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)

We have tried to establish a model for lymph node metastasis in nude mice transplanted with clone A of methylcholanthrene-induced rat fibrosarcoma. Tumor cells transplanted either subcutaneously or intrafootpad metastasized exclusively to the lymph nodes in nude mice treated with antiasialo GM1 antiserum. In the experiments of intrafootpad transplantation, all the mice died of disseminated lymph node metastasis if the leg was not resected, or was resected more than 3 weeks after the transplantation of clone A. Some mice whose legs were amputated 1 or 2 weeks after transplantation could be cured by amputation alone. The maximum effective dose of in vitro active drug could improve the survival in mice, and 3/5, 4/5, and 3/5 mice treated with MMC, ACNU and CDDP respectively were cured even if their legs were amputated 3 weeks after transplantation. This tumor-bearing animal system was considered to provide a valuable experimental model for lymph node metastasis.
Invasion Metastasis 1991
PMID:The development of a treatment model for lymph node metastasis in nude mice transplanted with rat fibrosarcoma clone A. 193 77

Lymphokine-activated killer (LAK) cells were generated from splenocytes of rats bearing a weakly immunogenic Dunning prostate tumor (R-3227 AT-3) and activated with recombinant interleukin-2 (rIL-2). The maximal LAK activity was obtained from splenocytes of rats bearing tumors for 10 to 14 days after incubation with 1000 U/ml./day of rIL-2 for five to eight days. The majority of these LAK cells expressed high levels of asialo GM1 (89%), laminin (83%), OX-19 (80%) and OX-8 (88%) surface markers. LAK cells exhibited higher cytotoxicity to rat prostate tumor cells and mouse lymphoma in vitro than to other non-prostate tumor cells or normal rat splenocytes and thymocytes. Splenocytes of rats bearing prostate tumors have higher LAK activity than normal splenocytes. The Winn type assay showed that Dunning prostate tumor growth was inhibited effectively by LAK cells at a tumor cell:LAK cell ratio of 1:50. The therapeutic efficacy of LAK cells in the treatment of primary solid prostate tumors and pulmonary metastases of Dunning rats was evaluated. LAK cells in combination with rIL-2 showed a greater therapeutic benefit in 1) prevention of prostate tumor metastases to lung, 2) retardation of the primary tumor growth, 3) regression of spontaneously established pulmonary metastases, and 4) prolongation of survival as compared to untreated controls or those groups treated with LAK cells or rIL-2 alone. The results of this study indicate that the conjunctive therapeutic approach of using surgical therapy to remove primary solid tumors followed by adoptive immunotherapy with LAK cells plus in vivo administration of IL-2 may be potentially valuable in the treatment of prostate tumors, particularly for the spontaneous pulmonary metastases.
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PMID:Adoptive immunotherapy using lymphokine-activated killer cells and recombinant interleukin-2 in preventing and treating spontaneous pulmonary metastases of syngeneic Dunning rat prostate tumor. 205 87

The carcinoma SC42 was transplanted into the liver of its syngeneic mice DS, and the immunological integrity of the spleen and the effects of splenectomy on the growth and pulmonary metastasis of the liver tumor were assessed. On day 7 after liver tumor transplantation, the natural killer (NK) activity of the splenocytes was significantly elevated; it subsequently decreased at a later stage of the tumor. The response of the splenocytes to PHA and Con-A decreased significantly from the early stage of the tumor. However, the mixed lymphocyte-tumor cell reaction increased significantly from day 14 to day 28. The survival rate of the mice, which had undergone simultaneous splenectomy and liver tumor transplantation, was significantly lower than that of sham-operated control mice. The number of pulmonary metastases in splenectomized mice was significantly greater than in the control mice. There was, however, no difference between the two groups in the weight of the liver tumor. By contrast, splenectomies performed 14 days before or 14 days after tumor transplantation had no significant influence on the survival of the mice. Splenectomies performed on day 0 and on day 3 after tumor transplantation significantly increased the number of pulmonary metastases. Furthermore, the intravenous injection of anti-asialo GM1 antisera on day 0 and day 3 significantly increased the number of pulmonary metastases, but injection of anti-Thy 1.2 antisera had no effect. These results suggest that splenic NK cells may play an important role in the suppression of pulmonary metastasis at early stages of the liver tumor.
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PMID:Effects of splenectomy on pulmonary metastasis and growth of SC42 carcinoma transplanted into mouse liver. 207 2

