Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Major advances in our understanding of the synthesis and release of anterior pituitary hormones have been made over the past several years. Neurons of the hypothalamus have been found to serve as "neuroendocrine transducers" in that they have both electrical and secretory functions. Peptidergic neurons respond to appropriate stimuli with a release of hypothalamic factors into the hypophyseal-portal system. These factors or hormones ultimately control the endocrine function of anterior pituitary cells. Three hormones, Thyrotropin Releasing Hormone (TRH), Gonadotropin Releasing Hormone (GnRH or LHRH) and somatostatin have been identified, synthesized and tested for clinical applications. The clinical assessment of pituitary function has been greatly improved by new and improved radioimmunoassays. One of the recent clinical advances in the area of pituitary disease has been the determination of the relatively high frequency of prolactinomas. Prolactin secreting microadenomas are an important and treatable cause of amenorrhea and infertility in young women. In addition, many pituitary tumors previously believed to be non-functional or "chromophobe adenomas" appear to be prolactinomas. Many new diagnostic and therapeutic techniques are continuing to be developed to improve our management of patients with hypothalamic-pituitary disease.
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PMID:Recent advances in the control and function of the anterior pituitary. 627 29

With the introduction of longer-acting somatostatin analogues symptomatic relief is easy to achieve in patients with functionally active endocrine tumours and will be further facilitated by still longer-acting formulations. The consequences of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome can be prevented by all proton-pump inhibitors currently on the market. Despite the various antiproliferative strategies that have been offered to patients with metastatic disease, available data are controversial and, more importantly, are supported by few prospective and controlled studies. Most experts agree that surgery with curative extirpation of the primary in the absence of metastases and tumour debulking in metastatic disease should be intended wherever possible. Controversy concerns residual disease. According to our view, any further antiproliferative strategy should consider the growth characteristics and biology of a given tumour (Figure 4). In the case of rapid progression, chemotherapy should be offered if tumours originate from the pancreas or reveal an undifferentiated histology. In contrast, chemotherapy should not be offered to patients with well-differentiated non-functional or functional tumours (carcinoid syndrome) arising from the intestine. The same applies for patients with tumours with no or only slow growth within an given observation period of 3-12 months. These patients should be treated only symptomatically. Patients with tumours of slow progression might favourably respond to long-acting somatostatin analogues. We start with octreotide and offer patients not responding to octreotide monotherapy additional IFN alpha. If further tumour progression takes place, hepatic artery embolization is the next step (Figure 5) followed by chemotherapy, the latter in patients with tumours of pancreatic origin only. This strategy recognizes the severity of side-effects of the different therapeutic modalities and starts with octreotide because of its very few side-effects. Other groups start with chemoembolization followed by octreotide, alpha-interferon or its combinations (Ahlman et al, 1996). Ongoing studies will, it is hoped, answer the question of the ideal sequence of therapeutic strategies. Every available patient with metastasised gastrointestinal endocrine tumours should be included in one of the ongoing European multicentre trials.
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PMID:Gastrointestinal endocrine tumours: medical management. 911 20

Immunocytochemical and autoradiographic methods were used to localize the GABA(B) receptor in the normal rat hippocampus. GABA(B) receptor 1-like immunoreactivity (GBR1-LI) was most intense in presumed GABAergic interneurons of all hippocampal subregions. It was also present throughout the hippocampal neuropil, where it was most intense in the dendritic strata of the dentate gyrus, which are innervated by the perforant pathway and inhibitory dentate hilar cells, and in strata oriens and radiatum of area CA3. The dendritic regions of area CA1 exhibited less GBR1-LI than area CA3. GBR1-LI was detectable in the somata of CA1 pyramidal cells, but was minimal or undetectable within the somata of dentate granule cells and CA3 pyramidal cells. GBR1-LI was similarly minimal in the dentate hilar neuropil, and in stratum lucidum, the two regions that contain granule cell axons and terminals. Nor was GBR1-LI detectable in the inhibitory basket cell fiber systems that surround hippocampal principal cell somata. Fluorescence co-localization studies indicated that significant proportions of interneurons expressing somatostatin, neuropeptide Y, cholecystokinin, calbindin, or calretinin also expressed GBR1-LI constitutively. Conversely, parvalbumin-positive GABAergic basket cells of the dentate gyrus and hippocampus, which form GABA(A) receptor-mediated inhibitory axo-somatic synapses, rarely contained detectable GBR1-LI. High resolution autoradiography with the GABA(B) receptor antagonist CGP 62349 revealed a close correspondence between receptor ligand binding and GBR1-LI, with several notable exceptions. Ligand binding closely matched GBR1-LI throughout the hippocampal, cortical, thalamic, and cerebellar neuropil. However, the hippocampal interneuron somata and dendrites that exhibited the most intense GBR1-LI, and the GBR1-positive somata of CA1 pyramidal cells, did not exhibit a similar density of [3H]-CGP 62349 binding. These data clarify the relationship between immunocytochemically identified receptor protein and potentially functional receptors, indicating that GBR1-LI reflects both non-functional cytoplasmic GBR1 and the ligand-bindable form of the protein, both before dimerization with GBR2 and after translocation to functional sites within cells. The staining and binding patterns further suggest that GBR1 is constitutively expressed in specific neuronal populations, and may exist in higher concentration in the axons of inhibitory hippocampal pathways that innervate dendritic zones, than in axo-somatic inhibitory terminals. Whether GBR1 is inducible in cells that contain GBR1 mRNA, but no detectable constitutive protein, remains to be determined in experimental studies.
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PMID:Localization of GABA(B) (R1) receptors in the rat hippocampus by immunocytochemistry and high resolution autoradiography, with specific reference to its localization in identified hippocampal interneuron subpopulations. 1058 87

