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)

Several immunologic parameters have been reported to correlate with the clinicopathologic status of lung cancer patients. However, these studies were based on relatively small numbers of patients and often yielded conflicting results. We prospectively studied cellular immunologic parameters related to age, gender, and stage in lung cancer patients. We obtained pretreatment peripheral blood samples from 287 lung cancer patients. Lymphocyte subsets (percentage of lymphocytes positive for CD3, CD4, CD8, HLA-DR, or representing FcgammaR IIIa-positive T cells), natural killer (NK) cell activity, and lymphoblastogenesis (LB) after stimulation by phytohemagglutinin (PHA) were evaluated. Significant decline was seen in older patients in percentages of cells positive for CD3 or CD4, in the CD4/CD8 ratio and in LB. The percentage of FcgR IIIa-positive T cells increased with age. LB as well as CD4 positivity were significantly greater in women than in men. NK cell activity showed the greatest cytotoxic responses in stage IIIA, with significantly less response in stage IV than in IIIA. Node-negative patients showed higher reactivities for LB and lower positivity for HLA-DR than node-positive patients. Patients with no distant metastases had a higher level of NK cell activity than patients with distant metastases. Immune parameters are variously related to age, gender, and the stage in lung cancer patients, some may prove to be useful predictors of survival.
Lung Cancer 2000 May
PMID:Cellular immunologic parameters related to age, gender, and stage in lung cancer patients. 1071 31

The clinical improvement obtained with combination treatment has modified the therapeutic approach of lung cancer in HIV-positive patients. Aggressive surgical treatment has become a viable option for those patients in whom the CD4(+) cell count was greater than 200 lymphocytes/mm(3). We recently extended our surgical indications to include two HIV-positive patients with lung cancer (stage IIIA and IIB) and low (<200 lymphocytes/mm(3)) CD4(+) count. Both patients underwent a lobectomy and mediastinal nodal dissection. The postoperative course was uneventful. No evidence of recurrent cancer was seen at 12 and 20 months after the operation. Based on this limited experience, we conclude that a low CD4(+) count should not represent, per se, an exclusion criterion for the surgical treatment of pleuropulmonary conditions in HIV-positive patients.
Lung Cancer 2000 Aug
PMID:Pulmonary resection for lung cancer in HIV-positive patients with low (<200 lymphocytes/mm(3)) CD4(+) count. 1096 45

We obtained a lytic CD4 T-cell clone that recognized an antigen presented by HLA-DRB1*1101 on the tumor cells of a melanoma patient who enjoyed an unusually favorable clinical evolution. The antigen appeared to be shared between several melanoma cell lines. To identify the encoding gene, we used a new method, based on the cotransfection into human embryonal kidney cell line 293 of a cDNA library from the tumor together with a cDNA clone encoding the class II transactivator, which induces the expression of HLA class II molecules. The product of the gene coding for the antigenic peptide is EphA3, a member of the Eph family of tyrosine kinase receptors, which mediate the repulsion of neural cells by cells carrying the ligand Ephrins on their surface. EphA3 is expressed at a high level in the retina and fetal brain, at a lower level in several normal tissues, and not at all in hematopoietic cells, the only cells that constitutively express HLA class II molecules. It is overexpressed in several types of tumors, including melanoma, lung carcinoma, and sarcoma. On the basis of this pattern of expression, EphA3 may be a source of tumor-specific antigens recognized on tumor cells that express HLA class II molecules. Anti-EphA3 T cells may have participated in a tumor rejection response in the patient, because the cells of metastases collected several years later than the metastasis used to characterize the antigen had lost expression of HLA-DR or EphA3, therefore escaping recognition by these lymphocytes.
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PMID:Identification of a tumor-specific shared antigen derived from an Eph receptor and presented to CD4 T cells on HLA class II molecules. 1098 98

