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)

An extract of the meningococcus antigens (MA) prepared from N. meningitidis was tested for an anti-tumor effect in rat and murine metastasizing tumor models. Effectiveness of MA in each model varied with dose and was manifested as significantly improved survival of the treated animals. Growth of the primary Fischer bladder carcinoma (FBCa) and metastases to lungs and lymph nodes were significantly inhibited in F344 rats treated weekly with 1 mg MA. Administration of MA at 100 micrograms per animal significantly prolonged survival of P815 mastocytoma-inoculated DBA/2 mice. Survival of C-26 colon adenocarcinoma-bearing Balb/c mice was significantly improved in animals that received weekly injections of 20 micrograms MA, without significant effect on the development of local tumor. The meningococcal antigens demonstrate strong mitogenic activity in B-cell-enriched murine spleen cultures. Thus the immunostimulatory activity of MA in experimental malignancy could involve, directly or indirectly, activation of B lymphocytes.
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PMID:Menningococcal antigens (MA): a novel immune stimulant in experimental neoplasia. 641 53

Intracameral inoculation of allogeneic P815 mastocytoma cells (DBA/2) into BALB/c mice resulted in progressively growing intraocular tumors. Intraocular tumor cells disseminated rapidly to the spleen and cervical lymph nodes, yet extraocular nests of tumor cells never developed into fulminant tumors. Further experiments showed that tumor cells were continuously seeded from the primary intraocular tumor and were rapidly cleared from extraocular sites. Hosts harboring intraocular P815 mastocytomas rejected tumorigenic doses of P815 cells inoculated subcutaneously or even into the contralateral anterior chamber. This systemic tumor immunity was found to be radiosensitive and T cell dependent. Spleen cells from animals with progressively growing intraocular tumors protected recipient mice challenged with intracamerally inoculated tumor cells and thus suggests that a cell-mediated mechanism is the underlying basis for this form of tumor immunity. The data indicate that mice harboring progressively growing intraocular tumors develop a potent state of "concomitant immunity," that prevents the development of metastases, yet is ineffective in controlling the primary tumor.
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PMID:Intracamerally induced concomitant immunity: mice harboring progressively growing intraocular tumors are immune to spontaneous metastases and secondary tumor challenge. 641 74

MDW3, a highly immunogenic and non-tumorigenic (tum-) mutant of the poorly immunogenic metastatic murine tumor called MDAY-D2, has been employed in an immune therapy scheme for the treatment of widespread established visceral MDAY-D2 metastases in syngeneic mice. MDW3 was selected from a mutagenized population of MDAY-D2 cells for the ability to grow in the presence of toxic concentrations of wheat-germ agglutinin (WGA) in vitro. The mutant expresses a common tumor-associated antigen (TAA) present on MDAY-D2 as well as a new antigen whose presence enhances the anti-TAA cell-mediated immune response in vivo and in mixed lymphocyte tumor cultures (MLTC) in vitro. For immune therapy, spleen cells from DBA/2 mice which had rejected an inoculum of MDW3 cells were restimulated in MLTC and injected i.v. into MDAY-D2 tumor-bearing mice. Two protocols were used. In the first, mice were given an i.v. injection of 10(3) MDAY-D2 cells ("artificial metastasis") and subsequently treated with 400 R whole-body irradiation and MDW3-stimulated T cells. Such mice had a 75% long-term survival rate, whereas 400 R alone, or no treatment, resulted in 25% and 0% long-term survivors, respectively. In the second protocol, treatment of mice bearing a 12-day-old subcutaneous MDAY-D2 tumor by surgical removal of the solid tumor, 400 R whole-body irradiation, and systemic administration of MDW3-stimulated spleen cells, resulted in a 75-100% survival rate, whereas omitting any part of the treatment resulted in 0-50% survival rates. The treatment increased splenic anti-TAA CTL activity, and the mice acquired immunity against the new antigen on MDW3, suggesting that the injected lymphocytes were proliferating in the host. The optimal combination of resection, whole-body irradiation and passive infusion of MDW3-stimulated spleen cells was ineffective when used on mice bearing a tumor-antigen-loss variant of MDAY-D2, suggesting that success of our immune therapy protocol required specific recognition of the tumor-associated antigen of MDAY-D2.
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PMID:Adoptive immune therapy in mice bearing poorly immunogenic metastases, using T lymphocytes stimulated in vitro against highly immunogenic mutant sublines. 643 92

