AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due t...AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the f irst year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.展开更多
BACKGROUND: Somatostatin, a neuropeptide and hor- mone , exists in the biliary tract of several species. The effects of somatostatin and its analogues on the sphincter of Oddi motility have been controversial. The aim...BACKGROUND: Somatostatin, a neuropeptide and hor- mone , exists in the biliary tract of several species. The effects of somatostatin and its analogues on the sphincter of Oddi motility have been controversial. The aim of this study was to observe the action of stilamin and sandostatin on the sphincter of Oddi via choledochofiberscope manometry. METHODS: Twenty patients who had had'T' duct after cholecystectomy and choledochotomy were divided into 2 groups randomly: stilamin and sandostatin. They were subjected to manometry via a choledochofiberscope through the'T' duct tract. The following data recorded in- cluded duodenal pressure (DP), sphincter of Oddi basal pressure (SOBP), sphincter of Oddi contractive amplitude (SOCA), frequency of the sphincter of Oddi (SOF), dura- tion of the sphincter of Oddi, and the common bile duct pressure (CBDP). RESULTS: After intravenous administration of stilamin at a dose of 250 μg/h, the mean SOCA increased from 89.18 (26.50) to 128.57(54.21) mmHg (P <0.05). After the ad- ministration of stilamin at a dose of 500 μg/h the mean SO- CA declined to 92.18(42.81) mmHg (P<0.05), and mean SOBP declined from 17.63(13.36) to 8.16(4.01) mmHg (P<0.05). Although SOF had declined from 9.25(2.45) to 7.46(1.52) n/min, it was not significantly influenced. After intravenous administration of sandostatin at a dose of 100 μg, the mean CBDP increased obviously. CONCLUSIONS: Intravenous administration of stilamin at a dose of 250 μg/h stimulates the motility of the sphincter of Oddi whereas the injection of stilamin at a dose of 500 μg/h inhibits its motility. Intravenous injection of sandosta- tin of 100 μg has no effect on the sphincter of Oddi.展开更多
AIM: To discuss the protective effect of electroacupuncture at the Foot-Yangming Meridian on gastric mucosal lesion, somatostatin (SS) and the expression of SS receptor genes (SSR1mRNA) in rabbits with gastric ul...AIM: To discuss the protective effect of electroacupuncture at the Foot-Yangming Meridian on gastric mucosal lesion, somatostatin (SS) and the expression of SS receptor genes (SSR1mRNA) in rabbits with gastric ulcer and to further explore the relative specificity of meridians and viscera at gene expression level. METHODS: Forty rabbits were randomly divided into control group (A), gastric ulcer model group (B), FootYangming Meridian group (C), Foot-Shaoyang Meridian group (D) and Foot-Taiyang Meridian group (E). The gastric ulcer model was prepared by infusing alcohol into stomach. Groups C-E were treated with electroacupuncture at points along the above meridians using meridian stimulating instruments for 7 days respectively. By the end of treatment, the index of gastric ulcer was determined, the amount of epidermal growth factor(EGF) and somatostatin was measured by radioimmunoassay (PJA). SS-R1mRNA expression in gastric mucosa was determined by RT-PCR. RESULTS: The value of EGF in model group was obviously lower(73.6±14.8 vs 91.3±14.9 pg/mL, P〈 0.01) than that in control group. The index of gastric ulcer, content of SS and expression of SSRtmRNA in gastric mucosa were significantly higher than those in control group (24.88 ± 6.29 vs 8.50 ± 2.98 scores, P〈 0.01; 2978.6 ± 587.6 vs 1852.4 ± 361.7 mIU/mL, P〈 0.01; 2.56±0.25 vs 1.04±0.36, P〈0.01) . The value of EGF in Foot-Yangming Meridian group was higher than that in model group(92.2±6.7 vs 73.6±14.8 pg/mL, P〈 0.01). The index of gastric ulcer, content of SS and expression of SS-R1mRNA in gastric mucosa were significantlylower than those in control group(10.88±3.23 vs 24.88±6.29 scores, P〈0.01; 1800.2±488 vs 2978.6±587.6 mIU/mL, P 〈 0.01; 1.07±0.08 vs 2.56±0.25mIU/mL, P〈0.01). Compared to the model group, the content of SS and expression of SSRlmRNA in gastric mucosa in Foot-Shaoyang Meridian group decreased (2441.0±488. vs 2978.6± 587.6 mIU/mL, P〈 0.05; 1.73±0.16 vs 2.56±0.25 mIU/mL, P〈0.01). But the above parameters in Foot-Taiyang Meridian group did not improve and were significantly different from those in Footoyangming Meridian group (P〈0.05) CONCLUSION: Electro-acupuncture at Foot-Yangming Meridian can protect gastric mocusa against injury. The mechanism may be releted to the regulation of brain-gut peptides and the expression of SSRtmRNA.展开更多
AIM: To explore the correlation between expression of somatostatin (SS), gastrin (GAS) and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma.METHODS: Sixty-two large intestine cancer tissue samples...AIM: To explore the correlation between expression of somatostatin (SS), gastrin (GAS) and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma.METHODS: Sixty-two large intestine cancer tissue samples were randomly and retrospectively selected from patients with large intestine carcinoma. Immunohistochemical staining for bcl-2, bax, GAS, SS was performed according to the standard streptavidin-biotin-peroxidase (S-P) method.According to the semi-quantitative integral evaluation, SS and GAS were divided into three groups as follows. Scores1-3 were defined as the low expression group, 4-8 as the intermediate expression group, 9-16 as the high expression group. Bax and bcl-2 protein expressions in different GAS and SS expression groups of large intestine carcinoma were assessed.RESULTS: The positive expression rate of bax had a prominent difference between SS and GAS high, intermediate and low expression groups (P<0.05, x2ss = 9.246; P<0.05,x2GAS = 6.981). The positive expression rate of bax in SS high (80.0%, 8/10) and intermediate (76.5%, 13/17)expression groups was higher than that in low expression group (40.0%, 14/35) (P<0.05, x2high vs low = 5.242; P<0.05,x2middle vs low = 6.097). The positive expression rate of bax in GAS high expression group (27.3%, 3/8) was lower than that in low expression group (69.4%, 25/36) (P<0.05,x2 = 4.594). However, bax expression in GAS intermediate expression group (46.7%, 7/15) was lower than that in low expression group, but not statistically significant. The positive expression rate of bcl-2 had a prominent difference between SS and GAS high, intermediate and low expression groups (P<0.05, x2ss = 7.178; P<0.05, x2GAS = 13.831). The positive expression rate of bcl-2 in GAS high (90.9%, 10/11)and intermediate (86.7%, 13/15) expression groups was higher than that in low expression group (44.4%, 16/36)(P<0.05,x2high vs low = 5.600; P<0.05, x2 middle vs low = 7.695).However, the positive expression rate of bcl-2 in SS high (40.0%, 4/10) and intermediate (47.1%, 8/9) expression groups was lower than that in low expression group (77.1%, 27/35)(P<0.05, x2 high vs low = 4.710; P<0.05, x2 middle vs low = 4.706).There was a significant positive correlation between the integral ratio of GAS to SS and the integral of bcl-2 (P<0.01,r=0.340). However, there was a negative correlation between the integral ratio of GAS to the SS and bax the integral of (P<0.05, r = -0.299).CONCLUSION: The regulation and control of gastrin,somatostatin in cell apoptosis of large intestine carcinoma may be directly related to the abnormal expression of bcl-2, bax.展开更多
