• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.161-171
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• 1999

Background: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-$\alpha$, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules. Methods: Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-$\alpha$, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin. In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were oberved in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF-$\alpha$ increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues. Conclusions: These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may playa role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF-$\alpha$ may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.

• Biomedical Science Letters
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• v.30 no.2
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• pp.37-48
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• 2024

Liposomes are one of the most actively studied and promising drug delivery systems for the treatment of various diseases. In this study, an aptamer-conjugated liposome called "aptamosome" was used, in which an anti-PD-L1 aptamer targeting cancer cells was conjugated to the liposome. These aptamosomes showed remarkable cellular uptake and efficient delivery to Lewis lung carcinoma 2 (LL/2) cancer cells. In addition, suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), was delivered through this aptamer to induce a strong anticancer immunotherapeutic effect. The results of this study showed that when LL/2 cells were treated with SAHA-entrapped aptamosome [SAHA] and liposome [SAHA] and free SAHA, aptamosome [SAHA] improved cell death compared with that of liposomes [SAHA] or free SAHA, and it has demonstrated anticancer efficacy. Moreover, aptamosome [SAHA] induce the secretion of chemokines that promote the migration of activated T cells into tumor tissues. Finally, in vivo experiments showed that aptamosome [SAHA] significantly inhibited the growth rate of LL/2 tumors. Therefore, liposomes combined with an anti-PD-L1 aptamer for efficient SAHA delivery are suggested as an excellent model for drug delivery systems suitable for targeting cancer cells.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.299-304
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• 2023

This study sought to evaluate the anticancer effects of Crataegus pinnatifida Bunge root extract (CPE) on murine Lewis lung carcinoma cells (LLC1) in vitro. CPE treatment (2.5, 5, 10 ㎍/mL, 24 h) of LLC cells led to a dose-dependent decrease in cell viability, while CPE treatment did not have a cytotoxic effect on non-cancer cells (NIH/3T3). CPE affects LLC by flipping the plasma membrane and making the membrane more permeable; by flow cytometry, CPE-induced annexin V and propidium iodide positivity, indicating induction of apoptosis in LLC cells. In addition, CPE enhanced the expression of apoptotic proteins caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1). CPE upregulated the proapoptotic protein BCL-2-associated X while downregulating the anti-apoptotic protein B-cell lymphoma 2 (BCL-2), suggesting that CPE induces apoptosis via the mitochondrial pathway. Furthermore, CPE upregulated the phosphorylation of the mitogen activated protein kinase p38. In conclusion, the results suggest that CPE has an anticancer effect in LLC cells by inducing apoptosis via p38.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.135-146
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• 2001

Background : One of the important mechanisms responsible for a tumor escaping the immune response is an absence of the tumor associated antigen (TAA) on the cancer cell surface. To overcome this, combination gene therapy using a herpes simplex thymidine kinase (HSTK) gene, prototype of drug sensitizing gene, was conducted to enhance T AA release by cell destruction, as well as the cytokine genes for immune cell attraction. Methods : We investigated whether or not transduction with the adenovirus-HSTK (Ad-HSTK) enhanced the sensitivity of Lewis lung carcinoma (LLC) to ganciclovir (GCV) and induced a bystander effect. A Tumor vaccine trial was performed using LLC with ad-HSTK$\pm$ad-GM-CSF$\pm$ad-IL-2 to determine if they exhibit some antitumor effect on established lung cancer xenografts. Results : LLC with ad-HSTK revealed a much higher sensitivity to ganciclovir (GCV). LLC transduced with ad-HSTK and/or ad-IL-2, ad-GM-CSF showed a lower in vivo tumorigenicity. In the treatment experiment, vaccination with LLC transduced with ad-HSTK, ad-IL-2, or ad-GM-CSF alone modestly suppressed the growth of an established tumor. Combined transduction with HSTK and GM-CSF induced stronger growth suppression of a established lung cancer, while HSTK and IL-2 combination transduction did not have any antitumor effect on individual transduction. Vaccination with LLC-HSTK-GM-CSF increased the infiltration of dendritic cells in the spleen. Conclusion : It was concluded that a tumor vaccine transduced with HSTK and GM-CSF induces strong antitumor immunity by activating the dendritic cells.

• BMB Reports
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• v.56 no.7
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• pp.404-409
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• 2023

This study investigates the relationship between cancer cachexia and the gut microbiota, focusing on the influence of cancer on microbial composition. Lewis lung cancer cell allografts were used to induce cachexia in mice, and body and muscle weight changes were monitored. Fecal samples were collected for targeted metabolomic analysis for short chain fatty acids and microbiome analysis. The cachexia group exhibited lower alpha diversity and distinct beta diversity in gut microbiota, compared to the control group. Differential abundance analysis revealed higher Bifidobacterium and Romboutsia, but lower Streptococcus abundance in the cachexia group. Additionally, lower proportions of acetate and butyrate were observed in the cachexia group. The study observed that the impact of cancer cachexia on gut microbiota and their generated metabolites was significant, indicating a host-to-gut microbiota axis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.1
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• pp.1-6
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• 2022

