Mitochondria-Targeted Nanosystem with Reactive Oxygen Species-Controlled Release of CO to Enhance Photodynamic Therapy of PCN-224 by Sensitizing Ferroptosis.

The apoptosis-resistant mechanism of photodynamic therapy (PDT) usually results in limited therapeutic efficacy. The development of new strategies for sensitizing targeted ferroptosis that bypass apoptosis resistance is of great significance to improve the antitumor efficacy of PDT. In this study, a novel amphiphilic copolymer whose main chain contains reactive oxygen species (ROS)-responsive groups and the end of side chains contains triphenylphosphine is synthesized, to encapsulate porphyrinic metal-organic framework PCN-224 via self-assembly which are hydrothermally synthesized by coordination of zirconium (IV) with tetra-kis(4-caboxyphenyl) porphyrin, and loaded carbon monoxide releasing molecule 401 (CORM-401) by their hollow structures (PCN-CORM), and finally, surface-coated with hyaluronic acid. The nanosystem can sequentially localize to mitochondria which is an important target to induce apoptosis and ferroptosis in cancer cells. Upon excitation with near-infrared light, PCN-224 is activated to produce amounts of ROS, and simultaneously triggers the rapid intracellular release of CO. More importantly, the released CO can sensitize ferroptosis and promote apoptosis to significantly enhance the antitumor efficacy of PCN-224 both in vitro and in vivo. These results illustrate that the mitochondria-targeted drug delivery system combined PDT with CO leads to an effective antitumor efficacy, which maybe a promising way to enhance the treatment efficiency of PDT.

The influence of subjective well-being on mental health in nursing students: the role of student cynicism.

Previous studies have reported high rates of poor mental health among nursing students, but few studies focused on the internal pathway of mental health. This cross-sectional study was conducted at a vocational medical school and investigated 384 nursing students. Symptom Check List-90, Index of Well-Being Scale and Cynical Attitudes Toward College Scale were used to test mental health, subjective well-being (SWB) and cynicism of nursing students, respectively. Academic cynicism, social cynicism and institutional cynicism were negatively related to mental health. SWB not only directly had positive effect on mental health, but had an indirect effect on mental health through academic cynicism, social cynicism and institutional cynicism.

Tongguan capsule for treating myocardial ischemia-reperfusion injury: integrating network pharmacology and mechanism study.

CONTEXT: Although Tongguan capsule (TGC) is used in the treatment of coronary atherosclerotic disease, the exact mechanism remains unclear. OBJECTIVE: Network pharmacology and experimental validation were applied to examine the mechanism of TGC for treating myocardial ischemia-reperfusion injury (MIRI). MATERIALS AND METHODS: The components and candidate targets were searched based on various databases such as TCMSP, TCMID, BATMAN-TCM. The binding ability was determined by molecular docking. The ischemia-reperfusion (I/R) model was constructed by ligating the left anterior descending (LAD) coronary artery. APOE-/- mice were divided into three groups (n = 6): Sham group, I/R group, and TGC group (1 g/kg/d). To further verification, HCAEC cells were subjected to hypoxia-reoxygenation (H/R) to establish in vitro model. RESULTS: The compounds, such as quercetin, luteolin, tanshinone IIA, kaempferol and bifendate, were obtained after screening. The affinity values of the components with GSK-3ß, mTOR, Beclin-1, and LC3 were all <-5 kcal/mol. In vivo, TGC improved LVEF and FS, reducing infarct size. In vitro, Hoechst 33258 staining result showed TGC inhibited apoptosis. Compare with the H/R model, TGC treatment increased the levels of GSK-3ß, LC3, and Beclin1, while decreasing the expression of mTOR and p62 (p < 0.05). DISCUSSION AND CONCLUSION: The findings revealed that TGC exerted a cardioprotective effect by up regulating autophagy-related proteins through the mTOR pathway, which may be a therapeutic option for MIRI. However, there are still some limitations in this research. It is necessary to search more databases to obtain information and further demonstrated through randomized controlled trials for generalization.

Extracellular vesicles in pancreatic cancer immune escape: Emerging roles and mechanisms.

