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A Raz

Publications and source records attributed to A Raz.

At least 91 records · Page 5Linked to original sources
PubMed1996

Autocrine motility factor signals integrin-mediated metastatic melanoma cell adhesion and invasion.

The binding of autocrine motility factor (AMF) to its cell surface receptor, gp78, stimulates tumor cell motility. In this report, we provide evidence that stimulation of gp78 by either AMF or a monoclonal antibody to gp78 (3F3A) increases adhesion and spreading of metastatic murine melanoma (B16a) cells on fibronectin. This gp78-regulated increase is mediated by up-regulation of surface alphaIIbbeta3++ and alpha5beta1 integrin receptors. In addition, AMF treatment of B16a cells increased translocation of alphaIIbbeta3 and alpha5beta1 from the cytoplasm to the cell surface. However, alphaIIbbeta3 and alpha5beta1 demonstrate separate and unique staining patterns at the surface of B16a cells in response to stimulation of gp78. Furthermore, stimulation of B16a cells with AMF increased their invasion through Matrigel. This stimulated invasion was inhibited by antibodies to alphaIIbbeta3 but not by antibodies to alpha5beta1. The increased integrin surface expression and function in response to AMF was blocked by N-benzyl-N-hydroxy-5-phenylpentanamide, an inhibitor of 12-lipoxygenase, and calphostin C, an inhibitor of protein kinase C. The results demonstrate that AMF stimulates integrin-mediated B16a cell adhesion, spreading, and invasion, and these events are regulated by a signaling pathway involving 12-lipoxygenases and protein kinase C.

Animals↗
PubMed1996

Expression and function of autocrine motility factor receptor in human choriocarcinoma.

OBJECTIVE: Our purpose was to determine whether human choriocarcinoma cells express autocrine motility factor receptor (AMF-R) and to study its function in this tumor system. STUDY DESIGN: The expression and localization of AMF-R were compared in choriocarcinoma and normal placental trophoblasts using both cell lines and tissue sections. In addition, migratory properties of choriocarcinoma cells and normal placental cells was determined. RESULTS: Using immunofluorescence and immunoperoxidase staining, we have detected the expression of AMF-R in choriocarcinoma cells with receptor clustering on the cell surface, while term placenta cells expressed AMF-R less intensely with no receptor clustering. In choriocarcinoma tissues, AMF-R was strongly expressed in malignant cytotrophoblasts cells while adjacent normal villous trophoblast cells and necrotic regions were weakly or negatively stained. Choriocarcinoma cells responded to AMF-R stimulation with increased cell motility, while term placental cells were unresponsive. CONCLUSION: Human choriocarcinoma cells express functional cell surface AMF-R in vitro and in choriocarcinoma tissue suggesting that this receptor may play an important role in cancer cell motility.

Cell Movement↗
PubMed1996

Differential effects of 1,25-(OH)2D3 on acyl hydrolase and cyclooxygenase activities in interleukin 1 beta-stimulated human synovial fibroblast cultures.

Effects of proinflammatory cytokines on synovial fibroblasts are considered to play a role in the accumulation of prostaglandin E2 (PGE2) in the inflamed joint in rheumatoid arthritis. We have previously shown that interleukin 1 beta (IL-1 beta) induces PGE2 production in synovial fibroblast cultures and that this effect is suppressed by the active metabolite of vitamin D3, 1,25-(OH)2D3. To study the mechanism of the inhibitory action of 1,25-(OH)2D3, its effect on acyl hydrolase (arachidonic acid (AA) release) and cyclooxygenase (COX) activities were investigated. Our findings indicate that IL-1 beta caused an increase in AA release and COX activity and that in the presence of 1,25-(OH)2D3 AA release, but not COX activity, is suppressed. In comparison, dexamethasone, which also inhibits IL-1 beta induction of PGE2, had inhibitory effects on both parameters.

Arachidonic Acid↗
PubMed1996

Expression of autocrine motility factor receptor correlates with disease progression in human gastric cancer.

