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)

Murine fibrosarcoma cells that vary in their transplantability in syngeneic mice were isolated from a heterogeneous parent tumor (induced in a female C57BL/6 inbred mouse) and maintained in culture by serial passage. Several biologic properties that discriminate between the high- and low-transplantable lines (including adhesiveness, motility, and levels of chymotrypsin-like esterase activity), as well as properties that do not separate these lines (e.g., in vitro growth rates and levels of protease and glycosidase activities), were measured at periodic intervals over 2 years. Ability to induce primary tumors and to induce metastases from these tumors were evaluated at the same intervals. The high- and low-transplantable lines were also transplanted into syngeneic mice at tumorigenic doses. Isolates from primary and metastatic tumors induced in the animals were reestablished in culture and examined for the various characteristics of passages 5, 10, 20, and 30. The properties of the cells maintained continually in culture remained stable throughout the 2-year observation period. Tumor isolates showed some evidence of modulation immediately after reestablishment in culture, but by passage 10 they appeared to be identical to the prototype parent lines. These data show that the fibrosarcoma cells do not undergo continual phenotypic "drift" as has been suggested to occur with other tumor lines maintained by serial passage in animals or in culture.
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PMID:Phenotypic stability of murine tumor cells in vitro and in vivo. 695 74

The effects of Corynebacterium parvum and retinyl palmitate given at various levels, schedules, and routes of administration on primary Lewis lung carcinoma and its metastases have been evaluated in C57BL/6J mice given s.c. inoculations of 5 X 10(5) tumor cells. Single i.v., but not i.p., s.c., or i.m., administration of C. parvum (0.35 mg/mouse given on Days 0, 1, or 3) reduced growth of tumor and prolonged survival time. Retinyl palmitate (3000 IU/mouse/day) given alone i.p. either before, after, or both before and after tumor inoculation showed no effect on tumor growth, survival of mice, or lung metastases. The combination of retinyl palmitate i.p. (6 daily injections of 1500 IU/mouse after tumor implantation) and C. parvum (0.175 mg/mouse) given i.v. resulted in an increase in life span over control of 146% and appeared to be therapeutically synergistic. This combination produced 90-day cures in about 20% of the treated animals, all of which were found to be tumor free. Two nonparametric statistical procedures, the Kruskal-Wallis and the Dunn test, were used to assess the effects of treatments on survival time and tumor growth and may be generally applicable to animal tumor studies. They provide multiple comparisons of different treatments and allow the inclusion of long-term survivors into the analysis.
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PMID:Antitumor activity of Corynebacterium parvum and retinyl palmitate used in combination on the Lewis lung carcinoma. 743 95

In the present report, we investigated the possible importance of beta 1 integrins in the growth and metastasis of a murine mammary carcinoma, SP1, and a metastatic variant, SP1-3M in vivo. CBA/J female mice bearing SP1 tumor transplants were injected with anti-beta 1 integrin IgG or control nonimmune IgG (200 micrograms per mouse; i.p.) every two days. Animals received anti-CD4 antibody (100 micrograms per mouse) at time zero to suppress immunity against rabbit IgG. Outgrowth of macroscopic metastases from SP1, but not from SP1-3M primary tumors, was markedly inhibited in animals receiving anti-beta 1 integrin IgG but not nonimmune IgG. To assess the stage(s) in the metastatic cascade affected, we examined the number and diameter of micrometastatic nodules in treated and untreated groups. The diameter of micrometastases was significantly reduced in SP1-tumor-bearing mice treated with anti-beta 1 integrin IgG compared to control IgG, although the number of nodules per cm2 of lung sections examined remained unchanged. No change in the number or size of micrometastases in SP1-3M tumor-bearing mice was observed. No difference in the binding, or complement-mediated and antibody-dependent cell-mediated cytotoxicity of anti-beta 1 integrin IgG with SP1 and SP1-3M cells was detected. The results suggest that under these conditions anti-beta 1 integrin inhibits metastatic tumor growth in lung tissue, but has minimal effect on intravasation, adhesion to target organs and extravasation.
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PMID:Anti-beta 1 integrin IgG inhibits pulmonary macrometastasis and the size of micrometastases from a murine mammary carcinoma. 752 59

