Anh Tuan Dinh-Xuan

Publications (20)68.23 Total impact

• Article: Angiotensin II receptor blockade ameliorates systemic fibrosis in the mouse.

  Wioleta Marut, Niloufar Kavian, Amélie Servettaz, Thong Hua-Huy, Carole Nicco, Christiane Chéreau, Bernard Weill, Anh Tuan Dinh-Xuan, Frédéric Batteux
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  ABSTRACT: OBJECTIVE.: Systemic sclerosis (SSc) is characterized by microvascular damages, fibrosis of skin and visceral organs, and autoimmunity. Previous studies have shown that angiotensin II is involved in the synthesis of type I collagen. We investigated whether the blockade of angiotensin II receptor type-I (AT(1) R) by irbesartan reduces skin and lung fibrosis in two murine models of systemic systemic. METHODS.: SSc was induced by daily intradermal injection of hypochlorous acid (HOCl) in the back of BALB/c mice (HOCl-SSc).Mice were treated daily with irbesartan by oral gavage. RESULTS.: Irbesartan reduced dermal thickness, collagen concentration, smad 2/3 and αSMA expression as well as fibroblast proliferation and H-Ras expression in the skin of HOCl-SSc mice that displayed less lung fibrosis, less inflammation, and a lower concentration of collagen in the lung than non treated mice. Exhaled nitric oxide, iNOS and 3-nitrosotyrosine expression in the lung were decreased following irbesartan. Moreover, irbesartan reduced the number and the proliferation of splenicB and T-cells, and the serum levels of anti-DNA-topoisomerase-1 autoantibodies. CONCLUSIONS.: Irbesartan, an AT(1) R antagonist, prevents fibrosis, inflammation and inhibits nitric oxide production in HOCl induced models of systemic fibrosis. This report extends the indication of an AT(1) R antagonist to SSc patients with diffuse fibrosis, especially those with lung involvement.
  Arthritis & Rheumatism 01/2013; · 7.87 Impact Factor
• Article: Role of Rho-kinase and its inhibitors in pulmonary hypertension.

  Sy Duong-Quy, Yihua Bei, Zhongmin Liu, Anh Tuan Dinh-Xuan
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  ABSTRACT: Pulmonary hypertension (PH) is an incurable disease with a dreadful survival rate. The disease is characterized by sustained vasoconstriction, progressive vascular remodeling, and irreversible right heart dysfunction. While hypoxic pulmonary vasoconstriction (HPV) is known to be the main pathophysiological factor causing the rise in pulmonary arterial pressure, biological mechanisms leading to HPV and vascular remodeling are multiple and complex and, as yet, incompletely understood. It is thought that molecular interactions and cross talks are involved in the pathogenesis of PH, perturbing the physiological balance between substances controlling vascular tone, cell growth and apoptosis. This balance is achieved by subtle interactions between factors acting as both vasodilators and inhibitors of cell growth like nitric oxide, prostacyclin, vasoactive intestinal peptide and molecules with potent vasoconstrictor and cell growth activities like endothelin-1. Recent in vivo studies showed that the Rho GTPase/RhoA pathway and its downstream effectors, the Rho-kinases (ROCK-1 and ROCK-2), had an important role in PH, due to its lasting effects on vasoconstriction and pulmonary cell proliferation leading to vascular remodeling. Beneficial effects obtained in vivo with Rho-kinase inhibitors (e.g.Y-27632 and fasudil) in experimental PH will hopefully lead to future clinical trials with new compounds selectively targeting this pathway, which is now proven to be detrimental when over-activated in both experimental animals and human patients.
  Pharmacology [?] Therapeutics 12/2012; · 8.56 Impact Factor
• Article: High alveolar concentration of nitric oxide is associated with alveolitis in scleroderma.

