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Biomedical subjects

J Abecassis

Publications and source records attributed to J Abecassis.

At least 37 records · Page 2Linked to original sources

[Short term memory and severe language disorders in the child].

Memory, and particularly short-term memory or "working memory" (Baddeley), is involved in language acquisition in children. We have studied short-term memory, with verbal-and non verbal tests, of 8 children suffering from developmental dysphasia compared with other ones, matched in terms of age and performance I.Q. (W.I.S.C.-R.). The digit span did not significantly differ in the two groups, while the visuo-spatial span was lower in the dysphasic group. The memorization of a list of monosyllabic words by dysphasic children was poor in the absence of visual presentation and improved by it. Differences between dysphasic and control-children are unlikely to be due to speech rate which does not significantly differ from one group to the other one. The results suggest the existence, in language disordered children, of cognitive functions disorders much more important than those directly involved in the speech production.

Case-Control Studies↗

Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas.

Matrix metalloproteinases are believed to play an important role in tumor invasion and metastasis. To examine the expression of the stromelysin 3 (ST3) gene, a new member of the matrix metalloproteinase gene family, 111 head and neck squamous cell carcinomas and 21 metastatic lymph nodes were analyzed by Northern blot. ST3 gene expression was observed in 106 carcinomas and 19 metastatic nodes, but in only 2 of 60 samples of corresponding normal tissue tested in parallel. ST3 RNA, by in situ hybridization, and ST3 protein, by immunohistochemical analysis, were specifically detected in fibroblastic cells immediately surrounding invasive cancer cells. This fibroblastic expression of the ST3 gene is characteristic among the matrix metalloproteinase genes known to be overexpressed in head and neck carcinomas, since stromelysin 2 transcripts were specifically detected in neoplastic cells, and type I collagenase transcripts in both neoplastic cells and stromal fibroblasts. Furthermore, there was a highly significant positive correlation (P < 0.0001) between ST3 RNA levels and local invasiveness by the cancer cells, suggesting that enhanced expression of the ST3 gene may contribute to the neoplastic phenotype in head and neck carcinomas.

Carcinoma, Squamous Cell↗

Influence of mastectomy techniques on estrogen and progesterone receptor analysis in carcinoma of the breast.

Gradual tumor tissue devascularization during mastectomy is thought to decrease estrogen (ER) and progesterone (PgR) receptor activity. To determine whether or not hormone receptor values could be influenced by different mastectomy techniques, 62 patients with carcinoma of the breast had a Tru-cut needle (Baxter Healthcare Corporation) biopsy (premastectomy sample) and underwent modified radical mastectomy (postmastectomy sample) either before (group 1, 40 patients) or after (group 2, 22 patients) axillary lymph node dissection. When the two surgical procedures were compared in 33 patients in whom it could be assessed, no significant tendency (p = 0.51 for ER and p = 0.36 for PgR) for the postmastectomy sample to have hormone receptors levels less than samples taken at biopsy was detected. Overall, in the two groups (44 assessable patients), comparison with respect of each patient, between premastectomy and postmastectomy samples showed that the variations in either ER or PgR receptor values, determined by immunoenzymatic assays, were not statistically significant (p = 0.32 for ER and p = 0.21 for PgR). The current results indicated the relative stability of steroid receptors during the two modified radical mastectomy procedures and suggested that a systematic reference determination of hormone receptors on biopsy before modified radical mastectomy is unnecessary.

Aged↗

Expression of collagenase-related metalloproteinase genes in human lung or head and neck tumours.

We address the question as to whether increased metalloproteinase production might be related to the high regional recurrence rate of some carcinomas, and particularly head and neck squamous-cell carcinomas (SCC). Northern blot of total RNA prepared from 26 lung carcinomas, 107 head and neck carcinoma samples and corresponding normal tissue samples demonstrates the frequent and sometimes concomitant over-expression of the 2 stromelysin genes, the type-I collagenase gene and the pump-I gene in the head and neck tumour tissue samples. In these SCC, over-expression of the 2 stromelysin genes and the type-I collagenase gene (but not the pump-I gene) is associated with a high degree of tumour differentiation. Moreover, a tumour with high levels of the stromelysin mRNAs is more likely to show high local invasiveness, suggesting that the stromelysins may be implicated in the clinical course of head and neck tumours. Evaluation of the corresponding mRNA levels may prove a useful indicator for predicting the clinical aggressiveness of these tumours.

