Éditeur(s) : HAL CCSD Elsevier Elsevier Masson
Résumé : International audience
Prostate cancer is the most frequent cancer affecting men in most Western countries. Certain risk factors have been identified (age, family history, ethnic origin), but the aetiology of this cancer remains largely unknown. However, a role for environmental factors is strongly suspected. Questions have been raised concerning the role of the chemical substances generated by human activities in the occurrence of this disease. Diverse studies have consistently demonstrated a higher risk of prostate cancer in agricultural populations than in the general population. The hypothesis that this higher risk is linked to the use of pesticides has been tested in a number of studies, mostly in North America and Europe. However, to date, with a few possible exceptions, it has been impossible to demonstrate a significant association between exposure to pesticides or a chemical family of pesticides and prostate cancer. Studies have also been carried out on the role of exposure to trace metals, such as cadmium, or to pollutants from industry, such as polychlorobiphenyls. However, no firm conclusions have been drawn. Finally, the effect of chemical substances with endocrine disruptor activity on the occurrence of prostate cancer remains largely unexplored in epidemiological studies. In the face of these uncertainties, rigorous studies are required, with objective measurements of exposure, taking into account confounding factors and individual risk factors, making it possible to assess gene-environment interactions.
ISSN: 1297-9589

inserm-00524579
http://www.hal.inserm.fr/inserm-00524579
DOI : 10.1016/j.gyobfe.2008.07.005
PUBMED : 18693059

Éditeur(s) : HAL CCSD
Résumé : International audience
Purpose: Social inequalities in cancer incidence and mortality have been reported in France, but no data are available for the French overseas territories. Our objective was to explore the association between cancer incidence and the socioeconomic level of the residence area in the French West Indies. Methods: Cancer incidence data were obtained from the cancer registries of Guadeloupe and Martinique (2009–2010). To assess socioeconomic status, we developed a specific index of social deprivation from census data at a small area level. We used Bayesian methods to evaluate the association between cancer incidence and the deprivation index, for all cancers combined and for the major cancer sites. Results: There was no clear association between area‐based deprivation and the incidence of all cancers combined. In men, higher area deprivation was associated with a higher incidence of prostate cancer (relative risk (RR) 1.25, 95% credible interval (CI) 1.04–1.49; RR 1.08, CI 0.91–1.29 in the categories of intermediate and high deprivation, respectively, compared to low deprivation), but was not associated with respiratory cancer. Women living in the most deprived areas had a higher incidence of stomach (RR 1.77, CI 1.12–2.89), breast (RR 1.15, CI 0.90–1.45), and cervical (RR 1.13, CI 0.63–2.01) cancers and a lower incidence of respiratory cancer (RR 0.65, CI 0.38–1.11). Conclusion: These first results in the French West Indies suggest specific patterns for some cancer sites that need to be further investigated. © 2017, Springer International Publishing AG.
Cancer Causes and Control

hal-01671494
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01671494
DOI : 10.1007/s10552-017-0946-3
PUBMED : 28849411

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
A number of men receiving prolonged suppressive HAART still shed HIV in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with SIVmac251 submitted to HAART for 4 months, intensified over the last seven weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen, or in testis, epididymis, seminal vesicles and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens, and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of non-productively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organs infection in long term treated infected individuals. A substantial subset of men receiving prolonged suppressive HAART in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV-infected macaques treated by HAART. We demonstrated that persistent seminal shedding was not linked to poor drug penetration in semen or semen-producing prostate, seminal vesicle, epididymis and testis. We revealed that HAART decreased SIV RNA to various extents in all male genital organs, with the exception of the urethra, in which SIV RNA+ macrophages were observed despite HAART. Importantly also, HAART did not impact SIV DNA levels in the male genital organs. These results suggest that infection of male genital organs, and particularly the urethra, could be involved in the release of virus in semen during HAART.
ISSN: 0022-538X

hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01139816/file/Detection%20of%20SIV%20in%20Semen%2C%20Urethra%2C%20and%20Male%20Reproductive%20Organs%20during%20Efficient%20Highly%20Active%20Antiretroviral%20Therapy.pdf
PUBMEDCENTRAL : PMC4442442

Éditeur(s) : HAL CCSD John Libbey Eurotext
Résumé : International audience
Prostate cancer is the most frequent cancer affecting men in most Western countries. Certain risk factors have been identified (age, family history, ethnic origin), but the aetiology of this cancer remains largely unknown. However, a role for environmental factors is strongly suspected. Questions have been raised concerning the role of the chemical substances generated by human activities in the occurrence of this disease. Diverse studies have consistently demonstrated a higher risk of prostate cancer in agricultural populations than in the general population. The hypothesis that this higher risk is linked to the use of pesticides has been tested in a number of studies, mostly in North America and Europe. However, to date, with a few possible exceptions, it has been impossible to demonstrate a significant association between exposure to pesticides or a chemical family of pesticides and prostate cancer. In the face of these uncertainties, rigorous studies are required, with objective measurements of exposure, taking into account confounding factors and individual risk factors, making it possible to assess gene-environment interactions.
ISSN: 0007-4551

inserm-00504733
http://www.hal.inserm.fr/inserm-00504733
DOI : 10.1684/bdc.2008.0812
PUBMED : 19258224