AIM: To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/ FasL and caspases in large intestinal carcinoma (LI...AIM: To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/ FasL and caspases in large intestinal carcinoma (LIC). METHODS: Expression of GAS and SS mRNAs were detected by nested RT-PCR in 79 cases of LIC. Cell apoptosis was detected by molecular biology in situ apoptosis detecting methods (TUNEL). Immunohistochemical staining for GAS, SS, Fas/FasL, caspase-3 and caspase-8 was performed according to the standard streptavidin-biotin-peroxidase (S-P) method. RESULTS: There was a significant positive correlation between mRNA and protein expression of GAS and SS (GASrs=0.99, P < 0.01; SSrs = 0.98, P < 0.01). There was significant difference in positive expression rates of GAS, SS mRNAs and protein among different histological differentiation, histological types and Dukes’ stage of LIC. The AI in GAS high and moderate expression groups was significantly lower than that in low expression groups (3.75 ± 2.38 vs 7.82 ± 2.38, P < 0.01; 5.51 ± 2.66 vs 7.82 ± 2.38, P < 0.01), and the AI in SS high and moderate expression groups was significantly higher than that in low expression groups (9.03 ± 1.76 vs 5.35 ± 3.00, P < 0.01; 7.44 ± 2.67 vs 5.35 ± 3.00, P < 0.01). There was a significant negative correlation between the integral ratio of GAS to SS and the AI (rs = -0.41, P < 0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than thatin low expression group (90.9% and 81.0% vs 53.2%, P < 0.05). The positive expression rates of Fas, caspase-8 and caspase-3 in SS high (90.0%, 90.0% and 100%) and moderate (80.0%, 70.0%, 75.0%) expression groups were higher than that in low expression group (53.1%, 42.9%, 49.0%) (90.0% and 80.0% vs 53.1%, P < 0.05; 90.0% and 70.0% vs 42.9%, P < 0.05; 100.0% and 75.0% vs 49.0%, P < 0.05). There was a significant positive correlation between the integral ratio of GAS to SS and the semiquantitative integral of FasL (rs = 0.32, P < 0.01). CONCLUSION: GAS and SS play important roles in the regulation and control of cell apoptosis in LIC, and the mechanism may be directly related to the aberrant expression of Fas/FasL. The GAS and SS will be valuable targets of the biological behavior of LIC.展开更多
AIM: To investigate the in vivo effect of beta-casomorphin-7on the regulation of gastric somatostatin and gastrin messenger RNA in rat gastric mucosa.METHODS: Somatostatin and gastrin mRNA were quantified by RT-PCR ...AIM: To investigate the in vivo effect of beta-casomorphin-7on the regulation of gastric somatostatin and gastrin messenger RNA in rat gastric mucosa.METHODS: Somatostatin and gastrin mRNA were quantified by RT-PCR and in situ hybridization (ISH)in 24 rats. The rats were divided into three treatment groups: basal diet + physiological saline (n = 8), basal diet + beta-casomorphin-7 (7.5 × 10^-7 mol) (n = 8),and basal diet + poly-Gly-7 (containing equal mol of N with 7.5 × 10^-7 mol beta-casomorphin-7) (n = 8).After oral administration for 30 days, rats were killed by exsanguinations.RESULTS: After intra-gastric administration of betacasomorphin-7 for 30 d, gastrin mRNA increased by 52.8% (P 〈 0.05, n = 8), and somatostatin mRNA levels decreased by 30.7% compared with the controls (P 〈0.01, n = 8). No significant differences in the expression of the two genes were observed in the poly-Gly-treated group, although gastrin mRNA expression was elevated by 35.6% as against the control group (P = 0.15, n =8). The long-term oral administration of a casomorphin solution significantly decreased the even gray of D-cells,but did not lower the number of D-cells both in the antrum and fundus. Interestingly, the number of G-cells increased in the antrum and fundus, but its average density was augmented only in the antrum.CONCLUSION: Beta-casomorphin-7 is capable of modulating gene expression of the regulatory peptides from G and D cells. Data from in situ hybridization studies indicate that beta-casomorphin-7 affects gastrin gene expression indirectly by means of the paracrine action of somatostatin, and depends on its intrinsic molecular function.展开更多
AIM: To explore the correlation between the expressions of gastrin (GAS), somatostatin (SS) and cyclin, cyclin- dependent kinase (CDK) in colorectal cancer, and to detect the specific regulatory sites where gas...AIM: To explore the correlation between the expressions of gastrin (GAS), somatostatin (SS) and cyclin, cyclin- dependent kinase (CDK) in colorectal cancer, and to detect the specific regulatory sites where gastrointestinal hormone regulates cell proliferati6n. METHODS: Seventy-nine resected large intestine carcinomatous specimens were randomly selected. Immunohistochemical staining for GAS, SS, cyclin D1, cyclin E, cyclin A, cyclin B1, CDK2 and CDK4 was performed according to the standard streptavidinbiotin-peroxidase (S-P) method. According to the semiquantitative integral evaluation, SS and GAS were divided into high, middle and low groups. Cyclin D1, cyclin E, cyclin A, cydin B1, CDK2, CDK4 expressions in the three GAS and SS groups were assessed. RESULTS: The positive expression rate of cyclin D1 was significantly higher in high (78.6%, 11/14) and middle GAS groups (73.9%, 17/23) than in low GAS group (45.2%, 19/42) (P〈0.05, X^2 high vs low = 4.691; P〈0.05, X^2 middle vs low = 4.945). The positive expression rate of cyclin A was significantly higher in high (100%, 14/14) and middle GAS groups (82.6%, 19/23) than in low GAS group (54.8%, 23/42) (P〈0.01, X2high vs low = 9.586; P〈0.05, X^2 middle vs low = 5.040). The positive expression rate of CDK2 was significantly higher in high (92.9%, 13/14) and middle GAS groups (87.0%, 20/23) than in low GAS group (50.0%, 21142) (P〈0.01, X^2 high vs low = 8.086; P〈0.01,X^2 middle low = 8.715). The positive expression rate of CDK4 was significantly higher in high (78.6%, 11/14)and middle GAS groups (78.3%, 18/23) than in low GAS group (42.9%, 18/42) (P〈0.05, X^2 high vs low= 5.364; P〈0.01, X^2 middle vs low = 7.539). The positive expression rate of cyclin E was prominently higher in low SS group (53.3%, 24/45) than in high (9.1%, 1/11) and middle (21.7%, 5/23) SS groups (P〈0.05, X^2 high vs low = 5.325; P〈0.05, X^2 middle vs low = 6.212). The positive expression rate of CDK2 was significantly higher in low SS group (77.8%, 35/45) than in high SS group (27.3%, 3/11) (P〈0.01, X^2 high vs low = 8.151). There was a significant positive correlation between the integral ratio of GAS to SS and the semi-quantitative integral of cyclin D1, cyclin E, cyclin A, CDK2, CDK4 (P〈0.05, 0% = 0.252; P〈0.01, E^rs = 0.387; P〈0.01,A^rs = 0.466; P〈0.01, K2^rs = 0.519; P〈0.01, K4^rs = 0.434). CONCLUSION: The regulation and control of gastrin, SS in colorectal cancer cell growth may be directly related to the abnormal expressions of cyclins D1, A, E, and CDK2, CDK4. The regulatory site of GAS in the cell cycle of colorectal carcinoma may be at the G2, S and G2 phases. The regulatory site of SS may be at the entrance of S phase.展开更多
