The mRNA expression of hTERT in human breast carcinomas correlates with VEGF expression

Background Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase) is the rate-limiting determinant of telomerase reactivation. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any correlation between hTERT and the negative prognostic indicators VEGF and PCNA by quantitatively measuring the mRNA expression of these genes in human breast cancer and in adjacent non-cancerous tissue (ANCT). Materials and methods RNA was extracted from 38 breast carcinomas and 40 ANCT. hTERT and VEGF165, VEGF189 and PCNA mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology. Results The level of expression of VEGF-165 and PCNA was significantly higher in carcinoma tissue than ANCT (p = 0.02). The ratio of VEGF165/189 expression was significantly higher in breast carcinoma than ANCT (p = 0.025). hTERT mRNA expression correlated with VEGF-189 mRNA (p = 0.008) and VEGF165 (p = 0.07). Conclusions hTERT mRNA expression is associated with the expression of the VEGF189 and 165 isoforms. This could explain the poorer prognosis reported in breast tumours expressing high levels of hTERT. The relative expression of the VEGF isoforms is significantly different in breast tumour to ANCT, and this may be important in breast carcinogenesis

There is no correlation between c-Myc mRNA expression and telomerase activity in human breast cancer

Background Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. The hTERT (human telomerase reverse transcriptase) subunit seems to be the rate-limiting determinant of telomerase and knowledge of factors controlling hTERT transcription may be useful in therapeutic strategies. The hTERT promoter contains binding sites for c-Myc and there is experimental and in vitro evidence that c-Myc may increase hTERT expression. Materials and methods RNA was extracted from 18 breast carcinomas and c-Myc mRNA expression was estimated by quantitative reverse transcriptase-PCR (RT-PCR) with Taqman methodology. These tumours had already been analysed for ER and PgR status using ligand-binding assays and had had their DNA ploidy and S-phase fractions measured by flow cytometry. Telomerase activity had already been determined by using a modified telomeric repeat and amplification protocol (TRAP) assay. Results Telomerase activity ranged from 0 to 246 units of Total Protein Generated (TPG), where one unit of TPG was equal to 600 molecules of telomerase substrate primers extended by at least three telomeric repeats. Median levels of TPG were 60 and mean levels 81. There was no significant correlation between levels of c-Myc mRNA expression, telomerase activity, S phase fraction or PgR. There was a significant negative correlation with ER status. Conclusion Although the hTERT promoter contains potential binding sites for c-Myc oncoprotein, we have found no correlation between c-Myc mRNA levels and telomerase activity

Two conversational languages for control theoretical computations in the time sharing mode

Two conversational languages for control theory applications on direct-access time sharing compute

Passing crisis and emergency risk communications: the effects of communication channel, information type, and repetition.

Three experiments explore several factors which influence information transmission when warning messages are passed from person to person. In Experiment 1, messages were passed down chains of participants using five different modes of communication. Written communication channels resulted in more accurate message transmission than verbal. In addition, some elements of the message endured further down the chain than others. Experiment 2 largely replicated these effects and also demonstrated that simple repetition of a message eliminated differences between written and spoken communication. In a final field experiment, chains of participants passed information however they wanted to, with the proviso that half of the chains could not use telephones. Here, the lack of ability to use a telephone did not affect accuracy, but did slow down the speed of transmission from the recipient of the message to the last person in the chain. Implications of the findings for crisis and emergency risk communication are discussed

Is telomerase reactivation associated with the down-regulatoin of TGFβ receptor-II expression in human breast cancer?

Background Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in chromosomal stability and cellular immortalisation. Telomerase activity is detectable in most human cancers but not in normal somatic cells. TGF beta (transforming growth factor beta) is a member of a family of cytokines that are essential for cell survival and seems to be down-regulated in human cancer. Recent in vitro work using human breast cancer cell lines has suggested that TGF beta down-regulates the expression of hTERT (human telomerase reverse transcriptase) : the catalytic subunit of telomerase. We have therefore hypothesised that telomerase reactivation is associated with reduced immunohisto-chemical expression of TGF beta type II receptor (RII) in human breast cancer. Methods TGF beta RII immunohistochemical expression was determined in 24 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 7 telomerase-negative). Immunohistochemical expression of TGF beta RII was determined by a breast pathologist who was blinded to telomerase data. Results TGF beta RII was detected in all lesions. The percentage of stained cells ranged from 1–100%. The difference in TGF beta RII expression between telomerase positive and negative tumours was not statistically significant (p = 1.0). Conclusion The results of this pilot study suggest that there is no significant association between telomerase reactivation and TGF-beta RII down-regulation in human breast cancer

