• Title/Summary/Keyword: In vitro cytotoxicity

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Radioimmunotherapy of Nude Mice Bearing Human Colon Carcinoma with I-131 Labeled Anti-carcinoembryonic Antigen Monoclonal Antibody (누드마우스에 이식된 인체대장암에서 I-131표지 항태아성암항원 단일클론항체를 이용한 방사면역치료법 : 치료성적에 관계되는 인자분석)

  • Kim, Byung-Tae;Lee, Kyung-Han;Kim, Sang-Eun;Choi, Yong;Chi, Dae-Yoon;Chung, June-Key;Lee, Myung-Chul;Koh, Chang-Soon;Chung, Hong-Keun
    • The Korean Journal of Nuclear Medicine
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    • v.29 no.3
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    • pp.332-342
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    • 1995
  • This study was designed to evaluate the effects of various factors on the therapeutic effect of the I-131 labeled anti-carcinoembryonic antigen monoclonal antibody(anti-CEA antibody). Tetrazolium-based colorimetric assay (MTT) was used to compare in vitro cytotoxicity of 3 Korean colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5) for selection of proper 2 cell lines in this study. The changes of the size of tumor which was xenografted to nude mice (balb/c nu/nu) were compared in 4 groups (group treated I-131 labeled anti-CEA antibody, group treated with non-radiolabeled anti-CEA antibody, group treated with I-131 labeled anti-human chorionic gonadotropin monoclonal antibody (anti-hCG antibody) as nonspecific antibody, and group injected with normal saline as a control). Immunohistochemical staining and in vivo autoradiography were performed after excision of the xenografted tumor. The results were as below mentioned. The in vitro cytotoxic effect of I-131 labeled anti-CEA antibody is most prominent in SNU-C5 cell line between 3 cancer cell lines. The changes of xenografted tumor size in both SNU-C4 and SNU-5S cell tumors at the thirteenth day after injection of the antibodies were smallest in the group treated with I-131 labeled anti-CEA antibody (SNU-C4/SNU-C5; 324/342%) comparing with other groups, group treated with anti-CEA antibody (622/660%), group treated with I-131 anti-hCG antibody (538/546%), and control group(1030/724%)(P<0.02 in SNU-C4 and P<0.1 in SNU-C5 at the 13th day after injection of antibodies). On the thirteenth day after injection of the antibodies nude mice were sacreficed to count the radiouptake of tumor and to check the changes of tumor size. Correlations between radiouptake and change of tumor size were calculated in each groups and significant negative correlation was only obtained in the group treated with I-131 anti-CEA antibody (p<0.05). There were no correlations between antigenic expression of carcinoembryonic antigen and distribution of anti-CEA antibody in both SNU-C4 and SNU-C5 cell tumors on immunoperoxidase staining. On in vivo autoradiography the distributions of anti-CEA antibody were heterogeneous and the intensities of binding were various in SNU-C4 and SNU-C5 cell tumors. It is concluded that I-131 labeled tumor-specific monoclonal antibody, anti-CEA antibody is effective in suppressing the xenografted tumor growth and the effect is influenced by sensitivity of tumor cell itself to the radiolabeled antibody and other local factors instead of specificity of antibody.

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Study on Comparison of Ingredient Quantities and Biological Activities of Galgeun-tang according to Extraction Solvent (용매별 갈근탕 추출물의 성분 분석 및 효능 비교)

  • Kim, Ye Ji;Kim, Ohn Soon;Seo, Chang Seob;Lim, Hye Sun;Yoo, Sae Rom;Jeon, Woo Young;Jin, Seong Eun;Shin, In Sik;Kim, Jung Hoon;Shin, Na Ra;Kim, Seong Sil;Lee, Mee Young;Jeong, Soo Jin;Ha, Hye Kyung;Shin, Hyeun Kyoo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.6
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    • pp.908-914
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    • 2012
  • To investigate the difference and change of ingredient and efficacy of Galgeun-tang (GGT) according to extraction solvent, water and 70% EtOH, the quantities of index components and the several in vitro activities of two kinds of GGT extract were compared. The contents of extracts were analyzed with HPLC. The biological activities such as anti-inflammatory and anti-obesity effects were measured through cell line-based in vitro assay. The cytotoxicity was measured by CCK-8 assay in RAW 264.7 cell, BEAS-2B cell, HaCaT cell and 3T3-L1 cell. We compared effects of two kinds of extract by measuring NO, PGE2, IL-6 and TNF-${\alpha}$ in RAW264.7 cell, RANTES in BEAS-2B cell, MDC and RANTES in HaCaT cell and GPDH activity and leptin level in differentiated 3T3-L1. 70% EtOH extract of GGT contained more compositions than water extract. The inhibitory effect of water extract of GGT on NO in RAW 264.7 cell and GPDH activity in 3T3-L1 was stronger than that of 70% EtOH. 70% EtOH has a stronger inhibitory effect on PGE2 in RAW264.7 cell, RANTES in BEAS-2B cell, MDC, RANTES in HaCaT cell, leptin in 3T3-L1 cell than water extraction. These results suggest that the ingredient and efficacy from 70% EtOH extract of GGT are more effective than water extract.

