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Altered sialylation is closely associated with tumor progression and invasiveness. Micro-RNAs endogenous regulators of gene expression have been implicated in human thyroid carcinoma invasiveness. The objective of this study is to examine the alterations of miR-4299 and ST6GALNAC family in human follicular thyroid carcinoma during metastatic process. qRT-PCR showed the differential expressional profiles of miR-4299 and ST6GALNAC family in three kinds of thyroid cell lines (FTC-133,FTC-238, Nthy-ori 3-1) and clinical tissue specimens(malignant and borderline). The altered expression levels of ST6GALNAC4 were corresponding to invasive phenotypes of FTC-133 and FTC-238 cells both in vitro and in vivo. Further date indicated that miR-4299 regulated tumor progression and invasiveness by directly targeting ST6GALNAC4. This study implies the potential therapeutic application of miR-4299 and ST6GALNAC4 in modulating the invasion and tumorigenicity of follicular thyroid carcinoma cell. © 2015 IUBMB Life, 68(2):136-144, 2016 [ABSTRACT FROM AUTHOR]

The invasion and chemoresistance are crucial causes of morbidity and death for cancer patients. Axl is closely associated with malignant phenotype of breast tumor cells, including invasiveness and metastasis. Both breast cancer cell line and tissue displayed increased expression of Axl, especially in highly metastatic breast cancer. On the contrary, experimental inhibition of Axl or transforming growth factor beta 1 (TGF-β1) by RNAi assay could suppress cell invasion ability and chemoresistance. Moreover, the up-regulation of Axl was induced by TGF-β1, further activated phosphatidylinositol 3-kinase (PI3K)/Akt and PAK1 translocation, and resulted in greater cell motility, invasion, and chemoresistance in vitro and in vivo. After the detection and statistics in human breast cancer specimens, we found that the Axl expression was closely correlated with TGF-β1 level, tumor differentiation, lymph node metastasis, and clinical stage ( p < 0.01). Our findings support the possibility that Axl is a significant regulator of invasion and chemosensitivity, and it means by targeting Axl or its related signaling pathways, we can reduce the invasion and chemosensitivity of breast tumor. [ABSTRACT FROM AUTHOR]

A stable skull layer formed on the inner surface of the hearth could effectively protect the lining and extend blast furnace campaign life. This is the first comprehensive work of using integrated heat transfer, fluid flow dynamics and solidification numerical simulation to investigate skull formation phenomena in a blast furnace hearth. The impact of hearth design and furnace operation parameters on skull formation is examined, including lining property and structure, cooling water temperature and flow rate, hot metal production rate, temperature and viscosity, and cast practice. The findings from this study are compared with operating experience of United States Steel blast furnaces. [ABSTRACT FROM AUTHOR]

[Objective] The paper was to verify the disinfection effect of ozone on livestock and poultry houses. [Method] The empty chicken house was disinfected by ozone with the help of ozone disinfector. [Result] As the ozone disinfector was worked for 60 min, the average sterilizing rate of air was 85.33%; the average sterilizing rate on the surface of chicken coop was 86.77%; and the average sterilizing rate of wall was 89.13%. The disinfection effect was obvious. [Conclusion] The results will provide references for promotion and application of ozone disinfector in breeding industry. [ABSTRACT FROM AUTHOR]

Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials. However, the underlying mechanism remains to be elucidated. Here we show that LGX818 potently decreased ERK phosphorylation and inhibited proliferation in BRAFV600E melanoma cell lines. Moreover, LGX818 downregulated CyclinD1 in a glycogen synthase kinase 3β-independent manner and induced cell cycle arrest in the G1 phase, Surprisingly, LGX818 triggered cellular senescence in BRAFV600E melanoma cells, as evidenced by increased β-galactosidase staining, while no appreciable induction of apoptosis was detected, as determined by Annexin V and propidium iodide staining and immunoblot analysis of caspase-3 processing and poly (ADP-ribose) polymerase cleavage. Increased p27KIP1 expression and retinoblastoma protein activation were detected during LGX818-induced senescence. Additionally, inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 1B by AZ191 reversed LGX818-induced CyclinD1 turnover and senescence. Interestingly, autophagy is triggered through inhibition of the mTOR/70S6K pathway during LGX818-induced senescence. Moreover, autophagy inhibition by pharmacological and genetic regulation attenuates LGX818-induced senescence. Notably, combining LGX818 with autophagy modulators has anti-proliferative effect in LGX818-resistant BRAF mutant melanoma cells. Altogether, we uncovered a mechanism by which LGX818 exerts its anti-tumor activity in BRAFV600E melanoma cells. [ABSTRACT FROM AUTHOR]

Aiming at corrosion issues of structural materials in supercritical carbon dioxide Brayton systems, the corrosion behaviors of T91 and 316 were studied under S-CO 2 at 500 ℃, 600℃and 20 MPa. The corrosion kinetics conform to the parabolic law. The corrosion products of T91 are mainly composed of outer columnar Fe 3 O 4 and inner Fe-Cr spinel, which had porous structure and no protective effect for further corrosion. Thin and dense Cr 2 O 3 formed on the 316 surface after 500℃corrosion.While large numbers of Fe-oxide nodules formed on surface of Cr-rich scale at 600 ℃. The corrosion mechanism was discussed. • The corrosion behavior and mechanism of T91 and 316 exposed to supercritical carbon dioxide at 500 ℃, 600 ℃ and 20 MPa up to 1000 h was studied. • The morphology, structure and composition of oxide layers and carburization behavior of T91 and 316 were compared and analyzed. • The corrosion mechanism of T91 and 316 were discussed. [ABSTRACT FROM AUTHOR]

Purpose: The immediate plasma metabolism and development of chemo-resistance (single agent) severely hampers the clinical effectiveness of Sorafenib (SRF) in liver cancer therapy. MicroRNA27a inhibition is a promising biological strategy for breast cancer therapy. Methods: In this study, we aimed to prepare SRF and anti-miRNA27a-loaded anti-GPC3 antibody targeted lipid nanoparticles to enhance the therapeutic efficacy against liver cancers. In this study, we have employed a unique cationic switchable lipid (CSL) as a mean to encapsulate miRNA as well as to confer pH-responsiveness to the nanocarrier system. Results: The G-S27LN was nanosized and offered a pH-responsive release of SRF from the carrier system and we have demonstrated the specific affinity of G-S27LN towards the GPC3-overexpressed HepG2 cancer cells. Anti-microRNA27a significantly increased the protein expression of FOXO1 and PPAR-γ which are crucial components involved in proliferation and apoptosis of tumor cells. Combination of SRF and anti-miRNA27a (G-S27LN) resulted in significantly lower cell viability with a marked increase in the apoptosis cell proportion compared to that of free SRF indicating the synergistic anticancer effect. Animal studies in liver cancer xenograft model demonstrated significant suppression of tumor burden, reduced tumor cell and elevated TUNEL positive apoptosis with no toxicity concerns in animals treated with G-S27LN formulation. Conclusion: The CSL-based G-S27LN efficiently co-delivered anti-microRNA27a and SRF and therefore represents a promising therapy to treat liver cancer. This study also brings forth a platform strategy for the effective treatment of number of other advanced cancers. [ABSTRACT FROM AUTHOR]

