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Solanum muricatum Ait. (Pepino) is a plant food commonly cultivated in the Penghu Island, Taiwan. This present study aimed to investigate the protective effects of aqueous extract of Pepino leaves (AEPL) in mice with metabolic syndrome. Metabolic syndrome animal model was induced by continuous high‐fat diet feeding and low‐dose streptozotocin (40 mg/ml) for 5 days. A 1% AEPL or metformin were given for 6 weeks after streptozotocin injection. The results revealed that 1% AEPL effectively reduced fasting blood glucose, insulin resistance, and hyperlipidemia in metabolic syndrome mice. Histologic examination revealed lipid accumulation in liver decreased by 1% AEPL treatment. Further, western blot analysis revealed 1% AEPL treatment managed enzymes related to lipid synthesis and oxidation pathways and hepatic glucose production. Besides, 1% AEPL treatment increased liver antioxidant activities to against oxidative stress. These results concluded that AEPL treatment attenuated insulin resistance, hyperlipidemia, and hyperglycemia of metabolic syndrome. Practical applications: Metabolic syndrome (MS) is a multifactorial chronic disease which is characterized by dyslipidemia, insulin resistance, and hyperglycemia. However, there is no single drug or defined medication for MS so far. The present study revealed that AEPL treatment was able to regulate lipid metabolism and glycemic control at the molecular level to alleviate MS. AEPL has the potential to be a novo complementary medication for metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background & Aims: The impact of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection upon B vitamins status and antioxidative defense in infected patients was examined. Methods: Dietary record and blood levels of B vitamins and oxidative stress-associated biomarkers were determined for 195 healthy controls, 132 HBV, and 114 HCV patients. Results: HBV-infected patients had significantly higher levels of total cholesterol, free fatty acids (FFA), and lower ghrelin level ( p < 0.05); and HCV-infected patients had significantly higher Ishak inflammation score and lactate dehydrogenase activity ( p < 0.05). HBV patients had significantly lower red blood cell (RBC) vitamins B and B levels, and HCV infection significantly decreased vitamins B B and folate levels in RBC and/or plasma ( p < 0.05). Correlation coefficients of RBC vitamin B versus serum FFA in HBV patients, RBC vitamins B and B versus HCV RNA and Ishak inflammation score, and plasma vitamin B vs Ishak inflammation score in HCV patients were <−0.5. HBV-infected patients had significantly higher oxidized glutathione level and lower glutathione peroxidase activity ( p < 0.05), but HCV patients had significantly lower superoxide dismutase and catalase activities ( p < 0.05). Conclusion: HBV or HCV infection enhanced oxidative stress and lowered B vitamins in circulation. In order to avoid other healthy risk, nutrition status should be monitored and limitation or supplementation of certain nutrients might be helpful for HBV- or HCV-infected patients. [ABSTRACT FROM AUTHOR]

Background/aim: In the literature, the studies about the role of matrix metalloproteinase-2 (MMP-2) in pterygium diagnosis are mainly based on its protein expression. The role of MMP-2 variants has never been examined. The aim of this study was to examine the association of MMP-2 genotypes with pterygium risk., Materials and Methods: MMP-2 rs243865 and rs2285053 were genotyped in 140 pterygium cases and 280 non-pterygium controls by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping technology., Results: The genotypic frequency of MMP-2 rs243865 CC, CT and TT were 86.4%, 12.9% and 0.7% in the pterygium group and 81.1%, 17.1% and 1.8% in the non-pterygium group (p for trend=0.3389). The variant CT and TT carriers had a 0.70- and 0.38-fold pterygium risk (95%CI=0.39-1.26 and 0.04-3.25, p=0.2982 and 0.6686, respectively). As for MMP-2 rs2285053, the genotypic frequency of CC, CT and TT were 67.1%, 28.6% and 4.3% in the pterygium group, non-significantly different from those in non-pterygium group (p for trend=0.7081). The CT and TT carriers had a 0.88- and 0.71-fold pterygium risk (95%CI=0.56-1.38 and 0.27-1.88, p=0.6612 and 0.6456, respectively). The allelic analysis results showed that MMP-2 rs243865 variant T allele was not associated with pterygium risk (7.1% versus 10.4%, OR=0.67, 95%CI=0.39-1.13, p=0.1649). As for MMP-2 rs2285053, the T allele was not associated with pterygium risk either (18.6% versus 21.1%, OR=0.85, 95%CI=0.59-1.23, p=0.4136)., Conclusion: The genotypes at MMP-2 rs243865 or rs2285053 played minor role in determining individual susceptibility for pterygium among Taiwanese., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Triple