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Biomedical subjects

J M Vignaud

Publications and source records attributed to J M Vignaud.

At least 19 recordsLinked to original sources
PubMed2002

Clinical factors influencing the eosinophil infiltration of nasal polyps.

AIMS AND METHODS: Our study, based on a retrospective chart analysis, was aimed 1) to describe the varying degree of eosinophil infiltration in a series of 263 adult patients operated on diffuse and bilateral nasal polyposis (NPS) after failure of medical treatment, in 15 cystic fibrosis patients with bilateral nasal polyps, and in 31 patients with chronic sinusitis without polyps (18 bilateral, 13 unilateral) 2) to search for clinical factors that might influence the degree of eosinophil infiltration. Eosinophil infiltration was expressed semi-quantativity as a percentage of inflammatory cells. RESULTS: Our study confirms that eosinophil infiltration is a striking feature of nasal polyposis. All patients with chronic sinusitis showed less than 10% eosinophils (mean +/- SEM = 2 +/- 2%) whereas 88% of patients with NPS showed more than 10% eosinophils (50 +/- 2%). Cystic fibrosis lied in between with 40% of patients showing more than 10% eosinophils. In idiopathic bilateral NPS the number of eosinophils was increased in patients with asthma (58 +/- 3%) and even more in Widal's triad (75 +/- 4%). Atopic patients did not have more eosinophils (52 +/- 5%). Patients treated with systemic steroids within two months before surgery showed decreased eosinophil infiltration (22 +/- 3% vs 50 +/- 2 for treated versus untreated) whereas patients treated with topical steroids did not (47 +/- 2%). CONCLUSIONS: Thus, a link might exist between clinical presentation and eosinophil infiltration. Chronic sinusitis and nasal polyps are probably not the same disease. Eosinophils appear as a link between nasal polyps, asthma and aspirin intolerance. Atopic status does not modify eosinophil infiltration of nasal polyps. Systemic steroids appear significantly more effective to reduce the eosinophil infiltrate than topical steroids in our selected group of operated patients.

Adolescent↗
PubMed2001

Efficacy of external fractionated radiation therapy in the treatment of meningiomas: a 20-year experience.

BACKGROUND: This is a retrospective analysis of a series of meningiomas treated by radiotherapy. MATERIALS AND METHODS: From 1978 to 1997, 45 patients with intracranial meningiomas were referred for external fractionated radiotherapy at Centre Alexis Vautrin. All patients were given 50-70Gy to the tumor bed (median: 56Gy), 1.8-2Gy per fraction. RESULTS: Evaluation was performed in June 1999 using the Kaplan-Meyer actuarial method with a median follow-up of 30 months (range: 1-166), relapse-free survivals (RFSs) were 75% at 5 years and 67% at 8 years; overall survival (OS) was 74% at 5 and 8 years. For the 26 benign histologically documented lesions, RFSs were 95% at 5 years and 81% at 8 years; OS was 85% at 5 and 8 years. One major radiation-induced complication occurred in this series (decline of cognitive function). According to the indication of radiotherapy, we divided the series into four groups: postoperative irradiation after a first subtotal resection (11 patients), 5-year RFS was 90%; after first recurrence (+/-salvage surgery, 14 patients), 73%; after further recurrence (+/-salvage surgery, 11 patients), 67%; as exclusive treatment (nine patients), 80%. Atypical and malignant lesions (n=7) all relapsed before 24 months of follow-up, all patients but one died before 42 months. Age at the time of irradiation (> or =60 vs. <60 years) and radiotherapy dose (> or =60 vs. <60Gy) did not influence local control or OS. Atypical and malignant lesions (WHO grades II and III) meningiomas had a worse outcome than benign lesions (WHO grade I, P<0.01). CONCLUSIONS: These results compare favorably with previously published data. External fractionated radiotherapy is well tolerated and effective. There is still a debate about the place of radiotherapy in the treatment of meningiomas: after subtotal resection, should radiotherapy be given postoperatively or at the time of progression? Should radiotherapy replace surgery when the risk of postoperative sequellae is high? Prospective randomized trials would be required to address these issues.

Adult↗
PubMed2001

Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma.