Pancreatic cancer (PC) is the most lethal malignancy worldwide due to its delayed diagnosis and limited treatment options. Despite great progress in clinical trials of immunotherapies for various cancers, their effectiveness in PC is very low, indicating that immune evasion is still a major obstacle to immunotherapy in PC. However, the mechanism of immune escape in PC is not fully understood, which substantially restricts the development of immunotherapy. As an important component of intercellular communication networks, extracellular vesicles (EVs) have attracted increasing attention in relation to immune escape. This review aims to provide a better understanding of the roles of EVs in tumor immune escape and the potential to expand their application in cancer immunotherapy. The relationship between PC and the tumor immune microenvironment is briefly introduced. Then, the mechanism by which EVs are involved in immune regulation is summarized, and the latest progress in determining the role of EVs in regulating PC immune escape is highlighted.

Endoplasmic reticulum stress promotes breast cancer cells to release exosomes circ_0001142 and induces M2 polarization of macrophages to regulate tumor progression.

Breast cancer (BC) has a high morbidity and mortality rate. It is imperative to explore the pathogenesis of BC in order to find potential prognostic biomarkers and therapeutic targets. This study screened and verified the differential expression of circ_0001142 in BC tissues and cell lines through bioinformatics and qRT-PCR. Perform dual luciferase reporter gene assay and pull-down detection to verify the correlation between circ_0001142 and miRNA-361-3p and between miR-361-3p and PIK3CB. QRT-PCR, flow cytometry and ELISA were used to study the regulatory effects and regulatory mechanisms of different treatment groups on macrophage polarization. The role of exosomes circ_0001142 in the tumor microenvironment and its influence on BC growth, metastasis and macrophage polarization were investigated through in vivo and in vitro studies. We first found that circ_0001142 is highly expressed in BC. In addition, ERs promote the secretion of tumor exosomes, enhance the entry of circ_0001142 into macrophages and interfere with the process of autophagy and polarization. Finally, it was found that the circ_0001142/miR-361-3p/PIK3CB pathway plays an important role in the polarization of macrophages.

Personalized Nanovaccine Coated with Calcinetin-Expressed Cancer Cell Membrane Antigen for Cancer Immunotherapy.

A cancer vaccine has been widely applied in clinical tumor therapy as one of the main strategies of immunotherapy. However, the traditional cancer vaccine for a single antigen has a low benefit rate due to the individual differences in patients. Here, we report a R837-loaded poly(lactic-co-glycolic acid) nanovaccine coated with a calcinetin (CRT)-expressed cancer cell membrane antigen for immunotherapy. The cell membrane antigen that possessed a complete antigen array was obtained by inducing immunogenic cell death in vitro, avoiding the severe systemic toxicity of chemotherapy in vivo. The nanovaccine codelivers the adjuvant R837 and the Luc-4T1 membrane antigen, triggering a personalized immune response to the corresponding tumor. Moreover, the calcinetin exposed on the surface of the nanovaccine induces the active uptake of dendritic cells, consequently enhancing the antitumor effect. Meanwhile, the nanovaccine activates immune memory cells to provide long-term protection. Our work provides a new strategy for a clinical personalized antitumor vaccine.

Urinary concentrations of phenols, oxidative stress biomarkers and thyroid cancer: Exploring associations and mediation effects.

Phenols have been shown to influence the cellular proliferation and function of thyroid in experimental models. However, few human studies have investigated the association between phenol exposure and thyroid cancer, and the underlying mechanisms are also poorly understood. We conducted a case-control study by age- and sex-matching 143 thyroid cancer and 224 controls to investigate the associations between phenol exposures and the risk of thyroid cancer, and further to explore the mediating role of oxidative stress. We found that elevated urinary triclosan (TCS), bisphenol A (BPA) and bisphenol S (BPS) levels were associated with increased risk of thyroid cancer (all P for trends < 0.05), and the adjusted odds ratios (ORs) comparing the extreme exposure groups were 3.52 (95% confidence interval (CI): 2.08, 5.95), 2.06 (95% CI: 1.06, 3.97) and 7.15 (95% CI: 3.12, 16.40), respectively. Positive associations were also observed between urinary TCS, BPA and BPS and three oxidative stress biomarkers measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), as well as between urinary 8-isoPGF2α and HNE-MA and the risk of thyroid cancer. Mediation analysis showed that urinary 8-isoPGF2α mediated 28.95%, 47.06% and 31.08% of the associations between TCS, BPA and BPS exposures and the risk of thyroid cancer, respectively (all P < 0.05). Our results suggest that exposure to TCS, BPA and BPS may be associated with increased risk of thyroid cancer and lipid peroxidation may be an intermediate mechanism. Further studies are warranted to confirm the findings.

