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)

We have used the gastrinoma syndrome to examine the effects of SMS. Acutely, SMS decreased acid secretion and restored the BAO/MAO to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized. Treatment for up to 2 years with SMS controlled symptoms, suppressed serum gastrin, and suppressed acid secretion. Treatment for 1 year or longer decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted for 48 hours after withdrawal of SMS. SMS treatment arrested progression of tumor growth only in patients in whom there was a reduction in gastrin and gastric acid secretion. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 24 months did not inhibit tumor growth or decrease gastrin levels. In those patients in whom a reduction in the blood flow to liver tumors was shown angiographically, there was a progressive improvement in hormone secretion and in tumor size in the ensuing year of treatment, suggesting that a major target of SMS is that vascular supply of the tumors. Tumors shown to produce peptides other than gastrin, for example ACTH, were found to be markedly resistant to the action of SMS and continued to grow in an unbridled manner.
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PMID:The use of somatostatin analog in gastroenteropancreatic tumors other than carcinoid. 240 20

We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels.
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PMID:Somatostatin analogue (SMS 201-995) in patients with gastrinomas. 290 62

The activities of 13 enzymes in 40 carcinomas of the large bowel have been studied using histochemical techniques. Five enzymes-non-specific esterase, monoamine oxidase, succinate dehydrogenase, cytochrome oxidase, and acid phosphatase-commonly show much less activity in the tumours than in adjacent normal colon. The tumours have been classified based upon the number of enzymes which show marked reduction in activity in each tumour (types 1-5). The enzyme histochemical type and the size of the tumours have been jointly correlated with the presence of lymph node metastasis. Small type 1 or 2 tumours do not appear to be associated with metastatic disease. Small type 5 tumours were commonly associated with secondary carcinoma in the lymph nodes. Large tumours (greater than 25 sq cm surface area) of any histochemical type were frequently associated with lymph node metastasis. Discussion of the possible reasons for these findings and their clinical significance is presented.
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PMID:The significance of enzyme histochemical patterns in carcinomas of the large intestine in man. 435 9

Neuroblastomas are malignant tumors derived embryonically from the neural crest. Biological diagnosis relies on assay of urinary excretion of homovanillic acid (HVA), vanillylmandelic acid (VMA), and dopamine (DA). Spontaneous regression of these neoplasms has been reported by numerous investigators. The authors report the case of a child with neuroblastoma that illustrates the relationship between catecholamine metabolites and tumor maturation. At 1 month of age, this infant presented an adrenal neuroblastoma with multiple metastases (stage IV); the initial histological diagnosis based on examination of cutaneous metastases was neuroblastoma. At the age of 6 months, after chemotherapy, the primary tumor was resected; hepatic metastases were discovered at laparotomy. The histological diagnosis for all lesions was highly differentiated, mature ganglioneuroma-like tissue. The main biochemical abnormality at the time of diagnosis was an elevation in normetanephrine (NMN). HVA was only slightly increased but rose progressively during chemotherapy; it dropped back to normal levels after the sixth course. This case illustrates the potential benefits of separate assays of urinary methylated catecholamine metabolites for biochemical diagnosis and therapeutic management of neuroblastoma in addition to assays of HVA, VMA, and DA. Case findings suggest existence of a transformation process with maturation of the tumor involving enzymatic regulation and expression of MAO.
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PMID:Urinary excretion of methylated catecholamine metabolites in a child with neuroblastoma maturing into ganglioneuroma. 749 13

Carcinoid is the most common endocrine digestive tumor. The carcinoid syndrome resulting from the variety of amines and peptides produced by this tumor is usually apparent once there are metastases to the liver. Tumors with direct systemic venous drainage seldom produce a carcinoid syndrome without the presence of liver metastasis. This may occur because the hormone escapes the normal metabolic pathway (monoamine oxidase) in the liver. The most significant and important advance in diagnosis for tumor localization has been the introduction of scintigraphy using 111In-labeled octreotide. Current management of carcinoid syndrome should consider the spontaneous course of the disease and the severity of clinical symptoms, and includes different therapeutic options as hepatic resection, chemoembolization, medical treatment with the long-acting analogues of somatostatin and liver transplantation.
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PMID:[Carcinoid syndrome: advances in diagnosis and treatment]. 1008 88

