sincalide and Precancerous-Conditions

sincalide has been researched along with Precancerous-Conditions* in 5 studies

Other Studies

5 other study(ies) available for sincalide and Precancerous-Conditions

ArticleYear
An NF-κB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice.
    The Journal of clinical investigation, 2012, Volume: 122, Issue:4

    Genetic mutations that give rise to active mutant forms of Ras are oncogenic and found in several types of tumor. However, such mutations are not clear biomarkers for disease, since they are frequently detected in healthy individuals. Instead, it has become clear that elevated levels of Ras activity are critical for Ras-induced tumorigenesis. However, the mechanisms underlying the production of pathological levels of Ras activity are unclear. Here, we show that in the presence of oncogenic Ras, inflammatory stimuli initiate a positive feedback loop involving NF-κB that further amplifies Ras activity to pathological levels. Stimulation of Ras signaling by typical inflammatory stimuli was transient and had no long-term sequelae in wild-type mice. In contrast, these stimuli generated prolonged Ras signaling and led to chronic inflammation and precancerous pancreatic lesions (PanINs) in mice expressing physiological levels of oncogenic K-Ras. These effects of inflammatory stimuli were disrupted by deletion of inhibitor of NF-κB kinase 2 (IKK2) or inhibition of Cox-2. Likewise, expression of active IKK2 or Cox-2 or treatment with LPS generated chronic inflammation and PanINs only in mice expressing oncogenic K-Ras. The data support the hypothesis that in the presence of oncogenic Ras, inflammatory stimuli trigger an NF-κB-mediated positive feedback mechanism involving Cox-2 that amplifies Ras activity to pathological levels. Because a large proportion of the adult human population possesses Ras mutations in tissues including colon, pancreas, and lung, disruption of this positive feedback loop may be an important strategy for cancer prevention.

    Topics: Animals; Carcinoma, Pancreatic Ductal; Cell Transformation, Neoplastic; Ceruletide; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Enzyme Induction; Esters; Feedback, Physiological; Gabexate; Gene Expression Regulation, Neoplastic; Gene Knock-In Techniques; Genes, ras; Guanidines; Humans; I-kappa B Kinase; Inflammation; Inflammation Mediators; Lipopolysaccharides; Mice; Mice, Transgenic; Neoplasm Proteins; NF-kappa B; Pancreas; Pancreatic Neoplasms; Pancreatitis, Chronic; Precancerous Conditions; Proto-Oncogene Proteins p21(ras); Sincalide

2012
Growth of azaserine-induced putative preneoplastic nodules in the rat pancreas is mediated specifically by way of cholecystokinin-A receptors.
    Annals of the New York Academy of Sciences, 1994, Mar-23, Volume: 713

    Topics: Animals; Azaserine; Carcinogens; Cell Division; Cholecystokinin; Male; Pancreas; Pancreatic Neoplasms; Peptide Fragments; Precancerous Conditions; Rats; Rats, Inbred Lew; Receptors, Cholecystokinin; Sincalide; Tetragastrin

1994
Stimulation of growth of azaserine-induced putative preneoplastic lesions in rat pancreas is mediated specifically by way of cholecystokinin-A receptors.
    Cancer research, 1993, Sep-01, Volume: 53, Issue:17

    Cholecystokinin (CCK) has been shown to stimulate the growth of both normal pancreas and azaserine-induced putative preneoplastic pancreatic lesions in the rat. The present study was performed to determine whether these effects are mediated by way of CCK-A receptors, CCK-B receptors, or both. Sixteen-day-old male Lewis rats were given i.p. injections of azaserine at 30 mg/kg body weight. Starting on day 21, rats were given s.c. injections, 5 days/week for 16 consecutive weeks, of either (a) CCK octapeptide (nonselective CCK agonist) (2.50 micrograms/kg body weight, n = 17), (b) tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2-methylphenylaminocarbonyl++ +)-Asp- (N-methyl)-Phe-NH2 (highly selective CCK-A agonist) (1.84 micrograms/kg body weight, n = 18), (c) [(2R,3S)-beta-MePhe28,N-MeNle31]CCK26-33 (highly selective CCK-B agonist) (2.40 micrograms/kg body weight, n = 18), or (d) normal saline solution (control, n = 17). Rats were subsequently sacrificed, pancreatic weights were determined, and quantitative morphometric analysis of atypical acinar cell foci and nodules was performed. Both CCK octapeptide and the selective CCK-A agonist tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2- methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 stimulated pancreatic growth and the development of acidophilic atypical acinar cell foci and nodules. Furthermore, the effect produced by the selective CCK-A agonist tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2- methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 was greater than that produced by CCK octapeptide. In contrast, the selective CCK-B agonist [(2R,3S)-beta-MePhe28,N-MeNle31]CCK26-33 had no effect. These findings suggest that the growth of putative preneoplastic lesions (acidophilic atypical acinar cell foci and nodules) in the rat pancreas during the early stages of azaserine-induced pancreatic carcinogenesis is mediated specifically by way of CCK-A receptors.

