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https://www.readbyqxmd.com/read/28913658/liver-specific-reconstitution-of-ceacam1-reverses-the-metabolic-abnormalities-caused-by-its-global-deletion-in-male-mice
#1
Lucia Russo, Harrison T Muturi, Hilda E Ghadieh, Simona S Ghanem, Thomas A Bowman, Hye Lim Noh, Sezin Dagdeviren, Godwin Y Dogbey, Jason K Kim, Garrett Heinrich, Sonia M Najjar
AIMS/HYPOTHESIS: The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Mice with global null mutation (Cc1 (-/-)) or with liver-specific inactivation (L-SACC1) of Cc1 (also known as Ceacam1) gene display hyperinsulinaemia resulting from impaired insulin clearance, insulin resistance, steatohepatitis and obesity. Because increased lipolysis contributes to the metabolic phenotype caused by transgenic inactivation of CEACAM1 in the liver, we aimed to further investigate the primary role of hepatic CEACAM1-dependent insulin clearance in insulin and lipid homeostasis...
September 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28887602/correlation-between-immunohistochemical-staining-of-ceacam1-and-clinicopathological-findings-in-oral-pre-neoplastic-lesions-and-squamous-cell-carcinoma
#2
Oriana Simonetti, Guendalina Lucarini, Corrado Rubini, Antonio Zizzi, Simone Domenico Aspriello, Roberto Di Primio, Anna Maria Offidani
Squamous cell carcinoma of the oral cavity represents the sixth most common cancer worldwide and it is often preceded by pre-neoplastic lesions. Sometimes it is still difficult for pathologists to make objective differential diagnoses only on histological characteristics. Tumorigenesis is accompanied by altered expression of cell adhesion molecules, like carcinoembryonic antigen cell adhesion molecule (CEACAM)1. We wanted to investigative CEACAM1 in oral dysplastic lesions, carcinoma in situ (CIS) and oral squamous cell carcinoma (OSCC)...
September 8, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28811966/ceacam1-as-a-multi-purpose-target-for-cancer-immunotherapy
#3
REVIEW
Matthew Dankner, Scott D Gray-Owen, Yu-Hwa Huang, Richard S Blumberg, Nicole Beauchemin
CEACAM1 is an extensively studied cell surface molecule with established functions in multiple cancer types, as well as in various compartments of the immune system. Due to its multi-faceted role as a recently appreciated immune checkpoint inhibitor and tumor marker, CEACAM1 is an attractive target for cancer immunotherapy. Herein, we highlight CEACAM1's function in various immune compartments and cancer types, including in the context of metastatic disease. This review outlines CEACAM1's role as a therapeutic target for cancer treatment in light of these properties...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28800960/ets-transcription-factor-elf5-induces-lumen-formation-in-a-3d-model-of-mammary-morphogenesis-and-its-expression-is-inhibited-by-jak2-inhibitor-tg101348
#4
Jennifer Chean, Charng-Jui Chen, John E Shively
The loss of expression of a single gene can revert normal tissue to a malignant phenotype. For example, while normal breast has high lumenal expression of CEACAM1, the majority of breast cancers exhibit the early loss of this gene with the concurrent loss of their lumenal phenotype. MCF7 cells that lack CEACAM1 expression and fail to form lumena in 3D culture, regain the normal phenotype when transfected with CEACAM1. In order to probe the mechanism of this gain of function, we treated these cells with the clinically relevant Jak2 inhibitor TG101348 (TG), expecting that disruption of the prolactin receptor signaling pathway would interfere with the positive effects of transfection of MCF7 cells with CEACAM1...
August 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#5
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28655144/up-regulation-of-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-in-gastrointestinal-cancer-and-its-clinical-relevance
#6
Muqing Zhou, Zhiming Jin, Yiwen Liu, Yiqing He, Yan Du, Cuixia Yang, Yingzhi Wang, Jiajie Hu, Lian Cui, Feng Gao, Manlin Cao
Serum carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is dysregulated in various malignant tumors and has been associated with tumor progression. However, the expression and regulatory mechanisms of serum CEACAM1 in gastrointestinal cancer are still unclear. The expression ratio of the CEACAM1-L and CEACAM1-S isoforms has seldom been investigated in gastrointestinal cancer. In this study, we intended to explore the expression and diagnostic value of CEACAM1 in gastrointestinal cancer. Serum CEACAM1 levels were measured by enzyme-linked immunosorbent assay...
