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)

Fourteen breast cancer lines (8 human, 5 rat, and 1 mouse) have been studied in terms of their ability to form multicellular tumor spheroids (MTS) with the agar-base method. Only 8 of the lines formed MTS in contrast to a 100% efficiency in a series of 11 varied tumors reported in the initial studies with this method. We have compared the lines that do and do not form MTS in terms of a variety of characteristics (e.g., estrogen receptors, time in serial passage, growth in nude mice, etc.), and only one characteristic, the source of the original tumor cells, was predictive of MTS-forming ability. All 8 of the breast cancer lines (and the original 11 lines) that formed MTS had been obtained from solid growths (primaries or metastases), while the 6 breast cancer lines that did not form MTS were all derived from pleural effusions. Similarly, artificial selection for an ascites variant of the MTS-forming rat 13762 adenocarcinoma line produced the 13762-A line, which could no longer form MTS. These results suggest that breast cancer cells derived from pleural effusions are genetically different from the bulk of the tumor cells in solid breast cancer samples, that they are unable to grow in true solid form, and that these differences persist in spite of prolonged propagation in tissue culture.
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PMID:Multicellular tumor spheroid formation by breast cancer cells isolated from different sites. 66 44

The present paper reports the highly metastasis of mammary tumors in Chinese wild mouse M. m. musculus Sub-Jyg (JYG mouse), which was recently inbred at the National Institute of Genetics, Mishima, Japan. The incidence of mammary tumors at 18th generation was 89% at about 9 months of age. Histology of mammary tumors in 19 cases examined were medullary or papillary adenocarcinoma (Comedo type) with highly anaplastic features. Metastasis was found not only in the lungs (53%), but also in the liver (21%) and spleen (16%), respectively. MMTV antigen and particle were also found in various organs by immunoperoxidase method and electronmicroscopy. As a result of present observation, JYG mouse was considered to be a unique model in the study of the metastasis of mammary tumors to the liver and spleen.
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PMID:[Highly metastatic mammary tumors in M. m. musculus Sub-Jyg (JYG mouse)]. 204 72

The purpose of this study was to examine whether organ specific metastasis can be produced by different subpopulations of cells isolated from a single human melanoma. Three clones, SB1, SB2, SB3, and a variant line SB1 Asc (obtained from ascites fluid after i.v. inoculation of SB1 cells in a nude mouse) - all isolated from a primary human cutaneous melanoma - were inoculated into the left ventricle (i.c.) or intravenously (i.v.) into nude mice. Three to 16 weeks later, the animals were killed and autopsied. The clones produced different patterns of metastasis. Three to 4 weeks after i.c. inoculation of 2 x 10(6) cells, cells of clone SB1 produced numerous rapidly progressing metastases in the brain, whereas cells of SB1 Asc produced large metastases in the adrenals and sometimes in the ovaries. Cells of clones SB2 and SB3 produced a few small metastases without any characteristics pattern. The initial arrest of tumor cells in various organs did not predict the outcome of metastasis. This conclusion is based on studies of distribution and fate of tumor cells labeled with 111Indium Oxine. Therefore, organ specific metastasis produced by human melanoma cells inoculated i.c. into nude mice is likely to depend on the interaction of unique metastatic cells with organ environment.
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PMID:Specific organ metastases of human melanoma cells injected into the arterial circulation of nude mice. 206 8

A variety of biologic and synthetic agents protect BALB/c mice against experimental M109 micrometastases. We have presented evidence that eradication of these metastases is mediated by the activation of host macrophages to the tumoricidal state. We now present evidence that injection of H22, a neutralizing hamster IgG monoclonal antibody to murine interferon-gamma (IFN-gamma; macrophage activating factor), 2 days prior to i.v. tumor inoculation markedly increases the metastatic capacity of M109 lung carcinoma cells. Therefore, we tested several cytokines that induce or mediate macrophage-mediated cytotoxicity, including IFN-gamma, tumor necrosis factor-alpha, and interleukin-1 beta (IL-1 beta), for their ability to inhibit the development of experimental M109 lung metastases. Intraperitoneal treatment with recombinant murine (rMu) IFN-gamma (greater than or equal to 10,000 units/mouse) or recombinant murine TNF-alpha (greater than or equal to 10,000 units/mouse) produced greater than 60% inhibition of metastasis formation. Optimal therapy was observed when cytokines were administered 2 days prior to i.v. tumor cell inoculation. Neither IFN-gamma nor TNF-alpha inhibited colony formation of M109 cells in vitro, suggesting a host-mediated mechanism for antitumor activity. Peritoneal macrophages were primed for tumor cytotoxicity by treatment with either IFN-gamma or TNF-alpha. Intraperitoneal treatment with recombinant human IL-1 beta (1 X 10(5) units) lacked antimetastatic activity. The results further support the role of activated macrophages in the destruction of M109 micrometastases.
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PMID:Protective activity of recombinant murine tumor necrosis factor-alpha and interferon-gamma against experimental murine lung carcinoma metastases. 211 56

