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Fissistigma cavaleriei (Levl) Rehd (Annonaceae) is used as a folklore medicine for treatment of inflammation, arthritis, and tuberculosis by Miao people in China. In the present study, the antiangiogenic activity of F. cavaleriei was investigated. The chorioallantoic membrane of the fertilized hen's egg (CAM assay) was used to determine antiangiogenic activity of the plant extract. Compound (1), a compound with antiangiogenic activity, was isolated by bioassay-guided fractionation from F. cavaleriei for the first time. The structure of compound (1) was elucidated on the basis of spectroscopic methods. Colorimetric COX (ovine) inhibitor screening assay was used to determine its inhibitory effect on COX-1 and COX-2. MTT and Sulforhodamine B assays were used to investigate its cytotoxic effects on tumor cell lines. As a result, compound (1) showed a selectively inhibiting effect on COX-2 and could inhibit the growth of tumor cells in vitro. The antitumor activity of compound (1) was further confirmed by the observation that compound (1) administration significantly inhibited the growth of S-180 cells in mice. Moreover, compound (1) was able to enhance the antitumor activity of doxorubicin in the mice bearing with S-180 cells while combined with doxorubicin. In conclusion, compound (1) is a multi-target molecule and further experimental investigations are needed to determine whether it can be used as a lead molecule for tumor treatment.
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Alcaloides/aislamiento & purificación , Inhibidores de la Angiogénesis/farmacología , Annonaceae/química , Antineoplásicos Fitogénicos/farmacología , Bioensayo/métodos , Raíces de Plantas/química , Alcaloides/química , Alcaloides/farmacología , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/aislamiento & purificación , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Fraccionamiento Químico , Embrión de Pollo , Membrana Corioalantoides/química , Membrana Corioalantoides/efectos de los fármacos , Ciclooxigenasa 1/metabolismo , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/farmacología , Doxorrubicina/farmacología , Sinergismo Farmacológico , Formazáns/química , Humanos , Isoindoles/farmacología , Células K562 , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Rodaminas/química , Sales de Tetrazolio/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To study the predictive value of ALT, HBeAg and HBV DNA levels at baseline and HBV DNA levels at week 12 adefovir dipivoxil (ADV) treatment to the efficacy of it at week 52 in patients with HBeAg-positive chronic hepatitis B (CHB). METHODS: Ninety-eight HBeAg-positive CHB patients with serum HBV DNA>or=1x10(6) copies/ml and ALT levels between 1.5 to 10 times of upper limits of normal (ULN) were enrolled in the study. Ten mg/d of ADV was administered for 52 weeks. Line serum samples were collected for measuring HBV DNA and HBV markers. The efficacy of the treatment at week 52 was evaluated in patients with different ALT, HBeAg and HBV DNA levels at baseline and HBV DNA levels at week 12 after treatment. RESULTS: At week 52 of ADV treatment, the rates of HBV DNA<10(3) were 72.7%, 66.7% and 53.0% respectively in patients with ALT>5xULN, HBeAg
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Adenina/análogos & derivados , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Adulto , ADN Viral/sangre , Femenino , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/sangre , Humanos , Masculino , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Entecavir demonstrated superior virologic and biochemical benefits over lamivudine at 48 weeks in nucleoside-naïve Chinese patients with chronic hepatitis B (CHB). We evaluated the effect of continued entecavir and lamivudine treatment in patients who continued treatment in year 2 and the off-treatment durability of patients who achieved a protocol-defined consolidated response at week 48. METHODS: Chinese adults (n = 519) with CHB were randomized to a minimum of 52 weeks of treatment with entecavir 0.5 mg/day or lamivudine 100 mg/day. Patients with a consolidated response at week 48 (HBV DNA <0.7 MEq/ml for >/=24 weeks, ALT <1.25 times ULN, and, if HBeAg(+) at baseline, loss of HBeAg for at least 24 weeks) stopped treatment at week 52 and were followed off-treatment. Patients with a partial response at week 48 (HBV DNA <0.7 MEq/ml in the absence of other criteria for a consolidated response) could continue blinded treatment for up to 96 weeks. Patients were assessed for HBV DNA, ALT normalization, safety, and, if HBeAg(+) at baseline, for HBe seroconversion. Cumulative proportions of all treated patients who ever achieved these responses were also analyzed. RESULTS: Among patients treated during year 2 (entecavir: n = 193; lamivudine: n = 145), 74% of entecavir-treated and 41% of lamivudine-treated patients had HBV DNA <300 copies/ml by PCR at end of dosing and 96% of entecavir-treated and 82% of lamivudine-treated patients normalized ALT. Eleven percent of entecavir-treated versus 19% of lamivudine-treated patients underwent HBe seroconversion during year 2. Cumulative confirmed analysis for all treated patients through 96 weeks showed that 79% of entecavir-treated versus 46% of lamivudine-treated patients (p < 0.0001) achieved HBV DNA <300 copies/ml by PCR. Similar proportions of entecavir- and lamivudine-treated patients achieved confirmed ALT normalization and HBe seroconversion. Safety profile was comparable for both treatment groups. CONCLUSIONS: Through 96 weeks of treatment, entecavir resulted in continued clinical benefit in nucleoside-naïve Chinese patients with CHB, with a safety profile comparable with lamivudine.
