Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0025202 (melanoma)
69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure to oxygen deprivation in vitro has been reported to cause drug resistance in CHO cells (Rice et al., 1986; PNAS 83, 5978) and enhancement of experimental metastatic (colonisation) ability of murine tumour cells (Young et al., 1988; PNAS 85, 9533). Both these studies also demonstrated the induction of a subpopulation of cells with excess DNA content. Since the micromilieu in tumours results in exposure of the tumour cells to conditions of acid pH and nutrient deprivation, as well as hypoxia, we have examined the effect of exposure to acidosis (pH 6.5) and glucose starvation on drug resistance, cellular DNA content and the experimental metastatic ability of KHT sarcoma and B16F1 melanoma cells. Cells were exposed to these conditions for 24 and 48 h and tested for resistance to methotrexate (MTX) or experimental metastatic ability either immediately following these exposures or after 24 or 48 h of recovery in normal growth medium. Both cell lines demonstrated an enhancement of colonisation potential, which was most marked when cells were injected after 48 h of exposure followed by a 24 or 48 h recovery period. Flow cytometric analysis demonstrated an increase in the fraction of KHT cells with excess DNA following both glucose starvation and acidosis we observed only a small increase in MTX resistance following acidic exposure of cells and no change following glucose starvation. Since both acidosis and glucose starvation are known to induce glucose regulated proteins (grp), a subset of the stress protein family, we studied the effect of treatment with another known inducer, 2-deoxyglucose. We found that this agent affected the metastatic efficiency of KHT cells in a manner similar to that observed following exposure to glucose starvation and acidosis. However, further studies are required to establish what role, if any, grp play in this effect. In conclusion this study shows that transient exposure of murine tumour cells to an acidic or glucose deprived environment can cause progression in terms of metastatic potential.
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PMID:Glucose starvation and acidosis: effect on experimental metastatic potential, DNA content and MTX resistance of murine tumour cells. 191 Dec 14

Rodent and human cells were tested for response to Lonidamine (LND) (1-(2,4 dichlorobenzyl) 1-indazol-3-carboxylic acid) combined with radiation or hyperthermia. Lonidamine exposure before, during, and after irradiation caused varying degrees of inhibition of potentially lethal damage (PLD) repair which was cell line dependent. In human glioma, melanoma, squamous cell carcinoma, and fibroblasts, LND exposure did not inhibit or only partially inhibited repair of potentially lethal damage. LND up to 100 micrograms/ml produced only a low level of toxicity in these cells and only slightly inhibited glucose consumption at the maximum concentration. In human glioma cells, LND treatment alone did not inhibit PLD repair, but when combined with hyperthermia treatment at moderate levels easily achievable in the clinic, there was complete inhibition of potentially lethal damage repair. These data suggest that LND effectiveness is cell type dependent. Combinations of LND, hyperthermia, and radiation may be effective in cancer therapy especially in tumors such as glioma in which repair of potentially lethal damage may be extensive.
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PMID:The effect of lonidamine (LND) on radiation and thermal responses of human and rodent cell lines. 199 36

The positron-emitting glucose analogue 18F-2-fluoro-2-deoxy-d-glucose (FDG) was evaluated for its accretion into the following subcutaneous human tumor xenografts in nude mice: B-cell lymphoma (Namalwa or Raji), ovarian carcinoma (HTB77), colon cancer (SW948), choriocarcinoma (BEWO), bladder cancer (UM-UC-2), renal cell carcinoma (UM-RC-3), neuroblastoma (Mey), melanoma (HTB63), and small cell lung carcinoma (NCI69). Two hours postinjection, tumor uptakes ranged from 0.027 (colon cancer) to 0.125% kg injected dose/g (melanoma); and was greater than 0.085 in the Namalwa lymphomas and the renal cell carcinomas. Tumor-blood ratios of up to 23:1 were seen 2 hours postinjection (melanoma) with a mean tumor-blood ratio for all tumors of 12.3 +/- 1.8. Uptake in the other tumors was intermediate. When evaluated, tumor uptake was slightly greater at 1 than at 2 hours postinjection, although target-background ratios were generally higher at 2 hours postinjection. This compound, FDG, may have broad applicability as a tracer for positron-emission tomographic imaging of many human malignancies.
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PMID:18F-2-deoxy-2-fluoro-D-glucose uptake into human tumor xenografts. Feasibility studies for cancer imaging with positron-emission tomography. 200 43

