Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The soybean-derived Bowman-Birk inhibitor (BBI) has been shown to inhibit carcinogenesis in both in vitro and in vivo model systems. In the present study, protease enzyme activity in selected tissues of male strain A mice was measured by hydrolysis of the synthetic substrate Boc-Val-Pro-Arg-MCA (t-butoxycarbornylvalylprolylarginine 7-amido-4-methylcoumarin). When added to homogenates of lung, liver and kidney in vitro, purified BBI inhibited hydrolytic activity at concentrations ranging from 10-100 microM. In vivo, hydrolytic activity was found to be significantly and in a dose-dependent manner, decreased in the lung as early as 2 h after i.p. injection of purified BBI. Less inhibition was found in the liver and kidney after in vivo administration of purified BBI. A crude preparation of BBI, given at 100 mg/kg, had no influence on the overall disposition of radiolabeled benzo[alpha]pyrene in mice although it decreased the hepatic activities of cytochrome P-450, 7-ethoxycoumarin-O-deethylase and ethoxy resorufin-O-deethylase. It is concluded that the chemopreventive effects of BBI on mouse lung tumor development are most likely mediated through its protease-inhibitory properties in the target organ rather than by a non-specific effect on metabolism and disposition of carcinogens.
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PMID:Acute effects of the Bowman-Birk protease inhibitor in mice. 194 45

Tumor-infiltrating lymphocytes (TILs) are host T cells that can be grown from fresh murine and human tumors using interleukin-2 (IL-2) in bulk cultures. These activated T cells have been shown to have significant antitumor activity both in vitro and in vivo. A technique is described for the separation of Thy-1.2-positive TILs from fresh murine tumors using antibody-coated magnetic beads, permitting the examination of growth conditions for these cells. TILs with increased therapeutic efficacy are obtained from the immunogenic MCA 38 and MCA 105 tumors when culture conditions employing low levels of IL-2 (10 vs. 1,000 U/ml) and irradiated autologous tumor restimulation are used. TILs grown under these conditions can mediate a 93% reduction of 3-day-old established pulmonary metastases when as few as 2.5 x 10(5) cells are adoptively transferred with systemic IL-2. These culture conditions are utilized to grow TILs from the nonimmunogenic MCA 102 tumor for which bulk TIL culture methods are unsuccessful. MCA 102 TILs grown in this fashion demonstrate in vivo therapeutic efficacy against established autologous pulmonary metastases.
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PMID:An improved method for growing murine tumor-infiltrating lymphocytes with in vivo antitumor activity. 197 2

We have previously reported that murine splenocytes incubated in the lymphokine interleukin-2 acquire the ability to mediate the lysis of a variety of fresh tumor cells in short-term chromium-51 release assays. This study was designed to evaluate the effect of lymphokine-activated killer (LAK) cells on fresh normal murine tissues. The susceptibility to lysis by LAK cells of single cell suspensions from a variety of murine tissues including lung, kidney, bone marrow, peripheral blood mononuclear cells, intestinal mucosa, liver, and fetus was studied. While kidney, intestinal mucosa, and peripheral blood mononuclear cells were clearly not lysed, there was a very low level of lysis of lung, bone marrow, liver, and fetus in repeated experiments. Separation of the cell suspensions of lung and bone marrow demonstrated much higher lysis of the adherent cell population, corresponding to an increased number of macrophages in the target cell suspension. Macrophages represent a population of cells particularly sensitive to lysis by LAK cells. All of the normal tissues were highly lysable by LAK cells in antibody-dependent cellular cytotoxicity assays in the presence of the appropriate anti-H-2 antibody. In a series of cold target inhibition studies, fresh normal murine kidney, lung, and bone marrow did not inhibit the lysis of the LAK-sensitive tumor target MCA-102, further demonstrating that fresh normal tissues share little if any of the determinant recognized by LAK cells on tumor targets. However, the MCA-105 and MCA-106 tumors, and the YAC cell line, all of which are sensitive to LAK cell lysis, did inhibit the lysis of MCA-102 tumor. These studies suggest that a common determinant is present on LAK-sensitive tissues that is absent or present in very low amounts on fresh normal tissues.
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PMID:The specificity of lymphokine-activated killer (LAK) cells in vitro: fresh normal murine tissues are resistant to LAK-mediated lysis. 198 27

Recently, we reported enhanced tumor reduction using recombinant interferon-alpha A/D (IFN) combined with interleukin-2 (IL-2). Similar synergism affecting survival was assessed in treatment of both early and advanced pulmonary metastases. This combination was compared with the current "standard" IL-2 and lymphokine activated killer (LAK) therapy in the treatment of early and advanced pulmonary metastases. C57BL/6 mice injected via tail vein with the weakly immunogenic methylcholanthrene-induced murine fibrosarcoma MCA-106 were treated intraperitoneally with IL-2 (50,000 units b.i.d.), IFN (50,000 units q.d.), LAK (2.5-10 x 10(7)), or various combinations of above. Treatment of both early Day 3 and advanced Day 10 metastases using IL-2/IFN reduced metastases and prolonged survival over both controls and IL-2 alone. It was superior to IFN, LAK, and IFN/LAK. Addition of LAK to IL-2/IFN demonstrated no added benefit. Although no mortality was observed during treatment of Day 3 metastases, treatment of Day 10 advanced pulmonary metastases for 9 days with IL-2/IFN resulted in early deaths (33%) without visible tumor, indicating possible toxicity of treatment. These results show survival benefit of IL-2/IFN over IL-2, IFN, or LAK treatment in the therapy of early and advanced pulmonary metastases, albeit with added toxicity. Its relative simplicity and comparable efficacy to the more complex and costly IL-2/LAK provide important advantages for potential clinical applications.
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PMID:Enhanced survival of IFN-alpha augmented IL-2 therapy of pulmonary metastases: efficacy comparable to interleukin-2 and lymphokine activated killer cells. 198 29

