Normalized ratios of hybridization intensities of the erbA beta probe to intensities of probes for somatostatin (3q28) and raf(3p24-25) ranged from 0.28 to 0.56 and 0.32 to 0.71, respectively, in the six tumors and tumor lines.
Twenty-four tumor samples were shown to contain receptors for somatostatin and in eight of these SSR-positive tumors we observed a mutation in the RB gene.
These results suggest that patients with constitutively active adenylyl cyclase have hyperactive tumors; the sensitivity of these tumors to inhibitory agents (somatostatin and dopamine), possibly counteracting the expression of activating mutations, might explain the low rate of tumor growth.
It can be concluded that meningioma tissue is not synthesizing significant amounts of SS in situ and that the low amount of tissue SS found in these tumors is likely to be due to SS transported there from a distant source, via blood, cerebrospinal fluid, or axons from nerve fibers terminating in this tissue.
SSTR subtypes have unique pharmacological properties, including specific GTP-binding protein coupling, ion channel regulation, and cAMP inhibition; therefore, identification of isotypes expressed in tumor cells facilitates current efforts to design potent anti-tumorSRIF analogues.
Accordingly, SRIF analogs, such as octreotide, potently inhibit the growth of SRIF receptor-positive tumors in various rodent models, and, in particular, xenotransplanted human tumors in nude mice.
The presence of SRIH receptors in most of the neuroendocrine tumors together with the ability of many of those tumors to synthesize SRIH point toward an autocrine regulatory feedback mechanism of SRIH in these tissues.
This small tumor size and the large size of the tumor sections used for autoradiography can explain the high incidence of somatostatin expression in our series.
Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors.
The introduction of somatostatin analogues and interferons alone, or in combinations, have further improved the quality-of-life for patients with these tumors and probably has also prolonged the overall survival.
We previously reported that dexamethasone (DEX) induces dose-dependent biphasic effects on steady state somatostatin (SS) messenger RNA (mRNA) levels in normal rat islet and islet SS-producing tumor cells (1027B2), characterized by stimulation at low doses and marked inhibition at high doses.
Several veins and the ganglion cells from the prostatic plexus in the surroundings of the tumors were expressing SRIH-R with high affinity for octreotide as well.
Experiments with the human cholangiocarcinoma cell line showed specific, saturable binding of an SS analogue (MK-678) with high affinity for SSTR2 on cholangiocarcinoma membranes; inhibition in vitro of tumor cell proliferation by SS-14 and its analogue, octreotide; and inhibition in vivo of tumor growth in athymic mice implanted with human cholangiocarcinoma cells and treated with lanreotide, another SS analogue.
The current study examines whether inhibition of the growth of pancreatic cancer by the somatostatin analog, octreotide, requires tumor expression of somatostatin receptors.
Such a good GH suppressibility by somatostatin makes patients with gsp-mutated tumors the best candidates for medical treatment with somatostatin analogs.
The loss of sst2 expression could represent a growth advantage in these tumors and provide an explanation for the lack of therapeutic effect of somatostatin analogues in such adenocarcinomas.
The long-acting somatostatin analogue octreotide is frequently useful as a tracer to localize tumors and as symptomatic therapy for limiting release of secretory products produced by the tumors.
Somatostatin receptor mRNA subtypes are widely expressed in endocrine GEP tumours, but their distribution is not correlated with tumour characteristics or scintigraphy positivity.
Imaging of somatostatin receptors by indium-111-pentetreotide correlates with quantitative determination of somatostatin receptor type 2 gene expression in neuroblastoma tumors.
All tumors were positive for panendocrine immunohistochemistry markers (chromogranin A and/or synaptophysin); 35% of NETs demonstrated focal positivity for pancreatic polypeptide, somatostatin, insulin, and/or glucagon; and no immunostaining for pancreatic and gastrointestinal hormones was observed in 65% of tumors.
We have characterized the in vitro binding properties of the novel SSTR ligand 99mTc-P829 using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3, 4, and 5.
The current medical treatment of neuroendocrine tumors is based on chemotherapy for the more highly proliferating tumors, such as malignant endocrine pancreatic tumors and foregut carcinoids, whereas biotherapy, including interferon alfa and somatostatin analogues, is used in slow-growing neoplasms such as midgut carcinoids.