CXCL13/CXCR5 axis facilitates endothelial progenitor cell homing and angiogenesis during rheumatoid arthritis progression.

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays important roles in several cellular functions such as infiltration, migration, and motility. We report significantly higher levels of CXCL13 expression in collagen-induced arthritis (CIA) mice compared with controls and also in synovial fluid from RA patients compared with human osteoarthritis (OA) samples. RA synovial fluid increased endothelial progenitor cell (EPC) homing and angiogenesis, which was blocked by the CXCL13 antibody. By interacting with the CXCR5 receptor, CXCL13 facilitated vascular endothelial growth factor (VEGF) expression and angiogenesis in EPC through the PLC, MEK, and AP-1 signaling pathways. Importantly, infection with CXCL13 short hairpin RNA (shRNA) mitigated EPC homing and angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with CIA. CXCL13 is therefore a novel therapeutic target for RA.

Association of Matrix Metalloproteinase-1 Genotypes With Bladder Cancer Risk.

AIM: There is very little literature reporting the association of matrix metalloproteinase-1 (MMP1) with personal susceptibility to bladder cancer. In the current study, we carried out the first examination of the contribution of MMP1 rs1799750 to bladder cancer risk in Taiwanese. MATERIALS AND METHODS: A total of 375 bladder cancer cases and 375 healthy controls were genotyped for MMP1 rs1799750 via polymerase chain reaction-restriction fragment length polymorphism methodology and this was evaluated for association with clinicopathological factors. RESULTS: The frequencies of MMP1 rs1799750 2G/2G, 1G/2G, and 1G/1G genotypes were 35.7%, 44.8% and 19.5% in the group with bladder cancer and 32.5%, 46.4%, and 21.1% in the healthy control group (p for trend=0.6362). The odds ratios (ORs) for bladder cancer risk after adjusting for age and gender for those carrying 1G/2G and 1G/1G genotypes at MMP1 rs1799750 were 0.88 (95% CI=0.62-1.24, p=0.4357) and 0.83 (95% CI=0.61-1.26, p=0.3990), respectively, compared with the wild-type 2G/2G genotype. In allelic frequency analysis, the adjusted OR for those carrying the 1G allele at MMP1 rs1799750 was 0.87 (95% CI=0.71-1.23, p=0.3479) compared to those people carrying a 2G allele. CONCLUSION: Our findings indicated that the genotypes at MMP1 rs1799750 appear to play little role in determining personal susceptibility to bladder cancer for Taiwanese.

The Significant Interaction of Excision Repair Cross-complementing Group 1 Genotypes and Smoking to Lung Cancer Risk.

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.

Association of Murine Double Minute 2 Genotypes and Lung Cancer Risk.

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.

Significant Association of Interleukin-16 Genetic Variations to Taiwanese Lung Cancer.

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.

Association of Nijmegen Breakage Syndrome 1 Genotypes With Bladder Cancer Risk.

BACKGROUND/AIM: We aimed to examine the association of the genotypes of Nijmegen breakage syndrome 1 (NBS1), a critical gene in DNA double strand break repair machinery, with bladder cancer risk in Taiwan. MATERIALS AND METHODS: NBS1 rs1805794 genotypes among 375 bladder cancer patients and 375 non-cancer healthy controls were determined via the polymerase chain reaction-restriction fragment length polymorphism methodology and their association with bladder cancer risk were evaluated. RESULTS: The results showed that the percentages of GG, CG and CC of NBS1 rs1805794 genotypes were 45.4%, 43.7% and 10.9% in the bladder cancer patient group and 47.2%, 43.2% and 9.6% in the non-cancer control group, respectively (p for trend=0.7873). The analysis of allelic frequency distributions showed that the variant C allele of NBS1 rs1805794 does not contribute to an increased bladder cancer susceptibility (p=0.5066). CONCLUSION: The genotypes of NBS1 rs1805794 are not closely associated with personal susceptibility to bladder cancer.

Significant Association Between the MiR146a Genotypes and Susceptibility to Childhood Acute Lymphoblastic Leukemia in Taiwan.

BACKGROUND/AIM: Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). CONCLUSION: MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan.

