Optimizing DC Vaccination by Combination With Oncolytic Adenovirus Coexpressing IL-12 and GM-CSF

Zhang, Song-Nan,Choi, Il-Kyu,Huang, Jing-Hua,Yoo, Ji-Young,Choi, Kyung-Ju,Yun, Chae-Ok Nature Publishing Group 2011 MOLECULAR THERAPY Vol.19 No.8

<P>Dendritic cell (DC)-based vaccination is a promising strategy for cancer immunotherapy. However, clinical trials have indicated that immunosuppressive microenvironments induced by tumors profoundly suppress antitumor immunity and inhibit vaccine efficacy, resulting in insufficient reduction of tumor burdens. To overcome these obstacles and enhance the efficiency of DC vaccination, we generated interleukin (IL)-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-coexpressing oncolytic adenovirus (Ad-ΔB7/IL12/GMCSF) as suitable therapeutic adjuvant to eliminate immune suppression and promote DC function. By treating tumors with Ad-ΔB7/IL12/GMCSF prior to DC vaccination, DCs elicited greater antitumor effects than in response to either treatment alone. DC migration to draining lymph nodes (DLNs) dramatically increased in mice treated with the combination therapy. This result was associated with upregulation of CC-chemokine ligand 21 (CCL21<SUP>+</SUP>) lymphatics in tumors treated with Ad-ΔB7/IL12/GMCSF. Moreover, the proportion of CD4<SUP>+</SUP>CD25<SUP>+</SUP> T-cells and vascular endothelial growth factor (VEGF) expression was decreased in mice treated with the combination therapy. Furthermore, combination therapy using immature DCs also showed effective antitumor effects when combined with Ad-ΔB7/IL12/GMCSF. The combination therapy had a remarkable therapeutic efficacy on large tumors. Taken together, oncolytic adenovirus coexpressing IL-12 and GM-CSF in combination with DC vaccination has synergistic antitumor effects and can act as a potent adjuvant for promoting and optimizing DC vaccination.</P>

야생 설치류의 한타바이러스 감염에 대한 연구

백락주,송진원,송기준,박광숙,최영주,강주일,이용주 대한감염학회 1997 감염 Vol.29 No.6

목적:국내 야서중에 한타바이러스의 숙주는 등줄쥐와 집쥐로 알려져 있으나, 한국에 서식하고 있는 다양한 야생 설치류를 채집하여 한타바이러스에 대한 항체검사를 실시하여 새로운 혈청형의 한타바이러스가 있는지를 혈청학적으로 규명하고자 하였다. 방법:국내에 서식하고 있는 야생 설치류를 1995년 10월부터 1996년 10월까지 7종 551수의 야시와 4종 97수의 소형동물을 채집하여 한타바이러스에 대한 항체검사를 간접형광항체법으로 실시하였다. 결과: 1) 야서 7종 551수와 소형동물 4종 97수를 대상으로 한탄바이러스의 감염율은 등줄쥐 17.2%(29/162), 흰넓적다리붉은쥐 8.7%(2/23), 대륙밭쥐는 25%(2/8), 그리고 땃쥐는 7.1%(1/14)이었다. 그리고 야생토끼는 8.8%(7/80)가 서울바이러스에 대한 항체를 가지고 있었다. 등줄쥐의 양성혈청중 대부분은 서울바이러스와 일부는 푸말라바이러스, 프로스펙트힐바이러스, 뉴욕바이러스와도 교차반응이 있었다. 흰넓적다리붉은쥐 2수와 대륙밭쥐 2수는 5가지 한타바이러스 모두에 교차 반응이 있었다. 2) 다람쥐는 9.5%(28/283)가 채집지역에 관계없이 한탄바이러스에 대한 항체를 가지고 있었고 항체기는 1:16 내지 1:256으로 비교적 낮았으며 서울바이러스, 푸말라바이러스, 프로스켁트힐바이러스와 뉴욕바이러스에 각각 반응하는 것도 일부는 교차반응을 보이는것도 있다. 청설모는 10.3%(7/68)가 한탄바이서르에 대한 항체를 가지고 있었으며 항체가는 1:16 내지 1:1,024이었으며 일부는 교차반응이 있었다. 3) 야생토끼의 서울바이러스에대한 항체양성율은 8.8%(7/80)이었으며 이중에 2수는 한탄바이러스와 교차반응이 있었고, 푸말라바이러스, 프로스켁트힐바이러스, 뉴욕바이러스와는 교차반응이 없었다. 항체가는 1:16 내지 1:64로 비교적 낮았다. 결론:등줄쥐는 한탄바이러스에 의한 감염이지만 흰넓적다리붉은쥐, 대륙밭쥐, 다람쥐 그리고 청설모의 일부는 한탄바이러스가 보다 다른 한타바이러스에 대한 항체가가 높았고 특히 일부 다람쥐 혈청은 푸말라바이러스 혹은 프로스켁트힐바이러스에만 반응하였다. 그리고 야생토끼는 서울바이러스에 대한 감염율이 높은 것으로 보아 국내에 한탄바이러스와 서울 바이러스 이외에 새로운 혈청형의 한타바이러스가 있는 것을 사료된다. Background: Hantavirus are widley distributed in rodents populations even in geographical areas where hemorrhagic fever with renal syndrome(HFRS) has not been reported. Multiple species of Murid and Arvicolid rodents serve as the natural reserviors of hantaviruses. Serologic diagnosis using hantaviral antigens indicates that hantaviruses are widley distibuted in wild rodents. This study were designed to find the distribution of hantaviruses among wild rodents and small mammals in Korea, 1995-1996. Methods: Rodents were trapped alive in selected areas. A total of 551 wild rodents from 7 species and 97 small mammals from 4 species were captured in Korea. Serologic evidence for hantavirus infection were tested using five hantavirus antigens by indirect immunofluorescent antibody technique(IFA). Among 162 Apodemus agrarius, 23 Apodemus peninsulae, 8 Clethrionomys regulus, 6 Microtus fortis, 1 Mus musculus, 283 Tamias sibiricus, 68 Sciurus vulgaris, 14 Crocidura laciura, 80 Lepus sinensis, 2 Capereolus capereolus and 1 Nyctereutes procyonoides. Results: 29 A. agrarius, 2 A. peninsulae, 1 C. laciura, 2 C. regulus, 27 T. sibiricus and 7 S. vulgaris were sero positive agaist hantaan virus and 7 L. sinensis were IF antibody positive against Seoul virus. Some of Tamias sibiricus were only seropositive against puumala virus or prospect hill virus. Conclusion: This data suggests that new serotypes of hantavirus might distribute among rodents in Korea.

