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https://www.readbyqxmd.com/read/28535374/discovery-of-stromal-regulatory-networks-that-suppress-ras-sensitized-epithelial-cell-proliferation
#1
Huayang Liu, James A Dowdle, Safiya Khurshid, Nicholas J Sullivan, Nicholas Bertos, Komal Rambani, Markus Mair, Piotr Daniel, Esther Wheeler, Xing Tang, Kyle Toth, Michael Lause, Markus E Harrigan, Karl Eiring, Connor Sullivan, Matthew J Sullivan, Serena W Chang, Siddhant Srivastava, Joseph S Conway, Raleigh Kladney, Joseph McElroy, Sooin Bae, Yuanzhi Lu, Ali Tofigh, Sadiq M I Saleh, Soledad A Fernandez, Jeffrey D Parvin, Vincenzo Coppola, Erin R Macrae, Sarmila Majumder, Charles L Shapiro, Lisa D Yee, Bhuvaneswari Ramaswamy, Michael Hallett, Michael C Ostrowski, Morag Park, Helen M Chamberlin, Gustavo Leone
Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28534513/protein-disulfide-isomerase-a4-acts-as-a-novel-regulator-of-cancer-growth-through-the-procaspase-pathway
#2
T-F Kuo, T-Y Chen, S-T Jiang, K-W Chen, Y-M Chiang, Y-J Hsu, Y-J Liu, H-M Chen, K K Yokoyama, K-C Tsai, H-H Yeh, Y-R Chen, M-T Yang, C-Y Yang, W-C Yang
Protein disulfide isomerase a4 (PDIA4) is implicated in the growth and death of tumor cells; however, its molecular mechanism and therapeutic potential in cancer are unclear. Here, we found that PDIA4 expression was upregulated in a variety of tumor cell lines and human lung adenocarcinoma tissues. Knockdown and overexpression of PDIA4 in tumor cells showed that PDIA4 facilitated cell growth via the reduction of caspases 3 and 7 activity. Consistently, Lewis lung carcinoma cells overexpressing PDIA4 grew faster than did parental cells in tumor-bearing mice, as shown by a reduced survival rate, increased tumor size and metastasis, and decreased cell death and caspases 3 and 7 activity...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28532671/ochratoxin-a-transport-by-the-human-breast-cancer-resistance-protein-bcrp-multidrug-resistance-protein-2-mrp2-and-organic-anion-transporting-polypeptides-1a2-1b1-and-2b1
#3
Xiaozhe Qi, Els Wagenaar, Wentao Xu, Kunlun Huang, Alfred H Schinkel
Ochratoxin A (OTA) is a fungal secondary metabolite that can contaminate various foods. OTA has several toxic effects like nephrotoxicity, hepatotoxicity, and neurotoxicity in different animal species, but its mechanisms of toxicity are still unclear. How OTA accumulates in kidney, liver, and brain is as yet unknown, but transmembrane transport proteins are likely involved. We studied transport of OTA in vitro, using polarized MDCKII cells transduced with cDNAs of the efflux transporters mouse (m)Bcrp, human (h)BCRP, mMrp2, or hMRP2, and HEK293 cells overexpressing cDNAs of the human uptake transporters OATP1A2, OATP1B1, OATP1B3, or OATP2B1 at pH7...
May 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28532456/mechanisms-of-tanshinone-ii-a-inhibits-malignant-melanoma-development-through-blocking-autophagy-signal-transduction-in-a375-cell
#4
Xiaojing Li, Zhifeng Li, Xianping Li, Baoguo Liu, Zhijun Liu
BACKGROUND: Malignant melanoma (MM) is one of the high degree of malignancy and early prone to blood and lymph node metastasis. There is not cured for MM. Tan II A has been reported to reduce cancer cell proliferation. But the mechanism by which Tan II A inhibited melanoma growth are not well characterized. We sought to explore the possible mechanism by which Tan II A regulated cell proliferation through autophagy signaling pathway in A375 cells. METHODS: We tested the effects of Tan II A on melanoma A375, MV3, M14, and other human cell lines including Hacat and HUVEC cells in cell culture model...
