Relationship between expression of somatostatin receptors subtype 2 mRNA and estrogen and progesterone receptors in breast cancer

Objectives To observe the expression of somatostatin receptor subtype 2 (SSTR2) mRNA, and investigate the relationship between the expression of SSTR2 mRNA and the expressions of estrogen and progesterone receptors (ERs and PRs) in benign and malignant breast tissues.Methods Samples from a total of 23 breast carcinomas, 16 mammary hyperplasias, and 9 mammary fibroadenomas were analyzed. SSTR2 mRNA expression was examined by in situ hybridization using multiphase oligoprobes. ER and PR expressions were detected by immunohistochemical staining. A computerized image analysis system was utilized to estimate the relative content of SSTR2 mRNA.Results The rate of expression (87.0%) and relative content (0.47) of SSTR2 mRNA in breast cancer were higher than those in benign breast tissue (64%,0.26) (P<0.05). SSTR2 mRNA expression was closely correlated with ER and PR expressions in breast cancer (P<0.05). SSTR2 mRNA was also positively correlated with ER expression in benign breast tissues.Conclusions SSTR2 mRNA expression is higher or in benign breast tissues than in malignant ones. There is a significant positive correlation between SSTR2 mRNA and ER and PR expressions. Combined antiestrogen and somatostatin analogue in treatment of ER-positive breast cancers should be further investigated.

Relationship between somatostatin receptors and activation of hepatic stellate cells

Background Somafostatin receptors (SSTRs) have been sug gested to involve in mediating the effect of somatostatin on hepatic stellate ce lls (HSCs) in an activation-dependent way. We, therefore, try to investigate th e relationship between expression of SSTRs and activation of rat HSCs.Methods HSCs were isolated from rats by in situ perfusion and single-step density gradient centrifugation.SSTR 1-5 mRNA levels in the differentiated first passage HSCs were detected by means of a reverse transcription polymerase chain reaction. On the other hand, hepatic fibrosis was induced in adult male Sprague-Dawley rats by carbon tetrachloride intoxication, and the expression of SSTR 1-5 in normal as well as fibrotic livers was measured by immunohistochemical staining.Results SSTR mRNA and SSTR could not be found in freshly isolated rat HSCs or normal rat liver. However, SSTR 1-3 mRNA appeared as HSCs became wholly activated, and could also be identified on the membrane of activated HSCs in the perisinusoid space, fibrous septa, etc.Conclusion The expression of SSTR 1-3 in the rat HSC is closely related to its activation. This may reflect one of the main negative regulation mechanisms in the course of HSC activation.

An Experimental Study on Somatostatin Receptors in the Brains of Hepatic Encephaiopathy Rats

The present study was undertaken to evaluate the effect of somatostatin (SS) receptor,a brain-gut peptide receptor which is capable of inhibiting central neurons, on the pathogenesis of hepatic encephalopathy (HE).By means of radioligand binding assay, SS receptors in crude synaptosomal membrane of rat brains were investigated in a rat model of HE induced by partial hepatectomy following carbon tetrachloride intoxication and in controls. Binding to SS receptor was studied using125 I-SS as radiolgand Scatchard analysis of binding data was linear, yielding a dissociation constant (Kd) of 3.99 ±0.22 nmol/L and a maximal binding capacity (Bmax) of 238± 14.2 fmol/mg of protein in HE rats.Only increased Bmax values were observed (P< 0.005),while the Kd values were statistically unchanged (P>0.50),in HE rats as compared with those in controls.The results suggest that the changes of SS receptors in brains play a significant role in the pathogenesis of HE.The mechanism of HE induced by the alterations of SS receptors in the brains was discussed in this paper.

Somatostatin receptor subtypes in hormone-refractory （castration-resistant） prostatic carcinoma

The aim of this study was to examine the tissue expression and Iocalisation of the somatostatin receptors （SSTRs） in hormone-refractory （HR） prostate cancer （PCa）. Five SSTRs were evaluated immunohistochemically in 20 radical prostatectomies （RPs） with Gleason score （GS） 3＋3=6 PCa, in 20 RPs with GS 4＋4=8 and 4＋5=9 PCa, and 20 transurethral resection of the prostate specimens with HR PCa. The mean values in the cytoplasm （all five SSTRs were expressed）, membrane （only SSTR3 and SSTR4 were expressed） and nuclei （only SSTR4 and SSTR5 were expressed） of the glands in HR PCa were 20-70% lower than in the other two groups, the differences being statistically significant. All five SSTRs were expressed in the smooth muscle and endothelial cells of HR PCa, the mean values being lower than in the other two groups. In conclusion, this study expands our knowledge on the expression and Iocalisation of five SSTRs in the various tissue components in the HR PCa compared with hormone-sensitive PCa.