IM METHODS By using in situ hybridization and immunohistochemical techniques, the expression of somatostatin mRNA and somatostatin immunoreactivity in the normal gastric mucosa, the poorly, moderately and welldiffer...IM METHODS By using in situ hybridization and immunohistochemical techniques, the expression of somatostatin mRNA and somatostatin immunoreactivity in the normal gastric mucosa, the poorly, moderately and welldifferentiated gastric carcinomas, and various clinical stages of carcinoma were observed.RESULTS In comparison with the normal gastric mucosa, the significantly increased expression of somatostatin mRNA positive cells was displayed in gastric carcinoma (t=2681, P<001). The positive signal cells were distributed in a scattered form or aggregated as a mass or a cord, and the positive cells were more significantly enhanced in poorly differentiated carcinomas than those in well and moderately differentiated carcinomas (t=2962, P<001). The somatostatin mRNA hybridization signals in stages Ⅲ and Ⅳ of gastric carcinoma were significantly higher than those in stages Ⅰ and Ⅱ. The results of somatostatin immunoreactivity were consistent with those of in situ hybridization.CONCLUSION The alteration of the expression of somatostatin mRNA was associated with the development of gastric carcinoma and may play an important role in the process of tumor differentiation..展开更多
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 ...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.展开更多
AIM: To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells. METHODS: Immunohistochemical stainin...AIM: To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells. METHODS: Immunohistochemical staining of five SSTR subtypes, Ki-67, Bcl-2 and p53 was performed by the standard streptavidin-peroxidase (SP) technique for the paraffin sections of 127 colorectal cancers, and expression of five SSTR subtypes in 40 specimens of normal colorectal mucosae was detected with the same method. RESULTS: Positive staining for five SSTR subtypes was observed in colorectal cancer cells and normal colorectal mucosae. SSTR1 was the most predominant subtype in both colorectal cancer and normal colorectal mucosa, and the second was SSTR5 or SSTR2. As compared with normal colorectal mucosa, SSTR4 was more frequently expressed in colorectal cancer cells (2.5% vs 18.9%, P〈 0.05); the expression of SSTR2, 4, 5 in moderately to well differentiated colorectal adenocarcinoma was significantly higher than that in poorly differentiated ones (P〈 0.05), the SSTR1 expression in colorectal cancer with positive lymph node metastasis was significantly higher than that with negative lymph node metastasis (72.2% and 54.5%, P〈 0.05). In addition, in the ulcerative type of colorectal cancer, SSTR2 expression was obviously decreased (P 〈 0.05); the correlation did not reach a statistical significance between the five SSTR subtypes expression and Dukes'stages (P〉 0.05), but the frequency of SSTR1 expression increased with Dukes' stage, while SSTR3 and SSTR5 expression decreased with Dukes' stage. Moreover, there was no correlation between expression of the five SSTR subtypes and other clinicopathological factors such as age, sex, tumor site, tumor depth, distant metastasis. The proliferative indexes in colorectal cancer cells with negative expression of SSTR2 and SSTR3 were significantly higher than that with positive expression (P〈0.05). The Bcl-2 expression in colorectal cancer cells with positive expression of SSTR1, 2, 3, 5 was significantly lower than that with negative expression (P〈 0.05). There was no correlation between five SSTR subtypes and p53 expression. CONCLUSION: The most predominant SSTR subtype is SSTR1, and the second is SSTR2 or SSTR5, Five SSTR subtypes play different roles in the development of colorectal cancer, SSTR2 and SSTR3 can inhibit the proliferation and promote apoptosis of tumor cells.展开更多
AIM- To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, w...AIM- To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were ex- amined in wild-type mice and mice infected with Helico- bacter pylori (H. pylorO. Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ, alone, mice were given a subcutaneous infusion of IFNγ, for 7 d. Finally, the influ- ence of IFNγ, and somatostatin on the ghrelin promoter was characterized. RESULTS: H. py/ori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was in- versely correlated with gastric inflammation in achlorh- dyric mouse models. Subcutaneous infusion of IFNγ, suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of soma- tostatin but not under that of IFNγ. CONCLUSION: Gastric infection and inflammation is associated with increased IFNγ, expression and reduced ghrelin expression. IFNγ, does not directly control ghre- lin expression but inhibits it indirectly via somatostatin.展开更多
BACKGROUND Major depressive disorder(MDD)is a highly disabling psychiatric syndrome associated with deficits of specific subpopulations of cortical GABAergic interneurons;however,the underlying molecular mechanism rem...BACKGROUND Major depressive disorder(MDD)is a highly disabling psychiatric syndrome associated with deficits of specific subpopulations of cortical GABAergic interneurons;however,the underlying molecular mechanism remains unknown.Type 3 adenylyl cyclase(ADCY3,AC3),which is important for neuronal excitability,has been implicated in MDD in a genome-wide association study in humans.Moreover,a study reported that ablation of AC3 in mice caused similar symptoms as MDD patients.AIM To determine if disruption of the AC3 gene in different subtypes of GABAergic interneurons of mice causes depression-like behaviors.METHODS Using immunohistochemistry,we investigated the expression of AC3 in two major subtypes GABAergic interneurons:Somatostatin-positive(SST+)and parvalbumin-positive(PV+)neurons.Genetic manipulations were used to selectively disrupt AC3 expression in SST+or PV+interneurons.A series of behavior tests including rotarod test,open field test(OFT),elevated plus maze test(EPM),forced swimming test(FST),and tail suspension test(TST)were used to evaluate the motor ability,anxiety-and depression-like behaviors,respectively.RESULTS Our results indicate that approximately 90.41%of SST+and 91.22%of PV+interneurons express AC3.After ablation of AC3 in SST+interneurons,the mice spent comparable time in the center area in OFT,but significantly less time in the open arms and low frequency of entries to the open arms in EPM.Furthermore,these mice showed prolonged immobility in FST and more freezing in TST.However,there were no significant changes in these behaviors after specific disruption of AC3 in PV+interneurons.CONCLUSION This study indicates that ablation of AC3 in SST+interneurons of mice increases anxiety-and depression-like behaviors in mice,supporting the general hypothesis that decreased AC3 activity may play a role in human depression.展开更多
Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine ca...Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with yon Recklinghausen's neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.展开更多
In present study, the developmental patterns of somatostatin (SS) gene expression in gastric tissue were compared between Erhualian and Large White pigs. A semi-quantitative RT-PCR was applied to determine the levels ...In present study, the developmental patterns of somatostatin (SS) gene expression in gastric tissue were compared between Erhualian and Large White pigs. A semi-quantitative RT-PCR was applied to determine the levels of SS mRNA. The results indicated that: (1) The gastric SS mRNA expression was high at birth, followed by a significant decrease (P<0. 05) at 3 days of age in both breeds of pigs; (2) From 3 to 30 days of age, the expression of SS mRNA in gastric tissue exhibited remarkable up-regulation in both breeds, after which a strain difference in the developmental pattern was observed. In Erhualian pigs, SS mRNA expression reached a peak at 90 days of age, declined thereafter towards 180 days of age. In Large White pigs, however, the expression of SS mRNA remained constant from 30 days of age onwards; (3) In general, Erhualian pigs expressed higher levels of SS mRNA in gastric tissue compared with Large White pigs at the same age. The strain difference was significant from birth to 90 days of age, but vanished at 120 and 180 days of age. The results suggest that the gastric expression of SS in the pig is regulated following an instinct timetable in a strain-specific manner, its relationship with the development of gastric function as well as its interactions with environmental factors are to be elucidated.展开更多
Purpose of the present study: To explore the effect of electroacupuncture (EA) on canine pyloric pressure and its relation to somatostain (SS) of blood plasma and nitric oxide (NO).Methods: An intragastric pressure de...Purpose of the present study: To explore the effect of electroacupuncture (EA) on canine pyloric pressure and its relation to somatostain (SS) of blood plasma and nitric oxide (NO).Methods: An intragastric pressure detector and radioimmunoassay (RIA) and biochemical assay are used to determine changes of pyloric pressure and frequency, contents of SS and NO of blood plasma after EA stimulation of different acupoints. Results: Following EA of Zusanli (ST 36), the total pressure, basic pressure and systolic frequency of the sphincter muscle of pylorus lowered, plasma SS content decreased and NO content increased. After EA of Shangjuxu (ST 37), the total pressure, basic pressure and systolic frequency of the sphincter muscle of pylorus decreased, plasrna NO content increased but changes of these indexes are less obvious than those of EA of Zusanli (ST 36). These indexes in other groups had no any apparent changes. Conclusion: EA could lower pyloric pressure and systolic frequency of the pyloric sphincter muscle, whicb may be the important pathway of EA in regulating functional activities of the stomach and intestines. The effect of EA is associated with the contents of some plasma biological substances affecting pyloric pressure and the action of meridians and acupoints is of specificity to a certain degree.展开更多
The amounts of somatostatin and sulfhydryl group were measured in malignant tumors of melanoma S91,Lewis lung cancer, sarcoma S180 and their surrounding tissues. All the tumors had decreased levels of somatostatin com...The amounts of somatostatin and sulfhydryl group were measured in malignant tumors of melanoma S91,Lewis lung cancer, sarcoma S180 and their surrounding tissues. All the tumors had decreased levels of somatostatin compared to their surrounding tissues whereas the amounts of sulfhydryl group in tumors increased evidently. The results suggest that the loss of somatostatin in tumor tissues may be induced by sulfhydryl group, which reduce the intramolecular disulfide bond of somatostatin.展开更多
Background: Somatostatin analogues have shown to be effective in controlling the levels of growth hormone and are recommended for the treatment of acromegaly. These treatments have high costs of acquisition and their ...Background: Somatostatin analogues have shown to be effective in controlling the levels of growth hormone and are recommended for the treatment of acromegaly. These treatments have high costs of acquisition and their use might be restricted in limited resource settings. Objective: To evaluate the cost-effectiveness of somatostatin analogues for acromegaly in Colombia. Setting/Subjects/Intervention: A decision model was developed using a hypothetical cohort of patients with Acromegaly. Patients were treated according to the clinical practice of the country. Response to treatment and transition probabilities were derived from published literature. Costs and resource utilization were extracted from public and private sources in Colombia. Main Outcome Measure(s): Cost-effectiveness ratio, measured in Colombian pesos in a 2 year time-horizon. Results: The total medical treatment costs for the octreotide group were (Colombian Pesos) COP$ 53,807,616, compared to the total costs for the lanreotide group of COP$ 83,126,567. In the octreotide arm 65.30% of the patients and in the lanreotide arm 59.50% of the patients were successfully controlled. The number of deaths was 295 (13.1%) and 302 (13.4%) for octreotide and lanreotide, respectively. Because the costs are lower and the effectiveness is higher for octreotide in comparison with lanreotide, octreotide is more cost-effective than lanreotide. Probabilistic sensitivity analyses were consistent showing octreotide as the most cost-effective option. Conclusions: Costs and effects of octreotide compare favorably to those of lanreotide in the treatment of acromegaly in Colombia. Sensitivity analysis showed that despite the uncertainty in cost-effectiveness ratio this result is robust.展开更多
文摘AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the f irst year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.
