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Biomedical subjects

A Fuchs

Publications and source records attributed to A Fuchs.

At least 73 records · Page 4Linked to original sources
PubMed1997

Signs of vagal reinnervation 4 years after heart transplantation in spectra of heart rate variability.

Several investigators have shown signs of possible sympathetic but not parasympathetic reinnervation in heart transplanted patients. Spectral analysis of heart rate and blood pressure variability is a noninvasive tool appropriate to detect a functional autonomous reinnervation to the heart. In a follow-up study, 13 patients after heart transplantation (HTx) were investigated, mean age 50.6+/-8.5 years, 18 healthy volunteers were selected as control group. For each patient two recordings were performed which took part 14+/-5 months respectively 42+/-8 months after HTx. ECG and systolic blood pressure (SBP) have been recorded simultaneously for 5 min in supine position during controlled respiratory rate of 12 or 15 cycles/min. No graft rejection has been detected in the endomyocardial biopsy performed right after the recordings. Power spectral densities (PSD) were calculated for the beat-to-beat time series of RR-intervals (distance of two following QRS complexes) and SBPs. The area of PSD in the range of 0.05-0.17 Hz was defined as low frequency (LF) and that of 0.18-0.35 Hz as high frequency (HF). LF and HF are indicative of efferent sympathetic respectively parasympathetic activity at the sinus node. A significant increase of LF (226%) and HF (213%) during a mean period of 28 months could be found. No differences were to be shown for systolic blood pressure variability. Previous findings confirm that LF band increases 4 years after transplantation, suggesting a possible sympathetic reinnervation of the heart. On the other hand an increase of the HF band also suggests a parasympathetic reinnervation.

Adolescent↗
PubMed1997

Polymorphous low-grade adenocarcinoma: flow cytometric, p53, and PCNA analysis.

Polymorphous low-grade adenocarcinoma of minor salivary glands (terminal duct carcinoma, lobular carcinoma) was first defined more than a decade ago. A 17% recurrence rate and a 9% metastasis rate have been reported. Fifteen formalin-fixed, paraffin-embedded archival cases were analyzed. Ploidy and proliferative activity were evaluated with flow cytometric analysis. Demonstration of an abnormal p53 gene product and proliferative cell nuclear antigen analyses were also performed with routine immunohistochemical procedures. The purpose of this investigation was to evaluate these parameters and determine if a correlation existed. Flow cytometry was performed on 10 cases; 3 showed an aneuploid cell line (mean, S-phase diploid tumor cells 5.9%; S-phase aneuploid 26.7%). Products of a mutation of the p53 tumor suppressor gene have been noted to accumulate in salivary gland tumors, both benign and malignant. Qualitative assessment revealed p53 positive staining in 4 of 15 tumors; positive cells comprised 5% to 10% of the tumor. The percentage of tumor cells positive for proliferative cell nuclear antigen staining ranged from 0.5% to 70%. There was no correlation between proliferative activity as determined by proliferative cell nuclear antigen when compared with results of flow cytometric analysis except for one case that exhibited p53 staining, a 26% proliferative cell nuclear antigen fraction, and a distinct aneuploid cell line.

Adenocarcinoma↗
PubMed1997

[On-site laboratory monitoring on the intensive care unit. Blood gas, electrolyte, glucose, hemoglobin and lactate determination with the CIBA Corning 865 Analysis System].

INTRODUCTION: For decision-making in the ICU, rapid and accurate analysis of vital laboratory parameters is essential. The industry provides devices which analyse these parameters on a decentralised setting and which are designed for use by non-laboratory personnel. We investigated whether accuracy and handling of a new analyser (Ciba-Corning 865, Chiron Diagnostics, Medfield, USA) are good enough for basing clinical decisions on the measured parameters. MATERIALS AND METHODS: The Ciba-Corning 865 allows measurement of blood gases, electrolytes, haemoglobin, glucose and lactate by use of photometric, ion-selective, enzymatic and electrochemical sensors in less than 18 microliters of whole blood. In a cardiac surgical intensive-care unit the accuracy of the device was tested by comparison to 61 measurements of quality control reagents, 48 tonometered blood samples and 536 parallel measurements in the clinical laboratory. Besides a 10-minute instruction, the participating personnel had no formal training with the device. RESULTS: The differences between measurements in quality control reagents and tonometered blood and the expected value were lower than 5%. The comparison with clinical laboratory measurements showed correlation coefficients from 0.94 (sodium) to 0.99 (glucose, lactate). The biases in Bland-Altman analyses were below 5%, the limits of agreement were found to be in a clinically acceptable range for all parameters. During the test period no technical problems occurred with the analyser and good acceptance by the personnel was found. CONCLUSIONS: The measured parameters were accurate enough to be used for therapeutic decisions in acute care medicine. Although it should not be a complete alternative to the clinical laboratory, because of rapid analyses, small sample volumes and easy handling the use of the Ciba-Corning 865 is advantageous for patients and users.

