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)

Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy. Interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106 pulmonary metastases. This effect was evident in irradiated mice, indicating that a host response to the interferon alfa was not required. Interferon alfa treatment increased class I major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells. These results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer.
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PMID:Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa. 199 72

The administration of recombinant human macrophage colony-stimulating factor (M-CSF) i.p. in doses of 25 or 100 micrograms twice daily for 5 consecutive days to non-tumor-bearing C57BL/6 mice resulted in a dose-dependent infiltration of mononuclear cells in the livers but not the lungs of these treated animals. Immunohistochemical examination of fixed liver tissue with the murine macrophage-specific monoclonal antibody, F4/80, revealed a greater than 5-fold increase in the number of hepatic macrophages. Quantification of F4/80-positive cells in a mononuclear single cell suspension derived from liver revealed a greater than 25-fold expansion in the number of hepatic macrophages compared to control mice. These cells were then tested in 18-h 51Cr release assays for tumoricidal activity, after an 18-h incubation with or without gamma-interferon, against cultured P815 targets. Significant tumor cell lysis by these liver-associated mononuclear cells occurred, which was enhanced by gamma-interferon preincubation. The systemic administration of M-CSF alone at high dose had no antitumor impact in vivo against 3-day pulmonary metastases from the MCA-203 sarcoma and B16 melanoma or hepatic metastases from the B16 melanoma or MCA-105, -203, or -207 sarcomas. Although the systemic administration of M-CSF in combination with tumor-specific monoclonal antibody had no effect on 3-day pulmonary metastases from the B16 melanoma, significant reductions in liver metastases were seen. These murine studies demonstrate the biological activity of recombinant human M-CSF in vivo and suggest that the administration of this cytokine in combination with specific monoclonal antibody may be useful in the treatment of patients with metastatic disease at sites of monocyte/macrophage accumulation.
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PMID:Biological and antitumor effects of recombinant human macrophage colony-stimulating factor in mice. 202 43

A study of the epithelial mucin marker MCA was made in 233 patients with breast cancer. Only 6% of 72 patients with Stage I-III disease had a raised MCA (greater than 15 U ml-1) when assessed following surgical treatment of the primary tumour. Raised levels of MCA occurred in one out of 20 (10%) patients with stable local recurrence, and six out of ten (60%) patients with progressive local recurrence. In 115 patients with metastases 89 (77%) had a raised MCA, tumour extent and disease activity both influenced the MCA level. The change of MCA level during the treatment of 11 cases of local recurrence and 55 cases of metastatic disease showed a 64 and 84% concordance respectively with the change in clinical status. Coincidental measurement of MCA and bone scans showed a raised MCA in one out of 63 (1.5%) patients with negative or equivocal scans, and 26 out of 35 (74%) with positive scans. MCA provides a useful marker for the monitoring of the treatment of local recurrence and metastatic disease, and an independent indicator of the effects of changes in treatment.
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PMID:Use of mucin like cancer associated antigen (MCA) in the management of breast cancer. 206 33

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

An experimental model of hepatic metastases in C57BL/6 mice was used to compare the antitumor effects of lymphokine-activated killer (LAK) cells, anti-CD3-activated T-cells (ATC), and anti-CD3 alone. Liver metastases were produced by in vivo passage of MCA-38-LD adenocarcinoma via the ileocolic vein. LAK cells and ATC were generated by 3-day in vitro incubation of spleen cells in interleukin 2 and anti-CD3, respectively. Percentage of tumor volume in livers was determined with a morphometric technique. With less than therapeutic LAK cell doses (0.5-1.0 x 10(7) cells), no effect was seen in mean (+SE, -SE) percentage of tumor volume of control [23.3 (29.3, 18.5)] compared to LAK cell-treated [21.6 (29.3, 15.9)] animals. The same number of ATC significantly reduced the mean percentage of tumor volume [2.7 (4.7, 1.4)] (P less than 0.005). High dose interleukin 2 also significantly decreased tumor volume. More strikingly, a single dose of anti-CD3 alone had a beneficial effect on mean percentage of tumor volume when given i.p. [1.0 (1.9, 0.4)] or i.v. [1.2 (1.7, 0.7)] (P less than 0.0003). A total of 33% of anti-CD3-treated mice had no detectable liver metastases. In 51Cr release assays, the cytotoxicity of ATC was shown to be partially mediated by nylon wool-adherent accessory cells. The effectiveness of anti-CD3 in this immunotherapy model suggests that a similar approach may be taken to immunotherapy of human malignancies, without the requirements for in vitro-generated killer cells or exogenously administered interleukin 2.
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PMID:Comparison of cellular immunotherapies and anti-CD3 in the treatment of MCA-38-LD experimental hepatic metastases in C57BL/6 mice. 213 7