BACKGROUND/AIM: Recently, mounting evidence has shown that caspase-8 (CASP8) rs3834129 (-652, 6N insertion/deletion) polymorphism may serve as a genetic biomarker for personal risk of various cancer types. The contribution of CASP8 rs3834129 polymorphism has been investigated in several oral cancer populations, but not in Taiwan. This study investigated the role of CASP8 rs3834129 polymorphism on oral risk in Taiwan. MATERIALS AND METHODS: CASP8 rs3834129 polymorphic genotypes were determined and their associations with oral cancer risk were investigated among 788 patients with oral cancer and 956 age- and gender-matched healthy controls via polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) methodology. In addition, the interaction of CASP8 rs3834129 genotype with personal behavior and clinicopathological features were also examined. RESULTS: The frequencies of II, ID and DD genotypes for CASP8 rs3834129 were 57.5, 36.5 and 6.0% in the patient group and 54.0, 39.0 and 7.0% in the healthy control group, respectively (p for trend=0.3052), genotypes were not significantly differentially distributed between the two groups. The comparisons in allelic frequency distribution also supported the findings that the D variant allele may not serve as a determinant of risk for oral cancer. There was no interaction of CASP8 rs3834129 genotype with age, gender, smoking, alcohol or betel quid consumption in regard to oral cancer risk. CONCLUSION: Our results indicate that the caspase-8 genotype does not appear to play a direct role in personal susceptibility to oral cancer in Taiwan.

Contribution of Caspase-8 Genotypes to Colorectal Cancer Risk in Taiwan.

BACKGROUND/AIM: The aim of this study was to examine the role of caspase-8 rs3834129 polymorphism on colorectal cancer (CRC) risk in Taiwanese CRC patients and healthy controls. MATERIALS AND METHODS: The caspase-8 rs3834129 (-652 6N insertion/deletion) polymorphic genotypes were analyzed in 362 patients with CRC and the same number of age- and gender-matched healthy subjects. The interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were also examined. RESULTS: The percentage of variants ID and DD for caspase-8 rs3834129 genotype were 37.6 and 5.8% in CRC group and 39.0 and 6.6% in the control group, respectively (p for trend=0.7987). The allelic frequency distribution analysis showed that caspase-8 rs3834129 D allele conferred a non-significant lower susceptibility for CRC compared with I allele (OR=0.92, 95%CI=0.74-1.20, p=0.5063). There was no obvious link between caspase-8 rs3834129 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No statistically significant correlation was observed between caspase-8 rs3834129 genotypic distribution and age, gender, tumor size, location or metastasis status. CONCLUSION: Overall, caspase-8 rs3834129 genotypes may not serve as predictors for CRC risk or prognosis.

Contribution of Matrix Metalloproteinase-2 Promoter Genotypes to Nasopharyngeal Cancer Susceptibility and Metastasis in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinase 2 (MMP2) is up-regulated in many cancers. However, the association of MMP2 genotype to nasopharyngeal cancer (NPC) susceptibility in Taiwan remains elusive. MATERIALS AND METHODS: In this study, the role of MMP2 promoter C-1306T (rs243865) and C-735T (rs2285053) genotypes were investigated among 208 NPC patients and 416 healthy controls, and their role in NPC staging and TNM classifications were examined. RESULTS: There was no differential distribution as for the genotypic or allelic frequencies at MMP2 promoter C-1306T or C-735T between the control and case groups. Noticeably, those with MMP2 C-1306T CT+TT genotypes had a lower metastatic risk than those with CC (p=0.0295). As for staging, T and N classifications, there was no differential distribution in C-1306T genotypes (p>0.05). Also, there was no differential distribution of C-735T genotypes according to different behavioral/clinicopathological characteristics. CONCLUSION: CT and TT genotypes at MMP2 C-1306T were associated with a significantly decreased risk of NPC metastasis.

Association of Matrix Metallopeptidase-2 Promoter Polymorphisms With the Risk of Childhood Leukemia.

BACKGROUND/AIM: The association of matrix metalloproteinase-2 (MMP-2) genotypes with adult leukemia has been reported only once, but never for childhood leukemia. This study aimed to determine the role of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes in childhood leukemia risk. MATERIALS AND METHODS: This case-control study included 266 patients and 266 age- and gender-matched healthy controls. The polymorphic sites of MMP-2 were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The CC, CT and TT of rs243865 genotype were 75.2, 23.7 and 1.1% in the case group and 69.2, 28.9 and 1.9% in the control group, respectively. The CT and TT genotypes caused a 0.75- and 0.55-fold increase in the risk of childhood leukemia, respectively. There was no differential distribution of rs2285053 genotypes. Allelic frequency analysis showed that the T allele of MMP-2 promoter -1306 and -735 conferred lower susceptibility than the C allele. CONCLUSION: The MMP-2 promoter genotypes play a minor role in determining personal susceptibility to childhood leukemia among the Taiwanese.