    Topics: Animals; Azaserine; Cholecystokinin; Chronic Disease; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Pancreatitis; Peptide Fragments; Precancerous Conditions; Rats; Rats, Inbred Lew; Receptors, Cholecystokinin; Sincalide; Tetragastrin

1993
Overexpression of cholecystokinin receptors in azaserine-induced neoplasms of the rat pancreas.
    Cancer research, 1992, Jun-15, Volume: 52, Issue:12

    Cholecystokinin (CCK) is a growth factor for normal pancreas. Numerous studies also suggest that CCK promotes pancreatic carcinogenesis in the rat. Our previous studies suggested that growth of preneoplastic pancreatic foci was stimulated by CCK more than that of normal pancreas. We hypothesized that such differential growth might be due to increased numbers of CCK receptors in neoplastic tissue. Azaserine-induced pancreatic carcinoma (DSL6) had an increased high-affinity CCK receptor binding capacity of 122 +/- 23 (SD) fmol/mg protein compared to 12 +/- 2 fmol/mg protein in normal pancreas (P less than 0.001). The Kd of the high-affinity site was 0.33 +/- 0.04 nM for carcinoma and 0.46 +/- 0.08 nM for normal pancreas (P less than 0.01). The amount of cholecystokinin octapeptide (CCK-8) bound to high-affinity receptor was 8.6 +/- 1.9 fmol/mg protein for DSL6 compared to 0.6 +/- 0.2 fmol/mg protein in normal pancreas (P less than 0.001). Azaserine-induced premalignant nodules were compared to remaining internodular pancreas. Nodules demonstrated a mean high-affinity CCK receptor binding capacity of 38 +/- 9 fmol/mg protein compared to 6 +/- 3 fmol/mg protein in internodular pancreas (P less than 0.001). The amount of CCK-8 bound to high-affinity receptor was 3.1 +/- 0.8 fmol/mg protein in nodules compared to 0.6 +/- 0.3 fmol/mg protein in internodular pancreas (P less than 0.001). Overexpression of high-affinity CCK-8 receptor in premalignant and malignant azaserine-induced tumors may result in a growth advantage relative to normal pancreas.

    Topics: Animals; Azaserine; Binding, Competitive; DNA, Neoplasm; Hydrogen-Ion Concentration; Male; Pancreatic Neoplasms; Precancerous Conditions; Rats; Receptors, Cholecystokinin; Sincalide; Succinimides; Temperature; Time Factors

1992
Modulation by CR-1409 (lorglumide), a cholecystokinin receptor antagonist, of trypsin inhibitor-enhanced growth of azaserine-induced putative preneoplastic lesions in rat pancreas.
    Cancer research, 1989, May-01, Volume: 49, Issue:9

    Feeding of raw soya flour or other trypsin inhibitors such as camostate is a well-established method for promoting growth of (pre)neoplastic foci induced in the exocrine pancreas of rats by azaserine. The effect of trypsin inhibitors is thought to be mediated through an increased release of cholecystokinin. Using the specific cholecystokinin receptor antagonist lorglumide (CR-1409), we performed a 16-wk study to investigate the potential of this drug in inhibiting growth of putative preneoplastic foci and to determine whether and to what extent cholecystokinin is responsible for the effect of trypsin inhibitors on pancreatic growth. After initiation with 30 mg/kg of azaserine at 19 days of age, six groups of 15 rats each received one of the following treatments: camostate, cholecystokinin-8, or gelatin control, either or not in combination with CR-1409, once daily, 3 days wk for 16 wk. Plasma cholecystokinin levels, measured 30 min after the stimulus, were similar after camostate and cholecystokinin octapeptide administration. After 16 wk the pancreata were removed, weighted, and quantitatively analyzed for the number and size of putative preneoplastic foci by light microscopy. Both camostate and cholecystokinin octapeptide stimulated pancreatic growth and development of acidophilic putative preneoplastic foci, whereas growth of basophilic putative preneoplastic foci was inhibited by camostate but stimulated by cholecystokinin. CR-1409 almost completely abolished the effect of cholecystokinin and was found to cause a significant decrease in the effects of camostate. It is concluded that (a) cholecystokinin plays a significant role in camostate-stimulated growth of acidophilic putative preneoplastic foci in rat pancreas and (b) CR-1409 inhibits growth of putative preneoplastic foci induced in rat pancreas by azaserine and hence may be of potential value for the treatment of pancreatic cancer in humans.

    Topics: Animals; Azaserine; Cholecystokinin; Esters; Gabexate; Glutamine; Guanidines; Male; Pancreatic Neoplasms; Precancerous Conditions; Proglumide; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; Sincalide; Trypsin Inhibitors

1989
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