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Background/Aim: In literature, few studies have examined the diagnostic or prognostic potential of matrix metalloproteinases (MMP) in pterygium, whose formation and progression are closely related to imbalance in the extracellular microenvironment. In this study, we investigated the contribution of MMP7 promoter (A-181G and C-153T) polymorphic genotypes to pterygium risk. Materials and Methods: A total of 134 cases and 268 controls were collected and their MMP7 genotypes at A-181G and C-153T were examined by polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The AA, AG and GG genotypes at MMP7 promoter A-181G were non-significantly differentially distributed between the two groups at 85.8, 11.2 and 3.0%, respectively, in pterygium cases and 88.4, 9.7 and 1.9% in controls, respectively (p for trend=0.6822). There was no polymorphic genotype for MMP7 C-153T among our Taiwanese cohort. Conclusion: A-181G and C-153T genotypes at MMP7 do not have a direct role in determining Taiwanese susceptibility to pterygium.

Background/aim Oral cancer is of the highest incidence worldwide in Taiwan, and a better marker for personalized therapeutic strategies such as immunotherapies is urgently needed. Interleukin-12 (IL12) is a cytokine that has been reported to exhibit potent tumoricidal effects, however, its genotypic contribution to oral cancer is still largely unknown. The current study aimed at investigating whether IL12B rs3212227 genotype is associated with oral cancer in Taiwan. Materials and methods Genotypic characteristics of IL12B rs3212227 were determined among 958 oral cancer cases and age- and gender-matched individuals via typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results The AA, AC and CC genotypes of IL12B rs3212227 were 38.2, 38.9 and 22.9% in the case group and 36.2, 41.5 and 22.3% in the control group (p=0.5189), respectively. Conclusion IL12B rs3212227 genotype was associated with oral cancer risk only in betel quid chewers.

BACKGROUND/AIM Breast cancer incidence is highest among women worldwide, and practical markers for personalized therapeutic strategies are few. Interleukin-12 (IL-12) is a cytokine that is reported to be significantly lower in healthy controls than breast cancer cases, however, its genotypic contribution to carcinogenesis has never been revealed in breast cancer. We examined whether IL-12A rs568408 and rs2243115 genotypes contribute to elevated breast cancer risk and summarized related literature among other cancers. MATERIALS AND METHODS IL-12A genotypic profiles were determined among 1,232 breast cancer cases and 1,232 healthy controls via polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS The variant genotypes of IL-12A rs568408 and rs2243115 were not found to be significantly associated with elevated breast cancer risk (both p>0.05). CONCLUSION IL-12A rs568408 and rs2243115 genotypes may not serve as good predictors of breast cancer risk.

Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk.MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples.MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index.Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

Background/Aim: Matrix metalloproteinase-1 is responsible for extracellular matrix regulation, and its genetic role in colorectal cancer (CRC) is unclear. The aim of the study was to investigate the contribution of Matrix metalloproteinase-1 genotypes to CRC risk in Taiwan. Materials and Methods: A total of 362 cases and 362 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined. The environmental factors and clinical-pathological records were also analyzed. Results: The genotypic frequency of MMP-1 rs1799750 were different between the CRC and control groups (p for trend=0.0083). 1G/2G and 1G/1G were associated with lower risk (p=0.0438 and 0.0030, adjusted OR=0.73 and 0.54, 95%CI=0.54-0.90 and 0.37-0.83). Among non-smokers, those with 1G/2G and 1G/1G genotypes were at 0.70- and 0.48-fold odds of having CRC. Among non-alcohol drinkers, people with 1G/2G and 1G/1G genotypes were at 0.71- and 0.54-fold odds. The 1G/1G genotypes were statistically lower among CRC patients with lymph node metastasis (7.2%) than those without (19.0%). Conclusion: The genotypes at MMP-1 rs1799705 play a role in determining susceptibility to CRC risk in Taiwan.

The DNA repair capacity plays a critical role in maintaining the genomic stability and gatekeeping for individual cancer risk. In this study, we aim at evaluation the role of the Asp148Glu (rs1130409) variant at apurinic/apyrimidinic endonuclease (APE) gene in renal cell carcinoma (RCC) risk and the contribution of different genotypes to its transcriptional mRNA levels. In the case-control study, 92 RCC patients and 580 cancer-free patients matched by age and gender were recruited. The apurinic/APE genotyping work was conducted with typical restriction fragment length polymorphism methodology after polymerase chain reaction. At the meanwhile, thirty renal tissue samples with variant genotypes were examined for their apurinic/APE mRNA and protein expressions by real-time quantitative reverse transcription method and Western blotting. The results showed that compared with the wild-type TT genotype, the people with TG and GG genotypes of apurinic/APE Asp148Glu had 0.88- and 1.09-fold risk of RCC, respectively. We have also examined the in vivo transcriptional (RNA) and translational (protein) levels with renal tissues of various apurinic/APE Asp148Glu genotypes, revealing that the apurinic/APE mRNA and protein were of similar levels among people of TT, TG, or GG genotypes. There was no joint gene-environment effect of apurinic/APE Asp148Glu genotype and smoking habit on RCC risk. The evidence indicated that apurinic/APE Asp148Glu genotypic variants did not alter its mRNA and protein expression among RCC patients. The genotype of apurinic/APE Asp148Glu may not serve as a proper predictive marker for RCC risk in Taiwan.

