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)

Medulloblastoma is a pediatric malignancy, which arises in cerebellum. The neuropeptide somatostatin (SS-14) is a neuromodulator and growth regulator in the developing cerebellum. SS-14 has previously been demonstrated in medulloblastomas with immunohistochemical techniques, but somatostatin receptor (sst) expression is less well understood. We analyzed somatostatin and sst subtype expression (sst1-5) in central primitive neuroectodermal tumors (cPNET), including 23 medulloblastomas, 6 supratentorial PNET, and 10 cPNET cell lines. The expression of SS-14 and sst genes in cPNET was compared with expression of these genes in 17 tumors of the Ewing's sarcoma family of tumors using reverse transcriptase-PCR, Southern hybridization, quantitative in vitro receptor autoradiography, and competitive membrane binding assays. The sst1 subtype was expressed in similar frequency in cPNET (83%) and Ewing's sarcoma family of tumors (71%). Nine of the 10 cell lines and 76% of the cPNET expressed mRNA for sst2 compared with 35% of the Ewing's sarcoma family of tumors. High-affinity binding of SS-14 was demonstrated in cPNET by quantitative autoradiography as well as by competitive binding assays. The cPNET cell line D283 Med bound SS-14 and octreotide with high affinity; SS-14 inhibited proliferation of D283 Med cells as measured by a decrease in [3H]thymidine uptake. We conclude that both sst1 and sst2 are highly expressed in cPNET and suggest that somatostatin may regulate proliferation and differentiation in these developmental tumors.
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PMID:High expression of somatostatin receptor subtype 2 (sst2) in medulloblastoma: implications for diagnosis and therapy. 1023 68

Surgical excision has been the mainstay of treatment for neuroendocrine tumors of the pancreas (PNET). Compounds like streptozocin and dacarbazin have been traditionally used in inoperable cases and somatostatin to treat syndromes deriving from functional tumors. However, a lot of progress has taken place in the area of molecular characterization of these tumors, revealing activation of mammalian target of rapamycin (mTOR) and VEGF pathways. Recent data from the 2010 ASCO Gastrointestinal Cancers Symposium demonstrate antitumor activity of everolimus, an mTOR inhibitor in combination with temozolomide in a phase I/II trial and of sunitinib versus placebo in a randomized double blinded phase III trial. The role of modern biologic compounds in the treatment of PNET is not clear yet. In addition, combination of resection and transarterial chemoembolization (TACE) has been proven effective over either modality alone in the treatment of PNET metastatic to the liver in a retrospective analysis. This comes to address the problem of selecting local intervention in a metastatic disease, which has been a reasonable choice for this group of tumors in the past. Last but not least the role of Ki-67 in decision-making in PNET is being discussed.
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PMID:Neuroendocrine tumors of the pancreas: what's new. Highlights from the "2010 ASCO Gastrointestinal Cancers Symposium". Orlando, FL, USA. January 22-24, 2010. 2020 21

Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors can be functional, i.e., hormone secreting tumors, e.g., insulinoma, gastrinoma or VIPoma, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNET's, usually present later either incidentally or due to tumor bulk symptoms. The recent WHO classification system in 2010 classified PNET's into different stages and grades depending on the mitotic activity and Ki-67 labeling index. PNET's have a broad range of prognoses depending on the histologic grade, differentiation and biologic behavior. Computerized tomographic scanning (CT), magnetic resonance imaging (MRI) and octreoscan are imaging tools used to diagnose PNET, in addition to a confirmatory tissue diagnosis with immunohistochemical stains, typically obtained by either cytologic or histologic assessment. Symptomatic advanced PNET's can be treated with a long-acting somatostatin analogue for those tumors with somatostatin receptor positivity and which may also have antiproliferative activity. Another treatment modality is peptide receptor radionucleotide therapy (PRRT) in somatostatin receptor-positive tumors, albeit as yet with limited availability in the United States. Systemic therapies with combination cytotoxic agents e.g., streptozocin, anthracyclines, and capecitabine and temozolomide, all have established activity in PNET's. Biologic agents targeting the VEGF and mTOR signaling pathways, e.g., sunitinib, bevacizumab or everolimus are becoming integrated as treatments for PNET's. Poorly differentiated, high grade PNETs with a very high mitotic rate are treated with platinum-based chemotherapy regimens similar to treatment paradigms for small cell carcinoma of the lung. For liver confined or predominant disease, strategies such as cytoreductive surgery, hepatic artery embolization or radioembolization are treatment modalities to effect locoregional tumor control. The next generation of studies in PNET will help define optimal sequencing strategies of available therapies and also will attempt to use biomarker-guided approaches to select therapies.
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PMID:Emerging therapies for pancreas neuroendocrine cancers. 2584 79