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https://www.readbyqxmd.com/read/28635650/the-application-of-heptamethine-cyanine-dye-dz-1-and-indocyanine-green-for-imaging-and-targeting-in-xenograft-models-of-hepatocellular-carcinoma
#1
Caiqin Zhang, Yong Zhao, He Zhang, Xue Chen, Ningning Zhao, Dengxu Tan, Hai Zhang, Changhong Shi
Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28633632/antagonizing-mir-455-3p-inhibits-chemoresistance-and-aggressiveness-in-esophageal-squamous-cell-carcinoma
#2
Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li
BACKGROUND: The plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways. METHODS: A chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness...
June 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28629523/significance-of-erythropoietin-receptor-antagonist-emp9-in-cancers
#3
Yoshiko Yasuda, Mitsugu Fujita
We have clarified that cancer cells express their own erythropoietin (Epo) and its receptor (EpoR) mRNA levels, and the respective proteins, which are under the control of Epo-EpoR signaling. Then we explored to inhibit the Epo-EpoR signaling with an EpoR antagonist Epo mimetic peptide 9 (EMP9) that is a derivative of an Epo-mimicking peptide EMP1. In the study of the cancer cell lines in vitro, rhEpo accelerated the cancer cell growth, whereas the EMP9 inhibited the cell growth along with the inhibition of STAT5 tyrosine phosphorylation...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28625978/the-alkylating-chemotherapeutic-temozolomide-induces-metabolic-stress-in-idh1-mutant-cancers-and-potentiates-nad-depletion-mediated-cytotoxicity
#4
Kensuke Tateishi, Fumi Higuchi, Julie Miller, Mara V A Koerner, Nina Lelic, Ganesh M Shankar, Shota Tanaka, David E Fisher, Tracy Batchelor, A John Iafrate, Hiroaki Wakimoto, Andrew S Chi, Daniel P Cahill
IDH1-mutant gliomas are dependent upon the canonical coenzyme nicotinamide adenine dinucleotide (NAD+) for survival. It is known that Poly(ADP-ribose) polymerase (PARP) activation consumes NAD+ during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD+ biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide (TMZ) could potentiate NAD+ depletion-mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of TMZ on NAD+ metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to TMZ, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD+ biosynthesis...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28625826/drug-discovery-and-therapeutic-delivery-for-the-treatment-of-b-and-t-cell-tumors
#5
Regan Stephenson, Ankur Singh
Hematological malignancies manifest as lymphoma, leukemia, and myeloma, and remain a burden on society. From initial therapy to endless relapse-related treatment, societal burden is felt not only in the context of healthcare cost, but also in the compromised quality of life of patients. Long-term therapeutic strategies have become the standard in keeping hematological malignancies at bay as these cancers develop resistance to each round of therapy with time. As a result, there is a continual need for the development of new drugs to combat resistant disease in order to prolong patient life, if not to produce a cure...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28625518/histone-chaperone-asf1a-predicts-poor-outcomes-for-patients-with-gastrointestinal-cancer-and-drives-cancer-progression-by-stimulating-transcription-of-%C3%AE-catenin-target-genes
#6
Xiuming Liang, Xiaotian Yuan, Jingya Yu, Yujiao Wu, Kailin Li, Chao Sun, Shuyan Li, Li Shen, Feng Kong, Jihui Jia, Magnus Björkholm, Dawei Xu
Epigenetic mechanisms play a key role in gastrointestinal cancer (GIC) development and progression, and most studies have been focused on aberrant DNA methylation and histone modifying enzymes. However, the histone H3-H4 chaperone ASF1A is an important factor regulating chromatin assembling and gene transcription, while it is currently unclear whether ASF1A is involved in cancer pathogenesis. The present study is thus designed to address this issue. Here we showed that ASF1A expression was widespread in GIC-derived cell lines and up-regulated in primary GIC...