Policy Areas Impinging on Elderly Transportation Mobility: An Explanation with Ontario, Canada as Example

As countries face the challenges posed by rising numbers of older persons, the need to reassess their respective policies to address transport needs in aging societies is increasingly recognized in relation to health and sustainability goals. This paper proposes the examination of six interrelated policy areas affecting elderly mobility in a country or administrative region. A general survey of policy developments in each of these areas could improve current strategies and existing processes in the planning and implementation of mobility services that will be responsive to both elderly and the general population now and in the future. These include: 1) general transport policy framework; 2) travel mode preference; 3) alternative transport infrastructure stock and investments; 4) housing-land-use-transportation linkage; 5) research and technology applications that improve travel mode and environment; and 6) institutional and legal reforms. These policy areas are discussed and given concrete elucidation in the case of Ontario, Canada. Reflections and recommendations for further research and policy action deemed critical in the case region are highlighted.transportation, aging, regional policy, Canada

Evaluating the application of research-based guidance to the design of an emergency preparedness leaflet

UNLABELLED: Guidelines for the design of emergency communications were derived from primary research and interrogation of the literature. The guidelines were used to re-design a nuclear emergency preparedness leaflet routinely distributed to households in the local area. Pre-test measures of memory for, and self-reported understanding of, nuclear safety information were collected. The findings revealed high levels of non-receipt of the leaflet, and among those who did receive it, memory for safety advice was poor. Subjective evaluations of the trial leaflet suggested that it was preferred and judged easier to understand than the original. Objective measures of memory for the two leaflets were also recorded, once after the study period, and again one week or four weeks later. Memory for the advice was better, at all time periods, when participants studied the trial leaflet. The findings showcase evaluation of emergency preparedness literature and suggest that extant research findings can be applied to the design of communications to improve memory and understandability. STATEMENT OF RELEVANCE: Studies are described that showcase the use of research-based guidelines to design emergency communications and provide both subjective and objective data to support designing emergency communications in this way. In addition, the research evaluates the effectiveness of emergency preparedness leaflets that are routinely distributed to households. This work is of relevance to academics interested in risk communication and to practitioners involved in civil protection and emergency preparedness

Telemedicine: Bridging the Gap between Refugee Health and Health Services Accessibility in Hamilton, Ontario

Refugees face considerable challenges upon seeking asylum in Canada, and accessing health care services remains a prominent issue. Recurrent themes in the literature outlining barriers to health-services accessibility include geographic, economic, and cultural barriers. Drawing on the experiences of service providers in Hamilton, Ontario, we explored the efficacy of telemedicine services in bridging the gap between refugee health and health services accessibility. Research methodology included structured interviews with clinicians who provide health-care services to refugees, complemented by a scoping literature review. The results of this exploratory study demonstrate the efficacy of telemedicine in encouraging dialogue and policy change in the greater health-care setting, and its potential to increase access to specialist health-care services.Les réfugiés doivent faire face à des défis considérables lors du processus de demande d’asile au Canada, et l’accès aux services de santé demeure un enjeu important. Parmi les préoccupations qui reviennent fréquemment dans la documentation portant sur l’accessibilité aux services de santé sont les obstacles de nature géographique, économique, et culturelle. En nous basant sur l’expérience vécue des fournisseurs de service établis à Hamilton, en Ontario, nous étudions l’efficacité des services de télémédecine à combler l’écart entre les besoins en matière de santé des réfugiés et l’accessibilité aux services de santé. La méthodologiede recherche comportait des entrevues structurées avec le personnel traitant chargé de fournir des services de santé aux réfugiés, accompagnée d’une revue exploratoire de la documentation sur le sujet. Les résultats de cette étude exploratoire ont démontré l’efficacité de la télémédecine à stimuler le dialogue et le changement en matière de politique dans le contexte général des services de santé, ainsi que sa capacité à accroître l’accès aux services de santé spécialisés

hTERT protein expression is independent of clinicopathological parameters and c-Myc protein expression in human breast cancer

Background Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age. Methods Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression. Results The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients ≤ 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples. No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen. Conclusion The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (≤ 40 years) and this may have therapeutic implications in the context of hTR targeting strategies