This study was carried out to determine the effect of local irradiation of the NFSa tumors on the incidence of lung metastases. The spontaneous lung metastases were found in those animals whose tumors had grown in size bigger than 10 mm in diameter. The incidence of metastases and the number of lung nodules were increased in those animals of irradiated group when compared to those of control group with the same size. This is probably because the irradiation of tumors resulted some retardation in their growth and thus, the irradiated tumors took a longer time to reach a given size than those unirradiated control tumors. The incidence of spontaneous lung metastases was significantly reduced by subcutaneous administration of OK-432 (2.5KE/mouse) locally into the surroundings of the tumor immediately after irradiation. The administration of OK-432 after the metastasis development was no longer effective. Both of intraperitoneal and subcutaneous administrations of OK-432 into opposite side of unirradiated thigh showed no suppression of metastasis. These results suggest that an appropriate immunostimulation combined with radiotherapy may be important for the suppression of tumor metastases.
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PMID:[Modification of spontaneous lung metastasis by local radiation combined with or without immunomodifier]. 224 55

The efficacy of local adoptive immunotherapy with human lymphokine-activated killer cells and recombinant interleukin 2 (rIL-2) in growth inhibition of established squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a nude mouse model. The model of xenografted SCCHN was established by s.c. injections of in vitro maintained tumor cells (2-10 x 10(6) cells/mouse) into the flank of splenectomized animals pretreated with cyclophosphamide (200 mg/kg). The SCCHN line used was tumorigenic in 95% of the appropriately conditioned nude mice. Inhibition of tumor growth by locally administered effector cells was the end point of the study, since the tumors did not metastasize within 6 weeks of tumor challenge. Either i.p. or local administration of rIL-2 alone (1000 units/day) to the tumor site daily for 2 weeks resulted in a significant inhibition of tumor growth. In the absence of detectable natural killer activity in these mice, a modest dose of rIL-2 had a direct antitumor effect on SCCHN cells in vivo. In addition, complete inhibition of tumor growth was achieved with 3 times weekly injections of 5-10 x 10(6) lymphokine-activated killer cells delivered to the tumor site and 1000 units of rIL-2 administered locally every day for 2 weeks. Our data indicate that local or systemic immunotherapy with rIL-2 alone or local adoptive immunotherapy with an adequate dose of lymphokine-activated killer cells plus rIL-2 may be effective in preventing the growth of established SCCHN tumors in vivo.
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PMID:Local adoptive immunotherapy of human head and neck cancer xenografts in nude mice with lymphokine-activated killer cells and interleukin 2. 233 6

In a reproducible murine model of liver metastases, it was demonstrated that liposomal muramyl dipeptide (MDP) as an adjuvant therapy reduces and prevents the development of metastases. C26 colon adenocarcinoma cells were injected into the spleen (5 x 10(4) cells per mouse) of syngeneic BALB/c mice. On day 3, the spleen was removed to prevent a large tumor burden in the spleen. On day 17, 100% of the mice had developed tumor foci in the liver. Liposomal MDP treatment consisted of the i.v. or i.p. administration of 1 mumol of liposomal lipid containing 5 micrograms of MDP per mouse for ten consecutive days. When therapy was initiated two days after tumor cell inoculation, the number of metastases that had developed on day 17 was strongly reduced compared to control mice. Approximately 20% of the mice were free of liver metastases. Initiation of therapy two days prior to tumor cell inoculation enhanced the effect significantly: about 45% of the mice were free of metastases on day 17. The treatment protocol for survival studies was slightly different; liposomal MDP was administered on the first six consecutive days followed by administration twice weekly, through day 24. Control mice died between day 21 and 33 after tumor cell inoculation, whereas liposomal MDP treated mice died between day 26 and 46 with 1 out of 25 mice surviving for more than 120 days. The mortality of the liposomal MDP treated mice that were free of liver metastases was caused by a local tumor at the site of operation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapy of murine liver metastases by administration of MDP encapsulated in liposomes. 236 53

