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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spleen cells of C57BL/6N mice bearing lung metastases were induced to the cytotoxic state by subcutaneous injection of recombinant human interleukin-2 (IL-2) at a minimum dose of 5 x 10(4) U/mouse three times a day for 3 consecutive days. A single intraperitoneal injection of lentinan alone at concentrations of up to 10 mg/kg body weight did not render spleen cells cytotoxic to P-29 cells, but a combination of subthreshold doses of these agents (5 x 10(4) U/ml IL-2 and 5 mg/kg lentinan) induced significant in vivo lymphokine-activated killer activity in spleen cells of tumor-bearing mice. Similarly, spleen cells from mice treated i.p. with lentinan became cytotoxic on in vitro treatment with IL-2. The in vitro responsiveness of spleen cells to IL-2 was maximal 3 days after i.p. injection of lentinan. Synergism between IL-2 and lentinan was also observed in mice bearing spontaneous lung micrometastases: neither IL-2 (less than 5 x 10(4) U/mouse) nor lentinan (less than 2.5 mg/kg) alone had a therapeutic effect, but multiple injections of IL-2 with a single injection of lentinan resulted in significant inhibition of spontaneous pulmonary metastases. From these results we conclude that IL-2 and lentinan in combination are more effective than either one alone for inducing destruction of pulmonary metastases.
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PMID:Synergistic induction of lymphokine (IL-2)-activated killer activity by IL-2 and the polysaccharide lentinan, and therapy of spontaneous pulmonary metastases. 278 52

Previous studies have indicated the efficacy of adoptive immunotherapy utilizing recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in the treatment of advanced neoplastic disease. However, this therapeutic approach is associated with considerable toxicity, primarily due to the systemic administration of rIL-2. The present study was undertaken to determine the efficacy of a newly developed water-soluble glucan, when administered in combination with LAK cells, in the therapy of experimental hepatic metastases. Mice were challenged subcutaneously (1 X 10(4) cells) with reticulum cell sarcoma M5076 on day 0. Therapy was initiated on day 15, when a palpable primary tumor mass and hepatic micrometastases were evident, and continued at 3-day intervals up to day 54. Sarcoma-bearing mice received glucan (250 mg/kg) intravenously, either alone or in combination with LAK cells (1 X 10(7)/mouse). Control mice received 5% (wt/vol) dextrose in water. Glucan-LAK cell therapy significantly suppressed primary tumor growth, inhibited the progression of hepatic metastases and prolonged survival in sarcoma-bearing mice. Splenocytes, incubated with rIL-2 for 72 h, exhibited significant natural killer (NK) cell activity and were cytotoxic to sarcoma cells in vitro. Glucan-LAK cell administration resulted in significant increases in splenic NK cell activity and Kupffer cell-mediated tumoricidal activity. In addition, bone marrow proliferation was enhanced following the co-administration of glucan and LAK cells. Due to its nontoxic nature and immunostimulating properties, soluble glucan may prove to be an attractive biological response modifying agent for utilization in adoptive immunotherapy of advanced neoplastic disease.
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PMID:Soluble glucan and lymphokine-activated killer (LAK) cells in the therapy of experimental hepatic metastases. 328 99

Two cell lines (EH and HK) with hairy cell leukemia (HCL) immunophenotypes were recently derived from two HCL patients. Both cell lines were transplanted subcutaneously (2 x 10(5) or 2 x 10(6)/mouse) in male BALB/c nu/nu mice (n = 128) with a 97% success rate when coimplanted with nonproliferative HT-1080 fibrosarcoma cells (2 x 10(6)/mouse) in recipients preconditioned with total-body irradiation (200 R weekly for 3 weeks). Tumors appeared five to ten days postimplant and reached up to 25% of body weight after a mean survival of 8 weeks (range, 30 to 90 days). Tumor histology suggested large cell lymphoma. Cytochemically and immunophenotypically, tumor cells were indistinguishable from their parent cells. Species and lineage derivation of tumor cells was confirmed by antibody probes against the mouse histocompatibility antigen H-2, human T and B lymphocyte antigens, and the HCL-associated common chronic lymphocytic leukemia antigen (cCLLa). In order of decreasing frequency, metastases occurred in the spleen, lungs, pleura, lymph nodes, bone marrow, and kidneys. Up to 12% of circulating lymphoid cells in mice were cCLLa-positive, which suggested hematogenous tumor dissemination. This HCL xenotransplantation model might be useful in preclinical studies for exploring novel experimental therapies for the management of human HCL.
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PMID:Transplantation of human hairy cell leukemia in radiation-preconditioned nude mice: characterization of the model by histological, histochemical, phenotypic, and tumor kinetic studies. 328 6

