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C Mougin

Publications and source records attributed to C Mougin.

At least 19 recordsLinked to original sources
PubMed2006

Identification and formation pathway of laccase-mediated oxidation products formed from hydroxyphenylureas.

Hydroxyphenylureas are the first main metabolites formed in the environment from pesticide and biocide urea compounds. Because fungi release potent exocellular oxidases, we studied the ability of laccases produced by the white rot fungus, T. versicolor, to catalyze in vitro the transformation of five hydroxyphenylureas, to identify transformation pathways and mechanisms. Our results establish that the pH of the reaction has a strong influence on both the kinetics of the reaction and the nature of the transformation products. Structural characterization by spectroscopic methods (NMR, mass spectrometry) of eleven transformation products shows that laccase oxidizes the substrates to quinones or to polyaromatic oligomers. Slightly acidic conditions favor the formation of quinones as final transformation products. In contrast, at pH 5-6, the quinones further react with the remaining substrate in solution to give hetero-oligomers via carbon-carbon or carbon-oxygen bond formation. A reaction pathway is proposed for each of the identified products. These results demonstrate that fungal laccases could assist the transformation of hydroxyphenylureas.

Chlorine Compounds↗
PubMed2006

Modulation of p53 transcriptional activity by PRIMA-1 and Pifithrin-alpha on staurosporine-induced apoptosis of wild-type and mutated p53 epithelial cells.

We recently argued for a major role of p53 in staurosporine(ST)-induced apoptosis of immortalized epithelial cells, depending on their p53 status. Here, we studied the effects of PRIMA-1 (p53 reactivation and induction of massive apoptosis) and Pifithrin-alpha (p fifty-three inhibitor) in combination with ST to reinforce our previous results by respectively restoring or inhibiting the p53 transcriptional activity in different cell lines.PRIMA-1 does modify neither expression of apoptosis-related proteins nor the percentage of wild-type p53 HeLa and CaSki cells with [symbol: see text]delta psi m and DNA cleavage, whilst it increases by 45% Bax expression and apoptosis of mutated p53 C33A cells. Pifithrin-alpha, does modify neither Bax expression nor apoptosis level of C33A cells, but readily inhibits both [symbol: see text]delta psi m and DNA fragmentation of p53wt cells with decreasing Bax expression. These data support the evidence that PRIMA-1 could be a good candidate, as an anti-cancer drug targeting mutant p53, in order to increase ST efficiency. Moreover, Pifithrin-alpha could be used in combination with ST and PRIMA-1 to prevent side effects of anti-tumor therapies in cells expressing mutant P53.

Apoptosis↗
PubMed2005

Shifting the optimal pH of activity for a laccase from the fungus Trametes versicolor by structure-based mutagenesis.

Laccases are oxidizing enzymes of interest because of their potential environmental and industrial applications. We performed site-directed mutagenesis of a laccase produced by Trametes versicolor in order to improve its catalytic properties. Considering a strong interaction of the Asp residue in position 206 with the substrate xylidine, we replaced it with Glu, Ala or Asn, expressed the mutant enzymes in the yeast Yarrowia lipolytica and assayed the transformation of phenolic and non-phenolic substrates. The transformation rates remain within the same range whatever the mutation of the laccase and the type of substrate: at most a 3-fold factor increase was obtained for k(cat) between the wild-type and the most efficient mutant Asp206Ala with 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic) acid as a substrate. Nevertheless, the Asn mutation led to a significant shift of the pH (DeltapH = 1.4) for optimal activity against 2,6-dimethoxyphenol. This study also provides a new insight into the binding of the reducing substrate into the active T1 site and induced modifications in catalytic properties of the enzyme.

Amino Acid Sequence↗
PubMed2005

Dynamics of HPV16 DNA load reflect the natural history of cervical HPV-associated lesions.

