This study was to observe the effect and possible mechanism of somatostatin analogue octreotide (OCT) on cross excitation of adjacent segment of spinal nerve in rat. Cutaneous branches of T9-T13 spinal dorsal rami were chosen and dissected free for the following recording and stimulation. Only single unit fiber was used for recording, and the adjacent segment of nerve stem was used for antidromic electrical stimulation. To investigate the change of discharge rate and mechanical threshold, OCT and (or) somatostatin receptor antagonist cyclo-somatostatin (c-SOM) were applied to the receptive field following the antidromic electrical stimulation. The result showed that injection of OCT inhibited the increase of discharge rate and the decrease of mechanical threshold induced by the electrical stimulation (cross excitation); c-SOM reversed the effects of OCT. Application of c-SOM alone enhanced the cross excitation effects. The results suggest local application of somatostatin analogue OCT can inhibit the cross excitation between the two segments of spinal nerve by somatostatin receptor.
Animals ; Electric Stimulation ; Octreotide ; pharmacology ; Peptides, Cyclic ; pharmacology ; Rats ; Receptors, Somatostatin ; physiology ; Somatostatin ; analogs & derivatives ; Spinal Nerves ; drug effects

To investigate the effects of sorafenib and octreotide combination treatment on cellular proliferation and explore the underlying molecular mechanisms by using an in vitro cell culture system with the human hepatoma cell line, HepG2. HepG2 cells were treated with different concentrations of sorafenib and octreotide alone or in combination. Untreated HepG2 cells were used as controls. Treatment-induced cytotoxicity was determined with the cell counting kit-8 by Sigma-Aldrich, and rate of apoptosis was detected by flow cytometry. Fluorescent microscopy was used to observe rates of cell growth under the various treatments. Treatment-induced changes in protein expressions were detected by enzyme-linked immunosorbent assay (for vascular endothelial growth factor (VEGF)) and Western blotting (for the Mcl-1 apoptosis mediator and the ERK1/2 and PERK1/2 kinases). Sorafenib and octreotide, used alone or in combination, inhibited proliferation and induced apoptosis in HepG2 cells. Combination treatment was more effective than either mono-treatment (F = 200.398, P less than 0.05). Fluorescent microscopy showed that combination treatment stimulated phosphatidylserine, the marker of early apoptosis, better than either mono-treatment. VEGF expression in cultures exposed to combination treatment was also significantly lower than in mono-treatment or untreated control cultures (F = 1019.725, P less than 0.05). Western blotting showed that octreotide mono-treatment had no effect on Mcl-1 expression (vs. control group; P more than 0.05) and that combination treatment significantly lowered Mcl-1 expression (vs. mono-treatment and control groups; P less than 0.05). None of the treatments affected ERK1/2 expression (all, P more than 0.05), while all treatments significantly lowered PERK1/2 expression (vs. control group; F = 2.401, P less than 0.05) and the combination treatment lowered PERK1/2 significantly more than either mono-treatment (P less than 0.05). Sorafenib and octreotide can inhibit proliferation and induce apoptosis in the human hepatoma cell line, HepG2. Combination treatment is significantly more efficacious (P less than 0.05) and produced synergistic effects. The mechanism underlying this phenomenon may depend on synergistic inhibition of VEGF, the anti-apoptotic protein Mcl-1, and the proliferation-inducing PERK1/2.
Apoptosis ; drug effects ; Benzenesulfonates ; pharmacology ; Cell Proliferation ; drug effects ; Hep G2 Cells ; drug effects ; Humans ; Niacinamide ; analogs & derivatives ; Octreotide ; pharmacology ; Phenylurea Compounds ; Pyridines ; pharmacology

Adolescent ; Adult ; Female ; Heart Neoplasms ; diagnosis ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Octreotide ; analogs & derivatives ; Organotechnetium Compounds ; Pheochromocytoma ; diagnosis ; surgery ; Tomography, Emission-Computed ; Tomography, X-Ray Computed

Objective To analyze Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) imaging features of tumor-indud osteomalacia (TIO) patients with negative Tc-HYNIC-TOC single photo emission computed tomography (SPECT) findings and to investigate the value of Ga-DOTA-TATE PET/CT in accurate localization of culprit tumors.Methods We retrospectively analyzed Ga-DOTA-TATE PET/CT imaging features including location,size,density,the maximum and mean standardized uptake value in 37 TIO patients with negative Tc-HYNIC-TOC SPECT findings.Results Totally 37 solitary TIO tumors,including 35 phosphaturic mesenchymal tumors and 2 spindle cell tumors confirmed by pathological examinations,were detected via Ga-DOTA-TATE PET/CT scans in the included 37 cases. These 37 TIO tumors showed obviously increased activities,with an maximum standardized uptake value of 7.2±4.3 and mean standardized uptake value of 4.3±2.4. The average maximum diameter was (1.9±0.7) cm. The majority of the tumors occurred in the lower extremities (19/37),followed by the trunk (11/37),maxillary/mandibular bone (5/37),and upper extremities (2/37). In addition,24 bone lesions were located in long bones of lower extremities (13/24),most of which demonstrated eccentric growth (8/13). Osteolytic changes (14/24) were observed mainly in the lesions via the corresponding CT imaging;meanwhile,sclerotic changes presented in nine cases. Of the 13 soft-tissue lesions,the majority (10/13) showed well-circumscribed isodense or hypodense nodules on the CT images,with spot calcification in one lesion located in the pleura.Conclusions Ga-DOTA-TATE PET/CT scans can detect the TIO culprit tumors miss-diagnosed by Tc-HYNIC-TOC SPECT. Somatostatin-receptors highly expressed lesions with focal osteolytic or osteosclerotic change in bone and isodense or hypodense nodules in soft tissue will favor the diagnosis of TIO tumors.
Humans ; Neoplasms ; complications ; diagnostic imaging ; Octreotide ; analogs & derivatives ; Organotechnetium Compounds ; Osteomalacia ; diagnostic imaging ; etiology ; Positron Emission Tomography Computed Tomography ; Retrospective Studies

