, Vera J Suman, Richard Weinshilboum, Judy C Boughey, Matthew P Goetz, Liewei Wang
Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis that lacks targeted therapies, especially in patients with chemotherapy-resistant disease. Since DNA methylation-induced silencing of tumor suppressors is common in cancer, reversal of promoter DNA hypermethylation by 5-aza-2'-deoxycytidine (decitabine), an FDA-approved DNA methyltransferase (DNMT) inhibitor, has proven effective in treating hematological neoplasms. However, its antitumor effect varies in solid tumors, stressing the importance of identifying biomarkers predictive of therapeutic response...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29706843/nirf-optical-pet-dual-modal-imaging-of-hepatocellular-carcinoma-using-heptamethine-carbocyanine-dye
#20
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
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