The tuber of Pinellia ternata (Thunb.) Brei (TPT) used in traditional Oriental medicine for the treatment of cough, sputum, vomiting, and insomnia, possesses antioxidant, antibacterial, and anti-inflammatory effects. Although recent studies have reported the anticancer effects of TPT in several cancer cells, it is still unclear whether TPT regulates tumor-associated macrophage (TAM) characterized by the immunosuppressive M2 macrophage phenotype. Our results showed that the ethanol extract of TPT (ETPT) suppressed the migration of RAW264.7 mouse macrophage cells and THP-1 human monocytes differentiated into macrophages towards the conditioned media (CM) collected from lung cancer cells, suggesting that ETPT would attenuate the recruitment of macrophages into tumors. In addition, ETPT suppressed the interleukin (IL)-4 or IL-6-induced M2 macrophage polarization in RAW264.7 cells. ETPT treatment not only downregulated the mRNA expression of M2 macrophage markers including arginase-1, mannose receptor C type 1 (MRC-1), and IL-10, but also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and STAT6, general regulators of M2 macrophage polarization. Finally, the transwell assay results showed that the CM from M2-polarized RAW264.7 cells increased the migration of mouse lewis lung carcinoma (LLC) cells, while those from RAW264.7 cells co-treated with ETPT and IL-6 significantly reduced the migration of LLC cells. Taken together, our observations clearly demonstrate that ETPT suppressed the cancer cell migration by regulating macrophage recruitment and M2 macrophage polarization.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.990-994
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• 2004

Cancer is an intractable disease for humans to overcome. Recently natural products or Oriental prescriptions have been on the spotlight to develop anticancer agents with little side-effects and good efficacy. KamikeKyuktang has been used for the treatment of cancer in Oriental medicine. However, its anti-cancer mechanism still remains unclear. KMKKTE is an ethanol extract of KamikeKyuktang composed of 12 medicinal herbs. Anti-proliferative effects of KMKKT was investigated on Lewis lung carcinoma cell (LLC) and A549 (human lung cancer cells). Half-maximal inhibition of the LLC and A549 cell proliferation by KMKKTE was found approximately 125㎍/㎖ and 250㎍/㎖, respectively. It also effectively inhibited the proliferation of HUVEC cells treated by bFGF and VEGF up to 30% of control at 125㎍/㎖ and the cell migration to 80% at 25 ㎍/㎖ in concentration dependent manner. Tube formation of HUVEC cells on matrigel also was significantly suppressed from 25㎍/㎖ of KMKKTE. Taken together, these results demonstrate that KMKKTE has antiangiogenic activity and be applied to angiogenesis dependent cancers.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.354.2-354.2
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• 2002

Fifty of 3.4-diaryl-2(5H)-furanone derivatives were synthesized and evaluated for their cytotoxicity in a small panel of cancer cell lines. Eleven compounds in this series, were found to have significant cytotoxic activities with ED$_{50}$ values of less than 1 4{\mu}$M in most of the cell lines tested. Compound RTMSI, 3-(3.4, 5-trimethoxyphenyl)-4-(3-amino-4-methylamino)-2(5H)-furanone exhibited the most potent cytotoxic activity with ED$_{50}$ value of 0.003 4{\mu}$M and antitumor activity on BDF1 mice bearing Lewis lung carcinoma cells with inhibition ratio of 72 %.%.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.199-199
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• 1994

Thioglycerol과 glycerol로부터 rac-1-S-octa-decyl-2-O-palmitoyl-1-S-thioglycerol-3-phosphate (DL -PTBA-P)와 rac-1-O-octadecyl-2-O-palmitoyl-g1ycerol-3-phosphate (DL-PBA-P)등을 합성하였고, 이들에 ara-C 유도체인 ara-CMP morpholidate를 반응시켜 최종 산물인 ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara-CDP-DL-PTCA 및 ara-CDP-DL-PTBA등을 합성하였다. 이들 최종산믈의 항암효과는 L1210 lymphoid leukemia, colon 26 carcioma, M5076 sarcoma, C-1300 neuroblastoma, 3-Lewis lung carcinoma, WEHI-3B leukemia, human colon cancer, hum an pancreatic cancer 등의 암세포주를 사용하여 실험하였다. L1210를 DB/2J의 뇌막 또는 복강, DBA/1J의 복강내에 이식하여 ara-C, Ehss thioether lipid의 ara-C 유도체 (ara-CDP-L-DP, ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara -CDP-DL-PTCA, ara-CDP-D-PTBA, ara-CDP-L-PTBA, ara-CDP-DL-PTBA)를 단일 투여 또는 중복 투여하였고, 3-Lewis는 C57BL/6 의 발바닥 피하, colon26은 BALB/C의 견갑상부 히아조직, M5076은 C57BL/6의 피하, WEHI-3B는 BALB/C의 복강, C-1300는 A/strong Ros에 각각 이식한 후 ara-C 또는 ara-CDP-DL-PTBA를 단일 또는 중복 투여하였다.

• Nutrition Research and Practice
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• v.18 no.4
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• pp.451-463
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• 2024

BACKGROUND/OBJECTIVES: The umami taste receptor (TAS1R1/TAS1R3) is endogenously expressed in skeletal muscle and is involved in myogenesis; however, there is a lack of evidence about whether the expression of the umami taste receptor is involved in muscular diseases. This study aimed to elucidate the effects of the umami taste receptor and its mechanism on muscle wasting in cancer cachexia using in vivo and in vitro models. MATERIALS/METHODS: The Lewis lung carcinoma-induced cancer cachexia model was used in vivo and in vitro, and the expressions of umami taste receptor and muscle atrophy-related markers, muscle atrophy F-box protein, and muscle RING-finger protein-1 were analyzed. RESULTS: Results showed that TAS1R1 was significantly downregulated in vivo and in vitro under the muscle wasting condition. Moreover, overexpression of TAS1R1 in vitro in the human primary cell model protected the cells from muscle atrophy, and knockdown of TAS1R1 using siRNA exacerbated muscle atrophy. CONCLUSION: Taken together, the umami taste receptor exerts protective effects on muscle-wasting conditions by restoring dysregulated muscle atrophy in cancer cachexia. In conclusion, this result provided evidence that the umami taste receptor exerts a therapeutic anti-cancer cachexia effect by restoring muscle atrophy.