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)

This study was designed to analyze the possible immunomodulation induced in vivo by haematopoietic growth factors following anti-cancer chemotherapy. Haematologic and cytokine kinetics (IL-1, IL-6, TNF alpha and soluble interleukin-2 receptor (sIL-2R)) were studied in patients with SCLC receiving high dose regimens of chemotherapy and recombinant human GM-CSF (group A), or standard doses of chemotherapy without rhGM-CSF (group B). Six patients were prospectively enrolled and randomized in each group. The kinetics of haematopoiesis following chemotherapy did not significantly differ between the two groups. In group A, the plasma sIL-2R level increased regularly during rhGM-CSF treatment reaching a 2.5-fold elevation at day 12 whereas it remained stable in group B. Conversely, IL-1 alpha decreased to an undetectable level in group A whereas it increased slightly from day 14 to day 18 in group B. As sIL-2R could compete with lymphocyte surface receptors and as IL-I is an important cytokine involved in acute phase response, our results might be regarded as reflecting a transient decrease in the cell-mediated immune response in small cell lung cancer patients receiving high dose chemotherapy combined with rhGM-CSF.
Lung Cancer 1995 Oct
PMID:Interleukin-1 alpha and soluble interleukin-2 receptor during small cell lung cancer chemotherapy: comparison of high chemotherapy dose with rhGM-CSF and standard chemotherapy dose without rhGM-CSF. 858 94

Cloned high-metastatic Lewis lung carcinoma. A11 cells were retrovirally transduced with either granulocyte macrophage-colony stimulating factor (GM-CSF) or beta-galactosidase gene and examined for their tumorigenicity. GM-CSF-engineered A11 cells produced a much higher amount of GM-CSF than the parental and control cells. Unexpectedly, GM-CSF-engineered A11 cells grew more rapidly than the control cells, while in vitro growth rates of these cells were almost the same. The enhanced tumor growth seemed to be unique to GM-CSF among various cytokines, because interleukin 2 (IL-2), interleukin 4 (IL-4) and interleukin 6 (IL-6) producer cells exhibited suppressed tumor growth.
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PMID:Augmentation of in vivo growth of Lewis lung carcinoma cells transduced with granulocyte macrophage-colony stimulating factor gene. 868 29

Expression of various cytokines by cytokine gene-transduced tumor cells has been shown to increase antitumor immunity of tumor-bearing hosts. In the present study, macrophage-colony stimulating factor (M-CSF) cDNA was retrovirally transfected into Lewis lung carcinoma cells (3LL) of C57BL/6 mouse origin, and the effects of M-CSF expression were studied by inoculating syngeneic C57BL/6 mice with M-CSF-expressing 3LL cells. The mice inoculated with the lowest M-CSF-producing 3LL clone showed significant prolongation of the survival compared with wild-type 3LL-Inoculated mice, and 70% or more of the mice inoculated with 3LL clones with higher M-CSF production rejected inoculation. Mice injected with radiation-inactivated M-CSF-expressing 3LL cells before or after Inoculation of wild-type 3LL cells showed prolonged survival compared with mice injected with radiated control 3LL cells before or after transplantation of wild-type cells. In vivo depletion of effector subpopulations by injection of antibodies against CD4+ T cells, CD8+ T cells, or natural killer (NK) cells suggested involvement of NK cells and CD4+ T cells in M-CSF-mediated antitumor cytotoxicity in M-CSF-producing 3LL cells-inoculated mice. Severe combined immunodeficiency (SCID) mice with defective T- and B-cell function showed prolonged survival duration after inoculation with M-CSF-expressing 3LL cells compared with those transplanted with control 3LL cells, and this effect of M-CSF expression by 3LL-cells in SCID mice was also abolished by in vivo depletion of NK cells by antibody injection. These findings together with the previous reports that M-CSF augments antibody-dependent and-independent antitumor cytotoxicity suggest that M-CSF induces tumor immunity in this cytokine-expressing tumor-transplantation model.
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PMID:Tumor vaccination with macrophage colony-stimulating factor-producing Lewis lung carcinoma in mice. 870 54

