Spatial and temporal expression pattern of somatostatin receptor 2 in mouse / 生物工程学报

Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.

Expression and clinical significance of SSTR2, ADAM-12 and FLI-1 in small cell lung cancer tissue / 中国基层医药

Objective:To investigate the expression and clinical significance of somatostatin receptor 2 (SSTR2), a disintegrin and metalloproteinase-12 (ADAM-12), and friend leukemia virus integration-1 (FLI-1) in small cell lung cancer tissue.Methods:Eighty-two patients with small cell lung cancer who received treatment in Haiyang People's Hospital from January 2020 to January 2021 were included in this study. All patients underwent radical surgical resection. Small cell lung cancer tissues and adjacent tissues more than 2 cm from the edge of cancer tissues were harvested. The positive expression rates of SSTR2, ADAM-12, and FLI-1 in cancer tissues and adjacent tissues were determined by immunohistochemistry. The relationship between SSTR2, ADAM-12, FLI-1, and clinical characteristics were analyzed. The 1-year survival rate of patients with small cell lung cancer was calculated.Results:The positive rates of SSTR2, ADAM-12, and FLI-1 in small cell lung cancer tissue were 79.27% (65/82), 76.83% (63/82), and 78.05% (64/82), respectively, which were significantly higher than 19.51% (16/82), 17.07% (14/82), 20.73% (17/82) in the adjacent tissue ( χ2 = 58.57, 58.78, 53.90, all P < 0.05). SSTR2, ADAM-12, and FLI-1 were positively associated with lymph node metastasis, clinical stage, tissue invasion, tumor size, and histological grade (all P < 0.05). After controlling for gender, age, and others, SSTR2, ADAM-12, and FLI-1 were associated with lymph node metastasis, clinical stage, tissue invasion, tumor size, and histological grade (all P < 0.05). All patients were followed up for 1 year. Six patients were lost to follow-up. The 1-year survival rate of 76 patients with small cell lung cancer was 67.11% (51/76). The survival rate of patients with positive SSTR2, ADAM-12, and FLI-1 expression were lower than that of patients with negative SSTR2, ADAM-12, and FLI-1 expression ( χ2 = 3.93, 6.43, 7.52, all P < 0.05). Conclusion:SSTR2, ADAM-12, and FLI-1 are highly expressed in small cell lung cancer tissue. Combined detection of SSTR2, ADAM-12, and FLI-1 is conducive to the prognosis and evaluation of small cell lung cancer in patients. This study is innovative and scientific.

Clinical Research Progress of the Non-Peptide Oral Somatostatin Receptor Ligand Paltusotine / 罕见病研究

The research and development of somatostatin analogues is a hot area in endocrinology and metabolism. The first generation octreotide, lanreotide and the second generation pareotide have been approved to be effective for the treatment of neuroendocrine tumors such as acromegaly. However, paltusotine, a somatostatin receptor ligand, is a novel non-peptide small molecule drug which can be administered orally and inhibits excessive secretion of growth hormone and insulin-like growth factor 1. This review summarizes the research progress of the pharmacokinetics, pharmacodynamics, clinical efficacy, telerability, and safety of paltusotine.

Imaging Characteristics of 68Ga-DOTATATE PET/CT in Tumor-Induced Osteomalacia / 罕见病研究

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumors secreting fibroblast growth factor 23 (FGF23) that promotes urinary phosphorus excretion. Thus, TIO is typically characterized by phosphoruria, hypophosphatemia, and osteomalacia. Diagnosis and localization of the tumor is often difficult due to its small size, slow growth and concealed location. Due to the high expression of somatostatin receptors in pathogenic tumors, nuclear medicine functional imaging, particularly somatostatin receptor imaging, is used for diagnosis and localization of culprit tumors with high sensitivity and specificity. Here we retrospectively analyze 25 cases in which 68Ga-DOTATATE PET/CT successfully localized and diagnosed TIO culprit tumors. The clinical features, pathological results and image characteristics of 68Ga-DOTATATE PET/CT imaging were analyzed and compared with other imaging diagnostic techniques. It was confirmed that 68Ga-DOTATATE PET/CT imaging was the preferred imaging technique for successful diagnosis and localization of TIO pathogenic tumors.