The Anti-inflammatory Effect of Skipjack Tuna (Katsuwonus pelamis) Oil in LPS-induced RAW 264.7 Cells and Mouse Models (LPS 유도 RAW 264.7 세포와 마우스 모델에서 참치(Katsuwonus pelamis) 유의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Min-Ji;Kim, Koth-Bong-Woo-Ri;Ahn, Na-Kyung;Choi, Yeon-Uk;Bark, Si-Woo;Pak, Won-Min;Kim, Bo-Ram;Park, Ji-Hye;Bae, Nan-Young;Ahn, Dong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.43 no.1
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    • pp.45-55
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    • 2015
  • This study was carried out to demonstrate the anti-inflammatory effect of tuna oil (TO) using LPS-induced inflammation responses and mouse models. First, nitric oxide (NO) and pro-inflammatory cytokines levels were suppressed up to 50% with increasing concentrations of TO without causing any cytotoxicity. Also, the expression of a variety of proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB), was suppressed in a dosedependent manner by treatment with TO. Furthermore, TO also inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 protein kinase (p38). Moreover, in in vivo testing the formation of ear edema was reduced at the highest dose tested compared to that in the control, and a reduction of ear thickness and the number of mast cells was observed in histological analysis. In acute toxicity test, no mortalities occurred in mice administrated 5,000 mg/kg body weight of TO over a two-week observation period. Our results suggest that TO has a considerable anti-inflammatory property through the suppression of inflammatory mediator productions and that it could prove to be useful as a potential anti-inflammatory therapeutic material.

The Change in Biological Activities of Brown Rice and Germinated Brown Rice (품종별 현미 발아 전후의 생리활성물질 변화)

  • Kim, Dae-Jung;Oh, Sea-Kwan;Yoon, Mi-Ra;Chun, A-Reum;Choi, Im-Soo;Lee, Dong-Hyun;Lee, Jun-Soo;Yu, Kwang-Won;Kim, Yeon-Kyu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.6
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    • pp.781-789
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    • 2011
  • We studied the biological activities, including antioxidant compounds, antioxidant activities, anti-proliferative activities, and immunological activities of brown rice and germinated brown rice. We examined the DPPH, ABTS radical scavenging activity, and reducing power of 70% ethanol extracts from some cultivars of brown rice and germinated brown rice. The total polyphenol, total flavonoid, and ${\gamma}$-oryzanol contents of the extracts were measured with spectrophotometric methods. The Hongjinjubeyo brown rice and germinated brown rice extracts showed markedly higher antioxidative activity than those of 70% ethanol extracts from other cultivars. The 70% ethanol extracts from brown rice and germinated brown rice had the most effective anti-proliferative activity (cytotoxicity) against breast cancer cells (MCF-7) compared to colorectal cancer cells (HCT-116). A $500\;{\mu}g$/mL concentration of 70% Hongjinjubyeo ethanol extract had higher macrophage and mitogenic activities of immunological activity than other cultivars.