The Zollinger-Ellison syndrome is characterized pathophysiologically by a significant hypergastrinemia derived from a gastrin-secreting neuroendocrine tumor with a primary location in the pancreas or duodenum. Chronic hypergastrinemia in turn triggers gastric acid hypersecretion yielding in chronic or recurrent or refractory peptic ulcer disease and/or chronic diarrhea. One half of patients with ZES will have distant metastases in the liver by the time the diagnosis is established and one half of all patients with ZES will experience chronic diarrhea as chief complaint rather than peptic ulcer-related symptoms and signs. Gastrinomas have been reported to either manifest sporadically or to occur in conjunction with the genetic background of the MEN-I syndrome. Diagnosis is based on the patients history which is typically characterized by recurrent episodes of peptic ulcer disease or by severe reflux esophagitis and/or diarrhea or by acid-related symptoms which fail to respond to standard treatment regimens. Upper gastrointestinal tract endoscopy will provide evidence for peptic ulcer disease in anatomical regions located aborally the duodenal bulb within the descending part of the duodenum or even farther distally within the jejunum. Peptic ulcers frequently occur in groups indicating some substantial acid hypersecretion. A gastric pH > 2 is mutually exclusive for ZES. Increased serum gastrin levels confirm the diagnosis biochemically. Gastrin secretion can be determined in the basal state or following stimulation with secretin or calcium. High sensitivity and specificity for the diagnosis of ZES is provided by determining the ratio of basal versus pentagastrin-stimulated gastric acid secretion: The ratio of BAO / MAO > 0.6 is highly specific for gastrinoma. To localize the gastrin-secreting tumor computer-assisted tomography, endoscopic ultrasound, and somatostatin receptor scintigraphy provide useful help but most recently, endoscopic ultrasound with high resolution transducers appear to improve preoperative site localization. If modern imaging techniques fail to elucidate the site of the tumor, intraoperative diaphany may help to detect gastrinomas within the duodenal wall. Definitive treatment will only be achieved by total surgical resection of the gastrin-producing tumor in the pancreas or duodenum including dissection of the regional lymph nodes. Control of symptoms will have to be achieved by administration of highly potent proton pump inhibitors in up to 2-3-fold increased standard doses to inhibit gastric acid hypersecretion. Elevation of gastric pH > 4 will be the therapeutic target to protect the mucosa of the upper gastrointestinal tract. Basal acid output should be reduced to less than 10 mEq H(+) per hour which requires administration of highly potent proton pump inhibitors with a recommended starting dose of 60 mg omeprazole equivalents per day.
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PMID:Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. 1798 90

Selective up-regulation of the mRNA of LOXL4, a member of the LOX matrix amine oxidase family, significantly correlated with lymph node metastases and higher tumour stages in head and neck squamous cell carcinomas (HNSCC). To evaluate the diagnostic and prognostic value of the protein we produced an antibody specific for LOXL4 and assessed the expression in 317 human HNSCC specimens. The LOXL4 protein was detected in 92.7% of primary tumours, in 97.8% of lymph node metastases and in affected oral mucosa with high-grade dysplasia, but was absent in various non-neoplastic tissues of the head and neck. TNM categories and overall survival did not link to grades of immunoreactivity. Studies in cultured primary hypopharyngeal HTB-43 carcinoma cells detected perinuclear and cell surface expression of LOXL4, but no nuclear localisation. Therefore, its interactive SRCR-domains and catalytic activity combined with tumour cell specific expression and cell surface associated location indicate multiple functions in tumour cell adhesion and interactions with the extracellular matrix. Our data suggest that LOXL4 is useful both as tumour marker and target in the treatment of HNSCC.
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PMID:LOXL4 is a selectively expressed candidate diagnostic antigen in head and neck cancer. 1849 40