Effects of somatostatin receptor ligands on bone metabolism in acromegaly / 中华内分泌代谢杂志

Objective:To investigate the effect of somatostatin receptor ligands (SRLs) on bone metabolism in patients with acromegaly.Methods:Retrospective analysis of clinical data of acromegaly patients( n=100) received surgery or SRLs alone for 3 months. The changes of growth hormone (GH), insulin-like growth factor-1 (IGF-1), osteocalcin (OC), N-mid fragment of osteocalcin (N-MID), amino-terminal peptide of type I procollagen (P1NP) and C-terminal peptide degradation product of type I collagen(CTX) were compared before and after treatment. Patients were divided into drug treatment group and surgical group according to treatment methods. According to the decline of GH after medication, patients in the drug treatment group were further divided into drug sensitive group and drug insensitive group. Results:The average dynamic GH and IGF-1 indexes in the drug treatment group were significantly decreased after treatment compared with before treatment (both P<0.05), and CTX was also significantly decreased after treatment [1.25 (0.67, 1.40) ng/mL vs 1.34 (0.57, 1.68) ng/mL, P<0.05]. The mean dynamic GH, IGF-1 index, OC, N-MID, P1NP, and CTX in surgical group were significantly decreased after treatment compared with before treatment (all P<0.01). In the surgical group, there was a positive correlation between GH difference (ΔGH) and N-mid difference (ΔN-MID; r=0.454, P=0.026), and there was a positive correlation between IGF-1 index difference (ΔIGF-1 index) and CTX difference (ΔCTX; r=0.339, P=0.036). After treatment, the mean dynamic GH, IGF-1 index, CTX, P1NP, and N-MID in drug treatment group were significantly higher than those in surgical group (all P<0.001). CTX and N-MID decreased significantly after treatment in drug sensitive group compared with drug insensitive group (35.3% vs 7.2%, P<0.001; 24.1% vs 11.8%, P<0.05), and ΔGH was positively correlated with ΔCTX ( r=0.328, P=0.004). Conclusion:SRLs treatment can reduce bone formation marker N-MID and bone resorption marker CTX, improving the high turnover state of bone metabolism in patients with acromegaly, which may attribute to the reduction of GH and IGF-1 levels.

Value of octreotide suppression test in predicting the efficacy of long-acting somatostatin receptor ligands in pituitary GH adenomas / 中华内分泌代谢杂志

Objective:To explore the value of octreotide suppression test(OST) in predicting the efficacy of somatostatin receptor ligands(SRLs) in the treatment of active acromegaly.Methods:The clinical data of 76 patients with active acromegaly from 2011 to 2020 was retrospectively analyzed. OST was carried out as follows: After an overnight fasting and baseline sampling of growth hormone(GH), 100 μg octreotide was subcutaneously injected, and sampling for GH was obtained every 2 hours for 8 hours. All patients were treated with SRLs for at least 3 months. A good GH response is defined as a post-treatment random GH<1 μg/L or >80% fall compared with the baseline GH. A good insulin-like growth factor Ⅰ(IGF-Ⅰ) response is defined as IGF-Ⅰ<1.3 upper limit of normal(ULN) or >50% reduction compared with the baseline. If both GH and IGF-Ⅰ fulfill the criteria of a good response, it is defined as a good GH and IGF-Ⅰ response.Results:The baseline level of GH during OST was 15.00(6.38, 34.20) μg/L, the median time to reach the nadir GH was(3.65±1.65) hours, and the nadir GH level was 1.47(0.50, 4.19) μg/L. The median GH suppression rate was 89.12%(72.71%, 95.09%). When the cutoff value of GH suppression rate in predicting a good GH response was 89.32%, the area under the curve(AUC) was 0.74, with a sensitivity of 81.80% and specificity of 66.00%. When the cutoff value of GH suppression rate in predicting a good IGF-Ⅰ response was 93.14%, the AUC was 0.64, with a sensitivity of 50.00% and specificity of 75.60%. When the GH suppression rate was 90.71%, the AUC was 0.78, with the sensitivity of 83.30% and specificity of 70.00% in predicting a good GH and IGF-Ⅰ response. Compared with GH/IGF-Ⅰ non-responders, GH/IGF-Ⅰ responders displayed lower nadir GH during OST, higher GH suppression rate and IGF-Ⅰ reduction rate, and lower ratio of IGF-1 to ULN( P<0.05). Conclusion:GH suppression rate during the OST is a valuable predictor to evaluate the efficacy of SRLs in patients with acromegaly, with the highest sensitivity and specificity when the cutoff value is 90.71%.

