• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.9039-9043
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• 2014

There is a continuing need for innovative alternative therapies for liver cancer. DNA vaccines for hormone/growth factor immune deprivation represent a feasible and attractive approach for cancer treatment. We reported a preventive effect of a DNA vaccine based on six copies of the B cell epitope GRP18-27 with optimized adjuvants against H22 hepatocarcinoma. Vaccination with pCR3.1-VS-HSP65-TP-GRP6-M2 (vaccine) elicited much higher level of anti-GRP antibodies and proved efficacious in preventing growth of transplanted hepatocarcinoma cells. The tumor size and weight were significantly lower (p<0.05) in the vaccine subgroup than in the control pCR3.1-VS-TP-HSP65-TP-GRP6, pCR3.1-VS-TP-HSP65-TP-M2 or saline subgroups. In addition, significant reduction of tumor-induced angiogenesis associated with intradermal tumors of H22 cells was observed. These potent effects may open ways towards the development of new immunotherapeutic approaches in the treatment of liver cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.265-271
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• 2014

Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.3
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• pp.177-185
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• 2010

Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.

• Journal of the Korean Chemical Society
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• v.34 no.4
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• pp.331-339
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• 1990

It has been studied that relations between electronic structure and anti-tumor activity by variation of amine group in cis-diamminedichloroplatinum (Ⅱ) complexes. We were also interested in these Pt (Ⅱ) complexes interaction with 1-methylcytosine of DNA base and the electronic structure of these complexes in order to understand the mechanism of the metal-nucleobases interaction. The results showed that net charge of center metal in Pt complexes effect anti-tumor activity. The mechanisgm of the bonding between metal and ligands largely based on charge transfer from ligand to metal atom. Furthermore, the established molecular orbitals showed that metal 6p-orbitals played an important role in the bonding scheme for the interactions between platinum (Ⅱ) complexes and 1-methylcytosine. We also found that the stronger Pt-N3 bonding strength became, the better anti-tumor agents were.

• Bulletin of the Korean Chemical Society
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• v.32 no.3
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• pp.947-955
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• 2011

The complexes [Pd(bpy)(Hex-dtc)]$NO_3$ and [Pt(bpy)(Hex-dtc)]$NO_3$ (bpy is 2,2'-bipyridine and Hex-dtc is hexyldithiocarbamato ligands) were synthesized and characterized by elemental analysis and spectroscopic studies. The cytotoxicity assay of the complexes has been performed on chronic myelogenous leukemia cell line, K562, at micromolar concentration. Both complexes showed cytotoxic activity far better than that of cisplatin under the same experimental conditions. The binding parameters of the complexes with calf thymus DNA (CT-DNA) was investigated using UV-visible and fluorescence techniques. They show the ability of cooperatively intercalating in CT-DNA. Gel filtration studies demonstrated that platinum complex could cleave the DNA. In the interaction studies between the Pd(II) and Pt(II) complexes with CT-DNA, several binding and thermodynamic parameters have been determined, which may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.

• Natural Product Sciences
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• v.23 no.4
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• pp.281-285
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• 2017

The purpose of this study was to confirm the anti-tumor activity of an ethanol extract of Saussurea laniceps against pancreatic tumor and to isolate the active compound from S. laniceps extract. Treatment with S. laniceps extract and hispidulin inhibited proliferation of pancreatic cell lines, such as Capan-1, Capan-2, Panc-1 and S2-013 in a dose-dependent manner using the hollow fiber assay. Hispidulin showed typical hallmarks of apoptotic cell death a significant anti-tumor activity on Capan-2 cells at a dose of 100 mg/kg and 200 mg/kg. S. laniceps has potential cytotoxic and apoptotic effects on human pancreatic carcinoma cells. Its mechanism of action might be associated with the apoptotic cell death through DNA fragmentation.

• Bulletin of the Korean Chemical Society
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• v.33 no.2
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• pp.651-656
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• 2012

Cationic immunoliposomes were prepared by conjugation of Fab' fragments of the recombinant humanized monoclonal antibody (HuCC49) against tumor-associated glycoprotein (TAG)-72 to sterically unilamella liposomes. The cationic immunoliposomes are composed of cationic lipid (O,O'-dimyristyl-N-lysyl aspartate, DMKD), cholesterol, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethyleneglycol)$_{2000}$] (DPPE-PEG-maleimide) with a molar ratio of 0.5:0.47:0.03. Plasmid DNA was effectively condensed by addition of transferrin (Tf) during the formation of anti-TAG-72 PEG-immunolipoplexes (PILPs). These anti-TAG-72 PILPs were able to adhere to the surface of TAG-72-overexepressing LS174T human colon cancer cells more effectively than conventional liposomes, thereby facilitating gene delivery in vitro. Furthermore, intravenous administration of the anti-TAG-72 PILPs into the tumor-carrying mice exhibited efficient localization of the reporter gene in the tumor tissues.

• Biomedical Science Letters
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• v.25 no.4
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• pp.398-406
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• 2019

Cancer immunotherapy using gene-modified tumor cells is safe and customized cancer treatment method. In this study, we made gene-modified tumor cells by transferring costimulatory molecules, 4-1BBL and OX40L, into tumor cells using lentivirus vector, and identified anti-cancer effect of gene-modified tumor cells in CT26 mouse colorectal tumor model. We construct pLVX-puro-4-1BBL, -OX40L vector for lentivirus production and optimized the transfection efficiency and transduction efficiency. The transfection efficiency is maximal at DNA:cationic polymer = 1:0.5 and DNA 2 ㎍ for lentivirus production. Then, the lentiviral including 4-1BBL and OX40L was used to deliver CT26 mouse tumor cells to establish optimal delivery conditions according to the amount of virus. The transduction efficiency is maximal at 500 μL volume of lentiviral stock without change in cell shape or growth rate. CT26-4-1BBL, CT26-OX40L significantly inhibited the tumor growth compare with CT26-WT or CT26-β-gal cell line. These data showed the possibility the use of genetically modified tumor cells with costimulatory molecule as cancer immunotherapy agent.

• Biomedical Science Letters
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• v.29 no.4
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• pp.280-286
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• 2023

In humic substances, fulvic acid (FA) is a subclass of diverse compounds known as humic substances, which are by-products of organic degradation from microorganisms. FA can suppress the proliferation of tumor cells. Despite numerous studies, the exact mechanism for the various effects of FA is not clearly understood. Based on results demonstrating anti-proliferation effects on human cancer, we investigated whether FA has similar effects on lung cancer in this study. Firstly, the anti-cancer effect of FA in pulmonary epithelial tumor cell lines (TC-1 cells) was examined by confirming its inhibitory effect on the cell proliferation of TC-1 cells. TC-1 cell proliferation was reduced by FA on a dose-dependent and time-dependent manner. After 24 hours of FA treatment, cell morphological changes such as cell volume decrease, non-adherence and increased number of apoptotic cells were clearly observed. In addition, FA induced a DNA ladder pattern by increased of DNA fragments in TC-1 cells. In the intracellular regulatory pathway by FA, we confirmed that FA induced the reduction of the anti-apoptotic protein, Bcl-2 protein levels. These results indicate that FA has anticancer effect by inducing intracellular apoptotic pathway. Further research on the mechanism of anticancer effects will be basic data for the development of potential anticancer drugs.

• BMB Reports
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• v.56 no.11
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• pp.612-617
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• 2023

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.