Breast cancer cell-derived extracellular vesicles transfer miR-182-5p and promote breast carcinogenesis via the CMTM7/EGFR/AKT axis.

BACKGROUND: Extracellular vesicles (EVs) derived from tumor cells are implicated in the progression of malignancies through the transfer of molecular cargo microRNAs (miRNAs or miRs). We aimed to explore the role of EVs derived from breast cancer cells carrying miR-182-5p in the occurrence and development of breast cancer. METHODS: Differentially expressed miRNAs and their downstream target genes related to breast cancer were screened through GEO and TCGA databases. miR-182-5p expression was examined in cancer tissues and adjacent normal tissues from patients with breast cancer. EVs were isolated from breast cancer cell line MDA-MB-231 cells and identified. The gain- and loss-of function approaches of miR-182-5p and CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) were performed in MDA-MB-231 cells and the isolated EVs. Human umbilical vein endothelial cells (HUVECs) were subjected to co-culture with MDA-MB-231 cell-derived EVs and biological behaviors were detected by CCK-8 assay, flow cytometry, immunohistochemical staining, Transwell assay and vessel-like tube formation in vitro. A xenograft mouse model in nude mice was established to observe the tumorigenesis and metastasis of breast cancer cells in vivo. RESULTS: miR-182-5p was highly expressed in breast cancer tissues and cells, and this high expression was associated with poor prognosis of breast cancer patients. miR-182-5p overexpression was shown to promote tumor angiogenesis in breast cancer. Moreover, our data indicated that miR-182-5p was highly enriched in EVs from MDA-MD-231 cells and then ultimately enhanced the proliferation, migration, and angiogenesis of HUVECs in vitro and in vivo. Moreover, we found that CMTM7 is a target of miR-182-5p. EVs-miR-182-5p promotes tumorigenesis and metastasis of breast cancer cells by regulating the CMTM7/EGFR/AKT signaling axis. CONCLUSIONS: Taken altogether, our findings demonstrates that EVs secreted by breast cancer cells could carry miR-182-5p to aggravate breast cancer through downregulating CMTM7 expression and activating the EGFR/AKT signaling pathway.

Efficient Degradation of Organoarsenic by UV/Chlorine Treatment: Kinetics, Mechanism, Enhanced Arsenic Removal, and Cytotoxicity.

Roxarsone (ROX) has been widely used as an organoarsenic additive in animal feeding operations and poses a risk to the environment. Here, we first report the efficient degradation of ROX by UV/chlorine, where the kinetics, removal of total arsenic (As), and cytotoxicity were investigated. The kinetics study presented that reactive chlorine species (RCS) and HO• were the dominant species to react with ROX. Furthermore, the degradation rate of ROX can reach the maximum value at pH 7.5 due to the formation of more RCS. The degradation of ROX was affected by the amount of chlorine, pH, and water matrix. Through product analysis and Gauss theoretical calculation, two possible ROX degradation pathways were proposed. The free radicals attacked the As-C bond of ROX and resulted in releasing arsenate (As(V)). It was the reason that for an enhancement of the removal of total As by ferrous appeared after UV/chlorine, and over 98% of the total As was removed. In addition, cytotoxicity studies indicated that the cytotoxicity significantly enhanced during the degradation of ROX by UV/chlorine. However, by combination of UV/chlorine and adsorption, cytotoxicity can be greatly eliminated, probably due to the removal of As(V) and chlorinated products. These results further demonstrated that UV/chlorine treatment could be an effective method for the control of the potential environmental risks posed by organoarsenic.

Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy.

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules.

Kidney diseases have become a global public health problem. The application of kidney-targeted drug-delivery systems in the management of kidney diseases has profound transformative potential. Kidney-targeted drug delivery can reduce the undesired side effects of often potent drugs and enhance drug efficacy in alleviating the kidney disease. Here, we review the literature on the potential strategies for targeting drugs to the kidneys. Specifically, we provide a broad overview of the targeting vectors and targeting pathways for renal tubules and glomeruli, as well as how the unique structural features of the glomerulus and the receptor-mediated internalization pathways of the tubules allows for drug targeting. Finally, we summarized the literature examples of drug delivery to the kidneys and elaborated strategies suitable for renal targeting to provide new therapeutic approaches for kidney diseases.

