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

Meningioma is one of a variety of human tumors that exhibit a very high density of somatostatin receptors and in many cases show a true positive somatostatin receptor scintigraphy. However, the level of expression of individual somatostatin receptor proteins in meningioma has not been investigated. We have recently developed a panel of somatostatin receptor subtype-specific antibodies that effectively stain formalin-fixed, paraffin-embedded tumor tissue (S. Schulz et al., Clin. Cancer Res., 4: 2047-2052, 1998). In the present study, we have used these antibodies to determine the somatostatin receptor status of 40 randomly selected meningiomas. Immunoreactive staining for all somatostatin receptors was clearly located at the plasma membrane of the tumor cells and completely blocked with antigenic peptide. The vast majority of tumors (29 cases; 70%) were positive for sst2A immunoreactivity; among these, 20 (69%) tumors showed high levels of sst2A immunoreactivity. In contrast, all other somatostatin receptors were only detected sporadically, and none of these cases revealed a particularly strong staining. However, it is uncertain to what extent somatostatin receptor-immunoreactive staining intensity may translate into somatostatin receptor protein expression on the tumor cells. Therefore, in a prospective study, 16 surgically removed meningiomas were collected, and the level of sst2A expression was determined using Western blot analysis. Whereas sst2A was readily detectable as a broad band migrating at Mr 70,000 in 12 (75%) of these tumors, 8 tumors (50%) showed particularly high levels of immunoreactive sst2A receptors. There was an excellent correlation (P < 0.001) between the level of sst2A protein expression detected in Western blots and the sst2A- immunoreactive staining seen in tissue sections. Thus, the frequent overexpression of the sst2A receptor may explain the high tracer uptake often observed in meningioma patients during somatostatin receptor scintigraphy. Moreover, this simple immunohistochemical method could prove useful in identifying those cases of recurrent disease that may possibly respond to therapy with sst2-selective agonists.
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PMID:Immunohistochemical determination of five somatostatin receptors in meningioma reveals frequent overexpression of somatostatin receptor subtype sst2A. 1081 9

Somatostatin and other neuropeptides are expressed in tumors originating from neuronal precursors and paraganglia, namely medulloblastoma, central Primitive Neuro-Ectodermal Tumors (cPNETs), neurocytoma, gangliocytoma. olfactory neuroblastoma, paraganglioma. In medulloblastoma, the most common malignant tumor in childhood, there is an extensive expression of somatostatin in addition to somatostatin receptors (SSTR) type 2. Although density of SSTR-2 and intensity of expression of somatostatin genes have no prognostic significance in medulloblastoma. their presence may bring along important information on oncogenesis and relate medulloblastoma to cPNETs. Radio-labeled octreotide scintigraphy may be useful in the follow-up of these patients. allowing differentiation between scar and tumoral tissue. Moreover, on the basis of octreotide-induced inhibition of cell proliferation in medulloblastoma, a trial with octreotide in patients with recurrent or high-risk tumor is warranted. Meningiomas and low-grade astrocytic gliomas, even if not displaying a clear neuroendocrine phenotype, have high levels of SSTR-2. In meningiomas, SSTRs-scintigraphy is not part of the routine pre-operative assessment; moreover, a therapeutic trial with somatostatin-analogues in patients with recurrent or inoperable meningiomas should be carried-out with great caution, because somatostatin and octreotide slightly increase cell proliferation in cultured meningiomatous cells. Low-grade gliomas (WHO grade 2), and a smaller fraction of anaplastic astrocytomas, express SSTR-2, while glioblastomas usually do not. Unfortunately, radiolabeled-octreotide scintigraphy is not useful in the differential diagnosis of gliomas, because the results are altered by the disruption of the blood brain barrier (BBB); in addition, radionuclide-labeled somatostatin analogues are not useful in the therapy of low-grade gliomas, because the intact BBB prevents them from reaching the target SSTR-2. Recently, a pilot study in gliomas, has proposed the use of a radio-labeled somatostostatin analogue with a loco-regional approach in order to overcome the intact BBB.
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PMID:Neuroendocrine tumors in the brain. 1176 40

