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

Metastases arising from a subcutaneous injection of the DBA/2 tumor, MDAY-D2, as well as four drug-resistant variants (either wheat germ agglutinin-resistant, ouabain-resistant, or both, i.e., WGAR/OuaR) of MDAY-D2, were examined for the presence of a tumor-associated antigen (TAA). Of 15 mice examined, tumor antigen-loss variants were detected in only 1 animal. These antigen-loss metastases arose in a mouse injected with the WGAR variant called MDW4. The tumor at the site of inoculation retained the TAA, whereas all four of the metastases removed from liver, spleen and other tissues were antigen-loss variants. The antigen-loss variants were not killed by cytotoxic T cells (CTL) directed against the TAA of the parental tumor, did not competitively inhibit CTL lysis of MDW4 targets in a 'cold target' inhibition test, and were not able to elicit a CTL response. In vivo immunization-protection (challenge) experiments also showed that the metastases did not express the TAA of MDAY-D2. Unlike the WGAR phenotypes, which were lost in all spontaneous metastases recovered from MDW4-injected mice, loss of the TAA appeared to be an uncommon event. Antigen-loss tumor cell variants are discussed in terms of their relevance to metastasis, and in regard to their use in the study of T cell-mediated cytotoxicity of tumor cell populations.
Invasion Metastasis 1981
PMID:An examination of tumor antigen loss in spontaneous metastases. 698 58

The sequential intraperitoneal injection of five different A strain tumors into DBA/2 mice resulted in the de novo generation of new DBA/2 tumors. These new tumors share many identical characteristics including the expression of surface H2d, FcR, LY6.2 and tumor antigens. All have the same karyotype which differs in number and in the presence of two metacentric chromosomes from the original A strain tumors. Phenotypically, all are vigorously metastatic after intraperitoneal, subcutaneous, intradermal or intravenous injection. None of the original A strain tumors are metastatic in the A strain host. These tumors have thus provided us with a good model for the study of metastasis while raising questions regarding the oncogenicity of tumors.
Invasion Metastasis 1981
PMID:Generation of highly metastatic tumors in DBA/2 mice. Oncogenicity of a strain tumor cells. 718 80

The ability of two highly metastatic tumor lines of DBA/2 (H-2d) origin to metastasize in various allogeneic normal or nude (nu/nu) mouse strains was investigated. Normal mice differing from DBA/2 at either the major histocompatibility complex or at minor histocompatibility loci were both able to reject rather high subcutaneous inocula of these tumor cells. F1 hybrids between susceptible and resistant strains could not reject the metastatic tumors. This suggests that tumor rejection was dependent on the recognition of allogeneic histocompatibility antigens. Two mouse strains appeared to be selectively resistant to the establishment of tumor metastases but could not prevent the progressive tumor growth at a local site. One was a new variant subline of DBA/2, provisionally designated as DBA/2/HD, the other was C57B1/6 (nu/nu), an athymic 'nude' mouse of C57B1/6 background. 'Nude' mice of BALB/c or C3H background were more or less susceptible to these tumors and their metastases. These studies demonstrate that the establishment of tumor metastasis is greatly influenced by genetic factors of the host. Resistance to local tumor growth seemed to require the presence of mature T lymphocytes while resistance to metastasis formation could be established in T-cell-deficient nude mice of certain genetic backgrounds.
Invasion Metastasis 1981
PMID:Immunogenetic studies on the resistance of mice to highly metastatic DBA/2 tumor cell variants. I. Effect of incompatibilities at H-2 or non-H-2 genes in normal and nude (nu/nu) mice. 718 81

KLN205 cells, a cloned cell line established from the Nettesheim lung carcinoma, grow in various synthetic media such as MEM, Fisher's or Roswell Park Memorial Institute Medium (RPMI) with the addition of 5 to 20% fetal bovine serum (FBS), calf-serum (CS) or horse serum (HS). They grow optimally in minimum Eagle's medium plus nonessential amino acids (NEAA) plus 5 to 10% FBS or HS. The cells are transplantable to DBA/2, BDF1, AKD2F1, and BALB/c, but not to C3H/He or ICR mice. The growth curves, plating efficiency, ultrastructural characteristics, modal number of chromosomes and transplantability to mice of various strains are almost the same for early and late passage of cells passaged in vitro. These parameters for 16th and 36th passages were: doubling time, 31 and 33 hr; plating efficiency, 12.4 +/- 1.2 and 14.6 +/- 2.6%; modal number of chromosomes, 73 and 76; lung colony formation in DBA/2, 50 and 45.9/mouse; and subcutaneous tumor diameter 24.5 and 27.4 mm, respectively. Only the numbers of lung colonies formed in BDF1 mice were different: 24.4/mouse with 16th passage cells, and 10.2/mouse with 36th passage cells. The results suggest that KLN205 is a relatively stable cultured cell line through 36 passages. As was expected, immunosuppression by higher concentrations of triaminolone acetonide (TA) enhanced lung colony formation in BDF1 mice. On the other hand, a low concentration of TA inhibited lung colony formation in DBA/2 mice, which was unexpected. These results suggest that KLN205 offers a model for investigations on metastases to lungs as well as chemotherapy for lung carcinoma.
 ...
PMID:KLN205--a murine lung carcinoma cell line. 741 33