Intramuscular (i.m.) injection of a plasmid encoding human carcinoembryonic antigen (CEA) elicited immunity against transplanted syngeneic (C57BL/6) CEA-positive Lewis lung carcinoma (CEA/LLC) cells, but tumors still appeared in all mice. In wild-type mice, coinjection of an IL-12 plasmid markedly enhanced anti-CEA humoral, T-helper-1 and cytotoxic T lymphocyte (CTL) responses, and resistance to a CEA/LLC tumor challenge such that 80% of mice remained tumor free. Injection of the IL- 12 plasmid alone was not protective. To analyze immune requirements, we immunized gene knockout (KO) mice of C57BL/6 background, deficient in either CD3, CD4, CD8, interferon gamma (IFNgamma), perforin or Fas ligand (FasL). Only CD3+ mice expressing both CD4 and CD8, which appear equally important, as well as IFNgamma and perforin, could fully resist a tumor challenge. IL-12 stimulated CTL activity, which was strictly CD3/CD8/perforin-dependent. FasL-KO mice had normal CTL activity and tumor resistance, indicating that only the perforin lytic pathway was involved. CD4-KO and IFNgamma-KO mice still generated CTLs. CEA-stimulated IFNgamma production occurred in both CD4- or CD8-KO mice and in both cases was augmented by IL-12. In IFNgamma-KO mice, IL-12 still enhanced anti-CEA antibody production but only moderately restored impaired DTH and tumor resistance. We conclude that the immune requirements for tumor rejection are stringent, involving multiple mechanisms which are all enhanced by IL-12.
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PMID:IL-12 plasmid-enhanced DNA vaccination against carcinoembryonic antigen (CEA) studied in immune-gene knockout mice. 1102 90

We have investigated the results of neonatal inoculation with a protein-bound polysaccharide, PSK, as it affects the defense mechanism of animals against cancer. Male BALB/c mice received a single i.p. injection of 10 mg/kg PSK within 48 h of birth. When the mice were 8 weeks of age, colon adenocarcinoma 26 (C26 tumor) cells were transplanted s.c. Injection of PSK increased the number of tumor-rejecting mice from 10 to 50% compared with the control mice transplanted with 5 x 10(3) tumor cells and prolonged the median survival period to 174% of control mice with tumors. When the number of transplanted tumor cells was increased to 1 x 10(6), PSK injection significantly prolonged the survival period, although tumors grew in all mice. The survival period was also significantly prolonged in male C57BL/6 mice that received an injection neonatally with PSK and were given a s.c. transplant of Lewis lung carcinoma or B16 melanoma at 8 weeks of age. The effect on survival was dependent on the PSK dose and the number of transplanted tumor cells. PSK was as effective for male mice 30 weeks of age as for mice 8 weeks of age treated with PSK during the neonatal period. However, prolongation of the survival period of tumor-bearing mice was not observed in the offspring (F1). Neonatal injection of PSK also significantly reduced the number of metastatic foci in the liver of mice inoculated with 1 x 10(5) C26 tumor cells in the splenic vein after 8 weeks of age. In addition, neonatal injection of PSK significantly reduced the number of aberrant crypts and aberrant crypt foci, the precancerous lesions in the colon of F344 rats that received injections s.c. with azoxymethane after 7 weeks of age, to 47% of that of rats that received an injection with saline at the same age. The effect on precancerous lesions was dependent on the timing of PSK injection and the dose. Regarding the mechanism, when animals thymectomized during the neonatal period or when congenitally athymic animals were used instead of healthy animals, the effect on survival or precancerous lesions did not appear. Neonatal injection of PSK significantly reduced the number of CD4+ CD8+ T cells and significantly increased the number of CD4+ CD8- and CD4- CD8+ T cells in the thymus of healthy mice 10 weeks of age and C26 tumor-bearing mice. Furthermore, neonatal injection of PSK significantly elevated the T-cell differentiation induced by a mouse thymus extract 10 weeks of age. These findings suggest that neonatal injection of PSK induces resistance in adult mice to challenge by syngeneic tumor cells and reduces the azoxymethane-induced precancerous lesions in the colon of adult rats via the thymus functions.
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PMID:Neonatal inoculation with the protein-bound polysaccharide PSK increases resistance of adult animals to challenge with syngeneic tumor cells and reduces azoxymethane-induced precancerous lesions in the colon. 1114 16