In pressurized water reactors, LiOH may be concentrated in some areas, leading to the accelerated corrosion of fuel claddings. Injecting boric acid into primary coolants can mitigate the accelerated corrosion effect of LiOH on Zircaloys, but the effects of boron content on the corrosion behavior of the Zr-Sn-Nb alloy are still unknown. This work focused on the corrosion and hydrogen absorption behavior at 360 °C/18.6 MPa in 100 mg/kg LiOH solutions with 0 mg/kg, 50 mg/kg, and 200 mg/kg boron contents for up to 510 days, aiming to study the effect of boron content on corrosion resistance in LiOH solutions. Corrosion kinetics, microstructures of oxide films, hydrogen absorption concentrations and hydride morphology were obtained after the test. The results show that injecting boron in LiOH solutions can significantly reduce the corrosion weight gain, hydrogen concentration, and hydrogen length of Zr-Sn-Nb alloys, that is, improving corrosion resistance effectively. During the oxidation of the Zr-Sn-Nb alloy, B 3+ and Li + incorporate in oxide films. The incorporation of Li + may lead to the generation of oxygen vacancies, which can carry oxygen from the solutions to O/M interface, accelerating corrosion. The incorporation of B 3+ in oxide films will slow down the oxidation of Zr-Sn-Nb alloys by reducing the oxygen vacancies caused by Li + aggregation.

Endoscopic optical coherence tomography (OCT) possesses the capability to non-invasively image internal lumens; however, it is susceptible to saturation artifacts arising from robust reflective structures. In this study, we introduce an innovative deep learning network, ATN-Res2Unet, designed to mitigate saturation artifacts in endoscopic OCT images. This is achieved through the integration of multi-scale perception, multi-attention mechanisms, and frequency domain filters. To address the challenge of obtaining ground truth in endoscopic OCT, we propose a method for constructing training data pairs. Experimental in vivo data substantiates the effectiveness of ATN-Res2Unet in reducing diverse artifacts while preserving structural information. Comparative analysis with prior studies reveals a notable enhancement, with average quantitative indicators increasing by 45.4-83.8%. Significantly, this study marks the inaugural exploration of leveraging deep learning to eradicate artifacts from endoscopic OCT images, presenting considerable potential for clinical applications.

The predictive value of allele frequency (AF) of BRAF V600E and TERT mutations in papillary thyroid carcinoma (PTC) remains controversial. We aimed to investigate the AF of BRAF V600E and TERT mutations in intermediate-to-high risk PTC and their association between tumor invasiveness, prognosis, and other mutations. Probe hybridization capture and high-throughput sequencing were used to quantitatively test 40 gene loci in 94 intermediate-to-high recurrence risk PTC patients, combined with clinical characteristics and follow-up for retrospective analysis. BRAF V600E mutation AF was linked to a increased risk of thyroid capsule penetration, recurrence, and concurrent mutations. Concurrent mutations could lead to a worse prognosis and increased invasiveness. TERT promoter mutation frequently accompanied other mutations and resulted in a poorer prognosis. However, there was no clear association between the TERT mutation AF and tumor invasiveness or recurrence. The sensitivity and specificity of predicting recurrence in intermediate-to-high risk PTC with BRAF V600E mutation AF > 28.2% were 60 and 80%. Although genetic alterations in PTC can differ among different ethnicities, the AF of BRAF V600E and TERT mutations may be similar. The AF of BRAF V600E has the potential to be a novel indicator in predicting PTC invasiveness and prognosis., (© 2024. The Author(s).)

Objective. The high-precision segmentation of retinal vessels in fundus images is important for the early diagnosis of ophthalmic diseases. However, the extraction for microvessels is challenging due to their characteristics of low contrast and high structural complexity. Although some works have been developed to improve the segmentation ability in thin vessels, they have only been successful in recognizing small vessels with relatively high contrast. Approach. Therefore, we develop a deep learning (DL) framework with a multi-stage and dual-channel network model (MSDC&#95;NET) to further improve the thin-vessel segmentation with low contrast. Specifically, an adaptive image enhancement strategy combining multiple preprocessing and the DL method is firstly proposed to elevate the contrast of thin vessels; then, a two-channel model with multi-scale perception is developed to implement whole- and thin-vessel segmentation; and finally, a series of post-processing operations are designed to extract more small vessels in the predicted maps from thin-vessel channels. Main results. Experiments on DRIVE, STARE and CHASE&#95;DB1 demonstrate the superiorities of the proposed MSDC&#95;NET in extracting more thin vessels in fundus images, and quantitative evaluations on several parameters based on the advanced ground truth further verify the advantages of our proposed DL model. Compared with the previous multi-branch method, the specificity and F 1 score are improved by about 2.18%, 0.68%, 1.73% and 2.91%, 0.24%, 8.38% on the three datasets, respectively. Significance. This work may provide richer information to ophthalmologists for the diagnosis and treatment of vascular-related ophthalmic diseases., (© 2024 Institute of Physics and Engineering in Medicine.)