Somatostatin receptor scintigraphy in the follow up of neuroendocrine neoplasms of appendix

BACKGROUND Neuroendocrine tumors of appendix(ANETs)known as carcinoids,are rare endocrine neoplasms originated from enterochromaffin cells of gastrointestinal tract.ANETs are the third most frequent(16.7%)gastrointestinal neuroendocrine tumors,with the incidence of 0.08-0.2 cases/100000 during one year.Incidental ANETs occur in 0.2%-0.7%of emergency surgical resections because of suspected appendicitis which is usually the first manifestation of ANET.Although there are a lot of papers about application of somatostatin receptor scintigraphy in gastrointestinal neuroendocrine tumors,there are very rare sporadic cases described about ANETs particularly.AIM To establish the role of somatostatin receptor scintigraphy(SRS)in the management of patients with neuroendocrine tumors of appendix(ANET).METHODS The total of 35 patients was investigated,23 females and 12 males,average age(43.7±17.3 years).All patients had histological diagnosis of ANET(34 carcinoids of appendix and one tubular carcinoid).Majority of tumors have been found incidentally during surgery of:Acute appendicitis(n=15),perforated appendicitis(n=2),ileus(n=3),hysterectomy(n=3),ruptured ovarian cyst(n=2),caecal volvulus(n=1),while 9 patients had diagnosis of appendiceal tumor before the surgery.Seventeen patients had tumor grade(G)G1,12 G2 and 6 G3.The right hemicolectomy was performed in 13,while the rest of the patients had appendectomy only.SRS was done early(2 h)and late(24 h)after i.v.application of 740 MBq technetium-99 m ethylenediamine-N,N’-diacetic acid Hydrazinonicotinyl-Tyr3-Octreotide(technetium-99 m-Tektrotyd,Polatom,Poland).SRS was performed for restaging in all the patients after surgery.RESULTS There were 12 true positive(TP),19 true negative,3 false positive and 1 false negative SRS result.Sensitivity of the method was 92.31%,specificity was 86.36%,positive predictive value was 80.00%,negative predictive value was 95.00%and accuracy 88.57%.Receiver operating characteristics analysis showed that SRS scintigraphy is a good test for detection TP cases[area under the curve of 0.850,95%confidence interval(CI):0.710-0.990,P<001].Single photon emission computed tomography contributed diagnosis in 7 TP findings.In 10 patients Krenning score was 4 and in 2 was 3.In 8 patients SRS significantly changed the management of the patients(in two surgery was repeated,in 4 somatostatin analogues and in two peptide receptor radionuclide therapy).Median progression-free survival in SRS positive patients was 52 months(95%CI:39.7-117.3 mo)while in SRS negative patients it was 60 months(95%CI:42.8-77.1 mo),without statistically significant difference between the two groups(P=0.434).CONCLUSION In conclusion,our results confirmed the value of SRS in the follow-up of the patients with ANET after surgery,if recurrences or metastases are suspected.

Guipi decoction effects on brain somatostatin levels and receptor mRNA expression in rats with spleen deficiency

