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)

The purpose of this study was to examine the effective anti-metastatic activity by multiple i.v. administrations of mouse recombinant interferon-gamma (IFN-gamma) against pulmonary metastases of 3LL or B16-BL6 melanoma cells after surgical excision of primary tumors. Multiple treatments with IFN-gamma reduced effectively the incidence of pulmonary tumor metastases. Repeated 4 consecutive treatment modalities with IFN-gamma showed remarkable reduction of lung tumor colonies, and also rendered alveolar macrophages (AM) cytotoxic against B16-BL6 cells. In contrast, 14 consecutive administrations of IFN-gamma at any doses (10(2) and 10(3) U/mouse) could not activate macrophages to become cytotoxic, but were effective in regressing metastases. Thus, antimetastatic activity of IFN-gamma may be due to the stimulation of host immune defense systems such as induction of tumoricidal macrophages, presumably the direct antiproliferative action to tumor cells, or both actions under the appropriate administration conditions. We found that the systemic administration of IFN-gamma under appropriate multiple treatment modalities results in the reduction of the lung metastases and can activate AM to become tumor cytotoxic at relatively low doses (10(2) U). High-dose IFN-gamma in the multiple administration schedule was also effective for the reduction of lung tumor colonies, but strongly suppressed the nonspecific immune function and could not activate tumoricidal properties of AM.
Mol Biother 1989
PMID:Effect of systemic administration of mouse recombinant interferon-gamma on the lung tumor metastases in mice. 251 71

We examined the activities of activated lymphocytes, interferon-gamma (IFN-gamma), and interleukin 2 (IL-2) in adoptive immunotherapy of pulmonary metastases. Pulmonary metastases produced in Balb/c mice by a single tail-vein injection of 5 X 10(5) murine sarcoma (MCB8) tumor cells on day 0 were treated with combinations of Con A-activated lymphocytes (CAL) (3 X 10(7) cells on days 3 and 7), IL-2 (5 X 10(4) U three times a day on days 3 to 8), and IFN-gamma (5 X 10(4) U/mouse on days 1 to 8). Treated tumors contained increased numbers of infiltrating Thy-1.2+ lymphocytes and a predominance of L3T4+(CD4+) lymphocytes. The level of expression of class I and class II MHC antigens by tumor cells in the lung was increased after treatment. Mice that received CAL + IL-2 + IFN-gamma showed approximately 80% reduction in tumor burden as compared to controls (P = 0.001). Mice treated with IL-2 + CAL, or IL-2 + IFN-gamma, displayed approximately 50% reduction (both P less than 0.02 as compared to triple therapy), whereas IL-2, IFN-gamma, or CAL administered as single agents had little effect on pulmonary metastases. We conclude that adoptive immunotherapy with activated lymphocytes and IL-2 is enhanced by IFN-gamma.
Am J Respir Cell Mol Biol 1989 Nov
PMID:Adoptive immunotherapy of murine pulmonary metastases with interleukin 2 and interferon-gamma. 251 74

Transforming growth factor beta (TGF beta) exerts a wide spectrum of activity on many different cell types. Since TGF beta inhibits the growth of a variety of epithelial tumor cells in vitro, we examined the effects of TGF beta on the human prostate cancer cell lines DU145, PC3 and LNCaP for possible inhibitory activity. Growth in monolayer was initially inhibited in a dose-response fashion in the two androgen-independent cell lines, PC3 and DU145 but not in the androgen-dependent LNCaP cells. The rate of growth of the PC3 and DU145 cells treated with TGF beta, however, eventually returned to control levels despite retreatment with TGF beta. Anchorage-independent growth was inhibited to 55% and 16% control levels in PC3 and DU145, respectively. Scatchard analysis showed 1500 and 2900 TGF beta binding sites/cell on DU145 and PC3 cells with Kd = 6.9 and 12 x 10(-12) M, respectively. High-affinity binding could not be demonstrated on LNCaP cells. We also explored the possibility that TGF beta was secreted by these cells. Analysis of conditioned media by immunoprecipitation and a radioreceptor assay showed secretion of TGF beta into the media by DU145 and PC3 but not by LNCaP. Northern analysis showed the presence of TGF beta mRNA in DU145 and PC3, but not in LNCaP. These data indicate that TGF beta might serve as an autocrine inhibitory factor in prostate cancer. In addition, because TGF beta affects a wide range of cell types, TGF beta production by prostate cancer cells may contribute an important paracrine function in the development of tumor stromal tissue and metastases.
Mol Cell Endocrinol 1989 Mar
PMID:Differential effects of transforming growth factor beta on human prostate cancer cells in vitro. 254 87