Lymph nodes draining the progressively growing, weakly immunogenic, MCA 105 sarcoma contained tumor-sensitized but not fully functional pre-effector T-cells. These cells could further differentiate to acquire full antitumor effector function for adoptive therapy in an established in vitro sensitization (IVS) procedure. In this study, we utilized selective depletion with antibodies of lymphocyte subsets bearing the L3T4 (CD4) or Lyt-2 (CD8) antigen and of cells bearing the asialo-GM1 (ASGM-1) glycosphingolipid to identify the phenotype of pre-effector cells elicited during progressive tumor growth. Cells from lymph nodes draining a progressive MCA 105 tumor in the footpad were treated with antibodies plus complement prior to IVS. The antitumor efficacy of resulting IVS cells was assessed in adoptive therapy of 3-day established pulmonary MCA 105 metastases. Depletion of Lyt-2+ cells eliminated in vivo antitumor reactivity with concurrent elimination of in vitro cytotoxic activity against the MCA 105 tumor, whereas depletion of L3T4+ cells did not have an impact on either in vivo or in vitro antitumor reactivities. Treatment with ASGM-1 antiserum plus complement was also found to abrogate therapeutic efficacy. However, the in vitro cytotoxic activity was not affected. These results indicate that the pre-effector cells were Lyt-2+, L3T4-, and ASGM-1+. We next examined whether the sensitization of pre-effector cells in vivo required the participation of L3T4+ helper cells. To approach this, mice were depleted of L3T4+, Lyt-2+, or ASGM-1+ cells by antibody injections before tumor inoculation. Treatment with Lyt-2 monoclonal antibody abrogated the pre-effector cell response in the draining lymph nodes, as evidenced by failure to generate therapeutically effective cells following IVS. On the other hand, neither L3T4 nor ASGM-1 antibody treatment affected the generation of pre-effector cells. Thus, sensitization of Lyt-2+ pre-effector cells in response to progressive tumor occurred in the absence of L3T4+ helper cells.
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PMID:Phenotype analyses and cellular mechanisms of the pre-effector T-lymphocyte response to a progressive syngeneic murine sarcoma. 211 15

We have investigated the effect of sulfated chitin derivatives on the intravascular events in the metastatic cascade. 6-O-Sulfated carboxymethyl chitin (SCM-chitin III), as well as heparin, significantly inhibited the arrest of B16-BL6 cells in lungs after co-injection with radiolabeled tumor cells, but carboxymethylated chitin (CM-chitin) had no effect. Heparin showed a potent inhibitory effect on tumor cell-elicited platelet aggregation and on blood coagulation, which can subsequently enhance the survival, arrest and invasiveness of tumor cells, whereas SCM-chitin III showed much weaker properties. In contrast, SCM-chitin III was found to inhibit the adhesion of tumor cells to subendothelial matrix, while heparin did not. SCM-chitin III was still active in inhibiting experimental lung metastasis even in mice which had been pretreated with anti-asialo GM1 serum or carrageenan to eliminate NK cells or macrophages. Thus, these results suggest that SCM-chitin-mediated inhibition of tumor metastases is distinct from that by heparin and may be due to interference with tumor cell arrest in the capillaries and consequently to the inhibition of tumor cell adhesion to subendothelial matrix.
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PMID:Inhibition of tumor cell arrest in lungs by antimetastatic chitin heparinoid. 211

Using a recently described technique for direct expansion of human T-lymphocytes isolated from small intestine biopsies, we have investigated the local cellular immune response in six patients with B-cell lymphomas of various subtypes. T-cell lines (TCL) were established by seeding tumor-infiltrating T-lymphocytes (T1TL) at limiting dilution in the presence of irradiated feeder cells in culture medium containing rIl-2 and phytohemagglutinin (PHA). About 1/50 T-cells gave rise to a TCL; they all were CD3+. The CD4/CD8 ratio was 3.8:1 before and after cloning. Of 45 TCLs analysed so far from one patient with B-cell lymphoma of the lung, 4 were cytotoxic as shown by their ability to exert lectin-dependent cytotoxicity against allogeneic target cells. Of these, 3 demonstrated specificity for the autologous malignant B-cells. Five TCLs lysed the NK-sensitive K562 cell line in a HLA-unrestricted manner. When tested for antigen-specific proliferative activity, 4 TCLS only responded to the autologous lymphoma cells, but 5 TCLs reacted to the autoantigenic ganglioside GM1. Southern Blot analyses did not show a clonal pattern of T-cell receptor gene rearrangement within all TITL populations. The peripheral T-lymphocytes of the lymphoma patients showed a drastically reduced response to the mitogens PHA. Concanavalin A, and pokeweed mitogen. The present report demonstrates that it is possible to analyze TITL at clonal level. This technique may be the only means of investigating the specificity of the TITL and may help us to identify the relevant tumor-associated autoantigens if tumor-induced autoimmunization is indeed one of the mechanisms that control the growth of tumors and metastases.
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PMID:Characteristics of T-lymphocytes infiltrating human B-cell lymphomas. 214 23