Although non-functional islet cell tumor (NFICT) and solid and papillary neoplasm (SPN) share similar clinical and pathological features, the outcome of each is different. Because NFICT often follow a malignant course and SPN are usually benign, the correct differential diagnosis is very important. We investigated the clinical and pathological findings in 10 cases of NFICT and 12 cases of SPN, including immunohistochemical analysis for chromogranin, vimentin, neuron-specific enolase, somatostatin, alpha-1-antitrypsin, estrogen receptor, progesterone receptor, CD99, p21 and Ki-67. The current study shows that chromogranin is the most valuable marker in differentiating between the tumors (P < 0.01). In contrast to previous reports stating that SPN express the progesterone and/or estrogen receptors, which are absent in other pancreatic tumors, our results show that one-third of SPN were positive for the progesterone receptor. Downregulation of p21 was found more frequently in NFICT (40%) than SPN (17%). The mean value of the Ki-67 proliferation index for NFICT (2.77% +/- 2.53%) was significantly higher than that for SPN (0.94% +/- 0.89%; P = 0.043). These results are consistent with NFICT having more malignant behavior than SPN.
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PMID:Comparative study of non-functional islet cell tumors and pancreatic solid and papillary neoplasms: biological behavior and immunohistochemistry. 1210 May 18

Histidine decarboxylase (HDC) is an enzyme for decarboxylating l-histidine to histamine and is expressed in various types of cells including neuroendocrine tumors. Recent findings have demonstrated a high percentage of HDC immunoreactivity in many neuroendocrine tumors, including carcinoid tumors, small cell carcinomas of the lung, pheochromocytomas, and medullary carcinomas of the thyroid. HDC immunostaining was applied to pancreatic islet cells and related tumors to explore possible expression of HDC as a wide spectrum marker for neuroendocrine differentiation. A total of 24 cases (22 pancreatic endocrine neoplasms, one small cell carcinoma of the pancreas, and one mixed exocrine-endocrine carcinoma) along with normal pancreatic tissue were immunostained with the anti-HDC antibody. In a normal pancreas, a double immunostaining revealed possible colocalization of HDC with glucagon- or insulin-positive cells in the islets. Seventeen of 22 pancreatic endocrine neoplasms (77%) were found to be positive for HDC, and no distinct relation to hormonal activity was observed. One small cell carcinoma was strongly positive to HDC. One non-functional tumor with mixed exocrine and endocrine components showed a diffuse positive immunostaining for HDC, and some neoplastic glucagon- or somatostatin (SRIF)-positive cells coexpressed HDC. In conclusion, we demonstrated that the majority of pancreatic endocrine tumors expressed HDC, and we suggest that HDC is a wider new marker for neuroendocrine differentiation.
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PMID:Histidine decarboxylase expression in pancreatic endocrine cells and related tumors. 1514 99

This consensus report gives a detailed description of the use of somatostatin analogs in the management of neuroendocrine tumors of the gastroenteropancreatic system. As background information we have outlined critical aspects of the pathology, the use of tumor markers, a definition of functional and non-functional digestive neuroendocrine tumors, different imaging modalities, surgical considerations, liver embolization and the use of cytotoxic drugs as well as interferon. Included in the report is an overview of somatostatin, somatostatin analogs and its receptor expression in different neuroendocrine tumors. It will also define the binding affinities of different somatostatin analogs to the five different subtypes of somatostatin receptor. We compare the efficacy of octreotide and lanreotide in reducing diarrhea and flushing. Side-effects are described and we provide practical information on somatostatin analog treatment.
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PMID:Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. 1515 56