BACKGROUND: High burden of high risk human papillomavirus (HR HPV) has been shown to be predictive for the development of high grade cervical lesions and invasive cancers. However, low viral load cannot inevitably exclude progression towards cervical diseases. Moreover, few studies addressed whether viral load could predict infection clearance. OBJECTIVES: We carried out a retrospective study to analyze the variations of HPV16 load over time as a predictive marker of clinical outcome. STUDY DESIGN: The population consisted of 38 women who were found HR HPV positive by HCII test at study entry. Among them, 13 had developed a CIN2/3 (cases) and 25 had a negative HCII test and a normal cytology (controls) at study exit. The HPV16 DNA loads were quantified in 132 longitudinal cervical samples using quantitative real-time PCR. RESULTS: At study entry, the median of HPV16 load was not statistically different between controls and cases. However, when using a cut-off value of 200 copies/10(3) cells, the rate of cumulative incidence of CIN2/3 at 18 months increased from 14% in women with a load 200 copies/10(3) cells. The longitudinal analysis performed on follow-up samples showed that in cases the progression to CIN2/3 was linked to HPV16 burden increasing over time, whereas in controls a decrease of at least 1 log HPV16 DNA load was observed over>or=2 time points. CONCLUSIONS: These results show that kinetics of HPV load, rather than a single HPV detection, might be more reliable to estimate whether a HPV infection will progress or be cleared.

Adolescent↗
PubMed2005

Circulating vascular endothelial growth factor in cutaneous malignant melanoma.

BACKGROUND: Angiogenesis has been reported as a parameter of potential prognostic value in solid tumours, as it may facilitate tumour growth and metastasis. One of the most important growth factors involved in angiogenesis is vascular endothelial growth factor (VEGF). OBJECTIVES: To determine the predictive value of circulating VEGF levels in a cohort of patients with melanoma. METHODS: In a prospective cohort study, 324 patients with cutaneous melanoma at different clinical stages were investigated over 2 years (2002-04). VEGF was measured in plasma using enzyme-linked immunosorbent assay. Two hundred and eight patients were able to be followed up for progression of their disease and for blood sample collection (mean +/- SD follow-up 13.4 +/- 0.8 months). Data were compared with the extent of the disease and the clinical course. RESULTS: A significant increase in plasma VEGF levels was found in patients with melanoma compared with healthy controls, with statistically significant differences between patients in stages I, II and III vs. those in stage IV, but not between patients in stages I, II and III. When considering the 237 patients in stages I and II, no statistical correlation was found between plasma VEGF levels and tumour thickness. Baseline plasma VEGF levels were not significantly higher in patients who relapsed compared with nonprogressing patients. Among the 35 patients (two stage I, eight stage II and 25 stage III) who experienced a progression during follow-up, an increase in plasma VEGF level to > 100 pg mL(-1) was found in 20 (sensitivity 57.1%), while 38 of the 173 remaining nonprogressing patients demonstrated an increase in VEGF level, indicating a specificity of 78%. In addition, an increase in plasma VEGF level was found in 58 patients during follow-up, of whom 20 showed evidence of progression, indicating a positive predictive value of 34.5%. However, among the 150 remaining patients who did not demonstrate any increase in plasma VEGF level during follow-up, only 15 experienced a progression, indicating a negative predictive value of 90%. CONCLUSIONS: Our data confirm that blood VEGF levels are significantly increased in patients with melanoma and, more interestingly, that the absence of plasma VEGF level increase during follow-up appears to be associated with remission.

Disease Progression↗
PubMed2004

Detection of cervical precancer and cancer in a hospital population; benefits of testing for human papillomavirus.

The aim was to determine the relevance of human papillomavirus (HPV) testing in identifying high-grade cervical intraepithelial neoplasia or worse (CIN2/3+) in a hospital population (n=3574) characterised by a high rate of cytological abnormalities and high-risk HPV infections. According to the results of the initial Papanicolaou and HPV test, women were directly referred for colposcopy/biopsy or recalled for a control visit. Sensitivity and specificity were corrected for verification bias. HPV-testing sensitivity was 94.3%, higher than that of cytological testing at any cut-off point (65.1%-86.8%), while specificity was greater for cytology than for HPV testing (99.3% or 91.8% versus 83.4%). The combination of both tests allowed 100% sensitivity and negative predictive value. We conclude that HPV testing is a relevant tool for the detection of cervical disease. The best way of combining cytology and HPV detection in screening programmes should be evaluated in large-scale studies.