Tumor-infiltrating lymphocytes (TILs) comprise a subpopulation of lymphoid cells that infiltrate into growing tumors. These cells can be activated in vitro with recombinant interleukin-2 (rIL-2) to become highly cytotoxic against fresh tumor targets in vitro and against a variety of systemic metastases in vivo. OK-432 is a well-known inducer of NK cells and immune effector T cells. This study was designed to evaluate the effects of OK-432 on (a) the generation and (b) the cytotoxic potential of rIL-2-induced TILs. When TILs obtained from a murine colon adenocarcinoma (the MC-38 tumor) were cultured in complete media supplemented with 100 U of rIL-2/ml and 1.0 microgram of OK-432/ml, the number of TILs generated was greater than that seen with rIL-2 or OK-432 alone (number of TILs on day 15 of culture: 100 U of rIL-2/ml: 268 x 10(5) TILs; 1.0 microgram of OK-432/ml: 30 x 10(5) TILs; 100 U of rIL-2/ml + 1.0 microgram of OK-432/ml: 528 x 10(5) TILs). Higher concentrations of OK-432 had deleterious effects on TIL growth characteristics. TILs generated in 100 U of rIL-2 and 1.0 microgram of OK-432/ml of complete media demonstrated greater tumor lysis compared to rIL-2 alone (% lysis against MCA-102 target; 100 U of rIL-2/ml: 12%; 100 U of rIL-2/ml and 1.0 microgram of OK-432/ml: 50%; effector target ratio 20:1; p less than 0.001). Similar results were seen against the NK-sensitive YAC-1 lymphoma target.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synergistic actions of picibanil (OK-432) on recombinant interleukin-2 induction of tumor-infiltrating lymphocyte expansion, cytotoxicity, and phenotypic differentiation. 218 Oct 72

"New" carbohydrate structures on the surface of or secreted by cancer cells, identified as epitopes by monoclonal antibodies, are reviewed. These structures may represent the accumulation of precursor chains because of decreased activity of synthesizing enzymes, the production of new oligosaccharides due to increased or aberrant glycosylation of carbohydrate chains, a change in density of carbohydrates on the cell surface, or exposure of chains usually covered by other structures. Alterations in glycolipid synthesis include aberrant fucosylation and/or sialyation of the lacto series, sialylation or fucosylation of the globo series, and sialyation of the ganglio series. Many of these carbohydrate epitopes have become useful for the diagnosis, prognosis, and monitoring of patients with cancer. Some of the important markers include CA 15.3, CA 19.9, CA 50, CA 125, CA 242, MCA, SLEX, etc. Incomplete glycosylation of O-linked mucin oligosaccharide is recognized as the important "cancer antigen" B72.3, which is sialyated Tn. The oligosaccharide components of alpha-fetoprotein, carcinoembryonic antigen, and epidermal growth factor receptor are also reviewed. In many instances the glycosylation seen in cancer cells or their products reflects patterns seen during normal development. Thus, cancer-associated oligosaccharides are oncodevelopmental in nature. The biologic significance of carbohydrates on cell surfaces is not known, but several possibilities include a role in cell to cell recognition, intracellular processing of glycoproteins, cell activation, and ability of cancer cells to metastasize.
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PMID:Cancer-associated carbohydrates identified by monoclonal antibodies. 221 Jul 23