文摘BACKGROUND: Somatostatin, a neuropeptide and hor- mone , exists in the biliary tract of several species. The effects of somatostatin and its analogues on the sphincter of Oddi motility have been controversial. The aim of this study was to observe the action of stilamin and sandostatin on the sphincter of Oddi via choledochofiberscope manometry. METHODS: Twenty patients who had had'T' duct after cholecystectomy and choledochotomy were divided into 2 groups randomly: stilamin and sandostatin. They were subjected to manometry via a choledochofiberscope through the'T' duct tract. The following data recorded in- cluded duodenal pressure (DP), sphincter of Oddi basal pressure (SOBP), sphincter of Oddi contractive amplitude (SOCA), frequency of the sphincter of Oddi (SOF), dura- tion of the sphincter of Oddi, and the common bile duct pressure (CBDP). RESULTS: After intravenous administration of stilamin at a dose of 250 μg/h, the mean SOCA increased from 89.18 (26.50) to 128.57(54.21) mmHg (P <0.05). After the ad- ministration of stilamin at a dose of 500 μg/h the mean SO- CA declined to 92.18(42.81) mmHg (P<0.05), and mean SOBP declined from 17.63(13.36) to 8.16(4.01) mmHg (P<0.05). Although SOF had declined from 9.25(2.45) to 7.46(1.52) n/min, it was not significantly influenced. After intravenous administration of sandostatin at a dose of 100 μg, the mean CBDP increased obviously. CONCLUSIONS: Intravenous administration of stilamin at a dose of 250 μg/h stimulates the motility of the sphincter of Oddi whereas the injection of stilamin at a dose of 500 μg/h inhibits its motility. Intravenous injection of sandosta- tin of 100 μg has no effect on the sphincter of Oddi.
基金Supported by the National Natural Science Foundation of China, No.30171136
文摘AIM: To discuss the protective effect of electroacupuncture at the Foot-Yangming Meridian on gastric mucosal lesion, somatostatin (SS) and the expression of SS receptor genes (SSR1mRNA) in rabbits with gastric ulcer and to further explore the relative specificity of meridians and viscera at gene expression level. METHODS: Forty rabbits were randomly divided into control group (A), gastric ulcer model group (B), FootYangming Meridian group (C), Foot-Shaoyang Meridian group (D) and Foot-Taiyang Meridian group (E). The gastric ulcer model was prepared by infusing alcohol into stomach. Groups C-E were treated with electroacupuncture at points along the above meridians using meridian stimulating instruments for 7 days respectively. By the end of treatment, the index of gastric ulcer was determined, the amount of epidermal growth factor(EGF) and somatostatin was measured by radioimmunoassay (PJA). SS-R1mRNA expression in gastric mucosa was determined by RT-PCR. RESULTS: The value of EGF in model group was obviously lower(73.6±14.8 vs 91.3±14.9 pg/mL, P〈 0.01) than that in control group. The index of gastric ulcer, content of SS and expression of SSRtmRNA in gastric mucosa were significantly higher than those in control group (24.88 ± 6.29 vs 8.50 ± 2.98 scores, P〈 0.01; 2978.6 ± 587.6 vs 1852.4 ± 361.7 mIU/mL, P〈 0.01; 2.56±0.25 vs 1.04±0.36, P〈0.01) . The value of EGF in Foot-Yangming Meridian group was higher than that in model group(92.2±6.7 vs 73.6±14.8 pg/mL, P〈 0.01). The index of gastric ulcer, content of SS and expression of SS-R1mRNA in gastric mucosa were significantlylower than those in control group(10.88±3.23 vs 24.88±6.29 scores, P〈0.01; 1800.2±488 vs 2978.6±587.6 mIU/mL, P 〈 0.01; 1.07±0.08 vs 2.56±0.25mIU/mL, P〈0.01). Compared to the model group, the content of SS and expression of SSRlmRNA in gastric mucosa in Foot-Shaoyang Meridian group decreased (2441.0±488. vs 2978.6± 587.6 mIU/mL, P〈 0.05; 1.73±0.16 vs 2.56±0.25 mIU/mL, P〈0.01). But the above parameters in Foot-Taiyang Meridian group did not improve and were significantly different from those in Footoyangming Meridian group (P〈0.05) CONCLUSION: Electro-acupuncture at Foot-Yangming Meridian can protect gastric mocusa against injury. The mechanism may be releted to the regulation of brain-gut peptides and the expression of SSRtmRNA.
