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Mesothelin

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https://www.readbyqxmd.com/read/28196410/mesothelin-expression-in-gastric-adenocarcinoma-and-its-relation-to-clinical-outcomes
#1
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...
February 15, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28170372/prognostication-and-monitoring-of-mesothelioma-using-biomarkers-a-systematic-review
#2
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...
February 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28165915/humanization-of-rabbit-monoclonal-antibodies-via-grafting-combined-kabat-imgt-paratome%C3%A2-complementarity-determining-regions-rationale-and-examples
#3
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 five 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...
February 6, 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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28007619/malignant-mesothelioma-biomarkers-from-discovery-to-use-in-clinical-practise-for-diagnosis-monitoring-screening-and-treatment
#8
REVIEW
Jenette Creaney, Bruce W S Robinson
Malignant pleural mesothelioma is a highly aggressive tumour associated with asbestos exposure. There are few effective treatment options for mesothelioma and patients have a very poor prognosis with a median survival of less than 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management and the search for a mesothelioma biomarker has been on-going for the past thirty years. Many traditional soluble (glyco)-protein biomarkers have been evaluated over this time and an ever increasing list of new biomarkers, including mRNA, DNA, miRNA and antibodies, are being reported from biomarker discovery projects...
December 19, 2016: Chest
https://www.readbyqxmd.com/read/27999204/mesothelin-targeted-immunotoxin-rg7787-has-synergistic-anti-tumor-activity-when-combined-with-taxanes
#9
Emily Kolyvas, Michael Rudloff, Marianne Poruchynsky, Rebekah Landsman, Kevin Hollevoet, David Venzon, Christine Alewine
Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin payload. The RG7787 RIT targets the cancer antigen mesothelin to deliver a recombinantly-engineered, reduced immunogenicity variant of Pseudomonas exotoxin A (PE) to the cytosol where it inhibits protein synthesis. Here we demonstrate that maximal doses of RG7787 temporarily halt growth of pancreatic cancer tumor xenografts, similar to the approved drugs gemcitabine and nab-paclitaxel, however, combination of the RIT with nab-paclitaxel produces durable complete regressions in most mice...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27906723/safety-and-outcome-measures-of-first-in-human-intraperitoneal-%C3%AE-radioimmunotherapy-with-212pb-tcmc-trastuzumab
#10
Ruby F Meredith, Julien J Torgue, Tania A Rozgaja, Eileen P Banaga, Patty W Bunch, Ronald D Alvarez, J Michael Straughn, Michael C Dobelbower, Andrew M Lowy
PURPOSE: One-year monitoring of patients receiving intraperitoneal (IP) Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome. METHODS: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of Pb-TCMC-trastuzumab, delivered <4 h after 4 mg/kg IV trastuzumab. Seven tumor markers were studied for correlation with outcome...
November 30, 2016: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27900083/primary-malignant-pericardial-mesothelioma-with-increased-serum-mesothelin-diagnosed-by-surgical-pericardial-resection-a-case-report
#11
Takeyuki Kurosawa, Keishi Sugino, Kazutoshi Isobe, Yoshinobu Hata, Yuri Fukasawa, Sakae Homma
A 37-year-old female smoker without a history of exposure to asbestos was referred to our hospital with persistent pericardial effusion. Chest computed tomography imaging examination revealed an irregular thickened pericardium with large amounts of pericardial effusion and a small pleural effusion. Fluorodeoxyglucose (FDG) positron emission tomography imaging demonstrated intrapericardial FDG accumulation. Blood tests revealed an increase in serum mesothelin levels. Examination of a surgically resected specimen revealed a grayish-white thickening of the pericardium, with a straw-colored mucinous pericardial effusion...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27884852/diagnostic-and-prognostic-biomarkers-in-the-rational-assessment-of-mesothelioma-diaphragm-study-protocol-of-a-prospective-multicentre-observational-study
#12
Selina Tsim, Caroline Kelly, Laura Alexander, Carol McCormick, Fiona Thomson, Rosie Woodward, John E Foster, David B Stobo, Jim Paul, Nick A Maskell, Anthony Chalmers, Kevin G Blyth
INTRODUCTION: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies...
November 24, 2016: BMJ Open
https://www.readbyqxmd.com/read/27869238/response-to-the-letter-to-editors-concerning-validity-of-mesothelin-in-occupational-medicine-practice
#13
Petra Smolková, Marie Nakládalová, Jana Zapletalová
No abstract text is available yet for this article.
November 18, 2016: International Journal of Occupational Medicine and Environmental Health
https://www.readbyqxmd.com/read/27863199/mesothelin-immunotherapy-for-cancer-ready-for-prime-time
#14
Raffit Hassan, Anish Thomas, Christine Alewine, Dung T Le, Elizabeth M Jaffee, Ira Pastan
Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27853672/novel-antibody-therapeutics-targeting-mesothelin-in-solid-tumors
#15
Xiao-Yan Zhao, Babu Subramanyam, Nenad Sarapa, Sven Golfier, Harald Dinter
ABSTRACT BACKGROUND: Monoclonal antibodies have become attractive clinical anti-cancer drugs in the last 3 decades due to their targeting specificity and suitable pharmacokinetic properties. Mesothelin is a tumor-associated antigen with limited expression in normal tissues. It is frequently over-expressed on the cell membrane of a number of epithelial malignancies (e.g. mesothelioma, pancreatic, ovarian, lung, triple negative breast and gastric cancers). METHODS: Mesothelin is validated as a suitable antibody target for cancer therapy...
