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)

The aim of this study is to report the synthesis and photochemical and phototherapeutic activities of tetraamido-substituted 2,3-naphthalocyanine zinc(II) complexes (ZnNcs 5-8). Four naphthalocyanine complexes, tetrabenzamido- (ZnNc 5), tetramethoxybenzamido- (ZnNc 6), tetrahexylamido- (ZnNc 7) and tetradodecylamido- (ZnNc 8) naphthalocyanine zinc complexes absorbing at around 770 nm were synthesized. The dye-sensitized photo-oxidation of 1,3-diphenylisobenzofuran via 1O2 was studied in more detail in order to compare the quantum yields of these different sensitizers. Pharmacokinetic and photodynamic therapy studies of Lewis lung carcinoma in mice were carried out after administration of liposome incorporated ZnNcs 5-8. The phototherapeutic efficiency was evaluated by changes in the mean tumour diameter with time, regrowth delay (days), average survival time (days) and electron microscopy observations. According to all assessment criteria used, the most promising photosensitizer seems to be tetrabenzamido-substituted ZnNc 5. We suggest that mainly structural properties are the reason for the better results observed. The morphological analysis confirms the mechanism of photonecrosis, which was observed in our previous work with unsubstituted and substituted ZnNcs 1-4. Direct photodamage to the membrane, mitochondria and rough endoplasmic reticulum in the neoplastic cells and delayed photodestruction of the endothelial cells surrounding the tumour tissue were detected. Also, changes in lysosomes were observed. The data presented through different parameters are compared with such obtained for other photodynamic therapy sensitizers.
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PMID:Tetraamido-substituted 2,3-naphthalocyanine zinc(II) complexes as phototherapeutic agents: synthesis, comparative photochemical and photobiological studies. 893 23

HLA class I molecules present antigenic peptides to cytotoxic T lymphocytes and thus play an important role in immune surveillance of cells infected with virus or altered by malignant transformation. Immunochemical studies have demonstrated a marked deficiency or lack of expression of class I molecules on the surface of many different types of tumor cells. It is likely that this allows these cells to escape immune surveillance. In the present study, we examined the molecular basis for lack of expression of class I antigens in small-cell lung carcinoma cell lines. Our results demonstrate that these cell lines also lacked products of MHC-encoded proteasome subunit LMP2 and the putative peptide transporter TAP1. In contrast, LMP7 and TAP2 genes were expressed in these cell lines. Pulse-chase experiments showed that class I molecules were unstable and thus not transported to the cell surface from endoplasmic reticulum. Our results suggest that antigenic peptides were not available for binding to class I alpha chains due to lack of TAP1 and LMP2 gene products. Investigations of the regulatory mechanisms of TAP1 and LMP2 genes showed that the tumor cells lacked trans -regulatory nuclear protein(s), which binds to the interferon-gamma (IFN-gamma) response element (ISRE) in the TAP1, LMP2 bidirectional intergenic promoter. Treatment of tumor cells with IFN-gamma induced ISRE-binding nuclear protein(s) and resulted in expression of TAP1 and LMP2 genes with a concomitant increase in cell-surface expression of class I molecules. Our data provide credence for a role of TAP and LMP genes in immune response.
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PMID:Molecular basis for lack of expression of HLA class I antigens in human small-cell lung carcinoma cell lines. 893 46

Neuroendocrine-specific protein (NSP)-reticulons are endoplasmic reticulum-associated protein complexes, which have been identified as markers for neuroendocrine differentiation. In this study, the expression of two members of the family of NSP-reticulons, NSP-A and NSP-C, have been investigated in different types of lung cancer and compared with the expression patterns of five conventional neuroendocrine markers, the neural cell adhesion molecule (NCAM), synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. NSP-A and NSP-C antibodies were reactive with most carcinoid tumour and small cell lung carcinoma (SCLC) cases, while atypical carcinoid tumours showed a variable expression. In the total group of neuroendocrine tumours, a high concordance of expression was found between NSP-A and NSP-C, while their expression correlated well with NCAM and synaptophysin positivity. Chromogranin A, Leu-7, and neurofilament proteins were shown to be expressed to a limited extent in these neuroendocrine tumours. In a selected group of non-SCLCs known to exhibit neuroendocrine features, NSP-A expression was detected at much higher frequency than NSP-C. In virtually all NSP-A positive cases, this expression was associated with one or more of the other neuroendocrine markers. NSP-A expression showed a stronger correlation with conventional neuroendocrine markers than NCAM. In detecting neuroendocrine differentiation in non-SCLC, NSP-A is more sensitive than synaptophysin, chromogranin A, Leu-7, and neurofilament proteins. It is concluded that NSP-reticulons are valuable markers in the diagnosis of neuroendocrine differentiation in non-SCLC and should be used in conjunction with NCAM.
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PMID:A comparison of NSP-reticulons with conventional neuroendocrine markers in immunophenotyping of lung cancers. 922 37

