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Mesothelin

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https://www.readbyqxmd.com/read/29914087/biomarkers-for-early-diagnosis-and-prognosis-of-malignant-pleural-mesothelioma-the-quest-goes-on
#1
Caterina Ledda, Paola Senia, Venerando Rapisarda
Malignant pleural mesothelioma (MM) is a highly aggressive tumor characterized by a poor prognosis. Although its carcinogenesis mechanism has not been strictly understood, about 80% of MM can be attributed to occupational and/or environmental exposure to asbestos fibers. The identification of non-invasive molecular markers for an early diagnosis of MM has been the subject of several studies aimed at diagnosing the disease at an early stage. The most studied biomarker is mesothelin, characterized by a good specificity, but it has low sensitivity, especially for non-epithelioid MM...
June 15, 2018: Cancers
https://www.readbyqxmd.com/read/29882407/coupled-fluorometer-potentiostat-system-and-metal-free-mono-chromatic-luminophores-for-high-resolution-wavelength-resolved-electrochemiluminescent-multiplex-bioassay
#2
Yanqin Lv, Zhixin Zhou, Yanfei Shen, Qing Zhou, Jingjing Ji, Songqin Liu, Yuanjian Zhang
The sensitive simultaneous detection of multiple biomarkers is critical for the early diagnosis of diseases. Among them, electrochemiluminescence (ECL) offers outstanding advantages, e.g. low background, over other optical sensing techniques. However, multiplexed ECL bioassay is hindered by not only the lack of generally available ECL spectrometers but also the limited number of biocompatible monochromatic ECL luminophores for decades. Herein, we report the addressing of these issues by re-examination of the recent tabletop spectrofluorometer coupled potentiostat as a high-resolution ECL spectrum acquisition system and using carbon nitrides as monochromatic luminophores...
June 8, 2018: ACS Sensors
https://www.readbyqxmd.com/read/29859625/engineered-car-t-cells-targeting-mesothelin-by-piggybac-transposon-system-for-the-treatment-of-pancreatic-cancer
#3
Jiangchuan He, Zhiwei Zhang, Saiqun Lv, Xiangzhen Liu, Lianzhen Cui, Duqing Jiang, Qi Zhang, Linfang Li, Wenxia Qin, Huajun Jin, Qijun Qian
Patients with pancreatic cancer have a poor prognosis largely due to the poor efficacy of the available treatment modalities. In this study, we engineered mesothelin-targeting chimeric antigen receptor T cells (mesoCAR T) using the piggyBac transposon based plasmid electroporation technique for specific targeting of pancreatic cancer cells expressing mesothelin. In vitro, mesoCAR T cells exhibited rapid and robust killing effect against ASPC1 cells with high expression levels of mesothelin with high production of IFN-γ; the cytotoxic effect on PANC1 cells with low expressions of mesothelin was relatively attenuated...
April 30, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29797583/anti-tumor-specific-t-cell-responses-induced-by-oncolytic-adenovirus-oncos-102-in-peritoneal-mesothelioma-mouse-model
#4
Lukasz Kuryk, Anne-Sophie W Møller, Mariangela Garofalo, Vincenzo Cerullo, Sari Pesonen, Ramon Alemany, Magnus Jaderberg
Oncolytic adenoviral immunotherapy activates the innate immune system with subsequent induction of adaptive tumor-specific immune responses to fight cancer. Hence, oncolytic viruses do not only eradicate cancer cells by direct lysis, but also generate antitumor immune response allowing for long-lasting cancer control and tumor reduction. Their therapeutic effect can be further enhanced by arming the oncolytic adenovirus with co-stimulatory transgenes and/or co-administration with other anti-tumor therapies...