Up-regulation of autocrine motility factor receptor (AMF-R) expression has been shown to be associated with invasion and metastasis of experimental tumour systems and human neoplasms. Monoclonal antibodies against AMF-R (gp78) were used to stain 221 primary gastric cancer specimens, and level of expression was examined in relation to pathological stage and prognostic values. In 125 out of 221 (56.6%) patients, gp78 was detected. Expression of gp78 was associated with macroscopic type, lymphatic and venous invasions, and lymph node and peritoneal metastasis. The level of gp78 expression in the cancer specimens was associated with histopathological stage and grade of tumour penetration. Positive gp78 expression was significantly associated with poor prognosis (P < 0.001). This significant relationship remained among patients in stage II and III. The results suggest that gp78 expression could be used as a prognostic marker in gastric cancer patients.

Adenocarcinoma↗
PubMed1996

Salivary eicosanoid concentration in patients with Sjögren's syndrome.

OBJECTIVE: To investigate eicosanoid concentrations in the saliva of patients with primary Sjögren's syndrome (SS). METHODS: Whole mixed saliva of 36 subjects was assayed for eicosanoid concentrations using a radioimmunoassay. Patients with primary SS having positive lip biopsy served as the study group; their results were compared with data from patients with dry mouth and negative lip biopsy (dry mouth group), and with a group of normal healthy controls. RESULTS: Concentrations of thromboxane B2 were significantly (p < 0.01) increased in 18 patients with primary SS compared with 10 patients with dry mouth and eight healthy normal controls (1.95 (SD 0.51) ng/ml saliva compared with 0.52 (0.1) ng/ml and 0.3 (0.1) ng/ml, respectively). Similarly, prostaglandin E2 concentrations were also significantly increased (p < 0.01) in 11 patients with primary SS compared with five patients with dry mouth and eight normal controls (3.75 (0.82) ng/ml saliva compared with 0.32 (0.1) ng/ml and 0.41 (0.1) ng/ml, respectively). CONCLUSION: Salivary concentrations of eicosanoids are significantly increased in patients with primary SS, and this may prove helpful in the diagnosis of this disease.

Biomarkers↗
PubMed1996

Neuronal synchronization of tonically active neurons in the striatum of normal and parkinsonian primates.

1. Previous studies indicate that tonically active neurons (TANs) are the cholinergic interneurons of the striatum and predict that their activity is synchronized. To test whether TANs do fire synchronously, and whether dopamine depletion affects their synchronization, we recorded the simultaneous activity of several TANs in the putamens of two vervet monkeys before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. Cross-correlation analysis revealed that most pairs of TANS (33 of 54; 61.1%) fire synchronously at +/- 60-ms delay. Correlated activity was more common between neurons with characteristic response to reward (17 of 19 pairs; 89.5%). 3. Cross-correlation study of 24 triplets of TANS showed synchronization of spiking activity of all 3 TANS in only 29.2% of cases (7 of 24 triplets). Correlated activity of two of three possible pairs was found in 25% of the cases. 4. After MPTP treatment and the development of parkinsonian symptoms, most TANS' auto- and cross-correlograms (22 of 28 units; 78.6%; and 23 of 28 pairs; 82.1%) became oscillatory. The number of correlated pairs was slightly increased (24 of 28; 85.7%). The strength of the synchronization was not significantly different from the normal values. 5. These findings support the notion that TANs function as distributed, partially overlapping synchronized networks. However, a normal dopaminergic system is not essential for synchronization of TANs; on the contrary, dopaminergic activity may even have a desynchronizing effect on the basal ganglia's system.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Autocrine motility factor receptor as a possible urine marker for transitional cell carcinoma of the bladder.

PURPOSE: To determine whether autocrine motility factor receptor (AMFR) is detectable in the urine of patients with transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: We assayed the urine of 89 patients with bladder pathology and 28 normal controls for AMFR. A monoclonal antibody to AMFR was used. RESULTS: All patients with muscle-invasive TCC tested positive for AMFR. Autocrine motility factor receptor was detectable for 80% of superficial tumors, with a correlation between AMFR and tumor grade. Seventy-five percent of control urines tested negative. CONCLUSIONS: Autocrine motility factor receptor is detectable in the urine of patients with TCC. Long-term follow-up and refinements in the assay should define the marker's utility for detection and prognosis.