BACKGROUND： Somatostatin is abundant in the hypothalamus, cerebral cortex, limbic system, and mesencephalon. Somatostatin mRNA expression in the brain of rats with spleen deficiency is noticeably reduced, as well as attenuation of cognitive function. OBJECTIVE： To observe the interventional effect of Guipi decoction on somatostatin level and somatostatin receptor 1 （SSTRl） mRNA expression in different encephalic regions of rats with spleen deficiency, and to compare the interventional effects of Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet. DESIGN： A randomized controlled observation. SETTING： Basic Medical College, Beijing University of Traditional Chinese Medicine. MATERIALS： Fifty adult Wistar male rats, of clean grade, weighing （160 ± 10） g, were provided by Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd. The protocol was performed in accordance with ethical guidelines for the use and care of animals. Somatostatin 1 polyclonal anti-rabbit antibody and SSTRl in situ hybridization kit were provided by Department of Neuroanatomy, Shanghai Second Military Medical University of Chinese PLA. The drug for developing rat models of spleen deficiency was composed of Dahuang, Houpu and Zhishi, and prepared at 2：1：1. Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet recipes were made according to previous studies. METHODS： This study was performed at the Basic Medical College, Beijing University of Traditional Chinese Medicine from March 2002 to March 2005. The rats were randomly divided into 5 groups, with 10 rats in each group： normal, model, Guipi decoction, Chaihu Shugan powd.er, and Tianwang Buxin pellet groups. Rat models of the latter 4 groups were developed by methods of purgation with bitter and cold nature drugs, improper diet, and overstrain. The rats received 7.5 g/kg of the drugs each morning and were fasted every other day, but were allowed free access to water at all times. The rats were forced to swim in 25 ℃ water until fatigued. Rats in the normal group were intragastrically administered the same amount of normal saline. Rats in the Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet groups were intragastrically administered 7.5 g/kg Guipi decoction, Chaihu Shugan powder, and Tianwang Buxin pellet, respectively, every afternoon. All rats were treated for 6 weeks. MAIN OUTCOME MEASURES： Somatostatin protein and SSTRI mRNA expression in the ventral nucleus of hypothalamus, hippocampal CAl region, and cortex of prefrontal lobe were determined by immunohistochemistry and in situ hybridization, respectively. RESULTS： Fifty rats were included in the final analysis. In the model group, expression of somatostatin protein and SSTRl mRNA in the ventral nucleus of hypothalamus, hippocampal CAl region, and cortex of prefrontal lobe were significantly less than in the normal group （P 〈 0.01）. Above-mentioned indices were identical in the Chaihu Shugan powder and model groups. However, expression of somatostatin protein and SSTRl mRNA were significantly higher in the Guipi decoction group compared to model group （P 〈 0.01）. In the Tianwang Buxin pellet group, SSTRl mRNA expression in rat ventral nucleus of hypothalamus and somatostatin level in rat hippocampal CAl region and cortex of prefrontal lobe, as well as ventral nucleus of hypothalamus, were significantly higher compared to model group （P 〈 0.01 ）. CONCLUSION： Somatostatin level and SSTRl mRNA expression in rats with spleen deficiency were lower than in normal rats. Guipi decoction and Tianwang Buxin pellet up-regulated somatostatin level and SSTRl mRNA expression.

Inhibition of Metastatic Progression of SSTR2 Gene Transfection Mediated by Adenovirus in Human Pancreatic Carcinoma Cells

The inhibition of metastatic progression of Somatostatin receptor type 2 （SSTR2） gene transfection mediated by adenovirus in human pancreatic carcinoma cells and the mechanisms involved in this effect were studied. The full-length human SSTR2 cDNA was introduced into the pancreatic cancer cell line BXPC-3 by adenovirus-mediated transfection. Stable expression of mRNAs and protein of SSTR2 was detected by RT-PCR and Western-blot. The Matrigel-coated Transwell was used to detect the migratory and invasive ability of SSTR2-expressing cells, Adv-GFP control cells and mock control cells. Furthermore, the expression of matrix metalloproteinase-2 （MMP-2） and tissue inhibitor of metalloproteinase-2 （TIMP-2） was detected by RT-PCR in these cells. The stable expression of SSTR2 was detected in BXPC-3 transfected by Adv-GFP-SSTR2. A dramatic decrease of BXPC-3 expressing sst2 cells migrating through a Matrigel-coated filter was observed, as compared with Adv-GFP control and mock control cells （P〈0. 01）. Moreover, the expression of MMP-2 mRNA was significantly reduced in the SSTR2-expressing cells and converse- ly the expression of TIMP-2 mRNA was significantly increased in the SSTR2-expressing cells when compared with the Adv-GFP control and mock control （P〈0. 01）. The expression of reintroduced human SSTR2 gene in BXPC-3 cells by Adv-GFP-SSTR2 had the anti-migratory and anti-invasive effects, and the mechanisms involved in this effect may be due to the down-regulated expression of MMP-2 and up-regulated expression of TIMP-2.