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BACKGROUND/AIMS: Chronic hepatitis B has a high prevalence (>8%) in China. We compared the safety and efficacy of entecavir with that of lamivudine for the treatment of patients with chronic hepatitis B in China. METHODS: A total of 519 nucleoside-naive Chinese patients with chronic hepatitis B were randomized (1:1) and treated with entecavir 0.5 mg/d or lamivudine 100 mg/d. The primary endpoint was serum HBV DNA <0.7 MEq/ml by bDNA assay and alanine aminotransferase <1.25 x upper limit of normal (ULN) at week 48. Patients with missing week 48 measurements were considered non-responders. RESULTS: About 90% (231/258) of entecavir-treated versus 67% (174/261) of lamivudine-treated patients achieved the primary endpoint (P < 0.0001). The mean reduction from baseline in HBV DNA was greater with entecavir than lamivudine (5.90 vs. 4.33 log(10) copies/ml, P < 0.0001). Greater proportions of entecavir-treated patients achieved undetectable HBV DNA (<300 copies/ml) by polymerase chain reaction assay (76% vs. 43%, P < 0.0001) and alanine aminotransferase normalization (
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OBJECTIVE: To study the specific cellular immunoresponse of peripheral blood lymphocytes in the chronic hepatitis B patients treated with different doses of recombinant hepatitis B vaccine. METHODS: Seventy-two chronic hepatitis B patients who did not use any anti-HBV drugs within 6 months were randomized into 3 groups (90 micrograms, 60 micrograms, and placebo) in a ratio of 1:1:1. The patients in different groups were treated with different doses of recombinant hepatitis B vaccine in combination with IFN alpha 1b 50 micrograms with 3 times a week for 24 weeks. All patients were followed up for 24 weeks (W24). HBV DNA, HBeAg and liver functions were detected at different time points, and the number of cells that secrete IFN-gamma were detected by ELISPOT. RESULTS: There were no significant difference in ELISPOT positive ratio among the 3 groups on baseline detection. At W24, 12 cases, 12 cases, and 7 cases showed ELISPOT positive in the group of 90 micrograms, 60 micrograms, and placebo. The proportion of patients who were ELISPOT positive was higher in the groups treated with recombinant hepatitis B vaccine (including the dose of 90 micrograms and 60 micrograms) than that in the placebo group (P=0.0446). HBV DNA turned negative in 6/24 of the patients treated with recombinant hepatitis B vaccine (at both the doses of 90 micrograms and 60 micrograms), and HBeAg/Anti-HBe seroconversion or HBeAg became negative in 7/24 of them. In the placebo group, none of the patients showed undetectable HBV DNA, HBeAg/Anti-HBe seroconversion or HBeAg disappearance. At the 24W of follow up, in the patients who were ELISPOT positive, HBV DNA became undetectable in 4 of the patients treated with recombinant hepatitis B vaccine (at doses of 90 micrograms and 60 micrograms), and HBeAg/Anti-HBe seroconversion or HBeAg disappearance were found in 9 of the cases. In the placebo group, none of the cases showed undetectable HBV DNA, and only 1 case had HBeAg/Anti-HBe seroconversion. CONCLUSION: The recombinant hepatitis B vaccine may increase the function of specific T lymphocytes in patients with chronic hepatitis B. There were no significant differences between the patients treated with the dose of 90 micrograms and 60 micrograms hepatitis B vaccine.