BACKGROUND/AIMS: Terlipressin and octreotide had been used to control acute variceal bleeding and to prevent early rebleeding after endoscopic hemostasis. We compared the efficacy and safety of terlipressin and octreotide combined with endoscopic variceal ligation (EVL) for the treatment of acute esophageal variceal bleeding and we evaluated their clinical significance as related to rebleeding. METHODS: The eighty eight cirrhotic patients were randomized to the terlipressin group (n=43; 2 mg i.v. initially and 1 mg i.v. at every 4 hours for 3 days) or the octreotide group (n=45; continuous infusion of 25 microgram/h for 5 days) combined with EVL for the treatment of acute esophageal variceal bleeding. RESULTS: The initial hemostasis rates were 98% (42/43 cases) in the terlipressin group and 96% (43/45 cases) in the octreotide group. The 5-day and 42-day rebleeding rates were 12% (5/43 cases) and 28% (12/43 cases), respectively, in the terlipressin group and 9% (4/45 cases) and 24% (11/45 cases), respectively, in the octreotide group. No significant difference was demonstrated between the terlipressin and octreotide groups. The mortality at 42 days was similar in both group, but a high mortality rate (48%) was shown to be related to 42-day rebleeding. The risk factors related to 42-day rebleeding were Child-Pugh class C (aOR=30.2, 95% CI=7.7-117.9), ascites above grade II (aOR=6.6, 95% CI=2.2-19.2) and advanced hepatocellular carcinoma (aOR=4.6, 95% CI=1.1-18.9). CONCLUSIONS: Comparing terlipressin and octreotide combined with EVL showed them to be equally safe and effective therapeutic agents in patients with acute esophageal variceal bleeding. The high risk factors related to early rebleeding were poor liver function and advanced hepatocellular carcinoma.
Acute Disease ; Aged ; Esophageal and Gastric Varices/drug therapy/surgery/*therapy ; Female ; Gastrointestinal Hemorrhage/drug therapy/surgery/*therapy ; Humans ; Liver Cirrhosis/drug therapy/surgery/*therapy ; Lysine Vasopressin/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Octreotide/*therapeutic use ; Vasoconstrictor Agents/*therapeutic use

Esophageal and Gastric Varices ; drug therapy ; etiology ; Female ; Gastrointestinal Agents ; therapeutic use ; Gastrointestinal Hemorrhage ; drug therapy ; etiology ; Glucagon ; blood ; Humans ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Nitric Oxide ; blood ; Octreotide ; therapeutic use ; Somatostatin ; analogs & derivatives

OBJECTIVETo evaluate the value of (99 m)Tc-sandostatin scintigraphy in targeted diagnosis of pancreas carcinoma and the correlation with expression of somatostatin receptor (SSTR) reporter gene in tumor tissue.

METHODSNude mice bearing human pancreas carcinoma xenograft were established in advance. (99 m)Tc-sandostatin imaging was performed in 18 nude mice and tumor to normal tissue ratio (T/NT) was calculated. mRNA expression of SSTR1, SSTR2 and SSTR5 in tumor tissue was detected by RT-PCR.

RESULTSOut of 18 nude mice, 13 mice showed intense uptake of (99 m)Tc-sandostatin. Six hours after (99 m)Tc-sandostatin administration, the T/NT ratio was 2.53 +/- 0.84. Five mice showed negative findings, and the T/NT ratio was 1.04 +/- 0.06. Positive correlations were obtained between the T/NT ratio and the expression of SSTR1 and SSTR2 mRNA, especially SSTR2 (r = 0.807, P < 0.01).

CONCLUSIONHigh expression of SSTR1, SSTR2 and SSTR5 mRNA were found in human pancreas tumor xenograft in nude mice, especially SSTR2. There is a significant correlation between the tumor uptake of (99 m)Tc-sandostatin and SSTR2 mRNA level. This approach may allow SSTR-targeted diagnosis and therapy of human pancreas cancer.

