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https://www.readbyqxmd.com/read/29793116/patterns-of-invasive-growth-in-malignant-gliomas-the-hippocampus-emerges-as-an-invasion-spared-brain-region
#1
Awais A Mughal, Lili Zhang, Artem Fayzullin, Andres Server, Yuping Li, Yingxi Wu, Rainer Glass, Torstein Meling, Iver A Langmoen, Trygve B Leergaard, Einar O Vik-Mo
BACKGROUND: Widespread infiltration of tumor cells into surrounding brain parenchyma is a hallmark of malignant gliomas, but little data exist on the overall invasion pattern of tumor cells throughout the brain. METHODS: We have studied the invasive phenotype of malignant gliomas in two invasive mouse models and patients. Tumor invasion patterns were characterized in a patient-derived xenograft mouse model using brain-wide histological analysis and magnetic resonance (MR) imaging...
May 21, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29790671/upregulation-of-mir-374a-promotes-tumor-metastasis-and-progression-by-downregulating-lactb-and-predicts-unfavorable-prognosis-in-breast-cancer
#2
Jun Zhang, Yuting He, Yan Yu, Xiaolong Chen, Guangying Cui, Weiwei Wang, Xiaojian Zhang, Yonggang Luo, Juan Li, Fang Ren, Zhigang Ren, Ranran Sun
Breast cancer (BRCA) is the second leading cause of cancer-related death among female worldwide. Recent studies have revealed that LACTB was frequently repressed and functioned as a bona fide new tumor suppressor in a series of cancers, including BRCA. However, the molecular mechanisms underlying LACTB dysregulation in BRCA have not been reported. In the present study, we find that LACTB is repressed in BRCA and associated with poor prognosis by BRCA tissue microarray (TMA) analysis. Moreover, we confirm that LACTB is a direct target of miR-374a, which is significantly overexpressed and associated with malignancies in BRCA...
May 23, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29790588/the-lncrna-casc9-and-rna-binding-protein-hnrnpl-form-a-complex-and-co-regulate-genes-linked-to-akt-signaling
#3
Marcel Klingenberg, Matthias Groß, Ashish Goyal, Maria Polycarpou-Schwarz, Thilo Miersch, Anne-Sophie Ernst, Jörg Leupold, Nitin Patil, Uwe Warnken, Heike Allgayer, Thomas Longerich, Peter Schirmacher, Michael Boutros, Sven Diederichs
The identification of viability-associated long non-coding RNAs (lncRNA) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied the first RNAi screening approach in hepatocellular carcinoma (HCC) cell lines to find viability-associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected CASC9 (Cancer Susceptibility 9) due to the strength of its phenotype, expression, and upregulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by CRISPR interference, single siRNA- and siPOOL-mediated depletion of CASC9...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790189/the-identification-of-a-novel-antibody-for-cd133-using-human-antibody-phage-display
#4
Paige M Glumac, Colleen L Forster, Hong Zhou, Paari Murugan, Shilpa Gupta, Aaron M LeBeau
BACKGROUND: The transmembrane glycoprotein CD133 is believed to be a marker of adult prostate stem cells and cancer stem/initiating cells. Investigating the role of CD133 in the normal biology of the prostate and in cancer is complicated by the lack of a sensitive and accurate antibody for its detection. Here, we describe the characterization of a unique antibody identified using human antibody phage display that can recognize CD133 in both formalin-fixed tissues and cell lines. METHODS: A human single-chain variable fragment (scFv) antibody phage display library possessing a diversity of 8 × 109 was screened against fully glycosylated recombinant CD133...
May 22, 2018: Prostate
https://www.readbyqxmd.com/read/29790111/potential-of-the-dual-mtor-kinase-inhibitor-azd2014-to-overcome-paclitaxel-resistance-in-anaplastic-thyroid-carcinoma
#5
Zorica Milošević, Jasna Banković, Jelena Dinić, Chrisiida Tsimplouli, Evangelia Sereti, Miodrag Dragoj, Verica Paunović, Zorka Milovanović, Marija Stepanović, Nikola Tanić, Kostantinos Dimas, Milica Pešić
PURPOSE: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate...
