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colorectal cancer And cancer stem cell

Qi-Bing Wu, Xin Sheng, Ning Zhang, Ming-Wei Yang, Fan Wang
Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1...
April 2018: Molecular and Clinical Oncology
Mitsuaki Nishioka, Yutaka Suehiro, Kouhei Sakai, Toshihiko Matsumoto, Naoko Okayama, Hidekazu Mizuno, Koji Ueno, Nobuaki Suzuki, Shinichi Hashimoto, Taro Takami, Shoichi Hazama, Hiroaki Nagano, Isao Sakaida, Takahiro Yamasaki
Tumor necrosis factor receptor superfamily member 19 ( TROY ) is involved in the Wnt/β-catenin signaling pathway and interacts with leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5), which is a well-known biomarker of cancer stem cells and a prognostic marker of colorectal cancer (CRC). Because there have been no studies to evaluate the prognostic significance of TROY , we performed the present study to determine whether TROY can be a prognostic biomarker in CRC patients. We evaluated TROY expression levels in 100 CRC tissues by quantitative real-time PCR and investigated the association of TROY expression levels with clinicopathologic features...
April 2018: Oncology Letters
Shingo Kishi, Rina Fujiwara-Tani, Yi Luo, Isao Kawahara, Kei Goto, Kiyomu Fujii, Hitoshi Ohmori, Chie Nakashima, Takamitsu Sasaki, Hiroki Kuniyasu
Trans fatty acids (TFAs) are risk factors for cardiovascular disorders, and the cancer-promoting effects of TFAs have been previously reported. The present study examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA was found to increase metastasis of HT29 human CRC cells. Results indicated that, in the plasma membrane, EA was integrated into cholesterol rafts, which contain epidermal growth factor receptors (EGFR). EA increased nanog and c-myc, and decreased PGC-1A through lipid raft-associated EGFR signaling in HT29 cells...
April 2018: Oncology Letters
Wenguang Liu, Manwu Wu, Hechun Du, Xiaoliang Shi, Tao Zhang, Jie Li
Silent information regulator 6 (SIRT6) is broadly considered as a tumor suppressor due to its function in the suppression of oncogene expression. However, the role of SIRT6 in colorectal cancer stem cells (CSCs) remains uncharacterized. In the present study, it was demonstrated that SIRT6 expression was reduced in colorectal CSCs. Overexpression of SIRT6 in colorectal CSCs did not induce cell apoptosis. However, SIRT6 significantly inhibited cell proliferation, colony formation and induced G0/G1 phase arrest in colorectal CSCs...
April 2018: Oncology Letters
Sayon Basu, Nancy Gavert, Thomas Brabletz, Avri Ben-Ze'ev
Aberrant Wnt/β-catenin signaling is a common event during human colorectal cancer (CRC) development. Previously, we characterized members of the L1 family of cell adhesion receptors as targets of β-catenin-LEF1/TCF transactivation that are expressed at the invasive CRC tissue edge. Overexpression of L1 in CRC cells confers enhanced motility, tumorigenesis and liver metastasis. We identified several downstream targets of L1-mediated signaling that are considered key intestinal stem cell signature genes. Here, we investigated the involvement of ASCL2, a Wnt target gene and key determinant of intestinal stem cell state, in L1-mediated CRC progression...
March 15, 2018: Cancer Letters
Barry H Smith, Lawrence S Gazda, Thomas J Fahey, Angelica Nazarian, Melissa A Laramore, Prithy Martis, Zoe P Andrada, Joanne Thomas, Tapan Parikh, Sudipta Sureshbabu, Nathaniel Berman, Allyson J Ocean, Richard D Hall, David J Wolf
Objective: The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival (OS) responses, to the use of one such system, implantable macrobeads [RENCA macrobeads (RMBs)], in phase I and IIa clinical trials in advanced, treatment-resistant metastatic colorectal cancer (mCRC) are described here...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Zhenhua Wu, Mingzhu Huang, Yiwei Gong, Chen Lin, Weijian Guo
Mutations in the oncogene BRAF(V600E) are found in ~10% of colorectal cancers (CRCs) and are associated with poor prognosis. However, BRAF(V600E) has a limited response to the small-molecule drug, vemurafenib, a BRAF inhibitor, and BRAF inhibition is thought to cause a feedback activation of EGFR signaling that supports continued proliferation. In this study, we explored the effect of combined use of dabrafenib, a BRAF inhibitor, and cetuximab, an EGFR inhibitor, on BRAF(V600E)-mutant CRC stem cells and its possible mechanisms...