基金Supported by National Natural Science Foundation of China, No.39270769, Natural Science Foundation of Anhui Province, No.03043704, Natural Science Foundation of Education Bureau of Anhui Province, No.2002kj307
文摘AIM: To explore the correlation between expression of somatostatin (SS), gastrin (GAS) and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma.METHODS: Sixty-two large intestine cancer tissue samples were randomly and retrospectively selected from patients with large intestine carcinoma. Immunohistochemical staining for bcl-2, bax, GAS, SS was performed according to the standard streptavidin-biotin-peroxidase (S-P) method.According to the semi-quantitative integral evaluation, SS and GAS were divided into three groups as follows. Scores1-3 were defined as the low expression group, 4-8 as the intermediate expression group, 9-16 as the high expression group. Bax and bcl-2 protein expressions in different GAS and SS expression groups of large intestine carcinoma were assessed.RESULTS: The positive expression rate of bax had a prominent difference between SS and GAS high, intermediate and low expression groups (P<0.05, x2ss = 9.246; P<0.05,x2GAS = 6.981). The positive expression rate of bax in SS high (80.0%, 8/10) and intermediate (76.5%, 13/17)expression groups was higher than that in low expression group (40.0%, 14/35) (P<0.05, x2high vs low = 5.242; P<0.05,x2middle vs low = 6.097). The positive expression rate of bax in GAS high expression group (27.3%, 3/8) was lower than that in low expression group (69.4%, 25/36) (P<0.05,x2 = 4.594). However, bax expression in GAS intermediate expression group (46.7%, 7/15) was lower than that in low expression group, but not statistically significant. The positive expression rate of bcl-2 had a prominent difference between SS and GAS high, intermediate and low expression groups (P<0.05, x2ss = 7.178; P<0.05, x2GAS = 13.831). The positive expression rate of bcl-2 in GAS high (90.9%, 10/11)and intermediate (86.7%, 13/15) expression groups was higher than that in low expression group (44.4%, 16/36)(P<0.05,x2high vs low = 5.600; P<0.05, x2 middle vs low = 7.695).However, the positive expression rate of bcl-2 in SS high (40.0%, 4/10) and intermediate (47.1%, 8/9) expression groups was lower than that in low expression group (77.1%, 27/35)(P<0.05, x2 high vs low = 4.710; P<0.05, x2 middle vs low = 4.706).There was a significant positive correlation between the integral ratio of GAS to SS and the integral of bcl-2 (P<0.01,r=0.340). However, there was a negative correlation between the integral ratio of GAS to the SS and bax the integral of (P<0.05, r = -0.299).CONCLUSION: The regulation and control of gastrin,somatostatin in cell apoptosis of large intestine carcinoma may be directly related to the abnormal expression of bcl-2, bax.
基金The Natural Science Foundation of Educational Bureau of Anhui Province, No. 2006kj115c, 2005kj302Natural Science Foundation of Anhui Province, No. 03043704
文摘AIM: To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/ FasL and caspases in large intestinal carcinoma (LIC). METHODS: Expression of GAS and SS mRNAs were detected by nested RT-PCR in 79 cases of LIC. Cell apoptosis was detected by molecular biology in situ apoptosis detecting methods (TUNEL). Immunohistochemical staining for GAS, SS, Fas/FasL, caspase-3 and caspase-8 was performed according to the standard streptavidin-biotin-peroxidase (S-P) method. RESULTS: There was a significant positive correlation between mRNA and protein expression of GAS and SS (GASrs=0.99, P < 0.01; SSrs = 0.98, P < 0.01). There was significant difference in positive expression rates of GAS, SS mRNAs and protein among different histological differentiation, histological types and Dukes’ stage of LIC. The AI in GAS high and moderate expression groups was significantly lower than that in low expression groups (3.75 ± 2.38 vs 7.82 ± 2.38, P < 0.01; 5.51 ± 2.66 vs 7.82 ± 2.38, P < 0.01), and the AI in SS high and moderate expression groups was significantly higher than that in low expression groups (9.03 ± 1.76 vs 5.35 ± 3.00, P < 0.01; 7.44 ± 2.67 vs 5.35 ± 3.00, P < 0.01). There was a significant negative correlation between the integral ratio of GAS to SS and the AI (rs = -0.41, P < 0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than thatin low expression group (90.9% and 81.0% vs 53.2%, P < 0.05). The positive expression rates of Fas, caspase-8 and caspase-3 in SS high (90.0%, 90.0% and 100%) and moderate (80.0%, 70.0%, 75.0%) expression groups were higher than that in low expression group (53.1%, 42.9%, 49.0%) (90.0% and 80.0% vs 53.1%, P < 0.05; 90.0% and 70.0% vs 42.9%, P < 0.05; 100.0% and 75.0% vs 49.0%, P < 0.05). There was a significant positive correlation between the integral ratio of GAS to SS and the semiquantitative integral of FasL (rs = 0.32, P < 0.01). CONCLUSION: GAS and SS play important roles in the regulation and control of cell apoptosis in LIC, and the mechanism may be directly related to the aberrant expression of Fas/FasL. The GAS and SS will be valuable targets of the biological behavior of LIC.
基金Supported by the National Natural Science Foundation of China, No. 39770540
文摘AIM: To investigate the in vivo effect of beta-casomorphin-7on the regulation of gastric somatostatin and gastrin messenger RNA in rat gastric mucosa.METHODS: Somatostatin and gastrin mRNA were quantified by RT-PCR and in situ hybridization (ISH)in 24 rats. The rats were divided into three treatment groups: basal diet + physiological saline (n = 8), basal diet + beta-casomorphin-7 (7.5 × 10^-7 mol) (n = 8),and basal diet + poly-Gly-7 (containing equal mol of N with 7.5 × 10^-7 mol beta-casomorphin-7) (n = 8).After oral administration for 30 days, rats were killed by exsanguinations.RESULTS: After intra-gastric administration of betacasomorphin-7 for 30 d, gastrin mRNA increased by 52.8% (P 〈 0.05, n = 8), and somatostatin mRNA levels decreased by 30.7% compared with the controls (P 〈0.01, n = 8). No significant differences in the expression of the two genes were observed in the poly-Gly-treated group, although gastrin mRNA expression was elevated by 35.6% as against the control group (P = 0.15, n =8). The long-term oral administration of a casomorphin solution significantly decreased the even gray of D-cells,but did not lower the number of D-cells both in the antrum and fundus. Interestingly, the number of G-cells increased in the antrum and fundus, but its average density was augmented only in the antrum.CONCLUSION: Beta-casomorphin-7 is capable of modulating gene expression of the regulatory peptides from G and D cells. Data from in situ hybridization studies indicate that beta-casomorphin-7 affects gastrin gene expression indirectly by means of the paracrine action of somatostatin, and depends on its intrinsic molecular function.