Friend erythroleukemia cells (FLC), serially passaged in vitro or by intraperitoneal injection in DBA/2 mice, exhibit markedly different tumorigenicity and capacity to metastasize. We have attempted to determine whether the differences in tumorigenicity between these two lines of FLC were correlated with any biochemical changes in their cell membranes. Although consistent modifications of FLC membrane gangliosides were detected after FLC multiplied in the peritoneum, the pattern of FLC gangliosides was not a stable characteristic and did not correlate with tumorigenicity. In contrast, analysis of FLC membrane glycoproteins by cell surface labelling techniques (i.e., galactose-oxidase-borohydride techniques and polyacrylamide gel electrophoresis-fluorography) or by metabolic labelling of glycoproteins with 3H-galactose, revealed consistent differences in the high MW region of the gels between parental in vitro passaged FLC (either 745 or 3Cl-8 cells) and clones derived from in vivo passaged cells. No significant differences in the membrane proteins were detected between in vitro and in vivo passaged FLC when lactoperoxidase-catalyzed iodination and polyacrylamide gel electrophoresis-autoradiography were used. It is seen that repeated in vivo passages of FLC resulted in the appearance of different patterns of membrane glycoproteins and that these changes appeared to be associated consistently with the capacity of these cells to grow as tumor ascites and to metastasize to the liver and spleen.
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PMID:Biologic and biochemical differences between in vitro and in vivo passaged Friend erythroleukemia cells. II. Changes in cell surface glycoproteins associated with a highly malignant phenotype. 648 Jan 57

A metastasizing mouse cell line (TS/A), originated from a mammary adenocarcinoma which arose spontaneously in a BALB/c female retired breeder, has been established in vitro. It displayed a remarkable morphologic heterogeneity, which is evident in plastic adherent cultures (cell types ranging from epithelial-like to fibroblast-like) as well as in semi-solid agar cultures. The TS/A line exhibited the presence of specific cytoplasmic estradiol receptor, with a binding activity of 16 fmoles/mg cytosol protein. The in vivo growth pattern was as follows: a s.c. inoculum of 105 cells caused a 100 per cent tumor take and kill in syngeneic animals; mean survival time was 54 +/- 1 days; it did not show significant transplant immunogenicity in syngeneic animals; it was able to give rise to both spontaneous lung metastases and artificial lung colonies; it had a high capacity to grow in H-2 matched, minor histocompatibility antigen incompatible hosts (10(6) cells killed 100 per cent DBA/2 mice in 58 +/- 2 days). This line of spontaneous mammary tumor cells is proposed as a useful model for studies on the heterogeneity of the neoplastic population in relation to metastatic spread, on tumor immunogenicity, and on therapy of mammary neoplasia.
Clin Exp Metastasis
PMID:TS/A: a new metastasizing cell line from a BALB/c spontaneous mammary adenocarcinoma. 654 7

To follow the cellular progeny of the multiple-drug-marked benign murine tumor cell line MDW4 during its progression in vivo toward metastatic spread in DBA/2 mice, the following parameters were analyzed: retention of the drug-resistant markers ouabain resistance (OuaR) and thioguanine resistance (ThgR), lectin-resistance pattern (WGAR), and the karyotype of cell populations (and clones derived from these cells) removed at intervals from the solid tumor growing at the site of inoculation, as well as distant metastatic nodules. It was determined that the initially homogeneous inoculum composed of OuaR, ThgR, and WGAR hypotetraploid cells (mode: 68 +/- 2 chromosomes) was gradually overgrown and replaced by a new population of cells that were either OuaR or ouabain-sensitive but that became thioguanine-and lectin-sensitive and hyperploid (mode: 95 +/- 5). Regardless of the composition of the individual drug marker combinations, only cells with high chromosome contents were found to be able to disseminate to distant visceral organs and to rapidly produce metastases upon sc or iv reinjection. The presence of the same number of metacentric chromosomes in metastatic cells as in MDW4 and the coextinction of two recessive drug-resistant markers (WGAR and ThgR) suggested that cells endowed with invasive-metastatic potential represent the product of spontaneous somatic hybridization between the original nonmetastatic MDW4 cells and normal host cells of unknown origin. Such a fusion was followed by more or less extensive chromosome segregation that accounts for the karyotype mosaicism and the occasional drug marker heterogeneity identified in cell populations of metastatic nodules.
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PMID:Genotypic and phenotypic evolution of a murine tumor during its progression in vivo toward metastasis. 657 2

