• 제목/요약/키워드: human alpha-2 interferon

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Acute Oral, Intramuscular and Intravenous Toxicity Studies of Recombinant Interferon-$\alpha$2a in Sprague-Dawley Rats

  • Lee, Yong-Soon;Park, Jin-Sung;Che, Jeong-Hwan;Li, Guang-Xun;Kim, Tea-Won;Kim, Hyung-Sub;Park, Jie-Eun;Yun, Jun-Won;Kang, Kyung-Sun
    • Toxicological Research
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    • 제16권1호
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    • pp.73-76
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    • 2000
  • Acute oral, intramuscluar, and intravenous toxicity studies of recombinant human interferon $\alpha$2$\alpha$(rhIFN $\alpha$2$\alpha$) were performed in Sprague-Dawley (SD) rats. SD rats were administered with doses of 31.25, 62.5, 125, 250 and 500 MIU/kg, respectively, and clinical signs, mortality and body weight changes were observed for 2 weeks. In all animals administered with rhIFN $\alpha$2$\alpha$, there was neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical signs and autopsy findings. Therefore, $LD_{50}$ of rhIFN $\alpha$2$\alpha$ was considered to be higher than 500 MIU/kg in SD rats.

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만성 골수성 백혈병에 대한 유전자 재조합 인터페론 α-2a와 hydroxyurea의 항암효과 (Antitumor effects of recombinant human interferon α-2a and hydroxyurea against chronic myelogenous leukemia)

  • 김창환;이범준;박종환;박재학
    • 대한수의학회지
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    • 제40권1호
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    • pp.166-172
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    • 2000
  • Prior to a clinical trial, the in vitro and in vivo antitumor effects of a new recombinant human interferon ${\alpha}-2a$ (rHu/IFN ${\alpha}-2a$) with/without hydroxyurea (HU) were investigated using chronic myelogenous leukemia (CML)-derived cell lines (K562 and KU812F) and BALB/c nude. mice transplanted with KU812F cells. The rHu/IFN ${\alpha}-2a$ ($10^4-10^6IU/ml$) strongly inhibited proliferation of both cell lines and the combined treatments with HU ($10{\mu}g/ml$) were more effective. In nude mice transplanted with KU812F cells. rHu/IFN ${\alpha}-2a(1{\times}10^6IU$) inhibited tumor growth by 42-65% at 15-21 days post-transplantation (DPT). The combined treatment of rHu/IFN ${\alpha}-2a (5{\times}10^5IU$) with HU (0.25mg/g b.w.) inhibited the tumor growth by 48-67% at 12-21 DPT. In addition, the treatment of rHu/IFN ${\alpha}-2a$ ($5{\times}10^6IU\;or\;1{\times}10^7IU$) rejected tumor transplantation by 40%. These results suggest that the new rHU/IFN ${\alpha}-2a$ alone or with HU is effective on CML cell lines.

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재조합 인간 인터페론 알파와 Pentoxifylline을 이용한 고양이 전염성 복막염의 치료 증례 (Successful Management of Feline Infectious Peritonitis with Human Recombinant Interferon-alpha and Pentoxifylline in a Cat)

  • 강민희;박희명
    • 한국임상수의학회지
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    • 제28권4호
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    • pp.427-430
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    • 2011
  • 6개월령의 잡종 수컷 고양이가 갑작스런 호흡곤란과 식욕부진 증상으로 내원 하였다. 신체검사상 심음의 감소와 함께 확연한 호흡곤란이 확인 되었다. 혈액학적 검사에서 고글로블린 혈증을 동반한 고단백혈증이 관찰되었으며, 다클론성 감마글로블린병증이 확인 되었다. 환축은 흉부 방사선 검사에서 흉수가 확인 되었으며, 흉수는 비감염성 삼출물로, 흉수 역시 다클론성 감마글로블린병증을 동반한 고글로블린증과 감소한 알브민 대 글로블린 비율이 관찰되었다. 또한 흉강 삼출물을 통한 역전사 중합효소연쇄반응에서 고양이 코로나바이러스에 양성반응을 확인하였다. 따라서, 환축은 고양이 전염성 복막염이 강하게 의심되었으며, 재조합 인간 인터페론 알파, pentoxifylline 과 스테로이드제를 이용한 적극적인 치료가 시작 되었다. 환축은 초기 치료에 반응이 좋았으며, 치료 이후 5개월간 재발 증상이 관찰되지 않았다. 결론적으로 본 증례는 재조합 인간 인터페론 알파와 pentoxifylline을 이용한 고양이 전염성 복막염의 치료 반응에 대한 국내 첫 증례보고이다.

