Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we assessed various tissue culture conditions on the motility and invasiveness of benign and malignant prostatic epithelial cells using the Boyden chamber system. In DME and RPMI-1640 media, benign human prostatic epithelial cells were unable to penetrate through a basement-membrane-coated filter. However, the prostatic carcinoma cell lines, PC3 and DU145, showed a significant frequency of invasion under those conditions. When cultured in the low-calcium WAJC 404 medium, benign prostatic epithelial cells efficiently penetrated through the basement-membrane-coated filter. PC3 and DU145 cells showed an attenuated capability to invade when cultured in WAJC 404 medium. The effect of extracellular calcium on the behavior of these cells in the Boyden chamber was further evaluated by gradual addition of calcium chloride in WAJC 404 medium. These studies showed that the number of benign prostatic epithelial cells penetrating through the filter decreased as the calcium ion concentration increased. Conversely, the number of PC3 cells invading through the filter increased as calcium ion concentration was increased to 0.4 mM and decreased at higher calcium ion concentrations. These results suggest that the extracellular calcium concentration is one of the factors which may affect cell behavior in the Boyden chamber system.
Invasion Metastasis 1992
PMID:Utilization of the Boyden chamber to further characterize in vitro migration and invasion of benign and malignant human prostatic epithelial cells. 128 46

In this study NK cell activity of 88 breast cancer patients in various stages of disease was investigated and a significantly lower activity in clinical stages I-III and especially in stage IV was found. Short term culture of peripheral blood lymphocytes (PBL) of these patients in medium RPMI 1640 with fetal calf serum (FCS) alone, gave a significant enhancement of NK cell activity and even more significantly if rhIL 2 was added to this medium. Considering the finding of diminished native NK cell activity in breast cancer patients and its augmentation by the above stated in vitro treatment, it was of interest to investigate the effect of sera of these patients, which represent the natural in vivo environment of NK cells, in order to see if the sera modulate the antitumor cytotoxic activity of these cells. In this sense, the in vitro treatment was performed on PBL of patients and controls with sera of patients with stages I-III (CaSa), stage IIIb (CaSb), stage IV (CaSm) and healthy control sera (HS). The results obtained for patients and controls show that compared to FCS all sera act in an inhibitory manner, but in contrast to HS, CaSa has a stimulative effect, while CaSb and CaSm give the greatest degree of NK cell inhibition of both controls and patients. Pooled metastatic sera (CaSp) and these sera after removal of molecules up to 8-10 kD by dyalisis (CaSd) show a similar degree of inhibition of NK cell activity of healthy controls and interfere in a reversible manner with NK cell activation by recombinant human interleukin 2 (rhIL 2). Analysis of soluble IL 2 receptor (s IL 2R) concentration, as a potential inhibitory factor in metastatic sera, rarely showed an increase. In conclusion, an impaired NK cell activity was found in patients with breast cancer. The impairment of NK cell activity progressed with the advancement of the disease. Along with this, the finding of a marked inhibitory effect of sera of breast cancer patients in advanced stage with metastases on the activity of NK cells and their activation by interleukin 2 may pose a problem for adjuvant immunotherapy with LAK cells and IL 2 and may indicate a need for prior plasmapheresis.
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PMID:Evaluation of different effects of sera of breast cancer patients on the activity of natural killer cells. 134 51

The growth and metastatic behavior of three human tumor cell lines and a human colon carcinoma previously passaged in vivo were compared between nude mice and scid mice after xenotransplantation. The three human tumor lines included a bladder carcinoma (T24B), a melanoma (RPMI 7931) and a lacZ gene-transduced breast cancer (MDA-MB-435 BAG). The lacZ gene codes for beta-galactosidase, which can be stained blue with chromogenic substrate X-gal, thus allowing the highly sensitive detection and quantitative examination of human cancer metastasis in host mice. Adult (7-14 weeks) NMRI nude and C.B-17 SCID mice were inoculated with 0.5-5 x 10(6) tumor cells s.c. Comparable take rate, latent period and growth rate of implanted tumors were observed in nude and scid mice for each of the cell lines tested. At the time of autopsy, which varied from 6 to 11 weeks after inoculation, a significantly higher incidence of spontaneous lung metastasis was discovered in scid mice (96%) than in age-matched nude mice (27%, total P less than 0.001). In vitro assays for NK cell-mediated cytotoxicity revealed no significant differences between the two strains of mice. Our results suggest that nude and scid mice are equally suitable for propagating human tumors. However, the metastatic capacity of human tumor cells appears to be better expressed in scid mice. Scid mice may therefore provide an advantageous model for the study of human tumor metastasis.
Clin Exp Metastasis 1992 May
PMID:Comparative studies between nude and scid mice on the growth and metastatic behavior of xenografted human tumors. 158 90

