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Patient derived xenograft PDX

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https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#1
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29142067/jq1-induces-dna-damage-and-apoptosis-and-inhibits-tumor-growth-in-a-patient-derived-xenograft-model-of-cholangiocarcinoma
#2
Patrick L Garcia, Aubrey L Miller, Tracy L Gamblin, Leona N Council, John D Christein, J Pablo Arnoletti, Marty J Heslin, Sushanth Reddy, Joseph H Richardson, Xiangqin Cui, Robert C A M van Waardenburg, James E Bradner, Eddy S Yang, Karina J Yoon
Cholangiocarcinoma (CCA) is a fatal disease with a five-year survival of <30%. For a majority of patients chemotherapy is the only therapeutic option, and virtually all patients relapse. Gemcitabine is the frontline agent for treatment of CCA. Patients treated with gemcitabine monotherapy survive ~8 months. Combining this agent with cisplatin increases survival by ~3 months, but neither regimen produces durable remissions. The molecular etiology of this disease is poorly understood. To facilitate molecular characterization and development of effective therapies for CCA, we established a panel of patient-derived xenograft (PDX) models of CCA...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29141689/patient-derived-xenograft-in-zebrafish-embryos-a-new-platform-for-translational-research-in-gastric-cancer
#3
Jia-Qi Wu, Jing Zhai, Chong-Yong Li, Ai-Min Tan, Ping Wei, Li-Zong Shen, Ming-Fang He
BACKGROUND: Gastric cancer (GC) is among the most commonly cancer occurred in Asian, especially in China. With its high heterogeneity and few of validated drug targets, GC remains to be one of the most under explored areas of precision medicine. In this study, we aimed to establish an in vivo patient-derived xenograft (PDX) model based on zebrafish (Danio rerio) embryos, allowing for a rapid analysis of the angiogenic and invasive potentials, as well as a fast drug sensitivity testing...
November 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29141225/a-comprehensive-patient-derived-xenograft-collection-representing-the-heterogeneity-of-melanoma
#4
Clemens Krepler, Katrin Sproesser, Patricia Brafford, Marilda Beqiri, Bradley Garman, Min Xiao, Batool Shannan, Andrea Watters, Michela Perego, Gao Zhang, Adina Vultur, Xiangfan Yin, Qin Liu, Ioannis N Anastopoulos, Bradley Wubbenhorst, Melissa A Wilson, Wei Xu, Giorgos Karakousis, Michael Feldman, Xiaowei Xu, Ravi Amaravadi, Tara C Gangadhar, David E Elder, Lauren E Haydu, Jennifer A Wargo, Michael A Davies, Yiling Lu, Gordon B Mills, Dennie T Frederick, Michal Barzily-Rokni, Keith T Flaherty, Dave S Hoon, Michael Guarino, Joseph J Bennett, Randall W Ryan, Nicholas J Petrelli, Carol L Shields, Mizue Terai, Takami Sato, Andrew E Aplin, Alexander Roesch, David Darr, Steve Angus, Rakesh Kumar, Ensar Halilovic, Giordano Caponigro, Sebastien Jeay, Jens Wuerthner, Annette Walter, Matthias Ocker, Matthew B Boxer, Lynn Schuchter, Katherine L Nathanson, Meenhard Herlyn
Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29137269/local-blockage-of-self-sustainable-erythropoietin-signaling-suppresses-tumor-progression-in-non-small-cell-lung-cancer
#5
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/29129044/anti-sema3a-antibody-a-novel-therapeutic-agent-to-suppress-gbm-tumor-growth
#6
Jaehyun Lee, Yong Jae Shin, Kyoungmin Lee, Hee Jin Cho, Jason K Sa, Sang-Yun Lee, Seok-Hyung Kim, Jeongwu Lee, Yeup Yoon, Do-Hyun Nam
Purpose: Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression...