Locoregional recurrent and distant metastases from squamous cell carcinomas, despite multimodality therapy, remain troublesome clinical realities. Discrepancies in success rates of various surgery and radiation treatment regimens dealing with these problems are confusing to the clinician attempting to recommend the most beneficial treatments. There is a need for an experimental model to assess therapeutic effectiveness quantitatively from which guidelines for developing clinical trials may be suggested. In this study, we provide such a model. We injected DBA-2 mice with defined numbers of KLN-205 squamous carcinoma cells to obtain baseline growth characteristics; 216 animals had no previous irradiation. The remaining 131 received 30 Gy irradiation to the right leg 50 days before injection of the tumor cells. Tumor incidence, growth and number, and location of tumor metastasis were determined in both previously irradiated and nonirradiated groups. The data demonstrate a growth-retardant effect on tumor groups by the previous irradiation (tumor bed effect). The data also show that the incidence of hematogenously spread metastases was more frequent in mice in which tumors developed in previously irradiated tissue than in mice with tumors in nonirradiated tissue.
 ...
PMID:Squamous cell carcinoma growth in irradiated tissue: a murine model for quantitative assessment of treatment. 748 40

Altered expression of ABH blood group substances is a common feature of human colorectal carcinoma, yet it remains unclear how these structural changes influence the biological properties of tumor cells. Azoxymethane-induced rat colon tumors display many features of the human disease, thereby providing a potentially useful model to study the role of blood group substances in colon cancer progression. We have prepared monoclonal antibodies to a microsomal fraction isolated from an azoxymethane-induced rat colon tumor and selected an antibody that detects cancer-associated changes. Monoclonal antibody (mAb) 3A7 recognizes a determinant on type 2 chain blood group A (GalNAc alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) and B (Gal alpha 1-3[Fuc alpha 1-2]Gal beta 1-4GlcNAc-R) oligosaccharides. Expression of the epitope detected by this antibody was developmentally regulated in rat colon, with maximal expression from day 4-21 after birth. Immunohistochemical staining and Western blotting analyses of azoxymethane-induced colon tumors revealed increased expression of the epitope in all of the 21 colonic tumors examined, including preneoplastic glands within transitional mucosa. Conventional and signet-ring adenocarcinomas that had invaded through the muscularis propria (Duke's B2) consistently showed the most intense staining with mAb 3A7, including regions depicting angioinvasion. Some of the lymph node metastases (Duke's C2) stained poorly with the antibody. The epitope was also expressed in blood group A positive human colon carcinoma cell lines, including HT29 and SW480 but not by SW620, a cell line derived from a lymph node metastasis isolated in vivo from the SW480 primary tumor, or in the blood group B cell line SW1417. The glycoproteins detected by mAb 3A7 in rat colon tumors and HT29 cells ranged in size between 50 and 200 kd, including a major species of 140 kd. Affinity chromatography of detergent lysates of normal rat colon on the blood group A specific lectin Dolichos biflorus (DBA)-agarose resulted in nearly quantitative binding of glycoprotein species detected by the antibody. By contrast, immunoreactive glycoproteins from rat colon tumors or HT29 cells bound poorly to DBA-agarose but were retained by another blood group A-binding lectin, Helix-pomatia (HPA)-agarose. These results indicate that colon carcinogenesis results in quantitative as well as qualitative changes in oligosaccharides detected by mAb 3A7 and suggest that the combined use of mAb 3A7 and blood group A-specific lectins may provide a useful tool for early detection of colon cancer.
 ...
PMID:Monoclonal antibody recognizing a determinant on type 2 chain blood group A and B oligosaccharides detects oncodevelopmental changes in azoxymethane-induced rat colon tumors and human colon cancer cell lines. 753 50

Tumor growth and metastasis of lacZ-transduced murine lymphoma ESbL cells inoculated into syngeneic DBA/2 mice are characterized by a transient plateau phase with a constant tumor diameter and low metastatic load, indicating a host response against the tumor. Here we show that endothelial cells participate in a T-cell-dependent, anti-metastatic response by producing NO in situ. Liver endothelial cells were isolated and examined directly ex vivo without further manipulation. NO production in liver endothelial cells reached the highest level during the plateau phase but declined toward the end of it, followed by an overall breakdown of host response, leading to progressive tumor growth and high load of liver metastasis. Mice subjected to anti-tumor immunization and subsequent challenge with a tumorigenic dose of ESbL-lacZ cells showed, in comparison to non-immunized challenged controls, reduced liver metastasis and increased endothelial NO production. Adoptive transfer of anti-tumor immune spleen cells from semi-allogeneic B10.D2 mice into tumor-bearing animals during the plateau phase caused a regression of primary tumor and metastases, together with a preservation of the high level of NO synthesis in endothelial cells. In immuno-incompetent (SCID) mice, tumor growth and metastasis were progressive and there was no endothelial NO response. Pre-immunization of immuno-competent mice with both live and irradiated tumor cells at different sites of the body led to an induction of NO production by liver endothelial cells. These results reveal a novel role of endothelial cells in the suppression of lymphoma metastasis in the liver. The inducible endothelial cell NO response is apparently dependent and induced by mature T lymphocytes.
 ...
PMID:Liver endothelial cells participate in T-cell-dependent host resistance to lymphoma metastasis by production of nitric oxide in vivo. 759 Dec 40

