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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
#1
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
#2
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...
April 5, 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
#3
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)...
April 1, 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
#4
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
#5
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...
March 15, 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
#6
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
#7
Yu Ikezono, Jun Akiba, Mitsuhiko Abe, Takafumi Yoshida, Fumitaka Wada, Toru Nakamura, Hideki Iwamoto, Atsutaka Masuda, Takahiko Sakaue, Hirohisa Yano, Takuji Torimura, Osamu Tsuruta, Hironori Koga
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...
February 8, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27872404/unique-cellular-lineage-composition-of-the-first-gland-of-the-mouse-gastric-corpus
#14
Andrew O'Neil, Christine P Petersen, Eunyoung Choi, Amy C Engevik, James R Goldenring
The glandular stomach has two major zones: the acid secreting corpus and the gastrin cell-containing antrum. Nevertheless, a single gland lies at the transition between the forestomach and corpus in the mouse stomach. We have sought to define the lineages that make up this gland unit at the squamocolumnar junction. The first gland in mice showed a notable absence of characteristic corpus lineages, including parietal cells and chief cells. In contrast, the gland showed strong staining of Griffonia simplicifolia-II (GSII)-lectin-positive mucous cells at the bases of glands, which were also positive for CD44 variant 9 and Clusterin...
January 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27868042/epithelial-dclk1-cells-are-not-neural-crest-derived
#15
COMMENT
C Benedikt Westphalen, Moritz Middelhoff, Michael Quante, Timothy C Wang
No abstract text is available yet for this article.
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27807078/goblet-cell-ratio-in-combination-with-differentiation-and-stem-cell-markers-in-barrett-esophagus-allow-distinction-of-patients-with-and-without-esophageal-adenocarcinoma
#16
Raphael Schellnegger, Anne Quante, Susanne Rospleszcz, Martina Schernhammer, Bettina Höhl, Moritz Tobiasch, Agnieszka Pastula, Anna Brandtner, Julian A Abrams, Konstantin Strauch, Roland M Schmid, Michael Vieth, Timothy C Wang, Michael Quante
The increasing incidence of esophageal adenocarcinoma (EAC) is mirrored by the increasing prevalence of Barrett esophagus, a precursor lesion resulting in a large number of individuals "at risk" for this lethal malignancy. Among patients with Barrett esophagus, only about 0.3% annually will develop EAC. Because large numbers of patients are followed in endoscopic surveillance, there is a need for risk prediction among a growing population of patients with Barrett esophagus. We identified four potential biomarkers from an inflammation (IL1β)-dependent mouse model of Barrett esophagus and tested them in 189 patients with Barrett esophagus with and without high-grade dysplasia (HGD)/early cancer (T1)...
January 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/27802206/evaluation-of-circulating-cellular-dclk1-protein-as-the-most-promising-colorectal-cancer-stem-cell-marker-using-immunoassay-based-methods
#17
Alireza Mirzaei, Zahra Madjd, Azade Amini Kadijani, Masoumeh Tavakoli-Yaraki, Mohammad Hossein Modarresi, Javad Verdi, Abolfazl Akbari, Gholamreza Tavoosidana
BACKGROUND: DCLK1, as the most potential colorectal cancer stem cell (CSC) marker has been the core of many recent investigations. However, no study has been performed to evaluate the circulating cellular DCLK1 protein (CCDP) that might reflect the presences of colorectal CSC in circulation. OBJECTIVES: We aimed to evaluate CCDP in the peripheral blood mononuclear cells (PBMCs) of colorectal cancer (CRC) patients applying immunoassay based methods including PLA, IPCR and ELISA in order to introduce the method of choice for clinical detection of CCDP...
September 26, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27777940/epigenetic-regulation-of-human-dclk-1-gene-during-colon-carcinogenesis-clinical-and-mechanistic-implications
#18
COMMENT
Pomila Singh, Malaney O'Connell, Sarkar Shubhashish
Colorectal carcinogenesis is a multi-step process. While ~25% of colorectal cancers (CRCs) arise in patients with a family history (genetic predisposition), ~75% of CRCs are due to age-associated accumulation of epigenetic alterations which can result in the suppression of key tumor suppressor genes leading to mutations and activation of oncogenic pathways. Sporadic colon-carcinogenesis is facilitated by many molecular pathways of genomic instability which include chromosomal instability (CIN), micro-satellite instability (MSI) and CpG island methylator phenotype (CIMP), leading towards loss of homeostasis and onset of neoplastic transformation...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27694285/apsa-awardee-submission-tumor-cancer-stem-cell-marker-doublecortin-like-kinase-1-in-liver-diseases
#19
Charles B Nguyen, Courtney W Houchen, Naushad Ali
Liver diseases are the fourth leading cause of mortality among adults in the United States. Patients with chronic liver diseases such as viral hepatitis, fibrosis, and cirrhosis have significantly higher risks of developing hepatocellular carcinoma (HCC). With a dismal five-year survival rate of 11%, HCC is the third most common cause of cancer-related deaths worldwide. Regardless of the underlying cause, late presentation and a lack of effective therapy are the major impediments for successful treatment of HCC...
February 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27677532/doublecortin-like-kinase-1-positive-enterocyte-a-new-cell-type-in-human-intestine
#20
Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H Kauppila, Ilkka Miinalainen, Veli-Pekka Ronkainen, Juha Saarnio, Petri P Lehenkari, Tuomo J Karttunen
Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated kinase. In murine intestine, DCLK1 marks tuft cells with characteristic microvilli, features of neuroendocrine cells and also quiescent stem cell-like properties. The occurrence and pathological role of DCLK1-positive cells in human intestinal mucosa is unknown. We analysed DCLK1 expression in healthy duodenal, jejunal and colorectal mucosa samples (n = 35), and in duodenal specimens from patients with coeliac disease (n = 20). The samples were immunohistochemically double-stained with DCLK1, and synaptophysin, chromogranin A and Ki-67...
November 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
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