Laurent Guy

University of Auvergne, Clermont, Auvergne, France

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Publications (148)263.16 Total impact

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    ABSTRACT: With 13 million new cases worldwide every year, prostate cancer is as a very real public health concern. Prostate cancer is common in over-50s men and the sixth-leading cause of cancer-related death in men worldwide. Like all cancers, prostate cancer is multifactorial – there are non-modifiable risk factors like heredity, ethnicity and geographic location, but also modifiable risk factors such as diet. Diet–cancer linkages have risen to prominence in the last few years, with accruing epidemiological data pointing to between-population incidence differentials in numerous cancers. Indeed, there are correlations between fat-rich diet and risk of hormone-dependent cancers like prostate cancer and breast cancer. Diet is a risk factor for prostate cancer, but certain micronutrients in specific diets are considered protective factors against prostate cancer. Examples include tomato lycopene, green tea epigallocatechin gallate, and soy phytoestrogens. These micronutrients are thought to exert cancer-protective effects via anti-oxidant pathways and inhibition of cell proliferation. Here, we focus in on the effects of phytoestrogens, and chiefly genistein and daidzein, which are the best-researched to date. Soy phytoestrogens are nonsteroid molecules whose structural similarity lends them the ability to mimic the effects of 17ß-estradiol. On top of anti-oxidant effects, there is evidence that soy phytoestrogens can modulate the epigenetic modifications found in prostate cancer. We also studied the impact of phytoestrogens on epigenetic modifications in prostate cancer, with special focus on DNA methylation, miRNA-mediated regulation and histone modifications.
    Annales d Endocrinologie 01/2015; 76(1). DOI:10.1016/j.ando.2014.09.001 · 0.66 Impact Factor
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    ABSTRACT: It is well established that genetic and epigenetic alterations are common events in prostate cancer, which may lead to aberrant expression of critical genes. The importance of epigenetic mechanisms in prostate cancer carcinogenesis is increasingly evident. In this study, the focus will be on histone modifications and the primary objectives are to map H3K27me3 marks and quantify RAR beta 2, ER alpha, SRC3, RGMA, PGR, and EZH2 gene expressions in prostate cancer tissues compared to normal tissues. In addition, a data analysis was made in connection with the clinicopathological parameters.Patients and methods: 71 normal specimens and 66 cancer prostate tissues were randomly selected in order to assess the proportion of the repressive H3K27me3 chromatin marks and gene expression. H3K27me3 level was evaluated by ChIP-qPCR and mRNA expression using RT-qPCR between prostate cancer and normal tissues. Subsequently, western-blotting was performed for protein detection. The analysis of variance (ANOVA) was performed, and Tukey's test was used to correct for multiple comparisons (p-value threshold of 0.05). The principal component analysis (PCA) and discriminant factorial analysis (DFA) were used to explore association between H3K27me3 level and clinicopathological parameters. The study demonstrated that H3K27me3 level was significantly enriched at RAR beta 2, ER alpha, PGR, and RGMA promoter regions in prostate cancer tissues compared to normal tissues. After stratification by clinicopathological parameters, the H3K27me3 level was positively correlated with Gleason score, PSA levels and clinical stages for RAR beta 2, ER alpha, PGR, and RGMA. High H3K27me3 mark was significantly associated with decreased RAR beta 2, ER alpha, PGR and RGMA gene expressions in prostate cancer sample compared to the normal one. Moreover, the results showed that mRNA level of EZH2, AR and SRC3 are upregulated in prostate cancer compared to normal prostate tissues and this correlates positively with Gleason score, PSA levels and clinical stages. Obviously, these observations were confirmed by protein level using western-blot. This data clearly demonstrated that H3K27me3 level correlated with aggressive tumor features. Also this study revealed that reverse correlation of RAR beta 2, ER alpha, PGR, and RGMA expressions with EZH2, SRC3, and AR expressions in prostate cancer tissues suggests that these genes are the target of EZH2. Therefore, all therapeutic strategies leading to histone demethylation with epigenetic drugs such as histone methyltransferase inhibitor may be relevant treatments against prostate cancer.
