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  • gastrin  (3)
  • bombesin  (2)
  • cyclosporine  (2)
  • pancreatic cancer  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Effect of aging on gastric acid secretion, serum gastrin, and antral gastrin content in rats (1988)
    Springer
    Digestive diseases and sciences 33 (1988), S. 1544-1548 
    Details
    ISSN: 1573-2568
    Keywords: aging ; gastric secretion ; gastrin ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to characterize the effects of aging on gastric acid secretion and on serum and antral concentrations of gastrin in rats. Young and old Fischer 344 rats were prepared with gastric fistulas. Twenty-four hours after surgery, graded doses of human synthetic gastrin-17 (SHG-17) (2, 5, 10, 20, and 40 μg/kg) were given intravenously in random order. Gastric secretions were collected for gastric acid measurement before and at 15-min intervals after each dose of gastrin. In a separate study, blood was collected and the stomachs were removed for antral gastrin extraction from fed young and old rats. Serum and antral gastrin was measured by radioimmunoassay. The basal and gastrin-stimulated acid secretions were significantly decreased in aged rats compared to the young rats. The basal acid output was 0.4±0.2 μeq/15 min in the aged rats and 1.5±0.5 μeq/15 min in the young. The maximal acid output stimulated by gastrin was 11.1±1.8 μeq/15 min in the aged rats and 24.2±2.8 μeq/15 min in the young. Both serum and antral concentrations of gastrin were significantly decreased in aged rats. Serum gastrin concentration was 114.8±7.4 pg/ml in the aged rats and 192.0±14.4 pg/ml in the young. Antral gastrin concentration was 3.9±0.5 μg/g tissue in the aged rats, which was significantly less than the concentration in the young (6.5±0.4 μg/g tissue). Antral gastrin content did not change with aging. Gastric acid secretion in aged rats is significantly decreased compared to the young in both the basal condition and in response to fixed doses of exogenous gastrin. Diminished concentrations of circulating gastrin may well be responsible, at least in part, for the diminished acid secretion in the aged rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01535944
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  • 2
    Electronic Resource
    Electronic Resource
    Circadian rhythms in gastrin receptors in rat fundic stomach (1988)
    Springer
    Digestive diseases and sciences 33 (1988), S. 931-937 
    Details
    ISSN: 1573-2568
    Keywords: circadian rhythms ; gastrin receptors ; gastrin ; rat ; stomach
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Circadian rhythmicity in the number of gastrin receptors in rat fundic mucosa was characterized and was related to the concentrations of gastrin in serum and in antrum. Male Sprague-Dawley rats were acclimated to 12 hr light alternating with 12 hr darkness. Subgroups of six rats each were killed at 4-hr intervals. Fundic mucosa was collected for measurement of gastrin receptors; serum and antral tissues were collected for measurement of gastrin levels by radioimmunoassay. Circadian periodicity in the data was determined by cosinor analyses. In both freely fed and fasted rats, gastrin receptors showed circadian variation (range 2.5–10 fmol/mg protein), as did serum gastrin concentrations (range in fed rats 195–407 pg/ml). The phasing of the intrinsic circadian variation in gastrin receptor level that was observed in the fasted rats was advanced by a few hours in fed rats. This shift is probably due to food-induced gastrin release, resulting in gastrin-mediated down-regulation of gastrin receptors, followed by up-regulation of gastrin receptors. Food-related effects were thus superimposed upon the intrinsic circadian rhythms in gastrin receptor levels, causing the circadian variation in gastrin receptor levels in the fed rats to be shifted forward compared to that in the fasted rats. No significant circadian rhythms, on the other other hand, were found in concentrations of gastrin in the antrum. These results suggest that changes in sensitivity of target tissues to hormones are related to both intrinsic circadian rhythms in levels of hormone receptors and also to food-related changes in hormone-receptor levels mediated by changing serum hormone levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01535987
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  • 3
    Electronic Resource
    Electronic Resource
    Differential sensitivity of pancreatic and colon cancer to cyclosporine and α-difluoromethylornithine in vivo (1988)
    Springer
    Investigational new drugs 6 (1988), S. 265-272 
    Details
    ISSN: 1573-0646
    Keywords: polyamines ; pancreatic cancer ; colon cancer ; cyclosporine ; DFMO
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have previously reported that the in vitro growth of MC-26 mouse colon cancer and H2T hamster pancreatic cancer cells are inhibited by cyclosporine (CsA) and α-difluoromethylornithine (DFMO). The present study was designed to investigate the effects of these two drugs on the two experimental tumors (MC-26 and H2T) growing in vivo. Forty-eight male Balb/c mice or Syrian golden hamsters were inoculated with MC-26 (250,000) or H2T (500,000) cells, respectively, and then were randomized into four groups of 12 each: group I was control; group II received CsA; group III received DFMO; group IV received a combination of CsA and DFMO. MC-26 tumors were significantly more sensitive than H2T tumors to the effects of CsA and DFMO. MC-26 tumor growth and tumor weight, as well as the tumor content of DNA, RNA, and protein were all significantly more reduced by CsA and DFMO than were the H2T tumors. Our present study shows that both CsA and DFMO are potent inhibitors of MC-26 colon carcinoma growth in vivo, though DFMO is more than twice as effective as CsA. DFMO also produced greater reductions in the tumor content of DNA, RNA, and protein than did CsA. DFMO significantly decreased the concentrations of polyamines in both H2T and MC-26 tumors; the MC-26 tumors were affected to a greater degree.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00173644
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  • 4
    Electronic Resource
    Electronic Resource
    Hyperphosphorylation of retinoblastoma protein and stimulation of growth by okadaic acid in human pancreatic cancer (1996)
    Springer
