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)

Based upon the reasoning that protein-carbohydrate recognition is involved in diverse intercellular activities including growth control and cell motility 14 probes have been employed to characterize epitope presence in sections of 80 cases with operated lung carcinomas, 20 patients with mesothelioma, and 20 cases with non-malignant lung diseases. As parts of the innate immune system with supposed relevance for host defense the mannan-binding lectin (MBL) and serum amyloid P component (SAP) were employed. The naturally occurring immunoglobulin G fractions with selectivity for alphaa-galactosides (alpha+) and beta-galactosides (beta+) and their subfractions with enhanced target selectivity (alpha+beta-,alpha-beta+) allowed the monitoring of expression of reactive sites for these autoantibodies as a step to elucidate potential anti-tumor activity. Due to the diversity of cellular galactoside-containing glycoconjugates two galectins and a plant lectin were included. As a measure of receptor activities for carbohydrates, neoglycoconjugates with alpha-galactose, the B-disaccharide, the Forssman-disaccharide, and alpha-glucose as histochemically crucial ligand part were tested in addition to an antibody against heparin-binding lectin. Quantitative image analysis revealed significant differences between cases with small cell and non-small cell lung cancer for the plant lectin and one galectin, cases with non-tumorous lung disease and lung carcinoma for serum amyloid P component and the beta-galactoside-selective autoantibody fraction. Prognostic relevance was observed for the presence of glucose-specific sites in small cell lung cancer and meso-thelioma cases, and of galectin- and alpha-galactoside-selective immunoglobulin G fraction-binding sites in non-small cell lung cancer patients.
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PMID:Glycohistochemical properties of malignancies of lung and pleura. 953 48

Expression of facilitative glucose transporter (Glut) isoforms was studied immunohistochemically in lung carcinomas. Glut-1 was expressed in 45 (74%) of 61 lung carcinomas, including 19 (100%) of 19 squamous cell carcinomas. No Glut-1 staining was seen in normal lung epithelium surrounding the tumors. In squamous cell carcinomas and small cell carcinomas, Glut-1 immunostaining was stronger in the central area of tumor cell nests corresponding to the hypoperfused region. Focal staining was seen in 14 (58%) of 24 adenocarcinomas, and positive staining was correlated to lesser differentiation, larger tumor size, and positive lymph node metastasis. Glut-2 was detected in normal airway epithelium, but no positive staining was seen in lung carcinomas. Glut-3 and Glut-4 were not positively stained in normal lung epithelia, but a few lung carcinoma samples showed positive reaction (9 of 61 in Glut-3; 4 of 61 in Glut-4). Glut-4 immunoexpression was seen in regenerating alveolar and bronchiolar epithelia around and in cancer tissues. Glut-5 expression was not detected in normal and tumor tissues. Reverse transcriptase-polymerase chain reaction for Glut-1, Glut-3, and Glut-4 confirmed the expression revealed by immunohistochemical analysis. Overexpression of Glut could enhance uptake of glucose into lung carcinoma cells, and the increased glucose influx could be involved in cell biologic activities.
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PMID:Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage. 983 Dec 15

A retrospective analysis was performed to determine whether coronal thoracic [18F]fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) scans, if viewed at the time of radiotherapy (RT) planning, would have influenced the anterior-posterior (AP) RT volumes that were administered to a group of unoperated lung cancer patients. Viewing of PET and diagnostic images enabled a qualitative assessment of whether abnormal thoracic PET activity was present in areas regarded as normal by diagnostic imaging; this would, therefore, have influenced the RT volume if done prospectively. Additionally a method of graphical co-registration was devised to quantitate the adequacy of coverage of each patient's abnormal PET activity by his/her actual RT field. Of 15 patients analyzed, 26.7% (four patients) would have had their RT volume influenced by PET findings, highlighting the potential value of PET in treatment planning.
Lung Cancer 1998 Mar
PMID:The contribution of 18F-fluoro-2-deoxy-glucose positron emission tomographic imaging to radiotherapy planning in lung cancer. 963 64

