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At least 955 records · Page 53Linked to original sources
PubMed1997

Elevated levels of shed syndecan-1 correlate with tumour mass and decreased matrix metalloproteinase-9 activity in the serum of patients with multiple myeloma.

Sera from 20 myeloma patients and 12 normal controls were analysed for the presence of syndecan-1 and matrix metalloproteinase-9 (MMP-9). The level of syndecan-1 in the serum was elevated in 7/20 (3 5%) myeloma patients whilst 6/19 patients (31%) had decreased serum MMP-9 activity. The presence of increased syndecan-1 was associated with decreased serum MMP-9. Both elevated syndecan-1 and decreased MMP-9 were associated with higher marrow plasmacytosis, serum beta-2 microglobulin and paraprotein levels. These data provide evidence that the syndecan-1 ectodomain is shed in vivo. Quantitation of serum syndecan-1 may be a useful measure of tumour mass and may have important implications for myeloma biology.

Adult↗
PubMed2002

Membrane type 1 matrix metalloproteinase regulates cellular invasiveness and survival in cutaneous epidermal cells.

Membrane type 1 matrix metalloproteinase is a member of the membrane-anchored matrix metalloproteinase family and is involved in tissue remodeling events ranging from tumor invasion and angiogenesis to growth and development. We sought to clarify the role of membrane type 1 matrix metalloproteinase in cutaneous epidermal cells using anti-sense cDNA expression in human keratinocytes. Modulation of membrane type 1 matrix metalloproteinase transcript and protein levels was achieved via retroviral expression of a 5' 1.4 kb anti-sense membrane type 1 matrix metalloproteinase construct and a 3.4 kb full-length sense membrane type 1 matrix metalloproteinase construct in primary and immortalized keratinocytes and SCC-25 cells. Maximal reductions were observed 48-72 h after transduction with 1.4 kb anti-sense membrane type 1 matrix metalloproteinase construct that correlated with significant decreased pro-matrix metalloproteinase-2 activation. Functionally, we found decreased cell migration, reduced cellular proliferation, and increased apoptotic nuclear fragmentation after 1.4 kb anti-sense membrane type 1 matrix metalloproteinase construct expression. Our findings suggest a role for membrane type 1 matrix metalloproteinase in human cutaneous epidermal cell invasion and survival mechanisms in vivo.

Antisense Elements (Genetics)↗
PubMed2004

Correlation between functional genotypes in the matrix metalloproteinases-1 promoter and risk of oral squamous cell carcinomas.

BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF), which are highly associated with areca use, are prevalent in most Asian countries. Matrix metalloproteinases (MMPs) are superfamily of metal-dependent proteolytic enzymes, mediating the degradation of extracellular matrix. Insertion/deletion (-1607 2G-->1G) polymorphism has been described in the promoter region of the human matrix metalloproteinases-1 (MMP-1) genes, which cause an alteration in the transcriptional activity. This genotype is associated with risks of cancer genesis and metastasis. In this paper, we studied the relationship between such genotype and areca-associated oral diseases. METHODS: Genomic DNA from the blood of OSCC (n = 121), OSF (n = 58) cases and controls (n = 147) were amplified by polymerase chain reaction (PCR)-based genotyping. The OSCC were further grouped into buccal squamous cell carcinoma (BSCC) and non-buccal suqmaous cell carcinoma (NBSCC), in accord with the site of involvement. The significance of the differences was assessed by Fisher's exact test. RESULTS: The 2G genotype in MMP-1 promoter was observed with a higher frequency in both OSCC (0.69, P = 0.06) and NBSCC (0.76, P = 0.03) cases compared with controls (0.63), with an odds ratio of 2.17 and 4.58, respectively. This genotype was not related to the risk of OSF. No other clinicopathologic parameter was associated with the genotypes in OSCC cases. CONCLUSION: The results showed that 2G genotype in MMP-1 promoter was associated with the risk of OSCC.