Certain "membrane-mutant," lectin-resistant (Lecr) variants derived from the highly metastatic and poorly immunogenic DBA/2 mouse tumor MDAY-D2 previously were found to differ substantially in their ability to grow and to metastasize. In the present study, the parental MDAY-D2 tumor and several wheat germ agglutinin-resistant (WGAr) variants were examined for alterations in sensitivity to activated macrophage (M phi)- and natural killer cell (NK)-mediated lysis. The results indicated that selection in WGA after mutagenic treatment of a metastatic parental tumor cell line (MDAY-D2), which was M phi-sensitive (M phi S) and NK-resistant (NKR), can result in the isolation of a significantly M phi-resistant (M phi R) and NK-sensitive (NKS) tumor variant, MDW4. The in vivo hybridization of the M phi R, NKS, Lecr MDW4 variant with a normal host-derived cell within a primary subcutaneous tumor, previously demonstrated to result in the progressive and selective outgrowth and metastasis of hybrid products, was found to be associated directly with reversion to the M phi S, NKR phenotype of the metastatic parental MDAY-D2 cell line. DMA/2 mice given iv injections of 10(5) M phi R, NKS cells (MDW4 or MDW4-110c1, a cloned line isolated from a subcutaneous primary tumor of an MDW4-injected animal) survived for a significantly prolonged period as compared to animals given injections of either the parental tumor or M phi S, NKR hybrid products isolated from a MDW4 subcutaneous primary tumor (MDW4-110c2) or visceral metastases (MDW4-24a, MDW4-24b, and MDW4-24c). The results clearly indicate an inverse relationship among the tumor variants in their ability to be lysed by either M phi or NK and suggest a central role for NK rather than M phi surveillance in this tumor system.
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PMID:Alterations in sensitivity to nonspecific cell-mediated lysis associated with tumor progression: characterization of activated macrophage- and natural killer cell-resistant tumor variants. 658 40

Single-step mutants were isolated from the murine metastatic MDAY-D2 cell line after selection in toxic concentrations of wheat-germ agglutinin. They were partially characterized by measuring their relative level of resistance to WGA, PHA, Con A, RIC, and LCA (Lec phenotype), and by comparing their karyotype and their ability to produce metastases upon transplantation into syngeneic DBA/2 mice. Based on their Lec phenotype, a total of 19 independent isolates were ranked into 10 distinct classes. Among them, two EMS-induced mutants were nontumorigenic (Lec II, Lec III), one nonmetastatic (Lec IV), and one spontaneous mutant (Lec I) failed to produce blood-borne metastases. Other spontaneous mutants belonging to Lec I, Lec II, and other classes were as metastatic as their parents. The Lec IV phenotype was found to segregate independently from metastatic potential in somatic hybrids. Metastatic ability was recovered in mutants expressing the Lec IV phenotype, after further selection for resistance to RIC. Our results strongly suggest that the loss or reduction of the invasive property of tumor cells is associated with only few Lecr1 phenotypes and, therefore, that a restricted number of cell surface glyconjugates are essential for this particular function.
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PMID:Metastatic properties of distinct phenotypic classes of lectin-resistant mutants isolated from murine MDAY-D2 cell line. 659 45

A solid medullar carcinoma, which arose spontaneously in DBA/2W mouse was passed in vivo in syngeneic and semisyngeneic recipients for ten generations without alteration of its morphology. This cancer, which we named WAMIB, has a relatively slow growth ratio with MST 59 days and can be easily reproduced from cell cultures and/or from cryopreserved tumor fragments. WAMIB tumor is nearly diploid and does not metastasize, does not regress spontaneously and is rejected when grafted into allogeneic recipient animals.
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PMID:Strain specific transplantable medullar carcinoma in DBA/2W mice. 665 82

A fluctuation analysis was performed on cell populations of a nonmetastatic, wheat germ agglutinin-resistant mutant (MDW4-1) of the murine MDAY-D2 tumor in order to determine the spontaneous frequency of occurrence of metastatic revertants during in vitro proliferation. A number of clones derived from the MDW4-1 mass culture were expanded in vitro and equal samples were inoculated intravenously into groups of DBA/2 mice. The number of metastatic cells present in each clonal population was estimated on the basis of the mean survival time per animal group, by making reference to a standard dose-response relationship. The final calculation indicated that metastatic cells arise randomly in vitro at a rate of 2 X 10(-5) cell per MDW4-1 cell per generation (upper estimate). The lower estimate of the rate reveals that only few metastatic revertants preexisted prior to inoculation when wheat germ agglutinin-sensitive cells are counterselected in the presence of the lectin. We conclude that the reexpression of the metastatic potential in the MDW4-1 tumor cell line may occur spontaneously, outside the host-selective environment, and may be linked to the loss of the wheat germ agglutinin-resistance phenotype.
Invasion Metastasis 1983
PMID:A fluctuation analysis of the rate of reexpression of the metastatic potential in a nonmetastatic mutant of the MDAY-D2 murine tumor. 667 20


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