A Forward-Secure Certificate-based Signature Scheme

Cryptographic computations are often carried out on insecure devices for which the threat of key exposure raises a serious concern. In an effort to address the key exposure problem, the notion of forward security was first presented by Günther in 1990. In a forward-secure scheme, secret keys are updated at regular periods of time; exposure of the secret key corresponding to a given time period does not enable an adversary to ‘break’ the scheme for any prior time period. In this paper, we first introduce forward security into certificate-based cryptography and define the security model of forward-secure certificate-based signatures (CBSs). Then we propose a forward-secure CBS scheme, which is shown to be secure against adaptive chosen message attacks under the computational Diffie–Hellman assumption in the random oracle model. Our result can be viewed as the first step toward solving the key exposure problem in CBSs and thus improving the security of the whole system

Serial in Vivo Imaging Using a Fluorescence Probe Allows Identification of Tumor Early Response to Cetuximab Immunotherapy

Cetuximab is an antiepidermal growth factor receptor (EGFR) monoclonal antibody that has received the approval of the Food and Drug Administration (FDA) for cancer treatment. However, most clinical studies indicate that cetuximab can only elicit positive effects on a subset of cancer patients. In this study, we investigated whether near-infrared fluorescence (NIRF) imaging of tumor vascular endothelial growth factor (VEGF) expression could be a biomarker for tumor early response to cetuximab therapy in preclinical wild-type and mutant tumor models of the <i>KRAS</i> gene. The treatment efficacy of cetuximab was determined in both HT-29 (wild-type <i>KRAS</i>) and HTC-116 (mutant <i>KRAS</i>) human colon cancer models. A VEGF-specific optical imaging probe (Dye755-Ran) was synthesized by conjugating ranibizumab (an anti-VEGF antibody Fab fragment) with a NIRF dye. Serial optical scans with Dye755-Ran were performed in HT-29 and HTC-116 xenograft models. By using longitudinal NIRF imaging, we were able to detect early tumor response on day 3 and day 5 after initiation of cetuximab treatment in the cetuximab-responsive HT-29 tumor model. Enzyme-linked immunosorbent assay (ELISA) confirmed that cetuximab treatment inhibited human VEGF expression in the <i>KRAS</i> wild-type HT-29 tumor but not in the <i>KRAS</i> mutant HCT-116 tumor. We have demonstrated that the antitumor effect of cetuximab can be noninvasively monitored by serial fluorescence imaging using Dye755-Ran. VEGF expression detected by optical imaging could serve as a sensitive biomarker for tumor early response to drugs that directly or indirectly act on VEGF