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https://www.readbyqxmd.com/read/29435293/a-case-of-peritoneal-malignant-mesothelioma-following-radiation-therapy-for-cervical-cancer
#1
Mitsutake Yano, Yuji Ikeda, Tomomi Kato, Mika Sakaki, Sho Sato, Akira Yabuno, Eito Kozawa, Masanori Yasuda
The present study presents a case of peritoneal malignant mesothelioma (PMM) following radiation therapy for cervical cancer. A 34-year-old Japanese woman, without asbestos exposure, was referred to the Department of Gynecologic Oncology, Saitama Medical University International Medical Center due to a cervical mass, and was diagnosed with cervical squamous cell carcinoma (SCC). The serum levels of tumor markers, including SCC antigen and cancer antigen 125 (CA125) were 229.0 ng/ml and 54.4 U/ml, respectively...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29434985/capture-of-mesothelioma-cells-with-universal-ctc-chip
#2
Kazue Yoneda, Yasuhiro Chikaishi, Taiji Kuwata, Takashi Ohnaga, Fumihiro Tanaka
Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29431691/low-dose-methotrexate-prevents-primary-and-secondary-humoral-immune-responses-and-induces-immune-tolerance-to-a-recombinant-immunotoxin
#3
Emily M King, Ronit Mazor, Nicolas Çuburu, Ira Pastan
Recombinant immunotoxins (RITs) are chimeric proteins being developed for cancer treatment. They are composed of an Ab fragment that targets a cancer Ag and a cytotoxic portion of Pseudomonas exotoxin A. They are effective for patients with hematologic malignancies with defective immunity, but their efficacy against solid tumors is limited by anti-drug Ab (ADA) responses in immune-competent patients. Pre-existing Abs or immune memory owing to previous toxin exposure represent additional hurdles because they induce rapid and strong ADA responses...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29426060/discovery-and-validation-of-novel-protein-biomarkers-in-ovarian-cancer-patient-urine
#4
Jarrod J Sandow, Adam Rainczuk, Giuseppe Infusini, Ming Makanji, Maree Bilandzic, Amy L Wilson, Nicole Fairweather, Peter G Stanton, Daniel Garama, Daniel Gough, Thomas W Jobling, Andrew I Webb, Andrew N Stephens
PURPOSE: For the vast majority of ovarian cancer patients, optimal surgical debulking remains a key prognostic factor associated with improved survival. A standardized, biomarker-based test, to pre-operatively discriminate benign from malignant disease and inform appropriate patient triage, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. EXPERIMENTAL DESIGN: We conducted a pilot study consisting of 40 patient urine samples (20 from each group), using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in urine from individual ovarian cancer patients...
February 9, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29404524/overexpression-of-periostin-and-distinct-mesothelin-forms-predict-malignant-progression-in-a-rat-cholangiocarcinoma-model
#5
Miguel Á Manzanares, Deanna J W Campbell, Gabrielle T Maldonado, Alphonse E Sirica
Periostin and mesothelin have each been suggested to be predictors of poor survival for patients with intrahepatic cholangiocarcinoma, although the clinical prognostic value of both of these biomarkers remains uncertain. The aim of the current study was to investigate these biomarkers for their potential to act as tumor progression factors when assessed in orthotopic tumor and three-dimensional culture models of rat cholangiocarcinoma progression. Using our orthotopic model, we demonstrated a strong positive correlation between tumor and serum periostin and mesothelin and increasing liver tumor mass and associated peritoneal metastases that also reflected differences in cholangiocarcinoma cell aggressiveness and malignant grade...
February 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29361614/-systemic-treatment-of-malignant-pleural-mesothelioma
#6
Takashi Nakano
Malignant pleural mesothelioma(MPM)is a highly aggressive tumor with a poor prognosis and an increasing incidence worldwide. The only standard first-line chemotherapy for patients with unresectable MPM is cisplatin(CDDP)plus peme- trexed(PEM)(CDDP/PEM), with a median overall survival of about 12months and a median progression-free survival(PFS) of less than 6 months. There are no treatments with proven benefit on survival for relapsed MPM patients. Therefore, novel therapeutic strategies are urgently required...
