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https://www.readbyqxmd.com/read/29416778/modified-mir-15a-has-therapeutic-potential-for-improving-treatment-of-advanced-stage-colorectal-cancer-through-inhibition-of-bcl2-bmi1-yap1-and-dclk1
#1
Andrew Fesler, Hua Liu, Jingfang Ju
Despite advances in colon cancer treatments, resistance and recurrence remain a significant challenge in treating patients. Novel therapeutic strategies are in urgent need to overcome resistance and improve patient outcomes. MicroRNA based therapeutics have potential to help combat resistance. In this study, we have shown that low miR-15a expression correlates with poor patient prognosis. We have demonstrated the therapeutic potential of miR-15a in colon cancer. miR-15a inhibits several important genes (BCL2, BMI1, YAP1 and DCLK1), decreasing cancer progression and resistance...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29399338/expression-of-doublecortin-and-cam-kinase-like-1-protein-in-serrated-neoplasia-of-the-colorectum
#2
Keiko Morio, Kazuo Yashima, Akihiro Tamoto, Kohei Hosoda, Sohei Yamamoto, Taku Iwamoto, Naoki Ueda, Yuichiro Ikebuchi, Koichiro Kawaguchi, Kenichi Harada, Yoshikazu Murawaki, Hajime Isomoto
The adenoma-carcinoma sequence (ACS) and the serrated pathway are two distinct developmental routes leading to the formation of colorectal carcinoma. Recently, the doublecortin and CaM kinase-like-1 protein (DCLK1) has been reported to serve as an intestinal cancer stem cell marker and has been demonstrated to be overexpressed through the ACS; however, there is a lack of reports on the role of DCLK1 in the serrated pathway. To clarify the correlation between DCLK1 protein expression and clinicopathological characteristics of the serrated tumorigenic pathway, the present study used immunohistochemistry to examine the expression of DCLK1 in endoscopically resected samples of 62 serrated polyps [20 hyperplastic polyps (HPs), 16 traditional serrated adenomas (TSAs) and 26 sessile serrated adenoma-polyps (SSA/Ps)], as well as 20 non-serrated adenomas, 20 carcinoma in adenomas (CIAs) and 18 early pure colorectal carcinomas without any adenoma component (EPCs)...
January 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29344199/expression-and-prognostic-significance-of-doublecortin-like-kinase-1-in-patients-with-hepatocellular-carcinoma
#3
Mengjiao Fan, Niansong Qian, Guanghai Dai
Doublecortin-like kinase 1 (DCLK1), a putative cancer stem cell marker in intestinal and pancreatic tumors, is associated with tumor pathogenesis and progression, and poor survival outcomes in numerous types of cancer. However, DCLK1 expression and its prognostic value remain unclear in hepatocellular carcinoma (HCC). In the present study, the expression of DCLK1 was assessed using immunohistochemistry in 96 resected HCC and 68 adjacent tissue specimens. The staining intensity and the percentage of stained cells were scored on a scale of 0-3 and 0-4, respectively...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29277893/dclk1-promotes-epithelial-mesenchymal-transition-via-the-pi3k-akt-nf-%C3%AE%C2%BAb-pathway-in-colorectal-cancer
#4
Weiying Liu, Shixing Wang, Qi Sun, Zhen Yang, Min Liu, Hua Tang
Double cortin-like kinase 1 (DCLK1) plays important roles during the epithelial-mesenchymal transition (EMT) process in human colorectal cancer (CRC). However, the role of DCLK1 in regulating the EMT of CRC is still poorly understood. In this study, we report evidence that DCLK1 acts as a potent oncogene to drive its extremely malignant character of EMT in an NF-κB-dependent manner in CRC cells. Mechanistic investigations showed that DCLK1 induced the NF-κBp65 subunit expression through the PI3K/Akt/Sp1 axis and activated NF-κBp65 through the PI3K/Akt/IκBα pathway during the EMT of CRC cells...