March 9, 2018: Acta Biochimica et Biophysica Sinica
Fu-Shu Jin, Hong-Mei Wang, Xiao-Yan Song
Long non-coding RNA (lnc)TCF7 has been reported to promote the self‑renewal of human cancer stem cells, and enhance the aggressiveness of human non‑small cell lung cancer and hepatocellular carcinoma cells. However, the effect of lncTCF7 on colorectal cancer (CRC) tumorigenesis and progression is currently unclear. In the present study, reverse transcription‑quantitative polymerase chain reaction results demonstrated that lncTCF7 expression was higher in CRC tissues compared with adjacent normal tissues and was significantly associated with tumor size, differentiation degree, tumor‑node‑metastasis grade, lymph node metastasis and invasion depth...
March 9, 2018: Molecular Medicine Reports
Rafidah Ahmad, I Sahidin, Muhammad Taher, ChenFei Low, Normah Mohd Noor, Chanin Sillapachaiyaporn, Siriporn Chuchawankul, Tewarit Sarachana, Tewin Tencomnao, Faizah Iskandar, Nor Fadilah Rajab, Syarul Nataqain Baharum
Polygonumins A, a new compound, was isolated from the stem of Polygonum minus. Based on NMR results, the compound's structure is identical to that of vanicoside A, comprising four phenylpropanoid ester units and a sucrose unit. The structure differences were located at C-3″″'. The cytotoxic activity of polygonumins A was evaluated on several cancer cell lines by a cell viability assay using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The compound showed the highest antiproliferative (p < 0...
March 9, 2018: Scientific Reports
Mona Alibolandi, Khalil Abnous, Sajjad Anvari, Marzieh Mohammadi, Mohammad Ramezani, Seyed Mohammad Taghdisi
Poor aqueous solubility of chemotherapeutics such as SN38 (7-ethyl-10-hydroxycamptothecin) and the associated systemic adverse effects are serious limitations of their clinical use. To improve the drug delivery efficiency of such compounds, they were covalently conjugated to hydrophilic macromolecular carriers that specifically deliver the drug moiety to the tumour cells. In the current study, we developed a PEGylated acetylated carboxymethylcellulose conjugate of SN38 which was covalently attached to an aptamer against a cancer stem cell marker, CD133...
March 8, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Sophie Paquet-Fifield, Shir Lin Koh, Lesley Cheng, Laura Marie Beyit, Carolyn E Shembrey, Christina Moelck, Corina Behrenbruch, Marina Papin, Meritxell Gironella, Sophie Guelfi, Ramona Nasr, Fanny Grillet, Michel Prudhomme, Jean-François Bourgaux, Antoni Castells, Jean-Marc Pascussi, Alexander G Heriot, Alain Puisieux, Melissa J Davis, Julie Pannequin, Andrew F Hill, Erica K Sloan, Frédéric Hollande
Post-treatment recurrence of colorectal cancer (CRC), the third most lethal cancer worldwide, is often driven by a subpopulation of cancer stem cells (CSCs). The tight junction (TJ) protein claudin-2 is overexpressed in human CRC where it enhances cell proliferation, colony formation, and chemoresistance in vitro. While several of these biological processes are features of the CSC phenotype, a role for claudin-2 in the regulation of these has not been identified. Here we report that elevated claudin-2 expression in stage II/III colorectal tumors is associated with poor recurrence-free survival following 5-FU-based chemotherapy, an outcome in which CSC play an instrumental role...
March 6, 2018: Cancer Research
Ning Wu, Andrew Fesler, Hua Liu, Jingfang Ju
Background: Resistance to 5-Fluorouracil (5-FU) based chemotherapy is the major reason for failure of treating patients with advanced colorectal cancer. Materials and methods: In this study, we developed a novel miR-129 mimic with potent efficacy in eliminating resistant colon cancer stem cells both in vitro and in vivo . We integrated 5-FU into miR-129 by replacing Uracil (U) to generate 5-FU-miR-129 mimics (Mimic-1). Results: Mimic-1 is a strong therapeutic candidate with a number of unique features...
February 6, 2018: Oncotarget
Dimitrios Tsoumas, Sofia Nikou, Efstathia Giannopoulou, Spyridon Champeris Tsaniras, Chaido Sirinian, Ioannis Maroulis, Stavros Taraviras, Vassiliki Zolota, Haralabos P Kalofonos, Vasiliki Bravou
BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critically implicated in cancer metastasis and chemoresistance. Herein, we investigated integrin-linked kinase (ILK)'s role in human colon cancer (CRC) progression and chemoresistance in relation to EMT and CSC markers. PATIENTS AND METHODS: Expression of ILK, EMT and CSC markers were evaluated by immunohistochemistry in 149 CRC samples. We also generated colon cancer cells resistant to 5-FU and oxaliplatin and studied the effect of ILK inhibition on drug response by MTT assay and on EMT and CSC markers' expression...
March 2018: Cancer Genomics & Proteomics
Peng Xu, Junhua Wang, Bo Sun, Zhongdang Xiao
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. Recently, miRNAs are reported to be relevant to the self-renewal ability of cancer stem cells. In this study, we first isolated colorectal cancer stem cell from colorectal cancer cell line HCT-116 by 1% low serum culture. Then we conducted a comprehensive analysis based on the miRNAs profiles data of both colorectal cancer stem cells and normal cultured colorectal cancer cells...