  Kiet Phong Tiev, Thong Hua-Huy, Sébastien Rivière, Nhat-Nam Le-Dong, Michel Febvre, Jean Cabane, Anh Tuan Dinh-Xuan
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  ABSTRACT: Alveolar concentration of nitric oxide (C(A)NO) is a non invasive prognostic marker of systemic sclerosis (SSc) lung disease. There is, however, as yet no direct evidence showing concomitant increase of C(A)NO and the presence of inflammatory cells in alveoli. We have therefore measured C(A)NO and performed broncho-alveolar lavage (BAL) in SSc patients. Exhaled NO was measured, by the means of two different models, the two-compartment model (2CM) and the trumpet model with axial diffusion (TMAD), in 22 SSc patients and compared with 15 healthy controls. BAL was performed in all SSc patients. Alveolitis was defined as lymphocytes> 14%, polymorphonuclears> 4%, or eosinophils> 3% on cell count in BAL fluid. Comparisons of C(A)NO levels were made between SSc patients with, and without, alveolitis. Levels of C(A)NO were significantly higher in SSc patients as compared with controls (p<0.001). Median C(A)NO was significantly higher in SSc patients with alveolitis as compared with SSc patients without alveolitis (8.4 ppb; 1(st) and 3(rd) interquartile range: 6.0-10.5 vs 3.3 ppb; 2.2-3.5; p=0.004 for 2CM and 5.4 ppb; 3.2-9.2 vs 3.2 ppb; 1.4-3.3, p=0.02 for TMAD), while bronchial airway output of NO (J'aw NO, p= 0.19), and fractional exhaled NO (F(E)NO, p=0,12) were comparable. C(A)NO was consistently high in SSc patients with alveolitis irrespective of the methods chosen (TMAD or 2CM). Our findings showed that increased C(A)NO was associated with alveolitis in patients with SSc. We submit that C(A)NO could be used as a reliable non-invasive surrogate biomarker of alveolitis in scleroderma lung disease.
  Nitric Oxide 10/2012; · 3.55 Impact Factor
• Article: Measuring exhaled nitric oxide in animal models: methods and clinical implications.

  Nhât-Nam Le-Dong, Sy Duong-Quy, Yihua Bei, Thông Hua-Huy, Weihua Chen, Anh Tuan Dinh-Xuan
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  ABSTRACT: Animal models such as rats and mice are useful for studying the multiple roles of nitric oxide (NO) in various respiratory disorders. The production of NO is catalyzed by the three isoforms of the enzymes (NO synthases; NOS). Indirect assessment of NOS gene or protein expression only provides partial information on the role of NO in health and lung disease. NO can also be measured in exhaled air by invasive or non-invasive approaches as a direct and quantitative marker of NO production in animal models. Whilst addressing the different methods of exhaled NO analysis in small animals (rats and mice), this review also focuses on the possible clinical implications, and discusses the advantages and limitations of these methods.
  Journal of Breath Research 09/2012; 6(4):047001. · 2.54 Impact Factor
• Article: Alveolar concentration of nitric oxide predicts pulmonary function deterioration in scleroderma.

  Kiet Phong Tiev, Thong Hua-Huy, Adrien Kettaneh, Yannick Allanore, Nhat-Nam Le-Dong, Sy Duong-Quy, Jean Cabane, Anh Tuan Dinh-Xuan
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  ABSTRACT: Respiratory failure is a life-threatening and unpredictable complication of systemic sclerosis (SSc). A study was undertaken to assess the value of alveolar nitric oxide (NO) in predicting the risk of lung function deterioration leading to respiratory failure or death in patients with SSc. 105 patients with SSc were enrolled in this prospective cohort and were followed longitudinally over a 3-year period during which the risk of occurrence of deleterious events was analysed according to alveolar concentration (C(A)NO), conducting airway output (J'(aw)NO) and fractional concentration (F(E)NO(0.05)) of exhaled NO measured at inclusion. Comparison was made between each NO parameter to predict the occurrence of deleterious events, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death. The area under the receiver operating characteristic curve of C(A)NO to predict the occurrence of the combined events was 0.84 (95% CI 0.76 to 0.92; p<0.001), which was significantly higher than those of J'(aw)NO and F(E)NO(0.05) (p<0.001). A cut-off of C(A)NO of 5.3 ppb had a sensitivity of 88% and a specificity of 62% for the prediction of the occurrence of combined events during follow-up, and was validated in an independent cohort of patients with SSc. Combined events occurred more frequently in patients whose C(A)NO was >5.3 ppb. The adjusted HR for patients with C(A)NO >5.3 ppb was 6.06 (95% CI 2.36 to 15.53; p<0.001). C(A)NO accurately predicted the occurrence of combined events irrespective of forced vital capacity values or the presence of interstitial lung disease at baseline. Increased C(A)NO accurately identifies patients with SSc with a high risk of developing lung function deterioration and may help to initiate early appropriate treatment.
  Thorax 02/2012; 67(2):157-63. · 6.84 Impact Factor
• Article: Nitric oxide activity through guanylate cyclase and phosphodiesterase modulation is impaired in fetal lambs with congenital diaphragmatic hernia.