May 24, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29772559/gitr-domain-inside-car-co-stimulates-activity-of-car-t-cells-against-cancer
#5
Vita M Golubovskaya, Robert Berahovich, Qumiao Xu, Hua Zhou, Shirley Xu, Jasper Guan, Hizkia Harto, Le Li, Lijun Wu
T cells expressing Chimeric antigen receptors or CAR-T cells are used as a novel treatment against hematological and solid cancers. In this report, we designed CAR with glucocorticoid-induced TNFR-related protein (GITR) co-stimulatory domain to study its ability to co-activate CAR-T cells. EGFR-GITR-CD3 CAR-T cells were cytotoxic against EGFR-positive: pancreatic and ovarian cancer cells but not against EGFR-negative cancer cells. The cytotoxic activity of EGFR-GITR-CD3 CAR-T cells was comparable or better than EGFR-28-CD3 or EGFR-41BB-CD3 CAR-T cells...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29761164/periostin-and-mesothelin-potential-predictors-of-malignant-progression-in-intrahepatic-cholangiocarcinoma
#6
EDITORIAL
Pranoti Mandrekar, Vincenzo Cardinale
No abstract text is available yet for this article.
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29757709/how-to-assess-the-best-immunohistochemical-panel-in-the-diagnosis-of-malignant-pleural-mesothelioma-in-a-pathology-lab
#7
Mona Mlika, Oumeima Lamzibri, Saoussen Bacha, Soumeya Laabidi, Chokri Haddouchi, Faouzi El Mezni
BACKGROUND: malignant pleural mesothelioma (MPM) is a rare tumor with a challenging diagnosis. Even if, clinical data are mandatory to suspect the diagnosis, the positive diagnosis is based on microscopic features. Morphologic features are still the port of call of the diagnosis but their non specific character and the multiplicity of differential diagnoses made the immunohistochemical markers mandatory for the diagnosis. Many antibodies with a positive diagnostic value including claretinin, mesothelin, WT1 and antibodies with a negative diagnostic value including TTF1, EMA, CD15 are recommended by the scientific societies...
May 14, 2018: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/29749501/placental-protein-14-as-a-potential-biomarker-for-diagnosis-of-preterm-premature-rupture-of-membranes
#8
Yanyun Wang, Haibo Luo, Guanglu Che, Yanqin Li, Jun Gao, Qiongli Yang, Bin Zhou, Linbo Gao, Tao Wang, Yujie Liang, Lin Zhang
Premature rupture of membranes (PROM) is a common pregnancy complication that frequently results in maternal and perinatal morbidity. The present methods for diagnosing PROM do not satisfy clinical requirements. The present study aimed to examine the proteome profile of amniotic fluid (AF) and maternal plasma, screen unique proteins in AF, and evaluate their diagnostic value for diagnosing PROM. The proteome profiles of AF and maternal plasma were examined via liquid chromatography coupled with tandem mass spectrometry‑based proteomic techniques...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29738555/fn3-proteins-engineered-to-recognize-tumor-biomarker-mesothelin-internalize-upon-binding
#9
Allison R Sirois, Daniela A Deny, Samantha R Baierl, Katia S George, Sarah J Moore
Mesothelin is a cell surface protein that is overexpressed in numerous cancers, including breast, ovarian, lung, liver, and pancreatic tumors. Aberrant expression of mesothelin has been shown to promote tumor progression and metastasis through interaction with established tumor biomarker CA125. Therefore, molecules that specifically bind to mesothelin have potential therapeutic and diagnostic applications. However, no mesothelin-targeting molecules are currently approved for routine clinical use. While antibodies that target mesothelin are in development, some clinical applications may require a targeting molecule with an alternative protein fold...
2018: PloS One
https://www.readbyqxmd.com/read/29720923/tumor-shed-antigen-affects-antibody-tumor-targeting-comparison-of-two-89-zr-labeled-antibodies-directed-against-shed-or-nonshed-antigens
#10
Jae-Ho Lee, Heejung Kim, Zhengsheng Yao, Lawrence P Szajek, Luigi Grasso, Insook Kim, Chang H Paik
We investigated the effect of shed antigen mesothelin on the tumor uptake of amatuximab, a therapeutic anti-mesothelin mAb clinically tested in mesothelioma patients. The B3 mAb targeting a nonshed antigen was also analyzed for comparison. The mouse model implanted with A431/H9 tumor, which expresses both shed mesothelin and nonshed Lewis-Y antigen, provided an ideal system to compare the biodistribution and PET imaging profiles of the two mAbs. Our study demonstrated that the tumor and organ uptakes of 89 Zr-B3 were dose-independent when 3 doses, 2, 15, and 60  μ g B3, were compared at 24 h after injection...
