Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer. Past molecular and morphological studies on cell lines, animal models and human tissue samples have ...unambiguously demonstrated that IBC is highly (lymph)angiogenic. Nevertheless, two vital questions remain unanswered: A. what is the role of the differential distribution of the molecular subtypes (particularly Luminal A) between IBC and nIBC in determining the observed difference in (lymph)angiogenesis and B. what are the exact molecular mechanisms that support angiogenesis in IBC? In this study, we aim to provide a clue for both questions by analyzing a gene expression data set of 137 IBC samples and 252 nIBC samples. In order to resolve the first question, a Gene Ontology analysis focusing on angiogenesis-related GO-terms was performed on the original data set and on the same data set after removing molecular subtype-specific variation in gene expression. In order to provide an answer to the second question, we identified angiogenesis-related IBC-specific genes that were subjected to Ingenuity Pathway Analysis. In addition, we focused part of our analysis on angiomiRs, microRNA-families that are known to regulate angiogenesis. Comparative analysis of all our data suggests that angiogenesis in IBC is not VEGFA-driven but is merely a consequence of a disturbed balance between proangiogenic and antiangiogenic factors, possibly involving PGF, TSP1 (THBS1) and the miR-221/-222-family. TSP1, a TGFβ-inducible gene that is upregulated in nIBC, is involved in the inhibition of angiogenesis, a process that also involves miR-221/-222. Therefore, we conclude that lack of inhibition of angiogenesis in IBC in conjunction with the increased expression of several angiogenesis-stimulating genes (PGF, mir-221/-222 gene targets) results in increased levels of angiogenesis-related histomorphometrical parameters in IBC.
Two methods were developed for the determination of mexiletine enantiomers in plasma samples suitable for studies on the stereoselective disposition of this drug. Both methods used fluorescence ...detection to improve sensitivity and selectivity. The direct enantioselective separation was based on the chiral resolution of mexiletine-2-naphthamide derivatives on a Chiralcel OJ column. The calibration curves were linear over the concentration range 50–500 ng/ml for each enantiomer; therefore the method can be used only for therapeutic monitoring, drug interaction and multiple dose pharmacokinetic studies. The indirect method was based on the formation of diastereomers using
o-phthaldialdehyde and N-acetyl-
l-cysteine reagents. The diastereomers were resolved on a reversed-phase RP-18 column. The method proved to be suitable for single or multiple dose pharmakokinetic studies based on the loq quantification limit ng/ml) and the broader linear range (1–1000 ng/ml) obtained.
Lab tests designed to reveal the presence of pathological liver and haemopoietic organ alterations were run in 72 alcohol addicts. It was found that chronic alcoholism is more often accompanied by ...hypoazotaemia (90.28% of cases), increased globular volume (90.28%), increased IgA (85%), decreased blood transferrin (95.45%), and increase Ig A: blood transferrin ratio (90%) than by other signs. Liver biopsy and sternal puncture, together with gastroendoscopy, showed that these signs are constant and early evidence of initial anatomical and functional damage to the liver and blood production organs due to alcohol.