돼지의 백혈구 인터폐론 생산에 관한 비교연구 (Comparative Study on the Production of Interferons from Porcine Blood Leukocytes)

  • 한수남;이장락;이창업
    • 대한수의학회지
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    • 제27권2호
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    • pp.191-200
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    • 1987
  • Attempts were to produce porcine leukocyte interferon(PorLeIF) and porcine immune interferon (PorIIF) in the culture of porcine leukocytes. The interferons produced were tested for antiviral activity against vesicular stomatitis virus on poreine-derived PK(15) cells, human-derived FL cells, and Korean native black goat-derived BGK cells. The results were summarized as follws: 1. In the isolation of porcine leukocytes, the mean isolation rate by the buffy coat separation method (28.7%) was higher than that by the hydroxyethyl starch-RBC sedimentation method (9.2%). 2. When NDV(BI)-induced PorLeIFs were assyed on PK(15) cells and FL cells, the mean titers were 129 IU/ml and 72 IU/ml respectively, being 55.8% of the activity in homologous species system expressed in heterologous system. 3. The activities of PHA P-induced PorIIFs were 197 IU/ml on PK (15) cells and no activity on human FL cells. The mean antiviral activity of PorIIF was 1.5 times that of PorLeIF in PK (15) cells. 4. The cytopathic effect of vesicular stomatitis virus was observed in BGK cells derived from Korean native black goat kidney permitting interferon assay on the cells. While the cross-species antiviral activity of reference human ${\alpha},\;{\beta}-interferon$ was observed on the cells, PorLeIF and PorIIF did not show any activity.

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Attenuated Expression of Interferon-induced Protein Kinase PKR in a Simian Cell Devoid of Type I Interferons

  • Park, Se-Hoon;Choi, Jaydo;Kang, Ju-Il;Choi, Sang-Yun;Hwang, Soon-Bong;Kim, Jungsuh P.;Ahn, Byung-Yoon
    • Molecules and Cells
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    • 제21권1호
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    • pp.21-28
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    • 2006
  • The interferon-induced, double-stranded RNA (dsRNA)-dependent protein kinase PKR plays a key role in interferon-mediated host defense against viral infection, and is implicated in cellular transformation and apoptosis. We have isolated a cDNA of simian PKR encoding a product with 83% amino acid identity to the human homolog and showed that PKR expression is significantly attenuated in the Vero E6 African green monkey kidney cells devoid of type I interferon genes. A variant form of PKR lacking the exon 12 in the kinase domain is produced in these cells, presumably from an alternatively spliced transcript. Unlike wild type PKR, the variant protein named PKR-${\Delta}E12$ is incapable of auto-phosphorylation and phosphorylation of eIF2-${\alpha}$, indicating that the kinase sub-domains III and IV embedded in exon 12 are indispensable for catalytic function. PKR-${\Delta}E12$ had no dominant negative effect but was weakly phosphorylated in trans by wild type PKR.

High-level Production of Recombinant Human IFN-$\alpha2a$ with Co-expression of $tRNA^{Arg(AFF/AGA)}$ in High-cell-density Cultures of Escherichia coli

