Meager, A.; Das, R. G.
(2005):
Biological standardization of human interferon beta: establishment of a replacement world health organization
international biological standard for human glycosylated interferon beta. In: J. Immunol. Methods. 306
, 1-15- Titel des Artikels
Biological standardization of human interferon beta: establishment of a replacement world health organization
international biological standard for human glycosylated interferon beta
- Abstract
Human interferon beta (IFN-beta) has been developed as a major biotherapeutic agent for the treatment of multiple
sclerosis. Since World Health Organization (WHO) international standards (IS) for IFN-beta were established several
years prior to the development of clinical grade IFN-beta products, a number of scientific issues with regard to the
biological standardisation of natural and recombinant IFN-beta products have emerged. In order to address these issues,
an international collaborative study to evaluate WHO IS and candidate international standards (CIS) of IFN-beta was
instigated by the National Institute for Biological Standards and Control (NIBSC) in 2000 and was carried out in the
succeeding year. Sixteen expert laboratories from 8 countries worldwide participated in the study. They performed
titrations on 8 different IFN-beta preparations, including IS and new CIS, in a variety of mainly antiviral- but also
including some antiproliferative- and reporter gene-assays, and contributed raw data from these assays to NIBSC for
statistical analysis and calculation of potencies. While both intra- and inter-laboratory variation of potency estimates
was evident, overall validity of the study as a whole was clearly shown by comparison of two pairs of internal coded
duplicates, which gave the expected relative potency of 1 and the lowest inter-laboratory variability of potency
estimates in all assay types. The CIS containing Chinese hamster ovary (CHO) cell- or human fibroblast-derived,
glycosylated, IFN-beta gave similar low inter-laboratory variation in potency estimates one to another as the coded
duplicates, which was significantly less than to the 2nd WHO IS of IFN-beta, human fibroblast-derived, Gb23-902-531. One
of these CIS, designated 00/572, containing CHO cell-derived IFN-beta and formulated with both bovine casein and human
serum albumin, could be assigned a potency, consistent for all assay types, of 40,000 international units (IU) per
ampoule relative to the IU of the 2nd IS of IFN-beta, Gb23-902-531. Other CIS containing glycosylated IFN-beta, either
CHO cell- or human-fibroblast-derived, could also be assigned potency values that were continuous with the IU of
Gb23-902-531 and 00/572. However, greater inter-laboratory variations in estimates were evident from comparisons of
Gb23-902-531 or 00/572 with either the 1st IS for E. coli-derived, non-glycosylated, IFN-beta with serine substitution
at position 17 (IFN-beta Ser 17 mutein), Gxb02-901-535, or with a CIS (00/574) containing IFN-beta Ser 17 mutein.
Indeed, variations in potency estimates for preparations containing IFN-beta Ser 17 mutein were sufficiently large to
indicate that assays could distinguish preparations of IFN-beta Ser 17 mutein from preparations of glycosylated
IFN-beta. Thus, neither the 2nd IS of IFN-beta, Gb23-902-531, containing fibroblast-derived IFN-beta, nor CIS, 00/572,
containing CHO cell-derived IFN-beta, was appropriate for standardisation of preparations of IFN-beta Ser 17 mutein.
Conversely, neither the IS of IFN-beta Ser 17 mutein, Gxb02-901-535, or a CIS of IFN-beta Ser 17 mutein, 00/574, was
appropriate for the standardisation of preparations of glycosylated IFN-beta. CIS 00/572, containing CHO cell-derived,
glycosylated IFN-beta, was clearly shown to be suitable to serve as a primary standard for glycosylated forms of
IFN-beta, especially clinical grade IFN-beta-1a products. It was further shown to exhibit high thermal and long-term
stability. Since the CHO cell-derived IFN-beta used for preparation of 00/572 was of a greater purity than the IFN-beta
used for the 2nd IS of IFN-beta, Gb23-902-531, it was recommended by the WHO Informal Consultation on the
Standardisation of Cytokines, Growth Factors and Other Endocrinological Substances, which met in October 2003, that
00/572 should replace Gb23-902-531 as the IS for glycosylated IFN-beta. This recommendation was accepted by the WHO
Expert Committee on Biological Standardization (ECBS) at its annual meeting in November 2003 and 00/572 was established
as the 3rd IS for human glycosylated IFN-beta with an assigned potency of 40,000 IU. As this study identified no
advantage to replacing the existing 1st IS for IFN-beta Ser 17 mutein, Gxb02-901-535, WHO ECBS accepted that this should
continue to serve as the IS for this material.
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Ishikawa, T.
(2008):
Secondary prevention of recurrence by interferon therapy after ablation therapy for hepatocellular carcinoma in chronic
hepatitis C patients.. In: World J. Gastroenterol.. 14
, 6140-4- Titel des Artikels
Secondary prevention of recurrence by interferon therapy after ablation therapy for hepatocellular carcinoma in chronic
hepatitis C patients.
- Abstract
Chronic hepatitis C is a leading cause of hepatocellular carcinoma (HCC) worldwide. Interferon (IFN) therapy
decreases the incidence of HCC in patients with chronic hepatitis C. Prevention of chronic-hepatitis-C-related HCC is
one of the most important issues in current hepatology. We have previously reported that male gender and high titer of
hepatitis C virus (HCV) RNA are predictive factors for the development of HCC in HCV-related cirrhosis. Clinical efforts
at eradicating or reducing the viral load may reduce the risk for HCC. Furthermore, because HCC often recurs after
ablation therapy, we performed a trial of IFN in patients with chronic liver disease caused by HCV to see whether IFN
therapy decreases recurrence after ablation therapy of HCV-related HCC. By using IFN therapy as a secondary prevention,
patients with HCC who had received complete tumor ablation showed better survival, primarily as a result of the
preservation of liver function and also probably prevention of recurrence. Postoperative IFN therapy appears to decrease
recurrence after ablation therapy such as radiofrequency ablation (RFA) therapy of HCV-related HCC. We believe that
there is a survival benefit in secondary prevention using IFN therapy. However, a controlled study is essential to
obtain conclusive evidence of the efficacy of this strategy.
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