Several polyribonucleotides are currently in clinical trials for the treatment of cancer or viral diseases. The present report in mice demonstrates that polyinosinic-polycytidylic acid and poly-L-lysine which has been stabilized in carboxymethylcellulose (poly (ICLC) as well as polyadenosinic-polyuridylic acid (poly AU), both potently augment natural killer (NK) activity in the liver, which is often a target organ for the formation of metastases during the progression of human cancer. Following the administration of poly ICLC (10 micrograms/mouse), greater NK activity as measured by lytic units (LU), was observed in the liver (445 LU) than in blood (63 LU) or spleen (20 LU). The high level of NK activity in the liver was in contrast to the low levels observed in untreated mice, and was maintained for at least 9 days post injection. NK activity in the blood and spleen returned to normal levels by day 6. Similar results were obtained with poly AU except that approximately 10-fold more poly AU (100 micrograms/mouse) was required to induce optimal augmentation of NK activity. Further studies demonstrated that the increase in liver-associated NK activity induced by poly ICLC was associated with a 10- to 20-fold increase in liver-associated leukocytes, termed nonparenchymal cells (NPC). Fractionation of the NPC on discontinuous density gradients of Percoll demonstrated that the NK activity mediated by NPC was associated with cells morphologically characterized as large granular lymphocytes (LGL). Further studies demonstrated that the repeated administration of poly ICLC resulted in significantly higher levels of liver-associated NK activity and total liver-associated LGL as compared to a single injection.
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PMID:Increase in liver-associated natural killer activity by polyribonucleotides. 344 88

The effects of allogenic blood transfusion on the subcutaneous growth and metastatic spread of two types of mouse tumour (B16 melanoma syngeneic to the C57/BL6 mouse and UV-2237 fibrosarcoma syngeneic to the C3H/He mouse) were studied. The growth rates of the primary tumour were not altered by transfusing the animals with allogeneic blood 14 days before tumour inoculation, but spontaneous metastasis from tumours formed at the inoculation site was augmented and accelerated for both tumour types. This effect was dependent on the strain of the blood donor, metastases of B16 melanoma being augmented by transfusion with blood from Balb/c animals, and UV-2237 fibrosarcoma by transfusion with C57/BL6 blood, but not by blood from other donor strains tested.
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PMID:Effect of pre-operative blood transfusion on tumour metastases. 360 15

Glucan, a particulate beta-1,3-polyglucose immunomodulator, was evaluated for its ability to modify hepatic metastases and survival in mice with reticulum cell sarcoma. Sarcoma M5076 cells were injected subcutaneously (1 X 10(5) cells) into syngeneic C57BL/6J male mice. On Day 20, histopathological studies indicated the presence of hepatic micrometastases. At this time, glucan (0.45 mg per mouse) or dextrose was administered intravenously. Therapy was continued at 3-day intervals up to Day 50. By Day 36 postchallenge, the glucan-treated group, when compared to the control group, showed a marked decrease in hepatic metastases, both grossly and histopathologically. A significant inhibition in the growth of the primary tumor also occurred. Plasma clearance of bromosulfophthalein measured on Day 36, denoted that glucan therapy maintained hepatic parenchymal cell functional integrity, while a 4-fold impairment in bromosulfopthalein removal was observed in control mice. Glucan-treated mice showed a 28% (p less than 0.05) long-term survival. In contrast, control mice showed a 100% mortality by Day 42 postchallenge. Studies to evaluate the mechanism of the anti-metastatic action of glucan indicated that 8 days after glucan administration, isolated hepatic macrophages were significantly more cytotoxic to sarcoma cells in vitro than were normal Kupffer cells. At this time, the cytotoxic activity of peritoneal and splenic macrophages from glucan-treated mice were unaltered. Additionally, co-incubation of particulate glucan with diverse populations of normal or tumor cells in vitro indicated that glucan exerted a direct cytostatic effect on sarcoma and melanoma cells and, in contrast, had a proliferative effect on normal spleen and bone marrow cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic efficacy of glucan in a murine model of hepatic metastatic disease. 388 76