Biomarkers, Tumor↗

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↗

[Procoagulant and aggregating platelet activities of human mammary tumor cells].

The ability of tumor cells to initiate coagulation, platelet aggregation and subsequent thrombotic alterations is believed to facilitate metastatic process. The mechanisms by which tumor cells develop thrombotic events in malignancy are discussed. We have examined the procoagulant activity and the modifications of rheologic platelet functions induced by 3 human mammary tumor cell lines (MCF-7, ZR-75-1, BT-20) using a laser-thromborheometer. According to experimental conditions, these 3 tumor cell lines aggregate platelets via a thrombin-dependent mechanism. Moreover, MCF-7 cells also induce ADP-like platelet aggregation. These data suggest the existence of several mechanisms of mammary tumor cell-induced platelet aggregation.

Blood Coagulation↗

Modes of inhibition of protein kinase C by triphenylacrylonitrile antiestrogens.

Protein kinase C (PKC) I (gamma), II (beta) and III (alpha) subspecies' activities are inhibited by three triphenylacrylonitrile (TPE) antiestrogens at micromolar concentrations. TPE 1 (having a p-hydroxy and a p-diethylaminoethoxy group on the 3-, and 3'- phenyl rings respectively) and TPE 2 (having a p-diethylaminoethoxy group on both the 3-, and 3'- phenyl rings) are competitive with the mechanism of activation by phosphatidylserine (PS). TPE 3 (having p-hydroxy groups on each of the three phenyl rings) is non-competitive with PS and inhibits the Ca2+- and PS-independent phosphorylation of protamine sulfate by PKC subspecies. This evidence suggests that PKC activity can be inhibited by different routes depending on the TPE structure: diethylaminoethoxy side chain-substituted TPEs (TPE 1 and 2) interact with PS as well as with the regulatory domain, whereas the trihydroxylated derivative (TPE 3) inhibits the enzyme by interacting with the catalytically active site.

Acrylonitrile↗

Effect of triphenylacrylonitrile derivatives on estradiol-receptor binding and on human breast cancer cell growth.

In a study of a series of 26 triphenylacrylonitrile derivatives (TPEs), we investigated the influence of several possibly interrelated factors on the proliferation of human breast cancer cell lines. (1) Chemical substituents: the test compounds were for the most part para-hydroxylated with increasingly bulky hydrophobic and/or basic side chains [isopropyloxy or (diethylamino)ethoxy] or standard reference compounds. (2) Relative binding affinities (RBAs): they competed diversely for [3H]estradiol (E2) binding to calf uterus cytosol and little, if at all, for binding to the [3H]tamoxifen-labeled antiestrogen binding site (AEBS) in lower speed supernatant. A multiparametric comparison of RBAs recorded for calf, rat, and mouse uterus cytosol estrogen receptor (ER) revealed a possible influence of species-specific receptor conformation and/or environment on binding. (3) Estrogen/antiestrogen potency: their stimulation and inhibition of the proliferation of the ER-positive human breast cancer cell line (MCF7) was measured. Compounds with only hydroxy substituents stimulated proliferation more markedly than methylated derivatives and had a maximum effect at 10(-11)-10(-6) M. Stimulation was related to the RBA for ER. Compounds with isopropyloxy or (diethylamino)ethoxy side chains only weakly stimulated MCF7 cell growth and more powerfully antagonized E2-promoted growth. The extent of inhibition depended upon the bulk of the side chain and could be reversed by 10(-7) M E2. Within the same concentration ranges, the test compounds were without effect on the BT20 ER-negative cell line. (4) Cytostatic and/or cytolytic activity: most compounds could arrest the proliferation of both MCF7 and BT20 cells at concentrations above 3 x 10(-6) M. This activity was thus independent of ER. Nevertheless, those compounds with a charged hydrophobic side chain, which were the most powerful antagonists of E2-promoted cell growth, were also the most cytotoxic. The overall results for all molecules on all parameters were submitted to a multivariate analysis (correspondence analysis) which revealed the progressive influence of increasing substitution by hydroxy and more bulky groups on the generation of antagonist activity and cytotoxicity.

