Exosomal miR-30a and miR-222 derived from colon cancer mesenchymal stem cells promote the tumorigenicity of colon cancer through targeting MIA3.

BACKGROUND: Multipotent mesenchymal stem cells (MSCs) derived from virus tumors have been reported to contribute to malignant cell growth, invasion, and metastasis. However, the mechanism of communication between MSCs and colon cancer cells is poorly understood. Recent studies have suggested that exosomes are an important player in crosstalk between cells and could significantly suppress the invasion ability of human cancer cells (hCCs) when transfected with a microRNA inhibitor. However, to date, no study has illuminated the miRNA changes in exosomes derived from hCC-MSCs. METHODS: Colon cancer stem cells were cultured in medium and passaged to develop fibroblast-like morphology. Exosomes were collected using ExoQuick precipitation and exosome morphology was visualized by transmission electron microscopy. Small RNA sequencing was analyzed using an Illumina HiSeq4000 analyzer, and the expression of MIA3 was assessed by real-time PCR and Western blot. The functional roles of miR-30a and miR-222 in colon cancer cells were evaluated through cell and animal experiments. RESULTS: Our results showed that the characteristics of MSC-like cells (hCC-MSCs) derived from human colon cancer stem cells were comparable to those of bone marrow-derived MSCs, including surface antigens and the ability to multi-differentiate to osteocytes and adipocytes. Furthermore, we screened the microRNA (miRNA) profiles of exosomes derived from hCC-MSCs and the corresponding parent hCC-MSCs. We found a significant enrichment in the miR-30a and miR-222 level in hCC-MSC-derived exosomes. Furthermore, in vitro and in vivo experiments demonstrated that miR-30a and miR-222 bound to their shared downstream target, MIA3, to promote the ability of colon cells to proliferate, migrate, and metastasize, thus evidencing their functional roles as oncogenic miRNAs. CONCLUSIONS: These data suggest that hCC-MSC-secreted exosomes promote colon cancer cell proliferation and metastasis through delivering miR-30a and miR-222. Subsequently, exosomal miR-30a and miR-222 simultaneously target MIA3, suppress its expression, and promote colon cell proliferation, migration, and metastasis.

Efficacy and safety of lapatinib in Chinese breast cancer patients: a real-world study.

BACKGROUND: Lapatinib is approved for the treatment of metastatic HER2-overexpressed breast cancer with capecitabine after progress on anthracycline, taxane, and trastuzumab in China. A post-marketing pharmacovigilance program was carried out to verify the real-world safety and the efficacy information of lapatinib. METHODS: This was a prospective, non-interventional, long-term study in the real-world setting. All patients treated with lapatinib during the program (inclusion period 12 months) in Fudan University Shanghai Cancer Center (FUSCC) were included. The main outcome measures were progression-free survival (PFS) and incidence of adverse events. RESULTS: A total of 112 patients were enrolled. The median age was 52 years, 64.3% of patients were post-menopausal, 90 patients (80.4%) had stage IV disease, and the most common metastatic site was in the lung (43.8%), bone (30.4%), liver (26.8%), and brain (18.8%). About half of the patients (46.4%) experienced 3 or more systemic regimens before lapatinib. After a median follow-up of 34.3 months (range, 17.9-57.9 months), the median PFS was 8.1 months (95% CI, 5.8 to 10.4 months). Later phase of disease (stage IV), 3 or more prior treatments, pulmonary metastasis, liver metastasis, prior anthracycline or taxane, and poor adherence strongly correlated with worse survival (P<0.005). The grade 3 or 4 adverse events were diarrhea (9.8%), hand-foot syndrome (5.4%), and rash (4.5%). CONCLUSIONS: Upon implementation of lapatinib therapy in a real-world setting, the case mix was characterized by more early-stage breast cancer patients. The median PFS was slightly superior to what was published in the clinical trials. Pulmonary metastasis or liver metastasis significantly correlated with worse survival. We reported a similar prevalence of adverse events.

lncRNA SLC16A1-AS1 as a novel prognostic biomarker in non-small cell lung cancer.

