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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
#1
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...
July 27, 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
#2
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
#3
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...
July 6, 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
#4
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
#5
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
#6
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
#7
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...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28414327/a-novel-antibody-against-cancer-stem-cell-biomarker-dclk1-s-is-potentially-useful-for-assessing-colon-cancer-risk-after-screening-colonoscopy
#8
Shubhashish Sarkar, Vsevolod L Popov, Malaney R O'Connell, Heather L Stevenson, Brian S Lee, Robert A Obeid, Gurinder K Luthra, Pomila Singh
DCLK1 expression is critically required for maintaining growth of human colon cancer cells (hCCCs). Human colorectal tumors (CRCs) and hCCCs express a novel short isoform of DCLK1 (DCLK1-S; isoform 2) from β-promoter of hDCLK1 gene, while normal colons express long isoform (DCLK1-L; isoform 1) from 5'(α)-promoter, suggesting that DCLK1-S, and not DCLK1-L, marks cancer stem cells (CSCs). Even though DCLK1-S differs from DCLK1-L by only six amino acids, we succeeded in generating a monospecific DCLK1-S-Antibody (PS41014), which does not cross-react with DCLK1-L, and specifically detects CSCs...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28382517/doublecortin-and-cam-kinase-like-1-expression-in-pathological-stage-i-non-small-cell-lung-cancer
#9
Hiroyuki Tao, Toshiki Tanaka, Kazunori Okabe
PURPOSE: Doublecortin and CaM kinase-like-1 (DCLK1) regulates microtubule polymerization in migrating neurons. Recently, DCLK1 has been reported to act as an intestinal tumor stem cell marker and has been shown to be expressed in cancer cells and in the stroma of breast, colon, pancreatic, and prostate cancers. Here, we studied DCLK1 expression in non-small cell lung cancer (NSCLC) by immunohistochemistry in association with clinicopathological factors and patient prognosis. METHODS: DCLK1 expression was analyzed by immunohistochemical staining of surgical specimens from 232 patients with pathological stage I NSCLC, including 187 adenocarcinomas...
August 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28375676/tyrosine-phosphorylation-of-an-actin-binding-protein-girdin-specifically-marks-tuft-cells-in-human-and-mouse-gut
#10
Daisuke Kuga, Kaori Ushida, Shinji Mii, Atsushi Enomoto, Naoya Asai, Masato Nagino, Masahide Takahashi, Masato Asai
Tuft cells (TCs) are minor components of gastrointestinal epithelia, characterized by apical tufts and spool-shaped somas. The lack of reliable TC-markers has hindered the elucidation of its role. We developed site-specific and phosphorylation-status-specific antibodies against Girdin at tyrosine-1798 (pY1798) and found pY1798 immunostaining of mouse jejunum clearly depicted epithelial cells closely resembling TCs. This study aimed to validate pY1798 as a TC-marker. Double-fluorescence staining of intestines was performed with pY1798 and known TC-markers, for example, hematopoietic-prostaglandin-D-synthase (HPGDS), or doublecortin-like kinase 1 (DCLK1)...
June 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28351564/role-of-cancer-stem-cell-marker-doublecortin-like-kinase-1-in-head-and-neck-squamous-cell-carcinoma
#11
Lorenz Kadletz, Dietmar Thurnher, Robert Wiebringhaus, Boban M Erovic, Ulana Kotowski, Sven Schneider, Rainer Schmid, Lukas Kenner, Gregor Heiduschka
BACKGROUND: So far, no data is available on the role of the tumor stem cell marker doublecortin-like kinase 1 (DCLK1) in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate DCLK1 expression in HNSCC patients that underwent surgery and postoperative radiotherapy, and to assess its potential as a therapeutic target in vitro. METHODS: We immunohistochemically stained for DCLK1 in 127 sections of HNSCC samples obtained during surgery of HNSCC patients and correlated the expression to patients' overall- and disease-free survival, as well as human papilloma virus (HPV) status...