Blood Chemical Analysis↗
PubMed1997

Urinary and tissue levels of scatter factor in transitional cell carcinoma of bladder.

PURPOSE: We previously reported increased titers of scatter factor in urine of 20 patients with transitional cell carcinoma of the bladder compared to noncancer and cancer control groups. Scatter factor was also found in bladder tumor extracts but the number of samples examined was too small for detailed analysis. We report a followup study of larger numbers of patients with transitional cell carcinoma and controls. MATERIALS AND METHODS: The scatter factor content of urine samples and bladder tissue extracts was measured by enzyme-linked immunosorbent assay. Values were normalized per milligram creatinine or tissue protein. Statistical analysis was performed using the Mann-Whitney U test or, for multiple comparisons, the Kruskal-Wallis H test. RESULTS: Patients with transitional cell carcinoma of the bladder (52) had higher urinary scatter factor titers than did 24 normal subjects (p < 0.001) or 14 with benign prostatic hypertrophy (p < 0.001), 49 with prostate cancer (p < 0.001) and 13 with other genitourinary tract cancers (p < 0.01). Transitional cell carcinoma cases with clinicopathological evidence of disease had greater urinary scatter factor levels than those with no evidence of disease at urine sampling (p < 0.01). However, patients with transitional cell carcinomas in remission still had much greater urinary scatter factors than did normal subjects (p < 0.001). In contrast, patients with active prostate cancer had urinary scatter factor levels similar to those in remission. Patients with muscle invasive or high grade transitional cell carcinomas tended to have higher urinary scatter factor levels than patients with nonmuscle invasive or low grade tumors, respectively, but the differences were not significant. Greater levels of scatter factor were present in tissue extracts of muscle invasive transitional cell carcinomas than in nonmuscle invasive tumors (p < 0.001) or nontumor tissue (p < 0.02). Invasion was more closely related to tissue scatter factor content than tumor grade, since high grade noninvasive transitional cell carcinomas had a scatter factor content similar to that of low grade noninvasive transitional cell carcinomas. CONCLUSIONS: These studies suggest that scatter factor may be a marker of bladder cancer, urinary scatter factor titers tend to reflect disease activity and particularly high tissue titers of scatter factor are found in muscle invasive cancers. A larger prospective study will be necessary to determine the clinical significance of elevated scatter factor titers in transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗
PubMed1997

Scatter factor stimulates tumor growth and tumor angiogenesis in human breast cancers in the mammary fat pads of nude mice.