Thyroid cancer is the most common malignant neoplasm within the endocrine system and the field of head and neck surgery. Although the majority of thyroid cancers, more than 90%, are well-differentiated thyroid carcinomas with a favourable prognosis, the escalating incidence of this disease has contributed to an increasing number of patients with a propensity for recurrent disease, rapid disease progression, and poor or no response to conventional treatments. These clinical challenges are commonly attributed to alterations in key thyroid oncogenes or signaling pathways, thereby initiating tumour cell dedifferentiation events, accompanied by reduced or virtually absent expression of the sodium/iodine symporter (NIS). As a result, the disease evolves into iodine-refractory differentiated thyroid cancer (RAIR-DTC), an entity that is insensitive to conventional radioiodine therapy. Despite being classified as a differentiated thyroid cancer, RAIR-DTC has an extremely poor clinical prognosis, with a 10-year survival rate of less than 10%. Therefore, it is of paramount importance to comprehensively elucidate the underlying pathogenesis of RAIR-DTC and provide specific targeted interventions. As the pathogenic mechanisms of RAIR-DTC remain elusive, here we aim to review recent advances in understanding the pathogenesis of RAIR-DTC and provide valuable insights for the development of future molecularly targeted therapeutic approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Zhao, Zhao and Wang.)

A comprehensive pan-human spectral library is critical for biomarker discovery using mass spectrometry (MS)-based proteomics. DPHL v.1, a previous pan-human library built from 1,096 data-dependent acquisition (DDA) MS data of 16 human tissue types, allows quantifying of 10,943 proteins. Here, we generated DPHL v.2 from 1,608 DDA-MS data. The data included 586 DDA-MS data acquired from 18 tissue types, while 1,022 files were derived from DPHL v.1. DPHL v.2 thus comprises data from 24 sample types, including several cancer types (lung, breast, kidney, and prostate cancer, among others). We generated four variants of DPHL v.2 to include semi-tryptic peptides and protein isoforms. DPHL v.2 was then applied to two colorectal cancer cohorts. The numbers of identified and significantly dysregulated proteins increased by at least 21.7% and 14.2%, respectively, compared with DPHL v.1. Our findings show that the increased human proteome coverage of DPHL v.2 provides larger pools of potential protein biomarkers., Competing Interests: T.G. is shareholder of Westlake Omics, Inc. N.X., X.Y., and W.L. were employees of Westlake Omics, Inc., when they participated in this project., (© 2023 The Author(s).)

Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people., Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer., Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint.", Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Follicular thyroid cancer (FTC) is a highly aggressive type of endocrine malignancy. It is necessary to investigate the mechanisms of tumorigenesis and therapeutic pathways in patients with FTC. Haem oxygenase-1 (HO-1) can regulate oxidative stress and the occurrence of tumors and diseases. In this study, we discovered that HO-1 was abnormally overexpressed in FTC compared with adjacent tissues. However, the HO-1 overexpression was demonstrated to decrease cell viability and to potentially activate the ferroptosis signalling pathway. Ferroptosis is a newly identified form of oxidative cell death and is currently being targeted as a new cancer treatment. Tumorigenesis is significantly inhibited by curcumin. The present study shows that curcumin inhibits the growth of FTC by increasing the HO-1 expression, further activating the ferroptosis pathway. This study demonstrates that the HO-1-ferroptosis signalling pathway might play an important role in FTC tumorigenesis, and that curcumin inhibits the growth of FTC cells by affecting this pathway., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Huanjie Chen et al.)