negative breast cancer (TNBC) is one of the most challenging breast cancer types. Interleukin-8 (IL-8) is a pro-tumorigenic cytokine, promoting tumor proliferation and migration. This study aimed to examine the contribution of IL-8 rs4073 genotypes to breast cancer risk and provide a summary of related literature., Materials and Methods: IL-8 genotypic profiles were determined among 1,232 breast cancer cases and 1,232 controls via polymerase chain reaction-restriction fragment length polymorphism methodology., Results: The IL-8 rs4073 AT and AA genotypes had significantly lower prevalence in the case group compared to control group. Allelic frequency analysis showed that individuals carrying the A allele have relatively decreased risk for breast cancer. The stratification analysis showed that IL-8 rs4073 genotypes were protective markers for those with younger (≤55) age., Conclusion: IL-8 rs4073 A allele is a novel predictor for breast cancer, especially TNBC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) is responsible for folate metabolism, and we aimed to investigate its genetic role in colorectal cancer (CRC) among Taiwanese., Materials and Methods: A total of 362 cases and 362 controls were recruited and their MTRR rs1801394 (A66G) and rs1532268 (C524T) genotypes were examined. The behavioral factors and clinicalpathological factors were also analyzed., Results: MTRR rs1801394 genotypes were associated with CRC risk (p for trend=0.0087). In detail, G/G genotype was associated with lower risk (p=0.0049, OR=0.39, 95%CI=0.20-0.76). As for allelic frequency analysis, G allele was also associated with decreased CRC risk (p=0.0026, OR=0.68, 95%CI=0.53-0.88). There was no significant association as for MTRR rs1532268. Among non-smokers and non-alcohol drinkers, those with G/G genotype were at 0.38- and 0.46-fold odds of having CRC. There were no significant protective effects among smokers or alcohol drinkers., Conclusion: MTRR rs1801394 GG genotype can be a protective marker for CRC risk in Taiwan., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Matrix metalloproteinase-2 (MMP-2) plays a critical role in the regulation of the extracellular matrix; however, its genotypes have seldom been examined in gastric cancer (GC). This study aimed to investigate the contribution of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes to GC risk in a cohort of Taiwanese individuals., Materials and Methods: This study included 121 GC cases and 363 age- and sex-matched controls. The genotypes of MMP-2 were determined by typical polymerase chain reaction-restriction fragment length polymorphism., Results: The genotypic and allelic frequency analysis showed that MMP-2 rs243865 variant genotypes decreased the risk of GC. Stratification analysis showed that MMP-2 rs243865 genotypes associate with smoking, alcohol drinking, and Helicobacter pylori infection status to confer personal susceptibility to GC. There is no such association for MMP-2 rs2285053 genotype with GC risk., Conclusion: The MMP-2 rs243865 genotypes may serve as a novel predictive marker for GC personal susceptibility among Taiwanese., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Accumulating evidence shows that caspase-8 (Cas-8) rs3834129 genotypes determine susceptibility to various cancers, but their association with nasopharyngeal carcinoma (NPC) has not been examined. We aimed at investigating the association of Cas-8 rs3834129 with NPC risk., Materials and Methods: Cas-8 rs3834129 genotypes and their associations with NPC risk were investigated among 176 NPC patients and 352 non-cancer subjects by the PCR-RFLP method. Additionally, the interaction of Cas-8 rs3834129 genotypes with smoking was examined., Results: The II, ID and DD frequencies were 56.8, 36.9 and 6.3% among NPC patients and 54.8, 38.1 and 7.1% among control subjects (p trend =0.8830). Allelic frequency distribution analysis also indicated that the D allele is not a risk factor for NPC (p=0.6183). There was no interaction between Cas-8 rs3834129 and smoking and NPC risk (p=0.8305)., Conclusion: Cas-8 rs3834129 genotypes play a minor role in the risk for NPC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The study aims to evaluate the contribution of excision repair cross-complementing group 1 (ERCC1), which plays an important role in genome integrity maintenance, to lung cancer risk., Materials and Methods: ERCC1 rs11615 and rs3212986 genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and their association with lung cancer risk was examined among 358 lung cancer patients and 716 controls., Results: The proportions of CC, CT and TT for the rs11615 genotype were 43.6%, 41.6% and 14.8% in the case group and 50.0%, 41.1% and 8.9% in the control group, respectively (p for trend=0.0082). Allelic analysis showed that ERCC1 