Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological studies indicate that low serum total cholesterol level may increase the risk of death due to cancer, mainly lung cancer. The aim of our study was to evaluate serum levels of total cholesterol (TC) and triglycerides (TG) in patients with squamous cell and small cell lung cancer and their dependence on the histological type and the clinical stage of the neoplasm. Lung cancer patients (n=135) and healthy controls (n=39) entered the study. All lung cancer patients had higher rate of hypocholesterolemia and lower TC and TG levels than the control group. TC concentration was lower in lung cancer patients and in both histological types in comparison with the control group, TG level was lower only in patients with squamous cell lung cancer. There were no statistically significant differences of TC and TG levels between the histological types, or between the clinical stages of each histological type.
Int J Mol Med 2000 Feb
PMID:Serum total cholesterol and triglycerides levels in patients with lung cancer. 1063 2

Lung cancer, particularly small cell lung cancer (SCLC), is characterized by production of numerous peptides and their resulting clinical syndromes. Such peptides can act as autocrine growth factors for these tumors. In this study, we investigated the role of endothelin (ET)-1 in lung cancer. Using reverse transcription/polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and immunocytochemistry, we screened a panel of lung cancer cell lines for ET-1, its receptors, and endothelin converting enzyme-1 (ECE-1), which generates the active form of ET-1. ET-1 messenger RNA was expressed in five of seven SCLC, four of four non-small cell lung cancer (NSCLC), and human bronchial epithelial (HBE) cells. The intracellular isoform of ECE-1, important in processing ET-1 if an autocrine growth loop is to function, was downregulated in the lung cancer cell lines as compared with expression of the extracellular isoform. Endothelin A receptor (ETAR), which mediates the mitogenic effects of ET-1 in prostate and ovarian cancer, was upregulated in HBE cells compared with expression in three of seven SCLC and two of four NSCLC cell lines. Endothelin B receptor (ETBR) was more widespread, being expressed in seven of seven SCLC, four of four NSCLC, and the HBE cells. We used flow cytometry to measure mobilization of intracellular calcium as a functional assay for the ETAR. These data concurred with the RT-PCR results, indicating that the ETAR was downregulated or was involved in an alternative signal transduction pathway in lung cancer, and no evidence of functional receptor mediating an autocrine growth loop was found. From our study, the data do not support the putative functional autocrine growth role of ET-1 in lung cancer. We propose instead that ET-1 may act as a paracrine growth factor for surrounding epithelial and endothelial cells via alternative pathways, promoting angiogenesis and stromal growth.
Am J Respir Cell Mol Biol 2000 Apr
PMID:Studies on the expression of endothelin, its receptor subtypes, and converting enzymes in lung cancer and in human bronchial epithelium. 1074 23

Cancer patients often present altered serum lipid profile including changes of HDL cholesterol level. The aim of our work was to evaluate serum level of HDL cholesterol in patients with squamous cell and small cell lung cancer and its dependence on histological type and clinical stage of lung cancer. Fasting serum level of HDL cholesterol was analysed in 135 patients with newly diagnosed lung cancer and compared to a control group of healthy men. All lung cancer patients, as well as subgroups of squamous cell and small cell lung cancer had statistically significantly lower HDL cholesterol concentration than controls. There were no statistically significant differences of HDL cholesterol level between the histological types or between clinical stages of each histological type of lung cancer.
Int J Mol Med 2000 Sep
PMID:Serum HDL cholesterol concentration in patients with squamous cell and small cell lung cancer. 1093 94

Previous studies have shown that the expression of the cell-cell adhesion molecule (C-CAM1), located at chromosome 19, is down-regulated in several types of human cancers, including prostate and breast cancers. Two major isoforms of C-CAM1, the long or L-form C-CAM1 and the short or S-form C-CAM1, are derived from the C-CAM1 gene through alternative splicing. Tumor cells transfected with L-form C-CAM1, which contains a cytoplasmic domain, display significantly lower growth rates and less tumorigenicity in both in vitro and in vivo models compared with untransfected tumor cells, suggesting that L-form C-CAM1 may be a tumor suppressor. The transfection of the cytoplasmic domain of L-form C-CAM1 could also cause suppression of tumor growth, further supporting the role of L-form C-CAM1 in tumorigenesis. In contrast to reports of most of the tumor types tested, Ohwada et al. (Am. J. Respir. Cell Mol. Biol., 11: 214-220, 1994) reported that C-CAM1 was not down-regulated or even up-regulated in lung cancer. Because the cytoplasmic domain of L-form C-CAM1 is critical for the tumor suppressor function of C-CAM1, we hypothesized that switching of the isoform rather than down- regulation of C-CAM1 gene expression occurs during lung tumorigenesis. To test this hypothesis, we analyzed pairs of tumor tissue and corresponding normal-appearing lung tissue from 51 patients with non-small cell lung cancer (NSCLC) and 43 cell lines to determine expression profiles of L-form C-CAM1 and S-form C-CAM1 using reverse transcription-PCR. We found that L-form C-CAM1 was the predominant form (75%; 38 of 51) in normal-appearing lung tissue, whereas most (84%; 43 of 51) of the primary NSCLC tissue samples expressed predominantly S-form C-CAM1 (P < 0.0001). Similarly, 19 (79%) of the 24 NSCLC cell lines and 17 (85%) of the 20 small cell lung cancer cell lines expressed predominantly S-form C-CAM1. The frequent alteration of the C-CAM1 expression pattern suggests that C-CAM1 has an important role in lung tumorigenesis.
 ...
PMID:C-CAM1, a candidate tumor suppressor gene, is abnormally expressed in primary lung cancers. 1095 75