June 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28625393/establishment-and-characterization-of-uterine-sarcoma-and-carcinosarcoma-patient-derived-xenograft-models
#7
Tine Cuppens, Jeroen Depreeuw, Daniela Annibali, Debby Thomas, Els Hermans, Ellen Gommé, Xuan Bich Trinh, David Debruyne, Philippe Moerman, Diether Lambrechts, Frédéric Amant
OBJECTIVE: Uterine sarcomas (US) and carcinosarcomas (CS) are rare, aggressive cancers. The lack of reliable preclinical models hampers the search for new treatment strategies and predictive biomarkers. To this end, we established and characterized US and CS patient-derived xenograft (PDX) models. METHODS: Tumor fragments of US and CS were subcutaneously implanted into immunocompromised mice. Engrafted xenograft and original tumors were compared by means of histology, immunohistochemistry, whole-genome low-coverage sequencing for copy number variations, and RNA sequencing...
June 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28624783/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#8
Liyong Zhang, Yan Wang, Mohammad H Rashid, Min Liu, Kartik Angara, Nahid F Mivechi, Nita J Maihle, Ali S Arbab, Lan Ko
Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 (PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198+ pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623128/targeting-pi3k-akt-mtor-by-ly3023414-inhibits-human-skin-squamous-cell-carcinoma-cell-growth-in-vitro-and-in-vivo
#9
Ying Zou, Minggai Ge, Xuemin Wang
Abnormal activation of PI3K-AKT-mTOR signaling is detected in human skin squamous cell carcinoma (SCC). LY3023414 is a novel, potent, and orally bio-available PI3K-AKT-mTOR inhibitor. Its activity against human skin SCC cells was tested. We demonstrated that LY3023414 was cytotoxic when added to established (A431 line) and primary (patient-derived) human skin SCC cells. LY3023414 induced G0/1-S arrest and inhibited proliferation of skin SCC cells. Moreover, LY3023414 induced activation of caspase-3/-9 and apoptosis in skin SCC cells...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28622397/looking-for-the-most-suitable-orthotopic-retinoblastoma-mouse-model-in-order-to-characterize-the-tumoral-development
#10
Stéphanie Lemaitre, Florent Poyer, Sergio Marco, Paul Fréneaux, François Doz, Isabelle Aerts, Laurence Desjardins, Nathalie Cassoux, Carole D Thomas
Purpose: Because retinoblastoma therapies have many adverse effects, new approaches must be developed and evaluated on animal models. We describe orthotopic xenograft models of retinoblastoma using different strains of mice, suitable for this purpose. Methods: Human retinoblastoma tumors were established on immunodeficient mice by subcutaneous engraftment of tumors from enucleated eyes. The orthotopic model was obtained by subretinal injections of suspension cells into the right eye of immunodeficient (Swiss-nude, severe combined immunodeficiency [SCID]) and immunocompetent mice (C57BL/6N, B6Albino)...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28622299/a-circular-rna-promotes-tumorigenesis-by-inducing-c-myc-nuclear-translocation
#11
Qi Yang, William W Du, Nan Wu, Weining Yang, Faryal Mehwish Awan, Ling Fang, Jian Ma, Xiangmin Li, Yan Zeng, Zhenguo Yang, Jun Dong, Azam Khorshidi, Burton B Yang
Circular RNAs (circRNAs) are a subclass of noncoding RNAs widely expressed in mammalian cells. We report here the tumorigenic capacity of a circRNA derived from angiomotin-like1 (circ-Amotl1). Circ-Amotl1 is highly expressed in patient tumor samples and cancer cell lines. Single-cell inoculations using circ-Amotl1-transfected tumor cells showed a 30-fold increase in proliferative capacity relative to control. Agarose colony-formation assays similarly revealed a 142-fold increase. Tumor-take rate in nude mouse xenografts using 6-day (219 cells) and 3-day (9 cells) colonies were 100%, suggesting tumor-forming potential of every cell...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28622068/salmonella-typhimurium-a1-r-targeting-of-a-chemotherapy-resistant-braf-v600e-melanoma-in-a-patient-derived-orthotopic-xenograft-pdox-model-is-enhanced-in-combination-with-either-vemurafenib-temozlomide
#12
Kei Kawaguchi, Kentaro Igarashi, Bartosz Chmielowski, Takashi Murakami, Tasuku Kiyuna, Ming Zhao, Yong Zhang, Scott D Nelson, Tara A Russell, Sarah M Dry, Arun S Singh, Yunfeng Li, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
A metastatic melanoma obtained from the right chest wall of a patient was previously established orthotopically in the right chest wall of nude mice as a patient-derived orthotopic xenograft (PDOX) model. We previously showed that the combination of tumor targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) and chemotherapy was highly effective against the melanoma PDOX. In the present study, we investigated the mechanism of the high efficacy of this combination. Two weeks after implantation, 40 PDOX mouse models were randomized into four groups of 10 mice each: untreated control (n = 10); treated with S...