Long non-coding RNAs (lncRNAs) have proved to act as crucial biomarkers in tumors. Novel biomarkers in non-small cell lung cancer (NSCLC) need to be investigated badly. To identify the differentially expressed lncRNAs between NSCLC tissue and adjacent tissue, microarray analysis was performed. lncRNA SLC16A1-AS1 was significantly less expressed in NSCLC tissue than that in adjacent tissue. Gain-of-function experiments was performed to determine the biological functions of SLC16A1-AS. In situhybridization and survival analysis were applied in lung cancer tissue samples to determine the prognostic role of SLC16A1-AS1. It was showed that SLC16A1-AS1 was remarkably downregulated in NSCLC tissues and cell lines. Functionally, SLC16A1-AS1 overexpression could inhibit the viability and proliferation of lung cancer cell, block the cell cycle and promote cell apoptosis in vitro which may result from reduced phosphorylation of rat sarcoma (RAS)/ proto-oncogene serine/threonine-protein kinase (RAF)/ mitogen-activated protein kinase kinase (MEK)/ extracellular regulated protein kinases (ERK) pathway caused by elevated expression of SLC16A1-AS1. Clinical sample analysis showed that SLC16A1-AS1 had a favorable impact on the overall survival and progression-free survival of patients with NSCLC. Our results suggested that SLC16A1-AS1 may act as a potential biomarker for patients with NSCLC.

LINC00612 enhances the proliferation and invasion ability of bladder cancer cells as ceRNA by sponging miR-590 to elevate expression of PHF14.

BACKGROUND: Bladder cancer (BC) is a common type of cancer that involves tumors of the urinary system and poses a serious threat to human health. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNA biomarkers in BC urgently need to be investigated in regard to its function and regulatory mechanisms. METHODS: Identification of differentially expressed lncRNAs in BC tissue was performed via microarray analysis. To investigate the biological functions of LINC00612, loss-of-function and gain-of-function experiments were performed in vitro and in vivo. Bioinformatics analysis, dual-luciferase reporter assays, AGO2-RIP assays, RNA pull-down assays, real-time quantitative PCR (RT-qPCR) arrays, fluorescence in situ hybridization assays, and western blot assays were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). RESULTS: LINC00612 was upregulated in BC tissues and cell lines. Functionally, downregulation of LINC00612 inhibited cell proliferation and invasion in vitro and in vivo, whereas overexpression of LINC00612 resulted in the opposite effects. Bioinformatics analysis and luciferase assays revealed that miR-590 was a direct target of LINC0061, which was validated by dual-luciferase reporter assays, AGO2-RIP assays, RNA pull-down assays, RT-qPCR arrays, and rescue experiments. Additionally, miR-590 was shown to directly target the PHD finger protein 14 (PHF14) gene. LNIC00612 modulated the expression of E-cadherin and vimentin by competitively sponging miR-590 to elevate the expression of PHF14, thus affecting BC cellular epithelial-mesenchymal transition (EMT). CONCLUSIONS: Our results indicate that LINC00612 enhances the proliferation and invasion ability of BC cells by sponging miR-590 to upregulate PHF14 expression and promote BC cellular EMT, suggesting that LINC00612 may act as a potential biomarker and therapeutic target for BC.

Translation and validation of the Chinese version of the Cancer Stigma Scale.

PURPOSE: To test the reliability and validity of the Chinese version of the Cancer Stigma Scale (CASS). METHODS: After translation, back-translation and cross-cultural adaptation of the CASS into Chinese (C-CASS), a random online survey of the general population in China was conducted. Reliability was analyzed by internal consistency (Cronbach's α) and construct validity was analyzed by confirmatory factor analysis. The C-CASS was evaluated in a sample of 382 non-cancer patients through online format. RESULTS: The study found that the C-CASS had satisfactory internal reliability (Cronbach's α of the overall scale and six components was 0.88 and 0.70-0.89, respectively). Confirmatory factor analysis confirmed the six-factor structure (χ2/df = 2.2, GFI = 0.91, CFI = 0.94, RMSEA = 0.056, SRMR = 0.065). Younger individuals and those who had less knowledge of cancer showed more negative attitudes towards cancer. CONCLUSION: The C-CASS had adequate internal consistency, reliability and indices of model fit, allowing its feasible use to assess levels of cancer stigma in Chinese populations.

Diagnostic potential of serum exosomal colorectal neoplasia differentially expressed long non-coding RNA (CRNDE-p) and microRNA-217 expression in colorectal carcinoma.

In this study, we investigated the diagnostic potential of serum exosomal colorectal neoplasia differentially expressed (CRNDE-p) long coding RNA and microRNA-217 in colorectal carcinoma (CRC). We detected high CRNDE-p and low miR-217 levels in exosomes released by multiple CRC cell lines into culture media as well as in sera from CRC xenograft mice and CRC patients. Conversely, we observed lower CRNDE-p and higher miR-217 levels in serum exosomes from post-chemotherapy than from pre-chemotherapy patient samples. The area under curve (AUC) value for the serum exosomal CRNDE-p and miR-217 combination was higher than CRNDE-p or miR-217 alone. Moreover, high CRNDE-p and low miR-217 serum exosomal levels correlated with advanced clinical stages (III/IV), tumor classification (T3/T4), and lymph node or distant metastasis. Thus combined evaluation of serum exosomal CRNDE-p and miR-217 levels show diagnostic and prognostic potential for CRC patients.

