We present a mathematical formulation to evaluate the effects of gestational mutations on cancer risk. The hazard or incidence function of cancer is expressed in terms of the Probability Generating Function (PGF) of the number of normal and mutated cells at birth. Using Filtered Poisson Process Theory, we obtain the PGF for several models for the accumulation of gestational mutations. In particular, we develop expressions for the hazard function when one or two successive mutations could occur during gestation. We also calculate the hazard when the background gestational mutation rates are increased due to exposure to mutagens, such as prenatal radiation. To illustrate the use of our models, we apply them to colorectal cancer in the SEER database. We find that the proportion of cancer risk attributable to developmental mutations depends on age and that it could be quite significant when gestational mutation rates are high. The analysis of the SEER data also shows that gestational mutations could contribute to inter-individual variations in colorectal cancer risk. 相似文献
The genetic background and the antigenic landscape of cancer cells play a critical role in the response to immunotherapies. A high tumor antigenicity, together with an increased adjuvanticity potentially induced by a peculiar type of cell death, namely immunogenic cell death (ICD), could foster the response to immunogenic therapies. The gestational trophoblastic neoplasm (GTN) is a one-of-a-kind cancer in the oncological landscape due to its exclusive genomic makeup. The prognosis of GTN is significantly better than non-gestational trophoblastic neoplasm (nGTN). Due to its peculiar genetic inheritance, GTN potentially constitutes a singular archetype in the immuno-oncological field. 相似文献
Although vanadium is found abundantly in animal and plant kingdoms its biological effects are not clear. Vanadate compounds have been shown to normalize blood glucose levels in streptozotocin treated rats, enhance glucose oxidation and improve the sensitivity to insulin by enhanced receptor binding in rat adipocytes. The aim of the present study was to investigate the effect of vanadate, at high (0–8 mmol l?1) and low (0–1·0 mmol l?1) physiological concentrations, on [125I]-insulin binding in the placenta of three groups of pateints, namely from normal (N) controls, gestational diabetics (GDM) and women with risk factors in their medical history for developing diabetes mellitus (RF). Vanadate at low concentrations (0·2–0·6 mmol l?1) enhanced the maximal binding 2-fold in GDM placenta but only increased (up to 1·2-fold) the binding slightly at high cncentrations (5 mmol l?1). However with placenta from normal or women at risk, vanadate increased the [125I]-insulin binding up to 1·2-fold both at low and high concentrations. Thus it appears that vanadate augements insulin binding in the placenta from women with gestational diabetes mellitus. 相似文献
BackgroundResults of the studies about association between serum selenium concentration and gestational hyperglycemia are inconsistent. Some studies have demonstrated that women with gestational diabetes mellitus (GDM) have lower Se concentrations while contrary results are reported in other studies.AimThe aim of this study is to compare the serum Se concentration in women with GDM and normoglycemic pregnant women via a systematic review and meta-analysis.MethodsA computerized literature search on four databases (PubMed, Cochrane register of control trials, Scopus and Google scholar) was performed from inception through August 2013. Necessary data were extracted and random effects model was used to conduct the meta-analysis.ResultsSix observational studies (containing 147 women with GDM and 360 normoglycemic pregnant women) were found, which had compared serum Se concentration in women suffering from GDM with normal pregnant ones. Our meta-analysis revealed that serum Se concentration was lower in women with GDM compared to normoglycemic pregnant women (Hedges = −1.34; 95% CI: −2.33 to −0.36; P < 0.01). Stratified meta-analysis demonstrated that concentration of Se in the sera of women with GDM was lower than normal pregnant women both in second and third trimesters, but the result was not significant in second trimester (second trimester: Hedges = −0.68; 95% CI: −1.60−0.25; P = 0.15, third trimester: Hedges = −2.81; 95% CI: −5.21 to −0.42; P < 0.05). It was also demonstrated that serum Se status was lower in pregnant women with impaired glucose tolerance (IGT) compared to normoglycemic pregnant women (Hedges = −0.85; 95% CI: −1.18 to −0.52).ConclusionThe available evidences suggest that serum Se concentration is significantly lower in pregnant women with gestational hyperglycemia compared to normal pregnant women. 相似文献
Background: There is paucity of information on mechanisms constituting adverse birth outcomes. We assessed here the relationship between vascular integrity and adverse birth effects.Methods and results: Third trimester maternal plasma (n?=?144) from the Maternal-Infant Research on Environmental Chemicals Study (MIREC) was analysed for vascular, inflammatory and oxidative stress markers by HPLC-fluorescence, protein array and EIA method. Analysis of the <25th and >75th percentile birth weight subgroups revealed markers associated with birth weight (ETs, MMP-9, VEGF, and 8-isoPGF-2α) and gestational age (ET-1, MMP-2, and VEGF).Conclusions: Mechanistic insights into adverse birth outcome pathways can be achieved by integrating information on multiple biomarkers, physiology using systems biology approach. 相似文献