Allyl sulfur compounds play a major role in the chemoprevention against carcinogenesis. The present study compared the antiproliferative effects of diallyl sulfide (DAS), diallyl disulfide (DADS) and garlic extract on p53-wild type H460 and p53-null type H1299 non small cell lung cancer cells (NSCLC). The DAS and DADS treatment of both H460 and H1299 cells resulted in the highest numbers of cells in apoptotic state as measured by acridine orange staining, however, garlic extract treatment did not induce any significant apoptotic cells by MTT assay. DADS was found to be more effective in inducing apoptosis on NSCLC. The level of p53 protein in H460 cell was increased following DADS treatment. DAS and garlic extract treatment of H460 cells induced a rise in the level of Bax and a fall of Bcl-2 level. These results demonstrate that DAS, DADS and garlic extract are effective in reduction of anti-proliferative gene in NSCLC and suggest that modulation of apoptosis-associated cellular proteins by DAS, DADS and garlic extract may be the mechanism for apoptosis which merit further investigation as potential chemoprevention agents.
Exp Mol Med 2000 Sep 30
PMID:Effects of allyl sulfur compounds and garlic extract on the expression of Bcl-2, Bax, and p53 in non small cell lung cancer cell lines. 1104 43

Ectopic secretion of ACTH, from sites such as small cell lung cancer (SCLC), results in severe Cushing's syndrome. ACTH is cleaved from POMC. The syndrome may occur when the highly tissue-specific promoter of the human POMC gene (POMC) is activated. The mechanism of activation is not fully understood. This promoter is embedded within a defined CpG island, and CpG islands are usually considered to be unmethylated in all tissues. We demonstrate that much of this CpG island is methylated in normal nonexpressing tissues, in contrast to somatically expressed CpG island promoters reported to date, and is specifically unmethylated in expressing tissues, tumors, and the POMC-expressing DMS-79 SCLC cell line. A narrow 100-bp region is free of methylation in all tissues. E2F factors binding to the upstream domain IV region of the promoter have been shown to be involved in the expression of POMC in SCLC. We show that these sites are methylated in normal nonexpressing tissues, which will prevent binding of E2F, but are unmethylated in expressing tissue. Methylation in vitro is sufficient for silencing of expression, which is not reversed by treatment with Trichostatin A, suggesting that inhibition of expression may be mediated by means other than recruitment of histone deacetylase activity. The DMS-79 cells lack POMC demethylating activity, implying that the methylation and expression patterns are likely to be set early or before neoplastic transformation, and that targeted de novo methylation might be a potential therapeutic strategy.
Mol Endocrinol 2001 Feb
PMID:The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. 1115 38

ACTH-producing tumors of nonpituitary origin characteristically exhibit insensitivity to the negative feedback effects of glucocorticoids. In the DMS-79 cell line derived from an ACTH-producing small cell lung cancer we have previously identified an aberrantly spliced glucocorticoid receptor (GRDelta) that lacks a ligand-binding domain. We examined the interactions of this truncated form of GR with the proximal human proopiomelanocortin (POMC) promoter. In electrophoretic mobility shift assays GRDelta bound to the negative glucocorticoid response element (nGRE) at position -78 to -50 in the human POMC promoter. Nur77, an orphan nuclear receptor that exerts positive regulatory effects on the POMC gene is also known to bind to this DNA element. The functional properties of GR and GRDelta binding to this DNA element were examined in transient transfection experiments in murine AtT-20 corticotroph tumor cells. Reporter gene expression under the control of proximal POMC promoter elements was stimulated by addition of forskolin to the culture medium or by transfection with expression constructs for human Nak1, the human homologue of Nur77. Treatment of transfected cells with dexamethasone resulted in suppression of forskolin- or Nak1-stimulated POMC-reporter gene expression in the presence of co-transfected GR but not with GRDelta. The experiments indicate that in the human POMC promoter GRDelta is capable of binding to the nGRE but cannot effect trans-repression of POMC-reporter gene expression.
J Mol Endocrinol 2001 Feb
PMID:Function of a truncated glucocorticoid receptor form at a negative glucocorticoid response element in the proopiomelanocortin gene. 1117 53