To investigate the association between adiponectin (ADIPOQ) genotypes and colorectal cancer (CRC) risk among Taiwanese.Polymerase chain reaction-restriction fragment length polymorphism was adopted to identify ADIPOQ rs266729, rs2241766 and rs1501299 genotypes among 362 CRC patients and 362 healthy controls.ADIPOQ rs266729 GG genotype (p=0.0075) and G allele (p=0.0061) are associated with a significantly increased CRC risk. There is no differential distribution of rs2241766 and rs1501299 genotypes. As for the gene-lifestyle interaction, there are obvious joint effects of rs266729 genotype on the CRC risk among non-smoker, non-alcohol drinker, while not on smoker or non-drinker subgroups. No significant correlation was observed between rs266729 genotypic distributions and age, gender, tumor size, location or metastasis status. Interestingly, a correlation of rs266729 genotype and larger BMI on CRC risk was found.G allele at ADIPOQ rs266729 may serve as a determiner for CRC risk, especially for those with BMI ≥24.

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.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.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.The genotypes at rs1799705 play a role in determining personal susceptibility to pterygium.

Few studies have examined the genetic role of matrix metalloproteinases (MMPs) to early detection or prediction in gastric cancer development. In this study, the contribution of MMP7 promoter (A-181G and C-153T) polymorphic genotypes to gastric cancer risk in Taiwanese was investigated for the first time.A total of 121 cases and 363 controls were enrolled and their MMP7 genotypes at A-181G and C-153T were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using genomic DNA from serum.The GG genotype at MMP7 A-181G was found to represent a risk factor for gastric cancer, especially among smokers. No individual with variant genotype carrier at MMP7 C-153T was found among this Taiwanese population.The G allele of MMP7 A-181G may serve as an early predictor for gastric cancer risk in Taiwanese; other gastric cancer markers are still urgently needed.

Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a physiological neurotoxin reported to induce oxidative-induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. In the study, we aim at examining the feasibility of VPA as a protector for dopaminergic neurons against damage from 6-OHDA, and the intracellular mechanisms. The 6-OHDA-induced neurotoxicity to the human dopaminergic cell line SH-SY5Y was applied for examining VPA protective effects. Pretreatment with VPA was able to improve cell viability and reduce 6-OHDA-induced reactive oxygen species. Furthermore, a significant suppression of apoptotic caspases including cleaved caspase-3, caspase-7, and caspase-9 was observed. The results also revealed VPA decreased the 6-OHDA-induced Bax/Bcl2 ratio, as measured at protein level. These novel findings indicate that VPA may be capable of protecting the SH-SY5Y dopaminergic neuronal cells from 6-OHDA-induced toxicity via the deceasing of apoptotic caspases (cleaved caspase-3, caspase-7, and caspase-9) and reducing of the Bax/Bcl2 ratio. Very possibly, VPA could serve as not only a mood stabilizer but also a potential antidote for PD prevention.

Interleukin-18 (IL-18) is a multi-functional immuno-mediator in the development and progression of many types of infectious and inflammatory diseases. In this study, we evaluated the contribution of IL-18 genotypes to renal cell carcinoma (RCC) in Taiwan via the genotyping of IL-18 -656 (A/C), -607 (A/C), and -137 (G/C). Moreover, we analyzed their interactions with smoking, alcohol drinking, hypertension, and diabetes status. The results showed an association of the AC and CC genotypes of IL-18 &minus, 607 with a significant decrease in the risk of RCC compared with the AA genotype (odds ratio (OR) = 0.44 and 0.35, 95% confidence interval (CI) = 0.27&ndash, 0.72 and 0.18&ndash, 0.66, p = 0.0008 and 0.0010, respectively). Furthermore, a significantly lower frequency of the C allele at -607 was observed in the RCC group (35.3% vs. 49.8%, OR = 0.53, 95% CI = 0.35&ndash, 0.71, p = 0.0003). However, IL-18 -656 and -137 did not exhibit a likewise differential distribution of these genotypes between the control and case groups. Stratifying the population according to smoking, alcohol drinking, hypertension, and diabetes status revealed a different distribution of IL-18 -607 genotypes among non-smokers, non-drinkers, and patients without diabetes, but not among smokers, drinkers, or patients with diabetes. These findings suggest that IL-18 -607 genotypes may play a role in the etiology and progression of RCC in Taiwan and may serve as a useful biomarker for early detection.

Cantharidin (CTD), a component of natural mylabris (Mylabris phalerata Pallas), has been shown to have biological activities and induce cell death in many human cancer cells. In the present study, we investigated the effect of CTD on cell migration and invasion of NCI-H460 human lung cancer cells. Cell viability was examined and results indicated that CTD decreased the percentage of viable cells in dose-dependent manners. CTD inhibited cell migration and invasion in dose-dependent manners. Gelatin zymography analysis was used to measure the activities of matrix metalloproteinases (MMP-2/-9) and the results indicated that CTD inhibited the enzymatic activities of MMP-2/-9 of NCI-H460 cells. Western blotting was used to examine the protein expression of NCI-H460 cells after incubation with CTD and the results showed that CTD decreased the expression of MMP-2/-9, focal adhesion kinase (FAK), Ras homolog gene family, member A (Rho A), phospho-protein kinase B (AKT) (Thr308)(p-AKT(308)), phospho-extracellular signal-regulated kinase1/2 (p-ERK1/2), phospho-p38 mitogen-activated protein (MAP) kinase (p-p38), phospho c-Jun N-terminal kinase 1/2 (p-JNK1/2), nuclear factor-κB (NF-κB) and urokinase plasminogen activator (UPA). Furthermore, confocal laser microscopy was used to confirm that CTD suppressed the expression of NF-κB p65, but did not significantly affect protein kinase C (PKC) translocation in NCI-H460 cells. Based on those observations, we suggest that CTD may be used as a novel anticancer metastasis agent for lung cancer in the future.