May 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28530705/ccn5-wisp-2-restores-er-%C3%A2-in-normal-and-neoplastic-breast-cells-and-sensitizes-triple-negative-breast-cancer-cells-to-tamoxifen
#5
S Sarkar, A Ghosh, S Banerjee, G Maity, A Das, M A Larson, V Gupta, I Haque, O Tawfik, S K Banerjee
CCN5/WISP-2 is an anti-invasive molecule and prevents breast cancer (BC) progression. However, it is not well understood how CCN5 prevents invasive phenotypes of BC cells. CCN5 protein expression is detected in estrogen receptor-α (ER-α) -positive normal breast epithelial cells as well as BC cells, which are weakly invasive and rarely metastasize depending on the functional status of ER-α. A unique molecular relation between CCN5 and ER-α has been established as the components of the same signaling pathway that coordinate some essential signals associated with the proliferation as well as delaying the disease progression from a non-invasive to invasive phenotypes...
May 22, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28530655/a-quantitative-and-multiplexed-approach-to-uncover-the-fitness-landscape-of-tumor-suppression-in-vivo
#6
Zoë N Rogers, Christopher D McFarland, Ian P Winters, Santiago Naranjo, Chen-Hua Chuang, Dmitri Petrov, Monte M Winslow
Cancer growth is a multistage, stochastic evolutionary process. While cancer genome sequencing has been instrumental in identifying the genomic alterations that occur in human tumors, the consequences of these alterations on tumor growth remain largely unexplored. Conventional genetically engineered mouse models enable the study of tumor growth in vivo, but they are neither readily scalable nor sufficiently quantitative to unravel the magnitude and mode of action of many tumor-suppressor genes. Here, we present a method that integrates tumor barcoding with ultradeep barcode sequencing (Tuba-seq) to interrogate tumor-suppressor function in mouse models of human cancer...
May 22, 2017: Nature Methods
https://www.readbyqxmd.com/read/28530639/calcium-binding-protein-s100a4-confers-mesenchymal-progenitor-cell-fibrogenicity-in-idiopathic-pulmonary-fibrosis
#7
Hong Xia, Adam Gilbertsen, Jeremy Herrera, Emilian Racila, Karen Smith, Mark Peterson, Timothy Griffin, Alexey Benyumov, Libang Yang, Peter B Bitterman, Craig A Henke
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a prevalence of 1 million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli and leads to death by asphyxiation. We previously discovered that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs) that serve as a cell of origin for disease-mediating myofibroblasts. In a prior genomewide transcriptional analysis, we found that IPF MPCs displayed increased expression of S100 calcium-binding A4 (S100A4), a protein linked to cancer cell proliferation and invasiveness...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530537/aspergillus-fischeri-mediated-biosynthesis-of-gold-nanoparticles-and-their-beneficially-comparative-effect-on-normal-and-cancer-cell-lines
#8
Kangkana Banerjee, Ravishankar Rai Vittal
Background Along with the intensified use of metal nanoparticles, growing concern of their adverse outcome on human health has also expanded, indicating that this work is an integral part of nanobioscience study. Objective The aim of this study was to evaluate varied effect of biosynthesized gold nanoparticles (AuNPs) on normal and cancerous mammalian cells. Methods AuNP synthesized and characterized by different characterization methods, here are produced by specifically isolated Aspergillus species, which is hardly explored in precious scientific findings...