Physiological role and neuroprotective effects of somatostatin in retina / 中华实验眼科杂志

Somatostatin, also called somatotropin release-inhibiting factor (SRIF), is a kind of neurotransmitter, neuromodulator and neurotrophic factor, which participates in a variety of physiological functions in the central nervous system by activating the five G-protein-coupled receptors (sst 1-sst 5). SRIF and its receptors are extensively expressed and distributed in retina.Activation of SRIF receptors modulates voltage-gated K + and Ca 2+ channels, and regulates multiple intracellular signaling pathways in retinal cells, then influences neurotransmitter release and synaptic transmission, which plays an important role in the regulation of retinal visual information processing.In addition, SRIF and its receptors may provide protective effects against retinal injuries, such as retinal ischemia, excitotoxic injury and diabetic retinopathy.In this article, connected with related previous researches of our team, the distribution of SRIF and its receptor in retina, as well as the role of SRIF and its receptor in the physiological regulation and neuroprotection of retina were reviewed.

Análogos de somatostatina radiomarcados en el acercamiento diagnóstico del síndrome de Sjögren: Imágenes moleculares aportando a los criterios clínicos y paraclínicos hoy conocidos / Radiolabelled somatostatin analogues in the diagnostic approach to Sjögren's syndrome: molecular imaging contributing to the current clinical and para-clinical criteria

RESUMEN El diagnóstico del síndrome de Sjögren se basa en los criterios del consenso americano y europeo (AECG), sin embargo, en muchas oportunidades no se alcanza a detectar el compromiso glandular o extraglandular. Presentamos la evidencia de la utilidad de la gammagrafía con los análogos de somatostatina radiomarcados como prueba novedosa en el acercamiento diagnóstico al compromiso glandular y extraglandular del síndrome de Sjögren.

ABSTRACT Sjögren syndrome is diagnosed using American European Consensus Group (AECG) criteria, although frequently these criteria are not enough to detect the glandular and extra-glandular compromise. Evidence is presented on the use of whole body somatostatin scintigraphy as a novel probe in the diagnostic approach to the glandular and extra-glandular compromise in Sjögren s syndrome.

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.

Octreotide modulates expression of somatostatin receptor subtype 4 and 5 in unweaned rat jejunum inflamed by Cryptosporidium parvum / 中国药理学通报

Aim To investigate the effects of intestinal infection induced by Cryptosporidium parvum on the ex-pression pattern of SSTR4 and SSTR5 subtype, and to examine the effect of octreotide on modulating short-term and long-term SSTR4 and SSTR5 subtype expres-sion in rat jejunum. Methods Five-day-old suckling Sprague-Dawley rats were orally gavaged with 105Cryp-tosporidium oocysts to establish the model of post-infec-tion irritable bowel syndrome (PI-IBS). Rats then re-ceived 50 μg·kg-1·d-1of octreotide by intraperito-neal injection from day 10 to day 17 post-infection. Animals were sacrificed on day 17,37 and 50 post-in-fection for immunohistochemical analysis and on day 14,35 and 50 for mRNA expression analysis of SSTR4 and SSTR5 subtypes. Results Immunohistological a-nalysis of jejunum tissues demonstrated that SSTR5 was mainly expressed in submucosa while a little in crypt,while SSTR4 was mainly expressed in crypt while a lit-tle in submucosa and absorptive cells. Real-time PCR analysis indicated a significant increase of SSTR4 and SSTR5 expression in the inflamed jejunum. Octreotide treatment decreased the expression of SSTR4 and SSTR5 on day 50 post-infection. Conclusions SSTR4 and SSTR5 may be involved in the inflammatory reac-tion in PI-IBS rats induced by Cryptosporidium parvu-man, which shows an increase in SSTR4 and SSTR5 mRNA expression in jejunum. Octreotide therapy in-hibits the jejunum hypersensitivity and relieve PI-IBS symptoms, which may be related to the decrease of SSTR4 and SSTR5 expression.

