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)

We evaluated the efficiency/tolerability of and the immunological changes induced by the adoptive immunotherapy (AIT) with IL-2-activated killer cells, and preparation of native cytokines from swine spleen (PSS) in treatment of 20 patients with advanced cancer (10 patients with primary lung cancer; 3 with metastatic melanoma; 2 with advanced neuroblastoma; 2 with ovarian cancer; renal cancer; gastric adenocarcinoma; and colorectal cancer). The partial/minor response of duration period 2-10 months was observed in 20% of patients. 2/4 patients, who underwent partial surgical tumor resection and following AIT course, sustained the event-free survival for more than 24 months. The response to the therapy was revealed in 4/10 patients with lung cancer, 2/2 patients with neuroblastoma, of whom each had ovarian and colorectal cancers. The evaluation of a dose of infused LAKcells as well as combined i.v./local (endobronchial or endoperitoneal) LAK administration were necessary to assure positive response in patients. The cytokine and/or side effects were moderate and the combined LAK-PSS infusions were generally well tolerated by the patients. The treatment was followed by activation of the patient immune system that included: (i) rebound in amount of peripheral blood lymphocytes; (ii) gain in amount of CD3(+) T cells and those CD4(+) helper/inducer; (iii) enchantment of lymphocyte proliferation and cytokine production (IL-2, IL-1, TNF-alpha). Being injected to patients in combination with LAK cells, cytokines related to PSS action and/or those, either exogenous or secondary, and released by in vitro and in vivo, activated lymphocytes and could cause the therapeutic effects.
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PMID:IL-2-Activated Killer Cells and Native Cytokines in Treatment of Patients with Advanced Cancer. 1268 71

Th2 cytokine is predominant in tumor patients and was found to be associated with tumor progression. Reversing of Th2 dominant status is thought to be a promising strategy. In the present study, peripheral blood mononuclear cells (PBMNC) of 37 lung cancer patients and 19 healthy subjects were prepared and used for examination of cytokine secretion and gene expression. The positive percentage of mRNA transcripts of Th1 cytokines (8.1% for IFNgamma and 13.5% for IL-2) in patients' PBMNC were lower than those of Th2 cytokines (70.3% for IL-4, 64.9% for IL-6 and 83.8% for IL-10). The gene expression capacity (measured as relative intensity to ratio of beta-actin) of patients for Th1 cytokines was low, but constitutively relatively high for Th2 cytokines. Both positive percentage and relative intensity were lower in transcript factor for Th1 cytokine, T-bet (40.5% and 0.139, respectively) than those for Th2 cytokine, GATA3 (89.2% and 0.364, respectively). Traditional Chinese medicine, Astragalus (AG) was observed to reverse Th2 status of lung cancer. AG enhanced culture supernatant and gene expression levels of Th1 cytokine (IFNgamma and IL-2) and its transcript factor (T-bet), and reduced those of Th2 cytokines in cultured PBMNC of lung cancer patients. These results demonstrated that traditional Chinese medicine AG might reverse the Th2 predominant status in lung cancer patients, which is a probable alternative therapeutic regime in future.
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PMID:Traditional Chinese medicine Astragalus reverses predominance of Th2 cytokines and their up-stream transcript factors in lung cancer patients. 1288 32

