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)

Methotrexate (MTX) covalently bound to bovine serum albumin (MTX-BSA), injected ip (10 mg/kg) once every 4 days for a total of 4 doses, was more effective than an equivalent dose of free MTX in reducing the number of metastases observed in female (C57BL/6 X DBA/2)F1 mice bearing the sc implanted Lewis lung carcinoma. Treatment with the high-molecular-weight derivative of MTX in addition caused a decreased rate of growth of the primary tumor and a modest increase in the life-span of the tumor-bearing animal. When tumor-bearing mice were killed after receiving injections of [3H]MTX or [3H]MTX-BSA, no difference in the amount of drug was found at the tumor site after 1 hour; however, after 8 or 24 hours, twice as much radioactivity was found in the tumors of mice treated with carrier-bound drug. Analysis of this radioactivity indicated a ratio of 60--80% carrier-bound to 20--40% free MTX.
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PMID:Control of solid tumor metastases with a high-molecular-weight derivative of methotrexate. 28 78

The course of the disease, cutaneous leishmaniasis, caused by the intracellular protozoan parasite Leishmania tropica, differs markedly amongst various common inbred mouse strains. After intradermal injection of 1 x 10(6) promastigotes to young female specific pathogen-free (SPF) derived mice, persistent infection characterized by an expanding ulcerous lesion is seen in BALB/c and DBA/2 mice. In the strains CBA/H, C3H/He and A/J, lesions resolve within 8 weeks, and in C57B1/6 mice no real lesion typical of cutaneous leishmaniasis develops at the injection site. NZB mice are highly resistant. Macrophages harvested from the thioglycollate-stimulated peritoneal cavity of NZB and C57B1/6 mice appear to differ from macrophages of the other mouse strains in not supporting multiplication of L. tropica organisms in vitro. Nevertheless, hypothymic nude (nu/nu) mice of C57B1/6 genotype, as well as CBA/H-nu/nu and BALB/c-nu/nu mice, develop large lesions with metastases to other cutaneous and visceral locations. In the intact mice in which infection resolves spontaneously, resistance to reinfection is complete. Using mouse antipromastigote sera and an indirect fluorescent antibody test in carefully controlled experiments, L. tropica antigens were detected on in vitro infected macrophages of both highly susceptible BALB/c and relatively resistant CBA/H genotypes. After incubation with a crude soluble antigen preparation from cultured promastigotes, infected BALB/c macrophages differed from infected CBA/H macrophages (and uninfected macrophages of both genotypes) in being unable to sensitize syngeneic recipients for a delayed-type hypersensitivity response to that antigen. When infected and uninfected macrophages were used as "blocking cells" in an in vitro alloreactive cytotoxic T cell system involving cells from congenic mice, evidence was obtained for reduced H-2d expression on infected macrophages of the susceptible mouse strains, BALB/c. The data in this model system of cutaneous leishmaniasis raise the possibility that genetic susceptibility is associated with both a permissive macrophage and defective T cell recognition of parasite antigens on infected macrophages. Defective recognition may be the result of reduced functional expression of H-2d antigens on infected BALB/c macrophages required for efficient recognition by syngeneic T cells of one or more subpopulations.
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PMID:Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages. 31 86

DBA/2 mice were treated with four successive subcutaneous injections of rabbit anti-theta-gamma-globulin followed by the subcutaneous implantation of chemically induced mastocytoma (P-815-X2). Another series of animals received rabbit anti-thymus-gammaglobulin according to the same schedule and still another series of animals served as non-treated controls. A definite augmentation of the tumor growth, as evidenced by the dissemination of the tumor into the spleen, liver and kidney, was evident in the globulin-treated series. Such dissemination was not observed in the control animals, where the metastases were limited to the reginal lymph nodes. The studied gammaglobulins were different in two important respects; the death rate of animals and the frequency of thymic metastases were higher in the anti-theta-globulin series. These findings advocate the conclusion that anti-theta-globulin, prepared against the brain tissue, is the more specific and more potent T-lymphocyte suppressor of these two globulins studied. T-lymphocyte population seems to play an important role in host resistance against experimental neoplasia.
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PMID:The influence of anti-theta-globulin treatment on the growth of mastocytoma in mice. 41

