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MS-153, (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline, is a new neuroprotective drug. Recent data in the literature suggest that it inhibits glutamate accumulation occurring during ischemia and the translocation of protein kinase C gamma (PKC gamma). The present study was undertaken to prove the hypothesis that MS-153 blocks neuroreceptors and ion channels involved in glutamate accumulation. Neurons isolated from rat dorsal root ganglia and frontal cortex were used for recording channel currents by the whole-cell patch clamp technique. The effects of bath-applied MS-153 were examined on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels and high voltage-gated calcium channels of dorsal root ganglion neurons, and channels activated by glutamate, N-methyl-D-aspartate (NMDA), kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxarole propionic acid (AMPA), gamma-aminobutyric acid (GABA) and acetylcholine (ACh) in cortical neurons. MS-153 at a concentration of 300 microM had no effect on either tetrodotoxin-sensitive or tetrodotoxin-resistant sodium channels. High voltage-gated calcium channels were either suppressed or not affected by 1-300 microM MS-153. The variable blocking effect of MS-153 was due to the variable activity of intracellular components in individual neurons, especially that of PKC, whose translocation is known to be inhibited by MS-153. When 100 nM phorbol 12-myristate-13-acetate (PMA) was applied to neurons, MS-153 suppressed the calcium channel current more frequently. Calphostin C (0.5 microM), a specific PKC inhibitor, applied intracellularly via recording patch pipette, completely abolished MS-153 suppression of the calcium channel current. Currents induced by glutamate, NMDA, kainate, AMPA, GABA or ACh were not affected by MS-153 at 300 microM. It was concluded that MS-153 inhibited high voltage-gated calcium channels through interactions with PKC, thereby preventing massive release of glutamate from nerve terminals in ischemic conditions.

Clinical trials to date demonstrate that standard cancer treatments are currently the most efficient treatments for large numbers of cancer patients. Cancer treatments will increasingly require approaches that allow patients to live with cancer, by increasing their natural healing power and tumor immunity, as well as attenuating the progression of their cancers, instead of only attacking the cancer cells directly. Complementary and alternative medicine, including Kampo medicine, compensates for the drawbacks of western medicine by increasing patients' self-defense mechanisms. In Japan, clinicians who have studied both western medicine and Kampo treat cancer patients by fusing the two medical systems into a unitary one. The goal of the system is to assist the functional maintenance and recovery of the living body complex with the physical, mental, social, and spiritual balance, rather than addressing direct antitumor effects. In this review, we describe the usefulness of Kampo medicine, especially juzentaihoto, and outline the reports on evidence, in addition to the report on an attitudinal survey about the use of Kampo medicine in cancer treatment in Japan.

The current standard treatment for cancer is a multidisciplinary therapy whereby various types of treatment are properly combined. Chemotherapy with multiple anticancer drugs is now common, and traditional, complementary, and alternative therapies are adopted as supportive measures. Medical care in Japan is distinguished by the ability for patients to access both Western and Kampo medical cares at the same time. There is a high degree of trust in the safety of Kampo therapies because they are practiced by medical doctors who are educated with fundamental diagnosis of Western medicine. Highly reliable clinical studies are being published, demonstrating that palliative or supportive care for cancer patients using Kampo preparations alleviates adverse effects of chemotherapy or radiotherapy. This paper reports the circumstances around cancer care in Japan where traditional therapeutic Kampo formulas are used for patients undergoing cancer treatment with cutting-edge chemotherapy, specifically to alleviate adverse effects of anticancer drugs.

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