Scatter factor (SF) (also known as hepatocyte growth factor) is a plasminogen-related growth factor that induces tumor cell motility, invasion, and angiogenesis. Its receptor is a tyrosine kinase encoded by c-met, a protooncogene. Human breast cancer cells express SF and c-met in vivo; but human breast cancer cell lines do not produce SF in vitro. To determine whether SF can modulate the in vivo growth of human breast cancers within a natural mammary environment, we studied the orthotopic growth of SF-transfected (SF+) versus control (SF-) clones of MDAMB231 human mammary carcinoma cells in the mammary fat pads of athymic nude mice. SF+ clones expressed SF mRNA and produced very high titers of SF protein, whereas SF- clones did not express SF mRNA or produce detectable SF protein. Two SF+ clones (21 and 29) showed significantly increased tumor growth rates, reaching 3- to 4-fold larger primary tumor volumes and weights by time of killing (p < 0.001), as well as higher rates of axillary lymph node metastasis (p < 0.02), as compared with two SF- clones (32 and 34). In contrast, in vitro proliferation rates, two-dimensional colony formation, and soft agar colony formation were no greater in SF+ than in SF- clones. We performed further studies to investigate the discrepancy between the in vivo and in vitro growth results. Tumor extracts from SF+ clone (21 + 29) tumors had 50-fold higher SF content than did SF- clone (32 + 34) tumors, confirming high-level SF expression in vivo in SF+ tumors. Immunostaining of tumor sections for proliferating cell nuclear antigen revealed only a modest increase in the proportion of cycling cells in SF+ versus SF- tumors (70% versus 60%, respectively). The terminal deoxytransferase-labeling index was equally low (approximately 1%) in SF+ and SF- tumors, suggesting that apoptosis was not responsible for the slower growth of SF- tumors. However, SF+ tumors had significantly higher tumor microvessel densities than SF- tumors (p < 0.001). Moreover, there were much higher titers of chemotactic activity for microvascular endothelial cells in cell-conditioned media and primary tumor extracts from SF+ clones as compared with SF- clones. As demonstrated using the rat cornea assay, there was more angiogenic activity in SF+ tumor extracts than in SF- extracts. The increased chemotactic and angiogenic activities in SF+ tumor extracts were not explained by secondary alterations in the content of the angiogenic mediator, vascular endothelial growth factor, or the antiangiogenic glycoprotein, thrombospondin-1; and those activities were neutralized using an anti-SF monoclonal antibody. These findings suggest that SF promotes the orthotopic growth of human breast cancers, at least in part, by stimulating tumor angiogenesis.

Adipose Tissue↗
PubMed1997

O6-Alkylguanine-DNA alkyltransferase in normal colon tissue and colon cancer.

O6-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that reverses alkylation damage produced by chloroethylnitrosoureas and is a major determinant of cellular resistance to adjuvant chemotherapy with these drugs. AGT activity was measured in 119 samples from 69 patients, including normal, tumor, and diseased tissue, and 42 patients in which both normal and tumor tissue were assayed. The activity varied among individuals, but there was no statistically significant difference in average AGT activity among tumor, normal, and diseased tissue, or between men and women, or between young and old patients (< 70 or > 70 years). Few (3/49) tumor samples showed an absence of AGT activity (Mer- phenotype). The results indicate that nearly all colon cancers have significant AGT activity, and adjuvant chloroethylnitrosoureas chemotherapy must be modified, perhaps by the use of AGT biochemical modulators, to overcome this natural drug resistance.

Adolescent↗
PubMed1997

Tacrolimus: a superior agent to OKT3 for treating cases of persistent rejection after intrathoracic transplantation.

Acute myocardial rejection refractory to treatment still contributes significantly to patient death after intrathoracic transplantation. A historical series of 25 patients who received OKT3 (5 mg/day for 10 days) was compared with our current experience with 14 patients treated with tacrolimus (0.1 mg/kg/day targeting whole blood concentrations of 13 to 18 ng/ml): all 39 patients having persistent rejection unresponsive to treatment at the time of conversion. Mean periods of follow-up were 842.9 days and 342.6 days, respectively. Actuarial 1-year patient survival rates were 64.0% and 76.2% for the OKT3 and tacrolimus treatment groups, with most of the deaths in the OKT3 group occurring early (p = 0.064). Causes of death for patients receiving OKT3 included acute rejection (n = 5), infection (n = 3), carcinoma (n = 2), multiorgan failure (n = 1) and graft vessel disease (n = 1). The two deaths in the tacrolimus treatment group were the result of infections. Eighty percent of patients treated with OKT3 subsequently experienced further rejection episodes, in many cases necessitating methotrexate therapy. In contrast, only one patient (7.1%) from the tacrolimus group was diagnosed with rejection after conversion (p < 0.001). In conclusion, when compared with OKT3 therapy, a switch in baseline immunosuppression from cyclosporine to tacrolimus seems to be markedly more effective, as well as being safe for the treatment of persistent acute rejection.

Actuarial Analysis↗
PubMed1997

[Problems in the interpretation of blood chemistry results in birds].

In 837 birds which died or were euthanatized because of their disease, blood could be taken within 12 hours before death. Blood chemistry results were compared with specific necropsy findings of different organs. The parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinine kinase (CK), glutamate dehydrogenase (GLDH), glucose, total protein, uric acid, urea and creatinine were measured. Possible reasons for the bad comparability of blood chemistry results and organ lesions are discussed. Glucose and creatinine were found not to be useful in a routine panel for avian patients.

