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Ombretta Melaiu, Justin Stebbing, Ylenia Lombardo, Elisa Bracci, Norihisa Uehara, Alessandra Bonotti, Alfonso Cristaudo, Rudy Foddis, Luciano Mutti, Roberto Barale, Federica Gemignani, Georgios Giamas, Stefano Landi
[This corrects the article DOI: 10.1371/journal.pone.0085935.].
2017: PloS One
Shingo Inaguma, Zengfeng Wang, Jerzy Lasota, Masanori Onda, Piotr Czapiewski, Renata Langfort, Janusz Rys, Joanna Szpor, Piotr Waloszczyk, Krzysztof Okoń, Wojciech Biernat, Hiroshi Ikeda, David S Schrump, Raffit Hassan, Ira Pastan, Markku Miettinen
Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein highly expressed in several types of malignant tumors sometimes in association with increased tumor aggressiveness and poor clinical outcome. In the present study, 1562 tumors were immunohistochemically analyzed for mesothelin expression using two different types of mouse monoclonal antibodies (5B2 and MN-1) to determine the clinical usefulness of mesothelin immunohistochemistry as well as to pinpoint potential targets for future anti-mesothelin therapy...
April 18, 2017: Oncotarget
Shengnan Yu, Anping Li, Qian Liu, Tengfei Li, Xun Yuan, Xinwei Han, Kongming Wu
The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types...
March 29, 2017: Journal of Hematology & Oncology
Chiara De Santi, Perla Pucci, Alessandra Bonotti, Ombretta Melaiu, Monica Cipollini, Roberto Silvestri, Veronika Vymetalkova, Elisa Barone, Elisa Paolicchi, Alda Corrado, Irene Lepori, Irene Dell'Anno, Lucia Pellè, Pavel Vodicka, Luciano Mutti, Rudy Foddis, Alfonso Cristaudo, Federica Gemignani, Stefano Landi
BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hinder its usefulness in surveillance programmes. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of the mesothelin (MSLN) gene could affect the levels of SMRP. OBJECTIVES: To focus on SNPs located within MSLN promoter as possible critical genetic variables in determining SMRP levels...
June 2017: Occupational and Environmental Medicine
Xiaoqing He, Liying Wang, Heimo Riedel, Kai Wang, Yong Yang, Cerasela Zoica Dinu, Yon Rojanasakul
BACKGROUND: Lung cancer and pleural mesothelioma are two of the most deadly forms of cancer. The prognosis of lung cancer and mesothelioma is extremely poor due to limited treatment modalities and lack of understanding of the disease mechanisms. We have identified mesothelin as a potentially unique therapeutic target that as a specific advantage appears nonessential in most cell types. Mesothelin (MSLN), a plasma membrane differentiation antigen, is expressed at a high level in many human solid tumors, including 70% of lung cancer and nearly all mesotheliomas...
March 14, 2017: Molecular Cancer
Yukinori Koyama, Ping Wang, Shuang Liang, Keiko Iwaisako, Xiao Liu, Jun Xu, Mingjun Zhang, Mengxi Sun, Min Cong, Daniel Karin, Kojiro Taura, Chris Benner, Sven Heinz, Tapan Bera, David A Brenner, Tatiana Kisseleva
Cholestatic liver fibrosis is caused by obstruction of the biliary tract and is associated with early activation of portal fibroblasts (PFs) that express Thy-1, fibulin 2, and the recently identified marker mesothelin (MSLN). Here, we have demonstrated that activated PFs (aPFs) and myofibroblasts play a critical role in the pathogenesis of liver fibrosis induced by bile duct ligation (BDL). Conditional ablation of MSLN+ aPFs in BDL-injured mice attenuated liver fibrosis by approximately 50%. Similar results were observed in MSLN-deficient mice (Msln-/- mice) or mice deficient in the MSLN ligand mucin 16 (Muc16-/- mice)...
April 3, 2017: Journal of Clinical Investigation
Chiara De Santi, Sebastian Vencken, Jonathon Blake, Bettina Haase, Vladimir Benes, Federica Gemignani, Stefano Landi, Catherine M Greene
MicroRNAs (miRNAs) are small non-coding RNAs that regulate mRNA expression mainly by silencing target transcripts via binding to miRNA recognition elements (MREs) in the 3'untranslated region (3'UTR). The identification of bona fide targets is challenging for researchers working on the functional aspect of miRNAs. Recently, we developed a method (miR-CATCH) based on biotinylated DNA antisense oligonucleotides that capture the mRNA of interest and facilitates the characterisation of miRNAs::mRNA interactions in a physiological cellular context...
