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colorectal cancer And cancer stem cell

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https://www.readbyqxmd.com/read/29169144/targeting-the-wnt-beta-catenin-pathway-in-cancer-update-on-effectors-and-inhibitors
#1
REVIEW
Nithya Krishnamurthy, Razelle Kurzrock
The Wnt/beta-catenin pathway is a family of proteins that is implicated in many vital cellular functions like stem cell regeneration and organogenesis. Several intra-cellular signal transduction pathways are induced by Wnt, notably the Wnt/beta-catenin dependent pathway or canonical pathway and the non-canonical or beta-catenin-independent pathway, the latter includes the Wnt/Ca2+ and Planar Cell Polarity pathway (PCP). Wnt activation occurs at the intestinal crypt floor, and is critical to optimal maintenance of stem cells...
November 13, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29167573/metformin-transiently-inhibits-colorectal-cancer-cell-proliferation-as-a-result-of-either-ampk-activation-or-increased-ros-production
#2
Angela Mogavero, Maria Valeria Maiorana, Susanna Zanutto, Luca Varinelli, Fabio Bozzi, Antonino Belfiore, Chiara C Volpi, Annunziata Gloghini, Marco A Pierotti, Manuela Gariboldi
Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce cancer risk and improve the prognosis of certain malignancies. However, the mechanism underlying its anti-cancer effect is still unclear. We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin reduced cell proliferation and migration by inducing cell cycle arrest in the G0/G1 phase. This was accompanied by a sharp decrease in the expression of c-Myc and down-regulation of IGF1R...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29160937/microrna-26b-promotes-colorectal-cancer-metastasis-by-down-regulating-pten-and-wnt5a
#3
Dejun Fan, Xutao Lin, Feng Zhang, Weijie Zhong, Jiancong Hu, Yufeng Chen, Zerong Cai, Yifeng Zou, Xiaowen He, Xiuting Chen, Ping Lan, Xiaojian Wu
Invasion and metastasis are crucially important factors in the survival of malignant tumors. The epithelial-mesenchymal transition (EMT) is an early step in metastatic progression and the presence of cancer stem cells is closely related to tumor survival, proliferation, metastasis, and recurrence. Here we report that ectopic overexpression of microRNA 26b (miR-26b) in colorectal cancer (CRC) cell lines promoted EMT and stem cell-like phenotypes in vitro. Furthermore, miR-26b directly targeted and suppressed multiple tumor suppressors, including phosphatase and tensin homolog (PTEN) and wingless-type MMTV integration site family member 5A (WNT5A)...
November 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/29158811/transforming-doxorubicin-into-a-cancer-stem-cell-killer-via-epcam-aptamer-mediated-delivery
#4
Dongxi Xiang, Sarah Shigdar, Andrew G Bean, Matthew Bruce, Wenrong Yang, Motilal Mathesh, Tao Wang, Wang Yin, Phuong Ha-Lien Tran, Hadi Al Shamaileh, Roberto A Barrero, Pei-Zhuo Zhang, Yong Li, Lingxue Kong, Ke Liu, Shu-Feng Zhou, Yingchun Hou, Aina He, Wei Duan
Chemotherapy-resistant cancer stem cells (CSCs) are a major obstacle to the effective treatment of many forms of cancer. To overcome CSC chemo-resistance, we developed a novel system by conjugating a CSC-targeting EpCAM aptamer with doxorubicin (Apt-DOX) to eliminate CSCs. Incubation of Apt-DOX with colorectal cancer cells resulted in high concentration and prolonged retention of DOX in the nuclei. Treatment of tumour-bearing xenograft mice with Apt-DOX resulted in at least 3-fold more inhibition of tumour growth and longer survival as well as a 30-fold lower frequency of CSC and a prolonged longer tumourigenic latency compared with those receiving the same dose of free DOX...
