gastrins and Rectal-Neoplasms

Increased basal serum gastrin level has been described in patients presenting with colorectal cancer. The aim of this work was to study the evolution of serum gastrin levels after cancer treatment. We measured basal serum gastrin levels before and 1 to 2 months after treatment in 15 patients (7 men, 8 women; mean age: 61.6 years). There were 3 malignant polyps, 4 Dukes A, 3 Dukes B, 4 Dukes C and 1 Dukes D colonic cancers. Treatment included 3 endoscopic polypectomies, 2 laser photodestructions, and 10 surgical resections, Mean basal gastrin level after treatment (49.07 +/- 12.65 mIU/l) was significantly lower (P less than 0.002) than before treatment (104.47 +/- 26.98 mIU/l). In the 2 patients treated by laser therapy, recurrences were associated with reincreasing serum gastrin levels. These results suggest an "autocrine" secretion of gastrin.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Colonic Neoplasms; Endoscopy, Gastrointestinal; Female; Gastrins; Humans; Laser Therapy; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Preoperative Care; Rectal Neoplasms; Time Factors

Topics: Appendiceal Neoplasms; Carcinoid Tumor; Carcinoma, Small Cell; Cholecystokinin; Digestive System; Duodenum; Endocrine Glands; Fetus; Gastric Mucosa; Gastrins; Humans; Ileum; Peptides; Rectal Neoplasms; Respiratory System; Secretin; Substance P; Vasoactive Intestinal Peptide

Topics: Air; Anemia, Pernicious; Angiography; Barium; Biopsy; Cholangiography; Colonic Diseases; Contrast Media; Cytodiagnosis; Duodenal Diseases; Endoscopy; Enema; Esophageal Diseases; Gastrins; Gastroenterology; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Gastroscopy; Glucose; Glucuronidase; Gold Isotopes; Insulin; Liver Diseases; Methionine; Pancreatic Diseases; Peptic Ulcer; Peptides; Rectal Neoplasms; Rose Bengal; Selenium; Silicones; Stomach Neoplasms; Vagotomy

Twelve patients with rectal carcinoma were treated for 2 weeks with the somatostatin analogue SMS 201.995. Effects of this therapy were assessed using serum marker concentration, Ki67 and gastrin-immunoreactivity of the primary tumour. In four out of 12 patients, a significant decrease in Ki67 immunoreactivity was seen during SMS 201.995 treatment while in the remaining eight patients there was no significant change in Ki67 expression. Four patients had elevated pretreatment serum carcinoembryonic antigen (CEA) levels. In two of these four patients, serum CEA levels fell modestly during SMS 201.995 therapy. This is the first clinical evidence that a somatostatin analogue can inhibit the growth of some colorectal cancers.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Agents; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Division; Gastrins; Humans; Infusions, Parenteral; Ki-67 Antigen; Kinetics; Nuclear Proteins; Octreotide; Rectal Neoplasms

Although several neuroendocrine cell types constitute gastroenteropancreatic neuroendocrine tumors (NETs), the clinical and prognostic implications of the expression of multiple peptide hormones have not been comprehensively evaluated in rectal NETs.. To identify the clinicopathologic characteristics and prognostic impact of peptide hormone expression.. We evaluated the expression of peptide YY (PYY), glucagon, somatostatin, serotonin, insulin, and gastrin using immunolabeling in 446 endoscopically or surgically resected rectal NETs.. PYY, glucagon, serotonin, somatostatin, insulin, and gastrin were expressed in 261 of 389 (67.1%), 205 of 446 (46.0%), 36 of 446 (8.1%), 33 of 446 (7.4%), 2 of 446 (0.4%), and 1 of 446 cases (0.2%), respectively. Immunoreactivity to any peptide hormone was present in 345 of 446 cases (77.4%). Tumors expressing serotonin or somatostatin were associated with lymphovascular invasion, chromogranin A expression, and shorter disease-free survival (DFS). Rectal NETs were classified as L-cell, enterochromaffin-cell, D-cell, null-expression, or mixed-expression type based on peptide hormonal expression status. Patients with D-cell NET had the shortest DFS (10-year DFS, 54.5%), followed by those with enterochromaffin-cell NET (89.5%), null expression (97.0%), L-cell NET (99.6%), and mixed-expression NET (100%; P < .001). Multivariable analyses revealed that somatostatin expression was an independent indicator of poor prognosis with respect to DFS in rectal NETs (P = .001).. Somatostatin expression is a poor prognostic indicator in patients with rectal NETs. Therefore, additional peptide hormonal immunolabeling, including somatostatin, serotonin, and PYY, in rectal NETs can provide more information regarding DFS.

