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Biomedical subjects

P Fouret

Publications and source records attributed to P Fouret.

At least 19 recordsLinked to original sources

Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers.

BACKGROUND: Non-small-cell lung cancer arising in never-smokers is usually of adenocarcinoma subtype. The oncogenic pathway of such tumors is poorly understood. To better define the biological characteristics of these tumors, we have compared the expression of a panel of epidermal growth factor receptor (EGFR)-related biomarkers in lung adenocarcinomas from smokers versus those in never-smokers. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed EGFR, pAKT, PTEN, Ki-67, p27 and hTERT expression in specimens from 190 patients with completely resected lung adenocarcinomas (43 never-smokers and 147 smokers). These analyses were performed on tissue microarrays. RESULTS: EGFR expression was higher in tumors from smokers (P < 0.01), while pAKT was overexpressed mainly in tumors from never-smokers (P = 0.01). As expected, the tumors from smokers presented a higher expression of Ki-67 and a more frequent loss of expression of p27 (P < 0.01). In a multivariate model, two biological factors (p27 and Ki-67) and two clinical factors (age and sex) showed independent significant correlation with never-smoking status. CONCLUSIONS: Lung adenocarcinomas in never-smokers have a very distinct immunohistochemical expression profile of EGFR-related biomarkers as compared with lung adenocarcinomas in smokers. High levels of EGFR and Ki-67 are observed in smokers, while never-smokers are characterized by high levels of pAKT and p27.

Adenocarcinoma↗

Tumour stage, node stage, p53 gene status, and bcl-2 protein expression as predictors of tumour response to platin-fluorouracil chemotherapy in patients with squamous-cell carcinoma of the head and neck.

The purpose of this study was to establish the relative contribution of tumour stage, node stage, p53 gene status, p53 expression, and bcl-2 protein expression to tumour response to platin-fluorouracil chemotherapy in 141 patients with squamous-cell carcinomas of the head and neck. Tumour response was measured at the primary site after three cycles of chemotherapy. Exons 2-10 and the coding part of exon 11 were sequenced on both strands. Bcl-2 or p53 expression was detected by immunohistochemistry. Predictor variables of objective response (reduction of at least 50% of tumour size) were tested in univariate and multivariate analyses. P53 mutations were found in 52 patients (37%). Tumour cells expressed p53 in 84 cases (59%) and bcl-2 in 25 cases (18%). T1 or T2 stage (adjusted odds ratio, 3.3; 95% confidence interval 1.3-8.7; P=0.01), N0 node stage (adjusted odds ratio, 2.7; 95% confidence interval 1.1-6.4; P=0.03), p53 wild-type gene (adjusted odds ratio, 4.0; 95% confidence interval 1.7-9.5; P=0.002), and bcl-2 protein expression (adjusted odds ratio, 20; 95% confidence interval 2.3-170; P=0.006), were positively associated with tumour response. P53 protein expression was not predictive of response. In conclusion, tumour stage, node stage, p53 gene status, and bcl-2 expression are independent predictors of tumour response to platin-fluorouracil in patients with squamous-cell carcinomas of the head and neck.

Adult↗

Telomerase activation cooperates with inactivation of p16 in early head and neck tumorigenesis.

Alteration of the p16/pRb pathway may cooperate with telomerase activation during cellular immortalization and tumour progression. We studied p16 expression status by immunohistochemistry and telomerase activity using the TRAP assay in 21 premalignant lesions of the head and neck epithelium as well as 27 squamous-cell carcinomas. We also examined expression of other components of the pathway (cyclin D1 and pRb) as well as presence of human papillomavirus genomes which can target these molecules. 4 of 9 mild dysplastic lesions (44%), 8 of 12 moderate/severe dysplastic lesions (67%), and 25 of 27 squamous-cell carcinomas (92%) demonstrated high telomerase activity (P = 0.009). There was a parallel increase with severity of lesions for the trend in proportions of cases demonstrating p16 inactivation or cyclin D1 overexpression (P = 0.02 and P = 0.01, respectively). For Ki67, a marker of cell proliferation, this trend was not significant (P = 0.08). Human papillomavirus infection was only found in 4 cases among the 48 samples tested (8.3%). In conclusion, progression of disease is accompanied by a parallel and continuous increase in telomerase activity and alterations in cell cycle regulators (p16, cyclin D1), as proposed by in vitro models.

Adult↗

p53 gene status as a predictor of tumor response to induction chemotherapy of patients with locoregionally advanced squamous cell carcinomas of the head and neck.