May 22, 2017: Pharmaceutical Nanotechnology
https://www.readbyqxmd.com/read/28529594/an-active-molecule-from-pulsatilla-chinensis-pulsatilla-saponin-a-induces-apoptosis-and-inhibits-tumor-growth-of-human-colon-cancer-cells-without-or-with-5-fu
#9
Liming Xu, Guilian Cheng, Yi Lu, Shaofeng Wang
Colon cancer is one of the common types of digestive malignancy. The efficacy of the first-line chemotherapy drug for colon cancer, fluorouracil (5-FU), remains limited in clinical settings due to poor efficacy and significant side effects. In the present study, the anticancer activity of an active compound from Pulsatilla chinensis extracts, Pulsatilla saponin A (PsA), was isolated and examined in vitro and in vivo. It was demonstrated that PsA significantly inhibited the growth of human colon cancer HT-29 cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529455/dipalmitoylphosphatidic-acid-inhibits-tumor-growth-in-triple-negative-breast-cancer
#10
Qian-Qian Zhang, Jian Chen, Da-Lei Zhou, You-Fa Duan, Cui-Ling Qi, Jiang-Chao Li, Xiao-Dong He, Min Zhang, Yong-Xia Yang, Lijing Wang
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis, accounting for approximately 12-24% of breast cancer cases. Accumulating evidence has indicated that there is no effective targeted therapy available for TNBC. Dipalmitoylphosphatidic acid (DPPA) is a bioactive phospholipid. However, the function of DPPA in the growth of TNBC has not yet been studied. In this study, we employed TNBC cells and a subcutaneous tumor model to elucidate the possible effect of DPPA on tumor growth in TNBC...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28529141/z-505-hydrochloride-an-orally-active-ghrelin-agonist-attenuates-the-progression-of-cancer-cachexia-via-anabolic-hormones-in-colon-26-tumor-bearing-mice
#11
Makoto Yoshimura, Yoshihiro Shiomi, Yuta Ohira, Mineo Takei, Takao Tanaka
Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505...
May 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28528814/preclinical-study-using-malat1-small-interfering-rna-or-androgen-receptor-splicing-variant-7-degradation-enhancer-asc-j9-%C3%A2-to-suppress-enzalutamide-resistant-prostate-cancer-progression
#12
Ronghao Wang, Yin Sun, Lei Li, Yuanjie Niu, Wanying Lin, Changyi Lin, Emmanuel S Antonarakis, Jun Luo, Shuyuan Yeh, Chawnshang Chang
BACKGROUND: While androgen-deprivation-therapy with the recently developed antiandrogen enzalutamide (Enz) shows promising therapeutic benefits in men with metastatic castration-resistant prostate cancer (PCa), many patients develop resistance to Enz, which may involve the induction of the androgen receptor (AR) splicing variant 7 (AR-v7). OBJECTIVE: Our aim is to identify the mechanisms responsible for AR-v7 production and to develop novel preclinical approaches to suppress the Enz-resistant (EnzR) PCa...
May 18, 2017: European Urology
https://www.readbyqxmd.com/read/28527569/estrogen-hormone-biology
#13
Katherine J Hamilton, Sylvia C Hewitt, Yukitomo Arao, Kenneth S Korach
The hormone estrogen is involved in both female and male reproduction, as well as numerous other biological systems including the neuroendocrine, vascular, skeletal, and immune systems. Therefore, it is also implicated in many different diseases and conditions such as infertility, obesity, osteoporosis, endometriosis, and a variety of cancers. Estrogen works through its two distinct nuclear receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). Various transcriptional regulation mechanisms have been identified as the mode of action for estrogen, mainly the classical mechanism with direct DNA binding but also a nongenomic mode of action and one using tethered or indirect binding...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28526770/therapeutic-ige-antibodies-harnessing-a-macrophage-mediated-immune-surveillance-mechanism-against-cancer
#14
REVIEW
Sophia N Karagiannis, Debra H Josephs, Heather J Bax, James F Spicer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526008/cleavage-of-the-urokinase-receptor-upar-on-oral-cancer-cells-regulation-by-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-and-potential-effects-on-migration-and-invasion
#15
