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colorectal cancer And cancer stem cell

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https://www.readbyqxmd.com/read/27916539/inhibiting-the-sumo-pathway-represses-the-cancer-stem-cell-population-in-breast-and-colorectal-carcinomas
#1
Maria V Bogachek, Jung M Park, James P De Andrade, Allison W Lorenzen, Mikhail V Kulak, Jeffrey R White, Vivian W Gu, Vincent T Wu, Ronald J Weigel
Many solid cancers have an expanded CD44(+/hi)/CD24(-/low) cancer stem cell (CSC) population, which are relatively chemoresistant and drive recurrence and metastasis. Achieving a more durable response requires the development of therapies that specifically target CSCs. Recent evidence indicated that inhibiting the SUMO pathway repressed tumor growth and invasiveness, although the mechanism has yet to be clarified. Here, we demonstrate that inhibition of the SUMO pathway repressed MMP14 and CD44 with a concomitant reduction in cell invasiveness and functional loss of CSCs in basal breast cancer...
November 24, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27915990/possible-molecular-mechanisms-by-which-vitamin-d-prevents-inflammatory-bowel-disease-and-colitis-associated-colorectal-cancer
#2
Zijian Luan, Yiming Ma, Yu Xin, Jiaming Qian, Hongying Wang
It is well accepted that inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is one of high risk factors for colorectal cancer (CRC). This supports the notion that inflammation plays a key role in cancer development. Epidemiologic studies have shown that vitamin D (Vit D) deficiency is associated with IBD and various types of cancer including colorectal cancer. Clinical trials and mouse models have shown that Vit D is beneficial in preventing or ameliorating inflammation and carcinogenesis...
December 2, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27913197/doxorubicin-induced-mitophagy-contributes-to-drug-resistance-in-cancer-stem-cells-from-hct8-human-colorectal-cancer-cells
#3
Chen Yan, Lan Luo, Chang-Ying Guo, Shinji Goto, Yoshishige Urata, Jiang-Hua Shao, Tao-Sheng Li
Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133(+)/CD44(+) CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27909729/self-renewal-molecular-mechanisms-of-colorectal-cancer-stem-cells
#4
Tianhui Pan, Jinghong Xu, Yongliang Zhu
Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal...
November 30, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27908725/par3l-enhances-colorectal-cancer-cell-survival-by-inhibiting-lkb1-ampk-signaling-pathway
#5
Taiyuan Li, Dongning Liu, Xiong Lei, Qunguang Jiang
Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908290/bile-acid-a-potential-inducer-of-colon-cancer-stem-cells
#6
Lulu Farhana, Pratima Nangia-Makker, Evan Arbit, Kathren Shango, Sarah Sarkar, Hamidah Mahmud, Timothy Hadden, Yingjie Yu, Adhip P N Majumdar
BACKGROUND: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. METHODS: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27904609/deciphering-biological-characteristics-of-tumorigenic-subpopulations-in-human-colorectal-cancer-reveals-cellular-plasticity
#7
Hamed Mirzaei, Hossein Salehi, Amirhossein Sahebkar, Amir Avan, Mahmoud Reza Jaafari, Afshin Namdar, Abbas Rezaei, Hamid Reza Mirzaei
BACKGROUND: It is supposed that human colorectal cancer consists of a phenotypically distinct population of tumorigenic cancer cells known as cancer stem cells (CSCs) which play a pivotal role in cancer progression, maintenance, metastasis, and the relapse. The aim of this effort was to investigate and compare biological characterizations of CD133(+) with CD133(-) cell subsets isolated from both primary and metastatic human colorectal tumors. MATERIALS AND METHODS: Using our optimized protocols, unfixed colorectal tumors were enzymatically and mechanically dissociated into single cells followed by evaluation of postdigestion viability...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27899379/transcriptional-regulator-cnot3-defines-an-aggressive-colorectal-cancer-subtype
#8
Paloma Cejas, Alessia Cavazza, Chandri Yandava, Víctor Moreno, David Horst, Juan Moreno-Rubio, Emilio Burgos, Marta Mendiola, Len Taing, Ajay Goel, Jaime Feliu, Ramesh A Shivdasani
Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent and impact of these alterations are still being unraveled. Here we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers (CRC), as compared to corresponding benign precursor adenomas. Modification of certain CRC sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC)...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27896624/autologous-bone-marrow-stem-cell-transplantation-for-the-treatment-of-ulcerative-colitis-complicated-with-herpes-zoster-a-case-report
#9
Hang Xiang, Xiaomei Zhang, Chao Yang, Wenhuan Xu, Xin Ge, Rong Zhang, Ya Qiu, Wanjun Sun, Fan Li, Tianyuan Xiang, Haixu Chen, Zheng Wang, Qiang Zeng
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with continuous or recurrent symptoms. A 42-year-old male patient with intermittent diarrhea accompanied by bloody mucopurulent stools was admitted to our hospital. The diagnosis of UC was confirmed by a combination of laboratory examination, colonoscopy, and histological assay. The patient developed herpes zoster in the hospital, which challenged traditional treatments. Therefore, we performed an autologous bone marrow cells to modulate the immune system with his permission...
