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)

Multiple malignant melanocytic lesions developed in a 54-year-old man 4 years after a primary malignant melanoma (Clark level IV) had been excised and 2 months after taking L-Dopa for Parkinsonism. Several of the recurrent lesions that showed junctional melanocytic components were considered primary melanomas and it was suggested that L-Dopa was responsible for malignant transformation of nevi and for rapid progression of the disease. The case was re-examined and on recent evidence it is likely that these lesions were epidermotropic metastases and that L-Dopa played no part in the progress of this unusual tumor.
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PMID:Epidermotropism in melanoma. 735 82

The secretion of calcitonin (CT) by thyroid C cells has been reported to be reduced by dopamine in vitro and by L-dopa in patients with medullary thyroid carcinoma (MTC). These results have suggested that dopa uptake ad decarboxylation to dopamine may play an inhibitory role in the control of CT secretion. We studied the effects of either L-dopa or bromocriptine, a dopamine agonist, on CT secretion in 11 patients with MTC. Seven patients had multiple endocrine adenomatosis type II (MEA II), 1 had MEA III, and 3 had sporadic MTC. Metastatic disease was confirmed in 8, was probable in 2, and was absent in 1. L-Dopa (500 mg orally) was given to 10 patients in 12 trials. Serum obtained serially for CT measurement RIA over a 4-h period showed a fall in 4 instances in 3 patients; there was no decrease in 7 patients. Absorption of L-dopa was confirmed by the finding of the expected rise in serum GH concentration in all nonresponders except 1. Bromocriptine administered in increasing doses (7.5-50 mg/day) for periods from 4-18 weeks in 5 patients with metastatic disease failed to lower the serum CT concentration in any patient. In 2 of 4 cases, pentagastrin-induced CT release was augmented during bromocriptine administration. These results show L-dopa suppression of CT secretion only in a minority of patients with MTC; the lack of response to bromocriptine suggessts that dopamine receptor stimulation by dopaminergic ergots does not inhibit CT secretion in this same group of patients.
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PMID:Effects of L-dopa and bromocriptine on calcitonin secretion in medullary thyroid carcinoma. 741 66

In the treatment of cutaneous melanoma, provisional therapeutic strategies have been designed to combat tumour load using T cells that are sensitized with peptides derived from melanoma autoantigens, such as glycoprotein 100 (gp100), melanoma antigen recognized by T cells 1 (MART-1 or MelanA), tyrosinase and tyrosinase-related protein 1 (TRP-1). We recently found that gp100, MART-1 and tyrosinase are heterogeneously expressed in human cutaneous melanoma (De Vries et al (1997) Cancer Res 57: 3223-3229). Here, we extended our investigations on expression of these immunotherapy candidate proteins to uveal melanoma lesions. Cryostat sections from 11 spindle-type, 21 mixed and epithelioid tumours and four metastasis lesions were stained with antibodies specifically recognizing gp100, MART-1, tyrosinase and TRP-1. In addition, we used the DOPA reaction to detect tyrosinase enzyme activity as a confirmation of the tyrosinase immunohistochemical results. High expression of gp100, MART-1 and tyrosinase was found in the uveal melanoma lesions: 80% of the lesions displayed 75-100% positive tumour cells. TRP-1 positivity was slightly less: approximately 65% of the lesions stained in the 75-100% positive tumour cell category. All uveal melanoma lesions were positive for the four markers studied, this being in contrast to cutaneous melanoma where 17% of the advanced primary lesions and metastases were negative. The presence of these antigens was a little lower in metastases. We conclude that uveal melanomas and their metastases express melanocyte-lineage immunotherapy candidate proteins very abundantly. Uveal melanomas differ in this respect from cutaneous melanoma, in which the expression of these immunotherapy antigens was much more heterogeneous. This makes uveal melanoma a suitable candidate tumour for immunotherapeutic approaches.
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PMID:High expression of immunotherapy candidate proteins gp100, MART-1, tyrosinase and TRP-1 in uveal melanoma. 982 Jan 72

Determination of blood tyrosinase mRNA by RT-PCR and markers of tyrosinase activity (L-DOPA/L-tyrosine ratio) by HPLC have been proposed as biological tools for the detection of metastases in melanoma patients. We prospectively evaluated their significance and clinical value in a group of 30 stage III (n = 10) and IV (n = 20) melanoma patients and one with melanosis of Dubreuilh. L-DOPA/L-tyrosine ratio was elevated in 30% of stage III, 41% of stage IV patients (range: 7.5-261.0 x 10(5)) and in melanosis of Dubreuilh (184.8) (reference values: 6-16 X 10(5)). One stage III and four stage IV melanoma patients were positive for tyrosinase mRNA. In stage IV patients, tyrosinase mRNA positivity was associated with disease progression (P<0.01). The presence of tyrosinase mRNA in blood is more related to clinical status than level of melanin precursors, which probably reflects tumor burden.
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PMID:Simultaneous analysis of tyrosinase mRNA and markers of tyrosinase activity in the blood of patients with metastatic melanoma. 1034 Apr 38