Adolescent↗
PubMed2004

[Effects of imiquimod on latent human papillomavirus anal infection in HIV-infected patients].

INTRODUCTION: High risk human papillomaviruses (HPV) have emerged as risk factors for anal carcinoma particularly in HIV-infected patients who demonstrate a high rate of anal HPV infection. Considering the relationship between the presence of anal infection and the development of neoplastic lesions, we wished to assess the capacity of imiquimod to eradicate latent HPV infection in HIV-infected patients. PATIENTS AND METHODS: We conducted a prospective, randomized, double-blind and vehicle controlled study. Two consecutive anal swabs were taken at 2 month intervals and only patients with two consecutive tests positive for the detection of HPV-DNA (Hybrid Capture II) were included. Patients with persistent latent HPV infection were divided into 2 groups who applied imiquimod versus vehicle during 6 weeks. HPV-DNA presence was then investigated 2 and 4 months following the onset of treatment. RESULTS: Among the 80 HIV-infected patients, 26 (32.5 p. 100) had 2 positive consecutive assays, and 19 patients were included in the study. After randomization, 9 patients received imiquimod and 10 vehicle. There was no significant difference between treatment groups according to the following criteria: gender, route of HIV transmission, CDC stage, prior medical history of sexually transmitted diseases or anogenital warts. 33.3 p. 100 (3/9) of patients treated with imiquimod were negative at M2, whereas 100 p. 100 (10/10) vehicle treated-patients remained positive (p=0.08). Similar results were observed at the M4 visit. DISCUSSION: Our study confirmed the increased prevalence of latent HPV-DNA infection in HIV-infected patients. In spite of the low number of treated patients, we did not observe a statistically significant decrease in HPV-DNA in anal swabs from imiquimod-treated patients as compared to placebo-treated patients.

Adjuvants, Immunologic↗
PubMed2004

Mitochondrial translocation of p53 and mitochondrial membrane potential (Delta Psi m) dissipation are early events in staurosporine-induced apoptosis of wild type and mutated p53 epithelial cells.

The mitochondrial localization of p53 is an important event in p53-dependent apoptosis. Some p53 mutants defective for transcription also facilitate apoptosis through changes of the mitochondria. Here, apoptosis of HeLa and CaSki cells (p53(wt)), C33A and HaCat cells (p53(mt)) and SaOs-2 cells (p53 deficient) was induced by 300 nM staurosporine. We showed that wild-type p53, as well as p53 mutants, were transiently located to the mitochondria with changes in the mitochondrial membrane potential (Delta Psi m). However, in C33A cells harboring a p53 mutated on its DNA binding domain, Delta Psi m collapse and Sub-G1 DNA content were reduced compared to p53(wt) cells, whereas no significant difference was observed in HaCat cells with a p53 mutated on UV hot spots. In addition, inhibition of the mitochondrial permeability transition pores by cyclosporine A significantly reduced the Delta Psi m loss and the sub-G1 DNA content in p53 positive cells. These results indicate that Delta Psi m collapse is an early and necessary event, which plays an important role in apoptosis of immortal mammalian cells.

Apoptosis↗
PubMed2004

High-risk papillomavirus infection is associated with altered antibody responses in genital tract: non-specific responses in HPV infection.