  Anthony de Buys Roessingh, Virginie Fouquet, Yves Aigrain, Jean-Christophe Mercier, Pascal de Lagausie, Anh Tuan Dinh-Xuan
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  ABSTRACT: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension and death. Administration of nitric oxide (NO) alone remains ineffective in CDH cases. We investigated in near full-term lambs with and without CDH the role of guanylate cyclase (GC), the enzyme activated by NO in increasing cyclic 3'-5'-guanylosine monophosphate, and the role of phosphodiesterase (PDE) 5, the enzyme-degrading cyclic 3'-5'-guanylosine monophosphate. Congenital diaphragmatic hernia was surgically created in fetal lambs at 85 days of gestation. Pulmonary hemodynamics were assessed by means of pressure and blood flow catheters (135 days). In vitro, we tested drugs on rings of isolated pulmonary vessels. In vivo, sodium nitroprusside, a direct NO donor, and methyl-2(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5 trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032) and Zaprinast, both PDE 5 blockers, reduced pulmonary vascular resistance in CDH and non-CDH animals. The activation of GC by sodium nitroprusside and the inhibition of PDE 5 by T-1032 were less effective in CDH animals. In vitro, the stimulation of GC by 3(5'hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1) (a benzyl indazole derivative) and the inhibition of PDE 5 by T-1032 were less effective in pulmonary vascular rings from CDH animals. The YC-1-induced vasodilation in rings from CDH animals was higher when associated with the PDE 5 inhibitor T-1032. Guanylate cyclase and PDE 5 play a role in controlling pulmonary vascular tone in fetal lambs with or without CDH. Both enzymes seem to be impaired in fetal lambs with CDH.
  Journal of Pediatric Surgery 08/2011; 46(8):1516-22. · 1.45 Impact Factor
• Article: Clopidogrel protects from cell apoptosis and oxidative damage in a mouse model of renal ischaemia-reperfusion injury.

  Honglin Hu, Frédéric Batteux, Christiane Chéreau, Niloufar Kavian, Wioleta Marut, Camille Gobeaux, Didier Borderie, Anh Tuan Dinh-Xuan, Bernard Weill, Carole Nicco
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  ABSTRACT: Renal ischaemia-reperfusion injury (IRI) is consecutive to tissue oxidative damage and cell apoptosis that lead to acute renal failure (ARF) in renal allografts. The aim of this study was to investigate the beneficial effects of a pretreatment by clopidogrel on renal IRI in mice. IRI was induced by bilateral renal ischaemia for 45 min followed by reperfusion. Sixty-two healthy male BALB/c mice were randomly assigned to one of the following groups: PBS + ischaemia-reperfusion (IR); clopidogrel + IR; PBS + sham IR; clopidogrel + sham IR. Clopidogrel (25 mg/kg) or PBS was administered per os to the animals via a gastric cannula 24 h before operation. All mice were given a single dose of clopidogrel or PBS. Renal function histological damage, renal cell apoptosis, renal antioxidant activities, and CD41 expression were determined 24 h after reperfusion. The survival rates were evaluated over 7 days. Animals pretreated with clopidogrel had lower plasma levels of blood urea nitrogen (BUN) and creatinine, lower histopathological scores, and improved survival rates following IR. Renal cell apoptosis induced by IR was decreased in kidneys of mice pretreated by clopidogrel, with an increase in Bcl-2 and Bcl-xL expression and a decrease in caspase-3, caspase-8, and Bax expression. Renal reduced glutathione, superoxide dismutase, and catalase activities were unmodified by the pretreatment with clopidogrel. However, clopidogrel resulted in an increased total antioxidant capacity of the kidney. Furthermore, pretreatment by clopidogrel decreased the number of CD41-positive cells. Thus, clopidogrel exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis as a consequence of improved renal antioxidant capacity and could be tried as a novel therapeutic tool in renal IRI.
  The Journal of Pathology 04/2011; 225(2):265-75. · 6.32 Impact Factor
• Article: Increased alveolar concentration of nitric oxide is related to serum-induced lung fibroblast proliferation in patients with systemic sclerosis.