Background: Ferroptosis plays a critical role in suppressing cancer progression, and its essential regulator is glutathione peroxidase 4 (GPX4). High GPX4 expression can inhibit accumulation of iron, thus suppressing ferroptosis. However, its function in thyroid cancer has not been fully illuminated. Here, we explore the effect of GPX4 on thyroid cancer tumorigenesis and prognosis., Methods: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, GPX4 expression was investigated in cancer tissues and adjacent tissues. We determined the biological functions of GPX4-associated differentially expressed genes (DEGs) by using the "clusterProfiler" R package. In addition, the predictive value of GPX4 in thyroid cancer was assessed by using Cox regression analysis and nomograms. Finally, we conducted several in vitro experiments to determine the influence of GPX4 expression on proliferation and ferroptosis in thyroid cancer cells., Results: GPX4 expression was obviously elevated in thyroid cancer tissues compared with normal tissues. Biological function analysis indicated enrichment in muscle contraction, contractile fiber, metal ion transmembrane transporter activity, and complement and coagulation cascades. GPX4 overexpression was associated with stage T3-T4 and pathologic stage III-IV in thyroid cancer patients. Cox regression analysis indicated that GPX4 may be a risk factor for the overall survival of thyroid cancer patients. In vitro research showed that knockdown of GPX4 suppressed proliferation and induced ferroptosis in thyroid cancer cells., Conclusions: GPX4 overexpression in thyroid cancer might play an essential role in tumorigenesis and may have prognostic value for thyroid cancer patients.

The identification and preservation of parathyroid glands (PGs) during thyroid surgery can be challenging. Many techniques have been developed to help surgeons find PGs. We have developed a novel mitoxantrone hydrochloride injection that can be used for lymphatic targeting. After local application during surgery, mitoxantrone hydrochloride injection for tracing (MHI) helps surgeons better identify and preserve PGs and helps pathologists find more lymph nodes. We conducted an open-label, multicenter, randomized clinical trial (CTR20171137) in six centers in China from 08/2017 to 12/2018. Patients with thyroid carcinoma were randomized to the MHI group or the control group. All patients received total thyroidectomy and bilateral central compartment lymph node dissection. The primary outcomes were the PG resection rate and lymph node staining rate. The full analysis set (FAS) included 461 patients, of which 228 were assigned to the MHI group, and 233 were assigned to the control group. The PG resection rates of the MHI group and the control group were 6.6% (15/228) and 26.6% (62/233), respectively, with a significant difference (P < 0.001). No PGs were stained blue with MHI. The central lymph nodes were stained blue with MHI, and the staining rate was 90.5%±12.0%. More lymph nodes were detected in the MHI group than in the control group (13.0±7.3 vs. 10.1±6.4 nodes/patient, P < 0.001). No adverse events related to MHI were observed. MHI is a safe and effective tracer that may help to preserve PGs and identify more central lymph nodes in patients with thyroid cancer., Competing Interests: None., (AJCR Copyright © 2022.)

Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods., (© 2022. The Author(s).)

