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C Clavel

Publications and source records attributed to C Clavel.

At least 55 records · Page 3Linked to original sources
PubMed1994

Expression of stromelysin 3 and tissue inhibitors of matrix metallo-proteinases, TIMP-1 and TIMP-2, in rheumatoid arthritis.

Rheumatoid hyperplastic synovial lining cells and sublining fibroblasts are known to produce, in vivo and in vitro, matrix metallo-proteinases which degrade extracellular matrix components of joints. We have studied by immunohistochemistry and in situ hybridization the presence of matrix metallo-proteinase stromelysin 3 and its potential inhibitors TIMP-1 and TIMP-2 in 5 cases of normal synovia, 5 cases of chronic synovitis and 12 cases of rheumatoid arthritis. Few hyperplastic synoviocytes and some sparse fibroblasts have been found to produce stromelysin 3 in all rheumatoid arthritis and 2 chronic synovitis. Stromelysin 3 seems to have a limited role in the destructive process of extracellular matrix. TIMP-1 and TIMP-2 were largely expressed principally in hyperplastic synoviocytes and in endothelial cells of all rheumatoid synovitis and 2 chronic synovitis. These findings plead for a balance between matrix metallo-proteinases and their inhibitors in these inflammatory lesions.

Arthritis, Rheumatoid↗
PubMed1993

Localization by in situ hybridization of mRNAs encoding stromelysin 3 and tissue inhibitors of metallo-proteinases TIMP-1 and TIMP-2 in human head and neck carcinomas.

The presence and distribution of mRNAs encoding a matrix metalloproteinase (MMP) stromelysin 3 and two tissue inhibitors of MMP, TIMP1 and TIMP-2 have been studied by in situ hybridization of 18 human epidermoid head and neck carcinomas and four normal tissues. We found that in 16 tumors out of 18, stromelysin 3 mRNAs were only expressed by fibroblasts which were in close contact to invasive cancer cells. Tumor cells and normal tissues were not labeled. TIMP-1 mRNAs were detected in well differentiated cancer cells and in endothelial cells in all the cancers. In 13 out of the 18 carcinomas, TIMP-2 mRNAs were localized in only a few stromal cells near well differentiated invasive cancer cells and in endothelial cells. The significant expression of TIMP-1 and TIMP-2 mRNAS may lead to less aggressive MMPs, especially in the case of stromelysin 3, in the invasive process of the stroma.

Blotting, Northern↗
PubMed1993

[Cell interactions in the extracellular matrix in tumoral invasion in mammary pathology].

Tumoral invasion in breast lesions is associated with a progressive loss of the basement membrane (BM) components. In situ hybridization reveals a loss of synthetic ability of type IV collagen by invasive cells in a murine model. The loss of BM components does not seem related to the expression of the plasmin system by cancer cells. By contrast, there is a cooperation between fibroblasts and cancer cells for the expression of matrix metallo-proteinases involved in BM degradation in breast carcinomas in vivo.

Animals↗
PubMed1993

Non radioactive single-strand conformation polymorphism (SSCP) analysis of exon 11 of the CFTR gene using the Pharmacia PhastSystem.

The authors report here the use of the PhastSystem (Pharmacia) to perform the single strand conformation polymorphism analysis of polymerase chain reaction products of the exon 11 of the CFTR gene. It provides a rapid (2 hours) safe and reliable technique for the development of carrier testing for individuals or couples with a family history of cystic fibrosis.

Cystic Fibrosis↗
PubMed1993

Detection and localization of mRNAs encoding matrix metalloproteinases and their tissue inhibitor in human breast pathology.

