Laurent Guy

University of Auvergne, Clermont, Auvergne, France

Are you Laurent Guy?

Claim your profile

Publications (175)314.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Favorable phase I results justified this pilot phase II study to assess the efficacy of docetaxel/curcumin in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (CRPC). Methods: Thirty patients with progressing CRPC and a rising prostate-specific antigen (PSA) received docetaxel/prednisone in standard conditions for 6 cycles in combination with per os curcumin, 6,000 mg/day (day -4 to day +2 of docetaxel). The co-primary endpoint was the overall response rate determined by PSA and target assessments. An ancillary study assessed the seric values of chromogranin A (CgA) and neuron-specific enolase (NSE). Results: Twenty-six patients received the scheduled treatment, 2 progressed and 2 died before the end of treatment. A PSA response was observed in 59% of patients (14% of PSA normalization) and achieved within the first three cycles for 88% of responders. Partial response was reached for 40% of evaluable patients. The regimen was well tolerated, and no adverse event was attributed to curcumin. Twenty patients were 100% curcumin compliant. The PSA level and objective response rate were not correlated with the serum values of CgA and NSE. Conclusion: This study produced additional data on curcumin as a treatment for cancer, with a high response rate, good tolerability and patient acceptability, justifying the interest to conduct a randomized trial.
    No preview · Article · Jan 2016 · Oncology

  • No preview · Article · Nov 2015

  • No preview · Article · Nov 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Previous radiation for prostate cancer (PC) contra-indicates neoadjuvant chemoradiotherapy for rectal cancer (RC) because of risk of cumulative radiation dose toxicity. Postoperative outcomes after proctectomy have not been well studied in these patients who did not receive optimal treatment. Methods: Eighty-four consecutive male patients underwent surgery for stage II-III mid or low RC between 2002 and 2011. Patients who previously received radiation for PC (n = 8) and patients who had not previously undergone radiation for PC but who received neoadjuvant chemoradiotherapy for RC (n = 64) were retrospectively compared. Results: Previous radiation for PC was an independent factor that significantly increased intraoperative (25% vs. 1.6%, P = 0.002) and postoperative morbidities (62.5% vs. 28.1%, P = 0.028), anastomotic leakage (62.5% vs. 12.5%, P < 0.001) and definitive stoma rates (25% vs. 17.4%, P = 0.022). It significantly altered median overall survival (32.0 vs. 130.6 months, P = 0.05) and local recurrence-free survival rates (14.0 months vs. "median not reached," P = 0.016). Conclusions: This is the first report of altered survival rates after proctectomy in patients who had previously received radiation for PC. Postoperative morbidity and definitive defunctioning stoma rates were significantly increased in these patients with poor prognoses. Therapeutic strategies should thus be individualized. Large, multicenter cohort studies are needed. J. Surg. Oncol. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Oct 2015 · Journal of Surgical Oncology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To compare Bricker and Wallace anastomosis in ileal conduit and search other risk factors of hydronephrosis. Methods: Retrospective study in two French Hospitals with two different surgical practices. Hydronephrosis are separated in two groups: complicated hydronephrosis requiring reoperation and no complicated hydronephrosis. Results: One hundred and sixty patients were included in the study and 317renal units were explored (141 in Bricker's group and 176 in Wallace's group). The rate of complicated and non-complicated hydronephrosis are respectively 9.9 and 20.6% in Bricker's group against 10.8 and 13.6% in Wallace's group, without significant difference (P=0.8 and 0.1). In the other risk factors, only body mass index over 25kg/m(2) was found as significant for complicated hydronephrosis. The left side and preoperative hydronephrosis are only associated to a risk of no complicated hydronephrosis (P=0.006 and 0.026). Conclusion: We found no difference between the two most common types of ureteroenteric anastomotic techniques. However, a high body mass index increases the rate of reoperation for hydronephrosis. Level of evidence: 5.
    No preview · Article · Oct 2015 · Progrès en Urologie
  • [Show abstract] [Hide abstract]
    ABSTRACT: Soy phytoestrogens are dietary components with considerable effects on reducing the incidence of prostate cancer. Epidemiological studies demonstrated that occurrence of prostate cancer is relatively low in Asia and Southern Europe, a status associated with consuming of soy isoflavones, such as genistein, daidzein, and glycitein. Soy phytoestrogens exert their activity on molecular mechanisms, including cell-cycle control, induction of apoptosis, inhibition of angiogenesis, and metastasis. In addition, they have antioxidant activity and show regulatory effect on the expression of genes involved in DNA damage and repair. Furthermore, the epigenetic regulation of gene expression can be modified by soy phytoestrogens. They show regulatory effects on gene activity by altering DNA methylation and/or histone modification patterns. In this chapter, we discuss the role of soy phytoestrogens on the genetic and epigenetic mechanisms of prostate cancer. We attempt to provide further insight in order to understand the underlying mechanisms of protective effects of soy phytoestrogens in preventing prostate cancer.
    No preview · Article · Aug 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To evaluate the accuracy of reduced-dose abdominal computed tomographic (CT) imaging by using a new generation model-based iterative reconstruction (MBIR) to diagnose acute renal colic compared with a standard-dose abdominal CT with 50% adaptive statistical iterative reconstruction (ASIR). Materials and Methods: This institutional review board-approved prospective study included 118 patients with symptoms of acute renal colic who underwent the following two successive CT examinations: standard-dose ASIR 50% and reduced-dose MBIR. Two radiologists independently reviewed both CT examinations for presence or absence of renal calculi, differential diagnoses, and associated abnormalities. The imaging findings, radiation dose estimates, and image quality of the two CT reconstruction methods were compared. Concordance was evaluated by k coefficient, and descriptive statistics and t test were used for statistical analysis. Results: Intraobserver correlation was 100% for the diagnosis of renal calculi (κ = 1). Renal calculus (τ = 98.7%; κ = 0.97) and obstructive upper urinary tract disease (τ = 98.16%; κ = 0.95) were detected, and differential or alternative diagnosis was performed (τ = 98.87% κ = 0.95). MBIR allowed a dose reduction of 84% versus standard-dose ASIR 50% (mean volume CT dose index, 1.7 mGy ± 0.8 [standard deviation] vs 10.9 mGy ± 4.6; mean size-specific dose estimate, 2.2 mGy ± 0.7 vs 13.7 mGy ± 3.9; P < .001) without a conspicuous deterioration in image quality (reduced-dose MBIR vs ASIR 50% mean scores, 3.83 ± 0.49 vs 3.92 ± 0.27, respectively; P = .32) or increase in noise (reduced-dose MBIR vs ASIR 50% mean, respectively, 18.36 HU ± 2.53 vs 17.40 HU 6 3.42). Its main drawback remains the long time required for reconstruction (mean, 40 minutes). Conclusion: A reduced-dose protocol with MBIR allowed a dose reduction of 84% without increasing noise and without an conspicuous deterioration in image quality in patients suspected of having renal colic.
    Full-text · Article · Apr 2015 · Radiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: In prostate cancer, DNA methylation is significantly associated with tumor initiation, progression, and metastasis. Previous studies have suggested that soy phytoestrogens might regulate DNA methylation at individual candidate gene loci and that they play a crucial role as potential therapeutic agents for prostate cancer. The purpose of our study was to examine the modulation effects of phytoestrogens on a genome-wide scale in regards to DNA methylation in prostate cancer. Prostate cancer cell lines DU-145 and LNCaP were treated with 40 μM of genistein and 110 μM of daidzein. DNMT inhibitor 5-azacytidine (2 μM) and the methylating agent budesonide (2 μM) were used to compare their demethylation/methylation effects with phytoestrogens. The regulatory effects of phytoestrogens on DNA methylation were analyzed by using a methyl-DNA immunoprecipitation method coupled with Human DNA Methylation Microarrays (MeDIP-chip). We observed that the methylation profiles of 58 genes were altered by genistein and daidzein treatments in DU-145 and LNCaP prostate cancer cells. In addition, the methylation frequencies of the MAD1L1, TRAF7, KDM4B, and hTERT genes were remarkably modified by genistein treatment. Our results suggest that the modulation effects of phytoestrogens on DNA methylation essentially lead to inhibition of cell growth and induction of apoptosis. Genome-wide methylation profiling reported here suggests that epigenetic regulation mechanisms and, by extension, epigenetics-driven novel therapeutic candidates warrant further consideration in future "omics" studies of prostate cancer.
    No preview · Article · Apr 2015 · Omics: a journal of integrative biology

