peptide-yy and Adenocarcinoma

Peptide YY (PYY) is a naturally occurring gut hormone with mostly inhibitory actions on multiple tissue targets. PYY has been identified in several carcinoid tumors and a decreased expression of PYY may be relevant to the development and progression of colon adenocarcinoma. Treatment with PYY decreases growth in pancreatic and breast tumors, most likely through a reduction in intracellular cAMP. In cancer patients, PYY may also improve malnutrition that results from iatrogenic causes or cachexia associated with advanced disease. PYY plays a significant role in multiple aspects of cancer from regulation of cell growth to potential therapeutic applications.

Topics: Adenocarcinoma; Breast Neoplasms; Cachexia; Carcinoid Tumor; Cell Division; Colonic Neoplasms; Cyclic AMP; Humans; Pancreatic Neoplasms; Peptide YY; Time Factors

To investigate the relationship between the function of vagus nerve and peptide YY(3-36) and ghrelin levels after subtotal gastrectomy.. We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY(3-36), ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.. Vagus nerve preservation group showed less body weight loss and less increase of peptide YY(3-36) compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY(3-36) level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].. Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY(3-36).

Topics: Adenocarcinoma; Aged; Body Weight; Female; Gastrectomy; Ghrelin; Humans; Male; Middle Aged; Organ Sparing Treatments; Peptide YY; Stomach Neoplasms; Vagotomy; Vagus Nerve; Weight Loss

Peptide hormone receptors overexpressed in human malignant neoplasms are potential targets for diagnostic scintigraphy and radiotherapy. One such receptor is the neuropeptide Y (NPY) receptor, mediating primarily feeding behavior in the brain but shown recently to play a role in breast cancer. In this study, the presence of NPY receptors was evaluated in another group of gynecological tumors, namely ovarian tumors, using in vitro receptor autoradiography with (125)I-labeled peptide YY and receptor subtype selective analogs. Remarkably, all 10 investigated inhibin-expressing granulosa cell tumors, Leydig cell tumors, and Sertoli-Leydig cell tumors expressed NPY receptors. In contrast, receptors were found in only seven of 22 ovarian adenocarcinomas (32%). Pharmacological characterization of the expressed NPY receptor subtypes in the various tumors revealed the presence of Y1, Y2, or both. In addition, Y1 receptors were observed in intra- and peritumoral blood vessels as well. NPY receptors were not expressed in three ovarian adenomas, three borderline tumors, four fibromas and fibrothecomas, and one dysgerminoma. This is the first time that NPY receptors are described in human ovarian tissue. They may play a role in the pathogenesis and also in the pathophysiology of ovarian malignancies. Moreover, the high incidence and density of NPY receptors in sex cord-stromal tumors suggest that these receptors represent a new potential target for the diagnostic and therapeutic administration of NPY analogs in these tumors.

Topics: Adenocarcinoma; Adenoma; Autoradiography; Biomarkers, Tumor; Cell Line, Tumor; Female; Fluorescent Antibody Technique, Indirect; Humans; Iodine Radioisotopes; Neoplasms, Gonadal Tissue; Ovarian Neoplasms; Ovary; Peptide YY; Receptors, Neuropeptide Y

Peptide YY (PYY) is an endogenous gut hormone that inhibits the growth of certain cancers. Adenocarcinoma of the esophagus usually arises from Barrett's esophagus. We hypothesized that treatment of Barrett's adenocarcinoma with PYY would result in decreased proliferation.. Barrett's cancer cell lines (BIC and SEG-1) were treated with PYY (3-36) at 500 pmol/mL. Viability was measured by MTT at 24 and 72 hours. Apoptosis and necrosis was evaluated by flow cytometry.. PYY reduced proliferation in SEG-1 cells at 24 hours (21.2% +/- 3.4%, P <0.001) and 72 hours (14.2% +/- 6.2%, P <0.001). In the BIC cells, growth was inhibited by 7.9% +/- 7.0%, P = 0.021 after 72 hours. PYY increased late apoptotic activity in SEG-1 cells by 31%, P = 0.014.. This is the first report of antiproliferative effects of PYY against Barrett's carcinoma in vitro. Reductions in cell growth appear to be mediated by proapoptotic mechanisms. Further investigation of PYY in the treatment of Barrett's adenocarcinoma is warranted.