February 26, 2018: Gene
Wojciech Marlicz, Agata Poniewierska-Baran, Sylwia Rzeszotek, Rafał Bartoszewski, Karolina Skonieczna-Żydecka, Teresa Starzyńska, Mariusz Z Ratajczak
BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in the western world, and its incidence increases with patient age. It is also known that with age there occur changes in the levels of certain hormones, including an increase in the secretion of pituitary gonadotropins (PtGs) as a result of the loss of gonadal hormone feedback. We recently reported that functional PtG receptors are expressed in human lung cancer cells, rhabdomyosarcoma cells, and malignant hematopoietic stem cells...
2018: PloS One
Norikatsu Miyoshi, Shiki Fujino, Masayuki Ohue, Masayoshi Yasui, Yusuke Takahashi, Keijiro Sugimura, Akira Tomokuni, Hirofumi Akita, Shogo Kobayashi, Hidenori Takahashi, Takeshi Omori, Hiroshi Miyata, Masahiko Yano
PURPOSE: The POU5F1 gene, which encodes the POU domain, class 5, transcription factor 1 (also known as Oct-4), is expressed in embryonic stem cells where it regulates pluripotency and proliferation. Few studies have examined the expression and significance of POU5F1 in cancer tissues. The aim of this study was to clarify its significance in colorectal cancer (CRC). METHODS: The study included 95 patients who underwent surgery for CRC from 2009 to 2011. The correlations between the POU5F1 gene expression and the clinical parameters were assessed in these patients...
February 27, 2018: Surgery Today
Maria Laura De Angelis, Alessandro Bruselles, Federica Francescangeli, Flavia Pucilli, Sara Vitale, Ann Zeuner, Marco Tartaglia, Marta Baiocchi
Biobanking of molecularly characterized colorectal cancer stem cells (CSCs) generated from individual patients and growing as spheroids in defined serum-free media offer a fast, feasible, and multi-level approach for the screening of targeted therapies and drug resistance molecular studies. By combining in vitro and in vivo analyses of cetuximab efficacy with genetic data on an ongoing collection of stem cell-enriched spheroids, we describe the identification and preliminary characterization of microsatellite stable (MSS) CSCs that, despite the presence of the KRAS (G12D) mutation, display epidermal growth factor (EGF)-dependent growth and are strongly inhibited by anti-EGF-receptor (EGFR) treatment...
February 24, 2018: Cell Biology and Toxicology
Yun Zhu, Cindy Wang, Scott A Becker, Katie Hurst, Lourdes M Nogueira, Victoria J Findlay, E Ramsay Camp
Epithelial-to-mesenchymal transition (EMT) has been closely linked with therapy resistance and cancer stem cells (CSCs). However, EMT pathways have proven challenging to therapeutically target. MicroRNA 145 (miR-145) targets multiple stem cell transcription factors and its expression is inversely correlated with EMT. Therefore, we hypothesized that miR-145 represents a therapeutic target to reverse snail family transcriptional repressor 1 (SNAI1)-mediated stemness and radiation resistance (RT). Stable expression of SNAI1 in DLD1 and HCT116 cells (DLD1-SNAI1; HCT116-SNAI1) increased expression of Nanog and decreased miR-145 expression compared to control cells...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Michael K Dame, Durga Attili, Shannon D McClintock, Priya H Dedhia, Peter Ouillette, Olaf Hardt, Alana M Chin, Xiang Xue, Julie Laliberte, Erica L Katz, Gina M Newsome, David R Hill, Alyssa J Miller, Yu-Hwai Tsai, David Agorku, Christopher H Altheim, Andreas Bosio, Becky Simon, Linda C Samuelson, Jay A Stoerker, Henry D Appelman, James Varani, Max S Wicha, Dean E Brenner, Yatrik M Shah, Jason R Spence, Justin A Colacino
The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, while less is known about human intestinal stem cells due to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas, and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC) associated genes. Normal and neoplastic colon tissue organoids were analyzed by immunohistochemistry and fluorescent-activated cell sorting for LGR5...
February 21, 2018: Development
Laura C Panelo, Mileni Soares Machado, María F Rubio, Felipe Jaworski, Cecilia V Alvarado, Leonardo A Paz, Alejandro J Urtreger, Elba Vazquez, Mónica A Costas
RAC3 is a transcription coactivator, usually overexpressed in several tumors and required to maintain the pluripotency in normal stem cells. In this work we studied the association between RAC3 overexpression on cancer cell stemness and the capacity of this protein to induce cancer stem properties in non tumoral cells. We performed in vitro and in vivo experiments using two strategies: by overexpressing RAC3 in the non tumoral cell line HEK293 and by silencing RAC3 in the human colorectal epithelial cell line HCT116 by transfection...
January 19, 2018: Oncotarget
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