November 28, 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27895148/trpc5-regulates-differentiation-through-the-ca2-wnt5a-signal-pathway-in-colorectal-cancer
#10
Zhen Chen, Chunlei Tang, Yaodan Zhu, Mingxu Xie, Dongxu He, Qiongxi Pan, Peng Zhang, Dong Hua, Teng Wang, Linfang Jin, Xiaowei Qi, Yifei Zhu, Xiaoqiang Yao, Jian Jin, Xin Ma
Transient receptor potential channel 5 (TrpC5) is member of the TrpC subgroup, and it forms a receptor-activated non-selective Ca(2+) channel. The architecture of the TrpC5 channel is poorly understood. Here, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer. Through a study of specimens from a large cohort of patients with colorectal cancer, we found that TrpC5 was highly expressed and its cellular level correlated with tumor grade. We further showed that up-regulated TrpC5 caused a robust [Ca(2+)]i rise, increased Wnt5a expression, and the nuclear translocation of β-catenin, leading to a reduction of cancer differentiation and an increase of cancer cell stemness...
November 28, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27894099/peroxiredoxin-2-is-essential-for-maintaining-cancer-stem-cell-like-phenotype-through-activation-of-hedgehog-signaling-pathway-in-colon-cancer
#11
Rong Wang, Jinlai Wei, Shouru Zhang, Xingye Wu, Jinbao Guo, Maoxi Liu, Kunli Du, Jun Xu, Linglong Peng, Zhenbing Lv, Wenxian You, Yongfu Xiong, Zhongxue Fu
Cancer stem cells (CSCs) are a key target for reducing tumor growth, metastasis, and recurrence. Redox status is a critical factor in the maintenance of CSCs, and the antioxidant enzyme Peroxiredoxin 2 (Prdx2) plays an important role in the development of colon cancer. Therefore, we investigated the contribution of Prdx2 to the maintenance of stemness of colon CSCs. Here, we used short-hairpin RNAs and a Prdx2-overexpression vector to determine the effects of Prdx2. We demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere formation and resulted in increased 5-FU-induced apoptosis in human colon CSCs...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27880730/loss-of-zg16-is-regulated-by-mir-196a-and-contributes-to-stemness-and-progression-of-colorectal-cancer
#12
Xiaobing Chen, Peng Du, Junjun She, Liang Cao, Yingchao Li, Hongping Xia
Colorectal cancer (CRC) is one of the most common malignant tumour and the leading cause of cancer-related mortality worldwide. Clarification of the mechanism that underlies CRC tumorigenesis and progression therefore is urgently needed ffor developing novel therapies. Through analysis of The Cancer Genome Atlas (TCGA) dataset, we identified an interesting gene, ZG16, which is significantly decreased in CRC samples compared to adjacent non-tumor tissues and associated with prognosis of patients. We found that the expression of ZG16 correlated with CRC related genes which were regulated by APC/CTNNB1 pathway...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863474/hypoxic-resistance-of-kras-mutant-tumor-cells-to-3-bromopyruvate-is-counteracted-by-prima-1-and-reversed-by-n-acetylcysteine
#13
Andrea Orue, Valery Chavez, Mary Strasberg-Rieber, Manuel Rieber
BACKGROUND: The metabolic inhibitor 3-bromopyruvate (3-BrPA) is a promising anti-cancer alkylating agent, shown to inhibit growth of some colorectal carcinoma with KRAS mutation. Recently, we demonstrated increased resistance to 3-BrPA in wt p53 tumor cells compared to those with p53 silencing or mutation. Since hypoxic microenvironments select for tumor cells with diminished therapeutic response, we investigated whether hypoxia unequally increases resistance to 3-BrPA in wt p53 MelJuso melanoma harbouring (Q61L)-mutant NRAS and wt BRAF, C8161 melanoma with (G12D)-mutant KRAS (G464E)-mutant BRAF, and A549 lung carcinoma with a KRAS (G12S)-mutation...