Adoptive transfer of splenic T lymphocytes from DBA/2 mice immunized against Friend erythroleukemia cells (FLC) inhibited the development of visceral metastases and increased the survival time of DBA/2 mice challenged i.v. with parental FLC 24 hr to 2 months later. Immune spleen cells were ineffective in mice pre-treated with potent neutralizing antibody to mouse IFN alpha/beta (but not to IFN gamma), demonstrating the essential participation of endogenous IFN alpha/beta in the inhibitory action of immune T lymphocytes against FLC metastases. These findings suggest that the reported inability of immune T lymphocytes to exert an anti-FLC effect in immunodeficient DBA/2 mutant beige (bg/bg) mice (unless these mice had also been treated with IFN alpha/beta), may have been due to lower levels of endogenous IFN alpha/beta in DBA/2 bg/bg mice than in normal DBA/2+/bg mice. Experimental results in support of this hypothesis are presented.
 ...
PMID:The essential role of endogenous IFN alpha/beta in the anti-metastatic action of sensitized T lymphocytes in mice injected with Friend erythroleukemia cells. 759 Dec 92

In this study, we describe the origin and characterization of a new metastatic tumor cell line (p11-R-Eb) obtained after i.p. passages of the nonmetastatic Eb lymphoma cells into DBA/2 mice. The p11-R-Eb cells exhibited the same morphology and in vitro growth properties and chromosome markers as the original Eb cells. FACS analysis of the p11-R-Eb cells also revealed a close similarity to the Eb cells. Moreover, the p11-R-Eb cells were specifically killed by anti-Eb cytotoxic lymphocytes. In spite of all these characteristics of the Eb line, p11-R-Eb cells metastasized to the liver when injected i.v. or s.c. in DBA/2 mice. Peritumoral interleukin (IL)-2 treatment resulted in a potent antitumor response in DBA/2 mice transplanted s.c. with p11-R-Eb cells. In contrast, the same IL-2 regimen did not significantly increase the survival time of mice transplanted with the highly metastatic ESb cell line. Combined IL-1/IL-2 treatments of established p11-R-Eb tumors resulted in a synergistic antitumor effect and in tumor regression in 70% of the injected mice. Similarly, combined peritumoral treatment with IL-1 and interferon-alpha/beta, which were poorly effective or ineffective as single cytokine therapy, resulted in a marked antitumor effect, and 30% of the mice were cured. Spleen cells from IL-1/IL-2-treated p11-R-Eb-cell-injected mice showed a marked antitumor activity when assayed in a Winn assay with homologous tumor cells. This antitumor activity was eliminated by preincubation of spleen cells with antibodies to CD4 and complement and markedly inhibited by anti-asialo GM1 antibodies. P11-R-Eb cells represent, therefore, a new tumor model which may be useful for investigating the relevant mechanisms which need to be activated to achieve a potent antitumor response to cytokine therapy in the DBA/2 mouse host.
Invasion Metastasis 1993
PMID:Isolation and characterization of a metastatic Eb-like tumor variant highly responsive to interleukin (IL)-2 and to combination cytokine therapy with IL-2/IL-1 beta and IL-1 beta/interferon-alpha/beta. 811 75

Daily IFN-alpha/beta therapy was totally ineffective in inhibiting the development of visceral metastases in DBA/2 mice injected i.v. with the ESb lymphoma regardless of the number of tumor cells injected. The finding that IFN-alpha/beta therapy increased the survival time of ESb-immunized mice rechallenged with ESb cells suggested that cooperation between the immune system and IFN-alpha/beta was important. Adoptive transfer of Esb-immune spleen cells (but not normal cells) together with IFN-alpha/beta treatment did inhibit the development of ESb metastases in immunocompetent DBA/2 mice. Either treatment alone was ineffective. The anti-metastatic effect was specific for the ESb lymphoma as spleen cells from ESb-immunized mice together with IFN-alpha/beta treatment did not inhibit the development of metastases in mice challenged with IFN-alpha/beta-resistant 3C18 FLC. Depletion of CD8+ T cells (but not CD4+ T cells or B lymphocytes) prior to transfer eliminated the protective effect of ESb-immune splenocytes in IFN-alpha/beta-treated mice. As few as 1 x 10(6) ESb-immune spleen cells highly enriched for CD8+ cells increased the survival time of IFN-alpha/beta-treated ESb-challenged DBA/2 mice. The combined therapy of ESb-specific immune cells and IFN-alpha/beta resulted in long-term immunity to this tumor.
 ...
PMID:Successful immunotherapy of the highly metastatic murine ESb lymphoma with sensitized CD8+ T cells and IFN-alpha/beta. 818 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>