CA 약침액의 항산화,항염증 효능 및 염증성 사이토카인 억제 효과

김학주 ( Hak Ju Kim ),최일환 ( Il Hwan Choi ),정철 ( Chul Jung ),임형호 ( Hyung Ho Lim ),송윤경 ( Yun Kyung Song ) 대한면역약침학회 2012 대한면역약침학회지 Vol.1 No.1

Objectives: This purpose of this study was to analyzed the Biological Activities of CA Yakchim Fluid. Methods: The protein content, glucose content, crude fat content, crude ash content in CA Yachim fluid were analyzed, and DPPH radical scavenging, inhibition of COX-2 activities were investigated. Also TNF-α, IL-6, GAPDH as inflammatory cytokines were measured. Results: The protein, 1.46%, glucose, 0.13%, crude fat 96.18%, crude ash 0.51% in CA Yachim fluid were confirmed. The electron donation ability of CA Yakchim on DPPH WAS 21%. The inhibition of COX-2 activity of CA Yakchim fluid was 68%. The TNF-α, IL-6 were increased in RAW 264.7 treated with LPS, and were decreased in RAW 264.7 pre-treated with CA Yakchim fluid. Conclusions: We conclude that the CA Yakchim fluid has anti-oxidant, anti-inflammatory activities and inhibition effect of the inflammatory cytokines.

Therapeutic and Tumor-specific Immunity Induced by Combination of Dendritic Cells and Oncolytic Adenovirus Expressing IL-12 and 4-1BBL

Huang, Jing-Hua,Zhang, Song-Nan,Choi, Kyung-Ju,Choi, Il-Kyu,Kim, Joo-Hang,Lee, Mingul,Kim, Hoguen,Yun, Chae-Ok Nature Publishing Group 2010 MOLECULAR THERAPY Vol.18 No.2

<P>Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.</P>

LPS로 유도한 대식세포의 염증반응에서 우슬의 항염증 효과

김민선 ( Min Sun Kim ),정진수 ( Jin Soo Jeong ),이혜윤 ( Hye Youn Lee ),주영승 ( Young Sung Ju ),배기상 ( Gi Sang Bae ),서상완 ( Sang Wan Seo ),조일주 ( Il Joo Cho ),박성주 ( Sung Joo Park ),송호준 ( Ho Joon Song ) 대한본초학회 2011 大韓本草學會誌 Vol.26 No.2