Isothiocyanates (ITCs) occur in many cruciferous vegetables. These compounds, which have significant anticancer actions, can induce apoptosis in different human cancer cell lines. In the present study, we investigated if allyl isothiocyanate (AITC) would induce toxicity in human breast cancer MCF-7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor negative) cells. We found that AITC stimulated reactive oxygen species and Ca[Formula: see text] production, and decreased the mitochondrial membrane potential. Activity of caspase-8, -9 and -3 was increased by AITC in both cell lines. AITC also induced mitochondrial-mediated apoptosis, as shown by cytochrome c, AIF and Endo G release from mitochondria, activation of caspase-9 and caspase-3, and formation of DAPI-positive cells. There was a significant reduction in the levels of the anti-apoptotic protein Bcl-2 along with a marked increase in the pro-apoptotic protein Bax in both cell lines. AITC induced apoptosis in human breast cancer MCF-7 cells via AIF and Endo G signaling pathways, but in MDA-MB-231 cells apoptosis occurred via the GADD153 pathway. This study has revealed novel anti-cancer mechanisms of AITC, a compound that is ordinarily present in human diets and may have potential therapeutic effects in various cancers.

Casticin, a polymethoxyflavone occurring in natural plants, has been shown to have anticancer activities. In the present study, we aims to investigate the anti-skin cancer activity of casticin on melanoma cells in vitro and the antitumor effect of casticin on human melanoma xenografts in nu/nu mice in vivo. A flow cytometric assay was performed to detect expression of viable cells, cell cycles, reactive oxygen species production, levels of [Formula: see text] and caspase activity. A Western blotting assay and confocal laser microscope examination were performed to detect expression of protein levels. In the in vitro studies, we found that casticin induced morphological cell changes and DNA condensation and damage, decreased the total viable cells, and induced G2/M phase arrest. Casticin promoted reactive oxygen species (ROS) production, decreased the level of [Formula: see text], and promoted caspase-3 activities in A375.S2 cells. The induced G2/M phase arrest indicated by the Western blotting assay showed that casticin promoted the expression of p53, p21 and CHK-1 proteins and inhibited the protein levels of Cdc25c, CDK-1, Cyclin A and B. The casticin-induced apoptosis indicated that casticin promoted pro-apoptotic proteins but inhibited anti-apoptotic proteins. These findings also were confirmed by the fact that casticin promoted the release of AIF and Endo G from mitochondria to cytosol. An electrophoretic mobility shift assay (EMSA) assay showed that casticin inhibited the NF-[Formula: see text]B binding DNA and that these effects were time-dependent. In the in vivo studies, results from immuno-deficient nu/nu mice bearing the A375.S2 tumor xenograft indicated that casticin significantly suppressed tumor growth based on tumor size and weight decreases. Early G2/M arrest and mitochondria-dependent signaling contributed to the apoptotic A375.S2 cell demise induced by casticin. In in vivo experiments, A375.S2 also efficaciously suppressed tumor volume in a xenotransplantation model. Therefore, casticin might be a potential therapeutic agent for the treatment of skin cancer in the future.

Open data has been noted as one of the main objectives of open government, and eventually as a foundation for creating value-added business and public applications in various domains such as e-Tourism and e-Participation. Value proposition to and creation for all stakeholders in the open data service chain are key factors to the success of developing and delivering Open Data Applications (ODAs). As critical is the design and development of suitable business models that help direct value proposition, creation, and assessment, and further sustain continuous business operations. In the literature, there is still a lack of studies comprehensively addressing issues regarding value creation and business model design of open data applications. This article introduces an ODA applicable value-centric Business Model (ODA-vBM) framework for guiding the development of operational business models that support the full value management process, including value identification, proposition, creation, and assessme...

Nonsmall cell lung carcinoma (NSCLC) is a devastating primary lung tumor resistant to conventional therapies. Bisdemethoxycurcumin (BDMC) is one of curcumin derivate from Turmeric and has been shown to induce NSCLC cell death. Although there is one report to show BDMC induced DNA double strand breaks, however, no available information to show BDMC induced DNA damage action with inhibited DNA repair protein in lung cancer cells in detail. In this study, we tested BDMC-induced DNA damage and condensation in NCI-H460 cells by using Comet assay and DAPI staining examinations, respectively and we found BDMC induced DNA damage and condension. Western blotting was used to examine the effects of BDMC on protein expression associated with DNA damage and repair and results indicated that BDMC suppressed the protein levels associated with DNA damage and repair, such as 14-3-3σ (an important checkpoint keeper of DDR), O6-methylguanine-DNA methyltransferase, DNA repair proteins breast cancer 1, early onset, mediator of DNA damage checkpoint 1 but activate phosphorylated p53 and p-H2A.X (phospho Ser140) in NCI-H460 cells. Confocal laser systems microscopy was used for examining the protein translocation and results show that BDMC increased the translocation of p-p53 and p-H2A.X (phospho Ser140) from cytosol to nuclei in NCI-H460 cells. In conclusion, BDMC induced DNA damage and condension and affect DNA repair proteins in NCI-H460 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1859-1868, 2016.