  • No preview · Article · Apr 2015 · The Journal of Urology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Jan 2015 · Annales d Endocrinologie
  • Source
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Dec 2014 · BMC Cancer
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Oct 2014 · Progrès en Urologie
  • Source
    [Show abstract] [Hide abstract]
    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.
    Preview · Article · Sep 2014 · International Journal of Urology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Aug 2014 · Epigenomics
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · May 2014 · World Journal of Urology

  • No preview · Article · May 2014 · Medecine Nucleaire
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Apr 2014 · BJU International
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Mar 2014 · Nutrition and Cancer
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Mar 2014 · Progrès en Urologie

  • No preview · Article · Feb 2014 · Omics: a journal of integrative biology

Publication Stats

1k Citations
314.12 Total Impact Points


  • 2010-2015
    • University of Auvergne
      Clermont, Auvergne, France
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2009-2015
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
    • Institut Arnault Tzanck
      Saint-Laurent, Provence-Alpes-Côte d'Azur, France
  • 2006-2015
    • Polytech Clermont-Ferrand
      Aubière, Auvergne, France
  • 2013
    • Centre Hospitalier Universitaire Rouen
      • Service d'Urologie
      Rouen, Haute-Normandie, France
  • 2009-2013
    • Académie de Clermont-Ferrand
      Clermont, Picardie, France
  • 2012
    • Le Centre de Recherche en Nutrition Humaine Rhône-Alpes
      Pierre-Bénite, Rhône-Alpes, France
  • 1998-2012
    • Centre Hospitalier Universitaire de Clermont-Ferrand
      Clermont, Auvergne, France
  • 2011
    • University of Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2008
    • Centre Jean Perrin
      Clermont, Auvergne, France