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https://www.readbyqxmd.com/read/29148597/three-dimensional-analysis-of-bone-remodeling-following-ridge-augmentation-of-compromised-extraction-sockets-in-periodontitis-patients-a-randomized-controlled-study
#1
Mario Aimetti, Valeria Manavella, Lisa Corano, Elena Ercoli, Cristina Bignardi, Federica Romano
OBJECTIVES: The aim of this study was to analyze linear and volumetric hard tissue changes in severely resorbed alveolar sockets after ridge augmentation procedure and to compare them with spontaneous healing using three-dimensional cone beam computed tomography (CBCT). MATERIAL AND METHODS: Thirty patients (mean age 53.2 ± 6.3 years) requiring tooth extraction for advanced periodontitis were randomly allocated to test and control groups. The test sites were grafted using a collagenated bovine-derived bone (DBBM-C) covered with a collagen membrane, while control sites had spontaneous healing...
November 17, 2017: Clinical Oral Implants Research
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#2
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/29145505/spontaneous-development-of-epstein-barr-virus-associated-human-lymphomas-in-a-prostate-cancer-xenograft-program
#3
Alberto J Taurozzi, Ramprakash Beekharry, Michelle Wantoch, Marie-Christine Labarthe, Hannah F Walker, Robert I Seed, Matthew Simms, Greta Rodrigues, James Bradford, Geertje van der Horst, Gabri van der Pluijm, Anne T Collins
Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and the clinical heterogeneity of human prostate cancer. To overcome these limitations we propagated and characterised a new collection of patient-derived prostate cancer xenografts. Tumour fragments from 147 unsupervised, surgical prostate samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours of surgery. Histologic and molecular characterisation of xenografts was compared with patient characteristics, including androgen-deprivation therapy, and exome sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/29143983/growth-of-doxorubicin-resistant-undifferentiated-spindle-cell-sarcoma-pdox-is-arrested-by-metabolic-targeting-with-recombinant-methioninase
#4
Kentaro Igarashi, Shukuan Li, Qinghong Han, Yuying Tan, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Yunfeng Li, Scott D Nelson, Sarah M Dry, Arun S Singh, Irmina A Elliott, Tara A Russell, Mark A Eckardt, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Undifferentiated spindle-cell sarcoma (USCS) is a recalcitrant -cancer in need of individualized therapy. A high-grade USCS from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In a previous study, we evaluated the efficacy of standard first-line chemotherapy of doxorubicin (DOX), gemcitabine (GEM) combined with docetaxel (DOC), compared to pazopanib (PAZ), a multi-targeting tyrosine-kinase inhibitor, in an USCS PDOX model...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29143813/ship1-but-not-an-aml-derived-ship1-mutant-suppresses-myeloid-leukemia-growth-in-a-xenotransplantation-mouse-model
#5
M Täger, S Horn, E Latuske, P Ehm, M Schaks, M Nalaskowski, B Fehse, W Fiedler, C Stocking, J Wellbrock, M Jücker
Constitutive activation of the PI3K/AKT signaling pathway is found in ~50-70% of AML patients. The SH2-containing inositol 5-phosphatase 1 (SHIP1) is a negative regulator of PI3K/AKT signaling in hematopoietic cells. SHIP1 knockout mice develop a myeloproliferative syndrome and concomitant deletion of SHIP1 and the tumor suppressor PTEN leads to the development of lethal B-cell lymphomas. In the study presented here, we investigated the role of SHIP1 as a tumor suppressor in myeloid leukemia cells in an in vivo xenograft transplantation model...
November 16, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29142069/cat-02-106-a-site-specifically-conjugated-anti-cd22-antibody-bearing-an-mdr1-resistant-maytansine-payload-yields-excellent-efficacy-and-safety-in-preclinical-models
#6
Penelope M Drake, Adam Carlson, Jesse M McFarland, Stefanie Banas, Robyn M Barfield, Wesley Zmolek, Yun Cheol Kim, Betty C B Huang, Romas Kudirka, David Rabuka
Hematologically-derived tumors make up ~10% of all newly-diagnosed cancer cases in the U.S. Of these, the non-Hodgkin lymphoma (NHL) designation describes a diverse group of cancers that collectively rank among the top 10 most commonly diagnosed cancers worldwide. Although long-term survival trends are improving, there remains a significant unmet clinical need for treatments to help patients with relapsed or refractory disease, one cause of which is drug efflux through upregulation of xenobiotic pumps, such as MDR1...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29142067/jq1-induces-dna-damage-and-apoptosis-and-inhibits-tumor-growth-in-a-patient-derived-xenograft-model-of-cholangiocarcinoma
#7
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/29142066/characterization-of-sgn-cd123a-a-potent-cd123-directed-antibody-drug-conjugate-for-acute-myeloid-leukemia
#8
Fu Li, May Kung Sutherland, Changpu Yu, Roland B Walter, Lori Westendorf, John Valliere-Douglass, Lucy Pan, Ashley Cronkite, Django Sussman, Kerry Klussman, Michelle Ulrich, Martha E Anderson, Ivan J Stone, Weiping Zeng, Mechthild Jonas, Timothy S Lewis, Maitrayee Goswami, Sa A Wang, Peter D Senter, Che-Leung Law, Eric J Feldman, Dennis R Benjamin
Treatment choices for acute myeloid leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. Interleukin-3 receptor alpha (IL-3Rα, or CD123) is expressed on the majority of AML blasts and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here we report the generation and preclinical characterization of SGN-CD123A, an antibody-drug conjugate utilizing the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation...
