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https://www.readbyqxmd.com/read/29596890/immuno-modulators-enhance-antigen-specific-immunity-and-anti-tumor-effects-of-mesothelin-specific-chimeric-dna-vaccine-through-promoting-dc-maturation
#1
Yu-Li Chen, Ming-Cheng Chang, Ying-Cheng Chiang, Han-Wei Lin, Nai-Yun Sun, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng
As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes...
March 26, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29574096/measurement-of-indicator-genes-using-global-complementary-dna-cdna-amplification-by-polyadenylic-acid-reverse-transcriptase-polymerase-chain-reaction-poly-a-rt-pcr-a-feasibility-study-using-paired-samples-from-tissue-and-ductal-juice-in-patients-undergoing
#2
Sudip Sanyal, Ajith K Siriwardena, Richard Byers
OBJECTIVES: The aim of this study is to compare gene expression profiles in RNA isolated from pancreatic ductal juice with the RNA expression profiles of the same genes from matched intra-operative tissue samples from pancreatic tumours. METHODS: Intra-operative sampling of pancreatic juice and collection of matched tissue samples was undertaken in patients undergoing pancreatoduodenectomy for clinically suspected pancreatic cancer and a precursor lesion, main-duct intraductal papillary mucinous neoplasm...
March 20, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29572027/a-novel-multiple-biomarker-panel-for-the-early-detection-of-high-grade-serous-ovarian-carcinoma
#3
Chanhee Han, Stefania Bellone, Eric R Siegel, Gary Altwerger, Gulden Menderes, Elena Bonazzoli, Tomomi Egawa-Takata, Francesca Pettinella, Anna Bianchi, Francesco Riccio, Luca Zammataro, Ghanshyam Yadav, Jarrod A Marto, Marie-France Penet, Douglas A Levine, Ronny Drapkin, Abhijit Patel, Babak Litkouhi, Elena Ratner, Dan-Arin Silasi, Gloria S Huang, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
INTRODUCTION: Since the majority of patients are diagnosed at an advanced stage, ovarian cancer remains the most lethal gynecologic malignancy. There is no single biomarker with the sensitivity and specificity required for effective cancer screening; therefore, we investigated a panel of novel biomarkers for the early detection of high-grade serous ovarian carcinoma. METHODS: Twelve serum biomarkers with high differential gene expression and validated antibodies were selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN, and OPN...
March 20, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29560830/qsurface-fast-identification-of-surface-expression-markers-in-cancers
#4
Yourae Hong, Choa Park, Nayoung Kim, Juyeon Cho, Sung Ung Moon, Jongmin Kim, Euna Jeong, Sukjoon Yoon
BACKGROUND: Cell surface proteins have provided useful targets and biomarkers for advanced cancer therapies. The recent clinical success of antibody-drug conjugates (ADCs) highlights the importance of finding selective surface antigens for given cancer subtypes. We thus attempted to develop stand-alone software for the analysis of the cell surface transcriptome of patient cancer samples and to prioritize lineage- and/or mutation-specific over-expression markers in cancer cells. RESULTS: A total of 519 genes were selected as surface proteins, and their expression was profiled in 14 cancer subtypes using patient sample transcriptome data...
March 19, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29558951/accurate-control-of-dual-receptor-engineered-t-cell-activity-through-a-bifunctional-anti-angiogenic-peptide
#5
Erhao Zhang, Jieyi Gu, Jianpeng Xue, Chenyu Lin, Chen Liu, Mengwei Li, Jingchao Hao, Sarra Setrerrahmane, Xiaowei Chi, Weiyan Qi, Jialiang Hu, Hanmei Xu
BACKGROUND: Chimeric antigen receptors (CARs) presented on T cell surfaces enable redirection of T cell specificity, which has enormous promise in antitumor therapy. However, excessive activity and poor control over such engineered T cells cause significant safety challenges, such as cytokine release syndrome and organ toxicities. To enhance the specificity and controllable activity of CAR-T cells, we report a novel switchable dual-receptor CAR-engineered T (sdCAR-T) cell and a new switch molecule of FITC-HM-3 bifunctional molecule (FHBM) in this study...
