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Mesothelin

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https://www.readbyqxmd.com/read/28440189/better-predictive-value-of-cancer-antigen125-ca125-as-biomarker-in-ovary-and-breast-tumors-and-its-correlation-with-the-histopathological-type-grade-of-the-disease
#1
Aarifa Nazmeen, Smarajit Maiti, Kusumita Mandal, Samir K Roy, Tamal Kanti Ghosh, Nirmalya K Sinha, Kamalika Mandal
BACKGROUND: Both ovarian/breast cancers are the most prevalent hormone-associated gynecological-cancers, where uncontrolled cellular proliferations/genetic-errors are noticed. The cancer-antigen125 (CA125), which we assessed presently is an important biomarker in the early detection/monitoring of this disease-pathogenesis. METHODS: Serum/tissue CA125 was measured by solid-phase-Enzyme-linked-immunosorbent-assay in women with ovarian/breast tumors of different types (epithelial/non-epithelial; benign/borderline/malignant)/stages...
April 24, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28394698/generation-of-therapeutic-immunoconjugates-via-residue-specific-conjugation-technology-respect-utilizing-a-native-cysteine-in-the-light-chain-framework-of-oryctolagus-cuniculus
#2
Earl F Albone, Jared L Spidel, Xin Cheng, Young Chul Park, Sara Jacob, Andrew Z Milinichik, Ben Vassen, Janet Butler, J Bradford Kline, Luigi Grasso
The conjugation of toxins, dyes, peptides, or proteins to monoclonal antibodies is often performed via free thiol groups generated by either partial reduction methods or engineering free cysteine residues into the antibody sequence. Antibodies from the rabbit Oryctolagus cuniculus have an additional intrachain disulfide bond, whereby the light chain variable kappa domain is bridged to the constant kappa region between cysteine residues at positions 80 and 171, respectively. Chimerization of rabbit antibodies with human constant domains allows for the generation of a free thiol group at the light chain position 80 (C80) that can be utilized for site-specific conjugation...
April 10, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28381173/mesothelin-targeting-chimeric-antigen-receptor-modified-t-cells-by-piggybac-transposon-system-suppress-the-growth-of-bile-duct-carcinoma
#3
Jie-Ying Xu, Zhen-Long Ye, Du-Qing Jiang, Jiang-Chuan He, Yong-Mei Ding, Lin-Fang Li, Sai-Qun Lv, Ying Wang, Hua-Jun Jin, Qi-Jun Qian
Chimeric antigen receptor modified T cell-based immunotherapy is revolutionizing the field of cancer treatment. However, its potential in treating bile duct carcinoma has not been fully explored. Herein, we developed the second-generation mesothelin-targeting chimeric antigen receptor-modified T cells with the 4-1BB co-stimulatory module by the piggyBac transposon system. Mesothelin-targeting chimeric antigen receptor was expressed by 66.0% of mesothelin-targeting chimeric antigen receptor-modified T cells post electrophoretic transfection and stimulation with K562-meso cells; the expressions of activation markers were tested by flow cytometry assay and showed greater activation of mesothelin-targeting chimeric antigen receptor-modified T cells than control T cells (CD107α: 71...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28356156/chimeric-antigen-receptor-t-cells-a-novel-therapy-for-solid-tumors
#4
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/28353419/a-new-anti-mesothelin-antibody-targets-selectively-the-membrane-associated-form
#5
Kamal Asgarov, Jeremy Balland, Charline Tirole, Adeline Bouard, Virginie Mougey, Diana Ramos, António Barroso, Vincent Zangiacomi, Marine Jary, Stefano Kim, Maria Gonzalez-Pajuelo, Bernard Royer, Hans de Haard, Andy Clark, John Wijdenes, Christophe Borg
Mesothelin is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that shows promise as a target for antibody-directed cancer therapy. High levels of soluble forms of the antigen represent a barrier to directing therapy to cellular targets. The ability to develop antibodies that can selectively discriminate between membrane-bound and soluble conformations of a specific protein, and thus target only the membrane-associated antigen, is a substantive issue. We show that use of a tolerance protocol provides a route to such discrimination...
April 2017: MAbs
https://www.readbyqxmd.com/read/28348450/a-novel-panel-of-serum-biomarkers-for-mpm-diagnosis
#6
A Bonotti, R Foddis, S Landi, O Melaiu, C De Santi, L Giusti, E Donadio, F Ciregia, M R Mazzoni, A Lucacchini, M Bovenzi, M Comar, E Pantani, A Pistelli, A Cristaudo
Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type...
