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)

Carcinoid tumors originate from the neuroendocrine cells throughout the body and are capable of producing various peptides. Their clinical course is often indolent but can also be aggressive and resistant to therapy. We examined all aspects of carcinoid tumors including the molecular biology oncogenesis, role of angiogenesis, recent advances in imaging, and therapy. The Medline and Cancerlit databases were searched using carcinoid as the keyword. English language manuscripts were reviewed and relevant references from a total of 7741 were found. All titles were screened and all the relevant manuscripts were analyzed; we found 307 references pertinent to the history, epidemiology, clinical behavior, pathology, pathophysiology, molecular biology, radiologic imaging, supportive care of carcinoid syndrome, and results of therapeutic clinical trials. Management of patients with carcinoid tumors requires an understanding of the disease process and a multimodality approach. Introduction of long-acting somatostatin analogues has resulted in significant advances in the palliative care of patients with carcinoid syndrome. However, advanced carcinoid tumor remains incurable. Existing therapies for advanced disease have low biologic activity, high toxicity, or both. Clearly, more research is necessary in the areas of molecular biology, targeted therapy, and development of new drugs Future advances in this field need to focus on clinical and biological predictors of outcome. Early works in the area of tumor biology such as the role of p53, bcl-2, bax, MEN1, FGF TGF PDGF and VEGF expression are of interest and need to be explored further.
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PMID:Carcinoid--a comprehensive review. 1469 Jan 53

Somatostatin receptors (SSTRs) have been detected in many normal and malignant tissues. This wide expression has been used for diagnostic, prognostic and therapeutic purposes. Five SSTR subtypes (SSTR 1-5) have been identified whose activation is responsible for the signal transduction through many different intracellular pathways. In the present study the expression of SSTR mRNA was determined by reverse-transcriptase (RT)-PCR in 42 meningiomas. About 88% of the tumors analyzed (37/42) were positive for at least one of the five SSTR subtypes displaying a variable pattern of expression of the different SSTR subtypes. SSTRI and SSTR2 were the most frequently mRNA detected (69% and 79% of the sample analyzed, respectively). The other subtypes were found in the 43%, 33% and 33% of cases for SSTR3, SSTR4 and SSTR5, respectively. In 22, out of 42 patients (52%) three or more SSTRs were detected. The expression of the different SSTR subtypes did not correlate with the expression of bcl-2 (apoptosis-associated protein) and MIB-1 (a proliferation marker), assessed by immunohistochemistry in a series of 34 tumor samples, while a correlation between the expression of SSTR3 and p53 was observed (p = 0.08). To evaluate a possible role of SSTR in the control of human meningioma cell proliferation, seven primary cell cultures obtained from fresh meningioma surgical tissues, were analyzed for their proliferative behavior by MTT assay and for their response to SST by [3H]-thymidine incorporation. In four out of six tumors (in one case no SSTR were detected) the treatment with SST caused a significant inhibition of DNA synthesis induced by the tumor-promoter phorbol myristate acetate. The evidence of the expression of SSTRs, mainly of SSTR2, in this series of specimens we analyzed altogether with in vitro antiproliferative effects of SST may open interesting perspectives for the diagnosis and the therapy of meningiomas.
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PMID:Expression of somatostatin receptor mRNA in human meningiomas and their implication in in vitro antiproliferative activity. 1501 81

Small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. Although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. In this study, the authors tentatively defined small cell neuroendocrine carcinoma (SCNEC) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin A immunoreactivity, and synaptophysin immunoreactivity. We found 10 cases fulfilling these requirements. Five of the 10 tumors were composed mainly of small ("oat") cells and 5 of mainly larger "intermediate" cells. The majority of both subtypes showed an insular pattern. Three of the 10 SCNECs were pure, whereas the other seven were mixed with adenocarcinoma and/or squamous cell carcinoma or cervical intraepithelial neoplasia. In addition to the definitional markers noted earlier, the tumors were immunoreactive for serotonin (6 cases), somatostatin, gastrin, glucagon, and pancreatic polypeptide. No tumors were immunoreactive for cytokeratin 20. Human papillomavirus (HPV)-18 was detected in all of the pure tumors and both the SCNEC and adenocarcinomatous components in four of the mixed tumors. No other types of HPV were detected. The tumors showed a relatively low frequency of loss of heterozygosity for representative tumor suppressor gene sites; p53 mutations were found in only one case.
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PMID:Small cell neuroendocrine carcinomas of the uterine cervix: a histological, immunohistochemical, and molecular genetic study. 1538 6

