Three- dimensional assessment of craniofacial asymmetry in children with transverse maxillary deficiency after rapid maxillary expansion: A prospective study

ObjectiveThe aim of this study was to evaluate craniofacial asymmetry in children with transverse maxillary deficiency, with or without functional unilateral posterior crossbite (UPC), before and after rapid maxillary expansion (RME).Setting and sample populationA sample of 51 children with cone beam computed tomography scans obtained before RME (T1) and a year after RME (T2).Material and methodsThis prospective study consisted of 2 groups: 25 children with functional UPC (6.77 ± 1.5 years) and 26 children without UPC (7.41 ± 1.31 years). Linear and angular measurements were obtained from zygomatic, maxilla, glenoid fossa and mandible, using original and mirrored 3D overlapped models. All right and left side comparisons in both groups and intergroups asymmetries were compared using MANOVA and t test for independent samples, respectively, statistically significant at P < .05.ResultsThe UPC group showed no side differences, but mandibular horizontal rotation at T1, and this asymmetry was improved in T2. The non- UPC group showed at baseline significant lateral asymmetry in orbitale, position of palatine foramen, respectively, in average 2.95 mm and 1.16 mm, and 0.49 mm of average asymmetry in condylar height. The glenoid fossa was symmetric in both groups at T1 and T2.ConclusionsChildren with transverse maxillary deficiency showed slight morphological asymmetry, located in the mandible position in cases of UPC, and in the orbital and maxillary regions in cases without UPC. One year after RME, patients improved their craniofacial asymmetry, with significant changes in the mandible and correction of the mandibular rotation in patients who presented UPC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156195/2/ocr12370_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156195/1/ocr12370.pd

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

High connectivity of the Crocodile Shark between the Atlantic and Southwest Indian Oceans: highlights for conservation

Among the various shark species that are captured as bycatch in commercial fishing operations, the group of pelagic sharks is still one of the least studied and known. Within those, the crocodile shark, Pseudocarcharias kamoharai, a small-sized lamnid shark, is occasionally caught by longline vessels in certain regions of the tropical oceans worldwide. However, the population dynamics of this species, as well as the impact of fishing mortality on its stocks, are still unknown, with the crocodile shark currently one of the least studied of all pelagic sharks. Given this, the present study aimed to assess the population structure of P. kamoharai in several regions of the Atlantic and Indian Oceans using genetic molecular markers. The nucleotide composition of the mitochondrial DNA control region of 255 individuals was analyzed, and 31 haplotypes were found, with an estimated diversity Hd = 0.627, and a nucleotide diversity pi = 0.00167. An analysis of molecular variance (AMOVA) revealed a fixation index phi(ST) = -0.01118, representing an absence of population structure among the sampled regions of the Atlantic Ocean, and between the Atlantic and Indian Oceans. These results show a high degree of gene flow between the studied areas, with a single genetic stock and reduced population variability. In panmictic populations, conservation efforts can be concentrated in more restricted areas, being these representative of the total biodiversity of the species. When necessary, this strategy could be applied to the genetic maintenance of P. kamoharai.Foundation for Research Support of the Sao Paulo State - FAPESP [2011/23787-0, 2010/51903-2]; Portuguese Foundation for Science and Technology (FCT) [SFRH/BPD/93936/2013]; Foundation for Research Support of the Sao Paulo State - FAPESP [2011/23787-0, 2010/51903-2]; Portuguese Foundation for Science and Technology (FCT) [SFRH/BPD/93936/2013]info:eu-repo/semantics/publishedVersio

In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

<p>Abstract</p> <p>Background</p> <p>New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear whether <it>in situ </it>carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved in the synthesis of aromatase, has been suggested as a surrogate marker for aromatase expression.</p> <p>Methods</p> <p>Primary tumor material was retrospectively collected from 88 patients who participated in a randomized clinical trial comparing the AI letrozole to the anti-estrogen tamoxifen for first-line treatment of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate Wilcoxon analysis and the Cox-analysis were performed to evaluate time to progression (TTP) in relation to marker expression.</p> <p>Results</p> <p>Aromatase expression was associated with ER, but not with PR or COX-2 expression in carcinoma cells. Measurements of aromatase in WS were not comparable to results from TMAs. Expression of COX-2 and aromatase did not predict response to endocrine therapy. Aromatase in combination with high PR expression may select letrozole treated patients with a longer TTP.</p> <p>Conclusion</p> <p>TMAs are not suitable for IHC analysis of <it>in situ </it>aromatase expression and we did not find COX-2 expression in carcinoma cells to be a surrogate marker for aromatase. <it>In situ </it>aromatase expression in tumor cells is associated with ER expression and may thus point towards good prognosis. Aromatase expression in cancer cells is not predictive of response to endocrine therapy, indicating that <it>in situ </it>estrogen synthesis may not be the major source of intratumoral estrogen. However, aromatase expression in combination with high PR expression may select letrozole treated patients with longer TTP.</p> <p>Trial registration</p> <p>Sub-study of trial P025 for advanced breast cancer.</p