The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis

Background: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. Objectives: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. Methods: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. Results: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2 = 0%), while a significant heterogeneity (I2 > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. Conclusions: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding

A Possible Role for CD8+ T Lymphocytes in the Cell-Mediated Pathogenesis of Pemphigus Vulgaris

Pemphigus vulgaris (PV) is an autoimmune blistering disease whose pathogenesis involves both humoral and cell-mediated immune response. Though the pathogenetic role of autoantibodies directed against desmoglein 3 is certain, a number of other factors have been suggested to determine acantholysis in PV. In this study we examined the possible role of CD8+ T cells in the development of acantholysis by a passive transfer of PV autoantibodies using CD8 deficient mice, and we also studied the inflammatory infiltrate of PV skin lesions by immunohistochemical staining. The results of the immunohistochemical staining to study the expression of CD3, CD4, and CD8 in PV skin lesions showed that CD4+ are more expressed than CD8+ in the inflammatory infiltrate of PV lesions, confirming the data of the previous literature. The passive transfer study showed a lower incidence of pemphigus in the group of CD8 deficient mice compared to the control one of wild-type mice. These results suggest that CD8+ T cells may play a role in the pathogenesis of PV, perhaps through the Fas/FasL pathway

Radiomics Analysis on [68Ga]Ga-PSMA-11 PET and MRI-ADC for the Prediction of Prostate Cancer ISUP Grades: Preliminary Results of the BIOPSTAGE Trial

Prostate cancer (PCa) risk categorization based on clinical/PSA testing results in a substantial number of men being overdiagnosed with indolent, early-stage PCa. Clinically non-significant PCa is characterized as the presence of ISUP grade one, where PCa is found in no more than two prostate biopsy cores.MRI-ADC and [68Ga]Ga-PSMA-11 PET have been proposed as tools to predict ISUP grade one patients and consequently reduce overdiagnosis. In this study, Radiomics analysis is applied to MRI-ADC and [68Ga]Ga-PSMA-11 PET maps to quantify tumor characteristics and predict histology-proven ISUP grades. ICC was applied with a threshold of 0.6 to assess the features’ stability with variations in contouring. Logistic regression predictive models based on imaging features were trained on 31 lesions to differentiate ISUP grade one patients from ISUP two+ patients. The best model based on [68Ga]Ga-PSMA-11 PET returned a prediction efficiency of 95% in the training phase and 100% in the test phase whereas the best model based on MRI-ADC had an efficiency of 100% in both phases. Employing both imaging modalities, prediction efficiency was 100% in the training phase and 93% in the test phase. Although our patient cohort was small, it was possible to assess that both imaging modalities add information to the prediction models and show promising results for further investigations

The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis

Background: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. Objectives: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. Methods: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. Results: A total of nine studies (two case–controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories ‘herbicides – ever exposure’, ‘insecticides – ever exposure’, ‘any pesticide – ever exposure’ and ‘any pesticide – high exposure’ resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2 = 0%), while a significant heterogeneity (I2 > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. Conclusions: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding

Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2

The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH(2); EM1 and Tyr-Pro-Phe-Phe-NH(2); EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) exhibit an extremely high selectivity for mu-opioid receptor. Here a series of novel EM2 and morphiceptin analogues containing in place of the proline at position 2 the S and R residues of beta-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid (HPrs) and of 3-pyrrolidinesulphonic acid (beta Prs) have been synthesized and their binding affinity and functional activity have been investigated. The highest p-receptor affinity is shown by [(S)beta Prs(2)]EM2 analogue (6e) which represents the first example of a beta-sulphonamido analogue in the field of mold peptides. (C) 2010 Elsevier Masson SAS. All rights reserved