Successful primary medical therapy with somatostatin receptor ligand in acromegaly with thyroid cancer / Journal of the ASEAN Federation of Endocrine Societies

@#Acromegaly is a rare disease with an annual incidence of 3 to 4 cases in a million.[1] Diagnosis is often delayed due to the slow progression of the disease. Persistent elevation of growth hormone (GH) in acromegaly causes a reduction in life expectancy by 10 years. Aside from multiple cardiovascular, respiratory and metabolic co-morbidities, it has also been proven to cause an increased incidence of cancer. The main treatment of acromegaly is surgical excision of the functioning pituitary adenoma. Multiple comorbidities, including obstructive sleep apnea (OSA), left ventricular hypertrophy (LVH) and soft tissue swelling, make surgery complicated, if not impossible. Medical therapy to reduce co-morbidities may be indicated in certain situations. Somatostatin receptor ligands (SRL) are able to reduce, and possibly normalize, IGF-1 levels.[2] Reduction of insulin-like growth factor-1 (IGF-1), the main mediator of GH, is able to resolve headache, sweating, fatigue and soft tissue swelling, and also reduce ventricular hypertrophy. This case report illustrates the successful use of the SRL octreotide LAR in treating acromegaly. It also confirms the observation from several case series that thyroid cancer is the most common malignancy in acromegaly.

Diagnostic work-up of gastroenteropancreatic neuroendocrine tumors

Neuroendocrine tumors are a heterogeneous group of malignancies that present a diagnostic challenge. The majority of patients (more than 60%) present with metastatic disease at diagnosis. The diagnosis is based on histopathology, imaging, and circulating biomarkers. The histopathology should contain specific neuroendocrine markers such as chromogranin A, synaptophysin, and neuron-specific enolase and also an estimate of the proliferation by Ki-67 (MIB1). Standard imaging procedures consist of computed tomography or magnetic resonance imaging together with somatostatin receptor scintigraphy. 68Ga-DOTA-octreotate scans will in the future replace somatostatin receptor scintigraphy because they have higher specificity and sensitivity. Other positron imaging tomographic scanning tracers that will come into clinical use are 18F-DOPA and 11C-5HTP. Neuroendocrine tumors secrete many different peptides and amines that can be used as circulating biomarkers. The most useful general marker is chromogranin A, which is both a diagnostic and prognostic marker in most neuroendocrine tumors. However, there is still a need for improved biomarkers for early detection and follow-up of patients during treatment. In addition, molecular imaging can be further developed for both detection and evaluation of treatment.

SSTR2A Protein Expression in Neuroendocrine Neoplasms of the Colorectum

BACKGROUND: Expression studies of somatostatin receptor type 2A (SSTR2A) in neuroendocrine neoplasms (NENs) led to the development of clinically relevant diagnostic and therapeutic strategies. However, most of these strategies used in-house-developed antibodies and were focused on lung tumors. We evaluated commercially available SSTR2A antibodies in NENs of the colorectum to observe their subcellular localization and distribution within the resected tumor. METHODS: The immunohistochemistry of 77 NENs located in the colorectum were studied using a commercially available antibody against SSTR2A. RESULTS: Most neuroendocrine tumors (NET) grade (G)1 and G2 expressed the SSTR2A in the cytoplasm with apical or luminal localization. However, all neuroendocrine carcinomas (NEC) G3 were negative for SSTR2A. CONCLUSIONS: Our data indicate that SSTR2A immunohistochemistry shows cytoplasmic staining with distinct subcellular localization in most NET G1 in the colorectum using a commercially available antibody. Low or no expression of SSTR2A in NET G2 and NEC G3 raises the possibility that SSTR2A may correlate with histologic differentiation and proliferative activity. Further validation studies in large case series are needed.