2017: Theranostics
https://www.readbyqxmd.com/read/29158786/fh535-inhibits-proliferation-and-motility-of-colon-cancer-cells-by-targeting-wnt-%C3%AE-catenin-signaling-pathway
#5
Yanyan Chen, Xianping Rao, Kangmao Huang, Xiaoxia Jiang, Haohao Wang, Lisong Teng
Aberrant Wnt/β-catenin pathway activation is frequently observed in human colorectal cancer (CRC) and has become a promising target for CRC treatment. Our study aimed to evaluate the effect of FH535, a small molecule inhibitor of Wnt/β-catenin pathway, on two colon cancer cell lines, HT29 and SW480. We found FH535 significantly inhibited colon cancer cell proliferation in vitro and induced cell cycle arrest. Moreover, FH535 inhibited colon cancer xenograft growth in vivo. Wound-healing assay and Transwell assay revealed that FH535 notably suppressed migration and invasion of SW480 cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29156796/downregulation-of-dna-repair-proteins-and-increased-dna-damage-in-hypoxic-colon-cancer-cells-is-a-therapeutically-exploitable-vulnerability
#6
Jennifer M J Jongen, Lizet M van der Waals, Kari Trumpi, Jamila Laoukili, Niek A Peters, Susanne J Schenning-van Schelven, Klaas M Govaert, Inne H M Borel Rinkes, Onno Kranenburg
Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149105/lgr5-expression-is-regulated-by-egf-in-early-colorectal-adenomas-and-governs-egfr-inhibitor-sensitivity
#7
R G Morgan, E Mortensson, D N Legge, B Gupta, T J Collard, A Greenhough, A C Williams
BACKGROUND: LGR5 serves as a co-receptor for Wnt/β-catenin signalling and marks normal intestinal stem cells; however, its role in colorectal cancer (CRC) remains controversial. LGR5(+) cells are known to exist outside the stem cell niche during CRC progression, and the requirement for epidermal growth factor (EGF) signalling within early adenomas remains to be fully elucidated. METHODS: Epidermal growth factor and gefitinib treatments were performed in EGF-responsive LGR5(+) early adenoma RG/C2 cells...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29137267/tumacrophage-macrophages-transformed-into-tumor-stem-like-cells-by-virulent-genetic-material-from-tumor-cells
#8
Yizhuang Zhang, Na Zhou, Xiuyan Yu, Xuehui Zhang, Shanxin Li, Zhen Lei, Ruobi Hu, Hui Li, Yiqing Mao, Xi Wang, Jinshu Zhang, Yuan Li, Hongyan Guo, David M Irwin, Gang Niu, Huanran Tan
Tumor-associated macrophages are regarded as tumor-enhancers as they have key roles in the subversion of adaptive immunity and in inflammatory circuits that promote tumor progression. Here, we show that cancer cells can subvert macrophages yielding cells that have gained pro-tumor functions. When macrophages isolated from mice or humans are co-cultured with dead cancer cell line cells, induced to undergo apoptosis to mimic chemotherapy, up-regulation of pro-tumor gene expression was identified. Phagocytosis of apoptotic cancer cells by macrophages resulted in their transformation into tumor stem (initiating)-like cells, as indicated by the expression of epithelial markers (e...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135091/remarkably-higher-efficacy-and-a-wider-safety-window-for-nonfrontline-over-first-line-drug-combinations-in-the-adenocarcinoma-colo-320dm-cell-line
#9
Elsa N Garza-Trevino, Martha S Rodriguez-Gonzalez, Paulina Delgado Gonzalez, Yesenia G Alonso-Cruz, Yesenia G Alonso-Cruz, Adolfo Soto-Dominguez, Juan F Gonzalez Guerrero, Yanko Castro-Govea, Emiliano Michel Sanchez, Salvador Said Fernandez, Herminia G Martinez-Rodriguez
PURPOSE: To determine in vitro, the efficacy and safety window of not-front-line and first-line anti-colorectal (CRC) drug combinations. METHODS: The adenocarcinoma cell line Colo 320DM and normal human mesenchymal stem cells derived from adipose tissue were used respectively to determine the anti-CRC efficacy (% of Colo 320DM cell death [CD]) and safety window [SW] - % Colo 320DM percent cancer death (PCD)/% of mesenchymal stem cell's death) of drug combinations, using the adenosine triphosphate-based chemotherapy response assay (ATP-CRA)...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29128131/the-clinical-and-biological-roles-of-transforming-growth-factor-beta-in-colon-cancer-stem-cells-a-systematic-review
#10
REVIEW
Anna Chruścik, Vinod Gopalan, Alfred King-Yin Lam
BACKGROUND: Transforming growth factor beta (TGF-β) is a multipurpose cytokine, which plays a role in many cellular functions such as proliferation, differentiation, migration, apoptosis, cell adhesion and regulation of epithelial to mesenchymal transition. Despite many studies having observed the effect that TGF-β plays in colorectal cancer, its role in the colorectal stem cell population has not been widely observed. METHOD: This systematic review will analyse the role of TGF-β in the stem cell population of colorectal cancer...