A thyroid tumor cell line has been established from the metastases of a follicular carcinoma in a female patient. Although the primary tumor released thyroglobulin (Tg) into the circulation (greater than 10,000 ng/ml), the uptake of I131 was less than 2%. After 37 replications the doubling time was 4 days and confluency was reached after 7 days from inoculation of 3 x 10(7) cells. This human thyroid tumor cell line has now been growing in culture for several years. An aneuploid chromosomal pattern was observed (62-82 chromosomes). A pair of X chromosomes was present but no Y chromosome was found which is compatible with the female origin of the cell line. EM studies revealed the presence of microvilli. Immunoperoxidase staining using specific anti-human Tg antisera indicated the presence of Tg within the cells. Nude mice developed solid-cystic tumors within 6 months after injection of the cells. The basal release of immunodetectable Tg, as measured in a perifusion system, increased in response to thyroid stimulating hormone (TSH) (P less than 0.025) or TSH combined with theophylline (P less than 0.001). Unusual isoenzyme patterns for galactose-1-phosphate-uridyltransferase (GALT) and phosphoglucomutase1 (PGM1) were detected in the tumor, compared with normal human fibroblasts and blood cells and isoenzyme patterns from the patient's lymphocytes. Because this malignant human thyroid follicular cell line has retained the ability to synthesize Tg it represents a valuable model for the study of human follicular carcinomas.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Characterization of a human follicular thyroid carcinoma cell line (UCLA RO 82 W-1). 257 Apr 83

DNAs from 37 human gastric carcinomas and seven lymph node metastases were analyzed for alterations of the epidermal growth factor receptor (EGFR) gene and oncogenes by the Southern blot hybridization method. The probes used were EGFR gene, c-Ha-ras, v-Ki-ras, N-ras, c-myc, v-myb, v-fos, c-erbB-2, v-erbA, v-abl and v-fes. Amplification of the EGFR gene was detected in only one poorly differentiated adenocarcinoma. Amplifications of c-myc gene and c-erbB-2 gene were each observed in two well differentiated adenocarcinomas. One of these tumors had coamplification of c-erbB-2 and c-erbA genes but there were no amplifications nor rearrangements of other oncogenes. The poorly differentiated adenocarcinom with amplified EGFR gene also showed enhanced expression of EGFR gene by Northern blot analysis and additionally had strong synchronous immunoreactivity for EGFR and EGF.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Amplification of epidermal growth factor receptor (EGFR) gene and oncogenes in human gastric carcinomas. 257 Apr 89

Chemosensitivity assays were carried out as part of a tumor acquisition, propagation, and preservation program for cancer biotherapy. In addition to biopsy specimens, tumor cells propagated in culture or tumor xenografts grown in nude mice were submitted for chemosensitivity assay when sufficient biopsy material was unavailable. Chemosensitivity was tested utilizing the adhesive tumor cell culture system. A total of 154 specimens was submitted for testing; 96 specimens were assayed. Success rates were 55% for primary cancer biopsies, 67% for metastases, 69% for xenografts, and 70% for cell lines. There were no significant differences evident when the sensitivity to drugs of tumor cells originating from biopsies, xenografts, or tissue culture were compared. Sufficient data were available for 18 patients to compare clinical results of drug treatment with predictive results from the chemo-sensitivity assay. Assay results indicating insensitivity appeared to predict resistance; however, assays indicating sensitivity were not predictive. These results suggest that propagated tumor material, such as xenografts and cultured cell lines, may be useful when biopsy tissue is not available.
Mol Biother 1989
PMID:Chemosensitivity testing in a tumor acquisition, propagation, and preservation program. 261 45

The expression of the c-myc oncogene was studied in paraffin-embedded specimens of cervical biopsies using a monoclonal antibody which binds to the 62,000 Dalton protein encoded by the c-myc gene. A range of cervical cancers from intraepithelial neoplasia to advanced grade IV tumours were studied together with normal cervical biopsies; c-myc status was correlated to clinical progress. There was no correlation seen between the clinical stage of the disease at presentation and c-myc expression. The 15 patients with c-myc negative cervical cancers were shown to have better disease free (mean--95.4 mos) and total survival (mean 118.0--mos) compared to the 16 patients that were c-myc positive 28.4 and 48.4 mos respectively). The pattern of recurrence differed between the two groups with c-myc positive tumours more likely to develop extra pelvic metastatic disease. The c-myc status of cervical cancer offers a prognostic indicator that could be useful in guiding treatment decisions.
Mol Cell Probes 1989 Jun
PMID:c-myc oncogene expression and clinical outcome in carcinoma of the cervix. 267 79

