Lipids play roles in membrane structure, energy storage, and signal transduction as well as in human cancers. Here we adopt lipidomics to identify plasma lipid markers for early screening and ...detection of lung cancer.
Using mass spectrometry, we profiled 390 individual lipids using training and validation strategy in a total of 346 plasma samples from 199 early NSCLC patients, including 113 adenocacinoma and 86 squamous cell cancers (SqCC), and from 147 healthy controls.
In the training stage, we found distinct lipid groups that were significantly distributed between NSCLC cases and healthy controls. We further defined a panel of four lipid markers (LPE(18:1), ePE(40:4), C(18:2)CE and SM(22:0)) for prediction of early cancer with a accuracy of 82.3% AUC (Area under ROC curve), sensitivity of 81.9% and specificity of 70.7% at the training stage and yielded the predictive power with accuracy (AUC,80.8%), sensitivity 78.7%, specificity 69.4% and in the validation stage.
Using lipidomics we identified several lipid markers capable of discerning early stage lung carcinoma from healthy individuals, which might be further developed as a quick, safe blood test for early diagnosis of this disease.
Expression of the long non-coding RNA (lncRNA) LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of the ...present study was to explore the relationship between LOC285194 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC), so as to assess whether it could be a novel biomarker for prognosis and prediction of response to therapy on ESCC patients.
The method of quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure LOC285194 expression in pretreatment biopsy specimens and matched normal tissue derived from ESCC patients who underwent preoperative chemoradiotherapy followed by surgical resection (CRT + S group; n = 55) or from those who received surgical resection alone (S group; n = 87). The association between LOC285194 expression and clinicopathological features and prognosis were then analyzed.
LOC285194 expression was significantly down-regulated in ESCC tumor tissues when compared with the adjacent normal tissues (p < 0.001). Low expression of LOC285194 was associated with larger tumor size (p = 0.002), advanced TNM stage (p = 0.018), more lymph node metastases (p = 0.013) and distant metastases (p = 0.015). In the CRT + S group, the pathological complete response rate was 57% (16/28) for the LOC285194-high group, and 15% (4/27) for the LOC285194-low group. Univariate analysis revealed that low expression of LOC285194 was significantly correlated with CRT response (p = 0.002). Moreover, Kaplan-Meier survival analysis revealed that patients with low expression of LOC285194 had a decreased disease free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Multivariable analysis further identified low expression of LOC285194 as an independent prognosis factor for CRT response (p = 0.011), DFS (p < 0.001) and OS (p = 0.002).
Decreased expression of LOC285194 could serve as a molecular marker to predict the clinical outcome of ESCC patients after surgery, and select patients who would benefit from preoperative CRT.
Background: A previous meta-analysis suggested that use of bevacizumab is associated with an increased risk of infection in cancer patients. With the continuous accumulation of evidence in ...non-small-cell lung cancer (NSCLC), we performed a new, focused meta-analysis of randomized controlled trials (RCTs) to quantify the relative risk (RR) and incidence of infectious complications in those individuals treated with bevacizumab. Methods: Electronic databases were searched, including PubMed, Embase, and Cochrane databases. Eligible studies were prospective randomized clinical trials of NSCLC patients treated with bevacizumab with toxicity data on infectious complications. RR, overall incidence rates, and 95% confidence intervals (CI) were calculated using fixed- or random-effects models, depending on the heterogeneity of the included studies. Results: A total of 4,545 patients from 14 prospective RCTs were included in the meta-analysis. Treatment with bevacizumab was not associated with an increased risk of all-grade (RR 1.12, 95% CI: 0.84–1.49) or high-grade (RR 1.11, 95% CI: 0.86–1.41) infections, respectively. The summary incidences of all-grade and high-grade infections in patients receiving bevacizumab in the treatment group were 16.4% (95% CI: 15.7–17.2%) and 4.3% (95% CI: 3.0–6.1%), respectively. Conclusions: The use of bevacizumab is not associated with a significantly higher risk of infections in NSCLC patients. These data provide reassurance regarding the risk of infection in patients with NSCLC receiving bevacizumab.
Aberrant expression of miR-196a has been frequently reported in cancer studies. However, the expression and mechanism of its function in gastric cancer remains unclear. Quantitative real-time PCR was ...carried out to detect the relative expression of miR-196a in gastric cancer cell lines and tissues. SGC7901 cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cell proliferation. Higher expression of miR-196a in gastric cancer tissues was associated with tumor size, a higher clinical stage, and was also correlated with shorter overall survival of patients with gastric cancer. Exogenous downregulation of miR-196a expression significantly suppressed the in vitro cell-cycle progression, proliferation, and colony formation of gastric cancer cells, and ectopic miR-196a expression significantly enhanced the development of tumors in nude mice. Luciferase assays revealed that miR-196a inhibited p27(kip1) expression by targeting one binding site in the 3'-untranslated region (3'-UTR) of p27(kip1) mRNA. qPCR and Western blot assays verified that miR-196a reduced p27(kip1) expression at both mRNA and protein levels. The p27(kip1)-mediated repression in cell proliferation was reverted by exogenous miR-196a expression. A reverse correlation between miR-196a and p27(kip1) expression was noted in gastric cancer tissues. Our study shows that aberrant overexpression of miR-196a and consequent downregulation of p27(kip1) could contribute to gastric carcinogenesis and would be targets for gastric cancer therapies and further developed as potential prognostic factors.
