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

Prostaglandins and serotonin are vasoactive compounds with profound effects on the gastrointestinal tract. Both cause inhibition of gastric acid secretion (although serotonin stimulates gastric pepsin secretion), stimulation of intestinal motility, and conversion of small intestinal mucosa from absorption to secretion of water and electrolytes. Their effects on pancreatic and biliary function are still not clear. Although prostaglandins appear to elicit their effects primarily by a paracrine mode of action, and serotonin is primarily a neurotransmitter (neurocrine), it is clear that even under normal conditions both can function as humoral agents. For example, we have shown that serotonin plays a physiologic role as a humoral inhibitor of gastric acid secretion. However, the effects of these agents become more pronounced in patients with humorally mediated diarrheogenic syndromes. Serotonin (and related indoles, particularly 5-hydroxytryptophan) has been firmly implicated as a cause of diarrhea in patients with carcinoid syndrome; our recent studies suggest that the diagnosis can be more effectively made by measuring circulating immunoreactive serotonin concentrations than urinary excretion of 5-HIAA; that some circulating serotonin escapes hepatic inactivation and, thus, large intestinal tumors can cause carcinoid syndrome in the absence of hepatic metastases; and that large amounts of serotonin are produced by some noncarcinoid diarrheogenic tumors, including medullary carcinomas of the thyroid and tumors associated with the WDHA syndrome. A large number of tumors of probable neural crest origin, including medullary thyroid carcinoma, carcinoids, and tumors associated with the WDHA syndrome, secrete large amounts of prostaglandins, particularly PGE2. The clinical response of at least some of the patients harboring these tumors to inhibitors of prostaglandin synthesis (particularly indomethacin) suggests that prostaglandins play a role in the etiology of these diarrheogenic syndromes.
 ...
PMID:Prostaglandins and serotonin: nonpeptide diarrheogenic hormones. 39 Aug 99

A case of primary carcinoid tumor of the right testis with metastases to the cervical and thoracic vertebrae and epidural is reported. A 53-year-old man was first recognized as being with dysthesia of the left arm and shoulder in April 1986. In June, 1987, he was admitted to the Neurology service, complaining of sudden occurrence of abasia. Myelography and computerized tomography demonstrated an epidural mass and several high density areas in the vertebral bodies of Th1 and Th2. The patient underwent laminectomy from C7 to Th2. At operation, the neurosurgeons noticed a tumor mass in the right scrotum and requested our consultation. Thus right high orchiectomy was performed. Pathological examination including Grimerius' and Fontana-Masson's stain revealed carcinoid tumor of the right testis associated with metastases to the spinal column. Postoperatively, tumor maker studies revealed elevation of blood 5-hydroxytryptophan and marked increase of urinary 5-hydroxy-indoleacetic acid excretion. They showed remarkable decreases after a course of PVB chemotherapy. The patient has been under our observation as an out-patient for the past 27 months with metastases. This is the first case of primary carcinoid tumor of the testis with metastases so far reported in the domestic literature.
 ...
PMID:[Primary carcinoid tumor of the testis with metastasis to the upper vertebrae. Report of a case]. 189 29

A 67-year-old man presented with a pulmonary atypical carcinoid tumor with marked elevation of the serum alpha-fetoprotein (AFP) level to 181,000 ng/ml and no hepatic metastases. Immunohistochemistry revealed AFP-positive fine granules, sparsely distributed in some cells. The proportion of the concanavalin A nonbinding subfraction was 33.7%. Light microscopy revealed hyaline globules within or outside the clear and reticular cytoplasm of a few cells. These were ultrastructurally electron-dense materials similar to the hyaline bodies observed in yolk sac tumors. The Grimelius silver method stained only a few cells and very few cells showed a positive Masson-Fontana reaction. Electron microscopy revealed secretory granules measuring 220 nm on the average in scattered cells. Immunohistochemical studies showed 5-hydroxytryptophan in many cells and 5-hydroxytriptamine or serotonin in only a few cells. As for polypeptide hormones, gastrin was detected and in autopsy specimens carcinoembryonic antigen (CEA) immunoreactive cells were observed. Past case reports on the coexistence of carcinoid tumors and adenocarcinomas in the digestive tract suggest that the tumor cells in our case are also derived from primitive or stem cells of endodermal origin and expressed unusual differentiation in the course of treatment.
 ...
PMID:Pulmonary atypical carcinoid tumor with marked alphafetoprotein production and features of an adenocarcinoma differentiation. 246 82

Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.
 ...
PMID:Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors. 768 63