Gammagrafía con receptores de somatostatina en un caso de carcinoma medular de tiroides / Somatostatin receptor scintigraphy for thyroid medullary carcinoma: a case report

La gammagrafía con radiotrazadores que tienen afinidad por los receptores de somatostatina se ha convertido en metodología eficaz para el diagnóstico y estadificación de los tumores neuroendocrinos. Se presenta un caso en el cual el procedimiento radioisotópico muestra su efectividad en la localización del tumor primario.

Somatostatin receptor scintigraphy has become an important tool for diagnosis and evaluation of neuroendocrine tumors. This case report shows about the importance of the radionuclide procedure for the localization of the primary tumor.

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly / Expressão dos receptores da somatostatina subtipos 2 e 5 e do receptor da dopamina tipo 2 e gsp status como preditores de resposta ao octreotide LAR® na acromegalia

We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR® therapy response. Case reports: Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181 percent above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR® therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA - SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114 percent ULRV, respectively. Patient underwent non-curative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/mL and 137 percent ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR® therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA - SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be conflicting as predictors of octreotide LAR® responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients.

Apresentamos dois pacientes acromegálicos nos quais dados clínicos e moleculares são discutidos quanto à sua capacidade de predizer a resposta a longo prazo ao tratamento com octreotide LAR®. Relato dos casos: Paciente 1: Feminina, 36 anos de idade ao diagnóstico. GH e IGF-I ao diagnóstico 133 ng/mL e 181 por cento acima do limite superior do valor de referência (LSVR), respectivamente. GH durante o teste agudo com octreotide subcutâneo diminuiu de 133 para 13 ng/mL. Foi iniciado tratamento primário com octreotide LAR® (20 mg q28 dias) e a paciente alcançou os parâmetros bioquímicos de controle de doença depois de seis meses. Análise molecular do tumor: gsp +; análise quantitativa do mRNA de SSTR (receptores de somatostatina) e DR (receptor de dopamina) - SSTR2 23.954; SSTR5 2.407; DR2 total 17.016 cópias. Paciente 2: Masculino, 38 anos de idade ao diagnóstico. GH e IGF-I ao diagnóstico 120 ng/mL e 114 por cento LSVR, respectivamente. Paciente foi submetido à cirurgia trans-esfenoidal não-curativa. GH e IGF-I pós-operatórios 112 ng/mL e 137 por cento LSVR, respectivamente. GH durante o teste agudo diminuiu de 112 para 7 ng/mL. Foi iniciado tratamento com octreotide LAR® (20 mg q28 dias). Após seis meses o paciente não alcançou controle bioquímico e apresentou aumento do volume tumoral. Análise molecular do tumor: gsp não estudado; análise quantitativa do mRNA de SSTR e DR - SSTR2 416; SSTR5 3.767; DR2 total 3.439 cópias. Em conclusão, estes dois casos ilustram como dados laboratoriais podem ser conflitantes enquanto preditores de resposta ao tratamento com octreotide LAR® e como a análise molecular de fragmentos do tumor pode ajudar a explicar comportamentos diferentes em pacientes clinicamente semelhantes.

Inhibition of Metastatic Progression of SSTR2 Gene Transfection Mediated by Adenovirus in Human Pancreatic Carcinoma Cells / 华中科技大学学报（医学）（英德文版）

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 byRT-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 conversely 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.

Expression of somatostatin receptors in nasopharyngeal carcinoma cell line CNE_2 / 中国癌症杂志

Background and purpose:Somatostatin receptors have been found in a variety of tumors and are therefore amenable to treatment with somatostatin analogs, like octreotide. However, the study of SSTRs expression has been rarely studied in nasopharyngeal cancer.We investigated the expression of somatostatin receptors gene subtypes in human nasopharyngeal cancer cell line CNE_ 2 . Methods:We have harvested cultured human nasopharyngeal cancer cell line CNE_ 2 . Using both techniques, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical assay, we analysed mRNA of different subtypes of somatostatin receptors in human nasopharyngeal cancer cell line CNE_ 2 .Results:The positive rate of somatostatin receptors subtype SSTR_ 1 SSTR_ 2 SSTR_ 4 was manifested in the human nasopharyngeal carcinoma cell line CNE_ 2 by RT-PCR and immunohistochemical assay. According to immunohistochemical assay, SSTR_ 1 and SSTR_ 2A showed strongly positive expression and SSTR_ 3 and SSTR_ 5 negative expression,respectively.Conclusions:There are more than one SSTR subtypes expressed in the human nasopharyndeal carcinoma cell line CNE_ 2 . This study demonstrated the presence of SSTR_1,SSTR_ 2 in the human nasopharyndeal carcinoma cell line CNE_ 2 .

