Showing papers by "Hiroshi Maeda published in 2018"

Analyses of repeated failures in cancer therapy for solid tumors: poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs

Abstract: For over six decades reductionist approaches to cancer chemotherapies including recent immunotherapy for solid tumors produced outcome failure-rates of 90% (±5) according to governmental agencies and industry. Despite tremendous public and private funding and initial enthusiasm about missile-therapy for site-specific cancers, molecular targeting drugs for specific enzymes such as kinases or inhibitors of growth factor receptors, the outcomes are very bleak and disappointing. Major scientific reasons for repeated failures of such therapeutic approaches are attributed to reductionist approaches to research and infinite numbers of genetic mutations in chaotic molecular environment of solid tumors that are bases of drug development. Safety and efficacy of candidate drugs tested in test tubes or experimental tumor models of rats or mice are usually evaluated and approved by FDA. Cost-benefit ratios of such ‘targeted’ therapies are also far from ideal as compared with antibiotics half a century ago. Such alarming records of failure of clinical outcomes, the increased publicity for specific vaccines (e.g., HPV or flu) targeting young and old populations, along with increasing rise of cancer incidence and death created huge and unsustainable cost to the public around the globe. This article discusses a closer scientific assessment of current cancer therapeutics and vaccines. We also present future logical approaches to cancer research and therapy and vaccines.

Augmentation of the Enhanced Permeability and Retention Effect with Nitric Oxide-Generating Agents Improves the Therapeutic Effects of Nanomedicines

Abstract: Enhanced permeability and retention (EPR) effect-based nanomedicine is a promising strategy for successful anticancer therapy. The EPR effect is based on tumor blood flow. Because advanced large tumors, as frequently seen in clinical settings, are heterogeneous, with regions of defective vasculature and blood flow, achieving the desired tumor drug delivery is difficult. Here, we utilized the EPR effect to increase drug delivery. To augment the EPR effect for improved therapeutic effects of nanomedicine, we exploited vascular mediators-the nitric oxide (NO) generators nitroglycerin (NG), hydroxyurea, and l-arginine. These compounds generate NO in tumors with relatively high selectivity. Using different nanosized drugs in our protocol significantly increased (1.5-2 times) delivery of nanomedicines to different solid tumor models, along with markedly improving (2-3-fold) the antitumor effects of these drugs. Also, in 7,12-dimethylbenz[a]anthracene-induced advanced end-stage breast cancer, often seen in clinical settings, 2 mg/kg polymer-conjugated pirarubicin (P-THP) with NG (0.2 mg/mouse) showed better effects than did 5 mg/kg P-THP, and 5 mg/kg P-THP used with NG resulted in cures or stable tumors (no tumor growth) for up to 120 days. Moreover, in a murine autochthonous azoxymethane/dextran sulfate sodium-induced colon cancer model, NO donors markedly improved the therapeutic effects of P-THP even after just one injection, results that were comparable with those achieved with three weekly P-THP treatments. These findings strongly suggest the potential usefulness of NO donors as EPR effect enhancers to improve the therapeutic efficacy of nanomedicines.

Modeling process device, modeling process system, and medium

Abstract: A modeling process device for performing a three-dimensional object modeling process is provided. The modeling process device includes an accumulation unit configured to accumulate a plurality of three-dimensional object information sets each including corresponding surface shape information items for three-dimensional objects; a searching unit configured to, based on surface shape information of a three-dimensional object generated by a scanning unit that scans a surface of the three-dimensional object, search for a three-dimensional object information set used for modeling in the plurality of the three-dimensional object information sets accumulated in the accumulation unit; and an extraction unit configured to extract a modeling condition that has been used for modeling the three-dimensional object according to the surface shape information that has been generated by the scanning unit.

Information processing device, solid object modeling system, and information processing method

Abstract: There is provision of an information processing device for processing three-dimensional information representing a three-dimensional shape of a solid object to be modeled by a solid object modeling device configured to model the solid object by depositing a plurality of layers each of which is formed by discharging the filamentary molding material on the flat surface. The information processing device is configured to acquire the three-dimensional information, generate a plurality of pieces of layer information corresponding to the respective layers of the filamentary molding materials, by slicing the three-dimensional information, generate deposition information used for depositing the filamentary molding material from the layer information, generate gap region information representing a gap region to be formed between the filamentary molding materials based on the deposition information, and generate discharging information for controlling discharge of the filamentary molding material, in accordance with the deposition information and the gap region information.

Information-processing device, three-dimensional manufacturing system, information-processing method, information-processing program, and computer-readable recording medium

Abstract: An information-processing device for processing three-dimensional information representing the three-dimensional shape of a three-dimensional object to be manufactured using a three-dimensional manufacturing apparatus, which discharges a linear material on a flat surface and laminates layers of the material to manufacture the three-dimensional object. The information-processing device comprises: a three-dimensional information-acquiring unit for acquiring three-dimensional information; a layer information-generating unit for dividing the acquired three-dimensional information according to the various layers of the material and generating layer information for each layer; a deposition information-generating unit for generating, from the layer information, deposition information to be used when discharging and depositing the linear material on the flat surface; a gap region information-generating unit for generating gap region information that represents gap regions between the linear material when the linear material is deposited on the basis of the deposition information; and a discharge information-generating unit for generating discharge information for controlling the discharge of the linear material according to the deposition information and the gap region information.

Shaping processing apparatus, shaping processing system, and program

Abstract: Provided are an apparatus, a system, and the like with which, when duplicating a shaped three-dimensional object, a shaped object similar to the three-dimensional object can be obtained. The apparatus is a shaping processing apparatus for performing processing to shape a three-dimensional object, and includes: an accumulation unit 30 that accumulates a plurality of three-dimensional object information items each of which includes information relating to a surface shape of the three-dimensional object; a retrieval unit 31 that retrieves three-dimensional object information used for shaping, from the accumulated plurality of three-dimensional object information items, on the basis of information relating to the surface shape of the three-dimensional object generated by a reading unit 34 that reads the surface of the three-dimensional object; and an extraction unit 32 that extracts, from the generated information relating to the surface shape, a shaping condition at the time when the three-dimensional object was shaped.