• 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.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.67-75
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• 2001

Background : Two tumor suppressor genes, p53 and p16, which have different roles in controlling the cell cycle and inducing apoptosis, are frequently inactivated during carcinogenesis including lung cancer. Single tumor suppressor gene therapies using either with p53 or p16 have been studied extensively. However, there is a paucity of reports regarding a combined gene therapy using these two genes. Methods : The combined effect of p53 and p16 gene transfer by the adenoviral vector on the growth of lung cancer cell lines and its interactive mechanism was investigated. Results : An isobologram showed that the co-transduction of p53 and p16 exhibited a synergistic growth in hibitory effect on NCI H358 and an additive effect on NCI H23. Cell cycle analysis demonstrated the induction of a synergistic G1/S arrest by a combined p53 and p16 transfer. This synergistic interaction was again confirmed in a soft agar confirmed in a soft agar clonogenic assay. Conclusion : These observations suggest the potential of a p53 and p16 combination gene therapy as another potent strategy in cancer gene therapy.

• Journal of Chest Surgery
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• v.30 no.7
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• pp.701-707
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• 1997

Although many reseraches have been persued to detect the molecular tumor marker to define the cancer, ideal tumor marker which speak for the characteristics of malignancy and has high sensitivity and specificity is not known. One of the characteristics of the malignant cells is indefinite proliferative potential, in other word, immortality. The expression of telomerase and stabilization of te10meres are con omitant with the attaiunent of immortality in tumor cells; thus the measurement of telomerase activity in clinically obtained tumor samples may provide important information which would be useful as a diagnostic marker to detect immortal cancer cells. Telomerase activity was analyzed in 12 non-small cell . lung cancer cell lines and 41 primary non-small cell lung cancers with the use of a PCR-based assay. All the cell lines and the majority of tumors displayed telomerase activity, but telomerase was not detectable in most of the corresponding pathologically-normal tissues. Telomere length was not correlated with telomerase activity. The present study indicate that measurement of telomerase activity may be useful as a molecular tumor marker in non-small cell lung cancer.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.337-344
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• 2018

Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

• 한국약용작물학회:학술대회논문집
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• 2012.05a
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• pp.305-306
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• 2012

• Tuberculosis and Respiratory Diseases
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• v.50 no.6
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• pp.668-675
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• 2001

Background : Non-smalll lung cancer(NSCLC) develops as a result of the accumulation of multiple genetic abnormalities. Loss of heterozygosity(LOH) is one of the most frequent genetic alterations that is found in NSCLC, and the chromosomal regions that display a high rate of LOH are thought to harbor tumor suppressor genes(TSGs). This study was done to determine the frequency of LOH in 21q with the aim of identifying potential TSG loci. Method : Thirty-nine surgically resected NSCLCs were analysed. Patients peripheral lymphocytes were used as the source of the normal DNA. Five microsatellite Inarkers of 21q were used to study LOH : 21q21.1(D21S1432, and D21S1994); 21q21.2-21.3(D21S1442) ; 21q22.1(21S1445) ; and 21q22.2-22.3(D21S266). The fractional allelic loss(FAL) in a tumor was calculated as the ratio of the number of markers showing LOH to the number of informative markers. Result : LOH for at least one locus was detected in 21 of 39 tumors(53.8%). Among the 21 tumors with LOH, 5(21.8%) showed LOH at almost all informative loci. Although statistically not significant, LOH was found more frequently in squamous cell carcinomas(15 of 23, 65.2%) than in adenocarcinomas(6 of 16, 37.5%). In the squamous cell carcinomas the frequency of LOH was higher in stage II-III (80.0%) than in stage I (53.8%). The FAL value in squamous cell carcinomas($0.431{\pm}0.375$) was significantly higher than that found in adenocarcinomas($0.l92{\pm}0.276$). Conclusion : These results suggest that LOH on 21q may be involved in the development of NSCLC, and that TSG(s) that contribute to the pathogenesis of NSCLC may exist on 21q.

• Journal of Life Science
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• v.34 no.7
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• pp.520-530
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• 2024

Tumor suppressor genes (TSGs) play a crucial role in maintaining cellular homeostasis. When the function of these genes is lost, it can lead to cellular plasticity that drives the development of various cancers, including small-cell lung cancer (SCLC), which is known for its aggressive nature. SCLC is primarily driven by numerous loss-of-function mutations in TSGs, often involving genes that encode epigenetic regulators. These mutations pose a significant therapeutic challenge as they are not directly targetable. However, understanding the molecular changes resulting from these mutations might provide insights for developing tumor intervention strategies. We propose that despite the heterogeneous genomic landscape of SCLC, the effects of mutations in patient tumors converge on a few critical pathways that drive malignancy. Specifically, alterations in epigenetic regulators lead to transcriptional dysregulation, pushing mutant cells toward a highly plastic state that makes them immune evasive and highly metastatic. This review will highlight studies showing how an imbalance of epigenetic regulators with opposing functions leads to the loss of immune recognition markers, effectively hiding tumor cells from the immune system. Additionally, we will discuss the role of epigenetic regulators in maintaining neuroendocrine features and how aberrant transcriptional control promotes epithelial-to-mesenchymal transition during tumor development. Although these pathways seem distinct, we emphasize that they often share common molecular drivers and mediators. Understanding the connection among frequently altered epigenetic regulators will provide valuable insights into the molecular mechanisms underlying SCLC development, potentially revealing preventive and therapeutic vulnerabilities for SCLC and other cancers with similar mutations.