April 2017: Oral Oncology
https://www.readbyqxmd.com/read/28320089/mir-448-is-a-novel-prognostic-factor-of-lung-squamous-cell-carcinoma-and-regulates-cells-growth-and-metastasis-by-targeting-dclk1
#12
Changting Shan, Fan Fei, Fengzhu Li, Bo Zhuang, Yulong Zheng, Yufeng Wan, Jianhui Chen
MicroRNA-448 (miR-448) has been showed to be low-expressed and function as tumor suppressor in most human cancers. However, there are limited reports on the clinical significance and biological function of miR-448 in lung squamous cell carcinoma. In this study, we observed that miR-448 expression was decreased in lung squamous cell carcinoma tissues and cell lines. Meanwhile, miR-448 expression associated with differentiated degree, T classification (tumor size), N classification (lymph node metastasis), M classification (distant metastasis), clinical stage and prognosis of lung squamous cell carcinoma patients...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28244691/up-regulation-of-glycolysis-promotes-the-stemness-and-emt-phenotypes-in-gemcitabine-resistant-pancreatic-cancer-cells
#13
Hengqiang Zhao, Qingke Duan, Zhengle Zhang, Hehe Li, Heshui Wu, Qiang Shen, Chunyou Wang, Tao Yin
Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT)-type cells are considered as underlying causes of chemoresistance, tumour recurrence and metastasis in pancreatic cancer. We aimed to describe the mechanisms - particularly glycolysis - involved in the regulation of the CSC and EMT phenotypes. We used a gemcitabine-resistant (GR) Patu8988 cell line, which exhibited clear CSC and EMT phenotypes and showed reliance on glycolysis. Inhibition of glycolysis using 2-deoxy-D-glucose (2-DG) significantly enhanced the cytotoxicity of gemcitabine and inhibited the CSC and EMT phenotypes in GR cells both in vitro and in vivo...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28179411/pancreatic-neuroendocrine-tumors-and-emt-behavior-are-driven-by-the-csc-marker-dclk1
#14
Yu Ikezono, Hironori Koga, Jun Akiba, Mitsuhiko Abe, Takafumi Yoshida, Fumitaka Wada, Toru Nakamura, Hideki Iwamoto, Atsutaka Masuda, Takahiko Sakaue, Hirohisa Yano, Osamu Tsuruta, Takuji Torimura
Doublecortin-like kinase 1 (DCLK1), a marker for intestinal and pancreatic cancer stem cells, is highly expressed in neuroblastomas. This study was conducted to assess DCLK1 expression levels in pancreatic neuroendocrine tumor (PNET) tissues and to explore the roles of this molecule in clinical tissue from multiple PNET patients, cells (BON1, QGP1, and CM) and tumor xenografts. Immunohistochemically, all PNET tissues highly and diffusely expressed DCLK1 as a full-length isoform, identical to that detected in primary liver NETs...
June 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28161486/microrna-424-inhibits-cell-migration-invasion-and-epithelial-mesenchymal-transition-by-downregulating-doublecortin-like-kinase-1-in-ovarian-clear-cell-carcinoma
#15
Xin Wu, Yuanyuan Ruan, Hua Jiang, Congjian Xu
Doublecortin-like kinase 1 (DCLK1) is overexpressed in many cancers and acts as a tumor stem cell marker. Here, we investigated the role of DCLK1 and microRNA-424 (miR-424) in ovarian clear cell carcinoma (OCCC), a histopathologically distinct subtype of epithelial ovarian cancer associated with poor prognosis and chemotherapy resistance. Analysis of samples from 30 OCCC patients showed that DCLK1 was upregulated and miR-424 was downregulated in tumors compared with adjacent non-tumor tissues. DCLK1 overexpression promoted OCCC cell proliferation, migration, and invasion, whereas DCLK1 knockdown reduced cell viability and invasion and induced growth arrest in vitro and in vivo...
February 2, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28148261/dclk1-a-tumor-stem-cell-marker-regulates-pro-survival-signaling-and-self-renewal-of-intestinal-tumor-cells
#16
Parthasarathy Chandrakesan, Jiannan Yao, Dongfeng Qu, Randal May, Nathaniel Weygant, Yang Ge, Naushad Ali, Sripathi M Sureban, Modhi Gude, Kenneth Vega, Eddie Bannerman-Menson, Lijun Xia, Michael Bronze, Guangyu An, Courtney W Houchen
BACKGROUND: More than 80% of intestinal neoplasia is associated with the adenomatous polyposis coli (APC) mutation. Doublecortin-like kinase 1 (Dclk1), a kinase protein, is overexpressed in colorectal cancer and specifically marks tumor stem cells (TSCs) that self-renew and increased the tumor progeny in Apc (Min/+) mice. However, the role of Dclk1 expression and its contribution to regulating pro-survival signaling for tumor progression in Apc mutant cancer is poorly understood. METHODS: We analyzed DCLK1 and pro-survival signaling gene expression datasets of 329 specimens from TCGA Colon Adenocarcinoma Cancer Data...
