Metastasis-associated gene, mag-1 improves tumour microenvironmental adaptation and potentiates tumour metastasis.

Metastasis is a major cause of death from malignant diseases, and the underlying mechanisms are still largely not known. A detailed probe into the factors which may regulate tumour invasion and metastasis contributes to novel anti-metastatic therapies. We previously identified a novel metastasis-associated gene 1 (mag-1) by means of metastatic phenotype cloning. Then we characterized the gene expression profile of mag-1 and showed that it promoted cell migration, adhesion and invasion in vitro. Importantly, the disruption of mag-1 via RNA interference not only inhibited cellular metastatic behaviours but also significantly reduced tumour weight and restrained mouse breast cancer cells to metastasize to lungs in spontaneous metastatic assay in vivo. Furthermore, we proved that mag-1 integrates dual regulating mechanisms through the stabilization of HIF-1α and the activation of mTOR signalling pathway. We also found that mag-1-induced metastatic promotion could be abrogated by mTOR specific inhibitor, rapamycin. Taken together, the findings identified a direct role that mag-1 played in metastasis and implicated its function in cellular adaptation to tumour microenvironment.

lncRNA DANCR Promotes Proliferation and Metastasis of Breast Cancer Cells Through Sponging miR-4319 and Upregulating VAPB.

Background: Breast cancer is one of the most prevalent cancers that often occur in females. Long noncoding RNA differentiation antagonizing nonprotein coding RNA (DANCR) has been involved in the pathogenesis of various tumors, including breast cancer. This study aimed to investigate the role and underlying mechanism of DANCR in breast cancer. Materials and Methods: The level of DANCR was detected in breast cancer tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell apoptosis was assessed using flow cytometry. Cell migration and invasion were estimated by the Transwell assay. The relationship between DANCR, miR-4319, and vesicle-associated membrane protein-associated protein B (VAPB) was confirmed by bioinformatic analysis and dual-luciferase reporter assay. The level of microRNA-4319 (miR-4319) was tested by qRT-PCR. The expression of VAPB was measured by qRT-PCR or Western blot assay. Results: DANCR and VAPB were upregulated, while miR-4319 was downregulated in breast cancer tissues and cells. Knockdown of DANCR hindered proliferation, migration, and invasion and promoted apoptosis of breast cancer cells. DANCR knockdown inhibited breast cancer development through regulating miR-4319. Inhibition of miR-4319 restrained breast cancer cell progression by targeting VAPB. Moreover, DANCR regulated VAPB expression by sponging miR-4319 in breast cancer cells. Conclusion: DANCR facilitated breast cancer cell progression through regulating the miR-4319/VAPB axis, indicating that DANCR might be a potential biomarker and therapeutic target for breast cancer treatment.

Malignancy in dermatomyositis: A retrospective paired case-control study of 202 patients from Central China.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy that is closely related to malignant diseases. Our study aims to investigate the incidence and predictive factors for occurrence of malignancy among DM patients from Central China.We performed a retrospective, paired, case-control study of 736 DM patients admitted to the First Affiliated Hospital of Zhengzhou University between 2010 and 2017. We paired the 65 patients with malignancy with age-matched and sex-matched patients without malignancy in a ratio of 1:2. Two hundred two patients were finally enrolled and their clinical and laboratory data were collected.The incidence of malignancy in DM patients was 8.83% (65/736). Most malignancies were detected in the most recent 1 year before (9/65, 13.85%) or within 3 years after (40/65, 61.54%) the onset of DM. Males (35/65, 53.85%) and patients aged between 50 and 69 years (43/65, 66.15%) were prone to develop malignancies. Lung cancer (n = 11, 31.43%) was the most common malignancy in male patients, while for females, thyroid, breast and cervical cancer (n = 4 each, 13.33%) were more prevalent. Adenocarcinoma and squamous cell carcinoma (both 18/65, 27.69%) were the top two most common pathological types. Univariate analysis demonstrated that Gottron's sign (P = .02), dysphagia (P = .04), albumin (ALB) reduction (P = .003), aspartate aminotransferase (AST, P = .03), creatine kinase-MB (P = .02), absence of fever (P = .02), arthralgia (P = .04) and interstitial lung disease (ILD, P = .05) were closely related to the occurrence of malignancy. Multivariate analysis revealed the independent risk factors of ALB reduction (odds ratio = 1.546, P = .04) and the protective factor of ILD (odds ratio = 0.349, P = .003). There was no significant difference in the follow-up period between patients with and without ILD (P = .38).ALB reduction and the absence of ILD were the risk factors for malignancy in DM patients. The protective mechanism of ILD for DM patients needs further study.

Decontamination of Bacillus subtilis var. niger spores on selected surfaces by chlorine dioxide gas.

OBJECTIVE: Chlorine dioxide (CD) gas has been used as a fumigant in the disinfection of biosafety laboratories. In this study, some experiments were conducted to assess the inactivation of spores inoculated on six materials [stainless steel (SS), painted steel (PS), polyvinyl chlorid (PVC), polyurethane (PU), glass (GS), and cotton cloth (CC)] by CD gas. The main aims of the study were to determine the sporicidal efficacy of CD gas and the effect of prehumidification before decontamination on sporicidal efficacy. METHODS: Material coupons (1.2 cm diameter of SS, PS, and PU; 1.0 cm×1.0 cm for PVC, GS, and CC) were contaminated with 10 µl of Bacillus subtilis var. niger (ATCC 9372) spore suspension in mixed organic burden and then dried in a biosafety cabinet for 12 h. The spores were recovered by soaking the coupons in 5 ml of extraction liquid for 1 h and then vortexing the liquid for 1 min. RESULTS: The log reductions in spore numbers on inoculated test materials exposed to CD gas [0.080% (volume ratio, v/v) for 3 h] were in the range of from 1.80 to 6.64. Statistically significant differences were found in decontamination efficacies on test material coupons of SS, PS, PU, and CC between with and without a 1-h prehumidification treatment. With the extraction method, there were no statistically significant differences in the recovery ratios between the porous and non-porous materials. CONCLUSIONS: The results reported from this study could provide information for developing decontamination technology based on CD gas for targeting surface microbial contamination.

Adenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2 interactions.

We generated replication-defective adenovirus Ad-p53AIP1 and studied its anti-tumor efficacy both in vitro and in vivo. We demonstrated that Ad-p53AIP1 infection elicited high levels of p53AIP1 expression in cancer cells. We also found that Ad-p53AIP1 expression induced marked apoptosis and cell cycle arrest in HepG2 cells. Moreover, Ad-p53AIP1 infection significantly inhibited the tumorigenesis of 4T1 mouse mammary cancer cells in vivo. In particular, we discovered that p53AIP1 overexpression up-regulated the protein levels of p53 in HepG2 cells, which was accompanied by down-regulation of MDM2 mRNA and protein, suggesting an interaction between MDM2 and p53 in p53AIP1-induced apoptosis and cell cycle arrest. Our data demonstrated the feasibility of Ad-p53AIP1-mediated cancer gene therapy. p53AIP1-induced up-regulation of p53 protein through MDM2 suggests that p53AIP1 gene therapy may be more advantageous in tumors expressing high levels of oncoprotein MDM2 or having a mutation in MDM2 inhibitor p16INK4.