Amphetamine (AMPH) is a psychostimulant whose chronic abuse may cause impairments in attention and memory in humans. These cognitive deficits might be related to neurotoxic effects of the drug. One such toxic effect is the well-described destruction of striatal dopaminergic terminals in mammals. In the present study, we investigated the possibility that AMPH might also cause neuronal apoptosis in the rodent striatum. Administration of a dose of the drug (10 mg/kg, 4 times, every 2 h) that is toxic to dopaminergic terminals resulted in the appearance of striatal cells that were positive for cleaved caspase-3 and for terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL), observations that are indicative of an ongoing apoptotic process. Dual immunofluorescence staining revealed that cleaved caspase-3-positive cells express calbindin and DARPP-32, but not somatostatin, parvalbumin, or cholinergic markers. In addition, AMPH also caused increased expression of p53 and Bax at both transcript and protein levels; in contrast, Bcl-2 levels were decreased after the AMPH injections. Moreover, Bax knockout mice showed resistance to AMPH-induced apoptotic cell death but not to AMPH-induced destruction of dopaminergic terminals. When taken together, these observations indicate that injections of doses of AMPH that are known to destroy striatal dopamine terminals can also cause apoptotic death of postsynaptic medium spiny projection neurons via mitochondria-dependent mechanisms.
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PMID:Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway. 1573 Dec 93

Gastric endocrine tumours (gastric carcinoids) usually grow from enterochromaffin-like (ECL) cells. Three types of tumour may be distinguished on the basis of the background gastric pathology: type I, which develops in atrophic body gastritis (ABG); type II, which is associated with multiple endocrine neoplasia and Zollinger-Ellison syndrome; and the sporadic type III, which is not associated with any background pathology. This classification plays a major role in determining the optimal approach to these diseases. In fact, type I carcinoids can be considered to be benign lesions, with exceptional risk of metastases. Type II, in contrast, may be associated with distant metastases, which are also common in type III carcinoids. The therapeutic approach is based mainly on endoscopic excision and somatostatin analogues in types I and II, or on surgical resection in type III. Both types I and II grow under the stimulus of hypergastrinaemia through a well-described sequence. However, gastrin is sufficient to cause ECL cell hyperplasia and dysplasia, but not transformation, which is due to menin defects in MEN-I patients, or to other unknown alterations in ABG. Several other candidates--including Bcl2, p53 and MMP9--have been linked with carcinoid initiation and progression. The biology of type III tumours which are not associated with hypergastrinaemia is still poorly understood.
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PMID:Endocrine tumours of the stomach. 1625 92

Pancreatic ductal adenocarcinomas can display disseminated neuroendocrine (NE) cells. Controversies exist as to their relative incidence, histogenesis, hormone production, and the prognostic implications of their presence. These issues were elucidated by means of a broad immunohistochemical (IHC) investigation of the resected specimens from 47 patients. Chromogranin A (CgA) was chosen as the major NE marker. In addition, the sensitivity of the conventional IHC procedure was increased by means of the TSA (Tyramide Signal Amplification) technique. In tumours with CgA immunoreactive (IR) cells, detected by the conventional or the TSA methods, these NE cells were further IHC analyzed, using antisera raised against a broad spectrum of neurohormonal peptides, serotonin, and IGF-1. The IHC observations were correlated with clinical and histopathological data, the nuclear IR for the Ki67 antigen (proliferation) of the neoplastic cells, and their IR against the p53 protein. Distinct CgA IR cells were found in 5 out of 47 (11%) tumours when studied by the conventional method, and in 9 out of 47 (19%) when examined by the TSA technique. Corresponding figures, if tumours with only questionable IR against CgA were also included, were 14 (30%) and 23 (50%), respectively. Out of the 9 cases with unequivocal CgA IR, only 3 displayed an IR to an additional hormone or growth factor; this hormone turned out to be somatostatin (only minimal foci). Insulin and glucagon cells also appeared exceptionally. The NE differentiation was found to be unrelated to proliferation, p53 protein expression, and to the survival of the patients. It occurred mainly (7 out of 9) in poorly differentiated adenocarcinomas. Thus, the plain NE immunoprofile of the CgA IR cells, together with the increased IR observed when the TSA technique was used, indicates that the NE cells in these adenocarcinomas are only poorly differentiated. When the CgA IR cells exceptionally become highly differentiated, they can express islet hormones. Using strict structural and IHC criteria, a NE differentiation occurs in less than 20 % of cases; its clinico-pathological significance seems to be non relevant.
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PMID:Neuroendocrine cells in pancreatic duct adenocarcinoma: an immunohistochemical study. 1691 33

Somatostatin analogs currently used in the treatment of acromegaly and other neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways coupled to these receptors have been only partially characterized. The aim of this study was to evaluate the effect of octreotide and super selective SST2 (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene expression in human somatotroph tumor cells. Eight somatotroph tumors expressing similar levels of SST2 and SST5 evaluated by real-time PCR and western blot analyses were included in the study. In cultured cells obtained from these tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160+/-20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172+/-25% vs basal) at concentrations higher than 0.1 nM. This effect was due to SST2 activation since BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120-stimulated apoptosis was dependent on phosphatases, since it was abrogated by the inhibitor orthovanadate, and independent from the induction of apoptosis-related genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the present study showed that octreotide-induced apoptosis in human somatotroph tumor cells by activating SST2. This effect, together with the cytostatic action exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs.
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PMID:Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2. 1695 43