The effect of 60 Co gamma ray irradiation on the physicochemical and crystalline properties of native corn starch were investigated. Fourier transform infrared spectroscopy and X-ray diffraction showed that irradiation had a slight effect on the molecular structure of corn starch with crystallinity decreasing with increasing irradiation dose. Particle size analysis showed that 59.1% of native corn starch granules had sizes of ≥8 μm, which decreased to only 24.1% after treatment with an irradiation dose of 40 kGy. Irradiated-corn-starch films were prepared by casting gelatinized irradiated-corn-starch solutions. An increased irradiation dose was found to increase the tensile strength of the resultant films, but caused a significant decrease in water vapor permeability. The irradiated-corn-starch films showed potential for the development of biodegradable starch films with improved properties., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Mycotoxins produced by different species of fungi may coexist in cereals and feedstuffs, and could be highly toxic for humans and animals. For quantification of multiple mycotoxins in cereals, we developed a paper-based mycotoxin immune-affinity array. First, paper-based microzone arrays were fabricated by photolithography. Then, monoclonal mycotoxin antibodies were added in a copolymerization reaction with a cross-linker to form an immune-affinity monolith on the paper-based microzone array. With use of a competitive immune-response format, paper-based mycotoxin immune-affinity arrays were successfully applied to detect mycotoxins in samples. The detection limits for deoxynivalenol, zearalenone, T-2 toxin, and HT-2 toxin were 62.7, 10.8, 0.36, and 0.23 μg·kg -1 , respectively, which meet relevant requirements for these compounds in food. The recovery rates were 81-86% for deoxynivalenol, 89-117% for zearalenone, 79-86% for T-2 toxin, and 78-83% for HT-2 toxin, and showed the paper-based immune-affinity arrays had good reproducibility. In summary, the paper-based mycotoxin immune-affinity array provides a sensitive, rapid, accurate, stable, and convenient platform for detection of multiple mycotoxins in agro-foods. Graphical abstract Paper-based immune-affinity monolithic array. DON deoxynivalenol, HT-2 HT-2 toxin, T-2 T-2 toxin, PEGDA polyethylene glycol diacrylate, ZEN zearalenone.

Sulfamethoxazole (SMX) was decomposed by using gamma irradiation in the presence of different additives such as NO 3 - , NO 2 - , Cr(VI), 2-propanol, and tert-butanol. The results demonstrated that NO 3 - , NO 2 - , 2-propanol, and tert-butanol inhibited SMX radiolytic removal. However, there existed a synergetic effect for radiolytic removal of the mixture containing SMX and Cr(VI). At an absorbed dose of 150 Gy, the removal percentages of SMX and Cr(VI) in the mixture were 73.5 and 84.6%, respectively, which was higher than the removal percentages of 70.6 and 4.1% for the single component of SMX and Cr(VI). This provides us an insight into treating the combined pollution in micro-polluted water. The SMX radiolytic removal followed a pseudo first-order reaction kinetic model, and the rate constant ratios of ·OH, e aq - , and H· towards SMX radiolysis were 10.4:1:2.9. In addition, 24-h bio-inhibitory to the macroalgae of SMX solution during gamma irradiation reached the maximum of 0.85 at an adsorbed dose of 100 Gy, then gradually decreased with the increasing adsorbed dose. Based on LC-MS analysis and quantum chemical calculation, the degradation intermediates were determined and concluded that SMX radiolytic removal was mainly via ·OH radical attack and direct decomposition of SMX molecule by gamma ray.