A correlation between increased beta-1,6 branching of N-linked carbohydrates and the ability of a cell to metastasize or to form a tumor has been observed in several experimental models. Lec9 Chinese hamster ovary (CHO) mutants exhibit a drastic reduction in tumorigenicity in nude mice, and this phenotype directly correlates with their ability to attach an increased proportion of beta-1,6-branched carbohydrates to the G glycoprotein of vesicular stomatitis virus (J. Ripka, S. Shin, and P. Stanley, Mol. Cell. Biol. 6:1268-1275, 1986). In this paper we provide evidence that cellular carbohydrates from Lec9 cells also contain an increased proportion of beta-1,6-branched carbohydrates, although they do not possess significantly increased activity of the beta-1,6 branching enzyme (GlcNAc-transferase V). Biosynthetic labeling experiments show that a substantial degree of underglycosylation occurs in Lec9 cells and that this affects several classes of glycoproteins. Lec9 cells synthesize ca. 40-fold less Glc3Man9GlcNAc2-P-P-lipid and ca. 2-fold less Man5GlcNAc2-P-P-lipid than parental cells do. In addition, Lec9 cells possess ca. fivefold less protein-bound oligosaccharide intermediates, and one major species is resistant to release by endo-beta-N-acetylglucosaminidase H (endo H). Membranes of Lec9 cells exhibit normal mannosylphosphoryldolichol synthase, glucosylphosphoryldolichol synthase, and N-acetylglucosaminylphosphate transferase activities in the presence of exogenous dolichyl phosphate. However, in the absence of exogenous dolichyl phosphate, mannosylphosphoryldolichol synthase and glucosylphosphoryldolichol synthase activities are reduced in membranes of Lec9 cells, indicating that membranes of Lec9 cells are deficient in lipid phosphate. This was confirmed by analysis of lipids labeled by [3H]mevalonate, which showed that Lec9 cells have less lipid phosphate than parental CHO cells. Mechanisms by which a defect in the synthesis of dolichol-oligosaccharides might alter the degree of beta-1,6 branching in N-linked carbohydrates are discussed.
Mol Cell Biol 1989 Mar
PMID:Control of carbohydrate processing: increased beta-1,6 branching in N-linked carbohydrates of Lec9 CHO mutants appears to arise from a defect in oligosaccharide-dolichol biosynthesis. 272 6

Epithelial cell islets in primary monolayer cultures of human breast biopsies were characterized by combined immuno-, enzyme- and DNA cytochemistry as well as by analysis of attachment-, spread- and growth patterns. For cultivation we used explants from reduction mammoplasties, benign lesions, primary carcinomas and metastases. Milk fat globule membrane antigen (MFGM-A) was detected with a monoclonal antibody, and the tetrazolium reaction for glucose 6-phosphate dehydrogenase (G6PDH) as well as DNA content of the cultured cells were quantified. Spreading and growth of individual islets were studied by image analysis. Fibroblast-like cells did not express MFGM-A, and whereas epithelial (MFGM-A positive) cell islets of normal and benign origin showed cells with no or low G6PDH reaction, respectively, the majority of epithelial cell islets from 11 out of 21 carcinomas showed strong reaction. Cell islets with strong G6PDH reaction were sometimes hyperdiploid. Moreover, whereas cell islets with no or low reaction from both benign lesions and carcinomas readily attached and spread in a serum-free medium and showed population doubling times of 30 to 110 h, cell islets with strong reaction from carcinomas and metastatic lesions required serum for attachment and their growth rate was too low to be determined.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Characterization of epithelial cell islets in primary monolayer cultures of human breast carcinomas by the tetrazolium reaction for glucose 6-phosphate dehydrogenase. 286 41

Chronic oral administration of lead acetate and/or N-nitrosodiethylamine to rats produces three different types of renal cell tumors composed of basophilic, chromophobic or oncocytic cells. The most frequent tumor, often visible macroscopically, is made up of basophilic cells and forms tubular, cystic, pseudo-papillary or solid structures; it may show considerable cellular atypia but does not metastasize or invade the surrounding parenchyma. Chromophobic and oncocytic tumors are rare and can only be detected with the microscope; they usually form cystic or solid structures. Basophilic and chromophobic tumors arise from specific segments of the proximal tubules, characteristic for each carcinogen: P2, P3C and P3M for lead acetate; P2 and P3C for N-nitrosodiethylamine. Karyomegalia in proximal tubule cells appears to be irrelevant in renal carcinogenesis. However, the appearance of basophilic and chromophobic cells in P2, P3C and P3M segments is considered to be an early change in tumor development. Oncocytic microadenomas originate from collecting ducts showing focal oncocytic transformation. Synergistic or inhibitory effects are not observed after chronic simultaneous administration of lead acetate and N-nitrosodiethylamine, although both carcinogens act in common on P2 and P3C proximal tubule segments.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Rat renal carcinogenesis after chronic simultaneous exposure to lead acetate and N-nitrosodiethylamine. 289 Dec 21


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