Antitumor and Immuno-potentiating activity against Mouse Sarcoma 180 by Crude Polysaccharides from Fruiting Body of Lentinus giganteus (대향고(Lentinus giganteus)의 자실체에서 추출한 조다당류가 생쥐의 Sarcoma 180에 미치는 항암 및 면역 증강효과)

  • Lee, Geon-Woo;Kim, Hye-Young;Hur, Hyun;Lee, Tae-Soo;Lee, U-Youn
    • The Korean Journal of Mycology
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    • v.36 no.1
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    • pp.75-83
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    • 2008
  • Lentinus giganteus, one of edible and medicinal mushroom belongs to Pleurotaceae of Agaricales, has been known to contain some inhibitive substances on Sarcoma 180 and curative effect on high blood pressure. Neutral saline soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr. NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from fruiting body of the mushroom. In vitro cytotoxicity tests, crude polysaccharides were not cytotoxic against cancer cell lines such as Sarcoma 180 and HepG2 at the concentration of $10{\sim}2,000\;{\mu}g/ml$, but crude polysaccharides from Fr. NaCl was toxic to NIH3T3 at the concentration of $10{\sim}2,000\;{\mu}g/ml$. Intraperitoneal injection with crude polysaccharides showed life prolongation effect of $14.3{\sim}67.5%$ in mice previously inoculated with Sarcoma 180, respectively. Fr. NaCl exhibited the immuno-potentiating activity of B lymphocyte by increasing the alkaline phosphatase activity by $1.53{\sim}1.68$ folds compared with control at the concentration of $50{\sim}200\;{\mu}g/ml$, respectively. The numbers of peritoneal exudate cells and circulating leukocytes were increased by 7.7 and 1.6 folds by injecting Fr. NaCl and Fr. MeOH into the mice at the concentration of 50 mg/ml body weight, respectively.

Studies on Immuno-Modulatory and Antitumor Effects of Crude Polysaccharides Extracted from Fruiting Body of Oudemansiella radicata (민긴뿌리버섯(Oudemansiella radicata)의 자실체로부터 추출한 조다당류의 항암 및 면역 활성 효과에 관한 연구)

  • Kim, Sang-Beom;Lee, Geon-Woo;Lee, U-Youn;Lee, Tae-Soo
    • The Korean Journal of Mycology
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    • v.35 no.2
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    • pp.109-114
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    • 2007
  • Oudemansiella radicata, edible and medicinal mushroom belonging to Agaricales of Basidiomycota, has been known to exhibit outstanding curative effects on the fungal infection and hypertension caused by high blood pressure. Neutral saline soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr, NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from fruiting body of the mushroom. In vitro cytotoxicity test showed that Fr. NaCl was not cytotoxic against NIH3T3 and Sarcoma 180 at the concentration of $10{\sim}1,000\;{\mu}g/ml$. Intraperitoneal injection with Fr. NaCl exhibited antitumor activity with life prolongation effect of $42.9{\sim}66.7%$ in mice inoculated with Sarcoma 180. Fr. NaCl improved the immunopotentiating activity of B lymphocyte by increasing the alkaline phosphatase activity by $1.4{\sim}3$ folds compared with controlled and LPS groups, respectively. Intraperitoneal injection with Fr. MeOH increased the numbers of peritoneal exudate cells and circulating leukocytes by 3.5 and 2.5 folds, respectively. Therefore, the antitumor effect exhibited on mouse Sarcoma 180 cells was likely due to immune-modulating activity of crude polysaccharides extracted from fruiting body of O. radicata.

Studies on Immuno-Modulatory and Antitumor Effects of Crude Polysaccharides Extracted from Paecilomyces sinclairii (매미눈꽃동충하초(Paecilomyces sinclairii)로부터 추출한 조다당류의 면역 활성과 항암 효과에 관한 연구)

  • Shim, Sung-Mi;Im, Kyung-Hoan;Lee, U-Youn;Kim, Jung-Wan;Shim, Mi-Ja;Lee, Min-Woong;Lee, Tae-Soo
    • The Korean Journal of Mycology
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    • v.31 no.3
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    • pp.155-160
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    • 2003
  • Neutral salt soluble [0.9% NaCl (Fr. NaCl)], hot water soluble (Fr. HW) and methanol soluble (Fr. MeOH) materials were extracted from Paecilomyces sinclairii. In vitro cytotoxicity tests. Fr. HW was not cytotoxic against MH3T3, Sarcoma 180 and HepG2 cancer cell lines at the concentration of $0{\sim}2,000\;{\mu}g/ml$, while HT-29 cell line was cytotoxic at the concentration of $100\;{\mu}g/ml$. Fr. NaCl and Fr. MeOH were slightly cytotoxic to the cell lines. Intraperitoneal injection with Fr. NaCl and Fr. MeOH exhibited antitumor activity with life prolongation effect of 32.3% in mice inoculated with Sarcoma 180. Fr. NaCl improved proliferation of spleen cells and the immunopotentiation activity of B lymphocyte by increasing spleen cell numbers and the alkaline phosphatase activity by $2.4{\sim}2.6\;and\;2.7{\sim}3.9$ folds, respectively. Fr. NaCl generated $89\;{\mu}M$ of nitric oxide (NO) when cultured with RAW 264.7, a mouse macrophage cell line, at the concentration of $50\;{\mu}g/ml$, while iipopolysaccharide, a positive control, produced $79\;{\mu}M$. The Fr. NaCl showed the hightest antitumor effect and activation of B lymphocytes and macrophage. From these results, antitumor effect of P. sinclaitii was likely due to immunopotentiation activity.