December 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29336814/inhibition-of-interleukin-10-in-the-tumor-microenvironment-can-restore-mesothelin-chimeric-antigen-receptor-t-cell-activity-in-pancreatic-cancer-in-vitro
#7
Ramesh B Batchu, Oksana V Gruzdyn, Ebrahem M Mahmud, Fatme Chukr, Rajesh Dachepalli, Santosh K Manmari, Gamal Mostafa, Donald W Weaver, Scott A Gruber
BACKGROUND: Pancreatic cancer cells are known to shield themselves from immunosurveillance by secreting immune inhibitory cytokines such as Interleukin-10. Using mesothelin, a differentiating antigen that is overexpressed in pancreatic cancer, we assessed the negative effect of the tumor microenvironment on chimeric antigen receptor T cell-based immunotherapy and its reversal via depletion of Interleukin-10. METHODS: T cells cultured in pancreatic cancer-cell-conditioned medium were transduced with lentiviruses encoding mesothelin-chimeric antigen receptor in the presence or absence of anti-Interleukin-10-blocking antibody...
January 11, 2018: Surgery
https://www.readbyqxmd.com/read/29334771/development-of-anti-human-mesothelin-targeted-chimeric-antigen-receptor-car-messenger-rna-mrna-transfected-peripheral-blood-lymphocytes-carma-hmeso-for-ovarian-cancer-therapy
#8
Chien-Fu Hung, Xuequn Xu, Linhong Li, Ying Ma, Qiu Jin, Angelia Viley, Cornell Allen, Pachai Natarajan, Rama Shivakumar, Madhusudan V Peshwa, Leisha A Emens
CD19-targeted chimeric antigen receptor (CAR) engineered T/natural kill (NK)-cell therapies can result in durable clinical responses in B-cell malignancies. However, CAR-based immunotherapies have been much less successful in solid cancers, in part due to 'on-target off-tumor' toxicity related to expression of target tumor antigens on normal tissue. Based on preliminary observations of safety and clinical activity in proof-of-concept clinical trials, tumor antigen-specific messenger RNA (mRNA) CAR transfection into selected, activated, and expanded T/NK-cells may permit prospective control of 'on-target off-tumor toxicity'...
January 15, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29275459/sulfatase-1-knockdown-promotes-in-vitro-and-in-vivo-aggressive-behavior-of-murine-hepatocarcinoma-hca-p-cells-through-up-regulation-of-mesothelin
#9
Salma Abdi Mahmoud, Mohammed Mohammed Ibrahim, Ahmed Hago Musa, Yuhong Huang, Jun Zhang, Jingwen Wang, Yuanyi Wei, Li Wang, Shunting Zhou, Boyi Xin, Wei Xuan, Jianwu Tang
Our previous study (Oncotarget 2016; 7:46) demonstrated that the over-expression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line (a murine HCC cell with lymph node metastatic [LNM] rate of >75%) downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo. In current work, we investigated the effects of Sulf-1 knockdown on mesothelin (Msln) and it's effects on the in vitro cell proliferation, migration, invasion, and in vivo tumor growth and LNM rate for Hca-P cells (a murine HCC cell with LNM rate of <25%)...
December 23, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29273809/a-re-engineered-immunotoxin-shows-promising-preclinical-activity-in-ovarian-cancer
#10
Gwendlyn Kollmorgen, Klara Palme, Annette Seidl, Stefan Scheiblich, Fabian Birzele, Sabine Wilson, Christian Clemens, Edgar Voss, Martin Kaufmann, Klaus Hirzel, Natascha Rieder, Ben-Fillippo Krippendorff, Frank Herting, Gerhard Niederfellner
RG7787 is a re-engineered mesothelin-targeted immunotoxin with reduced immunogenicity composed of a humanized anti-mesothelin Fab fragment and a B-cell epitope silenced 24 kD fragment of Pseudomonas exotoxin A. High prevalence of mesothelin-positive cases and a large unmet medical need make ovarian cancer a promising indication for the clinical development of RG7787. However, ovarian cancer patients also frequently have elevated serum levels of the cancer antigen 125 (CA-125). In principle this could pose a problem, since the binding sites for CA-125 and RG7787 on mesothelin were reported to overlap...
