Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth of tumors was inhibited or enhanced in mice by a synthetic (pyran) or a biologic (corynebacterium parvum) immunopotentiator. Marked inhibition of leukemogenesis induced by Friend leukemia virus was produced by prophylactic intraperitoneal treatment with pyran, while intravenous treatment with pyran (in the same dose and regimen) significantly enhanced growth of tumor virus. Paradoxical effects were also seen with the biologic immunopotentiator C. parvum in solid tumor systems. Treatment with C. parvum either potentiated disease or had no effect on the life span of most mice bearing the Lewis lung carcinoma. In contrast, the same treatment could produce a high percentage of tumor regressions in mice bearing the MCA 2182 sarcoma, although the effect was somewhat variable. These data, which show that a change in route of drug administration or in the type of tumor treated may reverse the effect of treatment, emphasize that the mechanism of action of immunopotentiators must be elucidated before consistent beneficial treatment of tumor viruses or tumors can be achieved.
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PMID:Paradoxical effects of immunopotentiators on tumors and tumor viruses. 93 3

Systemic administration of the synthetic immunopotentiator pyran, was as effective as the use of the biologic immunopotentiator BCG in activating macrophages and in inhibiting the Lewis lung carcinoma and MCA 2182 sarcoma. Several other synthetic polyanions also activated macrophages and exhibited some anti-tumor activity, but none were as effective as pyran. Cell-wall fractions such as the Ribi vaccine and MER were considerably less effective than BCG. The anti-tumor activity of pyran against the virtually non-immunogenic Lewis lung carcinoma involved non-specifically activated macrophages, and both anti-tumor activity and macrophage activating ability persisted over a 100-fold range of drug from 0.5 mg/kg to 50 mg/kg. The ability of activated macrophages to destroy tumor cells was abrogated by treatment with trypan blue, an inhibitor of macrophage lysosomal enzymes. In addition, preincubation of tumor cells with activated peritoneal cells at effector-cell:target-cell ratios of 20:1 and 5:1 markedly decreased tumor incidence and mortality. Glycogen-stimulated or unstimulated peritoneal cells were completely inactive in inhibiting tumor growth in vivo or exhibiting cytotoxicity in vitro, demonstrating the requirement for activated macrophages selective for tumor-cell destruction.
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PMID:Macrophage activation and anti-tumor activity of biologic and synthetic agents. 124 2

While close contact between lymphokine-activated killer (LAK)/adherent, lymphokine-activated killer (A-LAK) cells and tumor cells is believed to be a prerequisite for initiating the events leading to tumor cell lysis, clear evidence for the ability of these effector cells to infiltrate tumors or tumor metastases in vivo still has to be obtained. In the present study, we report that a significant fraction of adoptively transferred A-LAK cells, labeled with fluorochromes for identification, accumulates in lung and liver metastases of the B16 melanoma, the MCA 102 sarcoma and the Lewis lung carcinoma lines. Thus, 5- to 10-fold higher numbers of A-LAK cells were found in the malignant lesions compared to the surrounding normal tissue. The infiltration seemed very heterogeneous after intravenous injection of moderate numbers of A-LAK cells (15 x 10(6)). However, after adoptive transfer of 45 million A-LAK cells, an A-LAK cell/tumor cell ratio higher than 1:1 in most metastases was observed. Surprisingly, approximately 5% of the lung metastases seemed totally resistant to infiltration even though neighboring metastases were highly infiltrated. While substantial infiltration of lung metastases was seen after i.v. injection, significant infiltration of liver metastases was seen only after intraportal injection of the A-LAK cells indicating impaired traffic of intravenous injected A-LAK cells through the lung capillaries. These results present direct evidence that A-LAK cells, upon a proper route of administration, have the potential to migrate to and heavily infiltrate metastases from murine tumors of different origin.
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PMID:Accumulation of adoptively transferred adherent, lymphokine-activated killer cells in murine metastases. 185 30

Adoptive immunotherapy with LAK-cells in conjunction with high-dose IL-2 has recently been introduced in the treatment of patients with advanced cancer. This therapeutic modality has thus far proved to be of limited efficacy, severe toxicity and entails complicated logistics. Our present study is aimed at establishing a model system to test for increasing efficacy and reducing toxicity by using AIT cojointly with chemotherapy. Mice implanted i.v. or i.p. with weakly immunogenic tumors (M109 lung carcinoma, MCA-105 sarcoma) were treated 7 to 20 days after tumor inoculation with or without CTX, with and without recombinant human IL-2, and with and without syngeneic/allogeneic LAK-cells. Whereas IL-2 or IL-2 + LAK-cells without CTX was largely ineffective, and CTX alone cured 0 to 20% of the animals with an i.p. tumor and only slightly reduced pulmonary tumor mass, the combination of CTX + IL-2 cured 50 to 80% of the mice bearing i.p. tumors and reduced pulmonary tumor growth by greater than or equal to 80%. The combination of CTX + IL-2 + LAK-cells proved no more beneficial than CTX + IL-2 without LAK-cells. Also relevant were the observations that murine LAK-cells are transiently sensitive to moderate doses of CTX (greater than or equal to 100 mg/kg body weight) and X-irradiation (greater than equal to 400 rad), and that administration of IL-2 by the i.v. or i.p. route variously affects LAK-cell activation in different tissues and eradication of growths localized at different sites. With the regimens used, no signs of toxicity were detected. It is proposed that instillation of IL-2 (and perhaps of additional immunostimulating cytokines as well) as an adjunct to chemotherapy (or chemoradiotherapy), each given at a subtoxic dose, is both safe and effective in the treatment of metastatic advanced tumors, and that the additional administration of LAK-cells may not be required.
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PMID:Therapy of advanced solid tumors in mice using chemotherapy in combination with interleukin-2 with and without lymphokine-activated killer cells. 326 51

