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Mesothelin

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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
#1
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/28558669/calretinin-as-a-blood-based-biomarker-for-mesothelioma
#2
Georg Johnen, Katarzyna Gawrych, Irina Raiko, Swaantje Casjens, Beate Pesch, Daniel G Weber, Dirk Taeger, Martin Lehnert, Jens Kollmeier, Torsten Bauer, Arthur W Musk, Bruce W S Robinson, Thomas Brüning, Jenette Creaney
BACKGROUND: Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin...
May 30, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28540060/microparticle-formation-in-peritoneal-dialysis-a-proof-of-concept-study
#3
Shareef Akbari, Rima Abou-Arkoub, Suzy Sun, Swapnil Hiremath, Arkadiy Reunov, Brendan B McCormick, Marcel Ruzicka, Dylan Burger
BACKGROUND: Injury to the mesothelial layer of the peritoneal membrane during peritoneal dialysis (PD) is implicated in loss of ultrafiltration capacity, but there are no validated biomarkers for mesothelial cell injury. Microparticles (MPs) are 0.1 to 1.0 µm membrane vesicles shed from the cell surface following injury and are sensitive markers of tissue damage. Formation of MPs in the peritoneal cavity during PD has not been reported to date. METHODS: We designed a single-center, proof of concept study to assess whether peritoneal solution exposure induces formation of mesothelial MPs suggestive of PD membrane injury...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28507279/prognostic-significance-of-soluble-mesothelin-in-malignant-pleural-mesothelioma-a-meta-analysis
#4
Long Tian, Rujun Zeng, Xin Wang, Cheng Shen, Yutian Lai, Mingming Wang, Guowei Che
BACKGROUND: Soluble mesothelin is beneficial to detect the progression and the treatment response of malignant pleural mesothelioma. However, the prognostic value of soluble mesothelin in malignant pleural mesothelioma remains unclear. METHODS: Hazard ratio with 95% CI was used to evaluate the prognostic value of soluble mesothelin and the effect of clinicopathological characteristics on the survival of malignant pleural mesothelioma. RESULTS: Eight eligible studies involving 579 patients were selected for this meta-analysis...
April 26, 2017: Oncotarget
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
#5
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/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
#6
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
#7
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 used 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
#8
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
#9
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
#10
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
#11
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
#12
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/28335760/midkine-is-a-potential-novel-marker-for-malignant-mesothelioma-with-different-prognostic-and-diagnostic-values-from-mesothelin
#13
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
#14
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...
April 29, 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
REVIEW
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
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