June 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28619982/jak1-2-and-bcl2-inhibitors-synergize-to-counteract-bone-marrow-stromal-cell-induced-protection-of-aml
#13
Riikka Karjalainen, Tea Pemovska, Mihaela Popa, Minxia Liu, Komal K Javarappa, Muntasir M Majumder, Bhagwan Yadav, David Tamborero, Jing Tang, Dmitrii Bychkov, Mika Kontro, Alun Parsons, Minna Suvela, Mireia Mayoral Safont, Kimmo Porkka, Tero Aittokallio, Olli Kallioniemi, Emmet McCormack, Bjørn T Gjertsen, Krister Wennerberg, Jonathan Knowles, Caroline A Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be due to the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the impact of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28619968/breast-cancer-neoantigens-can-induce-cd8-t-cell-responses-and-antitumor-immunity
#14
Xiuli Zhang, Samuel Kim, Jasreet Hundal, John M Herndon, Shunqiang Li, Allegra A Petti, Savas D Soysal, Lijin Li, Michael D McLellan, Jeremy Hoog, Tina Primeau, Nancy Myers, Tammi L Vickery, Mark Sturmoski, Ian S Hagemann, Christopher A Miller, Matthew J Ellis, Elaine R Mardis, Ted Hansen, Timothy P Fleming, Peter Goedegebuure, William E Gillanders
Next-generation sequencing technologies have provided insights into the biology and mutational landscape of cancer. Here we evaluate the relevance of cancer neoantigens in human breast cancers. Using patient-derived xenografts from three patients with advanced breast cancer (xenografts were designated as WHIM30, WHIM35, and WHIM37), we sequenced exomes of tumor and patient-matched normal cells. We identified 2091 (WHIM30), 354 (WHIM35), and 235 (WHIM37) nonsynonymous somatic mutations. A computational analysis identified and prioritized HLA class I-restricted candidate neoantigens expressed in the dominant tumor clone...
June 15, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28619757/cdk4-6-inhibitors-sensitize-rb-positive-sarcoma-cells-to-wee1-kinase-inhibition-through-reversible-cell-cycle-arrest
#15
Ashleigh M Francis, Angela Alexander, Yanna Liu, Smruthi Vijayaraghavan, Kwang Hui Low, Dong Yang, Tuyen Bui, Neeta Somaiah, Vinod Ravi, Khandan Keyomarsi, Kelly K Hunt
Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28619753/inhibition-of-hsp90-suppresses-pi3k-akt-mtor-signaling-and-has-antitumor-activity-in-burkitt-lymphoma
#16
Lisa Giulino-Roth, Herman J Van Besien, Tanner Dalton, Jennifer E Totonchy, Anna Rodina, Tony Taldone, Alexander Bolaender, Hediye Erdjument-Bromage, Jouliana Sadek, Amy Chadburn, Matthew J Barth, Filemon S Dela Cruz, Allison Rainey, Andrew L Kung, Gabriela Chiosis, Ethel Cesarman
Heat shock protein 90 (Hsp90) is a molecular chaperone that protects proteins, including oncogenic signaling complexes, from proteolytic degradation.  PU-H71 is a next-generation Hsp90 inhibitor that preferentially targets the functionally distinct pool of Hsp90 present in tumor cells.  Tumors that are driven by the MYC oncoprotein may be particularly sensitive to PU-H71 due to the essential role of Hsp90 in the epichaperome which maintains the malignant phenotype in the setting of MYC.  Burkitt lymphoma (BL) is an aggressive B-cell lymphoma characterized by MYC dysregulation...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28619066/hepatocyte-growth-factor-produced-in-lung-fibroblasts-enhances-non-small-cell-lung-cancer-cell-survival-and-tumor-progression
#17
Nobuhiro Kanaji, Masanao Yokohira, Yuko Nakano-Narusawa, Naoki Watanabe, Katsumi Imaida, Norimitsu Kadowaki, Shuji Bandoh