The Comparative Understanding between Red Ginseng and White Ginsengs, Processed Ginsengs (Panax ginseng C. A. Meyer) (홍삼과 백삼의 비교 고찰)

  • Nam, Ki-Yeul
    • Journal of Ginseng Research
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    • v.29 no.1
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    • pp.1-18
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    • 2005
  • Ginseng Radix, the root of Panax ginseng C. A. Meyer has been used in Eastern Asia for 2000 years as a tonic and restorative, promoting health and longevity. Two varieties are commercially available: white ginseng(Ginseng Radix Alba) is produced by air-drying the root, while red ginseng(Ginseng Radix Rubra) is produced by steaming the root followed by drying. These two varieties of different processing have somewhat differences by heat processing between them. During the heat processing for preparing red ginseng, it has been found to exhibit inactivation of catabolic enzymes, thereby preventing deterioration of ginseng quality and the increased antioxidant-like substances which inhibit lipid peroxide formation, and also good gastro-intestinal absorption by gelatinization of starch. Moreover, studies of changes in ginsenosides composition due to different processing of ginseng roots have been undertaken. The results obtained showed that red ginseng differ from white ginseng due to the lack of acidic malonyl-ginsenosides. The heating procedure in red ginseng was proved to degrade the thermally unstable malonyl-ginsenoside into corresponding netural ginsenosides. Also the steaming process of red ginseng causes degradation or transformation of neutral ginsenosides. Ginsenosides $Rh_2,\;Rh_4,\;Rs_3,\;Rs_4\;and\;Rg_5$, found only in red ginseng, have been known to be hydrolyzed products derived from original saponin by heat processing, responsible for inhibitory effects on the growth of cancer cells through the induction of apoptosis. 20(S)-ginsenoside $Rg_3$ was also formed in red ginseng and was shown to exhibit vasorelaxation properties, antimetastatic activities, and anti-platelet aggregation activity. Recently, steamed red ginseng at high temperature was shown to provide enhance the yield of ginsenosides $Rg_3\;and\;Rg_5$ characteristic of red ginseng Additionally, one of non-saponin constituents, panaxytriol, was found to be structually transformed from polyacetylenic alcohol(panaxydol) showing cytotoxicity during the preparation of red ginseng and also maltol, antioxidant maillard product, from maltose and arginyl-fructosyl-glucose, amino acid derivative, from arginine and maltose. In regard to the in vitro and in vivo comparative biological activities, red ginseng was reported to show more potent activities on the antioxidant effect, anticarcinogenic effect and ameliorative effect on blood circulation than those of white ginseng. In oriental medicine, the ability of red ginseng to supplement the vacancy(허) was known to be relatively stronger than that of white ginseng, but very few are known on its comparative clinical studies. Further investigation on the preclinical and clinical experiments are needed to show the differences of indications and efficacies between red and white ginsengs on the basis of oriental medicines.

