1,222 research outputs found
A systems approach to clinical oncology: Focus on breast cancer
During the past decade, genomic microarrays have been applied with some success to the molecular profiling of breast tumours, which has resulted in a much more detailed classification scheme as well as in the identification of potential gene signature sets. These gene sets have been applied to both the prognosis and prediction of outcome to treatment and have performed better than the current clinical criteria. One of the main limitations of microarray analysis, however, is that frozen tumour samples are required for the assay. This imposes severe limitations on access to samples and precludes large scale validation studies from being conducted. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), on the other hand, can be used with degraded RNAs derived from formalin-fixed paraffin-embedded (FFPE) tumour samples, the most important and abundant source of clinical material available. More recently, the novel DASL (cDNA-mediated Annealing, Selection, extension and Ligation) assay has been developed as a high throughput gene expression profiling system specifically designed for use with FFPE tumour tissue samples. However, we do not believe that genomics is adequate as a sole prognostic and predictive platform in breast cancer. The key proteins driving oncogenesis, for example, can undergo post-translational modifications; moreover, if we are ever to move individualization of therapy into the practical world of blood-based assays, serum proteomics becomes critical. Proteomic platforms, including tissue micro-arrays (TMA) and protein chip arrays, in conjunction with surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS), have been the technologies most widely applied to the characterization of tumours and serum from breast cancer patients, with still limited but encouraging results. This review will focus on these genomic and proteomic platforms, with an emphasis placed on the utilization of FFPE tumour tissue samples and serum, as they have been applied to the study of breast cancer for the discovery of gene signatures and biomarkers for the early diagnosis, prognosis and prediction of treatment outcome. The ultimate goal is to be able to apply a systems biology approach to the information gleaned from the combination of these techniques in order to select the best treatment strategy, monitor its effectiveness and make changes as rapidly as possible where needed to achieve the optimal therapeutic results for the patient
Recommended from our members
The effect of cycling on cognitive function and well-being in older adults
It has been demonstrated that, on their own, both exercise and stimulation from the environment can improve cognitive function and well-being in older adults. The combined effect of exercising in the outdoor environment on psychological function is less well studied. The aim of the current study was to investigate the effect of an outdoor cycling intervention on cognitive function and mental health and well-being in older adults. A total of 100 older adults took part in the study (aged 50–83), 26 of which were non-cycling controls, 36 were conventional pedal cyclists and 38 were participants using an e-bike (a bike fitted with an electric motor to provide assistance with pedaling), as part of a larger project (www.cycleboom.org). Participants took part in the study for an eight-week period, with cycling participants required to cycle at least three times a week for thirty minutes in duration for each cycle ride. Cognitive function and well-being were measured before and after the intervention period. For executive function, namely inhibition (the Stroop task) and updating (Letter Updating Task), both cycling groups improved in accuracy after the intervention compared to non-cycling control participants. E-bike participants also improved in processing speed (reaction times in go trials of the Stop-It task) after the intervention compared to non-cycling control participants. Finally, e-bike participants improved in their mental health score after the intervention compared to non-cycling controls as measured by the SF-36. This suggests that there may be an impact of exercising in the environment on executive function and mental health. Importantly, we showed a similar (sometimes larger) effect for the e-bike group compared to the pedal cyclists. This suggests that it is not just the physical activity component of cycling that is having an influence. Both pedal cycles and e-bikes can enable increased physical activity and engagement with the outdoor environment with e-bikes potentially providing greater benefits
Wigner Representation Theory of the Poincare Group, Localization, Statistics and the S-Matrix
It has been known that the Wigner representation theory for positive energy
orbits permits a useful localization concept in terms of certain lattices of
real subspaces of the complex Hilbert -space. This ''modular localization'' is
not only useful in order to construct interaction-free nets of local algebras
without using non-unique ''free field coordinates'', but also permits the study
of properties of localization and braid-group statistics in low-dimensional
QFT. It also sheds some light on the string-like localization properties of the
1939 Wigner's ''continuous spin'' representations.We formulate a constructive
nonperturbative program to introduce interactions into such an approach based
on the Tomita-Takesaki modular theory. The new aspect is the deep relation of
the latter with the scattering operator.Comment: 28 pages of LateX, removal of misprints and extension of the last
section. more misprints correcte
Patellar cartilage volume of the back leg versus the higher loaded front leg in current elite male english cricket fast bowlers
Patellar cartilage volume of the back leg versus the higher loaded front leg in current elite male english cricket fast bowler
Recommended from our members
'You can go out 14 miles away with the knowledge that you’ve got the battery to help you back if you need it!': Narratives of ranging behaviour and wellbeing in diaries of e-bike trial participants.