Tamoxifen, an antiestrogen with efficacy in treatment of both estrogen receptor-positive and negative breast tumors, may be immunomodulatory. We tested tamoxifen's ability to augment the antitumor activity of interleukin-2 (IL-2), a lymphokine capable of expanding and activating lymphocytes, in the treatment of established pulmonary metastases of the weakly immunogenic murine fibrosarcoma MCA-106. Age-matched C57BL/6 female mice bearing pulmonary metastases induced by a tail vein injection of MCA-106 tumor suspension (5 x 10(5) cells/mouse) were treated from days 3 through 12 with intraperitoneal saline solution or IL-2 (50,000 units twice a day). Half of the mice in each group received plain and the remainder received tamoxifen-treated (2 units/ml) drinking water ad libitum for the duration of the experiment. All mice were killed on day 18 for enumeration of pulmonary metastases. Compared with saline-treated control mice, IL-2 and tamoxifen reduced metastases by 66% (p less than 0.0002) and 30% (p less than 0.005), respectively. IL-2 and tamoxifen combined reduced metastases 95% (p less than 0.0002), significantly better than did IL-2 (p less than 0.02) or tamoxifen (p less than 0.0003) alone. In vitro, tamoxifen inhibited proliferation of the weakly estrogen receptor-positive MCA-106 tumor by approximately 30%. Tamoxifen had no effect on the generation of 3-day IL-2-activated lymphocyte cytotoxicity against both natural killer-sensitive (YAC) and natural killer-resistant (MCA-106) target cells. Both YAC and MCA-106 tumor became more resistant to lysis with increased concentration of tamoxifen. This is the first demonstration of in vivo potentiation of IL-2 antitumor activity by tamoxifen and suggests its possible use clinically.
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PMID:Tamoxifen potentiates in vivo antitumor activity of interleukin-2. 238 15

We have previously established that type I interferon (IFN), a mixture of alpha- and beta-IFN, augments the antitumor activity of alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, against B16 melanoma. The objective of the present investigation was to extend these earlier observations to metastatic Lewis lung carcinoma and to determine specifically which component(s) of type I IFN potentiates the antitumor activity of DFMO. Furthermore, we wanted to determine whether type II (gamma) IFN can also potentiate the antitumor activity of DFMO. Treatment of animals bearing Lewis lung carcinoma with DFMO, 2% in drinking water (3 g/kg/day), or IFN-alpha/beta (1000 units/mouse) given subcutaneously on alternate days for a total of ten doses alone resulted in 42 and 5% inhibition of tumor growth, respectively. A combination of DFMO and interferon brought about complete elimination of tumors in 12 of the 18 animals, and 94% inhibition of tumor growth in the remainder. DFMO or type I IFN administered alone caused 94 and 26% inhibition of metastasis, respectively. Combination treatment with these two agents resulted in complete elimination of visible metastases. Treatment of mice bearing B16 melanoma with DFMO resulted in 81% inhibition of tumor growth compared to controls. The administration of interferons alone resulted in tumor growth inhibition of 15, 3, 1, and 43% for type I, alpha-, beta-, and gamma-interferons, respectively. Treatment of animals with combination of DFMO and various interferons resulted in inhibition of 94, 93, 86, and 94% of B16 tumor growth for type I, alpha-, beta-, and gamma-interferons, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of murine alpha-, beta-, and gamma-interferons in combination with alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on the tumor growth and metastasis of B16 melanoma and Lewis lung carcinoma in mice. 249 64

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.
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PMID:Effect of systemic administration of mouse recombinant interferon-gamma on the lung tumor metastases in mice. 251 71


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