Somatostatin (SRIF) is a widely distributed peptide with growth-inhibiting effects in various tumors. So far, five distinct human SRIF receptor subtypes (sst1-sst5) have been identified. We investigated expression of the five ssts in various adrenal tumors and in normal adrenal gland. Tissue was obtained from ten pheochromocytomas (PHEOs), nine cortisol-secreting adenomas (CPAs), eleven aldosterone secreting adenomas (APAs) and eight non-functional adenomas (NFAs) after retroperitoneoscopic surgery, and used for RNA extraction. Adrenal tissue surrounding the tumor was available for analysis in twenty-seven cases. Receptor expression was studied by RT-PCR using sst-specific primers and subsequently confirmed by Southern blotting. Expression of all five receptor subtypes was observed in RNA obtained from normal adrenal gland. Furthermore, each receptor subtype was expressed in more than 50 % of all tumors analyzed. No sst5 expression was found in PHEOs, while sst1 was present in nearly all of these tumors. Only a few of the CPAs expressed subtypes sst1 and sst4. Expression of all five subtypes was distributed equally in APAs. No sst4 was found in any of the NFAs. Differential expression of ssts in various adrenal tumors may point to new aspects in the pathogenesis of these adenomas. Furthermore, the presence of specific ssts could expand the diagnostic and therapeutic strategies during management. New subtype specific analogues of SRIF may be used in the future depending on the type of adrenal tumor and receptor subtype expressed.
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PMID:Differential expression of the human somatostatin receptor subtypes sst1 to sst5 in various adrenal tumors and normal adrenal gland. 1637 24

Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term "carcinoid". Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases, alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocin-based chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived. Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver. However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or locoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.
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PMID:Liver transplantation for metastatic neuroendocrine tumor: a case report and review of the literature. 1643 98

The prevalence, clinical profiles and management of gastroenteropancreatic endocrine tumours (GEP) in France are not known. From August 1, 2001 to September 1, 2002, standardized records on patients with GEP were prospectively completed in 87 participating centres. The total group amounted to 668 patients (median age: 56 years, range: 12-89). WHO performance status was 0/1 for 80.2% of patients. The primary sites were the small bowel and colon (288), pancreas (211), unknown (77), stomach (33), non-digestive primary sites (24), appendix (20), rectum-anus (12), and oesophagus or cardia (3). GEP were functional in 260 patients (39%). Most pancreatic tumours were non-functional (72%). Metastatic disease was observed in 73.4% of cases. Most tumours (85.8%) were well or moderately differentiated. Somatostatin receptor scintigraphy was performed in only 55% of patients. The following treatment modalities were employed: resection of primary tumour: 66%; systemic chemotherapy: 41%; somatostatin analogues: 44 and 26% for GEP of small intestine and pancreas, respectively; interferon: 12%, and intra-arterial hepatic (chemo)embolization in 23 and 15% of GEP arising from the midgut and pancreas, respectively. Despite their low prevalence, well-differentiated GEP represent a significant and heterogeneous clinical group, which warrants improved medical education, referral to expert centres at an early stage, and the design of prospective therapeutic trials.
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PMID:Thirteen-month registration of patients with gastroenteropancreatic endocrine tumours in France. 1871 44

Somatostatin analogs (SSAs) have an important role in the management of patients with neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP NETs). These compounds can control the symptoms induced by the production of hormones and peptides. The antiproliferative effects of SSAs and especially tumour shrinkage are less obvious in patients with GEP NETs than in those with acromegaly. However, based upon phase II experience there is a strong suggestion of a disease stabilizing effect of SSAs in selected patients. Those patients with a progressive, non-functional GEP NET, positive octreotide scintigraphy, a low proliferation index and in the absence of surgical options may benefit from a first-line medical therapy with SSAs. The exploration of the mechanisms of this effect are unclear and hampered by the lack of suitable preclinical models. The better understanding of the tumour biology of GEP NETs, together with the development of new SSAs with better affinity on all somatostatin receptors, represent an unmet medical need.
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PMID:The antiproliferative effect of somatostatin analogs: clinical relevance in patients with neuroendocrine gastro-entero-pancreatic tumours. 1940 73


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