Animals↗

The collagenase gene family in humans consists of at least four members.

Stromelysin is a collagenase-related connective-tissue-degrading metalloproteinase. We have detected RNAs capable of hybridizing to a rat stromelysin cDNA in 11 of 69 human tumours tested. Molecular cloning of cDNAs to these RNAs has identified them as a mixture of stromelysin RNA and a transcript of a hitherto-undescribed related human gene, the stromelysin-2 gene. We have also isolated cDNAs corresponding to a more distantly related new human gene, the pump-1 gene. A comparison of the cDNA-derived amino acid sequences of stromelysin-2 and pump-1 with the known sequences of stromelysin and collagenase reveals significant similarities, with conservation of sequence motifs believed to have functional importance in metalloproteinase action. We conclude that the collagenase gene family in humans consists of at least four members, and speculate that expression of these genes plays a role in cancer.

Amino Acid Sequence↗

Adhesion of human breast cancer cell line MCF-7 to human vascular endothelial cells in culture. Enhancement by activated platelets.

The interactions of MCF-7 tumor cells with human vascular endothelial cells (EC) and subendothelial extracellular matrices (ECM) were morphologically observed by electron microscopy and quantitatively evaluated by labelling tumor cells with 111Indium-oxine. MCF-7 tumor cells adhered more rapidly to ECM than to the apical surface of a confluent monolayer of EC. The affinity of MCF-7 cells for type-IV collagen was greater than for fibronectin, suggesting that type-IV collagen contributes to the higher rate of adhesion of MCF-7 cells to the subendothelial ECM. Otherwise, the attachment of tumor cells to EC was increased in the presence of both washed platelets and 0.1% citrated platelet-poor plasma (cPPP), a condition accelerating platelet aggregation by tumor cells. The enhancement of MCF-7 adhesion to EC in the presence of platelets and cPPP was completely blocked by the addition of prostacyclin, or hirudin, a specific thrombin inhibitor. In ultrastructural studies, MCF-7 initiated EC retraction, and firm attachment and flattening occurred on exposed ECM. When MCF-7 cells were incubated with platelets and cPPP, most of the tumor cells adhering to the EC and inducing disruption of endothelial monolayer were closely packed and associated with platelet aggregates. MCF-7 cells appeared to adhere more efficiently to exposed subendothelial ECM when they were associated into multicellular aggregates containing platelets and trapped in a fibrin thrombus. Thus, this homologous human system of cultured vascular EC and breast carcinoma line MCF-7 cells may be used to assess anti-aggregant compounds for their ability to alter tumor-cell implantation on EC-lined surfaces.

Adenosine Diphosphate↗

Characterization of cell types in human breast tumor primary cultures.

Primary cultures of cells from breast carcinomas were attempted in 74 cases. Growth was observed in 46 cases. Using immunochemical demonstration of keratin proteins (KER), epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), three morphologically distinct cell populations were characterized and described. Two cell types (E- and E'-cells) were identified as epithelial by their positive staining for KER and EMA. The third type (F cells) displayed a negative staining for these two epithelial markers; they were considered as stromal cells (fibroblasts). More than 50% of the cultures consisted of pure epithelial cells. Positive CEA staining was observed only in KER- and EMA-positive cells. Out of the 30 cultures, 15 displayed positive staining for CEA. In 7 of these, 30-50% of cells displayed positive, diffuse staining for CEA. The other 8 cultures consisted of more than 50% CEA-positive cells. Strong and homogeneous positivity was restricted to the E-cells, while in the same cultures, E'-cells displayed heterogeneous and diffuse staining. Efficiency and value of this cell culture system are discussed, in comparison with other human breast tumor cell (HBTC) culture techniques. Identification of growing cells and cellular composition of primary cultures are emphasized.

