Maternal autoimmune disease is not associated with cancer in the offspring

Aim Autoimmune disease and its medication are associated with increased cancer risk in adults, but it is unknown whether maternal autoimmune disease and/or medication use in pregnancy are associated with increased cancer risk in offspring. Methods In this case-control study, we identified all patients under 20 years of age with their first cancer diagnosis in 1996-2014 from the Finnish Cancer Registry (n = 2029) and 1:5 population-based controls (n = 10,103) from the Medical Birth Register. We obtained information on maternal autoimmune disease and its medication from the relevant Finnish registries and used conditional logistic regression to analyse the risk of offspring cancer after maternal autoimmune disease exposure. Results The odds ratio (OR) for cancer in offspring following maternal autoimmune exposure was 0.76 (95% confidence interval [CI] 0.47-1.23). Individual ORs for inflammatory bowel and connective tissue diseases were 1.08 (95% CI 0.56-2.01) and 0.50 (95% CI 0.23-1.08), respectively. The OR for maternal autoimmune medication was 0.95 (95% CI 0.80-1.14) overall and similar by drug subtype. There was an increased risk with medication in late pregnancy but the ORs were unstable owing to small numbers. Conclusion Our study does not support an increased cancer risk among offspring of women with autoimmune disease or its medication during pregnancy.Peer reviewe

Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha‐tocolpherol, beta‐carotene cancer prevention (ATBC) study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113106/1/ijc29576.pd

Prospective serum metabolomic profiling of lethal prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152026/1/ijc32218.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152026/2/ijc32218_am.pd

Individual variations in serum melatonin levels through time: Implications for epidemiologic studies

Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p = 0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding

Serum Metabolomic Response to Long-Term Supplementation with all-rac

Background. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however. Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac-α-tocopheryl acetate (ATA), 20 mg/day β-carotene, both, placebo). Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.). Results. After correction for multiple comparisons, five metabolites were statistically significantly altered (β is the change in metabolite level expressed as number of standard deviations on the log scale): α-CEHC sulfate (β=1.51, p=1.45×10-38), α-CEHC glucuronide (β=1.41, p=1.02×10-31), α-tocopherol (β=0.97, p=2.22×10-13), γ-tocopherol (β=-0.90, p=1.76×10-11), and β-tocopherol (β=-0.73, p=9.40×10-8). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation (β range 0.40 to −0.36), but not statistically significantly. Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC)

Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however. Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac--tocopheryl acetate (ATA), 20 mg/day -carotene, both, placebo). Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.). Results. After correction for multiple comparisons, five metabolites were statistically significantly altered ( is the change in metabolite level expressed as number of standard deviations on the log scale): -CEHC sulfate ( = 1.51, = 1.45 × 10 −38 ), -CEHC glucuronide ( = 1.41, = 1.02 × 10 −31 ), -tocopherol ( = 0.97, = 2.22 × 10 −13 ), -tocopherol ( = −0.90, = 1.76 × 10 −11 ), and -tocopherol ( = −0.73, = 9.40 × 10 −8 ). Glutarylcarnitine, betaalanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation ( range 0.40 to −0.36), but not statistically significantly. Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings

Ring-Closing Metathesis of Olefinic Peptides: Design, Synthesis, and Structural Characterization of Macrocyclic Helical Peptides

Heptapeptides containing residues with terminal olefin-derivatized side chains (3 and 4) have been treated with ruthenium alkylidene 1 and undergone facile ring-closing olefin metathesis (RCM) to give 21- and 23-membered macrocyclic peptides (5 and 6). The primary structures of peptides 3 and 4 were based upon a previously studied heptapeptide (2), which was shown to adopt a predominantly 3_(10)-helical conformation in CDCl_3 solution and an α-helical conformation in the solid state. Circular dichroism, IR, and solution-phase ^1H NMR studies strongly suggested that acyclic precursors 3 and 4 and the fully saturated macrocyclic products 7 and 8 also adopted helical conformations in apolar organic solvents. Single-crystal X-ray diffraction of cyclic peptide 8 showed it to exist as a right-handed 3_(10)-helix up to the fifth residue. Solution-phase NMR structures of both acyclic peptide 4 and cyclic peptide 8 in CD_2Cl_2 indicated that the acyclic diene assumes a loosely 3_(10)-helical conformation, which is considerably rigidified upon macrocyclization. The relative ease of introducing carbon−carbon bonds into peptide secondary structures by RCM and the predicted metabolic stability of these bonds renders olefin metathesis an exceptional methodology for the synthesis of rigidified peptide architectures

New Horned Dinosaurs from Utah Provide Evidence for Intracontinental Dinosaur Endemism

Background:\ud During much of the Late Cretaceous, a shallow, epeiric sea divided North America into eastern and western landmasses. The western landmass, known as Laramidia, although diminutive in size, witnessed a major evolutionary radiation of dinosaurs. Other than hadrosaurs (duck-billed dinosaurs), the most common dinosaurs were ceratopsids (large-bodied horned dinosaurs), currently known only from Laramidia and Asia. Remarkably, previous studies have postulated the occurrence of latitudinally arrayed dinosaur “provinces,” or “biomes,” on Laramidia. Yet this hypothesis has been challenged on multiple fronts and has remained poorly tested.\ud \ud Methodology/Principal Findings:\ud Here we describe two new, co-occurring ceratopsids from the Upper Cretaceous Kaiparowits Formation of Utah that provide the strongest support to date for the dinosaur provincialism hypothesis. Both pertain to the clade of ceratopsids known as Chasmosaurinae, dramatically increasing representation of this group from the southern portion of the Western Interior Basin of North America. Utahceratops gettyi gen. et sp. nov.—characterized by short, rounded, laterally projecting supraorbital horncores and an elongate frill with a deep median embayment—is recovered as the sister taxon to Pentaceratops sternbergii from the late Campanian of New Mexico. Kosmoceratops richardsoni gen. et sp. nov.—characterized by elongate, laterally projecting supraorbital horncores and a short, broad frill adorned with ten well developed hooks—has the most ornate skull of any known dinosaur and is closely allied to Chasmosaurus irvinensis from the late Campanian of Alberta.\ud \ud Conclusions/Significance:\ud Considered in unison, the phylogenetic, stratigraphic, and biogeographic evidence documents distinct, co-occurring chasmosaurine taxa north and south on the diminutive landmass of Laramidia. The famous Triceratops and all other, more nested chasmosaurines are postulated as descendants of forms previously restricted to the southern portion of Laramidia. Results further suggest the presence of latitudinally arrayed evolutionary centers of endemism within chasmosaurine ceratopsids during the late Campanian, the first documented occurrence of intracontinental endemism within dinosaurs