Adult↗
PubMed1996

Tumor autocrine motility factor responses are mediated through cell contact and focal adhesion rearrangement in the absence of new tyrosine phosphorylation in metastatic cells.

Autocrine motility factor (AMF) is a tumor-secreted cytokine that acts as a motogen as well as a mitogen via a receptor-mediated signaling pathway(s). Expression of the AMF receptor (AMF-R) in normal cells is regulated by cell contact whereas in transformed cells AMF-R is constitutively expressed irrespective of cell density. Here we have analyzed the regulation of AMF-R expression in a BALB/c angiosarcoma tumor system that allows investigation of cellular characteristics associated with tumor progression. The metastatic cell variant (A31-M) displayed a higher rate of unstimulated motility and responded to tumor-derived AMF locomotory stimulus as compared with the nonmetastatic cell variants (A31-TR and A31-TU) and, although a similar level of receptor expression was detected in cellular extracts from subconfluent cultures of these sublines, surface localization differed and cell contact down-regulated AMF-R expression in the normal but not the transformed cell counterparts. AMF promoted marked rearrangement of focal adhesion plaque proteins in the AMF migration-responsive cells exclusively. Reorganization of vinculin after AMF stimulation was paralleled by morphological redistribution of tyrosine-phosphorylated proteins and the tyrosine kinase pp125FAK in the migration-responsive cells; however, we did not observe a concomitant change in the pp125FAK phosphorylation state or the general level of cellular tyrosine phosphorylation in response to treatment, suggesting that the induction of cellular migration by AMF is independent of tyrosine phosphorylation events at the focal contacts and may therefore represent a novel pathway of cytokine-induced migration regulation.

Animals↗
PubMed1996

Repeated fasting and refeeding with 20:5, n-3 eicosapentaenoic acid (EPA): a novel approach for rapid fatty acid exchange and its effect on blood pressure, plasma lipids and hemostasis.

Twenty hypertensive subjects participated in three clinical trials of 13 days each, to examine the effects of Alsepa fish oil [20:5, n-3 eicosapentaenoic acid (EPA) 180 mg, and 22:6 n-3 docosahexaenoic acid (DHA) 120 mg] on n-3 for n-6 polyunsaturated fatty acids (PUFA) exchange on serum phospholipids, blood pressure (BP), triglycerides (TG) and primary hemostasis. After 13 days, plasma phospholipids showed an increase in sigma n-3 (EPA and DHA) from 2.0 to 5.9% (P < 0.01), and a decrease in sigma n-6 (arachidonic acid and linoleic acid) from 29.8 to 22.6% (P < 0.01). A concomitantly significant reduction in systolic BP (SBP) (158.7 +/- 23.8 mm Hg to 146.5 +/- 17.0 mm Hg, P = 0.04), and diastolic BP (DBP) (80.8 +/- 8.4 mm Hg to 72.9 +/- 14.9 mm Hg, P = 0.04) as well as a significant decrease in platelet adhesion and aggregation on extra cellular matrix measured as a percentage of surface coverage (11.9 +/- 4.8% to 4.2 +/- 3.2%, P = 0.0001) was observed. In addition, a significant reduction in baseline dependent TG was observed; the higher the baseline level TG, the more pronounced the reduction (average 159.2 +/- 74.6 mg% to 108.0 +/- 46.1 mg%, P = 0.001). No change was observed in total cholesterol, high and low density lipoprotein (HDL, LDL), platelet and fibrinogen. Repeated fasting and refeeding with fish oil facilitated plasma exchange of n-3 for n-6 PUFA, improved BP, clinical metabolic parameters and lowered platelet reactivity in the vessel wall (primary hemostasis). In severe and life-threatening situations, the beneficial effects of fish oil should be considered for rapid exchange of n-3 for n-6 PUFA. In this study we describe a novel approach for rapid fatty acid exchange by fasting/refeeding with fish oil supplementation, as well as improved BP, plasma lipids and primary hemostasis. Further research is required on the therapeutic use of fish oils and the physiological mechanisms involved in fatty acid exchange.