Position emission tomography (PET) was performed on two patients with hormone-refractory prostatic adenocarcinoma in order to characterize the mechanism behind an earlier observed increased uptake of tracer hydroxytryptophan (5-HTP) in bone metastases. The osseous metastases were investigated with 5-hydroxytryptophan, radio-labelled with 11C in the carboxyl group (5-HTC), and with 5-HTP in order to elucidate in vivo the presence of hydroxytryptophan decarboxylation. An increased uptake, measured as standard uptake value (SUV), in the metastatic lesions was observed using 5-HTP. The uptake varied between lesions. Using 5-HTC a corresponding uptake was observed. The time-activity rates were similar. The congruence in uptake patterns between 5-HTP and 5-HTC in the investigated lesions, demonstrates that decarboxylation of 5-hydroxytryptophan to serotonin is not a dominant factor in the uptake. It was concluded that 5-HTC could be used in vivo to investigate the chemical event of decarboxylation of 5-hydroxytryptophan and provide information about characteristics in metastatic lesions.
 ...
PMID:PET with hydroxytryptophan as tracer in hormone-refractory prostatic adenocarcinoma: evaluation of decarboxylation in vivo. 942 38

A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MelmAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1-5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.
 ...
PMID:Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors. 958 30

In three patients with carcinoid liver and/or lymph node metastases, we studied the process of tumor tracer uptake and decarboxylation by means of positron emission tomography (PET) using 5-hydroxy-L-tryptophan (5-HTP) 11C-labeled in the beta-position (HTP) and later the same day with 5-HTP 11C-labeled in the carboxyl group (HTC). With HTP, in which the 11C-label follows the molecule through decarboxylation to form 11C-serotonin, a high tumor accumulation of the tracer was found. With HTC, in which the label is rapidly eliminated from the tissues as 11CO2 if decarboxylation takes place, there was virtually no uptake by the tumors. By utilizing data from PET scanning with both tracers, we could quantify the decarboxylation rate and tissue accumulation of [11C]-serotonin and hence the enzymatic action of aromatic amino acid decarboxylase.
 ...
PMID:Demonstration of [11C] 5-hydroxy-L-tryptophan uptake and decarboxylation in carcinoid tumors by specific positioning labeling in positron emission tomography. 1075 43

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.
 ...
PMID:Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies. 1093 3

The authors briefly review radiopeptides currently approved for use in the United States. They present a short review of the peptide somatostatin's actions and also note the five somatostatin receptors (SSTRs) to which the peptide and its synthetic analogs octreotide, lanreotide, and vapreotide bind. The many conditions besides neuroendocrine tumors having SSTRs are listed. Labeled octreotide and the other two analogues have a strong affinity for SSTR2 and SSTR5, which thereby produce positive imaging. The various neuroendocrine tumors best imaged by somatostatin receptor scintigraphy (SRS) are discussed, and the exceptions (insulinoma and medullary thyroid carcinoma) are noted to be seen better with labeled VIP and (99m)Tc-dimethylsuccinic acid (DMSA), respectively. SRS and VIP receptor scintigraphy are also noted to image many nonneuroendocrine tumors, which often have appropriate receptors. Several of the currently emerging and very effective new imaging techniques are described. These include (99m)Tc-DMSA for medullary thyroid carcinoma, (18)F dihydroxyphenylalanine positron emission tomography, and C(11) 5-hydroxytryptophan positron emission tomography scanning for all neuroendocrine tumor, but especially carcinoid tumor, metastases. The special role of SRS in identifying gastric carcinoid tumors in hypergastrinemic patients is reviewed. Various pitfalls in interpreting SRS are presented and receptor-enhancing techniques described. Besides use of SRS (mainly Octreoscan, Mallinckrodt Medical, St. Louis, MO) only for detecting and localizing primary tumors and metastases for staging, there are many additional special uses for clinical management of SRS-positive tumors. These include the intraoperative use of the handheld gamma-detecting probe. A brief enumeration is given of the most promising of other non-SST G-protein-coupled receptors and ligands currently under development. Finally, we have posed a number of questions for which answers are needed in the immediate future to facilitate better imaging. Extrapolations of current knowledge and experience with radiolabeled peptide pharmaceutical imaging are converted to reasonable speculations of anticipated future developments in this field.
 ...
PMID:Radiolabeled peptides in diagnosis and tumor imaging: clinical overview. 1196 2

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.
 ...
PMID:The role of PET in localization of neuroendocrine and adrenocortical tumors. 1238 51


1 2 Next >>