August 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28593707/soluble-ceacam1-and-ceacam6-are-differently-expressed-in-blood-serum-of-pregnant-women-during-normal-pregnancy
#7
Pawel Mach, Alexandra Gellhaus, Sebastian Prager, Tom Moore, Gunther Wennemuth, Rainer Kimmig, Angela Köninger, Bernhard B Singer
PROBLEM: CEACAM1 and CEACAM6 belong to the carcinoembryonic antigen (CEA) family and may play an immune-modulatory role during pregnancy. The aim of the study was to determine the blood serum levels of soluble CEACAM1 and CEACAM6 over the course of pregnancy and postpartum. METHOD OF STUDY: CEACAM1 and CEACAM6 levels were determined with customized in-house Sandwich-enzyme-linked immunosorbent assay (ELISA) systems. The study population (n=125) was divided into four groups according to the pregnancy trimester and postpartum...
June 8, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28567513/age-dependent-insulin-resistance-in-male-mice-with-null-deletion-of-the-carcinoembryonic-antigen-related-cell-adhesion-molecule-2-gene
#8
Simona S Ghanem, Harrison T Muturi, Anthony M DeAngelis, Jiang Hu, Rohit N Kulkarni, Garrett Heinrich, Sonia M Najjar
AIMS/HYPOTHESIS: Cc2 (-/-) mice lacking the gene encoding the carcinoembryonic-antigen-related cell adhesion molecule 2 (Cc2 [also known as Ceacam2]) exhibit hyperphagia that leads to obesity and insulin resistance. This starts at 2 months of age in female mice. Male mutants maintain normal body weight and insulin sensitivity until the last age previously examined (7-8 months), owing to increased sympathetic tone to white adipose tissue and energy expenditure. The current study investigates whether insulin resistance develops in mutant male mice at a later age and whether this is accompanied by changes in insulin homeostasis...
May 31, 2017: Diabetologia
https://www.readbyqxmd.com/read/28467911/the-induction-of-selected-wnt-target-genes-by-tcf1-mediates-generation-of-tumorigenic-colon-stem-cells
#9
Daisuke Shiokawa, Ai Sato, Hirokazu Ohata, Michihiro Mutoh, Shigeki Sekine, Mamoru Kato, Tatsuhiro Shibata, Hitoshi Nakagama, Koji Okamoto
The generation of tumor-initiating cells during colon carcinogenesis is associated with the dysregulation of Wnt signaling, which is known to act on Lgr5-positive intestinal stem cells. Here, using single-cell qPCR analysis, we identified a subset of Lgr5-positive stem cells that emerged during tumorigenesis in a mouse model of colon cancer. These tumor-specific Lgr5-positive cells expressed low levels of Ceacam1 and increased levels of a specific subset of Wnt targets and showed enhanced tumorigenicity. Among the Wnt targets that were specifically expressed, the long isoform of Tcf1 was required for the proliferation of tumor organoids and drove a unique Wnt target gene expression profile...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28402947/overexpression-of-the-transcription-factor-atf3-with-a-regulatory-molecular-signature-associates-with-the-pathogenic-development-of-colorectal-cancer
#10
Feng Yan, Le Ying, Xiaofang Li, Bin Qiao, Qiaohong Meng, Liang Yu, Xiangliang Yuan, Shu-Ting Ren, David W Chan, Liyun Shi, Peihua Ni, Xuefeng Wang, Dakang Xu, Yiqun Hu
The identification of novel biomarkers of cancer is important for improved diagnosis and prognosis. With an abundant amount of resources in the publicly available database, such as the Cancer Genome Atlas (TCGA) database, an integrative strategy is used to systematically characterize the aberrant patterns of colorectal cancer (CRC) based on RNA-Seq, chromatin immunoprecipitation sequencing (ChIP-Seq), tissue microarray (TMA), gene profiling and molecular signatures. The expression of the transcription factor ATF3 was elevated in human CRC specimens in a TMA by immunochemistry analysis compared to the adjacent normal tissues...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396653/reduced-hepatic-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-level-in-obesity
#11