  • Shin, Chul-Soo;Hong, Min-Seon;Shin, Hang-Chel;Lee, Jeewon
    • Biotechnology and Bioprocess Engineering:BBE
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    • 제6권4호
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    • pp.301-305
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    • 2001
  • The co-expression of the arg U gene in a double-vector expression system of recombi-nant Escherichia coli BL22(DE3)[pET-IEN2a+pAC-argU] significantly enhanced the production level of reconminant human interferon -$\alpha$2a(rhIFN-$\alpha$2a) in high cell density cultures, compared to a recombinant E. coli culture containing only the single expression vector, pET-IEN2a. The dry cell mass concentration increased to almost 100 g/L, and more than 4 g/L of rhIFN-$\alpha$2a was accumu-lated in the culture broth. Evidently, the synthesis of rhIFN-$\alpha$2a was strongly dependent on the pre-induction growtih rate and more efficient at a higher specific growth rate. The additional sup-ply of tRN $A^{Arg(AGG/AGA)}$ enhanced the expression level of the rhIFN-$\alpha$2a gene in the early stage of the post-induction phase, yet thereafter the specific production rate of rhIFN-$\alpha$2a rapidly de-creased due to severe segregational instability of plasmid vector pET-IEN2a. It would appear that the plasmid instability with only occurred to pET-IEN2a in the double vector system, was re-lated to the effect of translational stress due to the over expression of rhIFN-$\alpha$2a.

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인터페론 알파에 대한 단세포 군항체의 제조 및 특성 (Production and Characteriuation of Monoclonal Antibodies against Human Interferon-$\alpha$)

  • Park, Kyung-Hee;Lee, Ihn-Sook
    • 한국동물학회지
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    • 제35권1호
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    • pp.1-7
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    • 1992
  • Seven monoclonal antibodies were produced by fusing splenocytes from Balb/C mouse immunized with partially purified human interferon-a (HUIFN-a) with NSO plasmacytoma cells. aery were identified as five IgG class (432.22: IgG2b/n, 460.52: IgG2b/a , 548.46: IgG2a/n , 573.10: IgG2b/h , 625.12: IgG2b/n ), one IgA class (460.50: IgA/n ) and one IsM class (465.27: IgA/n ), and all of them revealed highly sensitive to HUIFN- a IgG class monoclonal antibodies have pts ranged from 8.2 to 8.6. Ascites fluids produced from primed Balb/c mice and were purified through column chromatography. The cytopathic effect (CPE) inhibition assay to examine neutralization of HuIFU-a by IgG class monoclonal antibodies, gave that MAbs 460.52, 548.46, 573.10 can neutralize HUIFU- a arith varying degrees except 432.22. Therefore, it is deduced that these various monoclonal antibodies may recognize the distinct epitopes on HUIFN-a.

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Induction of pro-inflammatory cytokines by 29-kDa FN-f via cGAS/STING pathway

  • Hwang, Hyun Sook;Lee, Mi Hyun;Choi, Min Ha;Kim, Hyun Ah
    • BMB Reports
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    • 제52권5호
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    • pp.336-341
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    • 2019
  • The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon ($IFN-{\alpha}$), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines.

Considerations in the Design of the Preclinical Safety Program for PegIntron

  • Davis, Thomas
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2003년도 추계학술대회
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    • pp.87-88
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    • 2003
  • PegIntron is the pegylated form of human recombinant interferon alfa-2b (IFN${\alpha}$2b). IFN ${\alpha}$2b, known as Intron A, has been in approved clinical use since the 1980's for various cancer indications, and for the treatment of Hepatitis C. In the mid 1990's, several clinical investigators reported that combination therapy with ribavirin and Intron A dramatically increased the therapeutic efficacy for treatment of Hepatitis C.(omitted)

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Pharmacokinetics of DA-3021 (mono-PEGylated recombinant human interferon ($\alpha$-2a) after Subcutaneous Administrations to Experimental Animals

  • Jo, Yeong-Woo;Kim, Won-Geun;Choi, Yun-Kyu;Jeon, Hyun-Kyu;Kim, Dong-Hwan;Park, Beom-Soo;Lee, Sung-Hee;Kim, Won-Bae;Youn, Yu-Seok
    • 대한약학회:학술대회논문집
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    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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    • pp.424.1-424.1
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    • 2002
  • Interferon has therapeutic potential for a wide range of infectious and proliferative disorders such as chronic hepatitis C and malignant melanoma. However. it has some therapeutic problems as other protein therapeutics do. A variety of approaches have been developed to circumvent these problems. Among them. the attachment of a polyethylene glycol (PEG) moiety 10 interferon is considered as one of the most promising solutions for its ability of extending the plasma residence time. (omitted)

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