Vascular endothelial growth factor (VEGF) is a potent stimulator of endothelial cell proliferation. It has been implicated in tumor growth of human thyroid carcinomas. Using the VEGF immunohistochemistry staining score, we correlated the level of VEGF expression with the metastatic spread of 19 cases of thyroid papillary carcinoma. The VEGF immunostaining score, ranging from 0-9, was determined as the multiplication of a percentage of labeled thyrocytes score (0, no labeling; 1, <30%; 2, 31--60%; 3, >61% of labeled thyrocytes) and an intensity score (0, no staining; 1, weak; 2, mild; 3, strong staining). The mean score +/- SD was 5.74 +/- 2.59 for all carcinomas. The mean score for metastatic papillary carcinoma was 8.25 +/- 1.13 vs. 3.91 +/- 1.5 for nonmetastatic papillary cancers (P < 0.001). By discriminant analysis, we found a threshold value of 6.0, with a sensitivity of 100% and a specificity of 87.5%. There were no statistical differences between metastatic and nonmetastatic carcinomas when age, tumor size, or thyroglobulin levels were considered. The VEGF immunostaining score seems to be a helpful marker for metastasis spread in differentiated thyroid cancers. An increased production of VEGF could assess an aggressive disease and be the hallmark of a trend to produce metastasis. We propose the VEGF immunostaining score as a marker for the prognosis in differentiated thyroid cancers. A value of 6 or more, should be considered as at high risk for metastasis threat, prompting the physician to institute a tight follow up of the patient.

Adolescent↗
PubMed2001

[Chemoprevention perspectives for bronchial cancer].

Lung cancer, with a high incidence and a 14% survival rate at 5 years is the leading cause of death in France. Because of past and present smoking habits in the French population and the lack of real expectations for significant therapeutic progress within a short or mid-term delay, the only reasonable way to try to limit the predictable hecatomb in the next 2 decades is to reduce exposure to the main risk factors (tobacco smoke, asbestos.), implement an early and effective (radiographic and/or endoscopic) screening system, and/or determine an active chemoprevention scheme. The principle of chemoprevention is based on the fundamental concept that since lung cancer develops through several stages, subjects exposed to risk factors could be given a compound or compounds counteracting the deleterious effect of carcinogenic substances on DNA and/or blocking the subsequent cascade of molecular events. Two families of products have been considered as potential chemoprevention agents: antioxidants (selenium, beta-caroten, vitamin E, and N-acetyl-cystein) and vitamin A and its analogs. Unfortunately, despite promising experimental data, large-scale clinical trials have not evidenced any protective effect of these compounds that have even been observed to produce opposing effects. To date, no chemopreventive substance can be reasonable proposed for subjects at risk. Due to the lack of proof of the efficacy of the different screening systems proposed, the only preventive action with proven efficacy is to limit exposure to risk factors. All health care givers must actively participate in the fight against active and passive smoking.

Antioxidants↗
PubMed2000

Retinoic acid receptor and retinoid X receptor alterations in lung cancer precursor lesions.

Smoking prevention will decrease lung cancer incidence in time. However, early detection would improve lung cancer prognosis in subjects at risk provided that specific markers could be identified. We previously reported that retinoic acid receptor (RAR) and retinoid X receptor (RXR) expression was altered in lung tumors. RAR-beta gene status could be derived from corresponding allelotyping and immunohistochemistry data. We now report the continued study on lung cancer precursor lesions. Fluorescence PCR-based assays were used for allelotyping at the RAR/RXR loci of: (a) 66 lung precursor lesions found at the free resection margins of 41 patients undergoing surgery for lung cancer (+ 31 paired tumors); and (b) bronchial cells also found at the free resection margins from 16 current and 8 never smokers operated on for noncancerous diseases. Three microsatellites located at 3p14-21 and 9p21 were also used for interwork comparison. Immunohistochemistry was additionally performed to evaluate P53 and RAR-beta expression in precursor lesions. Chi2 tests showed significant differences (P < 0.05) when comparing the results obtained from never smokers, smokers, squamous metaplasia, dysplasia + in situ carcinoma, and tumors. Microsatellite changes occurred frequently in all samples, but without specificity for any group (P < 0.08-0.52). They were globally correlated with tobacco exposure (P < 0.04), for which the RAR-gamma marker appeared as a preferential target (P < 0.004). Few reparation error phenotypes were observed, mostly at the RXR-alpha and RXR-gamma markers for which combined changes were also linearly increasing from never smokers to dysplasia + in situ carcinoma (P < 0.05 and P < 0.03). RAR-beta marker losses also increased from the first to the last group studied (P < 0.01), with a concomitant decrease in RAR-beta protein expression and correlated p53 increased immunoreactivity (P < 0.02). Losses at 3p14, 3p21, and P16 were frequent, but no significant differences between groups could be found. Unexpectedly, high constitutive homozygosity was observed near the RAR-alpha locus in squamous cell lung cancer cases. RARs/RXRs form homodimers or heterodimers involved in ligand binding. Their added alterations could result in a state of functional vitamin A deficiency in the affected bronchial cells. Further deletion events drawn from a limited repertoire of specific regions such as 3p14-21 and 9p21 could subsequently drive the deficient cells to invasive carcinoma.

Alleles↗
PubMed2000

Predictive survival markers in patients with surgically resected non-small cell lung carcinoma.