The optimal goal for pathologists is to provide important information to clinicians in order to predict tumor biology. Specific morphologic features may serve as predictive markers of tumor behavior. Macroscopic invasion of the perisellar tissues, defined as radiographic or gross operative finding, is considered a more consistent prognostic indicator. Regarding morphology, cytologic atypia is not a reliable feature. In contrast, the number of mitoses is very important for prognosis. Given that only scarce mitoses can be identified in some aggressive cases, Ki-67 represents an alternative key feature to assess tumor proliferation. In the recent World Health Organization classification, the Ki-67 labeling index (LI) represents a major prognostic indicator for pituitary adenomas. Expression of the p53 gene product is very important for tumor biology. Adenomas with more than 3% Ki-67 LI and extensive p53 immunoreactivity are classified as 'atypical adenomas'. Apoptosis and mitoses represent two adverse and asynchronous events, maintaining the optimal cell numbers. Using DNA labeling techniques, we can identify apoptotic cells. A higher apoptotic LI was found in functioning compared with nonfunctioning adenomas, in microadenomas, particularly in corticotrope adenomas, and in untreated adenomas, particularly prolactinomas. Cytogenetic analysis of chromosomes may provide important information regarding tumor development and progression. Increased chromosome 11 copies are more frequent in functioning, aneuploid pituitary adenomas. Monosomy or partial loss of chromosome 11 in adenomas with a normal or increased DNA LI indicates complex genomic abnormalities of chromosomes, other than chromosome 11. Immunohistochemical detection of somatostatin receptors is important, as their density in the cytoplasmic membrane is directly related to the effectiveness of somatostatin analogues. Therefore, morphologic assessment of the somatostatin receptor profile can predict the responsiveness and validate the effectiveness of treatment with somatostatin analogues. We can conclude that among the currently available predictive factors, tumor invasiveness is important, whereas the presence of mitoses, the Ki-67 LI, p53 expression and apoptosis are very important; DNA ploidy and fluorescent in situ hybridization analysis, although important, are difficult to apply. Finally, in the near future, immunohistochemistry for somatostatin receptors will be a very important application.
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PMID:Predictive markers of pituitary adenoma behavior. 1704 81

Composite adenoma-carcinoid tumors are rare colorectal lesions consisting of intermingled adenomatous and carcinoid components. Unlike other mixed endocrine-glandular colorectal neoplasms, which are generally malignant, their glandular component is histologically benign and their natural history is favorable. We present 4 cases of colonic adenomas containing microcarcinoids, a hitherto undescribed lesion that is either a precursor of composite adenoma-carcinoids or a related but independent entity. The cases, identified among our surgical and consultation files, were endoscopically routine sessile polyps removed from 4 otherwise normal individuals, 3 from the cecum and 1 from the distal colon. The microcarcinoids were 0.5 to 1.5 mm in size and situated within the basal lamina propria, where they interposed between the crypts and muscularis mucosae without disturbing the overall polyp architecture. Histologically, they consisted of collections of low-grade epithelial cells arranged in nests, cords, tubules, and irregular clusters and characterized by eosinophilic, granular, or clear cytoplasm and by round central nuclei with stippled or dusty chromatin. Endocrine differentiation of the microcarcinoids was confirmed by the expression of 3 or more of the following: Grimelius argyrophil, chromogranin, synaptophysin, neuron-specific enolase and somatostatin. No mitotic figures or MIB-1 or p53 positivity were observed. The glandular component of the polyps was unremarkable in 3 cases, but 1 polyp, in addition to a microcarcinoid, showed a diffuse pattern of mixed adenomatous-endocrine differentiation. The patients' clinical course was benign on the basis of 2 years' median follow-up (range, 6 mo to 10 y). Two patients with incomplete polypectomies underwent hemicolectomy revealing no residual endocrine neoplasia. Awareness of microcarcinoids in colonic adenomas should help avert potential diagnostic pitfalls posed by their pleomorphism, basal location, and infiltrative patterns, and may help clarify their natural history and possible relationship to composite glandular-carcinoid tumors.
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PMID:Microcarcinoids in large intestinal adenomas. 1712 8

The clinical and histochemical examination of hormone-producing serous cystadenomas of the pancreas are presented. The study material was obtained from five female patients. The patients underwent diagnostic examinations, including ultrasonography, computer tomography (CT), magnetic resonance imaging (MRI) and Doppler ultrasonography examination of abdomen. In all cases the presence of serous cystadenoma of pancreas was detected in the histopathologically verified sections. The test applied to immunohistochemically localize paraffin-embedded sections of neoplastic tissues of the pancreas was the LSAB2-HRP test using monoclonal antibodies against epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), synaptophysin, p53 and polyclonal antibodies against insulin, glucagon, somatostatin and pancreatic polypeptide. In one patient, ultrasonography revealed an irregular space filled with fluid resembling a multicellular cystic lesion. The Doppler ultrasonography examination showed a pathologically vascularized focus in the pancreatic head. In the adenoma sections of this patient, the immunohistochemical techniques revealed a strong positive somatostatin, pancreatic polypeptide and synaptophysin expression in the lining epithelium of neoplastic cysts.
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PMID:Hormone-producing serous cystadenoma of the pancreas. 1716 18


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