Long period fiber grating transverse load effect-based sensor for the omnidirectional monitoring of rebar corrosion in concrete.

From the angle of sensitivity of the long period fiber grating (LPFG) resonant transmission spectrum, we demonstrate the sensitivity of LPFG resonance peak amplitude changing with transverse loads. The design of a resonant peak modulation-based LPFG rebar corrosion sensor is described by combining the spectral characteristics of LPFG with the expansion state monitoring of rebar corrosion. LPFG spectrum curves corresponding with different rebar corrosion status of the environment under test are captured by the monitoring technique of LPFG transmission spectra, and the relationship between the resonance peak amplitude change and the state of rebar corrosion is obtained, that is, the variation of LPFG resonance peak amplitude increases with the intensifying of the degree of rebar corrosion. The experimental results numerically show that the sensor response has good regularity for a wide range of travel.

[Surface plasmon resonance spectral based fiber optic sensor for detection of total dissolved solids in water quality analysis].

As surface plasmon resonance (SPR) spectrum is sensitive to refractive index of the mediums, we explored its sensitivity characteristic of ions composition detection in a solution so as to measure the total dissolved solid value in water. Seven ionic (NaCl, KCl, CaCl2, MgCl2, Na2CO3, MgSO4 and ZnSO4) and 3 non-ionic (glucose, glycerol and sucrose) liquid samples were studied experimentally with a fiber optic SPR sensor. The influence of ion concentration on the resonance wavelength shift in SPR spectrum was investigated and discussed, and with that, the response curves were established to realize the detection of total dissolved solid in water quality analysis. The FO-SPR sensor spectral curve for TDS measurement was in conformity with ionic conductivity in 8 different water samples, and results show that the spectral method was better in high ion concentration detection of water. This research will broaden the SPR application in the field of water quality monitoring.

[Study on ammonia-N degradation monitoring by analyzing long-period fiber grating spectrum character].

In the present paper, the principle of a long-period fiber grating (LPFG) ammonia-nitrogen degradation monitoring sensor was discussed in detail firstly based on a sensitive characteristic that the resonance spectrum of long-period fiber grating changes with refractive index in external environment. The relationship between the resonance peaking wavelength of long-period fiber grating and the concentration of ammonia-nitrogen solutions was also analyzed detailedly. Then, the long-period fiber grating spectrum measurement technology was selected to obtain long-period fiber grating spectrum curves corresponding to seven different kinds of concentration of ammonia-nitrogen solutions, and the resonance wavelengths increased with the increase in the concentration of ammonia-nitrogen solutions. The variations of the resonance wavelength decreased from 2.707 to 0.068 nm and had a relatively good corresponding relationship with the concentration values of ammonia-nitrogen solutions. The responsivity of this correlation is 52.78 pm x mg(-1) x L. The concentration of ammonia-nitrogen solutions was acquired exactly through the way of monitoring the changes of the spectrum attribute, at the same time, the process and the extent of ammonia-nitrogen wastewater degradation were estimated. This method, which can directly monitor the concentration of ammonia-nitrogen solutions, is simple and easy to operate. The measurement and transmission section of the system are completely composed of optical fiber, which can avoid the electronic interference. There is no necessary to use chemic reagent to sign the solutions, which are going to be degraded. In conclusion, the late-model long-period fiber grating ammonia-nitrogen degradation monitoring system could achieve a real time, rapid, accurate and long distance measurement.

On the chemical constituents of Dipsacus asper.

Bioassay-guided fractionation of 95% EtOH extract from the roots of Dipsacus asper lead to the isolation of some phenolic acids (caffeic acid, 2,6-dihydroxycinnamic acid, vanillic acid, 2'-O-caffeoyl-D-glucopyranoside ester, and caffeoylquinic acid) as the major active components, and five new iridoid glucoside dimers (1-5) and one new iridoid glucoside monomer (6), other known iridoid glycosides loganin, cantleyoside, triplostoside A, lisianthioside, 6'-O-beta-D-apiofuranosyl sweroside, as well as triterpenoids oleanic acid and akebiasaponin D. The structures of new compounds 1-6 were determined as dipsanosides C (1), D (2), E (3), F (4), G (5), and 3'-O-beta-D-glucopyranosyl sweroside (6) by spectroscopic, including 1D and 2D NMR techniques, and chemical methods.