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 report the histological, immunohistochemical and ultrastructural changes in mice containing a chimeric glucagon-simian virus 40 T antigen (SV40Tag) gene. Transgene expression was detected in endocrine cells of pancreas, small and large intestine. Hyperplasia of glucagon-containing cells developed in pancreas and large bowel by gestational day 19. In large bowel, hyperplastic cells increased in number postnatally and invasive carcinomas were identified at 4 weeks; several animals had lymph node metastases. In contrast, no pathology was detected in the small bowel in any of the transgenic mice. Colonic tumours expressed SV40Tag, proglucagon-derived peptides and peptide YY (PYY); scattered cells contained cholecystokinin or glycoprotein hormone alpha-subunit. Somatostatin or serotonin was also detected in some tumours. By electron microscopy, the colonic tumours retained features of endocrine differentiation, but secretory granules were smaller than those of non-tumorous intestinal glucagon-producing L cells. In postnatal pancreas, atypical cells containing SV40Tag and glucagon were initially clustered at the periphery of islets; this atypical hyperplasia progressed to neoplasia by 11-12 weeks. Some neoplastic pancreatic cells contained glucagon, PYY or vasoactive intestinal peptide immunopositivity, but most were negative for all peptides; they contained immunoreactivity for tyrosine hydroxylase and by electron microscopy, pancreatic tumour cells had neuronal features. Pancreatic polypeptide was not detected in the non-tumorous islets of transgenic animals. This line of transgenic mice provides a model for the analysis of endocrine tumour progression in the gut and pancreas.
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PMID:Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene. 860 71

The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.
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PMID:The glucagonoma syndrome. Clinical and pathologic features in 21 patients. 860 27

Recent data suggest that functional receptors (R) for vasoactive intestinal peptide (VIP) are expressed on various tumor cells. The high-level expression of VIPR on tumor cells provided the basis for the successful use of 123I-labeled VIP for the in vivo localization of intestinal adenocarcinomas and endocrine tumors. We here report an update of our imaging results using 123I-VIP (150-200 MBg/1 microgram/patient) in 169 patients. In patients with pancreatic adenocarcinomas without liver metastases, the primary/recurrent tumor was visualized in 16 of 18 patients (89%) and liver metastases were imaged in 15 of 16 patients. In 11 of 12 patients with colorectal adenocarcinomas, the primary/recurrent tumor (92%) was imaged by 123I-VIP. Also, in 21 of 25 patients, liver metastases (84%); in 3 of 6 patients, lung metastases (50%); and in 4 of 5 patients, lymph-node metastases (80%) were imaged by 123I-VIP. In 10 of 10 patients with gastric adenocarcinomas, the primary/recurrent tumor; in 3 of 4 patients, liver metastases; and in 2 of 2 patients, lymph-node metastases were visualized by 123I-VIP. 123I-VIP localized primary intestinal carcinoid tumors in 15 of 17 patients (88%) and 8 of 10 primary insulinomas (80%). We conclude that the 123I-VIPR scintigraphy localizes intestinal adenocarcinomas and endocrine tumors as well as metastatic tumor sites.
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PMID:123I-vasoactive intestinal peptide (VIP) receptor scanning: update of imaging results in patients with adenocarcinomas and endocrine tumors of the gastrointestinal tract. 894 Jul 11