Cancer is the second cause of death in children. Osteosarcoma is the most common primary malignancy of solid bone cancer primarily affecting adolescents and young adults. In the Chinese population, the crude extract of Rheum palmatum L. (CERP) has been used for treating different diseases, including SARS, rheumatoid arthritis, coxsackievirus B3, and human colon cancer cell, pancreatic cancer. There are no reports on CERP and human osteosarcoma cells. The present study examined effects of CERP on cytotoxicity including cell cycle distribution and cell death (apoptosis) in U-2 OS human osteosarcoma cells. CERP significantly induced S phase arrest in U-2 OS cells in a dose-dependent. CERP produced DNA damage and DNA condensation. Other effects of CERP were stimulation of ROS and Ca(2+) , mitochondria impairment, and activation of caspase-3, -8, and -9. CERP increased the levels of Bax, Bak, Bad, cyclin B, Fas, PARP, GRP78, GADD153, AIF, Endo G, Calpain-2, p21, and p27, but decreased the levels of Bcl-2, BCL-X, XIAP, Akt, CDC25A, CDK2, Cyclin A, and Cyclin E of U-2 OS cells. It was also observed that CERP promoted the expression of AIF, Endo G, GADD153, and cytochrome c. These results indicate that CERP has anticancer effects in vitro and provide the foundation for in vivo studies of animal models of osteosarcoma. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 957-969, 2016.

Skeletal class III malocclusion treated with orthognathic surgery usually can achieve a better facial profile and stable occlusion outcome. We describe a 37-year-old patient who sought orthodontic treatment for skeletal class III, but refused recommendations for orthognathic surgery because of personal considerations. After careful analysis of the X-ray images and study models, this patient was subjected to active orthodontic treatment to correct malocclusion using upper and lower arch with improved superelastic NiTi alloy wire (ISW) for efficient leveling of the teeth. In the lower arch, the multibends edgewise archwire (MEAW) technique was used to tip back and intrude the canine and posterior teeth. After the completion of treatment, anterior teeth crossbite was successfully corrected and proper occlusal relationships were reestablished. How to cite this article Chang YC, Jian-Hong YU, Tsai YY, Chien-Chih Y, Pan PW. Nonsurgical Correction of Skeletal Class III Malocclusion by Multibends Edgewise Archwire Technique in an Adult. Int J Experiment Dent Sci 2015;4(2): 137-142.

Background/purpose In this study, we investigated the effects of a gel form of eucalyptol oil used for debonding orthodontic brackets. It was hypothesized that the use of this gel would lower the shear bonding forces between the bracket and the surfaces of human teeth. Materials and methods Two types of brackets (metal and ceramic materials) and two kinds of gel forms were used. All experimental samples were debonded using a JSV H1000 testing machine. Results A statistically significant decrease was observed in the shear bonding force for metal brackets using eucalyptol, regardless of whether it was in a liquid or a gel form (P Conclusion The most efficient way to reduce shear bonding forces between a metal orthodontic bracket and a tooth surface during a debonding procedure may be to use eucalyptol mixed with Carbopol for 15 minutes.

Angiogenesis inhibitors are beneficial for the prevention and treatment of angiogenesis-dependent diseases including cancer. We examined the cytotoxic, anti-metastatic, anti-cancer and anti-angiogenic effects of diallyl trisulfide (DATS). In HT29 cells, DATS inhibited migration and invasion through the inhibition of focal adhesion kinase (FAK), extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 which was associated with inhibition of matrix metalloproteinases-2, -7 and -9 and VEGF. In human umbilical vein endothelial cells (HUVEC), DATS inhibited the migration and angiogenesis through FAK, Src and Ras. DATS also inhibited the secretion of VEGF. The capillary-like tube structure formation and migration by HUVEC was inhibited by DATS. The chicken egg chorioallantoic membrane (CAM) assay indicated that DATS treatment inhibited ex-vivo angiogenesis. We investigated the anti-tumour effects of DATS against human colon cancer xenografts in BALB/c(nu/nu) mice and its anti-angiogenic activity in vivo. In this in-vivo study, DATS also inhibited the tumour growth, tumour weight and angiogenesis (decreased the levels of haemoglobin) in HT29 cells. In conclusion, the present results suggest that the inhibition of angiogenesis may be an important mechanism in colon cancer chemotherapy by DATS.

Aim A decrease of systolic blood pressure in excess of 20 mmHg during haemodialysis treatment (IDD) is common for haemodialysis patients. Intradialytic hypotension (IDH) is symptomatic IDD by definition. Overproduction of nitric oxide (NO) is a possible cause of IDD. Dialysate nitrate and nitrite amount can be used as an indicator of intradialysis NO production. Our aim was to find the predictor of NO production in IDD patients. Methods Partial dialysate samples were collected during the whole haemodialysis session and total dialysate nitrate and nitrite amount was measured to assess the association of intradialysis NO production with blood pressure change. Results There were 31 IDD patients and 71 patients who did not develop IDD (NIDD) included in the study. Among the IDD patients, 13 were IDH patients with a mean systolic blood pressure lower than that of the other 18 symptomless IDD patients (96.6 ± 3.4 mmHg vs 125.0 ± 3.8 mmHg, P

Diallyl trisulfide (DATS), a chemopreventive dietary constituent and extracted from garlic, has been shown to against cultured many types of human cancer cell liens but the fate of apoptosis in murine leukemia cells in vitro and immune responses in leukemic mice remain elusive. Herein, we clarified the actions of DATS on growth inhibition of murine leukemia WEHI-3 cells in vitro and used WEHI-3 cells to generate leukemic mice in vivo, following to investigate the effects of DATS in animal model. In in vitro study, DATS induced apoptosis of WEHI-3 cells through the G0/G1 phase arrest and induction of caspase-3 activation. In in vivo study DATS decreased the weight of spleen of leukemia mice but did not affect the spleen weight of normal mice. DATS promoted the immune responses such as promotions of the macrophage phagocytosis and NK cell activities in WEHI-3 leukemic and normal mice. However, DATS only promotes NK cell activities in normal mice. DATS increases the surface markers of CD11b and Mac-3 in leukemia mice but only promoted CD3 in normal mice. In conclusion, the present study indicates that DATS induces cell death through induction of apoptosis in mice leukemia WHEI-3 cells. DATS also promotes immune responses in leukemia and normal mice in vivo.