Sixty-six chemotherapy-naive patients with non-small-cell carcinoma of the lung were given two courses of systemic chemotherapy consisting of mitomycin C, vindesine, and cisplatin. The effect of the timing of administration of grannulocyte colony-stimulating factor (G-CSF) on the incidence of neutropenic fever, the nadir leukocyte count, the duration of neutropenia ( < or = 1000/mm3), and the time needed for recovery from neutropenia was studied. Patients were assigned at random to begin receiving G-CSF (50 microns/m2, subcutaneously) either when the leukocyte count was less than or equal to 1000/mm3 (group I) or when it was between 1000/mm3 and 2000/mm3 (group II), in a crossover fashion. The nadir leukocyte count was lower in group I than in group II (859/mm3 and 1215/mm3, respectively). The duration of leukopenia (defined as a leukocyte count less than or equal to 1000/mm3) was greater in group I than in group II (1.5 days and 0.8 day, respectively), as was the time needed for recovery to a leukocyte count of 2000/mm3 (1.9 days and 1.6 days, respectively) (p < 0.05). No differences were found in the incidence of neutropenic fever (group I: 44%, group Ii: 45%), in the duration of fever (group I: 2.3 days, group II: 2.8 days), or in the duration of G-CSF use (group I: 6.3 days, group II: 6.8 days). There were no treatment-related deaths in either group. We conclude that when this type of combination chemotherapy is given for non-small-cell carcinoma of the lung, administration of G-CSF can be postponed without clinical problems until the leukocyte count is less than of equal to 1000/mm3.
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PMID:[Effect of timing of granulocyte-colony stimulating factor administration on leukopenia induced by systemic chemotherapy in patients with non-small-cell lung cancer--multi-center randomized crossover study]. 875 9

Human Recombinant Granulocyte Colony Stimulating Factor (G-CSF) allows rapid neutrophil recovery after chemotherapy-induced leukopenia. In a prospective series of 54 patients with extensive small cell lung cancer, we evaluated the feasibility and efficacy of accelerated delivery of the AVI chemotherapy regimen. Treatment consisted of Doxorubicin 50 mg/m2 day 1, Etoposide 120 mg/m2 day 1-3 and Ifosfamide 2 g/m2 (+ Mesna 4 g) day 1 and 2 given every 2 weeks and followed by G-CSF (Neupogen, Amgen Roche 5 micrograms/kg/day s.c. day 4-14). Twenty-seven (50%) patients could not receive the total of six courses, seven because of severe septic complication, 10 because of Grade 4 thrombopenia, seven because of non-response and three because of patient refusal. Chemotherapy had to be delayed in 58 out of the 244 administered courses and this was due to thrombopenia in 48% of cases. The probability of optimal dose-on-time administration was 64% at three courses. The mean actually received dose intensity was 93% at six courses (27 patients treated). It was increased by 76% compared to our previously published conventional 3-week interval chemotherapy. The median neutrophil nadirs were stable during the successive treatment courses while haemoglobin and platelet values significantly worsened from cycle 1 to cycle 6. The overall response rate after three courses was 77% in the 48 evaluable patients. The median survival is 8 months overall and 5 months disease free. The actuarial survival is 22% at 2 years. We conclude that substantial dose intensification with accelerated chemotherapy and G-CSF support is feasible. However, the rate of severe infectious episodes is too high and thrombopenia is the main limiting factor. Either growth factors active on the megacaryocytic lineage or haematological rescue with peripheral blood stem cells might be useful in this setting.
Lung Cancer 1996 Jun
PMID:The limits of chemotherapy dose intensification using granulocyte colony stimulating factor alone in extensive small cell lung cancer. 879 14

Twenty patients with locally advanced or metastatic non-small cell lung cancer entered a study of recombinant human methionyl G-CSF (r-metHuG-CSF) as an adjunct to ifosfamide, cisplatin and etoposide (IPE) regimen. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection) and etoposide 100 mg/m2 given on days 1-4 of a 21-day cycle. r-metHuG-CSF, 5 micrograms/kg, was administered subcutaneously from day 5 to day 14. Eighteen out of 20 patients completed the three courses (57 evaluable cycles). Grade 3-4 neutropenia affected 50, 42 and 22% of the patients during cycles 1, 2 and 3, respectively, whereas thrombocytopenia was observed in 25% of the patients throughout the chemotherapy protocol. Haematological toxic events requiring transfusions and/or antibiotics were responsible for 11 unplanned hospitalizations. Among these only three were exclusively devoted to febrile neutropenia care, the remaining eight being mainly required for blood transfusions. There were no deaths during the study duration. Dose reductions were needed in 65% of the patients and chemotherapy was delayed by thrombocytopenia in five patients. The total relative dose intensity was 84%. Eleven (55%) patients responded (one complete and 10 partial responses). Median survival was 9.5 months. We concluded that IPE combination chemotherapy can be administered safely with the support of r-metHuG-CSF inasmuch as neutropenia appears as mild to moderate and manageable. Optimal delivery of chemotherapy is still limited by other toxicities, mainly thrombocytopenia, but the successful relative dose intensity observed herein deserves further studies designed to analyze a dose intensity-survival relationship in non-small cell lung cancer.
Lung Cancer 1996 Jun
PMID:r-metHuG-CSF support to ifosfamide, cisplatin, etoposide chemotherapy in non-small cell lung cancer. 879 15

