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

Cytogenetic analysis has indicated that deletion of chromosome 9p occurs in a significant number of non-small cell lung and mesothelioma tumors. Using paired oligonucleotide primers, we have undertaken an extensive analysis of 9p markers to determine homozygous and heterozygous loss of marker sequences. Homozygous loss of D9S169 and D9S171, both of which map centromeric to the IFN gene cluster, were noted in three cell lines (27%) and hemizygous deletions of one or both of these loci was found in a further six cell lines (54%). These data suggest the presence of a potential tumor suppressor gene for lung cancer in proximity to D9S169 and D9S171 at 9p21.
 ...
PMID:Homozygous and hemizygous deletions of 9p centromeric to the interferon genes in lung cancer. 816 70

Interferons have been shown to increase in vitro cytotoxicity of platinum compounds. The Hoosier Oncology Group has conducted a Phase II clinical trial to determine if interferon alpha-2a (IFN-alpha-2a) given in combination with carboplatin (CBDCA) can increase response rates or survival in patients with metastatic or recurrent inoperable non-small-cell lung cancer. Forty-four patients with no prior chemotherapy and high KPS (80-100) were enrolled. CBDCA 400 mg/m2 was given intravenously on day 1 and IFN-alpha-2a 9 million units was given subcutaneously on days 1, 3, and 5. Treatment was administered every 4 weeks until onset of progressive disease or to a maximum of 4 courses: 37 patients (84%) received at least 2 courses, whereas only 16 (36%) received the full 4 courses. Dose-limiting toxicities were leukopenia (27%) and thrombocytopenia (20%) attributable to CBDCA. Grade 2-3 anemia occurred in 32%. Only 4-7% of patients experienced severe fever, fatigue, or flu-like symptoms attributable to interferon administration. Of 41 patients evaluable for response, there were no complete responses and only 3 (7.3%) partial remissions. The overall median survival was 6 months. The combination of CBDCA and IFN-alpha-2a given in this dose and schedule does not appear to have superior activity compared to CBDCA alone in patients with non-small-cell lung cancer.
 ...
PMID:Carboplatin (CBDCA) plus alpha interferon in metastatic non-small cell lung cancer. A Hoosier Oncology Group phase II trial. 825 69

Thirteen human lung cancer cell lines, 7 representing small cell lung cancer (SCLC) and 6 different types of non-SCLC, were tested for sensitivity to tumour necrosis factor alpha (TNF-alpha) and interferon alpha and gamma (IFN-alpha and gamma) using an automated fluorometric microculture cytotoxicity assay (FMCA). One SCLC line (H-82) was found to be sensitive to IFN-alpha in short-term (72 h) culture, whereas after prolonged (5 days) culture two additional SCLC cell lines responded to IFN-gamma. TNF-alpha inhibited the growth of one large cell carcinoma cell line (H-157), whereas all SCLC lines were found to be insensitive. The combination of IFN-gamma and TNF-alpha produced no further response compared with the single agents used alone. By continuous cultivation of the IFN-alpha-sensitive cell line H-82 in the presence of increasing concentrations of IFN-alpha, an IFN-alpha-resistant subline (H-82) was established. This line displayed a high degree of resistance ( > 100 fold) to IFN-alpha and cross-resistance to IFN-gamma. There was no alteration in the number of IFN binding sites, in the growth rate, the expression of selected surface markers for SCLC or the expression of multidrug resistance markers in the H-82R subline compared with the parental H-82 cell line. The results demonstrate a heterogeneous response of SCLC cell lines to IFN-alpha and gamma and TNF-alpha with only a minority of the cell lines responding to these agents by growth inhibition. The IFN-alpha and gamma H-82R subline may serve as a valuable tool in future studies on the mechanisms of IFN antitumour activity.
 ...
PMID:Effects of interferons and tumour necrosis factor-alpha on human lung cancer cell lines and the development of an interferon-resistant lung cancer cell line. 869 64

Despite increasing survival rates for patients with colorectal cancer, additional treatment options are required, including active or passive immunotherapy for patients with metastatic disease. Freshly harvested colorectal cancer specimens and in vitro cultured colorectal cancer cell lines were examined for IL-7 protein secretion in order to examine the potential role of this cytokine in the interaction between tumour cells and the host immune system. Freshly harvested colorectal cancer specimens (21/21), or normal adjacent mucosa (3/3), as well as long-term established colorectal cancer cell lines (3/4) exhibited IL-7 mRNA expression as detected by RT-PCR and confirmed by Southern Blot analysis. Freshly harvested colorectal cancer tissue (16/18), or long-term established colorectal cancer cell lines (2/4) secreted in vitro IL-7 as detected by ELISA. In contrast, breast, pancreatic, or lung cancer cell lines, as well as several haematopoietic cancer cells lines, tested negative for IL-7 mRNA and protein. The authors tested different cytokines (IL-1 beta, IL-2, IL-7, or a combination of IL-1 beta/IL-7) in vitro for the ability to expand tumour-infiltrating T lymphocytes (TIL) from individual patients (n = 9) with colorectal cancer. TIL populations were tested at day 14 after in vitro propagation for phenotypic analysis by FACS and for reactivity directed against NK and LAK sensitive target cells and autologous cancer cells as measured by cytotoxicity and cytokine release. TIL obtained from colorectal cancer lesions can be efficiently expanded in the presence of IL-7, some(3/9) of which appear to exhibit autologous tumour recognition as measured by cytolytic effector functions and by detection of IFN gamma and TNF alpha release. Detection of IL-7 mRNA expression in colorectal cancer, in normal mucosa adjacent to tumour, as well as the ability of colorectal cancer tissue to secrete IL-7, raises new questions about the biology of the host/tumour interactions in colorectal cancer.
 ...
PMID:Interleukin-7 (IL-7) in colorectal cancer: IL-7 is produced by tissues from colorectal cancer and promotes preferential expansion of tumour infiltrating lymphocytes. 904 31

