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https://www.readbyqxmd.com/read/29245156/selection-and-targeting-of-epcam-protein-by-ssdna-aptamer
#1
Walhan Alshaer, Nida Ababneh, Mamon Hatmal, Heba Izmirli, Moujab Choukeife, Alaa Shraim, Nour Sharar, Aya Abu-Shiekah, Fadwa Odeh, Abeer Al Bawab, Abdalla Awidi, Said Ismail
Aptamers are molecules that reveal highly complex and refined molecular recognition properties. These molecules are capable of binding with high affinity and selectivity to targets, ranging from small molecules to whole living cells. Several aptamers have been selected for targeting cellular proteins and they have also used in developing therapeutics and diagnostic strategies. Epithelial cell adhesion molecule (EpCAM) is considered as a cancer stem cell (CSC) biomarker and one of the most promising targets for aptamer selection against CSCs...
2017: PloS One
https://www.readbyqxmd.com/read/29245008/on-the-design-of-combination-cancer-therapy
#2
James H Doroshow, Richard M Simon
Combination therapy programs are the hallmark of the successful treatment of all forms of human malignancies. In this issue of Cell, Palmer and Sorger present data suggesting that cell culture results indicative of synergistic anticancer drug interactions rarely translate clinically and that the results of combination therapies in mouse models or human clinical trials, even if successful, are best explained by the independent activities of the individually administered drugs.
December 14, 2017: Cell
https://www.readbyqxmd.com/read/29243303/genotoxic-and-mutagenic-properties-of-ni-and-nio-nanoparticles-investigated-by-comet-assay-%C3%AE-h2ax-staining-hprt-mutation-assay-and-toxtracker-reporter-cell-lines
#3
Emma Åkerlund, Francesca Cappellini, Sebastiano Di Bucchianico, Shafiqul Islam, Sara Skoglund, Remco Derr, Inger Odnevall Wallinder, Giel Hendriks, Hanna L Karlsson
Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. The aim of this study was to investigate genotoxicity and mutagenicity of Ni and NiO NPs and compare the effect to soluble Ni from NiCl2 . We employed different models; i.e., exposure of (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay and γ-H2AX staining); (2) six different mouse embryonic stem (mES) reporter cell lines (ToxTracker) that are constructed to exhibit fluorescence upon the induction of various pathways of relevance for (geno)toxicity and cancer; and (3) mES cells followed by mutagenicity testing (Hprt assay)...
December 15, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29242607/the-impact-of-stromal-hic-5-on-the-tumorigenesis-of-colorectal-cancer-through-lysyl-oxidase-induction-and-stromal-remodeling
#4
Tomokatsu Omoto, Joo-Ri Kim-Kaneyama, Xiao-Feng Lei, Akira Orimo, Koji Ohnishi, Kosuke Yoshihara, Aya Miyauchi, Shuo Li, Lin Gao, Takahiro Umemoto, Junichi Tanaka, Kenta Nakahara, Motohiro Takeya, Fumio Ishida, Shin-Ei Kudo, Shogo Haraguchi, Takuro Miyazaki, Akira Miyazaki
Carcinoma-associated fibroblasts (CAFs) influence tumor initiation, progression, and metastasis within the tumor-associated stroma. This suggests that CAFs would be a potential target for tumor therapy. Here we found that Hydrogen peroxide-inducible clone-5 (Hic-5), also named transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was strongly induced in CAFs found in human colorectal cancer. To investigate the role of Hic-5 in CAFs, we isolated CAFs and the control counterpart normal fibroblasts (NFs) from human colorectal cancer and non-cancerous regions, respectively...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29239135/oxymatrine-inhibits-non-small-cell-lung-cancer-via-suppression-of-egfr-signaling-pathway
#5
Wei Li, Xinfang Yu, Shiming Tan, Wenbin Liu, Li Zhou, Haidan Liu
Epidermal growth factor receptor (EGFR) plays a crucial role in human non-small cell lung cancer (NSCLC) tumorigenesis. In this study, oxymatrine was identified as an EGFR signaling pathway inhibitor in NSCLC. Oxymatrine inhibited anchorage-dependent and independent growth of NSCLC cell lines but had no cytotoxicity in normal lung cells. We found that exposure to oxymatrine not only suppressed the activity of wild-type EGFR but also inhibited the activation of exon 19 deletion and L858R/T790M mutated EGFR. Flow cytometry analysis suggested that oxymatrine-induced cell cycle G0/G1 arrest was dependent on EGFR-Akt signaling...
