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21.
The receptor for urokinase-plasminogen activator 总被引:8,自引:0,他引:8
Many human cells and cell lines possess a specific receptor that binds urokinase plasminogen activator (uPA) with an affinity of about 10(-10) M. Bound enzyme is not internalized, is slowly dissociated, and retains its enzymatic activity. The amino acid sequence of uPA responsible for receptor binding is located within the first 35 aminoterminal residues, ie, in the growth factor domain. Binding, however, is not competed for by other proteins that contain the growth factor domain (including epidermal growth factor). Cells that produce uPA secrete the pro-uPA form, which subsequently binds to the receptor. A431 cells, in fact, have their receptors completely saturated with pro-uPA. It is proposed that uPA:uPA-receptor interaction plays a direct role in physiological and pathological processes that require cell migration. 相似文献
22.
Differential expression of metastasis-associated cell surface glycoproteins and mRNA in a murine large cell lymphoma 总被引:1,自引:0,他引:1
G L Nicolson R A LaBiche M L Frazier M Blick R J Tressler C L Reading T Irimura V Rotter 《Journal of cellular biochemistry》1986,31(4):305-312
A metastatic variant cell subline of the Abelson virus-transformed murine large lymphoma/lymphosarcoma RAW117 has been selected in vivo ten times for liver colonization. Highly metastatic subline RAW117-H10 forms greater than 200 times as many gross surface liver tumor nodules as the parental line RAW117-P. Analysis of cellular proteins and glycoproteins indicates reduced expression of murine Moloney leukemia virus-associated p15, p30, and gp70, and increased expression of a sialoglycoprotein, gp150, in the highly metastatic H10 cells. Northern analyses of oncogene expression suggested that mRNA of various oncogenes was expressed equally or not expressed in the RAW117 cells of differing metastatic potential. Differential gene expression was examined using a cDNA library of 17,600 clones established from poly A+ mRNA isolated from H10 cells. The cDNA library was screened by the colony hybridization technique using probes made from both RAW117-P and -H10 cells. Approximately 99.5% of these cDNA clones were expressed identically in P and H10 cells. Of the few differentially expressed cDNA clones (approx. 150/17,600), one-half of these were identified as Moloney leukemia virus sequences in a separate probing with a radiolabeled Moloney leukemia virus probe. The remainder of the differentially expressed mRNA detected by colony hybridization of the cDNA library were expressed at higher levels (approx. 1/6) or lower levels (approx. 1/3) in the highly metastatic H10 cells. 相似文献
23.
K Morgan T M Holmes M Grace S Kemel D Robson 《American journal of physical anthropology》1983,62(1):3-10
The Hutterite Brethren comprise a religious isolate and live on communal agricultural farms (colonies) in North America. In 1976 there were approximately 15,000 Canadian Brethren living in 179 colonies of the three endogamous subdivisions, the Dariusleut, Lehrerleut, and Schmiedeleut. Dariusleut and Lehrerleut colonies are located in both Alberta and Saskatchewan, and the Schmiedeleut are in Manitoba. Brethren were identified on population-based cancer registries of the three Prairie Provinces and among death registrations in the vital statistics of Alberta and Saskatchewan. The method of ascertainment was by a search for the 15 contemporary surnames and verification by address. 89 male and 91 female Brethren were identified who had cancer during the period, 1956--1975. The numbers of observed cancers were less than expected from provincial incidence rates for males and females in each province. The largest deficits were for female Brethren in Manitoba and Saskatchewan. There is a marked deficiency of cancer of the uterine cervix among female Brethren. In males there is a significant deficit of lung cancer. The Hutterite way of life contributes to a low risk for cancers of smoking-associated sites. However, there is evidence that male Brethren in Alberta may be at relatively increased risk for stomach cancer and leukemias. The site distribution patterns of cancers among the three endogamous leut are similar. 相似文献
24.
The association between bleomycin-induced chromatid aberrations and BUdR-label exchange between sister chromatids was investigated in order to evaluate Revell's exchange hypothesis for the formation of chromatid aberrations. The results of this study indicate that a larger than expected proportion of chromatid breaks can be accounted for by the exchange hypothesis though not all breaks are the result of incomplete exchange. 相似文献
25.