October 2016: Clinical Cancer Drugs
https://www.readbyqxmd.com/read/27794397/expression-of-mesothelin-in-thymic-carcinoma-and-its-potential-therapeutic-significance
#16
Anish Thomas, Yuanbin Chen, Arlene Berman, David S Schrump, Giuseppe Giaccone, Ira Pastan, David J Venzon, David J Liewehr, Seth M Steinberg, Markku Miettinen, Raffit Hassan, Arun Rajan
OBJECTIVES: Advanced thymic epithelial tumors (TETs) lack adequate treatment options in part due to absence of well characterized tumor-specific antigens. Mesothelin, a cell surface antigen, has been used successfully as a target for tumor-directed therapy. We sought to determine tumor expression and serum levels of mesothelin in patients with TETs. PATIENTS AND METHODS: Tissue samples were obtained from 71 patients with histologically confirmed, unresectable advanced TETs and evaluated for mesothelin expression by immunohistochemistry...
November 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27760836/preclinical-efficacy-of-an-antibody-drug-conjugate-targeting-mesothelin-correlates-with-quantitative-89zr-immunopet
#17
Anton G T Terwisscha van Scheltinga, Annie Ogasawara, Glenn Pacheco, Alexander N Vanderbilt, Jeff N Tinianow, Nidhi Gupta, Dongwei Li, Ron Firestein, Jan Marik, Suzie J Scales, Simon-Peter Williams
Antibody-drug conjugates (ADC) use monoclonal antibodies (mAb) as vehicles to deliver potent cytotoxic drugs selectively to tumor cells expressing the target. Molecular imaging with zirconium-89 ((89)Zr)-labeled mAbs recapitulates similar targeting biology and might help predict the efficacy of these ADCs. An anti-mesothelin antibody (AMA, MMOT0530A) was used to make comparisons between its efficacy as an ADC and its tumor uptake as measured by (89)Zr immunoPET imaging. Mesothelin-targeted tumor growth inhibition by monomethyl auristatin E (MMAE), ADC AMA-MMAE (DMOT4039A), was measured in mice bearing xenografts of ovarian cancer OVCAR-3×2...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27713145/glycodelin-is-a-potential-novel-follow-up-biomarker-for-malignant-pleural-mesothelioma
#18
Marc A Schneider, Thomas Muley, Nicolas C Kahn, Arne Warth, Michael Thomas, Felix J F Herth, Hendrik Dienemann, Michael Meister
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short survival time arising from the mesothelial cells of the pleura. Soluble mesothelin-related peptide (SMRP), osteopontin or EFEMP1 (Fibulin-3) are well described biomarkers for malignant mesothelioma with moderate sensitivity and specificity. In this study, we characterized the expression of glycodelin, a marker for risk pregnancy, in MPM by RNA and protein analyses and investigated its potential as a MPM biomarker. We were able to detect glycodelin in the serum of MPM patients...
1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27646775/serum-mesothelin-osteopontin-and-vimentin-useful-markers-for-clinical-monitoring-of-malignant-pleural-mesothelioma
#19
Alessandra Bonotti, Silvia Simonini, Elena Pantani, Laura Giusti, Elena Donadio, Maria Rosa Mazzoni, Antonio Chella, Letizia Marconi, Nicolino Ambrosino, Marco Lucchi, Alfredo Mussi, Alfonso Cristaudo, Rudy Foddis
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a relatively rare tumor, with the epithelioid type occurring more frequently. Several biomarkers have been suggested for screening and early diagnosis of MPM. Currently, high levels of soluble mesothelin-related peptides (SMRP), plasma osteopontin (pOPN) and vimentin have been reported in patients with MPM as promising markers for diagnosis, but their clinical use in monitoring is still discussed. The aim of our study was to evaluate the usefulness of these substances as markers of the clinical response to treatment in patients suffering from epithelioid mesothelioma...
September 14, 2016: International Journal of Biological Markers
https://www.readbyqxmd.com/read/27635089/efficacy-of-anti-mesothelin-immunotoxin-rg7787-plus-nab-paclitaxel-against-mesothelioma-patient-derived-xenografts-and-mesothelin-as-a-biomarker-of-tumor-response
#20
Jingli Zhang, Swati Khanna, Qun Jiang, Christine Alewine, Markku Miettinen, Ira Pastan, Raffit Hassan
PURPOSE: Evaluate anti-tumor efficacy of the reduced immunogenicity anti-mesothelin immunotoxin RG7787 plus nab-Paclitaxel against primary mesothelioma cell lines and tumor xenografts and utility of mesothelin as a biomarker of tumor response. EXPERIMENTAL DESIGN: Early passage human malignant mesothelioma cell lines NCI-Meso16, NCI-Meso19, NCI-Meso21 and NCI-Meso29 were evaluated for sensitivity to RG7787 or nab-Paclitaxel alone or in combination. In addition, the anti-tumor activity of RG7787 plus nab-Paclitaxel was evaluated using NCI-Meso16, NCI-Meso21 and NCI-Meso29 tumor xenografts in immunodeficient mice...
September 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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