Gastric neuroendocrine neoplasms: A review

Gastric neuroendocrine neoplasms(g-NENs)or neuroendocrine tumors are generally slow-growing tumors with increasing incidence.They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features.Type 1 and 2 are gastrin dependent,whereas type 3 and 4 are sporadic.The reason for hypergastrinemia is atrophic gastritis in type 1,and gastrin releasing tumor(gastrinoma)in type 2 g-NEN.The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy.g-NENs are positively stained with chomogranin A and synaptophysin.Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis.It is crucial to discriminate between types of g-NENs,because the management,treatment and prognosis differ significantly between subtypes.Treatment options for g-NENs include endoscopic resection,surgical resection with or without antrectomy,medical treatment with somatostatin analogues,netazepide or chemotherapy regimens.Follow-up without excision is another option in appropriate cases.The prognosis of type 1 and 2 g-NENs are good,whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.

Time to give up traditional methods for the management of gastrointestinal neuroendocrine tumours

Neuroendocrine tumors(NETs)are a rare and heterogeneous disease group and constitute 0.5%of all malignancies.The annual incidence of NETs is increasing worldwide.The reason for the increase in the incidence of NETs is the detection of benign lesions,incidental detection due to the highest use of endoscopic and imaging procedures,and higher recognition rates of pathologists.There have been exciting developments regarding NET biology in recent years.Among these,first of all,somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis,hormone secretion,and proliferation.Subsequently,activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism.Finally,the importance of proangiogenic factors(platelet-derived growth factor,vascular endothelial growth factor,fibroblastic growth factor,angiopoietin,and semaphorins)in the progression of NET has been determined.Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.

Impact of antagonist peptides and chelators on the diagnostic performance of PET/CT using gallium-68-labeled somatostatin receptor antagonists

Objective: Different SSTR2 antagonists have been developed. This study aims to evaluate the impact of different peptides and chelators on the diagnostic performance of SSTR2 antagonists in well-differentiated NETs.Methods: In this prospective study, participants were equally randomized into 2 arms: arm A, participants would undergo a whole-body^(68)Ga-NODAGA-LM3 PET/CT scan on the first day and^(68)Ga-DOTA-LM3 PET/CT scan on the second day;arm B, participants would undergo a whole-body^(68)Ga-NODAGA-LM3 PET/CT scan on the first day and^(68)Ga-NODAGA-JR11 PET/CT scan on the second day. Biodistribution in normal organs, lesion detection ability, and tumor uptakes were compared within each arm.Results: A total of 40 participants (age, 49.5 ± 13.4, 21 men), 20 in each arm, were recruited in the study. In arm A,^(68)Ga-DOTA-LM3 showed lower background. However, the lesion detection ability (overall lesion detected, 445 vs 548;P = .005) and the lesion uptake (overall lesions SUVmax, 19.8 ± 17.2 vs 35.3 ± 28.8;P < .001) was significantly lower than those of^(68)Ga-NODAGA-LM3. In arm B, both^(68)Ga-NODAGA-LM3 and^(68)Ga-NODAGA-JR11 showed similar biodistribution and lesion uptake (SUVmax, 28.5 ± 23.8 vs 25.0 ± 20.0;P < .001) despite minor differences. The lesion detection ability was the same between these 2 tracers (overall lesion detected, 503 vs 503).Conclusions: The diagnostic performance of SSTR2 antagonists was sensitive to chelators. Both^(68)Ga-NODAGA-LM3 and^(68)Ga-NODAGA-JR11 outperformed^(68)Ga-DOTA-LM3 with higher lesion uptake and detection ability, of which^(68)Ga-NODAGA-LM3 had marginally but significantly higher lesion uptake.

Highly variable biodistribution of ^(68)Ga labeled somatostatin analogues ^(68)Ga-DOTA-NOC and ^(68)Ga-DOTA-TATE in neuroendocrine tumors: clinical implications for somatostatin receptor directed PET/CT