2017: Disease Markers
https://www.readbyqxmd.com/read/28343162/mesothelin-promoter-variants-are-associated-with-increased-soluble-mesothelin-related-peptide-levels-in-asbestos-exposed-individuals
#7
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...
March 25, 2017: Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28335760/midkine-is-a-potential-novel-marker-for-malignant-mesothelioma-with-different-prognostic-and-diagnostic-values-from-mesothelin
#8
Guntulu Ak, Yuji Tada, Hideaki Shimada, Selma Metintas, Masaaki Ito, Kenzo Hiroshima, Masatoshi Tagawa, Muzaffer Metintas
BACKGROUND: We evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker. METHODS: Serum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined specimens from 95 Turkish cases with malignant pleural mesothelioma, 56 metastatic cancers to pleura, 27 other types of benign pleural diseases and 20 benign asbestos pleurisy...
March 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28322788/a-recombinant-polypeptide-of-the-megakaryocyte-potentiating-factor-is-a-potential-biomarker-in-plasma-for-the-detection-of-mesothelioma
#9
Irina Raiko, Hans-Peter Rihs, Jan Gleichenhagen, Ingrid Sander, Jens Kollmeier, Martin Lehnert, Thomas Brüning, Georg Johnen
Malignant mesothelioma (MM) is a fatal disease mostly associated with asbestos exposure and difficult to detect by non-invasive methods. This study aimed to use recombinant fragments of the megakaryocyte potentiating factor (MPF) for the development of cost-effective MPF ELISAs. Three polypeptides spanning the MPF region (MPF1-148, MPF 34-288, MPF/MSLN254-400) were produced in E.coli as maltose-binding protein hybrids. After isolation, Factor Xa digest, and purification, the polypeptides were used for the generation of rabbit antibodies and development of ELISAs...
March 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314308/comparison-of-the-diagnostic-performance-of-fibulin-3-and-mesothelin-in-patients-with-pleural-effusions-from-malignant-mesothelioma
#10
COMPARATIVE STUDY
Enrico Battolla, Pier Aldo Canessa, Paola Ferro, Maria Cristiana Franceschini, Vincenzo Fontana, Paolo Dessanti, Valentina Pinelli, Anna Morabito, Franco Fedeli, Maria Pia Pistillo, Silvio Roncella
BACKGROUND: In the literature, there exist conflicting data on the value of fibulin-3 (FBLN3) for the diagnosis of pleural effusion (PE) in malignant pleural mesothelioma (MPM). Therefore we compared the diagnostic performance of FBLN3 against that of soluble mesothelin-related peptide (SMRP) in a cohort of Italian patients. MATERIALS AND METHODS: FBLN3 and SMRP were detected in PE from 33 patients with MPM, 64 with pleural benign lesions and 23 with non-MPM pleural metastases using a commercial enzyme-linked-immunosorbent(ELISA)-assay kit according to manufacturers' instructions...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28288656/incorporation-of-a-hinge-domain-improves-the-expansion-of-chimeric-antigen-receptor-t-cells
#11
Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Yao Yao, Duanqing Pei, Xin Du, Peng Li
BACKGROUND: Multiple iterations of chimeric antigen receptors (CARs) have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined. METHODS: We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo...
March 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28288645/mesothelin-promotes-epithelial-to-mesenchymal-transition-and-tumorigenicity-of-human-lung-cancer-and-mesothelioma-cells
#12
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
#13
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
https://www.readbyqxmd.com/read/28196410/mesothelin-expression-in-gastric-adenocarcinoma-and-its-relation-to-clinical-outcomes
#14
Song-Hee Han, Mee Joo, Hanseong Kim, Sunhee Chang
BACKGROUND: Although surgical resection with chemotherapy is considered effective for patients with advanced gastric cancer, it remains the third leading cause of cancer-related death in South Korea. Several studies have reported that mesothelial markers including mesothelin, calretinin, and Wilms tumor protein 1 (WT1) were positive in variable carcinomas, associated with prognosis, and were evaluated as potential markers for targeted therapy. The aim of this study was to assess the immunohistochemical expression of mesothelial markers (mesothelin, calretinin, and WT1) in gastric adenocarcinoma and their relations to clinocopathological features and prognosis...