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
#9
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
#10
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/29141224/genetic-and-genomic-characterization-of-462-melanoma-patient-derived-xenografts-tumor-biopsies-and-cell-lines
#11
Bradley Garman, Ioannis N Anastopoulos, Clemens Krepler, Patricia Brafford, Katrin Sproesser, Yuchao Jiang, Bradley Wubbenhorst, Ravi Amaravadi, Joseph Bennett, Marilda Beqiri, David Elder, Keith T Flaherty, Dennie T Frederick, Tara C Gangadhar, Michael Guarino, David Hoon, Giorgos Karakousis, Qin Liu, Nandita Mitra, Nicholas J Petrelli, Lynn Schuchter, Batool Shannan, Carol L Shields, Jennifer Wargo, Brandon Wenz, Melissa A Wilson, Min Xiao, Wei Xu, Xaiowei Xu, Xiangfan Yin, Nancy R Zhang, Michael A Davies, Meenhard Herlyn, Katherine L Nathanson
Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29137305/mir-93-3p-inhibition-suppresses-clear-cell-renal-cell-carcinoma-proliferation-metastasis-and-invasion
#12
Lu Wang, Guang Yang, Xiangwei Zhu, Ziqi Wang, Hongzhi Wang, Yang Bai, Pengcheng Sun, Li Peng, Wei Wei, Guang Chen, Guangbin Li, Andrey A Zamyatnin, Peter V Glybochko, Wanhai Xu
miRNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of miR-93-3p on clear cell renal cell carcinoma (ccRCC). We found that miR-93-3p is upregulated an average of 38-fold in 138 ccRCC specimens compared to matched normal kidney tissues, which correlated with poor patient outcome. miR-93-3p inhibition reduced ccRCC cell growth, invasion, and migration in vitro and in a mouse xenograft model. A search of the TargetScan, miRanda, and PicTar databases revealed that miR-93-3p is predicted to regulate pigment epithelium-derived factor (PEDF)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137269/local-blockage-of-self-sustainable-erythropoietin-signaling-suppresses-tumor-progression-in-non-small-cell-lung-cancer
#13
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/29136505/inhibition-of-trf1-telomere-protein-impairs-tumor-initiation-and-progression-in-glioblastoma-mouse-models-and-patient-derived-xenografts
#14
Leire Bejarano, Alberto J Schuhmacher, Marinela Méndez, Diego Megías, Carmen Blanco-Aparicio, Sonia Martínez, Joaquín Pastor, Massimo Squatrito, Maria A Blasco
Glioblastoma multiforme (GBM) is a deadly and common brain tumor. Poor prognosis is linked to high proliferation and cell heterogeneity, including glioma stem cells (GSCs). Telomere genes are frequently mutated. The telomere binding protein TRF1 is essential for telomere protection, and for adult and pluripotent stem cells. Here, we find TRF1 upregulation in mouse and human GBM. Brain-specific Trf1 genetic deletion in GBM mouse models inhibited GBM initiation and progression, increasing survival. Trf1 deletion increased telomeric DNA damage and reduced proliferation and stemness...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29133617/response-and-resistance-to-paradox-breaking-braf-inhibitor-in-melanomas-in-vivo-and-ex-vivo
#15
Edward J Hartsough, Curtis H Kugel, Michael J Vido, Adam C Berger, Timothy J Purwin, Allison Goldberg, Michael A Davies, Matthew J Schiewer, Karen E Knudsen, Gideon Bollag, Andrew E Aplin
FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox breaking RAF inhibitor (PLX8394) has been designed. Here we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29133593/adipose-derived-vegf-mtor-signaling-promotes-endometrial-hyperplasia-and-cancer-implications-for-obese-women
#16
Subhransu S Sahoo, Janine Lombard, Yvette Ius, Rachel O'Sullivan, Lisa G Wood, Pravin Nahar, Kenneth Simon Jaaback, Pradeep Tanwar
Obesity is responsible for increased morbidity and mortality in endometrial cancer (EC). Despite the positive correlation of body mass index (BMI) or obesity in endometrial carcinogenesis, the contribution of adipose tissue to the pathogenesis of endometrial hyperplasia and cancer is unclear. This study clarifies the role of adipocytes in the pathogenesis of EC by demonstrating that adipocyte-conditioned medium (ACM) increases proliferation, migration, and survival of EC cells compared to pre-adipocyte-conditioned medium (PACM)...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29129044/anti-sema3a-antibody-a-novel-therapeutic-agent-to-suppress-gbm-tumor-growth
#17
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
#18
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
#19
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/29118061/venetoclax-is-effective-in-small-cell-lung-cancers-with-high-bcl-2-expression
#20
Timothy L Lochmann, Konstantinos V Floros, Mitra Naseri, Krista M Powell, Wade Cook, Ryan J March, Giovanna T Stein, Patricia Greninger, Yuki Kato Maves, Laura R Saunders, Scott J Dylla, Carlotta Costa, Sosipatros A Boikos, Joel D Leverson, Andrew J Souers, Geoffrey W Krystal, Hisashi Harada, Cyril H Benes, Anthony C Faber
PURPOSE:  Small cell lung cancer (SCLC) is an often-fatal neuroendocrine carcinoma usually presenting as extensive disease, carrying a 3% five-year survival. Despite notable advances in SCLC genomics, new therapies remain elusive, largely due to a lack of druggable targets. EXPERIMENTAL DESIGN:  We used a high-throughput drug screen to identify a venetoclax sensitive SCLC sub-population, and validated the findings with multiple patient-derived xenografts of SCLC...
November 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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