March 20, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29426060/discovery-and-validation-of-novel-protein-biomarkers-in-ovarian-cancer-patient-urine
#6
Jarrod J Sandow, Adam Rainczuk, Giuseppe Infusini, Ming Makanji, Maree Bilandzic, Amy L Wilson, Nicole Fairweather, Peter G Stanton, Daniel Garama, Daniel Gough, Thomas W Jobling, Andrew I Webb, Andrew N Stephens
PURPOSE: For the vast majority of ovarian cancer patients, optimal surgical debulking remains a key prognostic factor associated with improved survival. A standardized, biomarker-based test, to pre-operatively discriminate benign from malignant disease and inform appropriate patient triage, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. EXPERIMENTAL DESIGN: We conducted a pilot study consisting of 40 patient urine samples (20 from each group), using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in urine from individual ovarian cancer patients...
February 9, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29275459/sulfatase-1-knockdown-promotes-in-vitro-and-in-vivo-aggressive-behavior-of-murine-hepatocarcinoma-hca-p-cells-through-up-regulation-of-mesothelin
#7
Salma Abdi Mahmoud, Mohammed Mohammed Ibrahim, Ahmed Hago Musa, Yuhong Huang, Jun Zhang, Jingwen Wang, Yuanyi Wei, Li Wang, Shunting Zhou, Boyi Xin, Wei Xuan, Jianwu Tang
Our previous study (Oncotarget 2016; 7:46) demonstrated that the over-expression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line (a murine HCC cell with lymph node metastatic [LNM] rate of >75%) downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo. In current work, we investigated the effects of Sulf-1 knockdown on mesothelin (Msln) and it's effects on the in vitro cell proliferation, migration, invasion, and in vivo tumor growth and LNM rate for Hca-P cells (a murine HCC cell with LNM rate of <25%)...
December 23, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29241375/peritoneal-dissemination-of-ovarian-cancer-role-of-muc16-mesothelin-interaction-and-implications-for-treatment
#8
Ricardo Coelho, Lara Marcos-Silva, Sara Ricardo, Filipa Ponte, Antonia Costa, Jose Manuel Lopes, Leonor David
Peritoneal dissemination is a particular form of malignant progression in ovarian cancer, preceding hematogenic or lymphatic dissemination. Thus, prevention of peritoneal implantation of cancer cells is envisioned to inhibit neoplastic dissemination and therefore prolong disease remission and patient's survival. Areas covered: An extended review on the role of MUC16 (CA125) and mesothelin (MSLN), expressed in a high percentage of ovarian carcinomas, indicate that this duet is relevant for the contact between cancer cells and mesothelial cells in homotypic (cancer cell-cancer cell) and heterotypic (cancer cell-mesothelial cell) interactions...
February 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29184420/amatuximab-and-novel-agents-targeting-mesothelin-for-solid-tumors
#9
REVIEW
Paolo Baldo, Sara Cecco
Mesothelin (MSLN) is considered a promising target for cancer therapy. Originally extracted in 1992 after the immunization of mice with a human ovarian cancer (OC) cell line and cloned in 1996, MSLN seems to be involved in cell adhesion and metastasis. MSLN is prevalent in mesothelia tissues but is expressed in several human cancers, such as OC, pancreatic cancer, mesothelioma, and lung cancer. Amatuximab (MORAb-009) is a mouse-human chimeric monoclonal antibody with a selective affinity for MSLN. The principal mechanism of action comprises inhibition of binding of MSLN with the antigen CA125/MUC16...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29100432/cancer-antigen-profiling-for-malignant-pleural-mesothelioma-immunotherapy-expression-and-coexpression-of-mesothelin-cancer-antigen-125-and-wilms-tumor-1
#10
Takashi Eguchi, Kyuichi Kadota, Marissa Mayor, Marjorie G Zauderer, Andreas Rimner, Valerie W Rusch, William D Travis, Michel Sadelain, Prasad S Adusumilli
Background: To develop cancer antigen-targeted immunotherapeutic strategies for malignant pleural mesothelioma (MPM), we investigated the individual and coexpressions of the cancer-associated antigens mesothelin (MSLN), cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) in both epithelioid and non-epithelioid MPM. Methods: All available hematoxylin and eosin-stained slides from patients who were diagnosed with MPM (1989-2010) were reviewed. We constructed tissue microarrays from 283 patients (epithelioid = 234; non-epithelioid = 49)...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093164/the-immunopeptidomic-landscape-of-ovarian-carcinomas
#11