Lung cancer is one of the leading causes of death in cancer-related diseases. Cantharidin (CTD) is one of the components of natural mylabris (Mylabris phalerata Pallas). Numerous studies have shown that CTD induced cytotoxic effects on cancer cells. However, there is no report to demonstrate that CTD induced apoptosis in human lung cancer cells. Herein, we investigated the effect of CTD on the cell death via the induction of apoptosis in H460 human lung cancer cells. Flow cytometry assay was used for examining the percentage of cell viability, sub-G1 phase of the cell cycle, reactive oxygen species (ROS) and Ca²⁺ productions and the levels of mitochondrial membrane potential (∆Ψm). Annexin V/PI staining and DNA gel electrophoresis were also used for examining cell apoptosis. Western blot analysis was used to examine the changes of apoptosis associated protein expression and confocal microscopy for examining the translocation apoptosis associated protein. Results indicated that CTD significantly induced cell morphological changes and decreased the percentage of viable H460 cells. CTD induced apoptosis based on the occurrence of sub-G1 phase and DNA fragmentation. We found that CTD increased gene expression (mRNA) of caspase-3 and -8. Moreover, CTD increased ROS and Ca2+ production and decreased the levels of ∆Ψm. Western blot analysis results showed that CTD increased the expression of cleavage caspase-3 and -8, cytochrome c, Bax and AIF but inhibited the levels of Bcl-xL. CTD promoted ER stress associated protein expression such as GRP78, IRE1α, IRE1β, ATF6α and caspase-4 and it also promoted the expression of calpain 2 and XBP-1, but inhibited calpain 1 that is associated with apoptosis pathways. Based on those observations, we suggest that CTD may be used as a novel anticancer agent for the treatment of lung cancer in the future.

Osteosarcoma is the most common primary bone malignancy and primarily occurs in adolescents and young adults. Crude extract of Rheum palmatum L. (CERP) has been used as a traditional Chinese medicine for different diseases and there is experimental evidence that it may have anti-cancer effects. However, there is no information showing that CERP can affect the mobility of human osteosarcoma cells. In this study we determined the effects of CERP on U-2 OS human osteosarcoma cells. We found that CERP significantly inhibited the migration and invasion of U-2 OS cells. CERP also reduced the activity of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased expression levels of the proteins FAK, GRP78, PKC, HIF-1, SOS1, VEGF, PI3K, GRB2, Ras, p-ERK1/2, ERK1/2, p-p38, JNK1/2, p-JNK1/2, MEKK3, MKK7, PERK, p-PERK, iNOS, COX-2, NF-κB p65, IRE-1, UPA, and RhoA in U-2 OS cells. Confocal laser microscopy revealed that CERP decreased the expression of NF-κB p65, RhoA and Rock 1. These in vitro studies suggest that CERP may have novel anti-cancer actions in the treatment of osteosarcoma. Further studies including animal models of bone cancer are warranted.

Osteosarcoma is the most common primary malignancy of the bone cancers. In the Chinese population, the crude extract of Corni Fructus (CECF) has been used as Traditional Chinese medicine to treat several different diseases for hundreds of years. In the present study, effects of CECF on inhibition of migration and invasion in U-2 OS human osteosarcoma cells were examined. CECF significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells. We also found that CECF inhibited activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). CECF decreased protein levels of FAK, PKC, SOS1, MKK7, MEKK3, GRB2, NF-κB p65, COX-2, HIF-1α, PI3K, Rho A, ROCK-1, IRE-1α, p-JNK1/2, p-ERK1/2, p-p38, Ras, p-PERK, MMP-2, MMP-9, and VEGF in U-2 OS cells. Results of this study indicate that CECF may have potential as a novel anticancer agent for the treatment of osteosarcoma by inhibiting migration and invasion of cancer cells.

We have reported previously that phenethyl isothiocyanate (PEITC) induces apoptosis in human osteosarcoma U-2 OS cells. Cytotoxic activity of PEITC towards other cancer cells such as human malignant melanoma and skin cancer cells has not been reported. In this study, the anticancer activity of PEITC towards human malignant melanoma cancer A375.S2 cells was investigated. To determine the mechanisms of PEITC inhibition of cell growth, the following end points were determined in A375.S2 cells: cell morphological changes, cell cycle arrest, DNA damage and fragmentation assays and morphological assessment of nuclear change, reactive oxygen species (ROS) and Ca2+ generations, mitochondrial membrane potential disruption, and nitric oxide and 10- N-nonyl acridine orange productions, expression and activation of caspase-3 and -9, B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2, poly (adenosine diphosphate-ribose) polymerase, and cytochrome c release, apoptosis-inducing factor and endonuclease G. PEITC induced morphological changes in time- and dose-dependent manner. PEITC induced G2/M phase arrest and induced apoptosis via endoplasmic reticulum stress-mediated mitochondria-dependent pathway. Western blot analysis showed that PEITC promoted Bax expression and inhibited Bcl-2 expression associated with the disintegration of the outer mitochondrial membrane causing cytochrome c release, and activation of caspase-9 and -3 cascade leading to apoptosis. We conclude that PEITC-triggered apoptotic death in A375.S2 cells occurs through ROS-mediated mitochondria-dependent pathways.

