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)

Dominant rearrangements of T-cell receptor (TCR) beta-chain genes are reported among tumor-infiltrating lymphocytes (TIL). After interleukin-2 expansion of TIL from renal and lung carcinoma and melanoma biopsy tissues, rearrangements of TCR beta-chain genes were analyzed by Southern blotting. Nongermline restriction fragments, indicating dominant rearrangements, were detected among the TIL from all 6 patients with renal cell carcinoma, 17 of 20 patients with melanoma, and 3 of 6 patients with lung tumors. The restriction-fragment sizes of these dominant rearrangements were heterogeneous among the various patients. Rearrangements into C beta 1 were more common than C beta 2 rearrangements. Phenotypic analyses indicated that dominant rearrangements occurred in both CD4 and CD8 predominant TIL populations. The TIL populations that were extracted were expanded to derive large cell numbers suitable for in vivo transfer in an interleukin-2 and TIL immunotherapy program. The data indicated that the cells delivered to these patients usually were characterized by dominant populations of T-cells with selective TCR gene rearrangements. The significance of selective TCR use requires evaluation of the function and specificity of the TIL comprising these dominant populations both in their native in vivo setting and in the context of therapeutic transfer.
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PMID:Dominant rearrangements among human tumor-infiltrating lymphocytes. Analysis of T-cells derived from 32 patients with melanoma, lung, and renal cell carcinoma. 131 29

We studied lung and blood lymphocytes from 12 asymptomatic patients with peripheral bronchogenic carcinoma. Bronchoalveolar lavage was performed in the lung segment with tumor and a contralateral uninvolved lung segment and analyzed separately. After partial removal of macrophages by plastic adherence, cells were labeled with markers for CD4 and CD8 and analyzed by flow cytometric analysis. We found no significant difference in the percentages of mononuclear cells in either immune subset when comparing the lung containing tumor with the uninvolved lung. We did find, however, a depressed CD4/CD8 ratio in the peripheral blood. We conclude that a lung carcinoma does not change the local immunologic milieu of the lung parenchyma containing the carcinoma. It is not clear if the immunologic findings in the lungs and blood are due to the bronchogenic carcinoma, smoking, or the underlying chronic obstructive pulmonary disease.
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PMID:Regional and systemic CD4 and CD8 subsets in bronchogenic carcinoma. 168 75

In this study we have investigated the effects of thymosin alpha 1 (T alpha 1) and interleukin-2 (IL-2), singly or in combination with cyclophosphamide (CY), on tumor growth, survival and cytotoxicity in C57Bl/6NCrlBR mice with Lewis lung carcinoma (3LL). Combined administration of T alpha 1 plus IL-2, after CY treatment, was much more effective than use of each biological response modifier (BRM) alone, and induced complete tumor regression in all of the mice studied. Combination immunotherapy alone without CY only slightly reduced the rate of tumor growth, and these results are in accordance with previous studied which showed that the 3LL carcinoma is resistant to cytokines. Combined chemo-immunotherapy also increased the cytotoxicity of spleen cells and markedly enhanced long-term survival in all treated animals. Depletion of immune cells, using either total-body sub-lethal irradiation (400 rads) or antibodies directed against T-cell (anti-CD4 and CD8) or NK-cell (anti-asialo GM1) populations, abolished the positive response to combination therapy. Histological analysis of the tumors obtained from mice treated with combination chemo-immunotherapy revealed a high number of infiltrating lymphoid cells surrounding a well-circumscribed area of necrosis consisting solely of dead cells. Our studies show that T alpha 1 potentiates IL-2-induced cytotoxic activities in vitro as well in vivo, and that these compounds have a powerful anti-tumor action when associated with chemotherapy.
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PMID:Combination therapy with thymosin alpha 1 potentiates the anti-tumor activity of interleukin-2 with cyclophosphamide in the treatment of the Lewis lung carcinoma in mice. 173 18

