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A Pap

Publications and source records attributed to A Pap.

117 records · Page 7Linked to original sources
PubMedDate not supplied

In vivo antitumor activity of TT-232 a novel somatostatin analog.

The somatostatin analog TT-232 containing a 5 residue ring, was previously shown to inhibit the proliferation of a large number of cancer cell lines in vitro and reduce the size of tumors in animal models in vivo. Its action is accompanied by inhibition of tyrosine kinases and is characterized by the induction of programmed cell death. On the other hand, it was proved to be free of the endocrine effects of the natural compound. The aim of this study was to find the optimal dose and administration route for in vivo tumor therapy in an animal model. We have investigated the dose--and administration route-dependent antitumor activity of TT-232 on S-180 sarcoma tumor transplanted to inbred BDF1 mice from SPF breeding. Long-term administration (i.p., s.c. and i.v. injections) was started either on the day subsequent to tumor transplantation or after the development of tumor. The antineoplastic potential of TT-232 was evaluated on the basis of survival and tumor growth inhibition. In long-term administration (injections twice a day for 2 weeks) a significant, but dose- and administration route-dependent therapeutic efficacy of TT-232 was observed. The optimum dose of TT-232 15 micrograms/kg which resulted in a 30-40% cure rate and 50-70% growth inhibition in S-180 sarcoma tumor. A moderate antitumor effect was achieved by TT-232 when it was administered after the evelopment of tumor. Our study suggests that TT-232 can be a promising antitumor agent.

Animals↗
PubMedDate not supplied

Influence of various administration routes on the antitumor efficacy ofTT-232, a novel somatostatin analog.

TT-232 a novel tumor-selective somatostatin analog with a five residue ring structure (D-Phe-Cys-Tyr-D-Trp-Lys-Cys-Thr-NH2) was developed by us and published in an earlier work. This synthetic heptapeptide had no effect on growth hormone release, but had a remarkable tyrosine-kinase inhibitory effect and inducted apoptosis. The aim of this study was to compare the therapeutic efficacy of TT-232 used in various long-term administration routes and treatment schedules. The effectiveness of TT-232 was studied on different rodent tumors transplanted to inbred mice from SPF breeding. Intermittent treatment by injections and continuous infusion of TT-232 using a s.c., i.p. or i.v. implanted Alzet type osmotic minipump were compared for therapeutic efficacy. The treatments were started either on the day subsequent to tumor transplantation or after the development of a tumor. On the basis of survival and tumor growth inhibition the infusion of TT-232 for 14 days using an implantable osmotic pump proved to be a much more effective route of treatment in both s.c. and i.v. administration than the intermittent injections applied twice a day for 2 weeks. In the case of S-180 sarcoma the continuous administration of TT-232 for 14 days using s.c. implanted osmotic pump resulted in 60% the i.v. infusion produced 40% long-term (over 80 days) and tumor free survivors. By the continuous administration of TT-232, an 80-100% tumor growth inhibitory effect and a considerable retardation of tumor development could be achieved. Continuous infusion from implanted pumps ensured a constant drug level and resulted in a well-defined, consistent pattern of drug exposure over the full duration of drug administration. In our study the route of infusion has been shown to increase drug efficacy relative to conventional delivery methods.

Animals↗
PubMedDate not supplied

Antiproliferative efficacy of the somatostatin analogue TT-232 in human melanoma cells and tumours.

BACKGROUND: TT-232, a somatostatin analogue, induces apoptosis in various tumours. The aim of our study was to characterise its effect on human melanoma cells and tumours. MATERIALS AND METHODS: Proliferation of seven melanoma cell lines was tested in vitro with the methylene blue test. D10 and 205 cells were also implanted into CB17-scid mice which received 30-150-750 micrograms/kg/day of TT-232 or saline. Animals with 205 cells received twice-daily subcutaneous injections whereas animals with D10 cells were treated with osmotic mini-pumps. In addition, TT-232 metabolites were generated with tissue homogenates and tested in vitro. RESULTS: TT-232 strongly inhibited proliferation of all cell lines in vitro and tumour growth in vivo. Two out of 8 animals (30-150 micrograms/kg) in the 205 model and one out of 8(150 micrograms/kg) in the D10 model became completely tumour-free at the 11th and 9th day of treatment, respectively. TT-232 was degraded only by liver homogenate whilst its metabolite had no antiproliferative effect in vitro. CONCLUSIONS: TT-232 is a promising drug candidate for melanoma.