This paper draws on data from a large UK study that aimed to understand cycling among the older population and how this affected independence, health and wellbeing. Part of the study involved an ‘e-bike trial’ where participants aged 50 and over, who were returning to cycling after a hiatus, were loaned an e-bike for an eight-week trial period. Pre-trial and post-trial cognitive tests of trial participants, reported previously Leyland et al. (2019), demonstrated how e-bikes, provide positive benefits to cognitive function and wellbeing. The paper builds on these findings, drawing specifically on the qualitative component, predominantly biographical interviews, written and visual material provided in rider diaries and a focus group discussion, to understand the reasons for this positive impact.
The findings demonstrate how power assistance can provide riders with the opportunity to extend the distance and types of area they are willing to cycle from their homes (their ‘ranging behaviour’) and how this can promote health and wellbeing. Our evidence suggests that e-bikes have the potential to support cycling for leisure as well as everyday travel and that consideration should be given to the positive effects of e-cycling on mental wellbeing in addition to physical activity. This is particularly pertinent in the context of an ageing society, the push towards zero-emission cities and the need to ensure socially inclusive mobility, particularly in the context of the Covid-19 global pandemic
Independent Validation of EarlyR Gene Signature in BIG 1-98: A Randomized, Double-Blind, Phase III Trial Comparing Letrozole and Tamoxifen as Adjuvant Endocrine Therapy for Postmenopausal Women with Hormone Receptor-Positive, Early Breast Cancer
Background
EarlyR gene signature in estrogen receptor–positive (ER+) breast cancer is computed from the expression values of ESPL1, SPAG5, MKI67, PLK1, and PGR. EarlyR has been validated in multiple cohorts profiled using microarrays. This study sought to verify the prognostic features of EarlyR in a case-cohort sample from BIG 1–98, a randomized clinical trial of ER+ postmenopausal breast cancer patients treated with adjuvant endocrine therapy (letrozole or tamoxifen).
Methods
Expression of EarlyR gene signature was estimated by Illumina cDNA-mediated Annealing, Selection, and Ligation assay of RNA from formalin-fixed, paraffin-embedded primary breast cancer tissues in a case-cohort subset of ER+ women (N = 1174; 216 cases of recurrence within 8 years) from BIG 1–98. EarlyR score and prespecified risk strata (≤25 = low, 26–75 = intermediate, >75 = high) were “blindly” computed. Analysis endpoints included distant recurrence–free interval and breast cancer–free interval at 8 years after randomization. Hazard ratios (HRs) and test statistics were estimated with weighted analysis methods.
Results
The distribution of the EarlyR risk groups was 67% low, 19% intermediate, and 14% high risk in this ER+ cohort. EarlyR was prognostic for distant recurrence–free interval; EarlyR high-risk patients had statistically increased risk of distant recurrence within 8 years (HR = 1.73, 95% confidence interval = 1.14 to 2.64) compared with EarlyR low-risk patients. EarlyR was also prognostic of breast cancer–free interval (HR = 1.74, 95% confidence interval = 1.21 to 2.62).
Conclusions
This study confirmed the prognostic significance of EarlyR using RNA from formalin-fixed, paraffin-embedded tissues from a case-cohort sample of BIG 1–98. EarlyR identifies a set of high-risk patients with relatively poor prognosis who may be considered for additional treatment. Further studies will focus on analyzing the predictive value of EarlyR signature
Variation in RNA expression and genomic DNA content acquired during cell culture
Specific chromosomal abnormalities are increasingly recognised to be associated with particular tumour subtypes. These cytogenetic abnormalities define the sites of specific genes, the alteration of which is implicated in the neoplastic process. We used comparative genomic hybridisation (CGH) to examine DNA from different breast and ovarian cancer cell lines for variations in DNA sequence copy number compared with the same normal control. We also compared different sources of the MCF7 breast line by both CGH and cDNA expression arrays. Some of the differences between the subcultures were extensive and involved large regions of the chromosome. Differences between the four subcultures were observed for gains of 2q, 5p, 5q, 6q, 7p, 7q, 9q, 10p, 11q, 13q, 14c, 16q, 18p and 20p, and losses of 4q, 5p, 5q, 6q, 7q, 8p, 11p, 11q, 12q, 13q, 15q, 19p, 19q, 20p, 21q, 22q and Xp. However, few variations were found between two subcultures examined, 5 months apart, from the same initial source. The RNA arrays also demonstrated considerable variation between the three different subcultures, with only 43% of genes expressed at the same levels in all three. Moreover, the patterns of the expressed genes did not always reflect our observed CGH aberrations. These results demonstrate extensive genomic instability and variation in RNA expression during subculture and provide supportive data for evidence that cell lines do evolve in culture, thereby weakening the direct relevance of such cultures as models of human cancer. This work also reinforces the concern that comparisons of published analyses of cultures of the same name may be dangerous
- …