45 research outputs found
Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study
Background
The association of fitness with cancer risk is not clear.
Methods
We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.
Results
After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min−1⋅kg−1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86–0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.
Discussion
Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention
An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk
It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for Cp
A review of FGF18: Its expression, signaling pathways and possible functions during embryogenesis and post-natal development
FGF18 is a novel growth factor first reported
in 1998. Current evidence suggests that FGF18 may play
a prominent role in chondrogenesis and osteogenesis
during skeletal development and growth. However, its
function extends to many other biological processes.
Although there remains much to be discovered and
investigated on the functions and mechanisms of FGF18,
it may play a role as a useful therapeutic target for
various applications. The following review summarizes
the current knowledge on FGF18 with special emphasis
on its skeletal functions and highlights its potential areas
for future research
Efficient in vitro delivery of Noggin siRNA enhances osteoblastogenesis
Several types of serious bone defects would not heal without invasive clinical intervention. One approach to such defects is to enhance the capacity of bone-formation cells. Exogenous bone morphogenetic proteins (BMP) have been utilized to positively regulate matrix mineralization and osteoblastogenesis, however, numerous adverse effects are associated with this approach. Noggin, a potent antagonist of BMPs, is an ideal candidate to target and decrease the need for supraphysiological doses of BMPs. In the current research we report a novel siRNA-mediated gene knock-down strategy to down-regulate Noggin. We utilized a lipid nanoparticle (LNP) delivery strategy in pre-osteoblastic rat cells. In vitro LNP-siRNA treatment caused inconsequential cell toxicity and transfection was achieved in over 85% of cells. Noggin siRNA treatment successfully down-regulated cellular Noggin protein levels and enhanced BMP signal activity which in turn resulted in significantly increased osteoblast differentiation and extracellular matrix mineralization evidenced by histological assessments. Gene expression analysis showed that targeting Noggin specifically in bone cells would not lead to a compensatory effect from other BMP negative regulators such as Gremlin and Chordin. The results from this study support the notion that novel therapeutics targeting Noggin have the clinically relevant potential to enhance bone formation without the need for toxic doses of exogenous BMPs. Such treatments will undeniably provide safe and economical treatments for individuals whose poor bone repair results in permanent morbidity and disability
An immunohistochemical analysis of the temporal and spatial expression of growth factors FGF 1, 2 and 18, IGF 1 and 2, and TGFß1 during distraction osteogenesis
Distraction osteogenesis (DO) is a well
established surgical technique that generates new bone
by gradual distraction of two bony segments. In this
study, we investigated the temporal and spatial profile of
FGF 1, 2 and 18, IGF 1 and 2, and TGFß1 during
distraction osteogenesis using immunohistochemistry.
An osteotomy was performed on the right tibia of 13
white male New Zealand rabbits. After a delay of 7 days,
distraction was started at a rate of 0.25mm/12hrs for 3
weeks which was followed by a 3 week period of
consolidation. Immunohistochemical analysis was
performed on a weekly interval to determine the
expression of the growth factors. Staining of all growth
factors was apparent at various levels in the centre and
callus region in fibroblasts and chondrocyte cells. FGF2
however, showed continued high expression in
osteoblasts. Within two weeks after the end of
distraction all growth factors showed a reduction in
expression except for FGF18 which maintained high
levels of expression (up to 100% staining) throughout
the distraction and consolidation phases. The study
suggests that in comparison to the other investigated
growth factors, FGF18 may play in important role
throughout the entire process of distraction osteogenesis