Abstract 314P
Background
Recently, the gene therapy is attacked attention for a new cancer therapy. We invented for cancer gene therapy by a Del1 fragment. Del1 protein is composed of five domains, including three epidermal growth factor (EGF) repeats (E1–E3) and two discoidin domains (C1, C2). It consists of E2 has been reported to contain an RGD sequence that binds to integrin receptors and supports endothelial cell survival. The C1 domain is essential for the deposition of Del1 in the ECM. Additionally, the E3 domain can increase transfection efficiency. The Del1 protein was deposited in ECM, increased apoptosis, and enhanced the efficiency of a following transfection.At high concentrations, E3 induces apoptosis. And more, Dell is known to show pro-angiogenic or anti-angiogenic activities depending on the experimental conditions. In the present study, mouse ex-planted tumors were treated with the Del1 protein by a non-viral vector.
Methods
Cells of the human oral squamous cell carcinoma cell line, SCCKN, were injected into nude mice to generate explanted tumors. cDNAs encoding, the E3 and C1 domains of Del1 (E3C1), were inserted into pcDNA3D (pE3C1)and injected into the tumors every 7 days with a transfection reagent, jet-PEI. Tumor angiogenesis was evaluated by immunohistochemistry with antibodies for PECAM, von Willebrand factor and PDGF-beta and intravenous injection of lycopersicon esculentum lectin. The signal transduction of Notch was analyzed by western blotting.
Results
Treatment with pE3C1 suppressed the growth of explanted tumors and improved life prognosis of mice. In localization with immunostaining of PECAM or von Willebrand factor, and angioglaphy with lycopersicon esculentum lectin, vasculature without lumen were increased by gene therapy of Del1 fragment. Among the treatment with pE3C1 and control, the PDGF beta staining cells, which is marker of tip cells in angiogenesis, were increased. Western blotting of human umbilical endothelial cells cultured with an E3C1 recombinant protein showed the decreased expression of active Notch and hey1.
Conclusions
In the present study, we provide evidence that an E3C1 fragment suppresses Notch signaling and angiogenesis in explanted tumor model.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hisataka Kitano.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
9P - XRCC1 Arg194Trp, Palb2 T1100T (3300T>G), HMMR V353A, TNF aG308A polymorphisms as diagnostic and prognostic markers of breast cancer in the Kyrgyz ethnic group
Presenter: Aigul Semetei kyzy
Session: Poster display session
Resources:
Abstract
232P - Early Results from the Phase I Study of SY-1365, a Potent and Selective CDK7 inhibitor, in Patients with Ovarian Cancer and Advanced Solid Tumors
Presenter: Debra Richardson
Session: Poster display session
Resources:
Abstract
382P - Drug metabolizing enzymes pharmacogenomic: Biomarkers for improved chemotherapy in head and neck cancer squamous cell carcinoma
Presenter: Sunishtha Bhatia
Session: Poster display session
Resources:
Abstract
401P - Women in oncology: Alarming figures from India
Presenter: Sharada Mailankody
Session: Poster display session
Resources:
Abstract
416P - Multidisciplinary management of sarcomas of the head and neck: An institutional experience
Presenter: Kavitha Jain
Session: Poster display session
Resources:
Abstract
523P - Co-morbilities and survival of patients initially diagnosed with extensive-stage small cell lung cancer: Impact of hypertension, diabetes and chronic hepatitis B viral infection
Presenter: Weigang Xiu
Session: Poster display session
Resources:
Abstract
529P - Osimertinib for patients with EGFR-mutant advanced NSCLC and asymptomatic brain metastases: An open-label, two-arm, phase II study
Presenter: Roni Gillis
Session: Poster display session
Resources:
Abstract