Somatostatin receptors are highly expressed in almost all meningiomas but in this setting their functional role is not clear. A 59-yr-old woman had been treated with octreotide after an unsuccessful operation for a GH-secreting pituitary adenoma. After 8 yr of treatment, a nuclear magnetic resonance (NMR) scan disclosed a 3 cm meningioma of the tentorium. Mean GH was 2.2 ng/ml and IGF-I 325 ng/ml. Meningioma was resected and tissue was digested to obtain tumor cell suspension. Aim of the study was to measure epidermal growth factor (EGF)-induced proliferation of cultured meningioma cells in the presence of either somatostatin or octreotide. Cells were grown to semiconfluency in Dolbecco's modified eagle medium (D-MEM) supplemented with 10% fetal calf serum (FCS). After 48 h in D-MEM without serum, the medium was replaced by fresh medium plus recombinant EGF (10 ng/ml) and somatostatin or octreotide were added in the final concentrations of 1, 10 and 100 nM. 20 h later 1 microcgCi of 3H-thymidine was added to each well. After 4 h, incorporated radioactivity was measured. While octreotide did not influence significantly cell growth at the three dose tested, somatostatin increased thymidine incorporation dose-dependently (peak 100 nM: 150% +/- 27% vs medium plus EGF, p<0.05). Octreotide effectively suppressed GH secretion in our acromegalic patient but is unlikely that its long-term use could have stimulated the growth of meningioma since it did not significantly influence the in vitro proliferation of the meningioma cells. These results suggest that somatostatin-mediated proliferative effect on meningioma cells is not mediated by the subtype 2 of the somatostatin receptor.
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PMID:Development of a meningioma in a patient with acromegaly during octreotide treatment: are there any causal relationships? 1284 45

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

Coexistence of pituitary adenoma, intracranial meningioma and cerebral aneurysm has never been described. We report on a patient with GH-secreting pituitary macroadenoma associated with a right frontal meningioma and with two intracavernous asymptomatic aneurisms. A 61-year-old woman was referred to our Endocrine Unit 13 years after a right frontal craniotomy for a pituitary tumour. Endocrine investigation showed high levels of IGF-1 (560 ng/ml) and increased basal serum GH (56 ng/ml) levels, not suppressed after OGTT. MRI showed persistence of a homogeneously enhancing intra- and suprasellar lesion, compressing the visual pathways, with bilateral intracavernous invasion and simultaneous coexistence of a right intracavernous internal carotid artery (ICA) aneurysm in direct contact with the pituitary tumour. Somatostatin analog treatment normalized GH and IGF-1 levels. Eight months later, the patient underwent a balloon ICA occlusion with disappearance of the right ICA aneurysm. One year later, a new MRI confirmed the presence of the pituitary mass showing also a right intracranial frontal meningioma and a new ICA aneurysm on the left side. Previous studies have suggested that prolonged GH hypersecretion could play a role in the genesis of intracranial aneurysms, inducing atherosclerotic and/or degenerative modification of the arterial walls. Other aetiological factors include a mechanical effect due to a direct contact between adenoma and aneurysm. Coexistence of pituitary adenoma and intracranial meningioma is a rare event, but also for this association it has been suggested that GH or other growth factors could play a role in appearance or in growth of meningioma. In our case, meningioma appeared and grew, despite the effective treatment of acromegaly.
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PMID:MRI finding of simultaneous coexistence of growth hormone-secreting pituitary adenoma with intracranial meningioma and carotid artery aneurysms: report of a case. 1733 27

Meningiomas, the most common intracranial tumors, are dura-based tumors that occur in middle-aged or older adults and have a predilection for women and African Americans. They are almost always benign, but atypical and malignant forms exist. The optimal treatment for symptomatic tumors is complete surgical resection when feasible. Tumors in poor locations can have a higher rate of morbidity and often can be only partially removed. Radiation therapy should be used to treat lesions that are partially removed and lesions of higher grade, despite complete removal. Small lesions may be amenable to radiosurgery, which may obviate surgery in high-risk patients. For lesions that recur or grow despite surgery and radiation, the only option is systemic chemotherapy. No agent is optimal, but hydroxyurea is used most often. Newer approaches such as the use of inhibitors of somatostatin receptors or signal transduction pathways are under investigation.
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PMID:Meningiomas. 1857 18