基金Supported by the Natural Science Foundation of Anhui Province,No.03043704
文摘AIM: To explore the correlation between the expressions of gastrin (GAS), somatostatin (SS) and cyclin, cyclin- dependent kinase (CDK) in colorectal cancer, and to detect the specific regulatory sites where gastrointestinal hormone regulates cell proliferati6n. METHODS: Seventy-nine resected large intestine carcinomatous specimens were randomly selected. Immunohistochemical staining for GAS, SS, cyclin D1, cyclin E, cyclin A, cyclin B1, CDK2 and CDK4 was performed according to the standard streptavidinbiotin-peroxidase (S-P) method. According to the semiquantitative integral evaluation, SS and GAS were divided into high, middle and low groups. Cyclin D1, cyclin E, cyclin A, cydin B1, CDK2, CDK4 expressions in the three GAS and SS groups were assessed. RESULTS: The positive expression rate of cyclin D1 was significantly higher in high (78.6%, 11/14) and middle GAS groups (73.9%, 17/23) than in low GAS group (45.2%, 19/42) (P〈0.05, X^2 high vs low = 4.691; P〈0.05, X^2 middle vs low = 4.945). The positive expression rate of cyclin A was significantly higher in high (100%, 14/14) and middle GAS groups (82.6%, 19/23) than in low GAS group (54.8%, 23/42) (P〈0.01, X2high vs low = 9.586; P〈0.05, X^2 middle vs low = 5.040). The positive expression rate of CDK2 was significantly higher in high (92.9%, 13/14) and middle GAS groups (87.0%, 20/23) than in low GAS group (50.0%, 21142) (P〈0.01, X^2 high vs low = 8.086; P〈0.01,X^2 middle low = 8.715). The positive expression rate of CDK4 was significantly higher in high (78.6%, 11/14)and middle GAS groups (78.3%, 18/23) than in low GAS group (42.9%, 18/42) (P〈0.05, X^2 high vs low= 5.364; P〈0.01, X^2 middle vs low = 7.539). The positive expression rate of cyclin E was prominently higher in low SS group (53.3%, 24/45) than in high (9.1%, 1/11) and middle (21.7%, 5/23) SS groups (P〈0.05, X^2 high vs low = 5.325; P〈0.05, X^2 middle vs low = 6.212). The positive expression rate of CDK2 was significantly higher in low SS group (77.8%, 35/45) than in high SS group (27.3%, 3/11) (P〈0.01, X^2 high vs low = 8.151). There was a significant positive correlation between the integral ratio of GAS to SS and the semi-quantitative integral of cyclin D1, cyclin E, cyclin A, CDK2, CDK4 (P〈0.05, 0% = 0.252; P〈0.01, E^rs = 0.387; P〈0.01,A^rs = 0.466; P〈0.01, K2^rs = 0.519; P〈0.01, K4^rs = 0.434). CONCLUSION: The regulation and control of gastrin, SS in colorectal cancer cell growth may be directly related to the abnormal expressions of cyclins D1, A, E, and CDK2, CDK4. The regulatory site of GAS in the cell cycle of colorectal carcinoma may be at the G2, S and G2 phases. The regulatory site of SS may be at the entrance of S phase.
文摘IM METHODS By using in situ hybridization and immunohistochemical techniques, the expression of somatostatin mRNA and somatostatin immunoreactivity in the normal gastric mucosa, the poorly, moderately and welldifferentiated gastric carcinomas, and various clinical stages of carcinoma were observed.RESULTS In comparison with the normal gastric mucosa, the significantly increased expression of somatostatin mRNA positive cells was displayed in gastric carcinoma (t=2681, P<001). The positive signal cells were distributed in a scattered form or aggregated as a mass or a cord, and the positive cells were more significantly enhanced in poorly differentiated carcinomas than those in well and moderately differentiated carcinomas (t=2962, P<001). The somatostatin mRNA hybridization signals in stages Ⅲ and Ⅳ of gastric carcinoma were significantly higher than those in stages Ⅰ and Ⅱ. The results of somatostatin immunoreactivity were consistent with those of in situ hybridization.CONCLUSION The alteration of the expression of somatostatin mRNA was associated with the development of gastric carcinoma and may play an important role in the process of tumor differentiation..
基金the National Natural Science Foundation of China, No. 30171188
文摘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.
基金Supported by Youth Scientific Research Foundation of Health Department of Fujian Province. No.2003-1-11
文摘AIM: To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells. METHODS: Immunohistochemical staining of five SSTR subtypes, Ki-67, Bcl-2 and p53 was performed by the standard streptavidin-peroxidase (SP) technique for the paraffin sections of 127 colorectal cancers, and expression of five SSTR subtypes in 40 specimens of normal colorectal mucosae was detected with the same method. RESULTS: Positive staining for five SSTR subtypes was observed in colorectal cancer cells and normal colorectal mucosae. SSTR1 was the most predominant subtype in both colorectal cancer and normal colorectal mucosa, and the second was SSTR5 or SSTR2. As compared with normal colorectal mucosa, SSTR4 was more frequently expressed in colorectal cancer cells (2.5% vs 18.9%, P〈 0.05); the expression of SSTR2, 4, 5 in moderately to well differentiated colorectal adenocarcinoma was significantly higher than that in poorly differentiated ones (P〈 0.05), the SSTR1 expression in colorectal cancer with positive lymph node metastasis was significantly higher than that with negative lymph node metastasis (72.2% and 54.5%, P〈 0.05). In addition, in the ulcerative type of colorectal cancer, SSTR2 expression was obviously decreased (P 〈 0.05); the correlation did not reach a statistical significance between the five SSTR subtypes expression and Dukes'stages (P〉 0.05), but the frequency of SSTR1 expression increased with Dukes' stage, while SSTR3 and SSTR5 expression decreased with Dukes' stage. Moreover, there was no correlation between expression of the five SSTR subtypes and other clinicopathological factors such as age, sex, tumor site, tumor depth, distant metastasis. The proliferative indexes in colorectal cancer cells with negative expression of SSTR2 and SSTR3 were significantly higher than that with positive expression (P〈0.05). The Bcl-2 expression in colorectal cancer cells with positive expression of SSTR1, 2, 3, 5 was significantly lower than that with negative expression (P〈 0.05). There was no correlation between five SSTR subtypes and p53 expression. CONCLUSION: The most predominant SSTR subtype is SSTR1, and the second is SSTR2 or SSTR5, Five SSTR subtypes play different roles in the development of colorectal cancer, SSTR2 and SSTR3 can inhibit the proliferation and promote apoptosis of tumor cells.
基金Supported by The Danish MRC Grant271-08-0378(LFH)the ALF grant(TW)The Lundbeck foundation(KBVD)
文摘AIM- To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were ex- amined in wild-type mice and mice infected with Helico- bacter pylori (H. pylorO. Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ, alone, mice were given a subcutaneous infusion of IFNγ, for 7 d. Finally, the influ- ence of IFNγ, and somatostatin on the ghrelin promoter was characterized. RESULTS: H. py/ori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was in- versely correlated with gastric inflammation in achlorh- dyric mouse models. Subcutaneous infusion of IFNγ, suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of soma- tostatin but not under that of IFNγ. CONCLUSION: Gastric infection and inflammation is associated with increased IFNγ, expression and reduced ghrelin expression. IFNγ, does not directly control ghre- lin expression but inhibits it indirectly via somatostatin.