In order to gain more information about local humoral immune responses to HPV infection, we quantified IgG, IgM, secretory-IgA (S-IgA), and total-IgA by ELISA, and lysozyme and lactoferrin by TR-IFMA, in cervical and cervicovaginal secretions of 40 healthy women and 28 high-risk HPV infected patients (11 were HPV16+). IgG, total-IgA, and S-IgA concentrations in cervicovaginal secretions (p < 0.0001) and high IgG and total-IgA concentrations (p < 0.001 and p < 0.01, respectively) in endocervical secretions were significantly higher in HPV+ patients than in the healthy group. Since the S-IgA/total-IgA ratio was significantly lower in cervicovaginal (7.5%) and endocervical secretions (36.5%) in HPV+ women compared to the control group (p < 0.003 and p < 0.001, respectively), HPV could be responsible for an increase in local production of non-secretory IgA (monomeric and dimeric forms). IgG and total-IgA concentrations in cervicovaginal and endocervical secretions fell in the same general percentage range in both HPV16+ and HPV+ groups (80% and 15%, respectively). However, the S-IgA/total-IgA ratio was much lower in HPV16+ than in HPV+ women, in both cervicovaginal secretions (3.4%) (p < 0.003) and in endocervical secretions (23.3%) (p < 0.001). Innate immunity proteins and local S-IgA response could not stop the spread of HPV infection in spite of high lysozyme and lactoferrin concentrations. HPV16+ disturbed the local humoral immune system, which could partly explain its low clearance.

Adolescent↗
PubMed2003

Detection of the human papillomavirus and analysis of the TP53 polymorphism of exon 4 at codon 72 in penile squamous cell carcinomas.

Human papillomaviruses (HPV) are thought to be involved in penile squamous cell carcinomas (SCC). A common polymorphism at codon 72 of exon 4 encoding either arginine (Arg) or proline (Pro) has been shown to affect HPV-mediated degradation of p53 in vitro, and may represent a risk factor for HPV-induced carcinogenesis. The presence of HPV DNA as well as the TP53 polymorphism at codon 72 of exon 4 were investigated in a series of 45 penile SCC. HPV detection and typing were carried out by polymerase chain reaction (PCR) with generic primers (MY09-MY11 and FAP59-FAP64), and type-specific DNA probes. TP53 polymorphism was further investigated using Denaturing Gradient Gel Electrophoresis (DGGE). HPV DNA was detected in 67% of penile SCC and 32% of benign lesions (BL) (P<0.05). Among the TP53 amplified samples, the rate of Arg homozygosity in penile SCC was 61% compared with 68% in BL (non-significant (NS)). Our results demonstrate a strong association between penile SCC and the presence of HPV DNA. The TP53 Arg/Arg genotype does not appear to represent a risk factor for the development of genital SCC in men, and no correlation was found between the TP53 polymorphism at codon 72 and the presence of HPV DNA.

Adult↗
PubMed2003

[Carbon dioxide laser vaporization of genital condyloma in pregnancy].

OBJECTIVE: To evaluate therapeutic effectiveness of the carbon dioxide laser on genital condyloma in pregnancy. PATIENTS AND METHODS: From 1998 to 2002, 18 pregnant women with genital condyloma were treated with laser vaporization. Treatment was given without regard to the gestational period. All the women were treated at least once. Condyloma localisation, treatment gestational age and complication rate were analysed. RESULTS: Patients were treated at a gestational age of 15-38 weeks. During pregnancy follow-up, 2 patients had recurrences that required repeated treatment before delivery. In each case, no condylomas were found during delivery. There were no abortions, no premature birth and no complications (bleeding, infections) in our study. CONCLUSION: Laser vaporisation is a safe and effective treatment for condyloma during pregnancy.

Carbon Dioxide↗
PubMed2003

Apoptosis participates to liver damage in HSV-induced fulminant hepatitis.

BACKGROUND: HSV fulminant hepatitis is a rare pathology. Rapid hepatic failure, as a consequence of extended liver damage, has generally been attributed to necrosis. As apoptosis can constitute another way for hepatocytes to die, we decided to investigate whether programmed cell death took place during HSV fulminant hepatitis. METHODS: Liver sections were obtained from two cases of fulminant herpetic hepatitis as well as from hepatitis B virus and Rickettsia-infected livers. Herpes simplex virus infection was confirmed using in situ hybridization. Apoptosis was assessed by histopathological examination, p53, activated-caspase 3 and Fas immunohistochemistry and TUNEL labeling. RESULTS: We report that the number of cells expressing activated-caspase 3 was largely increased in fulminant herpes simplex virus hepatitis, when compared to livers chronically infected by hepatitis B virus or from a Rickettsial acute hepatitis. Apoptosis of hepatocytes was confirmed by a positive double-staining for activated-caspase 3 and hepatocytes. Finally, the apoptotic process has progressed beyond the step of nuclear DNA cleavage as demonstrated by TUNEL labeling. CONCLUSION: These data as a whole show that apoptosis is responsible, at least partially, for liver damage during HSV fulminant hepatitis.