Synnove Norvoll Magnussen, Elin Hadler-Olsen, Daniela Elena Costea, Eli Berg, Cristiane Cavalcanti Jacobsen, Bente Mortensen, Tuula Salo, Inigo Martinez-Zubiaurre, Jan-Olof Winberg, Lars Uhlin-Hansen, Gunbjorg Svineng
BACKGROUND: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28525890/a-novel-egfr-tki-inhibitor-camp-h3bo3%C3%A2-complex-combined-with-thermal-therapy-is-a-promising-strategy-to-improve-lung-cancer-treatment-outcomes
#16
Yongpeng Tong, Chunliu Huang, Junfang Zhang
PURPOSE: Although EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) induce favorable responses as first-line non-small cell lung cancer treatments, drug resistance remains a serious problem. Meanwhile, thermal therapy also shows promise as a cancer therapy strategy. Here we combine a novel EGFR-TKI treatment with thermal therapy to improve lung cancer treatment outcomes. RESULTS: The results suggest that the cAMP-H3BO3 complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest in vitro...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525387/sestrin-2-suppresses-cells-proliferation-through-ampk-mtorc1-pathway-activation-in-colorectal-cancer
#17
Jin-Lai Wei, Min Fang, Zhong-Xue Fu, Shou-Ru Zhang, Jin-Bao Guo, Rong Wang, Zhen-Bing Lv, Yong-Fu Xiong
Sestrin 2 is a conserved antioxidant protein that reduces reactive oxygen species (ROS) and inhibits mammalian target of rapamycin complex 1 (mTORC1). We previously showed that sestrin 2 is abnormally decreased in colorectal cancer (CRC). To elucidate the molecular mechanism behind the potential contribution of sestrin 2 to CRC, we used a lentiviral expression vector system to determine the effects of sestrin 2 overexpression on human CRC cells. We found that sestrin 2 overexpression decreased ROS production, inhibited cell growth, and stimulated apoptosis in two CRC cell lines...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525381/the-cell-of-origin-dictates-the-temporal-course-of-neurofibromatosis-1-nf1-low-grade-glioma-formation
#18
Anne C Solga, Joseph A Toonen, Yuan Pan, Patrick J Cimino, Yu Ma, Guillaume A Castillon, Scott M Gianino, Mark H Ellisman, Da Yong Lee, David H Gutmann
Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2+ cells and that Olig2+ oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2+ OPCs could be tumor-initiating cells for Nf1 optic glioma...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525366/mesenchymal-stem-cell-carriers-enhance-antitumor-efficacy-of-oncolytic-adenoviruses-in-an-immunocompetent-mouse-model
#19
Esther Rincón, Teresa Cejalvo, Deepak Kanojia, Arantzazu Alfranca, Miguel Ángel Rodríguez-Milla, Raul Andrés Gil Hoyos, Yu Han, Lingjiao Zhang, Ramón Alemany, Maciej S Lesniak, Javier García-Castro
Oncolytic virotherapy represents a promising alternative for cancer treatment; however, viral delivery to the tumor represents a major challenge. Mesenchymal stem cells (MSCs) chemotax to tumors, and can serve as a viral delivery tool. Previously, we demonstrated antitumor therapeutic efficacy for mesenchymal stem cells (MSCs) infected with the oncolytic human adenovirus ICOVIR5 (Celyvir) for treatment of neuroblastoma patients. Given the lack of suitable immunocompetent preclinical models, the mechanism underlying Celyvir antitumor activity remains unknown...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524599/modulation-of-nuclear-rest-by-alternative-splicing-a-potential-therapeutic-target-for-huntington-s-disease
#20
Guo-Lin Chen, Qi Ma, Dharmendra Goswami, Jianyu Shang, Gregory M Miller
Huntington's disease (HD) is caused by a genetically mutated huntingtin (mHtt) protein with expanded polyQ stretch, which impairs cytosolic sequestration of the repressor element-1 silencing transcription factor (REST), resulting in excessive nuclear REST and subsequent repression of neuronal genes. We recently demonstrated that REST undergoes extensive, context-dependent alternative splicing, of which exon-3 skipping (∆E3 )-a common event in human and nonhuman primates-causes loss of a motif critical for REST nuclear targeting...
May 19, 2017: Journal of Cellular and Molecular Medicine
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