    BMC Cancer 12/2014; 14(1):994. DOI:10.1186/1471-2407-14-994 · 3.32 Impact Factor
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    ABSTRACT: Objective The aim of this study was to demonstrate the feasibility of extracorporeal lithotripsy using lithotripter Sortz MODULITH SLK® without analgesics. Materials and methods An anonymous self-administered questionnaire was sent to 854 patients post-shock wave lithotripsy for urinary lithiasis. No patient had pain medication. The questionnaire included seven questions to assess the pain symptoms due to treatment. After 15 days, a reminder letter was sent. Results The response rate was 69% (591/854). The extracorporeal lithotripsy without analgesic treatment was generally well tolerated. About 70% of patients felt just a few or no pain and average pain assessment was 3.6/10 on VAS. The pain was often considered to be multifactorial, related to the treatment itself, the duration of the session and the position on the table. Anxiety seemed to play an equally important role in pain relief with an average VAS 4.5 against 2.9 for non-anxious patients. If a new session of extracorporeal lithotripsy was necessary, 53% of patients would require no pain medication. Conclusions The extracorporeal lithotripsy could easily be done without systematic analgesics allowing for outpatient care. In contrast, anxiety seemed to be an important predictor of poor tolerance of sessions so the idea of a prophylactic anxiolytic treatment based on psychological profile of the patient should allow less aggressive and less costly management of urolithiasis. Level of evidence 5.
    Progrès en Urologie 10/2014; DOI:10.1016/j.purol.2014.06.006 · 0.77 Impact Factor
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    ABSTRACT: Objectives To assess bacillus Calmette-Guerin maintenance treatment schedule for non-muscle invasive bladder cancer at 2 years, using one-third of the full dose and fewer instillations every 3 months or 6 months. Methods This was a prospective, randomized, multicenter study. All patients had an intermediate- or high-risk non-muscle invasive bladder cancer. They received three weekly instillations of one-third dose bacillus Calmette-Guerin every 6 months (group I) and two weekly instillations every 3 months (group II) during 3 years. In the two schedules we assessed efficacy, tolerance, leukocyturia and prostate-specific antigen. ResultsNo significant difference was observed between the two groups for recurrence at 6, 12 or 18 months. At 2 years, tumor recurrence was observed in 10.9% and muscle invasion in 2.9% of cases. Bacillus Calmette-Guerin tolerance was comparable - the adverse events score was 0.8 in group I and 1 in group II (P=0.242). No statistical correlation was observed between the adverse events score over 2 years, either for leukocyturia (P=0.8891) or prostate-specific antigen level (P=0.7155). Leukocyturia level was not significantly associated with tumor recurrence or progression. Conclusion One-third dose maintenance bacillus Calmette-Guerin is effective with no impact on tumor recurrence or muscle invasion. Furthermore, there seems to be no difference in tumor response or side-effects between patients receiving two or three maintenance instillations every 3 months or 6 months. In clinical practice, the use of leukocyturia or total prostate-specific antigen levels do not appear to be useful in predicting bacillus Calmette-Guerin toxicity.
    International Journal of Urology 09/2014; 22(1). DOI:10.1111/iju.12609 · 1.80 Impact Factor
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    ABSTRACT: Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.