Two cell lines were established from liver cells (BALB/c mouse) exposed to benzo(a)pyrene: one was highly metastatic (G-5) and the other poorly metastatic (G-1) to the lung when subcutaneously implanted. However, there was no difference in lung colonization between G-1 and G-5 cells when they were intravenously injected. When G-1 cells were subcutaneously inoculated on one side of the back of mice followed by a challenge on the other side with G-5 cells 10 days later, the growth of the latter tumor was inhibited and the number of metastatic nodules in the lung was reduced. The functional vascular volume of G-1 tumor was less than the G-5 one. In mice bearing G-1 tumors, the neovascularization of intradermally inoculated G-5 cells was reduced. The conditioned medium from G-1 culture contained an inhibitory activity on the growth of endothelial cells from calf pulmonary artery. The inhibitory substance(s) was heat-stable, trichloroacetic acid-soluble, nondialyzable and resistant to various proteinases. The present results imply that G-1 cells produce an antiangiogenic substance(s), probably a polysaccharide(s), which inhibits the angiogenesis required for growth and metastasis of the G-5 tumor.
Invasion Metastasis 1995
PMID:Antiangiogenic substance(s) in a tumor cell line with low metastatic potential originating from the BALB/c mouse liver. 754 55

In certain cases pleural adenocarcinoma can behave like a primary tumour of the pleura. If the origin of this type of tumour is not clearly established, the macroscopic aspect of the pleura explored by thoracoscopy enables a distinction to be made between isolated disease of the parietal pleura and mixed disease of both the parietal and visceral pleura. The object of this study was to evaluate the prognosis of tumour disease of the visceral pleura. Using a murine model (the nude mouse) of cancer of both visceral and parietal pleura induced by implanting histologically intact human carcinoma, we have compared the symptoms of survival of the two groups of mice as well as the local and regional dissemination and metastases of the implanted tumour. The growth of the tumour was suspected by the appearance of weight loss, signs of respiratory difficulty and/or cachexia. Autopsy examination allowed a measure of the size of tumour dissemination. A pleural cancer, histologically identical to the initial human tumour with invasion of the neighbouring structures as one sees in man, was obtained in all the implants. Nevertheless, contralateral mediastinal lymph node metastases were only found in mice with implants on the visceral pleura. The median survival was 27.9 days and 31 days respectively for implanted mice on the visceral pleura and on the parietal pleura. Mice with implants on the visceral pleural lost more weight than those implanted on the parietal pleura (p < 0.001). The results of this study show that the models of parietal pleura and visceral pleura each correspond to an early stage disease and to a stage of advanced disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An experimental model of pleural adenocarcinoma constructed by the implantation of intact human neoplastic tissue in the nude mouse. The prognostic value of a lesion of the visceral pleura]. 763 23

Despite considerable advancement in anticancer therapy, minimal residual disease (MRD) is still a major problem in the clinical management of cancer, including lymphoma. In this report, we have studied the antitumor effects of interleukin-12 (IL-12) against an aggressive liver metastatic murine RAW117-H10 lymphoma. Our results using three different doses of IL-12 (0.175, 0.35 and 0.7 micrograms/mouse) showed that a 0.35 micrograms dose is the most efficacious against lymphoma grown in intact mice. Furthermore, we have evaluated the therapeutic effects of IL-12 against residual lymphoma in a transplantation setting. BALB/c mice were treated with high-dose therapy (HDT) and transplanted with syngeneic bone marrow cells added with a known number of RAW117-H10 lymphoma cells to mimic the clinical situation of MRD. The mice were then treated with IL-12 (0.25 micrograms/mouse/day) alone or IL-12 plus activated cytotoxic effector cells. Our results showed that IL-12 had a significant (P < 0.05) antitumor therapeutic effect against liver metastatic lymphoma grown in intact mice as well as in lymphoma-bearing mice treated with HDT followed by stem cell transplantation as determined by survival period. The therapeutic effect of IL-12 was also demonstrated by a very significant decrease (P < 0.05) in the tumor burden in livers from the IL-12-treated mice. Mice that were treated with IL-12 following HDT and hematopoietic stem cell transplantation had a significant decrease in circulating white blood cells (P < 0.05), a significant increase in spleen weight and cellularity (P < 0.05), and hematopoietic progenitor cells (P < 0.05), a significant increase in the number of splenocytes expressing IL-2 alpha-chain receptor (P < 0.05), and an increase in the frequency of natural killer cells in their spleens. These studies suggest that cytokines such as IL-12 may have the potential to mediate antitumor effects against residual lymphoma without compromising lymphohematopoietic recovery.
Clin Exp Metastasis 1996 May
PMID:In vivo therapeutic effects of interleukin-12 against highly metastatic residual lymphoma. 867 76