  Thong Hua-Huy, Kiet Phong Tiev, Christiane Chéreau, Sy Duong-Quy, Jean Cabane, Anh Tuan Dinh-Xuan
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  ABSTRACT: Lung inflammation is present in patients with systemic sclerosis (SSc) and interstitial lung disease (ILD), but the mechanisms linking inflammatory and fibrotic processes in ILD are unknown. Our aim was to investigate whether alveolar inflammation, reflected by increased alveolar concentration of exhaled nitric oxide (C(A)NO), is related to the ability of serum from patients with SSc to induce pulmonary fibroblast proliferation (PFP) and myofibroblast conversion. C(A)NO was measured in all subjects (37 patients with SSc and 10 healthy controls) whose sera were used to stimulate PFP (assessed by BrdU labeling index) and myofibroblast conversion (detected by alpha-smooth muscle actin expression). The PFP index in patients with SSc was compared to control values, and between patients with SSc who had elevated (> 4.3 ppb) and normal (<or= 4.3 ppb) C(A)NO values. Both C(A)NO and the PFP index were significantly greater in patients with SSc compared to controls. In patients with SSc, the PFP index was directly related to C(A)NO levels (r = 0.48; p = 0.002). The median PFP index was significantly higher in patients with SSc who had elevated C(A)NO (> 4.3 ppb; n = 25, median 1.1, range 0.98-1.23) than in patients with SSc who had normal C(A)NO (<or= 4.3 ppb; n = 12, median 0.93, range 0.82-1.08; p = 0.01). Similarly, myofibroblast conversion induced by SSc serum was significantly greater in patients with C(A)NO > 4.3 ppb than in patients whose C(A)NO was <or= 4.3 ppb (p < 0.001) and controls (p < 0.001). Alveolar inflammation reflected by increased nitric oxide production was related to serum-induced PFP and myofibroblast conversion, linking the active alveolitis process to cell proliferation and lung fibrosis in patients with SSc.
  The Journal of Rheumatology 08/2010; 37(8):1680-7. · 3.69 Impact Factor
• Article: Lack of specificity of the 6-minute walk test as an outcome measure for patients with systemic sclerosis.

  Yoland Schoindre, Christophe Meune, Anh Tuan Dinh-Xuan, Jérôme Avouac, André Kahan, Yannick Allanore
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  ABSTRACT: The 6-minute walk test (6MWT) is an important prognostic tool in various cardiovascular diseases and has been considered as a surrogate endpoint. However, conflicting results have been reported in systemic sclerosis (SSc). Our objective was to evaluate the relationships of the 6-min walking distance (6MWD) and organ damage in SSc. Eighty-seven consecutive patients with SSc were included and prospectively investigated; they underwent 6MWT in addition to conventional assessment of possible lung, heart, kidney, skin, and muscle involvement, and disease activity scoring, severity, and quality of life determination. Twenty-six patients (30%) had an abnormal 6MWT and the mean 6MWD was 461.8 +/- 103.0 m. When considering 6MWT as a binary variable - normal or abnormal - C-reactive protein (CRP) was the only independent variable associated with abnormal 6MWT. Considered as a continuous variable, the 6MWD was associated with measures of lung involvement and inflammation, with the activity and severity of disease, and also with quality of life; nevertheless, calcinosis was the only independent factor associated in multivariate analyses with a trend for an association for CRP. The 6MWD relates to broad factors in SSc and these results raise doubts about the specificity of the 6MWD in this systemic disease, and its relevance to monitoring therapy.
  The Journal of Rheumatology 07/2009; 36(7):1481-5. · 3.69 Impact Factor
• Article: Offline exhaled nitric oxide in emergency department and subsequent acute asthma control.