Adult↗
PubMed2003

Migration through the extracellular matrix by the parasitic protozoan Leishmania is enhanced by surface metalloprotease gp63.

Leishmania species engineered to express high levels of the surface metalloprotease gp63 have enhanced capacity of migration through extracellular matrix in vitro. This correlates with gp63 degradation of extracellular matrix components, such as collagen type IV and fibronectin, and suggests an important role for gp63 in the pathogenesis of leishmaniasis.

Animals↗
PubMed2007

Glaucoma detection with matrix and standard achromatic perimetry.

BACKGROUND: Matrix perimetry is a new iteration of frequency-doubling technology (FDT) which uses a smaller target size in the standard achromatic perimetry presentation pattern. AIM: To compare the performance of matrix and Swedish interactive thresholding algorithm (SITA) perimetry in detecting glaucoma diagnosed by structural assessment. DESIGN: Prospective cross-sectional study. METHODS: 76 eyes from 15 healthy subjects and 61 consecutive glaucoma suspects and patients with glaucoma were included. All patients underwent optic nerve head (ONH) photography, SITA and matrix perimetries, and optical coherence tomography (OCT) within a 6-month period. Glaucoma diagnosis was established by either glaucomatous optic neuropathy or OCT by assessing retinal nerve fibre layer (RNFL) thickness. Mean deviation (MD), pattern standard deviation (PSD), glaucoma hemifield test and cluster of abnormal testing locations were recorded from matrix and SITA perimetries. RESULTS: Similar correlations were observed with matrix and SITA perimetry MD and PSD with either cup-to-disc ratio or OCT mean RNFL. The area under the receiver operating characteristic (AROC) curves of MD and PSD for discriminating between healthy and glaucomatous eyes ranged from 0.69 to 0.81 for matrix perimetry and from 0.75 to 0.77 for SITA perimetry. There were no significant differences among any corresponding matrix and SITA perimetry AROCs. CONCLUSIONS: Matrix and SITA perimetries had similar capabilities for distinguishing between healthy and glaucomatous eyes regardless of whether the diagnosis was established by ONH or OCT-RNFL assessment.

Adult↗
PubMed1996

Anti-invasive activity of ursolic acid correlates with the reduced expression of matrix metalloproteinase-9 (MMP-9) in HT1080 human fibrosarcoma cells.

We examined the anti-invasive activity of ursolic acid (UA) on the highly metastatic HT1080 human fibrosarcoma cell line. UA reduced tumor cell invasion through a reconstituted basement membrane in a transwell chamber. A significant down-regulation of matrix metalloproteinase-9 [MMP-9; Mr 92,000 gelatinase/type IV collagenase (gelatinase B)] by UA was detected by Northern blot analysis. However, MMP-2 [Mr 72,000 gelatinase/type IV collagenase (gelatinase A)] and membrane-type MMP were constantly expressed, and the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 also was not changed after 3 and 6 days of treatment with UA. Quantitative gelatin-based zymography confirmed a markedly reduced expression of MMP-9 but not MMP-2 after treatment with UA. To confirm the UA-induced down-regulation of MMP-9 expression, we constructed a secreted alkaline phosphatase (SEAP) reporter vector including MMP-9 promoter. After transfection of MMP-9/SEAP reporter vector into HT1080 cells, reduced SEAP activity was detected after treatment with UA. These results suggest that down-regulation of MMP-9 contributes to the anti-invasive activity of UA in HT1080 cells.

Basement Membrane↗
PubMedDate not supplied

Chemometric differentiation of raw and commercial milk by trace elements using principal component analysis.

Nine trace elements (Cr, Mn, Fe, Ni, Cu, Zn, Mo, Cd, and Pb) were determined in the dissolved ash of 36 samples of raw milk. The distribution of the concentration of each element was first investigated by means of a test of normality. The matrix of the correlation between the concentrations of the elements was then used as a starting matrix for principal component analysis. Nine variables were reduced to four principal components, accounting for 75% of the total variance. The biophilic elements Mn-Fe and Cu-Mo were positively associated with the first two principal components, while Cr was correlated to the third and Ni and Cd with the fourth principal component. Pb and Zn are both negatively correlated to the first principal component. Comparison with 42 samples of a commercial milk, by using a two-dimensional plot of the principal component scores, rendered possible the differentiation between raw and commercial milk.