rs11615 T-allele carriers have a 1.32-fold higher risk of lung cancer than wild-type C-allele carriers [95%confidence interval (CI)=1.09-1.60, p=0.0039]. In addition, a significant interaction between the rs11615 genotype and smoking status was observed., Conclusion: The T allele of ERCC1 rs11615 jointly with smoking habits may contribute to a higher lung cancer risk in Taiwan., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The studies about the roles of matrix metalloproteinases (MMPs) in pterygium diagnosis and/or prognosis are mainly based on their mRNA and protein levels, while the genomic roles of MMPs are seldom examined. The aim of this study was to investigate the contribution of MMP-9 genotypes to pterygium risk., Materials and Methods: MMP-9 rs3918242 was genotyped in 134 pterygium cases and 268 controls via polymerase chain reaction-restriction fragment length polymorphism., Results: The rs3918242 genotype percentages of CC, CT, and TT were 73.1, 25.4 and 1.5% among cases and 74.6, 23.1 and 2.3% among controls (p trend=0.7928). The odds ratios after adjusting for age and gender for CT and TT genotypes at rs3918242 were 1.08 and 0.92 (95%CI=0.66-1.73 and 0.45-2.89, p=0.6478 and 0.6389), respectively. In addition, allelic frequency analysis showed no significant difference in the distribution of allelic frequencies between the pterygium and control groups., Conclusion: The genotypes at MMP-9 rs3918242 play a minor role in determining personal susceptibility to pterygium., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Interleukin-16 (IL-16) is reported to play an important role in inflammation, carcinogenesis and tumoricidal processes, however, the contribution of IL-16 genotype to oral carcinogenesis is still largely unrevealed. Thus, the study aimed to investigate the contribution of IL-16 genotypes to Taiwan oral cancer risk., Materials and Methods: The genotypes of IL-16 rs4778889, rs11556218, and rs4072111 were revealed among 958 oral cancer cases and 958 control subjects by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP)., Results: First, the distributions of genotypic (p=0.0004) and allelic (p=0.0001) frequencies of IL-16 rs11556218 were significantly different between the case and control groups. In detail, the frequencies of IL-16 rs11556218 TG and GG were 28.1 and 5.8%, respectively, among oral cancer patients, significantly higher compared to those among controls (25.0% and 2.7%, respectively). Second, no difference was observed regarding IL-16 rs4778889 or IL-16 rs4072111. Last, there was a synergistic effect of betel quid chewing behavior and risky IL-16 rs11556218 genotype on oral cancer risk., Conclusion: The study indicates that the IL-16 rs11556218 G allele synergistically interacts with betel quid chewing behavior, contributing to increased risk of oral cancer in Taiwanese., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: The aim of this study was to evaluate the contribution of human mouse double minute 2 (MDM2) gene polymorphisms to the risk of Taiwan lung cancer., Materials and Methods: In this case-control study, the association of MDM2 rs2279744 genotypes with lung cancer risk was investigated among 358 lung cancer patients and 716 age-, gender- and smoking status-matched controls in Taiwan., Results: The percentages of MDM2 rs2279744 GT and GG genotypes were 50.0% and 27.4% in lung cancer group and 50.0% and 26.5% in control group, respectively [odds ratio (OR)=1.03 and 1.07, 95% confidence interval (CI)=0.75-1.43 and 0.75-1.53, respectively]. The analysis about allelic frequency showed that G allele at MDM2 rs2279744 conferred a non-significant increased cancer risk (OR=1.03, 95%CI=0.86-1.24)., Conclusion: Polymorphisms of MDM2 rs2279744 may play a role in lung carcinogenesis. However, the studied genotypes were not shown as predictors of lung cancer susceptibility., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genotypes to the risk of breast cancer in Taiwanese., Materials and Methods: A total of 1232 breast cancer patients and 1232 age-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology., Results: Genotypic frequencies of IL-4 rs2243248, rs2243250 and rs2070874 were not differentially distributed between case and control groups. Consistently, there was no difference in the distribution of allelic frequencies among patients and controls., Conclusion: IL-4 rs2243248, rs2243250 and rs2070874 do not confer breast cancer susceptibility in Taiwanese., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Interleukin-16 has been reported to exhibit tumoricidal effects, however, the contribution of IL-16 genotypes to lung cancer is still largely unrevealed. This study aimed at investigating whether IL-16 genotypes contribute to lung cancer susceptibility., Materials and Methods: IL-16 rs4778889, rs11556218, and