PURPOSE: To determine whether p53 gene status predicts tumor responses to platinum- and fluorouracil-based induction chemotherapy in locoregionally advanced squamous cell carcinomas of the head and neck. PATIENTS AND METHODS: Tumor responses of 105 patients were measured at the primary tumor site. Objective response and major response were defined by a 50% and 80% reduction in tumor size, respectively. All coding parts of p53 gene were directly sequenced. p53 expression in tumor cells was determined by immunohistochemistry. Human papillomavirus infection was detected by polymerase chain reaction. Odd ratios were adjusted by stepwise logistic regression analysis. RESULTS: p53 mutations, p53 expression, and tumor stage were sufficient to explain the variation in tumor responses to chemotherapy in multivariate models. p53 mutation was the only variable to significantly predict objective response (odds ratio, 0. 23; 95% confidence interval, 0.10 to 0.57; P =.002) and was the strongest predictor of major response (odds ratio, 0.29; 95% confidence interval, 0.11 to 0.74; P =.006). p53 expression (odds ratio, 0.39; 95% confidence interval, 0.16 to 0.98) and tumor stage (odds ratio, 0.31; 95% confidence interval, 0.10 to 0.96) also predicted major response. Specific mutations (contact mutations) accounted for much of the reduction in the risk of major response associated with overall mutations. In complementary analyses, p53 expression was weakly predictive of major response in the subgroup with wild-type p53, and p53 mutations also predicted histologic response. CONCLUSION: p53 gene mutations are strongly associated with a poor risk of both objective and major responses to chemotherapy. Contact mutations are associated with the lowest risk of major response to chemotherapy.

Adult↗

In vivo inaccessibility of somatostatin receptors to 111In-pentreotide in primary renal cell carcinoma.

The presence of somatostatin receptors on human renal cell carcinomas in surgically removed kidneys has been demonstrated by autoradiography. The aim of this study was to detect to in vivo presence of somatostatin receptors in primary renal tumours and their possible metastases before surgery, using 111In-pentreotide scintigraphy. 201Tl was used as a sensitive tumour-seeking agent with blood flow-dependent uptake. Fifteen patients were imaged before surgical removal of the renal tumour. Thirteen tumours were malignant. The large tumours (more than 4 cm in diameter) did not accumulate 111In-pentreotide or 201Tl. In contrast, the single small tumour accumulated both tracers. A scalp skin metastasis was demonstrated in one patient by 201Tl and 111In-pentreotide uptake. In one case, known lung metastases were visualized with both 201Tl and 111In-pentreotide, but the lung metastases of another three patients as well as one case of epidural metastasis were not identified. In one patient with a photopaenic lesion, positive labelling of the surgically removed tumour was demonstrated by in vitro autoradiography. Somatostatin receptor scintigraphy with 111In-pentreotide appears to have little value for the detection of metastases in patients with renal cell carcinoma, as some metastases (especially those of the lungs) were missed. The absence of 111In-pentreotide uptake by large primary tumours is an interesting finding, suggesting inaccessibility of these very large tumours to drugs.

Adult↗

Human papillomavirus in head and neck squamous cell carcinomas in nonsmokers.

OBJECTIVE: To establish relationships between smoking status and human papillomavirus in head and neck squamous cell carcinomas. DESIGN: Human papillomavirus was detected in paraffin-embedded samples using E6-directed consensus primers and type-specific oligonucleotide probes. Patients were classified as smokers and nonsmokers. Alcohol use was also recorded. Data were analyzed by means of the Fisher exact test. Sequence analysis of exons 5 to 8 of the p53 gene was performed in tumor samples from nonsmokers. SETTING: Academic medical center in Paris, France. PATIENTS: One hundred eighty-seven consecutive patients with head and neck squamous cell carcinoma. RESULTS: The overall prevalence of human papillomaviral infection was 10.7%. Human papillomavirus occurred more frequently (P = .02) in oropharyngeal squamous cell carcinoma (18.6%) than in other locations (6.1%). There were 10 nonsmokers (5%). The 50% incidence of human papillomavirus in nonsmokers (95% confidence interval, 19%-81%) differed significantly from the 8.5% incidence in smokers (95% confidence interval, 5%-14%; P = .003). No occupational risk factor was recorded in nonsmokers. None of these patients had p53 gene mutations in cancer cells. CONCLUSION: These findings suggest that human papillomavirus may play a role in head and neck squamous cell carcinomas in nonsmokers.