December 13, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29238973/demethylzeylasteral-zst93-inhibits-cell-growth-and-enhances-cell-chemosensitivity-to-gemcitabine-in-human-pancreatic-cancer-cells-via-apoptotic-and-autophagic-pathways
#6
Feng Wang, Xiaodong Tian, Zhengkui Zhang, Yongsu Ma, Xuehai Xie, Jian Liang, Chunxin Yang, Yinmo Yang
The overall 5-year survival rate of patients with human pancreatic cancer remains less than 8% because of its aggressive growth, early metastasis, and resistance to conventional chemoradiotherapy. It is essential to develop innovative and effective therapeutic agents to improve its prognosis. Demethylzeylasteral (ZST93) is a novel triterpenoid monomer extracted from the xylem of Tripterygium roots. This study aimed to assess the effects of ZST93 on cell proliferation and its role in the chemosensitivity to gemcitabine in human pancreatic cancer cells...
December 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29238081/pyridoxine-5-phosphate-oxidase-is-a-novel-therapeutic-target-and-regulated-by-the-tgf-%C3%AE-signalling-pathway-in-epithelial-ovarian-cancer
#7
Lingyun Zhang, Daibing Zhou, Wencai Guan, Weimin Ren, Wenwen Sun, Jimin Shi, Qunbo Lin, Jinguo Zhang, Tiankui Qiao, Yulong Ye, Yun Wu, Yaning Zhang, Xulei Zuo, Kristin L Connor, Guoxiong Xu
Pyridoxine 5'-phosphate oxidase (PNPO) is an enzyme that converts pyridoxine 5'-phosphate into pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 implicated in several types of cancer. However, the role of PNPO and its regulatory mechanism in epithelial ovarian cancer (EOC) are unknown. In the present study, PNPO expression in human ovarian tumour tissue and its association with the clinicopathological features of patients with EOC were examined. Further, the biological function of PNPO in EOC cells and in xenograft was evaluated...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29237705/cilia-loss-sensitizes-cells-to-transformation-by-activating-the-mevalonate-pathway
#8
Yue-Zhen Deng, Zhen Cai, Shuo Shi, Hao Jiang, Yu-Rong Shang, Ning Ma, Jing-Jing Wang, Dong-Xian Guan, Tian-Wei Chen, Ye-Fei Rong, Zhen-Yu Qian, Er-Bin Zhang, Dan Feng, Quan-Li Zhou, Yi-Nan Du, Dong-Ping Liu, Xing-Xu Huang, Lu-Ming Liu, Eugene Chin, Dang-Sheng Li, Xiao-Fan Wang, Xue-Li Zhang, Dong Xie
Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through β catenin-T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by β-catenin-TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples...
December 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29237264/dual-ratiometric-target-triggered-fluorescent-probe-for-simultaneous-quantitative-visualization-of-tumor-microenvironment-protease-activity-and-ph-in-vivo
#9
Tiancong Ma, Yi Hou, Jianfeng Zeng, Chunyan Liu, Peisen Zhang, Lihong Jing, Dihua Shangguan, Mingyuan Gao
The abnormal expression of tumor-associated proteases and lowered extracellular pH are important signatures strongly associated with cancer invasion, progression, and metastasis. However, their malignant effects were mainly identified using cell and tissue studies. To non-invasively visualize the heterogeneous distribution of these abnormal indicators in vivo and further disclose their collective behaviors, a target-triggered fluorescent nanoprobe composed of a ratiometric pH-sensitive dye, a near infrared dye (Cy5...
