Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adoptive immunotherapy using LAK cells and IL-2 was performed against stage III and IV primary lung cancer patients after surgery. A randomized controlled study consisting of control group A, chemotherapy (CDDP + VDS) group B and chemo-immunotherapy (CDDP+VDS, IL2+LAK cells) group C suggested better survival rate in the group C. Direct effects were studied against 8 recurrent or inoperable lung cancer cases. Complete response was obtained against a pleuritis and pericarditis carcinomatosa case when in vitro stimulated LAK cells (St-LAK) were administered locally. Partial response was observed against a inoperable case when LAK-BAI (bronchial arterial infusion) was combined with radiation therapy.
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PMID:[Adoptive immunotherapy with LAK cell and IL-2 against primary lung cancer]. 258 39

A 549, a human lung cancer cell line, spontaneously produces a tumor-derived immunosuppressive factor (TDSF) which inhibited PHA-stimulated T lymphocyte proliferation via a noncytotoxic mechanism. The inhibition increased in a dose-dependent pattern. The factor also markedly suppressed production of interleukin (IL-2) by PHA-stimulated lymphocytes and IL 2-dependent proliferation of activated lymphocytes. The fact that TDSF possessed very potent inhibitive action on IL-2 is especially noteworthy if we consider the use of IL-2 as immunotherapeutic agent. The synthesis of the factor was inhibited by mitomycin C, actinomycin D and cycloheximide, indicating that the factor is a genic product of A 549 cells. The factor is chemically a protein with a molecular weight greater than 150 KD and sensitive to extremes of pH, heating to 60 degrees C and trypsin treatment.
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PMID:Biologic characteristics of an immunosuppressive factor derived from a human lung cancer cell line. 260 Sep 79

Studies were made to determine whether freshly isolated monocytes from healthy donors could influence the induction of lymphokine (IL-2)-activated killer (LAK) activity. Highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated by counter-flow centrifugal elutriation from peripheral blood. Lymphocytes incubated for 4 days with IL-2 showed significant LAK activity against natural killer (NK) cell-resistant target (Daudi) cells, whereas monocytes treated for 4 days with IL-2 and/or IFN-gamma were not cytotoxic. Under the experimental conditions used, addition of monocytes to the lymphocyte cultures resulted in significant augmentation of the LAK activity, depending on the density of monocytes added. In contrast, monocytes stimulated by lipopolysaccharide (LPS) markedly suppressed LAK activity induced by IL-2, depending on the dose of LPS added. Similar up- and down-regulations of LAK cell induction by monocytes were observed with 4 lines of human lung cancer cells as targets for LAK activity. Although supernatants from untreated monocytes did not increase LAK induction, supernatants from LPS-stimulated monocytes suppressed LAK induction. The regulatory role of monocytes could not be replaced by the addition of exogenous interleukin I (IL-I) or tumor necrosis factor (TNF). Prostaglandin E did not seem to play a regulatory role, since addition of indomethacin did not affect the regulation of LAK cell induction by monocytes. These results clearly indicate that human monocytes may cause up- or down-regulation of the expression of IL-2-induced LAK activity, depending on their functional state.
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PMID:Up- and down-regulation of human lymphokine (IL-2)-activated killer cell induction by monocytes, depending on their functional state. 282 45

The current understanding in biology and function of 4 growth factors is reviewed. PDGF suggests functions for proto-oncogens in normal cells, which may interact in tightly linked hierachies to induce malignant growth. PDGF-requirement of normal fibroblast cell-lines is lost when the cells are infected with tumor viruses. TGF is able to stimulate growth of normally anchorage dependent cells in an anchorage independent manner in soft agar. This ability is thought to be the best in-vitro correlate of neoplastic transformation. The peptide hormones bombesin/gastrin releasing factor and EGF can act as autocrine growth factors in various lung cancer cell-lines and stimulate clonal tumor cell growth in-vitro. The potential clinical application of these types of growth factors may enable the in-vitro growth from any lung cancer patient and allow individual drug testing. TCGF produced by T-cells to activate T-cells, is central to immune stimulation and immune response. Models for potential indirect anticancer effects either by in-vivo administration or by in-vivo incubation plus passive transfer of T-cells are presented to be initiated in future clinical trials.
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PMID:[Growth factors. A new dimension in understanding oncogenesis]. 299 23