Resveratrol is a naturally occurring phytoalexine found in medicinal plants. We found that resveratrol, at doses of 2.5 and 10 mg/kg, significantly reduced the tumor volume (42%), tumor weight (44%) and metastasis to the lung (56%) in mice bearing highly metastatic Lewis lung carcinoma (LLC) tumors, but not at a dose of 0.6 mg/kg. Resveratrol did not affect the number of CD4(+), CD8(+) and natural killer (NK)1.1.(+) T cells in the spleen. Therefore, the inhibitory effects of resveratrol on tumor growth and lung metastasis could not be explained by natural killer or cytotoxic T-lymphocyte activation. In addition, resveratrol inhibited DNA synthesis most strongly in LLC cells; its 50% inhibitory concentration (IC(50)) was 6.8 micromol/L. Resveratrol at 100 micromol/L increased apoptosis to 20.6 +/- 1.35% from 12.1 +/- 0.36% (P < 0.05) in LLC cells, and decreased the S phase population to 22.1 +/- 1.03% and 29.2 +/- 0.27% from 35.2 +/- 1.72% (P < 0.05) at concentrations of 50 and 100 micromol/L, respectively. Resveratrol inhibited tumor-induced neovascularization at doses of 2.5 and 10 mg/kg in an in vivo model. Moreover, resveratrol significantly inhibited the formation of capillary-like tube formation from human umbilical vein endothelial cells (HUVEC) at concentrations of 10-100 micromol/L; the degree of the inhibition of capillary-like tube formation by resveratrol was 45.5% at 10 micromol/L, 50.2% at 50 micromol/L and 52.6% at 100 micromol/L. Resveratrol inhibited the binding of vascular endothelial growth factor (VEGF) to HUVEC at concentrations of 10-100 micromol/L, but not at concentrations of 1 and 5 micromol/L. The degree of inhibition of VEGF binding to HUVEC by resveratrol was 16.9% at 10 micromol/L, 53.2% at 50 micromol/L and 47.8% at 100 micromol/L. We suggest that the antitumor and antimetastatic activities of resveratrol might be due to the inhibition of DNA synthesis in LLC cells and the inhibition of LLC-induced neovascularization and tube formation (angiogensis) of HUVEC by resveratrol
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PMID:Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. 1138 77

An important goal of cancer immunology is the identification of antigens associated with tumor destruction. Vaccination with irradiated tumor cells engineered to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) generates potent, specific, and long-lasting antitumor immunity in multiple murine tumor models. A phase I clinical trial of this vaccination strategy in patients with advanced melanoma demonstrated the consistent induction of dense CD4(+) and CD8(+) T lymphocyte and plasma cell infiltrates in distant metastases, resulting in extensive tumor destruction, fibrosis, and edema. Antimelanoma antibody and cytotoxic T cell responses were associated with tumor cell death. To characterize the targets of these responses, we screened an autologous cDNA expression library prepared from a densely infiltrated metastasis with postvaccination sera from a long-term responding patient. High-titer IgG antibodies detected ATP6S1, a putative accessory unit of the vacuolar H(+)-ATPase complex. A longitudinal analysis of this patient revealed an association between the vaccine-induced increase in antibodies to ATP6S1 and tumor destruction. Three additional vaccinated melanoma patients and three metastatic non-small cell lung carcinoma patients vaccinated with autologous GM-CSF-secreting tumor cells similarly showed a correlation between humoral responses to ATP6S1 and tumor destruction. Moreover, a chronic myelogenous leukemia patient who experienced a complete remission after CD4(+) donor lymphocyte infusions also developed high-titer antibodies to ATP6S1. Lastly, vaccination with GM-CSF-secreting B16 melanoma cells stimulated high-titer antibodies to ATPS1 in a murine model. Taken together, these findings demonstrate that potent humoral responses to ATP6S1 are associated with immune-mediated destruction of diverse tumors.
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PMID:ATP6S1 elicits potent humoral responses associated with immune-mediated tumor destruction. 1198 66

The antitumor effects of cyclophosphamide were previously shown to be markedly reduced by the application of restraint stress in mice bearing Lewis lung carcinoma. The aim of this work was to determine the effects of rotational stress on the antitumor action of cyclophosphamide in the same animal-tumor system. Since the effects of rotational stress on metastasis were found to display a circannual rhythm, with a maximum in summer and a minimum in winter, the experiments were performed in June and February. Groups of 10 young female mice were kept under low stress housing conditions, with a 12-12 h light/dark cycle, starting 2 weeks before and during each experiment. Rotational stress caused an increase of metastasis volume to 361% of nonstressed controls in June and a decrease to 32.4% in February. In both seasons, the treatment with cyclophosphamide (240 mg/kg/day for 6 days) caused the absence of detectable metastasis at sacrifice in all mice; its combination with rotational stress caused the presence of metastases in similar proportions (6/10 and 10/10 for June vs February, respectively). The survival time of control mice was approximately twice as long in February as in June and was not appreciably modified by rotational stress; cyclophosphamide was similarly active in both seasons (4/10 and 6/10 long-term survivors for June vs February, respectively), and the number of long-term survivors was reduced to 0/10 in both seasons by rotational stress. The survival of the different experimental groups inversely correlated with the number of metastases as determined at sacrifice at the end of treatment and also with the number of CD3(+) and CD4(+) splenic T-lymphocyte subsets. These results do not appear to depend on the disruption of the circadian organization of the mice by rotational stress or by seasonal differences in cyclophosphamide activity. On the other hand, they can be interpreted assuming that cyclophosphamide reduces tumor metastasis and that T-lymphocyte-mediated immune responses of the host, amenable to modulation by stress and displaying seasonal differences uncoupled from circadian rhythms, further contribute to the tumor inhibitory effects of the drug. The observed differences in tumor metastasis caused by rotational stress and survival time in two different seasons, and the marked attenuation of cyclophosphamide antitumor action by rotational stress, appear of interest for their experimental and clinical implications.
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PMID:Seasonal dependency of the effects of rotational stress and cyclophosphamide in mice bearing lewis lung carcinoma. 1209 84