Adult↗

[Effect of microwave pretreatment on the detection of Epstein-Barr virus EBER RNA's using in situ hybridization].

We have tested the influence of microwave pretreatment of tissue sections on in situ hybridization applied to the detection of Epstein-Barr virus-encoded small RNAs (EBER). To this end, different protocols have been tested on slides of 4 lymph node lymphomas: microwave pretreatment, proteinase K pretreatment, microwave followed by proteinase K and no pretreatment. To compare the sensitivity of each technique, several dilutions of oligoprobes were used. Hybrids have been detected by immunohistochemistry. The analysis of the nuclear stainings obtained shows an enhancement of the sensitivity in protocols using microwaves.

Endopeptidase K↗

Human papillomavirus infection in the malignant and premalignant head and neck epithelium.

A prospective study was undertaken to determine the prevalence and histological correlates of human papillomavirus infection in the head and neck epithelium. Oral, pharyngeal, and laryngeal paraffin-embedded samples were analyzed by polymerase chain reaction with use of human papillomavirus E6 consensus sequence primers. Human papillomavirus infection was detected in 20 of 126 (15.9%) patients. Twenty-five of 230 (10.9%) samples contained human papillomavirus DNA. Papillomaviruses were detected in 15 of 131 (11.4%) head and neck squamous cell carcinomas, in 3 of 32 (9.4%) dysplasias, and 2 of 19 (10.5%) keratoses. The most commonly identified human papillomavirus in cancerous, precancerous, and keratotic lesions was type 16 (80.0% of the isolates). Five papillomas were shown to contain human papillomavirus type 6. No other lesion in 42 samples contained human papillomavirus. Our data are consistent with the hypothesis that infection with certain types of human papillomavirus contributes to head and neck cancer although this may be so only in a minority of cases. Human papillomavirus infection may play a role in the earliest stages of tumorigenesis, since papillomaviruses can be found in laryngeal premalignant and keratotic lesions, which are closely linked to tobacco use.

Adolescent↗

[The value of PSA density for the diagnosis of prostatic cancer and for the indication of radical prostatectomy].

We evaluated the diagnostic and prognostic value of PSA density (PSAD) in a prospective study of 100 men consulting for various urinary tract disorders. PSAD was calculated by the ratio of serum PSA over the ultrasonographic volume of the prostate gland, and was expressed in ng/ml/ml. The mean PSAD of 31 patients with prostate cancer was significantly higher than that of the 69 patients without prostate cancer (p = 0.0003). The patients were classified into two groups according to the serum PSA value. Forty nine patients had a serum PSA < or = 10 ng/ml, 31 of whom had a PSAD < or = 0.15 ng/ml/ml and 29 of these 31 patients (94%) did not have prostate cancer; 18 patients had a PSAD > 0.15 ng/ml/ml and six of them (33%) had prostate cancer (p = 0.04). Fifty one patients had a serum PSA > 10 ng/ml and 23 of them (45%) has prostate cancer; 14 of these 51 patients had a PSAD < or = 0.30 ng/ml/ml and two of them (14% à had prostate cancer; 37 patients had a PSAD > 0.30 ng/ml/ml, 21 of whom (57%) had prostate cancer (p = 0.016). Twenty one of these 31 patients with prostate cancer were candidates for radical prostatectomy. Four patients were N+ and 17 underwent radical prostatectomy. Capsular invasion was significantly correlated with PSAD. None of the four patients with PSAD < or = 0.30 ng/ml/ml showed capsular invasion, while 11 of the 13 patients (85%) with PSAD > 0.30 ng/ml/ml had capsular invasion. In conclusion, in patients with PSA < or = 10 ng/ml, calculation of the PSAD avoids approximately two-thirds of prostatic biopsies, with a very low risk of missing a clinically significant cancer. On the other hand, PSAD is of more limited value in patients with PSA > 10 ng/ml. In cancers considered to be operable clinically, the cut-off value of 0.30 ng/ml/ml for PSAD is predictive of capsular or lymph node invasion with a diagnostic accuracy of 94%.

Aged↗

Expression of p53 protein related to the presence of human papillomavirus infection in precancer lesions of the larynx.