The effects of FK317 (11-acetyl-8-carbamoyloxymethyl-4-formyl-6- methoxy-14-oxa-1,11-diazatetracyclo[7.4.1.0(2, 7). 0(10, 2] tetradeca-2,4,6-trien-9-yl acetate), a novel anti-cancer agent, on murine adenocarcinoma colon26- and human lung carcinoma LX-1-induced cachexia were investigated in mice. Mice bearing colon26 or LX-1 s.c. lost weight and became cachectic, associated with tumor growth. FK317 and mitomycin C (MMC) inhibited the growth of both tumors. FK317 ameliorated the weight loss induced by the presence of colon26 or LX-1, while MMC enhanced it. An attenuation of the reduction in the weights of epididymal fat, gastrocnemius muscle and carcass was observed in FK317-treated tumor-bearing mice in both cachexia models, but not in MMC-treated mice. The decreases in the circulating levels of triglyceride, glucose and non-esterified fatty acid, which were induced by the presence of colon26, was partially inhibited by treatment with FK317. Overall, this study revealed that FK317 is a potent anti-cancer drug with anti-cachectic activity, suggesting that FK317 has potential utility for the treatment of cancer.
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PMID:Anti-cachectic effect of FK317, a novel anti-cancer agent, in colon26 and LX-1 models in mice. 1008 93

Glucose uptake and metabolism are essential for proliferation and survival of cells, and are supposed to be enhanced in actively proliferating cell systems such as embryonic and cancer tissues. Glucose uptake is usually carried out through glucose transporters. In the developing fetal lung, metabolism of glucose is thought to be an important process in cell proliferation, differentiation and maturation. Active glucose uptake could result in accumulation of glycogen in epithelial cells, and utilization of glycogen could be a critical phenomenon for lung epithelial development. In hamsters, although facilitative glucose transporter isoform 1 (GLUT1) and isoform 4 (GLUT4) are not detected in adult lungs, expression of them is detected with immunohistochemical and Western blot analyses in the developing fetal lungs. In human lung carcinomas, GLUT1 expression is seen in most cases of lung carcinoma, and is seen especially frequently in squamous cell carcinoma. GLUT1 expression in adenocarcinoma of the lung is correlated with reduced cell differentiation, larger tumor size and positive lymph node metastasis. A few cases of lung carcinoma show positive staining for GLUT3 and GLUT4. Thus, expression of some facilitative glucose transporter isoforms is detected in developing fetal epithelium and in lung carcinomas. Overexpression of them could enhance uptake of glucose into these cells, and the increased influx of glucose could be involved in active cell proliferation, which is a common character of the developing lung epithelium and carcinoma.
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PMID:Glucose transporter expression in developing fetal lungs and lung neoplasms. 1042 60

The increased uptake of hexose by mammalian cells is considered to be a general response to stress. Nowadays, mistletoe lectin separated from the extracts of the European mistletoe (Viscum album L.) is often used in adjuvant cancer therapy. The present work studies the effect of the lectin on unirradiated and x-irradiated tumour cells. The response of cultured human lung carcinoma cells (Calu-1) was followed by radioactive glucose uptake as well as by tritiated thymidine incorporation. The cells were maintained either in a complete or a so-called restrictive medium. Slight metabolic changes were found in the restrictive medium but not in the complete one. Mistletoe lectin I at a very low concentration (0.001 ng/mL) increased the glucose uptake and thymidine incorporation. Ionizing radiation (1 Gy) did not influence the hexose uptake but it enhanced the incorporation of thymidine. It seems that the actions of two different factors (mistletoe lectin I and radiation) proved to be rather provoking stress effects for the tumour cells as detected in the restrictive medium.
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PMID:Effects of mistletoe lectin I and ionizing radiation on the glucose and thymidine uptake in tumour cells in vitro. 1059 33

The apoptosis-resistant phenotype of cloned high-metastatic A11 and low-metastatic P29 cells isolated from Lewis lung carcinoma was compared. The results showed that A11 cells were more resistant to apoptosis induced by microenvironmental stresses such as serum starvation, glucose deprivation and hypoxia than P29 cells as judged by viability, DNA laddering, and chromatin condensation and fragmentation. Both cell lines were insensitive to tumor necrosis factor-alpha-mediated apoptosis. P29 cells expressed a much higher level of Fas antigen on the cell surface than A11 cells. However, both cell lines were also insensitive to Fas-mediated apoptosis. The apoptosis resistant phenotype of A11 cells was associated with the expression level of caspase-3, but not with those of Bcl-2, Bcl-X(L) Bax, p27Kip1 and DAP kinase. There was no difference between A11 and P29 cells in the expression of E-cadherin, the adhesiveness to the extracellular matrix components or the expression levels of metastasis-associated genes such as c-Ha-ras, c-jun, p53 and nm23. Furthermore, A11 cells exhibited lower motile and invasive abilities than P29 cells. These results suggest that the apoptosis-resistant phenotype is an important factor for determining the metastatic ability of A11 cells. Supporting this, P29 cells became more apoptosis-resistant after treatment of the cells with dimethylsulfoxide which is reported to enhance the experimental metastatic potential of the cells.
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PMID:Resistance to apoptosis induced by microenvironmental stresses is correlated with metastatic potential in Lewis lung carcinoma. 1065 7