November 8, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29127276/multicolor-lineage-tracing-reveals-clonal-architecture-and-dynamics-in-colon-cancer
#11
Sebastian Lamprecht, Eva Marina Schmidt, Cristina Blaj, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
Colon cancers are composed of phenotypically heterogeneous tumor cell subpopulations with variable expression of putative stem cell and differentiation antigens. While in normal colonic mucosa, clonal repopulation occurs along differentiation gradients from crypt base toward crypt apex, the clonal architecture of colon cancer and the relevance of tumor cell subpopulations for clonal outgrowth are poorly understood. Using a multicolor lineage tracing approach in colon cancer xenografts that reflect primary colon cancer architecture, we here demonstrate that clonal outgrowth is mainly driven by tumor cells located at the leading tumor edge with clonal axis formation toward the tumor center...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29123962/distinctive-features-of-tumor-infiltrating-%C3%AE-%C3%AE-t-lymphocytes-in-human-colorectal-cancer
#12
S Meraviglia, E Lo Presti, M Tosolini, C La Mendola, V Orlando, M Todaro, V Catalano, G Stassi, G Cicero, S Vieni, J J Fourniè, F Dieli
γδ T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating γδ T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of γδ T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5-90%) and 4% γδ T cells on average, with the majority expressing Vδ1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29120019/cellular-protection-mechanisms-that-minimise-accumulation-of-mutations-in-intestinal-tissue
#13
Jacco van Rheenen, Lotte Bruens
The epithelial lining of the intestine is constantly exposed to a hostile environment containing a mixture of gastric acids, consumed harmful substances and microbes. It is widely accepted that the intestine has multiple mechanisms to protect itself against tissue damage. Here, we review three cellular protection mechanisms that protect intestinal tissue against accumulation of somatic mutations: the conveyer belt-like structure, stem cell competition and crypt fusion. We highlight the events that can perturb these cellular protection mechanisms, and their impact on accumulation of new (oncogenic) mutations...
November 9, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29115601/ginsenoside-rg3-targets-cancer-stem-cells-and-tumor-angiogenesis-to-inhibit-colorectal-cancer-progression-in-vivo
#14
Yu-Chen Tang, Yan Zhang, Jin Zhou, Qiaoming Zhi, Meng-Yao Wu, Fei-Ran Gong, Meng Shen, Lu Liu, Min Tao, Bairong Shen, Dong-Mei Gu, Jie Yu, Meng-Dan Xu, Yuan Gao, Wei Li
Anti-angiogenic therapy has been successfully applied to treat colorectal cancer (CRC). Ginsenoside Rg3, derived from the Chinese herb ginseng, has anti-vascularization effects and can inhibit tumor growth and metastasis, and can sensitize cancer cells to chemotherapy. Therefore, in the present study, we investigated whether Rg3 could be appropriate for CRC treatment. Growth of CRC cells was assessed by an MTT (methyl thiazolyl tetrazolium) assay in vitro and using orthotopic xenograft models in vivo. mRNA expression was evaluated using real-time PCR...
