Chemical Printing of Biological Tissue by Gold Nanoparticle-Assisted Laser Ablation

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Effects of adrenomedullin on the expression of inflammatory cytokines and chemokines in oviducts from women with tubal ectopic pregnancy: an in-vitro experimental study

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Utility of contrast-enhanced computed tomography in the evaluation of canine insulinoma location

OBJECTIVES: To determine 1) the sensitivity of contrast-enhanced CT (CECT) for detection of primary canine insulinomas and metastases 2) the sensitivity of CECT to locate canine insulinomas within the pancreas and 3) the CECT attenuation pattern of canine insulinomas and post-contrast phase in which insulinomas have the best visibility. METHODS: A retrospective review was performed of the medical records of 27 canine insulinoma patients. Simultaneous occurrence of blood glucose 10 mIU/L (reference interval: 1.4-24.5 mIU/L) were considered diagnostic for insulinoma. The dogs had a mean age of 9.0 ± 1.7 (SD) years and comprised 11 males and 17 females. RESULTS: Using CECT-scans, 26/27 insulinomas were successfully detected. However, CECT-scans predicted the correct location of insulinomas within the pancreas in only 14/27 dogs. In 9/13 inaccurately located insulinoma cases, the location error was major. There was no significant difference between triple, double and single-phase CECT-scans with location accuracies of 54%, 50% and 50%, respectively. Also, there was no specific post-contrast phase in which insulinomas could be visualised best. Detection of lymph node metastases with CECT-scans had a sensitivity of 67% (10/15 lymph node metastases). Detection of liver metastases had a sensitivity of 75% (6/8 liver metastases). This study highlights that major location errors mainly occurred if single- or double-phase CECT-scans were used (6/9 cases). CONCLUSION: It is suggested that triple-phase CECT-scans have superior outcome over single- or double-phase CECT-scans in pre-operative imaging of canine insulinomas

TSC1/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication

Objective We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. Design We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. Results We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC-mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2-mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. Conclusions Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.published_or_final_versio

Perception of urban park soundscape

2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor that inhibits plasmin-dependent activation of several metalloproteinases. Downregulation of TFPI-2 could thus enhance the invasive potential of neoplastic cells in several cancers, including lung cancer. In this study, TFPI-2 mRNA was measured using a real-time PCR method in tumours of 59 patients with non-small-cell lung cancer (NSCLC). Tumour TFPI-2 mRNA levels appeared well correlated with protein expression evaluated by immunohistochemistry and were 4–120 times lower compared to those of nonaffected lung tissue in 22 cases (37%). Hypermethylation of the TFPI-2 gene promoter was demonstrated by restriction enzyme-polymerase chain reaction in 12 of 40 cases of NSCLC (30%), including nine of 17 for whom tumour TFPI-2 gene expression was lower than in noncancerous tissue. In contrast, this epigenetic modification was shown in only three of 23 tumours in which no decrease in TFPI-2 synthesis was found (P=0.016). Decreased TFPI-2 gene expression and hypermethylation were more frequently associated with stages III or IV NSCLC (eight out of 10, P=0.02) and the TFPI-2 gene promoter was more frequently hypermethylated in patients with lymph node metastases (eight out of 16, P=0.02). These results suggest that silencing of the TFPI-2 gene by hypermethylation might contribute to tumour progression in NSCLC

Altering crystal growth and annealing in ice-templated scaffolds.

The potential applications of ice-templating porous materials are constantly expanding, especially as scaffolds for tissue engineering. Ice-templating, a process utilizing ice nucleation and growth within an aqueous solution, consists of a cooling stage (before ice nucleation) and a freezing stage (during ice formation). While heat release during cooling can change scaffold isotropy, the freezing stage, where ice crystals grow and anneal, determines the final size of scaffold features. To investigate the path of heat flow within collagen slurries during solidification, a series of ice-templating molds were designed with varying the contact area with the heat sink, in the form of the freeze drier shelf. Contact with the heat sink was found to be critical in determining the efficiency of the release of latent heat within the perspex molds. Isotropic collagen scaffolds were produced with pores which ranged from 90 μm up to 180 μm as the contact area decreased. In addition, low-temperature ice annealing was observed within the structures. After 20 h at -30 °C, conditions which mimic storage prior to lyophilization, scaffold architecture was observed to coarsen significantly. In future, ice-templating molds should consider not only heat conduction during the cooling phase of solidification, but the effects of heat flow during ice growth and annealing.The authors gratefully acknowledge the financial support of the Gates Cambridge Trust, the Newton Trust, and ERC Advanced Grant 320598 3D-E. A.H. held a Daphne Jackson Fellowship funded by the University of Cambridge.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10853-015-9343-

CR2Cancer: a database for chromatin regulators in human cancer

Identification of Master Regulators (MRs) during cancer development contributes greatly to the design of novel targeted therapy. However, it is challenging to trace the MR that regulate the gene signature (e.g. differentially expressed genes) derived from a limited number of transcriptome profiles. The main reason is that the targets (collectively termed as regulon) of MRs in cancer type-specific context is not available for enrichment analysis in the signature. To this aim, we generated the regulon of MRs using high throughput omics data from The Cancer Genome Atlas (TCGA), and developed a web server MR4Cancer, which can prioritize MRs driving phenotypic differentiation of interest in 26 cancer types. Based on the input gene list or expression profiles, it outputs six groups of ranked MRs, including transcription regulators, miRNAs, recurrently mutated genes, kinases, phosphatases, and hubs from protein-protein interaction network. Simultaneously, Gene Ontology and canonical pathway analyses are also conducted to further elucidate the function of MR candidates. Moreover, our tool presents dynamic network visualization for MR-target relations, and users can interactively customize it as high quality figures for their publications. We expect this user-friendly and powerful web application will provide researchers new insights into carcinogenesis and therapeutic intervention.published_or_final_versio

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica