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Biomedical subjects

B Boyer

Publications and source records attributed to B Boyer.

At least 55 records · Page 3Linked to original sources
PubMed1995

pp60c-src is a positive regulator of growth factor-induced cell scattering in a rat bladder carcinoma cell line.

The NBT-II rat carcinoma cell line exhibits two mutually exclusive responses to FGF-1 and EGF, entering mitosis at cell confluency while undergoing an epithelium-to-mesenchyme transition (EMT) when cultured at subconfluency. EMT is characterized by acquisition of cell motility, modifications of cell morphology, and cell dissociation correlating with the loss of desmosomes from cellular cortex. The pleiotropic effects of EGF and FGF-1 on NBT-II cells suggest that multiple signaling pathways may be activated. We demonstrate here that growth factor activation is linked to at least two intracellular signaling pathways. One pathway leading to EMT involves an early and sustained stimulation of pp60c-src kinase activity, which is not observed during the growth factor-induced entry into the cell cycle. Overexpression of normal c-src causes a subpopulation of cells to undergo spontaneous EMT and sensitizes the rest of the population to the scattering activity of EGF and FGF-1 without affecting their mitogenic responsiveness. Addition of cholera toxin, a cAMP-elevating agent, severely perturbs growth factor induction of EMT without altering pp60c-src activation, therefore demonstrating that cAMP blockade takes place downstream or independently of pp60c-src. On the other hand, overexpression of a mutated, constitutively activated form of pp60c-src does not block cell dispersion while strongly inhibiting growth factor-induced entry into cell division. Moreover, stable transfection of a dominant negative mutant of c-src inhibits the scattering response without affecting mitogenesis induced by the growth factors. Altogether, these results suggest a role for pp60c-src in epithelial cell scattering and indicate that pp60c-src might contribute unequally to the two separate biological activities engendered by a single signal.

Animals↗
PubMed1995

[Principles of magnetic resonance angiography].

Magnetic resonance angiography is a modality of functional imaging which can only be interpreted on the basis of a good understanding of vascular physiology and the physical principles of image acquisition. Magnetic resonance angiography is based on flow-related "artefacts". The oldest method is based on renewal of the image by proton flow: the flight time effect. Dephasing of the protons travelling in magnetic field gradients results in phase-contrast angiography. These two methods of angiography each have respective advantages and disadvantages: they are not mutually exclusive, but complementary.

Hemodynamics↗
PubMed1995

[Myxoid liposarcoma. MRI imaging].

PURPOSE: Myxoid liposarcoma is the most common type of liposarcoma (approximately 40 to 50% of all liposarcomas). The main tissue component is a myxoid matrix present primarily in extracellular compartments; proliferating lipoblasts account for less 10% of the tumor: MRI appearances are not typical for lipomatous tumor. Nevertheless histological features may permit understanding MRI findings and identifying patients with myxoid liposarcoma. MATERIALS AND METHODS: Clinical history and radiologic images of 7 patients with histologically verified myxoid liposarcoma were retrospectively studied. In all patients the tumor presented in a lower extremity as a painless, slowly growing mass. MR images were available for review in all cases (T1- and T2-weighted images); in addition fat-suppression before and after gadolinium enhancement were assessed with T1-weighted sequences. RESULTS: MRI examination revealed an "encapsulated" tumor, non infiltrating and septated. On T1-weighted sequences all the lesions show lacy, amorphous and linear foci of high signal within a low signal of the tumor due to the predominance of a myxoid matrix. The high sensitivity of MRI demonstrates the presence of small areas of high signal and fat-suppression technique is valuable for characterizing soft-tissue tumors: suppression of high signal intensity on fat-saturated T1-weighted images indicates the presence of fatty tissue components. CONCLUSION: Clinical correlation with MRI appearances on T1-weighted sequences (in addition to fat-suppression technique) may suggest the possibility of myxoid liposarcoma.

Adult↗
PubMed1994

An upstream enhancer regulating brown-fat-specific expression of the mitochondrial uncoupling protein gene.