Under microwave irradiation, perbenzylated pyranoid glycals were coupled with aryl bromides in the presence of 5% mol palladium(II) acetate in dimethylformamide to produce 2′,3′-unsaturated
...C-aryl-α-glycopyranosides in a rapid and stereospecific manner. The synthetic applicability of the method was further demonstrated by converting the resulting
C-aryl glycosides to 2′-deoxy
C-aryl-β-glycopyranosides through oxidation mediated by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) and stereoselective reduction.
Delayed rockburst experiments with different numbers of unloading surfaces (DNUS) were performed using an independently developed true triaxial multisurface unloading rockburst experimental system. ...Based on the rockburst excess energy theory, the energy storage characteristics, excess energy, excess energy release rate (EERR), and crack evolution characteristics of rockbursts with DNUS were studied, and the following main conclusions were obtained. The occurrence of rockbursts is mainly due to the generation of an excess energy Δ
E
. Δ
E
depends on the elastic strain energy stored in the rock before the rockburst, the energy input by the equipment after the peak, and the residual elastic strain energy. As the DNUS increases, Δ
E
gradually decreases, but the EERR value increases, and the rockburst becomes increasingly severe; Rapid unloading of the specimen under true triaxial high-pressure loading will produce an unloading platform in the stress–strain curve, causing unloading damage. The damage is mainly concentrated near the free surface in the form of tension failure, and the unloading damage gradually increases with increasing DNUS; Tensile cracks play a dominant role in the damage and destruction of sandstone. In the final rockburst stage, the slope of the shear crack curve was greater than that of the tensile cracks, indicating that shear cracks were a critical factor affecting the instability and failure of the specimen.
We examined the ability of partially synthesized new compounds from fangchinoline and tetrandrine to reverse P-glycoprotein (P-gp)-dependent multidrug resistance (MDR) in vitro and in vivo. All ...compound enhanced the in vitro cyctotoxic effect of vinblastin (VBL) at 0.1 μM as potent as 10 μM verapamil against the resistant cell line P388/ADR. The combination effect tended to be strong by substitution of bulky group, resulting 5,14-dibromotetrandrine (compound #9) showed the strongest effect. Compound #9 increased intracellular VBL accumulation in P388/ADR cells, much stronger than verapamil, as well as cytotoxic combined effect. This mechanism seems to inhibit the function of P-gp, but not the expression of P-gp. In combination with VBL, this compound also synergistically prolonged the life-span of P388/ADR-bearing mice. Bisbenzylisoquinoline alkaloids and their derivatives are possible to be good candidates as modifier of MDR in cancer chemotherapy.
Display omitted
•The total of 43 metabolites were identified in rat bile after oral administration of the combination of notoginseng total saponins and safflower total flavonoids.•Simultaneous ...determination of hydroxysafflor yellow A, ginsenosides Rg1, Re, and Rd in rat bile.•Herb pair notoginseng-safflower could reduce the excretion of the main bioactivity compounds in vivo.
The combination of notoginseng total saponins (NS) and safflower total flavonoids (SF), namely CNS, presents a synergistic protection effect on the myocardial ischemia rats. The aim of this study was to find the clues for their synergistic actions by comparing the biliary metabolism and excretion profiles after oral administration of CNS and its individual extracts. An ultra-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometer (UPLC-QTRAP-MS/MS) platform was used to identify and quantify the CNS-derived components in bile. The neutral losses, precursor ions, and predictive multiple reaction monitoring (pMRM) scans were firstly used to detect the CNS-derived ingredients in vivo. A total of 43 components, including 38 flavonoids and 5 ginsenosides were tentatively identified according to the previously established chemical and metabolic profiles of NS and SF. Afterwards, the primary circulating and biological components, hydroxysafflor yellow A (HSYA), ginsenosides Rg1 (GRg1), Re (GRe), and Rd (GRd) were chosen to compare the bile excretion between CNS and its individual extract groups, by using a validated LC-MRM-MS/MS method. The approach was proved to be well satisfied the related requirements from the guidelines of FDA (specificity, calibration curve, sensitivity, precision, accuracy, matrix effect, recovery, and stability). Comparing with the SF and NS groups, the combination group did not affect the metabolic pathways of the CNS-related components, however, it decreased the cumulative excretion ratios of HSYA, GRg1, GRe, and GRd. In conclusion, the compatibility of SF and NS could reduce the bile excretion of the CNS-derived compounds, which may be one of the reasons for the enhancement of anti-myocardial ischemia after combination.
We describe in this paper the tuning effect of silyl protecting groups on the donor reactivity of galactofuranosyl phenyl thioglycosides. Silyl ethers on the galactofuranose ring are found to have an ...arming effect on the glycosylation reactivity, but the cyclic 3,5-acetal protecting group decreases the reactivity. The reactive phenyl 2,6-di-O-Bz-3,5-di-O-TBS-1-thio-β-d-galactofuranoside 3 is proved to be a useful glycosyl building block. By taking advantage of this donor, we achieved the highly efficient one-pot solution-phase assembly of a panel of β-d-galactofuranosyl tri- and tetrasaccharides possessing diverse glycosidic linkages.
Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent ...model of Parkinson’s disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague–Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators—COX-2, iNOS—as well reduced the levels of cytokines—interleukins (IL)—IL-1β, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.
PDF