Garrett Heinrich, Harrison T Muturi, Khadijeh Rezaei, Qusai Y Al-Share, Anthony M DeAngelis, Thomas A Bowman, Hilda E Ghadieh, Simona S Ghanem, Deqiang Zhang, Robert S Garofalo, Lei Yin, Sonia M Najjar
Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28385529/matrix-metalloproteinase12-facilitated-platelet-activation-by-shedding-carcinoembryonic-antigen-related-cell-adhesion-molecule1
#12
Jing Wang, Yujia Ye, Guoqing Wei, Wei Hu, Linhua Li, Si Lu, Zhaohui Meng
Platelets express several MMPs that modulate their activation, which in turn regulates thrombosis, but the exact mechanism is unclear. This study evaluated the platelet expression of MMP12 and platelet activation by shedding CEACAM1 mediated by MMP12. Expression of MMP12 was measured by RT-PCR, Western blot (WB), and casein zymography in platelet from whole blood by gel filtration over plateletpheresis. The site of CEACAM1 cleavage by MMP12 was determined by high performance liquid chromatography (HPLC), mass spectrometry, WB and flow cytometry (FCM)...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28332308/ceacam1-long-isoform-has-opposite-effects-on-the-growth-of-human-mastocytosis-and-medullary-thyroid-carcinoma-cells
#13
Chiyuki Ueshima, Tatsuki R Kataoka, Yusuke Takei, Masahiro Hirata, Akihiko Sugimoto, Mitsuyoshi Hirokawa, Yoshimichi Okayama, Richard S Blumberg, Hironori Haga
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in a number of tumor cell types. The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing isoforms of this molecule which possess a long cytoplasmic tail (CEACAM1-L) generally play inhibitory roles in cell function by interacting with Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 and/or SHP-2. Src family kinases (SFKs) are also known to bind to and phosphorylate CEACAM1-L isoforms. Here, we report that CEACAM1 was uniquely expressed at high levels in both human neoplastic mast cells (mastocytosis) and medullary thyroid carcinoma cell (MTC) lines, when compared with their expression in nonneoplastic mast cells or nonneoplastic C cells...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28314278/elevated-preoperative-serum-cea-level-is-associated-with-poor-prognosis-in-patients-with-hepatocellular-carcinoma-through-the-epithelial-mesenchymal-transition
#14
Masato Yoshikawa, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Jun Higashijima, Shuichi Iwahashi, Y U Saito, Chie Takasu, Shinichiro Yamada, Daichi Ishikawa, Hiroki Teraoku, Atsushi Takata, Toshiaki Yoshimoto, Mitsuo Shimada
BACKGROUND: Serum carcinoembryonic antigen (CEA) is used as an indicator of tumor progression in a variety of carcinomas. A subset of patients with hepatocellular carcinoma (HCC) exhibit increased serum CEA level, but the significance of this is unclear. In this study, we investigated the prognosis of patients with HCC with increased serum CEA, and explored the correlations with expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and epithelial-mesenchymal transition (EMT) and tumor angiogenesis...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28292985/binding-of-candida-albicans-to-human-ceacam1-and-ceacam6-modulates-the-inflammatory-response-of-intestinal-epithelial-cells
#15
Esther Klaile, Mario M Müller, Miriam R Schäfer, Ann-Katrin Clauder, Sabina Feer, Kerstin A Heyl, Magdalena Stock, Tilman E Klassert, Peter F Zipfel, Bernhard B Singer, Hortense Slevogt
Candida albicans colonizes human mucosa, including the gastrointestinal tract, as a commensal. In immunocompromised patients, C. albicans can breach the intestinal epithelial barrier and cause fatal invasive infections. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM5 (CEA), and CEACAM6 (CD66c) are immunomodulatory receptors expressed on human mucosa and are recruited by bacterial and viral pathogens. Here we show for the first time that a fungal pathogen (i.e., C. albicans) also binds directly to the extracellular domain of human CEACAM1, CEACAM3, CEACAM5, and CEACAM6...