The expression of neurotrophins (NTs) and related high- and low-affinity receptors was studied in surgical samples of histologically diagnosed human tumors of the lower respiratory tract. The experiment was conducted with 30 non-small cell lung cancer specimens and in eight small cell lung cancer specimens by Western blot analysis and immunohistochemistry to assess expression and distribution of NT and NT receptor proteins in tissues examined. Immunoblots of homogenates from human tumors displayed binding of anti-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3 antibodies as well as of anti-tyrosine-specific protein kinase (Trk) A, TrkB, and TrkC receptor antibodies, with similar migration characteristics than those displayed by human beta-NGF and proteins from rat brain. A specific immunoreactivity for NTs and NT receptors was demonstrated in vessel walls, stromal fibroblasts, immune cells, and sometimes within neoplastic cell bodies. Approximately 33% of bronchioloalveolar carcinomas exhibited a strong membrane NGF and TrkA immunoreactivity, whereas 46% adenocarcinomas expressed an intense TrkA immunoreactivity but a weak immunostaining for NGF within tumor cells. Moreover, squamous cell carcinomas developed an intense TrkA immunoreactivity only within stroma surrounding neoplastic cells. A faint BDNF and TrkB immunoreactivity was documented in adenocarcinomas, squamous cell carcinomas, and small cell lung cancers. NT-3 and its corresponding TrkC receptor were found in a small number of squamous cell carcinomas within large-size tumor cells. No expression of low-affinity p75 receptor protein was found in tumor cells. The detection of NTs and NT receptor proteins in tumors of the lower respiratory tract suggests that NTs may be involved in controlling growth and differentiation of human lung cancer and/or influencing tumor behavior.
Am J Respir Cell Mol Biol 2001 Oct
PMID:Neurotrophins and neurotrophin receptors in human lung cancer. 1169 49

G-3139 is an antisense phosphorothioate oligodeoxynucleotide (AS PS ON) which suppresses bcl-2 expression and is being developed by Genta Inc for the potential treatment of various cancers [308375]. G-3139 is in various stages of phase I/lIa trials. One study, initiated in May 1999, at the Lombardi Cancer Center at Georgetown University Medical Center, US, will examine G-3139 in conjunction with docetaxel. In a phase I/IIa dose-escalating trial to treat non-Hodgkin's lymphoma (NHL), at the Royal Marsden NHS Trust, UK, no serious, clearly drug-attributable or doselimiting adverse effects were noted and in some patients encouraging signs of potential drug activity were observed. The responses included one patient in whom cancer mass was reduced and one who developed a complete response for over 38 weeks in duration [239159,291608,325262]. A new phase II protocol using G-3139 combined with standard chemotherapies in relapsed NHL patients has also begun [325262]. Other phase I/lIa studies include: the safety and efficacy of G-3139 in the treatment of hormone-resistant, metastatic prostate cancer, when administered with mitoxantrone [305822]; the treatment of relapsed follicular NHL, when administered with cyclophosphamide [311217]; the treatment of Stage III and IV metastatic malignant melanoma in combination with dacarbazine [289755]; the treatment of hormone-resistant, metastatic prostate cancer when administered over a significantly longer duration than studied previously and in combination with an androgen-receptor blocking agent [291608]. The National Cancer Institute (NCI) funded and conducted preclinical studies of G-3139 in July 1996 and in June 1998, the NCI and Genta entered into a Cooperative Research and Development Agreement (CRADA) for the development of G-3139 [290153]. Clinical trials,focusing on colorectal cancer, small cell lung cancer and leukemia, were underway as of April 1999. The company licensed the rights for the use of bcl-2 as a target for antisense and gene therapy-based treatments from the University of Pennnsylvania. In June 1998, Genta received two patents relating to its antisense compounds [289685].
Curr Opin Mol Ther 1999 Jun
PMID:Technology evaluation: G-3139. 1171 6

CD98, an early marker of T-cell activation, is an important regulator of integrin-mediated adhesion events. Previous studies suggest that CD98 is coupled to both cellular activation and transformation and is involved in the pathogenesis of viral infection, inflammatory disease, and cancer. Understanding of the molecular mechanisms underlying CD98 activity may have far-reaching practical applications in the development of novel therapeutic strategies in these disease states. Using small cell lung cancer cell lines, which are nonadherent, nonpolarized, and highly express CD98, we show that, in vitro, under physiological conditions, CD98 is constitutively associated with beta1 integrins regardless of activation status. Cross-linking CD98 with the monoclonal antibody 4F2 stimulated phosphatidylinositol (PI) 3-kinase, PI(3,4,5)P(3), and protein kinase B in the absence of integrin ligation or extracellular matrix engagement. Furthermore, cross-linking CD98 promoted anchorage-independent growth. Using fibroblasts derived from beta1 integrin null stem cells (GD25), wild-type GD25beta1, or GD25 cells expressing a mutation preventing beta1 integrin-dependent FAK phosphorylation, we demonstrate that a functional beta1 integrin is required for CD98 signaling. We propose that by cross-linking CD98, it acts as a "molecular facilitator" in the plasma membrane, clustering beta1 integrins to form high-density complexes. This results in integrin activation, integrin-like signaling, and anchorage-independent growth. Activation of PI 3-kinase may, in part, explain cellular transformation seen on overexpressing CD98. These results may provide a paradigm for events involved in such diverse processes as inflammation and viral-induced cell fusion.
Mol Biol Cell 2002 Aug
PMID:Cross-linking CD98 promotes integrin-like signaling and anchorage-independent growth. 1218 50


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