December 26, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29246000/increased-dclk1-correlates-with-the-malignant-status-and-poor-outcome-in-malignant-tumors-a-meta-analysis
#5
Wenhua Shi, Fangwei Li, Shaojun Li, Jian Wang, Qingting Wang, Xin Yan, Qianqian Zhang, Limin Chai, Manxiang Li
Doublecortin-like kinase 1 (DCLK1) has been found to be involved in malignant biological behavior of cancers and poor prognosis of cancer patients. The aim of this meta-analysis was to systematically clarify the relationships between expression level of DCLK1 and clinicopathological characteristics in tumors and assess its clinical value in cancer diagnosis and prognosis. 18 eligible studies with a total of 2660 patients were identified by searching the electronic bibliographic databases. Pooled results showed that DCLK1 was highly expressed in tissues from cancer patients compared to normal tissues (OR, 10...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224010/microrna-195-suppresses-the-progression-of-pancreatic-cancer-by-targeting-dclk1
#6
Bin Zhou, Chuandong Sun, Xiao Hu, Hanxiang Zhan, Hao Zou, Yujie Feng, Fabo Qiu, Shun Zhang, Liqun Wu, Bingyuan Zhang
BACKGROUND/AIMS: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor-specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays an important role in many types of tumors. However, the roles of DCLK1 in cancer and miRNAs that directly regulate DCLK1 have not been elucidated. The goal of this study is to assess the effects of miR-195 on inhibiting DCLK1 and to clarify the regulating mechanism of miR-195-DCLK1 in PC cells. METHODS: The expression of DCLK1 protein and miR-195 in PC tissues and adjacent healthy pancreatic tissues was detected by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively and the correlation between overall survival of PC patients and expression of DCLK1 was measured by Kaplan-Meier analysis...
December 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29212456/helicobacter-induced-gastric-inflammation-alters-the-properties-of-gastric-tissue-stem-progenitor-cells
#7
Wataru Shibata, Soichiro Sue, Sachiko Tsumura, Yasuaki Ishii, Takeshi Sato, Eri Kameta, Makoto Sugimori, Hiroaki Yamada, Hiroaki Kaneko, Tomohiko Sasaki, Tomohiro Ishii, Toshihide Tamura, Masaaki Kondo, Shin Maeda
BACKGROUND: Although Helicobacter-induced gastric inflammation is the major predisposing factor for gastric carcinogenesis, the precise mechanism by which chronic gastritis causes gastric cancer remains unclear. Intestinal and spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as precancerous lesions, changes in epithelial tissue stem/progenitor cells after chronic inflammation has not been clarified yet. In this study, we utilized three-dimensional gastric epithelial cell culture systems that could form organoids, mimicking gastric epithelial layer, and characterized the changes in epithelial cells after chronic Helicobacter felis infection...
December 6, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29053464/co-expression-network-approach-to-studying-the-effects-of-botulinum-neurotoxin-a
#8
Kavitha Mukund, Samuel R Ward, Richard L Lieber, Shankar Subramaniam
Botulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically clustered into 5 groups. Quantifying average expression and co-expression patterns across these groups revealed temporal aspects of muscle's response to BoNT-A...
October 16, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/29048622/enhancement-of-cytotoxic-effects-of-gemcitabine-by-dclk1-inhibition-through-suppression-of-chk1-phosphorylation-in-human-pancreatic-cancer-cells
#9
Daichi Kawamura, Yoshihiro Takemoto, Arata Nishimoto, Koji Ueno, Tohru Hosoyama, Bungo Shirasawa, Toshiki Tanaka, Naruji Kugimiya, Eijiro Harada, Kimikazu Hamano
Although gemcitabine (GEM) is frequently used in the treatment of pancreatic cancer, the effects are limited. To increase the inhibitory effect of GEM, the identification of a molecular target is needed. Recent studies have revealed that doublecortin-like kinase 1 (Dclk1) positively regulates tumor growth, invasion, metastasis, factors related to epithelial-mesenchymal transition (EMT), pluripotency, angiogenesis, and anti-apoptosis in pancreatic cancer cells. Therefore, Dclk1 is a potential therapeutic target for pancreatic cancer...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28946555/lgr5high-dclk1high-phenotype-is-more-common-in-early-stage-and-intestinal-subtypes-of-gastric-carcinomas
#10
Elham Kalantari, Mohammad Hossein Asadi Lari, Raheleh Roudi, Alireza Korourian, Zahra Madjd
BACKGROUND: Gastric carcinoma is the third most common malignancy and is one of the main causes of cancer deaths worldwide. Cancer stem cells (CSCs) are a subpopulation of tumour cells capable of self-renewal and differentiation, likely responsible for the initiation, recurrence, metastasis and chemo/radio-resistance. OBJECTIVE: This study was conducted to evaluate the expression patterns and clinicopathologic significance of putative CSC markers, Lgr5 and DCLK1, in gastric carcinoma...