Adult↗
PubMed1995

Galectin-3 is a nuclear matrix protein which binds RNA.

The endogenous galectin-3 is a carbohydrate-binding protein of M(r) approximately 30,000 serving in the cytoplasm and on the cell surface as a receptor for ligands containing poly-N-acetyllactosamine sequences. In addition, galectin-3 has been demonstrated to be associated in the nucleus with ribonucleoprotein complexes and to act as a pre-mRNA splicing factor and to be involved in spliceosome assembly. However, little is known about either its nuclear localization or its ligand(s), respectively. We demonstrate directly here that galectin-3 is associated with the RNA protein skeleton of the nucleus, i.e., the nuclear matrix, and binds with single-stranded DNA (ssDNA) and with RNA. The affinity of binding was determined to be 2.3 microM. Lactose, which inhibits galectin-3 binding to glycoconjugates, failed to inhibit either galectin-3-ssDNA or galectin-3-RNA binding. Galectin-3 exhibited the highest affinity to poly(A) ribonucleotide homopolymers. The results presented here shows that galectin-3 may act as a RNA-binding protein in the nuclear matrix in a non-carbohydrate-dependent manner.

Animals↗
PubMed1995

Expression of autocrine motility factor receptor in human esophageal squamous cell carcinoma.

Autocrine motility factor and its receptor (gp78) have been shown to play an important role in tumor cell migration, invasion and metastasis. We have detected gp78 expression in buffered-formalin-fixed, paraffin-embedded sections of esophageal squamous cell carcinomas using an anti-gp78 monoclonal antibody (MAb), 3F3A, and examined the relationship between gp78 expression and clinicopathological and prognostic factors. In 55 of 101 (54%) patients, gp78 was detected in the tumor cells. The frequency of gp78-positive expression was significantly associated with tumor size, infiltrative growth, depth of invasion and lymph node metastasis. The cumulative survival rate of patients with gp78 was significantly lower than that of patients without gp78. Our results suggest that autocrine motility factor receptor (gp78) expression could be a useful biomarker for malignancy grading and prognosis in patients with esophageal squamous cell carcinoma.

Adult↗
PubMed1995

Loss of cell-contact regulation and altered responses to autocrine motility factor correlate with increased malignancy in prostate cancer cells.

Tumor cell migration and proliferation in new organ environments are critical steps in cancer progression and can be modulated by tumor- and host-secreted molecules. Autocrine motility factor (AMF) is a tumor-secreted cytokine which regulates growth and motility by a receptor-mediated pathway. The AMF receptor, a 78-kDa cell surface glycoprotein (gp78), is regulated by cell contact in normal fibroblastic and bladder cells; however, this mechanism is disrupted during tumor progression. A prostatic carcinoma cell line which is low- to non-metastatic in nude mice (PC-3) and a derived metastatic variant (PC-3M) were examined to determine if gp78 cell density regulation is involved in prostate cancer progression. Both cell lines expressed gp78 and, although the basal migration of the parental PC-3 cells was higher than that of the metastatic variant, only the PC-3M cells were capable of responding to tumor-derived AMF with increased motility. Furthermore, these cells exhibited differential patterns of wound closure in an experimental system whereby the low-metastatic PC-3 cells migrated primarily along the wound edge while individual high-metastatic PC-3M cells entered the cell-free wound area directly. Cell surface gp78 distribution distinguished the cell populations with a markedly concentrated display of gp78 in polarized capped regions on the surface of the metastatic cells. Cell-cell contact down-regulated gp78 expression in the parental, but not the metastatic, cells, and mitogenic responses to exogenous AMF differed between these cell lines as well. In this model, metastasis appears to be associated with aberrant regulation of gp78 expression and distribution, coupled with enhanced exploitation of AMF's locomotory and proliferative effects.

Cell Movement↗
PubMed1995

Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion.