December 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29236321/murine-models-of-osteosarcoma-a-piece-of-the-translational-puzzle
#10
Mannu K Walia, Wilson Castillo-Tandazo, Anthony J Mutsaers, T John Martin, Carl R Walkley
Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensive research efforts, there has been no significant improvement in patient outcome for many years. An improved understanding of the biology of this cancer and how genes frequently mutated contribute to OS may help improve outcomes for patients. Whilst our knowledge of the mutational burden of OS is approaching saturation, our understanding of how these mutations contribute to OS initiation and maintenance is less clear...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29235204/plasma-activated-medium-pam-kills-human-cancer-initiating-cells
#11
Jun-Ichiro Ikeda, Hiromasa Tanaka, Kenji Ishikawa, Hajime Sakakita, Yuzuru Ikehara, Masaru Hori
Medical non-thermal plasma (NTP) treatments for various types of cancers have been reported. Cells with tumorigenic potential (cancer-initiating cells; CICs) are few in number in many types of tumors. CICs efficiently eliminate anti-cancer chemicals and exhibit high-level aldehyde dehydrogenase (ALDH) activity. We previously examined the effects of direct irradiation via NTP on cancer cells; even though we targeted CICs expressing high levels of ALDH, such treatment affected both non-CICs and CICs. Recent studies have shown that plasma-activated medium (PAM) (culture medium irradiated by NTP) selectively induces apoptotic death of cancer but not normal cells...
December 13, 2017: Pathology International
https://www.readbyqxmd.com/read/29234490/geminin-deficiency-enhances-survival-in-a-murine-medulloblastoma-model-by-inducing-apoptosis-of-preneoplastic-granule-neuron-precursors
#12
Savita Sankar, Ethan Patterson, Emily M Lewis, Laura E Waller, Caili Tong, Joshua Dearborn, David Wozniak, Joshua B Rubin, Kristen L Kroll
Medulloblastoma is the most common malignant brain cancer of childhood. Further understanding of tumorigenic mechanisms may define new therapeutic targets. Geminin maintains genome fidelity by controlling re-initiation of DNA replication within a cell cycle. In some contexts, Geminin inhibition induces cancer-selective cell cycle arrest and apoptosis and/or sensitizes cancer cells to Topoisomerase IIα inhibitors such as etoposide, which is used in combination chemotherapies for medulloblastoma. However, Geminin's potential role in medulloblastoma tumorigenesis remained undefined...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29233683/caspase-mediated-cleavage-of-x-ray-repair-cross-complementing-group-4-promotes-apoptosis-by-enhancing-nuclear-translocation-of-caspase-activated-dnase
#13
Yumi Sunatani, Radhika Pankaj Kamdar, Mukesh Kumar Sharma, Tadashi Matsui, Ryo Sakasai, Mitsumasa Hashimoto, Yasuhito Ishigaki, Yoshihisa Matsumoto, Kuniyoshi Iwabuchi
X-ray repair cross-complementing group 4 (XRCC4), a repair protein for DNA double-strand breaks, is cleaved by caspases during apoptosis. In this study, we examined the role of XRCC4 in apoptosis. Cell lines, derived from XRCC4-deficient M10 mouse lymphoma cells and stably expressing wild-type XRCC4 or caspase-resistant XRCC4, were established and treated with staurosporine (STS) to induce apoptosis. In STS-induced apoptosis, expression of wild-type, but not caspase-resistant, XRCC4 in XRCC4-deficient cells enhanced oligonucleosomal DNA fragmentation and the appearance of TUNEL-positive cells by promoting nuclear translocation of caspase-activated DNase (CAD), a major nuclease for oligonucleosomal DNA fragmentation...
December 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29233176/uncoordinated-expression-of-dna-methylation-related-enzymes-in-human-cancer
#14
Jiao Liu, Xiuliang Cui, Jinhua Jiang, Dan Cao, Yufei He, Hongyang Wang
BACKGROUND: In addition to the important roles played by 5-methylcytosine (5mC), emerging evidence suggests that 5mC derivatives, such as 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), also exhibit regulatory functions in physiological and pathological processes. Four cytosine modifications (5mC, 5hmC, 5fC and 5caC) are produced and erased by a cyclic enzymatic cascade mediated by DNA methyltransferases (DNMTs), ten-eleven translocation (TET) family enzymes and thymine DNA glycosylase (TDG)...