Topics: Gastrins; Glucagon; Humans; Insulin; Neuroendocrine Tumors; Rectal Neoplasms; Serotonin; Somatostatin

We have previously demonstrated that gastric and intestinal endocrine cell (End-cell) marker expression is important for assessment of the histogenesis of endocrine cell tumors. However, the End-cell phenotypes of carcinoid tumors in the rectum remain largely unclear. We therefore examined marker expression of rectal carcinoid tumors. We evaluated 20 rectal carcinoid tumors (as well as 8 from the stomach for comparison) phenotypically, using gastrin, gastric inhibitory polypeptide (GIP) and glucagons-like peptide-1 (GLP-1) as End-cell markers. Rectal carcinoid tumors were divided into 3 endocrine-gastric (e-G), 16 endocrine-gastric-and-intestinal mixed (e-GI), 1 endocrine-intestinal (e-I), and 0 endocrine-null (e-N) types, thus 19 (e-G+ e-GI types, 95%) had gastric phenotypic expression, while 17 (e-GI+ e-I types, 85%) harbored intestinal elements. Stomach carcinoid tumors were classified as 6 e-G and 2 e-N types, respectively. In conclusion, most rectal carcinoid tumors exhibited the e-GI type, suggesting the importance of gastric End-cell marker expression for histogenesis of the rectal carcinoid tumors. Further studies of pathological and biological analyses are needed to clarify the histogenesis of the carcinoid tumors.

Topics: Animals; Biomarkers, Tumor; Carcinoid Tumor; Endocrine Cells; Female; Gastric Inhibitory Polypeptide; Gastrins; Glucagon-Like Peptide 1; Humans; Immunohistochemistry; Male; Middle Aged; Phenotype; Rectal Neoplasms

To explore the correlation between the mRNAs and protein expression of gastrin (GAS), somatostatin (SS) and apoptosis index (AI), apoptosis regulation gene Fas/FasL and caspases in large intestinal carcinoma (LIC).. Expression of GAS and SS mRNAs were detected by nested RT-PCR in 79 cases of LIC. Cell apoptosis was detected by molecular biology in situ apoptosis detecting methods (TUNEL). Immunohistochemical staining for GAS, SS, Fas/FasL, caspase-3 and caspase-8 was performed according to the standard streptavidin-biotin-peroxidase (S-P) method.. There was a significant positive correlation between mRNA and protein expression of GAS and SS (GASrs = 0.99, P < 0.01; SSrs = 0.98, P < 0.01). There was significant difference in positive expression rates of GAS, SS mRNAs and protein among different histological differentiation, histological types and Dukes' stage of LIC. The AI in GAS high and moderate expression groups was significantly lower than that in low expression groups (3.75 +/- 2.38 vs 7.82 +/- 2.38, P < 0.01; 5.51 +/- 2.66 vs 7.82 +/- 2.38, P < 0.01), and the AI in SS high and moderate expression groups was significantly higher than that in low expression groups (9.03 +/- 1.76 vs 5.35 +/- 3.00, P < 0.01; 7.44 +/- 2.67 vs 5.35 +/- 3.00, P < 0.01). There was a significant negative correlation between the integral ratio of GAS to SS and the AI (r(s) = -0.41, P < 0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than that in low expression group (90.9% and 81.0% vs 53.2%, P < 0.05). The positive expression rates of Fas, caspase-8 and caspase-3 in SS high (90.0%, 90.0% and 100%) and moderate (80.0%, 70.0%, 75.0%) expression groups were higher than that in low expression group (53.1%, 42.9%, 49.0%) (90.0% and 80.0% vs 53.1%, P < 0.05; 90.0% and 70.0% vs 42.9%, P < 0.05; 100.0% and 75.0% vs 49.0%, P < 0.05). There was a significant positive correlation between the integral ratio of GAS to SS and the semiquantitative integral of FasL (rs = 0.32, P < 0.01).. GAS and SS play important roles in the regulation and control of cell apoptosis in LIC, and the mechanism may be directly related to the aberrant expression of Fas/FasL. The GAS and SS will be valuable targets of the biological behavior of LIC.

Topics: Adenocarcinoma; Adult; Aged; Apoptosis; Caspase 3; Caspase 8; Caspases; Colorectal Neoplasms; Fas Ligand Protein; fas Receptor; Female; Gastrins; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Rectal Neoplasms; Retrospective Studies; RNA, Messenger; Somatostatin

Human colorectal neuroendocrine cell carcinoma ( NECC ) is uncommon. Treatment of the disease has not yet been established, and NECC of the colon and rectum behave clinically more aggressively than their exocrine counterparts, so the prognosis is generally worse. One reason for the lack of established treatment is that there are no model systems of this disease. There have been a few reports on cell lines from neuroendocrine tumors, because these tumors are difficult to culture, and there are even fewer reports on colorectal carcinoma cell lines with neuroendocrine features. We therefore attempted to establish a permanent cell line in order to investigate the biological behavior and treatment of NECC. The cell line we succeeded in culturing is called N-TAK1. Gastrin promotes the growth of gastrointestinal epithelial cells and also stimulates the growth of gastrointestinal cancers. Hormone-receptor antagonists restrict the growth of hormone-dependent tumors. The growth of colon cancer was promoted by the application of gastrin, whereas it was restricted by proglumide, which is known to be a gastrin receptor antagonist. We demonstrated that gastrin has a stimulatory effect on the growth of N-TAK1 cells and that it could be detected by immunohistochemistry in the cells. We also showed that proglumide inhibited the growth effect of gastrin.