Galectin-3 (Gal-3) is a beta-galactoside-binding protein with M(r) approximately 30,000. Cell surface Gal-3 is postulated to be involved in homotypic aggregation of tumor cells in the circulation during metastasis through attachment to a complementary serum glycoprotein(s), which serves as a cross-linking bridge between adjacent cells. To test this hypothesis a recombinant strain of baculovirus encoding Gal-3 was used to infect Sf9 insect cells, which lack endogenous Gal-3. Immunoblotting and indirect immunofluorescence studies revealed that the infection with recombinant virus conferred Gal-3 expression on Sf9 cells, and the Gal-3 was localized on the cell surface as well as in the cytoplasm. Sf9 cells infected with recombinant virus underwent homotypic aggregation in the presence of exogenous glycoprotein (i.e., asialofetuin), whereas control cells uninfected or infected with wild-type virus did not. Lactose and Fab' fragments of anti-Gal-3 antibodies markedly inhibited the cell-cell aggregation. Moreover, cosuspension of Sf9 cells infected with the recombinant virus with uninfected cells in the presence of asialofetuin resulted in a preferential cell-cell adhesion of the Gal-3-expressing cells. These results directly demonstrate the ability of cell surface Gal-3 molecules to mediate homotypic cell adhesion by bridging through branched, soluble complementary glycoconjugates.

Animals↗
PubMed1995

Identification of an upstream region that controls the transcription of the human autocrine motility factor receptor.

We have isolated from a human placenta cosmid library a 0.7 kb genomic clone that contains the 5' terminal portion of the autocrine motility factor receptor (hAMFR) coding region. Chloramphenicol Acetyl Transferase (CAT) reporter gene assays have identified this region as the promoter of the hAMFR gene. A single transcription initiation site (+1) has been mapped to 129 bp upstream of the ATG start codon by primer extension. DNA sequence analysis and CAT assay revealed a TATA element at the position -485/-468 which was able to conduct only a marginal transcription (less than 5% of the total activity). The majority of the hAMFR promoter's activity is contributed by a transcription initiator (Inr) element overlapping the initiation site (+1) which independently controls the transcription of the hAMFR gene. Gel mobility shift assays showed that DNA-binding proteins in HeLa cells nuclear extract can bind specifically to both promoter's elements. DNA-binding proteins were found to be differentially expressed by sparse and dense cultured normal fibroblasts. The nuclear-binding protein expressed by sparse NIH-3T3 cells induced a DNA mobility shift similarly to the nuclear protein of HeLa cells, while a different DNA-protein complex size was observed with nuclear proteins extracted from dense cultured NIH-3T3 cells. Also CAT-reporter gene analysis revealed a significant lower activity in dense NIH-3T3 cells as compared with the sparse-cultured counterparts. These results help to explain the previously observed cell-cell contact regulation of AMFR expression in normal cells and its consecutive expression in tumor cells.

3T3 Cells↗
PubMed1995

Expression of an endogenous galactose-binding lectin correlates with neoplastic progression in the colon.

BACKGROUND: Galectin-3 is an endogenous galactose-binding protein that is expressed in a wide range of normal and neoplastic tissues and is thought to be involved in cellular adhesion and growth regulation. Conflicting data have been reported regarding the expression of galectin-3 during carcinogenesis in the colon. METHODS: The authors studied the expression of galectin-3 in 153 tissue specimens, including 29 adenomas containing early cancer, 66 colon carcinomas of known Dukes' stage with available long term patient survival data, and 23 additional primary carcinomas with 35 associated metastases. An immunohistochemical scoring system was used that considers tumor heterogeneity and yields an integrated numeric score subject to statistical analysis. Genetically related colon cancer cells with different metastatic capabilities also were compared by Western blot analysis. RESULTS: Galectin-3 expression was significantly higher in high grade dysplasia and early invasive cancers compared with the adenomatous tissue from which they evolved (mean staining score, 2.33 vs. 1.15; P = 0.001). Galectin-3 expression in invasive cancers varied according to Dukes' stage, indicating a linear relationship with advancing stage (P = 0.008). Enhanced expression correlated with decreased long term patient survival (P = 0.021). Metastases expressed a higher level of galectin-3 compared with the primary cancers from which they evolved (P < 0.005) as did cultured cells of high metastatic capability compared with their counterparts with low metastatic potential. CONCLUSION: Galectin-3 expression in colonic mucosa is related to neoplastic transformation and metastatic progression.