  Christophe Delclaux, Nicole Sembach, Yann-Erick Claessens, Guillaume Dolbeau, Brigitte Chevalier-Bidaud, Bertrand Renaud, Jean-Christophe Allo, Francoise Zerah-Lancner, Alain Davido, Anh-Tuan Dinh-Xuan
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  ABSTRACT: Few studies have evaluated exhaled NO measurement during acute asthma. To evaluate exhaled NO fraction (FE(NO)) and peak expiratory flow (PEF) time-courses during acute asthma treatment (beta 2-agonist plus systemic steroid) and to assess whether FE(NO) time-course predicts subsequent asthma control. Sixty-five asthmatic patients (mean +/- SD, 34 +/- 10 years) were prospectively enrolled in three Emergency Departments. Sixteen patients were excluded (failure of offline FE(NO) measurement at 100 mL/s [FE(NO 0.1)], n = 4, and early discharge). The 49 remaining patients performed FE(NO 0.1) and PEF on admission, at the 2nd (H2) and 6th hour (H6). Follow-up using an Asthma Control Diary was obtained in 27 of 49 patients, whether they were hospitalized (n = 9) or discharged (n = 18). All but 2 patients had elevated FE(NO) on admission (median [interquartile], 49 [26-78] ppb). Unlike PEF, mean FE(NO 0.1) of our sample was not significantly modified by treatment. No significant relationship was evidenced between exhaled NO and PEF variations. The variation of FE(NO 0.1) [H0 minus H6] was different in patients who were hospitalized (decrease of 8 +/- 20 ppb) versus discharged (increase of 5 +/- 20 ppb, p = 0.04). This variation of FE(NO 0.1) was correlated with the Diary score (control of subsequent week), an initial increase in FE(NO 0.1) being associated with better asthma control. Nevertheless, neither exhaled NO nor PEFR were good predictors of asthma control. An increase in FE(NO) is observed in almost all patients with acute asthma, and its subsequent increase within 6 hours is associated with a better degree of asthma control in the subsequent week.
  Journal of Asthma 01/2009; 45(10):867-73. · 1.52 Impact Factor
• Article: Exhaled nitric oxide, but not serum nitrite and nitrate, is a marker of interstitial lung disease in systemic sclerosis.

  Kiet Phong Tiev, Nhat-Nam Le-Dong, Sy Duong-Quy, Thông Hua-Huy, Jean Cabane, Anh Tuan Dinh-Xuan
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  ABSTRACT: Nitric oxide metabolites (NOx) in serum, and alveolar concentration of NO (CA(NO)), are markers of inflammation and alveolitis, respectively, in systemic sclerosis (SSc). We prospectively evaluated the usefulness of both NOx and CA(NO) to assess lung involvement and skin fibrosis in SSc. Serum NOx, and CA(NO) measured by two different methods, namely the two-compartment (2CM) and the "trumpet" models (TM), were concomitantly assessed in 65 patients with SSc and 17 healthy controls. Whilst serum NOx remained comparable between groups, CA(NO) were significantly higher in SSc patients (n=65, 6.7ppb; 4.8-9.7 and 5.9ppb; 3.9-8.9) as compared with controls (n=17, 3.0ppb; 2.0-3.8 and 1.8ppb; 1.1-2.9, p<0.001, p<0.001) using the 2CM and the TM, respectively). CA(NO) from SSc patients with interstitial lung disease (ILD) (n=26, 8.6ppb; 6.5-10.9 and 8.5ppb; 5.9-10.7) or pulmonary arterial hypertension (n=12, 7.3ppb; 6.5-10.4 and 6.9ppb; 5.4-9.9) were significantly higher as compared with patients without ILD (n=27, 4.9ppb; 3.8-6.5 and 4.7ppb; 2.8-5.7; p<0.001 and p<0.001) using the 2CM and the TM, respectively). CA(NO) assessed either by the 2CM or the trumpet model were directly related to the extent of ILD and inversely related to DLCO. There was no correlation between NOx and ILD, or DLCO. Neither CA(NO) nor NOx was correlated with skin fibrosis and no relationship was found between CA(NO) and NOx. Alveolar concentration of NO, but not serum NOx, closely correlates with the extent of ILD in patients with systemic sclerosis. Neither parameter, however, is related to skin fibrosis.
  Nitric Oxide 12/2008; 20(3):200-6. · 3.55 Impact Factor
• Article: The prognostic value of vascular endothelial growth factor (VEGF)-A and its receptor in clinically localized prostate cancer: a prospective evaluation in 100 patients undergoing radical prostatectomy.