Topics: Animals; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Neuroendocrine; Cell Division; Chromosomes; Female; Gastrins; Humans; Immunoenzyme Techniques; Karyotyping; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Phosphopyruvate Hydratase; Proglumide; Rectal Neoplasms; Tumor Cells, Cultured

Gastrin is a putative promoter of colorectal carcinomas. The aim of this study was to evaluate the temporal relationship between gastrinemia and development of colorectal malignancy.. We conducted a nested case-control study among 128,992 subscribers to a health maintenance program who had participated in a multiphasic health checkup between 1964 and 1969. Serum had been frozen since the checkup and the cohort followed up for cancer. Of 1881 incident colorectal carcinoma cases, 250 were randomly selected; 1 control without cancer was matched to each case by age, sex, education, and date of serum collection. Stored sera were tested for Helicobacter pylori immunoglobulin G and for gastrin and glycine-extended gastrin.. Verified cases included 166 colon cancers, 58 rectal cancers, and 9 with cancer in both locations. A mean of 15.3 years had elapsed between serum collection and diagnosis of cancer. Median gastrin levels were similar in cases and controls (41.7 vs. 40.7 pg/mL). However, a gastrin level above normal was associated with increased risk for colorectal malignancy (odds ratio, 3.9; 95% confidence interval, 1.5-9.8). If this association is causal, 8.6% of colorectal cancers could be attributed to high serum gastrin level.. Hypergastrinemia is associated with an increased risk of colorectal carcinoma.

Topics: Case-Control Studies; Cohort Studies; Colonic Neoplasms; Colorectal Neoplasms; Female; Gastrins; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prospective Studies; Rectal Neoplasms; Risk Factors

Numerous clinical and experimental studies suggest that gastrin plays an important part in the development of colorectal cancer in humans. This study was done to assess the influence of omeprazole induced hypergastrinaemia on the development of colorectal tumours in an experimental animal model. Forty female Sprague-Dawley rats received either omeprazole (40 mumol/kg) or vehicle (0.25% methylcellulose) by once daily oral gavage throughout the experiment. All animals received 12 consecutive weekly subcutaneous injections of azoxymethane (10 mg/kg/week) beginning at week 6. Serum gastrin concentrations were measured during weeks 1 and 5 and at death (week 27). Chronic omeprazole treatment resulted in appreciable hypergastrinaemia during the study, mean gastrin concentrations in omeprazole treated rats being raised by up to nine to 10 fold, compared with vehicle treated control rats (p < 0.001). Despite this, tumour incidence in the omeprazole group was significantly lower at 63%, compared with 95% in the vehicle only group (p < 0.02). The median number of tumours in the omeprazole group (1) compared with the vehicle group (3) was also significantly lower (p = 0.02). Average tumour size, site distribution, and the comparative frequencies of adenomas and adenocarcinomas were similar in the two groups. This study shows that omeprazole protects against colorectal carcinogenesis in this model despite causing appreciable hypergastrinaemia. The mechanism by which this occurs is unclear and merits further investigation. Because of the compounding protective effects of omeprazole, this model is not a suitable one for studying the longterm trophic effects of gastrin on the colon.

Topics: Animals; Azoxymethane; Body Weight; Colonic Neoplasms; Eating; Female; Gastrins; Omeprazole; Rats; Rats, Sprague-Dawley; Rectal Neoplasms

To evaluate the hypothesis that gastrin is a local growth factor in colonic carcinomas, the expression of gastrin messenger RNA (mRNA) and peptides were examined in five human colon carcinoma cell lines, 12 solid colon carcinomas, and normal colonic tissue.. Northern analysis, reverse-transcription PCR, and a library of sequence-specific radioimmunoassays were the principal methods.. Cell lines, tumors, and normal tissue all expressed a gastrin mRNA of 0.7 kilobases, and all cell lines contained incompletely processed progastrin (range, 17-54 fmol/10(6) cells). Two cell lines secreted progastrin into the media (LoVo, 25 +/- 3 pmol/L; HCT116; 12 +/- 2 pmol/L). Normal colonic tissue and all the solid tumors also contained progastrin, the concentration being higher in tumors (range, 0.4-2 pmol/g) than in normal tissue (range, 0.1-0.2 pmol/g). Only one tumor contained carboxyamidated gastrins.. Normal and neoplastic colonic mucosa both express the gastrin gene, but the posttranslational phase of expression is attenuated. The incomplete processing and low level of expression suggest that autocrine gastrin secretion has only minor significance for normal adult and most neoplastic colonic tissue.