BACKGROUND: The influence of lung fibroblasts on lung cancer progression is not fully understood. METHODS: Lung fibroblasts (HFL1, MRC5, and IMR90 cells) and non-small cell lung cancer (NSCLC)-derived cell lines (A549, EBC1, and HI1017) were cultured under serum-free conditions, and the resulting culture media were designated "cell-conditioned media". Cell survival (viability) was assessed by WST-1 assay. Concentrations of hepatocyte growth factor (HGF) were measured by ELISA...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28615371/a-phase-1b-open-label-multicentre-study-of-azd4547-in-patients-with-advanced-squamous-cell-lung-cancers
#18
Paul K Paik, Ronglai Shen, Michael F Berger, David Ferry, Jean-Charles Soria, Alastair Mathewson, Claire Rooney, Neil R Smith, Marie Cullberg, Elaine Kilgour, Donal Landers, Paul Frewer, A Nigel Brooks, Fabrice André
Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in ~20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with anti-tumor activity in FGFR1 amplified SQCLC cell lines and patient-derived xenografts. <br /><br />Experimental Design: Based on these data, we performed a phase 1 study of AZD4547 in patients with previously treated stage IV FGFR1 amplified SQCLCs (NCT00979134)...
June 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28615361/targeting-kras-dependent-tumors-with-azd4785-a-high-affinity-therapeutic-antisense-oligonucleotide-inhibitor-of-kras
#19
Sarah J Ross, Alexey S Revenko, Lyndsey L Hanson, Rebecca Ellston, Anna Staniszewska, Nicky Whalley, Sanjay K Pandey, Mitchell Revill, Claire Rooney, Linda K Buckett, Stephanie K Klein, Kevin Hudson, Brett P Monia, Michael Zinda, David C Blakey, Paul D Lyne, A Robert Macleod
Activating mutations in KRAS underlie the pathogenesis of up to 20% of human tumors, and KRAS is one of the most frequently mutated genes in cancer. Developing therapeutics to block KRAS activity has proven difficult, and no direct inhibitor of KRAS function has entered clinical trials. We describe the preclinical evaluation of AZD4785, a high-affinity constrained ethyl-containing therapeutic antisense oligonucleotide (ASO) targeting KRAS mRNA. AZD4785 potently and selectively depleted cellular KRAS mRNA and protein, resulting in inhibition of downstream effector pathways and antiproliferative effects selectively in KRAS mutant cells...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28611205/mouse-pdx-trial-suggests-synergy-of-concurrent-inhibition-of-raf-and-egfr-in-colorectal-cancer-with-braf-or-kras-mutations
#20
Yung-Mae M Yao, Gregory P Donoho, Philip Iversen, Youyan Zhang, Robert D Van Horn, Amelie Forest, Ruslan Novosiadly, Yue Webster, Ebert J Philip, Steven M Bray, Jason C Ting, Amit Aggarwal, James R Henry, Ramon V Tiu, Gregory D Plowman, Sheng-Bin Peng
Purpose: It is to evaluate the anti-tumor efficacy of cetuximab in combination with LSN3074753, an analogue of LY3009120 and pan-RAF inhibitor in 79 colorectal cancer (CRC) patient derived xenograft (PDX) models.<br />Experimental Design: 79 well characterized CRC PDX models were employed to conduct a single mouse per treatment group (n=1) trial.<br />Results: Consistent with clinical results, cetuximab was efficacious in wild type KRAS and BRAF PDX models, with an overall response rate (ORR) of 6...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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