The long noncoding RNA (lncRNA) H19 has been recently characterized as an oncogenic lncRNA in some tumors. However, the role of H19 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we found that not only the levels of H19 was overexpressed in PDAC compared with adjacent normal tissues, but also H19 expression was upregulated remarkably in primary tumors which subsequently metastasized, compared to those did not metastasis. Subsequently, the efficacy of knockdown of H19 by H19-small interfering RNA (siRNA) was evaluated in vitro, and we found that downregulation of H19 impaired PDAC cell invasion and migration. We further demonstrated that H19 promoted PDAC cell invasion and migration at least partially by increasing HMGA2-mediated epithelial-mesenchymal transition (EMT) through antagonizing let-7. This study suggests an important role of H19 in regulating metastasis of PDAC and provides some clues for elucidating the lncRNA-miRNA functional network in cancer.

OBJECTIVERecent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.METHODSTargeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher’s exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features.RESULTSGenomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among “mutation unknown” samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor’s underlying driver mutation.CONCLUSIONSUsing a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

Abstract:To develop a rat model of type 2 diabetic mellitus that simulated the common manifestation of the metabolic abnormalities and resembled the natural history of a certain type 2 diabetes in human population, male Sprague-Dawley rats (4 months old) were injected with low-dose (15 mg/kg) STZ after high fat diet (30% of calories as fat) for two months (L-STZ/2HF). The functional and histochemical changes in the pancreatic islets were examined. Insulin-glucose tolerance test, islet immunohistochemistry and other corresponding tests were performed and the data in L-STZ/2HF group were compared with that of other groups, such as the model of type 1 diabetes (given 50 mg/kg STZ) and the model of obesity (high fat diet). The body weight of rats in the group of rats given 15 mg/kg STZ after high fat diet for two months increased significantly more than that of rats in the group of rats given 50 mg/kg STZ (the model of type 1 diabetes) (595 ± 33 g vs. 352 ± 32 g, p<0.05). Fast blood glucose levels for L-STZ/2HF group were 16.92 ± 1.68 mmol/l, versus 5.17 ± 0.55 mmol/l in normal control and 5.59 ± 0.61 mmol/l in rats given high fat diet only. Corresponding values for fast serum insulin were 0.66 ± 0.15 ng/ml, 0.52 ± 0.13 ng/ml, 0.29 ± 0.11 ng/ml, respectively. Rats of type 2 diabetes (L-STZ/2HF) had elevated levels of triglyceride (TG, 3.82 ± 0.88 mmol/l), and cholesterol(Ch, 2.38 ± 0.55 mmol/l) compared with control (0.95 ± 0.15 mmol/l and 1.31 ± 0.3 mmol/l, respectively) (p<0.05). The islet morphology as examined by immunocytochemistry using insulin antibodies in the L-STZ/2HF group was affected and quantitative analysis showed the islet insulin content was higher than that of rats with type 1 diabetes (P<0.05). We concluded that the new rat model of type 2 diabetes established with conjunctive treatment of low dose of STZ and high fat diet was characterized by hyperglycemia and light impaired insulin secretion function accompanied by insulin resistance, which resembles the clinical manifestation of type 2 diabetes. Such a model, easily attainable and inexpensive, would help further elucidation of the underlying mechanisms of diabetes and its complications.

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2,5‐furandicarboxylic acid (FDCA) is a potential non‐phthalate based bio‐renewable substitute for terephthalic acid‐based plastics. Herein, we present an investigation of the oxidation rate of 5‐hydroxymethylfurfural (HMF) to FDCA in acetic acid medium using Co/Mn/Br catalyst. Transient concentration profiles of the reactant (HMF), intermediates [2,5‐diformylfuran (DFF), 5‐formyl‐2‐furancarboxylic acid (FFCA)], and the desired product (FDCA) were obtained for this relatively fast reaction in a stirred semi‐batch reactor using rapid in‐line sampling. Comparison of the effective rate constants for the series oxidation steps with predicted gas–liquid mass transfer coefficients reveals that except for the FFCA → FDCA step, the first two oxidation steps are subject to gas–liquid mass transfer limitations even at high stirrer speeds. Novel reactor configurations, such as a reactor in which the reaction mixture is dispersed as fine droplets into a gas phase containing oxygen, are required to overcome oxygen starvation in the liquid phase and further intensify FDCA production. © 2016 American Institute of Chemical Engineers AIChE J, 63: 162–171, 2017

BackgroundmicroRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in carcinogenesis. In the present study, we investigated the effect of miR-212 on pancreatic ductal adenocarcinoma (PDAC) and its target protein.MethodsQuantitative real-time PCR(qRT-PCR) was performed to detect the expression of miR-212 in PDAC tissues and pancreatic cancer cell lines. miR-212 mimic, miR-212 inhibitor and negative control were transfected into pancreatic cancer cells and the effect of miR-212 up-regulation and down-regulation on the proliferation, migration and invasion of cells were investigated. Furthermore, the mRNA and protein levels of Patched-1(PTCH1) were measured. Meanwhile, luciferase assays were performed to validate PTCH1 as miR-212 target in PDAC.ResultsmiR-212 was up-regulated in PDAC tissues and cells.Using both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-212 was demonstrated in PDAC. Moreover, up-regulated of PTCH1 could attenuate the effect induced by miR-212.ConclusionThese data suggest that miR-212 could facilitate PDAC progression and metastasis through targeting PTCH1, implicating a novel mechanism for the progression of PDAC.

Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. Approximately 50% of human melanoma is driven by B-Raf proto-oncogene mutation (BRAF mutant). Tumors with such mutation are desmoplastic, highly immunosuppressive, and often resistant to immune checkpoint therapies. We have shown that immunotherapy mediated by low-dose doxorubicin-induced immunogenic cell death was only partially effective for this type of tumor and not effective in long-term inhibition of tumor progression. Wnt family member 5A (Wnt5a), a signaling protein highly produced by BRAF mutant melanoma cells, has been implicated in inducing dendritic cell tolerance and tumor fibrosis, thus hindering effective antigen presentation and T-cell infiltration. We hypothesized that Wnt5a is a key molecule controlling the immunosuppressive tumor microenvironment in metastatic melanoma. Accordingly, we have designed and generated a trimeric trap protein, containing the extracellular domain of Fizzled 7 receptor that binds Wnt5a with a K ∼ 278 nM. Plasmid DNA encoding for the Wnt5a trap was delivered to the tumor by using cationic lipid-protamine-DNA nanoparticles. Expression of Wnt5a trap in the tumor, although transient, was greater than that of any other major organs including liver, resulting in a significant reduction of the Wnt5a level in the tumor microenvironment without systematic toxicity. Significantly, combination of Wnt5a trapping and low-dose doxorubicin showed great tumor growth inhibition and host survival prolongation. Our findings indicated that efficient local Wnt5a trapping significantly remodeled the immunosuppressive tumor microenvironment to facilitate immunogenic cell-death-mediated immunotherapy.

Tungsten-incorporated 3D mesoporous silicates, W-KIT-6, W-KIT-5, and W-SBA-16 catalysts, outperform supported tungsten oxide catalysts (WO 3 /SiO 2 and WO 3 /KIT-6) for the metathesis of ethylene and 2-butene to propene at 450°C. All catalysts exhibit steady activity and stability during 7 h runs in a fixed-bed reactor. Furthermore, on all mesoporous catalysts, a maximum propylene yield was obtained at an optimum W loading at which the catalyst acidity is also maximum. Slightly delayed addition of the W source during the one-pot synthesis protocol markedly improves the propene yield on W-KIT-6 catalyst. XPS results conclusively show that this enhancement is due to preferential enrichment of active W species on the catalyst surface. Extended runs lasting five days reveal very little loss of activity even which is easily recovered by calcination in air.