Matrix metalloproteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective-tissue-matrix remodelling and the accelerated breakdown associated with tumor development. These MMPs and tissue inhibitor of MMPs (TIMP1) could be expressed by either the cancer or the stromal cells. Expression of mRNAs encoding interstitial collagenase (MMP1), 72-kD type IV collagenase (MMP2) and stromelysin (MMP3), which are probably involved in tumor invasion and metastasis, and of TIMP1 were studied in human mammary pathology by in situ hybridization and Northern blot analysis. Out of 6 benign lesions, 2 expressed MMP2 mRNAs. mRNAs encoding MMP1 and MMP3 were detectable in occasional stromal and tumor cells in 2 out of 17 carcinomas. Thirteen out of 17 cancers expressed MMP2 mRNA throughout the tumor in stromal cells close to noninvasive tumor clusters and well-differentiated invasive cancer cells. TIMP1 mRNA expression was detected in noninvasive and well-differentiated invasive tumor cells. These data suggest that there is a cooperation between tumor and stromal cells, in particular for the production of 72-kD type IV collagenase, involved in the disruption of basement membranes. A lack of TIMP1 expression from invasive cancer cells would also contribute to matrix destruction.

Blotting, Northern↗
PubMed1992

[Modulation of the organization of the extracellular matrix and the production of collagen by interferon gamma in three-dimensional cultures of normal and sclerodermic fibroblasts].

Recent studies have shown inhibition of collagen synthesis by interferon gamma (IFN-gamma) in monolayer human fibroblast cultures on a plastic solid phase. However, the existence of this effect in vivo has not yet been demonstrated. Three-dimensional fibroblast cultures in collagen matrices (collagen lattices or dermal equivalents) provide a more physiological model than conventional cultures and fairly closely simulate in vivo conditions. This model was used for studying effects of IFN-gamma on normal and scleroderma fibroblasts. IFN-gamma induced a dose-dependent inhibition of fibroblast-mediated retraction of collagen lattices. IFN-gamma also inhibited total protein and collagen synthesis. Scleroderma fibroblasts were especially susceptible to the inhibitory effects of IFN-gamma. Since fibrotic scleroderma lesions are associated with tissue retraction and increased production of extracellular matrix macromolecules, these data confirm the potential value of IFN-gamma for the treatment of scleroderma and other fibrotic diseases.

Adult↗
PubMed1992

DNA content measurement and in situ hybridization in condylomatous cervical lesions.

The present study reports results obtained with DNA ploidy measurement by Feulgen cytophotometry and in situ hybridization (ISH) on the same sections of 36 cervical lesions containing human papillomavirus (HPV) DNA. Fifteen of 16 low grade lesions [11 flat condylomas and five condylomatous with intraepithelial neoplasias (CIN)-1, 1 with condylomatous features] were diploid. "Oncogenic" HPV (types 16 and 33) were detected in three of these cases, while the aneuploid case expressed HPV type 11. By contrast, in the 12 CIN-2 and eight CIN-3 with condylomas, there was a good correlation between presence of an aneuploid DNA pattern and detection of "oncogenic" HPVs. Demonstration of an aneuploid profile and "oncogenic" HPV as found in all our CIN-3, may indicative of a poor prognosis in low grade lesions. Hence, the combination of the two techniques (ISH and Feulgen cytophotometry) may provide significant prognostic information for condylomas and CINs.

Aneuploidy↗
PubMed1992

A new nonisotopic detection of human papillomavirus DNA using polymerase chain reaction.

A novel technique using a two-step polymerase chain reaction (PCR) with specific primers detecting human papillomavirus (HPV) DNA of types 6/11, 16, and 18 and a final nonisotopic colorimetric detection has been developed. Sixty formalin-fixed and paraffin-embedded sections were treated with this methodology and the results compared with those obtained with in situ hybridization (ISH). Twenty cases displaying HPV DNA with ISH were positive with PCR. Seven (35%) of 20 cases negative for ISH but evocative of HPV infection with classic histology displayed HPV DNA with the two-step PCR. Only one case (5%) of 20 normal tissues and/or inflammatory lesions not evocative of HPV infection and negative upon ISH showed HPV DNA. This original technique allows rapid, highly sensitive, and specific detection of HPV DNA and is suitable for most laboratories.

Base Sequence↗
PubMed1992

Immunolocalization of matrix metallo-proteinases and their tissue inhibitor in human mammary pathology.

