Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Breast cancers can express different types of peptide receptors such as somatostatin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP) and NPY(Y(1)) receptors. The aim of this in vitro study was to evaluate which is the most appropriate peptide receptor or peptide receptor combination for in vivo diagnostic and therapeutic targeting of breast cancers. Seventy-seven primary breast cancers and 15 breast cancer lymph node metastases were investigated in vitro for their expression of somatostatin, VPAC(1), GRP and NPY(Y(1)) receptors using in vitro receptor autoradiography on successive tissue sections with (125)I-[Tyr(3)]-octreotide, (125)I-VIP, (125)I-[Tyr(4)]-bombesin and (125)I-[Leu(31),Pro(34)]-PYY respectively. This study identified two groups of tumours: a group of 68 tumours (88%) with at least one receptor expressed at high density (>2,000 dpm/mg tissue) that may provide a strong predictive value for successful in vivo targeting, and a group of nine tumours (12%) with no receptors or only a low density of them (<2,000 dpm/mg tissue). In the group with high receptor density, 50 of the 68 tumours (74%) expressed GRP receptors, 45 (66%) expressed NPY(Y(1)) receptors, 25 (37%) expressed VPAC(1) receptors and 14 (21%) expressed somatostatin receptors. Mean density was 9,819+/-530 dpm/mg tissue for GRP receptors, 9,135+/-579 dpm/mg for NPY(Y(1)) receptors, 4,337+/-528 dpm/mg for somatostatin receptors and 3,437+/-306 dpm/mg for VPAC(1) receptors. It is of note that tumours expressing NPY(Y(1)) or GRP receptors, or both, were found in 63/68 (93%) cases. Lymph node metastases showed a similar receptor profile to the corresponding primary tumour. This in vitro study strongly suggests that the combination of radiolabelled GRP and Y(1) analogues should allow targeting of breast carcinomas and their lymph node metastases for in vivo peptide receptor scintigraphy and radiotherapy.
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PMID:Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting. 1211 Nov 25

During the past decade, proof of the principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been provided. The molecular basis for targeting rests on the in vitro observation that peptide receptors can be expressed in large quantities in certain tumors. The clinical impact is at the diagnostic level: in vivo receptor scintigraphy uses radiolabeled peptides for the localization of tumors and their metastases. It is also at the therapeutic level: peptide receptor radiotherapy of tumors emerges as a serious treatment option. Peptides linked to cytotoxic agents are also considered for therapeutic applications. The use of nonradiolabeled, noncytotoxic peptide analogs for long-term antiproliferative treatment of tumors appears promising for only a few tumor types, whereas the symptomatic treatment of neuroendocrine tumors by somatostatin analogs is clearly successful. The present review summarizes and critically evaluates the in vitro data on peptide and peptide receptor expression in human cancers. These data are considered to be the molecular basis for peptide receptor targeting of tumors. The paradigmatic peptide somatostatin and its receptors are extensively reviewed in the light of in vivo targeting of neuroendocrine tumors. The role of the more recently described targeting peptides vasoactive intestinal peptide, gastrin-releasing peptide, and cholecystokinin/gastrin is discussed. Other emerging and promising peptides and their respective receptors, including neurotensin, substance P, and neuropeptide Y, are introduced. This information relates to established and potential clinical applications in oncology.
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PMID:Peptide receptors as molecular targets for cancer diagnosis and therapy. 1292 Jan 49