Neuroendocrine-specific protein (NSP)-reticulons have recently been discovered and were shown to exhibit a restricted, neuroendocrine/neural-specific expression pattern. These protein aggregates are anchored to the membranes of the endoplasmic reticulum and occur in small cell lung cancer (SCLC), but not in typical non-SCLC. In the current study we have examined the occurrence of NSP-reticulons in non-SCLC cell lines known to express neuroendocrine features (non-SCLC-NE). NSP-reticulon expression was observed in all three non-SCLC-NE cell lines studied, albeit with variable intensity and in varying numbers of cells. Western blot analysis confirmed the presence of NSP-reticulon expression in these non-SCLC-NE cell lines, and showed that they were predominantly of the NSP-A type. When compared to conventional neuroendocrine markers, NSP-reticulons revealed a distinct staining profile, showing only partial overlap with the other markers. The non-SCLC-NE cell lines combined these neuroendocrine characteristics with some features of non-SCLC. We conclude that NSP-reticulon expression is restricted to lung carcinoma cells with a neuroendocrine phenotype and predict that these constituents may become clinically relevant markers for the detection of neuroendocrine differentiation in solid tumours.
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PMID:Neuroendocrine-specific protein (NSP)-reticulons as independent markers for non-small cell lung cancer with neuroendocrine differentiation. An in vitro histochemical study. 927 35

A major class of tumors lack expression of the transporters associated with antigen processing (TAP). These proteins are essential for delivery of antigenic peptides into the lumen of the endoplasmic reticulum (ER) and subsequent assembly with nascent major histocompatibility complex (MHC) class I, which results in cell surface presentation of the trimeric complex to cytolytic T lymphocytes. Cytolytic T lymphocytes are major effector cells in immunosurveillance against tumors. Here we have tested the hypothesis that TAP downregulation in tumors allows immunosubversion of this effector mechanism, by establishing a model system to examine the role of TAP in vivo in restoring antigen presentation, immune recognition, and effects on malignancy of the TAP-deficient small-cell lung carcinoma, CMT.64. To test the potential of providing exogenous TAP in cancer therapies, we constructed a vaccinia virus (VV) containing the TAP1 gene and examined whether VV-TAP1 could reduce tumors in mice. The results demonstrate that TAP should be considered for inclusion in cancer therapies, as it is likely to provide a general method for increasing immune responses against tumors regardless of the antigenic complement of the tumor or the MHC haplotypes of the host.
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PMID:TAP expression provides a general method for improving the recognition of malignant cells in vivo. 1080 11

Pyropheophorbide-a methyl ester (MPPa) is a semisynthetic photosensitizer derived from chlorophyll a. The absorption peak of MPPa in organic solvent and in cells was at 667 and 674 nm, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay showed that MPPa had no dark cytotoxicity. In vitro photodynamic activity was extensively evaluated using a human lung carcinoma cancer cell line (NCI-h446). MPPa exhibited no genotoxicity, as assayed by single-cell gel electrophoresis. Using confocal laser scanning microscopy and organelle-specific fluorescent probes, MPPa was found to localize in the intracellular membrane system, namely the endoplasmic reticulum, Golgi apparatus, lysosomes and mitochondria, in the NCI-h446 cells. Furthermore, nuclear staining and DNA gel electrophoresis revealed that DNA condensation and fragmentation occurred post-photodynamic therapy, indicating the cell death was in the apoptotic mode.
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PMID:Photodynamic therapy with pyropheophorbide-a methyl ester in human lung carcinoma cancer cell: efficacy, localization and apoptosis. 1208 27

Vascular endothelial growth factor (VEGF)/vascular permeability factor is one of the most frequently expressed angiogenic factors in several pathological tissues. Development of VEGF antagonists has become an important approach in the treatment of angiogenesis-dependent diseases. Here we describe a novel anti-VEGF strategy by preventing the secretion of VEGF. We utilize the fact that placenta growth factor (PlGF)-1, a member of the VEGF family lacking detectable angiogenic activity, preferentially forms intracellular heterodimers with VEGF in cells coexpressing both factors. We constructed a retroviral vector containing human PlGF-1 or VEGF with a C-terminal KDEL sequence, which is a mammalian retention signal for the endoplasmic reticulum. Transduction of murine Lewis lung carcinoma cells with the retro-hPlGF-1-KDEL construct almost completely abrogated tumor growth. Consistent with the dramatic antitumor effect, most mouse VEGF molecules remained as intracellular mVEGF/hPlGF-1 heterodimers, and only a negligible amount of mVEGF homodimers were secreted. As a result, in hPlGF-1-KDEL-expressing tumors, blood vessels remained at very low numbers and lacked branching and capillary networks. Gene transfer of a hVEGF-KDEL construct into tumor cells likewise produced a dramatic antitumor effect. Thus, our study provides a novel antiangiogenic approach by preventing the secretion of VEGF.
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PMID:Blockage of VEGF-induced angiogenesis by preventing VEGF secretion. 1519 38