In the present report, we have investigated TRAIL/APO2 ligand (APO2L) expression, regulation, and function in human lung carcinoma tumor-infiltrating lymphocytes. Using a panel of non-small cell lung carcinoma cell lines, we first showed that most of them expressed TRAIL-R1/DR4, TRAIL-R2/DR5, but not TRAIL-R3/DcR1 and TRAIL-R4/DcR2, and were susceptible to APO2L/TRAIL-induced cell death. Two APO2L/TRAIL-sensitive tumor cell lines (MHC class I(+)/II(+) or I(+)/II(-)) were selected and specific CD4(+) HLA-DR- or CD8(+) HLA-A2-restricted CTL clones were respectively isolated from autologous tumor-infiltrating lymphocytes. Interestingly, although the established T cell clones did not constitutively express detectable levels of APO2L/TRAIL, engagement of their TCR via activation with specific tumor cells selectively induced profound APO2L/TRAIL expression on the CD4(+), but not on the CD8(+), CTL clones. Furthermore, as opposed to the CD8(+) CTL clone which mainly used granule exocytosis pathway, the CD4(+) CTL clone lysed the specific target via both perforin/granzymes and APO2L/TRAIL-mediated mechanisms. The latter cytotoxicity correlated with APO2L/TRAIL expression and was significantly enhanced in the presence of IFN-alpha. More interestingly, in vivo studies performed in SCID/nonobese diabetic mice transplanted with autologous tumor and transferred with the specific CD4(+) CTL clone in combination with IFN-alpha resulted in an important APO2L/TRAIL-mediated tumor growth inhibition, which was prohibited by soluble TRAIL-R2. Our findings suggest that APO2L/TRAIL, specifically induced by autologous tumor and up-regulated by IFN-alpha, may be a key mediator of tumor-specific CD4(+) CTL-mediated cell death and point to a potent role of this T cell subset in tumor growth control.
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PMID:Tumor-infiltrating CD4+ T lymphocytes express APO2 ligand (APO2L)/TRAIL upon specific stimulation with autologous lung carcinoma cells: role of IFN-alpha on APO2L/TRAIL expression and -mediated cytotoxicity. 1209 84

Immunologic prognostic factors in lung cancer have not been fully clarified. We report the results of a prospective study undertaken to clarify the correlation between various cellular immunologic parameters and the survival of lung cancer patients. A total of 287 lung cancer patients were enrolled in this study. Representative in vitro cellular immune activities including lymphoblastogenesis and natural killer cell activities, in addition to the percentage of main lymphocyte subsets (CD3, CD4, CD8, HLA-DR, and Fc gamma R III on T cells) in the peripheral blood were evaluated before the initiation of therapy. The immune factors that influence the prognosis were analyzed by the log rank test and a multivariate analysis using the Cox proportional hazards model. Univariate analysis of the survival curves revealed a significant difference with regard to disease stage (P<0.0001), age (P=0.007), gender (P=0.0037), and HLA-DR (%) (P=0.048), when all the non-small cell lung cancer (NSCLC) patients (n=257) were analyzed together. This analysis, based on the histologic type, revealed that HLA-DR (%) was a significant predictor of survival in squamous cell carcinoma (P=0.0013) and small cell carcinoma (P=0.0025). A decreased CD4/CD8 ratio in small cell carcinoma (P=0.0062) and male gender in adenocarcinoma (P=0.0086) were factors associated with a worse prognosis. Multivariate analysis identified a significant correlation between survival and disease stage (P<0.0001) and gender (P=0.0243) in adenocarcinoma, disease stage (P<0.0001), age (P=0.0436) and HLA-DR (%) (P=0.0142) in squamous cell carcinoma, and HLA-DR (%) (P=0.0212) and CD4/CD8 (P=0.0112) in small cell carcinoma, suggesting independent prognostic significance. A variety of immunologic indices have prognostic significance for the different types of lung cancer. Among these, the HLA-DR (%) in the peripheral blood is the most reliable factor for squamous cell carcinoma and small cell carcinoma.
Lung Cancer 2002 Aug
PMID:Immunologic parameters as significant prognostic factors in lung cancer. 1214 Jan 39


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