September 15, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28887549/satb2-%C3%AE-catenin-tcf-lef-pathway-induces-cellular-transformation-by-generating-cancer-stem-cells-in-colorectal-cancer
#11
Wei Yu, Yiming Ma, Sharmila Shankar, Rakesh K Srivastava
Recent studies have demonstrated the involvement of colorectal cancer (CRC) stem cells (CSC) in transformation, cancer progression and metastasis. The main goal of this paper was to examine the molecular mechanisms by which SATB2 induced malignant transformation of colorectal epithelial cells. SATB2 induced malignant transformation and these transformed cells gained the characteristics of CSCs by expressing stem cell markers (CD44, CD133, LGR5 and DCLK1) and transcription factors (c-Myc, Nanog and Sox2). Overexpression of SATB2 in normal colorectal epithelial cells increased cell motility, migration and invasion, which were associated with an increase in N-cadherin and Zeb1, and decrease in E-cadherin expression...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883702/doublecortin-and-cam-kinase-like-1-as-an-independent-prognostic-factor-in-patients-with-resected-pancreatic-carcinoma
#12
Kohei Nishio, Kenjiro Kimura, Ryosuke Amano, Bunzo Nakata, Sadaaki Yamazoe, Go Ohira, Kotaro Miura, Naoki Kametani, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira
AIM: To elucidate the effect of expression of doublecortin and CaM kinase-like-1 (DCLK1) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Tumor specimens were obtained from 136 patients with pancreatic cancer who had undergone resection without preoperative therapy between January 2000 and December 2013 at the Department of Surgical Oncology, Osaka City University. The resected specimens were analyzed for associations with clinicopathological data, including DCLK1 expression, epithelial mesenchymal transition (EMT) marker expression, and cancer stem cell (CSC) marker expression...
August 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28851816/foxd3-regulates-csc-marker-dclk1-s-and-invasive-potential-prognostic-implications-in-colon-cancer
#13
Shubhashish Sarkar, Malaney R O'Connell, Yoshinaga Okugawa, Brian S Lee, Yuji Toiyama, Masato Kusunoki, Robert D Daboval, Ajay Goel, Pomila Singh
The 5' (α)-promoter of the human doublecortin-like kinase 1 (DCLK1) gene becomes epigenetically silenced during colon carcinogenesis, resulting in loss of expression of the canonical long(L)-isoform1 (DCLK1-L) in human colon adenocarcinomas (hCRCs). Instead, hCRCs express a short(S)-isoform2 (DCLK1-S) from an alternate (β)-promoter of DCLK1. The current study, examined if the transcriptional activity of the (β)-promoter is suppressed in normal-vs-cancerous cells. Based on in silico and molecular approaches it was discovered that FOXD3 potently inhibits the transcriptional activity of the (β)-promoter...
August 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28756295/actin-alpha-cardiac-muscle-1-gene-expression-is-upregulated-in-the-skeletal-muscle-of-men-undergoing-androgen-deprivation-therapy-for-prostate-cancer
#14
Ada S Cheung, Casey de Rooy, Itamar Levinger, Kesha Rana, Michele V Clarke, Jackie M How, Andrew Garnham, Catriona McLean, Jeffrey D Zajac, Rachel A Davey, Mathis Grossmann
Androgen deprivation therapy (ADT) decreases muscle mass and function but no human studies have investigated the underlying genetic or cellular effects. We tested the hypothesis that ADT will lead to changes in skeletal muscle gene expression, which may explain the adverse muscle phenotype seen clinically. We conducted a prospective cohort study of 9 men with localised prostate cancer who underwent a vastus lateralis biopsy before and after 4 weeks of ADT. Next-generation RNA sequencing was performed and genes differentially expressed following ADT underwent gene ontology mining using Ingenuity Pathway Analysis...