The aim of this study was to gain some insight into the relationship of human papillomavirus (HPV) infection to p53 expression and to some pathological parameters in precancerous lesions of the larynx. Formalin-fixed paraffin-embedded tissue sections containing human laryngeal precancerous lesions were screened for p53 protein by immunohistochemistry with the monoclonal antibody DO7 and for the presence of HPV infection by polymerase chain reaction with consensus primers directed against the E6 gene. The presence of p53 protein was detected in 31 of 57 specimens (54.4%) including 7 of 9 cases with mild dysplasia (78%), in 4 of 9 cases with moderate dysplasia (44%), and in 15 of 23 cases with severe dysplasia (65%). Of 16 samples with keratotic benign squamous metaplasia, 5 were also p53 positive (31%). Of 6 samples that were HPV positive, all were of type 16. Interestingly, 3 of the 6 HPV-positive samples were p53 negative. There was 1 HPV-positive case with strong p53 staining and 2 HPV-positive cases with minimal p53 staining. The 2 HPV-positive cases with minimal p53 staining had mild dysplasia. The HPV-positive case with strong p53 staining displayed severe dysplasia. Of 23 cases that were both HPV and p53 negative, 11 presented with keratosis and no dysplasia, 5 with moderate dysplasia, and 7 with severe dysplasia. Our data indicate that nuclear accumulation of p53 protein, presumably resulting from p53 gene mutation, may occur in HPV-infected epithelial tissues. On the other hand, there are many precancer lesions, some exhibiting moderate or severe dysplasia, that are both HPV negative and p53 unreactive, suggesting that alterations of genes other than the E6 oncogene and the p53 tumor suppressor gene play a role in early laryngeal carcinogenesis.

Adult↗

Isolated myocardial fibrosis as a cause of sudden cardiac death and its possible relation to myocarditis.

In performing medicolegal autopsies on sudden deaths, there occur a number of cases in which no cause of death can be found. In particular, no evidence of macroscopic cardiac abnormalities can be observed. However, extensive histological screening may reveal isolated areas of myocardial fibrosis. The five cases presented discuss the etiology of this fibrosis and its possible relation to myocarditis. The cases involve white women between the ages of 19 and 25 with no previous medical history. The weight of the heart in all five cases was normal. Macroscopic evidence of fibrosis was visible in four out of five cases. No other macroscopic abnormalities were observed. Histologically, there was evidence of scarring or interstitial fibrosis in all five cases. In four of the cases, additional screening permitted the observation of dispersed inflammatory foci consisting of lymphocytes, plasmocytes and macrophages. Two of the cases demonstrated eosinophil and neutrophil aggregates in the center of necrotic foci. No evidence of vascular inflammatory phenomena was observed in any of the five cases. According to the Dallas criteria, three of the five cases fulfill the requirements for myocarditis and one of the five cases for borderline myocarditis. The Dallas criteria, however, do not take into consideration the possible association between inflammation and myocardial fibrosis since many of the reported series of myocarditis have been from hospital autopsies or endomyocardial biopsies and have not taken into account sudden death from fibrotic sequelae of myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Adrenal myelolipoma. Review of the literature and case report].

Adrenal myelolipoma is a rare, benign tumour composed of adipose and haematopoietic cells. It is usually an incidental finding or may present in the form of a complication, the most severe being spontaneous retroperitoneal rupture. Computed tomography is the best examination, providing a preoperative diagnosis in 90% of cases. Adrenal aspiration cytology is useful in the case of a persistent doubt concerning the diagnosis. The principal differential diagnosis consists of an angiomyolipoma of the upper pole of the kidney. The indications for surgical resection are limited to symptomatic tumours, tumours larger than 5 cm in diameter and in the case of a doubtful diagnosis.

Adrenal Gland Neoplasms↗

Expression of the neutrophil elastase gene during human bone marrow cell differentiation.

Neutrophil elastase, a potent serine protease carried and released by activated neutrophils, is not synthesized by neutrophils, but by their bone marrow precursor cells. Using in situ hybridization with 35S-labeled antisense and sense neutrophil elastase cRNA probes, the present study demonstrates that expression of the neutrophil elastase gene is tightly controlled in bone marrow precursors and occurs during a very limited stage of differentiation of the neutrophil myeloid series, almost entirely at the promyelocyte stage. Neutrophil elastase mRNA transcript levels are detectable to a limited extent in blasts, increase markedly in the promyelocyte stage, and then disappear as promyelocytes further differentiate. Control probes specific for myeloperoxidase, lactoferrin, and beta-globin mRNA transcripts, respectively, demonstrated contrasting gene expression. Myeloperoxidase mRNA transcripts were also found almost exclusively at the promyelocyte stage, but myeloperoxidase mRNA levels disappeared earlier than do neutrophil elastase mRNA levels, suggesting that expression of these genes may be differently controlled. In comparison, lactoferrin mRNA transcripts were detected late in the neutrophil lineage, while beta-globin mRNA was detected only in cells of the erythroid lineage. Together these observations suggest that the expression of the neutrophil elastase gene is likely under very tight control, and is likely different than that for other constituents of the neutrophil granules.

