Impact of Tumour Epithelial Subtype on Circulating MicroRNAs in Breast Cancer Patients

While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45). Three miRNAs of interest were then quantified in the circulation(n = 166) and tissue (n = 100) of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes .2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of miRNAs, and highlights divergent miRNA profiles between tissue and blood samples from breast cancer patients

Automatisierte Planung von digitalen Hochgeschwindigkeitsnetzen

Der Ausbau von digitalen Hochgeschwindigkeitsnetzen ist gekennzeichnet durch neuartige Anforderungen an den Planungsprozess. Diese Anforderungen erfordern wiederum den Einsatz von neuartigen Paradigmen, die eine effiziente und zugleich genaue Planung von flächendeckenden Glasfasernetzen ermöglichen. Hierbei können wiederkehrende Planungsaufgaben durch eine gezielte computergestützte Automatisierung effizienter und genauer ausgeführt, als es mit bisherigen Planungskonzepten möglich ist. Dieses Arbeitspapier beschreibt die computergestützte Ausführung eines Planungsprozesses auf Basis von fünf grundlegenden, iterativen Planungsschritten und gibt Empfehlungen für eine effiziente und genaue Planung von Glasfasernetzen. Der hier vorgestellte Ansatz ermöglicht es Netzbetreibern und Investoren, den Ausbau beliebiger Siedlungs- und Gewerbegebiete auf der zuverlässigen Basis von belastbarem Faktenwissen wirtschaftlich zu priorisieren

The acquisition and retention of urinary catheterisation skills using surgical simulator devices: teaching method or student traits

Background: The acquisition of procedural skills is an essential component of learning for medical trainees. The objective of this study was to assess which teaching method of performing urinary catheterisation is associated with most efficient procedural skill acquisition and retention. We evaluated factors affecting acquisition and retention of skills when using simulators as adjuncts to medical training. Methods: Forty-two second year medical students were taught urinary catheter insertion using different teaching methods. The interactive group (n = 19) were taught using a lecture format presentation and a high fidelity human urinary catheter simulator. They were provided with the use of simulators prior to examination. The observer group (n = 12) were taught using the same method but without with simulator use prior to examination. The didactic group (n = 11) were taught using the presentation alone. Student characteristics such as hand dexterity and IQ were measured to assess for intrinsic differences. All students were examined at four weeks to measure skill retention. Results: Catheter scores were significantly higher in the interactive group (p < 0.005). Confidence scores with catheter insertion were similar at index exam however were significantly lower in the didactic group at the retention testing (p < 0.05). Retention scores were higher in the interactive group (p < 0.001). A significant positive correlation was observed between laparoscopy scores and time to completion with overall catheter score (p < 0.05). Teaching method, spatial awareness and time to completion of laparoscopy were significantly associated with higher catheter scores at index exam (p = 0.001). Retention scores at 4 weeks were significantly associated with teaching method and original catheter score (p = 0.001). Conclusion: The importance of simulators in teaching a complex procedural skill has been highlighted. Didactic teaching method was associated with a significantly higher rate of learning decay at retention testing

The acquisition and retention of urinary catheterisation skills using surgical simulator devices: teaching method or student traits

Background: The acquisition of procedural skills is an essential component of learning for medical trainees. The objective of this study was to assess which teaching method of performing urinary catheterisation is associated with most efficient procedural skill acquisition and retention. We evaluated factors affecting acquisition and retention of skills when using simulators as adjuncts to medical training. Methods: Forty-two second year medical students were taught urinary catheter insertion using different teaching methods. The interactive group (n = 19) were taught using a lecture format presentation and a high fidelity human urinary catheter simulator. They were provided with the use of simulators prior to examination. The observer group (n = 12) were taught using the same method but without with simulator use prior to examination. The didactic group (n = 11) were taught using the presentation alone. Student characteristics such as hand dexterity and IQ were measured to assess for intrinsic differences. All students were examined at four weeks to measure skill retention. Results: Catheter scores were significantly higher in the interactive group (p < 0.005). Confidence scores with catheter insertion were similar at index exam however were significantly lower in the didactic group at the retention testing (p < 0.05). Retention scores were higher in the interactive group (p < 0.001). A significant positive correlation was observed between laparoscopy scores and time to completion with overall catheter score (p < 0.05). Teaching method, spatial awareness and time to completion of laparoscopy were significantly associated with higher catheter scores at index exam (p = 0.001). Retention scores at 4 weeks were significantly associated with teaching method and original catheter score (p = 0.001). Conclusion: The importance of simulators in teaching a complex procedural skill has been highlighted. Didactic teaching method was associated with a significantly higher rate of learning decay at retention testing

