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)

Polyethylene glycolated (pegylated) interleukin-2 (PEG IL-2) was administered as a weekly i.v. bolus to patients with metastatic cancer in a phase-I trial. Efficacy, toxicity and pharmacokinetics have been described previously. To explore mechanism of IL-2 action and discover predictors of efficacy, the levels of several lymphokines were measured in pharmacokinetic serum samples. IL-1 beta and IL-6 were elevated in many patients before PEG IL-2 administration, forming a continuous, log-normal distribution among patients. The levels of the two lymphokines were strongly correlated. However, no significant correlation could be found between these levels, clinical chemistry, or tumor regression seen after PEG IL-2 administration. Three hours after PEG IL-2 administration, IL-1 beta and IL-6 levels, if elevated, fell to normal. In all patients, independent of initial levels, IL-6 and IFN-gamma, but not IL-1 beta, increased 4 to 6 h after the injection and then fell rapidly, even though PEG IL-2 levels were high and often changed only slightly during this period. This suggests an active shut down of lymphokine synthesis, or an increase in elimination rate. After the fourth administration of PEG IL-2, the peak level of IFN-gamma was 2 to 20 times higher than after the first, while the peak level of IL-6 did not change in a consistent direction. Responding patients had typical peak levels of IL-6 and IFN-gamma. Low levels of TNF and IL-4 were occasionally seen before and after PEG IL-2 administration, but no consistent pattern was evident.
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PMID:Suppression and transient induction of lymphokines in cancer patients after administration of polyethylene glycolated interleukin-2. 154 19

Aberrant signal transduction has been implicated in malignant transformation, growth, and progression. This has led to the proposal to use inhibitors of signal transduction pathways to treat cancer. One approach to circumventing potential toxicity and improving efficacy would be to target pathways upon which cancer cells selectively depend. Pathways associated with the malignant process involve calcium fluxes, the release of arachidonic acid, and the generation of phosphoinositides. In this report, CAI (L651582, NSC 609974), a substituted carboxyamido-imidazole and novel inhibitor of these selected signal transduction pathways, inhibits anchorage-dependent and -independent growth in a large series of human cancer cell lines. CAI pretreatment of HT-29 human colon cancer and 5R ras-transfected rat embryo fibroblast cells inhibits the formation and growth of experimental pulmonary metastases in nude mice. Oral administration of CAI in PEG-400 vehicle arrests growth and metastasis of transplanted human melanoma and ovarian cancer xenografts. No significant gross or histological toxicity was observed at CAI doses yielding blood levels in the concentration range demonstrated to inhibit select signal transduction pathways in vitro. These data indicate the feasibility and demonstrate a potential selectivity and sensitivity of using specific signal transduction inhibitors for the experimental treatment of cancer.
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PMID:In vivo efficacy of a novel inhibitor of selected signal transduction pathways including calcium, arachidonate, and inositol phosphates. 159 30

Polyethylene glycol-modified recombinant human interleukin-2 (PEG-IL-2) represents a cytokine with prolonged circulatory half-life and increased antitumor activity as compared to recombinant interleukin-2 (rIL-2) after systemic administration. We studied whether PEG-IL-2 would also be advantageous in locoregional immunotherapy using a syngeneic tumor model. Intradermal inoculation of line-10 tumor cells into the flanks of strain-2 guinea-pigs results in a fast-growing tumor and regional lymph-node metastases. Treatment schedules were started on day 7 after inoculation in animals with established tumors. First, groups of 5-6 animals were treated with repeated intratumoral and perilymphatic rIL-2 or PEG-IL-2 injections. PEG-IL-2 caused significant growth inhibition of both the primary tumor and the regional lymph-node metastases at lower doses and with less frequent administration than rIL-2. The best schedule for PEG-IL-2 was 3 injections a week for 5 weeks, resulting in cure of 4/17 and 5/5 (p less than 0.01) animals at the 2 most efficient dose levels tested. Subsequent experiments indicated that the intratumoral and not the perilymphatic injection route was essential for the obtained antitumor effect. Furthermore, 12/12 animals cured after PEG-IL-2 treatment rejected a rechallenge with line-10 tumor cells, whereas no cures were seen after rIL-2 injections. PEG-IL-2 therefore appears to be a valuable substance for intratumoral immunotherapy.
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PMID:Polyethylene-glycol-modified interleukin-2 is superior to interleukin-2 in locoregional immunotherapy of established guinea-pig tumors. 161 87