The metastasizing MDAY-D2 tumor of DBA/2 mice disseminates in BALB/c allogeneic athymic nude (nu/nu) mice in a manner identical to that observed in the syngeneic host. Both the kinetics and organ distribution pattern of metastases from s.c. implants of MDAY-D2 are routinely predictable at any given tumor dose. BALB/c heterozygote (nu/+) litter-mates reject MDAY-D2 grafts on the basis of the multiple minor histocompatibility differences that exist between DBA/2 and BALB/c mice. The in vitro cell-mediated cytotoxic response detected in tumor-bearing BALB/c nu/+ mice is "low grade" (isotope release is approximately 40 to 50% by 24-hr 111-indium-8-hydroxyquinoline assay and approximately 6 to 8% by 6-hr 51Cr assay) and yet correlates directly with tumor rejection. BALB/c nu/nu mice can be protected against MDAY-D2 by previous reconstitution with lymphoid cells from normal or MDAY-D2-sensitized BALB/c nu/+ mice. In addition, surgically documented, established visceral metastases in BALB/c nu/nu mice can be arrested and regressed by the adoptive transfer of MDAY-D2-sensitized BALB/c nu/+ spleen cells. This represents one of the few models where established metastases have been immunotherapeutically regressed. As such, the MDAY-D2 BALB/c nu/nu mouse model offers unique advantages for studying the role of the immune system in regulating the metastatic process.
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PMID:Immune-mediated arrest and reversal of established visceral metastases in athymic mice. 47 40

MDAY-D2 is a highly tumorigenic and anaplastic DBA/2 strain murine transplantable tumor capable of rapid and widespread spontaneous metastatic growth. It was therefore chosen as an ideal murine tumor model for the study of factors affecting metastatic growth. Two approaches were taken in an effort to obtain stable qualitative and quantitative low-metastatic variants of MDAY-D2, namely, cloning of multiple sublines and derivation of lectin-resistant (LecR) mutants. In the first method, 20 clones were isolated, and of these, three initially showed a marked reducstion in ability to metastasize from a subcutaneous site. However, these clones proved to be unstable both in vivo and in vitro. In the LecR selection experiments, 18 independent variants were obtained using chemical mutagenesis followed by treatment with wheat germ agglutinin (WGA), phytohemagglutinin (PHA), or concanavalin A (Con A). All of the variants proved to be highly metastatic except two WGAR variants, designated MDWI and MDW3. They proved to be nontumorigenic in normal DBA/2 hosts even when as many as 5 X 10(6) cells were injected, and this was found to be a stable change. Despite this fact, the nontumorigens an unchanged expression of H-2d and Ly-6.2 alloantigens and Fc receptors. The variants were, however, tumorigenic and metastatic in severely immunosuppressed (nude) mice, but not in moderately immunosuppressed 250-R-irradiated DBA/2 hosts. The results demonstrate that 1) stable membrane mutant sublines possessing radically altered growth properties in vivo can occasionally be obtained by selection of LecR variants, and 2) their growth and metastatic properties can be greatly affected by the immunologic status of the host. The possibility that the chemical mutagen treatment itself induced, or was responsible for, MDW1 and MDW3 variant formation is also discussed.
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PMID:Immunologic studies of membrane mutants of a highly metastatic murine tumor. 50 93

An H-2 heterozygous sarcoma, MDAY, originally induced with methylcholanthrene in an (A X DBA/2)F1 ((H-2a X H-2d) hybrid host was selected for growth in the H-2d homoxygous parental DBA/2 strain by serial intraperitoneal transplantation of ascites tumor cells. An apparent variant, designated MDAY-D2, was obtained which showed the expected loss of the private and public H-2Kk haplotype antigens normally associated with the A strain parent and the original MDAY tumor. Comparison of the original and variant lines revealed a wide variety of a cell surface antigen and receptor differences. Both tumors were found to be highly anaplastic and histologically unclasssifiable. Examination of the two tumor lines growing in vivo revealed a remarkable difference in their metastatic growth potential. The original MDAY line showed little propensity to spread to any organ site, with the occasional exception of liver, after subcutaneous inoculation of (A X DBA/2)F1 mice. In striking contrast, there was a rapid and massive spread of MDAY-D2 to liver, spleen, lungs and kidneys within 12-16 days: liver and spleen could be totally replaced by tumor within 2-3 weeks. These characteristics were observed in both (A X DBA/2)F1 and DBA/2 mice. The tendency to metastasize, as well as loss of the H-2Kk haplotype, appeared stable and irreversible. Although the precise origin of MDAY-D2 is not clear, its metastasizing properties are unique, making it a useful and desirable model to study the biology of metastasis.
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PMID:Induction of a tumor with greatly increased metastatic growth potential by injection of cells from a low-metastatic H-2 heterozygous tumor cell line into an H-2 incompatible parental strain. 72 18