Previous studies on the regulation of a Ucp minigene in transgenic mice demonstrated that the sequences necessary for brown-fat-specific expression and inducibility by norepinephrine were located in the 5' flanking region between 1 and 2.8 kb from the transcriptional start site. We have investigated this region in more detail in cultured mouse brown adipocyte tumor cells. Deletion analysis of two types of chloramphenicol acetyltransferase reporter gene constructs under control of either the Ucp promoter or a heterologous herpes simplex virus-tk promoter defined an enhancer in a 220-bp HindIII-XbaI fragment which was essential for both brown fat specificity and norepinephrine inducibility. Site-directed mutagenesis of the reporter gene constructs established that independent mutations to a cyclic AMP-responsive element (CRE-2) or one of two TTCC motifs (BRE [brown fat regulatory element]), all within 17 bp, eliminated transient expression. Competitive DNA mobility shift assays with probes of the CRE and BRE motifs indicate that nuclear proteins interact with these motifs in a cooperative, synergistic manner. While these CRE-BRE probes do not show changes in binding which is dependent on norepinephrine treatment, a probe containing a third TTCC motif located 130 bp downstream of BRE-1 does show this dependency. The results indicate that a complex interaction of the CRE and BRE motifs, which cannot be functionally separated, control Ucp expression.

Adipose Tissue, Brown↗
PubMed1994

[Role of MRI in pre-clinical breast lesions. Preliminary results].

The purpose of this study is to assess the value of MR imaging in nonpalpable breast tumors. Thirty-two women whose mammogram showed opacity, architectural distorsionor microcalcifications, underwent preoperative dynamic MR studies with quantitative evaluation of contrast enhancement. MR showed early contrast enhancement in 10/12 breast cancers (2 false-negative) and in 6/20 benign lesions (false-positive). Quantitative study of contrast enhancement does not allow clear differentiation between these lesions. Further studies are required to confirm these findings and purpose MR imaging for aid in detection of carcinomas. Multifocal sudden enhancements are possible in benign lesions and incite to limit MR to focal mammographic abnormalities.

Adult↗
PubMed1994

Spatiotemporal expression of molecules associated with junctional complexes during the in vivo maturation of renal podocytes.

Epithelial glomerular cells differentiate from mesenchymal cells of the metanephrogenic blastema. During the first stages of glomerulogenesis, the cells acquire the morphological features of epithelial cells. Then, podocytes lose these characteristics at the maturing glomerular stage. We have studied the molecules associated with junctional complexes during glomerular differentiation in human and pig fetal kidneys. We show for the first time the expression of P-cadherin in renal cells. Epithelial cells of ureteral buds and ampullae display all the molecules associated with junctional complexes and coexpress E- and P-cadherin. However, P-cadherin, plakoglobin and vinculin are the only markers detected in future glomerular cells. We have established a spatiotemporal correlation between the time of appearance and disappearance of junctional complexes as previously described (Saxén and Wartiovaara, Int. J. Cancer 1:271-290, 1966; Saxén et al., Adv. Morphog. 7:251-293, 1968; Reeves et al., Lab. Invest. 39:90-100, 1978), and the expression of their associated molecules. Epithelial cells with stable, typical junctional complexes strongly express the molecules associated with junctions, whereas cells endowed with transient, atypical junctional complexes express low amounts of components associated with junctions. These observations suggest a correlation between the level of expression of these components and an authentic, stable epithelial phenotype.

Animals↗
PubMed1994

Implication of scatter/growth factors in tumor progression.

Several steps during cancer progression have been distinguished on the basis of anatomo-pathological observations and experimental data. The first step, which consists of the detachment of the cancer cells from the primary tumor prior to their migration, has received much attention. Several lines of evidence have indicated that inducer molecules of tumor cell dispersion are scatter factors which are similar or identical to some growth factors. Our studies have focused on the dispersing effect of growth factors, such as acidic FGF (aFGF) on a rat bladder carcinoma cell line. These studies demonstrated that specific extracellular matrix components might contribute to the scattering effect of soluble growth factors. Additionally, our results indicated that the dispersing action of aFGF is counterbalanced by its mitogenic effect, since these two functions of aFGF cannot be observed simultaneously for the same cell. Depending on its location in the cell collective, a given cell chooses to enter mitosis or to scatter in response to aFGF. The choice between the two responses is apparently driven by molecules belonging to the transducing pathways of aFGF signaling. Finally, our data indicated that aFGF-induced tumor cell scattering leads to increased in vitro invasiveness and in vivo metastasis. Interestingly, the presence of few aFGF-producing tumor cells in a population of non-producing cells dramatically enhances the growth rate and the metastatic properties of the whole tumor, suggesting that a low proportion of highly metastatic cells in a heterogeneous cell population might modify the behavior of the tumor mass.

Animals↗
PubMed1993

Cyclic AMP distinguishes between two functions of acidic FGF in a rat bladder carcinoma cell line.