Adenoma↗
PubMed1995

Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin.

BACKGROUND: Prostate cancer is the most common cancer diagnosed in U.S. men and remains incurable once it has metastasized. Many stages of the metastatic cascade involve cellular interactions mediated by cell surface components, such as carbohydrate-binding proteins, including galactoside-binding lectins (galectins). Modified citrus pectin (pH-modified), a soluble component of plant fiber derived from citrus fruit, has been shown to interfere with cell-cell interactions mediated by cell surface carbohydrate-binding galectin-3 molecules. PURPOSE: The aim of this study was to determine whether modified citrus pectin, a complex polysaccharide rich in galactosyl residues, could inhibit spontaneous metastasis of prostate adenocarcinoma cells in the rat. METHODS: The ability of modified citrus pectin to inhibit the adhesion of Dunning rat prostate cancer MAT-LyLu cells to rat endothelial cells was measured by 51Cr-labeling. Modified citrus pectin inhibition of MAT-LyLu cell anchorage-independent growth was measured by colony formation in agarose. The presence of galectin-3 in rat MAT-LyLu cells and human prostate carcinoma was demonstrated by immunoblotting and immunohistochemistry. One million MAT-LyLu cells were injected subcutaneously into the hind limb of male Copenhagen rats on day 0. Rats were given 0.0%, 0.01%, 0.1%, or 1.0% (wt/vol) modified citrus pectin continuously in their drinking water (from day 4 until necropsy on day 30). The number of MAT-LyLu tumor colonies in the lungs were counted. RESULTS: Compared with 15 or 16 control rats that had lung metastases on day 30, seven of 14 rats in the 0.1% and nine of 16 rats in the 1.0% modified citrus-pectin group had statistically significant (two-sided; P < .03 and P < .001, respectively) reductions in lung metastases. The lungs of the 1.0% modified citrus pectin-treated rats had significantly (two-sided; P < .05) fewer metastatic colonies than control groups (9 colonies +/- 4 [mean +/- SE] in the control group compared with 1 colony +/- 1 in the treated group). Modified citrus pectin had no effect on the growth of the primary tumors. In vitro, modified citrus pectin inhibited MAT-LyLu cell adhesion to rat endothelial cells in a time- and dose-dependent manner as well as their colony formation in semisolid medium. CONCLUSIONS: We present a novel therapy in which oral intake of modified citrus pectin acts as a potent inhibitor of spontaneous prostate carcinoma metastasis in the Copenhagen rat. IMPLICATIONS: Further investigations are warranted to determine the following: 1) the role of galectin-3 in normal and cancerous prostate tissues and 2) the ability of modified citrus pectin to inhibit human prostate metastasis in nude mice.

Adenocarcinoma↗
PubMed1995

Impact of community educational programmes on foreign body aspiration in Israel.

The study objectives were to determine the impact of a nationwide educational campaign on the incidence of foreign body aspiration (FBA) in Israeli children. Impressed by the alarming number of FBAs, we conducted an educational campaign through the media during 1982-1983. The campaign included television and radio broadcasts, newspaper articles and interviews, and medical educational programmes in community paediatric care centres. Questionnaires were sent to all Departments of Paediatrics in Israel. Results showed a reduction in the incidence of FBA by 35% in 1983 as compared to 1981. Re-evaluation studies conducted in 1992 showed no further reduction of FBA. CONCLUSION. Continuous and extensive educational programmes should be undertaken by the health authorities if FBA is to be prevented. Furthermore, it is important to legislate mandatory labelling of seed and nut containers with the warning that the intake of seeds is dangerous to children under 5 years of age.

Adolescent↗