Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma

Background: Neuroblastoma (NB) tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Methods: Thirty-five NB tumours from patients diagnosed at < 18 months (25 stage 4 and 10 stage 4s), were evaluated by allelic and gene expression analyses. Results: All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36), 23% 11q and/or 14q LOH (27%) and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 < 12 months tumours revealed distinct gene expression profiles. A significant portion of genes mapped to chromosome 1 (P < 0.0001), 90% with higher expression in stage 4s, and chromosome 11 (P = 0.0054), 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 < 18m, yet, association with chromosomes 1 (P < 0.0001) and 11 (P = 0.005) was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 < 18 months without MYCN amplification. Conclusion: Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour

Breast tumour angiogenesis

The central importance of tumour neovascularization has been emphasized by clinical trials using antiangiogenic therapy in breast cancer. This review gives a background to breast tumour neovascularization in in situ and invasive breast cancer, outlines the mechanisms by which this is achieved and discusses the influence of the microenvironment, focusing on hypoxia. The regulation of angiogenesis and the antivascular agents that are used in an antiangiogenic dosing schedule, both novel and conventional, are also summarized

Rib biomechanical properties exhibit diagnostic potential for accurate ageing in forensic investigations

Age estimation remains one of the most challenging tasks in forensic practice when establishing a biological profile of unknown skeletonised remains. Morphological methods based on developmental markers of bones can provide accurate age estimates at a young age, but become highly unreliable for ages over 35 when all developmental markers disappear. This study explores the changes in the biomechanical properties of bone tissue and matrix, which continue to change with age even after skeletal maturity, and their potential value for age estimation. As a proof of concept we investigated the relationship of 28 variables at the macroscopic and microscopic level in rib autopsy samples from 24 individuals. Stepwise regression analysis produced a number of equations one of which with seven variables showed an R2=0.949; a mean residual error of 2.13 yrs ±0.4 (SD) and a maximum residual error value of 2.88 yrs. For forensic purposes, by using only bench top machines in tests which can be carried out within 36 hrs, a set of just 3 variables produced an equation with an R2=0.902 a mean residual error of 3.38 yrs ±2.6 (SD) and a maximum observed residual error 9.26yrs. This method outstrips all existing age-at-death methods based on ribs, thus providing a novel lab based accurate tool in the forensic investigation of human remains. The present application is optimised for fresh (uncompromised by taphonomic conditions) remains, but the potential of the principle and method is vast once the trends of the biomechanical variables are established for other environmental conditions and circumstances

A new approach to sex estimation using the mandibular canine index

Rao et al.’s mandibular canine index (MCI) is a simple odontometric method which uses the mandibular canine as the key to sex estimation. This index is defined as the ratio between the right canine mesiodistal dimension and the mandibular canine arch width. The aim of this study was to contribute to sex estimation using dental techniques by analysing the MCI efficiency, and to propose a new approach for its use. Measurements were taken from 120 plaster casts (70 females) in the 16–30 year age group. Although statistically significant sexual dimorphism was observed in both the mesiodistal dimension and the mandibular canine arch width, the MCI showed a low accuracy in sex classification (54.2% correct identifications). This accuracy was improved to 64.2% using receiver operating characteristics curve analysis. Yet, despite the better accuracy, these results reinforce the idea that the MCI may not be particularly useful in sex prediction, since it may not reflect the same degree of sexual dimorphism as its absolute measures

Sexual dimorphism in cranial morphology among modern South Africans

Pattern expressions of morphoscopic cranial traits vary across populations with classification accuracies being highly dependent on the reference collection to which unknown skulls are compared. Despite recent developments in populationspecific standards for South Africans, researchers have not addressed the accuracy of morphological methods. Several studies demonstrate differences in sexual dimorphism between South Africans and North Americans, warranting a need to re-evaluate sex estimation methods in South Africa. The purposes of this study were to test the reliability and accuracy of the Walker (2008) method and to examine patterns of sexual dimorphism among South Africans. A total of 245 modern Black and White South African male and female crania from the Pretoria Bone Collection, University of Pretoria, were scored using theWalker (2008) methodology. Cohen’s kappa was used to evaluate reliability of the method, and percent correct assessed validity of the method. Logistic regression was utilised to create modified population-specific formulae. Inter- and intra-observer agreement was moderate to excellent (0.60–0.90), except for the mental eminence (0.40). The percent correct results for sex were 80%or higher for combinations of glabella,mastoid andmenton and between 68 % and 73 % for menton, mastoid, orbital and nuchal margin using logistic equations of Walker (2008). White males had the highest (94–97 %) and White females had the lowest (31–62 %) percent correct. The low accuracies obtained when using Walker’s (2008) equations emphasised the need for population-specific sex estimation models. Modified formulae for South Africans were created, yielding higher classification rates (84–93 %) than when North American standards were employed.National Research Foundation (NRF)http://link.springer.com/journal/4142016-07-31hb201