A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B

Clevudine is a nucleoside analog with an unnatural β-L configuration. In a phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days were well tolerated, and produced significant antiviral activity. The present study was conducted to assess the degree and durability of the antiviral response to 12 weeks of clevudine treatment, and to investigate its safety and tolerability. A total of 98 patients with HBeAg-positive chronic hepatitis B were randomized to placebo (n = 32), 30-mg clevudine (n = 32), and 50-mg clevudine (n = 34) groups. Patients were followed up after 12 weeks of treatment for a further 24 weeks off-therapy. Median serum hepatitis B virus DNA reductions from baseline at week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg clevudine, and 50-mg clevudine groups, respectively (P < .0001). Posttreatment antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week 12 off-therapy and 2.28 and 1.40 log10 reductions at week 24 off-therapies in the 30- and 50-mg clevudine groups, respectively. Median serum alanine aminotransferase (ALT) levels decreased markedly from baseline during clevudine treatment and were maintained below the upper limit of normal throughout the 24 weeks off-therapy in the two clevudine-treated groups. The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the three groups. In conclusion, clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels. Copyright © 2006 by the American Association for the Study of Liver Diseases

ARS 유전자 발현도에 따른 표현형 분석 및 암 제어 기능 연구

ARS 유전자 발현도에 따른 표현형 분석 및 암 제어 기능 연구GFC001191

Pest control composition comprising Codonopsis pilosula (Franch.) Nannf. extract as active ingredient

본 발명은 만삼 추출물을 유효성분으로 포함하는 해충 방제용 조성물, 해충 방제제 및 이를 이용한 해충 방제 방법에 관한 것이다. 본 발명의 만삼 추출물 또는 이의 분획물을 유효성분으로 포함하는 해충 방제용 조성물은 곤충 특이적인 소형신경펩타이드의 수용체의 활성 억제를 통해 인간 유해성 및 환경 유해성이 최소화된 해충 방제 효과를 보임으로서, 상기 해충 방제용 조성물을 포함하는 해충 방제제 및 이를 이용한 해충 방제 방법은 친환경 해충 방제 용도로 활용될 수 있다.국

Clevudine therapy for 24 weeks further reduced serum hepatitis B virus DNA levels and increased ALT normalization rates without emergence of viral breakthrough than 12 weeks of clevudine therapy

Objectives: The objectives of the study were to evaluate the safety and antiviral activity of 24-week treatment with clevudine 30 mg in HBeAg(+) chronic hepatitis B patients. Biochemical and serological responses were also assessed. Method: Twenty-one patients received clevudine 30 mg for 24 weeks and were followed up for another 24 weeks off therapy. Results: Median decreases from baseline in HBV DNA were 4.65 and 1.96 log10 copies/ml at week 24 (end of treatment) and week 48 (24 weeks off therapy), respectively. Analysis of individual data showed that HBV DNA levels were below the lower limit of detection (300 copies/ml) by Amplicor PCR assay in 19, 57, 19 and 0% at week 12, 24, 34 and 48, respectively. The proportion of patients with normal ALT were 67, 81 and 75% at week 24 (end of treatment), 34 and 48 (24 weeks off therapy), respectively. The rates of HBeAg loss were 24 and 20% at week 24 and 48, respectively. No viral breakthrough during treatment was observed. Conclusion: Clevudine 30 mg treatment for 24 weeks was well tolerated and exhibited more potent antiviral activity and a higher ALT normalization rate than 12-week treatment with durable efficacy at week 24 off therapy. Copyright © 2007 S. Karger AG

Clevudine-induced viral response, associated with continued reduction of HBsAg titer, was durable after the withdrawal of therapy

Background: This study was conducted to evaluate the durability of clevudine-induced viral response after the withdrawal of treatment. Methods: Patients who showed a complete response [alanine aminotransferase (ALT) normalization and hepatitis B virus (HBV) DNA <4,700 copies/mL for hepatitis B envelope antigen (HBeAg)-negative patients; ALT normalization, HBV DNA <4,700 copies/mL, and HBeAg seroconversion for HBeAg-positive patients] in the previous clevudine phase III trials were followed for an additional 96 weeks without any treatment for hepatitis B. Results: Of the 63 patients in the study cohort, 73% and 35% of the patients had HBV DNA <141,500 and <4,700 copies/mL, respectively, and 75% of the patients had normal ALT at the end of follow-up. HBeAg seroconversion was maintained in 81% of the patients and hepatitis B surface antigen (HBsAg) loss occurred in 3 patients. Continued HBsAg titer decrease (-0.5 log IU/mL) was observed in the sustained viral responders, suggesting the reduction of covalently closed circular DNA in hepatocytes. Conclusions: The clevudine-induced viral response was durable in the majority of patients for 2 years after the withdrawal of treatment. © 2010 Springer

Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression

Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were -4.25 and -0.48 log10 copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log10 reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well-maintained during the post-treatment follow-up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment. Conclusion: A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission. Copyright © 2007 by the American Association for the Study of Liver Diseases

Association between insulin-like growth factor-2 and metastases after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma: A prospective study

BACKGROUND. Hypoxia up-regulates insulin-like growth factor-2 (IGF-2) and thus stimulates the growth of hepatocellular carcinoma (HCC) cells. In the current study, the authors prospectively evaluated changes in plasma IGF-2 levels in HCC patients after transcatheter arterial chemoembolization (TACE), which usually results in hypoxic insult to liver tissue. The authors also examined the association between changes in plasma IGF-2 levels after TACE and HCC progression, especially in relation to metastasis. METHODS. Plasma IGF-2 levels were measured before and 4 weeks after TACE in 46 patients with HCC. Three months after TACE, the patients were evaluated for the occurrence of metastatic HCC. RESULTS. In 13 of the 46 patients, post-TACE plasma IGF-2 levels decreased by > 20% (Group 1) compared with their basal levels; in 18 patients, the IGF-2 levels changed within 20% (Group 2) and in 15 patients the IGF-2 levels increased by > 20% (Group 3). Plasma IGF-2 levels had a tendency to increase in patients with large-sized tumors, high serum α-fetoprotein (AFP) levels, and the heterogeneous uptake of iodized oil. Metastatic foci were found in 9 patients in Group 3 (60%), in contrast to only 3 patients in Group 2 (17%) and in none of the patients in Group 1 (P = 0.001). On multivariate analysis, higher Child-Pugh scores and increased plasma IGF-2 levels (Group 3) were found to be independent risk factors for metastasis. CONCLUSIONS. Increased plasma IGF-2 levels after TACE, which are common in patients with large-sized tumors and high serum AFP levels, appear to be associated with the occurrence of metastatic HCC after TACE. © 2001 American Cancer Society

Individualization of interferon therapy using serum hepatitis B virus DNA to reduce viral relapse in patients with chronic hepatitis B: A randomized controlled trial

Objective: In patients with chronic hepatitis B, viral relapse following interferon (IFN) therapy may be the result of a treatment duration that is too short to prevent hepatitis B virus (HBV) from replicating later. To reduce viral relapse in patients with chronic hepatitis B who responded to IFN, we individualized the duration of therapy according to serum HBV-DNA levels. Method: Treatment duration was prolonged to maintain negative serum HBV-DNA levels for the next 6 months in 30 patients who became HBV-DNA-negative following IFN therapy (group A). Another 35 patients were treated for only 6 months (group B). All patients had HBV-DNA as well as hepatitis B surface antigen (HBsAg) in their sera for more than 6 months and were proven histologically to have chronic hepatitis. Interferon alfa (IFN-α) was administered subcutaneously at a dose of 5 MU/m 2 three times a week. Results: There were no differences in age, gender, hepatitis B e antigen (HBeAg) positivity, serum alanine aminotransferase (ALT) levels, or serum HBV-DNA levels between the two groups. The mean duration of IFN therapy in group A was 7.2 months. At the end of treatment, serum HBV-DNA was negative in 16 patients in group A and in 18 patients in group B. The loss of serum HBV-DNA was maintained to the end of follow-up in 13 patients in group A but in only eight patients in group B. Similarly, serum ALT levels were normal in 14 patients in group A but in only nine patients in group B at the end of follow-up. Conclusion: Individualization of the duration of treatment to maintain serum HBV-DNA negativity for at least 6 months may reduce the viral relapse rate following IFN therapy. © 2003 Lippincott Williams & Wilkins

MEDICINE FOR TREATING VASCULAR DISEASE AND METHOD FOR SCREENING THE SAME

본원은 EGTA를 포함하는 혈관질환의 예방 또는 치료용 약제학적 조성물, 및 혈관질환의 예방 또는 치료제의 스크리닝 방법에 관한 것으로, 특히 에틸렌 글리콜-비스(β-아미노에틸 에테르)-N,N,N',N'-테트라아세트산(ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid, EGTA) 및 약제학적으로 허용되는 담체 또는 부형제를 포함하는, 혈관질환의 예방 또는 치료용 약제학적 조성물이다.국

Pyrolo-pyridine derivatives, preparation method thereof, and pharmaceutical composition for use in preventing or treating protein kinase related disease as an active ingredient

국