Topics: Adenocarcinoma; Analysis of Variance; Apoptosis; Barrett Esophagus; Cell Proliferation; Esophageal Neoplasms; Humans; In Vitro Techniques; Peptide YY; Probability; Risk Factors; Sensitivity and Specificity; Tumor Cells, Cultured

Colonic carcinoma was induced in male Sprague-Dawley rats by injecting them with 1,2-dimethylhydrazine dihydrochloride. Control rats were injected with EDTA solution. Tissue specimens of colon from four groups of animals: (i) rats without tumour, (ii) with dysplasia and lymphoid hyperplasia, (iii) with colonic adenocarcinoma, and (iv) controls, were investigated. The colonic endocrine cells were detected by immunocytochemistry and quantified by computerised image analysis. Peptide YY (PYY)- and serotonin-immunoreactive cells were found in the colon of all the groups investigated. There were few somatostatin- or enteroglucagon-immunoreactive cells and no pancreatic polypeptide (PP)-immunoreactive cells in the colon of any of the groups studied. The density of PYY-immunoreactive cells increased significantly in rats with dysplasia and lymphoid hyperplasia and in rats with colon carcinoma. There was no statistically significant difference as regards cell secretory index (CSI) or nuclear area of PYY-immunoreactive cells in any of treated groups examined. Nor was there any statistically significant difference between all treated animal groups and controls, as regards cell density, CSI, or nuclear area of serotonin-immunoreactive cells. The present observations in an animal model of human colon carcinoma support the assumption that neuroendocrine peptides in the gut are involved in the carcinogenesis of colorectal carcinoma. However, The nature of the changes in the colonic endocrine cells observed here differed from those in patients with colon carcinoma, possibly due to a difference between the response of young rats to an induced colon carcinoma and a spontaneously developed carcinoma in elderly humans, or due to a species difference.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Carcinogens; Colon; Colonic Neoplasms; Enteroendocrine Cells; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Peptide YY; Rats; Rats, Sprague-Dawley

It has been shown in several studies that a colonic J-pouch obviates much of the early dysfunction after a low anterior resection in terms of urgent and frequent bowel movements. In search for specific mediators of the postoperative functional adaptation, two gut peptides, peptide YY and enteroglucagon, were studied. Plasma and "neorectal" mucosal levels of both peptides were measured in 12 patients with a straight coloanal anastomosis and in 11 patients with a colonic J-pouch anastomosis. Patients were part of a randomized trial comparing straight and colonic pouch anastomosis. Fasting plasma samples of both peptides were collected intraoperatively, after one week, before loop ileostomy closure, and at 1, 3, and 12 months after loop ileostomy closure.. There was no difference between the straight and the pouch groups in plasma concentrations of either peptide at any time period postoperatively. The only longitudinal hormonal changes were transient increases in mucosal peptide YY content at one-month follow-up and in mucosal enteroglucagon content before loop ileostomy closure.. Peptide YY and enteroglucagon responses in these patients appear not to be major factors for improved outcome after formation of a colonic pouch in low anterior resection.

Topics: Adaptation, Physiological; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Ileostomy; Intestinal Mucosa; Male; Middle Aged; Peptide YY; Peptides; Proctocolectomy, Restorative; Rectal Neoplasms

1. Confluent epithelial layers of a human adenocarcinoma cell line called Colony-6 have been shown to respond to nanomolar concentrations of vasoactive intestinal polypeptide (VIP), peptide YY (PYY), neuropeptide Y (NPY) and somatostatin (Som). 2. The VIP-induced increase in basal short-circuit current (SCC) was attenuated by basolateral application of Som, PYY or NPY, and also by the Y1-receptor agonist [Leu31,Pro34]NPY, as well as pancreatic polypeptide (PP). High concentrations (0.1-3.0 microM) of NPY(2-36) were effective but the C-terminal fragment NPY(13-36) (0.1-1.0 microM) and desamidoNPY (0.6 microM) were not active. A rank order of agonist EC50 values was: PYY > NPY > [Leu31,Pro34]NPY > PP > NPY(2-36) >> NPY (13-36). 3. Receptors for all these peptides were preferentially located within the basolateral domain. Apical addition of PP (1 microM) and Som (100 nM) had no effect upon basal SCC while apical VIP (10 nM) responses were 18%, and apical PYY (100 nM) were 27% the size of respective basolateral controls (100%). 4. Cross-desensitization was observed between [Leu31,Pro34]NPY (1 microM) and both PYY (100 nM) and PP (1 microM) and between PYY and NPY(2-36) (1 microM), but was not significant between PYY (100 nM) and PP (1 microM). We suggest that either these cells express a single new Y-receptor with an unusual phenotype or that two Y-receptor populations exist in Colony-6 cells.