    Digestive diseases and sciences 41 (1996), S. 1975-1980 
    Details
    ISSN: 1573-2568
    Keywords: okadaic acid ; retinoblastoma protein ; pancreatic cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Phosphorylation/dephosphorylation of intracellular proteins are important steps in the regulation of cell growth. Okadaic acid, an inhibitor of the serine/threonine protein phosphatases 1 and 2A, is a potent tumor promoter. This effect may be through the inhibition of dephosphorylation (termed “hyperphosphorylation”) and subsequent inactivation of tumor-suppressor proteins. We examined whether okadaic acid regulates growth of human pancreatic cancer cells (MIA PaCa-2 and Panc-1) or alters the phosphorylation of the retinoblastoma tumor-suppressor protein. Growth studies, nuclear labeling analyses, and Western blotting for retinoblastoma protein were performed. Okadaic acid stimulated cell growth and induced hyperphosphorylation of the retinoblastoma protein. The growth-stimulatory effect of okadaic acid on these human pancreatic cancer cells may be mediated by inactivation of the growth suppressive effect of the retinoblastoma protein by hyperphosphorylation. These studies suggest that the growth of these human pancreatic cancer cells is still regulated by tumor-suppressor proteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02093599
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  • 5
    Electronic Resource
    Electronic Resource
    Mechanisms of bombesin on growth of gastrinoma (PT)in vivo (1996)
    Springer
    Digestive diseases and sciences 41 (1996), S. 2180-2186 
    Details
    ISSN: 1573-2568
    Keywords: gastrinoma ; bombesin ; growth ; gastrin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The growth of the human gastrinoma model (PT) in athymic nude mice is stimulated by bombesin (BBS), an amphibian peptide homologous to both human gastrin-releasing peptide (GRP) and neuromedin B (NMB). The mechanism is not known, and a potent and specific GRP-R antagonist BIM26226, which has low affinity for NMB-R, was usedin vivo in athymic nude mice bearing gastrinoma subcutaneously. Both the BBS and BIM26226 stimulated the growth of PT, and the growth stimulation was even greater when given together. RT-PCR study of gastrinoma revealed the presence of both GRP-R and NMB-R mRNA, but much more abundant NMB-R mRNA. We conclude that BBS-stimulated growth of gastrinoma involves both GRP-R and NMB-R, and our findings suggest that GRP-R mediates negative and NMB-R produces positive growth effects on gastrinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02071398
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of aging on gastrin and somatostatin secretion from isolated perfused rat stomach (1993)
    Springer
    Digestive diseases and sciences 38 (1993), S. 303-308 
    Details
    ISSN: 1573-2568
    Keywords: bombesin ; carbachol ; peptone ; Fischer 344 rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have examined the release of gastrin and somatostatin from the isolated perfused stomach of rats of three different age groups (4 months, 12 months, and 24 months old) in response to bombesin and carbachol. The basal release of gastrin was diminished in 24-month-old rats. Basal somatostatin release showed an age-related decrease. Bombesin (10−10 and 10−9 M) and carbachol (10−8 and 10−7 M) stimulated gastrin release in each age group. The integrated release of gastrin in response to bombesin (10−10 and 10−9 M) or carbachol (10−8 M) did not differ among the three age groups, although integrated gastrin release in response to carbachol (10−7 M) decreased in 24-month-old rats. Bombesin-stimulated release of somatostatin decreased in 12- and 24-month-old rats. Carbachol inhibited release of somatostatin in each age group. Compared with 4-month-old rats, the inhibition of somatostatin release by carbachol was less in 24-month-old rats at 10−8 and 10−7 M, and less in 12-month-old rats at 10−7 M. The decreased basal gastrin secretion and well-preserved gastrin response were further confirmed in conscious aged rats tested by means of oral gavage with 10% peptone. Our findings indicate that gastrin response to the stimuli is well preserved with aging, whereas the response of somatostatin diminishes in an age-related manner. Aging has different effects on the release of gastrin and somatostatin from the rat stomach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01307548
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  • 7
    Electronic Resource
    Electronic Resource
    Cyclosporine and α-difluoromethylornithine exhibit differential effects on colon and pancreatic cancer in vitro (1987)
    Springer
    Investigational new drugs 5 (1987), S. 251-258 
    Details
    ISSN: 1573-0646
    Keywords: cancer ; cyclosporine ; pancreas ; colon ; polyamines ; α-difluoromethylornithine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract α-Difluoromethylornithine (DFMO) is a known irreversible inhibitor of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Cyclosporine (CsA) has been reported to inhibit ODC activity in vitro. In the present study, we compared the effects of DFMO and CsA on growth, survival, and polyamine levels in mouse colon cancer (MC-26) and hamster pancreatic cancer (H2T) cells in vitro. The growth and survival of MC-26 and H2T cells were inhibited by both DFMO and CsA. However, H2T cells were observed to be significantly more sensitive than MC-26 cells to both CsA and DFMO. The inhibitory effects of CsA were blocked by the addition of the polyamine, putrescine, in both MC-26 and H2T cells. Polyamine levels were altered significantly in both MC-26 and H2T cells treated with CsA and DFMO. However, the profile of these alterations differed between MC-26 and H2T cell lines. Putrescine and spermidine levels in MC-26 cells were more sensitive to DFMO inhibition than were H2T cells. Spermine levels were consistently elevated in MC-26 cells exposed to CsA or DFMO, while the level of spermine in H2T cells decreased significantly in response to the same drugs. These results suggest that CsA and DFMO exhibit different effects on colon and pancreatic cancer growth in vitro. In addition, the differences in the sensitivity of pancreatic and colon cancer to CsA and DFMO indicate potentially important differences in polyamine metabolism between the two cell lines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175295
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