• Journal of Pharmaceutical Investigation
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• 제17권4호
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• pp.213-216
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• 1987

The distribution features of recombinant human $alpha-interferon(rHuIFN-{\alpha}A)$ and $^{14}C-radiolabeled\;rHuIFN-{\alpha}A\;(^{14}C-rHuIFN-{\alpha}A)$ were investigated in ICR mice after i.v. injection. The level of $rHuIFN-{\alpha}A$ in the kidney was significantly higher than those in lung and liver at 10min after the injection. But the level was reduced significantly at 60min. The level of radioactivity in the kidney was also significantly higher than those in other organs after i.v. injection of $^{14}C-rHuIFN-{\alpha}A$, but it was reduced at much slower speed than was $rHuIFN-{\alpha}A$. These results show that interferon is distributed repidly and the kidney is the main site of distribution and metabolism of $rHuIFN-{\alpha}A$.

• Toxicological Research
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• 제3권1호
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• pp.65-72
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• 1987

A teratogenic study was carried out on New zealand White rabbits in order to examine the teratogenic potentiality of the recombinant human interferon-${\alpha}$A(rHuIFN-${\alpha}A$), an available therapeutic agent. The rHuIFN-${\alpha}A$ was intravenously administered at dose sevels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day for a period of13 days from day 6 to day 18 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 29 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal develpment of the offsprings was observed. The administration of rHuIFN-${\alpha}A$ during a period of organogenesis produced no embryotoxic and teratogenic effects.

• 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.

• Journal of Pharmaceutical Investigation
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• 제16권3호
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• pp.118-123
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• 1986

Time-concentration curves of recombinant human interferon alpha$(rIFN-{\alpha}A)$ in the skin and serum of nude mice or rats were studied after topical application of IFN ointment. IFN appeared in the skin and serum in less than 30 minutes and lasted for more than 10-12 hours at high concentration level after the application to nude mice at a dose of $9.0{\times}10^5\;IU/g$ mouse. But in the rats, IFN was not detected in the serum even 7 hours after the application at a dose of $6.0{\times}10^5\;IU/g$ rat. Topical application of IFN might be useful for the topical and systemic treatment if the human skin resembles that of nude mouse in respect to transport characteristics.

• Tuberculosis and Respiratory Diseases
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• 제58권1호
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• pp.11-17
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• 2005

연구배경 : 결핵의 발병에 유전적인 소인이 존재하며 숙주 면역 반응에 $IFN-{\gamma}$가 중요한 역할을 한다고 알려져 있다. 파종성 NTM 또는 BCG 감염증 환자에서 $IFN-{\gamma}$ 수용체 유전자 돌연변이가 밝혀져 있는데, 결핵 환자에서 $IFN-{\gamma}$ 수용체의 부분결핍 유무는 잘 알려져 있지 않았다. 방 법 : 2개 이상의 장기를 침범한 파종성 결핵 환자 6명을 대상으로 염기순서분석을 통해 $IFN-{\gamma}$ 수용체 1과 $IFN-{\gamma}$ 수용체 2의 부분결핍을 초래하는 유전자 이상이 있는지를 살펴보았다. 결 과 : $IFN-{\gamma}R1$의 부분결핍을 초래하는 I87T와 818delT 818del4, 818insA 그리고 $IFN-{\gamma}R2$의 부분결핍을 초래하는 R114C 돌연변이 등 기존에 보고된 유전자 이상은 발견되지 않았다. 결 론 : 본 연구의 대상인 6명의 파종성 결핵 환자에서 $IFN-{\gamma}$ 수용체의 부분결핍을 초래하는 유전자 이상은 발견되지 않았다.

• 농업과학연구
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• 제12권1호
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• pp.153-161
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• 1985

고단위(高單位)의 porcine leucocyte interferon(For IFN-${\alpha}$)을 대량생산(大量生産)하기 위한 기초연구(基礎硏究)로써 백혈구(白血球) 분리법(分離法), 백혈구(白血球)의 성상(性狀) 및 inducer에 따른 IFN 생산효과(生産效果) 시험(試驗)을 하였고 Por IFN-${\alpha}$의 역가측정(力價測定)을 micro-system에 확립(確立)하기 위해 시험(試驗)을 수행(遂行)하였던 바 다음과 같은 결과(結果)를 얻었다. 1. 돼지 말초백혈구(末梢稍白血球)를 분리(分離)하기 위해서 4 가지 방법(方法)을 응용(應用)하던 바 백혈구(白血球) 분리법(分離法)은 buffy coat 方法에서 가장 높았으나 적혈구(赤血球) 혼입율(混入率)이 높았고 Ficoll-paque 방법(方法)에서는 백혈구(白血球) 분리율(分離率)은 중등도(中等度)였으나 적혈구(赤血球) 혼입율(混入率)은 가장 낮았다. 2. 말초백혈구(末梢白血球)와 비장세포(脾臟細胞)의 활성도(活性度)는 IFN 생산(生産)에 영향(影響)을 주었으며 세포활성도(細胞活性度)가 높을수록 IFN 생산효능(生産效能)이 높았으며, 적혈구(赤血球)의 혼입도(混入度)가 높을수록 IFN 생산효능(生産效能)은 낮았다. 말초백혈구(末梢白血球)는 비장세포(脾臟細胞)에 비해 1.7배(倍)의 높은 IFN 생산효과(生産效果)가 인정(認定)되었다. 3. Inducer로 사용(使用)된 Sendai virus(Cantell 주(株))는 Newcastle disease virus(Lasota 주(株)) 보다 IFN 생산효과(生産效果)가 5.5 배(倍) 높았다. 4. 본(本) 시험(試驗)에서 확립(確立)된 micro-IFN assay 법(法)의 재현성(再現性)을 검사(檢査)한 바 4회반복시험(回反復試驗)에서 편차(偏差)는 0.05~0.21로 나타났다. 5. 시험생산(試驗生産) 9롯트의 IFN 역가(力價)는 330 내지 4,700 unit/ml로써 평균(平均) 1,200 unit/ml이었다.