To investigate whether the presence of an activated ras oncogene influences the ability of tumour cells to metastasize, the c-Ha-ras-1 oncogene cloned from EJ/T24 cells was introduced into MT1 Cl.5/7 mouse mammary carcinoma cells. Since the MT1 Cl.5/7 cells are already tumorigenic but have a low metastatic capacity, this experimental design allows a distinction to be made between the effects of the ras gene on metastasis and tumorigenicity. MT1 Cl.5/7 containing the EJ c-Ha-ras-1 metastasized more readily and to more tissue sites than control cells (2.8 sites/mouse vs 0.9 sites/mouse). The metastases expressed the EJ c-Ha-ras-1 p21 ras proteins; however, one metastasis was discovered that had lost the expression of the c-Ha-ras-1 gene. When these cells were re-tested for metastasis, the rate of metastasis was indistinguishable from that of controls. This observation, coupled with a demonstration that lung colonization potential following intravenous inoculation is unaffected by the presence of the activated ras gene, argues that the effect of mutant ras genes is exerted on the ability of cells to escape from the primary tumour, rather than on a survival in the circulatory systems and ability to seed a second site.
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PMID:Enhanced spontaneous metastasis of mouse carcinoma cells transfected with an activated c-Ha-ras-1 gene. 394 24

Tumor pairs, selected on the basis of their different capacities to metastasize in vivo (SP73/AS and ASML from the rat, Eb/ESb from the mouse), have been assayed for their membrane associated actin through the DNase inhibition assay. It is found that, provided inhibitions per cell are corrected for the influence of gross heterogeneities in size distributions, the more metastatic tumor cells have significantly higher DNase I inhibitions than their less invasive counterparts. This observation, which extends our previous study of normal recirculating lymphocytes, is rationalized by postulating a participation of these actin pools to a property critical for both normal recirculation and metastatic spreading, arguments are presented which favor cell surface deformability as a possible candidate.
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PMID:DNase I inhibitions in tumors of different metastasizing capacities: a possible index of invasiveness. 623 Jan 49

The purpose of these studies was to establish a procedure for determining the relative experimental metastatic potential of unrelated murine tumors. We used three tumors (the B16-F10 melanoma, which is syngeneic to the C57BL/6N mouse, and the K-1735 melanoma and the UV-2237 fibrosarcoma, which are syngeneic to the C3H/HeN mouse). Various numbers of tumor cells were injected into normal or immunosuppressed syngeneic recipients and into 3-week-old BALB/c nude mice. At appropriate intervals, the recipient mice were killed, and the metastatic burden was determined. The number of experimental metastases was not linearly correlated with cell input. Thus, simply comparing the incidence of metastasis resulting from the injection of one predetermined dose of tumor cells did not allow for determination of their relative metastatic capacities. More reproducible and meaningful results were obtained by introducing increasing numbers of viable tumor cells admixed with a constant number of nontumorigenic (X-irradiated) tumor cells serving as carrier. The incidence of metastasis by few or many injected cells is influenced by host factors such as immune status, and therefore determinations of the true metastatic nature of any given tumor necessitate the choice of an appropriate recipient.
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PMID:Comparative studies on the quantitative analysis of experimental metastatic capacity. 629 61

The in vitro sensitivities to differentiating agents of a murine neuroblastoma cell line (N18) and a selected variant cell line (N18-LM5) were examined. In addition, the sensitivities to differentiating agents of cells from spontaneous metastases produced by N18 cells were examined. When N18 cells (1 X 10(5) cells/mouse) were injected into the lateral tail vein of syngeneic A/J mice, only a few metastatic nodules formed in the liver and lung, while similar injection of N18-LM5 cells produced larger numbers of metastatic nodules. Exposure of N18 cells to differentiating agents, such as dibutyryl cyclic 3':5'-AMP (db-cAMP), prostaglandin E1, and dexamethasone, resulted in induction of differentiation in terms of neurite extension. N18-LM5 cells responded to differentiating agents to a greater extent than N18 cells, and most of the cells extended neurites when they were exposed to 1 mM db-cAMP for 3 days. On the other hand, not all cell lines from spontaneous metastases produced by N18 cells responded to db-cAMP. These results suggest that the colonizing potential of neuroblastoma cells is not necessarily correlated with loss of responsiveness to differentiating agents and that various spontaneous metastases show heterogeneity in responsiveness to differentiating agents.
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PMID:Differences in inducibility of morphological differentiation of parental cells, selected variant cells and cells from spontaneous metastases of mouse neuroblastoma cells. 630 60


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