The purpose of our study was to compare the therapeutic effects of doxorubicin in 3 different formulations: (1) in PBS, (2) in conventional liposomes composed of egg phosphatidylglycerol/egg phosphatidylcholine/cholesterol/dl-alpha tocopherol, and (3) in sterically stabilized, long-circulating "Stealth" liposomes composed of hydrogenated soy phosphatidylcholine/cholesterol/polyethylene glycol-distearoylphosphatidylethanolamine. The doxorubicin formulations were used to treat recently implanted and well-established, growing primary mouse mammary carcinomas, and to inhibit the development of spontaneous metastases from intra-mammary tumor implants. In the treatment of recently implanted primary tumors, the formulations were given in 3 i.v. injections over 15 days, starting 3 or 10 days after tumor implantation. In the treatment of well-established primary tumors, the mice received 4 i.v. injections over 22 days, starting an average 38 days after tumor implantation. In the preventive treatment against metastases, the formulations were given in 4 i.v. injections over 22 days, starting 22 days or 58 days after primary tumor implantation. The Stealth liposome formulation was significantly more effective than the conventional liposome formulation or the free drug in reducing the incidence of metastases from intra-mammary implants of tumor MC19 and tumor MC65, in curing mice with recent implants of tumor MC2A, tumor MC2B, and tumor MC65, and in increasing the 8-week survival of mice with well-established implants of tumor MC2B. It is concluded that the long circulation time of the Stealth liposome doxorubicin formulation accounts for its superior therapeutic effectiveness.
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PMID:Therapy of primary and metastatic mouse mammary carcinomas with doxorubicin encapsulated in long circulating liposomes. 163 42

A polyethylene glycol precipitation technique was used to determine the levels of circulating immune complexes (CIC) in breast cancer and melanoma patients. All patients in the study had undergone surgery and were free of distant metastatic disease. CIC were measured at two to four time intervals, of 3 to 6 months each, over an average follow-up period of 13.5 months (range 7-20 months). In both groups of patients, metastatic disease developed with a higher frequency in patients who had undetectable CIC levels throughout the follow-up period or had become negative at the time metastases were discovered.
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PMID:Serial circulating immune complex values and development of metastatic disease in breast cancer and malignant melanoma patients. 351 30

Somatic cell hybrids were produced by polyethylene glycol-induced cell fusion between metastatic CMT 167 (HGPRT-/OUAR) C57BL/Icrfat mouse lung carcinoma cells and 2 non-metastatic cell lines: C3H/He mouse L-M(TK-) cells of mesenchymal origin and EJ (OUAS) human bladder carcinoma cells. Fusion of 2 different CMT167 (HGPRT-) clones with L-M(TK-) cells followed by selection in HMT medium gave rise to 14 intraspecific hybrids, which were shown to express H-2 antigens specific for both the C57 and C3H mouse strains. Three interspecific hybrids arising from fusion of EJ(OUAS) and CMT167(HGPRT-/OUAR) cells were selected in HMT/ouabain medium and characterized by human isozyme analysis. All the hybrids produced large tumours after subcutaneous inoculation of 5 X 10(5) cells into adult athymic nu/nu mice. The intraspecific hybrid tumours were predominantly sarcomatous (mesenchymal) in structure but a few contained epithelial acini. Metastatic ability (as assessed by production of lung metastases) was completely suppressed in 13 of the 14 mouse/mouse hybrid cell clones. These results suggest that tumorigenicity, tumour structure and the ability to metastasize are expressed independently. The interspecific hybrids, which had not retained a full human chromosome complement, produced metastatic tumours that remained epithelial in structure.
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PMID:Selective suppression of metastasis but not tumorigenicity of a mouse lung carcinoma by cell hybridization. 369 33

