• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5929-5934
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• 2013

Background: Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. ${\beta}3$ integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and ${\beta}3$ integrin gene polymorphisms. Materials and Methods: The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of ${\beta}3$ integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM-1 K469E, ICAM-1 R241G and ${\beta}3$ integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively). Conclusions: This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5101-5106
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• 2016

Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein ${\times}$ NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p<0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P<0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5119-5124
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• 2012

Purpose: The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. Methods: We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine $1500mg/m^2$ and paclitaxel 150 mg/m2 administered every two weeks. Results: Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4 hematologic toxicities, including neutropenia (n=4, 8.4%), and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrile neutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. Conclusion: The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-line chemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containing chemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, this regimen was tolerated well by the patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3319-3322
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• 2013

Background: Helicobacter pylori (H. pylori) is one of the risk factors for gastric cancer (GC). Any prognostic effect of HER-2 status in gastric lymph node metastasis in H. pylori positive cases is unknown. Materials and Methods: A total of 74 patients, 47 (64%) male, and 27 (34%) female, who had subtotal or total gastrectomy and also positive lymph nodes, were included in the study. Age range was 29-87 years, and median age was 58 years. HER-2 expression was assessed in both gastric resection samples and lymph node material with carcinoma metastasis of the same patient by immunohistochemistry (IHC) and silver in situ hybridization (SISH) methods. H. pylori status was examined in gastric materials of all patients. Relationships between HER-2 status in gastric cancers and lymph nodes and H. pylori status were investigated. Results: H. pylori was positive in 40 cases (54%), and negative in 34 (46%). While in the primary tissues of H. pylori positive cases, SISH positivity for HER-2 was observed in 13 cases (86%), SISH negativity was observed in 2 (14%), in metastatic lymph nodes 21 cases (72%) were SISH positive and 8 cases (28%) were SISH negative (P=0.005 and P=0.019, respectively). Initial CEA values were high in 18 cases (78%) with positive H. pylori and in 5 cases (22%) with negative H. pylori (P=0.009). While SISH data of patients were negative in 59 cases (80%) and positive in 15 cases (20%) in primary tissues, they were negative in 56 cases (75%) and positive in 18 cases (25%) in lymph nodes. Discrepancy between primary tissue and lymph node results was detected in 3 cases, in which SISH was negative in the primary tissue and HER-2 expression was positive in the lymph nodes. Conclusions: Clinical progression was poor in H. pylori positive cases with HER-2 negativity in primary gastric tissue, but HER-2 positivity in the lymph nodes. SISH positivity can be expected in H. pylori positive cases, and it may be predicted that these cases can benefit from trastuzumab treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3249-3253
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• 2016

Background: Pemetrexed monotherapy has come to be recognized as one of the standard second-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. Materials and Methods: The records of non-squamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: The overall response rate and progression-free survival time (PFS) of the 53 patients with non-squamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. Conclusions: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non-squamous histology as predictors of the efficacy of pemetrexed monotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.4999-5005
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• 2013

Objective: This study aimed to investigate expression of the proto-oncogene POK erythroid myeloid ontogenic factor (Pokemon) in colorectal cancer (CRC), and assess inhibitory effects of a small interference RNA (siRNA) expression vector in SW480 and SW620 cells. Methods: Semi-quantitative reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry were performed to determine mRNA and protein expression levels of Pokemon in CRC tissues. Indirect immunofluorescence staining was applied to investigate the location of Pokemon in SW480 and SW620 cells. The siRNA expression vectors that were constructed to express a short hairpin RNA against Pokemon were transfected to the SW480 and SW620 cells with a liposome. Expression levels of Pokemon mRNA and protein were examined by real-time quantitative-fluorescent PCR and western blot analysis. The effects of Pokemon silencing on proliferation of SW480 and SW620 cells were evaluated with reference to growth curves with MTT assays. Results: The mRNA expression level of Pokemon in tumor tissues ($0.845{\pm}0.344$) was significantly higher than that in adjacent tumor specimens ($0.321{\pm}0.197$). The positive expression ratio of Pokemon protein in CRC (87.0%) was significantly higher than that in the adjacent tissues (19.6%). Strong fluorescence staining of Pokemon protein was observed in the cytoplasm of the SW480 and SW620 cells. The inhibition ratios of Pokemon mRNA and protein in the SW480 cells were 83.1% and 73.5% at 48 and 72 h, respectively, compared with those of the negative control cells with the siRNA. In the SW620 cells, the inhibition ratios of Pokemon mRNA and protein were 76.3% and 68.7% at 48 and 72 h, respectively. MTT showed that Pokemon gene silencing inhibited the proliferation of SW480 and SW620 cells. Conclusion: Overexpression of Pokemon in CRC may have a function in carcinogenesis and progression. siRNA expression vectors could effectively inhibit mRNA and protein expression of Pokemon in SW480 and SW620 cells, thereby reducing malignant cell proliferation.