November 10, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29127379/rspo3-antagonism-inhibits-growth-and-tumorigenicity-in-colorectal-tumors-harboring-common-wnt-pathway-mutations
#7
Marcus M Fischer, V Pete Yeung, Fiore Cattaruzza, Rajaa Hussein, Wan-Ching Yen, Christopher Murriel, James W Evans, Gilbert O'Young, Alayne L Brunner, Min Wang, Jennifer Cain, Belinda Cancilla, Ann Kapoun, Timothy Hoey
Activating mutations in the Wnt pathway are a characteristic feature of colorectal cancer (CRC). The R-spondin (RSPO) family is a group of secreted proteins that enhance Wnt signaling and RSPO2 and RSPO3 gene fusions have been reported in CRC. We have previously shown that Wnt pathway blockers exhibit potent combinatorial activity with taxanes to inhibit tumor growth. Here we show that RSPO3 antagonism synergizes with paclitaxel based chemotherapies in patient-derived xenograft models (PDX) with RSPO3 fusions and in tumors with common CRC mutations such as APC, β-catenin, or RNF43...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29125731/imaging-pd-l1-expression-with-immunopet
#8
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/29107218/dual-targeting-wnt-and-upa-receptors-using-peptide-conjugated-ultra-small-nanoparticle-drug-carriers-inhibited-cancer-stem-cell-phenotype-in-chemo-resistant-breast-cancer
#9
Jasmine Miller-Kleinhenz, Xiangxue Guo, Weiping Qian, Hongyu Zhou, Erica N Bozeman, Lei Zhu, Xin Ji, Y Andrew Wang, Toncred Styblo, Ruth O'Regan, Hui Mao, Lily Yang
Heterogeneous tumor cells, high incidence of tumor recurrence, and decrease in overall survival are the major challenges for the treatment of chemo-resistant breast cancer. Results of our study showed differential chemotherapeutic responses among breast cancer patient derived xenograft (PDX) tumors established from the same patients. All doxorubicin(Dox)-resistant tumors expressed higher level of cancer stem-like cell biomarkers, including CD44, Wnt and its receptor LRP5/6, relative to Dox-sensitive tumors...
October 21, 2017: Biomaterials
https://www.readbyqxmd.com/read/29100521/dce-mri-of-patient-derived-xenograft-models-of-uterine-cervix-carcinoma-associations-with-parameters-of-the-tumor-microenvironment
#10
Anette Hauge, Catherine S Wegner, Jon-Vidar Gaustad, Trude G Simonsen, Lise Mari K Andersen, Einar K Rofstad
BACKGROUND: Abnormalities in the tumor microenvironment are associated with resistance to treatment, aggressive growth, and poor clinical outcome in patients with advanced cervical cancer. The potential of dynamic contrast-enhanced (DCE) MRI to assess the microvascular density (MVD), interstitial fluid pressure (IFP), and hypoxic fraction of patient-derived cervical cancer xenografts was investigated in the present study. METHODS: Four patient-derived xenograft (PDX) models of squamous cell carcinoma of the uterine cervix (BK-12, ED-15, HL-16, and LA-19) were subjected to Gd-DOTA-based DCE-MRI using a 7...
November 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29100343/establishment-and-characterization-of-patient-derived-xenograft-models-of-gastrointestinal-stromal-tumor-resistant-to-standard-tyrosine-kinase-inhibitors
#11
Young-Soon Na, Min-Hee Ryu, Changhoon Yoo, Ju-Kyung Lee, Jung Min Park, Chae-Won Lee, Sun Young Lee, Young-Kyoung Shin, Ja-Lok Ku, Sung-Min Ahn, Yoon-Koo Kang
Gastrointestinal stromal tumors (GISTs) with KIT or platelet-derived growth factor receptor alpha (PDGFRa) oncogenic driver gene mutations, respond to tyrosine kinase inhibitors (TKIs) including imatinib, sunitinib, and regorafenib. However, most patients develop TKI resistance; therefore, novel agents are required. We established three TKI-resistant GIST patient-derived xenograft (PDX) models for effective drug development. These were PDX models harboring primary and secondary KIT and additional mutations; KIT exon 11 (p...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093017/a-population-of-heterogeneous-breast-cancer-patient-derived-xenografts-demonstrate-broad-activity-of-parp-inhibitor-in-brca1-2-wild-type-tumors
#12
Kurt W Evans, Erkan Yuca, Argun Akcakanat, Stephen M Scott, Natalia Paez Arango, Xiaofeng Zheng, Ken Chen, Coya Tapia, Emily Tarco, Agda K Eterovic, Dalliah M Black, Jennifer K Litton, Timothy A Yap, Debu Tripathy, Gordon B Mills, Funda Meric-Bernstam
Background: Breast cancer patients who do not respond to neoadjuvant therapy have a poor prognosis. There is a pressing need for novel targets and models for preclinical testing. Here we report characterization of breast cancer patient-derived xenografts (PDX) largely generated from residual tumors following neoadjuvant chemotherapy.Experimental Design: PDXs were derived from surgical samples of primary or locally recurrent tumors. Normal and tumor DNA sequencing, RNASeq, and reverse phase protein arrays (RPPA) were performed...
