Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glucose transporter of the human brain has been localized to endothelial cells expressing the blood-brain barrier, but little is known regarding its mechanism of induction or whether its expression is exclusively linked with restricted vascular permeability. We investigated glucose transporter expression by vessels in human astrocytic tumors and pulmonary metastases to the brain using immunohistochemical techniques. Vessels in 9 of 10 low-grade astrocytomas and 8 of 10 anaplastic astrocytomas were positive for glucose transporter. Glioblastoma vessels were transporter-positive in only 2 of 10 specimens. Vessels in all three metastatic tumors were negative for the glucose transporter. The decrease in transporter expression observed in higher-grade tumors occurred independently of increases in vascular permeability. In low-grade astrocytomas and glioblastomas transporter expression and contrast enhancement were inversely related, but vessels in 6 of 9 anaplastic astrocytomas were transporter-positive despite contrast enhancement. These findings suggest that separate mechanisms induce the glucose transporter and the permeability restrictions of the human blood-brain barrier. They also have potential implications for the therapy and prognosis of astroglial neoplasms.
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PMID:The glucose transporter and blood-brain barrier of human brain tumors. 217 29

The expression of the glucose transporter protein, GLUT 1, in endothelial cells of microvessels within and around hematogenous metastases of the human brain was investigated by immunohistochemistry using a polyclonal antibody raised against the carboxyl terminus of the transporter molecule. The metastases were obtained from 18 autopsy cases with pulmonary carcinomas. Endothelial cells of controls without evidence of brain pathology showed a strong immunoreactivity, indicating that the antigenic sites of the glucose transporter remained in the postmortem material. The endothelial cells of microvessels around the metastases did not show any changes with regard to expression of the glucose transporter. However, in 14 of the 18 tumor cases, microvessels located in the metastases did not express the transporter. Our results indicate that in human cases of brain metastases functional changes with regard to glucose transport occur within the metastases rather than in the peritumoral region.
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PMID:Vascular expression of glucose transporter in and around hematogenous metastases of the human brain. Immunohistochemical observations. 864 69

The brain is an important site of hematogenous metastases from malignant tumors in other organs. The effects on the brain is a combination of tissue destruction induced by invading tumor cells and reactive alterations occurring around the metastases. This review focuses on neuropathological changes around hematogenous metastases of the human brain. The peritumoral brain parenchyma shows structural and functional changes of the intracerebral microvessels and edema. The endothelial cells of peritumoral microvessels express glucose transporter protein (GLUT 1) in the same way as the normal brain. Reduction in immunostaining to GLUT 1 may occur in the microvessels located within the metastases. This would indicate abnormalities of the blood-brain barrier in tumor vessels but normal barrier function in the peritumoral region. Reactive astrocytes and activated microglial cells are both involved in the process of peritumoral gliosis. Activated glial cells produce numerous biological active compounds including endothelin-1 which after release from such cells can influence the structure and function of the peritumoral brain tissue. Lesions of oligodendrocytes and edema may be implicated in myelin degeneration. Finally, metastases will induce axonal and neuronal injuries as indicated by a recent study on expression of beta-amyloid precursor protein (beta APP) in reactive axonal swellings.
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PMID:Hematogenous metastases of the human brain--characteristics of peritumoral brain changes: a review. 926 44