Heiko Schuster, Janet K Peper, Hans-Christian Bösmüller, Kevin Röhle, Linus Backert, Tatjana Bilich, Britta Ney, Markus W Löffler, Daniel J Kowalewski, Nico Trautwein, Armin Rabsteyn, Tobias Engler, Sabine Braun, Sebastian P Haen, Juliane S Walz, Barbara Schmid-Horch, Sara Y Brucker, Diethelm Wallwiener, Oliver Kohlbacher, Falko Fend, Hans-Georg Rammensee, Stefan Stevanović, Annette Staebler, Philipp Wagner
Immunotherapies, particularly checkpoint inhibitors, have set off a revolution in cancer therapy by releasing the power of the immune system. However, only little is known about the antigens that are essentially presented on cancer cells, capable of exposing them to immune cells. Large-scale HLA ligandome analysis has enabled us to exhaustively characterize the immunopeptidomic landscape of epithelial ovarian cancers (EOCs). Additional comparative profiling with the immunopeptidome of a variety of benign sources has unveiled a multitude of ovarian cancer antigens (MUC16, MSLN, LGALS1, IDO1, KLK10) to be presented by HLA class I and class II molecules exclusively on ovarian cancer cells...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29059207/targeting-mesothelin-receptors-with-drug-loaded-bacterial-nanocells-suppresses-human-mesothelioma-tumour-growth-in-mouse-xenograft-models
#12
Mohamed A Alfaleh, Christopher B Howard, Ilya Sedliarou, Martina L Jones, Reema Gudhka, Natasha Vanegas, Jocelyn Weiss, Julia H Suurbach, Christopher J de Bakker, Michael R Milne, Bree A Rumballe, Jennifer A MacDiarmid, Himanshu Brahmbhatt, Stephen M Mahler
Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential...
2017: PloS One
https://www.readbyqxmd.com/read/29051346/data-driven-prioritization-and-review-of-targets-for-molecular-based-theranostic-approaches-in-pancreatic-cancer
#13
Marjory Koller, Elmire Hartmans, Derk Jan A de Groot, Xiao Juan Zhao, Gooitzen M van Dam, Wouter B Nagengast, Rudolf S N Fehrmann
Molecularly targeted therapeutic and imaging strategies directed at aberrant signaling pathways in pancreatic tumor cells may improve the poor outcome of pancreatic ductal adenocarcinoma (PDA). Therefore, relevant molecular targets need to be identified. Methods: We collected publicly available expression profiles of patient-derived normal pancreatic tissue ( n = 77) and PDA samples ( n = 103). Functional genomic messenger RNA profiling was applied to predict target upregulation on the protein level. We prioritized these targets based on current status of preclinical therapeutic and imaging evaluation in PDA...
December 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28964420/soluble-mesothelin-related-peptides-to-monitor-recurrence-after-resection-of-pleural-mesothelioma
#14
Bryan M Burt, Hyun-Sung Lee, Veronica Lenge De Rosen, Masatsugu Hamaji, Shawn S Groth, Thomas M Wheeler, David J Sugarbaker
BACKGROUND: Most patients undergoing surgical resection of malignant pleural mesothelioma (MPM) will experience recurrence, and radiographic diagnosis of recurrence can be difficult in the postoperative chest. Our objective was to determine the utility of the serum biomarker soluble mesothelin-related peptide (SMRP; or mesothelin) in monitoring of the postoperative MPM patient. METHODS: We retrospectively evaluated a prospectively maintained single institution clinical database...
November 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28640856/correction-msln-gene-silencing-has-an-anti-malignant-effect-on-cell-lines-overexpressing-mesothelin-deriving-from-malignant-pleural-mesothelioma
#15
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
https://www.readbyqxmd.com/read/28460459/comprehensive-immunohistochemical-study-of-mesothelin-msln-using-different-monoclonal-antibodies-5b2-and-mn-1-in-1562-tumors-with-evaluation-of-its-prognostic-value-in-malignant-pleural-mesothelioma
#16
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
https://www.readbyqxmd.com/read/28356156/chimeric-antigen-receptor-t-cells-a-novel-therapy-for-solid-tumors
#17
REVIEW
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
https://www.readbyqxmd.com/read/28343162/mesothelin-promoter-variants-are-associated-with-increased-soluble-mesothelin-related-peptide-levels-in-asbestos-exposed-individuals
#18
COMPARATIVE STUDY
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
https://www.readbyqxmd.com/read/28288645/mesothelin-promotes-epithelial-to-mesenchymal-transition-and-tumorigenicity-of-human-lung-cancer-and-mesothelioma-cells
#19
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
https://www.readbyqxmd.com/read/28287406/mesothelin-mucin-16-signaling-in-activated-portal-fibroblasts-regulates-cholestatic-liver-fibrosis
#20
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
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