Purpose: Increasing investigations have been performed on the association of -607C/A polymorphism in Interleukin-18 (IL-18) gene promoter with cancer risk and have yielded conflicting results. To derive a more precise estimation of the association, we performed an updated meta-analysis of all eligible studies., Methods: We searched all eligible studies by using PubMed, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. The odds ratios (ORs) were pooled by the fixed-effects/random-effects model in STATA 12.0 software., Results: This meta-analysis included 29 studies with 6,026 cases and 6,476 controls. Overall, significantly increased cancer risk was observed (A vs C: OR=1.10, 95% CI: 1.01,1.19, Pheterogeneity=0.001; AA vs CC: OR=1.17, 95% CI: 1.01,1.37, Pheterogeneity=0.007; CA vs CC: OR=1.15, 95% CI: 1.05,1.25, Pheterogeneity=0.152; AA/CA vs CC: OR=1.17, 95% CI: 1.06,1.31, Pheterogeneity=0.042). In subgroup analyses based on ethnicity, the results suggested a significantly increased risk of cancer in Asian population (CA vs CC: OR=1.11, 95% CI: 1.00-1.24, Pheterogeneity=0.353; AA/CA vs CC: OR=1.14, 95% CI: 1.02-1.29, Pheterogeneity=0.081) and in Mixed population (A vs C: OR=1.72, 95% CI: 1.22-2.43, Pheterogeneity=NA; AA vs CC: OR=2.84, 95% CI: 1.43-5.64, Pheterogeneity=NA; AA vs CC/CA: OR=2.43, 95% CI: 1.34-4.42, Pheterogeneity=NA; AA/CA vs CC: OR=1.69, 95% CI: 1.00-2.85, Pheterogeneity=NA); however, no significant association was found in Caucasian or African populations. In the subgroup analysis by cancer type we found a significantly increased susceptibility to breast cancer (A vs C: OR=1.33, 95% CI: 1.00-1.75,Pheterogeneity=0.155; AA vs CC: OR=1.80, 95% CI: 1.02-3.21,Pheterogeneity=0.162; AA7sol;CA vs CC: OR=1.33, 95% CI: 1.00-1.78,Pheterogeneity=0.546), nasopharyngeal carcinoma (A vs C: OR=1.16, 95% CI: 1.01-1.32, Pheterogeneity=0.921; AA vs CC: OR=1.34, 95% CI: 1.02-1.75, Pheterogeneity=0.863; CA vs. CC: OR=1.36, 95% CI: 1.08-1.70, Pheterogeneity=0.824; AA/CA vs CC: OR=1.35, 95% CI: 1.09-1.68,Pheterogeneity=0.904), and esophageal cancer (CA vs CC: OR=1.37, 95% CI: 1.04-1.80, Pheterogeneity=0.528; AA/CA vs CC: OR =1.29, 95% CI: 1.00-1.66, Pheterogeneity=0.700)., Conclusions: The current meta-analysis suggests that the -607C/A polymorphism in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially of breast cancer, nasopharyngeal carcinoma and esophageal cancer and in Asian and Mixed populations. More studies with diverse ethnic groups, larger sample size, and well controlled confounding factors are warranted to further investigate the association.

Cancer testis antigens (CTAs) are selectively expressed in malignant cells and can serve as ideal targets for immunotherapy. We investigated the expressions of MAGE-A3, MAGE-A4, MAGE-C2 and NY-ESO-1 to determine if combinatorial expressions of CTAs might be as potential prognostic markers for patients with hepatocellular carcinoma (HCC). In tumor tissues of 142 HCC patients, the mRNA expressions of MAGE-A3, MAGE-A4, MAGE-C2 and NY-ESO-1 were 78.9%, 33.8%, 74.6% and 14.1% respectively. Furthermore, the expressions of MAGE-A3, MAGE-A4 and combination of MAGE-A3, MAGE-A4 and NY-ESO-1 (CTAs-A3/A4/NY) showed positive correlations with serum AFP, tumor stages and Ki-67 (P < 0.05). In addition, mRNA expressions of CTAs were significantly consistent with protein expressions of CTAs by immunohistochemistry (P > 0.05). Receiver operating characteristic curves (ROC) analysis showed that CTAs-A3/A4/NY had larger areas under ROC curve (0.768), specificity (99.1%), Youden's index (44.6), positive predictive value (90.9%) and negative predictive value (89.9%) for predicting HCC recurrence than other CTAs. Moreover, the combinatorial expression of CTAs-A3/A4/NY was significantly associated with HCC recurrence by Kaplan-Meier analysis (HR = 69.36, P < 0.01) and multivariate Cox analysis (RR = 17.11, P < 0.01). The combinatorial expression of CTAs-A3/A4/NY mRNA promotes the predictive accuracy of HCC recurrence and itself may be a potential target for immunotherapy of HCC as well.