A5078346499- CAR-T cell therapy research
- Amino Acid Enzymes and Metabolism
- Prostate Cancer Treatment and Research
- Biosimilars and Bioanalytical Methods
- Melanoma and MAPK Pathways
- PARP inhibition in cancer therapy
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Virus-based gene therapy research
- Cancer therapeutics and mechanisms
- Neuroblastoma Research and Treatments
- Neuroscience and Neuropharmacology Research
- Aquatic Ecosystems and Phytoplankton Dynamics
- Synthesis and pharmacology of benzodiazepine derivatives
- Sarcoma Diagnosis and Treatment
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Computational Drug Discovery Methods
- Cancer Treatment and Pharmacology
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Advancements in Semiconductor Devices and Circuit Design
AstraZeneca (Brazil)
2024
Target (United States)
2024
AstraZeneca (United States)
2019-2022
AstraZeneca (Japan)
2021
Maryland Oncology Hematology
2017
Van Andel Institute
2010-2015
Naprogenix (United States)
2011
University of Kentucky
2007-2009
Harvard University
2004-2006
Dana-Farber Cancer Institute
2004
Abstract Microcystins are a family of cyclic peptides that potent inhibitors the protein phosphatase families PP1 and PP2A. Only three human proteins thought to be able mediate hepatic uptake microcystins (the organic anion-transporting polypeptides OATP1B1, OATP1B3, OATP1A2), predominant expression these transporters accounts for liver-specific toxicity microcystins. A significant obstacle in study as anticancer drugs is requirement specific transport cellular uptake. We report OATP1B3 mRNA...
Abstract BRAF and MEK1/2 inhibitors are effective in melanoma but resistance inevitably develops. Despite increasing the abundance of pro-apoptotic BIM BMF, ERK1/2 pathway inhibition is predominantly cytostatic, reflecting residual pro-survival BCL2 family activity. Here, we show that uniquely low BCL-X L expression biases pool towards MCL1. Consequently, or synthetic lethal with MCL1 inhibitor AZD5991, driving profound tumour cell death requires BAK/BAX, inhibiting growth vivo. Combination...
Abstract Background There is resurgence within drug and biomarker development communities for the use of primary tumorgraft models as improved predictors patient tumor response to novel therapeutic strategies. Despite perceived advantages over cell line derived xenograft models, there limited data comparing genotype phenotype tumorgrafts donor tumor, limiting determination molecular relevance model. This report directly compares genomic characteristics tumors including gene expression,...
Comparative oncology is a developing research discipline that being used to assist our understanding of human neoplastic diseases. Companion canines are preferred animal model due spontaneous tumor development and similarity disease at the pathophysiological level. We use paired RNA sequencing (RNA-Seq)/microarray analysis set four normal canine lymph nodes ten lymphoma fine needle aspirates identify technical biases variation between technologies convergence on biological pathways....
Vesicular stomatitis virus encoding the IFNβ transgene (VSV-IFNβ) is a mediator of potent oncolytic activity and undergoing clinical evaluation for treatment solid tumors. Emerging preclinical data suggest tumors with viruses may sensitize to checkpoint inhibitors increase anti-tumor immune response. New generations immuno-oncology molecules including T cell agonists are entering development could be hypothesized enhance viruses, VSV-IFNβ. Here, we show that VSV-IFNβ exhibits multiple...
Oncolytic viruses are engineered to selectively kill tumor cells and have demonstrated promising results in early-phase clinical trials. To further modulate the innate adaptive immune system, we generated AZD4820, a vaccinia virus express interleukin-12 (IL-12), potent cytokine involved activation of natural killer (NK) T reprogramming microenvironment. Testing cultured human cell lines broad vitro oncolytic activity IL-12 transgene expression. A surrogate expressing murine antitumor both...
Abstract Prostate-specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase that highly expressed in nearly all prostate cancers with the highest expression metastatic castration-resistant cancer (mCRPC). The prevalence of increased surface and constitutive internalization PSMA make it an attractive target for antibody–drug conjugate (ADC) approach to treating patients mCRPC. MEDI3726 (previously known as ADCT-401) ADC consisting engineered version anti-PSMA antibody...
Osteosarcoma (OS) is the most common type of solid bone cancer, with latent metastasis being a typical mode disease progression and major contributor to poor prognosis. For this occur, cells must resist anoikis be able recapitulate tumorigenesis in foreign microenvironment. Finding novel approaches treat osteosarcoma target those cell subpopulations that possess ability contribute metastatic imperative. Here we investigate anchorage-independent (AI) growth as model better characterize...
Background Precision (Personalized) medicine has the potential to revolutionize patient health care especially for many cancers where fundamental disease etiology remains either elusive or no available therapy. Here we outline a study in alveolar rhabdomyosarcoma, which use gene expression profiling and series of drug prediction algorithms combined with matched patient-derived xenograft (PDX) model test bioinformatically predicted therapies. Procedure A PDX was developed from biopsy number...
Organic and aqueous extracts of 145 Brazilian plants (538 extracts) from 34 families were evaluated for anti-tumour activity against the human tumour cell lines HT29 NCIH460. Of tested, 117 (22%) demonstrated cytotoxicity one or both at a concentration 100µg/ml. special interest are Anacardiaceae, Annonaceae, Asteraceae, Celestraceae, Leguminosae (Fabaceae), Meliaceae Myrtaceae, which contain high proportion active species. On basis these results we further examining cytotoxic species, with...
Abstract Background Malignant peripheral nerve sheath tumors (MPNST) are rare highly aggressive sarcomas that affect 8-13% of people with neurofibromatosis type 1. The prognosis for patients MPNST is very poor. Despite TOP2A overexpression in these tumors, doxorubicin resistance common, and the mechanisms chemotherapy poorly understood. Molecular-guided therapy prediction an emerging strategy treatment refractory involves identification response individual tumors. Here, we report results...
Aqueous and organic extracts of Asteraceae (Compositae) collected from the State Rio Grande do Sul, Brazil, have been tested in vitro for cytotoxic activity against human solid tumour cell lines. Twenty-five species, 125 total, were screened HT29 colon adenocarcinoma cells NCI-H460 non-small lung cancer cells. 11 species demonstrated cytotoxicity at 100µg/ml one or both lines tested. Further analysis was performed on active using three HT29, NCI-H460, U373 glioblastoma cells, to determine IC...
A successful therapeutic strategy, specifically tailored to the molecular constitution of an individual and their disease, is ambitious objective modern medicine. In this report, we highlight a feasibility study in canine osteosarcoma focused on refining infrastructure processes required for prospective clinical trials using series gene expression-based Personalized Medicine (PMed) algorithms predict suitable therapies within 5 days sample receipt. Tumor tissue samples were collected...
Cancer cells in order to survive are often mutated block apoptosis. One chemotherapeutic option is the re-establishment of An example such a therapy PKC inhibitor Gö6976, which activates apoptosis and shrinks vivo tumors estrogen receptor-negative breast cancers. We proposed as mechanism blockage activation transcription factor NF-κB, anti-apoptotic elevated Over recent years, questions have arisen regarding specificity these “small-molecule inhibitors.” therefore explored role NF-κB...
Chimeric antigen receptor (CAR) T cell therapy has yielded impressive clinical results in hematological malignancies and is a promising approach for solid tumor treatment. However, toxicity, including cytokine-release syndrome (CRS) neurotoxicity, concern hampering its broader use.In selecting lead CAR-T candidate against the oncofetal glypican 3 (GPC3), we compared CARs bearing low- high-affinity single-chain variable fragment (scFv) binding to similar epitope cross-reactive with murine...