Apoptosis↗
PubMed2003

[Non-melanoma skin cancers and human papillomavirus].

Ultraviolet radiation (UV) is considered as a key environmental risk factor of non-melanoma skin cancer (NMSC), but other factors such as immunological status, genetic predisposition and infection by human papillomavirus (HPV) may also be involved. Although there is overwhelming epidemiological and molecular evidence that indicates a direct role for specific mucosal HPV-types in anogenital cancers, in particular cervical cancer, the pathogenic role of HPV in the development of NMSC remains speculative. The association between HPV and NMSC was first identified in patients with epidermodysplasia verruciformis (EV) and later in recipients of organ transplants. All these patients develop NMSC at sun-exposed sites. Cutaneous and mucosal HPV-DNA have been detected in about 60 to 90 p. 100 of NMSC, but also in benign epithelial lesions, and even in normal skin. However and although at a lower rate (about 40 p. 100), HPV-DNA have also been detected in normal skin, in particular in hair follicles, and in premalignant lesions and in NMSC from non-EV and immunocompetent subjects. Furthermore, no particular HPV type predominates and the viral load in NMSC seems lower than in benign epithelial lesions. Although all these findings argue against a direct involvement of HPV in NMSC, they may suggest a "hit and run" mechanism which no longer requires the viral agent but the activity of HPV oncoproteins. High risk mucosal HPV-types encode two major oncoproteins, E6 and E7, which inactivate two suppressor proteins, p53 and pRb respectively, and are sufficient for host-cell immortalization. A polymorphism resulting in either a proline or an arginine at codon 72 may also be a relevant risk factor for mucosal HPV-types-associated NMSC. By contrast, E6 of skin HPV-types fails to interact with p53, but prevents infected cells from UV-induced apoptosis leading thus to the propagation of deleterious UV-induced mutations. Immunosuppressive activities of HPV E6 and E7 proteins permit persistent HPV infection and the impairment of immunologic removal of UV-damaged cells. These results support a role for HPV infection in skin carcinogenesis as a co-factor in association with UV and immunosuppression.

Apoptosis↗
PubMed2002

[Epidemiology and natural history of genital infection by human papillomavirus].

Human papillomavirus genital infection is a very common sexual transmitted disease, probably the most common of them. On one hand, this infection is more often than not transient and asymptomatic and induces an effective immunity which allows the infection cure; on the other hand it can be responsible for an intraepithelial lesion which can progress to an invasive cancer. In spite of the decrease of cervical cancer incidence thanks to Pap smear screening, it remains a real preoccupation for clinicians. If HPV is not sufficient for cervical carcinogenesis, it represents however a necessary factor. Near 100% of cervical cancers are indeed positive in HPV DNA. HPV infection is very frequent in young people aged less than 25 years and viral clearance average is 8 months. This clearance is the consequence of host immunity intervention which leads to spontaneous regression of infection and of the overwhelming majority of low grade squamous intraepithelial lesions (more than 80% within a period of two years). The major factor which permits the progression to high grade squamous intraepithelial lesions is the persistent feature of HPV infection. Cervical cancer is clearly the first viral-induced solid tumor discovered in human species. Furthermore it represents a woman death cause that can be avoided.

Adult↗
PubMed2002

Relationship between expression of genes involved in cell cycle control and apoptosis in diffuse large B cell lymphoma: a preferential survivin-cyclin B link.

