Kumamoto University

About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.

Identification of monocyte chemoattractant protein‐1 in senile plaques and reactive microglia of Alzheimer's disease

Abstract: It has been shown that human monocytes express monocyte chemoattractant protein-1 (MCP-1), an inflammatry factor, in response to non-fibrillar β-amyloid protein Reactive microglia and inflammatory factors were reported to be present in β-amyloid deposits (senile plaques) in Alzheimer's disease, suggesting the presence of MCP-1 in senile plaques To address this issue, we examined MCP-1-immunoreactivity in senile plaques using a mouse monoclonal anti-MCP-1 antibody Monocyte chemoattractant protein-1 was found immunohistochemically in mature senile plaques and reactive microglia but not in immature senile plaques of brain tissues from five patients with Alzheimer's disease These findings suggest that MCP-1-related inflammatory events induced by reactive microglia contribute to the maturation of senile plaques

Factors and Mechanism of “EPR” Effect and the Enhanced Antitumor Effects of Macromolecular Drugs Including SMANCS

Abstract: Both enhanced vascular permeability and angiogenesis of tumor sustain rapid growth of tumor involving many vascular mediators and high vascular density On the contrary, however, they can be utilized for macromolecular drug delivery to tumor Impaired reticuloendothelial/lymphatic clearance of macromolecules from the tumor, or lack of such clearance, is another unique characteristic of tumor tissue, which results intratumor retention of macromolecular drugs thus delivered (Figure 1) Consequently, enhanced permeability and retention (EPR) effect is the basis for the selective targeting of macromolecular drugs to tumor, and the EPR concept is now utilized for selective delivery of many macromolecular anticancer agents in aqueous formation for iv or ia as well as oily formation for ia dosing, which is not possible for low-molecular-weight drugs because of rapid washout by capillary vascular blood flow This EPR concept has been validated in clinical settings with hepatoma and other solid tumors In our laboratories, several promising macromolecular anticancer drugs after SMANCS, such as PEG-XO, PEG-DAO, PEG-ZnPP, were developed, warranting further investigation for clinical application More efficient drug delivery to tumor, especially of macromolecular drugs, may be possible by enhancing the EPR effect with the use of various vascular permeability mediators or potentiators Suppression of the EPR effect by the use of appropriate inhibitors or antidotes, such as the bradykinin antagonist HOE 140 and protease inhibitors or NOS inhibitors, may also be possible Thus, one may be able to suppress or retard tumor growth and tumor metastasis Also, by suppressing vascular permeability with antidotes such as the bradykinin antagonist HOE 140, pleural fluid in lung cancer and ascitic fluid in abdominal carcinomatosis may be controlled and the clinical course of cancer patients may be improved In summary, tumor vasculature can be an excellent target for delivery of macromolecular anticancer drugs; the most beneficial class of drugs in view of tumor-selective targeting based on the EPR effect in solid tumor as well as compliance of patients and ultimate therapeutic efficacy

Coronary Spasm: Clinical Features and Pathogenesis

Abstract: Coronary artery spasm (coronary spasm) is an abnormal contraction of an epicardial coronary artery resulting in myocardial ischemia and its incidence is relatively high in Japanese as compared with Caucasians. Coronary spasm occurs most often from midnight to early morning when the patient is at rest and it is usually not induced by exercise in the daytime. Coronary spasm can be induced by acetylcholine, an endothelium-dependent vasodilator which causes vasodilatation in the normal coronary artery. Spasm artery is hyperresponsive to the vasodilator effect of nitroglycerin, an nitric oxide (NO) donor and is deficient in NO activity. The major risk factor for coronary spasm is cigarette smoking. Coronary spasm can be a cause of not only variant angina but also ischemic heart disease in general, including unstable angina, acute myocardial infarction and sudden ischemic death.