The monoclonal antibody A33 recognises a tumour-associated antigen on human colorectal carcinoma, and has undergone preliminary evaluation in the clinic where selective localisation to hepatic metastases has been demonstrated [Welt et al. (1994) J. Clin. Oncol. 12, 1561-1571]. A33 and an A33 tri-fab fragment (TFM) were labelled with 90Y via a stable macrocyclic ligand for biodistribution and therapy studies in nude mice bearing SW1222 colon carcinoma xenografts. Biodistribution studies demonstrated tumour localisation for both A33 IgG and TFM with low bone, liver and kidney levels. Clearance of TFM from the blood was much faster than IgG and this led to lower tumour accumulation for TFM but superior tumour-blood ratios. The maximum per cent injected dose per g localised to tumour was 35.9% +/- 5.3% for A33 IgG and 12.9% +/- 4.6% for A33 TFM with tumour-blood ratios at 48 h after administration of 5.6 +/- 1.8 and 29.2 +/- 9.8 respectively. Autoradiography studies with 125I-labelled A33 IgG and TFM demonstrated a homogeneous distribution within tumour tissue which was not observed with other anti-colorectal tumour antibodies. TFM penetrated into the tumour tissue more rapidly than IgG. In therapy studies, a single dose of 90Y-A33 IgG (250 microCi per mouse) or 90Y-A33 TFM (300 microCi per mouse) led to complete regression of 2-week-old tumour xenografts with long-term tumour-free survivors. A transient drop in white blood cell count was observed with both IgG and TFM but was significantly more pronounced with IgG. The cell count fell to 8.4% of control for IgG, whereas with TFM cell counts fell to 51% of control before recovery. These results indicate that the more rapid blood clearance of 90Y-TFM confers reduced toxicity compared with 90Y-IgG although similar therapeutic effects are achieved. When the dose of 90Y-IgG was adjusted to give the same dose to tumour achieved with 300 microCi 90Y-TFM, a lesser therapeutic effect was observed. This may be owing to more rapid tumour penetration achieved with TFM. Both A33 IgG and TFM demonstrated potent anti-tumour effects against human tumour xenografts in this mouse model system. The stability of these 90Y-labelled conjugates and their effective tumour penetration are promising for the development of humanised reagents for clinical studies.
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PMID:Radioimmunotherapy of colorectal carcinoma xenografts in nude mice with yttrium-90 A33 IgG and Tri-Fab (TFM). 876 64

The antitumor effect of PSK was analysed with the "double grafted tumor system" in which BALB/c mice received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with PSK in the right tumor on day 3. PSK inhibited the growth of not only the right but also the left, non-treated tumor. Immunized spleen cells were taken from mice which had been cured by intratumoral administration of 5 mg of PSK. On day 3, one hour after intravenous injection of cyclophosphamide, immunized spleen cells (2 x 10(7) cells/mouse) were injected into the Meth-A tumor. Adoptive transfer of PSK immunized spleen cells caused the complete regression of Meth-A tumors. However, the intravenous administration of spleen cells showed no antitumor effect. Expansion of peripheral blood lymphocytes was stimulated with immobilized anti CD3 antibody plus IL-2 for use in adoptive immunotherapy. gamma delta T cells proliferated in response to immobilized anti CD3. About 5 x 10(9) BRM-activated killer (BAK) cells were treated in cancer patients who gave their informed consent. One patient with colon cancer and metastatic cancer of the liver was treated with BAK cells by transcatheter arterial infusion without side effect. During the course of BAK treatment, serum IAP CIAE (crossed immunoaffino electrophoresis) pattern of patient changed tumor IAP pattern to normal IAP pattern. Two patients with malignant tumor in maxillary sinus were treated with BAK cells and OK-432 intratumorally. BAK treatment induced more infiltration of T cells, M phi and granulocytes in the tumor than OK-432 treatment alone and showed an antitumor effect with extensive necrosis.
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PMID:[Regional adoptive immunotherapy using activated lymphocytes]. 885 2

Previously we have found that administration of thiorphan alone or in combination with bestatin exerts antitumor effect in mice, including reduction of B16 melanoma tumor growth and prolongation of survival time. These data prompted us to extend our studies to estimate the effect of treatment with thiorphan, captopril and bestatin on lung metastases in mice. Administration of thiorphan alone at a dose of 25 micrograms/mouse or in combination with bestatin (50 micrograms) or captopril (5 mg/mouse) decreased the number of spontaneous metastases in lungs of Lewis lung carcinoma bearing mice. Neither the injections of bestatin, captopril nor bestatin in combination with captopril influenced the number of lung tumor colonies. Treatment with thiorphan at a dose 25 micrograms augmented cytotoxic activity of natural killer (NK) cells and macrophages. These observations explain partly the mechanism of action of thiorphan.
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PMID:Effects of thiorphan, bestatin and captopril on the Lewis lung carcinoma metastases in mice. 886 34

We evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP's anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme's active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP's antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.
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PMID:Ancylostoma caninum anticoagulant peptide blocks metastasis in vivo and inhibits factor Xa binding to melanoma cells in vitro. 960 44


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