Changes in Somatostatin Receptor mRNA Levels by G Protein Mutation in GH3 Cells Which Show Responsiveness to Growth Hormone-Releasing Hormone / 대한내분비학회지

BACKGROUNDS: GH3 cells lack growth hormone(GH)-releasing hormone(GHRH) receptors. In this study, GH3 cells permanently transfected with human GHRH receptor cDNA(GH3-GHRHR cells), were established in order to examine the effects of GHRH and G protein mutation(gsp oncogene) on the levels of somatostatin receptor mRNA. METHODS: GH3 cells were permanently transfected with a plasmid expressing human GHRH receptor cDNA. The GHRH receptor mRNA was detected by RT-PCR. The responsiveness to GHRH was evaluated using a GHRH binding assay, Western blot analysis, Northern blot analysis, and measurements of the intracellular cAMP levels and GH release. Cells were transiently transfected with the gsp oncogene, and then treated with GHRH or octreotide for 4h. The sst1 and sst2 mRNA levels were measured using real-time RT-PCR analyses. RESULTS: GHRH receptor mRNA was detected in the GH3 cells permanently transfected with human GHRH receptor cDNA. The GHRH binding assay showed that GHRH was bound to the GH3-GHRHR cells. The GHRH treatment increased the intracellular cAMP levels, GH release, GH mRNA levels, and MAPK activity, as well as the levels of sst1 and sst2 mRNA. Transient expression of the gsp oncogene for 48h increased the cAMP, GH release, and levels of sst1 and sst2 mRNA. In the gsp-transfected GH3-GHRHR cells, GHRH stimulation resulted in decreases in the magnitude of the increase in the levels of sst1 and sst2 mRNA compared to those transfected with a control vector. Octreotide treatment did not alter the levels of sst1 and sst2 mRNA in either the control or gsp-transfected cells. CONCLUSION: These results suggest that GH3 cells permanently transfected with the GHRH receptor are useful in the in vitro studies on the actions of GHRH. The gsp oncogene was shown to increases the levels of sst1 and sst2 mRNA in GH3 cells, but these findings are unlikely to be the major mechanism by which gsp-positive pituitary tumors show a greater response to somatostatin. The discrepancy between the in vivo and these in vitro results should be examined further.

Clinical Application of ~(99m)Tc-Octreotide and ~(99m)Tc-MIBI Imaging in the Diagnosis of Breast Cancer / 中国普外基础与临床杂志

Objective To evaluate the value of 99mTc-Octreotide somatostatin receptor and 99mTc-MIBI imaging in the detection of breast cancer. Methods 99mTc-Octreotide and 99mTc-MIBI imaging were performed in 26 patients with breast masses before operation. The scintigraphy results were analysed compared with pathologic study.Results The sensitivity, specificity and accuracy of 99mTc-Octreotide scintigraphy for breast cancer were 94.4%, 87.5%and 92.3%respectively and those of 99mTc-MIBI were 88.9%, 75.0%and 84.6%respectively. Significant difference was found between 99mTc-Octreotide and 99mTc-MIBI in both of specificity and accuracy (P

The neoplastic action mechonism of somatostatin and its application in pancreatic cancer / 肠外与肠内营养

s: Pancreatic cancer remains a major unsolved health problem.Over the past decade,antiproliferative effects of somatostatin and analogs have been reported in many somatostatin receptor-positive normal and tumor cell types.Somatostatin and analogs act through five somatostatin receptors(SSTR1-5)which are variably expressed in normal and tumor cells.The present review focuses on recent advances in biological mechanisms involved in the antineoplastic activity of somatostatin and analogs.