Among patients with resected non-small cell lung carcinoma, about 50% will present a tumor recurrence. Thus, it would be of major importance to be able to predict and try to prevent these relapses by an active chemotherapy and/or radiotherapy. In an attempt to answer this question, the tumors of 227 patients with a surgically resected non-small cell lung carcinoma were evaluated as follows: tumors were classified as squamous cell carcinoma (n = 132) or adenocarcinoma (n = 95), and tumor differentiation was evaluated for each type. Then, all tumors were classified in respect to their pathological TNM staging (WHO) and screened by immunohistochemistry for the detection of the expression of the following antigens: Bcl-2, A+B+H blood group antigens, c-erb-b2, p53, and Pan-Ras antigens. Furthermore, adenocarcinomas were screened for the presence of point mutations in Ki-Ras codons 1-31. Finally, the patient blood group was defined, and patient survival was analyzed using nonparametric tests and proportional hazard Cox models. Using Kaplan-Meier survival curves, disease pathological TNM staging was shown to be a strong predictive factor of survival for both squamous cell carcinoma and adenocarcinoma. Patients with squamous cell carcinoma experienced fewer relapses than those with adenocarcinoma (42% versus 63%; P = 0.0002) and had a significantly better survival. All evaluated antigens were more often present in squamous cell carcinoma than in adenocarcinoma except for Pan-Ras (three times more frequent in adenocarcinoma). In patients with squamous cell carcinoma, only tumor staging had a significant prognosis value (P = 0.01). In patients with lung adenocarcinoma, a well-differentiated tumor (P = 0.009) as well as a positive Bcl-2 staining (P = 0.009) and an A+B+H antigen tumor staining (P = 0.024) were associated with a better survival. In contrast, patients with a stage I or II disease and a p53-positive tumor staining and patients with the O blood group (P = 0.01) had a shorter survival. Interestingly, no relation with patient survival was related to c-erb-b2 and Pan-Ras staining. Finally, 12 point mutations were found out of 81 tumors (15%) evaluated for Ki-Ras codons 1-31; they involved codon 12 but also 8, 14, and 15 without any relationship to survival. In respect to lung adenocarcinoma, using Cox proportional hazard models stratified on tumor staging, the following markers were shown to be related to survival: (a) Independent markers of longer survival (ie., high histological degree of tumor differentiation and positive Bcl-2 and A+B+H blood group antigen expression by tumor cells); and (b) Independent markers of shorter survival (i.e., O blood group for all patients and p53 tumor staining in patients with stage I and II diseases). This study suggests that, in patients who undergo surgery for lung adenocarcinoma, the presence or absence of these criteria could be used to define a subset of patients who may benefit from a more specific follow-up.

ABO Blood-Group System↗
PubMed1999

Expression of retinoid receptor genes and proteins in non-small-cell lung cancer.

BACKGROUND: Retinoids can suppress carcinogenesis in high-risk non-neoplastic bronchial lesions and can reduce the risk of second primary non-small-cell lung cancer (NSCLC). The effects of retinoids are mediated by nuclear receptors, i.e., the retinoic acid receptors (RARalpha, RARbeta, and RARgamma) and the retinoid X receptors (RXRalpha, RXRbeta, and RXRgamma). We investigated whether abnormalities in the in vivo expression of retinoid receptors are observed in NSCLC. METHODS: Expression of retinoid receptors in paired specimens of normal and cancerous tissues from the lungs of 76 patients with NSCLC was studied by use of antiretinoid receptor antibodies (except those against RXRgamma) and immunohistochemistry. RAR messenger RNAs were analyzed by use of in situ hybridization and by reverse transcription-polymerase chain reaction (RT-PCR). Samples were also studied for loss of heterozygosity (LOH) at chromosome 3p24. All P values are two-sided. RESULTS: All studied receptors were expressed in normal lung cells and in high- risk non-neoplastic lesions. In tumor cells, overexpression of RXRalpha and RARalpha was frequently observed. In contrast, RXRbeta expression decreased in 18% of the tumor specimens. Furthermore, there was a marked decrease in the expression of RARbeta in 63% of the tumors (P<.0001). Decreased expression of RARgamma was observed by RT-PCR in 41% of the tumors (P<.0001). LOH at 3p24 was observed in 41% of the tumor specimens from informative patients and in 20% of the non-neoplastic lesions. CONCLUSIONS: Expression of RARalpha and RXRalpha is either normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease in the expression of RARbeta, RARgamma, and RXRbeta as well as a high frequency of LOH at 3p24, which was also observed in non-neoplastic lesions. These data suggest that altered retinoid receptor expression may play a role in lung carcinogenesis.

Aged↗
PubMed1999

Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma.