Objectives: Achyranthes japonica (AJ ) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that AJ could show the anti-inflammatory effects in macrophages. In this experiment, we studied whether AJ could inhibit the inflammatory responses in macrophages. Methods: To measure out the cytotoxicity of AJ, we performed the MTT assay. We evaluated the nitric oxide (NO) production, and cytokine production such as interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF)-a. We also investigated the cellular mechanims such as mitogen activated protein kinases (MAPK)s and nuclear factor kappa B (NF-kB). Results: AJ inhibited lipopolysaccharide (LPS)-induced NO production. AJ also inhibited production levels of IL-1b, IL-6 and TNF-a in LPS-stimulated macrophage. Finally, western blot analysis showed that AJ treatment inhibited the activation of p38 but not of extracellular signal-regulated kinase, c-jun NH2-terminal kinase and NF-kB. Conclusions: These results showed that AJ down-regulated the inflammatory response via p38 in macrophages, which suggest that AJ could be a candidate on treating inflammatory diseases.

췌장의 점액성 낭선암 1예

송현주,김도영,정혜경,남승현,문일환,구혜수 梨花女子大學校 醫科大學 醫科學硏究所 2002 EMJ (Ewha medical journal) Vol.25 No.2

Nowadays increasing use of abdominal ultrasound in routine check-up may increase the detection rate asymtomatic cystic lesions of pancreas. Even through the majority of the cystic lesions of pancreas is pseudocyst, about 10-15% of those lesions are caused by pancreatic cystic tumor. In the pancreatic cystic tumor, especially, mucinous cystic tumor should be exicised due to its malignant potential, while the pancreatic pseudocyst or serous cystic tumon can be observed for a period or treated medically. Several clinical, radiological, biochemical and pathologic guidelines have been developed in order to distinguish among them. Among pancreatic cystic tumors, mucinous cystic adenocarcinoma is very rare and accounts for only 1% of all pancreatic neoplasms. Unlike extremely poor prognosis of pancreatic adenocarcinoma, mucinous cystic adenocarcinoma has an indolent course and shows a good prognosis after its curative resection. Recently we experienced a 69-year-old woman who had a mucinous cystic adenocarcinoma of the pancreas. We report this case with a review of literature.

Azotobacter sp.에 의한 Butyric Acid와 Valeric Acid로부터 Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)의 생산

송희주,이일석,방원기 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.1

Butyric acid 와 valeric acid로부터 poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3HV))를 생산하기 위하여 P(3HB-co-3HV)의 생산능력이 있는 10종의 균주를 토양으로부터 분리하였으며 분리된 균주들중에서 P(3HB-co-3HV)의 생산능력이 가장 우수한 균주 HJ-067을 선별하였고, Azotobacter sp.로 부분 동정하였다. P(3HB-co-3HV)의 생산에 있어서 butyric acid 와 valeric acid의 최적 기질 농도는 각각 3.0g/l이었다. 질소원으로는 (NH_4)_2SO_4가 가장 우수하였으며, 최적 농도는 0.75 g/l(C/N ratio=21.36)이었다. 금속이온(Zn^2+, Co^2+, Mn^2+)의 결핍은 P(3HB-co-3HV)의 생산에 영향을 미치며, 특히 Mn^2+을 첨가하지 않은 경우에 P(3HB-co-3HV)의 생산량이 증가하였다. P(3HB-co-3HV)의 생산을 위한 최적 배양 온도는 27℃였으며, 최적 초기 pH는 7.0이었다. 상기의 최적 조건하에서 36시간 배양하여 얻어진 건조균체량 및 P(3HB-co-3HV)의 생산량은 각각 3.00 g/l, 1.82 g/l이었다. 이때의 P(3HB-co-3HV) yield는 건조 균체량의 60.60%(w/w)이었으며, HV%는 15.92%(w/w)이었다. For the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3HV)) from butyric acid and valeric acid, 10 strains of bacteria capable of producing P(3HB-co-3HV) wee isolated from soil. Among them, the strain HJ-067 showed the best ability of producing P(3HB-co-3HV), and was identified as a Azotobacter sp. For the production of P(3HB-co-3HV), the optimum concentrations of butyric acid and valeric acid were 3.0 g/l, respectively. The most effective nitrogen source was (NH_4)_2SO_4 at an optimum concentration of 0.75 g/l, which was equivalent to 21.36 in C/N ratio. Deficiency of the cationic metal ions (Zn^2+, Co^2+, Mn^2+) in the production medium had stimulating effect on P(2HB-co-3HV) accumulation, especially in the managanese deficient medium. The optimum temperature for P(3HB-co-3HV) production was 27℃ and the optimum initial pH was 7.0. Under the optimum conditions, 1.82 g/l of P(3HB-co-3HV) and 3.00 g/l of dry biomass were produced after 36 hour cultivation, and the P(3HB-co-3HV) yield and HV% were 60.60% (w/w), 15.92% (w/w), respectively.