The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3-methylcholanthrene (3-MCA), was tested in NIH 3T3 transformation assay. Activation of K-ras and N-ras was found in 7 and 3 cases respectively. No H-ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K-ras mutation at codon 12, 3 at codon 13 and 1 at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N-ras were also found, one of which was simultaneous with a K12 mutation. Tumor-specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA+ tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3-MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA+ sarcomas, but none of the DNAs of the 6 TSTA- tumors showed ras mutation. The results suggest that 3-MCA-induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K- and N- but not H-ras gene and that such mutation is accompanied by the expression of TSTA.
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PMID:Activation of ras oncogenes and expression of tumor-specific transplantation antigens in methylcholanthrene-induced murine fibrosarcomas. 199 90

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

The presence of interleukin 4 receptor (IL-4R) on methylcholanthrene (MCA-106, MCA-102, and MC-38)- and viral DNA (G-2TS and 14-2TS)-induced murine sarcoma cells was demonstrated. MCA-106 tumor cells express about 500 to 1348 (median, 800) interleukin 4 (IL-4) binding sites/cell with a dissociation constant (Kd) of 115 +/- 26 pM (mean +/- SD, n = 4). By Northern blot analysis, tumor cells exhibited a single mRNA species of 3.9 kilobases. Other murine sarcoma (MCA-102), colon adenocarcinoma (MC-38), G-2TS, and 14-2TS tumor cells express low numbers of IL-4R. By immunoperoxidase staining, 81 to 92% of the cells from fresh MCA-106 tumors were positive for IL-4 receptors, while only 7 to 10% of tumor-infiltrating cells were Thy 1.2 and less than 1% Mac-1 positive. Using a chimeric protein composed of IL-4 and Pseudomonas exotoxin (IL-4-PE40), we observed that IL-4-PE40 was cytotoxic (determined by inhibition of protein synthesis by [3H]leucine uptake) to MCA-106 tumor cells in a dose-dependent manner. A nonchimeric protein (PE40) that cannot bind to the IL-4R did not inhibit protein synthesis in tumor cells. A chimeric mutant protein (IL4-PE40 asp553) that can bind to IL-4 receptors but does not have the capability to inhibit protein synthesis was not cytotoxic to tumor cells. These studies strongly suggest that IL-4R on murine MCA-106 sarcoma cells is internalized when occupied by IL-4 PE40. Furthermore, a neutralizing antibody (11B11) to IL-4 completely abolished the protein synthesis-inhibitory activity of IL-4-PE40. G-2TS tumor cells which expressed low numbers of IL-4 receptors were not vulnerable to cytotoxicity by IL-4-PE40. Taken together, these data suggest that IL-4 receptor may be a target for IL-4-toxin therapy.
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PMID:Expression of high-affinity interleukin 4 receptors on murine sarcoma cells and receptor-mediated cytotoxicity of tumor cells to chimeric protein between interleukin 4 and Pseudomonas exotoxin. 203 39

CA 15-3 and MCA assays were tested in 103 operable patients (preoperative determination) and 100 patients with advanced breast cancer. Normal CA 15-3 and MCA values were determined in a series of 68 healthy women. The negative/positive cut-off was set at 28.8 U/ml and 15.5 U/ml respectively for CA 15-3 and MCA (mean value + 2SD). Results were analyzed in the two groups and with respect to T and N pathological categories in the preoperative series. In pT1 (59 pts), pT2 (30 pts), pT3 + pT4 (14 pts), pNO (58 pts), pN1 (45 pts) and overall preoperative series CA 15-3 and MCA sensitivities were respectively 25%, 40%, 57%, 22%, 42%, 30% and 27%, 30%, 35%, 21%, 33%, 26%. In the patients affected by widespread disease, sensitivity was 92% and 80% for CA 15-3 and MCA. Results were significantly different among normal, preoperative and advanced patients (P less than 0.05). Our results suggest that CA 15-3 and MCA levels are correlated with the tumor mass. Nevertheless, the low sensitivity in pT1 and pNO cases indicates that these two assays have no role in the diagnosis of early breast cancer. In the advanced patients, too, the results can be questioned: in the present study, in fact, recurrent cases were characterized by gross disease with multiple site involvement and cannot be considered as an example of early diagnosis of breast cancer recurrence.
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PMID:The role of CA 15-3 and MCA monoclonal antibody assays in the detection of primary and recurrent breast cancer. 206 26

The monoclonal antibodies that define the tumor markers CA15.3, MCA, CAM26 and CAM29 were found to react with coexisting epitopes present on mucin-like glycoproteins. Despite their immunologic relationship, the markers showed distinct concentration levels in various body fluids. Particularly, MCA and CAM26 were high in urine and amniotic fluid. Sera collected from pregnant or lactating women and especially human milk samples contained considerable amounts of CAM29 and MCA, but comparably small quantities of CAM26 and CA15.3. The concentrations of CA15.3, MCA, CAM26 and CAM29 were correlated in serum samples from patients with metastatic breast cancer. The discrepancy between immunologic relationship and dissimilar biologic behavior could be explained by a limited coexistence of epitopes on subsets of heterogeneous polymorphic mucins. All mucin markers which were investigated showed improved sensitivity for metastatic breast cancer compared with the established marker CEA.
Tumour Biol 1991
PMID:CA15.3, MCA, CAM26, CAM29 are members of a polymorphic family of mucin-like glycoproteins. 206 12


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