Contribution of MMP2 Promoter Genotypes to Oral Cancer Susceptibility, Recurrence and Metastasis in Taiwan.

AIM: Metalloproteinase 2 (MMP2) is a multi-functional protein which has been shown to be up-regulated in patients with oral cancer, especially those with lymph node metastasis. However, the association of MMP2 genotype with oral cancer risk or metastatic behavior is unknown. This study aimed to evaluate the role of MMP2 promoter 1306 and -735 genotypes in the risk of oral cancer and metastasis. MATERIALS AND METHODS: In this case-control study, MMP2 promoter 1306 (rs243865) and -735 (rs2285053) genotypes and their interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated among 788 patients with oral cancer and 956 gender-matched healthy controls. In addition, their role in oral cancer metastasis were also examined. RESULTS: The distribution of CC, CT and TT for MMP2 promoter 1306 genotype was 79.0, 20.1 and 0.9% in the oral cancer group and 68.7, 29.2 and 2.1% in the non-cancer control group, respectively (p for trend=4.3E-6). The allelic frequency distributions showed that the variant T allele of MMP2 promoter 1306 conferred lower oral cancer susceptibility than the wild-type C allele (odds ratio=0.61, 95% confidence interval=0.50-0.75, p=1.1E-6). As for the MMP2 -735 genotypes, there was no differential distribution in genotypic or allelic frequencies. The variant CT and TT genotypes were also associated with lower metastasis rates within 5 years among the patients with oral cancer (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0102). CONCLUSION: The CT and TT genotypes of MMP2 promoter 1306 may have a protective effect on oral cancer susceptibility and metastasis risk within 5 years for Taiwanese. They may serve as predictive markers for oral cancer in precise medical practice.

Novel Combination of Arsenic Trioxide (As2O3) Plus Resveratrol in Inducing Programmed Cell Death of Human Neuroblastoma SK-N-SH Cells.

AIM: Arsenic trioxide (As2O3), known as pi-shuang and the most toxic compound in traditional Chinese medicine, has been used as an antitumor agent for thousands of years. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phenol that has significant anti-bacterial, anti-fungaI and antiaging activities. Our study aimed to examine the combined anticancer effects of As2O3 and resveratrol against human neuroblastoma SK-N-SH cells, and elucidate the underlying intracellular signaling. MATERIALS AND METHODS: SK-N-SH cells were treated with an extremely low-dose (2-4 µM) of As2O3 alone or combined with 75 µg/ml resveratrol for further comparisons. Cell viability, apoptotic signaling as well as synergistic cytotoxic effects were estimated using the MTT assay, microscopy observation, flow cytometric analysis for loss of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), and typical quantitative western blotting analysis. Student's t-test, and one- and two-way analysis of variance (ANOVA) were used for examination of significant differences. RESULTS: The combined treatment was more effective than single treatment of As2O3 or resveratrol alone in suppressing cell viability, which correlated with the elevation of ROS levels. The intracellular mechanisms of cytotoxicity of As2O3 plus resveratrol were revealed as ROS accumulation and relative decrease of MMP, leading to activation of caspase-3 and -9, but not of caspase-1, -7 and-8. Combination treatment reduced the expression of B-cell lymphoma 2 (BCL2), BH3 interacting domain death agonist (BID), and BCL-x/L. CONCLUSION: Combined treatment at extremely low concentration of two agents from natural products, As2O3 and resveratrol, has high potential as a cocktail of anticancer drugs for neuroblastoma.

