ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC.POCI/CVT/62940/2004 and by the PhD grants (SFRH/BD/23406/2005 and SFRH/BD/31754/2006, of the Science and Technology Foundation (FCT) from Portugal

Use of ‘Habit’ is not a habit in understanding individual technology adoption: A review of UTAUT2 based empirical studies

yes‘Habit’ was the most important theoretical addition into UTAUT2 to challenge the role of behavioural intention as a lone predictor of technology use. However, systematic review and meta-analysis of Price value the other UTAUT2 additional construct revealed major inconsistency of the model with just 41% UTAUT2 based studies including the construct in their research. Thus, the aim of this research is to understand the appropriateness of ‘habit’ construct usage among UTAUT2 based empirical studies and their reason for omission or inclusion. The findings from 66 empirical studies revealed only 23 studies a meagre (35%) utilised ‘habit’ construct and the remaining massive 43 studies (65%) excluded the construct from their research model. The major reason for studies not including “habit” construct was they were examining users of new technology at early stage of adoption where sufficient time hasn’t elapsed for users to form habit. Moreover this study caution the use of experience as an alternative for habit. Since experience can be gained under mandatory settings which is not sufficient enough to form habit that occurs more naturally under voluntary settings. This study also provided number of recommendations for theory and practice based on the findings

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Epigenetic modulators as therapeutic targets in prostate cancer

Prostate cancer is one of the most common non-cutaneous malignancies among men worldwide. Epigenetic aberrations, including changes in DNA methylation patterns and/or histone modifications, are key drivers of prostate carcinogenesis. These epigenetic defects might be due to deregulated function and/or expression of the epigenetic machinery, affecting the expression of several important genes. Remarkably, epigenetic modifications are reversible and numerous compounds that target the epigenetic enzymes and regulatory proteins were reported to be effective in cancer growth control. In fact, some of these drugs are already being tested in clinical trials. This review discusses the most important epigenetic alterations in prostate cancer, highlighting the role of epigenetic modulating compounds in pre-clinical and clinical trials as potential therapeutic agents for prostate cancer management.info:eu-repo/semantics/publishedVersio

Prognostic significance of GRP78 expression patterns in breast cancer patients receiving adjuvant chemotherapy

This study examined the associations between GRP78 expression and breast cancer recurrence and survival in patients treated with anthracyclines in the adjuvant setting. GRP78 expression was assessed in 106 stage II/III breast cancer patients. Tissue microarray was used to perform immunohistochemistry and to determine the GRP78 expression in endoplasmic reticulum and cell membrane of breast tumors. Four distinct scenarios (low and high thresholds) were developed. For high thresholds, 16% and 40% of our cases were GRP78-positive for endoplasmic reticulum and cell membrane, respectively. For low thresholds, 74% and 87% of our cases were GRP78-positive for endoplasmic reticulum and cell membrane, respectively. In the endoplasmic reticulum high-threshold scenario, GRP78 positive was found to be significantly frequent in T3 tumors (p = 0.02), and inversely related to ERBB2 overexpression (p = 0.03). There was a lower proportion of GRP78-positive cases among women between 50 and 65 years of age (p = 0.02). In the endoplasmic reticulum low-threshold scenario, the proportion of GRP78-positive cases was significantly higher in women younger than 50 years and in those who were premenopausal (p = 0.04). No statistically significant difference was found in survival probabilities among the scenarios examined. In our cohort, GRP78 overexpression was not a predictor of overall or disease-free survival of patients receiving anthracycline-based adjuvant chemotherapy.26318819