The sensitivity of an antigen prepared from tumor extract in three concentrations was examined in patients with cancers of the larynx of different extent (T1-T4) with or without metastases. At the same time circulating immune complexes in the serum were investigated by the polyethylene glycol precipitation method. Positive antigen reactions were found in 34% of the cases examined and enhanced immune complexes alone in 66%. These results were compared before and after the operative procedures and their relationship to the phytohaemagglutinin was assessed. Differences in these results appeared to be related to the size of the tumors (T1-T4) and to the presence of metastases.
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PMID:Tumor antigens and immune complexes in laryngeal cancer. 400 Jun 50

Circulating immune complexes (CIC) were found in 47% of 71 patients before treatment, in a horizontal study of the presence of CIC in primary lung cancer (PLC). The precipitation technique in PEG was used, and C1q, IgG and IgM fractions in the precipitate were assayed. Especially in epidermoid carcinoma, CIC were found in 1/6 cases with stage 1, 2/9 with stage II and 21/34 with stage III. The frequency was significantly higher in stage III cases, and showed a significant tendency to increase with progression of the clinical stage. If stage parameters are considered separately, this tendency correlates significantly (p less than 0.002) with the amount of lymph node involvement (N) but not to the tumor (T) size nor to the presence of metastases (M). Analysis of CIC behavior in comparison with the single fractions showed that C1q and/or IgG were elevated in 40% of cases. The presence of C1q and/or IgG associated with IgM is more characteristic of stage N2, while the presence of CIC with the fractions C1q and/or IgG not associated with IgM is more frequent in stage N1. There was a lower survival rate at 12 months in patients with CIC as compared to those without (p less than 0.05).
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PMID:Immunocomplexes and primary lung cancer. 627 Sep 95

Receptors for 1,25-dihydroxyvitamin D3 have been shown to exist in cultured breast cancer cells and in primary breast cancers. It is reported here that 1,25-dihydroxyvitamin D3 receptor (1,25-DR) was present in 80% of 54 unselected breast cancers. The concentration of 1,25-DR in the 43 receptor-positive tumors was 1.9 +/- 0.4 fmol/mg protein (S.E.). There was no correlation between 1,25-DR presence or concentration and the age of the patient or the concentration of estrogen, progesterone, androgen, or glucocorticoid receptors. 1,25-DR was also found in two of three renal cortical carcinomas but only in three of 14 gastrointestinal tract carcinomas. The relatively low concentration of 1,25-DR in these breast cancers, compared with that found in cultured breast cancer cells, is partially explained by incomplete "exchange" with occupied receptors. Since the serum vitamin D-binding protein is not precipitated from serum itself or from tissue homogenates using the polyethylene glycol method, artifactual 1,25-DR levels due to the inevitable contamination of tissue specimens with this protein can be excluded. These findings indicate that 1,25-DR is not a nonspecific marker of cancer. The high frequency of 1,25-DR in the breast cancers may be related to the calcium-transporting ability of breast cancer cells which allows them to grow as osteolytic metastases.
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PMID:Frequency of 1,25-dihydroxyvitamin D3 receptor in human breast cancer. 627 89

A low metastatic, thioguanine-resistant murine T lymphoma line (EbTGR) was hybridized in vitro, with the help of polyethylene glycol, with syngeneic bone marrow-derived macrophages. Two HAT-resistant hybrid lines (Eb-F1 and Eb-F2) were obtained from independent fusion cultures. A cytogenetic analysis revealed that most of the macrophage chromosomes except No. 12 had segregated or become rearranged 60 d after fusion, a time at which the cell lines had become stabilized in culture. Syngeneic mice inoculated subcutaneously with the tumor macrophage hybrid lines developed, very quickly, visceral metastases and died after less than 2 wk, while those inoculated with the parental line lived for greater than 6 wk and developed only localized, large primary tumors. The metastatic hybridomas expressed a similar tumor antigen as a spontaneous, in vivo derived, high metastatic variant (ESb) of the same tumor. This suggests that ESb cells might have arisen from a spontaneous fusion with a host macrophage.
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PMID:Acquisition of high metastatic capacity after in vitro fusion of a nonmetastatic tumor line with a bone marrow-derived macrophage. 649 5


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