Transforming growth factor-alpha (TGF-alpha), a potent growth factor belonging to the epidermal growth factor family, exerts its role in the proliferation and differentiation of normal and neoplastic cells by binding to epidermal growth factor receptor (EGFR). Coexpression of TGF-alpha and EGFR in carcinomas is believed to confer growth advantage to tumor cells. To evaluate their role in such indolent tumors as gastrointestinal (GI) carcinoids, we investigated the immunohistochemical expression of TGF-alpha and EGFR in 25 GI carcinoids (nine foregut, 13 midgut, and three hindgut) and studied the correlation of their expression with the secretory and clinicopathologic profiles of these tumors. TGF-alpha was expressed in 18 (72%) of these tumors, and whereas 16 of 17 tumors showed immunopositivity for the extracellular domain of EGFR, none expressed its intracellular domain. Ten TGF-alpha-positive tumors were positive for serotonin, seven for somatostatin, three for calcitonin, and one tumor each for gastrin, glucagon, pancreatic polypeptide, vasoactive intestinal peptide, and growth hormone-releasing factor, respectively. Seven TGF-alpha-positive tumors were multihormonal, eight were monohormonal, and three were completely nonreactive for the regulatory substances studied. Except for its correlation with 5-hydroxytryptamine (serotonin) expression by the tumor cells, expression of TGF-alpha showed no significant association with other pathologic attributes, for example, the site of origin, size, depth of intramural penetration, metastases, and the secretory profiles of the tumors. These findings indicate that although TGF-alpha is expressed by a high proportion of GI carcinoids, the absence of its intact receptor molecule (EGFR) on the tumor cells renders it functionally ineffective as a growth factor. Thus, unlike in carcinomas of the GI tract, TGF-alpha appears to play no role in the growth and progression of GI carcinoids, which perhaps explains the indolent behavior and slow biological progression of GI carcinoids.
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PMID:Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in gastrointestinal carcinoids. 906 Jun 3

Recent studies have shown that various gastrointestinal tumours express substantial amounts of vasoactive intestinal peptide (VIP) receptors. Based on these observations, we have developed a receptor scintigraphy using [123I]VIP as a radioligand. An initial series performed at our institution showed promising potential for visualization of various gastrointestinal adenocarcinomas by means of [123I]VIP. In this article, we now report the results obtained in 80 consecutive patients with colorectal adenocarcinoma. Eighty consecutive patients with histologically verified colorectal cancer underwent scanning by means of [123I]VIP (1 microg, approximately 150 MBq). Thirteen patients were free of tumour after complete resection of Dukes' C cancer, eight patients presented with primary and 14 with locally recurrent tumours but were free of metastases. Ten patients had locally recurrent disease and liver, lung or lymph node metastases. Disease confined to organ metastases (i.e. liver, lung or lymph nodes) was present in 35 patients. The size of the primary or recurrent tumours ranged between 3 and 6 cm, and the size of metastases was between 1 and 13 cm in diameter. Scan results were evaluated independently by two nuclear medicine physicians in a blinded way, and results were then compared with computerized tomography (CT)scans not older than 4 weeks. Seven out of eight primary (87%) and 21 out of 24 (82%) locally relapsing cancers were imaged with [123I]VIP. Negative VIP scans were obtained in all 13 patients in whom the cancers had been curatively resected. All patients with lymph node metastases showed positive VIP scans (four out of four), and positive scans were obtained in 25 out of 28 (89%) patients with liver metastases and in two out of three cases with lung metastases. In four patients with relapsing cancer, the VIP scan indicated the presence of disease before CT, and in two patients the diagnosis of scar tissue instead of a local recurrence of rectal cancer as suggested by CT could be established. We conclude that [123I]VIP receptor scanning is a sensitive method for radioimaging of colorectal cancer with the potential to provide valuable additional information to conventional radiological methods.
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PMID:123I-labelled vasoactive intestinal peptide receptor scintigraphy in patients with colorectal cancer. 966 42

