Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lewis lung carcinoma (LLC)-bearing mice were used as a mouse model to evaluate effects of recombinant human (rh) interleukin (IL) 6 and local X-irradiation (LR) on the growth of primary tumors and lung metastases. Mice were inoculated s.c. with LLC tumor cells and then treated with rhIL-6 (100 ng/dose) s.c. twice a day (b.i.d.) for 5 days, beginning 6 days after tumor inoculation. LR (800 cGy) was administered to the site of the primary tumor 6 days after tumor inoculation and again 1 wk later. Mice were then observed for survival or sacrificed at day 21 after tumor inoculation to determine size of primary tumor, numbers and size of lung metastases, and other hematological parameters including numbers of granulocyte-macrophage progenitor cells (CFU-gm). The size of the primary tumor and numbers of lung metastases were reduced by rhIL-6. LR enhanced the antitumor effect of rhIL-6 significantly, while LR alone had only a slight antitumor effect. Tumor-associated increases in peripheral blood, femoral marrow, splenic-nucleated cellularity, and marrow and splenic CFU-gm were reduced in mice treated with rhIL-6 plus LR. Prolonged survival time was observed only in tumor-bearing mice treated with rhIL-6 in combination with LR. The antitumor effects in vivo of rhIL-6 appear to be mediated indirectly as rhIL-6 had no effect on proliferation of LLC cells in vitro as assessed by colony and 3H-thymidine incorporation assays. These studies suggest that rhIL-6 may have therapeutic value in the treatment of certain malignancies, especially if used in combination with LR.
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PMID:In vivo effects of recombinant human interleukin 6, alone or in combination with local irradiation, on tumor growth in Lewis lung carcinoma-bearing mice. 195 39

Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was evaluated for efficacy, either alone or in combination with local X-irradiation (LR), in mice inoculated subcutaneously (s.c.) with Lewis lung carcinoma (LLC) cells. The size of the primary tumor and numbers of lung metastases, 21 days after tumor inoculation and 15 days after the start of treatment, were reduced by 87% in tumor-bearing mice treated with 20 micrograms/dose M-CSF s.c. twice a day for 5 days. LR (800 cGy) to the tumor once a week for 2 weeks had a moderate anti-tumor effect and enhanced the anti-tumor effect of M-CSF. Hematological parameters, including nucleated cellularity in peripheral blood, femoral marrow, spleen and peritoneal exudate, as well as marrow and splenic granulocyte-macrophage progenitor cells, and numbers of splenic Thy 1.2+ cell and peritoneal mast cells, were perturbed in LLC-bearing mice, and were influenced by treatment with M-CSF and LR. Treatment with M-CSF plus LR, but not with either agent alone, was associated with a significant, although slight, enhancement in survival time for LLC-bearing mice. Inability to obtain a better survival-enhancing effect appeared to be related to the limited treatment, since the anti-tumor effects of M-CSF were more notable early on in disease progression and were related to the dose of M-CSF used. The effects of M-CSF were most probably indirect ones on the host immune system. M-CSF, in combination with LR, may be of benefit in the treatment of human tumors that have metastatic potential.
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PMID:Anti-tumor effects of recombinant human macrophage colony-stimulating factor, alone or in combination with local irradiation, in mice inoculated with Lewis lung carcinoma cells. 198 70

Recombinant human (rhu) interleukin 2 (IL-2) was evaluated alone and in combination with local hyperthermia (LH) in mice inoculated s.c. with 5 x 10(5) Lewis lung carcinoma cells. Four treatment regimens were begun 6 days postinoculation at a time when the tumor had grown to approximately 8.0 mm in diameter. Treatments were: group 1, saline injected as control; group 2, LH; group 3, rhuIL-2; or group 4, LH combined with rhuIL-2. LH utilized hot water circulation by a Brann Thermomix 1420. The intratumor temperature was maintained at 43 +/- 0.2 degrees C for 30 min each on days 6 and 10 and rhuIL-2 was given s.c. at 5 x 10(4) units twice a day for 5 days. Thirty mice in each group were sacrificed 28 days after tumor inoculation. An additional 20 mice in each group were observed for survival time. The size of primary tumor and the number of lung metastases were reduced and the survival time was prolonged in mice treated by either LH or IL-2. However, a greater antitumor effect in Lewis lung carcinoma tumor-bearing mice was observed using IL-2 therapy combined with LH. Tumor growth was associated with increased splenic granulocyte-macrophage progenitor cells and an abnormal L3T4+/Lyt-2+ lymphocyte subset ratio (less than 1.0). Splenic granulocyte-macrophage progenitor cell numbers and the L3T4+/Lyt-2+ ratio returned to normal in the group treated with combination therapy, the best responder group. The L3T4+/Lyt-2+ ratio did not change in the groups treated with single therapy. These results suggest the efficacy and possible clinical relevance of combined therapy with rhuIL-2 and LH for certain metastatic tumors.
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PMID:Effects of interleukin 2 treatment combined with local hyperthermia in mice inoculated with Lewis lung carcinoma cells. 237 68

