Prediction of Multiple Basal Cell Carcinomas

Basal cell carcinoma (BCC) is the most common cancer in white-skinned individuals with increasing incidence rates worldwide. Patients with BCC place a large burden on healthcare systems, because of the high incidence and the increased risk of synchronous and metachronous BCCs and other ultraviolet radiation related skin cancers (i.e. field cancerization). In this thesis we have performed multiple studies to define who these patients who develop multiple BCCs are and created prediction models, using both non-genetic and genetic predictors

On volatile/mobile trace element trends in E3 chondrites

Contents of 3 non-mobile trace elements (U, Co, Au) and 12 slightly-to-highly volatile ones (Rb, Sb, Ag, Ga, Se, Cs, Te, Zn, Cd, Bi, Tl and In) determined by RNAA in the Yamato (Y)-691 and Qingzhen E3 chondrites generally fall within ranges reported for E4 chondrite falls. Contents of most elements are similar in the two E3 chondrites : highly volatile Cd, Bi and Tl differ markedly, with the Y-691 data falling at C1 levels and those of Qingzhen near the bottom of the E4 ranges. Trace element abundances and interelement comparisons indicate that both E3 chondrites compositionally reflect only nebular condensation, with Y-691 parent material having condensed at lower temperatures than Qingzhen. Both escaped the post-accretionary metamorphic episode that compositionally altered other enstatite chondrites. For volatiles, E3,4 chondrites differ markedly from E5,6 : for siderophiles, E3-5 differ markedly from E6. These trends could reflect enstatite chondrites\u27 origin in 1 or 2 parent bodies : we interpret the data as indicating a single body

The origin of aubrites: Evidence from lithophile trace element abundances and oxygen isotope compositions

We report the abundances of a selected set of “lithophile” trace elements (including lanthanides, actinides and high field strength elements) and high-precision oxygen isotope analyses of a comprehensive suite of aubrites. Two distinct groups of aubrites can be distinguished: (a) the main-group aubrites display flat or light-REE depleted REE patterns with variable Eu and Y anomalies; their pyroxenes are light-REE depleted and show marked negative Eu anomalies; (b) the Mount Egerton enstatites and the silicate fraction from Larned display distinctive light-REE enrichments, and high Th/Sm ratios; Mount Egerton pyroxenes have much less pronounced negative Eu anomalies than pyroxenes from the main-group aubrites. Leaching experiments were undertaken to investigate the contribution of sulfides to the whole rock budget of the main-group aubrites. Sulfides contain in most cases at least 50% of the REEs and of the actinides. Among the elements we have analyzed, those displaying the strongest lithophile behaviors are Rb, Ba, Sr and Sc. The homogeneity of the Δ17O values obtained for main-group aubrite falls [Δ17O = +0.009 ± 0.010‰ (2σ)] suggests that they originated from a single parent body whose differentiation involved an early phase of large-scale melting that may have led to the development of a magma ocean. This interpretation is at first glance in agreement with the limited variability of the shapes of the REE patterns of these aubrites. However, the trace element concentrations of their phases cannot be used to discuss this hypothesis, because their igneous trace-element signatures have been modified by subsolidus exchange. Finally, despite similar O isotopic compositions, the marked light-REE enrichments displayed by Mount Egerton and Larned suggest that they are unrelated to the main-group aubrites and probably originated from a distinct parent body

Experimental determination of the eutectic temperature in air of the CuO-TiO2 pseudobinary system

Eutectic temperature and composition in the CuO–TiO2 pseudobinary system have been experimentally determined in air by means differential thermal analysis (DTA), thermogravimetry (TG) and hot-stage microscopy (HSM). Samples of the new eutectic composition treated at different temperatures have been characterized by X-ray diffraction (XRD) and X-ray absorption near-edge structural spectroscopy (XANES) to identify phases and to determine the Cu valence state, respectively. The results show that the eutectic temperature in air is higher by 100 °C (∼1000 °C) for a Ti-richer composition (XTiO2=25 mol%) than the one calculated in the literature. The reduction of Cu2+ to Cu+ takes places at about 1030 °C. The existence of Cu2TiO3 and Cu3TiO4 has been confirmed by XRD in the temperature range between 1045 and 1200 °C

Molecular testing in metastatic basal cell carcinoma

Background: Metastatic basal cell carcinoma (mBCC) is a very rare entity, and diagnosis can be challenging. Therapeutic options are limited, and response to targeted therapy is poor. Objective: To demonstrate a clonal relationship between BCCs and their metastases and to explore which hedgehog pathway-related mutations are involved in mBCC. Methods: Genetic analysis was conducted in 10 primary BCCs and their metastases. Genes relevant for BCC development were analyzed in tumor and metastasis material with small molecule molecular inversion probes (smMIPs) for PTCH1, PTCH2, SMO, SUFU, GLI2, and TP53 or with targeted next generation sequencing of the same genes and CDKN2A, CDKN2B, CIC, DAXX, DDX3X, FUBP1, NF1, NF2, PTEN, SETD2, TRAF7, and the TERT promoter. Results: In 8 of 10 patients, identical gene mutations could be demonstrated in the primary tumors and their metastases. A broad spectrum of mutations was found. Four patients had SMO mutations in their tumor or metastasis, or both. All SMO mutations found were known to cause resistance to targeted therapy with vismodegib. Limitations: In 2 patients there was insufficient qualitative DNA available for genetic analysis. Conclusions: Molecular testing can help to identify the origin of a BCC metastasis and may be of prognostic and therapeutic value