March 14, 2017: MBio
https://www.readbyqxmd.com/read/28275050/novel-thiosemicarbazones-inhibit-lysine-rich-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-ceacam1-coisolated-lyric-and-the-lyric-induced-epithelial-mesenchymal-transition-via-upregulation-of-n-myc-downstream-regulated-gene-1-ndrg1
#16
Ruxing Xi, Ivan Ho Yuen Pun, Sharleen V Menezes, Leyla Fouani, Danuta S Kalinowski, Michael L H Huang, Xiaozhi Zhang, Des R Richardson, Zaklina Kovacevic
Tumor necrosis factor α (TNFα) plays a vital role in cancer progression as it is associated with inflammation and promotion of cancer angiogenesis and metastasis. The effects of TNFα are mediated by its downstream target, the oncogene lysine-rich CEACAM1 coisolated protein (LYRIC, also known as metadherin or astrocyte elevated gene-1). LYRIC plays an important role in activating the nuclear factor-ĸB (NF-κB) signaling pathway, which controls multiple cellular processes, including proliferation, apoptosis, migration, etc...
May 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28184213/loss-of-hepatic-ceacam1-a-unifying-mechanism-linking-insulin-resistance-to-obesity-and-non-alcoholic-fatty-liver-disease
#17
REVIEW
Garrett Heinrich, Hilda E Ghadieh, Simona S Ghanem, Harrison T Muturi, Khadijeh Rezaei, Qusai Y Al-Share, Thomas A Bowman, Deqiang Zhang, Robert S Garofalo, Lei Yin, Sonia M Najjar
The pathogenesis of human non-alcoholic fatty liver disease (NAFLD) remains unclear, in particular in the context of its relationship to insulin resistance and visceral obesity. Work on the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in mice has resolved some of the related questions. CEACAM1 promotes insulin clearance by enhancing the rate of uptake of the insulin-receptor complex. It also mediates a negative acute effect of insulin on fatty acid synthase activity. This positions CEACAM1 to coordinate the regulation of insulin and lipid metabolism...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28038383/co-expression-of-tim-3-and-ceacam1-promotes-t-cell-exhaustion-in-colorectal-cancer-patients
#18
Yang Zhang, Pengcheng Cai, Lei Li, Liang Shi, Panpan Chang, Tao Liang, Qianqian Yang, Yang Liu, Lin Wang, Lihua Hu
T-cell immunoglobulin domain and mucin domain-3(TIM-3) is an activation induced inhibitory molecule involved in immune tolerance and is recently reported to induce T cell exhaustion which is mediated by carcinoembryonic antigen cell adhesion molecule 1(CEACAM1), another well-known molecule expressed on activated T cells and involved in T cell inhibition. To investigate the expression of TIM-3 and CEACAM1 on circulating CD8(+) T cells and tumor infiltrating lymphocytes (TILs), 65 diagnosed colorectal cancer (CRC) patients and 38 healthy controls were enrolled in this study and the results showed that TIM-3 and CEACAM1 were both highly expressed on circulating CD8(+) T cells in CRC patients and elevated on TILs compared with paraneoplastic T cells...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28002407/identification-of-an-atypical-monocyte-and-committed-progenitor-involved-in-fibrosis
#19
Takashi Satoh, Katsuhiro Nakagawa, Fuminori Sugihara, Ryusuke Kuwahara, Motooki Ashihara, Fumihiro Yamane, Yosuke Minowa, Kiyoharu Fukushima, Isao Ebina, Yoshichika Yoshioka, Atsushi Kumanogoh, Shizuo Akira
Monocytes and macrophages comprise a variety of subsets with diverse functions. It is thought that these cells play a crucial role in homeostasis of peripheral organs, key immunological processes and development of various diseases. Among these diseases, fibrosis is a life-threatening disease of unknown aetiology. Its pathogenesis is poorly understood, and there are few effective therapies. The development of fibrosis is associated with activation of monocytes and macrophages. However, the specific subtypes of monocytes and macrophages that are involved in fibrosis have not yet been identified...
January 5, 2017: Nature
https://www.readbyqxmd.com/read/27852220/coevolution-of-paired-receptors-in-xenopus-carcinoembryonic-antigen-related-cell-adhesion-molecule-families-suggests-appropriation-as-pathogen-receptors
#20
Wolfgang Zimmermann, Robert Kammerer
BACKGROUND: In mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Human CEACAM1 and CEACAM3 which have inhibitory ITIM/ITSM and activating ITAM-like motifs, respectively, in their cytoplasmic regions are such paired receptors. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction...
November 16, 2016: BMC Genomics
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