We carried out an open, non-randomized phase II study including all patients treated with whatever chemotherapy or combined modality regimen for whatever cancer who were in clinical objective response (complete response, CR, or partial response, PR) or stable disease (SD). The treatment consisted of administration of recombinant interleukin-2 (rIL-2) at a dose of 1.8 MIU subcutaneously three times/week (every other day) for the first 2 weeks of every month plus medroxyprogesterone acetate (MPA) 500 mg/day every other day plus antioxidant agents alpha-lipoic acid 300 mg/day and N-acetyl cysteine 1800 mg/day or carbocysteine lysine salt oral solution 2.7 g/day. The treatment was administered for 1 year except when progression of disease occurred. The primary study endpoints were to define clinical outcome, i.e. duration of response, survival (overall survival, OS and progression-free survival, PFS), the toxicity profile, and the evaluation of quality of life (QL). As secondary endpoints, we measured the changes of lymphocyte count, serum levels of proinflammatory cytokines, IL-2, C-reactive protein (CRP) and leptin, blood levels of reactive oxygen species (ROS) and antioxidant enzymes (glutathione peroxidase, GPx and superoxide dismertase, SOD). From July 1998 to June 2003, 42 patients were enrolled in the study (M/F ratio, 39/3; mean age, 62.5 years). Twenty (47.6%) patients were elderly (> 65 years). The majority of patients had either head and neck cancer or lung cancer, 88% had locally advanced or metastatic disease at diagnosis, and 76% had ECOG 0. Forty patients were previously treated with chemotherapy (27 also with radiotherapy), two with IL-2 and interfiron (IFN), one with endocrine therapy and one with only surgery. We obtained an objective response to maintenance treatment of 50%. Median duration of response was 19 months and median PFS was 33 months. Median duration of maintenance treatment was 12 months, median follow-up duration from diagnosis to June 2003 was 40 months, and median follow-up duration from study entry to June 2003 was 17 months. The median overall survival has not been reached. Toxicity was negligible. As for QL, a significant improvement of cognitive functions was observed, whereas all other functioning and symptom scales did not change significantly. As for laboratory parameters, absolute lymphocyte count increased significantly, IL-6, IL-1 beta, tumor necrosis factor-alpha, CRP, and fibrinogen decreased significantly whereas IL-2 and leptin increased significantly after treatment. ROS decreased significantly, whereas GPx increased significantly after treatment. Patients alive at study end showed a significant increase in absolute lymphocyte count, IL-2, leptin, and GPx and a significant decrease of proinflammatory cytokines, CRP, fibrinogen, and ROS, whereas patients who died before study end exhibited only a significant increase in absolute lymphocyte count, IL-2, and GPx and a significant decrease of ROS. Long-term combined maintenance therapy with rIL-2 + MPA + antioxidant agents is feasible, has a very low toxicity, and results in the improvement of clinical outcome, QL, and laboratory parameters.
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PMID:Subcutaneous interleukin-2 in combination with medroxyprogesterone acetate and antioxidants in advanced cancer responders to previous chemotherapy: phase II study evaluating clinical, quality of life, and laboratory parameters. 1456 91

We devised an innovative type of immunocell therapy called BRM (biological response modifier)-activated killer (BAK) therapy, which utilizes most of non-MHC (major histocompatibility complex) restricted lymphocytes, CD56+ cells including gammadelta T cells and NK cells. Peripheral blood lymphocytes were selected by immobilizing them with anti-CD3 monoclonal antibody, cultured for 2 weeks with serum-free medium containing IL-2, and then were reactivated by 1,000 U/ml of IFN-alpha for 15 min. The patients were infused with about 6x10(9) BAK cells by intravenous drip infusion at 1-month intervals. All advanced solid cancer patients who had received chemotherapy but for whom it was not effective or have refused chemotherapy were included in the present study. A good marker of impairment of host immune response by chemotherapy is an immunosuppressive acidic protein (IAP) level in serum above 580 microg/ml; survival rates were compared with the high (> 580 microg/ml) and the low (< or = 580 microg/ml) serum IAP groups. We enrolled in this study 23 immunosuppressed patients whose IAP levels in serum were over 580 microg/ml, and 42 immunoreactive solid cancer outpatients whose IAP level in serum were under 580 degreesg/ml and whose performance statuses were over 80% on the Karnofsky scale. After giving informed consent, patients were treated with BAK therapy on an outpatient basis at our hospital. The ethical review board of the Miyagi Cancer Center approved this pilot study. Treated with BAK therapy, the mean survival of immunosuppressed patients was 4.6 months. On the other hand, survival for one of immunoreactive advanced postoperative patients (stage IV) and inoperable lung cancer patients (stage IIIb) was 24.7 months. The difference in survival between the 2 groups was significant (P < 0.01). This shows that BAK therapy is not indicated for an advanced cancer patient whose serum IAP is over 580 microg/ml, perhaps due to extensive chemotherapy. Overall response to BAK therapy was complete response (CR) in 5 cases, partial response (PR) in 1 case, and prolonged no change (NC) in 26 cases, with an effectiveness rate at 76.2% in 42 advanced stage IIIb and IV cancer patients. BAK therapy has a life-prolonging effect without any adverse effects and maintains satisfactory quality of life (QOL) for advanced cancer patients.
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PMID:Life-prolonging effect of immunocell BAK (BRM-activated killer) therapy for advanced solid cancer patients: prognostic significance of serum immunosuppressive acidic protein levels. 1462 27