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Androgen signaling, via the androgen receptor (AR), is crucial in mediating prostate cancer (PCa) initiation and progression. Identifying new downstream effectors of the androgens/AR pathway will allow a better understanding of these mechanisms and could reveal novel biomarkers and/or therapeutic agents to improve the rate of patient survival. We compared the microRNA expression profiles in androgen-sensitive LNCaP cells stimulated or not with 1 nM R1881 by performing a high-throughput reverse transcriptase-quantitative PCR and found that miR-135a was upregulated. After androgen stimulation, we showed that AR directly activates the transcription of miR-135a2 gene by binding to an androgen response element in the promoter region. Our findings identify miR-135a as a novel effector in androgens/AR signaling. Using xenograft experiments in chick embryos and adult male mice, we showed that miR-135a overexpression decreases in vivo invasion abilities of prostate PC-3 cells. Through in vitro wound-healing migration and invasion assays, we demonstrated that this effect is mediated through downregulating ROCK1 and ROCK2 expression, two genes that we characterized as miR-135a direct target genes. In human surgical samples from prostatectomy, we observed that miR-135a expression was lower in tumoral compared with paired adjacent normal tissues, mainly in tumors classified with a high Gleason score (⩾8). Moreover, miR-135a expression is lower in invasive tumors, showing extraprostatic extension, as compared with intraprostatic localized tumors. In tumor relative to normal glands, we also showed a more frequently higher ROCK1 protein expression determined using a semi-quantitative immunohistochemistry analysis. Therefore, in tumor cells, the lower miR-135a expression could lead to a higher ROCK1 protein expression, which could explain their invasion abilities. The highlighted relationship between miR-135a expression level and the degree of disease aggressiveness suggests that miR-135a may be considered as a prognostic marker in human PCa.Oncogene advance online publication, 28 July 2014; doi:10.1038/onc.2014.222.
ISSN: 0950-9232

hal-01063902
https://hal.archives-ouvertes.fr/hal-01063902
https://hal.archives-ouvertes.fr/hal-01063902/file/Androgen-regulated%20microRNA-135a.pdf
DOI : 10.1038/onc.2014.222
PUBMED : 25065599

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Objective Large-scale prospective studies do not support an association between neuroticism and extroversion with cancer incidence. However, research on other personality constructs is inconclusive. This longitudinal study examined the associations between four personality measures, Type 1, "suppressed emotional expression"; Type 5, "rational/antiemotional"; hostility; and Type A with cancer incidence. Methods Personality measures were available for 13,768 members in the GAZEL cohort study (baseline assessment in 1993). Follow-up for diagnoses of primary cancers was obtained from January 1, 1994 to December 31, 2009. Associations between personality and cancer incidence were evaluated using Cox proportional hazards analyses and adjusted for potential confounders. Results During a median follow-up of 16.0 years (range, 9 days-16 years), 1139 participants were diagnosed as having a primary cancer. The mean duration between baseline and cancer diagnosis was 9.3 years. Type 1 personality was associated with a decreased risk of breast cancer (hazard ratio per standard deviation = 0.81, 95% confidence interval = 0.68-0.97, p = .02). Type 5 personality was not associated with prostate, breast, colorectal, or smoking-related cancers, but was associated with other cancers (hazard ratio per standard deviation = 1.17, 95% confidence interval = 1.04-1.31, p = .01). Hostility was associated with an increased risk of smoking-related cancers, which was explained by smoking habits, and Type A was not associated with any of the cancer endpoints. Conclusions Several personality measures were prospectively associated with the incidence of selected cancers. These links may warrant further epidemiological studies and investigations about potential biobehavioral mechanisms.
ISSN: 0033-3174

inserm-00813178
http://www.hal.inserm.fr/inserm-00813178
http://www.hal.inserm.fr/inserm-00813178/document
http://www.hal.inserm.fr/inserm-00813178/file/PersonalityCancer_Lemogne_Psychosom_Med_2013.pdf
http://www.hal.inserm.fr/inserm-00813178/file/inserm-00813178_edited.pdf

Éditeur(s) : HAL CCSD
Résumé : International audience
Objectives: Using in silico simulations from histopathological cancer prostate specimen, the objectives were to identify the total dose corresponding to various fractionations necessary to destroy the tumor cells (50% to 99.9%) and to assess the impact of the Gleason score on those doses. © 2017 IEEE.
14th IEEE International Symposium on Biomedical Imaging, ISBI 2017
Melbourne, Australia

hal-01618934
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01618934
DOI : 10.1109/ISBI.2017.7950643