All eukaryotic cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by signaling an adaptive pathway termed the unfolded protein response (UPR). Glucose-regulated protein (Grp) 78 is a molecular chaperone involved in the UPR. The aim of this study was to detect Grp78 expression in lung cancer using immunohistochemical (IHC) staining, and also to evaluate the relationship between the Grp78 expression level and the prognosis of patients with lung cancer. We used immunohistochemistry to analyze the protein expression of Grp78 in paraffin-embedded tumor samples from 132 well-characterized lung cancer patients and compared the expression level of Grp78, clinical variables and survival outcome. A positive expression of Grp78 was detected in the cytoplasm of tumor cells in 88 of the 132 patients (66.7%) with lung cancer. No significant difference was observed between the Grp78 expression and the gender, age at operation, histological type, pathologic stage, pathologic T status, and pathologic N status. Lung cancer patients with a positive Grp78 expression tended to show a better prognosis than those with a negative Grp78 expression. In addition, a multivariate analysis of the clinicopathologic characteristics of lung cancer indicated a positive expression of Grp78 to be a significant factor for predicting a favorable prognosis (p < 0.001, risk ratio = 2.35). A positive expression of Grp78 may thus be a useful marker for predicting a favorable prognosis in patients undergoing a resection of lung cancer. The ER stress pathway mediated by Grp78 may therefore be responsible for controlling the growth of lung cancer cells.
Lung Cancer 2005 Jul
PMID:Expression of endoplasmic reticulum molecular chaperone Grp78 in human lung cancer and its clinical significance. 1594 90

Low oxygen tension (hypoxia) is a common feature of solid tumors and stimulates the expressions of a variety of genes including those related to angiogenesis, apoptosis and endoplasmic reticulum (ER) stress response. Here we show a close correlation between metastatic potential and the resistance to hypoxia- and ER stress-induced apoptosis among the cell lines with differing metastatic potential derived from Lewis lung carcinoma. An apoptosis-specific expression profiling and immunoblot analyses revealed that the expression of antiapoptotic Mcl-1 increased as the resistance to apoptosis increased. Downregulation of the Mcl-1 expression in the high-metastatic cells by Mcl-1 small interfering RNA increased the sensitivity to hypoxia-induced apoptosis and decreased the metastatic ability. The hypoxia-induced apoptosis was not associated with p53 accumulation, although at present it is not possible to conclude that apoptosis-induced apoptosis is p53-independent. There was no correlation between the expression levels of ER stress-response proteins GADD153, GRP78 and ORP150 and the resistance to hypoxia or ER stresses. In vitro, small numbers of the high-metastatic cells overtook the low-metastatic cells after exposure to several rounds of hypoxia and reoxygenation. In solid tumors initially established from equal mixtures, the proportion of the high-metastatic cells to low-metastatic cells was significantly higher in hypoxic areas. Moreover, the high-metastatic cells were overtaking the low-metastatic cells in some of the tumors. Thus, tumor hypoxia and ER stress may provide a physiological selective pressure for the expansion of the high-metastatic cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors.
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PMID:Hypoxia selects for high-metastatic Lewis lung carcinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors. 1624 70

Antrodia camphorata (niu-chang-chih) is a fungus native to Taiwan that is believed to be effective in preventing diseases. This study demonstrates that 0.2-2% v/v ethanol extracts of A. camphorata cultivated by solid-state fermentation (SACE) can effectively impede the proliferation of human non-small cell lung carcinoma A549 cells but not primary human fetal lung fibroblast MRC-5. The results of apoptotic analyses implicate that SACE might trigger the apoptosis in the A549 cells by inducing endoplasmic reticulum stress. Two-dimensional gel maps of non-treated and treated A549 cells were compared using PDQUEST analytical software to discover five statistically significant twofold or above-twofold differentially-expressed protein spots. The five protein spots that were significantly de-regulated were chosen for subsequent identification by high performance liquid chromatography electro-spray tandem mass spectrometry. The five proteins were later identified as human galectin-1, human eukaryotic translation initiation factor 5A, human Rho GDP dissociation inhibitor alpha, human calcium-dependent protease small subunit and human annexin V. All five proteins were confirmed to be down-regulated by Western blotting. The analytical results of this study help to provide insight into the effect of SACE on the gene expression of the tumor cells.
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PMID:Proteomic analysis of the effect of Antrodia camphorata extract on human lung cancer A549 cell. 1641 Dec 66


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