Recent significant advances in understanding the biology of gastrointestinal stromal tumours (GIST) have led to the introduction of a new targeted therapy (imatinib mesylate, Glivec). Hopes of a new era of a specific cancer therapy, however, have been tempered by the recognition that a significant proportion of patients who initially respond to the drug eventually become resistant to it. Given the successful development of peptide receptor scintigraphy and radiotherapy for neuroendocrine tumours, we postulated that a similar approach could offer a valid alternative in the diagnosis and therapy of GIST. Using in vitro receptor autoradiography to measure peptide receptors, we found that 16/19 GIST expressed bombesin subtype 2 receptors, 16/19 expressed vasoactive intestinal peptide subtype 2 receptors (VPAC(2)) and 12/19 expressed cholecystokinin subtype 2 receptors, in most cases in extremely high densities. All GIST metastases were shown to express two or more of these peptide receptors in very high density. Receptors were also expressed in non-responders to Glivec or after chemo-embolisation. Conversely, somatostatin subtype 2, cholecystokinin subtype 1, bombesin subtype 1 and 3, and neuropeptide Y subtype Y(1) and Y(2) receptors were not or only rarely expressed. These data represent a strong molecular basis for the use of radiolabelled bombesin, vasoactive intestinal peptide and/or cholecystokinin analogues as targeting agents to localise GIST tumours in patients by in vivo scintigraphy and/or to perform targeted radiotherapy to destroy GIST primaries, metastases and recurrences, including those resistant to Glivec.
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PMID:High expression of peptide receptors as a novel target in gastrointestinal stromal tumours. 1498 69

Pancreatic endocrine neoplasms are neoplastic proliferations of islet cells or islet cell precursors and are capable of secreting a variety of synthetic products, including insulin, glucagon, gastrin, and vasoactive intestinal peptide. The biological behavior of pancreatic endocrine neoplasms is often unpredictable, and there are few reliable histopathologic criteria reliably correlating with metastatic ability. We have used the Affymetrix U133 GeneChip set (HG_U133 A and B; Affymetrix; Santa Clara, CA) representing approximately 33,000 characterized transcripts to examine global gene expression profiles from well-differentiated nonmetastatic (n=5) and metastatic (n=7) pancreatic endocrine neoplasms to determine molecular markers that predict disease progression. Microarray hybridization data were normalized using the GeneLogic GeneExpress Software System to identify differentially up- and down-regulated genes in metastatic versus nonmetastatic pancreatic endocrine neoplasms. Using a 3-fold change in gene expression as a threshold, we have identified 65 overexpressed and 57 underexpressed genes in metastatic pancreatic endocrine neoplasms as compared with nonmetastatic pancreatic endocrine neoplasms. Several classes of genes, including growth factors and growth factor-related molecules (IGFBP1, IGFBP3, and MET), developmental factors (TBX3 and MEIS2), cytoskeletal factors (beta 1 tubulin and ACTN2), cholesterol homeostasis mediators (LRP5, SLC27A2, and RXRG), intracellular signaling pathway mediators (DYRK1A, PKIB, and AK2), methyltransferases (MGMT and GAMT), and DNA repair and regulatory molecules (CHEK1 and ZNF198), were identified as differentially over- or underexpressed via this method. Immunohistochemical validation of microarray data were performed for two overexpressed genes, namely, the met proto-oncogene (MET) and insulin-like growth factor binding protein 3 (IGFBP3) with tissue microarrays of nonmetastatic (n=24) and metastatic (n=15) pancreatic endocrine neoplasms. Increased expression of IGFBP3 was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (12 of 15, 80% versus 10 of 24, 42%), as well as in lymph node (6 of 7, 86%) and liver (9 of 9, 100%) metastases. Similarly, overexpression of MET was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (5 of 15, 33% versus 4 of 24, 17%), as well as in lymph node metastases (4 of 7, 57%) and liver metastases (5 of 9, 56%). The majority of genes that demonstrated altered expression has not been previously identified as differentially expressed in metastatic pancreatic endocrine neoplasm lesions and may therefore represent newly identified molecules in the progression of these lesions.
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PMID:Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. 1544 2

