Showing papers by "Hiroshi Maeda published in 2020"

Extracts of Phellinus linteus, Bamboo (Sasa senanensis) Leaf and Chaga Mushroom (Inonotus obliquus) Exhibit Antitumor Activity through Activating Innate Immunity.

Abstract: Natural products have attracted great interest for some time as alternative methods against cancers by fulfilling immunomodulating properties. In this study, we investigated the activity of hot water extracts (120 °C, >30 min) of Phellinus linteus, fresh leaves of Kumaizasa bamboo and Chaga mushroom which we called MeshimaMax, for cancer prevention and treatment by using different solid tumor models. In the implanted mouse sarcoma S180 tumor, MeshimaMax treatment significantly inhibited tumor growth when it was applied at the early stage of tumor inoculation. The effect was further confirmed by using carcinogen induced tumors, i.e., azoxymethane (AOM)/dextran sulfate sodium (DSS) induced mouse colon cancer and 7,12-dimethylbenz anthracene (DMBA) induced rat breast cancer. In both cases the occurrences of tumors were remarkably suppressed by administration of MeshimaMax which consists of three components above. More importantly, when MeshimaMax was combined with an anticancer chemotherapeutic drug, the therapeutic effect was remarkably improved. In vitro studies showed that when MeshimaMax was applied to mouse macrophage RAW264.7 cells the phagocytosis of macrophages was significantly activated, which was evaluated by using living yeast cells as well as synthetic nanoparticles. A cytotoxicity assay showed the 50% inhibitory concentration (IC50) was higher than 1 mg/mL and normal cells were 2-3 times more tolerant to MeshimaMax than cancer cells. These findings suggest the potential application of MeshimaMax for cancer prevention and as supplement regimen for anticancer chemotherapy, probably functioning through activation of innate immunity, which may benefit cancer patients as an alternative supplement.

Overcoming barriers for tumor-targeted drug delivery: the power of macromolecular anticancer drugs with the EPR effect and the modulation of vascular physiology

Abstract: In this chapter we describe the advantages of unique polymer–drug conjugates, the first example being called SMANCS: a conjugate of the proteinaceous anticancer agent neocarzinostatin and poly(styrene-co-maleic acid, SMA). Common characteristics of these conjugates are prolonged plasma half-life after intravenous injection, reduced immunogenicity, and resistance to proteolytic digestion. The SMA conjugate possesses hydrophobicity and albumin-binding properties, in addition to pH-responsive tumor cell uptake. Another critical feature of polymer conjugate is tumor-selective accumulation. This phenomenon—the enhanced permeability and retention (EPR) effect—is attributed to defective leaky tumor vessels and excessive production of permeability factors such as nitric oxide (NO). Blood flow in large, advanced tumors is so suppressed that drugs reach tumors much less effectively than in smaller tumors. NO-releasing agents can help enhance the EPR effect, blood flow, and therapeutic effects of nanomedicines. Compounds used for conventional cancer chemotherapy, photodynamic therapy, and boron neutron capture therapy are low molecular weight drugs, which demonstrate poor accumulation in tumors. We describe improvements in cancer therapy obtained by using macromolecular drugs combined with enhancers of the EPR effect, e.g., pirarubicin conjugated to the polymer poly(hydroxypropyl methacrylamide). Also, a final advantage of SMA conjugates is lipophilicity, so they can be used in oily formulations as oral and arterial agents.