Aflatoxin G1 induced TNF-α-dependent lung inflammation to enhance DNA damage in alveolar epithelial cells.

Aflatoxin G1 (AFG1 ), a member of the AF family with cytotoxic and carcinogenic properties, could cause DNA damage in alveolar type II (AT-II) cells and induce lung adenocarcinoma. Recently, we found AFG1 could induce chronic lung inflammation associated with oxidative stress in the protumor stage. Chronic inflammation plays a critical role in cigarette smoke or benzo[a]pyrene-induced lung tissues damage. However, it is unclear whether and how AFG1 -induced lung inflammation affects DNA damage in AT-II cells. In this study, we found increased DNA damage and cytochrome P450 (CYP2A13) expression in AFG1 -induced inflamed lung tissues. Furthermore, we treated the mice with a soluble tumor necrosis factor (TNF)-α receptor and AFG1 and found that TNF-α neutralization inhibited the AFG1 -induced chronic lung inflammation in vivo, and then reversed the CYP2A13 expression and DNA damage in AT-II cells. The results suggest that AFG1 induces TNF-α-dependent lung inflammation to regulate 2A13 expression and enhance DNA damage in AT-II cells. Then, we treated the primary mice AT-II cells and human AT-II like cells (A549) with AFG1 and TNF-α and found that TNF-α enhanced the AFG1 -induced DNA damage in mice AT-II cells as well as A549 cells in vitro. In AFG1 -exposed A549 cells, TNF-α-enhanced DNA damage and apoptosis were reversed by CYP2A13 small interfering RNA. Blocking NF-κB pathway inhibited the TNF-α-enhanced CYP2A13 upregulation and DNA damage confirming that the CYP2A13 upregulation by TNF-α plays an essential role in the activation of AFG1 under inflammatory conditions. Taken together, our findings suggest that AFG1 induces TNF-α-dependent lung inflammation, which upregulates CYP2A13 to promote the metabolic activation of AFG1 and enhance oxidative DNA damage in AT-II cells.

One-Step Preparative Separation of Phytosterols from Edible Brown Seaweed Sargassum horneri by High-Speed Countercurrent Chromatography.

Sargassum horneri, a sargassaceae brown alga, is one of the main species in the subtidal seaweeds flora extensively distributed in the Yellow and East China Sea. It has been proven that the phytosterols are an important class of bioactive substances in S. horneri. In this work, a counter-current chromatography approach is proposed for preparative separation of phytol and two analogue sterols from a crude extract of S. horneri. A two-phase solvent system composed of n-hexane-acetonitrile-methanol (5:5:6, v/v) was selected and optimized. The effects of rotary speed and flow rate on the retention of the stationary phase were carefully studied. Under the optimum conditions, phytol and two analogue sterols, fucosterol and saringosterol, were baseline separated, producing 19.8 mg phytol, 23.7 mg fucosterol, and 3.1 mg saringosterol from 300 mg of crude S. horneri extract in one-step separation. The purities of three target compounds were all above 85%. The structures of phytol and two sterols were identified by nuclear magnetic resonance spectroscopy.

ZEB1 stimulates breast cancer growth by up-regulating hTERT expression.

Dysfunctional cell proliferation and death are the foundation of the malignant biological characteristics of cancers. In this study, we discovered that ZEB1 was positively correlated with hTERT in breast invasive ductal carcinoma samples at both the mRNA and protein levels. Further, our in vitro study in breast cancer cell lines confirmed that ZEB1 regulates hTERT expression at the mRNA and protein levels; thus, hTERT promotes or inhibits telomerase activity, and telomere length is either protected or reduced. Finally, we verified that ZEB1, which mostly functions as a transcriptional repressor, can recruit the co-activator YAP to enhance the transcriptional activation of hTERT. Fascinatingly, instead of acting on E-boxes, the ZEB1/YAP complex tends to function as a transcriptional activator by binding with sequences potentially located in the hTERT promoter. Consequently, our research revealed a new ZEB1-hTERT signaling pathway involved in cell proliferation regulation that has never before been illuminated in breast cancer.

