A5014211772- Virus-based gene therapy research
- Cancer Research and Treatments
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- Effects of Radiation Exposure
- GDF15 and Related Biomarkers
- Viral gastroenteritis research and epidemiology
- interferon and immune responses
- Cancer Treatment and Pharmacology
- Apelin-related biomedical research
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Signaling Pathways in Disease
- Vitamin C and Antioxidants Research
- Immunotherapy and Immune Responses
- Peptidase Inhibition and Analysis
- Cell death mechanisms and regulation
- Cancer therapeutics and mechanisms
- DNA Repair Mechanisms
- Immune Cell Function and Interaction
- Advanced Breast Cancer Therapies
- Colorectal Cancer Treatments and Studies
- Sarcoma Diagnosis and Treatment
- Melanoma and MAPK Pathways
- Viral Infectious Diseases and Gene Expression in Insects
Institute of Cancer Research
2015-2024
Royal Marsden NHS Foundation Trust
2023
Institute of Cancer Research
2013-2023
Royal Marsden Hospital
2021
National Institute for Health Research
2019
Kyushu University
2010
Queen's University Belfast
2006-2010
Fukuoka University
2010
Oncolytic viruses, which preferentially lyse cancer cells and stimulate an antitumor immune response, represent a promising approach to the treatment of cancer. However, how they evade antiviral response their selective delivery to, replication in, tumor over normal tissue has not been investigated in humans. Here, we treated patients with single cycle intravenous reovirus before planned surgery resect colorectal metastases liver. Tracking viral genome circulation showed that could be...
Oncolytic viruses preferentially replicate in tumors as compared to normal tissue and promote immunogenic cell death induction of host systemic anti-tumor immunity. HSV-1 was chosen for further development an oncolytic immunotherapy this study it is highly lytic, infects human tumor cells broadly, kills mainly by necrosis a potent activator both innate adaptive also has large capacity the insertion additional, potentially therapeutic, exogenous genes. Finally, proven safety efficacy profile...
Background Despite therapeutic gains from immune checkpoint inhibitors (ICI) in many tumor types, new strategies are needed to extend treatment benefits, especially patients failing mount effective antitumor T-cell responses. Radiation and drug therapies can profoundly affect the microenvironment. Here, we aimed identify immunotherapies increase response conferred by combined ataxia telangiectasia Rad3-related kinase inhibition radiotherapy. Methods Using human papillomavirus (HPV)-negative...
We have shown previously that exposure to anticancer drugs can trigger the activation of human epidermal receptor survival pathways in colorectal cancer (CRC). In this study, we examined role ADAMs (a disintegrin and metalloproteinases) soluble growth factors acute drug resistance mechanism.In vitro vivo models CRC were assessed. ADAM-17 activity was measured using a fluorometric assay. Ligand shedding assessed by ELISA or Western blotting. Apoptosis flow cytometry blotting.Chemotherapy...
Abstract Activating epidermal growth factor receptor (EGFR) mutations have been linked with sensitivity to gefitinib and erlotinib; however, there are no established predictive markers for response the combination of EGFR inhibitors standard chemotherapy in non–small cell lung cancer (NSCLC) patients. In this study, we characterized a panel human wild-type mutant NSCLC cells their alone cisplatin or Taxol. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium...
Reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas the head and neck (SCCHN) over-express EGFR SCCHN lines are sensitive oncolytic reovirus, we conducted a detailed analysis effects reovirus in 15 cancer lines. Both pre- post-entry events were studied an attempt define biomarkers predictive sensitivity/resistance reovirus. In particular, analysed role EGFR/Ras determining virus-mediated cytotoxicity SCCHN.To test...
Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence safety and promising signs efficacy. Addition therapeutic genes to the viral genome may increase efficacy vaccinia. We evaluated potential expressing sodium iodide symporter (NIS) prostate cancer models, combining oncolysis, external beam radiotherapy NIS-mediated radioiodide therapy. The NIS-expressing (VV-NIS), GLV-1h153, was tested vitro analyzes cell killing, combination radiotherapy, NIS...
Reovirus type 3 (Dearing) (RT3D) infection is selective for cells harboring a mutated/activated RAS pathway. Therefore, in panel of melanoma cell lines (including mutant, BRAF mutant and RAS/BRAF wild-type), we assessed therapeutic combinations that enhance/suppress ERK1/2 signaling through use BRAF/MEK inhibitors. In cells, the combination RT3D with inhibitor PLX4720 (paradoxically increasing this context) did not enhance reoviral cytotoxicity. Instead, somewhat surprisingly, inhibition led...
Head and neck squamous cell carcinoma (HNSCC) is a significant cause of cancer deaths. Cisplatin-based chemoradiotherapy standard-of-care for locally advanced disease. ATR DNA-PK inhibition are actively being investigated in clinical trials with preclinical data supporting translation as radiosensitizers. Here, we hypothesized that targeting both small molecule inhibitors would increase radiosensitization HNSCC lines. Radiosensitization was assessed by Bliss independence analysis colony...
<div>Abstract<p>Radiation-induced fibrosis (RIF) is a progressive pathology deleteriously impacting cancer survivorship. CXCL12 an immune–stromal signal implicated in and innate response. We hypothesized that modulation of would phenotypically mitigate RIF. expression was characterized rodent model RIF its modulated by the intravascular delivery lentiviral vectors encoding small hairpin RNA to silence (LVShCXCL12) or overexpress (LVOeCXCL12) CXCL12. Multimodal fibrotic outcomes...
<p>CD3 expression across time course and examination of CXCL12 after irradiation in primary fibroblasts vitro.</p>
<p>RTOG acute effects after 50 Gy/3 Fr and cumulative later RTOG toxicities for LVSCR/PBS/LVOeCXCL12</p>
<p>Flow Cytometry of digested flap tissue: Macrophage subtype at day 90 and T-Cell examination 21</p>
<p>Analysis of metastasis in vivo samples A) Animals were culled at tumour severity limits per model described figure 5B. Livers, spleens, lungs and ormental mesenteric tissue harvested for examination metastasis. Every 10th 11th section stained consecutively H&E PanCK examined evidence Examples are shown B) Animal numbers with according to treatment group (LVSCR vs LVShCXCL12) (n=5 /group).</p>
<p>Knockdown sequence selection for CXCL12 and proof of modulation in vitro vivo. Primary fibroblasts were modified with lentivirus to overexpress a FLAG-epitope tag allow clear detection at protein level demonstrate effective silencing the candidate short-hairpin selection.</p>
Abstract Oncogenic mutations in Kras occur 40% to 45% of patients with advanced colorectal cancer (CRC). We have previously shown that chemotherapy acutely activates ADAM17, resulting growth factor shedding, receptor activation, and drug resistance CRC tumors. In this study, we examined the role mutant regulating shedding ADAM17 activity, using isogenic (MT) wild-type (WT) HCT116 cells. Significantly higher levels TGF-α VEGF were shed from KrasMT cells, both basally following treatment,...
Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT frequently ineffective in patients with disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these studies have not focused on HNSCC. Here, we evaluated the inhibitor, AUY922, combined CCRT. The ability of AUY922 to sensitize was assessed p53 mutant lines by clonogenic assay. Modulation induced DNA damage...