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Mesothelin

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https://www.readbyqxmd.com/read/28771103/overcoming-barriers-of-car-t-cell-therapy-in-patients-with-mesothelin-expressing-cancers
#1
Mark H O'Hara, Caitlin Stashwick, Gabriela Plesa, Janos L Tanyi
One obstacle to the application of immunotherapy to solid malignancies is to overcome the existing tolerance to self-antigens. Vaccine strategies aimed at harnessing endogenous antitumor T cells are limited by the T-cell receptor repertoire, which can be detected within the thymus as central tolerance or rendered nonfunctional by post-thymic mechanisms of peripheral tolerance. Adoptive immunotherapy can overcome these obstacles, since therapeutically effective T cells can be engineered to recognize tumors. Continued advancements in novel treatments, including immunotherapy, in solid malignancies are imperative...
August 3, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28740119/novel-insights-into-mesothelioma-biology-and-implications-for-therapy
#2
REVIEW
Timothy A Yap, Joachim G Aerts, Sanjay Popat, Dean A Fennell
Malignant mesothelioma is a universally lethal cancer that is increasing in incidence worldwide. There is a dearth of effective therapies, with only one treatment (pemetrexed and cisplatin combination chemotherapy) approved in the past 13 years. However, the past 5 years have witnessed an exponential growth in our understanding of mesothelioma pathobiology, which is set to revolutionize therapeutic strategies. From a genomic standpoint, mesothelioma is characterized by a preponderance of tumour suppressor alterations, for which novel therapies are currently in development...
July 25, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28713675/novel-systemic-therapy-against-malignant-pleural-mesothelioma
#3
REVIEW
Michael R Mancuso, Joel W Neal
Malignant pleural mesothelioma is an aggressive tumor of the pleura with an overall poor prognosis. Even with surgical resection, for which only a subset of patients are eligible, long term disease free survival is rare. Standard first-line systemic treatment consists of a platinum analog, an anti-metabolite, and sometimes anti-angiogenic therapy, but there is currently no well-established standard therapy for refractory or relapsed disease. This review focuses on efforts to develop improved systemic therapy for the treatment of malignant pleural mesothelioma (MPM) including cytotoxic systemic therapy, a variety of tyrosine kinase inhibitors and their downstream effector pathways, pharmacologic targeting of the epigenome, novel approaches to target proteins expressed on mesothelioma cells (such as mesothelin), arginine depletion therapy, and the emerging role of immunotherapy...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28713671/diagnostic-and-prognostic-biomarkers-for-malignant-mesothelioma-an-update
#4
REVIEW
Zhongjian Chen, Giovanni Gaudino, Harvey I Pass, Michele Carbone, Haining Yang
Malignant mesothelioma (MM) is an aggressive and lethal cancer, mostly related to inhalation of asbestos and erionite fibers. MM is associated with poor prognosis, because of its resistance to current therapies, even if higher survival occurs in patients diagnosed and treated when at stage I of the disease. However, these do not exceed 5% of the total number of cases, due to the inadequacy of the existing biomarkers for early and accurate diagnosis. Therefore, new effective biomarkers are needed for MM detection at earlier stages and to develop tailored therapies...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28706912/diagnosis-and-prognosis-review-of-biomarkers-for-mesothelioma
#5
REVIEW
Huan H Sun, Allen Vaynblat, Harvey I Pass
Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between 1940 and 1980. With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM...
June 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28674083/combining-local-immunotoxins-targeting-mesothelin-with-ctla-4-blockade-synergistically-eradicates-murine-cancer-by-promoting-anticancer-immunity
#6
Yasmin Leshem, James O'Brien, Xiufen Liu, Tapan K Bera, Masaki Terabe, Jay A Berzofsky, Birgit Bossenmaier, Gerhard Niederfellner, Chin-Hsien Tai, Yoram Reiter, Ira Pastan
Immune checkpoint blockade using antibodies to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) benefits a limited number of cancer patients. SS1P and LMB-100 are immunotoxins that target mesothelin. We observed delayed responses to SS1P in patients with mesothelioma suggesting that antitumor immunity was induced. Our goal was to stimulate antitumor immunity by combining SS1P or LMB-100 with anti-CTLA-4. We constructed a BALB/c breast cancer cell line expressing human mesothelin (66C14-M), which was implanted in one or two locations...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28652837/a-pilot-study-of-zoledronic-acid-in-the-treatment-of-patients-with-advanced-malignant-pleural-mesothelioma
#7
Muhammad Omer Jamil, Mary S Jerome, Deborah Miley, Katri S Selander, Francisco Robert
PURPOSE: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal median survival of <12 months with current therapy. Single and combination chemotherapy regimens have shown only modest clinical benefit. In preclinical studies, nitrogen-containing bisphosphonates (zoledronic acid) inhibit growth of mesothelioma cells by different mechanisms: inhibition of mevalonate pathway, inhibition of angiogenesis, activation of apoptosis through caspase activation, and alteration in activity of matrix metalloproteinases, thereby affecting invasiveness of cancer cells...
2017: Lung Cancer: Targets and Therapy
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
#8
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/28638449/plasma-mesothelin-as-a-novel-diagnostic-and-prognostic-biomarker-in-colorectal-cancer
#9
Shuwei Li, Lisheng Xie, Lei He, Zhimin Fan, Junhua Xu, Kaili Xu, Lingjun Zhu, Gaoxiang Ma, Mulong Du, Haiyan Chu, Zhengdong Zhang, Min Ni, Meilin Wang
Objective Mesothelin is a cell surface protein and overexpressed in many cancers. However, the potential value of mesothelin as plasma biomarker in colorectal cancer has not been explored. The purpose of this study was to identify whether plasma mesothelin is a suitable diagnostic and prognostic biomarker for colorectal cancer. Methods We performed a two-stage case-control study to evaluate plasma mesothelin levels in colorectal cancer using enzyme-linked immunosorbent assay (ELISA). Preoperative and postoperative plasma were collected to examine the level changes influenced by surgery...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28558669/calretinin-as-a-blood-based-biomarker-for-mesothelioma
#10
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
#11
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
#12
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...
July 11, 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
#13
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
#14
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
#15
Earl F Albone, Jared L Spidel, Xin Cheng, Young Chul Park, Sara Jacob, Andrew Z Milinichik, Ben Vaessen, 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...
May 4, 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
#16
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
#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/28353419/a-new-anti-mesothelin-antibody-targets-selectively-the-membrane-associated-form
#18
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
#19
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
#20
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
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