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Biomedical subjects

P Chaubert

Publications and source records attributed to P Chaubert.

51 records · Page 3Linked to original sources

Estrogen and progesterone receptors and pS2 and ERD5 antigens in gastric carcinomas from the European population.

We examined immunohistochemically 50 gastric carcinomas from European patients for estrogen receptors, progesterone receptors, and hormone-receptor-related proteins pS2 and ERD5. Unlike gastric carcinomas from non-Europeans reported previously, the carcinomas of the present series were all negative for estrogen and progesterone receptors. One-half of them, however, expressed pS2, and three-fourths were positive for ERD5. pS2 expression was significantly more frequent in carcinomas of the diffuse type than in those of the intestinal type and in advanced carcinomas compared with early ones. Our results indicate that pS2 and ERD5 are estrogen independent in the stomach. The possibility that estrogen and progesterone receptor status could be different in gastric carcinomas from Occidental and non-Occidental patients is discussed.

Biomarkers, Tumor↗

Germ cell tumors of the testis overexpress wild-type p53.

Several recent studies have suggested that testicular germ cell tumors express high levels of wild-type p53 protein. To clarify and confirm this unexpected result, we have investigated seminomatous and nonseminomatous germ cell tumors at the genomic, mRNA, and protein levels. Thirty-five tumors were examined for p53 overexpression using antibodies directed against the p53 (PAb1801, PAb240, and CM1), mdm2 (IF2), and p21Waf1/Clp1 (EA10) proteins. Thirty-two tumors were screened for p53 mutations by single-strand conformation polymorphism analysis. Eighteen tumors were screened with a functional assay that tests the transcriptional competence of human p53 protein expressed in yeast. On frozen sections, 100, 65, 35, 73, and 0% of tumors reacted with the CM1, PAb240, PAb1801, IF2, and EA10 antibodies, respectively. No p53 mutations were detected by single-strand conformation polymorphism or by functional assay. The fact that many tumors overexpress wild-type p53 but not mdm2 rules out mdm2 overexpression as a general explanation for the presence of wild-type p53 in these tumors. The absence of p21 overexpression suggests that p53 may be unable to activate transcription of critical target genes, which may explain why the presence of wild-type p53 is tolerated in this tumor type, although the mechanism for this transcriptional inactivity remains to be established.

Cyclin-Dependent Kinase Inhibitor p21↗

Improved polymerase chain reaction detection of clonal T-cell lymphoid neoplasms.

We have developed and tested a rapid and sensitive method of detecting expansion of T-cell clones using the polymerase chain reaction (PCR) and a single set of consensus primers for the V and J regions to amplify rearranged T-cell receptor-gamma (TCR-gamma) genes. Monoclonality was continued in all of the 18 cases of T-cell neoplasms tested, but not in reactive lymphadenopathy, non-Hodgkin's B lymphomas, and Hodgkin's disease. PCR analysis, using the primer sequence outlined in this study, had an overall specificity of 100% when compared with Southern blot analysis. No false-negative results were observed, certainly owing to the choice of consensus primers and to the control of PCR reactions on agarose gels before testing for clonality by separation of PCR products on polyacrylamide gels. This method for the detection of T-cell monoclonality can be especially useful in cases that are diagnostically problematic with standard histological and immunological analysis and in cases where the material available is limited.

Base Sequence↗

Detection of p53 gene mutation in cancer tissues by nonradioactive direct sequencing.

A simple procedure for direct sequencing of double-stranded PCR products by the dideoxy-termination method has been developed using biotinylated sequencing primers. Sequences of the p53 gene have been obtained from DNA extracted from frozen and formalin-fixed paraffin-embedded cancer tissues. Detection of sequencing ladders was done with chemiluminescent or colorimetric techniques. Both are highly sensitive, but colorimetric detection is less prone to diffusion artifacts, which are common in G-rich regions. Use of this nonradioactive PCR-sequencing protocol allowed rapid and simple determination of p53 gene alterations in human tumors.

Base Sequence↗

p53 Gene alterations and p53 protein accumulation in infiltrating ductal breast carcinomas: correlation between immunohistochemical and molecular biology techniques.