2018: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29716620/postprandial-increase-in-serum-ca125-as-a-surrogate-biomarker-for-early-diagnosis-of-ovarian-cancer
#11
Zhuowei Gu, Yifeng He, Yue Zhang, Mo Chen, Keqi Song, Yuting Huang, Qing Li, Wen Di
BACKGROUND: CA125 is a prevalently used serum biomarker for detecting ovarian cancer over the last three decades. However, it has a significant deficiency in screening for early-stage cancer. With the purpose of exploring an effective approach to improve its performance in early diagnosis, we investigated the postprandial fluctuation pattern of cancer-derived CA125 and the underlying mechanism. METHODS: In two medical centers, 551 patients sonographically diagnosed with ovarian (adnexal) cysts (< 5 cm in diameter) were enrolled and divided into five disease groups (pelvic inflammatory cysts, retention cysts, endometrioma, benign/borderline cystadenoma and malignant cysts)...
May 1, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29695631/improving-the-in-vivo-efficacy-of-an-anti-tac-cd25-immunotoxin-by-pseudomonas-exotoxin-a-domain-ii-engineering
#12
Gilad Kaplan, Ronit Mazor, Fred Lee, Youjin Jang, Yasmin Leshem, Ira Pastan
Tac (CD25) is expressed on multiple hematological malignancies and is a target for cancer therapies. LMB-2 is an extremely active anti-Tac recombinant immunotoxin composed of an Fv that binds to Tac and a 38kDa fragment of Pseudomonas exotoxin A (PE38). While LMB-2 has shown high cytotoxicity towards Tac-expressing cancer cells in clinical trials, its efficacy was hampered by the formation of anti-drug antibodies against the immunogenic bacterial toxin and by dose-limiting off-target toxicity. To reduce toxin immunogenicity and non-specific toxicity, we introduced six point mutations into domain III that were previously shown to reduce T cell immunogenicity and deleted domain II from the toxin, leaving only the 11aa furin cleavage site which is required for cytotoxic activity...
April 25, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29680194/the-challenge-of-evaluating-adnexal-masses-in-patients-with-breast-cancer
#13
REVIEW
Tomás Reinert, Angélica Nogueira-Rodrigues, Fabiola Procacci Kestelman, Patricia Ashton-Prolla, Márcia Silveira Graudenz, José Bines
This narrative literature review addresses the problem of an adnexal mass discovered during the course of breast cancer (BC) care, which may represent a benign condition, a metastatic process, or a primary ovarian cancer (OC), clinical scenarios associated with distinct physiopathology and prognosis. Furthermore, the coexistence of BC and OC in the same patient may be owing to a hereditary disorder, deserving specific management strategies and counseling. The initial detection and evaluation of an adnexal mass in a patient with BC requires a high index of suspicion, and the initial workup should include a thorough medical history and physical examination, measurement of tumor markers, complete blood count, and imaging tests...
March 12, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29676233/chimeric-antigen-receptor-t-cell-based-immunotherapy-for-cancer
#14
Feng Li, Tengfei Zhang, Ling Cao, Yi Zhang
Cancer immunotherapy, a new weapon against cancers by harnessing the patient's own immune system, potentiates an extended remission and possibly a cure for cancer. T cells genetically engineered with chimeric antigen receptor (CAR) vectors can specifically target the surface antigen of cancer cells and kill them in an MHC-independent manner. CD19 is extensively expressed on cancerous cells in B cell malignancies. To target this antigen, CAR T cells have gained great success in treating patients with B cell leukemia and lymphoma...
2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29656320/the-role-of-mesothelin-as-a-diagnostic-and-therapeutic-target-in-pancreatic-ductal-adenocarcinoma-a-comprehensive-review
#15
Federico Nichetti, Antonio Marra, Francesca Corti, Alessandro Guidi, Alessandra Raimondi, Natalie Prinzi, Filippo de Braud, Sara Pusceddu
Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors...