A differential pattern of sera exhibiting interferon-inhibiting activity in cases of histologically confirmed lung cancer patients have been observed. The sera distribution was dependent on the clinical entity and the cell line specificity used measuring IFN-inhibition. Although either small cell lung cancer (SCLC) or non small cell lung cancer (NSCLC) sera exhibiting in a high percentage (80 and 75% respectively) such an activity, in any of the 3 lines tested, the ratio of sera exerting inhibition in each cell line was different. Such cell specific systems could be of prognostic/predicting value for effective therapeutic schedules of specific clinical entities.
 ...
PMID:Interferon-inhibiting activities in sera of patients with lung cancer. 909 Apr 42

Ex vivo genetically engineered cytokine-secreting tumor cell vaccines have been shown to prevent metastatic disease in animal models of lung and breast cancer. Because of the inefficiency of existing modes of gene delivery in transducing primary human tumor cells, it has been difficult to clinically apply this strategy. In this study, liposome-mediated delivery of an adeno-associated virus (AAV)-based plasmid containing the sequence for murine gamma-interferon (gamma-IFN) (pMP6A-mIFN-gamma) was used to generate cytokine-secreting murine tumor cell vaccines. High levels of gamma-IFN and elevated class I major histocompatibility complex expression after transfer of pMP6A-mIFN-gamma into the murine lung cancer cell line, D122, was demonstrated. The efficiency of gene transfer was determined by two different methods and was estimated to be 10-15%. Irradiated gamma-IFN D122 cells generated by this novel gene delivery system (D122/pMP6A-mIFN-gamma) and also by standard retroviral methods (DIF2) were administered as weekly vaccinations by intraperitoneal injection to animals bearing 7-day-old intrafootpad D122 tumors. Hindlimb amputation was performed when footpad diameters reached 7 mm, and lungs were harvested 28 days later. Animals vaccinated with gamma-IFN-secreting D122 cells produced by AAV-based plasmids delivery demonstrated a significant delay in footpad tumor growth when compared with controls and DIF2 cells. Fifty-seven percent of animals vaccinated with D122/pMP6A-mIFN-gamma were free of pulmonary metastases 28 days after amputation, significantly improved from the 0, 7, and 15% observed in animals vaccinated with irradiated parental D122 cells, irradiated D122 cells lipofected with an empty-cassette vector (pMP6A), or DIF2 cells, respectively. These results and the ability to transfer genes with this delivery system to a broad range of tumor types support its use in the generation of cytokine-secreting tumor cell vaccinations for use in clinical trials.
 ...
PMID:Active immunization with tumor cells transduced by a novel AAV plasmid-based gene delivery system. 910 11

We have found that many synthetic selenoorganic compounds, including ebselen, have immunotropic activity. These studies were designed to assess the effect of the analog of ebselen bis[2-pyridyl (2-carbamoyl) phenyl]diselenide (AE-22) on human leukocytes that may express various activation states. The cells were obtained from bronchoalveolar lavage (BAL) cells of patients with various inflammatory lung diseases. The AE-22-treated BAL cells from patients with bronchial asthma (n = 6) and with small cell lung cancer (SCLC) (n = 6) were compared with these in the peripheral blood leukocytes (PBL) from the same donors. The control group comprised 5 patients who underwent diagnostic examination and were free of any cancer or concomitant diseases. Secretion of TNF-alpha, IL-6, and IFN-gamma was considered as a marker of BAL or PBL cell activation. Different response of the cells and various effects of AE-22 were observed in relation to the origin and functional state of leukocytes. It was established that AE-22 can induce TNF-alpha, IL-6, and IFN-gamma in a dose-dependent manner in BAL cells and PBL isolated from healthy individuals. However, BAL cells were found to be less reactive than PBL as cytokine producers. In contrast, AE-22 had no effect on BAL cells obtained from patients with lung cancer, which were found to be hyporeactive to phytohemagglutinin and bacterial lipopolysaccharide and did not produce TNF-alpha, IL-6, or IFN spontaneously. The spontaneous release of cytokines by BAL cells from bronchial asthma patients, but not by PBL from the same individuals, was significantly (p < 0.01) higher than that from the cultures of healthy control subjects. The high secretion of cytokines by the locally activated BAL cells was significantly (p < 0.01) reduced after administration of AE-22. The results suggest that AE-22 has immunomodulatory activity. AE-22 can downregulate the hyporeactive BAL cells from asthmatics, but it appears to be inactive in BAL cells of cancer patients who can tolerate the cytokine inducers.
 ...
PMID:Modulation of cytokine production by a selenoorganic compound (AE-22) in hyperreactive or hyporeactive bronchoalveolar leukocytes of asthmatics or lung cancer patients. 935 62