    Epigenomics 08/2014; 6(4):415-26. DOI:10.2217/epi.14.34 · 2.43 Impact Factor
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    ABSTRACT: To evaluate the influence of preoperative factors on the survival of patients diagnosed with upper tract urothelial carcinoma (UTUC) who underwent a radical nephroureterectomy (RNU). A multicentre retrospective study was performed on all patients with UTUC who underwent a RNU. Multiple preoperative criteria were tested as prognostic factors for cancer-specific survival (CSS) using univariate and multivariable Cox regression analyses. Overall, 476 patients with a median age of 69.2 (IQR 60.8-76.5) years were included. The median follow-up was 27.8 months (IQR 10.5-49.3). At the time of diagnosis, 400 (84.1 %) patients presented with symptoms and 76 patients (15.9 %) were asymptomatic. Renal failure, altered general health, a preoperative locally advanced tumour and multifocal disease appeared to be preoperative prognostic factors for CSS (p = 0.01, 0.03, 0.001 and 0.03, respectively) in the univariate analysis. Only renal failure (p = 0.03), a preoperative locally advanced tumour (0.004), and multifocal locations (p = 0.01) were confirmed as independent factors of CSS in the multivariate analysis. The independent prognosticators of definitive muscle-invasive stage and non-organ-confined disease were preoperative renal failure (p = 0.02, 0.027, respectively), locally advanced stage (p < 0.001, <0.001, respectively) and positive cytology (p = 0.006, 0.003 respectively). Female gender was independent factor only for prediction of final non-organ-confined disease (p = 0.007). The addition of these parameters in our preoperative complex model permitted the prediction of muscle-invasive or locally advanced disease in 65.3 and 67.2 % of patients, respectively. Patients with preoperative impaired renal function, locally advanced stage and multifocal tumours before RNU had worse survival outcomes compared to other patients.
    World Journal of Urology 05/2014; DOI:10.1007/s00345-014-1311-8 · 3.42 Impact Factor
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    ABSTRACT: Objective To evaluate the impact of ‘hereditary-like’ status in upper tract urothelial carcinoma (UTUC) on the survival of patients who have undergone radical nephroureterectomy (RNU) and adjuvant chemotherapy.Patients and MethodsA multicentre retrospective study was performed on all patients with high-risk UTUC who underwent RNU and adjuvant cisplatin-based chemotherapy.Using a patient risk identification tool, we distinguished tumours suspected to be hereditary from sporadic tumours and compared survival rates.ResultsA total of 112 patients with a median age of 67 years were included. Hereditary-like tumour status was detected in 35 patients (31.3%), while 77 patients (68.7%) had sporadic tumours.The median age was significantly younger in the hereditary-like tumour group (56.0 vs 69.8 years, P < 0.001). Overall survival (OS) after chemotherapy was significantly better in the group with hereditary-like tumours than in the group with sporadic tumours (5-year OS: 48.2 vs 32%; P = 0.008).The cancer-specific survival (CSS) rate was significantly better in the group with ‘hereditary-like’ tumours than in the group with sporadic tumours (5-year CSS: 58 vs 35%; P = 0.006).Although there was a trend in favour of the hereditary-like tumours, we observed no significant difference regarding progression-free survival (PFS) between the two groups (5-year PFS: 71 vs 52%; P = 0.07).Conclusion Adjuvant chemotherapy after RNU improves survival outcomes in patients with hereditary-like UTUC compared with those with sporadic tumours.
    BJU International 04/2014; 113(4). DOI:10.1111/bju.12308 · 3.13 Impact Factor
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    ABSTRACT: Major phytoestrogens genistein and daidzein have been reported to have the ability to reverse DNA methylation in cancer cell lines. The mechanism by which genistein and daidzein have an inhibiting action on DNA methylation is not well understood. The aim of this study was to investigate the effects of soy phytoestrogens and the natural estrogen 17β-estradiol (E2) to determine whether one of the estrogen receptors is mobilized for the action of these compounds on DNA methylation. We also made a comparative study with a DNA methylation inhibitor (5-azacytidine) and a DNA methylation activator (budesonide). Three prostate cell lines, PC-3, DU-145, and LNCaP, were treated with 40 μM genistein, 110 μM daidzein, 2 μM budesonide, 2 μM 5-azacytidine, and 10 μM E2. In these 3 human prostate cancer cell lines, we performed methylation quantification using methyl-profiler-DNA-methylation analysis. Soy phytoestrogens and E2 induced a demethylation of all the promoter regions studied except for those that were unmethylated in control cells. Our results showed that E2 induces, like soy phytoestrogen, a decrease in DNA methylation in prostate cancer cell lines. This action may be mediated through ERβ.