  Kaili Mao, Cécile Badoual, Philippe Camparo, Nicolas Barry Delongchamps, Annick Vieillefond, Anh-Tuan Dinh-Xuan, Michaël Peyromaure
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  ABSTRACT: To study the prognostic value of vascular endothelial growth factor (VEGF)-A and its receptor VEGFR-1 in localized prostate cancer. One hundred patients undergoing radical prostatectomy (RP) for clinically localized prostate cancer were prospectively included. Plasma levels of VEGF-A were measured preoperatively. After intervention, tissue microarrays were built from the RP specimens. VEGF-A and VEGFR-1 expressions in prostate cancer tissue were determined using immunochemistry. Then the associations between plasma levels of VEGF-A, VEGF-A and VEGFR-1 expressions in prostate cancer tissue, and the outcome of patients were analyzed. After a median follow-up of 22 months, 14 patients experienced biological recurrence of prostate cancer. There was no correlation between plasma VEGF-A and the risk of recurrence following RP. Moreover, there was no correlation between VEGF-A expression or VEGFR-1 expression in prostate cancer tissue and the risk of recurrence after RP. Plasma levels of VEGF-A, the expression of VEGF-A and that of VEGFR-1 in prostate cancer tissue did not affect patients outcome following RP. VEGF-A and its receptor VEGFR-1 may have no prognostic value in localized prostate cancer. Further studies with longer follow-up are mandatory to confirm these findings.
  The Canadian Journal of Urology 11/2008; 15(5):4257-62. · 0.64 Impact Factor
• Article: Neuronal nitric oxide synthase does not contribute to the modulation of pulmonary vascular tone in fetal lambs with congenital diaphragmatic hernia (nNOS in CDH lambs).

  Anthony S de Buys Roessingh, Pascal de Lagausie, Taline Ebrahimian, Taline Ibrahima, Sy Duong-Quy, Jean-Christophe Schneider, Xiao-Lin Huang, Jean-Christophe Mercier, Yves Aigrain, Chantal Boulanger, Anh Tuan Dinh-Xuan
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  ABSTRACT: The aim of this study was to determine the presence of the neuronal nitric oxide synthase (nNOS) in near full-term lambs with congenital diaphragmatic hernia (CDH) and its role in the modulation of pulmonary vascular basal tone. We surgically created diaphragmatic hernia on the 85th day of gestation. On the 135th, catheters were used to measure pulmonary pressure and blood flow. We tested the effects of 7-nitroindazole (7-NINA), a specific nNOS antagonist and of N-nitro-L-arginine (L-NNA), a nonspecific nitric oxide synthase antagonist. In vitro, we tested the effects of the same drugs on isolated pulmonary vessels. The presence of nNOS protein in the lungs was detected by Western blot analysis. Neither 7-NINA nor L-NNA modified pulmonary vascular basal tone in vivo. After L-NNA injection, acetylcholine (ACh) did not decrease significantly pulmonary vascular resistance (PVR). In vitro, L-NNA increased the cholinergic contractile-response elicited by electric field stimulation (EFS) of vascular rings from lambs with diaphragmatic hernia. We conclude that nNOS protein is present in the lungs and pulmonary artery of near full-term lamb fetuses with diaphragmatic hernia, but that it does not contribute to the reduction of pulmonary vascular tone at birth.
  Pediatric Pulmonology 05/2008; 43(4):313-21. · 2.53 Impact Factor
• Article: The association of vascular endothelial growth factor receptor-1 with the risk of cancer progression following radical prostatectomy.

