• Journal of Microbiology and Biotechnology
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• v.12 no.5
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• pp.711-715
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• 2002

Telomerase adds telomeric repeats to chromosomal ends and is known to play an important role in carcinogenesis through cellular immortalization. Since telomerase is an essential pathogenomic factor in malignant tumors, inhibiting telomerase activity is thought to be possible to make telomerase positive tumors more sensitive to cisplatin treatment, which is effective in ovarian cancers, but clinical success Is limited by chemo-resistance. In the present study, cisplatin-sensitive ovarian cancer cell line A2780 and cisplatin-resistant A2780/cp70 cell line were infected with antisense telomerase adenovirus Ad-OA. It was found that the Ad-OA suppressed ovarian cancer cell growth and this effect was mainly due to the induction of caspase-dependent apoptosis. Next, we infected the cisplatin resistant ovarian cancer cell line A2780/ cp70 with Ad-OA and cisplatin concurrently. Interestingly, cisplatin treatment with Ad-Oh was more effective to cisplatin-induced cell death in A2780/cp70 cells compared to cisplatin or the vector group only. These data suggest that cisplatin treatment with Ad-OA may be a new chemo-sensitizer for cisplatin resistant ovarian cancer.

• Korean Journal of Clinical Pharmacy
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• v.23 no.3
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• pp.213-222
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• 2013

Purpose: The aim of this study was to investigate the current state of antidepressant prescriptions in breast cancer patients and factors affecting the prescription of antidepressants. Methods: This study targeted female breast cancer patients who were prescribed antidepressants by a psychiatrist at least once between August 2010 and July 2011 at the Asan Medical Center in Seoul. The prescription history of each study subject was investigated to analyze the current state of antidepressant prescriptions in breast cancer patients. Results: The analysis of the prescription histories of 136 subjects in the antidepressant group determined that escitalopram, mirtazapine, and trazodone were the three most commonly prescribed medications with an average of 1.54 antidepressants prescribed per patient. A logistic regression analysis showed a statistically significant increase in antidepressant prescriptions in patients who were divorced or widowed, had sleep disturbances, or had undergone oncologic surgery for the breast cancer (p<0.050). In contrast, the prescription rate was lower for patients with tumour sizes greater than 50 mm (p<0.050). Conclusion: The sociodemographic factor of marital status, clinical factors of sleep disorders and tumour size, and a treatment-specific factor of the use of surgical therapy were identified as affecting the prescription of antidepressants in female breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.703-712
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• 2016

Monoclonal antibodies with specific antigens have been widely used as targeted therapy for cancer. Hep88 mAb is a monoclonal antibody which shows specific binding with anti-cancer effects against the HepG2 cell line. However, its mechanisms of action are still not completely understood. We examined cell cycling and apoptosis by flow cytometry and mRNA expression of factors involved in apoptosis and paraptosis in Hep88 mAb-treated HepG2 cells by real-time PCR. The cell-cycle analysis demonstrated that growth-inhibitory activity was associated with G2/M cell cycle arrest. Hep88 mAb induced a significant increase in apoptotic cell populations in a dose- and time-dependent manner. The mRNA expression results also suggested that the process triggered by Hep88 mAb involved up-regulation of tumor suppressor p53, pro-apoptotic Bax, Cathepsin B, Caspase-3 and Caspase-9, with a decrease of anti-apoptotic Bcl-2 - thus confirming paraptosis and apoptosis programmed cell death. These findings represent new insights into the molecular mechanisms underlying the anti-cancer properties of Hep88 mAb in liver cancer cells.

• Biomedical Science Letters
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• v.20 no.2
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• pp.85-95
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• 2014

Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the head and neck tumors. To investigate the mechanism of antiproliferation to EGFR inhibition in oral cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$). We have demonstrated that ZD1839 induces growth arrest and apotosis in oral cancer cell lines by independent of EGFR-mediated signaling. An exposure of oral cancer cells to ZD1839 resulted in a dose dependent up-regulation of the cyclin-dependent kinase inhibitor p21 and p27, down regulation of cyclin D1, inactivation of GSK-$3{\beta}$ and of active MAPK. In resistant cells, GSK-$3{\beta}$ is constitutively active and its activity is negatively regulated primarily through Ser 9 phosphorylation and further enhanced by Tyr216 phosphorylation. These results showed that the resistance to the antiproliferative effects of ZD1839, in vitro was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-$3{\beta}$ activation and degradation of its target cyclin D1 were indicators of high cell sensitivity to ZD1839. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in oral cancer.

• Journal of Gastric Cancer
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• v.19 no.4
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• pp.375-392
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• 2019

Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.