Éditeur(s) : HAL CCSD IEEE
Résumé : International audience
The main challenge in prostate cancer radiotherapy is to deliver the prescribed dose to the clinical target while minimizing the dose to the neighboring organs at risk and thus avoiding subsequent toxicity-related events. With the aim of improving toxicity prediction following prostate cancer radiotherapy, the goal of our work is to propose a new predictive variable computed with independent component analysis to predict late rectal toxicity, and to compare its performance to other models (logistic regression, normal tissue complication probability model and recent principal component analysis approach). Clinical data and dose-volume histograms were collected from 216 patients having received 3D conformal radiation for prostate cancer with at least two years of follow-up. Independent component analysis was trained to predict the risk of 3-year rectal bleeding Grade extgreater= 2. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve. Clinical parameters combined with the new variable were found to be predictors of rectal bleeding. The mean area under the receiving operating curve for our proposed approach was 0:75. The AUC values for the logistic regression, the Lyman-Kutcher-Burman model and the recent principal component analysis approach were 0:62, 0:53 and 0:62, respectively. Our proposed new variable may be an useful new tool in predicting late rectal toxicity. It appears as a strong predictive variable to improve classical models
2015 37th annual international conference of the IEEE Engineering in Medicine and Biology Society
Milan, Italy

hal-01304750
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01304750

Éditeur(s) : HAL CCSD Society for the Study of Reproduction
Résumé : International audience
Matrix-assisted laser desorption/ionization (MALDI) tissue imaging mass spectrometry is particularly promising among the numerous applications of mass spectrometry. It is used for probing and analyzing the spatial arrangement of a wide range of molecules, including proteins, peptides, lipids, drugs, and metabolites, directly in thin slices of tissue. In the field of proteomics, the technology avoids tedious and time-consuming extraction and fractionation steps classically required for sample analysis. MALDI imaging mass spectrometry is increasingly recognized as a powerful method for clinical proteomics, particularly in cancer research. The technology has particular potential for the discovery of new tissue biomarker candidates, classification of tumors, early diagnosis or prognosis, elucidating pathogenesis pathways, and therapy monitoring. Over recent years, MALDI imaging mass spectrometry has been used for molecular profiling and imaging directly in male and female reproductive tissues. This review will consider some of the recent publications in the field, addressing a range of issues covering embryo development, gene expression product profiling during gametogenesis, and seeking and identifying biomarkers of reproductive cancers. The wealth of advances in mass spectrometry imaging will inevitably attract biologists and clinicians as the advantages and power of this technology become more widely known. This review will also discuss bottlenecks and the many technical issues that remain to be resolved before laboratories in the field can adopt the technology. We foresee that MALDI imaging mass spectrometry will have a major impact in reproductive research by opening new avenues to the understanding of various molecular mechanisms and the diagnosis of reproductive pathologies.
ISSN: 0006-3363

hal-00877851
https://hal.archives-ouvertes.fr/hal-00877851
DOI : 10.1095/biolreprod.111.094896
PUBMED : 22156474

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Do mild analgesics affect the endocrine system of the human adult testis? SUMMARY ANSWER: Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. WHAT IS KNOWN ALREADY: Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. STUDY DESIGN, SIZE, DURATION: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. MAIN RESULTS AND THE ROLE OF CHANCE: The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. LIMITATIONS, REASONS FOR CAUTION: Our studies were performed in vitro. WIDER IMPLICATIONS OF THE FINDINGS: We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes.
ISSN: 0268-1161

inserm-00866016
http://www.hal.inserm.fr/inserm-00866016
PUBMED : 23670170
DOI : 10.1093/humrep/det112

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Worrying trends regarding human reproductive endpoints (e.g. semen quality, reproductive cancers) have been reported and there is growing circumstantial evidence for a possible causal link between these trends and exposure to endocrine disrupting chemicals (EDCs). However, there is a striking lack of human data to fill the current knowledge gaps. To answer the crucial questions raised on human reproductive health, there is an urgent need for a reproductive surveillance system to be shared across countries. METHODS: A multidisciplinary network named HUman Reproductive health and Global ENvironment Network (HURGENT) was created aiming at designing a European monitoring system for reproductive health indicators. Collaborative work allowed setting up the available knowledge to design such a system. Furthermore we conducted an overview of 23 potential indicators, based upon a weight of evidence (WoE) approach according to their potential relation with EDC exposure. RESULTS: The framework and purposes of the surveillance system are settled as well as the approach to select suitable reproductive indicators. The indicators found with the highest scores according to the WoE approach are prostate and breast cancer incidence, sex ratio, endometriosis and uterine fibroid incidence, indicators related to the testicular dysgenesis syndrome, precocious puberty incidence and reproductive hormone levels. CONCLUSION: Not only sentinel health endpoints, but also diseases with high burdens in public health are highlighted as prior indicators in the context of EDC exposure. Our work can serve as a basis to construct, as soon as possible, the first multi-country reproductive monitoring system
European Journal of Public Health

hal-01197348
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197348
DOI : 10.1093/eurpub/ckv153
PUBMED : 26330492