Animals ; Genes, Reporter ; genetics ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Octreotide ; analogs & derivatives ; Organotechnetium Compounds ; Pancreatic Neoplasms ; diagnostic imaging ; genetics ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Radionuclide Imaging ; Receptors, Somatostatin ; biosynthesis ; genetics ; Tumor Cells, Cultured

OBJECTIVETo evaluate the effect of 90Y-DOTATOC and 131I-MIBG in treatment of metastatic medullary thyroid carcinoma (MTC).

METHODSTwelve histologically confirmed patients with metastatic MTC were included. All patients underwent both 111In-DTPA-octreotide imaging and 131I/ 123I-meta-iodobenzylguanidine (MIBG) imaging. According to the results of the combined imaging, positive patients were selected to be treated with 90Y-DOTA-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) or 131I-MIBG, respectively. The therapeutic procedures of targeted internal radiation were performed with 3.33 GBq 90Y-DOTATOC at 6-week intervals, or 11.1 GBq 131I-MIBG with a minimum interval of three months.

RESULTSThe imaging procedure was positive in all 12 patients: 111In-DTPA-octreotide imaging in eight patients, 131I/ 123I-MIBG imaging in six patients. According to the results of combined imaging, we identified four patients to be treated with 90Y-DOTATOC, and five patients with 131 I-MIBG. After three to five sessions of treatment, three patients with partial remission and six with stable disease were observed. The effective rate was 3/9 (33.3%) and the overall tumor response rate was 9/9 (100%). No relevant toxicity was observed.

CONCLUSIONThe combined imaging technique can be used to identify patients for effective radionuclide treatment. The treatment with 90Y-DOTATOC or 131I-MIBG is well tolerated and may improve the fate of patients with metastatic MTC.

3-Iodobenzylguanidine ; therapeutic use ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Medullary ; metabolism ; radiotherapy ; secondary ; Female ; Follow-Up Studies ; Humans ; Indium Radioisotopes ; Male ; Middle Aged ; Octreotide ; analogs & derivatives ; therapeutic use ; Pentetic Acid ; analogs & derivatives ; Positron-Emission Tomography ; Remission Induction ; Thyroid Gland ; diagnostic imaging ; pathology ; radiation effects ; Thyroid Hormones ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology ; radiotherapy ; Treatment Outcome ; Yttrium Radioisotopes ; therapeutic use

Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bevacizumab ; Gastrointestinal Neoplasms ; classification ; epidemiology ; therapy ; Humans ; Indoles ; therapeutic use ; Neuroendocrine Tumors ; classification ; epidemiology ; therapy ; Octreotide ; therapeutic use ; Pancreatic Neoplasms ; classification ; epidemiology ; therapy ; Peptides, Cyclic ; therapeutic use ; Pyrroles ; therapeutic use ; Sirolimus ; analogs & derivatives ; therapeutic use ; Somatostatin ; analogs & derivatives ; therapeutic use

BACKGROUND/AIMS: Although carcinoid tumors usually have good prognosis, early and specific diagnosis is important. Computed tomography and magnetic resonance imaging do not provide findings that are specific for carcinoids, and somatostatin receptor scintigraphy suffers from low spatial resolution. 18-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has limited sensitivity for carcinoids due to low uptake of the marker. A PET/CT system that uses the somatostatin receptor-based PET tracer 1,4,7,10-tetraazacyclododecane-N(I),N(II),N(III),N(IIII)-tetraacetic acid (D)-Phe(1)-thy(3)-octreotide ((68)Ga-DOTATOC) has also been used in the evaluation of carcinoids, although information regarding its use for the detection of primary pulmonary carcinoids is limited. Thus, we investigated the value of (68)Ga-DOTATOC PET/CT for the diagnosis of primary pulmonary carcinoid tumors. METHODS: This was a retrospective analysis of patients with primary pulmonary tumors who underwent (68)Ga-DOTATOC PET/CT. All the patients had a histopathologic diagnosis of carcinoid. The rate of detection of primary pulmonary carcinoid tumors using (68)Ga-DOTATOC PET/CT was assessed. RESULTS: Twenty patients were diagnosed as having carcinoid, and 19 tumors showed significant uptake on (68)Ga-DOTATOC (detection rate, 95%). The maximal standardized uptake value (SUV(max)) ranged from 1.1 to 66, with a median value of 21.6. In one patient, (68)Ga-DOTATOC PET/CT revealed additional lesions. CONCLUSIONS: Our results demonstrate that (68)Ga-DOTATOC PET/CT is useful in the evaluation of primary pulmonary carcinoids and should be included in the diagnostic work-up of these patients.
Adolescent ; Adult ; Carcinoid Tumor/*diagnosis/radiography/radionuclide imaging ; Female ; Gallium Radioisotopes/*diagnostic use ; Humans ; Lung Neoplasms/*diagnosis/radiography/radionuclide imaging ; Male ; Middle Aged ; Octreotide/*analogs & derivatives/diagnostic use ; Positron-Emission Tomography/*methods ; Radiopharmaceuticals/*diagnostic use ; Retrospective Studies ; Tomography, X-Ray Computed/*methods