  Kaili Mao, Philippe Camparo, Cecile Badoual, Michaël Peyromaure, Nicolas Barry Delongchamps, Annick Vieillefond, Anh-Tuan Dinh-Xuan
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  ABSTRACT: In the current study, we analysed the prognostic value of vascular endothelial growth factor receptor-1 (VEGFR-1) in clinically-localized prostate cancer (PCa). Forty patients who had undergone radical prostatectomy (RP) for clinically-localized PCa were included. Two groups were compared: 17 patients who experienced cancer progression following RP (group 1) and 23 patients who remained free of recurrence after intervention (group 2). Paraffin-embedded sections obtained from the RP specimens of the 40 patients were used to build tissue microarrays. The expression of VEGFR-1 was examined in the RP specimens using immunohistochemistry and was compared between the groups of patients. The two groups had similar tumor characteristics in terms of PSA, Gleason score and pathological stage of cancer. The median intensity score of VEGFR-1 expression was significantly higher in pT3 tumors than in pT2 tumors. Nevertheless, the intensity scores of VEGFR-1 expression were similar in the two groups of patients. Our results suggest that VEGFR-1 expression is not associated with the risk of cancer progression following RP. Therefore, VEGFR-1 may not be of prognostic value in clinically-localized PCa.
  Oncology Reports 02/2008; 19(1):171-5. · 1.84 Impact Factor
• Article: Plasma levels and expression of vascular endothelial growth factor-A in human localized prostate cancer.

  Michaël Peyromaure, Cécile Badoual, Philippe Camparo, Sophie Grabar, Claire Goulvestre, Yvonne Fulla, Annick Vieillefond, Kaili Mao, Anh-Tuan Dinh-Xuan
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  ABSTRACT: Although the impact of vascular endothelial growth factor (VEGF) is clearly established in advanced prostate cancer (PCa), its role in localized PCa remains to be determined. The aim of our study was to analyse the plasma levels of VEGF-A and the expression of VEGF-A in prostatic tissue in a population of patients with localized PCa. We measured the preoperative plasma levels of VEGF-A in 100 patients undergoing radical prostatectomy (RP) for clinically-localized PCa. After intervention, we determined the expression of VEGF-A in all RP specimens using immunohistochemistry. We found no association between plasma levels of VEGF-A and the established prognostic factors of PCa. Moreover, there was no association between plasma levels of VEGF-A and the expression of VEGF-A in prostatic tissue. On the contrary, there was a strong correlation between the expression of VEGF-A in PCa tissue and the Gleason score of cancer: the expression of VEGF-A was significantly higher in patients with a high Gleason score on RP specimen (p=0.01). Our results suggest that the expression of VEGF may have a prognostic impact in clinically-localized PCa.
  Oncology Reports 08/2007; 18(1):145-9. · 1.84 Impact Factor
• Article: The expression of vascular endothelial growth factor is associated with the risk of cancer progression after radical prostatectomy.

  Michaël Peyromaure, Philippe Camparo, Cécile Badoual, Aurélien Descazeaud, Anh-Tuan Dinh-Xuan
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  ABSTRACT: To analyse the prognostic value of vascular endothelial growth factor (VEGF) in men with clinically localized prostate cancer. Paraffin wax-embedded sections from the radical prostatectomy (RP) specimens of 40 men operated for clinically localized prostate cancer were used to build tissue microarrays. Of these patients, 17 had cancer progression and bone metastases after RP (group 1), and 23 remained free-of-tumour recurrence after RP (group 2). VEGF-A expression was examined in the RP specimens using immunohistochemistry. The groups had similar tumour characteristics in terms of prostate-specific antigen level, Gleason score, and pathological stage. VEGF-A expression was significantly higher in group 1 than in group 2 (P=0.046). In logistic regression analysis, VEGF-A expression was the most significant predictive factor of cancer progression after RP. VEGF-A expression in prostate cancer tissue is associated with the risk of cancer progression after RP. These results suggest that VEGF-A expression has a prognostic impact in clinically localized prostate cancer.
  BJU International 06/2007; 99(5):1150-3. · 2.84 Impact Factor
• Article: Role of ATP-dependent potassium channels in pulmonary vascular tone of fetal lambs with congenital diaphragmatic hernia.