The expression of 4 thyroid tissue-specific genes [Na+/I- symporter (NIS), thyroid peroxidase (TPO), thyroglobulin (Tg), TSH receptor (TSH-R)] as well as of the glucose transporter type 1 (Glut1) gene was analyzed in 90 human thyroid tissues Messenger ribonucleic acids were extracted from 43 thyroid carcinomas (38 papillary and 5 follicular), 24 cold adenomas, 5 Graves' thyroid tissues, 8 toxic adenomas, and 5 hyperplastic thyroid tissues; 5 normal thyroid tissues were used as reference. A kinetic quantitative PCR method, based on the fluorescent TaqMan methodology and real-time measurement of fluorescence, was used. NIS expression was decreased in 40 of 43 thyroid carcinomas (10- to 1200-fold) and in 20 of 24 cold adenomas (2- to 700-fold); it was increased in toxic adenomas and Graves' thyroid tissues (up to 140-fold). TPO expression was decreased in thyroid carcinomas, but was normal in cold adenomas; it was increased in toxic adenomas and Graves' thyroid tissues Tg expression was decreased in thyroid carcinomas, but was normal in the other tissues. TSH-R expression was normal in most tissues studied and was decreased in only some thyroid carcinomas. In thyroid cancer tissues, a positive relationship was found between the individual levels of expression of NIS, TPO, Tg and TSH-R. No relationship was found with the age of the patient. Higher tumor stages (stages >I vs stage I) were associated with lower expression of NIS (P = 0.03) and TPO (P < 0.01). Expression of the Glut1 gene was increased in 1 of 24 adenomas and in 8 of 43 thyroid carcinomas. In 6 thyroid carcinoma patients, 131I uptake was studied in vivo; NIS expression was low in all samples; 3 patients with normal Glut-1 gene expression had 131I uptake in metastases, whereas the other 3 patients with increased Glut-1 gene expression had no detectable 131I uptake. In conclusion, this study shows 1) a reduced expression of NIS gene in most hypofunctioning benign and malignant thyroid tumors; 2) a differential regulation of the expression of thyroid-specific genes; 3) an increased expression of Glut-1 gene in some malignant tumors that may suggest a role for glucose derivative tracers to detect in vivo thyroid cancer metastases by positron emission tomography scanning.
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PMID:Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. 1048 92

Hypoxic tumors are known to be more malignant, to be more likely to metastasize, and to have a poor prognosis. They are also radio- and chemoresistant. For this reason, it is desirable that a clinically useful marker of hypoxia is found, so that treatment with radiotherapy and bioreductive chemotherapy can be rationally applied to individual patients. Glut-1 is a facilitative glucose transporter that is ubiquitously expressed in normal tissue and expressed at higher levels in a number of tumors. Its potential as an intrinsic hypoxia marker arises from its dual control in hypoxic conditions by reduced oxidative phosphorylation and the hypoxia-inducible factor (HIF-1) oxygen-sensing pathway. Eppendorf histography, by virtue of its proven predictive qualities, is a suitable gold standard used in our laboratory to validate new hypoxia markers. Using this technique, pretreatment pO(2) measurements were performed on 54 patients with locally advanced cervical carcinoma. Then, immunohistochemical staining was used to detect Glut-1 protein in individual tumor biopsy sections. Both measurements were made before initiation of treatment. By using a low-tech scoring system, pO(2) was found to correlate weakly with Glut-1 score (r = 0.28; P = 0.04). To extrapolate this correlation to the known adverse effects of tumor hypoxia on outcome, we examined the prognostic significance of Glut-1 staining in a retrospective series of 121 patients. An absence of Glut-1 significantly increased the likelihood of metastasis-free survival (P = 0.022) but did not significantly effect disease-free or recurrence-free survival. These findings suggest that Glut-1 be an intrinsic marker of hypoxia that can easily be applied in a clinical setting.
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PMID:Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix. 1130 43