May 22, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29789630/preclinical-evaluation-of-ribociclib-and-its-synergistic-effect-in-combination-with-alpelisib-in-non-keratinizing-nasopharyngeal-carcinoma
#6
Chi-Hang Wong, Brigette B Y Ma, Connie W C Hui, Kwok-Wai Lo, Edwin P Hui, Anthony T C Chan
Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that induces G1 arrest by blocking the formation of cyclin D1-Cdk4/6 complex and inhibiting retinoblastoma (RB) phosphorylation. Cyclin D1 is overexpressed in over 90% of nasopharyngeal carcinoma (NPC) and CCND1 gene activation plays a critical role in NPC pathogenesis. This study evaluated the preclinical activities of ribociclib in NPC cell lines and patient derived xenograft (PDX) models. Over 95% cell growth inhibition was observed at 96 hours after ribociclib treatment...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789628/targetable-vulnerabilities-in-t-and-nk-cell-lymphomas-identified-through-preclinical-models
#7
Samuel Y Ng, Noriaki Yoshida, Amanda L Christie, Mahmoud Ghandi, Neekesh V Dharia, Joshua Dempster, Mark Murakami, Kay Shigemori, Sara N Morrow, Alexandria Van Scoyk, Nicolas A Cordero, Kristen E Stevenson, Maneka Puligandla, Brian Haas, Christopher Lo, Robin Meyers, Galen Gao, Andrew Cherniack, Abner Louissaint, Valentina Nardi, Aaron R Thorner, Henry Long, Xintao Qiu, Elizabeth A Morgan, David M Dorfman, Danilo Fiore, Julie Jang, Alan L Epstein, Ahmet Dogan, Yanming Zhang, Steven M Horwitz, Eric D Jacobsen, Solimar Santiago, Jian-Guo Ren, Vincent Guerlavais, D Allen Annis, Manuel Aivado, Mansoor N Saleh, Amitkumar Mehta, Aviad Tsherniak, David Root, Francisca Vazquez, William C Hahn, Giorgio Inghirami, Jon C Aster, David M Weinstock, Raphael Koch
T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs)...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29789423/atp-binding-cassette-member-b5-abcb5-promotes-tumor-cell-invasiveness-in-human-colorectal-cancer
#8
Qin Guo, Tanja Grimmig, Gabriel Gonzalez, Anita Giobbie-Hurder, Gretchen Berg, Nolan Carr, Brian J Wilson, Pallavi Banerjee, Jie Ma, Jason S Gold, Bisweswar Nandi, Qin Huang, Ana Maria Waaga-Gasser, Christine G Lian, George F Murphy, Markus H Frank, Martin Gasser, Natasha Y Frank
ATP-binding cassette member B5 (ABCB5) mediates multidrug resistance (MDR) in diverse malignancies and confers clinically relevant 5-fluorouracil resistance to CD133-expressing cancer stem cells (CSCs) in human colorectal cancer (CRC). Because of its recently identified roles in normal stem cell maintenance, we hypothesized that ABCB5 might also serve MDR-independent functions in CRC. Here, in a prospective clinical study of 142 CRC patients, we found that ABCB5 mRNA transcripts previously reported not to be significantly expressed in healthy peripheral blood mononuclear cells are significantly enriched in patient peripheral blood specimens compared with non-CRC controls and correlate with CRC disease progression...
May 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29788985/establishment-of-lung-cancer-patient-derived-xenograft-models-and-primary-cell-lines-for-lung-cancer-study
#9
Yanan Jiang, Jimin Zhao, Yi Zhang, Ke Li, Tiepeng Li, Xinhuan Chen, Simin Zhao, Song Zhao, Kangdong Liu, Ziming Dong
BACKGROUND: The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) models and primary cells are both used to screen therapeutic regimens for cancer. However, PDX models and primary cells from the same patient are difficult to establish. Their consistency to the original tumor tissue is not well studied. METHODS: 31 lung cancer patient tissues were procured to establish the lung cancer PDX models and primary cell lines...
May 22, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29788332/constitutive-interferon-pathway-activation-in-tumors-as-an-efficacy-determinant-following-oncolytic-virotherapy
#10
Cheyne Kurokawa, Ianko D Iankov, S Keith Anderson, Ileana Aderca, Alexey A Leontovich, Matthew J Maurer, Ann L Oberg, Mark A Schroeder, Caterina Giannini, Suzanne M Greiner, Marc A Becker, E Aubrey Thompson, Paul Haluska, Mark E Jentoft, Ian F Parney, S John Weroha, Jin Jen, Jann N Sarkaria, Evanthia Galanis
Background: Attenuated measles virus (MV) strains are promising agents currently being tested against solid tumors or hematologic malignancies in ongoing phase I and II clinical trials; factors determining oncolytic virotherapy success remain poorly understood, however. Methods: We performed RNA sequencing and gene set enrichment analysis to identify pathways differentially activated in MV-resistant (n = 3) and -permissive (n = 2) tumors derived from resected human glioblastoma (GBM) specimens and propagated as xenografts (PDX)...