Association of Matrix Metalloproteinase-8 Genotypes with the Risk of Bladder Cancer.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) control the homeostasis of the extracellular matrix and their genetic polymorphisms may contribute to cancer susceptibility. The aim of this study was to reveal the genotypes of MMP8 among the Taiwanese and examine the contribution of MMP8 C-799T, Val436Ala and Lys460Thr polymorphisms to bladder cancer. MATERIALS AND METHODS: MMP8 C-799T, Val436Ala and Lys460Thr polymorphic genotypes were determined in 375 patients with bladder cancer and 375 healthy controls by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: Regarding MMP8 C-799T, there was no significant differential distribution between patient and control groups [p for trend=0.6629]. The odds ratios (ORs) after adjusting for age, gender, smoking and alcohol drinking status for those carrying CT and TT genotypes at MMP8 C-799T were 1.13 (95%CI=0.89-1.44, p=0.3688) and 1.10 (95%CI=0.87-1.52, p=0.9030), respectively, compared to those carrying the wild-type CC genotype. Regarding MMP8 Val436Ala, there was no significant differential distribution between patient and control groups [p for trend=0.8166]. The adjusted OR for those carrying AC and CC genotypes at MMP8 Val436Ala were 0.71 (95%CI=0.31-2.28, p=0.6094) and 1.00 (95%CI=0.21-4.73, p=0.7247), respectively. The polymorphism Lys460Thr at MMP8 was not found among Taiwanese patients. CONCLUSION: MMP8 C-799T, Val436Ala and Lys460Thr may only play an indirect role in determining personal cancer susceptibility for bladder cancer in Taiwan.

Eicosapentaenoic acid triggers Ca2+ release and Ca2+ influx in mouse cerebral cortex endothelial bEND.3 cells.

Eicosapentaenoic acid (EPA), an omega-3 fatty acid abundant in fish oil, protects endothelial cells (EC) from lipotoxicity and triggers EC NO release. The latter is related to an elevation of cytosolic Ca2+. Although EPA has been shown to cause human EC cytosolic Ca2+ elevation, the mechanism is unclear. Microfluorimetric imaging was used here to measure free cytosolic Ca2+ concentration. EPA was shown to cause intracellular Ca2+ release in mouse cerebral cortex endothelial bEND.3 cells; interestingly, the EPA-sensitive intracellular Ca2+ pool(s) appeared to encompass and was larger than the Ca2+ pool mobilized by sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition by cyclopiazonic acid. EPA also opened a Ca2+ influx pathway pharmacologically distinct from store-operated Ca2+ influx. Surprisingly, EPA-triggered Ca2+ influx was Ni2+-insensitive; and EPA did not trigger Mn2+ influx. Further, EPA-triggered Ca2+ influx did not involve Na+-Ca2+ exchangers. Thus, our results suggest EPA triggered unusual mechanisms of Ca2+ release and Ca2+ influx in EC.

The Association of MMP-8 Genotypes with Pterygium.

BACKGROUND/AIM: Pterygium is composed of proliferating fibrovascular tissue, and its formation and progression are closely related to the homeostasis of the extracellular microenvironment. However, few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnostic or prognostic potential in pterygium. In this study, we investigated the contribution of a polymorphism in the promoter region of MMP-8 (-799C/T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to pterygium. MATERIALS AND METHODS: In this study, 134 patients with pterygium and 268 non-cancer controls patients were collected and the MMP-8 -799C/T, Val436Ala and Lys460Thr polymorphic genotypes of each subject were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The results showed that the three polymorphisms investigated were not significantly associated with risk of pterygium. In addition, the stratified analysis showed that there was no interaction between MMP-8 genotype with age or gender on pterygium risk determination. CONCLUSION: Polymorphisms at MMP-8 -799C/T, Val436Ala and Lys460Thr may not mainly contribute to determining personal susceptibility to pterygium in the Taiwanese examined.

The Contribution of MMP-8 Promoter Genotypes to Childhood Leukemia.

BACKGROUND/AIM: Accumulated evidence has supported the notion that matrix metalloproteinase (MMP) genotypes are associated with the susceptibility of many types of cancers. However, few reports have studied the contribution of MMP genotypes to either diagnostic or prognostic potential in non-solid tumors such as leukemia. In this study, we firstly investigated the contribution of a polymorphism in the promoter region of MMP-8 (-799C/T) and two non-synonymous polymorphisms (Val436Ala and Lys460Thr) to childhood leukemia. PATIENTS AND METHODS: In this study, 266 patients with childhood acute lymphoblastic leukemia (ALL) and 266 non-cancer control patients were collected and the genomic DNA was isolated from their peripheral blood. MMP-8 -799C/T, Val436Ala and Lys460Thr polymorphic genotypes of each subject were determined by the typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The results showed that the three polymorphisms were not significantly associated with an increased risk of childhood ALL in the overall investigated population. Furthermore, when the analyses were stratified by age and gender, no significant association between these genotypes and increased ALL risk was found. CONCLUSION: Our findings suggest that the polymorphisms at MMP-8 -799C/T, Val436Ala and Lys460Thr may not play a major role in determining the personal susceptibility to childhood ALL in Taiwan.