• Toxicological Research
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• 제3권1호
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• pp.33-44
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• 1987

A fertility study was carried out in Sprague Daxley rats which have been given the intravenous or intraperitoneal injections of rHuIFN-${\alpha}$A, a commecially available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day. Male rats were treated with rHuIFN-${\alpha}$A from 60 days before pairing and until the completion of mating. Femal rats received rHuIFN-${\alpha}$A for 22days prior to mating and up to day of gestation. All pregnant females were sacrificed on day 20 of gestation and all fetuses were examined for abnormalities. Both the male and female animals treated with rHuIFN-${\alpha}$A did not show any abnormal responses. No abnormal signs were seen in reproducibility for the rats treated with rHuIFN-${\alpha}$A. No External, internal and skeletal anomalies attributable to rHuIFN-${\alpha}$A were observed in the fetuses. It was concluded that rHuIFN-${\alpha}A$ had no harmful effect on mating, fertilization, implantation, or embryonic development.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVI)
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• pp.35-35
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• 2005

Recombinant human $interferon-{\beta}-1a(rIFN-{\beta})$ is a single glycosylated protein (at N80, 1N) with anti-viral activity. However, present drugs have a relatively short serum half-life of $rIFN-{\beta}$, thus patients suffer from frequent $infections.^{1)}$ To improve its half-life, eight glycosylation analogs were prepared, which have additional N-linked glycosylation consensus sequences (N-X-T/S) within the $IFN-{\beta}$ molecule and/or at C-terminal. Each $rIFN-{\beta}$ analog was examined for the presence of additional N-linked glycosylation and the maintenance of anti-viral activity in CHO cells. The molecular weights of five analogs were not changed. However, two analogs, R27T within $rIFN-{\beta}$ (27 kDa, 2N) and GNITVNITV at C-terminal (29kDa, 2N), showed a clear increase in molecular weights, compared to native $rIFN-{\beta}$ (23 kDa, 1N). And another combined analog of R27T+GNITVNITV showed increased molecular weight (33 kDa, 3N). It was confimed that the molecular weight increment of analogs was caued by the N-linked glycosylation with the treatment of N-glycansae. In the case of anti-viral activity, the analog GNITVNITV showed a reduction in activity compared to native $IFN-{\beta}$, whereas the analogs R27T and R27T+GNITVNITV were found to have distinctly increased activities. Pharmacokinetic study in rats also disclosed that the analogs R27T and R27T+GNITVNITV had 2 3 fold increased serum half-life, respectively. In conclusion, the addition of N-linked glycosylation in $rIFN-{\beta}$ increased serum half-life, thereby its less frequent administration will be expected.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.131-131
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• 1993

위암의 화학요법 성적이 만족스럽지 못하므로 기존의 항암제와 alpha-interferon을 병용사용하므로써 상승적 항암효과가 있는가를 연구하였다. R-25 flask에 위암세포주 SNU-1 및 SNU-16을 배양하면서 항암제 5-FU 혹은 cisplatin에 alpha-interferon 2A(제일제당)를 분자량의 비에 따라 병요처리하였다. 96시간 배양후 cytotoxicity를 Mosman의 방법에 따른 MIT방법으로 분석하였으며, 이를 Chou등의 combination index 분석 program을 처리하였다. 위암세포주 SNU-1에 대하여 5-FU와 alpha-IFN은 상승작용을 보였다. 5-FU의 $IC_{50}$/가 14.25$\mu$M 이었고 IFN처리시는 $IC_{50}$/가 0.02$\mu$M이었으며 combination index(CI)는 모든 용량에서 1이하였다. SNU-16에 대하여도 5-FU와 alpha-IFN의 병용사용은 상승적 작용을 나타내었다. (CI<1.0). cisplatin과 alpha-IFN의 병용시에는 CI가 1이상을 나타내어 상승작용을 증명할 수 없었다.

• 한국가금학회:학술대회논문집
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• 한국가금학회 1999년도 제16차 정기총회및학술발표회
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• pp.34-50
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• 1999

A cDNA encoding chicken interferon-gamma (chIFN-${\gamma}$) was amplified from P34, a CD4$^{+}$ T-cell hybridoma by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into pUC18. THe sequences of cloned PCR products were determined to confirm the correct cloning. Using this cDNA as probe, chicken genomic library from White Leghorn spleen was screened. Phage clones harboring chicken interferon-gamma (chIFN-${\gamma}$) were isolated and their genomic structure elucidated. The chIFN-${\gamma}$ contains 4 exons and 3 introns spanning over 14 kb, and follows the GT/AG rule for correct splicing at the exon/intron boundaries. The four exons encode 41, 26, 57 and 40 amino acids, respectively, suggesting that the overall structure of IFN-${\gamma}$ is evolutionairly conserved in mammalian and avian species. The 5’-untranslated region and signal sequences are located in exon 1. Several AT-rich sequences located in the fourth exon may indicate a role in mRNA turnover. The 5’-flanking region contains sequences homologous to the potential binding sites for the mammalian transcription factors, activator protein-1(AP-1) activator protein-2(AP-2) cAMP-response element binding protein(CREB), activating transcription factor(ATF), GATA-binding fator(GATA), upstream stimulating factor(USF), This suggests that the mechanisms underlying transcriptional regulation of chicken and mammalian IFN-${\gamma}$ genes may be similar.r.