    Nutrition and Cancer 03/2014; 66(3). DOI:10.1080/01635581.2014.884236 · 2.70 Impact Factor
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    ABSTRACT: Objective To analyse the detection ability of a multiparametric 3 T MRI with phased-array coil in comparison with the pathological data provided by the prostatectomy specimens. Methods Prospective study of 30 months, including 74 patients for whom a diagnosis of prostate cancer had been made on randomized prostate biopsies, and all eligible to a radical prostatectomy. They all underwent multiparametric 3 T MRI with pelvic phased-array coil including T2-weighted imaging (T2 W), dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) with an ADC mapping. Each gland was divided in octants. Three specific criteria have been sought (detection ability, capsular contact [CC] and extracapsular extension [ECE]), in comparison with the pathological data provided by the prostatectomy specimens. Results Five hundred and ninety-two octants were considered with 124 significant tumors (volume ≥ 0.1 cm3). The general ability of tumor detection had a sensitivity, specificity, PPV and NPV respectively to 72.3%, 87.4%, 83.2% and 78.5%. The estimate of the CC and ECE had a high negative predictive power with specificities and VPN respectively to 96.4% and 95.4% for CC, and 97.5 and 97.7% for ECE. Conclusions Multiparametric 3 T MRI with pelvic phased-array coil appeared to be a reliable imaging technique in clinical and routine practice for the detection of localized prostate cancer. Estimation of the CC and millimeter ECE remains to be clarified, even if the negative predictive power for these parameters seems encouraging.
    Progrès en Urologie 03/2014; 24(3):145–153. DOI:10.1016/j.purol.2013.09.005 · 0.77 Impact Factor
  • Omics: a journal of integrative biology 02/2014; 18(3). DOI:10.1089/omi.2013.0117 · 2.29 Impact Factor
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    Progrès en Urologie 12/2013; 23(16):1455. DOI:10.1016/j.purol.2013.11.002 · 0.77 Impact Factor
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    Progrès en Urologie 12/2013; 23(16):1453–1454. DOI:10.1016/j.purol.2013.11.001 · 0.77 Impact Factor
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    ABSTRACT: To describe drugs used in the chemotherapy of testis and penis neoplasms. Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. Nowadays, the chemotherapy is perfectly codified in adjuvant treatment or in first-line treatment of metastatic testis cancer. A single dose of carboplatin for seminoma testicular (stade I) in adjuvant treatment situation is one of the latest advances. Concerning penis cancer, the optimal protocols validated by a high level of evidence are missing. The chemotherapy in testis and penis neoplasms knew few advances in recent years. So, it is necessary to include patients in clinical research protocols.
    Progrès en Urologie 11/2013; 23(15):1265-70. DOI:10.1016/j.purol.2013.08.321 · 0.77 Impact Factor
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    ABSTRACT: To define the terms of use of vaccines, probiotics, and cranberry in urology. A literature search was conducted on MEDLINE for all these treatments used in urology. Modes of action, indications in urology and adverse effects have been detailed for each treatment. Vaccines have been published in urinary tract infections. Products for bacterial interference such as probiotics are also used, their properties are described. As for the cranberry widely used in recurrent urinary tract infections, efficacy and mode of action are discussed. The anti-E. coli vaccines, cranberry and probiotics may be useful in urinary tract infection.
    Progrès en Urologie 11/2013; 23(15):1357-64. DOI:10.1016/j.purol.2013.09.002 · 0.77 Impact Factor
  • Progrès en Urologie 11/2013; 23(13):1090. DOI:10.1016/j.purol.2013.08.165 · 0.77 Impact Factor
  • Progrès en Urologie 11/2013; 23(13):1095. DOI:10.1016/j.purol.2013.08.177 · 0.77 Impact Factor
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    ABSTRACT: To describe drugs used in sexual medicine. Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM). 5PDIs and intracavernous injection of alprostadil are first- and second-line therapies of erectile dysfunction. Dapoxetine is the first specific and approved treatment of premature ejaculation. Androgene supplementation improves sexual desire among patient with hypogonadism as much as initial serum testosterone levels are low. Female sexual dysfunctions pharmacology is to date less developed, although candidate drugs reach phase III clinical studies. Pharmacology is one but not the only therapeutic avenue in sexual medicine. Despite real breakthrough such as 5PDIs for erectile dysfunction, incomplete knowledge and understanding of physiology, pathophysiology and pharmacology of human sexual function reduces its development particularly for women.