Breast Neoplasms↗

A simple in vitro model of mechanical injury of confluent cultured endothelial cells to study quantitatively the repair process.

A model of in vitro mechanical injury of confluent human endothelial cells (EC) in culture was developed. Human EC were obtained from umbilical veins and grown to confluence. Application on the EC monolayer of a calibrated disk of cellulose polyacetate paper resulted in removal of the EC, leaving a continuous subendothelial extracellular matrix (ECM) on the culture dish. The regeneration time depended on the original size of the lesion. Regeneration was similar with EC grown on different substrates such as human fibronectin, human subendothelial ECM, bovine collagen type I or surfaces coated with Transglutine, a surgical glue containing adhesive proteins. A human brain extract containing growth factor activity accelerated significantly the repair of the lesion, especially at low serum concentration. This simple in vitro model of mechanical injury allows the quantitative study of the effects of matrices, growth factors and pharmacological agents on the repair process.

Cells, Cultured↗

[Circulating immune complexes in breast cancer].

The occurrence of circulating immune complexes (CIC) was investigated in serum samples from 139 patients with breast cancer, using the 125I-C1q binding test. In the 85 cases of regional forms, the level of Clq binding activity did not appear to be correlated with the clinical TN stage, nor with the local treatment of the tumor. Conversely it was clearly elevated in the 13 cases of inflammatory breast tumors, and the decrease of CIC at the post-chemotherapy, but pre-surgical stage may involve the inflammatory signs in this augmentation of CIC. Frequency of occurrence and levels of CIC were slightly increased in the 41 metastatic breast cancer patients when compared to the cases of local breast carcinoma. In the disseminated forms, increase, no change, or decrease of CIC levels showed a poor correlation to progression, stabilisation, or improvement of the disease. CIC seems to be of slight prognostic value in breast cancer with local forms, but regarding progression of the disease, metastatic breast cancer patients with elevated CIC did not prove to be unfavorable group. So far, CIC did not appear to be a tumor marker or an evident prognostic factor of clinical relevance in breast cancer. Assays for antigen-specific CIC might be of greater clinical significance, in breast cancer, than the antigen non specific assays available at present.

Acute Disease↗

Proteinases and sialyltransferase in human breast tumors.

Proteolytic and sialyltransferase activities were determined in extracts of 65 human primary breast tumors, 6 lymph node metastases, 6 fibroadenomas and 27 normal tissues. Using proteins and synthetic selective substrates, we observed the presence of collagen-peptidases, plasminogen activator, cathepsin-B and cathepsin-D-like enzymes, and sialyltransferase. No active or trypsin-activatable type-IV collagenase activity was detected. Although individual variations between tumors were large, proteinase and sialyltransferase contents were significantly elevated in malignant breast tissues. Enzyme activities were found to be related to the epithelial volume of the tumor. No significant correlation was found between the proteinase or sialyltransferase activities and the degree of differentiation of the tumor cells, or the degree to which tumors had metastasized to regional lymph nodes. Since large variations of enzyme levels apparently reflect the heterogeneity of epithelial cell densities in tumor samples, proteolytic or sialyltransferase activities cannot therefore be used as a measure of quantitative evaluation of invasive properties in breast cancer.

Adenocarcinoma↗

Immunoradiometric assay for human thyroglobulin and variations in thyroid pathology.

A specific and sensitive double antibody radioimmunoassay for measuring human serum thyroglobulin (Tg) has been developed. Serum Tg levels are reported for patients with differentiated and undifferentiated thyroid carcinomas, post-treated and untreated hyperthyroidism, thyroiditis, and cold nodular goiters. We have studied results of serum Tg levels in the follow-up and care of patients who have undergone total thyroidectomy for differentiated thyroid carcinomas. Tg has no diagnostic value in the detection of thyroid cancer, but is a reliable index of metastatic growth in the follow-up of patients with differentiated carcinomas. In addition, serum Tg determination might be helpful in the aetiological diagnosis of bone or lung metastases of unknown origin.

Carcinoma↗