November 1, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29115557/hypoxia-induces-differential-expression-patterns-of-osteopontin-and-cd44-in-colorectal-carcinoma
#15
Gisela Wohlleben, Konstantin Hauff, Martin Gasser, Ana Maria Waaga-Gasser, Tanja Grimmig, Michael Flentje, Bülent Polat
The plasma protein osteopontin (OPN) is considered to be a tumor biomarker, where elevated plasma levels are associated with poor prognosis. Additionally, OPN is expressed in the presence of tumor hypoxia, which is an adverse prognostic factor in radiation oncology. One of its receptors, the proposed tumor stem cell marker CD44, is also associated with aggressive tumors, shown for example in colon cancer. The expression of CD44 and its splice variants (particularly CD44v6) can be upregulated by OPN itself. In the present study, we aimed to investigate the influence of hypoxia on the expression of OPN and its binding partners CD44 and CD44v6 in colon carcinoma cell lines in vitro, using SW480, SW620, HT29 and HCT116 cells...
November 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29109538/two-novel-diterpenoid-heterodimers-bisebracteolasins-a-and-b-from-euphorbia-ebracteolata-hayata-and-the-cancer-chemotherapeutic-potential-of-bisebracteolasin-a
#16
Wen-Juan Yuan, Xiao Ding, Zhe Wang, Bi-Juan Yang, Xiao-Nian Li, Yu Zhang, Duo-Zhi Chen, Shun-Lin Li, Quan Chen, Ying-Tong Di, Haji Akber Aisa, Xiao-Jiang Hao
Rare ent-abietane-rosane diterpenoid heterodimers, Bisebracteolasins A and B (1 and 2, respectively), were isolated from the roots of Euphorbia ebracteolata Hayata. Their structures and absolute configurations were elucidated from spectroscopic data and X-ray diffraction analysis. Compounds 1 and 2 exhibited moderate cytotoxic effects against five cancer cell lines. Compound 1 showed more effective antiproliferative activities against human tumour cells, HL-60 and SMMC-7721, with IC50 values of 2.61 and 4.08 μM, respectively, than 2...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29108242/characterization-and-functional-analysis-of-a-slow-cycling-subpopulation-in-colorectal-cancer-enriched-by-cell-cycle-inducer-combined-chemotherapy
#17
Feng-Hua Wu, Lei Mu, Xiao-Lan Li, Yi-Bing Hu, Hui Liu, Lin-Tao Han, Jian-Ping Gong
The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo. Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107689/semi-synthetic-salinomycin-analogs-exert-cytotoxic-activity-against-human-colorectal-cancer-stem-cells
#18
Johannes Klose, Sarah Kattner, Björn Borgström, Claudia Volz, Thomas Schmidt, Martin Schneider, Stina Oredsson, Daniel Strand, Alexis Ulrich
Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29100318/flt-1-positive-cells-are-cancer-stem-like-cells-in-colorectal-carcinoma
#19
Ye Huang, Yinpeng Huang, Di Liu, Tianyi Wang, Guang Bai
Recent evidence demonstrates an essential role of cancer stem cells (CSCs) in cancer initiation, progression, migration, metastasis as well as chemo-resistance. Nevertheless, identification of CSCs in different cancers has not been succeeded, since such CSCs are typically lack of a specific and unique marker. Therefore, the current strategy is basically using one or several markers to enrich CSCs, or to isolate CSC-like cells. Here, we showed that in clinically obtained colorectal carcinoma (CRC) specimens, Flt-1, the type 1 receptor for vascular endothelial growth factor A, was significantly upregulated...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100290/cd133-targeted-oncolytic-adenovirus-demonstrates-anti-tumor-effect-in-colorectal-cancer
#20
Mizuho Sato-Dahlman, Yoshiaki Miura, Jing Li Huang, Praveensingh Hajeri, Kari Jacobsen, Julia Davydova, Masato Yamamoto
Oncolytic Adenoviruses (OAds) are one of the most promising anti-cancer agents that can induce cancer specific cell death. Recently, we generated infectivity-selective OAd, and the resultant OAd tumor-specific binding shows strong efficacy and mitigates toxicity. In this study, we applied this strategy based on adenovirus library screening system for generation of CD133-targeted OAd, and examined their oncolytic activity against colorectal cancer (CRC) in vitro and in vivo. CD133 (Prominin-1) is an important cell surface marker of cancer stem (like) cells (CSCs) in various cancers, including CRC...
September 29, 2017: Oncotarget
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