One hundred and eighty-eight infiltrating ductal carcinomas of the breast were examined immunohistochemically (IMM) for p53, and the results were compared to those of single strand conformation polymorphism (SSCP). Of the 65 IMM+ cases (35%), 32 showed a genetic alteration in exons 5 to 9. In some of the IMM+ SSCP- cases, the number of 53+ cells in the tumor was too low to be detected by SSCP. Cases with only a few p53+ cells must not necessarily be considered negative, because a genetic alteration has been found in nine such cases. However, in a few cases, the accumulation of p53 protein could be caused by a factor other than mutation. Of the 123 IMM- cases, six showed gene polymorphism. p53 phenotype, as established with three monoclonal antibodies, did not correlate with genetic alteration in a particular exon. p53 IMM+ or SSCP+ tumors were generally ER-, grade III tumors and were uncommon in women older than 69 yr of age. The two methods have almost the same prognostic value. The accumulation of p53 protein is a good indicator of p53 mutation and therefore, immunohistochemistry remains a good method for the detection of such mutations.

Adult↗

K-ras mutations and p53 alterations in neoplastic and nonneoplastic lesions associated with longstanding ulcerative colitis.

We have analyzed K-ras mutations and p53 alterations in 39 tumor and nontumor samples taken from nine patients with longstanding ulcerative colitis and colorectal carcinoma. Two of nine invasive carcinomas contained a K-ras mutation. By a combination of immunohistochemistry and single-strand conformation polymorphism analysis, p53 alterations were found in three of nine carcinomas. Five of 13 dysplastic lesions harbored a mutated K-ras gene, even in the absence of detectable changes in associated invasive tumors. One single focus of dysplastic mucosa harbored concomitant K-ras and p53 gene alterations. In two patients, a K-ras mutation was detected in epithelial lesions considered to be devoid of malignant potential (villous regeneration, active colitis). Our results indicate that: 1) the prevalence of K-ras and p53 genetic alterations found in ulcerative colitis-associated colonic carcinomas appears to be lower than in sporadic carcinomas; 2) K-ras mutations can be detected in dysplasia, villous regeneration, and active colitis and affect a subpopulation of the cells composing the lesions; 3) diverse genetic alterations can be detected in the same patient and the dysplastic lesions can exhibit a different genotype than the carcinomas; and 4) at least part of active colitis and villous regeneration lesions should be considered as preneoplastic in ulcerative colitis.

Adult↗

Prognostic significance of K-ras mutations in colorectal carcinoma.

BACKGROUND: Mutations at codons 12, 13, and 61 of the ras genes have been found in a variety of human tumors and may have prognostic significance. K-ras mutations have been shown in 40%-50% of colorectal cancers. METHODS: Using a simple nonradioactive polymerase chain reaction-based technique, we have investigated the possible prognostic significance of point mutations of the K-ras gene in patients with human colorectal carcinomas. The prevalence and the type of ras mutations were compared between a group of 35 patients having recurrent disease within 5 years and a group of 64 patients who were disease free 5 years following surgery. RESULTS: First, we found that the overall prevalence of mutations within codons 12 and 13 of the K-ras gene was 25% in the nonrecurring group vs. 71% in the patients with recurrent disease (P < 0.0001) and, second, that mutations other than GGT to GAT occurred, with one exception, exclusively in recurring tumors. CONCLUSIONS: In Dukes' B and C primary tumors, mutations other than GGT to GAT identify patients at very high risk for recurrence. Our results indicate that determining the K-ras mutations provides a good prognostic factor in patients with advanced colorectal carcinoma.

Adult↗

[Rapidly destructive lumbar spondyloarthropathy in chronic hemodialysis].

Rapidly destructive spondyloarthropathy occurring in the lumbar spine of 2 chronically hemodialysed patients is reported. These lesions resembled infectious spondylitis. Histological examination revealed deposits of amyloid in the L3-L4 intervertebral space in one patient, which could be a causative factor in the joint destruction. The other favouring circumstances and pathogenesis of this condition are discussed.

