Genomic alterations in familial and sporadic epithelial ovarian carcinomas and their clinical relevance

Tesis doctoral inédita, leída en Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 29/04/201

Mechanical, pH and Thermal Stability of Mesoporous Hydroxyapatite

The stability of mesoporous hydroxyapatite (HAP) powder was studied following treatments of ultrasound, pH and heating. HAP was found to be mechanically stable up to (and including) 1 h continuous ultrasonic treatment in water. The HAP structure was also stable to pH, evidenced by practically identical XRD and FTIR spectra over the pH range 2–12. The surface area increased progressively with increasing acidity, reaching a maximum of 121.9 m 2 g −1 at pH 2, while alkaline conditions decreased the surface area to a minimum of 55.4 m 2 g −1 at pH 12. Heating in air had a significant influence on the structural and morphological properties of HAP, which underwent dehydroxylation to form oxyhydroxyapatite (OHAP) at temperatures ≥ 650 °C, and β-tricalcium phosphate (β-TCP) ≥750 °C. The surface area decreased at elevated temperatures due to agglomeration of HAP crystals by sintering, which was associated with an increased particle size

Can Ultrasound or pH Influence Pd Distribution on the Surface of HAP to Improve Its Catalytic Properties in the Dry Reforming of Methane?

The influence of ultrasound and different pH pre-treatments during the metal doping/modification of a hydroxyapatite (HAP) support is investigated. HAP is first synthesised via a hard-template synthetic route using carbon nanorods followed by their full physiochemical characterisation. The HAP was found to be crystalline and comprised a mesoporous structure as observed via XRD and nitrogen adsorption with a BET surface area of 97.57 (±1.16) m2 g−1. Ultrasound-assisted ion exchange (IE) and incipient wetness impregnation (IW) methodologies were employed to decorate the surface of HAP with Pd0 and are compared to previous procedures. The influence of pH upon the distribution of Pd0 throughout the samples during the doping process is also studied. All the prepared samples were evaluated for their catalytic activity towards dry reforming of methane (DRM) and the reaction was monitored via a thermal conductivity detector, coupled with gas chromatography (GC-TCD). It was found that ultrasound-assisted IE significantly accelerated the process from 3 days to 3 h and with the Pd0 metal remaining highly distributed upon the HAP with minor changes in catalytic conversions. Moreover, the ultrasound-assisted IW method successfully improved the Pd0 distribution and catalytic performance. On the other hand, the dispersion of the metal was unaffected after pH treatments in IE with no catalytic improvements observed, in contrast to IW, where considerable increase in metal distribution and subsequently catalytic performance was observed

The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5- silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5 -silenced ovarian cancer cells. Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization

Antimicrobial activity of graphene oxide-metal hybrids.

With resistant bacteria on the increase, there is a need for new combinations of antimicrobials/biocidal agents to help control the transmission of such microorganisms. Particulate forms of graphite, graphene oxide (GO) and metal-hybrid compounds (silver-graphene oxide (AgGO) and zinc oxide graphene oxide (ZnOGO)) were fabricated and characterised. X-Ray diffraction and Diffuse Reflectance Infrared Fourier Transform Spectroscopy demonstrated the composition of the compounds. Scanning Electron Microscopy and Energy Dispersive X-Ray Spectroscopy determined the compounds were heterogeneous and irregular in shape and size and that the level of silver in the AgGO sample was 57.9 wt% and the ZnOGO contained 72.65 wt % zinc. The compounds were tested for their antimicrobial activity against four prominent bacteria; Escherichia coli, Staphylococcus aureus, Enterococcus faecium and Klebsiella pneumoniae. AgGO was the most effective antimicrobial (Minimum inhibitory concentration E. coli/Enterococcus faecium 0.125 mg mL−1; S. aureus/K. pneumoniae 0.25 mg mL−1). The addition of Ag enhanced the activity of GO against the bacteria tested, including the generally recalcitrant K. pneumoniae and Enterococcus faecium. These findings demonstrated that GO-metal hybrids have the potential to be utilised as novel antimicrobials or biocides in liquid formulations, biomaterials or coatings for use in the treatment of wounds where medically relevant bacteria are becoming increasingly resistant

DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas

Background: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours. Methods: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non- BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features. Results: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours. Conclusion: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitorsThis study was funded by the Fondo de Investigacio´n Sanitaria (FIS), Instituto de Salud Carlos III (grants CP07/00113 and PS09/01094

Methane emission management in a dual-fuel engine exhaust using Pd and Ni hydroxyapatite catalysts

© 2017 Elsevier Ltd While dual-fuel engines reduce transportation costs and CO 2 emissions by using alternative energy sources e.g. natural gas, the exhaust streams often contain quantities of emissions that exceed limits and therefore require removal. Pd- and Ni-hydroxyapatite (HAP) catalysts were prepared using a soft-templating method and tested in the dry reforming of methane (DRM) in a fixed bed reactor that simulates an exhaust from a diesel-natural gas dual-fuel engine. XRD revealed the characteristic HAP crystal structure of all the prepared materials. The HAP phase was further confirmed by TEM, which also showed the presence of submicron sized particles. The BET surface areas of HAP prepared using a single surfactant was 27.7 m 2  g −1 and increased to 84.9 m 2  g −1 when mixed surfactants were used. Active metals were added to HAP using either incipient wetness impregnation, ion-exchange or solid dispersion. All the catalysts tested were active in DRM with the optimal samples converting over 85% of methane at 650 °C