We have partially characterized the T-cell subsets that control the growth of the C57BL/6 Lewis lung carcinoma 3LL transplanted into syngeneic mice. By analyzing the phenotypes of anti-tumor lymphocytes generated in vitro and in vivo, we have characterized a CD8 T-cell receptor (TcR) V beta 5,6 positive subpopulation of cytotoxic effectors important in retarding the growth of the transplanted tumor. In contrast, the rejection of 3LL appears to be hindered by the presence of a CD4 V beta II-positive subset since depletion of these lymphocytes in vivo with the appropriate monoclonal antibodies (MAbs) results in significant retardation of tumor growth. These results suggest that the cumulative positive and negative effects of distinct T-cell sub-populations determine the outcome of tumor progression and metastasis.
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PMID:T-cell subset analysis of 3LL tumor growth. 182 21

Tumor infiltrating (TIL) and peripheral blood lymphocytes (PBL) were isolated from 18 patients with non-small cell lung cancer undergoing radical surgery. Surface marker analysis revealed that TILs and PBLs mainly consisted of CD3+ T cells and that TILs generally displayed a lower CD4/CD8 ratio. Differences were found in the expression of CD25 (IL-2 receptor) and DR (MHC class II) antigens, which were increased in TILs, and in the percentage of CD16+ natural killer (NK) cells, which was reduced in TILs as compared to PBLs. Accordingly, the NK activity of TILs was lower than that of PBLs, whereas neither TILs nor PBLs expressed spontaneous cytolytic activity against fresh autologous tumor cells, melanoma cells and the "NK-resistant" A549 lung carcinoma cell line. After 4 days of culture in medium with recombinant-interleukin-2 (rIL-2), TILs and PBLs acquired cytolytic activity against all cell targets, but TILs expressed higher levels of cytotoxicity than autologous PBLs only in 3 patients out of 16 tested. More importantly, both TILs and PBLs displayed similar levels of cytotoxic activity against autologous tumor cells. TILs and PBLs from 8 patients were also analyzed by a limiting dilution microculture system. Cloning efficiency was remarkably lower in TILs, and surface marker analysis of T cell clones confirmed that an accumulation of CD8+ lymphocytes, which displayed cytolytic activity in a lectin-dependent assay, occurred at the tumor site. The non-MHC-restricted cytolytic activity of TIL- and PBL-derived T cell clones against K562, A549, and allogeneic melanoma cells and the cytolytic activity against autologous tumor cells showed no significant differences. Only 53% of TIL clones released IL-2 in response to PHA + TPA stimulation, whereas 68% of PBL-derived clones were IL-2 producers. Moreover, most PBL- and TIL-derived clones released tumor necrosis factor alpha in response to mitogen stimulation.
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PMID:Peripheral blood and tumor infiltrating lymphocytes in non-small cell lung cancer: analysis at the population and clonal level. 217 60

We investigated surface markers of lymphocytes infiltrating four different histological non-small cell lung cancer tissues obtained at surgery and the corresponding peripheral blood lymphocytes (PBL) of 40 clinical cases, who had undergone no prior anti-cancer treatment, by flowcytometry. In estimation of the mean proportion of each lymphocyte subset, a paired Wilcoxon test revealed that tumor-infiltrating lymphocytes (TIL) exhibited significantly higher values of CD3+ cells (P < 0.05), CD8+ cells (P < 0.05) and CD20+ cells (P < 0.01), and lower value of CD16+cells (P < 0.05), as compared with those in PBL. The Spearman test revealed that none of the values of surface markers in TIL statistically correlated with those in the corresponding PBL (r < 0.6, P > 0.05). Although there was no significant difference between the mean CD4/CD8 ratio of total TIL and that of PBL, TIL of 12 patients with squamous cell carcinoma almost always showed lower values of CD4/CD8 ratio than those in PBL (P < 0.05), while the CD4/CD8 ratio was similar between TIL and PBL in adenocarcinoma. These results suggest that TIL of lung cancers represent specific immunological responses, whose characteristic depend on the histological types of lung cancers.
Lung Cancer 1993 Oct
PMID:Phenotypes of lymphocytes infiltrating non-small cell lung cancer tissues and its variation with histological types of cancer. 806