Carcinoid tumour tissue from two patients was removed from lymph node metastases during surgery. Under sterile conditions the cells were prepared for tissue culture, and grew in clusters for a period of 3-4 weeks. Using immunofluorescence the neoplastic cells were investigated for the presence of various antigens characteristic for other amine handling cell types (adrenal medullary cells, adrenergic neurons, endocrine cells); thus, the presence of catecholamine synthesizing enzymes, 5-HT, MAOs, neuron specific enolase, synaptophysin, chromogranin A and neurofilaments was demonstrated in the carcinoid tumour cells. Also ?-adrenoceptor-like immunoreactivity was present, as was NGF-like immunoreactivity. The amine handling properties were investigated by measuring spontaneous and drug-induced release of 5-HT into the culture medium. Reserpine enhanced the 5-HT levels in the medium, and this was further potentiated by the MAO-inhibitor nialamide or the membrane pump blocker imipramine. The 5-HT synthetic capacity was pronounced, as indicated by measuring the cumulative 5-HT release into the medium after frequent changes of media (at 1 h intervals). If media were changed every 4 d 5-HT levels reached a saturation. In the fluorescence microscope the effect of reserpine in depleting the 5-HT stores was slow; at 24 h of reserpine presence in the media many cells still contained strong 5-HT fluorescence (partly with an agranular appearance) while some cells appeared depleted. Thus, there was a striking difference between individual cells in the reaction to reserpine. ?-Adrenoceptor activation with isoprenaline released 5-HT into the medium in a dose-dependent manner, not blocked by propranolol. This indicates unusual properties of the ?-adrenoceptor, also demonstrated to be present on these neoplastic cells by immunocytochemistry.
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PMID:Amine handling properties of human carcinoid tumour cells in tissue culture. 2050 34

Prostate cancer is highly heterogeneous in nature; while the majority of cases are clinically insignificant, some cases are lethal. Currently, there are no reliable screening methods for aggressive prostate cancer. Since most established serum and urine biomarkers are glycoproteins secreted or leaked from the diseased tissue, the current study seeks to identify glycoprotein markers specific to aggressive prostate cancer using tissue specimens. With LC-MS/MS glycoproteomic analysis, we identified 350 glycopeptides with 17 being altered in aggressive prostate cancer. ELISA assays were developed/purchased to evaluate four candidates, that is, cartilage oligomeric matrix protein (COMP), periostin, membrane primary amine oxidase (VAP-1), and cathepsin L, in independent tissue sets. In agreement with the proteomic analysis, we found that COMP and periostin expressions were significantly increased in aggressive prostate tumors while VAP-1 expression was significantly decreased in aggressive tumor. In addition, the expression of these proteins in prostate metastases also follows the same pattern observed in the proteomic analysis. This study provides a workflow for biomarker discovery, prioritization, and evaluation of aggressive prostate cancer markers using tissue specimens. Our data suggest that increase in COMP and periostin and decrease in VAP-1 expression in the prostate may be associated with aggressive prostate cancer.
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PMID:Identification, prioritization, and evaluation of glycoproteins for aggressive prostate cancer using quantitative glycoproteomics and antibody-based assays on tissue specimens. 2371 68

Lysyl oxidase is an extracellular matrix, copper - dependent amine oxidase that catalyzes a key enzymatic step in the crosslinking of collagen and elastin. The enzyme is synthesized as a propeptide that is cleaved by procollagen - C - proteinase into two distinct parts: the mature form and the LOX propeptide. The mature enzyme plays a key role in modifying the extracellular matrix and as a result has been implicated in playing a role in the formation of cancer "niches" where tumors will develop and eventually metastasize. On the other hand, the LOX propeptide has been shown to have an inhibitory effect in the development of cancer tumors. New approaches are being developed to test the use of small molecule inhibitors on LOX; however, the lack of a crystal structure has hampered these efforts as it is extremely difficult to design selective inhibitors without knowing what the target receptor looks like. In this mini review we discuss the lysyl oxidase enzyme and its role several types of cancers.
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PMID:Lysyl oxidase in cancer inhibition and metastasis. 2930 16


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