• Journal of Life Science
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• v.32 no.1
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• pp.63-69
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• 2022

The thioredoxin reductase (TrxR) system is essential for cell survival and function by playing a pivotal role in maintaining homeostasis of cellular redox and regulating signal transduction pathways. The TrxR system comprises thioredoxin (Trx), TrxR, and nicotinamide adenine dinucleotide phosphate. Trx reduced by the catalytic reaction of the TrxR enzyme reduces downstream proteins, resulting in protection against oxidative stress and regulation of cell differentiation, growth, and death. Cancer cells survive by improving their intracellular antioxidant capacity to eliminate excessively generated reactive oxygen species (ROS) due to infinite cell proliferation and a high metabolic rate. Therefore, cancer cells have high dependence and sensitivity to antioxidant systems, suggesting that focusing on TrxR, a representative antioxidant system, is a potential strategy for cancer therapy. Several studies have revealed that TrxR is expressed at high levels in various types of cancers, and research on anticancer activity targeting the TrxR system is increasing. In this review, we discuss the feasibility and value of the TrxR system as a strategy for anticancer activity research by examining the relationship between the function of the intracellular TrxR system and the development and progression of cancer, considering the anticancer activity and mechanism of TrxR inhibitors.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.1
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• pp.3-8
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• 2019

Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2555-2558
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• 2016

Background: Gastric cancer is the second most common gastrointestinal cancer and is still associated with significant morbidity and mortality due to late presentation and diagnosis at advanced stages. Studies have reported that a variable proportion of gastric cancer is positive for the human epidermal growth factor receptor 2 (HER2) and patients with HER2 positive (HER2 +ve) lesions can benefit from targeted therapy. This study was conducted to assess the prevalence of HER2 +ve gastric cancers in Brunei Darussalam, a developing Southeast Asian nation. Materials and Methods: Patients were identified from the Department of Pathology registry and retrospectively reviewed. HER2 expression was assessed by immunohistochemistry and only those staining 3+were considered positive. Results: Our study included 103 cases (66 males and 37 females) with a mean age of $65.1{\pm}14.8$ years old. There were 14 cases positive for HER2 (10 males and 4 females) giving a prevalence of 13.6%. The HER2 +ve cases were significantly older ($70.6{\pm}19.3$ years old) than the negative cases ($64.2{\pm}13.8$, p=0.041) and had significantly more advanced disease (stages 3 and 4, p=0.026). There were no significant differences in gender distribution, presence of intestinal metaplasia, EBV status, Helicobacter pylori status, tumor location (proximal vs. distal) and degree of tumor differentiation (all p values >0.05). Conclusions: Our study showed that 13.6% of our gastric cancers are positive for HER2, the affected patients being older and having more advanced disease at diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2851-2855
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• 2015

Background: Recent reports have shown that nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), contributes to the precise control of gene expression and is related to several human malignancies. However, limited data are available on the expression and function of NEAT1 in lung cancer. The major objective of the current study was to profile the expression and clinicopathological significance of NEAT1 in non-small cell lung cancers (NSCLCs). Materials and Methods: NEAT1 expression in 125 NSCLC cases and paired adjacent non-cancer tissues was assessed by real-time quantitative reverse transcription-PCR (qRT-PCR). Relationships between NEAT1 and clinicopathological factors were also investigated. Results: The relative level of NEAT1 was $6.98{\pm}3.74$ in NSCLC tissues, significantly elevated as compared to that of the adjacent non-cancer lung tissues ($4.83{\pm}2.98$, p<0.001). The area under curve (AUC) of high expression of NEAT1 to diagnose NSCLC was 0.684 (95% CI: 0.619~0.750, p<0.001). NEAT1 expression was positively correlated with patient age (r=-2.007, p=0.047), lymphatic metastasis (r=-2.731, p=0.007), vascular invasion (r=-3.617, p=0.001) and clinical TNM stage (r=-4.134, p<0.001). Conclusions: This study indicates that NEAT1 might be associated with oncogenesis and progression in NSCLC, and suggests application in molecular targeted therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2793-2800
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• 2015

In molecular-targeted cancer therapy, acquired resistance to gemcitabine is a major clinical problem that reduces its effectiveness, resulting in recurrence and metastasis of cancers. In spite of great efforts to reveal the overall mechanism of acquired gemcitabine resistance, no definitive genetic factors have been identified that are absolutely responsible for the resistance process. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets for cancer cell lines with acquired gemcitabine resistance, using the R-based RankProd algorithm, and were able to identify a total of 158 differentially expressed genes (DEGs; 76 up- and 82 down-regulated) that are potentially involved in acquired resistance to gemcitabine. Indeed, the top 20 up- and down-regulated DEGs are largely associated with a common process of carcinogenesis in many cells. For the top 50 up- and down-regulated DEGs, we conducted integrated analyses of a gene regulatory network, a gene co-expression network, and a protein-protein interaction network. The identified DEGs were functionally enriched via Gene Ontology hierarchy and Kyoto Encyclopedia of Genes and Genomes pathway analyses. By systemic combinational analysis of the three molecular networks, we could condense the total number of DEGs to final seven genes. Notably, GJA1, LEF1, and CCND2 were contained within the lists of the top 20 up- or down-regulated DEGs. Our study represents a comprehensive overview of the gene expression patterns associated with acquired gemcitabine resistance and theoretical support for further clinical therapeutic studies.