Relationship between circulating and tissue micrornas in a murine model of breast cancer

MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n = 60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. MicroRNAs were extracted from all samples (n = 98) and relative expression quantified using RQ-PCR. MiR-221 expression was significantly increased in tumour compared to healthy tissue (p<0.001). MiR-10b expression was significantly higher in MFP compared to SC tumours (p<0.05), with the highest levels detected in diseased lymph nodes (p<0.05). MiR-10b was undetectable in the circulation, with no significant change in circulating miR-221 expression detected during disease progression. MiR-195 and miR-497 were significantly decreased in tumour tissue (p<0.05), and also in the circulation of animals 3 weeks following tumour induction (p<0.05). At both tissue and circulating level, a positive correlation was observed between miR-497 and miR-195 (r = 0.61, p<0.001; r = 0.41, p<0.01 respectively). This study highlights the distinct roles of miRNAs in circulation and tissue. It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development

Relationship between circulating and tissue microRNAs in a murine model of breast cancer.

MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n = 60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. MicroRNAs were extracted from all samples (n = 98) and relative expression quantified using RQ-PCR. MiR-221 expression was significantly increased in tumour compared to healthy tissue (p,0.001). MiR-10b expression was significantly higher in MFP compared to SC tumours (p,0.05), with the highest levels detected in diseased lymph nodes (p,0.05). MiR-10b was undetectable in the circulation, with no significant change in circulating miR-221 expression detected during disease progression. MiR-195 and miR-497 were significantly decreased in tumour tissue (p,0.05), and also in the circulation of animals 3 weeks following tumour induction (p,0.05). At both tissue and circulating level, a positive correlation was observed between miR-497 and miR-195 (r = 0.61, p,0.001; r = 0.41, p,0.01 respectively). This study highlights the distinct roles of miRNAs in circulation and tissue. It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development.peer-reviewe

Relationship between circulating and tissue microRNAs in a murine model of breast cancer.

MiRNAs are key regulators of tumorigenesis that are aberrantly expressed in the circulation and tissue of patients with cancer. The aim of this study was to determine whether miRNA dysregulation in the circulation reflected similar changes in tumour tissue. Athymic nude mice (n = 20) received either a mammary fat pad (n = 8, MFP), or subcutaneous (n = 7, SC) injection of MDA-MB-231 cells. Controls received no tumour cells (n = 5). Tumour volume was monitored weekly and blood sampling performed at weeks 1, 3 and 6 following tumour induction (total n = 60). Animals were sacrificed at week 6 and tumour tissue (n = 15), lungs (n = 20) and enlarged lymph nodes (n = 3) harvested. MicroRNAs were extracted from all samples (n = 98) and relative expression quantified using RQ-PCR. MiR-221 expression was significantly increased in tumour compared to healthy tissue (p,0.001). MiR-10b expression was significantly higher in MFP compared to SC tumours (p,0.05), with the highest levels detected in diseased lymph nodes (p,0.05). MiR-10b was undetectable in the circulation, with no significant change in circulating miR-221 expression detected during disease progression. MiR-195 and miR-497 were significantly decreased in tumour tissue (p,0.05), and also in the circulation of animals 3 weeks following tumour induction (p,0.05). At both tissue and circulating level, a positive correlation was observed between miR-497 and miR-195 (r = 0.61, p,0.001; r = 0.41, p,0.01 respectively). This study highlights the distinct roles of miRNAs in circulation and tissue. It also implicates miRNAs in disease dissemination and progression, which may be important in systemic therapy and biomarker development