November 18, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27857154/a-van-der-waals-like-transition-between-normal-and-cancerous-phases-in-cell-populations-dynamics-of-colorectal-cancer
#14
Kang Qiu, Li-Fang Wang, Jian Shen, Alssadig A M Yousif, Peng He, Dan-Dan Shao, Xiao-Min Zhang, John B Kirunda, Ya Jia
Based on a deterministic continuous model of cell populations dynamics in the colonic crypt and in colorectal cancer, we propose four combinations of feedback mechanisms in the differentiations from stem cells (SCs) to transit cells (TCs) and then to differentiated cells (DCs), the four combinations include the double linear (LL), the linear and saturating (LS), the saturating and linear (SL), and the double saturating (SS) feedbacks, respectively. The relative fluctuations of the population of SCs, TCs, and DCs around equilibrium states with four feedback mechanisms are studied by using the Langevin method...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27855654/salinomycin-inhibits-metastatic-colorectal-cancer-growth-and-interferes-with-wnt-%C3%AE-catenin-signaling-in-cd133-human-colorectal-cancer-cells
#15
Johannes Klose, Jana Eissele, Claudia Volz, Steffen Schmitt, Alina Ritter, Shen Ying, Thomas Schmidt, Ulrike Heger, Martin Schneider, Alexis Ulrich
BACKGROUND: The polyether antibiotic Salinomycin (Sal) is regarded as an inhibitor of cancer stem cells. Its effectiveness on human colorectal cancer (CRC) cells in vitro has been demonstrated before. The aim of this study was to establish a murine model to investigate the effectiveness of Sal in vivo. Furthermore, we investigated the impact of Sal on Wnt/β-catenin signaling in human CD133(+) CRC cells. METHODS: The two murine CRC cell lines MC38 and CT26 were used to analyze the impact of Sal on tumor cell proliferation, viability, migration, cell cycle progression and cell death in vitro...
November 17, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27843459/tumor-budding-micropapillary-pattern-and-polyploidy-giant-cancer-cells-in-colorectal-cancer-current-status-and-future-prospects
#16
REVIEW
Shiwu Zhang, Dan Zhang, Zhengduo Yang, Xipeng Zhang
We previously reported that polyploid giant cancer cells (PGCGs) induced by CoCl2 could form through endoreduplication or cell fusion. A single PGCC formed tumors in immunodeficient mice. PGCCs are also the key contributors to the cellular atypia and associate with the malignant grade of tumors. PGCCs have the properties of cancer stem cells and produce daughter cells via asymmetric cell division. Compared with diploid cancer cells, these daughter cells express less epithelial markers and acquire mesenchymal phenotype with importance in cancer development and progression...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27835894/co-expression-of-lgr5-and-cxcr4-characterizes-cancer-stem-like-cells-of-colorectal-cancer
#17
Weidong Wu, Jun Cao, Zhengyi Ji, Jingjue Wang, Tao Jiang, Honghua Ding
Therapies designed to target cancer stem cells (CSCs) in colorectal cancer (CRC) may improve treatment outcomes. Different markers have been used to identify CSCs or CSC-like cells in CRC, but the enrichment of CSCs using these markers has yet to be optimized. We recently reported the importance of Lgr5-positive CRC cells in cancer growth. Here, we studied the possibility of using Lgr5 and CXCR4 as CSC markers for CRC. We detected high Lgr5 and CXCR4 levels in stage IV CRC specimens. Both high Lgr5 and CXCR4 levels were associated with poor prognosis in stage IV CRC patients...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833077/anti-egfr-antibody-sensitizes-colorectal-cancer-stem-like-cells-to-fluorouracil-induced-apoptosis-by-affecting-autophagy
#18
Ye Feng, Shuohui Gao, Yongjian Gao, Xuefeng Wang, Zhi Chen
Recent reports suggest that colorectal carcinoma (CRC) may be sustained by a small subpopulation of cells, termed cancer stem cells (CSCs), which have drug resistance properties as a key reason for chemotherapy failure. The epidermal growth factor receptor (EGFR) controls CRC initiation and progression. Monoclonal antibody against EGFR (cetuximab) has been used in treatment of several cancers. However, the effects of cetuximab on CSCs in the CRC chemotherapy remain unclear. Here, we studied the effects of cetuximab on the CSC-like cells in Fluorouracil (5-FU)-treated CRC cells...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832750/metastasis-associated-in-colon-cancer-1-and-aldehyde-dehydrogenase-1-are-metastatic-and-prognostic-biomarker-for-non-small-cell-lung-cancer
#19
Lei Zhou, Lan Yu, Bo Zhu, Shiwu Wu, Wenqing Song, Xiaomeng Gong, Danna Wang
BACKGROUND: Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC...
November 10, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27832659/elaidic-acid-a-trans-fatty-acid-enhances-the-metastasis-of-colorectal-cancer-cells
#20
Hitoshi Ohmori, Kiyomu Fujii, Yui Kadochi, Shiori Mori, Yukiko Nishiguchi, Rina Fujiwara, Shingo Kishi, Takamitsu Sasaki, Hiroki Kuniyasu
The effects of trans-fatty acids (TFAs) on cardiovascular disorders have been extensively studied, and the effect of TFAs on cancers has recently been recognized. This study examined the effects of elaidic acid (EA), a TFA, on colorectal cancer (CRC) progression. We demonstrated that EA enhanced the growth, survival, and invasion of the CRC cell lines, CT26, and HT29. Tumor growth and metastasis in the lung, liver, and peritoneum were significantly more enhanced in CRC cells treated with EA than those treated with the cis form of EA, oleic acid (OA), or vehicle...
November 11, 2016: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
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