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Vacunas contra Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Linfocitos T/inmunología , Vacunas Sintéticas/inmunología , Adulto , ADN Viral/sangre , Femenino , Humanos , Interferón gamma/biosíntesis , Masculino , Proteínas Recombinantes/inmunologíaRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of famciclovir on the decreasing levels of serum HBV-DNA and ALT and HBeAg/antiHBe seroconversion in chronic hepatitis B patients irresponsive to 3 months treatment with alpha interferon. METHODS: Two hundred and nineteen patients with chronic HBV infection, defined as positive HBsAg, HBeAg and HBV DNA, were enrolled and randomly half-and- half put into famciclovir and placebo groups. The two groups received either famciclovir 500 mg tid or a placebo treatment for 24 weeks, and then were followed-up for another 24 weeks with no treatment. RESULTS: At the end of 24 weeks, the log value of HBV DNA dropped from 6.54+/-1.26 to 5.70+/-2.03 in the famciclovirt group and were elevated from 6.30+/-1.32 to 6.51+/-1.65 in the placebo group (P < 0.01). The rate of cases with persistence HBV DNA dropped 2 log of quantity in the famciclovir group and was 28.28% (28/99); it was 9.47% (9/95) in the placebo group (P < 0.01). Those with persistence negative HBV DNA was 28.28% (28/99) in the flamciclovir treated group and 14.74% (14/95) in the placebo group (P < 0.05). Those persistently being HBeAg negative were 7.69% (7/91) in the famciclovir treated group and 3.33% (3/90) in the placebo group (P > 0.05). The HBeAg/antiHBe seroconversion was 4.40% (4/91) in the famciclovir group and 2.22% (2/90) in the placebo group (P > 0.05). The percentage of cases with normal of ALT level was 15.15% in the famciclovir group and 6.35% in the placebo group (P < 0.05). CONCLUSION: Famciclovir is effective in inhibiting HBV DNA replication and in decreasing serum ALT levels. The rate of HBeAg/antiHBe seroconversion in the famciclovir treated group was similar to that of the placebo group. Famciclovir was well tolerated without severe adverse effects during our treatment.
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2-Aminopurina/análogos & derivados , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , 2-Aminopurina/efectos adversos , 2-Aminopurina/uso terapéutico , Adolescente , Adulto , Antivirales/efectos adversos , Método Doble Ciego , Famciclovir , Femenino , Estudios de Seguimiento , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/virología , Humanos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Replicación Viral/efectos de los fármacosRESUMEN
BACKGROUND: The mortality rate of heavy type hepatitis is high. No special treatment is available except general treatment. This multicenter clinical study was designed to observe the safety and efficacy of promoting hepatic growth factor (PHGF) in the treatment of heavy type hepatitis and severe chronic hepatitis. METHODS: 347 patients with heavy type hepatitis and 324 with severe chronic hepatitis were subjected to administration of 120 microg of PHGF per day for 4 weeks on the basis of general treatment. Those who were being effectively treated would last additional 2 to 4 weeks. Blood routine, urine routine, blood urea nitrogen (BUN), blood creatinine (Cr), blood ammonia, alpha fetoprotein (AFP), electrolyte, alanine transaminase (ALT), aspartate transaminase (AST), serum total bilirubin (TBIL), serum direct bilirubin (DBIL), prothrombin time activity (PTA), total protein (TP) and albumin (ALB) were detected in the patients before treatment, 2 weeks after treatment, and at the end of the treatment. Any side-effect would be recorded. RESULTS: In the patients with severe chronic hepatitis, the total effective rate of the treatment was 88.9%. The levels of ALT, AST and TBIL decreased significantly (P<0.001), whereas those of PTA and ALB increased significantly (P<0.001), and the level of AFP increased slightly. In patients with heavy type hepatitis, the total effective rate of this treatment was 78.4%, and patients at different stage showed different results. The total effective rates of patients with early, medium and terminal stage heavy type hepatitis were 89.9%, 84.8% and 27.5%, respectively. No severe side-effect was shown. CONCLUSION: PHGF is effective and safe in the treatment of patients with heavy type hepatitis and severe chronic hepatitis. But it should be administered early in patients with heavy type hepatitis so as to get better curative effects.
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Hepatitis A/tratamiento farmacológico , Hepatitis B Crónica/tratamiento farmacológico , Factor de Crecimiento de Hepatocito/administración & dosificación , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Factor de Crecimiento de Hepatocito/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To analysis the efficacy and safety of lamivudine (made in China) therapy for 52 weeks in adolescent patients with chronic hepatitis B (CHB). METHODS: One hundred and five teenage CHB patients were treated with lamivudine 100 mg once daily for 52 weeks. Patients with elevated ALT at baseline were in group 1 and those with normal ALT were in group 2. The changes of HBV DNA, HBV seromarkers and ALT at the end of 12, 24 and 52 weeks after lamivudine therapy were compared with those at baseline. Adverse events were recorded and evaluated. RESULTS: At the end of 52 weeks of lamivudine therapy, HBV DNA-ve, HBeAg loss and anti-HBe seroconversion were observed in 92.0%, 24.4% and 22.0% in group 1 patients and 76.1%, 14.2% and 14.2% in group 2 patients respectively. No significant differences were found between two groups. At 12, 24 and 52 weeks, normalization rates of ALT were 59.0%, 66.7% and 76.0%, normal ALT with undetectable HBV DNA were 44.9%, 64.1% and 70.7% at the same time. During 52 weeks lamivudine treatment 26 mild adverse events were observed in 18 patients. CONCLUSION: Lamivudine can inhibit HBV replication rapidly and normalize ALT in majority adolescent CHB patients. HBeAg loss or seroconversion of anti-HBe was observed in some of these patients. All patients in this study were safety and well tolerated.