Since malignant tumors utilize more glucose than normal tissues, tumor uptake and autoradiographic imaging studies using the 14C-labeled glucose analog 2-deoxyglucose (DG) provide a useful preclinical system to determine if similar human tumors will image in vivo with positron emission tomography (PET) using 18F-labeled DG (FDG-PET). We studied B16 murine melanomas of increasing metastatic potential (F1, low; BL-6, intermediate; F10, high) as a feasibility study to determine the potential for human melanoma imaging using FDG-PET. Male C57BL-6 mice (50 g) were implanted sc with 1-mm3 fragments of B16 melanomas. Fourteen days later mice were injected ip with 1.25 muCi of [14C]DG. Sixty minutes later tumor (T) and gastrocnemius muscle (M) were harvested, solubilized, and counted for [14C]DG dpm/mg to estimate glucose utilization. Autoradiographic imaging was carried out similarly, using 2.0 muCi or [14C]DG with 30-day exposure of T and M tissue sections (20 microns thick) to X-ray film. The uptake of [14C]DG (expressed as dpm/mg; % injected dose/g; and tumor-to-muscle uptake ratios) was 6 to 10 times higher in tumors than in muscle tissue (P less than 0.001). All three melanoma cell lines imaged successfully with [14C]DG autoradiography. Tumor uptake of [14C]DG did not correlate with increasing metastatic potential. The experimental B16 murine melanomas F1, BL-6, and F10 extract glucose at higher rates than muscle tissue, a property necessary for successful PET imaging of cutaneous melanoma. The lack of correlation between glucose extraction and metastatic potential suggests that the demands for glucose during tumor growth and metastasis are not related. This is the first laboratory study to predict that human malignant melanoma will image with FDG-PET.
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PMID:[14C]deoxyglucose uptake and imaging in malignant melanoma. 205 77

MR imaging has been performed on malignant melanomas in vitro and in vivo. Changes of the water content in an enucleated malignant melanoma in vitro were followed by significant changes of the T1 and T2 values. In mice with implanted subcutaneous melanoma similar changes could be obtained after injection of glucose and fructose intraperitoneally. Malignant melanoma of the eye could be influenced in the same way in 10 consecutive patients after oral intake of glucose and fructose. The present study shows that the MR images may be significantly changed after a few hours by altered metabolism induced by glucose and fructose. It is anticipated that this is due to changes within the tumor leading to different water distribution. The finding may be of importance as a further help for diagnosing malignant melanoma of the eye.
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PMID:Changes in MR of malignant melanomas induced by glucose and fructose. A clinical and experimental investigation. 206 64

Three different biological properties--glucose metabolism, gallium imaging and antigen-antibody interaction--have been targeted to image human tumor xenografts implanted in nude mice. Seventy-two experiments were performed in 25 nude mice. Two types of human tumors were used: colorectal carcinoma SW 1116 and melanoma WM 9. Immunoscintigraphic studies produced the highest tumor sampling and confirmed earlier findings that F(ab')2 fragments generate better tumor images than whole antibodies.
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PMID:A comparison of 131I-labeled antibodies, 2-deoxy-2-[18F]fluoro-D-glucose and 68Ga-EDTA in the imaging of human tumor xenografts in nude mice. 211 Dec 98

The energy requirements via glycolytic pathways were directly measured in migrating tumor cells. Motility in the metastatic human melanoma cell line A2058, stimulated by insulinlike growth factor I (IGF-I), depends on glycolysis in the presence of glucose as its principal source of energy. Motility in glucose-free medium was 75% reduced and utilized mitochondrial respiration (inhibited by oligomycin). With increasing (physiologic) glucose concentrations, there was a dramatic shift to anaerobic glycolysis as the energy source and 93% elimination of the oligomycin inhibition of motility. Oxamate, an inhibitor of glycolysis, inhibited motility at all glucose concentrations. CO2 production from glycolysis and from the hexose monophosphate shunt was measured in migrating tumor cells. The time course and glucose-dose dependence of glycolytic CO2 production correlated directly with motility. In contrast, mitochondrial CO2 production was inversely related to glucose concentration. A monoclonal antibody for the IGF-I receptor inhibited both motility and glycolytic CO2 production, indicating that both processes are receptor mediated.
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PMID:Glycolysis as primary energy source in tumor cell chemotaxis. 217 62