2017: PloS One
Emily Kolyvas, Michael Rudloff, Marianne Poruchynsky, Rebekah Landsman, Kevin Hollevoet, David Venzon, Christine Alewine
Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin payload. The RG7787 RIT targets the cancer antigen mesothelin to deliver a recombinantly-engineered, reduced immunogenicity variant of Pseudomonas exotoxin A (PE) to the cytosol where it inhibits protein synthesis. Here we demonstrate that maximal doses of RG7787 temporarily halt growth of pancreatic cancer tumor xenografts, similar to the approved drugs gemcitabine and nab-paclitaxel, however, combination of the RIT with nab-paclitaxel produces durable complete regressions in most mice...
February 7, 2017: Oncotarget
Salma Mahmoud, Mohammed Ibrahim, Ahmed Hago, Yuhong Huang, Yuanyi Wei, Jun Zhang, Qingqing Zhang, Yu Xiao, Jingwen Wang, Munkaila Adam, Yu Guo, Li Wang, Shuting Zhou, Boyi Xin, Wei Xuan, Jianwu Tang
Lymphatic vessels function as transport channels for tumor cells to metastasize from the primary site into the lymph nodes. In this experiment we evaluated the effect of Sulfatase-1 (Sulf-1) on metastasis by upregulating it in murine hepatocarcinoma cell line Hca-F with high lymph node metastatic rate of >75%. The study in vitro showed that up regulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 down regulated Mesothelin (Msln) at both the protein and mRNA levels...
November 15, 2016: Oncotarget
Márta Sárközy, Gergő Szűcs, Veronika Fekete, Márton Pipicz, Katalin Éder, Renáta Gáspár, Andrea Sója, Judit Pipis, Péter Ferdinandy, Csaba Csonka, Tamás Csont
BACKGROUND: There is a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a significant proportion of T2DM patients are non-obese and they also have an increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a well-known model of non-obese T2DM, the goal of this study was to investigate the effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats. METHODS: Fasting blood glucose, serum insulin and cholesterol levels were measured at 7, 11, and 15 weeks of age in male GK and control rats...
August 5, 2016: Cardiovascular Diabetology
Xiaoqing He, Emily Despeaux, Todd A Stueckle, Alexander Chi, Vincent Castranova, Cerasela Zoica Dinu, Liying Wang, Yon Rojanasakul
Carbon nanotubes (CNTs) have been likened to asbestos in terms of morphology and toxicity. CNT exposure can lead to pulmonary fibrosis and promotion of tumorigenesis. However, the mechanisms underlying CNT-induced carcinogenesis are not well defined. Mesothelin (MSLN) is overexpressed in many human tumors, including mesotheliomas and pancreatic and ovarian carcinomas. In this study, the role of MSLN in the carcinogenic transformation of human bronchial epithelial cells chronically exposed to single-walled CNT (BSW) was investigated...
September 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Prince Awuah, Tapan K Bera, Messan Folivi, Oleg Chertov, Ira Pastan
Mesothelin (MSLN) is a differentiation antigen that is highly expressed in many epithelial cancers. MSLN is an important therapeutic target due to its high expression in cancers and limited expression in normal human tissues. Although it has been assumed that shed antigen is a barrier to immunotoxin action, a modeling study predicted that shed MSLN may enhance the action of MSLN-targeting recombinant immunotoxins such as SS1P and similar therapeutics by facilitating their redistribution within tumors. We aimed to determine whether shed MSLN enhances or reduces the antitumor effect of MSLN-targeting immunotoxins SS1P and RG7787...
July 2016: Molecular Cancer Therapeutics
Min Yu, Yixiao Zhang, Zhaoqiang Jiang, Junqiang Chen, Lihong Liu, Jianlin Lou, Xing Zhang
OBJECTIVES: This study investigated the mesothelin (MSLN) methylation and its relationship with soluble mesothelin-related protein (SMRP) levels in participants stratified by asbestos exposure scenarios and benign asbestos-related diseases (ARDs). METHODS: The presence of benign ARDs was confirmed through chest X-ray and the asbestos exposure history was obtained using a standardized questionnaire in this study, including 262 participants. Sera SMRP were measured using MESOMARK, and MSLN methylation in genomic DNA extracted from whole blood was detected by real-time methylation-specific PCR...
September 2015: Environmental Health and Preventive Medicine
Laetitia E Lamberts, Derk Jan A de Groot, Rico D Bense, Elisabeth G E de Vries, Rudolf S N Fehrmann
The membrane bound glycoprotein mesothelin (MSLN) is a highly specific tumor marker, which is currently exploited as target for drugs. There are only limited data available on MSLN expression by human tumors. Therefore we determined overexpression of MSLN across different tumor types with Functional Genomic mRNA (FGM) profiling of a large cancer database. Results were compared with data in articles reporting immunohistochemical (IHC) MSLN tumor expression. FGM profiling is a technique that allows prediction of biologically relevant overexpression of proteins from a robust data set of mRNA microarrays...
