Eruption of Metastatic Paraganglioma After Successful Therapy with ¹⁷⁷Lu/⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE / 대한핵의학회잡지

Metastatic paraganglioma treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been introduced as a novel management option for metastatic neuroendocrine tumors demonstrating safety, efficacy, and increased quality of life.We present two cases of marked progression of metastatic paraganglioma following initial partial response to PRRT. Given their positivity on ⁶⁸Ga-DOTATATE PET/CT and ¹¹¹In-octreotide SPECT, they underwent PRRT. Imaging following treatment revealed significant improvement in size and intensity, with some foci nearly completely resolved in one patient, and disease regression with a decrease in the number and size of bone and liver lesions in the second patient.Within months, repeat imaging in both patients revealed extensive metastatic disease with new lesions, which eventually lead to their deaths. The mechanism for rapid disease progression after partial response is not well understood, although it could be related to initially high Ki-67 levels or ¹⁸F-FDG PET/CT SUV(max) values. However, naturally rapid disease progression despite PRRT response cannot be excluded. This finding warrants the importance of proper patient counseling along with early and accurate pre-PRRT assessment, taking into consideration the above potential risk factors for therapy response in order to personalize treatment regimens and achieve maximum patient benefit.

Establishment and application of a drug screening model targeting somatostatin receptor 2 / 中国药理学通报

Aim To establish a cell model to detect the activity of somatostatin (SST) by targeting somatostatin receptor 2 (SSTR2), and to provide a simple and stable evaluation method for the drug screening of SSTR2 agonists and somatostatin analogues (SSTA). Methods The target gene of SSTR2 was integrated into the pEGFP-N3 vector, and the recombinant plasmid was constructed and transfected into HEK293 cells. After G418 screening, positive clone was selected and the stable cell lines were obtained by expanding culture. The stable cell lines were identified by fluorescence cell imaging, Western blot and qPCR. A calcium flow detection system was established to optimize cell number, fluorescence dye concentration and incubation time. Finally, the screening model was used to detect the different batches of the marketed somatostatin preparation Stilamin. Results SSTR2 stable cell lines were successfully constructed, and the receptors were mainly distributed on the cell membrane. The optimal conditions for calcium flow detection were determined as follows; 30 000 cells/Well, Fluo-4/AM indicator concentration was 3 p,mol • L -1 ~5 u,mol • L-1 , incubation time was 45 min. Under this condition, EC50 value of Stilamin in different batches was stable. Conclusions SSTR2 overexpressed stable cell lines are successfully constructed and calcium flow detection method is optimized to provide a simple and stable model for the screening of somatostatin receptor agonists.

Effect of aspirin on somatostatin receptors level in SD rat′s intestinal mucosa / 中国免疫学杂志

Objective:To investigate the optimal administration approach of using aspirin by observing the effects of the rats in-testinal mucosal barrier and somatostatin receptors level with different administration approaches of using non-steroid anti-inflammatory drugs-aspirin.Methods:32 SD rats were randomly divided into 4 groups:oral intake group,enema group,intraperitoneal injection group and control group.Every group had 8 rats.The ileum mucosal injury was scored.The level and distribution of SSTRs in every group was detected by ELISA and immunohistochemistry, respectively, The IOD score in each group was measured by image analysis.Results:(1) The scores of ileum mucosal injury in aspirin experimental groups were significantly higher than that in control group (P0.05).Conclusion:Aspirin can damage the rat intestinal mucosa.Aspirin could lead to the decrease of SSTR1-5 expression in the intestinal mucosa.All subtypes of SSTR in rat small intestine mucosa were expressed, suggesting that aspirin could affect the barrier function of the intestine.There were different influences on SSTR1-5 expression by different administration approaches,suggesting aspirin by parenteral approach may reduce the intestinal damage.

Immunoreactivity of Somatostatin Receptor Subtype 2 in Dorsal Root Ganglia in the Rat / 대한정형외과학회잡지

PURPOSE: Somatostatin has been suggested to play a role in the transmission of neurotransmitters and in the modulation of pain. Of the different subtypes of somatostatin receptors 2, sstr2A and sstr2B are important in the modulation and transmission of pain. The present study was carried out to investigate sstr2 immunoreactivity in rat. MATERIALS AND METHODS: Dorsal root ganglia (DRG) cells at the L4-L6 levels of the spinal cord of 10 rats (Sprague-Dawley, 200-250 g) were examined for sstr2 by immunohistochemistry. RESULTS: In the control group, sstr2A immunoreactivity was strongly positive in the dense network within laminae I and II of the dorsal horn at spinal levels (L4-L6). In contrast to sstr2A, sstr2B immunoreactivity was observed throughout laminae III-VI. In the DRG, sstr2A and sstr2B immunoreactivities were mainly found in medium-sized neurons. CONCLUSIONS: The distribution of sstr2A immunoreactive cells among sstr2 in the dorsal root ganglia (L4-6) resembles that of somatostatin. Incontrast to sstr2A, sstr2B immunoreactivity showed a different distribution. The presence of sstr2A at laminae I and II, and sstr2B at laminae III-VI of the dorsal horn may modulate sensory functions at these different regions of the spinal cord. Considering different actions according to the receptors of the neurotransmitter, the functions of the isoforms of sstr2 appear variable in terms of modulating and transmitting pain.

Differential Expression of Somatostatin Receptor Subtype 2 in Dorsal Root Ganglia after Ischemic Injury in the Rat / 대한정형외과학회잡지

PURPOSE: The somatostatin has been suggested to play a role in the transmission of neurotransmitters and the modulation of pain. Therefore, this study was carried out to investigate the spatial and temporal alterations of sstr2 (somatostatin receptors 2) immunoreactivity after an ischemic injury in rats. MATERIALS AND METHODS: Fifty-five rats (Sprague-Dawley, 200-250 g) were assigned to the experimental group, the other five to the control group. In the experimental group, an occlusion of the left common iliac artery was made using an aneurysm clip. Ten groups were classified according to the time after ischemiareperfusion. Dorsal root ganglia (DRG) cells in the L4, L5, L6 levels of the spinal cord, from the rats were examined the sstr2 using an immunohistochemistry technique. RESULTS: The sstr2A/B immunoreactivity (IR) appeared in the DRG after ischemia-reperfusion. The number of sstr2A- and sstr2B-IR neurons were markedly lower in the group of rats 12 hours after ischemia-reperfusion. In the group of rats one day after ischemia-reperfusion, the sstr2A- and sstr2B-IR neurons began to recover in both number and immunoreactivity. Furthermore, 3 days after ischemia-reperfusion, sstr2A/B immunoreactivity decreased in number and immunoreactivity, and 7 days after ischemia-reperfusion, very weak immunoreactivity was observed in the cytoplasm. CONCLUSION: The sstr2A/B immunoreactivity of the DRG exhibited different appearance according to the post-traumatic compartment syndrome or ischemic injury of the leg. In addition, the chronological alterations of sstr2A and sstr2B immunoreactivities may be important in controlling the pain after a transient ischemia-reperfusion event.