ABSTRACT
Objective:To investigate the prognostic significance of preoperative neutrophil-lymphocyte ratio(NLR)combined with tu-mor-associated neutrophils(TANs)in the stroma of gastric cancer tissues of patients.Methods:One hundred and twenty-six gastric cancer tissue samples from patients enrolled in Changhai hospital from June 2006 to May 2011 were divided into four groups accord-ing to NLRs in preoperative peripheral blood combined with high or low infiltration of neutrophils in gastric cancer tissues.The 5-year survival of the four groups was then compared,and their correlations with clinicopathologic features and prognosis were analyzed.Re-sults:High NLRs in peripheral blood combined with low infiltrating TANs in gastric tissues was associated with lower differential grade (P<0.001)and larger tumor size(P=0.026).Of the four groups,patients with high NLR in peripheral blood combined with low infiltrat-ing TANs in gastric cancer tissues demonstrated the lowest survival rates,whereas those with low NLR and high infiltrating TANs had highest survival rates, and this difference was statistically significant (P<0.05). Univariate and multivariate Cox regression analyses showed that high NLR in peripheral blood combined with low infiltrating TANs in gastric cancer tissues(P<0.05)was an independent factor indicating poor prognosis.Conclusions:NLR in preoperative peripheral blood combined with infiltrating TANs in gastric cancer tissues can be used as a prognostic indicator for patients with gastric cancer,especially high NLR in preoperative peripheral blood com-bined with low infiltrating TANs in gastric cancer tissue indicates poor prognosis.
ABSTRACT
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.
Subject(s)
Reproduction/drug effects , Saponins/toxicity , Triterpenes/toxicity , Animals , Astragalus Plant/chemistry , Astragalus Plant/toxicity , Astragalus propinquus , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/toxicity , Embryonic Development/drug effects , Female , Infertility, Female/chemically induced , Infertility, Male/chemically induced , Lactation , Male , Maternal Exposure/adverse effects , Paternal Exposure/adverse effects , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/mortality , Random Allocation , Rats , Rats, Sprague-Dawley , Saponins/administration & dosage , Toxicity Tests , Triterpenes/administration & dosageABSTRACT
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.
Subject(s)
Bryostatins/toxicity , Embryonic Development/drug effects , Fetus/drug effects , Toxicity Tests , Animals , Bryostatins/administration & dosage , Bryostatins/chemistry , Female , Male , Maternal Exposure , Pregnancy , Rats , Rats, Sprague-Dawley , Teratogens/toxicityABSTRACT
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.
Subject(s)
Berberine Alkaloids/pharmacology , Animals , Cell Line, Tumor , Chromosome Aberrations , DNA Damage/drug effects , DNA Damage/physiology , Mice , Mice, Inbred ICR , Micronucleus Tests , Mutagenicity Tests , Mutagens , Plant Extracts , United StatesABSTRACT
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.
