• Korean Journal of Veterinary Research
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• v.40 no.1
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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.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.266-269
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• 1993

The acute toxicity of a recombinant human interferon $\alpha$A (code name: LBD-007) was evaluated in both sexes of ICR mice, 5 weeks old, by the oral, subcutaneous and intravenous routes of administration. Based on the results, LBD-007 was not considered to induce any toxic effect on the mice in mortalities, clinical findigs, body weights and gross findings. It is suggested that LD$_{50}$ values in mice would be $>48{\times}10^8$ IU/kg in the oral, subcutaneous or intravenous routes.s.

• Toxicological Research
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• v.16 no.1
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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.

• Toxicological Research
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• v.3 no.1
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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.

• Molecules and Cells
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• v.21 no.1
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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.

• Neonatal Medicine
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• v.15 no.2
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• pp.183-189
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• 2008

Infantile hepatic hemangioendotheliomas (IHHEs) are benign vascular tumors, but can be associated with the life-threatening complications, such as congestive heart failure, disseminated intravascular coagulation, and massive bleeding. Various therapeutic options have been developed and the treatment response depends on the patient's clinical status and the nature of the lesion. In the case of a symptomatic IHHE, a non-invasive and precise diagnosis should be performed promptly before the therapeutic method is chosen. Additionally, it should be kept in mind that the residual lesions have malignant potential. We report a case of a congenital giant IHHE that was successfully reduced in size by interferon-$\alpha$ and completely removed by surgical tumor resection with a hepatic lobectomy.

• Clinical and Experimental Pediatrics
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• v.53 no.11
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• pp.975-978
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• 2010

A 7-year-old boy presented with hematochezia and abdominal pain. A 3.7-cm-sized mass was identified in the ascending colon by abdominal computed tomography and colonoscopy. The patient underwent surgical resection. Pathological examination revealed a low-grade perivascular epithelioid cell tumor (PEComa). PEComa in the colon is very rare. Only a few cases have been reported so far. An effective treatment method for this rare tumor has not been established yet. The patient received adjuvant interferon-${\alpha}$ immunotherapy for 1 year. He has been tumor-free for 26 months since the initial diagnosis. This report is the first documented case of the use of interferon-${\alpha}$ for pediatric PEComa of the colon.

• Toxicological Research
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• v.9 no.1
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• pp.83-98
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• 1993

LBD-007, a newly developed recombinant human interferon alpha A, was at dose levels of 0, 3 $\times$ $10^6$, 6 $\times$ $10^6$ and 12 $\times$ $10^6$ IU/kg/day administered subctaneously to pregnant Sprague-Dawley rats during the organogenetic period. Ethylenethiourea was used as a positive control. 2/3 of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. 1. No treatment-related changes in clinical signs, food consumption, body weight and necropsy findings of dams were observed.

• BMB Reports
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• v.52 no.5
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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.

• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.4
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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.