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Mesothelin

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https://www.readbyqxmd.com/read/27906723/safety-and-outcome-measures-of-first-in-human-intraperitoneal-%C3%AE-radioimmunotherapy-with-212pb-tcmc-trastuzumab
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
Anton G T Terwisscha van Scheltinga, Annie Ogasawara, Glenn Pacheco, Alexander Vanderbilt, Jeff Tinianow, Nidhi Gupta, Dongwei Li, Ron Firestein, Jan Marik, Suzie J Scales, Simon-Peter Williams
Antibody-drug conjugates (ADCs) use monoclonal antibodies (mAb) as vehicles to deliver potent cytotoxic drugs selectively to tumor cells expressing the target. Molecular imaging with zirconium-89 (89Zr) 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 89Zr 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 X2...
October 19, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27713145/glycodelin-is-a-potential-novel-follow-up-biomarker-for-malignant-pleural-mesothelioma
#9
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...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27646775/serum-mesothelin-osteopontin-and-vimentin-useful-markers-for-clinical-monitoring-of-malignant-pleural-mesothelioma
#10
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
#11
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
https://www.readbyqxmd.com/read/27626699/over-expression-of-sulfatase-1-in-murine-hepatocarcinoma-hca-f-cell-line-downregulates-mesothelin-and-leads-to-reduction-in-lymphatic-metastasis-both-in-vitro-and-in-vivo
#12
Salma Mahmoud, Mohammed Ibrahim, Ahmed Hago, Yuhong Huang, Yuanyi Wei, Jun Zhang, Qingqing Zhang, Yu Xiao, Jingwen Wang, Munkaila Adam, Yu Guo, Li Wang, Shuting Zhou, Boyi Xin, Wei Xuan
Lymphatic vessels function as transport channels for tumor cells to metastasize from the primary site into the lymph nodes. In this experiment we evaluated the effect of Sulfatase-1 (Sulf-1) on metastasis by upregulating it in murine hepatocarcinoma cell line Hca-F with high lymph node metastatic rate of >75%. The study in vitro showed that up regulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 down regulated Mesothelin (Msln) at both the protein and mRNA levels...
September 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27624915/expression-and-prognostic-impact-of-immune-modulatory-molecule-pd-l1-in-meningioma
#13
Seunggu J Han, Gerald Reis, Gary Kohanbash, Shruti Shrivastav, Stephen T Magill, Annette M Molinaro, Michael W McDermott, Philip V Theodosopoulos, Manish K Aghi, Mitchel S Berger, Nicholas A Butowski, Igor Barani, Joanna J Phillips, Arie Perry, Hideho Okada
While immunotherapy may offer promising new approaches for high grade meningiomas, little is currently known of the immune landscape in meningiomas. We sought to characterize the immune microenvironment and a potentially targetable antigen mesothelin across WHO grade I-III cases of meningiomas, and how infiltrating immune populations relate to patient outcomes. Immunohistochemistry was performed on tissue microarrays constructed from 96 meningioma cases. The cohort included 16 WHO grade I, 62 WHO grade II, and 18 WHO grade III tumors...
September 13, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27601652/actinomycin-d-enhances-killing-of-cancer-cells-by-immunotoxin-rg7787-through-activation-of-the-extrinsic-pathway-of-apoptosis
#14
Xiu Fen Liu, Laiman Xiang, Qi Zhou, Jean-Philippe Carralot, Marco Prunotto, Gerhard Niederfellner, Ira Pastan
RG7787 is a mesothelin-targeted immunotoxin designed to have low-immunogenicity, high-cytotoxic activity and fewer side effects. RG7787 kills many types of mesothelin-expressing cancer cells lines and causes tumor regressions in mice. Safety and immunogenicity of RG7787 is now being assessed in a phase I trial. To enhance the antitumor activity of RG7787, we screened for clinically used drugs that can synergize with RG7787. Actinomycin D is a potent transcription inhibitor that is used for treating several cancers...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27591765/distinct-pathways-of-pathogenesis-of-intraductal-oncocytic-papillary-neoplasms-and-intraductal-papillary-mucinous-neoplasms-of-the-pancreas
#15
Olca Basturk, Sun M Chung, Ralph H Hruban, N Volkan Adsay, Gokce Askan, Christine Iacobuzio-Donahue, Serdar Balci, Sui Y Zee, Bahar Memis, Jinru Shia, David S Klimstra
Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is classified as a variant of intraductal papillary mucinous neoplasm (IPMN) in the WHO guidelines. However, the neoplastic cells of IOPNs are unique, with distinctive architecture/oncocytic cytoplasm. Although molecular/immunohistochemical features of other IPMN variants have been extensively studied, those of IOPNs have not been well characterized. Expression profile of antibodies associated with genetic alterations previously described for ductal adenocarcinomas (DAs) and IPMNs (SMAD4/β-catenin/p53/mesothelin/claudin-4) as well as antibodies to mucins and differentiation markers [MUC1/MUC2/MUC5AC/MUC6/CDX2/hepatocyte paraffin-1 (HepPar-1)] was investigated in 24 IOPNs and 22 IPMNs to assess the similarities/differences between these tumors...
