Riki Toita

Bio: Riki Toita is an academic researcher from National Institute of Advanced Industrial Science and Technology. The author has contributed to research in topics: Peptide & Gene delivery. The author has an hindex of 20, co-authored 72 publications receiving 1017 citations. Previous affiliations of Riki Toita include Osaka University & Kyushu University.

Design of Polymeric Carriers for Cancer-Specific Gene Targeting: Utilization of Abnormal Protein Kinase Cα Activation in Cancer Cells

Abstract: We succeeded in cancer cell specific gene expression by using a polyplex responsive to protein kinase Cα, which is activated in various types of cancer cells.

Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways.

Abstract: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation These EGFR aberrations over-activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR pathways These pathways then activate many biological outputs that are beneficial to cancer cell proliferation, including their chronic initiation and progression through the cell cycle Here, we review the molecular mechanisms that regulate EGFR signal transduction, including the EGFR structure and its mutations, ligand binding and EGFR dimerization, as well as the signaling pathways that lead to G1 cell cycle progression We focus on the induction of CYCLIN D expression, CDK4/6 activation, and the repression of cyclin-dependent kinase inhibitor proteins (CDKi) by EGFR signaling pathways We also discuss the successes and challenges of EGFR-targeted therapies, and the potential for their use in combination with CDK4/6 inhibitors

Enzyme-responsive polymeric assemblies, nanoparticles and hydrogels

Abstract: Being responsive and adaptive to external stimuli is an intrinsic feature characteristic of all living organisms and soft matter. Specifically, responsive polymers can exhibit reversible or irreversible changes in chemical structures and/or physical properties in response to a specific signal input such as pH, temperature, ionic strength, light irradiation, mechanical force, electric and magnetic fields, and analyte of interest (e.g., ions, bioactive molecules, etc.) or an integration of them. The past decade has evidenced tremendous growth in the fundamental research of responsive polymers, and accordingly, diverse applications in fields ranging from drug or gene nanocarriers, imaging, diagnostics, smart actuators, adaptive coatings, to self-healing materials have been explored and suggested. Among a variety of external stimuli that have been utilized for the design of novel responsive polymers, enzymes have recently emerged to be a promising triggering motif. Enzyme-catalyzed reactions are highly selective and efficient toward specific substrates under mild conditions. They are involved in all biological and metabolic processes, serving as the prime protagonists in the chemistry of living organisms at a molecular level. The integration of enzyme-catalyzed reactions with responsive polymers can further broaden the design flexibility and scope of applications by endowing the latter with enhanced triggering specificity and selectivity. In this tutorial review, we describe recent developments concerning enzyme-responsive polymeric assemblies, nanoparticles, and hydrogels by highlighting this research area with selected literature reports. Three different types of systems, namely, enzyme-triggered self-assembly and aggregation of synthetic polymers, enzyme-driven disintegration and structural reorganization of polymeric assemblies and nanoparticles, and enzyme-triggered sol-to-gel and gel-to-sol transitions, are described. Their promising applications in drug controlled release, biocatalysis, imaging, sensing, and diagnostics are also discussed.

Management of hepatitis B: Summary of a clinical research workshop Potential conflict of interest: Dr. Lok is a consultant and received grants from GlaxoSmithKline, Bristol-Myers Squibb, Idenix, Gilead, Roche, and Innogenetics.

Abstract: Chronic hepatitis B is caused by persistent infection with the hepatitis B virus (HBV), a unique DNA virus that replicates through an RNA intermediate produced from a stable covalently closed circular DNA molecule. Viral persistence appears to be due to inadequate innate and adaptive immune responses. Chronic infection has a variable course after several decades resulting in cirrhosis in up to one‐third of patients and liver cancer in a proportion of those with cirrhosis. Sensitive assays for HBV DNA levels in serum have been developed that provide important insights into pathogenesis and natural history. Therapy of hepatitis B is evolving. Peginterferon induces long‐term remissions in disease in one‐third of patients with typical hepatitis B e antigen (HBeAg) positive chronic hepatitis B, but a lesser proportion of those without HBeAg. Several oral nucleoside analogues with activity against HBV have been shown to be effective in suppressing viral levels and improving biochemical and histological features of disease in a high proportion of patients with and without HBeAg, at least in the short term. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Long‐term therapy with nucleoside analogues may be the most appropriate approach to treatment, but the expense and lack of data on long‐term safety and efficacy make recommendations difficult. Clearly, many basic and clinical research challenges remain in defining optimal means of management of chronic hepatitis B. (HEPATOLOGY 2007;45:1056–1075.)

Energy Transfer with Semiconductor Quantum Dot Bioconjugates: A Versatile Platform for Biosensing, Energy Harvesting, and Other Developing Applications.

Abstract: Luminescent semiconductor quantum dots (QDs) are one of the more popular nanomaterials currently utilized within biological applications. However, what is not widely appreciated is their growing role as versatile energy transfer (ET) donors and acceptors within a similar biological context. The progress made on integrating QDs and ET in biological configurations and applications is reviewed in detail here. The goal is to provide the reader with (1) an appreciation for what QDs are capable of in this context, (2) how this field has grown over a relatively short time span, and, in particular, (3) how QDs are steadily revolutionizing the development of new biosensors along with a myriad of other photonically active nanomaterial-based bioconjugates. An initial discussion of QD materials along with key concepts surrounding their preparation and bioconjugation is provided given the defining role these aspects play in the QDs ability to succeed in subsequent ET applications. The discussion is then divided around...