We have shown that the sera of lung cancer patients affect the response of ConA-stimulated normal peripheral blood mononuclear cells by decreasing the expression of IL-2Ralpha and inhibiting the release of IL-1beta and IL-2. A tendency to enhance the release of IL-6 was also observed. We conclude that an imbalance in the Th1/Th2 cytokine response, typical for cancer patients, may at least partly be related to soluble factors circulating in the patients' blood. We discuss a putative role of serum IL-10, IL-1ra, and soluble IL-2Ralpha in the effects observed.
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PMID:Sera of lung cancer patients affect the release of Th1, Th2 and monocyte-derived cytokines, and the expression of IL-2Ralpha by normal, stimulated mononuclear cells. 1504 52

According to recent advances in psychoneuroimmunology concerning the neurobiochemistry of emotions, the pshychological status of cancer patients should be investigated in relation to the function of the psychoneurodocrine system, in an attempt to put into evidence possible cancer progression-related alterations, particularly those involving the dopaminergic pathways, which play a fundamental role in the perception of pleasure. In fact, the decreased capacity of feeling pleasure is one of the most frequent psychic symptoms occurring in cancer patients. Rorschach's test has been proven to be an appropriate psychological tool to investigate psychic condition including sexual and spiritual profiles. On this basis, a study was planned to evaluate if a relation exists between psychological response to Rorschach's test and immunoneuroendocrine status of cancer patients. The immune status was investigated by measuring lymphocyte subsets and serum levels of IL-2 and IL-10. The neuroendocrine status was analyzed by evaluating the endocrine response of PRL, GH and cortisol to an oral administration of apomorphine (0.01 mg/kg b.w.), a dopaminergic agent able to explore dopaminergic sensitivity. The study included 40 cancer patients (breast cancer: 15; colorectal cancer: 14; lung cancer: 11), 21 of whom showed distant organ metastases. Rorschach's test demonstrated a simultaneous suppression of sexual and spiritual profiles in 31/40 (78%) patients, without significant differences in relation to either tumor histotype or disease state. A normal decline in PRL levels and a normal increase in those of GH and cortisol was observed in 29/40 (73%), 5/40 (13%) and 9/40 (23%) patients. The percent of normal responses of PRL, GH and cortisol was higher in patients with normal than in those with altered response to Rorschach's test, even though only the difference in PRL and cortisol response was statistically significant. Patients with normal sexual and spiritual expression at Rorschach's test showed a significantly higher number of total lymphocytes, T lymphocytes, T helper lymphocytes and NK cells with respect to the patients with altered psychological response, whereas no difference was found in T cytotoxic lymphocyte mean number. IL-2 and IL-10 mean serum concentrations were lower and higher, respectively, in patients with altered than in those with normal response to Rorschach's test, even though only the difference in IL-10 values was statitistically significant. This preliminary study, carried out to analyze the psychological status of cancer patients in relation to neuroendocrine and immune conditions, would suggest that neoplastic disease is characterized by a simultaneous suppression of sexual and spiritual profiles, and that this is associated with neuroendocrine alterations and immunosuppression.
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PMID:A psychoncological study of lymphocyte subpopulations in relation to pleasure-related neurobiochemistry and sexual and spiritual profile to Rorschach's test in early or advanced cancer patients. 1506 61