February 1, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/27994463/a-novel-double-targeted-nondrug-delivery-system-for-targeting-cancer-stem-cells
#17
Shupei Qiao, Yufang Zhao, Shuai Geng, Yong Li, Xiaolu Hou, Yi Liu, Feng-Huei Lin, Lifen Yao, Weiming Tian
Instead of killing cancer stem cells (CSCs), the conventional chemotherapy used for cancer treatment promotes the enrichment of CSCs, which are responsible for tumor growth, metastasis, and recurrence. However, most therapeutic agents are only able to kill a small proportion of CSCs by targeting one or two cell surface markers or dysregulated CSC pathways, which are usually shared with normal stem cells (NSCs). In this study, we developed a novel nondrug delivery system for the dual targeting of CSCs by conjugating hyaluronic acid (HA) and grafting the doublecortin-like kinase 1 (DCLK1) monoclonal antibody to the surface of poly(ethylene glycol) (PEG)-poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which can specifically target CD44 receptors and the DCLK1 surface marker - the latter was shown to possess the capacity to distinguish between CSCSs and NSCs...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27989802/nerve-growth-factor-promotes-gastric-tumorigenesis-through-aberrant-cholinergic-signaling
#18
Yoku Hayakawa, Kosuke Sakitani, Mitsuru Konishi, Samuel Asfaha, Ryota Niikura, Hiroyuki Tomita, Bernhard W Renz, Yagnesh Tailor, Marina Macchini, Moritz Middelhoff, Zhengyu Jiang, Takayuki Tanaka, Zinaida A Dubeykovskaya, Woosook Kim, Xiaowei Chen, Aleksandra M Urbanska, Karan Nagar, Christoph B Westphalen, Michael Quante, Chyuan-Sheng Lin, Michael D Gershon, Akira Hara, Chun-Mei Zhao, Duan Chen, Daniel L Worthley, Kazuhiko Koike, Timothy C Wang
Within the gastrointestinal stem cell niche, nerves help to regulate both normal and neoplastic stem cell dynamics. Here, we reveal the mechanisms underlying the cancer-nerve partnership. We find that Dclk1(+) tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa. Cholinergic stimulation of the gastric epithelium induced nerve growth factor (NGF) expression, and in turn NGF overexpression within gastric epithelium expanded enteric nerves and promoted carcinogenesis. Ablation of Dclk1(+) cells or blockade of NGF/Trk signaling inhibited epithelial proliferation and tumorigenesis in an ACh muscarinic receptor-3 (M3R)-dependent manner, in part through suppression of yes-associated protein (YAP) function...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/27900578/potential-mechanism-of-neurite-outgrowth-enhanced-by-electrical-stimulation-involvement-of-microrna-363-5p-targeting-dclk1-expression-in-rat
#19
Xin Quan, Liangliang Huang, Yafeng Yang, Teng Ma, Zhongyang Liu, Jun Ge, Jinghui Huang, Zhuojing Luo
Electrical stimulation (ES) promotes neurite outgrowth and nerve regeneration, but the underlying mechanisms remain undefined. In the present study, we investigated the role of micro RNAs (miRNAs) in ES-mediated neurite outgrowth. First, we performed microarray analyses to identify changes in the miRNAs profile of dorsal root ganglion neurons (DRGNs) following ES. The expression of 16 known miRNAs was altered by ES. Bioinformatics showed that the potential targets of these differentially expressed miRNAs were involved in neurite outgrowth...
February 2017: Neurochemical Research
https://www.readbyqxmd.com/read/27876863/intestinal-tuft-cells-regulate-the-atm-mediated-dna-damage-response-via-dclk1-dependent-mechanism-for-crypt-restitution-following-radiation-injury
#20
Parthasarathy Chandrakesan, Randal May, Nathaniel Weygant, Dongfeng Qu, William L Berry, Sripathi M Sureban, Naushad Ali, Chinthalapally Rao, Mark Huycke, Michael S Bronze, Courtney W Houchen
Crypt epithelial survival and regeneration after injury require highly coordinated complex interplay between resident stem cells and diverse cell types. The function of Dclk1 expressing tuft cells regulating intestinal epithelial DNA damage response for cell survival/self-renewal after radiation-induced injury is unclear. Intestinal epithelial cells (IECs) were isolated and purified and utilized for experimental analysis. We found that small intestinal crypts of Villin(Cre);Dclk1(f/f) mice were hypoplastic and more apoptotic 24 h post-total body irradiation, a time when stem cell survival is p53-independent...
November 23, 2016: Scientific Reports
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