November 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29092942/pdx-mi-minimal-information-for-patient-derived-tumor-xenograft-models
#13
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
#14
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/29089295/patient-derived-xenografts-evolve-differently-than-tumors
#15
(no author information available yet)
In a study of 1,110 patient-derived xenografts (PDX) from 24 cancer types, researchers found that the genomic landscape of these tools changes dramatically over time. Some of the genetic changes observed have been associated with drug sensitivity in previous studies, raising questions about the use of PDXs to predict drug response in personalized medicine.
October 31, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29079660/dual-mtor-kinases-mln0128-inhibitor-sensitizes-hr-her2-breast-cancer-patient-derived-xenografts-to-trastuzumab-or-fulvestrant
#16
Pei-Yin Hsu, Victoria Shang Wu, Noriko Kanaya, Karineh Petrossian, Hang-Kai Hsu, Duc Nguyen, Daniel Schmolze, Masaya Kai, Chun-Yu Liu, Hannah Lu, Peiguo Chu, Courtney A Vito, Laura Kruper, Joanne Mortimer, Shiuan Chen
PURPOSE: Therapeutic strategies against hormonal receptor-positive (HR+)/HER2+ breast cancers with poor response to trastuzumab need to be optimized. EXPERIMENTAL DESIGN: Two HR+/HER2+ patient-derived xenograft (PDX) models named as COH-SC1 and COH-SC31 were established to explore targeted therapies for HER2+ breast cancers. RNA sequencing and RPPA (reverse phase protein array) analyses were conducted to decipher molecular features of the two PDXs and define the therapeutic strategy of interest, validated by in vivo drug efficacy examination and in vitro cell proliferation analysis...
October 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29068216/tumor-progression-of-non-small-cell-lung-cancer-controlled-by-albumin-and-micellar-nanoparticles-of-itraconazole-a-multi-target-angiogenesis-inhibitor
#17
Ling Zhang, Zhengsheng Liu, Kuan Yang, Chao Kong, Chun Liu, Huijun Chen, Jinfeng Huang, Feng Qian
Itraconazole (ITA), an old and widely-prescribed antifungal drug with excellent safety profile, has more recently been demonstrated to be a multi-target anti-angiogenesis agent affecting multiple angiogenic stimulatory signals and pathways, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, and mammalian target of rapamycin (mTOR). In this study, we developed two nanoparticle formulations, i.e., polymer micelles (IP2K) and albumin nanoparticles (IBSA), to solubilize the extremely hydrophobic and insoluble ITA to allow intravenous administration and pharmacokinetics (PK)/pharmacodynamics (PD) comparisons...
October 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29054984/overcoming-resistance-to-cetuximab-with-honokiol-a-small-molecule-polyphenol
#18
Hannah E Pearson, Mari Iida, Rachel A Orbuch, Nellie K McDaniel, Kwangok P Nickel, Randall J Kimple, Jack Arbiser, Deric L Wheeler
Overexpression and activation of the Epidermal Growth Factor Receptor (EGFR) have been linked to poor prognosis in several human cancers. Cetuximab is a monoclonal antibody against EGFR, that is used for the treatment in head and neck squamous cell carcinoma (HNSCC) and metastatic colorectal cancer. Unfortunately, most tumors have intrinsic or acquire resistance to cetuximab during the course of therapy. Honokiol is a natural compound found in the bark and leaves of the Chinese Magnolia tree and is established to have several anti-cancer properties without appreciable toxicity...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29039610/establishment-of-a-human-primary-pancreatic-cancer-mouse-model-to-examine-and-investigate-gemcitabine-resistance
#19
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/29033371/a-small-molecule-inhibitor-of-the-%C3%AE-catenin-tcf4-interaction-suppresses-colorectal-cancer-growth-in-vitro-and-in-vivo
#20
Seung Ho Shin, Do Young Lim, Kanamata Reddy, Margarita Malakhova, Fangfang Liu, Ting Wang, Mengqiu Song, Hanyong Chen, Ki Beom Bae, Joohyun Ryu, Kangdong Liu, Mee-Hyun Lee, Ann M Bode, Zigang Dong
Colorectal cancer is associated with aberrant activation of the Wnt pathway. β-Catenin plays essential roles in the Wnt pathway by interacting with T-cell factor 4 (TCF4) to transcribe oncogenes. We synthesized a small molecule, referred to as HI-B1, and evaluated signaling changes and biological consequences induced by the compound. HI-B1 inhibited β-catenin/TCF4 luciferase activity and preferentially caused apoptosis of cancer cells in which the survival is dependent on β-catenin. The formation of the β-catenin/TCF4 complex was disrupted by HI-B1 due to the direct interaction of HI-B1 with β-catenin...
September 27, 2017: EBioMedicine
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