September 29, 2015: Oncotarget
Kazuko Kobayashi, Takanori Sasaki, Fumiaki Takenaka, Hiromasa Yakushiji, Yoshihiro Fujii, Yoshiro Kishi, Shoichi Kita, Lianhua Shen, Hiromi Kumon, Eiji Matsuura
Mesothelin (MSLN) is a 40-kDa cell differentiation-associated glycoprotein appearing with carcinogenesis and is highly expressed in many human cancers, including the majority of pancreatic adenocarcinomas, ovarian cancers, and mesotheliomas, while its expression in normal tissue is limited to mesothelial cells lining the pleura, pericardium, and peritoneum. Clone 11-25 is a murine hybridoma secreting monoclonal antibody (mAb) against human MSLN. In this study, we applied the 11-25 mAb to in vivo imaging to detect MSLN-expressing tumors...
2015: Journal of Immunology Research
Dong-hui Wang, Xiao-hua Wu, Su-min Qian, Hai-Rong Yao
Epithelial ovarian cancer (EOC) has the highest mortality rate among the various types of gynecological cancers. As the current therapeutic approaches are not enough, the development of more effective treatments to improve the survival of patients with EOC is urgently needed. Mesothelin (MSLN) is a cell surface glycoprotein, which is overexpressed in ovarian cancer tissues. As an immunotherapeutic approach, in this study, we investigated whether the genetically modified dendritic cells (DCs) expressing MSLN could induce cytotoxic T lymphocytes (CTLs) to produce MSLN-specific cytotoxic activity against EOCs...
April 2015: Medical Oncology
Ombretta Melaiu, Erika Melissari, Luciano Mutti, Elisa Bracci, Chiara De Santi, Caterina Iofrida, Manuela Di Russo, Alfonso Cristaudo, Alessandra Bonotti, Monica Cipollini, Sonia I Garritano, Rudy Foddis, Marco Lucchi, Silvia Pellegrini, Federica Gemignani, Stefano Landi
In order to broaden knowledge on the pathogenesis of malignant pleural mesothelioma (MPM), we reviewed studies on the MPM-transcriptome and identified 119 deregulated genes. However, there was poor consistency among the studies. Thus, the expression of these genes was further investigated in the present work using reverse transcriptase-quantitative PCR (RT-qPCR) in 15 MPM and 20 non-MPM tissue samples. Fifty-nine genes showed a statistically significant deregulation and were further evaluated in two epithelioid MPM cell lines (compared to MET-5A, a non-MPM cell line)...
January 2015: Mutation Research
Daniel Steinbach, Peter Bader, Andre Willasch, Stephan Bartholomae, Klaus-Michael Debatin, Martin Zimmermann, Ursula Creutzig, Dirk Reinhardt, Bernd Gruhn
PURPOSE: This study evaluated the prognostic impact of a novel, simple, and standardized assay for monitoring minimal residual disease (MRD) in pediatric acute myelogenous leukemia (AML). EXPERIMENTAL DESIGN: The expression of seven leukemia-associated genes (WT1, PRAME, CCL23, GAGED2, MSLN, SPAG6, and ST18) was measured by TaqMan Low Density Arrays in 112 patients and 52 healthy controls. Patients were treated according to the multicenter study AML-BFM 2004. Samples were collected prospectively at standard time points...
March 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sonia Garritano, Chiara De Santi, Roberto Silvestri, Ombretta Melaiu, Monica Cipollini, Elisa Barone, Marco Lucchi, Roberto Barale, Luciano Mutti, Federica Gemignani, Alessandra Bonotti, Rudy Foddis, Alfonso Cristaudo, Stefano Landi
INTRODUCTION: Soluble mesothelin related peptide (SMRP) was proposed as a promising diagnostic marker for malignant pleural mesothelioma (MPM). In a previous study, we found that rs1057147 within the 3' untranslated region of MSLN gene was associated with SMRP levels. Thus, we aimed to (1) confirm the previous association on a large series of volunteers and (2) test the hypothesis that the SNP could affect microRNA binding sites. METHODS: The association analysis was verified in 759 subjects...
November 2014: Journal of Thoracic Oncology
Renee M Tholey, Shruti Lal, Masaya Jimbo, Richard A Burkhart, Fernando F Blanco, Joseph A Cozzitorto, Josh D Eisenberg, Wei Jiang, Christine A Iacobuzio-Donahue, Agnieszka K Witkiewicz, Melissa Glbert, Charles J Yeo, Jonathan R Brody, Janet A Sawicki, Jordan M Winter
UNLABELLED: Mucin1 (MUC1) is overexpressed in pancreatic ductal adenocarcinoma (PDA) and is associated with tumor aggressiveness, suggesting that MUC1 is a promising therapeutic target for promoter-driven diphtheria toxin A (DTA). Endogenous MUC1 transcript levels were analyzed by quantitative PCR (qPCR) in multiple PDA cells (Capan1, HPAFII, Su.86.86, Capan2, Hs766T, MiaPaCa2, and Panc1). Expression levels were correlated with luciferase activity and cell death after transfection with MUC1 promoter-driven luciferase and DTA constructs...
March 2015: Molecular Cancer Research: MCR
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