• Journal of Chest Surgery
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• v.29 no.11
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• pp.1223-1231
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• 1996

Immunohistochemical stains for RB and p53 tumor suppressor gene products were performed on 72 cases of resected primary lung cancer tissues to study the correlation between their expressions and the histologic types, the clinical stage, and the survival rate. The results were as follows. 1. The RB protein was altered or absent in 38 cases (52.8%), and the mutant p53 protein was detected in 35 cases (48.6%). 2. The incidences of RB and p53 protein expression were significantly different among the histologic types (p＜0.05) but were not correlated with the clinical stages of lung cancer (p＞0.05). 3. The two year survival rate of patients with alteration of both RB and p53 genes (RB-/p53＋) was 22. 4%, and that with no alteration of both genes (RB+/p53-) was 63.1%. This difference was statistically significant (p=0.01). 4. It was shown that alteration of RB protein greatly affects the prognosis of lung carcinoma by multivariate analysis of prognostic factors. The presence or absence of RB and mutant p53 protein in tumor cells is closely related to the survival of primary lung cancer patients, and it is suggested that RB gene expression is an independent prognostic factor of primary lung cancer.

• Journal of Life Science
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• v.28 no.6
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• pp.718-725
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• 2018

Toll-like receptor 4 (TLR4) has been implicated in cell proliferation and apoptosis in several types of cancer. In this study, the impact of TLR4 activation on apoptotic cell death in gynecologic cancers induced by lipopolysaccharide (LPS) was investigated. Cervical cancer cell lines were produced from isolated surgical specimens supplied by Paik Hospital. The primary cultures of normal myometrium and gynecologic cancers, including cervical, endometrial, and ovarian cancers, were used to examine the differences in morphological characteristics between normal and cancerous cells. A reverse transcription polymerase chain reaction analysis was used to determine the relative expression levels of TLR4 gene involved in apoptosis-associated signaling in cervical cancer cells. The cancer cell colonies showed a tendency to reach high levels of confluency compared with normal cells. In addition, an enhanced growth rate and loss of contact inhibition were observed in gynecologic cancer cells compared with normal cells (doubling times of 16.6 hr vs. 26 hr, respectively). The expression level of ITGA5, an alpha-5 integrin marker, was upregulated in normal myometrial cells, but this tendency was not exhibited in cervical cancer cells. Furthermore, p53 tumor suppressor gene expression was upregulated, whereas TLR4 and caspase-3 gene expressions were downregulated in cervical cancer cells. Notably, the expression levels of TLR4 and caspase-3 were increased significantly in LPS-treated cancer cells compared with those in non-LPS-treated cells. These results suggest that the TLR4-mediated caspase-dependent apoptotic signaling pathway could be suggested as a therapeutic target for the treatment of gynecologic cancers, including cervical cancers.

• Journal of Chest Surgery
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• v.43 no.6
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• pp.588-595
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• 2010

Background: Base on types of tumor, the types of expressed tumor is diverse and the difference in its expression rate is even more various. Due to such reasons an animal model is absolutely needed for a clinical research of lung cancer. The author attempted oncogenesis by cultivating a cell line of non-small cell carcinoma and then injecting it inside thoracic cavities of nude mice. The author conducted quantitative analyses of HER2/neu tumor gene - an epidermal growth factor receptor (EGFR) related to lung cancer, and TGF-${\beta}_1$, which acts as a resistance to cell growth inhibition and malignant degeneration. In order to investigate achievability of the oncogenesis, histological changes and the expression of cancer gene in case of orthotopic lung cancer is necessary. Material and Method: Among 20 immunity-free male BALB/c, five nude mice were selected as the control group and rest as the experimental group. Their weights ranged from 20 to 25 gm (Orient, Japan). After injection of lung cancer line (SW900 G IV) into the pleural cavity of nude mice, They were raised at aseptic room for 8 weeks. HER2/neu was quantitatively analyzed by separating serum from gathered blood via chemiluminiscent immunoassay (CLIA), and immunosandwitch method was applied to quantitatively analyze TGF-${\beta}_1$. SPSS statistical program (SPSS Version 10.0, USA) was implemented for statistical analysis. Student T test was done, and cases in which p-value is less than 0.05 were considered significant. Result: Even after lung cancer was formed in the normal control group or after intentionally injected lung cancer cell line, no amplification of HER2/neu gene showed reaction. However, the exact quantity of TGF-${\beta}_1$ was $28,490{\pm}8,549pg/mL$, and the quantity in the group injected with lung cancer cell was $42,362{\pm}14,449pg/mL$, meaning 1.48 times highly Significant (p<0.483). It proved that HER2/neu gene TGF-${\beta}_1$ had no meaningful interconnection. Conclusion: TGF-${\beta}_1$ gene expressed approximately 1.48 times amplification in comparison to the control group. The amplification of TGF-${\beta}_1$ meant somatic recuperation inhibition mechanism due to carcinogenesis in nude mice was definitely working. It may be implemented as a quantitative analysis that allows early detection of lung cancer in human body.