Core needle biopsy of the left pleura was made; the diagnosis of metastatic ACC from lacrimal gland was confirmed by pathologists Figure 1d. Next-generation sequencing was performed on the biopsied ...tissue, gene mutations were found on Cyclin D2 (CCND2) at c.721-110A>C, epidermal growth factor receptor(EGFR) at c.1298+722C>A and notch homolog 1 (NOTCH1)at c.4571C>T; and mutation frequencies were 7.1%, 4.3%, and 0.5%, respectively. The mutations in NOTCH genes were located in heterodimerization domain, notch intracellular domain, and epidermal growth factor (EGF)-like repeats;4 this finding suggested the possibility of targeted therapy aimed at the EGFR pathway. The EGFR pathway might play an important role in tumor proliferation and metastasis; more patients of LGACC are needed to enroll in the study in the future.
Nanovaccines
In article number 2311480, Yongbin Mou, Zhaogang Teng, Heng Dong, and co‐workers present a tumor microenvironment‐responsive and soft‐transformable nanovaccine that comprehensively ...addresses the major obstacles faced by in situ tumor vaccines. It includes promoting immunogenic cell death in tumor cells, fostering dendritic cell maturation, and encouraging macrophage M1 polarization, all while reprogramming the immunosuppressive tumor microenvironment.
Seven new merosesquiterpenoids, trichothecrotocins D–J (1–7), two new trichothecene sesquiterpenoids, trichothecrotocins K (12) and L (13), and six known compounds (8–11, 14, and 15), were isolated ...from a potato-associated fungus, Trichothecium crotocinigenum. Compounds 5 and 6 were racemates which were further separated as pure enantiomers. Structures together with absolute configurations were established by extensive spectroscopic analysis, as well as quantum chemistry calculations on ECD and optical rotations. Compounds 1–4 are rare meroterpenoids featuring a seco-phenyl group, while 1 and 2 possessed a novel 6–6/5 fused ring system. Compounds 1–4, 8, 11, and 12 showed antifungal activity against four plant pathogens with MIC values of 8–128 μg/mL. It is suggested that the meroterpenoids produced by T. crotocinigenum may play an important role in the antifungal property of the fungus, thereby protecting the host plant, i.e., potato.
Objectives: Cigarette smoking is the major risk factor of bladder cancer via exposure to chemical carcinogens. Nicotinamide adenine dinucleotide phosphate (NADP+): quinine oxidoreductase 1 (NQO1) and ...sulfotransferase 1A1 (SULT1A1) have been reported to involve in the metabolism of polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. Therefore, the risk of bladder cancer (BC) may be influenced by polymorphisms in the genes that modulate metabolic detoxification in particular by interacting with cigarette smoking. Considering the limited power by the individual studies with a relatively small sample size, especially when analyzing the combined effect of polymorphisms in NQO1 and SULT1A1 genes and smoking, these 2 meta-analyses have aimed to clarify the combined effects of them on BC risk by integrating related studies.
Two meta-analyses included 1341 cases and 1346 controls concerning NQO1 Pro187Ser and smoking, and 1921 cases and 1882 controls on SULT1A1 Arg213His and smoking were performed. Odds ratios (OR) and 95% confidence intervals (CI) were used for assessing the strength of the association.
The result has demonstrated that smokers with NQO1 Pro/Ser or Ser/Ser genotypes have a prominent association with the risk of BC as compared with non-smokers with NQO1 Pro/Pro genotype, with OR equal to 3.71 (95% CI: 2.87-4.78, p
= 0.376). Besides, smokers carrying SULT1A1 Arg/Arg genotypes were observed to confer 2.38 fold increased risk of BC (95% CI: 1.44-3.93, p
= 0.001) when compared with non-smokers with SULT1A1 Arg/Arg or His/His genotypes.
These findings have suggested that the NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism combination with smoking significantly confer susceptibility to BC. Int J Occup Med Environ Health 2017;30(5):791-802.
Vascular endothelial dysfunction and inflammatory response are early events during initiation and progression of atherosclerosis. In vitro studies have described that CIT markedly upregulates ...expressions of ICAM-1 and VCAM-1 of endothelial cells, which result from NF-κB activation induced by CIT. In order to determine whether it plays a role in atherogenesis in vivo, we conducted the study to investigate the effects of CIT on atherosclerotic plaque development and inflammatory response in apolipoprotein E deficient (apoE-/-) mice. Five-week-old apoE-/- mice were fed high-fat diets and treated with CIT for 15 weeks, followed by assay of atherosclerotic lesions. Nitric oxide (NO), vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were detected in serum. Levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), VEGF, and ET-1 in plaque areas of artery walls were examined. NF-κB p65 expression and NF-κB activation in aorta also were assessed. CIT treatment significantly augmented atherosclerotic plaques and increased expressions of ICAM-1, VCAM-1, VEGF and ET-1 in aorta. Mechanistic studies showed that activation of NF-κB was significantly elevated by CIT treatment, indicating the effect of CIT on atherosclerosis may be regulated by activation of NF-κB.
Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior ...cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the
N
-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells
via
chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons
via
optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
A novel compact dual-band antenna array with high isolations is presented in this paper. It consists of four antenna elements with two feeding networks, and it operates at dual-band of 0.89-0.96 and ...1.7-2.2 GHz with return loss more than 9 dB, respectively. Two feeding networks are made of a wideband balun and a Wilkinson power divider, respectively. The two-port symmetrical array is constructed using the neutralization technique (NT), leading to the array port isolation over 30 dB from 0.5 to 3.0 GHz. Such a compact dual-band antenna array is realized and its gains and normalized patterns for both ports P 1 and P 2 are measured, with good agreements obtained in comparison with the simulated ones.
Study Objectives
To compare the effectiveness of different taxane‐containing regimens and to identify the best strategy for the treatment of human epidermal growth factor receptor 2 (HER2)‐negative ...metastatic breast cancer (MBC).
Design
Network meta‐analysis of 20 randomized controlled trials (RCTs).
Patients
A total of 6577 patients with HER2‐negative MBC who received treatment (20 different regimens) with taxanes (paclitaxel 4267 patients or docetaxel 2310 patients).
Measurements and Main Results
The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched (through March 2019) for RCTs that evaluated any taxane‐containing regimens for the treatment of HER2‐negative MBC. A network meta‐analysis in a Bayesian framework was performed using the random‐effects model. We compared the surface under the cumulative ranking (SUCRA) curve for each regimen. Overall, paclitaxel‐based combinations were superior to paclitaxel alone in objective response rate (ORR) (odds ratio 1.60, 95% credible interval CrI 1.15–2.16) and overall survival (OS) (hazard ratio 1.08, 95% CrI 1.01–1.15). Docetaxel‐based combinations were also superior to paclitaxel alone in ORR. Among the paclitaxel‐based regimens, based on the results of SUCRA, paclitaxel + bevacizumab + capecitabine was likely to be the most efficacious in improving ORR, OS, and progression‐free survival (PFS), whereas paclitaxel + gemcitabine was likely to be the most efficacious in 1‐year OS rate. Among the docetaxel‐based regimens, based on the results of SUCRA, docetaxel + gemcitabine was likely to be the most efficacious in improving PFS and OS.
Conclusion
These findings demonstrated that paclitaxel‐based combinations can provide significant improvement in ORR and OS compared with paclitaxel alone. The regimens of paclitaxel + bevacizumab + capecitabine, docetaxel + gemcitabine, and paclitaxel + gemcitabine may be superior to other regimens for the treatment of HER2‐negative MBC.
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•10 of the 20 synthetic derivatives exhibited significant antitumor activity.•Compound 4g shows the most potent against A549 cells (14.34-fold of d-Tet).•Compound 4g inhibits A549 ...proliferation, migration, invasion and arrest G2/M cycle.•Compound 4g can induce apoptosis by inactivating the PI3K/Akt/mTOR pathway.
Cancer treatment is one of the major public health issues in the world. Tetrandrine (Tet) and fangchinoline (d-Tet) are two bis-benzyl isoquinoline alkaloids extracted from Stephania tetrandra S. Moore, and their antitumor activities have been confirmed. However, the effective dose of Tet and d-Tet were much higher than that of the positive control and failed to meet clinical standards. Therefore, in this study, as a continuation of our previous work to study and develop high-efficiency and low-toxic anti-tumor lead compounds, twenty new Tet and d-Tet derivatives were designed, synthesized and evaluated as antitumor agents against six cancer cell lines (H460, H520, HeLa, HepG-2, MCF-7, SW480 cell lines) and BEAS-2B normal cells by CCK-8 analysis. Ten derivatives showed better cytotoxic effects than the parent fangchinoline, of which 4g showed the strongest cell growth inhibitory activity with an IC50 value of 0.59 μM against A549 cells. Subsequently, the antitumor mechanism of 4g was studied by flow cytometry, Hoechst 33258, JC-1 staining, cell scratch, transwell migration, and Western blotting assays. These results showed that compound 4g could inhibit A549 cell proliferation by arresting the G2/M cell cycle and inhibiting cell migration and invasion by reducing MMP-2 and MMP-9 expression. Meanwhile, 4g could induce apoptosis of A549 cells through the intrinsic pathway regulated by mitochondria. In addition, compound 4g inhibited the phosphorylation of PI3K, Akt and mTOR, suggesting a correlation between blocking the PI3K/Akt/mTOR pathway and the above antitumor activities. These results suggest that compound 4g may be a future drug for the development of new potential drug candidates against lung cancer.
This study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome ...Atlas (TCGA) and Gene Expression Omnibus (GEO).
A total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis.
In TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway.
GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.
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