Malignant pancreatic islet tumors are slow-growing tumors. Their relatively benign behavior makes aggressive treatment worthwhile. From January, 1987, to January, 1998, five cases of malignant pancreatic islet tumors with liver metastasis were diagnosed at the Veterans General Hospital-Taipei. Of these, three were gastrinomas and the others were vasoactive intestinal peptide (VIPoma, 1 case) and insulinoma (1 case). Four patients (3 with gastrinomas and 1 with insulinoma) had undergone cytoreductive surgery when the diagnosis of metastasis was made. All five patients underwent transcatheter arterial chemoembolization (TACE). All patients had improved symptoms after cytoreductive surgery and TACE. The survival of patients who underwent combined surgery and TACE was 38 and 17 months in the two gastrinoma cases, more than eight months in one gastrinoma case and more than 20 months in the insulinoma case (these 2 patients are still alive). One VIPoma patient who underwent TACE survived for 12 months. In conclusion, treatment for metastatic pancreatic islet cell tumors require a multidisciplinary approach. Metastasis of the tumor is not a contraindication for aggressive therapy. Combined cytoreductive surgery and TACE can relieve symptoms and are of benefit for patients with pancreatic islet cell tumors with liver metastases.
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PMID:Functional pancreatic islet cell tumors with liver metastasis: the role of cytoreductive surgery and transcatheter arterial chemoembolization: a report of five cases. 988 50

We report the first case of metastatic Vipoma treated by orthotopic liver transplantation. A woman with explosive secretory diarrhea causing hypokalemic acidosis was diagnosed as having a vasoactive intestinal peptide secreting tumor with widespread hepatic metastases. The symptoms were initially controlled for 9 months with increasing doses of long-acting somatostatin analogue (Sandostatin, Sandoz Ltd, UK). Alpha interferon was not tolerated, causing an acute paranoid psychosis. Eventually orthotopic liver transplantation was performed with the removal of the primary tumor from the distal pancreas. Postoperatively, complications were associated with the distal pancreatectomy. The patient has no evidence of tumor recurrence on imaging or serum VIP level 12 months posttransplantation.
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PMID:Treatment of metastatic Vipoma by liver transplantation. 1015 88

Radioimaging of various human tumours by means of somatostatin analogues and vasoactive intestinal peptide has been introduced into clinical practice in recent years. The finding that human tumours express various subtypes of somatostatin receptors has led to the development and characterization of a novel peptide tracer, termed MAURITIUS. MAURITIUS identifies a broad range of somatostatin receptors with high binding affinity, and somatostatin receptor 1 with low binding affinity. In order to evaluate patients for tumour radiotherapy with 90Y-MAURITIUS, tumour dose calculation is performed with 111In-MAURITIUS [111In-DOTA-lanreotide]. Treatment is initiated in patients presenting a tumour uptake of > or = 10 Gy/GBq (i.e., standard dose for 1 treatment cycle with 90Y-MAURITIUS). In 25 patients with advanced cancer refractory to conventional antineoplastic treatment 111In-MAURITIUS (approximately 150 MBq; 10 nmol/patient), scintigraphy and dosimetry was performed. Dosimetry data were calculated based on scintigraphic results as well as urine, faeces and blood data. In all patients, at least one tumour site was visualized during the initial few minutes of application. Additional tumour sites not seen on conventional imaging (computerized tomography, magnetic resonance imaging bone scan) could be detected in 6 patients with carcinoids, one patient with prostate cancer and one patient with lymphoma. Liver metastases were visualized in all patients with gastrointestinal cancers, while the primary tumour was not detected in 2 patients with pancreatic, and in 1 patient with rectal, cancer. The calculated radiation dose for tumours and/or metastases ranged between 3-60 Gy/GBq for 90Y-MAURITIUS. MAURITIUS is a universal receptor ligand for a large variety of different human tumours, and is suitable for treatment when labelled with 90Y.
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PMID:"MAURITIUS": tumour dose in patients with advanced carcinoma. 1060 37