Matrix metallo-proteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumor development. The distribution of 3 major matrix metallo-proteinases was studied in human mammary pathology: collagenase (MMP1) which degrades fibrillar interstitial collagens, a 72-kDa gelatinase (MMP2) which mainly degrades type IV collagen and denatured collagens, and stromelysin (MMP3) which has a wider range of action, degrading several matrix components including the core proteins of proteoglycans, laminin and non-helical regions of collagens. These MMPs and the MMP tissual inhibitor (TIMP1) were detected by immunohistochemistry in 30 benign and 79 malignant lesions of the breast. MMPs were detected in 1 fibroadenoma (collagenase) and 22 breast carcinomas: collagenase (9 cases), stromelysin (12 cases) and gelatinase (16 cases) with a limited distribution. Tumor cells were preferentially labelled and the localization of gelatinase and stromelysin at the periphery of some non-invasive and well-differentiated clusters supports the role of these enzymes in the breakdown of basement membranes. Only a few stromal cells (fibroblasts) were found to be immunopositive. In contrast, TIMP1 was more frequently detected, and was found in 7 benign lesions and 55 carcinomas out of 79. It was mainly localized at the periphery of the endothelial cells but was occasionally detected in cancer cells and fibroblasts.

Adult↗
PubMed1992

Gamma-interferon inhibits extracellular matrix synthesis and remodeling in collagen lattice cultures of normal and scleroderma skin fibroblasts.

Three-dimensional collagen lattice cultures of fibroblasts mimic the in vivo situation better than monolayer cultures. Here, skin fibroblasts from scleroderma patients and healthy controls were cultivated in collagen lattices, and the effects of recombinant human gamma-interferon (IFN-gamma) on these cultures investigated. IFN-gamma inhibited collagen lattice retraction in a dose-dependent way at concentrations ranging from 10 to 10,000 U/ml. This effect was independent of any alteration to the cell proliferation within the lattices. The inhibition was of the same order of magnitude in normal and pathological fibroblasts. The synthesis of collagen and non-collagen proteins, particularly fibronectin, was increased in scleroderma cultures. It was inhibited in both normal and scleroderma fibroblasts by IFN-gamma, with a maximal effect at the concentration 1000 U/ml, but the inhibition of protein synthesis was far more intense in scleroderma than in normal cells. In situ hybridization, Northern blot and dot blot analyses showed that mRNA coding for pro alpha 1(I) collagen was decreased in IFN-gamma-treated cells, indicating an effect at the pretranslational level. IFN-gamma also inhibited glycosaminoglycan synthesis, but in scleroderma cells only. This study shows that IFN-gamma regulates cell behavior in three-dimensional collagen matrices: (i) it decreases protein and specifically glycosaminoglycan synthesis in scleroderma fibroblasts, (ii) it modulates the interactions between cells and matrix that lead to the retraction of the lattice. Whereas collagen synthesis is largely decreased in lattice cultures like in vivo, it remains increased in the case of scleroderma compared to normal fibroblasts and may be down-regulated by IFN-gamma. Similar conclusions may be drawn for fibronectin and glycosaminoglycans. The inhibitory effect of IFN-gamma on the retraction capacity of fibroblasts and on their ability to synthesize increased amounts of extracellular matrix macromolecules may be of potential interest for therapeutic use of IFN-gamma in scleroderma patients.

Adult↗
PubMed1991

Comparison of four non-radioactive and 35S-based methods for the detection of human papillomavirus DNA by in situ hybridization.

Human papillomavirus DNA was detected in 40 condylomatous lesions of various sites (vulva, cervix, larynx, penis and anus) by in situ hybridization using 35S-labelled probes and four non-radioactive probes to compare the various sensitivities of these techniques on the same material (formalin-fixed and paraffin-embedded sections). Radioactive probes yielded 28 positive results out of 40 (70%). Sulphonated probes (HybriCyte kit) also gave 28 positive results with a fine pattern of hybridization grains and equal sensitivity to 35S-labelled probes. Biotinylated and digoxigenin-labelled probes gave analogous results (25 positive reactions with the PathoGene kit, 26 with the Viratype kit, and 25 with digoxigenin-labelled probes) but are slightly less sensitive than radiolabelled and sulphonated probes especially when the signal is weak.