We describe here the chromosomal distribution of sister chromatid exchanges (SCEs) in four human tumor cell lines (two melanomas and two astrocytomas), and have mapped the sister chromatid recombination (SCR) sites. A higher incidence of SCR sites than expected on the basis of chromosome length occurred in chromosomes 2, 4, 5 and 15 in both the RPMI 5966 and MEL57 melanoma cell lines, and in chromosomes 1, 5, 13 and 15 of the IJKt and GUVW astrocytoma cell lines. A majority of the recombination sites occurred close to chromosomal fragile sites. A third of these occurred at the same bands as fragile sites. The recombination sites involved the N-ras and the epidermal growth factor gene in the melanomas. In the astrocytomas, the N-ras, Rb and c-mos genes appeared to be involved in the recombination events. The beta 2-microglobulin gene was involved in both astrocytomas and one melanoma. The erbB2 was involved in SCR only in the RPMI melanoma.
Clin Exp Metastasis
PMID:Genetic recombination in human melanoma and astrocytoma cell lines involves oncogenes and growth factor genes. 229 15

Synvinolin (MK-733), a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase) depressing de novo synthesis of cholesterol, was given to BN472 tumor cells in culture medium, 2 days prior to i.v. injection of the cells into syngeneic rats. Another group of rats received cells cultured under the same conditions but without synvinolin. Two different types of culture medium were used, a 'complete' medium (Hybridoma) and a medium (RPMI 1640) to which 1 per cent of fetal calf serum (FCS) was added. Tumor cells cultured in the presence of synvinolin showed significantly lower cholesterol values than untreated cells. Tumor cells treated with synvinolin had a decreased ability to form metastatic nodules when compared with control cells. The results supply further evidence for the suggestion that cholesterol modulates the ability of mononuclear cells to eliminate tumor cells, although it cannot be excluded that alteration of cell growth plays an important role as well.
Clin Exp Metastasis
PMID:Modulation of metastatic ability by inhibition of cholesterol synthesis. 275 4

The potential utility of tumor-infiltrating lymphocytes (TIL) in the adoptive immunotherapy of human tumors has been suggested by murine experiments showing these cells to be 50-100 times more powerful than LAK cells in treating advanced metastatic disease. A method for the large-scale expansion of human TIL for the use of these cells in clinical trials is described in this report. TIL were successfully expanded on an experimental scale from 24 of 25 consecutive human tumors, including six melanomas, ten sarcomas, and eight adenocarcinomas. Tumors were digested enzymatically to yield single cell suspensions which were cultured in RPMI 1640 medium with 10% human serum and 1000 U/ml recombinant interleukin-2. Lymphocytes constituted from 3% to 74% of single cell tumor suspensions, and expanded from 2.9-fold to 9.1 X 10(8)-fold over a culture period ranging from 14 to 100 days. Nine of 24 TIL cultures lysed fresh autologous tumor targets in 4 h chromium release assays. Cell surface phenotyping identified cultured TIL as activated cytotoxic/suppressor T cells. Subsequently, large-scale expansion of TIL was successful in generating more than 10(10) lymphocytes in five of eight consecutive cases. Clinical trials employing the adoptive transfer of expanded TIL to patients with metastatic disease have begun.
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PMID:Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. 330 8

Immunotherapy utilizing the adoptive transfer of lymphokine activated killer (LAK) cells in conjunction with recombinant interleukin 2 (RIL-2) is capable of reducing established metastatic cancer in a variety of animal tumor models. A major difficulty in the application of these efforts to the treatment of human cancer has been the activation in vitro of up to 2 X 10(11) human peripheral blood lymphocytes obtained by repeated leukaphereses. We have thus developed optimal and simplified techniques for the generation of human LAK cells for use in clinical trials. We have found that 1.5 X 10(9) lymphocytes separated on Ficoll-Hypaque gradients and incubated in 1000 ml of culture medium in a 2.3 liter roller bottle with 1000-1500 U of RIL-2 per ml, generated LAK cells capable of killing fresh human tumor cells in a 4 h chromium release assay. The culture medium used was RPMI 1640 with 2 mM glutamine, 2% heat-inactivated human AB serum, 50 micrograms/ml streptomycin and gentamicin and 50 U/ml penicillin. This technique allows activation of sufficient numbers of cells in a research laboratory setting to conduct human clinical trials. The administration of LAK cells generated in this fashion can mediate the regression of human tumors when administered in conjunction with IL-2.
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PMID:Large scale production of human lymphokine activated killer cells for use in adoptive immunotherapy. 348 92