Background:Somatostatin receptor(SSTR)-targeted positron emission tomography/computed tomography(PET/CT)imaging has risen to the forefront for neuroendocrine tumor(NET)detection and management,yet the variability of significant uptake variability(SUV)as a semiquantitative measure of disease detection and tumor response to treatment has not been fully explored.Methods:We assess the reproducibility and interscan variability of SUV metrics of normal tissue and NET in serial^(68)Ga-DOTA-NOC and^(68)Ga-DOTA-TATE PET imaging to clinically monitor disease state.Eighty-one patients were enrolled in this retrospective study.Results:Both primary and metastatic hepatic lesions demonstrated SUV(SUVmean 16.5±8.0).The median SUVmean was 16 for the spleen,9.7 for the pituitary,12.6 for the adrenal glands,and 4.8 for the liver.The normal pituitary gland demonstrates focal homogenous uptake with SUVmax range of 4.5–23.The adrenal gland showed uptake with SUVmax range of 4.1–29.4,which is more than two times greater than liver uptake(SUVmean range,2.3–12.4).Highest physiological uptake seen in the spleen(average SUVmean of 17.3,range of 5.4–34.4).Conclusions:The highly variable nature of regional SUVmean and SUVmax in both physiologic tissue and lesions suggests the need for incorporation of more reliable quantitative measures for clinical decision making.

Novel gold nanoparticles targeting somatostatin receptor subtype two with near-infrared light for neuroendocrine tumour therapy

Neuroendocrine tumours(NETs)are rare cancers with positive somatostatin receptor 2(SSTR2)expression,and treatment strategies for NETs are not satisfactory.Nanomaterial-mediated therapy targeting SSTR2 in NETs is very promising.This study firstly combined mesoporous silica-coated gold nanorods(AuNRs@mSiO_(2))and targeting-SSTR2 dodecane tetraacetic acidtyrosine3-octreotate(DOTA-TATE)into AuNRs@mSiO_(2)@DOTA-TATE to investigate NETs inhibition under near-infrared light.AuNRs@mSiO_(2)@DOTA-TATE showed good photothermal conversion efficiency.In vitro,under light irradiation,the cell viability significantly decreased with increasing AuNR@mSiO_(2)@DOTA-TATE concentration;in two successfully established neuroendocrine tumour organoids with SSTR2 expression,AuNRs@mSiO_(2)@DOTA-TATE with light inhibited tumours significantly better than AuNRs@mSiO_(2) with light.In vivo,the SSTR2-targeting ability and biodistribution of AuNRs@mSiO_(2)@DOTA-TATE were confirmed with AuNRs@mSiO_(2)@64Cu-DOTA-TATE under micro-positron emission tomography/computed tomography(micro-PET/CT);in the AuNRs@mSiO_(2)@DOTA-TATE with laser group,the tumour surface temperature increased rapidly,with tumour volumes similar to those in the octreotide group and significantly lower than those in other groups.There was no significant difference in mice body weight between the AuNRs@mSiO_(2)@DOTA-TATE with laser group and other groups.No significant inflammatory lesions or cell necrosis was found in the main organs.In summary,we presented a feasible strategy to construct AuNRs@mSiO_(2)@DOTA-TATE with good photothermal conversion efficiency,targetingSSTR2 ability,significant antitumour effects,and good biocompatibility,warranting further explorations of AuNRs@mSiO_(2)@DOTA-TATE for NETs therapy applications.

Using Homology Modeling, Molecular Dynamics and Molecular Docking Techniques to Identify Inhibitor Binding Regions of Somatostatin Receptor 1

The G protein coupled receptor（GPCR）, one of the members in the superfamily, which consists of thousands of integral membrane proteins, exerts a wide variety of physiological functions and responses to a large portion of the drug targets. The 3D structure of somatostatin receptor I（SSTR1） was modeled and refined by means of homology modeling and molecular dynamics simulation. This model was assessed by Verify-3D and Vadar, which confirmed the reliability of the refined model. The interaction between the inhibitor cysteamine, somatostatin（SST） and SSTR1 was investigated by a molecular docking program, Affinity. The binding module not only showed the crucial residues involved in the interaction, but also provided important information about the interaction between SSTR1 on the one hand and ligands on the other, which might be the significant evidence for the structure-based design.