The Contribution of Excision Repair Cross-complementing Group 1 Genotypes to Colorectal Cancer Susceptibility in Taiwan.

AIM: To evaluate the contribution of ERCC1 rs11615 and rs3212986 genotypes regarding the risk of colorectal cancer (CRC) in Taiwan. MATERIALS AND METHODS: In this case-control study, ERCC1 rs11615 and rs3212986 genotypes and their interaction with consumption of cigarettes and alcohol in determining CRC risk were investigated among 362 CRC patients and 362 age- and gender-matched healthy controls. RESULTS: The percentages of CC, CT and TT for ERCC1 rs11615 genotype were 44.2%, 36.2% and 19.6% in the CRC group and 49.7%, 38.4% and 11.9% in the control group, respectively (p for trend=0.0158). The allelic frequency distribution analysis showed that the variant T allele of ERCC1 rs11615 conferred increased CRC susceptibility to the wild-type C allele (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.08-1.67, p=0.0079). As for the gene-lifestyle interaction, there were obvious joint effects of ERCC1 rs11615 genotype on the risk of CRC among ever smokers and alcohol drinkers, but not non-smokers or non-drinkers. There is a positive correlation of ERCC1 rs11615 genotype with lymph node metastasis, but not other CRC prognosis, including tumor size and location. CONCLUSION: ERCC1 rs11615 T allele serves as a predictive marker for CRC risk and future studies with larger samples and functional evaluation are warranted to validate these findings.

The Contribution of Matrix Metalloproteinase-1 Genotypes to Hepatocellular Carcinoma Susceptibility in Taiwan.

BACKGROUND/AIM: Metalloproteinases (MMPs) are a family of proteases which have been shown to be overexpressed in various types of cancers. However, the contribution of MMP1 genotype to hepatocellular carcinoma (HCC) has not been well studied. This study aimed to evaluate the contribution of MMP1 promoter 1607 genotype to the risk of HCC in Taiwan, where HCC incidence is relatively high in the world. MATERIALS AND METHODS: In this case-control study, MMP1 genotype and its interaction with consumption of cigarettes and alcohol in determining HCC risk was investigated among 298 HCC patients and 889 age- and gender-matched healthy controls. RESULTS: The percentages of ever smokers and ever alcohol drinkers were much higher in the case group than in the control group. The percentages of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter 1607 genotype were 37.2%, 38.3% and 24.5% in the HCC group and 34.8%, 44.0% and 21.2% in the control group, respectively (p for trend=0.2048). The allelic frequency distribution analysis showed the variant 1G allele of MMP1 promoter 1607 conferred similar HCC susceptibility as the wild-type 2G allele (odds ratio (OR)=1.01, 95% confidence interval (CI)=0.84-1.22, p=0.8735). As for the gene-lifestyle interaction, there was an obvious protective effect of MMP1 promoter 1607 1G allele on the risk of HCC among non-smokers, but not non-smokers, even alcohol drinkers or non-drinkers. CONCLUSION: The 1G allele of MMP1 promoter 1607 may have a protective effect on HCC risk for non-smokers in Taiwan and further validations are needed in other population groups.

Baicalin Scavenged Reactive Oxygen Species and Protected Human Keratinocytes Against UVB-induced Cytotoxicity.

Ultraviolet B (UVB), with a wavelength of 280-320 nm, represents one of the most important environmental factors for skin disorders, including sunburn, hyperpigmentation, solar keratosis, solar elastosis and skin cancer. Therefore, protection against excessive UVA-induced damage is useful for prevention of sunburn and other human diseases. Baicalin, a major component of traditional Chinese medicine Scutellaria baicalensis, has been reported to possess antioxidant and cytostatic capacities. In this study, we examined whether baicalin is also capable of protecting human keratinocytes from UVB irradiation. The results showed that baicalin effectively scavenged reactive oxygen species (ROS) elevated within 4 h after UVB radiation and reversed the UVB-suppressed cell viability and UVB-induced apoptosis after 24 h. Our results demonstrated the utility of baicalin to complement the contributions of traditional Chinese medicine in UVB-induced damage to skin and suggested their potential application as pharmaceutical agents in long-term sun-shining injury prevention.