Incorporation of cholesterol hemisuccinate (CHS) into the membrane of tumor cell rigidifies the lipid layer, exposes cryptic antigens, and enhances immunogenicity. The local growth and metastatic spread of the 3LL Lewis lung carcinoma were studied in conjunction with immunizations by CHS-enriched 3LL cells. C57BL/6J mice received 2 consecutive immunizations with 10(7) CHS-treated, irradiated (10,000 rad) 3LL cells. Two control groups were immunized with MCA-102 sarcoma cells or CHS-enriched syngeneic spleen cells. All groups were challenged with viable 3LL cells after immunizations. Mice pre-immunized with CHS-enriched 3LL cells showed a delayed tumor growth after subsequent challenge with 3LL. Effect of immunization on the growth of established tumors was examined in 3LL-bearing mice which were treated with 10(7) CHS-enriched tumor cells on days 1-12 after initial tumor implantation. A second identical immunotherapy was given 6 days after the first immunization. Tumor growth was significantly inhibited in mice which received the first immunization 1 day after tumor implantation, while immunization on day 3 or after inhibited the growth rate to a lesser extent. Suppression of pulmonary metastases was assessed after excision of a primary 3LL tumor growing in the foot pad which had reached 8 mm in diameter. Immunization consisted of intraperitoneal injection of 10(7) irradiated CHS-enriched tumor cells following excision and repeated after 6 days. This immunization resulted in a significant decrease in pulmonary metastasis as scored by direct counts of metastatic nodules, by [125I]iododeoxyuridine (125IUdR) incorporation, and by lung weight. Metastatic 3LL cells from nodules which survived immune elimination were isolated and implanted into mice which were pre-immunized with primary 3LL cells enriched with CHS. For comparison, a group of mice was immunized and challenged with primary 3LL cells. Inhibition of tumor growth and pulmonary metastasis formation was observed only in the mice which were challenged with the primary tumor.
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PMID:Inhibition of growth and metastases in mice by immunization with cholesterol hemisuccinate-enriched tumor cells. 650 34

A tumor-derived suppressor factor ( TDSF ) has been isolated from 3 M KCl extracts of a chemically induced fibrosarcoma of C3H/HeJ mice by preparative isoelectric focusing. Incubation of TDSF with normal spleen cells induces suppressor cells that enhance tumor growth and inhibit DTH to the chemical sensitizer 2,4-dinitro-1-chlorobenzene (DNCB). Similar suppressogenic activity has been detected in extracts of the 10T1/2 fibroblast line, an ultraviolet-induced fibrosarcoma of C3H/HeN mice, the C57B1/6J Lewis lung carcinoma, and four human colonic adenocarcinoma. TDSF activity was not found in extracts of syngeneic muscle or spleen cells. Chemical characterization of TDSF from the murine fibrosarcoma MCA-F revealed sensitivity to treatment with heat and RNase, partial sensitivity to treatment with trypsin, but resistance to treatment with DNase, pronase, and neuraminidase. TDSF has an apparent molecular weight of greater than 300 kDa by high-performance gel permeation chromatography. Acidic soluble factors isolated from murine and human tumors induce suppressor cells to inhibit cell-mediated immunity in an intact host.
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PMID:Soluble factors from murine and human tumors induce suppressor cells. 653 7

We have developed a monoclonal antibody (BAT) to Daudi B lymphoblastoid cell line membranes. The antibody was selected for its ability to stimulate lymphocyte proliferation. Splenocytes of BALB/c or C57BL mice given i.v. injections of 10 micrograms/mouse of BAT exhibited increased proliferation and cytotoxic activity. A single i.v. administration of BAT monoclonal antibody 2 weeks after B16 melanoma cell inoculation resulted in a striking antitumor effect as manifested by the elimination of lung metastases and prolonged survival of the treated mice. BAT monoclonal antibody was also effective in the regression of tumors in mice bearing 3LL (Lewis lung carcinoma) and MCA-105 (fibrosarcoma). Transfer of 10(7)-10(8) splenocytes from mice that had been given injections of BAT to B16- or 3LL-inoculated recipients led to a reduction of lung metastases. Splenocytes from B16-inoculated mice that were cured by BAT were more effective than those from mice treated with BAT alone against recipients bearing either B16 or 3LL tumors. The antitumor activity of BAT is related to its immunostimulatory properties.
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PMID:A monoclonal antibody against a human B lymphoblastoid cell line induces tumor regression in mice. 795 1

