1. Role of Somatostatins in Gastroenteropancreatic Neuroendocrine Tumor Development and Therapy 
Kjell E. Öberg, Jean–Claude Reubi, Dik J. Kwekkeboom, Eric P. Krenning 
Gastroenterology 
Volume 139, Issue 3, Pages e1 (September 2010)
DOI: /j.gastro
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2. Figure 1
Neuroendocrine tumors that overexpress SSTRs. In vitro receptor autoradiography shown on the left side reveals a high SSTR density in the whole tumor (a, H&E-stained section [bar = 1 mm]; b, autoradiogram showing total binding of 125I-Tyr3-octreotide; c, autoradiogram showing nonspecific binding). On the right side, immunohistochemical analysis of SSTR2 (R2-88 antibody) shows membrane-bound receptor in neuroendocrine tumor cells (bar = 0.01 mm).
Gastroenterology  , e1DOI: ( /j.gastro )
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3. Figure 2
Cell internalization of SSTR2. (A) In vitro SS-28–induced SSTR2 internalization in endosomes (HEK cells). Compare with the control (no peptide) on the left, showing membrane-bound SSTSR2. The application of 100 nmol/L SS-28 induced a complete internalization of SSTR2, which colocalized with the endosomal marker Transferrin-Alexa 594. (B) In vivo [Tyr3]-octreotate-induced sst2 internalization in rat AR42J tumors. Compared with the control (no peptide) on the left, showing membrane-bound SSTR2, the intravenous application of [Tyr3]-octreotate induced a complete SSTR2 internalization 10 minutes and 1 hour later, whereas an antagonist against SSTR2 was not internalized. Bar = 0.01 mm. (C) In vivo internalization of SSTR2 in the neuroendocrine tumor of a patient who had been treated with octreotide, compared with the membrane-bound SSTR2 in a neuroendocrine tumor of a patient who did not receive octreotide (left). SSTR2 was internalized in the neuroendocrine tumor of a patient who received an octreotide infusion during tumor resection. Bar = 0.01 mm.
Gastroenterology  , e1DOI: ( /j.gastro )
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4. Figure 3
SRIF receptor-mediated modulation of signaling cascades leading to changes in hormone secretion, apoptosis, and cell growth. In most cells, SRIF inhibits hormone as well as other secretions. Increased secretion is observed, for example, in B cells. SRIF plays a role in the control of cell growth and apoptosis. In a G protein–dependent manner, PTPases, such as SHP-1, are activated, leading to dephosphorylation of signal transduction proteins. SRIF-induced inhibition of ERK1/2 blocks degradation of the cyclin-dependent kinase inhibitor p27kip1, leading to growth arrest. In rare cases, SRIF can stimulate proliferation. AC, adenylyl cyclase; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; Gά, Gβ, Gγ, G protein subunit; IP3, inositol triphosphate; PLC, phospholipase C; pHi, intracellular pH; PTPase, phosphotyrosine phosphatase.
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5. Figure 4 Chemical structure of SS-14, octreotide, and lanreotide.
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6. Figure 5
A patient with GEP-NET who received PRRT. Serial computed tomography scans (upper row) and octreoscans (second row) after PRRT with [177Lu-DOTA0,Tyr3]octreotate of a patient with a GEP-NET. PRRT (radioactivity symbol) and cycles (arrows; each 7.4 GBq) are indicated in the third row. The plot shows serum chromogranin A concentrations (red symbols, closed line) and the patient's weight (black symbols, dotted line). PR, partial remission; PD, progressive disease.
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7. Figure 6
Results from PRRT clinical studies. Overall survival, in months since diagnosis, from observational and interventional studies (blue bars) of patients with similar tumor types and disease stages treated with [177Lu-DOTA0,Tyr3]octreotate (red bars). Patients treated with [177Lu-DOTA0,Tyr3]octreotate survived 40 to 72 months longer than patients treated with cytotoxics or biologicals (IFN-α, octreotide). Adapted from Kwekkeboom et al.84 WDEC, well-differentiated endocrine carcinoma; Dx, diagnosis; PNET, pancreatic neuroendocrine tumor.
Gastroenterology  , e1DOI: ( /j.gastro )
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