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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
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...
September 10, 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...
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
Maria Santacana, Oscar Maiques, Joan Valls, Sònia Gatius, Ana Isabel Abó, María Ángeles López-García, Alba Mota, Jaume Reventós, Gema Moreno-Bueno, Jose Palacios, Carla Bartosch, Xavier Dolcet, Xavier Matias-Guiu
Histologic typing may be difficult in a subset of endometrial carcinoma (EC) cases. In these cases, interobserver agreement improves when immunohistochemistry (IHC) is used. A series of endometrioid type (EEC) grades 1, 2, and 3 and serous type (SC) were immunostained for p53, p16, estrogen receptor, PTEN, IMP2, IMP3, HER2, cyclin B2 and E1, HMGA2, FolR1, MSLN, Claudins 3 and 4, and NRF2. Nine biomarkers showed significant differences with thresholds in IHC value scale between both types (p53 ≥ 20, IMP2 ≥ 115, IMP3 ≥ 2, cyclin E1 ≥ 220, HMGA2 ≥ 30, FolR1 ≥ 50, p16 ≥ 170, nuclear PTEN ≥ 2 and estrogen receptor ≤ 50; P < ...
December 2014: Human Pathology
Suzie J Scales, Nidhi Gupta, Glenn Pacheco, Ron Firestein, Dorothy M French, Hartmut Koeppen, Linda Rangell, Vivian Barry-Hamilton, Elizabeth Luis, Josefa Chuh, Yin Zhang, Gladys S Ingle, Aimee Fourie-O'Donohue, Katherine R Kozak, Sarajane Ross, Mark S Dennis, Susan D Spencer
Mesothelin (MSLN) is an attractive target for antibody-drug conjugate therapy because it is highly expressed in various epithelial cancers, with normal expression limited to nondividing mesothelia. We generated novel antimesothelin antibodies and conjugated an internalizing one (7D9) to the microtubule-disrupting drugs monomethyl auristatin E (MMAE) and MMAF, finding the most effective to be MMAE with a lysosomal protease-cleavable valine-citrulline linker. The humanized (h7D9.v3) version, αMSLN-MMAE, specifically targeted mesothelin-expressing cells and inhibited their proliferation with an IC50 of 0...
November 2014: Molecular Cancer Therapeutics
Christine Alewine, Laiman Xiang, Takao Yamori, Gerhard Niederfellner, Klaus Bosslet, Ira Pastan
The RG7787 mesothelin-targeted recombinant immunotoxin (RIT) consists of an antibody fragment targeting mesothelin (MSLN) fused to a 24-kD fragment of Pseudomonas exotoxin A for cell killing. Compared with prior RITs, RG7787 has improved properties for clinical development including decreased nonspecific toxicity and immunogenicity and resistance to degradation by lysosomal proteases. MSLN is a cell surface glycoprotein highly expressed by many solid tumor malignancies. New reports have demonstrated that MSLN is expressed by a significant percentage of triple-negative breast and gastric cancer clinical specimens...
November 2014: Molecular Cancer Therapeutics
Renee Frank, Shaoying Li, Nuzhat A Ahmad, Antonia R Sepulveda, Nirag C Jhala
OBJECTIVES: Mesothelin (MSLN) is a differentiation antigen found to be overexpressed in intraductal papillary mucinous neoplasms (IPMNs) and is a potential treatment target in pancreatic ductal adenocarcinoma. METHODS: From institutional archives, 114 cases of resected pancreatic mucinous cysts were identified, including IPMN and mucinous cystic neoplasm (MCN). Immunohistochemical analysis of MSLN was performed on representative sections. RESULTS: MSLN was seen more frequently in neoplastic epithelial cells from IPMN (39/52; P < ...
September 2014: American Journal of Clinical Pathology
Jingli Zhang, Tapan K Bera, Wenhai Liu, Xing Du, Christine Alewine, Raffit Hassan, Ira Pastan
The mesothelin (MSLN) gene encodes a 71 kilodalton (kDa) precursor protein that is processed into megakaryocytic potentiating factor (MPF), a 31 kDa protein that is secreted from the cell, and mature mesothelin (mMSLN), a 40 kDa cell surface protein. The mMSLN binds to CA125, an interaction that has been implicated in the intra-cavitary spread of mesothelioma and ovarian cancer. To better define the role of MPF and mMSLN, growth of the lung cancer cell line A549 was evaluated in immuno-deficient mice with inactivation of the Msln gene...
2014: PloS One
Elizabeth B Somers, Daniel J O'Shannessy
Renal disease is the eighth leading cause of death in the United States. Early diagnosis is usually based on the detection of proteinuria or elevated serum creatinine, a relatively poor biomarker that does not accurately predict renal disease progression. As a result, more predictive biomarkers of renal function are sought. We present preliminary data on three protein biomarkers, folate receptor alpha (FRA), mesothelin (MSLN), and megakaryocyte potentiating factor (MPF), currently being pursued for applications in oncology diagnostics, and evaluate serum and urine levels in subjects with renal disease...
2014: Biomarker Insights
Jianping Yuan, Satoshi Kashiwagi, Patrick Reeves, Jean Nezivar, Yuan Yang, Nadiah Hashim Arrifin, Mai Nguyen, Gilberte Jean-Mary, Xiaoyun Tong, Paramjit Uppal, Svetlana Korochkina, Ben Forbes, Tao Chen, Elda Righi, Roderick Bronson, Huabiao Chen, Sandra Orsulic, Timothy Brauns, Pierre Leblanc, Nathalie Scholler, Glenn Dranoff, Jeffrey Gelfand, Mark C Poznansky
BACKGROUND: Although dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs...
2014: Journal of Hematology & Oncology
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
Genes involved in the carcinogenetic mechanisms underlying malignant pleural mesothelioma (MPM) are still poorly characterized. So far, mesothelin (MSLN) has aroused the most interest. It encodes for a membrane glycoprotein, frequently over-expressed in various malignancies such as MPM, and ovarian and pancreatic cancers. It has been proposed as a diagnostic and immunotherapeutic target with promising results. However, an alternative therapeutic approach seems to rise, whereby synthetic molecules, such as antisense oligonucleotides, could be used to inhibit MSLN activity...
2014: PloS One
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