    Progrès en Urologie 11/2013; 23(15):1299-311. DOI:10.1016/j.purol.2013.09.017 · 0.77 Impact Factor
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    ABSTRACT: To define the general use of anti-infectious treatments in urology. A review of national guidelines and articles published on the subject in the Medline database, selected by keywords, depending on the scientific relevance was performed. While the epidemiology clearly shows the non-reduction of the anti-infectious treatments use in France, the resistance increases to highlight foo-resistant germs. Urology is not an exception to this observation, and different means are set to improve the prescription made by urologists. The epidemiological observation confirms the urgent need to improve the prescription of anti-infectious treatments particularly in urology.
    Progrès en Urologie 11/2013; 23(15):1318-26. DOI:10.1016/j.purol.2013.08.324 · 0.77 Impact Factor
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    ABSTRACT: To describe drugs used in renal cell carcinoma. Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies websites (HAS and ANSM). Since 2007, a total of three different therapeutic classes in the management of metastatic renal cell carcinoma are available. These three classes are tyrosine kinase inhibitors with sunitinib and sorafenib, the anti-VEGF antibodies (bevacizumab which is associated with alpha interferon in the treatment of advanced kidney cancer) and mTOR inhibitors with temsirolimus and everolimus. These targeted therapies are a major progress in the treatment of patients with metastatic kidney cancer. The side effects encountered with these molecules are numerous but serious side effects are less than 5% of all reported side effects. A better understanding of molecular mechanisms has enabled the development of new therapies for the treatment of metastatic renal cell carcinoma. In the future, a personalized approach taking into account the biology of each tumor could be created to provide a more targeted treatment.
    Progrès en Urologie 11/2013; 23(15):1225-37. · 0.77 Impact Factor
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    ABSTRACT: To describe drugs used in bladder carcinoma. Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM). The drugs used in the treatment of bladder cancer are represented by the products referred to diagnosis (hexyl aminolevulinate), the intravesical instillations for the treatment of tumors not infiltrating the muscle and the infiltrating tumor chemotherapy (neo-adjuvant treatment or metastatic tumors). The hexyl aminolevulinate cystoscopy allows to identify a significantly greater number of lesions, including carcinoma in situ, compared to conventional white light cystoscopy. For intravesical instillations, BCG has a superior efficacy to mitomycin C with a lower tolerance. The chemotherapies for invasive tumors are effective in metastatic disease in 15-20% of cases with a mean survival of 12 to 14 months. Except the use of hexyl aminolevulinate for improving the diagnosis, there was no emergence in recent years of new drugs for the treatment of bladder cancer. Targeted therapies currently available for many neoplasms were ineffective for bladder cancer.
    Progrès en Urologie 11/2013; 23(15):1238-45. DOI:10.1016/j.purol.2013.09.015 · 0.77 Impact Factor

Publication Stats

720 Citations
263.16 Total Impact Points


  • 2008–2014
    • University of Auvergne
      • Faculty of medicine
      Clermont, Auvergne, France
  • 2013
    • Centre Hospitalier Universitaire Rouen
      • Service d'Urologie
      Rouen, Haute-Normandie, France
  • 2004–2013
    • Centre Jean Perrin
      Clermont, Auvergne, France
  • 2000–2013
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
  • 1998–2012
    • Centre Hospitalier Universitaire de Clermont-Ferrand
      Clermont, Auvergne, France
  • 2010
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2009
    • Institut Arnault Tzanck
      Saint-Laurent, Provence-Alpes-Côte d'Azur, France
    • Henan Institute of Occupational Health
      Cheng, Henan Sheng, China