항갑상선제로 치료한 그레이브스병 환자의 관해예측인자

남일송,윤여일,김선규,김용현,이주영,목지오,윤석기,김철희,김영선,변동원,서교일,유명희 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.2

Background: Most cases of Graves' disease have been treated by antithyroid drugs in Korea. The major drawbacks of antithyroid drugs are the relative high rate of relapse and the inconvinience of long term therapy. Measurement of TBII and TRH stimulation test have been considered as the most reliable tests predicting relapse, but the predictive power is not high enough to use in clinical situation. This study was performed to find good prognostic indicators in Graves' disease patients after the discontinuation of antithyroid drug therapy. Subjects and methods : We restrospectively evaluated 96 patients with Graves' disease who showed normal TRH test at the end of antithyroid drug therapy and were followed for more than one year. Serum T3, T4, T3/T4 ratio, TBII, Anti-TPO Ab and TGAb levels were measured at the time of diagnosis and at the end of therapy. Two to three months after withdrawal of antithyroid medication, serum TSH and free T3 responses to TRH were examined. These parameters were compared between the relapse group and the remission group. Results : Among the 96 patients, 22 patients(22.9%) relapsed(Group Ⅱ) and 74 patients(77.1%) remained in remmision(Group Ⅰ). No significant difference was observed between the relapse and the remission group in clinical parameters, serum T3, T4, TSH, T3/T4 ratio, TBⅡ and Anti-TPO Ab determined before and after treatment. Serum TSH and free T3 levels measured after TRH stimulation were also similar in both groups. Serum TGAb levels determined at the end of treatment were significantly higher in the remission group(p<0.05). Relapse following the discontinuation of therapy occured within 24 months in 72.7% of the relapsed cases. After 24 months, relapse rate was reduced significantly. Conclusion : These results suggest that high serum TGAb levels could be a favorable prognostic indicator for the long term remission of Graves' disease treated with antithyroid drugs, and may suggest that Hashimoto's thyroiditis is combined with Graves' disease in those patients.

Sodium Trans-Bis(methyliminodiacetato)Chromate(Ⅲ)의 두가지 다른 空間群 P1￣와 A2/n間의 相互 變換

李珍昊,宋柱昊,崔成山,郭相姬,吳美蘭,박성진,李揆旺,徐廷善,徐日煥 충남대학교 1996 忠南科學硏究誌 Vol.23 No.1

The structure of sodium trans-bis(methyliminodiacetato) chromate(Ⅲ), C_10H_14O_8N_2CrNa, has been elucidated with two space groups P 1-; a=8.9856(6), b=13.308(1), c=6.261(1)Å, α=76.38(1), β=110.361(9), r=107.394(6)˚, V=662(2)Å^3, Z=2, μ=0.47mn^(-1), d=1.831Mg/㎥, R=0.0295 for 1901 independent reflections with F^2>2σ(F^2), and A2/n; a=13.65(5), b=6.261(1), c=16.85(6)Å, β=113.05(1)˚, V=1324(7)Å^3, Z=4, R=0.0287 for 1013 independent reflections with F^2>2σ(F^2). There are two different asymmetric half molecules in triclinic system and one asymmetric half molecule in monoclinic system. The structures of three different molecules are very similar in conformations. The four carboxyl O atoms and the two imino N atoms in each molecule produce a distorted octahedral coordination geometry around the Cr atom. The average distances of Cr-O(carboxyl) and Cr-N(imino) are 1.956 and 2.061Å respectively. Molecules are held together by ionic forces. In this paper, it has been also shown that the cell constants, Miller indices, atomic coordinates, lattice directions and reciprocal lattices of the two space groups can be mutually transformed.

재발성 일과성 허혈 발작을 주소로 내원한 비-안와-대뇌 모균증 1예

강우열,이주헌,성영희,최일수,송홍기,이병철 대한노인병학회 2002 대한노인병학회지 Vol.6 No.3