Accumulating evidence suggests that lack of balance between proliferation and apoptosis may lead to clonal expansion and cancer emergence. In diffuse large B cell lymphoma (DLBCL), survivin expression by tumor cells has been recently described as a poor prognostic marker. We assessed the relationship between survivin gene up-regulation and several other factors involved in either cell cycle or apoptosis control. The expression of 34 genes from 27 cases of DLBCL with typical IPI factor-related poor prognostic outcome was analyzed by RNase protection assay. Using non-neoplastic tissues and low grade lymphomas as control, survivin expression was high in 80% of the cases without significant relation to patient overall survival (P = 0.64). However, the expression of several genes encoding for cell cycle inhibitors, cyclins, Bcl-2 or IAP family factors was significantly associated with the survivin up-regulation. Gene expression profiling showed that both survivin and cyclin B expression can define two subgroups of DLBCL: the previously described germinal center-like and activated B-like lymphomas, determined by protein expression analysis. We also identified a preferential survivin-cyclin B relationship (P = 0.017), suggesting that cyclin B over-expression, when linked to survivin over-expression in aggressive forms of lymphoma, might demonstrate a specific G2/M transition promotion.

Adolescent↗
PubMed2002

Validation of a high sensitive immunoenzymatic assay to establish the origin of immunoglobulins in female genital secretions.

Several studies were carried out to characterize the humoral immune response on mucosal genital surfaces. However, the results obtained so far were particularly conflicting due to the absence of validation methods. The aim of this study was to develop and validate a quantitative ELISA method, which is sensitive and reproducible, to measure immunoglobulin and secretory immunoglobulin concentrations in various biological fluids. This quantitative, sensitive (detection limit = 1 microg/L) and reproducible (coefficient of variation < 15%) method could be of interest to study the effects of viral infections on mucosal non-specific immune response in genital tract. To explore the humoral response, serum, saliva, vaginal secretions, and cervicovaginal secretions from 18 women, 20-45 years old, were evaluated for total-IgA, secretory IgA, IgM, and IgG. Albumin level was also evaluated by immuno-nephelometry. The secretion rates of immunoglobulins were measured by calculating their relative coefficients of excretion by reference to albumin. Despite large individual variations, median immunoglobulin levels were higher in the endocervical secretions than in the cervicovaginal secretions. When we compared the rates of immunoglobulins in genital fluids, IgG prevalence was higher (80%) in cervicovaginal and endocervical secretions than IgA prevalence (12%). In contrast, digestive mucosal secretions, such as saliva, contained mostly IgA (80%). In cervicovaginal and endocervical secretions, IgG and IgM originated mainly from serum, whereas a local synthesis provided total-IgA and secretory IgA. These results allowed us to raise a possible hypothesis for the origin of immunoglobulins in the genital tract. They illustrated the peculiar feature of the female reproductive tract and the difficulty for this tissue to contribute in the mucosal associated lymphoid tissue. The low secretory-IgA and total-IgA levels could explain the particular sensitivity of the vagina and the cervix to infections.

Adolescent↗
PubMed2001

c-myc box II mutations in Burkitt's lymphoma-derived alleles reduce cell-transformation activity and lower response to broad apoptotic stimuli.

In addition to c-myc rearrangement, over 50% of Burkitt's lymphoma cases present clustered mutations in exon 2, where many of the functional activities of c-Myc protein are based. This report describes the functional consequences induced by tumour-derived c-myc mutations located in c-myc box II. Two mutated alleles were studied, focusing on the P138C mutation, and compared to wild-type c-myc. The c-Myc transformation, transactivation and apoptosis activities were explored based on cells over-expressing c-Myc. While the transcriptional activation activity was not affected, our experiments exploring the anchorage-independent growth capacity of c-Myc-transfected Rat1a cells showed that c-Myc box II mutants were less potent than wild-type c-Myc in promoting cell transformation. Considering the possibility that these mutations could be interfering with the ability of c-Myc to promote apoptosis, we tested c-Myc-transfected Rat1a fibroblasts under several conditions: serum deprivation-, staurosporine- and TNFalpha-induced cell death. Interestingly, the mutated alleles were characterized by an overall decrease in ability to mediate apoptosis. Our study indicates that point mutations located in c-Myc box II can decrease the ability of the protein to promote both transformation and apoptosis without modifying its transactivating activity.

Alleles↗