[Development of intramolecular oxidative phenolic coupling reactions using hypervalent iodine (III) reagents and their application to the synthesis of Amaryllidaceae alkaloids].

Hypervalent iodine (III) reagents nowadays are used extensively in the field of organic chemistry. Especially, phenyliodine (III) diacetate (PIDA) or phenyliodine (III) bis(trifluoroacetate) (PIFA) have received much attention because of their reactivities similar to heavy metal reagents or anodic oxidation, low toxicity, ready availability and easy handling. In the continuous study of our oxidative phenolic coupling reactions using a hypervalent iodine (III) reagents, a versatile synthetic procedure for the galanthamine-type Amaryllidaceae alkaloids was accomplished. The first total synthesis of (+/-)-sanguinine and the total syntheses of (+/-)-galanthamine, (+/-)-narwedine, (+/-)-lycoramine, and (+/-)-norgalanthamine were also successfully carried out.

Rupture of hepatocellular carcinoma after transcatheter arterial embolization: an unusual case.

Rupture of hepatocellular carcinoma (HCC) as a complication of transcatheter arterial embolization (TAE) is very rare. An unusual rupture of HCC after TAE was treated with successful surgical resection. A 65 year-old woman with liver cirrhosis developed multiple HCC in both lobes of the liver. TAE was attempted for the HCCs, but the original left hepatic artery, obliterated due to the previous repeated TAEs, was replaced by the left gastric artery. Right hepatic arteries were embolized while preserving the replaced left hepatic artery. Nine days after TAE, the patient presented a rupture of HCC in the left lateral segment of the liver, in which no deposit of Lipiodol was recognized. Since additional TAE to achieve hemostasis failed, left lateral segmentectomy was carried out with concern for the poor hepatic functional reserve. The patient was discharged 3 weeks after surgery without any complication. This is the first case of ruptured HCC in the non-embolized part of the liver after TAE, which was resected successfully.

Immunopotentiation by a new antitumor polysaccharide, DMG, a degraded D-manno-D-glucan from Microellobosporia grisea culture fluid.

The immunopharmacological behavior of DMG, an antitumor polysaccharide, was studied in mice. DMG administered ip or sc stimulated peritoneal macrophages to produce high levels of interleukin-1 activity, which can amplify successive immune responses. DMG dose-dependently and schedule-dependently increased the cellular immune response against allogeneic tumor cells and the humoral immune response to sheep erythrocytes. DMG also enhanced nonspecific antitumor effector functions, such as natural killer activity of spleen and peritoneal cells, and the cytostatic activity of peritoneal macrophages. Peritoneal macrophages activated by ip or sc injection of DMG exhibited high cytostatic activity, especially after exposure in vitro to lymphokine supernatants containing macrophage activation factor. Moreover, granulocyte/macrophage colony-stimulating activity in the serum increased 2-10 hr after DMG administration. Thus, DMG potentiated antigen-specific immunological functions and nonspecific functions of host defense systems against cancer both qualitatively and quantitatively.

Host-mediated antitumor effect of DMG, a degraded D-manno-D-glucan from Microellobosporia grisea culture fluid.

DMG, a new polysaccharide with a well-characterized structure, isolated from the culture filtrate of an actinomycetes and then degraded by acid treatment, was tested for antitumor activity on allogeneic and syngeneic tumors in mice. In the allogeneic Ehrlich solid tumor system, DMG showed antitumor activity over a wide dose range, its optimal dose being 10-100 mg/kg. The optimal time of DMG administration was 1-2 weeks after tumor inoculation, but DMG was also effective when given before tumor inoculation. DMG was effective when given ip, sc, it (intratumorally) or iv. DMG also had antitumor effects on syngeneic tumors. It rapidly inhibited the growth of MM46 mammary carcinoma, MH134 hepatoma, and Meth A fibrosarcoma, and also inhibited spontaneous pulmonary metastases of B16-BL6 melanoma. However, it had no direct cytocidal action on tumor cells in vitro. Its antitumor activity was much less in athymic nude mice and in mice immunosuppressed by whole-body X-irradiation than in normal hosts.Thus, DMG was shown to exert antitumor activity via host-mediated mechanisms. Its antitumor activity is discussed in comparison with those of other antitumor polysaccharides.