Alanine Transaminase↗
PubMed1996

Scatter factor expression and regulation in human glial tumors.

Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a cytokine that induces cell motility in vitro and angiogenesis in vivo. SF appears to be a determinant of the malignant phenotype in certain systemic cancers. We detected SF in extracts prepared from human gliomas, with the highest levels found in malignant tumors. Human glioblastoma cells expressed both SF and its receptor (c-met protein) in vivo, as demonstrated by immunohistochemistry. Consistent with these observations, we found moderate to high levels of production of immunoreactive and biologically active SF by cultured human glioblastoma cells (3 of 8 lines) and by neural microvascular endothelial cells (NMVEC) (3 of 3 lines). SF stimulated the proliferation of glioblastoma and NMVEC cell lines by paracrine or autocrine mechanisms. Conditioned medium (CM) from both glioblastoma and NMVEC cells contained SF-inducing factor (SF-IF) activity, defined by its ability to stimulate SF production in an indicator cell line (MRC5 human fibroblasts). This activity consisted of a high-molecular-weight (> 30 kDa), heat-sensitive component and a low-molecular weight (< 30 kDa), heat-stable component. Furthermore, glioblastoma CM stimulated NMVEC SF production, and NMVEC CM stimulated glioblastoma cell SF production, by 3- to 6-fold in each case. Our findings demonstrate that SF-dependent interactions between glioma cells, and between glioma cells and endothelium, can contribute to the heterogeneous proliferative and angiogenic phenotypes of malignant gliomas in vivo.

Brain↗
PubMed1996

In vitro activation of the NADPH oxidase by fluoride. Possible involvement of a factor activating GTP hydrolysis on Rac (Rac-GAP).

The possible mechanism of activation of the NADPH oxidase by fluoride was investigated in the cell-free system. It is shown that the stimulatory effect of fluoride is inhibited by guanosine 5'-O-(2-thiodiphosphate) (GDP[S]) and potentiated by GTP. The effect of fluoride is not additive with GTP[S]. Fluoride activation requires the presence of Mg2+ in millimolar concentration but is independent of Al3+. The activating effect of fluoride is preserved in solubilized membrane extract after removal of the majority of heterotrimeric GTP-binding proteins by immunoadsorption. Fluoride has no direct action either on the nucleotide exchange of GTP hydrolysis of the isolated Rac protein. In contrast, fluoride effectively inhibits Rac-GTPase activity enhanced by a membrane component. In this way, fluoride could prolong the prevalence of Rac in the GTP-bound state and, as a consequence, activate NADPH oxidase. The possibility of the involvement of a membrane-bound Rac GTPase-activating protein activity in the physiological regulation of the enzyme is raised.

Animals↗
PubMed1996

Topological organization of the cytosolic activating complex of the superoxide-generating NADPH-oxidase. Pinpointing the sites of interaction between p47phoz, p67phox and p40phox using the two-hybrid system.

Activation of the superoxide-generating NADPH-oxidase in phagocytic cells requires the assembly of a membrane-bound flavocytochrome b and cytosolic factors p47phox and p67phox under the control of the GTP-binding protein, Rac. A novel cytosolic component p40phox was recently identified. Most of the components of the complex contain SH3 domains and/or polyproline motifs which are likely to mediate protein-protein interactions occurring in the formation of the active NADPH-complex. The two-hybrid system was used to explore associations between the cytosolic factors. Various constructs of p47phox, p67phox and p40phox cDNAs coding for functional domains were inserted into two-hybrid system vectors, expressing fusion proteins either with the DNA binding protein Lex A or with the activation domain of Gal 4. The site of interaction of p67phox with p47phox was restricted to the C-terminal SH3 domain of p67phox and to the polyproline motif of p47phox. The polyproline motif of p47phox was also found to mediate interaction with the SH3 domain of p40phox, as well as intramolecular interaction within p47phox. The site of interation of p67phox with p40phox was found to be in the 150 amino acid stretch between the two SH3 domains of p67phox. As the C-terminal tail of p40phox which interacts with p67phox contains neither a SH3 domain nor a polyproline consensus site, it is concluded that a novel type of interaction occurs between p40phox and p67phox. Taken together, the results of the two-hybrid experiments led us to formulate a model for oxidase activation, induced by phosphorylation, in which p40phox tends to prevent spontaneous activation.