Positron emission tomography (PET) performed with various radiolabelled compounds facilitates the study of tumor biochemistry. If the tumor uptake of an administered tracer is greater than that of surrounding normal tissue, it is also possible to localize the tumor. In initial studies, 18F-labeled deoxyglucose (FDG) was attempted to visualize the tumors, since this tracer had been successfully used in oncology, reflecting increased glucose metabolism in cancerous tissue. However, this tracer was not to any significant degree taken up by the neuroendocrine tumors. Instead, the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with 11C was used and showed an increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was selective and the resolution so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. One problem was, however, the high renal excretion of the tracer producing streaky artifacts in the area of interest. Using the decarboxylase inhibitor carbidopa, given as peroral premedication, the renal excretion decreased 6-fold and at the same time the tumor uptake increased 3-fold, hence improving the visualization of the tumors. When patients were followed during treatment with PET using 5-HTP as a tracer, a > 95% correlation between changes in urinary 5-hydroxyindoleacetic acid (U-5-HIAA) and changes in the transport rate constant for 5-HTP was observed. Thus, PET can be used to monitor treatment effects. Elevation of U-5-HIAA is considered to be uncommon in endocrine pancreatic tumors (EPTs). Initially, 11C-labeled L-DOPA was attempted as another amine important in the APUD system. With L-DOPA about half of the EPTs, mainly functioning tumors, could be detected. Recently, 5-HTP was explored as a universal tracer also for EPT and foregut carcinoids, extending the PET-examination to both thorax and abdomen (whole-body PET-examination). With this method we were able to visualize small lesions in the pancreas and thorax (e.g. ACTH-producing bronchial carcinoids) not detectable by any other method including octreotide scintigraphy, MRI and CT. Several other tracers have been investigated, e.g. the monoamineoxidase (MAO-A) inhibitor harmine with promising results in non-functioning EPTs. We are currently exploring a wide range of biochemical systems, including enzymes and receptors, both for neurotransmitters and for peptides and proteins in in vitro assays with the potential to use some of the developed tracers for in vivo visualization and tumor biological studies. In conclusion, PET is a valuable tool in the diagnosis of neuroendocrine tumors. It can detect small lesions in the thorax and abdomen not detected by other methods, which has been of great value preoperatively in several cases. It detects more lesions in the liver and lymph nodes than other methods and furthermore, it can be used to monitor treatment effects.
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PMID:Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies. 1093 3

In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F-fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F-DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.
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PMID:18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels. 1120 54

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

Diagnostic imaging has played a major role in the evaluation of patients with bone metastases. The imaging modalities have included bone scintigraphy, computed tomography, magnetic resonance imaging, and most recently PET/CT, which can be performed with different tracers, including fluorodeoxyglucose (FDG), 18F-fluoride, 18F-choline (FCH), and 18F-DOPA (dihydroxyphenylalanine). For most tumors the sensitivity of FDG in detecting bone metastases is similar to bone scintigraphy; additionally it can be used to monitor the response to chemotherapy and hormonal therapy. 18F-Fluoride may provide a more sensitive "conventional" bone scan and is superior for FDG nonavid tumors, but, nevertheless, FDG in "early disease" often has clear advantages over 18F-fluoride. Although more data need to be obtained, it appears that FCH is highly efficient in preoperative management regarding N and M staging of prostate cancer once metastatic disease is strongly suspected or documented. For neuroendocrine tumors and in particular in medullary thyroid cancer, DOPA is similar to 18F-fluoride in providing high quality information regarding the skeleton. Nevertheless, prospective studies with large patient groups will be essential to define the exact diagnostic role of FCH and DOPA PET in different clinical settings.
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PMID:The role of fluorodeoxyglucose, 18F-dihydroxyphenylalanine, 18F-choline, and 18F-fluoride in bone imaging with emphasis on prostate and breast. 1635 97

Standard nuclear medical procedures, such as functional, blood-pool and colloid scintigraphy, play a minor role in the routine workup of liver tumors. However, these techniques are capable of assessing specific organ functions and frequently allow the diagnosis of unclear liver lesions. The sensitivity of scintigraphic procedures can be increased using tomographic imaging (SPECT), the specificity with the introduction of hybrid scanners such as SPECT/CT. Whole body positron emission tomography with 18F-fluoro-deoxy-glucose (FDG) in combination with CT scanning (PET/CT) represents one of the most sensitive imaging modalities for the detection of hepatic metastases and extrahepatic tumor manifestations. For the staging and follow-up of colorectal cancer, FDG-PET/CT represents a standard imaging modality. Metastases from neuroendocrine tumors can be detected using PET and specific tracers such as [68Ga]DOTATOC and [18F]DOPA. Molecular imaging with PET allows the quantification of metabolic processes which can be used for the assessment of an early response to treatment.
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PMID:[Nuclear medical diagnostics for liver tumors]. 1719 61

In the diagnostic assessment of medullary thyroid carcinoma (MTC), nuclear medicine imaging provides its contribution mainly in the postoperative work-up to detect residual or recurrent tumor. With respect to scintigraphy with gamma-emitter radiopharmaceuticals, positron emission tomography (PET) offers interesting perspectives owing to its higher image quality, spatial resolution and speed. Moreover, the recent developments of hybrid machines allow to obtain images that simultaneously hold both anatomic (computed tomography) and functional (PET) information with great impact on diagnostic efficacy. (18)F-fluoro-deoxyglucose ((18)F-FDG) is the most frequently used PET tracer in oncology. Preliminary reports of FDG-PET in MTC patients show encouraging results with a higher sensitivity in detecting local recurrent and metastatic disease when compared with single photon emission tracers. However, (18)F-FDG uptake depends on lesion size and to some extent on the grade of differentiation and biologic aggressiveness of the tumor; so FDG-PET seems useful mainly in patients with very high calcitonin levels and high progression rate. Like other neuroendocrine tumors, MTC is characterized by the presence of amine uptake mechanism and/or peptide receptors at the cell membrane allowing the clinical use of specific radiopharmaceuticals that reflect the different metabolic pathways of MTC, and in particular the synthesis, storage and release of hormones ((18)F-dihydroxyphenilalanine, (18)F-DOPA and (18)F-fluorodopamine, (18)F-FDA) and the expression of receptors ((68)Ga-labeled somatostatin analogs). These tracers are currently under investigation and will further improve the diagnostic approach of MTC.
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PMID:Role of PET in medullary thyroid carcinoma. 1838 54


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