Preparative separation of phytosterol analogues from green alga Chlorella vulgaris using recycling counter-current chromatography.

The unicellular alga Chlorella vulgaris is a well-known health food. It has been proven that the minor phytosterols, ergosterol and its analogue, are an important class of bioactive substances in C. vulgaris. In this work, a recycling counter-current chromatographic approach was proposed for preparative separation of two analogue sterols from crude extract of C. vulgaris. The separation unit was set up with a type-J instrument coupled with a column switching valve. A two-phase solvent system composed of n-hexane/dichloromethane/acetonitrile (10:3:7, v/v/v) was selected and optimized. After five cycles of separation, two analogue sterols were baseline separated, producing 11.7 mg 26-nor-25-isopropyl-5,7,22-trien-3ß-ol and 20.3 mg ergosterol from 300 mg of C. vulgaris extract. Their purities were both above 95%. The structures of two sterols were identified by using NMR spectroscopy.

Influence of tumor extent on central lymph node metastasis in solitary papillary thyroid microcarcinomas: a retrospective study of 1092 patients.

BACKGROUND: The morbidity of papillary thyroid microcarcinomas is increasing worldwide. Surgery is the main treatment for papillary thyroid microcarcinomas, and the choice of surgical method partly depends on the T stage of the tumor. However, according to the American Joint Commission on Cancer staging system (7th edition), the T stage of papillary thyroid microcarcinomas with different tumor extent is unclear. We aimed to study the effect of tumor extent and other factors on central lymph node metastasis to explore the relationship between tumor extent and T stage and to identify the risk factors predicting central lymph node metastasis in papillary thyroid microcarcinomas. METHODS: We included 1092 patients diagnosed with solitary papillary thyroid microcarcinomas between July 2011 and April 2016. The tumor extent and other central lymph node metastasis risk factors were retrospectively analyzed. RESULTS: Univariate analysis revealed that capsule invasion and extracapsular extension (P = 0.013, <0.001; respectively) were significantly correlated with central lymph node metastasis. On multivariate analysis, extracapsular extension was independent central lymph node metastasis predictors (odds ratio 3.092, 95% CI 1.744-5.484), while capsule invasion was not (odds ratio 1.212, 95% CI 0.890-1.651). In addition, multivariate analysis revealed that male sex, tumor size >5 mm, and age <45 years were independent central lymph node metastasis predictors (odds ratio 2.072, 2.356, 2.302; 95% CI 1.483-2.894, 1.792-3.099, 1.748-3.031; respectively). CONCLUSIONS: This study supported that capsule invasion and tumor limited to the thyroid in papillary thyroid microcarcinomas were suitable for the lower T1, that is, capsule invasion in papillary thyroid microcarcinomas might not belong to the minimal extrathyroid extension included in T3 of TNM staging. In addition, patients with risk factors of extrathyroid extension, male sex, age <45 years, or tumor size >5 mm in papillary thyroid microcarcinomas should consider a more aggressive surgical treatment.

Diagnostic accuracy of ultrasonographic features for lymph node metastasis in papillary thyroid microcarcinoma: a single-center retrospective study.

BACKGROUND: Whether sonography is an appropriate imaging modality for cervical lymph nodes in patients with papillary thyroid microcarcinoma (PTMC) remains unclear. Hence, this study aimed to evaluate the diagnostic value of ultrasonography (US) features for lymph node metastasis in PTMC. METHODS: Seven hundred twelve patients with PTMC who underwent conventional ultrasonography examinations of the cervical lymph nodes were included. All included cases underwent total thyroidectomy plus prophylactic central lymph node dissection. The included lymph nodes were marked superficially, and the corresponding lymph nodes were completely removed and sent for pathological examination. The US features of lymph nodes with and without metastasis were compared, and the odds ratios of the suspicious US features were determined with univariate and multivariate analyses. RESULTS: Round shape, loss of an echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were significantly more common in metastatic than nonmetastatic lymph nodes, whereas the boundary and echo did not significantly differ. Multivariate logistic regression analysis showed that round shape, loss of echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were independent predictive factors for the assessment of metastatic lymph nodes. Round shape had the highest sensitivity of all variables, while loss of an echogenic fatty hilum had the highest specificity and accuracy. The area under the receiver operating characteristic curve, which was calculated to verify the relationship between the various US features and metastatic lymph nodes, was 0.793. CONCLUSIONS: Our study found that the US features of round shape, cystic change, calcification, loss of echogenic fatty hilum, and abnormal vascularity were useful sonographic criteria for differentiating between cervical lymph nodes with and without metastasis.