This article is a review of recent reports dealing with the usefulness of measuring serum soluble interleukin-2 receptors (sIL-2R) level to assess the immunological status in lung cancer patients. The main function of sIL-2R is a regulation of the immune response by binding IL-2 what results in blocking the biological functions of this cytokine. By the competition with cell surface interleukin-2 receptors (IL-2R), sIL-2R act as immunosuppressive factor inhibiting IL-2R related lymphoblast growth. It is still not clear, why elevated levels of sIL-2R are reported both in immunodeficiency and immunostimulation state. In lung cancer patients the positive correlation between values of concentrations of sIL-2R and more progressive course of the disease is reported. The level of sIL-2R may be used as valuable prognostic marker both in patients treated with chemotherapy and in the case of operable tumors.
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PMID:[The value of measuring the serum level of soluble interleukin-2 receptors in lung cancer patients]. 1517 8

In contemporary medicine cancer has an exceptionally important role, even though it is not a new disease. Tumors are found in all animals and plants, and today are more frequent than before, when they were found predominantly in advanced ages. The frequency occurrence depends of many factors, and it is more frequent in countries with higher degree of civilization, what is the consequence of irradiation of other diseases as well as more pronounced industrialization, leading to in proper nourishment, many sources of intoxication with carcinogenic factors arising from environmental pollution, and even by the use of some diagnostic and therapeutic procedures. Cancer is the result of disturbance in cell growth and differentiation. In the appearance and spreading of tumors many factors are involved. In the Department of Experimental and Clinical Oncology of the Institute for Oncology and Radiology, we in the first place investigated the role of immunity, hormones and central nervous system, predominantly in experimental conditions, based on the investigations on animals, the in vitro investigations is tissue cultures and some disturbances which are found in blood of patients with tumors. As in the processes of carcinogenesis the immune system has in important role, in the immunological investigations we primarily investigated parameters of the status of the immune system in patients with malignant processes. The number and function of particular cell subsets of the immune system was investigated, namely T and B lymphocytes and their subclasses, NK cells and monocytes-macrophages. In the majority of analyzed patients with breast and lung cancer, lymphoproliferative diseases and other malignancies, it was shown that the majority of them had a decreased number of immune cells that correlated with the clinical advances of disease and applied cytostatic therapy. However, it was shown that the function of these cells, primarily NK, but also of T lymphocytes, was markedly decreased even before changes in the cell number, indicating that a functional impairment is present even before the cell number decrease and proportional to the advancement of the disease. As the results of exploring of investigation of the immunological status indicate the concrete defects in the function of the separate components of the immune system, these findings make it possible to direct immunotherapy for the correction of existing defects. The activity and pathways of mechanisms of NK cells and the possibility of their modulation were also investigated. Also, the possibility of the application of mAbs in the precise diagnostics of some malignancies was explored. The role in carcinogenesis was investigated in tumors whose appearance, growth and spreading is hormone-dependent. One of the hormone-dependent tumors is breast cancer. It was shown that they are significantly dependent on estrogen and growth factor presence, steroid-receptor content, and that these characteristics can change during the disease and do not have to be identical in their metastasis. Numerous investigations that we performed were in the in vitro conditions, i.e. in cell cultures. The obtained data show how some tumor cells react to applied agents, cytostatical and biological. However their effect in vivo is very often different, as in the in vivo conditions many other factors are involved, suggesting a need for further investigations of these factors. The role of the central nervous system neurotransmiters in carcinogenesis in experimental animals exposed to chemical cancerogen (5-methylcholantrene) with simultaneous treatment of the monoamine system was investigated. It was shown that monoamines expressed their influence on carcinogenesis by regulating the brain homeostasis, as well as by direct influence on the intracellular processes during cell development and differentiation. The obtained results will direct our further investigations toward obtaining mAbs for receptors for TNFalpha and IFNgamma, transfection of suppressor gene into tumor cell cultures and genes for IL-2 and TNFalpha. At the same time we will work on isolation of malignant melanoma tumor antigen and construction of a vaccine using some epitopes and adjuvantes. We will try to introduce appropriate immunotherapy in the advancedehZAD.
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PMID:[Accomplishments and perspectives in tumor diagnostics and treatment]. 1607 39