We investigated the reaction of the cellular immune system of liver and blood in the C57BL/6 mouse to a metastasizing Lewis lung carcinoma. The cellular immune system of the liver consists of mature and immature macrophages, B-cells, T-cells including their subpopulations, and natural killer cells, and their percentage frequencies differ significantly from those in the corresponding mononuclear blood cell (MBC) compartment. This suggests that the hepatic immune cells represent a system with autonomous function showing a typical homing of its members. Imminent metastasis to the liver is signalled by impressive alterations in the percentage frequencies of nonparenchymal liver cells (NPLC). There are a dramatic loss of mature macrophages, an increase in immature macrophages, a reduction of T-helper cells leading to a low CD4/CD8 ratio, and an increase in natural killer cells. In the blood, the corresponding precursor cells show comparable changes with a delay of at least 2 days. Early metastasis is accompanied by a significant increase in mononuclear NPLC producing tumour necrosis factor alpha. The alterations in percentage frequencies of the NPLC during tumour metastasis differ markedly from the changes in these cells in the liver during endotoxinaemia.
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PMID:Early detection of metastasis by alterations in the cellular immune system in the murine liver and blood. 868 73

The co-expression of B7.1 (CD80) and intercellular adhesion molecule (ICAM)-1 (CD54) on tumor cells can induce tumor immunity and immunological memory. We show here that the non-immunogenic tumor lines Lewis lung carcinoma and B16F10 melanoma, co-transfected with B7.1 and ICAM-1, induced cytotoxic levels of membrane tumor necrosis factor (TNF) on naive syngeneic T cells within 24 h. Membrane TNF expression, primarily on CD4 cells, was responsible for tumor cell lysis by naive spleen cells and could be completely abolished by anti-TNF antiserum. It is suggested that the strong induction of TNF cytotoxicity may be important in the establishment of tumor immunity.
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PMID:Rapid induction of tumor necrosis factor cytotoxicity in naive splenic T cells by simultaneous CD80 (B7.1) and CD54 (ICAM-1) co-stimulation. 881 62

Lymphocytopenia is a prognostic factor for shorter survival in advanced lung cancer and it is likely related to an interleukin-2 (IL-2) deficiency occurring during cancer progression. Major surgery itself for cancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevented by preoperative administration of recombinant human (rhIL-2), indicating that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) administered preoperatively is able to prevent the lymphocyte decrease occurring after radical surgery in operable lung cancer. This phase II study included 40 patients with operable NSCLC screened as stage II or IIIA, randomized to receive rhIL-2, 9000000 IU subcutaneously twice daily for 3 days before surgery (treated group, 20 patients) or not (control group, 20 patients). At baseline, there were no significant differences in total lymphocyte number and lymphocyte subsets (T-cell, T-helper, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperatively the control group showed a decrease in total lymphocyte count, T-lymphocyte count, T-helper cell number and CD4/CD8 ratio, significant at the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and control group values of total lymphocyte count, T-cells and T-helper cells. NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantly over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control group resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated patients and 16/20 control patients were radically operated. After a 24-month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 radically operated were disease-free; 8/20 control patients were alive and 4/16 radically operated were disease-free. Toxicity was mild to moderate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administration of rhIL-2 is feasible and prevents lymphocyte decrease occurring postoperatively after surgery for lung cancer. Further studies are required to assess the impact on survival.
Lung Cancer 1998 Jun
PMID:Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC. 973 54

The protective effects of tea and/or its components on dysfunction of immune functions during tumor growth and carcinogenesis in mice were studied using two experimental models: C57/BL6J mice transplanted with Lewis lung carcinoma (LLC) and Kunming mice treated with a single dose of 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone (NNK). In C57/BL6J mice bearing LLC, the weight of the thymus decreased, the proportion of CD4(+)-positive T lymphocytes and the ratio of CD4+ to CD8+ decreased, luminol-enhanced chemiluminescence of white blood cells in peripheral blood stimulated by zymosan increased, and plaque-forming cells (PFC) decreased. However, in LLC-bearing mice given green tea as drinking water, all immune functions were improved, along with inhibition of tumor growth. In Kunming mice treated with NNK, during the four weeks of observation, their immunologic indicators, such as phagocytosis of macrophages in the abdominal cavity, luminol-enhanced chemiluminescence of white blood cells, plaque-forming cells, and delayed-type hypersensitivity, increased or decreased to various extents compared with normal controls. However, these changes were significantly prevented in the mice given green tea, mixed tea, or tea polyphenol as drinking water. In conclusion, tea and its components ameliorated immune dysfunction in mice bearing LLC or treated with the carcinogen NNK.
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PMID:Green tea and its major components ameliorate immune dysfunction in mice bearing Lewis lung carcinoma and treated with the carcinogen NNK. 1062 8


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