Absence of generalized immunosuppression in C57BL/6J mice implanted with Lewis T241 fibrosarcoma or Lewis lung carcinoma

Summary The immune status of C57BL/6J mice implanted with Lewis T241 fibrosarcoma or Lewis lung (LL) carcinoma was investigated on days 14 and 28 after implantation. Splenic lymphocyte responses were assessed in mitogen (Con A, LPS) mixed lymphocyte culture (MLC), natural killer (NK), graft-vs-host (GVH), and interleukin production assays. Except for NK-cell cytotoxicity, all other immunologic parameters were either comparable to those in medium-implanted controls or augmented. NK cytotoxicity was reduced in both tumor-bearing groups on day 28. The provision of NK potentiation therapy (-interferon, polyinosinic: polycytidylic acid) to T241 mice under various treatment conditions did not have any significant effect on lung metastasis or survival.The results of this study do not support the thesis that T241-or LL-bearing C57BL/6J mice are generally immunosuppressed. Indeed, when immune functions were assessed on the basis of total splenic activity, each of the measured immunologic parameters was substantially greater in animals with tumors than without. Further it seems improbable, considering the magnitude of the NK-cell defect in T241 mice on days 14 and 28 after implantation and the absence of a therapeutic response to NK-cell stimulants, that NK-cell cytotoxicity is intrinsically associated with resistance to tumor progression in this model.     

DNA repair variants,indoor tanning,and risk of melanoma

Although ultraviolet radiation (UV) exposure from indoor tanning has been linked to an increased risk of melanoma, the role of DNA repair genes in this process is unknown. We evaluated the association of 92 single nucleotide polymorphisms (SNPs) in 20 DNA repair genes with the risk of melanoma and indoor tanning among 929 patients with melanoma and 817 controls from the Minnesota Skin Health Study. Significant associations with melanoma risk were identified for SNPs in ERCC4, ERCC6, RFC1, XPC, MGMT, and FBRSL1 genes; with a cutoff of P < 0.05. ERCC6 and FBRSL1 gene variants and haplotypes interacted with indoor tanning. However, none of the 92 SNPs tested met the correction criteria for multiple comparisons. This study, based on an a priori interest in investigating the role of DNA repair capacity using variants in base excision and nucleotide excision repair, identified several genes that may play a role in resolving UV‐induced DNA damage.     

Crop residue harvest impacts wind erodibility and simulated soil loss in the Central Great Plains

Crop residue removal can affect the susceptibility to soil wind erosion in climates such as those of the Central Great Plains, United States. Six on‐farm trials were conducted in Kansas from 2011 to 2013 to determine the effects of winter wheat (Triticum aestivum L.), corn (Zea mays L.), and grain sorghum (Sorghum bicolor (L.) Moench), residue removal at 0, 25, 50, 75, and 100% of initial height on soil wind erosion parameters. Those parameters include soil surface random roughness (RR), and wind erodible fraction (EF; aggregates <0.84 mm), geometric mean diameter (GMD) and geometric standard deviation (GSD), stability of dry aggregates (DAS). Complete (100%) residue removal decreased the surface RR, increased EF, and decreased GMD. Overwinter EF values increased for five of six sites from fall 2011 to spring of 2012, particularly for the uppermost removal height (≥75%). Measured EF, GMD, GSD, DAS, and RR were also input into the Single‐event Wind Erosion Evaluation Program (SWEEP) to determine the effect of these parameters on simulated soil loss. The SWEEP simulated the wind velocity needed to initiate wind erosion as well as soil loss under each residue removal height at a wind velocity of 13 m s^?1 for three hours. Threshold wind velocity required to initiate wind erosion generally decreased with increasing crop residue removal height, particularly for >75% removal. Total estimated soil loss over the three‐hour event ranged from ≈2 to 25 Mg ha^?1, depending on EF, GMD, GSD, RR, and percent crop residue cover. Removing 75% residue increased simulated wind erosion at three of six sites while removing 50% appears sustainable at all six study sites. Findings reinforce the need for site‐by‐site consideration of the potential amount of crop residue that may be harvested while mitigating wind erosion. Study results indicate the value of maintaining residue at >75% of original height.     

Development of a Melanoma Risk Prediction Model Incorporating MC1R Genotype and Indoor Tanning Exposure: Impact of Mole Phenotype on Model Performance

Background

Identifying individuals at increased risk for melanoma could potentially improve public health through targeted surveillance and early detection. Studies have separately demonstrated significant associations between melanoma risk, melanocortin receptor (MC1R) polymorphisms, and indoor ultraviolet light (UV) exposure. Existing melanoma risk prediction models do not include these factors; therefore, we investigated their potential to improve the performance of a risk model.

Methods

Using 875 melanoma cases and 765 controls from the population-based Minnesota Skin Health Study we compared the predictive ability of a clinical melanoma risk model (Model A) to an enhanced model (Model F) using receiver operating characteristic (ROC) curves. Model A used self-reported conventional risk factors including mole phenotype categorized as “none”, “few”, “some” or “many” moles. Model F added MC1R genotype and measures of indoor and outdoor UV exposure to Model A. We also assessed the predictive ability of these models in subgroups stratified by mole phenotype (e.g. nevus-resistant (“none” and “few” moles) and nevus-prone (“some” and “many” moles)).

Results

Model A (the reference model) yielded an area under the ROC curve (AUC) of 0.72 (95% CI = 0.69, 0.74). Model F was improved with an AUC = 0.74 (95% CI = 0.71–0.76, p<0.01). We also observed substantial variations in the AUCs of Models A & F when examined in the nevus-prone and nevus-resistant subgroups.

Conclusions

These results demonstrate that adding genotypic information and environmental exposure data can increase the predictive ability of a clinical melanoma risk model, especially among nevus-prone individuals.