Angiogenesis is implicated in several pathological conditions, such as inflammation and tumor growth. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent stimulator of endothelial cell proliferation in vitro and in vivo. The present work aimed to compare VEGF expression in human normal thyroid glands, thyroiditis tissue and thyroid carcinomas using immunohistochemistry and in situ hybridization (ISH). Both chronic lymphocytic thyroiditis and differentiated thyroid carcinomas were found to strongly express VEGF mRNA and encode larger amounts of VEGF than normal thyroid tissue as attested by a VEGF immunostaining score. In addition, tumor samples from patients with metastases showed a higher immunostaining score than their non-metastatic counterparts (P<0.05). Carcinomas with the greatest contents of VEGF mRNA and VEGF protein had the most intense mitogenic activity. Special focus on endothelial cells showed intense mitogenic activity in neoplastic tissues in contrast to the total quiescence of endothelial cells in non-tumoral tissues. An intense VEGF production by differentiated thyroid carcinoma, attested either by a higher immunostaining score or a strong VEGF mRNA expression using ISH, could be a promising marker of tumor aggressiveness and may also be useful as a predictor of metastatic potential.

Adult↗
PubMed1998

[Lipoma of the internal auditory canal. Report of two cases simulating acoustic neuroma].

We report two cases of intra-auditory canal lipoma, presenting as acoustic neuroma, observed in respectively 45 and 53 year old patients. Cerebellopontine angle lipomas are unusual lesions, more exceptional than their intracranial counter-parts. The knowledge of these tumoral lesions and of their close relationships with cranial nerves incite to perform a frozen section when imagery is evocative, to limit functional postoperative sequelae.

Diagnosis, Differential↗
PubMed1997

Identification of human complement factor H as a chemotactic protein for monocytes.

We used chromatographic separation to purify to homogeneity a monomeric monocyte chemotactic protein of 150 kDa contained in mesothelioma pleural effusions. It was identified by N-terminal amino acid sequencing and immunoblotting as complement factor H, an inhibitor of the alternative complement pathway. Specific antibodies against factor H inhibited the monocyte chemotactic activity of the purified protein, which was most active at 10 nM. Factor H is a restrictive factor of alternative complement pathway activation. The new chemotactic function assigned to factor H in recruiting monocytes to the mesothelioma site might contribute to malignant cell phagocytosis via the iC3b/complement receptor type 3 pathway. These functions link the humoral and cellular immune systems.

Amino Acid Sequence↗
PubMed1997

Human immunodeficiency virus type 1 in an unusual cystic lymphoepithelial lesion of the lung.

AIMS: We present the clinical and histopathological findings of an unusual pulmonary cystic lymphoepithelial lesion in an HIV sero-positive patient. METHODS AND RESULTS: The 32-year-old female patient developed two nodules in the vicinity of the right and left hila. Left upper lobectomy showed a 40-mm wide cystic lesion. The cyst wall was lined by a squamous epithelium and lymphoid tissue with a marked follicular hyperplasia and a prominent follicular cell dendritic network expressing HIV major core protein p24. CONCLUSIONS: The absence of an Epstein-Barr virus infected lymphoid population and monoclonal immunoglobulin gene rearrangement supported the benign nature of the lesion.

Adult↗
PubMed1997

[The PRINS technique. Aplication to the detection of X and Y chromosomes for follow-up of bone marrow allografts performed with an opposite sex donor].

The PRimed IN Situ synthesis is a method for rapid identification of chromosomes in metaphase or interphase on cytological preparations and frozen tissue sections, using oligonucleotide primers derived from chromosome specific subsets of repeated DNA families. PRINS technique is an alternative to fluorescence in situ hybridization, as sensitive as FISH but faster and more specific. This technique is potentially of great interest for pathologists involved in transplantation pathology or cytogenetic interphasic oncology.

Adult↗
PubMed1997

[Amplification of immunologic reactions using catalytic deposition at the reaction sites of tyramine derivatives. A decisive gain in sensitivity in immunohistochemistry and in situ hybridization].

In the catalyzed reporter deposition technique, horseradish peroxidase catalyzes the activation of conjugated phenolic compounds resulting in the covalent binding of the radicalized intermediates to electron rich moieties in the protein molecules present at the site of reaction. Comparing the biotinyl-, digoxigeninyl-, and fluoresceinyl-derivatives of tyramine and four immunohistochemical formats, we showed that the most sensitive detection system was that using biotinyl-tyramide and an immunohistochemical technique using a biotinylated secondary antibody followed by a streptavidin peroxidase. Amplification without background staining was obtained in most biotin rich tissues with digoxigeninyl-tyramide. With fluoresceinyl-tyramide, clear signal amplification was observed in the fluorescent microscope. Finally, when compared with standard methods, increased sensitivity was obtained with the fluorescent derivative for detection of hybridized sequences in interphase chromosomes.

Binding Sites↗