Crude extract of Rheum palmatum L (CERP) has been used to treat different diseases in the Chinese population for decades. In this study, we investigated the effects of CERP on LS1034 human colorectal cancer cells in vitro and also examined possible mechanisms of cell death. Flow cytometric assays were used to measure the percentage of viable cells, cell cycle distribution including the sub-G1 phase (apoptosis), the activities of caspase-8, -9, and -3, reactive oxygen species (ROS) and Ca(2+) levels, and mitochondrial membrane potential (ΔΨm). DNA damage, nuclei condensation, protein expression, and translocation were examined by Comet assay, 4'-6-diamidino-2-phenylindole (DAPI) staining, Western blotting, and confocal laser system microscope, respectively. CERP induced apoptosis as seen by DNA fragmentation and DAPI staining in a concentration- and time-dependent manner in cancer cells. CERP was associated with an increase in the Bax/Bcl-2 protein ratio and CERP promoted the activities of caspase-8, -9, and -3. Both ROS and Ca(2+) levels were increased by CERP but the compound decreased levels of ΔΨm in LS1034 cells. Laser confocal microscope also confirmed that CERP promoted the expressions of AIF, Endo G, cytochrome c, and GADD153 to induce apoptosis through mitochondrial-dependent pathway.

4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR. K87 decreased the percentage of viable cells in dose-dependent manner. K87 suppressed cell mobility, migration and invasion of SCC-4 cells dose-dependently. K87 inhibited the enzymatic activities of MMP-2/9 of SCC-4 cells. Western blot analysis revealed that K87 decreased the protein levels in NF-κBp65, COX-2, ROCK1 and Rho A, MMP-1, -2,- 7, -9, VEGF, GRB2, SOS1, PI3K, PKC, PERK, p-PERK, FAK, MEKK3, MKK7, ERK1/2, JNK1/2, p-p38, p38, p-c-Jun, AKT, TIMP2, but increased the protein levels of iNOS, Ras, IRE-1α, p-c-JNK, p-AKT(308), p-AKT(473) and TIMP1. Results from PCR indicated that K87 inhibited the gene expression of MMP-2/-7, FAK and ROCK1 mRNA. Furthermore, confocal laser microscopy was used to confirm that K87 inhibited the translocation of RHOA and ROCK1 in SCC-4 cells. EMSA assay also show that K87 suppressed the nuclear activation of NF-κB and these effects are time-dependent. Western blotting assay indicated that expression of NF-κBp105, NF-κBp50 and NF-κBp65 proteins were decreased and these effects are time-dependent. Based on these observations, we suggest that K87 may be used as a potential agent for anticancer metastasis of human oral cancer in the future.

Crude extract of Corni Fructus (CECF) has been used in Traditional Chinese medicine for the treatment of different diseases for hundreds of years. The purpose of this study was to investigate the cytotoxic effects of CECF on U-2 OS human osteosarcoma cells. Flow cytometry was used for measuring the percentage of viable cells, cell-cycle distribution, apoptotic cells in sub-G1 phase, reactive oxygen species (ROS), Ca(2+) levels, and mitochondrial membrane potential (ΔΨm ). Comet assay and 4'-6-diamidino-2-phenylindole staining were used for examining DNA damage and condensation. Western blotting was used to examine apoptosis-associated protein levels in U-2 OS cells after exposed to CECF. Immunostaining and confocal laser system microscope were used to examine protein translocation after CECF incubation. CECF decreased the percentage of viability, induced DNA damage and DNA condensation, G₀/G₁ arrest, and apoptosis in U-2 OS cells. CECF-stimulated activities of caspase-8, caspase-9, and caspase-3, ROS, and Ca(2+) production, decreased ΔΨm levels of in U-2 OS cells. CECF increased protein levels of caspase-3, caspase-9, Bax, cytochrome c, GRP78, AIF, ATF-6α, Fas, TRAIL, p21, p27, and p16 which were associated with cell-cycle arrest and apoptosis. These findings suggest that CECF triggers apoptosis in U-2 OS cells via ROS-modulated caspase-dependent and -independent pathways.

The cytostatic drug from natural products has acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Apigenin, a type of flavonoid, exhibits anticancer actions, but there is no report to show that apigenin induced apoptosis in osteosarcoma cells. The aim of this study was to investigate the effects of apigenin on U-2 OS human osteosarcoma cells and clarify that the apigenin-induced apoptosis-associated signals. The cytotoxic effects of apigenin were examined by culturing U-2 OS cells with or without apigenin. The percentage of viable cells via PI staining, apoptotic cells, productions of ROS and Ca²⁺, and the level of mitochondrial membrane potential (ΔΨm) were assayed by flow cytometry. The levels of apoptosis-related proteins were measured by immunoblotting. Results indicated that apigenin significantly decreased cell viability. Apigenin effectively induced apoptosis through the activations of caspase-3, -8, -9, and BAX and promoted the release of AIF in U-2 OS cells. In nude mice bearing U-2 OS xenograft tumors, apigenin inhibited tumor growth. In conclusion, apigenin has anticancer properties for induction of cell apoptosis in U-2 OS cells and suppresses the xenograft tumor growth. These findings offer novel information that apigenin possibly possesses anticancer activity in human osteosarcoma.