Adolescent↗
PubMed1991

Detection of mRNAs encoding collagenase I and stromelysin 2 in carcinomas of the head and neck by in situ hybridization.

The mRNAs encoding 2 metalloproteinases, stromelysin 2 and collagenase I, have been detected by in situ hybridization in 26 carcinomas of the head and neck. 23 tumors of 26 expressed these mRNAs. Collagenase mRNAs were present in individual invasive cancer cells and in tumor cells at the periphery of poorly differentiated clusters (4 cases). Numerous stromal cells, principally fibroblasts were labeled (18 cases). Stromelysin mRNAs have been localized in tumor cells frequently arranged along disrupted basement membranes (8 cases). Many stromal cells in close contact to cancer cells also expressed the stromelysin mRNAs (17 cases). Normal residual cells were never labeled. These observations plead for the role of stromelysin produced by both stromal and tumor cells in the breakdown of basement membranes and the involvement of both collagenase and stromelysin in stromal invasion in carcinomas of the head and neck in vivo.

Blotting, Northern↗
PubMed1990

[Use of digoxigenin-labeled probes for the detection of papillomaviruses by in situ hybridization].

A technique of detection of human papillomaviruses by in situ hybridization in paraffin-embedded formalin-fixed sections of genito-anal lesions is described. The probes are labeled by incorporation of digoxigenin-labeled nucleotides. The hybrids are revealed by immunohistochemistry with an anti-digoxigenin antibody coupled with alkaline phosphatase. This technique is sensitive, cheap and may be used in routine in laboratories of pathology.

DNA Probes↗
PubMed1989

Detection by in situ hybridization of messenger RNAs of collagen types I and IV in murine mammary cancer.

Ten breast carcinomas developing in C3H/Bi female mice were studied by an in situ hybridization technique using cDNA probes encoding alpha-I chains of collagens of types I and IV. The results obtained are compared to histochemical data on antibodies to collagens of types I and IV and ultrastructural observations on these tumors. Immunohistochemistry has revealed the presence of type-IV collagen in basement membranes lining intraductal and well-differentiated cancer nests. Type-I collagen was detected in the stroma surrounding these cells. There was no cellular labelling when these antisera were used. In situ hybridization has shown that type-IV collagen mRNA is detected in non-invasive intraductal and well-differentiated tumor cells and in endothelial cells in the stroma. Good correlation between detection of type-IV collagen lining these cells and evidence of mRNA by in situ hybridization was thus observed. Invasive cancer cells did not express hybridization grains with the type-IV collagen probe. Type-I collagen mRNA was visualized in stromal cells, probably fibroblasts and myofibroblasts as shown by electron microscopy. The most active cells were localized close to non-invasive areas. Our data indicate persistent in-vivo biosynthesis of type-IV collagen by some cancer cells that produce their own limitative environment; they suggest that type-IV collagen is not produced by invasive tumor cells and that stromal cells lining the non-invasive regions have a peculiar behavior.

Animals↗
PubMed1988

[Proteases and breast carcinoma].

Proteasic systems are largely incriminated in tumoral invasion in breast carcinomas. They are numerous and ranged in three classes. Serine-proteinases include plasmin, elastases, thrombin and trypsine which after activation, attack some structural glycoproteins and elastin. Plasmin system is involved more in stromal invasion than in the disruption of basement membranes. Plasminogen activators do not seem to come under the influence of hormonal factors. The action of these various enzymes is limited by more or less specific anti-proteases. The activity of elastases is parallel to the abundance of elastin in the stroma. The second group is composed of cystein-proteinases. Cathepsin B has a lysosomial origin and represents the most active system. Invasive territories of mammary carcinomas contain this enzyme which can degrade collagens and activate collagenases. Metallo-proteinases with collagenases, constitute the most important proteasic system in the degradation of extra-cellular matrix. Physicochemical properties of collagenases, ionic and cellular environment condition their activity which is also enzyme dependent (activation by plasmin, cathepsin B...) Type IV collagenase activity is related to the invasive and metastatic ability of tumor cells. All these enzymatic productions are closely linked and intermittent, and moreover limited by seric and tissular anti-proteinases.

Breast Neoplasms↗