Identification of Lysine Acetylation in Mycobacterium abscessus Using LC-MS/MS after Immunoprecipitation.

Mycobacterium abscessus (MAB), which manifests in the pulmonary system, is one of the neglected causes of nontuberculous mycobacteria (NTM) infection. Treatment against MAB is difficult, characterized by its intrinsic antibiotic drug resistance. Lysine acetylation can alter the physiochemical property of proteins in living organisms. This study aimed to determine if this protein post-translational modification (PTM) exists in a clinical isolate M. abscessus GZ002. We used the antiacetyl-lysine immunoprecipitation to enrich the low-abundant PTM proteins, followed by the LC-MS/MS analysis. The lysine acetylome of M. abscessus GZ002 was determined. There were 459 lysine acetylation sites found in 289 acetylated proteins. Lysine acetylation occurred in 5.87% of the M. abscessus GZ002 proteome, and at least 25% of them were growth essential. Aerobic respiration and carbohydrate metabolic pathways of M. abscessus GZ002 were enriched with lysine acetylation. Through bioinformatics analysis, we identified four major acetyl motif logos (K(ac)Y, K(ac)F, K(ac)H, and DK(ac)). Further comparison of the reported M. tuberculosis (MTB) acetylomes and that of MAB GZ002 revealed several common features between these two species. The lysine residues of several antibiotic-resistance, virulence, and persistence-related proteins were acetylated in both MAB GZ002 and MTB. There were 51 identical acetylation sites in 37 proteins found in common between MAB GZ002 and MTB. Overall, we demonstrate a profile of lysine acetylation in MAB GZ002 proteome that shares similarities with MTB. Interventions that target at these conserved sections may be valuable as anti-NTM or anti-TB therapies.

Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells.

EZH2, the catalytic subunit of polycomb repressor complex 2, has oncogenic properties, whereas RASSF2A, a Ras association domain family protein, has a tumor suppressor role in many types of human cancer. However, the interrelationship between these two genes remains unclear. Here, we showed that the downregulation of EZH2 reduces CpG island methylation of the RASSF2A promoter, thereby leading to increased RASSF2A expression. Our findings also showed that knockdown of EZH2 increased RASSF2A expression in the human breast cancer cell line MCF-7 in cooperation with DNMT1. This was similar to the effect of 5-Aza-CdR, a DNA methylation inhibitor that reactivates tumor suppressor genes and activated RASSF2A expression in our study. The EZH2 inhibitor DZNep markedly suppressed the proliferation, migration, and invasion of MCF-7 cells treated with ADR and TAM. EZH2 inhibits the expression of tumor suppressor gene RASSF2A via promoter hypermethylation. Thus, it plays an important role in tumorigenesis and is a potential therapeutic target for the treatment of breast cancer.

Associations between BRAF(V600E) and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis.

BACKGROUND: The objective of this study is to perform a meta-analysis to evaluate the associations between the BRAF(V600E) mutation status and aggressive clinicopathological features and poor prognostic factors in papillary thyroid cancer. METHODS: A literature search was performed within the PubMed, MEDLINE, Web of Science databases, and EMBASE databases using the Medical Subject Headings and keywords from January 2003 to July 2015. Individual study-specific odds ratios and confidence intervals were calculated, as were the Mantel-Haenszel pooled odds ratios for the combined studies. RESULTS: Sixty-three studies of 20,764 patients were included in the final analysis. Compared with wild-type BRAF, the BRAF(V600E) mutation was associated with aggressive clinicopathological factors, including extrathyroidal extension, higher TNM stage, lymph node metastasis, and recurrence, and was associated with reduced overall survival; however, there was no significant association between the presence of BRAF mutation and distant metastasis. CONCLUSIONS: BRAF mutations are closely associated with aggressive clinicopathological characteristics and poorer prognosis in papillary thyroid cancer. Accordingly, aggressive treatment should be considered for papillary thyroid cancer patients with BRAF mutation.