Animals↗
PubMedDate not supplied

Influence of bile on the severity of acute experimental pancreatitis induced by closed duodenal loop in rat.

The study was performed to assess the ethiological role of bile in acute pancreatitis provoked by closed duodenal loop in rat. In group I a closed duodenal loop was created by method of Nevalainen. A similar operation was performed in group II, but the common pancreatico-biliary duct was ligated just under the liver. In the control group (group C) only the mobilization of duodenum was performed. After 24 hours the mortality rate was 20% in group I, but 0% in group II and C. The amount of ascitic fluid showed significant elevation in group I versus II and group C, and in group II as compared to group C, too. The serum amylase was significantly higher in group I than group II and group C, and in group II was also higher as compared to group C. Serum total protein differed significantly between all groups, while albumin and total calcium were significantly lower in group I than group II, but group II was only slightly reduced versus group C. Histology showed no differences between groups I and II, but both differed significantly from group C. In conclusion bile seems to be an aggressive factor in pathogenesis of acute pancreatitis induced by closed duodenal loop in rat, but other factors may play more important roles.

Acute Disease↗
PubMedDate not supplied

The effect of jejunal nutrition on pancreatic exocrine function.

Pancreatic juice was continuously diverted from the Wirsungial duct by nasopancreatic drainage of the remnant of the gland after pylorus preserving partial pancreato-duodenectomy in 14 patients. On the 7th postoperative day with stabilized pancreatic secretion the juice was collected in 10 min fractions, while interdigestive secretory phases of the parenchyma were established by volume changes. At the beginning of a phase, 100 ml slightly hyperosmolar (400 mOsm/l) oligopeptide diet with 360 kJ (90) kCal) was given as a bolus injection to another 7 patients or 60 min infusion into the second jejunal loop by fine-needle catheter jejunostomy to another 7 patients. Pancreatic water, bicarbonate, protein, chymotrypsin, peak amylase levels, and integrated secretory responses were measured. It was observed that infusion of the diet did not disturb cycling interdigestive phases and did not increase peak and integrated outputs. Bolus administration interrupted interdigestive phases and stimulated pancreatic water, bicarbonate, protein, chymotrypsin and amylase outputs nonparallelly. On the basis of the data it was concluded that pancreatic secretion seems to be well preserved without duodenal regulatory mechanisms, and continuous jejunal infusion feeding seems to be useful in pancreatic disease and in other postoperative states when pancreas has to be put into rest.

Anastomosis, Surgical↗
PubMedDate not supplied

The effect of early postoperative nutrition on exocrine pancreatic function.

Subsequent to pancreato-duodenectomy with preservation of the pylorus in 12 patients the effect of parenteral and enteral nutrition on pancreatic secretion were compared. The pancreatic juice was continuously diverted from the Wirsung duct by nasopancreatic drainage. Postoperative feeding was administered by fine-needle catheter jejunostomy in 7 patients and 5 patients received total parenteral nutrition. The pancreatic juice was collected in four-hour fractions and it was analysed for volume, bicarbonate, protein, chymotrypsin and amylase. It has been found that on the first two days after the operation there was a slow increase in the measured values and on the third postoperative day after an abrupt rise the pancreatic secretion became steady. No differences in exocrine pancreatic secretion were observed between the enteral and parenteral methods of feeding. According to these data the two methods seem to be of the same value in the postoperative therapy.

Adult↗