Aged↗

Mammary origin of metastases. Immunohistochemical determination.

Zinc-alpha 2-glycoprotein, gross cystic disease fluid protein 15, and estrogen receptors are expressed in a great proportion of breast carcinomas. These markers were investigated by immunohistochemistry in 28 metastases from breast carcinomas and for comparison on 24 metastases from other carcinomas. A group of 83 primary nonmammary tumors was also studied. Most (> 96%) breast carcinoma metastases expressed one or several markers, while all metastases of other origins were negative. This sensitive and apparently specific immunostaining proved to be of great utility in cases in which the mammary origin of metastases was difficult to establish. In four axillary lymph node metastases, it even led to the discovery of an occult homolateral breast carcinoma that was not detectable by clinical and mammographic investigations. This study indicates that the combined use of zinc-alpha 2-glycoprotein, gross cystic disease fluid protein 15, and estrogenic receptors represents a useful immunostaining technique that can help the pathologist in determining the origin of breast carcinoma metastases.

Apolipoproteins↗

Squamous cell carcinoma of the lung in a nonsmoking, nonirradiated patient with juvenile laryngotracheal papillomatosis. Evidence of human papillomavirus-11 DNA in both carcinoma and papillomas.

Malignant transformation of laryngeal juvenile papillomatosis most often occurs in patients with previous radiation therapy or smoking histories. We report the case of a 35-year-old, nonsmoking, nonirradiated man who developed squamous cell carcinoma of the lung with a 33-year history of laryngotracheal juvenile papillomatosis. Postmortem examination showed pulmonary cavitating papillomatosis and chest wall, vertebrae, and peribronchial lymph node involvement by tumor. Molecular studies (Southern blot, polymerase chain reaction) showed extrachromosomal human papillomavirus-11 (HPV11) DNA in both carcinoma and two laryngotracheal squamous cell papillomas, including one excised 20 years previously. Our observation is analogous to the previously reported cases of spontaneous (not related to irradiation or smoking) malignant transformation of juvenile laryngotracheal papillomatosis. Although HPV11 viral infection likely played a role in the malignant transformation, other less likely factors, such as drugs given for treatment and radiography performed throughout the illness, should be considered. Repeated pulmonary infections and the host immune response are additional considerations.

Adult↗

Is an endocardial connection necessary for growth factor induced angiogenesis in transmyocardial laser revascularization?

Transmyocardial laser revascularization (TMLR) and therapeutic angiogenesis had emerged as potential tools in the treatment of angina refractory to conventional therapies. This combination might potentiate their effects, because angiogenesis is believed to be a basic mechanism in TMLR. The influence of channel connection with endocardial blood flow on angiogenesis is unclear. Twenty-five pigs (mean weight, 72.3 +/- 5 kg) were randomly assigned into five groups. In the transmural laser group, five transmyocardial channels were drilled. In the transmural mixed group, the same protocol was used followed by the injection of 100 microg of bovine bone derived growth factor mixture within each channel. The nontransmural laser group and the nontransmural mixed group underwent the same procedures, respectively, but the laser channels were drilled through the outer two-thirds of the myocardial wall. The control group had sham operations. Animals were allowed to survive for 1 month. Vascular densities were determined by computed morphometric analysis of histologic sections. Vascular counts of areas adjacent to the channels in the non- and transmural laser groups did not differ significantly from control groups (arteriolar counts: 0.27 +/- 0.16 and 0.26 +/- 0.16 vs. 0.29 +/- 0.11/mm2, respectively). When bovine bone protein growth factor mixture is added, neovascularization is increased significantly in non- and transmural mixed groups (1.04 +/- 0.79 and 0.69 +/- 0.37/mm2, respectively, p < 0.001 for both comparisons with corresponding laser groups), and there was no significant difference between mixed groups (p = 0.13). In this porcine model, the combination of TMLR with injection of bone protein growth factor mixture induced angiogenesis around the laser channels. Whether the channels did or did not communicate with the endocardial cavity did not influence the neovascular density.

Animals↗