Animals↗
PubMed1993

Matrix metalloproteinase-9 (92 kDa gelatinase/type IV collagenase) from U937 monoblastoid cells: correlation with cellular invasion.

The role of matrix metalloproteinase-9 (MMP-9, 92 kDa gelatinase/type IV collagenase) in invasion of mononuclear phagocytes was studied with U937 monoblastoid cells. 12-o-tetradecanoyl 13-phorbol acetate (TPA) differentiated them to macrophage-like cells with induction of MMP-9, and tumor necrosis factor alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) stimulated the production of MMP-9 by TPA-treated cells. TNF alpha also induced the production of MMP-9 by TPA-untreated U937 cells without morphological differentiation. Other agents including dimethyl sulfoxide (DMSO), all-trans-retinoic acid (all-trans-RA), platelet-derived growth factor and 3';5'-cyclic monophosphate had no effects on MMP-9 production by TPA-treated or -untreated cells, but all-trans-RA and DMSO did have a morphological effect on the differentiation of the cells. These data suggest that MMP-9 production by U937 cells is regulated by a mechanism independent of the differentiation to macrophage-like cells. MMP-9 was purified to homogeneity as an inactive zymogen with M(r) 92,000 (proMMP-9) from TPA-differentiated U937 cells treated with TNF alpha. ProMMP-9 was activated by p-aminophenylmercuric acetate (APMA) generating an active species of M(r) 67,000. Trypsin and cathepsin G also attained activation of the zymogen to its full activity obtained by APMA activation, but plasmin, leukocyte elastase, thrombin and plasma kallikrein had no ability to activate it. APMA-activated MMP-9 degraded type I gelatin readily and cleaved native collagen types III, IV and V. Invasion assays using reconstituted basement membrane coupled with a type IV collagenolysis assay showed good correlations between invasiveness, type IV collagenolysis and proMMP-9 production. Invasion was significantly inhibited by EDTA, alpha 2-macroglobulin and tissue inhibitor of metalloproteinases-1, but not by inhibitors of cathepsin G and leukocyte elastase. These data suggest that MMP-9 plays an important role in the invasion of mononuclear phagocytes through basement membranes.

Basement Membrane↗
PubMed1999

Residue 2 of TIMP-1 is a major determinant of affinity and specificity for matrix metalloproteinases but effects of substitutions do not correlate with those of the corresponding P1' residue of substrate.

The unregulated activities of matrix metalloproteinases (MMPs) are implicated in disease processes including arthritis and tumor cell invasion and metastasis. MMP activities are controlled by four homologous endogenous protein inhibitors, tissue inhibitors of metalloproteinases (TIMPs), yet different TIMPs show little specificity for individual MMPs. The large interaction interface in the TIMP-1.MMP-3 complex includes a contiguous region of TIMP-1 around the disulfide bond between Cys1 and Cys70 that inserts into the active site of MMP-3. The effects of fifteen different substitutions for threonine 2 of this region reveal that this residue makes a large contribution to the stability of complexes with MMPs and has a dominant influence on the specificity for different MMPs. The size, charge, and hydrophobicity of residue 2 are key factors in the specificity of TIMP. Threonine 2 of TIMP-1 interacts with the S1' specificity pocket of MMP-3, which is a key to substrate specificity, but the structural requirements in TIMP-1 residue 2 for MMP binding differ greatly from those for the corresponding residue of a peptide substrate. These results demonstrate that TIMP variants with substitutions for Thr2 represent suitable starting points for generating more targeted TIMPs for investigation and for intervention in MMP-related diseases.

Cell Line↗
PubMedDate not supplied

Invasive potential and substrate dependence of attachment in the dunning R-3327 rat prostate adenocarcinoma model.