A 43-year-old patient presented to our department because her left eyelid had exhibited drooping to varying extents for 2-3 months. Furthermore, in extreme positions or after rapid eye movement, she perceived diplopic images and was sensitive to light. The diagnosis of sphenoid meningioma was reached. Subsequently two rounds of radiopeptide therapy with (90)Y-DOTATOC (somatostatin analog) were administered within 3 months. This treatment approach led to a reduction of tumor volume in our patient as well as clinical improvement followed by stabilization.
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PMID:[Stress-related vertical double vision and ptosis]. 1878 11

Meningiomas, which originate from arachnoid cells, represent one of the largest subgroups of intracranial tumors. They are generally benign, but can progress to malignancy. The aim of our study was to determine the expression of 4 genes, c-Myc, neurofibromatosis Type 2 (NF2), somatostatin receptor isoform 2 (sst2) and erb-B2, that have been associated with tumorogenesis or, possibly, with aggressive behavior or recurrence of meningiomas. We measured levels of mRNAs coding for these genes by qRT-PCR in 51 cases and levels ofc-Myc protooncogene and sst2 protein by immunohistochemistry in 26 cases of meningiomas of various grades and histotypes. C-Myc mRNA and protein levels were not grade-related, but validated subdivision of the 36 benign meningiomas into two groups, Groups IA and IB, based on histological and clinical features (Ki-67-proliferative index, absence or presence of mitoses, rate of recurrence and incidence of perilesional edema). In addition to histopathological grading, c-Myc expression may be useful in predicting tumor recurrence in patients with low-grade meningiomas. NF2 mRNA levels and sst2 mRNA and receptor levels were not grade-related, but were histotype-related, with significantly higher levels in the meningothelial subtype than in the fibroblastic subtype. Erb-B2 mRNA levels were not grade- or histotype-related. Furthermore, the high expression of sst2 in meningothelial meningioma suggests the possibility of a different tumorigenesis process in this meningioma subtype and may open perspectives for the diagnosis and therapy of this subtype using somatostatin as an antiproliferative agent.
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PMID:Expression of c-Myc, neurofibromatosis Type 2, somatostatin receptor 2 and erb-B2 in human meningiomas: relation to grades or histotypes. 1880 65

Meningiomas are the most common primary brain tumors in adults. Most of them are benign (World Health Organization grade I), slow-growing lesions, but some are classified as atypical (WHO grade II) or malignant (WHO grade III). Surgical resection is curative when complete removal of a benign meningioma is possible. Incompletely resected tumors and high-grade lesions are frequently treated with fractionated radiotherapy or stereotactic radiosurgery. Radiotherapy effectively reduces recurrence rates with limited toxicity. High-grade meningiomas tend to recur following maximal treatment with surgery and radiation. Chemotherapeutic agents, including hydroxyurea, have been used for recurrent disease with marginal efficacy. As the molecular pathogenesis of meningiomas is elucidated, targeted drug therapies may prove useful. Angiogenesis inhibitors, agents that target fundamental cell signaling pathways, somatostatin analogues, and a variety of other molecular treatments appear promising.
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PMID:Advances in meningioma therapy. 1934 12

Meningiomas are the most common primary brain tumor in adults. Although the majority of these tumors can be effectively treated with surgery and radiation therapy, an important subset of patients have inoperable tumors, or develop recurrent disease after surgery and radiotherapy, and require some form of medical therapy. There are increasing numbers of studies evaluating various medical therapies but the results remain disappointing. Chemotherapies and hormonal therapies have been generally ineffective, although somatostatin analogues may have therapeutic potential. There is also increasing interest in targeted molecular therapies. Agents inhibiting platelet derived growth factor receptors and epidermal growth factor receptors have shown little efficacy, but molecular agents inhibiting vascular endothelial growth factor receptors appear to have some promise. As with other tumors, advances in the medical therapies for meningiomas will require improved understanding of the molecular pathogenesis of these tumors, more predictive preclinical models, and efficient mechanisms for conducting clinical trials, given the small population of eligible patients.
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PMID:Medical therapies for meningiomas. 2082 Aug 75


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