Topics: Adenocarcinoma; Colon; Colonic Neoplasms; Epithelium; Humans; Neuropeptide Y; Pancreatic Polypeptide; Peptide YY; Peptides; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide Y; Secretory Rate; Sensitivity and Specificity; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

Neuropeptides exert inhibitory effects on pancreatic secretion, but their role in the regulation of growth is unknown. This study was executed to evaluate the effects of PYY and NPY on cell growth and 3H-thymidine incorporation in human (MiaPaCa-2, Capan-2) and hamster (H2T) exocrine pancreatic carcinoma cells in vitro. A significant increase in the number of cells after 96 h of treatment with NPY was observed at 0.01 microM in H2T, 0.1 microM in MiaPCa-2 and at 1 microM in Capan-2 cells. PYY was less potent and did not increase significantly cell growth in MiaPaCa-2, but did at 0.1 microM in Capan-2 and at 1 microM concentration in H2T. Stimulation for 48h with NPY increased 3H-thymidine incorporation significantly at 0.01 microM in all cell lines. With PYY, stimulation of 3H-thymidine incorporation occurred in H2T cells at 0.01 microM. 3H-thymidine incorporation after PYY treatment was significantly increased at 0.1 microM in MiaPaCa-2 and at 1 microM in Capan-2 cells. Receptor studies showed low but definite specific binding of both NPY and PYY in all cell lines. The results suggest that NPY and PYY may have a role in the regulation of growth of exocrine pancreatic carcinoma cells.

Topics: Adenocarcinoma; Cell Division; DNA Replication; DNA, Neoplasm; Humans; Neuropeptide Y; Pancreatic Neoplasms; Peptide YY; Peptides; Stimulation, Chemical; Tumor Cells, Cultured

Peptide YY has been localized within human ileocolonic endocrine cells and may contribute to the regulation of gastric secretion and gastric emptying in man. Since our previous studies had shown decreased colonic concentrations of peptide YY in the idiopathic inflammatory bowel diseases, a specific radioimmunoassay was used to measure fasting serum concentrations of peptide YY in healthy controls and in patients with adenocarcinoma of the rectum, idiopathic chronic active liver disease and hepatic cirrhosis, ulcerative colitis, and Crohn's disease. In healthy controls and in patients with adenocarcinoma of the rectum, serum concentrations of peptide YY ranged from 50 to 260 pg/ml. Serum concentrations of peptide YY in patients with hepatic cirrhosis ranged from 59 to 717 pg/ml. Serum concentrations of peptide YY in patients with ulcerative colitis were similar to healthy controls. In patients with Crohn's disease, serum concentrations of peptide YY were less than 50 pg/ml in three patients who had had a previous proctocolectomy, and were more than 260 pg/ml in 14 patients who had had previous resection of more than 48 cm of ileum or presently had symptomatic Crohn's disease subsequently requiring surgical resection of a total of more than 75 cm of ileum. These results suggest that most circulating peptide YY is released from the colorectal region. Hepatic cirrhosis, previous ileal resection, and symptomatic Crohn's disease were associated with elevation of fasting serum peptide YY. The mechanism of increased fasting serum peptide YY in patients with Crohn's disease could be the loss of an ileal inhibitory factor or possibly an increased release of colonic peptide YY in response to fat malabsorption. The effect of alteration of serum peptide YY concentrations on the pathophysiology of Crohn's disease is yet unknown.

Topics: Adenocarcinoma; Adult; Aged; Chromatography, High Pressure Liquid; Colitis, Ulcerative; Crohn Disease; Fasting; Female; Gastrointestinal Hormones; Humans; Ileum; Male; Middle Aged; Peptide YY; Peptides; Radioimmunoassay; Rectal Neoplasms

Peptide YY (PYY)-like immunoreactivity was detected in the mucosa and muscle layer of normal human colon and rectum and in well to moderately differentiated adenocarcinoma derived from the mucosa of the colon and rectum, using a sensitive and specific radioimmunoassay for PYY. The content of PYY-like immunoreactivity in the mucosa was markedly higher than those in the muscle layer and adenocarcinomatous tissue of any part of the colon and rectum. A high concentrations of PYY-like immunoreactivity was demonstrated throughout the colon mucosa (ascending colon 94.14 +/- 15.34 pmol/g, transverse colon 137.19 +/- 13.44 pmol/g, descending colon 168.89 +/- 15.63 pmol/g, and sigmoid colon 223.69 +/- 35.31 pmol/g), the highest being observed in the rectum (313.15 +/- 45.90 pmol/g). The major molecular form of PYY-like immunoreactivity both in the mucosa and muscle layer of normal human colon and rectum and in adenocarcinomatous tissue was judged by gel exclusion chromatography to be identical to pure porcine PYY. This study revealed the presence of PYY-like immunoreactivity not only in normal tissue of the colon and rectum but also in adenocarcinomas with the same elution pattern, and the mucosal concentrations of PYY-like immunoreactivity were found to be increasing distally throughout the colon and rectum.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibody Specificity; Chromatography, Gel; Colon; Colonic Neoplasms; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Muscle, Smooth; Peptide YY; Peptides; Radioimmunoassay; Rectum; Reference Values; Tissue Distribution; Tissue Extracts