The cytokinesis-block micronucleus (MN) assay was performed in three mouse tumors: two sarcomas (SaL, MCA) and Lewis lung carcinoma (LLC). To determine the optimal culture durations and cytochalasin B (cyt-B) concentrations to yield the highest proportion of binucleate cells (BC) for each tumor, the influence of the cyt-B concentration (1, 2 and 3 micrograms/ml) and culture duration (24-96) were studied. The amount of BC and the MN frequency was investigated for the different radiation doses (0-4 Gy). Dose response curves were constructed using the optimal culture duration and cyt-B concentration for each tumor. This was 24 h of incubation for MCA and 48 h for SaL and LLC and 2 micrograms/ml of cyt-B. The tumors examined differ in the mean number of spontaneously (0 Gy) occurring MN in binucleate cells. These were 0.008, 0.022 and 0.044 for MCA, SaL and LLC, respectively. The MN frequency increased with radiation dose. LLC was found to be the most radiosensitive, while MCA proved to be the least radiosensitive tumor. The average number of MN/BC at 2 Gy of irradiation (after subtraction of the value at 0 Gy) ranged from 0.05 to 0.36. The highest mean value -0.36 was shown in LLC, the middle-0.20 in SaL, and the lowest-0.05 in MCA tumor. After higher doses of irradiation numerous BC with two and more MN were found in LLC tumor, while they were not frequently observed in MCA tumor. We did not observe an increase in the MN frequency with culture duration or proliferation rate of the tumor cells. MCA has the shortest potential doubling time (Tpot) and had the lowest MN frequency from three examined tumors. The MN assay has promise to be a rapid predictive assay of radiosensitivity.
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PMID:Micronucleus assay in three transplantable mouse tumors. 855 3

The present study describes a new low molecular weight factor released by muscle cells, which inhibits proliferation of tumor cells in vitro and in vivo, is highly specific towards tumor cells, and has no observable effect on normal cells' proliferation. What first prompted us to investigate this factor was the observation that tumor metastases are extremely rare in striated muscles. Co-culturing of striated muscle cells with malignant cells led to marked morphological alterations in the latter, in contrast to the same cells when incubated without muscle cells. A conditioned medium of striated muscle cells was prepared and its effect tested on a variety of cells. This conditioned medium (CM) inhibited proliferation of tumor cell lines of murine (B16 melanoma, Madison 109 lung carcinoma, MCA-105 sarcoma, ESB lymphoma), or of human origin (HTB-38 adenocarcinoma, T47D breast carcinoma, CX1 colon carcinoma). The proliferation of normal cells (bone marrow cells, fetal liver erythroid cells) was not affected by the CM. Flow cytometric analysis of B16 melanoma cells following incubation with the CM revealed that 63% +/- 12 of the cells were in the G0/G1 phase of the cell cycle, compared to 47.8% +/- 8 of cells incubated with a medium (not conditioned) only. The activity of the CM and of certain fractions thereof was also demonstrated in vivo: they prevented tumor growth in mice inoculated intraperitoneally with MCA-105 sarcoma cells. Partial purification of the CM revealed that the active component was a non-proteinaceous compound with a molecular weight of about 500 D. The results clearly suggest that muscle cells produce a low molecular weight factor which can selectively inhibit the proliferation of tumor cells in vitro and in vivo. This factor is neither species nor tumor specific.
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PMID:Muscle cells produce a low molecular weight factor with anti-cancer activity. 867 72

The biological characteristics of three transplantable tumours: two sarcomas (SaL, MCA) and Lewis lung carcinoma (LLC) have been studied. We investigated histology, DNA ploidy and cell kinetics parameters of the tumours. All examined tumours were aneuploid and rapidly proliferating, with the hyperdiploid fraction greater than 60%. The SaL tumour was found to have the lowest mean aneuploid bromodeoxyuridine labelling index (LI) equal to 21%, while the highest LI of 35.8% was measured for the LLC tumour. The mean S-phase time was short, lasting 8.5 - 10.9 hrs. The potential doubling time (T(pot)) assessed by BrdUrd staining and flow cytometry were as follows: 37.1 hours for SaL, 22.7 hours for MCA and 21.4 hours for LLC tumour. The MCA had the shortest volume doubling time (T(d)) equal to 1.7 days and the longest one, equal to 4.7 days, was found for the LLC. The lowest cell loss was found in the MCA tumour (44%), while the highest in the LLC tumour (81%). As all the examined tumours proliferate rapidly, there is a capacity for accelerated repopulation and therefore the tumours seem to be good models for experimental radiotherapy.
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PMID:Lewis lung carcinoma and two transplantable sarcomas in mice as experimental therapy models: biological characteristics and cell population kinetics. 927 45


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