The protective effects of monoclonal antibodies in mice from Naegleyia fowleri infection (마우스에서 Naegleria fowleri감염에 대한 단세포를 항체의 영향)

  • So, Ui-Yeong;Sin, Ho-Jun;Im, Gyeong-Il
    • Parasites, Hosts and Diseases
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    • v.30 no.2
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    • pp.113-124
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    • 1992
  • Protective effects of monoclonal antibodies against n. fowleri were comparatively studied. nALB/c mice were treated with two types of monoclonal antibodies, Nf 2 and Nf 154, before and after the infection with N. fowleri. The mortality and mean survival times were then compared. Also, direct effect of the monoclonal antibodies on the N. fewleri trophozoites in vitro were observed. In vitro protective effects of the monoclonal antibodies were also studied in cells infected with N. fowleri. The observed results are summarized as follows: 1. Among mice pretreated twice before the infection with monoclonal antibody Nf 2 (McAb Nf 2), only 15.8% were killed, and the mean survival time was 17, 7 days. This was not much different from the mice pretreated once, as the mortality and mean survival time were 16.7% and 17 days. Those effects were compatible with monoclonal antibody Nf 154 (McAb Nf 154). The above findings contrast with the mortality and mean survival time of the control mice, which were 22.7% and 14.6 days respectively. 2. Mice which received twice the McAb Nf 2 following N. fowleri infection incurred a 19.4% mortality rate with 13.6 days survival time; 17.9% and 15.8 days with on time administration, in contrast to the 25% and 14.6 days in the control group. 3. Marked agglutination effect of McAb Nf 2 or McAb Nf 154 were observed on n. fowkwi, trophogoites. 4. When N, fowleri trophozoites were treated with McAb Nf 2 or McAb Mf 154 combined with comments, the proliferation rate was more significantly suppressed than in that the control, 5. N. fowleri trophozoites treated with McAb Nf 2 or McAb Nf 154 showed an increased number of swollen mitochondria, disfigured cisternal, lipid droplets, and osmiophilic granules in the cytoplasm. 6. A remarkable protective effect of monoclonal antibodies was noticed in CHO cells infected with N. fowleri. More than 90.6% of the infected CHO cells survived, contrasted with 27% of untreated cells. The overall results in this study suggest that N. fewleri treated with monoclonal antibodies against N. fowleri reduce the mortality and prolong the survivial time of the mice when the antibodies are administered before the infection. The protective effect of the monoclonal antibodies is surmised being caused by agglutination of the trophozoites.

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Herpes Simplex Virus Thymidine Kinase Gene Therapy Delivered by Retroviral or Adenoviral Vector in Mouse Model of Lewis Lung Carcinoma (Lewis 폐암 마우스 모델에서 Retroviral Vector나 Adenoviral Vector로 이입된 Herpes Simplex Virus Thymidine Kinase 유전자치료)

  • Kwon, Hee-Chung;Jeong, Jae-Min;Kim, Jung-Hyeon;Ham, Yong-Ho;Seo, Ji-Sook;Lee, Ki-Ho;Kim, Chang-Min;Lee, Han-Soo;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.3
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    • pp.298-309
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    • 2000
  • Background : The antitumor effects of herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategies for cancer gene therapy have a the following advantages : 1) a direct cytotoxicity to HSV-tk modified cancer cells by GCV 2) a cell death by the local transfer of toxic metabolites from the HSV-tk modified cells to nearby unmodified tumor cells (bystander effect), and 3) in vivo bystander effect such as antitumor-immunity. Retroviral and adenoviral sequences can silence transgene expression in cells and mice. In this study, we investigated the above described advantages of HSV-tk/GCV strategy in Lewis lung cell and mouse lung cancer model using retroviral vector and adenoviral vector. Also, we observed whether the expression of a silenced gene can be reactivated by treating cells with butyrate. Methods : Retrovirus-HSV-tk and adenovirus-HSV-tk vectors were used for the transduction of Lewis lung carcinoma (LLC) cells. The change of HSV-tk expression by butyrate was measured by Western blol The antitumor activities containing bystander effect were observed in vivo (by MTT assay) and in vivo tumor models of various combinations of LLC and LLC-tk. Results : 1. Butyrate induced the enhancement of HSV-tk expression from adenovirally transduced cells but not from retrovirally transduced cells. 2. Both retrovirus-HSV-tk and adenovirus-HSV-tk vectors with GCV treatment were effective for killing of tumor cell in vitro and suppression of LLC tumorigenicity. Bystander effect was responsible for killing of mixture of LLC-tk and LLC in vitro and in vivo-tumorigenicity model. Conclusion : Butyrate could augment adenovirus-mediated HSV -tk gene expression. Cancer gene therapy with HSV-tk suicide gene by retroviral and adenoviral vector seems to be an effective approach for lung cancer therapy.

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