Production of granulocyte-macrophage (GM) colony-stimulating factor by murine metastatic Lewis lung carcinoma cells (LLC-LN7) increases the number and distribution of GM progenitor cells that are suppressive to T cell responsiveness to interleukin 2 (IL-2). The presence of these GM suppressor cells can be diminished by treatment of LLC-LN7-bearing mice with low doses of 100 units IFN-gamma plus 10 units tumor necrosis factor alpha (TNF-alpha). The aim of this study was to determine whether treatment of LLC-LN7-bearing mice with IFN-gamma/TNF-alpha to diminish GM suppressor cell presence would increase the responsiveness to IL-2 immune stimulatory therapy (100-1000 IU, twice daily for 5 days). Treatment first with IFN-gamma/TNF-alpha and then also with low dose IL-2 increased both the numbers of CD4+ and CD8+ cells within the tumor and the levels of their expression of the p55 IL-2 receptor. These intratumoral T cells also had an increased cytolytic capacity toward autologous tumor cells and an increased capacity to proliferate and secrete IL-2. Such effects were observed to a lesser extent in mice that were treated with either IFN-gamma/TNF-alpha alone or with low doses of IL-2 only. The combination treatment regimen of IFN-gamma/TNF-alpha and then IL-2 was also significantly more effective at reducing the size of the primary tumor and the formation of metastatic lung nodules than were the individual treatments. These results show that treatment to minimize the presence of GM suppressor cells enhances the effectiveness of IL-2 to stimulate anti-tumor immune responses and to diminish tumor growth and metastasis.
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PMID:Treating tumor-bearing mice with low-dose gamma-interferon plus tumor necrosis factor alpha to diminish immune suppressive granulocyte-macrophage progenitor cells increases responsiveness to interleukin 2 immunotherapy. 785 Aug 4

Interleukin-12 (IL-12), a naturally occurring cytokine, has demonstrated antitumor activity in several murine solid tumors. The Lewis lung carcinoma was used to study the most effective scheduling of recombinant murine interleukin-12 (rmIL-12) administration with fractionated radiation therapy. The effect of the schedule of rmIL-12 administration alone or along with a 1- or 2-week fractionated radiation therapy regimen was examined. Beginning rmIL-12 prior to or at the same time as radiation therapy and extending rmIL-12 through the radiation regimen and beyond produced the longest tumor growth delays. Those treatment regimens which were most effective against the primary tumor were also most effective in decreasing the number of lung metastases on day 20. To further assess the immunotherapeutic effects from rmIL-12 administration, the efficacy of rmIL-12 with fractionated radiation therapy delivered to a right hind-limb tumor was measured as tumor growth delay in an unirradiated left hind-limb tumor. There was some difference in the tumor growth delay between the unirradiated tumor in the animals bearing an irradiated tumor in the contralateral leg, and the tumors in animals receiving rmIL-12 only. Recombinant murine granulocyte-macrophage-colony stimulating factor (rmGM-CSF) was also an antitumor agent active against the Lewis lung carcinoma and produced an additive effect in combination with fractionated radiation therapy in this tumor. rmIL-12 was a radiation sensitizer in the Lewis lung carcinoma. When rmIL-12 (45-microg/kg) and rmGM-CSF (45 microg/kg) were administered together with fractionated radiation therapy, a marked increase in tumor growth delay resulted. This treatment combination also nearly ablated lung metastases on day 20 in these animals. These results may serve as a useful guide in developing clinical protocols, including rmIL-12 and fractionated radiation therapy.
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PMID:Optimal scheduling of interleukin-12 and fractionated radiation therapy in the murine Lewis lung carcinoma. 957 83

According to a report by the National Cancer Institute, colorectal cancer (CRC) is one of the most common types of cancer worldwide. CRC is often recognized too late for successful therapy. Tumor markers have been sought for a number of years to detect the transformation of malignant cells at the earliest possible stage. They are usually proteins associated with a malignancy and might be clinically useful in patients with cancer. Several classical markers have been used to recognize colorectal cancer, including carcinoembryonic antigen (CEA), carbohydrate antigen (CA 19.9), tissue polypeptide specific antigen (TPS) and tumor-associated glycoprotein-72 (TAG-72). None of these tests, however, have excellent diagnostic accuracy. Recent studies have been conducted on the use of hematopoietic growth factors (HGFs) and various enzymes in the diagnosis and prognosis of colorectal cancer. These include macrophage-colony stimulating factor (M-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-3, interleukin-6 and enzymes (alcohol dehydrogenase and lysosomal exoglycosidases). Significantly, most cancer deaths are not caused by the primary tumor itself but by its spread. Analysis of circulating cancer cells (CTCs), ie, factors responsible for metastasis, may be a source of information useful in the treatment of patients with colorectal cancer. Currently available markers have significant limitations.
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PMID:Biochemical Markers of Colorectal Cancer - Present and Future. 3260 68