Bronchial arterial infusion (BAI) of Lymphokine activated killer (LAK) cells, stimulated in vitro by autologous tumor cells, was performed for a primary lung cancer patient, a 47-year-old male patient with primary squamous cell carcinoma of the lung who underwent probe thoracotomy and had part of the tumor tissue removed. Peripheral blood lymphocytes were cultured in 500 U/ml of recombinant IL-2(Shionogi Pharm. S6820) for 9 days after in vitro stimulation with mitomycin C-treated primary tumor cells for 3 days. These cells (designated St-LAK cells) were inoculated from the bronchial artery of patients who received 60 Gy irradiation of the primary site and mediastinal lymph nodes. The tumor regressed significantly from 8 X 7 to 3 X 2.5 cm in diameter. The advantages of LAK-BAI using St-LAK cells with irradiation were discussed.
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PMID:[Bronchial arterial infusion of lymphokine-activated killer cells stimulated by autologous tumor cells]. 313 76

Immune functions of peripheral blood (PBL), regional lymph node (RLNL), and tumor infiltrating lymphocytes (TIL) were evaluated in lung cancer patients. PBL had many natural killer (NK) cells and the highest NK activity, and it showed the highest augmentation of NK activity by interferon-gamma (IFN-gamma) + recombinant interleukin-2 (rIL-2) among the three groups of lymphocytes. PBL had high lymphokine-activated killer (LAK) activity of against a broad spectrum of cell lines and moderate activity against autologous tumor cells by increased effector to target (ET) ratio but the lowest ability of IL-2 production of the three groups of lymphocytes. The RLNL not associated with tumor metastasis had a few NK cells and lower NK activity than PBL, but its LAK activity was almost the same but not greater than that of PBL. RLNL had the highest ability of IL-2 production among the three groups of lymphocytes. All activities of RLNL associated with tumor metastasis were lower than those not associated with tumor metastasis. TIL exclusively consisted of T-cells, especially cytotoxic/suppressor T-lymphocytes. NK activity and lymphocyte blastogenesis of TIL were lower than those of other groups. The LAK activity of TIL differed greatly with the case, and it was the highest against autologous tumor cells among the three groups of lymphocytes in three of eight cases. These findings showed that PBL, RLNL, and TIL had characteristic subpopulations of lymphocytes and different functions of host immune responses in lung cancer. Efficient augmentation of the characteristic immune responses will lead to a more effective total cancer therapy.
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PMID:Different immune functions of peripheral blood, regional lymph node, and tumor infiltrating lymphocytes in lung cancer patients. 314 76

Nd-YAG or Argon dye laser irradiations combined with radiotherapy were performed for lung cancer patients with central airway obstructions due to recurrences. Remarkable effects of immediate airway dilatation and reduction of symptoms were obtained after laser irradiations. IL-2 and LAK injections or ethanol injections into the peripheral recurrent or metastatic lung lesions. In one out of 5 patients after IL-2 and LAK injection, and in one out of 2 patients after ethanol injection, tumor size was reduced by 43% and 34%, respectively. IL-2 and/or LAK were injected into the pleural or pericardial spaces with malignant effusion, showing significant effects on a lung cancer patient with cancerous pericarditis who survived more than 9 months after this localized therapy. According to these results, these localized therapies may not always prove effective, but they should be applied to unresectable recurrent lung cancers or metastatic lung tumors in order to prolong survival with good quality of life.
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PMID:[The effects of localized therapy with postsurgical local recurrences of lung carcinoma and metastatic lung tumors--laser irradiation, IL-2+ LAK or ethanol injection]. 326 90

Highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated by CCE from peripheral blood of healthy donors. Blood lymphocytes were separated by this CCE into 9 subpopulations. The NK activities of these lymphocyte fractions against NK-sensitive K-562 cells and their LAK activities against NK cell-resistant target (Daudi) cells were assayed promptly or after incubation of the fractions for 4 days with or without an optimal concentration of IL-2. NK and LAK activities were measured by 4-hr 51Cr-release assay. On the basis of their NK and LAK activities, these lymphocyte fractions were classified into 3 subpopulations of LAK precursors: one lacking both NK and LAK activities (Fr.2), one with moderate NK activity but low LAK activity (Fr.5), and one possessing both NK and LAK activities (Fr.8). Addition of autologous fresh monocytes to the lymphocyte cultures resulted in a significant increase in induction of LAK activity in Fr.2 and Fr.5. This up-regulation of lymphocytes in Fr. 2 and Fr.5 by monocytes was confirmed in parallel experiments by measuring the blastogenic response of the lymphocytes to IL-2. Deletion of lymphocytes in Fr. 8 of CD16+ (Leu-11+) NK cells resulted in 74% reduction in LAK induction, whereas depletion of mixtures of monocytes and lymphocytes in Fr. 2 of cells reacting with CD3+ (OKT3+) antibody resulted in a 66% reduction in LAK induction. This up-regulation of LAK cell induction from LAK precursors by monocytes was confirmed using 4 lines of human lung cancer cells as targets for LAK activity. These results clearly indicate that human monocytes may cause up-regulation of the expression of IL-2-induced LAK activity in T cells and in a subpopulation of NK cells.
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PMID:Heterogeneity of human lymphokine (IL-2)-activated killer (LAK) precursors and regulation of their LAK induction by blood monocytes. 326 92

OK-432, a streptococcal preparation, is known to have strong BRM functions and is expected to produce clinical improvement and prolongation of survival in treated cancer patients. In order to clarify the immunopharmacological mechanisms involved with its clinical effectiveness, intrapleural injection of OK-432 was attempted in patients with malignant pleural effusion due to metastasis from lung cancer. About 70-80% of patients thus treated showed clinical improvements with reduction or disappearance of effusion and effusion tumor cells within a week after the therapy. The clinical response was accompanied by an abrogation or reduction of suppressor macrophages and a stimulatory increase of effective cytotoxic cells resulting in an increase of NK and ATK activity. These in vivo effects observed in the OK-432-treated patients were reproducible in vitro by incubating normal or effusion lymphocytes with tumor-associated macrophages. OK-432 was also shown to reduce the locomotor inhibitory activity of macrophages toward LGL, and to augment the production of various sorts of cytokines, such as IL-1 and MCF by macrophages and IL-2 and NKCF by lymphocytes, all of them being exerted upon activation of the anti-tumor immunological mechanism.
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PMID:[Effective mechanisms of BRM, with special reference to induction of autologous tumor cell-killing (ATK) activity by OK-432]. 348 24

The cytotoxic activities, of the peripheral blood lymphocytes (PBL) and regional lymph node lymphocytes (LNL) generated by incubation with recombinant IL-2 (rIL-2) in vitro, have been studied to assess their effects on autologous pulmonary adenocarcinoma cells from 21 patients with lung cancer. The lymphokine-activated killer (LAK) activities of PBL were 22.9 +/- 14.8% for autologous pulmonary adenocarcinoma cells and 44.9 +/- 20% for PC-9 cells. A previous coculture of autologous tumor cells with PBL (ATS-LAK) showed no increase in induction of cytotoxicity to autologous tumor cells. The LAK activities of LNL were significantly lower than those of PBL. The cytotoxicities of rIL-2 activated lymphocytes seemed lower in well differentiated pulmonary adenocarcinoma than in moderately and poorly differentiated adenocarcinoma, and higher in patients with lymph node metastasis than in those without; they appeared, however, not to be related to clinical stage or degree of infiltration of T-zone histiocytes into the cancer stroma. The cytotoxicity to autologous tumor cells was not significantly different in the presence of the Ia antigen expressed on tumor cells, but the cytotoxicity to Ia positive PC-9 cells was significantly higher for rIL-2 activated lymphocytes from patients with lung cancer cells which were Ia positive than from those where they were Ia negative. The presence of Ia antigen on tumor cells seemed important for antitumor activity.
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PMID:Induction of lymphokine-activated killer activities in peripheral blood lymphocytes and regional lymph node lymphocytes against PC-9 cultured adenocarcinoma and autologous pulmonary adenocarcinoma cells. 349 85


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