Cancer cell attachment to and invasion of the extracellular matrix has been associated with the metastatic potential of cell lines of the Dunning R-3327 rat prostatic adenocarcinoma model. We investigated the cell-matrix interactions of prostate tumor cells by comparing the invasive ability through reconstructed extracellular matrix and attachment upon EHS NATRIX (natural extracellular matrix), fibronectin, laminin, and collagen Type IV. We observed a correlation between metastatic potential and substrate dependence of attachment in prostate cancer cells. Nonmetastatic AT-1 cells possessed a higher adhesive potential to extracellular matrix components than the highly metastatic cells (ML, MLL and AT-3). It was also found that the invasive potential of the three highly metastatic cell lines was significantly higher than that of the nonmetastatic cell line. Here, it is reported that the ability to traverse a matrigel matrix correlates with their metastatic potential. These observations suggest that the extracellular matrix components are highly involved in influencing prostate cancer cell activities. In addition, we investigated the effects of two differentiation agents, retinoic acid (RA) and difluoromethylornithine (DFMO), on the adhesive and invasive profiles of the tumor cells. After treatment with both agents, adhesion was increased to levels not different from nonmetastatic cells. Furthermore, the ability of highly metastatic cells to traverse a matrigel barrier was significantly reduced after treatment with both differentiation agents. These results suggest that RA and DFMO are capable in reversing the metastatic potential of prostate cancer cells in vitro and may give a possible insight into their role as potential therapeutic agents in vivo.

Adenocarcinoma↗
PubMed1997

Oriented and lengthwise growth of octacalcium phosphate on collagenous matrix in vitro.

A correlation among the oriented growth of octacalcium phosphate (OCP), the arrangement of the collagen fibrils in a collagenous matrix and direction of ionic flow was studied in vitro at pH7.0 and at 37 degrees, using two types of collagen disks made from sliced bovine Achilles tendon. Disk A and disk B were made from slices cut perpendicular and parallel to the collagen fibrils, respectively. The products on the collagen fibrils were a mixture of OCP and apatite in the both disks, but the relative amounts of apatite and OCP could not be determined. Short plate-like or flake-like OCP crystals grew parallel to the collagen fibrils and ionic flow on the Ca-side of the disk A. On the contrary, ribbon-like or rectangular OCP crystals grew along the collagen fibrils lying on the disk B. Apatite also grew with the same orientation as OCP in the both cases. The oriented and length-wise growth of OCP crystals on the disk B was ascribed to the arrangement of the collagen fibrils in the disk.

Achilles Tendon↗
PubMed2004

Formulation development and human in vitro-in vivo correlation for a novel, monolithic controlled-release matrix system of high load and highly water-soluble drug niacin.

Novel, controlled-release formulations for high drug load, highly water soluble compound niacin based on polyethylene oxide (PEO) and hydroxypropylmethyl cellulose (HPMC) matrices were developed and investigated. The effect of sodium bicarbonate as a modulator of swelling, erosion, and drug release and its impact on changes in the kinetics of axial swelling and gel strength were evaluated by textural analysis during dissolution study. The drug release rate from PEO-based matrices was faster and correlated with lower gel strength, greater water uptake, and greater matrix erosion. Slower release rate and greater release duration correlated significantly with greater matrix swelling with negligible matrix erosion for the HPMC-based matrix system. Inclusion of sodium bicarbonate in the polymeric matrix salted out the macromolecules and increased gel strength and gel viscosity, especially in the vicinity of the swelling fronts. An in vivo study in human subjects after administration of the formulations and a commercial product exhibited similar plasma concentrations. For the formulation of interest, the mean drug fraction absorbed by the body was calculated by the Wagner-Nelson technique, and a level A "in vitro-in vivo correlation" was observed between the percent released in vitro and percent absorbed in vivo. The developed formulations appear to be robust and easy to manufacture with maximum flexibility with respect to drug dose, polymeric carriers, duration, and kinetics of drug release.

Administration, Oral↗