December 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29241375/peritoneal-dissemination-of-ovarian-cancer-role-of-muc16-mesothelin-interaction-and-implications-for-treatment
#11
Ricardo Coelho, Lara Marcos-Silva, Sara Ricardo, Filipa Ponte, Antonia Costa, Jose Manuel Lopes, Leonor David
Peritoneal dissemination is a particular form of malignant progression in ovarian cancer, preceding hematogenic or lymphatic dissemination. Thus, prevention of peritoneal implantation of cancer cells is envisioned to inhibit neoplastic dissemination and therefore prolong disease remission and patient's survival. Areas covered: An extended review on the role of MUC16 (CA125) and mesothelin (MSLN), expressed in a high percentage of ovarian carcinomas, indicate that this duet is relevant for the contact between cancer cells and mesothelial cells in homotypic (cancer cell-cancer cell) and heterotypic (cancer cell-mesothelial cell) interactions...
December 14, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29227302/the-target-invites-a-foe-antibody-drug-conjugates-in-gynecologic-oncology
#12
Maira P Campos, Gottfried E Konecny
PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. RECENT FINDINGS: The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1, DM4), calicheamicin, pyrrolobenzodiazepines and SN-38...
December 8, 2017: Current Opinion in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29184420/amatuximab-and-novel-agents-targeting-mesothelin-for-solid-tumors
#13
REVIEW
Paolo Baldo, Sara Cecco
Mesothelin (MSLN) is considered a promising target for cancer therapy. Originally extracted in 1992 after the immunization of mice with a human ovarian cancer (OC) cell line and cloned in 1996, MSLN seems to be involved in cell adhesion and metastasis. MSLN is prevalent in mesothelia tissues but is expressed in several human cancers, such as OC, pancreatic cancer, mesothelioma, and lung cancer. Amatuximab (MORAb-009) is a mouse-human chimeric monoclonal antibody with a selective affinity for MSLN. The principal mechanism of action comprises inhibition of binding of MSLN with the antigen CA125/MUC16...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29157747/multiplex-proximity-ligation-assay-to-identify-potential-prognostic-biomarkers-for-improved-survival-in-locally-advanced-pancreatic-cancer-patients-treated-with-stereotactic-body-radiation-therapy
#14
Avani D Rao, Yufei Liu, Rie von Eyben, Charles C Hsu, Chen Hu, Lauren M Rosati, Arti Parekh, Kendall Ng, Amy Hacker-Prietz, Lei Zheng, Timothy M Pawlik, Daniel A Laheru, Elizabeth M Jaffee, Matthew J Weiss, Dung T Le, Ralph H Hruban, Ana De Jesus-Acosta, Christopher L Wolfgang, Amol K Narang, Daniel T Chang, Albert C Koong, Joseph M Herman
PURPOSE: To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer-specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40...
October 12, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29152082/panbinostat-decreases-cflip-and-enhances-killing-of-cancer-cells-by-immunotoxin-lmb-100-by-stimulating-the-extrinsic-apoptotic-pathway
#15
Xiu-Fen Liu, Qi Zhou, Raffit Hassan, Ira Pastan
LMB-100 (RG7787) is a recombinant immunotoxin, which kills mesothelin-expressing cancer cells and now being evaluated in phase 1 trials. To enhance the anti-tumor activity of LMB-100, we have searched for agents, already approved for cancer therapy, that can be combined with LMB-100 to increase its efficacy. Panbinostat is a pan-histone deacetylase inhibitor that is used to treat multiple myeloma. We incubated different types of cancer cells with panbinostat and LMB-100 and found that they interacted synergistically to cause cell death...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113296/mesothelin-as-a-novel-biomarker-and-immunotherapeutic-target-in-human-glioblastoma
#16
Zhenjiang Liu, Martin Rao, Thomas Poiret, Silvia Nava, Qingda Meng, Anna von Landenberg, Jiri Bartek, Shanshan Xie, Georges Sinclair, Inti Peredo, Ernest Dodoo, Markus Maeurer
Glioblastoma multiforme (GBM) presents the most malignant form of glioma, with a 5-year survival rate below 3% despite standard therapy. Novel immune-based therapies in improving treatment outcomes in GBM are therefore warranted. Several molecularly defined targets have been identified mediating anti-GBM cellular immune responses. Mesothelin is a tumor-associated antigen (TAA) which is expressed in several solid tumors with different histology. Here, we report the immunological significance of mesothelin in human malignant glioma...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29102228/macrocyclic-pyrrolobenzodiazepine-dimers-as-antibody-drug-conjugate-payloads
#17
Andrew F Donnell, Yong Zhang, Erik M Stang, Donna D Wei, Andrew J Tebben, Heidi L Perez, Gretchen M Schroeder, Chin Pan, Chetana Rao, Robert M Borzilleri, Gregory D Vite, Sanjeev Gangwar
Macrocyclic pyrrolobenzodiazepine dimers were designed and evaluated for use as antibody-drug conjugate payloads. Initial structure-activity exploration established that macrocyclization could increase the potency of PBD dimers compared with non-macrocyclic analogs. Further optimization overcame activity-limiting solubility issues, leading to compounds with highly potent (picomolar) activity against several cancer cell lines. High levels of in vitro potency and specificity were demonstrated with an anti-mesothelin conjugate...