Prevention of ultraviolet radiation- or chemical carcinogen-induced morphologic transformation and inhibition of tumor-producing transformed cell growth by lymphotoxin and by normal spleen leukocytes were quantitatively compared to define the antineoplastic activity spectra of these natural immune mediators. When Syrian golden hamster embryo cells seeded for colony formation in culture dishes were treated simultaneously with carcinogen and lymphotoxin, the number of morphologically transformed cell colonies was irreversibly reduced by 50% in the presence of 6 units of lymphotoxin/ml. Lymphotoxin inhibition of tumor cell growth, however, was reversible and 50% reduction in tumor cell growth in three transformed lines required 124, 330, and 477 units/ml. Thus, the anticarcinogenic activity of lymphotoxin can be 20-fold or more greater than its tumor growth-inhibitory activity. Similarly spleen leukocytes also were more effective as an anticarcinogen than as an inhibitor of tumor cell growth, consistent with previous observations that naturally occurring spleen leukocyte antineoplastic activity may result from lymphotoxin secretion. 相似文献
26.
Presence of mast cell precursors in the yolk sac of mice 总被引:3,自引:0,他引:3
Concentration of mast-cell precursors in hematopoietic tissues of mouse embryos was evaluated by a limiting dilution method. Cells from yolk sacs, livers, and bodies of (WB x C57BL/6)F1 (hereafter called WBB6F1)- +/+ embryos were injected directly into the skin of adult WBB6F1-W/Wv mice which were genetically depleted of tissue mast cells. Concentration of mast-cell precursors was calculated from the proportion of injection sites at which mast cells did not appear. Since the concentration of mast-cell precursors in the yolk sac was about 30 times as great as that of embryonic body at Day 9.5 of the pregnancy, the mast-cell precursors seemed to be generated within the yolk sac. The concentration in the yolk sac reached the maximum level at Day 11, and then dropped markedly at Day 13. In contrast, mast-cell precursors increased from Day 11 to Day 15 in the fetal liver. As a result, the concentration of 11-day yolk sacs was comparable to that of 15-day fetal liver. Although intravenous injection of 15-day fetal liver cells (2 x 10(6)) rescued the general mast-cell depletion of WBB6F1-W/Wv mice, the intravenous injection of the same number of 11-day yolk sac cells did not rescue it. In contrast with fetal livers, yolk sacs scarcely contained hematopoietic stem cells which were measured by spleen colony formation. Therefore, the mast-cell precursors of the yolk sac may not originate from such stem cells. 相似文献
27.
Ethanol Inhibits Basic Fibroblast Growth Factor-Mediated Proliferation of C6 Astrocytoma Cells 总被引:2,自引:0,他引:2
Abstract: Early ethanol exposure alters the proliferative activity of glial and neuronal precursors in the developing CNS. The present study tests the hypothesis that ethanol-induced alterations in cell proliferation result from interference with growth factors. An in vitro model of astroglia (C6 astrocytoma cells) was used to study the effects of ethanol on proliferation mediated by basic fibroblast growth factor (bFGF). bFGF stimulated the proliferation of C6 cells. This bFGF-enhanced proliferation was evident by increases in total cell number, DNA synthesis (as measured by [3 H]thymidine incorporation), and the number of cells that took up bromodeoxyuridine. A synthetic peptide that specifically blocked the binding of bFGF to its high-affinity receptor completely abolished the proliferation-promoting effect of bFGF. The action of another mitogen for C6 cells, insulin-like growth factor-1, was not affected by this peptide. Therefore, the bFGF-stimulated proliferation was mediated through a specific bFGF receptor. Ethanol inhibited bFGF-mediated proliferation in a concentration-dependent manner. Ethanol concentrations of 100 and 200 mg/dl partially inhibited bFGF-mediated proliferation (by 58 and 74%, respectively), whereas concentrations of ≥400 mg/dl completely abolished the growth-stimulating effect of bFGF. Our data show that ethanol alters proliferative activity of C6 cells by disrupting the action of bFGF. The target of ethanol neurotoxicity is a receptor-mediated activity. bFGF can affect cell proliferation by a non-receptor-mediated intracellular pathway, but ethanol does not have an impact on this pathway. 相似文献
28.