Dramatic increases in embedded data processing performance are becoming possible using platforms such as the NASA SpaceCube. With a flexible architecture and commercial devices, selected computations can be tuned for the highest performance while giving up perfect data reliability. More needs to be known about the nature of silent data corruption in this paradigm. When it occurs, how pervasive is it? To what extent can it be mitigated while near-optimal performance is maintained? This paper provides new insights into these questions, via a fault emulation-based study of two disparate applications running on a hard-core embedded processor. Two very low-cost methods of data error detection reduce the worst type of silent data corruption (SDC) by 89-97% with a performance overhead of

To elevate chemo-resistance of human cancer cells is a major obstacle in the treatment and management of malignant cancers. Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are presented in the Alliaceae family particularly in garlic. Although DAS, DADS and DATS have been shown to exhibit anticancer activities, there is little information on effects of these compounds on drug resistant genes in human colon cancer cells in vitro and in vivo. Herein, we are the first to show that DAS, DADS and DATS at 25 μM for 24-h and 48-h incubations promoted expression of drug resistant genes in colo 205 human colon cancer cells. In vitro experiments indicated that DATS promoted gene expression of multidrug resistant 1 (Mdr1) (p

In this study, we examined the effects of several plant-derived natural compounds on head and neck squamous cell carcinoma (HNSCC) cells. The results revealed that (-)-epigallocatechin gallate (EGCG) demonstrated the most efficient cytotoxic effects on HNSCC cells. We then investigated the underlying molecular mechanism for the potent proapoptotic effect of EGCG on HNSCC. Cell apoptosis was observed in the EGCG-treated SAS and Cal-27 cells in a time- and dose-dependent manner. In concert with the caspase-8 activation by EGCG, an enhanced expression in functional Fas/CD95 was identified. Consistent with the increased Fas/CD95 expression, a drastic decrease in the Tyr705 phosphorylation of STAT3, a known negative regulator of Fas/CD95 transcription, was shown within 15 min in the EGCG-treated cells, leading to downregulation of the target gene products of STAT3, such as bcl-2, vascular endothelial growth factor (VEGF), mcl-1, and cyclin D1. An overexpression in STAT3 led to resistance to EGCG, suggesting that STAT3 was a critical target of EGCG. Besides inhibiting constitutive expression, EGCG also abrogated the interleukin-6 (IL-6)-induced JAK/STAT3 signaling and further inhibited IL-6-induced proliferation on HNSCC cells. In comparison with apigenin, curcumin, and AG490, EGCG was a more effective inhibitor of IL-6-induced proliferation on HNSCC cells. Overall, our results strongly suggest that EGCG induces Fas/CD95-mediated apoptosis through inhibiting constitutive and IL-6-induced JAK/STAT3 signaling. This mechanism may be partially responsible for EGCG's ability to suppress proliferation of HNSCC cells. These findings provide that EGCG may be useful in the chemoprevention and/or treatment of HNSCC.

Benzyl isothiocyanates (BITC), a member of the isothiocyanate (ITC) family, inhibits cell growth and induces apoptosis in many types of human cancer cell lines. The present study investigated mechanisms underlying BITC-induced apoptosis in A375.S2 human melanoma cancer cells. To observe cell morphological changes and viability, flow cytometric assays, cell counting, and a contrast-phase microscopic examination were carried out in A375.S2 cells after BITC treatment. Cell cycle distribution and apoptosis were assessed with the analysis of cell cycle by flow cytometric assays, DAPI staining, propidium iodide (PI), and annexin V staining. Apoptosis-associated factors such as reactive oxygen species (ROS) formation, loss of mitochondrial membrane potential (ΔΨ(m)), intracellular Ca(2+) release, and caspase-3 activity were evaluated by flow cytometric assays. Abundance of cell cycle and apoptosis associated proteins was determined by Western blotting. AIF and Endo G expression was examined by confocal laser microscope. Results indicated that (1) BITC significantly reduced cell number and induced cell morphological changes in a dose-dependent manner in A375.S2 cells; (2) BITC induced arrest in cell cycle progression at G(2)/M phase through cyclin A, CDK1, CDC25C/Wee1-mediated pathways; (3) BITC induced apoptosis and increased sub-G(1) population; and (4) BITC promoted the production of ROS and Ca(2+) and loss of ΔΨ(m) and caspase-3 activity. Furthermore, BITC induced the down-regulation of Bcl-2 expression and induced up-regulation of Bax in A375.S2 cells. Moreover, BITC-induced cell death was decreased after pretreatment with N-acetyl-l-cysteine (NAC, a ROS scavenger) in A375.S2 cells. In conclusion, the results showed that BITC promoted the induction of G(2)/M phase arrest and apoptosis in A375.S2 human melanoma cells through ER stress- and mitochondria-dependent and death receptor-mediated multiple signaling pathways. These data suggest that BITC has potential as an agent for the treatment of melanoma.

It has been shown that deguelin, one of the compounds of rotenoids from flavonoid family, induced cytotoxic effects through induction of cell cycle arrest and apoptosis in many types of human cancer cell lines, but deguelin-affected DNA damage and repair gene expression (mRNA) are not clarified yet. We investigated the effects of deguelin on DNA damage and associated gene expression in human lung cancer NCI-H460 cells in vitro. DNA damage was assayed by using the comet assay and DNA gel electrophoresis and the results indicated that NCI-H460 cells treated with 0, 50, 250 and 500 nM deguelin led to a longer DNA migration smear based on the single cell electrophoresis and DNA fragmentation occurred based on the examination of DNA gel electrophoresis. DNA damage and repair gene expression (mRNA) were evaluated by using real-time PCR assay and the results indicated that 50 and 250 nM deguelin for a 24-h exposure in NCI-H460 cells, decreased the gene levels of breast cancer 1, early onset (BRCA1), DNA-dependent serine/threonine protein kinase (DNA-PK), O6-methylguanine-DNA methyltransferase (MGMT), p53, ataxia telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) mRNA expressions. Collectively, the present study showed that deguelin caused DNA damage and inhibited DNA damage and repair gene expressions, which might be due to deguelin-inhibited cell growth in vitro.