Bone Marrow Cells↗

[Respective frequency and radioclinical features of 150 lung diseases observed in 125 patients with human immunodeficiency virus infection].

Seventy out of 125 patients with HIV infection had diffuse alveolo-interstitial pneumonia usually caused by an opportunistic infection, notably pneumocystosis. Nineteen patients had only localized lung opacities due either to usual or tuberculous bacterial infections or to Kaposi's sarcoma. In 10 patients with pleural effusion or mediastinal adenopathy, the condition was due to Kaposi's sarcoma (n = 4) or to mycobacteriosis (n = 3). An opportunistic or usual infection was demonstrated in 17 of the 51 patients with normal radiography of the chest. Finally, 37 patients free from infectious or tumoral pathology had isolated lymphocytic alveolitis.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus-related lymphocytic alveolitis.

We observed 276 HIV-infected patients to determine the frequency, degree, and clinical presentation of the lymphocytic alveolitis in different stages of HIV disease, and also to identify the lymphocyte subsets involved. In 154 patients with proved lung infections or tumors (group A), bronchoalveolar lavage fluid showed lymphocytosis in 78 percent of cases. In 122 subjects (31 AIDS and 91 HIV-infected non-AIDS patients) without evidence of lung tumor or infection (group B), lymphocytic alveolitis was seen in 72 percent of cases. In 61 of 88 (69 percent) group B lymphocytic patients, we observed respiratory symptoms or diffuse interstitial opacities; however, we also observed such alveolitis in 27 of 46 (59 percent) group B patients free of respiratory symptoms and abnormality of chest x-ray film. This alveolitis was seen not only in AIDS or ARC patients but also at earlier stages of HIV infection. T-lymphocyte analysis showed a large majority (40 to 93 percent) of CD8 positive lymphocytes in the 37 patients tested. A dual fluorescence analysis revealed, in 18 subjects, that those cells were phenotypically cytotoxic (CD8 + D44 +). These findings suggest that, regardless of HIV-infection stages and of opportunistic lung infections, a CD8-positive T-lymphocyte alveolitis may be present in HIV-infected patients and could be responsible for cough, dyspnea, interstitial pneumonitis, and abnormalities of pulmonary function tests.

Acquired Immunodeficiency Syndrome↗

Evaluation of fibronectin gene expression by in situ hybridization. Differential expression of the fibronectin gene among populations of human alveolar macrophages.

Populations of alveolar macrophages recovered from the lower respiratory tract secrete fibronectin, a multi-functional glycoprotein capable of influencing cell migration, attachment, differentiation, and proliferation. Using in situ hybridization of 35S-labeled antisense and sense RNA fibronectin probes, the present study demonstrates that most, but not all, normal alveolar macrophages contain fibronectin mRNA transcripts, and that among those macrophages expressing this gene, the relative amount of fibronectin mRNA transcripts varies from cell to cell. Interestingly, while 66 +/- 3% of normal alveolar macrophages contain fibronectin mRNA transcripts, this is increased to 82 +/- 2% (P less than 0.01) of alveolar macrophages recovered from the lungs of individuals with idiopathic pulmonary fibrosis (IPF), a chronic inflammatory disorder associated with exaggerated amounts of fibronectin in the lower respiratory tract. Furthermore, of the macrophages expressing the fibronectin gene, those from IPF patients contain more fibronectin mRNA transcripts than those from normals. Consistent with this observation, evaluation of tissue samples from IPF patients demonstrated that of all cells present, alveolar macrophages showed the greatest numbers of fibronectin mRNA transcripts per cell. These observations demonstrate that there can be marked cell-to-cell variation in the expression of the gene for a macrophage product such as fibronectin, suggesting that there are processes that modulate similar cells in the same anatomic compartment to vary their expression of the same gene.

Adult↗

[Pulmonary bilharziasis due to Schistosoma mansoni simulating Carrington's disease].

A case of pulmonary Schistosoma mansoni bilharziasis observed in a female patient from Martinique is reported. In view of the unusual clinical and radiological features of the disease and of its rapidly worrying course, an open chest lung biopsy was performed which provided the diagnosis. A search for eggs in the stools was negative, and serological tests were weakly positive, treatment with Praziquantel resulted in rapid and complete cure.

Diagnosis, Differential↗