Methods of single-tracer whole-body autoradiography (WBAR) have been developed in our laboratory which allow imaging and measurement of the zonal distribution of radioiodinated antibodies and their fragments within GW-39 colon carcinoma xenografts varying in size from large, cystic masses with necrotic cores to micrometastases. The whole-animal distribution of 90Y-labeled anti-carcinoembryonic antigen monoclonal antibody NP-2 was evaluated by WBAR in nude mice bearing s.c. implants of GW-39 colon cancer and revealed antitumor uptake specifically as well as significant accumulation of 90Y in the bones. Dual-tracer qualitative WBAR methods have also been applied in order to examine the biodistribution of labeled immunoglobulins in the GW-39 animal tumor model as a function of the underlying rapid cell proliferation index ([3H]-thymidine assay) in the same tumor. In addition, extension of the WBAR method was made to permit imaging of the biodistribution of 10B compounds in mice bearing Harding-Passey melanoma implants by using a track-etch procedure to produce alpha-particle WBAR. Further applications of single and multiple radionuclide WBAR are offered and discussed as an effective means of assessing the degree of penetration of immunoglobulins in tumors in which vascular patterns, local glucose metabolism, protein synthesis, and rapid cell proliferation indices may be characterized.
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PMID:Use of whole-body autoradiography in cancer targeting with radiolabeled antibodies. 229 39

Polyacrylamide surfaces covalently derivatized with quantifiable gradients of glycosides superimposed on a uniform adhesive background of coimmobilized Arg-Gly-Asp-containing adhesion peptide were synthesized. Substrate-directed cell redistribution (haptotaxis) was measured by seeding derivatized surfaces uniformly with B16F10 murine melanoma cells. After 4-32 hr, cells on gradients of N-acetylglucosamine (GlcNAc) redistributed markedly; higher cell densities were found at gel positions having a higher immobilized GlcNAc density. In contrast, cells seeded on otherwise identical gels having a uniform concentration of immobilized GlcNAc, or on gels having gradients of glucose or galactose, did not redistribute. Soluble inhibitors containing nonreducing terminal GlcNAc (but not those with terminal GalNAc or Gal) blocked redistribution on immobilized GlcNAc gradients. Redistribution was not affected by the presence or absence of serum in the medium. An affinity-purified antibody against beta-1,4-galactosyltransferase, a GlcNAc-binding protein reported to be expressed on B16F10 cell surfaces, attenuated GlcNAc-directed redistribution. When cells were seeded on surfaces derivatized with various uniform densities of immobilized GlcNAc coimmobilized with an invariant density of immobilized Arg-Gly-Asp-peptide, neither cell attachment nor proliferation rate were enhanced on the gels having a higher GlcNAc density. These data indicate that the redistribution on immobilized GlcNAc gradients was due to cell motility. Although gels derivatized with Arg-Gly-Asp-peptide alone supported strong B16F10 cell adhesion, surfaces derivatized with uniform high concentrations of GlcNAc did not. We conclude that cell recognition of substratum gradients that support, at best, weak adhesion (GlcNAc) on an otherwise uniform strongly adhesive background (Arg-Gly-Asp-peptide) may be sufficient to direct cell migration.
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PMID:Tumor cell haptotaxis on immobilized N-acetylglucosamine gradients. 235 16

Experience in roentgenovascular interventions was summed up for 14 patients aged 17 to 38 (11 men and 3 women). Indications for them were closed liver damages (6), life-threatening hemorrhage resulting from repeated operations for liver echinococcosis (1), primary hepatocellular cancer (4), liver hemangioma (2), metastases of melanoma to the liver (1). Hemostatic sponge, Gianturco's spiral, 60% glucose solution in combination with aminocaproic acid were used as embolizing agents. Complications were observed in one case. Gall bladder necrosis developed after distal-proximal embolization with a hemostatic sponge and spirals. Roentgenovascular occlusion of the hepatic artery can be used to stop dangerous hemorrhage, in inoperable liver tumors as one of the palliative methods in order to prolong the patient's life; its combination with other therapeutic methods will make it possible to extend indications for its use.
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PMID:[The efficacy of x-ray endovascular interventions in hepatic lesions and diseases]. 236 17


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