Curcumin from the rhizome of the Curcuma longa plant has been noted for its chemo-preventative and chemo-therapy activities, and it inhibits the growth of many types of human cancer cell lines. In this study, the mechanisms of cell death involved in curcumin-induced growth inhibition, including cell cycle arrest and induction of apoptosis in human tongue cancer SCC-4 cells, were investigated. Herein, we observed that curcumin inhibited cell growth of SCC-4 cells and induced cell death in a dose-dependent manner. Treatment of SCC-4 cells with curcumin caused a moderate and promoted the G(2) /M phase arrest, which was accompanied with decreases in cyclin B/CDK1 and CDC25C protein levels. Moreover, curcumin significantly induced apoptosis of SCC-4 cells with a decrease of the Bcl-2 level, reduction of mitochondrial membrane potential (ΔΨ(m) ), and promoted the active forms of caspase-3. Curcumin also promoted the releases of AIF and Endo G from the mitochondria in SCC-4 cells by using confocal laser microscope. Therefore, we suggest that curcumin induced apoptosis through a mitochondria-dependent pathway in SCC-4 cells. In addition, we also found that curcumin-induced apoptosis of SCC-4 cells was partly through endoplasmic reticulum stress. In conclusion, curcumin increased G(2) /M phase arrest and induced apoptosis through ER stress and mitochondria-dependent pathways in SCC-4 cells.

Many anticancer drugs are obtained from phytochemicals and natural products. However, some phytochemicals have mutagenic effects. Safrole, a component of Piper betle inflorescence, has been reported to be a carcinogen. We have previously reported that safrole induced apoptosis in human oral cancer cells in vitro and inhibited the human oral tumor xenograft growth in vivo. Until now, there is no information addressing if safrole promotes immune responses in vivo. To evaluate whether safrole modulated immune function, BALB/c mice were intraperitoneally injected with murine myelomonocytic WEHI-3 leukemia cells to establish leukemia and then were treated with or without safrole at 4 and 16 mg/kg. Animals were sacrificed after 2 weeks post-treatment with safrole for examining the immune cell populations, phagocytosis of macrophages and the natural killer (NK) cells' cytotoxicity. Results indicated that safrole increased the body weight, and decreased the weights of spleen and liver in leukemic mice. Furthermore, safrole promoted the activities of macrophages phagocytosis and NK cells' cytotoxicity in leukemic mice when compared with untreated leukemic mice. After determining the cell marker population, we found that safrole promoted the levels of CD3 (T cells), CD19 (B cells) and Mac-3 (macrophages), but it did not affect CD11b (monocytes) in leukemic mice. In conclusion, safrole altered the immune modulation and inhibited the leukemia WEHI-3 cells in vivo.

Liver cancer is one of the most commonly diagnosed cancers and the leading cause of death in human populations. Butein, a tetrahydroxychalcone, has been shown to induce apoptosis in many human cancer cells, but the effects of butein on the migration and invasion of human liver cancer cells are not reported. Herein, we found that butein is effective in the suppression of migration and invasion in SK-HEP-1 human hepatocarcinoma cells by using the Matrigel cell migration assay and invasion system. The gelatin zymography assay indicated that butein inhibited the activity of matrix metalloproteinases 2 (MMP-2) and MMP-9. Western blotting analysis indicated that butein decreased the levels of MMP-2, -7, and -9, uPA, Ras, Rho A, ROCK1, ERK1/2, JNK1/2, p-p38, and p-c-Jun in SK-HEP-1 cells. Furthermore, butein inhibited the NF-κB binding activity in SK-HEP-1 cells by electrophoretic mobility shift assay. We also found that butein decreased the ERK, JNK, and p38 in SK-HEP-1 cells by in vitro kinase assay. In conclusion, this is the first study to demonstrate that butein might be a novel anticancer agent for the treatment of hepatocarcinoma through inhibiting migration and invasion.

We report the case of a 46-year-old patient who suffered from huge tophus masses involving the metatarsal joints of the big toes of both feet, with infection and skin necrosis secondary to chronic tophaceous gout. After conventional curettage and debridement of each lesion, a free anterolateral thigh flap (ALTF) was used to resurface the circumferential wound, protect the underlying structures, and provide a gliding surface for the exposed tendons. The flap was safely raised and debulked during revision surgery, and excellent functional and cosmetic results were apparent at the 2-year follow-up. We consider ALTF to be a valuable option for the coverage of necrotic skin over tophi after adequate debridement. © 2009 Wiley-Liss, Inc. Microsurgery 2010.

In oral cavity reconstruction, the fasciocutaneous flaps of the distal extremities have always been preferred to any other kind of flap because of their thinness and pliability, which makes them adaptable to different areas in the oral cavity. The radial forearm flap is frequently considered the first choice for intraoral reconstruction, but the disadvantages of donor site morbidity include sacrificing a major artery to the hand and leaving a conspicuous donor site scar. The search for another primarily thinned skin flap as an alternative has led to the application of the medial sural artery perforator flap, which is harvested from the medial aspect of the upper calf. Between June 2003 and March 2007, 22 free medial sural artery perforator flaps were transferred for intraoral defects after cancer ablation, including tongue and floor of mouth (15 cases), buccal mucosa (5 cases), retromolar trigone (1 case), and anterior floor of mouth (1 case). We paid attention to the major perforator (vein > or =1 mm), which was confirmed by the endoscope, as the vascular relay for the skin flap. The size of the skin paddle varied from 7.5 x 4 cm to 17 x 8 cm. The main advantage of this flap is that it provides thin and pliable coverage to achieve better accuracy in the oral cavity. Other advantages of minimizing donor site morbidity include maintaining the function of the medial gastrocnemius muscle, avoiding the need to sacrifice major arteries of the leg, and possible primary closure of the donor defect.