Background:
Areca quid chewing increases the prevalence of periodontal diseases. Areca nut extract (ANE) inhibits the defensive functions of human polymorphonuclear leukocytes (PMNs). This in vitro ...study investigates the effects of ANE on the production of cyclooxygenase (COX)‐2 and the inflammatory mediator prostaglandin E
2
(PGE
2
) by PMNs.
Methods:
The possible effects of ANE on the production of COX‐2 were examined using Western blotting analysis. The viability and production of PGE
2
of treated PMNs were determined using the propidium iodide staining method and the competition enzyme assay, respectively. The possible pathways involved were also examined using the COX‐2 inhibitor (NS398), the intracellular calcium chelator 1,2‐bis(2‐aminophenoxy)ethane‐N, N, N′, N′‐tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA‐AM), the p38 mitogen‐activated protein kinase (MAPK) inhibitor (SB203580), and the extracellular signal‐regulated protein kinase (ERK) inhibitor (U0126). The effects of ANE on the viability or PGE
2
production were statistically assessed using a one‐way analysis of variance and Tukey multiple‐comparison intervals with α = 0.05.
Results:
ANE significantly induced the production of PGE
2
in a time‐ and concentration‐dependent manner. This induction resulted from an increased expression of COX‐2. Moreover, the application of BAPTA‐AM, SB203580, and U0126 statistically significantly suppressed the induction of PGE
2
.
Conclusions:
ANE induced the production of PGE
2
. The activation of the intracellular calcium concentrations, p38 MAPK, and ERK may be involved in the inducing effects of ANE on PMNs. The findings suggest that areca nut chewing may induce an inflammatory response and affect the periodontal health of consumers.
Abstract
Background Sorafenib is currently the only approved systemic agent for advanced hepatocellular carcinoma (HCC); however, its efficacy is limited. Aberrant activation of WNT/β-catenin ...signaling pathway has been shown to mediate resistance to various types of anti-cancer therapy. We hypothesized that inhibition of WNT/β-catenin signaling pathway would improve the anti-tumor effect of sorafenib in HCC.
Materials and Methods Human HCC cell lines, including Huh7, HepG2, PLC5, and Hep3B, were included. Inhibition of WNT/β-catenin pathway was achieved by ICG-001, a small molecule disrupting the interaction of cAMP-responsive element binding (CREB)-binding protein (CBP) and β-catenin and inhibiting the β-catenin-mediated transcription activities, or by RNA interference (RNAi)- downregulation of β-catenin. The efficacy of sorafenib combined with WNT/β-catenin pathway inhibition in HCC cells was determined by MTT for cell viability, and by flow cytometry and Western blotting for apoptosis. The in vivo efficacy was evaluated in a subcutaneous xenograft mode of Huh7 cells.
Results In multiple HCC cell lines, ICG-001 enhanced the anti-proliferative effect of sorafenib dose-dependently; the combination of ICG-001 and sorafenib showed a synergistic antitumor effect. Downregulation of β-catenin by RNAi increased sorafenib sensitivity, whereas overexpression of β-catenin decreased sorafenib sensitivity in Huh7 cells. Furthermore, the sorafenib-sensitization effect by short hairpin RNA (shRNA)-mediated β-catenin downregulation in Huh7 cells was offset by β-catenin overexpression. Mechanistically, sorafenib in combination of ICG-001 or shRNA- mediated β-catenin downregulation augmented the induction of apoptosis, and resulted in a more prominent downregulation of Mcl-1 in HCC cells. Finally, ICG-001 in combination of sorafenib showed a more significantly growth-retarding effect in Huh7 xenograft than either drug alone.
Conclusion Our data indicate that inhibition of WNT/β- catenin signaling pathway improves the antitumor effect of sorafenib against HCC in vitro and in vivo.(This study was supported by grants NRPB-100CAP1020-2 and NSC-101-2314-B-002-141, 100CAP1020-2).
Citation Format: Hsiao-Hui Lin, Wen-Chi Feng, Li-Chun Lu, Yu-Yun Shao, Ann-Lii Cheng, Chih-Hung Hsu. Improved antitumor effect of combining WNT/beta-catenin inhibition with sorafenib in hepatocellular carcinoma. abstract. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5336. doi:10.1158/1538-7445.AM2015-5336
Hepatitis B virus (HBV) infection is one of the main etiologies of hepatocellular carcinoma (HCC). We explored the impact of HBV DNA levels on the prognosis of patients with advanced HCC.
The study ...was based on patients with advanced HCC and chronic HBV infection enrolled into three phase II trials evaluating first-line antiangiogenic therapy. Pre-treatment HBV DNA levels were measured by real-time quantitative polymerase chain reaction.
Seventy-two patients were included. Patients with detectable HBV DNA levels had poorer median overall survival (OS) compared to patients without detectable levels (4.8 vs. 9.3 months, p=0.037). After adjusting for other clinicopathologic variables, the baseline HBV DNA level was an independent predictor of poor OS (p=0.014). Baseline HBV DNA levels were not correlated with progression-free survival or disease control rate.
Baseline HBV DNA levels were associated with the prognosis of patients with chronic HBV infection receiving antiangiogenic therapy for advanced HCC.