March 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28170372/prognostication-and-monitoring-of-mesothelioma-using-biomarkers-a-systematic-review
#15
David T Arnold, Duneesha De Fonseka, Fergus W Hamilton, Najib M Rahman, Nick A Maskell
BACKGROUND: Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural fluid biomarkers that could act as an adjunct to radiological assessment would be of significant value. The aim of this review was to collate and summarise the literature relating to this topic. METHODS: A systematic review was performed on the databases Pubmed and EMBASE to identify relevant studies...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28165915/humanization-of-rabbit-monoclonal-antibodies-via-grafting-combined-kabat-imgt-paratome-complementarity-determining-regions-rationale-and-examples
#16
Yi-Fan Zhang, Mitchell Ho
Rabbit monoclonal antibodies (RabMAbs) can recognize diverse epitopes, including those poorly immunogenic in mice and humans. However, there have been only a few reports on RabMAb humanization, an important antibody engineering step usually done before clinical applications are investigated. To pursue a general method for humanization of RabMAbs, we analyzed the complex structures of 5 RabMAbs with their antigens currently available in the Protein Data Bank, and identified antigen-contacting residues on the rabbit Fv within the 6 Angstrom distance to its antigen...
April 2017: MAbs
https://www.readbyqxmd.com/read/28160193/correlation-between-tumor-mesothelin-expression-and-serum-mesothelin-in-patients-with-epithelial-ovarian-carcinoma-a-potential-noninvasive-biomarker-for-mesothelin-targeted-therapy
#17
Tatsuya Hanaoka, Kosei Hasegawa, Tomomi Kato, Sho Sato, Akira Kurosaki, Akiko Miyara, Shoji Nagao, Hiroyuki Seki, Masanori Yasuda, Keiichi Fujiwara
BACKGROUND: The cell surface glycoprotein mesothelin is highly expressed in several malignant diseases. Normal mesothelin expression is limited to mesothelial cells lining the pleura, peritoneum, and pericardium, making it a biomarker and an attractive target for cancer therapy. METHODS: We investigated tumor mesothelin expression and serum mesothelin levels in patients with epithelial ovarian cancer or borderline tumors. In total, 161 patients selected from a previous prospective study were analyzed for tumor mesothelin expression using immunohistochemistry and serum mesothelin expression using enzyme-linked immunosorbent assay...
February 3, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28153099/selective-blockade-of-the-ubiquitous-checkpoint-receptor-cd47-is-enabled-by-dual-targeting-bispecific-antibodies
#18
Elie Dheilly, Valéry Moine, Lucile Broyer, Susana Salgado-Pires, Zoë Johnson, Anne Papaioannou, Laura Cons, Sébastien Calloud, Stefano Majocchi, Robert Nelson, François Rousseau, Walter Ferlin, Marie Kosco-Vilbois, Nicolas Fischer, Krzysztof Masternak
CD47 is a ubiquitously expressed immune checkpoint receptor that is often upregulated in cancer. CD47 interacts with its counter-receptor SIRPα on macrophages and other myeloid cells to inhibit cancer cell phagocytosis and drive immune evasion. To overcome tolerability and "antigen sink" issues arising from widespread CD47 expression, we generated dual-targeting bispecific antibodies that selectively block the CD47-SIRPα interaction on malignant cells expressing a specific tumor-associated antigen; e.g., CD19 or mesothelin...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28125734/identification-of-mir-21-5p-as-a-functional-regulator-of-mesothelin-expression-using-microrna-capture-affinity-coupled-with-next-generation-sequencing
#19
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
https://www.readbyqxmd.com/read/28112042/peritoneal-deciduoid-mesothelioma
#20
Nicole Dominiak, Whitney Graybill, William Gunning, Mary S Richardson, Laura S Spruill
This report highlights a diagnostically challenging case of diffuse deciduoid mesothelioma occurring in the peritoneum of a 25-year-old woman, 8 months postpartum. Optimally debulked tumor consisted of sheets of polygonal cells arranged in solid, trabecular, and pseudopapillary configurations, with vesicular, occasionally grooved nuclei and small nucleoli. A barrage of immunohistochemical stains revealed an unusual staining pattern characterized by diffusely positive keratin, WT-1, and mesothelin staining, but lack of calretinin positivity...
January 1, 2017: International Journal of Surgical Pathology
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