Evidence that naturopathic therapy including Cordyceps sinensis prolongs survival of patients with hepatocellular carcinoma.

HYPOTHESIS: Naturopathic treatment will benefit patients with hepatocellular carcinoma (HCC). STUDY DESIGN: Retrospective analysis of case series of HCC patients treated with naturopathic agents. METHODS: HCC was diagnosed by dynamic computed tomography (CT) imaging and α-fetoprotein (AFP) or PIVKA II, or by histology. Tumor staging was determined by CT. A modified Childs-Pugh scoring was used to assess liver disease. Patients were treated with orally administered combinations of 12 naturopathic agents. Patients were monitored clinically and by CT tumor imaging, serial tumor markers, and liver function tests. PATIENT CHARACTERISTICS: 101 patients with HCC (67 men and 34 women, age 67.2 ± 8.8 years) were treated for a median of 13.4 months (range 0.8-100.8). Of these 84% had cirrhosis, 63% had hepatitis C virus, 18% had hepatitis B virus, 1% had both, and 9% had metastatic disease. Median modified Childs-Pugh score was 6 (range 3-13). Barcelona Clinic Liver Cancer tumor stages of 0, A, B, C, and D were found in 36%, 25%, 20%, 14%, and 6%, respectively. Median AFP was 40 (range 0-311,000). Median PIVKA II was 59 (0-378,000). Previous treatment was included none (27%), resection with relapse (20%), transarterial chemoembolization (50%), radiofrequency ablation (28%), percutaneous ethanol injection therapy (15%), chemotherapy (14%). OUTCOMES: Initial treatment was with 2.6 ± 0.8 agents (range 2-4). Overall, patients were treated with 3.7 ± 1.2 agents (range 2-7). There was a significant correlation between number of agents administered and survival (P < .0001). Patients treated with ≥4 agents survived significantly longer than patients treated with ≤3 agents (40.2 vs 6.4 months, P < .0001). This difference could not be attributed to statistically significant differences in severity of liver disease or tumor stage, delay in treatment, previous treatment, concurrent nondrug treatment, or censoring effects. The greatest effect was seen in patients treated with at least 4 agents that included Cordyceps sinensis. This prolonged survival was without toxic side effects and appeared to potentiate the survival benefit of conventional therapy. CONCLUSION: Treatment of HCC with a regimen of ≥4 agents prepared from natural products was associated with prolonged survival in a substantial portion of patients. The data provide level II evidence for the efficacy of naturopathic therapy in HCC.

Furanonaphthoquinones cause apoptosis of cancer cells by inducing the production of reactive oxygen species by the mitochondrial voltage-dependent anion channel.

The mitochondrial production of reactive oxygen species has been implicated in the anticancer activity of furanonaphthoquinone. However, the mechanism of the activation remains elusive. In the current study, we found that treatment of HeLa cells with 2-methyl-5(or -8)-hydroxy-furanonaphthoquinone (FNQ13) induces mitochondrial swelling, followed by apoptosis. This toxic effect of FNQ13 was reduced by the radical scavengers alpha-tocopherol and trolox. Cytochemical experiments in isolated mitochondria showed that a combination of FNQ13 and NADH induces the production of H(2)O(2) at the exterior mitochondrial membrane surface. This production of H(2)O(2) was reduced by an antibody to the voltage-dependent anion channel (VDAC). Overexpression of the VDAC by transfection with vdac1 cDNA increased the production of H(2)O(2) by HeLa cells, whereas transfection with a small interfering RNA to VDAC reduced FNQ13-induced H(2)O(2) production and cell death due to an almost complete knockdown of VDAC expression. We also found significant correlations between the expression of VDAC and the induction of H(2)O(2) production and cell death by FNQ13 in 11 human cancer cell lines. These results indicate that the anticancer activity of furanonaphthoquinones depends on the production of reactive oxygen species by mitochondrial permeability transition pores including the VDAC.

Plant self-defense mechanisms against oxidative injury and protection of the forest by planting trees of triploids and tetraploids.

The depletion of the ozone layer, and the resulting substantial increase in incident ultraviolet (UV) irradiation and subsequent oxygen radical formation on the Earth, have caused an extensive variety of damage to the world's forests. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px), which scavenge harmful oxygen radicals and inhibit lipid peroxides, were examined in two types of Japanese cedars, black pines, and cypresses, namely those with leaves showing premature withering, shedding, or dying and those with leaves not showing these effects prematurely. The effect of homogenates from these trees on lipid peroxide formation in a reaction system which UV light induces was also studied. The results indicate that strong black pines have significantly higher SOD activities than ordinary black pines, the leaves of which prematurely wither or die. Remarkably, trees that had triploid or tetraploid chromosomes showed higher SOD levels than diploid trees and markedly inhibited lipid peroxide formation since the SOD gene resides on a chromosome. This was especially true of plus trees of Japanese cypress, some of which had five times higher SOD activities than common Japanese cypresses although GSH-Px appears to play less of a role in this regard. Rice leaves and osmunda which are resistant to UV damage showed markedly higher SOD and GSH-Px activity. Our experiments suggest that the trees that have high SOD can protect themselves by scavenging oxygen radicals induced by UV irradiation and inhibit harmful lipid peroxide formation. In order to protect forests from oxidative damage by UV light, we should plant trees of natural mutants and artificially crossed triploids and tetraploids.

Effects of ondansetron, granisetron, ramosetron, and azasetron on human neutrophil functions.

Neutrophil functions play an important role in the antibacterial or antitumor host defense system. Ondansetron, granisetron, ramosetron, and azasetron are often used in gynecological patients as a prophylaxis against postoperative emesis or chemotherapy-induced emesis. In this study, using an ex vivo system, we have shown that these antiemetics at clinically relevant concentrations had no effect on superoxide (O(-)(2)) and hydrogen peroxide (H(2)O(2)) production of neutrophils, although high doses of these drugs significantly inhibited it to a similar degree. The drugs failed to impair chemotaxis or phagocytosis and to scavenge O(-)(2) or H(2)O(2) generated by an acellular system. Inhibition of the reactive oxygen species production may be due to attenuation of calcium elevation in neutrophils with these antiemetics. Our findings suggest that we are able to use these antiemetics in gynecological patients with cancer or those undergoing surgery without great caution.