Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients

Purpose: Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer. Methods: Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients. Results: Univariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67–28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = − 0.75 and − 0.76, respectively, p = 0.02 for both). Conclusions: Higher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients

Receipt of NCCN Guideline-Concordant Prostate Cancer Care among African- and Caucasian-American Men in North Carolina

African Americans have a higher incidence of prostate cancer and experience poorer outcomes compared to Caucasian Americans. Racial differences in care are well documented. However, few studies have characterized patients based on their prostate cancer risk category, which is required to differentiate appropriate from inappropriate guideline application

Patient Satisfaction Influenced by Interpersonal Treatment and Communication for African American Men: The North Carolina–Louisiana Prostate Cancer Project (PCaP)

Prostate cancer is the second leading cause of mortality in all men, and African American men (AAM) and Jamaican men of African descent have the highest prostate cancer incidence rates in the world (American Cancer Society, 2011). Over the past 25 years, the 5-year survival rate for prostate cancer has increased for both AAM and Caucasian men to nearly 100% when diagnosed and treated in the early stages (American Cancer Society, 2011). This improved survival rate has been attributed to early diagnosis and improved treatments; however, more AAM are diagnosed in late stages (metastatic disease) than Caucasian men where treatment options are less effective and outcomes are poorer, with only a 29% 5-year survival rate (American Cancer Society, 2011)

Ambient Seismic Noise Image of the Structurally Controlled Heat and Fluid Feeder Pathway at Campi Flegrei Caldera

The TIDES-COST Action (STSM-ES1401-34011) provided a travel grant to framework the research project. The Japan Society for the Promotion of Science - Short-Term Fellowship (JSPS/OF215/022) financed the work, undertaken at Tohoku University and concluded at the University of Aberdeen. We thank Giuseppe Vilardo and Eliana Bellucci Sessa for providing the geomorphological maps, and Simona Petrosino and Paola Cusano for the P- and S-wave pickings used to localise the seismicity. Informal revisions from Guido Ventura, Nick Rawlinson and Chris Kilburn helped us improving the analyses and interpretation, respectively. We acknowledge the help of Naveed Khan in parallelising the codes and two anonymous reviewers who improved the analysis, interpretation, and readibility with their comments. All data to reproduce the maps can be downloaded from the World Data Center PANGAEA data repository, permanent link https://doi.pangaea.de/10.1594/PANGAEA.890238.Peer reviewedPublisher PD

Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk

IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1α and IL1β. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case–control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) (haplotype-specific P=0.009). Evaluation of the prostate cancer risk associated with carrying the ‘ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR)=1.6, 95% confidence interval (CI)=1.2–2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR=1.0, 95% CI=0.8–1.2). Restricting analyses to advanced prostate cancer strengthened the association between the ‘ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI=1.3–2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association

Clinical Value of Prognostic Instruments to Identify Patients with an Increased Risk for Osteoporotic Fractures: Systematic Review

There is a plethora of evidence available studying the association of risk profiles and the development of osteoporotic fractures. The small number of out-of-sample validations, the large variety of study characteristics, outcomes and follow-up periods impedes from deriving robust summaries and from conclusions regarding the clinical performance of many tools. First and foremost, future activity in this field should aim at reaching a consensus among clinical experts in respect to the existing instruments. Then we call for careful validations and expedient adaptations for local circumstances of the most promising candidates

Cryptic Patterning of Avian Skin Confers a Developmental Facility for Loss of Neck Feathering

Vertebrate skin is characterized by its patterned array of appendages, whether feathers, hairs, or scales. In avian skin the distribution of feathers occurs on two distinct spatial levels. Grouping of feathers within discrete tracts, with bare skin lying between the tracts, is termed the macropattern, while the smaller scale periodic spacing between individual feathers is referred to as the micropattern. The degree of integration between the patterning mechanisms that operate on these two scales during development and the mechanisms underlying the remarkable evolvability of skin macropatterns are unknown. A striking example of macropattern variation is the convergent loss of neck feathering in multiple species, a trait associated with heat tolerance in both wild and domestic birds. In chicken, a mutation called Naked neck is characterized by a reduction of body feathering and completely bare neck. Here we perform genetic fine mapping of the causative region and identify a large insertion associated with the Naked neck trait. A strong candidate gene in the critical interval, BMP12/GDF7, displays markedly elevated expression in Naked neck embryonic skin due to a cis-regulatory effect of the causative mutation. BMP family members inhibit embryonic feather formation by acting in a reaction-diffusion mechanism, and we find that selective production of retinoic acid by neck skin potentiates BMP signaling, making neck skin more sensitive than body skin to suppression of feather development. This selective production of retinoic acid by neck skin constitutes a cryptic pattern as its effects on feathering are not revealed until gross BMP levels are altered. This developmental modularity of neck and body skin allows simple quantitative changes in BMP levels to produce a sparsely feathered or bare neck while maintaining robust feather patterning on the body

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants