• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4037-4040
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• 2015

Objective: To explore the clinical efficacy and toxic and side effects of recombinant human endostatin (rhendostatin/endostar) combined with chemotherapy in the treatment of advanced gastric cancer. Materials and Methods: A total of 70 patients with advanced gastrointestinal adenocarcioma confirmed by histopathology and/or cytological examination were divided into group A (37 patients) and group B (33 patients). Patients in group A were given intravenous drip of 15 mg endostar added into 500 mL normal saline, once every other day until the cessation of chemotherapy or patients' maximal tolerance to chemotherapy. Patients in group B received chemotherapy alone. Two groups selected the same chemotherapy regimens. FOLFIRI scheme: 90-min intravenous drip of $180mg/m^2$ irinotecan, intravenous drip of $200mg/m^2$ calcium folinate (CF) and $400mg/m^2$ 5-fluorouracil (5-Fu) on d1, and continuous intravenous pumping of 2 $400mg/m^2$ 5-Fu for 46 h. FOLFOX4 scheme: intravenous injection of $85mg/m^2$ oxaliplatin (L-OHP), $200mg/m^2$ calcium folinate (CF) and $400mg/m^2$ 5-FU on d1 for 2 h, and then continuous intravenous pumping of 2 $400mg/m^2$ 5-Fu for 46 h. XELOX scheme: oral administration of 1 $500mg/m^2$ xeloda (or tegafur 50~60 mg) in twice during d1~14 and intravenous drip of $135mg/m^2$ L-OHP on d1 for 2 h. The modified FOLFOX scheme: intravenous injection of $135mg/m^2$ L-OHP on d1 for 2 h, $200mg/m^2$ CF and 1.0 g tegafur during d1~5. Whereas, control Group B received chemotherapy regimens which were same as Group A, but no addition of endostar. Before chemotherapy, patients were given intravenous injection of 8 mg ondansetron, intramuscular injection of 10 mg metoclopramide and 20 mg diphenhydramine for prevention of vomiting, protection of liver and stomach as well as symptomatic supportive treatment. One cycle was 21 d, 4~6 cycles in total. The efficacy was evaluated every 2 cycles. Results: 32 patients in Group A could be evaluated, and the response rate (RR) and disease control rate (DCR) were 59.38% and 78.13%, respectively. 31 patients in Groups could be evaluated, and the RR and DCR were 32.26% and 54.84%, respectively. The differences between 2 groups were significant. The toxic effects include myelosuppression, gastrointestinal reaction, fatigue, cardiotoxicity and peripheral neurotoxicity. Conclusions: Preliminary observations show that endostar (once every other day) combined with chemotherapy is effective in the treatment of advanced gastrointestinal cancer, with low toxic effects, good tolerance, deserving further study.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.43-55
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• 1993

The present study was conducted to examine the characteristics of histamine on catecholamine secretion in the isolated perfused rat adrenal gland and to clarify the mechanism of its secretory action. Histamine (37.5 to 150 ug) injected into an adrenal vein evoked a dose-dependent significant secretory response of catecholamines (CA) from the rat adrenal gland. However, upon the repeated injection of histamine (150 ug) at 120 min intervals, CA secretion was rapidly decreased after third injection of histamine. Tachyphylaxis to releasing effects of CA evoked by histamine was observed by the repeated administration. The histamine-induced CA secretion was markedly inhibited by the pretreatment with chlorisondamine, diphenhydramine, ranitidine, $Ca^{++}-free$ Krebs solution, nicardipine and TMB-8 while was not affected by pirenzepine. Moreover, the CA secretion evoked by ACh was considerably reduced by the prior perfusion of histamine $(6.8{\times}10^{-5} M)$ for 30 min. These experimental data suggest that histamine causes secretion of CA in a calcium dependent manner from the perfused rat adrenal gland and that its secretory effect is mediated through activation of both $H_1-$ and $H_2-histaminergic$ receptors located in adrenal medulla, which may be associated with stimulation of cholinergic nicotinic receptors.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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• pp.259-270
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• 2001

The present study was attempted to investigate the characteristics of epibatidine on secretion of catecholamines (CA) from the isolated perfused model of the rat adrenal gland, and to establish the mechanism of action. Epibatidine $(3{\times}10^{-8}\;M)$ injected into an adrenal vein produced a great inhibition in secretory response of CA from the perfused rat adrenal gland. However, upon the repeated injection of epibatidine $(3{\times}10^{-8}\;M)$ at 15 min-intervals, CA secretion was rapidly decreased after second injection of epibatidine. However, there was no statistical difference between CA secretory responses of both 1st and 2nd periods by the successive administration of epibatidine at 120 min-intervals. Tachyphylaxis to releasing effects of CA evoked by epibatidine was observed by the repeated administration. Therefore, in all subsequent experiments, epibatidine was not administered successively more than twice only 120 min-intervals. The epibatidine-induced CA secretion was markedly inhibited by the pretreatment with atropine, chlorisondamine, pirenzepine, nicardipine, TMB-8, and perfusion of $Ca^{2+}-free$ Krebs solution containing EGTA, while was not affected by diphenhydramine. Moreover, the CA secretion evoked by ACh for 1st period $(0{\sim}4\;min)$ was greatly potentiated by the simultaneous perfusion of epibatidine $(1.5{\times}10^{-8}\;M),$ but followed by time-dependently gradual reduction after 2nd period. The CA release evoked by high potassium $(5.6{\times}10^{-8}\;M),$ for 1st period $(0{\sim}4\;min)$ was also enhanced by the simultaneous perfusion of epibatidine, but those after 2nd period were not affected. Taken together, these experimental data suggest that epibatidine causes catecholamine secretion in a calcium dependent fashion from the perfused rat adrenal gland through activation of neuronal cholinergic (nicotinic and muscarinic) receptors located in adrenomedullary chromaffin cells. It also seems that epibatidine-evoked catecholamine release is not relevant to stimulation of histaminergic receptors.