November 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27514374/association-between-mesothelin-expression-and-survival-outcomes-in-patients-with-triple-negative-breast-cancer-a-protocol-for-a-systematic-review
#16
Mei Wang, Aihua Li, Guangwen Sun, Lawrence Mbuagbaw, Susan Reid, Peter J Lovrics, Lehana Thabane
BACKGROUND: Mesothelin is a membrane-bound glycoprotein. Although the biologic function of mesothelin is not very clear, researchers have found that it plays a role in the survival, proliferation, and migration of tumor cells. Identified as a tumor-associated biomarker, mesothelin is more often overexpressed in triple-negative breast cancer (TNBC) than in common luminal breast tumor subtype or normal tissues. The objective of this review is to determine the association between the expression of mesothelin and overall survival in patients with TNBC...
2016: Systematic Reviews
https://www.readbyqxmd.com/read/27507537/characterization-of-a-re-engineered-mesothelin-targeted-pseudomonas-exotoxin-fusion-protein-for-lung-cancer-therapy
#17
Frieder Bauss, Martin Lechmann, Ben-Fillippo Krippendorff, Roland Staack, Frank Herting, Matthias Festag, Sabine Imhof-Jung, Friederike Hesse, Marc Pompiati, Gwendlyn Kollmorgen, Rita da Silva Mateus Seidl, Birgit Bossenmaier, Wilma Lau, Christian Schantz, Jan O Stracke, Ulrich Brinkmann, Masanori Onda, Ira Pastan, Klaus Bosslet, Gerhard Niederfellner
Mesothelin overexpression in lung adenocarcinomas correlates with the presence of activating KRAS mutations and poor prognosis. Hence SS1P, a mesothelin-targeted immunotoxin, could offer valuable treatment options for these patients, but its use in solid tumor therapy is hampered by high immunogenicity and non-specific toxicity. To overcome both obstacles we developed RG7787, a de-immunized cytotoxic fusion protein comprising a humanized SS1 Fab fragment and a truncated, B-cell epitope silenced, 24 kD fragment of Pseudomonas exotoxin A (PE24)...
October 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27485059/systematic-review-of-peri-operative-prognostic-biomarkers-in-pancreatic-ductal-adenocarcinoma
#18
REVIEW
Wilson Petrushnko, Justin S Gundara, Philip R De Reuver, Greg O'Grady, Jaswinder S Samra, Anubhav Mittal
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application. METHODS: A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability...
August 2016: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/27454297/human-car-t-cells-with-cell-intrinsic-pd-1-checkpoint-blockade-resist-tumor-mediated-inhibition
#19
Leonid Cherkassky, Aurore Morello, Jonathan Villena-Vargas, Yang Feng, Dimiter S Dimitrov, David R Jones, Michel Sadelain, Prasad S Adusumilli
Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells. This adaptive resistance compromises the efficacy of chimeric antigen receptor (CAR) T cell therapies, which redirect T cells to solid tumors. Here, we investigated whether programmed death-1-mediated (PD-1-mediated) T cell exhaustion affects mesothelin-targeted CAR T cells and explored cell-intrinsic strategies to overcome inhibition of CAR T cells. Using an orthotopic mouse model of pleural mesothelioma, we determined that relatively high doses of both CD28- and 4-1BB-based second-generation CAR T cells achieved tumor eradication...
August 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27422997/role-of-mesothelin-in-carbon-nanotube-induced-carcinogenic-transformation-of-human-bronchial-epithelial-cells
#20
Xiaoqing He, Emily Despeaux, Todd A Stueckle, Alexander Chi, Vincent Castranova, Cerasela Zoica Dinu, Liying Wang, Yon Rojanasakul
Carbon nanotubes (CNTs) have been likened to asbestos in terms of morphology and toxicity. CNT exposure can lead to pulmonary fibrosis and promotion of tumorigenesis. However, the mechanisms underlying CNT-induced carcinogenesis are not well defined. Mesothelin (MSLN) is overexpressed in many human tumors, including mesotheliomas and pancreatic and ovarian carcinomas. In this study, the role of MSLN in the carcinogenic transformation of human bronchial epithelial cells chronically exposed to single-walled CNT (BSW) was investigated...
September 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
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