基金Supported by National Natural Science Foundation of China,No.81771208 and No.81971043。
文摘BACKGROUND Major depressive disorder(MDD)is a highly disabling psychiatric syndrome associated with deficits of specific subpopulations of cortical GABAergic interneurons;however,the underlying molecular mechanism remains unknown.Type 3 adenylyl cyclase(ADCY3,AC3),which is important for neuronal excitability,has been implicated in MDD in a genome-wide association study in humans.Moreover,a study reported that ablation of AC3 in mice caused similar symptoms as MDD patients.AIM To determine if disruption of the AC3 gene in different subtypes of GABAergic interneurons of mice causes depression-like behaviors.METHODS Using immunohistochemistry,we investigated the expression of AC3 in two major subtypes GABAergic interneurons:Somatostatin-positive(SST+)and parvalbumin-positive(PV+)neurons.Genetic manipulations were used to selectively disrupt AC3 expression in SST+or PV+interneurons.A series of behavior tests including rotarod test,open field test(OFT),elevated plus maze test(EPM),forced swimming test(FST),and tail suspension test(TST)were used to evaluate the motor ability,anxiety-and depression-like behaviors,respectively.RESULTS Our results indicate that approximately 90.41%of SST+and 91.22%of PV+interneurons express AC3.After ablation of AC3 in SST+interneurons,the mice spent comparable time in the center area in OFT,but significantly less time in the open arms and low frequency of entries to the open arms in EPM.Furthermore,these mice showed prolonged immobility in FST and more freezing in TST.However,there were no significant changes in these behaviors after specific disruption of AC3 in PV+interneurons.CONCLUSION This study indicates that ablation of AC3 in SST+interneurons of mice increases anxiety-and depression-like behaviors in mice,supporting the general hypothesis that decreased AC3 activity may play a role in human depression.
文摘Poorly differentiated gastric neuroendocrine carcinomas, although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with yon Recklinghausen's neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.
基金The project was supported by the National Natural Science Foundation of China(39830290).
文摘In present study, the developmental patterns of somatostatin (SS) gene expression in gastric tissue were compared between Erhualian and Large White pigs. A semi-quantitative RT-PCR was applied to determine the levels of SS mRNA. The results indicated that: (1) The gastric SS mRNA expression was high at birth, followed by a significant decrease (P<0. 05) at 3 days of age in both breeds of pigs; (2) From 3 to 30 days of age, the expression of SS mRNA in gastric tissue exhibited remarkable up-regulation in both breeds, after which a strain difference in the developmental pattern was observed. In Erhualian pigs, SS mRNA expression reached a peak at 90 days of age, declined thereafter towards 180 days of age. In Large White pigs, however, the expression of SS mRNA remained constant from 30 days of age onwards; (3) In general, Erhualian pigs expressed higher levels of SS mRNA in gastric tissue compared with Large White pigs at the same age. The strain difference was significant from birth to 90 days of age, but vanished at 120 and 180 days of age. The results suggest that the gastric expression of SS in the pig is regulated following an instinct timetable in a strain-specific manner, its relationship with the development of gastric function as well as its interactions with environmental factors are to be elucidated.
文摘Purpose of the present study: To explore the effect of electroacupuncture (EA) on canine pyloric pressure and its relation to somatostain (SS) of blood plasma and nitric oxide (NO).Methods: An intragastric pressure detector and radioimmunoassay (RIA) and biochemical assay are used to determine changes of pyloric pressure and frequency, contents of SS and NO of blood plasma after EA stimulation of different acupoints. Results: Following EA of Zusanli (ST 36), the total pressure, basic pressure and systolic frequency of the sphincter muscle of pylorus lowered, plasma SS content decreased and NO content increased. After EA of Shangjuxu (ST 37), the total pressure, basic pressure and systolic frequency of the sphincter muscle of pylorus decreased, plasrna NO content increased but changes of these indexes are less obvious than those of EA of Zusanli (ST 36). These indexes in other groups had no any apparent changes. Conclusion: EA could lower pyloric pressure and systolic frequency of the pyloric sphincter muscle, whicb may be the important pathway of EA in regulating functional activities of the stomach and intestines. The effect of EA is associated with the contents of some plasma biological substances affecting pyloric pressure and the action of meridians and acupoints is of specificity to a certain degree.
文摘The amounts of somatostatin and sulfhydryl group were measured in malignant tumors of melanoma S91,Lewis lung cancer, sarcoma S180 and their surrounding tissues. All the tumors had decreased levels of somatostatin compared to their surrounding tissues whereas the amounts of sulfhydryl group in tumors increased evidently. The results suggest that the loss of somatostatin in tumor tissues may be induced by sulfhydryl group, which reduce the intramolecular disulfide bond of somatostatin.
文摘Background: Somatostatin analogues have shown to be effective in controlling the levels of growth hormone and are recommended for the treatment of acromegaly. These treatments have high costs of acquisition and their use might be restricted in limited resource settings. Objective: To evaluate the cost-effectiveness of somatostatin analogues for acromegaly in Colombia. Setting/Subjects/Intervention: A decision model was developed using a hypothetical cohort of patients with Acromegaly. Patients were treated according to the clinical practice of the country. Response to treatment and transition probabilities were derived from published literature. Costs and resource utilization were extracted from public and private sources in Colombia. Main Outcome Measure(s): Cost-effectiveness ratio, measured in Colombian pesos in a 2 year time-horizon. Results: The total medical treatment costs for the octreotide group were (Colombian Pesos) COP$ 53,807,616, compared to the total costs for the lanreotide group of COP$ 83,126,567. In the octreotide arm 65.30% of the patients and in the lanreotide arm 59.50% of the patients were successfully controlled. The number of deaths was 295 (13.1%) and 302 (13.4%) for octreotide and lanreotide, respectively. Because the costs are lower and the effectiveness is higher for octreotide in comparison with lanreotide, octreotide is more cost-effective than lanreotide. Probabilistic sensitivity analyses were consistent showing octreotide as the most cost-effective option. Conclusions: Costs and effects of octreotide compare favorably to those of lanreotide in the treatment of acromegaly in Colombia. Sensitivity analysis showed that despite the uncertainty in cost-effectiveness ratio this result is robust.