Antagonists of growth hormone-releasing hormone (GHRH) inhibit the proliferation of various human cancers in vitro and in vivo by mechanisms that include apparent direct effects through specific binding sites expressed on tumors and that differ from pituitary human GHRH (hGHRH) receptors. In this study, GHRH antagonist JV-1-38 (20 microgram/day per animal s.c.) inhibited the growth of orthotopic CAKI-1 human renal cell carcinoma (RCC) by 83% and inhibited the development of metastases to lung and lymph nodes. Using ligand competition assays with (125)I-labeled GHRH antagonist JV-1-42, we demonstrated the presence of specific high-affinity (K(d) = 0.25 +/- 0.03 nM) binding sites for GHRH with a maximal binding capacity (B(max)) of 70.2 +/- 4.1 fmol/mg of membrane protein in CAKI-1 tumors. These receptors bind GHRH antagonists preferentially and display a lower affinity for hGHRH. The binding of (125)I-JV-1-42 is not inhibited by vasoactive intestinal peptide (VIP)-related peptides sharing structural homology with hGHRH. The receptors for GHRH antagonists on CAKI-1 tumors are distinct from binding sites detected with (125)I-VIP (K(d) = 0.89 +/- 0.14 nM; B(max) = 183.5 +/- 2.6 fmol/mg of protein) and also have different characteristics from GHRH receptors on rat pituitary as documented by the insignificant binding of [His(1),(125)I-Tyr(10), Nle(27)]hGHRH(1-32)NH(2). Reverse transcription-PCR revealed the expression of splice variants of hGHRH receptor in CAKI-1 RCC. Biodistribution studies demonstrate an in vivo uptake of (125)I-JV-1-42 by the RCC tumor tissue. The presence of specific receptor proteins that bind GHRH antagonists in CAKI-1 RCC supports the view that distinct binding sites that mediate the inhibitory effect of GHRH antagonists are present on various human cancers.
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PMID:Human renal cell carcinoma expresses distinct binding sites for growth hormone-releasing hormone. 1096 30

Human adenocarcinomas of the gastroenteropancreatic system overexpress vasoactive intestinal peptide (VIP) receptors and therefore represent logical diagnostic targets for receptor scintigraphy. Using iodine-123 labelled VIP, the newly employed diagnostic procedure termed VIP receptor scintigraphy (VIP-RS) appears to detect tumour tissue, especially pancreatic metastatic tumours, in almost all cases. So far, however, only a single centre has demonstrated convincing positive results. The aim of this study was to compare the sensitivity and specificity of VIP-RS with those of computer tomography (CT) and transabdominal ultrasound in patients with extensive pancreatic metastatic adenocarcinomas and neuroendocrine tumours. VIP was radiolabelled with carrier-free 123I using the chloramine T-method and preparative high-performance liquid chromatography for purification. Patients with metastatic pancreatic (n=12) and colorectal (n=3) carcinomas (adenocarcinoma: n=13, neuroendocrine tumour: n=2) were studied by VIP-RS, CT, ultrasound and, in one case, also by radioligand receptor autoradiography. Carrier-free radioiodinated VIP of maximum specific radioactivity maintained a high biological activity as determined by cAMP formation in receptor-expressing tumour cell lines. Intravenous injection of 123I-VIP did not cause any side-effects. Biodistribution, determined over 24 h, was high in the lungs and low in abdominal organs. Although all patients had extensive metastatic disease as evidenced by CT and ultrasound, VIP-RS was unable to detect either primaries or metastases in these patients. Only in two patients could a significant uptake of radiolabel be detected in organs directly infiltrated by the primary. To exclude false-negative findings, tumour tissue in one patient with a large primary, undetectable by VIP-RS, was analysed by radioligand receptor autoradiography and shown to be receptor positive. Moreover, in vitro receptor determinations showed that pancreatic carcinomas usually have fewer VIP receptors than the normal tissues to which they metastasize, like the liver. It is concluded that VIP can be radioactively labelled with maximum specific radioactivity while maintaining biological activity. Intravenous administration leads to a biodistribution almost identical to that reported previously. However, in contrast to these reports, very low sensitivity and specificity were observed for the detection of pancreatic cancers. In retrospect, these findings are not surprising since VIP receptor expression was observed to be higher in normal tissues than in neoplastic ones.
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PMID:Vasoactive intestinal peptide receptor scintigraphy in patients with pancreatic adenocarcinomas or neuroendocrine tumours. 1110 25


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