Flavopiridol (L86-8275) ((-)-cis-5, 7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1-methyl)-piperidinyl] -4H-benzopyran-4-one), a potential antitumor drug, currently in phase II trials, has been shown to be an inhibitor of muscle glycogen phosphorylase (GP) and to cause glycogen accumulation in A549 non-small cell lung carcinoma cells (Kaiser, A., Nishi, K., Gorin, F.A., Walsh, D.A., Bradbury, E. M., and Schnier, J. B., unpublished data). Kinetic experiments reported here show that flavopiridol inhibits GPb with an IC(50) = 15.5 microm. The inhibition is synergistic with glucose resulting in a reduction of IC(50) for flavopiridol to 2.3 microm and mimics the inhibition of caffeine. In order to elucidate the structural basis of inhibition, we determined the structures of GPb complexed with flavopiridol, GPb complexed with caffeine, and GPa complexed with both glucose and flavopiridol at 1.76-, 2.30-, and 2.23-A resolution, and refined to crystallographic R values of 0.216 (R(free) = 0.247), 0.189 (R(free) = 0.219), and 0.195 (R(free) = 0.252), respectively. The structures provide a rational for flavopiridol potency and synergism with glucose inhibitory action. Flavopiridol binds at the allosteric inhibitor site, situated at the entrance to the catalytic site, the site where caffeine binds. Flavopiridol intercalates between the two aromatic rings of Phe(285) and Tyr(613). Both flavopiridol and glucose promote the less active T-state through localization of the closed position of the 280s loop which blocks access to the catalytic site, thereby explaining their synergistic inhibition. The mode of interactions of flavopiridol with GP is different from that of des-chloro-flavopiridol with CDK2, illustrating how different functional parts of the inhibitor can be used to provide specific and potent binding to two different enzymes.
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PMID:Flavopiridol inhibits glycogen phosphorylase by binding at the inhibitor site. 1092 12

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning has been useful in the management of various cancers. The normal glucose use of gray matter often limits the detection of metastatic lesions to the brain and skull with FDG PET. The authors report two cases of calvarial metastases: one with pheochromocytoma and the other with non-small-cell lung carcinoma. These cases illustrate the crucial role that FDG PET can play when patients are examined for metastases. The important concept of contrast resolution that is achieved with PET imaging is discussed as an advantage that significantly overcomes its limited spatial resolution in detecting small lesions that may not be detected by anatomic imaging techniques with high spatial resolution.
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PMID:Detection of cranial metastases by F-18 FDG positron emission tomography. 1131 19

A simplified three-dimensional Monte Carlo simulation model of in vitro tumor growth and response to fractionated radiotherapeutic schemes is presented in this paper. The paper aims at both the optimization of radiotherapy and the provision of insight into the biological mechanisms involved in tumor development. The basics of the modeling philosophy of Duechting have been adopted and substantially extended. The main processes taken into account by the model are the transitions between the cell cycle phases, the diffusion of oxygen and glucose, and the cell survival probabilities following irradiation. Specific algorithms satisfactorily describing tumor expansion and shrinkage have been applied, whereas a novel approach to the modeling of the tumor response to irradiation has been proposed and implemented. High-performance computing systems in conjunction with Web technologies have coped with the particularly high computer memory and processing demands. A visualization system based on the MATLAB software package and the virtual-reality modeling language has been employed. Its utilization has led to a spectacular representation of both the external surface and the internal structure of the developing tumor. The simulation model has been applied to the special case of small cell lung carcinoma in vitro irradiated according to both the standard and accelerated fractionation schemes. A good qualitative agreement with laboratory experience has been observed in all cases. Accordingly, the hypothesis that advanced simulation models for the in silico testing of tumor irradiation schemes could substantially enhance the radiotherapy optimization process is further strengthened. Currently, our group is investigating extensions of the presented algorithms so that efficient descriptions of the corresponding clinical (in vivo) cases are achieved.
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PMID:Modeling tumor growth and irradiation response in vitro--a combination of high-performance computing and web-based technologies including VRML visualization. 1175 34


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