October 16, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29100432/cancer-antigen-profiling-for-malignant-pleural-mesothelioma-immunotherapy-expression-and-coexpression-of-mesothelin-cancer-antigen-125-and-wilms-tumor-1
#18
Takashi Eguchi, Kyuichi Kadota, Marissa Mayor, Marjorie G Zauderer, Andreas Rimner, Valerie W Rusch, William D Travis, Michel Sadelain, Prasad S Adusumilli
Background: To develop cancer antigen-targeted immunotherapeutic strategies for malignant pleural mesothelioma (MPM), we investigated the individual and coexpressions of the cancer-associated antigens mesothelin (MSLN), cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) in both epithelioid and non-epithelioid MPM. Methods: All available hematoxylin and eosin-stained slides from patients who were diagnosed with MPM (1989-2010) were reviewed. We constructed tissue microarrays from 283 patients (epithelioid = 234; non-epithelioid = 49)...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093164/the-immunopeptidomic-landscape-of-ovarian-carcinomas
#19
Heiko Schuster, Janet K Peper, Hans-Christian Bösmüller, Kevin Röhle, Linus Backert, Tatjana Bilich, Britta Ney, Markus W Löffler, Daniel J Kowalewski, Nico Trautwein, Armin Rabsteyn, Tobias Engler, Sabine Braun, Sebastian P Haen, Juliane S Walz, Barbara Schmid-Horch, Sara Y Brucker, Diethelm Wallwiener, Oliver Kohlbacher, Falko Fend, Hans-Georg Rammensee, Stefan Stevanović, Annette Staebler, Philipp Wagner
Immunotherapies, particularly checkpoint inhibitors, have set off a revolution in cancer therapy by releasing the power of the immune system. However, only little is known about the antigens that are essentially presented on cancer cells, capable of exposing them to immune cells. Large-scale HLA ligandome analysis has enabled us to exhaustively characterize the immunopeptidomic landscape of epithelial ovarian cancers (EOCs). Additional comparative profiling with the immunopeptidome of a variety of benign sources has unveiled a multitude of ovarian cancer antigens (MUC16, MSLN, LGALS1, IDO1, KLK10) to be presented by HLA class I and class II molecules exclusively on ovarian cancer cells...
November 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29079264/diagnostic-and-prognostic-biomarkers-in-ovarian-cancer-and-the-potential-roles-of-cancer-stem-cells-an-updated-review
#20
REVIEW
Thingreila Muinao, Hari Prasanna Deka Boruah, Mintu Pal
Ovarian carcinomas relate to highest death rate in gynecologic malignancies as absence of symptoms shield the disease in the early stage. Current evidences have been devoted to discovering early effective screening mechanism prior to the onset of clinical symptoms. Therefore, biomarkers are the crucial tools that are capable of predicting progression, risk stratification and overall therapeutic benefit to fight against this deadly disease. Although recent studies have revealed serum protein markers, CA-125, HE4, mesothelin etc...
October 24, 2017: Experimental Cell Research
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