  Anthony S de Buys Roessingh, Pascal de Lagausie, Jacques-Patrick Barbet, Jean-Christophe Mercier, Yves Aigrain, Anh Tuan Dinh-Xuan
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  ABSTRACT: High mortality in newborn babies with congenital diaphragmatic hernia (CDH) is principally due to persistent pulmonary hypertension. ATP-dependent potassium (K(ATP)) channels might modulate pulmonary vascular tone. We have assessed the effects of Pinacidil, a K(ATP) channel opener, and glibenclamide (GLI), a K(ATP) channel blocker, in near full-term lambs with and without CDH. In vivo, pulmonary hemodynamics were assessed by means of pressure and blood flow catheters. In vitro, we used isolated pulmonary vessels and immunohistochemistry to detect the presence of K(ATP) channels in pulmonary tissue. In vivo, pinacidil (2 mg) significantly reduced pulmonary vascular resistance (PVR) in both controls and CDH animals. GLI (30 mg) significantly increased pulmonary arterial pressure (PAP) and PVR in control animals only. In vitro, pinacidil (10 microM) relaxed, precontracted arteries from lambs with and without CDH. GLI (10(-5) microM) did not raise the basal tone of vessels. We conclude that activation of K(ATP) channels could be of interest to reduce pulmonary vascular tone in fetal lambs with CDH, a condition often associated with persistent pulmonary hypertension of the newborn.
  Pediatric Research 12/2006; 60(5):537-42. · 2.70 Impact Factor
• Article: Role of vascular endothelial growth factor in prostate cancer.

  Nicolas Barry Delongchamps, Michaël Peyromaure, Anh Tuan Dinh-Xuan
  Urology 09/2006; 68(2):244-8. · 2.43 Impact Factor
• Article: Serum levels of vascular endothelial growth factor in patients undergoing prostate biopsy for suspicion of prostate cancer.

  Michaël Peyromaure, Claire Goulvestre, Yvonne Fulla, Sophie Grabar, Bernard Debré, Anh Tuan Dinh-Xuan
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  ABSTRACT: To analyze the correlation between serum levels of vascular endothelial growth factor (VEGF) and biopsy findings in patients with a suspicion of prostate cancer. Serum levels of VEGF were measured on frozen, archival serum obtained before prostate biopsy in 47 patients with clinical and/or biologic suspicion of prostate cancer. VEGF-A levels were measured using an enzyme-linked immunosorbent assay. The prostate biopsies showed cancer in 27 patients (group 1) and benign tissue in the remaining 20 patients (group 2). No statistically significant difference was found between the two groups in age, digital rectal examination findings, total prostate-specific antigen (PSA) levels, free PSA levels, and complexed PSA levels. The mean prostate volume was significantly lower in group 1 (45.5 g versus 53.9 g; P = 0.04), and the mean percentage of free PSA (free PSA/total PSA) was significantly lower in group 1 (11.3% versus 19%; P = 0.0003). Serum VEGF-A levels were not significantly different between the two groups. The mean VEGF level was 90.6 pg/mL in group 1 and 107.9 pg/mL in group 2 (P = 0.55). Multivariate analysis showed that VEGF-A levels were not predictive of prostate cancer. Our findings suggest that serum VEGF-A is not helpful to predict prostate cancer in patients with clinical and/or biologic suspicion of prostate cancer.
  Urology 10/2005; 66(3):687-91. · 2.43 Impact Factor
• Article: Pro PSA : a "pro cancer" form of PSA?

  Michaël Peyromaure, Yvonne Fulla, Bernard Debré, Anh Tuan Dinh-Xuan
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  ABSTRACT: Pro PSA, the precursor of PSA, is an inactive 244-amino acid protein secreted by prostatic cells. Pro PSA, a distinct molecular form of free PSA in serum, includes native as well as several truncated forms. Clinical studies have recently provided evidence that pro PSA is associated with prostate cancer (PCa). The truncated (-2) pro PSA form accounts for only 6-19% of free PSA in the serum of patients without PCa, but it represents up to 25-95% of free PSA in that of PCa patients. In the PSA range of 2-10 ng/ml, it has been suggested that pro PSA may be useful to detect PCa, and to spare 10-20% of unnecessary prostate biopsies. However, only scant information about the role of pro PSA is available to date, and its real impact on PCa detection remains to be determined. Furthermore, it is questionnable whether pro PSA could be predictive of tumor recurrence of PCa after therapy. Prospective clinical studies with long term followup are needed to clarify this point.
  Medical Hypotheses 02/2005; 64(1):92-5. · 1.39 Impact Factor