rs4072111 genotypic characteristics were determined among 358 lung cancer patients and 716 controls via the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology., Results: The highlight finding is that the distributions of genotypic (p=8.6E-10) and allelic (p=0.0001) frequencies of IL-16 rs11556218 was significantly different between cases and controls. In detail, the frequencies of IL-16 rs11556218 heterozygous variant TG and homozygous variant GG were 36.6 and 7.3% among the lung cancer patients, significantly higher than those among the controls (22.5% and 2.6%). On the other way, no difference was observed regarding IL-16 rs4778889 or IL-16 rs4072111., Conclusion: The present study indicates IL-16 rs11556218 G allele is significantly associated with increased Taiwan lung cancer risk., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnosis or prognosis of pterygium. The aim of this study was to investigate the contribution of MMP-1 genotypes to pterygium risk., Patients and Methods: A total of 134 cases and 268 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined by polymerase chain reaction-restriction fragment length polymorphism., Results: The percentages of 2G/2G, 1G/2G, and 1G/1G for rs1799705 genotypes were 48.5, 36.6 and 14.9% among patients and 33.9, 44.8, and 21.3% among controls (p trend=0.0167). The odds ratios (ORs) after adjusting for age and gender for 1G/2G and 1G/1G genotypes at rs1799705 were 0.54 (95%CI=0.33-0.89, p=0.0168) and 0.46 (95%CI=0.27-0.88, p=0.0192), respectively. Consistently, the adjusted OR for those carrying the 1G allele at MMP-1 -1607 was 0.61 (95%CI=0.41-0.78, p=0.0167), compared with the wild-type 2G allele., Conclusion: The genotypes at rs1799705 play a role in determining personal susceptibility to pterygium., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Overexpression of cyclooxygenase-2 in oral cancer increases lymph node metastasis and is associated with a poor prognosis. The potential of celecoxib (CXB) use is reported in cancer treatment by inhibiting proliferation through apoptosis, but the effects on the epithelial-mesenchymal transition (EMT) and cancer cell mobility remain unclear. We performed a preclinical study and population-based study to evaluate CXB use in the prevention of oral cancer progression and occurrence. The in-vitro findings showed that CXB is involved in the inhibition of EMT and cell mobility through blocking transcription factors (Slug, Snail and ZEB1), cytoplasmic mediators (focal adhesion kinase (FAK), vimentin and β-catenin), cell adhesion molecules (cadherins and integrins), and surface receptors (AMFR and EGFR). The murine xenograft model showed a 65% inhibition in tumour growth after a 5-week treatment of CXB compared to placebo. Xenograft tumours in placebo-treated mice displayed a well-to-moderate/moderate differentiated SCC grade, while those from CXB-treated mice were well differentiated. The expression levels of membrane EGFR, and nuclear FAK, Slug and ZEB1 were decreased in the xenograft tumours of CXB-treated mice. A retrospective cohort study showed that increasing the daily dose and medication time of CXB was associated with oral cancer prevention. The findings provide an alternative prevention strategy for oral cancer development with CXB use.

The alteration of caveolin-1 (Cav-1) during carcinogenesis is of great interest and its over-expression in the tumor cell cytoplasm can predict a poor prognosis of renal cell carcinoma (RCC). However, whether the over-expression in RCC is associated with inherited polymorphism is not clear. In this hospital-based case-control study, the association of Cav-1 genotypes with RCC risk in a central Taiwanese population was investigated. Ninety-two patients with RCC and five hundred and eighty of age/gender-matched healthy controls were recruited and genotyped for six polymorphic sites at Cav-1, C521A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992). The results showed that there were statistically different distributions of the genotypic (P = 0.0170 and 0.0011) and allelic (P = 0.0033 and 0.0352) frequencies for the Cav-1 G14713A and T29107A polymorphisms among RCC patients and control subjects, respectively. As for the haplotype analysis, subjects carrying "GG/AT or GG/AA" at Cav-1 G14713A/T29107A showed a 2.06-fold increased odds ratio of RCC compared to those with GG/TT, while those of any other combinations were of unaltered odds ratios. In conclusion, this is the first report providing evidence showing that Cav-1 genotype is associated with RCC. The results showed that the G allele of the Cav-1 G14713A and the A allele of the Cav-1 T29107A are risky genetic factors for RCC susceptibility and the combinative GG/AT or GG/AA haplotype at Cav-1 G14713A/T29107A can serve as one of the RCC predictors for Taiwanese.