December 12, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29232555/mtorc2-promotes-tumorigenesis-via-lipid-synthesis
#15
Yakir Guri, Marco Colombi, Eva Dazert, Sravanth K Hindupur, Jason Roszik, Suzette Moes, Paul Jenoe, Markus H Heim, Isabelle Riezman, Howard Riezman, Michael N Hall
Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, leading to steatosis and tumor development. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardiolipin) synthesis...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29232552/therapeutic-antibody-targeting-tumor-and-osteoblastic-niche-derived-jagged1-sensitizes-bone-metastasis-to-chemotherapy
#16
Hanqiu Zheng, Yangjin Bae, Sabine Kasimir-Bauer, Rebecca Tang, Jin Chen, Guangwen Ren, Min Yuan, Mark Esposito, Wenyang Li, Yong Wei, Minhong Shen, Lanjing Zhang, Nikolai Tupitsyn, Klaus Pantel, Chadwick King, Jan Sun, Jodi Moriguchi, Helen Toni Jun, Angela Coxon, Brendan Lee, Yibin Kang
Bone metastasis is a major health threat to breast cancer patients. Tumor-derived Jagged1 represents a central node in mediating tumor-stromal interactions that promote osteolytic bone metastasis. Here, we report the development of a highly effective fully human monoclonal antibody against Jagged1 (clone 15D11). In addition to its inhibitory effect on bone metastasis of Jagged1-expressing tumor cells, 15D11 dramatically sensitizes bone metastasis to chemotherapy, which induces Jagged1 expression in osteoblasts to provide a survival niche for cancer cells...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29232177/metformin-effects-on-metabolic-coupling-and-tumor-growth-in-oral-cavity-squamous-cell-carcinoma-coinjection-xenografts
#17
Patrick Tassone, Marina Domingo-Vidal, Diana Whitaker-Menezes, Zhao Lin, Megan Roche, Madalina Tuluc, Ubaldo Martinez-Outschoorn, Joseph Curry
Objective Many aggressive head and neck cancers contain 2 metabolically coupled tumor compartments: a glycolytic stromal compartment with low caveolin-1 (CAV1) and high monocarboxylate transporter 4 (MCT4) expression and a highly proliferative carcinoma cell compartment with high MCT1. Metabolites are shuttled by MCTs from stroma to carcinoma to fuel tumor growth. We studied the effect of carcinoma-fibroblast coinjection and metformin administration on a mouse model of head and neck squamous cell carcinoma...
December 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29229903/loss-of-pbrm1-rescues-vhl-dependent-replication-stress-to-promote-renal-carcinogenesis
#18
Judit Espana-Agusti, Anne Warren, Su Kit Chew, David J Adams, Athena Matakidou
Inactivation of the VHL (Von Hippel Lindau) tumour suppressor has long been recognised as necessary for the pathogenesis of clear cell renal cancer (ccRCC); however, the molecular mechanisms underlying transformation and the requirement for additional genetic hits remain unclear. Here, we show that loss of VHL alone results in DNA replication stress and damage accumulation, effects that constrain cellular growth and transformation. By contrast, concomitant loss of the chromatin remodelling factor PBRM1 (mutated in 40% of ccRCC) rescues VHL-induced replication stress, maintaining cellular fitness and allowing proliferation...
December 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29228668/tsc-22-inhibits-csf-1r-function-and-induces-apoptosis-in-cervical-cancer
#19
Min-Ji Cho, Ji-Yeon Lee, Min-Gwan Shin, Hyun-Ji Kim, Yu-Joung Choi, Seung Bae Rho, Boh-Ram Kim, Ik Soon Jang, Seung-Hoon Lee
Colony stimulating factor 1 receptor (CSF-1R) regulates the monocyte/macrophage system, which is an essential component of cancer development. Therefore, CSF-1R might be an effective target for anti-cancer therapy. The overexpression of transforming growth factor (TGF)-β stimulated clone-22 (TSC-22) inhibits cancer cell proliferation and induces apoptosis, and TSC-22 is emerging as a key factor in tumorigenesis. In this study, we discovered CSF-1R as a new interacting partner of TSC-22 and identified its elevated expression in cervical cancer cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228217/p19arf-inhibits-aggressive-progression-of-h-ras-driven-hepatocellular-carcinoma
#20
Dragana Kopanja, Akshay Pandey, Shuo Huang, Mohamed Rizwan Haroon Al Raheed, Grace Guzman, Pradip Raychaudhuri
Arf, a well-established tumor suppressor, is either mutated or downregulated in a wide array of cancers. However, its role in hepatocellular carcinoma (HCC) progression is controversial. Conflicting observations have been published regarding its expression in HCC. In this study, we provide clear genetic evidence demonstrating a protective role of p19Arf in hepatocarcinogenesis. Using Ras-induced mouse model, we show that p19Arf deficiency accelerates progression of aggressive HCC in vivo. To investigate the role of p14ARF in human liver cancers, we analyzed its expression in human HCC using immunohistochemistry...
December 8, 2017: Carcinogenesis
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