We have established a novel culture system to generate effector lymphocytes designated as peptide-pulsed dendritic cell-activated killer (PDAK) cells using cultured dendritic cells (DCs), synthetic peptide, peripheral blood lymphocytes, and interleukin-2 plus immobilized anti-CD3 antibody. A feasibility study of an adoptive immunotherapy trial using PDAK cells was conducted on HLA-A2 and HLA-A24 cancer patients with antigen-positive lung metastasis that was defined by serological analysis or PCR analysis. Eleven patients with lung metastasis participated in the study: 6 with colorectal cancer, 2 with pancreatic cancer, 1 each with breast and lung cancer, and 1 with melanoma. The patients received either Muc-1, CEA, gpl00, Her-2 or SART-3-PDAK cells generated in vitro, intravenously in combination with 350,000 U IL-2 weekly for 9 weeks, together with a planned dose-escalation schedule of three transfers each of 1 x 10(7), 3 x 10(7) and 1 x 10(8) PDAK cells/kg for 6 patients, and with a uniform dose of 3 x 10(7) PDAK cells/kg for the remaining 5 patients. Peptide/HLA-specific cytotoxic activity and TCRVbeta gene usage of PDAK cells were analyzed. All transfers of PDAK cells, which showed peptide/HLA-specific lysis, were well-tolerated in all patients, and adverse effects (elevation of transaminase, fever, and headache) were observed primarily at grade 1, but in no case greater than grade 2. The generation of sufficient cells to treat the patients with 3 x 10(7) PDAK cells/kg was feasible using our culture system, but we were able to generate and administer the dose of 1 x 10(8) PDAK cells/kg in only one patient. One partial response (PR) of lung metastasis occurred in a pancreatic cancer patient who received 3 x 10(7) Muc-1-PDAK cells/kg. The cytolytic units of PDAK cells in this patient appeared to be substantially higher compared to those in PD patients. TCR gene usage analysis on PDAK cells revealed preferential usage of TCRVbeta segments. These results suggest that adoptive immunotherapy using PDAK cells for cancer patients with antigen-positive lung metastasis is safe and feasible, and tumor response should be examined in a future clinical trial
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PMID:Feasibility study of adoptive immunotherapy for metastatic lung tumors using peptide-pulsed dendritic cell-activated killer (PDAK) cells. 1608 Apr 67

Preclinical studies have established that the polysaccharide fractions of Ganoderma lucidum have potential antitumor activity. Recent clinical studies have demonstrated that G. lucidum polysaccharides enhance host immune functions [e.g., enhanced natural killer (NK) cell activity] in patients with advanced solid tumors, although an objective response was not observed. This open-label study aimed to evaluate the effects of water-soluble G. lucidum polysaccharides (Ganopoly, Encore International Corp., Auckland, New Zealand) on immune functions in patients with advanced lung cancer. Thirty-six patients were enrolled and treated with 5.4 g/day Ganopoly for 12 weeks. In the 30 cancer patients who completed the trial, treatment with Ganopoly did not significantly alter the mean mitogenic reactivity to phytohemagglutinin, mean counts of CD3, CD4, CD8, and CD56, mean plasma concentrations of interleukin (IL)-2, IL-6, and interferon (IFN)-gamma, or NK activity in the patients, but the results were significantly variable. However, some cancer patients demonstrated markedly modulated immune functions. The changes in IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD8, and NK activity (P < .05), and IL-2 changes were correlated with those for IL-6, CD8, and NK activity. The results suggest that subgroups of cancer patients might be responsive to Ganopoly in combination with chemotherapy/radiotherapy. Further studies are needed to explore the efficacy and safety of Ganopoly used alone or in combination with chemotherapy/radiotherapy in lung cancer patients.
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PMID:Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer. 1611 7


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