The systemic administration of high dose recombinant interleukin 2 (RIL-2) can mediate significant reductions in the number of hepatic metastases in a murine system. This effect is sensitive to host irradiation. Both large granular (LGLs) and small (SLs) lymphocytes have been implicated as the cells mediating the antitumor effect. Utilizing selective Percoll fractionation of liver nonparenchymal lymphoid cells, we have attempted to determine the cell types involved in tumor immunotherapy of murine liver metastases during RIL-2 administration. At a RIL-2 dose of 25,000 units given i.p. three times a day, the total number of lymphoid cells seen in murine livers reached a peak on day 6 after the onset of RIL-2 therapy, lasting until day 10 and ranging from 25 to 29 times baseline values. Both LGLs and SLs were identified and SLs made up over one-half the cells present in murine livers. Phenotypic analysis of LGLs and SLs revealed that during exposure to RIL-2, bands 5 + 6 SLs expressed the Thy-1.2, Lyt-2, and Lyt-1 antigens to a greater degree than LGLs. LGLs exposed to RIL-2 demonstrated a decrease in the expression of the asialo GM1 antigen during exposure to RIL-2; however, the 49H.8 antigen normally expressed on natural killer cells and not on circulating T-cells was found only on LGLs. The role of murine liver LGLs and SLs needs to be further characterized.
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PMID:Analysis of liver lymphoid cell subsets pre- and post-in vivo administration of human recombinant interleukin 2 in a C57BL/6 murine system. 230 21

A murine mammary tumour model has been used to test the efficacy of a combination of heparin and the interferon inducer, poly I:C on spontaneous metastasis from a s.c. primary tumour and on experimental metastasis following i.v. injection of tumour cells. This treatment has no effect on the growth of primary tumours, but lung metastases arising from these tumours were reduced. When tumour cells were injected i.v. the number of lung colonies was significantly reduced and survival time extended. Short-term treatment did not prevent the subsequent growth of extravasated, but dormant tumour cells, although mice treated for 8 or 12 weeks survived at least 6 months without any sign of lung colonies. Several mechanisms may contribute to the overall effect of this treatment; a reduction in the mitotic indices of lung colonies (observed in poly I:C treated mice) and also NK cells appeared to be important for the effectiveness of poly I:C since the reduction in experimental metastasis was abrogated by concomitant treatment with anti-asialo GM1 serum.
Clin Exp Metastasis
PMID:Reduction of metastasis in a murine mammary tumour model by heparin and polyinosinic-polycytidylic acid. 231 56

The objective of the present investigation was to evaluate the immunomodulating properties of tetramethylenebisacetamide (N,N' 1-diacetylputrescine, DAP), a known inducer of cellular differentiation. We examined the effect of DAP administration in vivo on splenic and nonadherent peritoneal natural killer (NK) cell activity. A single i.p. injection of DAP (100 mg/kg) enhanced cytolytic activity directed against YAC-1 and MCA-38 tumor target cells 2- to 3-fold. Cytolytic activity peaked 3 days following DAP injection. DAP treatment increased the frequency of asialo-GM1-positive splenocytes to 15% compared with 5% for vehicle treated controls. Furthermore, cytolytic activity could be eliminated by treatment with anti-asialo-GM1 antibodies and complement. Lysis of NK-resistant P815 and EL4 tumor target cells was not observed in leukocytes from DAP-treated mice. DAP treatment of mice given injections i.p. of MCA-38 tumor cells increased survival time of the mice by 37%, curing 10% of the animals of the tumor. DAP treatment of mice given injections intrasplenically of MCA-38 tumor cells reduced both the number and the size of the hepatic metastases. The antitumor effect of DAP in vivo could be eliminated by pretreating mice with anti-asialo-GM1 antibodies or utilizing NK cell deficient beige (bg/bg) mice. These results indicate that the observed anti-tumor activity of DAP is mediated, at least in part, by NK cells.
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PMID:Potentiation of natural killer cell activity and tumor immunity by diacetylputrescine. 238 50

The ability of the host-immune defense mechanism of nude mice and their immunocompetent littermates to prevent liver metastases from the murine colon carcinoma, colon-26, was assessed. Give thousand tumor cells suspended in 0.05 ml of Hank's balanced salt solution were inoculated into the spleens of BALB/c nu/+ and BALB/c nu/nu mice. On the 21st day after inoculation, all the mice were sacrificed, and the liver metastases counted and the livers weighed. All the BALB/c nu/+ mice were found to have developed hepatic metastases with a mean of 10 nodules, whereas no hepatic metastases were observed in any of the 10 BALB/c nude mice. On the other hand, 4 of 6 nude mice developed hepatic metastases after treatment with anti-asialo GM1 antibody. These results indicate that the BALB/c nude mouse has an excellent host-immune defense mechanism for preventing liver metastasis, with NK cells in the liver and/or blood circulation perhaps playing an important role.
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PMID:Nude mouse resists hepatic metastasis of the allogeneic tumor, colon-26. 238 47


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