MCA serum levels were determined in 27 healthy subjects, 136 with benign pathology (42 breast) and in 289 patients with cancer (247 active). The last group includes 223 patients with breast cancer (96 without metastases, 89 with metastases and 38 no-evidence of disease). CEA and CA15-3 serum levels were determined in all the patients with breast diseases. The mean levels of MCA were 4.7 + 2.4 U/ml in the control group, considering less than 11 U/ml as normal. MCA values were abnormal in 15.4% of patients with benign pathology, mainly in those with liver cirrhosis (8/20) and lung diseases (4/20). In the majority of these cases, the rise was only moderate, lower than 15 U/ml in 97.5% of patients. In malignant diseases, important increments were found in breast cancer (19.8% Mo, 77.5% M1) and ovarian cancer stages III-IV (44.4%). When we compared MCA serum levels with CA15-3 and CEA in breast pathology, a similar specificity was observed: 92.3%, 92.3% and 100% in cases with benign pathology and 92.1%, 94.7%, and 97.4% in NED patients, respectively. MCA and CA15-3 sensitivity was similar in breast cancer without metastases (19.8%) and lower for CEA (16.7%). In patients with breast cancer without metastases, we found a relation between positivity of these tumor markers and prognostic factors (tumor size, nodal involvement). The disease free interval in patients with locoregional breast cancer was shorter in cases with abnormal presurgical levels of some of the tumor markers, but only the difference from MCA was significant (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:MCA in patients with breast cancer: correlation with CEA and CA15-3. 223 Mar 47

The effects of liposome formulations of interleukin 2 (IL-2) and local route were studied in C57BL/6 mice with MCA-106 sarcoma pulmonary metastases. IL-2 liposomes made by hydration of powdered dimyristoyl-phosphatidylcholine with aqueous recombinant IL-2 had 95% of the IL-2 associated with the lipid fraction. When mice with pulmonary micrometastases were treated once daily with free cytokine on days 5, 6, and 7 after tumor inoculation, the intrathoracic route was superior to the i.p. or s.c. routes. When IL-2 liposomes were administered by the local intrathoracic route, significantly better antitumor effects (P less than 0.01) were seen compared to empty liposomes or free IL-2 as determined by (a) increased survival and (b) reduced numbers of pulmonary metastases. Minimal toxicity was observed. Results indicate that local route and incorporation of IL-2 in liposomes may enhance therapeutic efficacy and facilitate more practical daily dosing regimens.
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PMID:Increased local antitumor effects of interleukin 2 liposomes in mice with MCA-106 sarcoma pulmonary metastases. 230 37

The MCA 102 sarcoma has been defined by a variety of immunologic studies as a tumor lacking intrinsic immunogenicity. Nevertheless, we have recently demonstrated the feasibility of generating therapeutically effective lymphocytes for adoptive immunotherapy of this tumor. Procedures to achieve this required in vivo priming of syngeneic mice to elicit preeffector cells followed by in vitro sensitization (IVS) with tumor cells in the presence of IL-2. By selective depletion of T cell subsets in vivo, we identified the involvement of both CD4+ (L3T4+) and CD8+ (Lyt-2+) T cells in mediating tumor regression. The CD4+ cells exerted their helper function via the secretion of IL-2 because antitumor effects abrogated by depletion of CD4+ cells could be reconstituted by exogenous IL-2. In order to elicit preeffector cells with reactivity against the MCA 102 tumor, we found that in vivo sensitization could be accomplished with either the MCA 102 or MCA 106 tumor but not with the MCA 101 or MCA 105 tumor. Analysis of specificity of tumor stimulation during IVS of MCA 102 tumor-primed preeffector cells demonstrated cross-reactivity between not only the MCA 102 and MCA 106 tumors but also the MCA 105 tumor whereas the MCA 101 tumor was ineffective. In adoptive immunotherapy, transfer of IVS cells generated from MCA 102 tumor-primed and stimulated lymph node cells was able to mediate reductions of pulmonary metastases established from the MCA 102, MCA 105, and MCA 106 tumors but not from the MCA 101 tumor. We conclude that regression of the MCA 102 tumor is probably mediated through T cell recognition of a set of common tumor-associated Ag shared by several other syngeneic tumors. Immunologically, the tumor-associated Ag are characteristically different from classical tumor-specific transplantation Ag (TSTA) because immunity to TSTA on the MCA 105 or MCA 106 tumor does not cross-react with the MCA 102 tumor. Thus, this study demonstrates that Ag other than TSTA on chemically induced tumors can serve as target molecules for T cell-mediated adoptive immunotherapy.
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PMID:Effector phenotype and immunologic specificity of T-cell-mediated adoptive therapy for a murine tumor that lacks intrinsic immunogenicity. 236 40


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