Increased local production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by genetically modified tumor cells can induce specific antitumor cellular immunity. We constructed a recombinant adenovirus expressing murine GM-CSF and tested it for therapeutic efficacy in a syngeneic murine lung cancer model system. In vitro transduction of Lewis lung carcinoma cells with adenovirus-mGM-CSF suppressed tumor formation in syngenic mice (C57BL/6), and transduced and irradiated Lewis lung carcinoma cells induced regression of pre-established wild-type tumors without in vitro selection for transductants. Low, but significant, levels of specific antitumor cytotoxic T lymphocytes (CTL) were observed in mice inoculated with GM-CSF but not with reporter virus-transduced tumor cells. GM-CSF-transduced cells induced the accumulation of dendritic cells at the site of tumor, consistent with a mechanism involving improved tumor antigen presentation. These data suggest that transduction of tumor cells with recombinant GM-CSF adenovirus may be an effective and practical cancer gene therapeutic strategy.
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PMID:Genetic immunotherapy of established tumors with adenovirus-murine granulocyte-macrophage colony-stimulating factor. 901 22

B7-1 (CD80) co-stimulatory molecule gene-transduced Lewis lung carcinoma (LLC) cells (LLC/B7 cells) resulted in remarkable loss of tumorigenicity in syngeneic C57BL/6 mice (87.5% rejection) compared to B7-negative, wild-type LLC (LLC/wt) cells (0% rejection). However, mice that had rejected LLC/B7 cells developed almost no systemic immunity protective against challenge with wild-type tumor cells after 4 weeks (11.8% rejection). Enhancement of MHC class I (H-2Kb) expression of LLC/B7 cells with in vitro interferon-gamma treatment did not result in enhancement of protective immunity. In vivo depletion assay revealed that abrogation of tumorigenicity in LLC/B7 depended on CD8+ T cells but not on CD4+ T cells. However, vaccination of C57BL/6 mice with irradiated LLC cells transduced with GM-CSF (LLC/GM) led to the induction of potent, specific immunity against challenge with the LLC/wt cells after 2 weeks (80.8% rejection). Next, we established a double transfectant of LLC cells expressing both B7-1 and GM-CSF (LLC/GM + B7). The tumorigenicity of these clonal cells was also remarkably suppressed (90% rejection) to the same degree as LLC/B7, whereas that of LLC/GM was not suppressed (0% rejection). Interestingly, mice that had rejected LLC/GM+B7 cells developed enhanced protective immunity against challenge with LLC/wt cells after 4 weeks (55.6% rejection) compared to the results of LLC/B7 cells (11.8%). To evaluate whether co-expression of GM-CSF and B7-1 enabled the tumor cells to activate cytotoxic T cells more efficiently than B7-1 alone, we performed an in vitro killing assay. We found that immunization with LLC/GM+B7 cells resulted in a 3-fold stronger cytotoxic response than that with LLC/B7. Our data indicate that co-transfection of the B7-1 co-stimulatory molecule and GM-CSF genes may be more effective for the induction of stronger protective immunity in this experimental system.
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PMID:GM-CSF and B7-1 (CD80) co-stimulatory signals co-operate in the induction of effective anti-tumor immunity in syngeneic mice. 938 72

Interleukin-12 (IL-12) is a heterodimeric cytokine that consists of p40 and p35 subunits. IL-12 has been regarded as a potent inducer of host antitumor immunity through interferon-gamma (IFN-gamma) production and development of Th1 helper T cells from Th0 cells. Here, we demonstrate the immunomodulatory actions of an IL-12-transduced murine lung cancer cell line, Lewis lung carcinoma (LLC) (LLC/IL12) cells, in syngeneic C57BL/6 mice. We also report on their therapeutic potency. Three LLC/IL12 cells producing different levels of IL-12 were cloned and found to have diminished tumorigenicity in C57BL/6 mice depending on their level of IL-12 production. In vivo depletion assay demonstrated that the loss of tumorigenicity of LLC/IL12 depended on both CD4+ and CD8+ T cells, and that natural killer (NK) cells were involved, especially in the early phase of immunity. The strong systemic antitumor immunity against challenge with wild type LLC (LLC/wt) cells was also induced by LLC/IL12 cells. The systemic antitumor memory was found to be dependent mainly on the CD4+ T-cell subset. 51Cr-release assay revealed that the killer activity consisted of a specific killer activity directed at the parental LLC/wt cells and a nonspecific killer activity directed at both LLC/wt and syngeneic EL-4 thymoma cells. In addition, LLC/IL12 apparently had a much stronger antitumor effect against the established LLC/wt tumor than LLC transduced with B7-1 or GM-CSF cDNA. IL-12 can be considered an efficient candidate molecule for immunogene therapy for lung cancer in this experimental system.
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PMID:Superiority of interleukin-12-transduced murine lung cancer cells to GM-CSF or B7-1 (CD80) transfectants for therapeutic antitumor immunity in syngeneic immunocompetent mice. 947 64

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


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