We report the synthesis, morphology, and photophysical properties of new conjugated rod-coil block copolymers consisting of poly2,7-(9,9-dihexylfluorene) (PF) conjugated rods and soft poly(
n
-butyl ...acrylate) (PBA) coils for stretchable light-emitting device applications. The PF-
b
-PBA thin films could form obvious self-assembled nanofibrillar structures after the solvent annealing treatment. Besides this, both the deformability and optical properties of block copolymers were controllable by varying the PF/PBA ratio. The annealed PF
4k
-
b
-PBA
7k
thin film exhibited pure blue emission with a high photoluminescence quantum yield of over 22.5% under 100% strain, validating the excellent stretchability and promising stability. Furthermore, a stretchable and fluorescent PF-
b
-PBA based microporous template with tunable regularity can be fabricated through the breath figure method. These results demonstrated that the novel intrinsically deformable and luminescent rod-coil block copolymers could have versatile applications in stretchable light-emitting devices.
Novel deformable and fluorescent PF-
b
-PBA copolymers with nanofibrillar structures were synthesized for unraveling strain-dependent optical properties.
Cancer-associated thrombosis (CAT) is a common complication of malignancies. Patients with CAT are at risk of venous thromboembolism recurrence, but also at risk of bleeding while anticoagulated. ...Taiwanese patients are perceived to have a lower incidence of CAT, likely leading to false reassurance for Taiwanese patients with cancer. Because of this, oncologists and cardiologists from multiple medical institutions in Taiwan have set forth to provide clinical consensus guidelines on the management of CAT, based on local clinical practices and guided by predominant international clinical practice guidelines. This paper aims to describe the current disease burden of cancer-associated venous thromboembolism in Taiwanese cancer patients, and discusses the unmet needs and gaps in the management of this medical complication. It also outlines diagnostic and management strategies relevant to the different treatment options available, such as non-vitamin K antagonist oral anticoagulants.
Whether serum triglyceride level correlates with clinical outcomes of patients with ST segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI) ...remains unclear.
From June 2008 to February 2012, all patients with STEMI who were treated with pPCI in this tertiary referral hospital and then had fasting lipid profiles measured within 24 hours were included and dichotomized into lower- (≦ 150 mg/dl) and higher-triglyceridemic (>150 mg/dl) groups. Baseline characteristics, in-hospital outcomes, and late major adverse cardiovascular events (MACE) were compared in-between. Independent predictors for in-hospital death and late adverse events were identified by multivariate logistic and Cox regression analyses.
A total of 247 patients were enrolled, including 163 lower-triglyceridemic and 84 higher-triglyceridemic subjects. The angiographic characteristics, pPCI results and in-hospital outcomes were similar between the two groups. However, multivariate logistic analysis identified triglyceride level as a negative predictor for in-hospital death (OR 0.963, 95% CI 0.931-0.995, p = 0.023). At follow-up for a mean period of 1.23 to 1.40 years, compared with the high-triglyceridemic group, low-triglyceridemic patients had fewer cumulative incidences of target vessel revascularization (TVR) (21.7% vs. 9.5%, p = 0.011) and overall MACE (26.1% vs. 11.9%, p = 0.0137). Cox regression analysis confirmed serum triglyceride as a negative predictor for TVR and overall MACE.
Serum triglyceride level inversely correlates with in-hospital death and late outcomes in patients with STEMI treated with pPCI. Thus, when managing such patients, a high serum triglyceride level can be regarded as a benign factor but not a target for aggressive therapy.
In this data, we present the details of the cross-sectional study from Mackay Memorial Hospital, Taipei, Taiwan that examined the relationship between three-dimensional (3D) peri-aortic root fat ...(PARF) volumes, cardiometabolic risk profiles, carotid artery morphology and remodeling. Our sample is composed of a total 1492 adults who underwent an annual cardiovascular risk survey in Taiwan.
PARF was measured using images of gated non-contrast cardiac computed tomography (CT) and a dedicated workstation (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). The stratified analyses were performed in order to assess the association between carotid morphology, remodeling and PARF by tertile. For further analyses and discussion, please see “The Association among Peri-Aortic Root Adipose Tissue, Metabolic derangements and Burden of Atherosclerosis in Asymptomatic Population” by Yun et al. (2015) 1.
The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease ...markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level.
Here, we build an integrative platform, the Encyclopedia of Hepatocellular Carcinoma genes Online, dubbed EHCO http://ehco.iis.sinica.edu.tw, to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25%) from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network) by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs.
This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract only
10569
Background: Childhood cancer survivors have excess risk of second malignant neoplasms, but data are limited in Asian populations. We established a nationwide retrospective cohort ...of childhood cancer survivors in Taiwan to study the risk of second malignant neoplasms in the population. Methods: Children and adolescents diagnosed with cancer before age 21 years between 1990 and 2011 were identified from the Taiwan Cancer Registry, the national cancer registry in Taiwan. One-year survivors of childhood cancer were ascertained through data linkage with the national death registry. Survivors were followed up through December 2012. Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of second malignant neoplasms were calculated. Results: A total of 186 second malignant neoplasms occurred among 15,263 1-year survivors of childhood cancer after a mean follow-up time of 8.0 years (SIR = 5.4, 95% confidence interval CI = 4.6-6.2; AER = 12.4 per 10,000 person-years). The most common types of second malignant neoplasms were gastrointestinal cancers (n = 37), leukemia (n = 28), endocrine cancers (n = 18), and brain cancer (n = 17). Cancers in the liver (n = 11, including 9 hepatocellular carcinoma) and colorectum (n = 16) accounted for 73% of second gastrointestinal malignant neoplasms in this population. The cumulative incidence of second malignant neoplasms at 10 and 20 years from follow-up was 1.0% (95% CI = 0.8-1.2%) and 3.0% (95% CI = 2.3-3.6%), respectively. Conclusions: Childhood cancer survivors in Taiwan experience excess risk of second malignant neoplasms, in particular gastrointestinal cancers, compared with the general population.
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