In the present study, anti-metastatic effect of Z-100 on the spontaneous pulmonary metastases of Lewis lung carcinoma (3LL)
was examined in an attempt to regulate suppressor T cells. When Z-100 (10 mg/kg) was daily injected i.p. after 3LL inoculation,
survival rate of these mice was increased significantly (p<0.05). In addition, the number of pulmonary metastatic colonies of 3LL in Z-100-treated mice were significantly decreased
by 38% at 21 days, as compared with that of control mice (p<0.05). Along with the decrease of pulmonary metastases, suppressor cell activity was also gradually reduced in these mice,
as compared with that of control mice. When splenic suppressor cells (5×107 cells) from 3LL-bearing mice were adoptively transferred into normal mice (recipients) just before inoculation of 3LL, the
development of pulmonary metastases in recipients was significantly accelerated. However, splenocytes from 3LL-bearing mice
treated with Z-100 did not affect the development of pulmonary metastasis. The potential to accelerate the metastasis of splenic
mononuclear cells from 3LL-bearing mice was decreased significantly by the treatment with anti-Thy 1.2 monoclonal antibody
(mAb), anti-Lyt 2.2 mAb or anti-CD11b mAb followed by complement. IL-4 activity in the sera of 3LL-bearing mice was detected
15 days after tumor inoculation (13 pg/ml) and gradually increased (18 pg/ml) 20 days after tumor inoculation. However, when
Z-100 (10 mg/kg) was daily injected i.p., IL-4 activity in sera was decreased significantly, and the IL-4 activity was not
detected in these mice on day 20. These results suggest that Z-100 could inhibit the pulmonary metastases in 3LL-bearing mice
through the inhibition of suppressor T cell activity and a possible candidate of its effector molecule, IL-4. 相似文献
29.
A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer 总被引:4,自引:0,他引:4
Dr. Giancarlo Pizza Caterina De Vinci Diego Cuzzocrea Domenico Menniti Ernesto Aiello Paolo Maver Giuseppe Corrado Piero Romagnoli Ennio Dragoni Giuseppe LoConte Umberto Riolo Aldopaolo Palareti Paolo Zucchelli Vittorio Fornarola Dimitri Viza 《Biotherapy》1996,9(1-3):123-132
As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have
suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA).
These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able
to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered this study and received one
intramuscular injection of 2–5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission
was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was
126 weeks, higher than the survival rates reported in the literature for patients of the same stage. 相似文献
30.
Santos Carlos Chandler Karen Zimmer Stephen Fisher Paul B. Gunthert Ursula Anderson Kimberly Ward 《Cell biochemistry and biophysics》1995,26(1):1-19
A parallel-plate flow chamber was used to quantify the detachment of normal cloned rat embryo fibroblasts (CREF) fibroblasts,ras-transformed CREF fibroblasts (CREF T24), and CREF T24 fibroblasts transfected with a Krev/RAP1A suppressor gene (HK B1) from
a confluent monolayer of normal CREF fibroblasts to determine if the expression patterns of CD44 variants (mol wt 110 and
140 kDa) corresponded with detachment properties and metastatic potential. In the detachment assay, known shear stresses ranging
from 20–24 dyn/cm2 were applied to the adherent cells and the number of cells detached from the monolayer after 180 s was determined. Results
showed that cellular expression of CD44 variants correlated with the metastatic potential of the cells and with the cells’
ability to detach from a monolayer of normal cells. Western blot analysis showed a low level of expression of the CD44 variants
in the normal cell line, CREF, and the lowly metastatic cell line, HK B1. Detachment studies showed a low percentage of detachment
of both of these cell lines from a normal cell monolayer. Tumor-derived (HK B1-T) and lung nodule-derived (HK B1-M) cell lines
were established and both formed tumors and metastasis with reduced latency periods as compared to HK B1, but still showed
a markedly delayed latency period compared to the highly metastatic cell line, CREF T24. Both of these cell lines showed a
higher expression of the CD44 variants as compared to CREF and HK B1, and detached easier than CREF and HK B1. CREF T24 showed
a much higher level of expression of the variants and had a higher percentage detachment than all other cell lines. To further
test the role of the CD44 variants in the ability of the cells to detach from the normal monolayer, CREF cells were transfected
with a DNA construct that constitutively expresses the CD44 variants and the detachment properties of three randomly selected
clones were studied. Clones 2 and 3 showed a low level of expression of the CD44 variants after transfection and detached
from the normal monolayer similar to CREF. Clone 1 showed a high level of expression of the CD44 variants and the detachment
of these cells was significantly higher than CREF. From these results, it is concluded that in the five cell lines studied,
expression of the CD44 variants play a significant role in the ability of the cells to detach from a monolayer of normal cells.
It is hypothesized that this detachment may be an important component of a cell’s ability to metastasize. 相似文献