Mycobacterial ribonucleic acid (RNA) and cell wall skeleton fraction isolated from H37Ra caused P-815 mastocytoma regression in DBA/2 mice provided the animals were presensitized with freshly harvested living H37Ra cells. In the absence of presensitization, only the RNA fraction inhibited. Cell wall skeleton fraction, under these conditions, stimulated tumor growth. Cell wall lipids (from H37Ra) added to H37Ra cell wall skeleton fraction did not increase the inhibitory activity of cell wall skeleton fraction alone. Mycobacterial RNA appeared to be an effective inhibitor of P-815 mastocytoma metastases as shown by (i) the inhibition of a second footpad lesion distant from the one treated and (ii) increase in survival time.
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PMID:Mycobacterial ribonucleic acid: comparison with mycobacterial cell wall fractions for regression of murine tumor growth. 82 69

Metastatic tumor incidence in BALB/C X DBA/8F1 female mice was examined in the presence and absence of adjuvant chemotherapy. Following surgical removal of spontaneous mammary adenocarcinomas, phenylalanine mustard, adriamycin, and 5-fluorouracil (PAF) were administered at 4, 2, and 50 mg/kg, respectively, once a week for six injections. Recurring tumors and new tumors developing in other breasts over the next 6 months were noted and surgically removed to allow time for originally undetectable pulmonary metastases to develop or to regress completely. This regimen of PAF significantly decreased original tumor recurrences from 58% in controls to 36% in treated mice. New tumor development also was significantly reduced during the 5 weeks of PAF therapy and for 8 weeks thereafter. However, the incidence of pulmonary metastasis was unaffected by the chemotherapy, being 42% in controls and 37% in PAF-treated mice. About 30% of these metastases would have been undetectable at the time of original surgery. The findings stress the importance of developing agents and/or schedules that will specifically affect metastatic cells when administered early to minimal numbers of tumor cells. This system represents a stringent clinimimetic model for evaluating adjuvant chemotherapy in this regard.
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PMID:Comparison of adjuvant chemotherapeutic activity against primary and metastatic spontaneous murine tumors. 83 74

A strain-specific transplantable melanoma (S-91) growing progressively in DBA/1 mice and metastasizing selectively to the lungs was maintained for 16 days in organ culture before being grafted to syngeneic (DBA/1) and allogeneic (BALB/c and C57BL/6) recipients. The cultured S-91 grew progressively in the syngeneic mice and to a moderate degree in the allogeneic strains; it showed an increased tendency to metastasize in both the DBA/1 and C57BL/6 recipients. Heterophilic cytoagglutination assays of cultured S-91 were less apt to aggregate in the presence of concanavalin A than were their noncultured counterparts, which suggested alteration of the plasma membrane. Organ culture explantation appeared to alter phenotypically the cell-surface membrane and thus increase the cell's ability to metastasize while possibly reducing the immunogenicity of the cultured tumor cells.
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PMID:Increased tumor metastasis after in vitro alteration of the cell surface. 113 53

Four murine cellular tumor models expressing various combinations of oncogenes (SV40 large T and v-Ha-ras, SV40 large T and v-src, SV40 large T and neu, adenovirus EIA and v-Ha-ras) induce sarcoma when they are inoculated s.c. into the DBA/2 syngenic mice. The metastatic patterns, distribution and fate of these tumor cells transplanted by two different routes into syngenic DBA/2 mice have been studied. All the tumor cell lines except EIA-ras, induce massive overt artificial metastases principally in the lung after i.v. injection. In s.c. tumor-bearing mice, a few resting cells colonize the lung as micrometastases. When removed from this tissue context and injected s.c. these cells regain their proliferative potential and grow as local tumors which again give rise to occult pulmonary micrometastases.
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PMID:Metastatic phenotype of murine tumor cells expressing different cooperating oncogenes. 131 11


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