The rat bladder carcinoma cell line NBT-II exhibits two completely different responses to acidic FGF (aFGF): at high cell density, aFGF is a potent mitogen whereas at low cell density, aFGF acts as a scattering agent that can convert the epithelial NBT-II cells into fibroblastic-like, motile cells. The basis of the dual action of aFGF has been approached by using substances interfering with the transducing pathways known to be activated by growth factors. Genistein and tyrphostin, two inhibitors of tyrosine kinases, inhibit both cell scattering and mitogenesis induced by aFGF. Conversely, sodium orthovanadate, a potent inhibitor of tyrosine phosphatases can reproduce the two effects of aFGF, indicating that protein tyrosine phosphorylations are determinant in the two pathways. In contrast, transforming growth factor (TGF)-beta 1 is a strong inhibitor of DNA synthesis induced by aFGF but has no effect on cell scattering, providing evidence that the two pathways are divergent. In an attempt to determine the specificity of the pathways of aFGF we found that the level of cAMP, which can be externally elevated, is of pivotal importance in distinguishing between the two transducing pathways leading to either DNA replication or cell dispersion. Forskolin, 8-bromo cAMP, dibutyryl-cAMP, and cholera toxin are all capable of potentiating the mitogenic effect of aFGF while strongly inhibiting its scattering action. Moreover, addition of any of these substances to NBT-II cells converted into fibroblasts immediately induces their reversion towards an epithelial phenotype. These findings support a role for cAMP as a modulator of the effects of aFGF. Moreover, basal cAMP synthesis, which is not affected by aFGF, is higher in sparse than in dense cultures indicating that the level of cAMP depends on the status of the cell. Altogether, these results suggest that establishment and maintenance of the epithelial state require a precise regulation of cAMP level.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Epithelium-mesenchyme interconversion as example of epithelial plasticity.

This review focuses on epithelium-mesenchymal transitions (EMT), defined as dynamic cell restructurations changing the epithelial state of differentiation into a mesenchymal phenotype. These transitions, known to occur during embryogenesis are also involved during some pathological events of adult life, such as wound repair and metastasis of cancer cells. Numerous studies of embryonic EMTs, found during some morphogenetic processes, have stressed the importance of intercellular and cell-matrix adhesive interactions as key elements regulating cell dissociation and acquisition of cell motility. On the other hand, in vitro studies indicate that growth factors, growth-factor related molecules and extracellular matrix components are involved in initiation of EMT. Therefore, the cellular targets of EMT-inducing molecules are likely to include molecules participating in cell adhesion systems.

Amphibians↗
PubMed1993

Direct coronal view of the shoulder with arthrographic CT.

Direct coronal oblique views of the shoulder were obtained with arthrographic computed tomography (CT) in 35 shoulders with surgical correlation. There were 18 complete cuff tears, four partial ones, two type 3 superior labral, anterior, and posterior (SLAP) lesions, and one type 4 SLAP lesion. The coronal sections were obtained after double-contrast shoulder arthrography and axial CT sections had already been obtained. The patient was seated directly on the slope of the gantry, and the shoulder to be studied was positioned in the center of the gantry. The maximal time needed for this procedure was 5 minutes. Rotator cuff tears were detected with a sensitivity of 95% and a specificity of 100%. The size of the tears as determined on the coronal sections was strongly correlated with surgical measurement (r = .939). All SLAP lesions were detected. The authors' experience shows that obtaining coronal oblique sections is an effective way to improve arthrographic CT.

Adolescent↗
PubMed1993

Transient effect of epidermal growth factor on the motility of an immortalized mammary epithelial cell line.

The effects of growth factors on epithelial cell motility and dispersion have been examined on an immortalized human mammary epithelial cell line, the 184A1 nontumorigenic cell line. Among all the molecules tested, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) were demonstrated to stimulate an increase in mammary epithelial cell motility and wound closure that was associated with a morphological transformation of the cells and was accompanied by modifications in cell-cell and cell-substrate adhesion systems. The EGF-induced increase in cell motility and monolayer wound closure occurred over a 24 hour period and was not dependent on an increase in cell number. The effect of EGF was abolished by inhibiting alpha 2 integrins with specific antibodies, indicating that part of the mechanism for the increase in cell motility and accelerated wound closure depends on alpha 2 integrin functional expression. After 72 hours of exposure to EGF, the EGF-induced alterations in cell morphology, motility and cell adhesion systems underwent a spontaneous reversion that was correlated with a 10-fold reduction in the number of EGF receptors. The ability to regulate the scattering response induced by growth factors might be an important feature distinguishing normal epithelial cells from their tumoral counterparts.

Breast↗