Positron emission tomography (PET) supplies a range of labeled compounds to be used for the characterization of tumor biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow up, and clinical research. The first routinely used PET tracer in oncology, (18)F-labeled deoxyglucose (FDG), was successfully used for diagnosis of cancer, reflecting increased expression of glucose transporter in cancerous tissue. This tracer, however, usually does not show sufficient uptake in well-differentiated tumors such as neuroendocrine tumors. We developed a tracer more specific to neuroendocrine tumors-the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with (11)C-and demonstrated increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was so selective and the resolution was so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. To further improve the method, especially to reduce the high renal excretion of the tracer producing streaky artifacts in the area of interest, we introduced premedication by the decarboxylase inhibitor carbidopa, leading to a six-fold decreased renal excretion while the tumor uptake increased three-fold, hence improving the visualization of the tumors. (11)C-labeled l-DOPA was evaluated as an alternative tracer, especially for endocrine pancreatic tumors, which usually do not demonstrate enhanced urinary serotonin metabolites. However, only half of the EPTs, mainly functioning tumors, could be detected with l-DOPA. Instead 5-HTP seems to be a universal tracer for EPT and foregut carcinoids. With new, more sensitive PET cameras, larger field of view and procedures for whole-body coverage, the PET examination with 5-HTP is now routinely performed as reduced whole-body PET examinations with coverage of the thorax and abdomen. With this method we have been able to visualize small neuroendocrine lesions in the pancreas and thorax (e.g., ACTH-producing bronchial carcinoids) not detectable by any other method, including octreotide scintigraphy, MRI, and CT. Another tracer, the 11beta-hydroxylase inhibitor, metomidate labeled with (11)C, was developed to simplify diagnosis and follow-up of patients with incidentalomas. A large series of patients with incidentally found adrenal masses have been investigated and so far all lesions of adrenocortical origin have been easily identified because of exceedingly high uptake of (11)C-metomidate, whereas noncortical lesions showed very low uptake. In addition, adrenocortical cancer shows high uptake, suggesting that this PET tracer can be used for staging purposes.
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PMID:The role of PET in localization of neuroendocrine and adrenocortical tumors. 1238 51

This review deals with the current, well-established indications for two-(18F)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scanning in patients with gastrointestinal cancers. FDG-PET is a non-invasive, functional imaging technique. FDG exploits the native glucose transporter to enter the cell. Since many tumours have enhanced glucose uptake, FDG is readily accumulated in malignant cells and can be detected by a PET camera. FDG-PET has been established as an important diagnostic tool in clinical oncology. This review deals with the current, well-established indications for FDG-PET scanning in patients with gastrointestinal cancers. In the current practice, FDG-PET is most commonly used to stage oesophageal carcinoma, to detect and stage recurrence of colorectal carcinoma and to differentiate between benign and malignant pancreatic lesions. The benefit of FDG-PET scanning in patients with oesophagus carcinoma is best established in stage IV disease, as the diagnostic accuracy to detect metastatic disease is higher compared to the combination of computed tomography (CT) and endoscopic ultrasound (EUS). In patients with a history of colorectal carcinoma, FDG-PET scanning is particularly effective in diagnosing recurrent disease, especially in those with a rising carcinoembryonic antigen without a suspect lesion on conventional imaging. Large series have indicated that the sensitivity and specificity for detecting recurrent colorectal carcinoma are in the range of 87%-100% and 66%-100%, respectively. Equally, FDG-PET has a high sensitivity (68%-96%) and specificity (78%-100%) in detecting pancreatic carcinoma in patients with a suspicious-looking pancreatic mass on CT scan. Lastly, we focus on the use of FDG-PET as a modality for early monitoring of treatment response in patients with gastrointestinal stromal cell tumours. Without doubt, future developments will further establish the diagnostic role of the FDG-PET scan in the care of patients with gastrointestinal cancers.
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PMID:FDG-PET scanning in the diagnosis of gastrointestinal cancers. 1569 55

