Oestrogen-Binding Components in Human Renal Cell Carcinoma

Peer Reviewe

Gene expression of circulating tumour cells and its correlation with tumour stage in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Breast cancer (BC) represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting.</p> <p>Materials and methods</p> <p>Circulating tumour cells (CTC) of 63 BC patients were isolated from peripheral blood (PB) through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes <it>ga733.2</it>, <it>muc-1</it>, <it>c-erbB2</it>, <it>mgb-1</it>, <it>spdef </it>and <it>c-erbB2 </it>were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls.</p> <p>Results</p> <p>Significant correlations with tumour stages were found in single gene analyses of <it>ga733.2</it>, <it>muc-1 </it>and in multi-gene analyses of <it>ga733.2</it>/<it>muc-1</it>/<it>mgb1</it>/<it>spdef</it>. Furthermore, a significant correlation of <it>Ca 15-3 </it>and all studied genes was also observed.</p> <p>Conclusion</p> <p>Herein, we demonstrated a positive correlation of a gene signature consisting of <it>ga733.2</it>, <it>muc-1</it>, <it>mgb1 </it>and <it>spdef </it>and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with <it>Ca 15-3 </it>positive cases.</p

Modelling the effects of standard prognostic factors in node-positive breast cancer

Prognostic models that predict the clinical course of a breast cancer patient are important in oncology. We propose an approach to constructing such models based on fractional polynomials in which useful transformations of the continuous factors are determined. The idea may be applied with all types of regression model, including Cox regression, the method of choice for survival-time data. We analyse a prospective study of node-positive breast cancer. Seven standard prognostic factors – age, menopausal status, tumour size, tumour grade, number of positive lymph nodes, progesterone and oestrogen receptor concentrations – were investigated in 686 patients, of whom 299 had an event for recurrence-free survival and 171 died. We determine a final model with transformations of prognostic factors and compare it with the more traditional approaches using categorized variables or assuming a straight line relationship. We conclude that analysis using fractional polynomials can extract important prognostic information which the traditional approaches may miss. © 1999 Cancer Research Campaig

Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes

Propionibacterium acnes (P. acnes) has been known to produce various exogenous proteases, however, their role in acne pathogenesis remains largely unknown. Proteases elicit cellular responses, at least in part, via proteinase-activated receptor-2 (PAR-2), which is known to mediate inflammation and immune response. In this study, we investigated whether proteases from P. acnes could activate PAR-2 on keratinocytes and induce pro-inflammatory cytokines, antimicrobial peptides (AMPs), and matrix metalloproteinases (MMPs) via PAR-2 signaling. We examined PAR-2 expression and protease activity in acne lesions using immunofluorescence staining and in situ zymography. The effect of the culture supernatant of P. acnes on Ca2+ signaling in immortalized keratinocytes (HaCaT) was measured using a fluorescence method. HaCaT cells were treated with P. acnes strain ATCC 6919 culture supernatant, with or without pretreatment with serine protease inhibitor or selective PAR-2 antagonist and the gene expression of pro-inflammatory cytokines, AMPs, and MMPs was detected using real-time reverse transcription-polymerase chain reaction. We found that the protease activity and PAR-2 expression were increased in acne lesions. The P. acnes culture supernatant induced calcium signaling in keratinocytes via PAR-2 and stimulated the mRNA expression of interleukin (IL)-1α, -8, tumor necrosis factor (TNF)-α, human beta defensin (hBD)-2, LL-37, MMP-1, -2, -3, -9, and -13 in keratinocytes, which was significantly inhibited by serine protease inhibitor as well as selective PAR-2 specific antagonist. These results indicate that PAR-2 plays an important role in the pathogenesis of acne by inducing inflammatory mediators in response to proteases secreted from P. acnes

Control of Propionibacterium acnes by natural antimicrobial substances: Role of the bacteriocin AS-48 and lysozyme