May 16, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29788155/phase-i-study-of-the-checkpoint-kinase-1-inhibitor-gdc-0575-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#11
A Italiano, J R Infante, G I Shapiro, K N Moore, P M LoRusso, E Hamilton, S Cousin, M Toulmonde, S Postel-Vinay, S Tolaney, E M Blackwood, S Mahrus, F V Peale, X Lu, A Moein, J Epler, K DuPree, M Tagen, E R Murray, J L Schutzman, J O Lauchle, A Hollebecque, J-C Soria
Background: Checkpoint kinase 1 (Chk1) inhibition following chemotherapy-elicited DNA damage overrides cell cycle arrest and induces mitotic catastrophe and cell death. GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage and growth delay in xenograft models. We evaluated the safety, tolerability, and pharmacokinetic properties of GDC-0575 alone and in combination with gemcitabine. Antitumor activity and Chk1 pathway modulation were assessed...
February 23, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29786784/generation-of-prostate-cancer-patient-derived-xenografts-to-investigate-mechanisms-of-novel-treatments-and-treatment-resistance
#12
Hung-Ming Lam, Holly M Nguyen, Eva Corey
Treatment advances lead to survival benefits of patients with advanced prostate cancer. These treatments are highly efficacious in a subset of patients; however, similarly to other cancers, after initial responses the tumors develop resistance (acquired resistance) and the patients succumb to the disease. Furthermore, there is a subset of patients who do not respond to the treatment at all (de novo resistance). Preclinical testing using patient-derived xenografts (PDXs) has led to successful drug development, and PDXs will continue to provide valuable resources to generate clinically relevant data with translational potential...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786783/a-xenograft-model-for-venous-malformation
#13
Jillian Goines, Xian Li, Yuqi Cai, Paula Mobberley-Schuman, Megan Metcalf, Steven J Fishman, Denise M Adams, Adrienne M Hammill, Elisa Boscolo
Vascular malformations are defects caused by the abnormal growth of the vasculature. Among them, venous malformation (VM) is an anomaly characterized by slow-flow vascular lesions with abnormally shaped veins, typically in sponge-like configuration. VMs can expand over years causing disfigurement, obstruction of vital structures, thrombosis, bleeding, and pain. Treatments have been very limited and primarily based on supportive care, compression garments, sclerotherapy, and/or surgical resection. Sirolimus treatment has recently shown efficacy in some patients with complicated vascular anomalies, including VMs...
May 21, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29785122/aloperine-executes-antitumor-effects-through-the-induction-of-apoptosis-and-cell-cycle-arrest-in-prostate-cancer-in-vitro-and-in-vivo
#14
Zhixin Ling, Han Guan, Zonghao You, Can Wang, Ling Hu, Lei Zhang, Yiduo Wang, Shuqiu Chen, Bin Xu, Ming Chen
Background: Prostate cancer (PCa) is one of the most common malignant diseases among male patients. Although androgen deprivation therapy remains the main treatment for PCa, most patients would inevitably progress to castration-resistant PCa, which is the main cause of cancer-related deaths. Thus, novel antitumor agents are urgently needed. Recent studies demonstrated that aloperine (ALO) as a natural alkaloid showed antitumor effects in other cancer types. However, the biological function and underlying mechanisms of ALO in PCa have not been investigated...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29784639/tyrosine-kinase-inhibitor-induced-defects-in-dna-repair-sensitize-flt3-itd-positive-leukemia-cells-to-parp1-inhibitors
#15
Silvia Maifrede, Margaret Nieborowska-Skorska, Katherine Sullivan, Yashodhara Dasgupta, Paulina Podszywalow-Bartnicka, Bac Viet Le, Martyna Solecka, Zhaorui Lian, Elizaveta A Belyaeva, Alina Nersesyan, Marcin M Machnicki, Monika Toma, Nicolas Chatain, Malgorzata Rydzanicz, Huaqing Zhao, Jaroslav Jelinek, Katarzyna Piwocka, Tomasz Sliwinski, Tomasz Stoklosa, Rafal Ploski, Thomas Fischer, Stephen M Sykes, Steffen Koschmieder, Lars Bullinger, Peter Valent, Mariusz Wasik, Jian Huang, Tomasz Skorski
Mutations in the FMS-like tyrosine-kinase 3 (FLT3) such as internal tandem duplications (ITD) can be found in up to 23% of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Current treatment options for FLT3(ITD)-positive AMLs include genotoxic therapy and FLT3 inhibitors (FLT3i), which are rarely curative. PARP1 inhibitors (PARP1i) have been successfully applied to induce synthetic lethality in tumors harboring BRCA1/2 mutations and displaying homologous recombination (HR) deficiency...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29781813/the-notch1-cd44-axis-drives-pathogenesis-in-a-t-cell-acute-lymphoblastic-leukemia-model
#16
Marina García-Peydró, Patricia Fuentes, Marta Mosquera, María J García-León, Juan Alcain, Antonio Rodríguez, Purificación García de Miguel, Pablo Menéndez, Kees Weijer, Hergen Spits, David T Scadden, Carlos Cuesta-Mateos, Cecilia Muñoz-Calleja, Francisco Sánchez-Madrid, María L Toribio
NOTCH1 is a prevalent signaling pathway in T cell acute lymphoblastic leukemia (T-ALL), but crucial NOTCH1 downstream signals and target genes contributing to T-ALL pathogenesis cannot be retrospectively analyzed in patients and thus remain ill defined. This information is clinically relevant, as initiating lesions that lead to cell transformation and leukemia-initiating cell (LIC) activity are promising therapeutic targets against the major hurdle of T-ALL relapse. Here, we describe the generation in vivo of a human T cell leukemia that recapitulates T-ALL in patients, which arises de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781107/pristimerin-targeting-nf-%C3%AE%C2%BAb-pathway-inhibits-proliferation-migration-and-invasion-in-esophageal-squamous-cell-carcinoma-cells
#17
Yuanqing Tu, Fuxing Tan, Jingfeng Zhou, Jingxuan Pan
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related death with poor prognosis in China. Identifying novel targeted therapies in ESCC is urgently needed. The aberrant activation of NF-κB signalling pathway is critical for prognosis and recurrence of ESCC, which make it a potential target in the treatment of ESCC. Here, we found that pristimerin inhibited ESCC cell proliferation, migration, invasion, induced cell apoptosis, and eliminated cancer stem-like cells (CSCs). It also showed a synergistic effect on ESCC when combined with 5-fluorouracil (5-FU)...
May 20, 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29780393/immunomodulatory-drugs-exert-anti-leukemia-effects-in-acute-myeloid-leukemia-by-direct-and-immunostimulatory-activities
#18
Aude Le Roy, Thomas Prébet, Rémy Castellano, Armelle Goubard, Florence Riccardi, Cyril Fauriat, Samuel Granjeaud, Audrey Benyamine, Céline Castanier, Florence Orlanducci, Amira Ben Amara, Frédéric Pont, Jean-Jacques Fournié, Yves Collette, Jean-Louis Mege, Norbert Vey, Daniel Olive
Immunomodulatory drugs (IMiDs) are anticancer drugs with immunomodulatory, anti-angiogenesis, anti-proliferative, and pro-apoptotic properties. IMiDs are currently used for the treatment of multiple myeloma, myelodysplastic syndrome, and B-cell lymphoma; however, little is known about efficacy in acute myeloid leukemia (AML). We proposed in this study to investigate the relevance of IMiDs therapy for AML treatment. We evaluated the effect of IMiDs on primary AML blasts ( n  = 24), and the impact in natural killer (NK) cell-mediated immunosurveillance of AML...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779580/animal-models-of-endometriosis-replicating-the-aetiology-and-symptoms-of-the-human-disorder
#19
REVIEW
Ioannis Simitsidellis, Douglas A Gibson, Philippa T K Saunders
Endometriosis is a chronic incurable disorder that affects 1 in 10 women of reproductive age: associated symptoms include chronic pain and infertility. The aetiology of endometriosis remains poorly understood but patients, clinicians and researchers are all in agreement that new non-surgical therapies are urgently needed to reduce the severity of symptoms. Preclinical testing of drugs requires the development and validation of models that recapitulate the key features of the disorder. In this review we describe the best-validated animal models (primate, rodent, xenograft) and their contributions to our understanding of the factors underpinning the development of symptoms...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29778888/rapid-phenotyping-of-cancer-stem-cells-using-multichannel-nanosensor-arrays
#20
Yingying Geng, Hira L Goel, Ngoc B Le, Tatsuyuki Yoshii, Rubul Mout, Gulen Y Tonga, John J Amante, Arthur M Mercurio, Vincent M Rotello
Cancer stem cells (CSCs) contribute to multidrug resistance, tumor recurrence and metastasis, making them prime therapeutic targets. Their ability to differentiate and lose stem cell properties makes them challenging to study. Currently, there is no simple assay that can capture and trace the dynamic phenotypic changes on the CSC surface. Here, we report rapid discrimination of breast CSCs from non-CSCs using a nanoparticle-fluorescent-protein based sensor. This nanosensor was employed to discriminate CSCs from non-CSCs, as well CSCs that had differentiated in vitro in two breast cancer models...
May 17, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
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