Amino Acid Sequence↗
PubMed1996

Extending the HKB model of coordinated movement to oscillators with different eigenfrequencies.

We study the dynamics of a system of coupled nonlinear oscillators that has been used to model coordinated human movement behavior. In contrast to earlier work we examine the case where the two component oscillators have different eigenfrequencies. Problems related to the decomposition of a time series (from an experiment) into amplitude and phase are discussed. We show that oscillations at multiples of the main frequency of the oscillator system may occur in the phase and amplitude due to the choice of a coordinate system and how these oscillations can be eliminated. We derive an explicit equation for the dynamics of the relative phase of the oscillator system in phase space that enables a direct comparison between theory and experiment.

Cybernetics↗
PubMed1996

Coordination dynamics of trajectory formation.

The present study aims to understand the neurally based coordination dynamics (multistability, loss of stability, transitions, etc.) of trajectory formation in a simple task. Six subjects produced two spatial patterns of coordination in the xy plane by alternating the abduction-adduction and flexion-extension motions of their right index finger. Each pattern was characterized by a unique temporal ratio between the x and y directions of motion: (1) a figure zero, a 1:1 temporal pattern; and (2) a figure eight, a 2:1 temporal pattern. The patterns were produced rhythmically and movement frequency was scaled across ten frequency plateaus, with ten cycles of motion per step. As movement frequency increased, switching from a figure eight to a figure zero was observed at critical cycling frequencies. The switch from pattern (2) to pattern (1) was identified in the spatial trajectory and power spectra of x(t) and y(t). En route to the transition, enhancement of fluctuations was observed in the Fourier amplitudes of x(t) and y(t), specifically at f0 (the metronome frequency) and 2f0 (the first harmonic of f0). Interestingly, there was no difference in the spatial variability of the two patterns. Overall, the data demonstrate that spatial patterns of coordination can be characterized in terms of the temporal relationship between the spatial components of the trajectory itself. We discuss the experimental findings in relation to other end-point planning and multijoint control strategies, as well as the much more general problem of temporal synchronization in many interlimb and intralimb coordination tasks.

Adult↗
PubMed1996

Bladder cancer mortality associated with arsenic in drinking water in Argentina.

Inorganic arsenic (In-As) is known to be a human carcinogen, causing lung cancer by inhalation and skin cancer by ingestion. Ecologic studies in Taiwan have found a dose-response relation between ingestion of In-As from drinking water and bladder cancer, but questions have been raised concerning the validity and generalizability of the findings. Several areas of Argentina have had high exposures to arsenic from naturally contaminated drinking water, particularly the eastern region of the province of Córdoba. In this study, we investigated bladder cancer mortality for the years 1986-1991 in Córdoba's 26 counties, using rates for all of Argentina as the standard for comparison. Bladder cancer standardized mortality ratios (SMRs) were consistently higher in counties with documented arsenic exposure. We grouped counties into low-, medium-, and high-exposure categories; the corresponding SMRs [with 95% confidence intervals (CI)] were 0.80 (95% CI = 0.66-0.96), 1.42 (95% CI = 1.14-1.74), and 2.14 (95% CI = 1.78-2.53) for men, and 1.21 (95% CI = 0.85-1.64), 1.58 (95% CI = 1.01-2.35), and 1.82 (95% CI = 1.19-2.64) for women. The clear trends found in a population with different genetic composition and a high-protein diet support the findings in Taiwan.

Adolescent↗
PubMed1996

Differentiating agents do not induce a true hairy cell phenotype in B-CLL cells in vitro.

B-Chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) are both differentiated B-cell lymphoproliferative disorders. Prior studies have suggested that phorbol esters and the macrocyclic lactone Bryostatin-1, which are both protein kinase-C activators, can induce the differentiation of B-CLL cells into HCL cells in vitro, as evidenced by morphology, phenotype and TRAP activity. The differentiating effect of all-trans retinoic acid on B-CLL cells has been less extensively studied. We studied the effects of incubating adherence purified B-CLL cells with phorbol myristic acetate (PMA), all-trans retinoic acid (ATRA), and Bryostatin-1. None of these agents induced a true HCL phenotype (CD5-, CD11c/CD25 coexpression) under the conditions studied.

Acid Phosphatase↗
PubMed1996

Malignant mesothelioma: immunohistochemistry and DNA ploidy analysis as methods to differentiate mesothelioma from benign reactive mesothelial cell proliferation and adenocarcinoma in pleural and peritoneal effusions.