Peripheral blood lymphocytes obtained from patients by leukapheresis were cultured in RPMI 1640 containing human plasma and interleukin 2. The morphology, phenotypes and cytotoxicity of induced LAK cells were studied. Lymphoblastoid cells mainly proliferated were OKIa1+ cells and were thought to be LAK cells. Maximal cytotoxicity was obtained after two weeks of incubation. IL-2 enhanced the cytotoxicity of LAK cells. Autologous LAK cells induced by two weeks of incubation were injected into patients. One case of pulmonary metastases of breast cancer showed reduction and two lesions showed partial regression. Also, no new lesions appeared in the lungs of a patient with alveolar soft-part sarcoma.
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PMID:[Adoptive immunotherapy of malignant diseases with LAK cells]. 349 32

The ability of RPMI 4788 cells, a human colon cancer cell line, to produce experimental metastases in the lung, intraperitoneal cavity, and liver was studied in nude mice. Injection of 2 X 10(6) tumor cells into the tail vein of nude mice produced metastatic lung tumors, and an intraportal injection of 5 X 10(6) cells produced metastatic liver tumors. An intraabdominal carcinomatosis with ascites was formed after an i.p. injection of 5 X 10(6) tumor cells. The nude mice with lung metastasis or intraabdominal carcinomatosis always died within a few weeks. Macroscopic observation showed that the number of lung metastatic nodules on day 21 after tumor inoculation was 311.3 +/- 78.2 (mean +/- SD) in BALB/C nude mice, and 187.5 +/- 26.7 in ICR nude mice. In survival experiments, the mice with intraabdominal carcinomatosis showed a mean survival of 29.0 +/- 1.7 (mean +/- SD) days in BALB/C nude mice and 43.6 +/- 6.1 days in ICR nude mice. These novel experimental models of metastases in nude mice produced by injection of RPMI4788 cells had high reproducibility and may be useful not only for the study of the metastatic process but also for testing anticancer drugs.
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PMID:Novel experimental models of human cancer metastasis in nude mice: lung metastasis, intraabdominal carcinomatosis with ascites, and liver metastasis. 368 Mar 63

Human epithelial cells contain, intermediate-sized filaments formed by polypeptides related to epidermal alpha-keratin ("cytokeratins") which are expressed in different combinations in different epithelia. Using cytoskeletal proteins from human biopsies and autopsies we have examined, by two-dimensional gel electrophoresis and immunoblotting experiments, the cytokeratin polypeptide patterns of diverse primary and metastatic carcinomas and have compared them with those of corresponding normal epithelial tissues and cultured cells. Five groups of carcinoma cytokeratin patterns can be discriminated. (1) Cytokeratins typical of simple epithelia (polypeptides Nos. 7, 8, 18, 19) are expressed, in various combinations, by many adenocarcinomas, for example those of gastrointestinal tract. (2) Cytokeratins typical of stratified epithelia (Nos. 1, 5, 6, 10, 11, 14-17) are found, in various combinations, in squamous cell carcinomas of skin and tongue. (3) Complex patterns showing polypeptides Nos. 7, 8, 18, 19, and one basic component (No. 5 or 6) are detected in certain carcinomas of the respiratory tract and the breast. (4) Complex patterns containing cytokeratins widespread in stratified epithelia (Nos. 4-6, 14-17) as well as components Nos. 8 and 19 occur in diverse squamous cell carcinomas derived from non-cornified stratified epithelia, with or without additional small amounts of cytokeratin No. 18. (5) Patterns of unusually high complexity can be found in some rare tumors as is shown for a cloacogenic carcinoma. No significant qualitative changes of expression of cytokeratins were found when primary tumors and metastases were compared. When compared with cytokeratin patterns of normal epithelia, carcinomas of the first type usually display a high degree of relatedness to the tissue of origin. Other carcinomas do not express some of the cytokeratins present in the tissue of their origin and, vice versa, certain components which are minor or apparently absent in normal tissue are major cytokeratins in the corresponding tumor. These differences may be explained by cell type selection during carcinogenesis, but changes of expression during tumor development cannot be categorically excluded. The possibility of cell type heterogeneity within a given tumor is also discussed. Similarly complex patterns of cytokeratin polypeptides have been noted in certain cultured human carcinoma cell lines (e.g., A-431, RPMI 2650, Detroit 562, A-549) and can also be observed in cell clones. The possible value of analyses of cytokeratin patterns, by gel electrophoresis or specific monoclonal antibodies, in distinguishing different carcinomas by non-morphologic criteria is discussed.
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PMID:Complex cytokeratin polypeptide patterns observed in certain human carcinomas. 618 57


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