Somatostatin receptors are expressed in selected human cancers. They are particularly frequently expressed in gastroenteropancreatic neuroendocrine tumors (GEP NET), including both primaries and metastases. The density is often high, the distribution is usually homogeneous. While various somatostatin receptor subtypes can be expressed in these tumors, sst2 is clearly predominant. These receptors represent the molecular basis for a number of clinical applications, including symptomatic therapy with cold octreotide in hormone-secreting GEP NET, in vivo diagnostic with Octreoscan to evaluate the extend of the disease, and 90Y-DOTATOC radiotherapy. GEP NET can, however, express peptide receptors other than somatostatin receptors: insulinomas have more glucagon-like peptide 1 receptors than somatostatin receptors, gut NET (carcinoids) may also express cholecystokinin 2, bombesin or vasoactive intestinal peptide receptors. Often, several of these peptide receptors are expressed simultaneously in GEP NET, providing a molecular basis for in vivo multireceptor targeting of those tumors.
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PMID:Somatostatin and other Peptide receptors as tools for tumor diagnosis and treatment. 1547 18

Although neuroendocrine tumors of the pancreas are traditionally managed by laparotomy, these rare neoplasms may be amenable to laparoscopic surgical resection. We present our experience with laparoscopic distal pancreatectomy in two such patients, and discuss the operative technique with emphasis on organ preservation. Two female patients aged 63 and 69 years presented with clinical and biochemical features of an insulinoma and a vasoactive intestinal peptide secreting tumor (VIPoma), and were found on cross-sectional imaging to have 1.2-cm and 4.5-cm solitary tumors in the tail of the pancreas. They underwent laparoscopic distal pancreatectomy with and without preservation of splenic vessels and spleen respectively. Both procedures were completed laparoscopically. The operating time was 180 and 210 minutes respectively. There were no postoperative complications. The postoperative hospital stay was 4 and 14 days respectively. Histology revealed a benign insulinoma and a malignant VIPoma with lymph node metastases respectively. Laparoscopic distal pancreatectomy for neuroendocrine tumors of the pancreas may be accomplished safely, with preservation of the spleen and splenic vessels in benign disease, and with benefits to the patients in terms of postoperative recovery.
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PMID:Laparoscopic distal pancreatectomy for neuroendocrine tumors of the pancreas. 1581 91

Numerous peptide receptors have recently been reported to be expressed or overexpressed in various human cancers. For instance, somatostatin receptors are particularly frequently expressed in gastroenteropancreatic neuroendocrine tumors (GEP-NET), including both primaries and metastases. The density is often high, and the distribution is usually homogenous. While various somatostatin receptor subtypes can be expressed in these tumors, the sst(2) is clearly predominant. These receptors represent the molecular basis for a number of clinical applications, including symptomatic therapy with octreotide in hormone-secreting GEP-NET, in vivo diagnostic with radiolabeled diethylene triamine pentaacetic acid octreotide (Octreoscan) to evaluate the extend of the disease, and (90)Y- or (177)Lu-[(90)Y-DOTA]-D: -Phe(1)-Tyr(3) octreotide radiotherapy. GEP-NET can, however, express peptide receptors other than somatostatin receptor: Insulinomas have more glucagon-like peptide 1 receptors than somatostatin receptors; gastrinomas express very high levels of secretin receptors. GEP-NET may also express cholecystokinin 2, bombesin, neuropeptide Y, or vasoactive intestinal peptide receptors. Often, several of these peptide receptors are expressed simultaneously in GEP-NET, providing a molecular basis for in vivo multireceptor targeting of those tumors.
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PMID:Peptide receptor expression in GEP-NET. 1768 67