• KSBB Journal
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• v.30 no.5
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• pp.223-229
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• 2015

In this study, extract from Artemisia annua in L. (AAE) is known as a medicinal herb that is effective against cancer. The cell cycle is regulated by the activation of cyclin-dependent kinase (CDK)/cyclin complex. We will focus on regulation of CDK2 by cyclin E. cyclin E is associated with CDK2 to regulate progression from G1 into S phase. Akt is known to play an important role in cell proliferation and cell survival. Activation of Akt increases mTOR activity that promotes cell proliferation and cancer growth. In this study, we investigated that AAE-induced cell cycle arrest at G1/S phase in HCT116 colon cancer. Treatment of AAE shows that reduced activation of Akt decreases mTOR/Mdm2 activity and then leads to increase the activation of p53. The active p53 promotes activation of p21. p21 induces inactivation of CDK2/cyclin E complex and occurs cell cycle arrest at G1/S phase. We treated LY294002 (Akt inhibitor) and Rapamycin (mTOR inhibitor) to know the relationship between the signal transduction of proteins associated with cell cycle arrest. These results suggest that AAE induces cell cycle arrest at G1/S phase by Akt/mTOR pathway in HCT116 colon cancer cell.

• 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 Gastric Cancer
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• v.23 no.3
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• pp.476-486
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• 2023

Purpose: The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC. Materials and Methods: Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined. Results: A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292-39.281) than in the TMB-L (3.31 months; 95% CI, 1.604-5.019; P=0.049). Conclusions: The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb. When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.

• Annals of Geriatric Medicine and Research
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• v.22 no.4
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• pp.167-175
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• 2018

Sarcopenia, a common clinical syndrome in older adults, is defined as decreased muscle mass, strength, and physical performance. Since sarcopenia is associated with the incidence of functional decline, falls, and even mortality in older adults, researchers and health care providers have been keen to accumulate clinical evidence to advocate the screening and prevention of sarcopenia progression in older adults. The factors that may accelerate the loss of muscle mass and function include chronic diseases, inactivity, and deficiency in appropriate nutritional support. Among these, nutritional support is considered an initial step to delay the progression of muscle wasting and improve physical performance in community-dwelling older adults. However, a nationwide study suggested that most Korean older adults do not consume sufficient dietary protein to maintain their muscle mass. Furthermore, considering age-associated anabolic resistance to dietary protein, higher protein intake should be emphasized in older adults than in younger people. To develop a dietary protein recommendation for older adults in Korea, we reviewed the relevant literature, including interventional studies from Korea. From these, we recommend that older adults consume at least 1.2 g of protein per kg of body weight per day (g/kg/day) to delay the progression of muscle wasting. The amount we recommend (1.2 g/kg/day) is 31.4% higher than the previously suggested recommended daily allowance (i.e., 0.91 g/kg/day) for the general population of Korea. Also, evidence to date suggests that the combination of exercise and nutritional support may enhance the beneficial effects of protein intake in older adults in Korea. We found that the current studies are insufficient to build population-based guidelines for older adults, and we call for further researches in Korea.