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)

A host of monoclonal antibodies directed against human endothelin-1 (ET-1) has been developed and characterized. The antibodies reacted with ET-1 specifically and with high affinity, as determined by competition analysis and sucrose density gradients. The antibodies did not cross-react with neuropeptide YY, beta-endorphin, calcitonin gene-related peptide, secretin or somatostatin. The antibodies cross-reacted with big endothelin (B-ET), endothelin-2 (ET-2), vasointestinal constrictor peptide (VIC), and endothelin-3 (ET-3) albeit with varying affinity but did not cross-react with sarafotoxin (SRTX-6b). None of the antibodies reacted with the C-terminal hexapeptide (HXPT) of ET-1, indicating that the epitopes are not located within this region of ET-1. The monoclonal antibodies exhibited binding activity in dilutions ranging from 1:1000, to 1:10(6). The isotypes of the monoclonal antibodies were determined by competition binding assay. Six of the monoclonal antibodies were of the IgG gamma 1, two were IgM and one of the IgG gamma 2a subclass. The antibodies detected immunoreactive ETs by radioimmunoassay and in immunocytochemical localization, suggesting the potential use of these antibodies as tools to determine the concentration of ETs in biological fluids and in immunocytochemical localization of ETs in specific cell types in various tissues.
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PMID:Monoclonal antibodies to human endothelin-1: characterization and utilization in radioimmunoassay and immunocytochemistry. 160 12

The mechanism for the efflux of taurocholic acid (TC) across the blood-brain barrier (BBB) was studied by examining the elimination of [3H]TC after microinjection into the cerebral cortex. The efflux of [3H]TC from the brain was saturable with a Vmax of 15.0 pmol/min/g brain and a Km value of 0.396 nmol/0.2 microl injectate. Efflux was inhibited by cholic acid (CA), a cationic cyclic octapeptide (octreotide; a somatostatin analogue) and an anionic cyclic pentapeptide (BQ-123; an endothelin receptor antagonist), with an IC50 value of 1.09 nmol/0.2 microl injectate, 1.12 nmol/0.2 microl injectate and 0.12 nmol/0.2 microl injectate, respectively. Probenecid (20 nmol/0.2 microl injectate), but not p-aminohippuric acid (10 nmol/0.2 microl injectate), inhibited the brain efflux of [3H]TC. In addition, elimination of [3H]BQ-123 after microinjection was saturable with a Vmax of 20.8 pmol/min/g brain and a Km of 2.92 nmol/0.2 microl injectate; it was also inhibited by TC with an IC50 value of 0.074 nmol/0.2 microl injectate. In contrast, no significant efflux of [14C]octreotide from the brain was observed until 60 min after microinjection. These results suggest that both TC and BQ-123 are transported from the brain to the circulating blood across the blood-brain barrier via specific mechanisms. Although mutual inhibition was observed between TC and BQ-123, kinetic analysis suggested that the two transport systems differ.
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PMID:Efflux of taurocholic acid across the blood-brain barrier: interaction with cyclic peptides. 969 47

Gastroenteropancreatic endocrine tumors (GEP ETs) constitute a spectrum of tumors that arise throughout the entire body but are drawn together under a common definition based on the expression of proteins derived from granules, vesicles, or both. GEP ET characterization is dependent on the primary tumor, and encompasses various factors: the WHO classification; hormone-related symptom recognition; hormone marker measurements; screening for inherited syndromes; staging; and somatostatin receptor characterization. Hypervascularization and somatostatin expression constitute major features of endocrine tumors that affect diagnosis, imaging, and therapy. GEP ET prognosis is characterized by its diversity, including a subgroup of patients with slowly progressive disease even at the metastatic stage. Prognosis assessment is mainly based on WHO classification and staging. A second cancer and cardiovascular comorbidity might also play a major prognostic part when present. Mastery of several key points analyzed in this Review, to be applied during the diagnostic and prognostic processes, is essential for defining a tailored therapeutic management.
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PMID:Gastroenteropancreatic endocrine tumors: clinical characterization before therapy. 1731 31

Gastroenteropancreatic endocrine tumours (GEP ETs) represent a relatively rare and heterogeneous group of neoplasms whose therapy can be challenging. The poorly differentiated, fast-growing cases are treated with chemotherapy. In the slow-growing ones, biotherapy is usually performed. Several categories of targeted therapies have been studied for their treatment in vitro and in vivo. A critical review of molecular alterations suggests a rationale for targeting angiogenesis, and the phosphatidylinositol 3 kinase (PI(3)K)/AKT/mammalian target of rapamycin (mTOR) pathway. Accordingly, antiangiogenic agents and mTOR inhibitors are presently the most tested agents in phase II and III studies. Bevacizumab, some multitarget inhibitors, and mTOR inhibitors showed promising results in patients with advanced GEP ETs. A limited activity has been reported for imatinib and epidermal growth factor receptor (EGFR) inhibitors. Combinations of molecular targeted therapies with different sites of action, and somatostatin analogues may be relevant to avoid molecular escape pathways. Future trials should include more homogeneous groups of patients and pay more attention to the subgroup with progressive disease.
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PMID:Molecular target therapy for gastroenteropancreatic endocrine tumours: biological rationale and clinical perspectives. 1924 26