This article describes a newly recognized highly malignant neoplastic entity in young bearded dragons (Pogona vitticeps), gastric neuroendocrine carcinomas, which readily metastasize. Ten bearded dragons with histories of anorexia (8), vomiting (3), hyperglycemia (2), and anemia (3) were included in this study. All animals had neoplastic masses in their stomach, with metastasis to the liver. Microscopically, 6 of these neuroendocrine carcinomas were well-differentiated and 4 were poorly differentiated. For further characterization, immunohistochemistry for protein gene product 9.5, neuron-specific enolase, endorphin, chromogranins A and B, synaptophysin, somatostatin, insulin, glucagon, gastrin, pancreatic polypeptide, and vasoactive intestinal peptide was performed on 5 animals. Because only immunolabeling for somatostatin was consistently observed in all neoplasms, a diagnosis of somatostatinoma was made for these 5 bearded dragons. Some neoplasms also exhibited multihormonal expression. Electron microscopy performed on 1 tumor confirmed the presence of neuroendocrine granules within neoplastic cells. Gastric neuroendocrine carcinomas, and specifically somatostatinomas, have not been previously reported in bearded dragons, or other reptiles, and may be underdiagnosed due to inconsistent, ambiguous clinical signs. In humans, pancreatic somatostatinomas are associated with a syndrome of hypersomatostatinemia, which includes hyperglycemia, weight loss, and anemia, as observed in some of these bearded dragons. Somatostatinomas in humans are commonly associated with neurofibromatosis type 1 (Von Recklinghausen's disease), caused by a mutation in the tumor suppressor gene NF1, which results in decreased expression of neurofibromin. In all 5 animals examined, neoplasms exhibited decreased neurofibromin expression compared with control tissues, suggesting that decreased functional neurofibromin may play a role in the pathogenesis of somatostatinomas in bearded dragons.
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PMID:Gastric neuroendocrine carcinomas in bearded dragons (Pogona vitticeps). 1960 3

Emerging evidence have suggested that calorie restriction (CR) is a reliable method to decrease cancer development since it produces changes in tumor microenvironment that interfere with cell proliferation, tissue invasion, and formation of metastases. Studies on the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) in cancer cells indicate that their influence on cell growth is either cell type specific or dependent on culture conditions. Evidence showing the effect of PACAP and VIP in glioma cells grown under conditions mimicking CR are currently unavailable. Therefore, we explored the effects of both PACAP and VIP in C6 glioma cells either grown in a normal growth medium or exposed to serum starvation, to resemble an acute condition of CR. Cell viability, expression of proteins related to cell proliferation (cyclin D1), apoptosis (Bcl2, p53, and cleaved caspase-3), and cell malignancy (GFAP and nestin) were assessed by MTT assay, immunoblot, and immunolocalization, respectively. Results demonstrated that CR significantly decreased cell proliferation, reduced levels of cyclin D1 and Bcl2, and increased the expression of p53 and cleaved caspase-3. Surprisingly, all of these CR-driven effects were further exacerbated by PACAP or VIP treatment. We also found that PACAP or VIP prevented GFAP decrease caused by CR and further reduced the expression of nestin, a prognostic marker of malignancy. In conclusion, these data demonstrate that PACAP and VIP possess antiproliferative properties against glioma cells that depend on the specific culture settings, further supporting the idea that CR might offer new avenues to improve peptide-oriented glioma cancer treatment.
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PMID:Antiproliferative effects of PACAP and VIP in serum-starved glioma cells. 2390 Jul 22

VIPoma is a rare neuroendocrine tumor (NET) with a high potential to develop hepatic metastases and poor prognosis. The primitive tumor is nonsymptomatic and usually localized within the pancreas. Liver metastasis drives the prognosis and induces profuse watery diarrhea or renal failure. We herein present severe renal failure or diarrhea in two patients hospitalized in intensive care justifying emergency treatment of liver metastasis. The two patients experienced severe diarrhea due to a hypersecretion of vasoactive intestinal peptide (VIP) from liver metastasis released into the blood circulation. Therapeutic management was discussed and liver transarterial chemoembolization (TACE) was performed with chemotherapy-loaded embospheres, which cause necrosis of tumor lesions. TACE controlled the hormonal syndrome and made patients eligible for curative surgery. Tumor necrosis occurred and VIP levels collapsed. Surgery was performed in one of the two cases after TACE and the patient was considered in remission. Both patients were still alive after 3 years of follow up. Thus, TACE is feasible and appears to be an effective emergency treatment in patients with a VIP-hormonal syndrome due to liver metastases. Despite the biological disorder due to the hormonal secretion, an aggressive approach is warranted in VIP liver metastasis.
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PMID:Emergency therapy for liver metastases from advanced VIPoma: surgery or transarterial chemoembolization? 2758 30


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