Glucose transport, mediated by proteins expressed from the glucose transporter genes, plays an essential role in cellular metabolism. Increased uptake of glucose compared to cells in normal tissue is a defining characteristic of malignant cells. This has been the basis for positron emission tomography imaging of thyroid tumor metastases using fluorodeoxyglucose uptake. Despite this key difference between tumor and normal cells, the mechanism which mediates increased glucose uptake is poorly understood. Several research studies have assessed the expression of different glucose transporter (GLUT) proteins and expression of the genes which code for them in thyroid tissues. While no consensus exists on the specifics of which GLUT genes or proteins are expressed, a picture has emerged that a single specific transporter, GLUT1, is expressed at higher levels in thyroid carcinomas compared to a variety of normal and nonmalignant forms of thyroid disease. Greater levels of GLUT1 expression may be associated with poorer prognosis. Experiments in established thyroid carcinoma cells lines may provide useful insights into glucose transport in the thyroid. Thyroid cells show increased glucose uptake in response to thyroid-stimulating hormone (TSH), but expression of GLUT genes does not appear to be significantly affected by TSH suggesting TSH affects glucose uptake by affecting GLUT localization/ translocation rather than through increased GLUT gene expression. Improving technologies are providing a stronger foundation for detailed analyses of glucose transporters in thyroid to better elucidate the mechanisms by which these genes and proteins are regulated in normal and pathogenic tissue.
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PMID:Glucose transporters in the thyroid. 1602 20

We, herein, explore the added aspect of FDG-PET to investigate an I-131 scan negative for differentiated thyroid carcinomas (DTCs), namely the identification of previously unsuspected second primary malignancies. We present 2 cases of DTC, showing metastatic lesions in the liver and the lungs but showing no I-131 uptake and hence was initially thought to be due to dedifferentiation. FDG-PET was performed as a part of a study to prospectively evaluate its usefulness in "noniodine concentrating metastases" of DTC and to look into the validity of the traditionally described "flip-flop" between I-131 whole-body scan (reflecting the sodium-iodide symporter status in the tumor) and FDG-PET (reflecting the glucose transporter status in the tumor). In addition to the uptake in the metastatic sites, FDG-PET demonstrated unusually intense foci of hypermetabolism in the gut and the right kidney. These were subsequently found to harbor clinically silent coexisting second primary malignancies at those sites giving rise to hepatic and pulmonary metastases. Thus FDG-PET, in both these cases, provided the correct explanation for the absence of radioiodine uptake in the metastatic sites, which were otherwise thought to be due to the loss of differentiation of DTC. This role of FDG-PET in incidentally detecting a coexisting additional primary malignancy giving rise to extensive metastases is relatively unexplored and adds a new dimension to its routine application of a metastatic survey in so-called noniodine avid thyroid carcinoma, which can have a significant bearing on subsequent patient management.
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PMID:Detection of unsuspected metachronous second primary malignancy giving rise to supposed "non-iodine avid metastasis" in differentiated thyroid carcinoma. 1766 46

Perineuriomas are usually benign soft-tissue tumors that arise from perineurial cells of the peripheral nerve sheath. Low-grade malignant perineurioma is a rare type of perineurioma, presenting with infiltrative growth, low mitotic activity, and a lack of necrosis. This report describes a case of low-grade malignant perineurioma in a 60-year-old man who presented with a growing tumor on the dorsal side of his left wrist. The tumor was surgically excised and showed no adhesion to the surrounding muscle and no continuity with nerves. There was no evidence of recurrence or metastases 12 months after surgery. Histology indicated that the tumor contained hypercellular and hypocellular areas with spindle-shaped cells proliferating in storiform patterns or perivascular whorling. There was moderate infiltrative growth into the surrounding tissue. There was an evident central infarction but no coagulative necrosis. Mitotic figures were observed at 5/10 high-power fields. On immunohistochemistry tumor cells were found to be positive for epithelial membrane antigen, glucose transporter protein 1, and claudin-1. Approximately 18.4% of tumor nuclei were labelled for Ki-67. Interphase fluorescence in situ hybridization on paraffin sections indicated a loss of chromosome 13. This suggests that chromosome 13 abnormalities could also be involved in perineurioma with low-grade malignant potential.
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PMID:Low-grade malignant soft-tissue perineurioma: interphase fluorescence in situ hybridization. 1884 38


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