We report the high susceptibility of several clinical isolates of Propionibacterium acnes from different sources (skin, bone, wound exudates, abscess or blood contamination) to the head-to-tail cyclized bacteriocin AS-48. This peptide is a feasible candidate for further pharmacological development against this bacterium, due to its physicochemical and biological characteristics, even when it is growing in a biofilm. Thus, the treatment of pre-formed biofilms with AS-48 resulted in a dose- and time-dependent disruption of the biofilm architecture beside the decrease of bacterial viability. Furthermore, we demonstrated the potential of lysozyme to bolster the inhibitory activity of AS-48 against P. acnes, rendering high reductions in the MIC values, even in matrix-growing cultures, according to the results obtained using a range of microscopy and bioassay techniques. The improvement of the activity of AS-48 through its co-formulation with lysozyme may be considered an alternative in the control of P. acnes, especially after proving the absence of cytotoxicity demonstrated by these natural compounds on relevant human skin cell lines. In summary, this study supports that compositions comprising the bacteriocin AS-48 plus lysozyme must be considered as promising candidates for topical applications with medical and pharmaceutical purposes against dermatological diseases such as acne vulgaris.This research was funded by a grant from the Spanish Ministry of Economy and Competitiveness (SAF2013-48971-C2-1-R that included funds from European Regional Development, ERDF), and the Research Group General (BIO160, UGR)

Differential Attraction of Malaria Mosquitoes to Volatile Blends Produced by Human Skin Bacteria

The malaria mosquito Anopheles gambiae sensu stricto is mainly guided by human odour components to find its blood host. Skin bacteria play an important role in the production of human body odour and when grown in vitro, skin bacteria produce volatiles that are attractive to A. gambiae. The role of single skin bacterial species in the production of volatiles that mediate the host-seeking behaviour of mosquitoes has remained largely unknown and is the subject of the present study. Headspace samples were taken to identify volatiles that mediate this behaviour. These volatiles could be used as mosquito attractants or repellents. Five commonly occurring species of skin bacteria were tested in an olfactometer for the production of volatiles that attract A. gambiae. Odour blends produced by some bacterial species were more attractive than blends produced by other species. In contrast to odours from the other bacterial species tested, odours produced by Pseudomonas aeruginosa were not attractive to A. gambiae. Headspace analysis of bacterial volatiles in combination with behavioural assays led to the identification of six compounds that elicited a behavioural effect in A. gambiae. Our results provide, to our knowledge, the first evidence for a role of selected bacterial species, common on the human skin, in determining the attractiveness of humans to malaria mosquitoes. This information will be used in the further development of a blend of semiochemicals for the manipulation of mosquito behaviour

First Evidence of Reproductive Adaptation to “Island Effect” of a Dwarf Cretaceous Romanian Titanosaur, with Embryonic Integument In Ovo

<div><h3>Background</h3><p>The Cretaceous vertebrate assemblages of Romania are famous for geographically endemic dwarfed dinosaur taxa. We report the first complete egg clutches of a dwarf lithostrotian titanosaur, from Toteşti, Romania, and its reproductive adaptation to the “island effect”.</p> <h3>Methodology/Findings</h3><p>The egg clutches were discovered in sequential sedimentary layers of the Maastrichtian Sânpetru Formation, Toteşti. The occurrence of 11 homogenous clutches in successive strata suggests philopatry by the same dinosaur species, which laid clutches averaging four ∼12 cm diameters eggs. The eggs and eggshells display numerous characters shared with the positively identified material from egg-bearing level 4 of the Auca Mahuevo (Patagonia, Argentina) nemegtosaurid lithostrotian nesting site. Microscopic embryonic integument with bacterial evidences was recovered in one egg. The millimeter-size embryonic integument displays micron size dermal papillae implying an early embryological stage at the time of death, likely corresponding to early organogenesis before the skeleton formation.</p> <h3>Conclusions/Significance</h3><p>The shared oological characters between the Haţeg specimens and their mainland relatives suggest a highly conservative reproductive template, while the nest decrease in egg numbers per clutch may reflect an adaptive trait to a smaller body size due to the “island effect”. The combined presence of the lithostrotian egg and its embryo in the Early Cretaceous Gobi coupled with the oological similarities between the Haţeg and Auca Mahuevo oological material evidence that several titanosaur species migrated from Gondwana through the Haţeg Island before or during the Aptian/Albian. It also suggests that this island might have had episodic land bridges with the rest of the European archipelago and Asia deep into the Cretaceous.</p> </div

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described