OBJECTIVE: To determine whether malignant mesotheliomas can be differentiated from adenocarcinomas and benign reactive mesothelial cells in pleural and peritoneal fluids using immunohistochemical analysis in conjunction with DNA ploidy analysis. DESIGN: Sixteen cases of malignant mesothelioma, including epithelial, sarcomatous, and biphasic types, were collected. DNA analysis using flow cytometry and/or image analysis was performed on paraffin-embedded tissue from 15 of the mesothelioma cases, as well as on cytospin cell preparations from samples of pleural and peritoneal fluids from cases with either cytologically proven adenocarcinoma (seven cases) or benign reactive mesothelial cells (seven cases). Immunohistochemical studies were done in 15 mesotheliomas, 5 adenocarcinomas, and 4 benign reactive mesothelial cell effusions. RESULTS: All malignant mesotheliomas tested (100%) stained positively for prekeratin, whereas stains for carcinoembryonic antigen, B72.3, Leu-M1, and Ber-EP4 were negative. Stains vimentin, epithelial membrane antigen, and CA125 were positive in 75%, 75%, and 25% of cases tested, respectively. Benign reactive mesothelial cell cases stained similarly. Adenocarcinomas were more likely to react positively with B72.3, Ber-EP4, and carcinoembryonic antigen, and negatively with vimentin. DNA analysis showed that all benign cases were diploid, while all adenocarcinomas were nondiploid. Fifty-three percent of the malignant mesotheliomas were nondiploid. Sensitivity for detection of nondiploidy was greater for image analysis than for flow cytometry (100% vs 75%). CONCLUSIONS: B72.3, Ber-EP4, carcinoembryonic antigen, and vimentin are useful immunohistochemical markers in differentiating malignant mesotheliomas from adenocarcinomas, whereas immunohistochemistry does not reliably distinguish malignant from benign hyperplastic mesothelial cells. The addition of DNA ploidy studies is useful for differentiating the latter two groups.

Adenocarcinoma↗
PubMed1996

Scatter factor binds to thrombospondin and other extracellular matrix components.

Scatter factor (SF) is an angiogenic growth factor that stimulates motility and invasion of carcinoma cells. SF is present in the extracellular matrix (ECM) of breast cancers, where it might act to promote tumor cell invasion and angiogenesis. To investigate how SF is incorporated into the ECM, we studied the binding of SF to various ECM components using a solid-phase binding assay based on the SF enzyme-linked immunosorbent assay. We found that SF binds to a variety of ECM molecules, with different binding capacities. The highest SF binding capacities were observed for thrombospondin-1 (TSP-1), fibronectin (Fn), and heparan sulfate proteoglycan, although SF did not bind to albumin. Mature two-chain SF and precursor single-chain SF bound approximately equally well to TSP-1 and Fn. Moreover, two SF alpha-chain peptides (NK1 and NK2) both bound to TSP-1 and Fn, suggesting that the whole SF molecule is not required for binding. Based on binding competition assays, TSP-1 exhibited higher affinity for SF than did nine other ECM molecules, including Fn and heparan sulfate proteoglycan. Although heparin in solution potently inhibited the binding of SF to TSP-1-coated surfaces, even very high concentrations of heparin could not elute SF already bound to TSP-1. SF binding was modulated by binding interactions among ECM molecules (TSP-1-Fn, TSP-1-collagen I, and Fn-collagen I), suggesting that the matrix capacity to bind SF depends upon its exact composition. SF bound in a dose-dependent fashion to ECMs secreted by three human breast carcinoma cell lines. Binding of SF to matrices from all three cell lines was significantly inhibited by preincubation of the matrices with antibodies against TSP-1, whereas antibodies against several other ECM components were less effective or ineffective in inhibiting SF binding. In addition, TSP-1 markedly inhibited chemotaxis of microvascular endothelial cells toward SF and SF-induced angiogenesis in the rat cornea neovascularization assay. Our findings suggest that 1) SF interacts with a variety of ECM components, 2) high affinity SF-TSP-1 interactions may mediate the binding of SF to the breast cancer matrix, and 3) the SF-TSP-1 interaction may contribute to modulation of angiogenesis. Possible implications of these findings for tumor angiogenesis are discussed.

Animals↗