Impact of antagonist peptides and chelators on the diagnostic performance of PET/CT using gallium-68 labeled somatostatin receptor antagonists

Objective:Different SSTR2 antagonists have been developed.This study aims to evaluate the impact of different peptides and chelators on the diagnostic performance of SSTR2 antagonists in well-differentiated NETs.Methods:In this prospective study,participants were equally randomized into two arms:Arm A,participants would undergo a whole-body 68Ga-NODAGA-LM3 PET/CT scan on the 1st day and 68Ga-DOTA-LM3 PET/CT scan on the 2nd day;Arm B,participants would undergo a whole-body 68Ga-NODAGA-LM3 PET/CT scan on the 1st day and 68Ga-NODAGA-JR11 PET/CT scan on the 2nd day.Biodistribution in normal organs,lesion detection ability,and tumor uptakes were compared within each Arm.Results:A total of 40 participants(age,49.5±13.4,21 men),20 in each arm,were recruited in the study.In Arm A,68Ga-DOTA-LM3 showed lower background.However,the lesion detection ability(overall lesion detected,445 versus 548,P=0.005)and the lesion uptake(overall lesions SUVmax,19.8±17.2 versus 35.3±28.8,P<0.001)was significantly lower than those of 68Ga-NODAGA-LM3.In Arm B,both 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 showed similar biodistribution and lesion uptake(SUVmax,28.5±23.8 versus 25.0±20.0,P<0.001)despite minor differences.The lesion detection ability was the same between these two tracers(overall lesion detected,503 versus 503).Conclusions:The diagnostic performance of SSTR2 antagonists was sensitive to chelators.Both 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 outperformed 68Ga-DOTA-LM3 with higher lesion uptake and detection ability,of which 68Ga-NODAGA-LM3 had marginally but significantly higher lesion uptake.

Perspective of molecular imaging and peptide receptor radionuclide therapy in pancreatic neuroendocrine tumors:where do we stand?

The clinical use of nuclear medicine imaging and therapy in pancreatic neuroendocrine tumors has been greatly strengthened since the approval of ^(68)Ga-DOTATATE and ^(177)Lu-DOTATATE.However,many aspects are still under discussion.In this 2-part article,we aim to collect and discuss current evidence of molecular imaging and peptide receptor radionuclide therapy(PRRT)in pancreatic neuroendocrine tumor.In the first part,we will address some critical aspects of ^(68)Ga-SSAs imaging,including diagnostic efficacy,recurrence detection and follow-up,patient selection for PRRT,and pitfalls in image interpretation.Besides,we will also briefly discuss the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography,special imaging strategy in regard to insulinoma,and the status of radiolabeled somatostatin receptor antagonist.In the second part,we aim to review the current evidence of PRRT in pancreatic neuroendocrine tumor,focusing on efficacy and safety in particular.We will also introduce the recent development of PRRT,including PRRT in high-grade neuroendocrine neoplasms,retreatment PRRT,upfront PRRT,PRRT in the setting of neoadjuvant therapy and conversion therapy,combination therapies with PRRT,PRRT withαradionuclides,and PRRT with antagonists.

Short-term Preoperative Octreotide for Thyrotropin-secreting Pituitary Adenoma

Background： Thyrotropin-secreting pituitary adenomas （TSHomas） are a rare cause of hyperthyroidism. Somatostatin （SST） analogs work by interacting with somatostatin receptors （SSTRs）. This study aimed to evaluate short-term preoperative octreotide （OCT） use in TSHoma patients and to investigate SSTR2 and SSTR5 expression and observe structural changes in tumor tissue. Methods： We reviewed records and samples from eight TSHoma patients treated between July 2012 and July 2015. We tested immunohistochemically for SSTR2/5 expression and examined TSHoma cells for morphological changes. Signed rank sum test was used to compare the efficacy of short-term preoperative OCT treatment. Results： OCT treatment （median time： 7.9 days, range： 3-16 days; median total dose： 1.8 mg, range： 0.94.2 mg） led to significant decrease in all patients＇ thyroid hormone levels （FT3 [nmol/L]： 8.33 [7.02, 12.29] to 4.67 [3.52, 5.37] [P = 0.008]; FT4 [pmol/L]： 25.36 [21.34, 28.99] to 16.66 [14.88, 21.49] [P = 0.016]; and TSH [gU/ml]： 5.80 [4.37, 6.78] to 0.57 [0.19, 1.24] [P = 0.008]）. All the eight tumor specimens expressed high SSTR2 protein levels; 5/8 expressed high SSTRS, but 3/8 that expressed low SSTR5 presented a significantly higher TS H suppression rate （P = 0.036）. Electron microscopy showed subcellular level impairments, including clumped nuclear chromatin and reduced cytoplasmic volume. Golgi complexes were observed in the OCT-treated TSHoma specimens. Conclusions： OCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.