April 14, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29652548/ca125-suppresses-amatuximab-immune-effector-function-and-elevated-serum-levels-are-associated-with-reduced-clinical-response-in-first-line-mesothelioma-patients
#16
Nicholas C Nicolaides, Charles Schweizer, Elizabeth B Somers, Wenquan Wang, Shawn Fernando, Erin N Ross, Luigi Grasso, Raffit Hassan, J Bradford Kline
The tumor-shed antigen CA125 has recently been found to bind certain monoclonal antibodies (mAbs) and suppress immune-effector mediated killing through perturbation of the Fc domain with CD16a and CD32a Fc-γ activating receptors on immune-effector cells. Amatuximab is a mAb targeting mesothelin whose mechanism of action utilizes in part antibody-dependent cellular cytotoxicity (ADCC). It is being tested for its therapeutic activity in patients with mesothelioma in combination with first line standard-of-care...
July 3, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29618658/pancreatic-cancer-therapy-with-combined-mesothelin-redirected-chimeric-antigen-receptor-t-cells-and-cytokine-armed-oncolytic-adenoviruses
#17
Keisuke Watanabe, Yanping Luo, Tong Da, Sonia Guedan, Marco Ruella, John Scholler, Brian Keith, Regina M Young, Boris Engels, Suvi Sorsa, Mikko Siurala, Riikka Havunen, Siri Tähtinen, Akseli Hemminki, Carl H June
Pancreatic ductal adenocarcinoma (PDA) is characterized by its highly immunosuppressive tumor microenvironment (TME) that limits T cell infiltration and induces T cell hypofunction. Mesothelin-redirected chimeric antigen receptor T cell (meso-CAR T cell) therapy has shown some efficacy in clinical trials but antitumor efficacy remains modest. We hypothesized that combined meso-CAR T cells with an oncolytic adenovirus expressing TNF-α and IL-2 (Ad5/3-E2F-D24-TNFa-IRES-IL2, or OAd-TNFa-IL2) would improve efficacy...
April 5, 2018: JCI Insight
https://www.readbyqxmd.com/read/29616141/randomised-controlled-trial-to-compare-the-diagnostic-yield-of-positron-emission-tomography-ct-pet-ct-targeted-pleural-biopsy-versus-ct-guided-pleural-biopsy-in-suspected-pleural-malignancy-target-trial
#18
Duneesha de Fonseka, Wendy Underwood, Louise Stadon, Najib Rahman, Anthony Edey, Chris Rogers, Nick A Maskell
Introduction: Pleural malignancy, particularly malignant pleural mesothelioma (MPM) is increasing in incidence due to the long latency period from exposure to asbestos to development of the disease. MPM can be challenging to diagnose. For patients presenting without a pleural effusion, CT-guided biopsy remains the primary choice of biopsy, but the diagnostic sensitivity of this investigation is 70%-75%. Therefore, a proportion of patients will go on to require further biopsies. If the first biopsy is non-diagnostic, the chances of further non-diagnostic biopsies are high in MPM...
2018: BMJ Open Respiratory Research
https://www.readbyqxmd.com/read/29596890/immuno-modulators-enhance-antigen-specific-immunity-and-anti-tumor-effects-of-mesothelin-specific-chimeric-dna-vaccine-through-promoting-dc-maturation
#19
Yu-Li Chen, Ming-Cheng Chang, Ying-Cheng Chiang, Han-Wei Lin, Nai-Yun Sun, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng
As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes...
July 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29581296/recombinant-immunotoxins-with-albumin-binding-domains-have-long-half-lives-and-high-antitumor-activity
#20
Junxia Wei, Tapan K Bera, Xiu Fen Liu, Qi Zhou, Masanori Onda, Mitchell Ho, Chin-Hsien Tai, Ira Pastan
Recombinant immunotoxins (RITs) are chimeric proteins consisting of a Fv that binds to a cancer cell and a portion of a protein toxin. One of these, Moxetumomab pasudotox, was shown to be effective in treating patients with some leukemias, where the cells are readily accessible to the RIT. However, their short half-life limits their efficacy in solid tumors, because penetration into the tumors is slow. Albumin and agents bound to albumin have a long half-life in the circulation. To increase the time tumor cells are exposed to RITs, we have produced and evaluated variants that contain either an albumin-binding domain (ABD) from Streptococcus or single-domain antibodies from Llama...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
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