November 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28717211/epithelial-cell-specific-raptor-is-required-for-initiation-of-type-2-mucosal-immunity-in-small-intestine
#15
Bola Aladegbami, Lauren Barron, James Bao, Jason Colasanti, Christopher R Erwin, Brad W Warner, Jun Guo
Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684459/dclk1-expressing-tuft-cells-critical-modulators-of-the-intestinal-niche
#16
REVIEW
Moritz Middelhoff, C Benedikt Westphalen, Yoku Hayakawa, Kelley S Yan, Michael D Gershon, Timothy C Wang, Michael Quante
Dclk1-expressing tuft cells constitute a unique intestinal epithelial lineage that is distinct from enterocytes, Paneth cells, goblet cells, and enteroendocrine cells. Tuft cells express taste-related receptors and distinct transcription factors and interact closely with the enteric nervous system, suggesting a chemosensory cell lineage. In addition, recent work has shown that tuft cells interact closely with cells of the immune system, with a critical role in the cellular regulatory network governing responses to luminal parasites...
October 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28570279/optimized-multiplex-immunofluorescence-single-cell-analysis-reveals-tuft-cell-heterogeneity
#17
Eliot T McKinley, Yunxia Sui, Yousef Al-Kofahi, Bryan A Millis, Matthew J Tyska, Joseph T Roland, Alberto Santamaria-Pang, Christina L Ohland, Christian Jobin, Jeffrey L Franklin, Ken S Lau, Michael J Gerdes, Robert J Coffey
Intestinal tuft cells are a rare, poorly understood cell type recently shown to be a critical mediator of type 2 immune response to helminth infection. Here, we present advances in segmentation algorithms and analytical tools for multiplex immunofluorescence (MxIF), a platform that enables iterative staining of over 60 antibodies on a single tissue section. These refinements have enabled a comprehensive analysis of tuft cell number, distribution, and protein expression profiles as a function of anatomical location and physiological perturbations...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28562528/microrna-profiling-in-the-dentate-gyrus-in-epileptic-rats-the-role-of-mir-187-3p
#18
Suya Zhang, Yubin Kou, Chunmei Hu, Yan Han
This study aimed to explore the role of aberrant miRNA expression in epilepsy and to identify more potential genes associated with epileptogenesis.The miRNA expression profile of GSE49850, which included 20 samples from the rat epileptic dentate gyrus at 7, 14, 30, and 90 days after electrical stimulation and 20 additional samples from sham time-matched controls, was downloaded from the Gene Expression Omnibus database. The significantly differentially expressed miRNAs were identified in stimulated samples at each time point compared to time-matched controls, respectively...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28560410/dclk1-is-correlated-with-met-and-erk5-expression-and-associated-with-prognosis-in-malignant-pleural-mesothelioma
#19
Hui Wang, Yu-Yuan Dai, Wen-Qian Zhang, Ping-Chih Hsu, Yi-Lin Yang, Yu-Cheng Wang, Geraldine Chan, Alfred Au, Zhi-Dong Xu, Shu-Juan Jiang, Wei Wang, David M Jablons, Liang You
Malignant pleural mesothelioma (MPM) is an aggressive cancer for which more effective treatments are needed. In this study, strong to moderate staining of MET and ERK5 was detected in 67.1 and 48% of the analyzed 73 human mesothelioma tumors, and significant correlation of MET and ERK5 expression was identified (P<0.05). We evaluated the doublecortin-like kinase 1 (DCLK1) expression in human mesothelioma tumors. Our results showed that 50.7% of the immunohistochemistry analyzed human mesothelioma tumors have strong to moderate staining of DCLK1, and its expression is significantly correlated with MET or ERK5 expression (P<0...
July 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28536281/distinct-roles-of-hes1-in-normal-stem-cells-and-tumor-stem-like-cells-of-the-intestine
#20
Norihiro Goto, Taro Ueo, Akihisa Fukuda, Kenji Kawada, Yoshiharu Sakai, Hiroyuki Miyoshi, Makoto Mark Taketo, Tsutomu Chiba, Hiroshi Seno
Cancer stem cells (CSC) have attracted attention as therapeutic targets; however, CSC-targeting therapy may disrupt normal tissue homeostasis because many CSC molecules are also expressed by normal stem cells (NSC). Here, we demonstrate that NSC-specific and CSC-specific roles of the stem cell transcription factor Hes1 in the intestine enable the feasibility of a specific cancer therapy. Hes1 expression was upregulated in NSCs and intestinal tumors. Lineage-tracing experiments in adult mouse intestine revealed that Hes1 deletion in Lgr5(+) or Bmi1(+) NSCs resulted in loss of self-renewal but did not perturb homeostasis...
July 1, 2017: Cancer Research
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