Independent factors and predictive score for extrahepatic metastasis of hepatocellular carcinoma following curative hepatectomy.

BACKGROUND: Postoperative extrahepatic metastasis (EHM) contributes to a poor prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. This study was aimed to develop a practical method that can be used to predict postoperative EHM. METHODS: In total, 578 patients were enrolled. We analyzed the clinicopathological features of the tumors and did a long-term follow-up to observe HCC recurrence. Postoperative EHM was detected in 136 patients, and multivariate analysis was used to confirm independent risk factors for postoperative EHM. After the factors were identified, a predictive scoring system was constructed as a weighted sum of these factors. The cutoff value that determines a high risk for EHM was defined by maximizing the Youden's index of the receiver operating characteristic curve. RESULTS: Microvascular invasion, incomplete capsule, and larger tumor diameter were the three independent factors predictive for a high risk for EHM. The scoring system was derived with an area under the curve (AUC) of 0.81 for postoperative 10-year EHM prediction. A cutoff value of 43 was derived and validated with a sensitivity >90% and specificity >60% to predict the development of EHM. This system was further verified in a subgroup of Barcelona Clinic Liver Cancer stage 0-A patients with an AUC of 0.82. When the cutoff value was set at 43, the sensitivity and specificity were 90.38% and 64.88%, respectively. CONCLUSIONS: Our predictive scoring system may be used to identify HCC patients who have a high risk for EHM following curative hepatectomy.

Effect of astragaloside IV on the general and peripartum reproductive toxicity in Sprague-Dawley rats.

Fertility and early embryonic developmental toxicity in rats were evaluated by intravenously administering astragaloside IV (AS-IV) daily at 0.25, 0.5, and 1.0 mg/kg for 4 weeks before mating, throughout the mating period, and continuing to day 6 of gestation period in females. Perinatal toxicity in rats was evaluated on gestational days (GD) 15 to 21 and lactational days LD (LD) 1 to 21. Astragaloside IV had no maternal toxicity at 0.25 to 1.0 mg/kg in rats. Although it has an inhibitory effect on female fertility in F0/F1 rats, AS-IV was devoid of early embryonic developmental toxicity in F0/F1 rats and in the survival parameters of F1 postnatal rats. Maternal AS-IV exposure at the dose of 1.0 mg/kg per d resulted in a significant delay in time for fur development, eye opening, and cliff parry reflex of pups compared to control group (P < .05), whereas it did not affect the memory and learning of F1 pups.

Toxicity of bryostatin-1 on the embryo-fetal development of Sprague-Dawley rats.

BACKGROUND: Bryostatin-1, a highly oxygenated marine macrolide with a unique polyacetate backbone isolated from the marine animal Bugula neritina (Linnaeus), is now being developed as an anti-cancer drug for treating malignancy. In the present study, developmental toxicity of bryostatin-1 was evaluated in Sprague-Dawley rats. METHODS: Bryostatin-1 was intravenously administered to rats on gestation days 6-15 at 4.0, 8.0, and 16.0 microg/kg on a daily basis. Then the reproductive parameters were determined in animals, and fetuses were examined for external, visceral, and skeletal malformations. RESULTS: The total weight gains were significantly different in animals between the control group and 8.0 and 16.0 microg/kg bryostatin-1 groups during and after treatment. The resorption and death fetus rates were significantly different between the bryostatin-1 group (16 microg/kg) and the control group. The fetal weight and fetal crown-rump length in the bryostatin-1 groups were significantly lower than that in the control group. CONCLUSIONS: Our results indicated that maternal toxicity occurred when the dose of bryostatin-1 was at 8.0 microg/kg, embryotoxicity at 16.0 microg/kg, and fetotoxicity at 4.0 microg/kg; but bryostatin-1 showed no teratogenic effect in rats. In light of our findings, bryostatin-1 should be used with caution in pregnant women with cancer, if they would like to continue the pregnancy.

Evaluation of genotoxicity of Yanhuanglian dehydrocavidine (YHL-DC) in vitro and in vivo.

It is reported that dehydrocavidine (DC), the main component of a traditional Chinese medicine, Yanhuanglian (YHL), can protect hepatic tissue against HBV and HAV impairment. As part of a safety evaluation on YHL-DC for use in the treatment of HBV, the present study evaluated the potential genotoxicity of YHL-DC by using the standard battery of tests (i.e., bacterial reverse mutation, chromosomal aberrations, and mouse micronucleus assays) recommended by the State Food and Drug Administration of China. The results showed that YHL-DC was not genotoxic under the conditions of the reverse mutation, chromosomal aberrations, and mouse micronucleus assay conditions. The anticipated clinical dose should be smaller than the doses used in the genotoxicity assays. With confirmation from further toxicity studies, YHL-DC would hopefully prove to be a useful anti-HBV agent.

Effect of astragaloside IV on the embryo-fetal development of Sprague-Dawley rats and New Zealand White rabbits.

Astragaloside IV, a natural product purified from the Chinese medicinal herb Astragalus membranaceus (Fisch) Bge, is now being developed as a cardioprotective agent for treating cardiovascular diseases. In the present study developmental toxicity of astragaloside IV in Sprague-Dawley rats and New Zealand White rabbits was evaluated by intravenously administering astragaloside IV daily to rats at 0.25, 0.5 and 1.0 mg kg(-1) on gestation days 6-15, and to rabbits at 0.5, 1.0 and 2.0 mg kg(-1) daily on gestation days 6-18. Reproductive parameters were determined and fetuses were examined for external, visceral and skeletal malformations. There was significant difference in total weight gain during and after treatment between the control group and 1.0 mg kg(-1) group in rats. The percentage of fetal deaths in 0.5 and 1.0 mg kg(-1) rat groups was significantly higher than that of the control group, and higher in all treatment groups than in the control in rabbits. These results indicated that astragaloside IV was maternally toxic at 1.0 mg kg(-1) in rats and fetotoxic at a dose higher than 0.5 mg kg(-1), but devoid of teratogenic effects in rats and rabbits. In light of these findings it is perhaps prudent to advise caution to women who might use astragaloside IV to combat cardiovascular disease during pregnancy.

Clinical observation of cinobufacini injection used to treat moderate and advanced primary liver cancer / 中西医结合学报

OBJECTIVE: To observe the clinical effect of cinobufacini injection in treating moderate and advanced primary liver cancer (PLC). METHODS: One hundred patients with moderate and advanced PLC were randomly divided into cino-treated group (50 patients) and control group (50 patients). The quality of life, tumor size, some changes of laboratory tests, and survival time were observed. RESULTS: The progressive rate of cino-treated group (18%) was lower than that of the control group (32%). The quality of life of the cino-treated group (80%) was better than that of the control group (72%), but without statistical significance. The survival rate of >12 months of the cino-treated group (30%) was higher than that of the control group (18%). The patients' liver function such as serum total bilirubin and ALT decreased obviously in the cino-treated group while increased a lot in the control group. The level of AFP increased after treatment with statistical significance in the control group while there was no statistical significance in the cino-treated group. CONCLUSION: Cinobufacini injection can not only inhibit the proliferation of cancer, but also protect liver function, improve quality of life and prolong survival time.