The effect of intrapleural instillation of recombinant human interferon gamma (IFN gamma) at increasing doses of (1-12) x 10(6) U was examined in six patients with cytologically positive pleural effusion due to lung cancer. Intrapleural instillation was repeated up to three times. Clinically, no reaccumulation of pleural effusion was observed in one patient and disappearance of lung cancer cells from the pleural effusion was seen in two other patients. No severe side-effects were observed. Considerable levels of IFN gamma remained in the pleural effusion as well as in patients' serum up to 7 days after instillation of 2 x 10(6) U and higher doses. The total cell number showed a transient decrease on day 1 of therapy. Levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin(IL)-1 beta and IL-6, in the pleural effusion remained almost stable after IFN gamma instillation. On the other hand, intrapleural IL-1 receptor antagonist levels were remarkably elevated by the instillation of IFN gamma. IL-2- and IL-12-inducible killer activity of pleural mononuclear cells tended to increase slightly. Despite the inability of IFN gamma to control pleural effusion in this treatment schedule, IFN gamma instilled by an intrapleural route had a potential local antitumor activity. Moreover, since IFN gamma persists in pleural effusions for a long time after a single instillation, such a therapy in combination with other fibrogenic biological response modifiers can be promising.
 ...
PMID:Intrapleural instillation of interferon gamma in patients with malignant pleurisy due to lung cancer. 939 Feb

Alveolar macrophages (AM) were obtained from 20 patients with primary lung cancer and 20 cases with nonmaligment pulmonary disease by BAL and were incubated in vitro in medium with and without BCG and/or IFN-alpha. Then the cell-free supernatants were harvested. The activity of arginase was assayed. It was found that: arginase was produced spontaneously by AM: The spontaneous production of arginase is lower in AMs from the tumor-bearing segments than either nontumor-bearing segments or AMs from the patients with nonmalignant pulmonary diseases (P < 0, .05). The production of arginase was icreased on AMs from the tumor-bearing segments stimulated with BCG and/or IFN-alpha (P < 0.05 or 0.01). The results suggested that (1) There are some function at defects of tumor. (2) The mechanism of anti-tumor and anti-infection activity of BCG and IFN-alpha may possibly increase the production of arginase of AMs.
 ...
PMID:[Study of arginase activity in alveolar macrophages from patients with lung cancer]. 986 39

The relationship and in situ interactions between interleukin 2 (IL-2)-regulated mediators remain unclear, particularly in lung cancer model. The purpose of the present study was to determine in vitro effect of IL-2 on the secretory activity of bronchoalveolar leukocytes from 11 patients with previously untreated small cell lung cancer (SCLC) and 9 patients with non-small cell lung cancer (NSCLC). Control group (n = 6) comprised patients who underwent diagnostic investigations and were free of any clinical or radiographic evidence of lung diseases. IL-2-induced secretion of mediators was compared with that following stimulation with lipopolisaccharide (LPS; 5 micrograms/ml) or Newcastle disease virus (NDV; 640 HU/ml). Obtained from bronchoalveolar lavages (BAL) cells were cultured for 24-48 h in the presence or absence of inducers. The levels of cytokines were determined in BAL cell supernatants by bioassays. Nitric oxide (NO) was estimated by colorimetric method in Griess reaction. Compared with normal controls, the spontaneous secretion of the above mediators excluding IFN-gamma in BAL cultures from NSCLC group was elevated by up to 20-30-fold and further increase was observed after stimulation with LPS. However, very low secretion of cytokines and NO was found in BAL leukocyte cultures activated by IL-2. In contrast, the cells obtained from SCLC group produced little detectable levels of TNF-alpha (median 12.0, range 3-45 U/ml), IFN-gamma (median 3, range 3-12 U/ml) and IL-6 (median 15, range 6-45 U/ml) in response to LPS and interferons, mainly IFN-alpha; (median 3, range 3-12 U/ml) in response to NDV. Although, upon IL-2-stimulation was observed only noteworthy production of IL-6 (median 405, range 45-1215 U/ml). IL-2-induced secretion of IL-6 was accompanied by up to 5-fold augmented secretion of NO in comparison with NSCLC group and healthy controls. These observations suggest that BAL cells from patients with lung cancers express a selective secretory activity and that IL-2 is an important regulatory factor of secondary production of IL-6 and NO. Utilization of IL-2 in therapeutic strategy in SCLC can lead to alterations in synthesis/release of biologically active IL-6 and NO that may contribute to the clinical settings.
 ...
PMID:Exogenous interleukin 2 regulates interleukin 6 and nitric oxide but not interferon gamma and tumor necrosis factor alpha production in bronchoalveolar leukocytes from patients with small cell lung cancer. 988 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>