Topics: Actins; Adenocarcinoma; Blotting, Northern; Colon; Colonic Neoplasms; Colorectal Neoplasms; Exons; Gastric Mucosa; Gastrins; Humans; Oligodeoxyribonucleotides; Polymerase Chain Reaction; Protein Precursors; Rectal Neoplasms; RNA Probes; RNA, Messenger; Tumor Cells, Cultured

Gastrin has been postulated to stimulate proliferation in colorectal neoplasms. Although gastrin mRNA has been demonstrated to be present in colon cancer cell lines, the intact peptide had not been recovered from human colorectal neoplasms. We demonstrate that gastrin and its precursors are present in both colorectal neoplasia and adjacent normal-appearing colonic mucosa. In colonic tissue, the glycine-extended precursor form of the peptide is over 10-fold more abundant than the amidated gastrin, and progastrin is more than 700-fold more abundant. In contrast, amidated gastrin in the human antrum is the predominant form of gastrin by a factor of 10. Furthermore, the ratio of gastrin precursors to gastrin is significantly increased in neoplastic colonic mucosa when compared with normal colonic tissue. These data suggest that the processing of gastrin is unique in the human colon and that further differences in processing occur in neoplastic colonic tissue.

Topics: Amino Acid Sequence; Colon; Colonic Neoplasms; Gastrins; Humans; Intestinal Mucosa; Molecular Sequence Data; Protein Precursors; Protein Processing, Post-Translational; Rectal Neoplasms; Tumor Cells, Cultured

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Colonic Neoplasms; Female; Gastrins; Humans; Male; Middle Aged; Postoperative Care; Preoperative Care; Prospective Studies; Rectal Neoplasms; Reference Values; Time Factors

Gastrin stimulates the growth of some human colon adenocarcinomas grown in vitro or as xenografts in nude mice. To evaluate the possibility of elevated plasma gastrin levels in patients with adenomatous polyps or colorectal cancer, we carried out a radioimmunoassay in subjects fasting overnight and undergoing colonoscopy. The study included 190 patients who were divided into three groups: controls (n = 65), those with benign adenomas (n = 63), and those with adenocarcinomas (n = 62). The mean values of plasma gastrin in the cancer group (112.71 +/- 16.65 pg/ml) were significantly higher than those of the control group (40.41 +/- 1.88 pg/ml) as well as those of the polyp group. Mean plasma gastrin values in the polyp group (54.27 +/- 5.29 pg/ml) were also significantly higher than those of the control group. In the cancer group, 32 of 62 patients (51.6%) had gastrin levels greater than the control mean +2 SD, as opposed to only 10 of 63 (15.9%) in the polyp group. The number, size, histologic type, and presence of dysplasia in the polyp group and the location or Dukes' stage in the cancer group had no significant influence on gastrin levels in this study. Preliminary results in cancer patients with elevated preoperative gastrin levels show a postoperative reduction in six of seven patients. The exact cause and role of hypergastrinemia in tumor growth in such patients remains to be determined. Measurements taken both before and after colectomy coupled with a systematic search for specific gastrin receptors would be useful.

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Colonic Polyps; Female; Gastrins; Humans; Male; Middle Aged; Radioimmunoassay; Rectal Neoplasms

Our objective was to determine whether chronic hypergastrinemia enhances chemical induction of rat colorectal cancers. Forty-five rats were randomized to sham operation or antral exclusion. Following a 2-week postoperative recovery period all rats were treated with 1,2-dimethylhydrazine (10 mg/kg) intraperitoneally for 20 weekly doses. Seven weeks later, the rats were killed. Blood was assayed for gastrin by radioimmunoassay. Tumor number, location, size, weight and histology were determined. The 23 rats receiving antral exclusion were hypergastrinemic compared with the 22 sham operated rats. All hypergastrinemic rats developed tumors while only 72.7% of normogastrinemic rats developed tumors. Hypergastrinemia increased the number of tumors/rat, total tumor weight/rat and total tumor volume/rat.

Topics: Animals; Colonic Neoplasms; Dimethylhydrazines; DNA, Neoplasm; Gastrins; Male; Neoplasm Proteins; Radioimmunoassay; Rats; Rats, Inbred Strains; Rectal Neoplasms; RNA, Neoplasm; Time Factors

A clinicopathological and immunohistochemical study was carried out on 32 cases of neuroendocrine tumors of the rectum. Typical carcinoids consisted of 27 cases, histologically showing uniform round to columnar cells forming solid alveolar nests and ribbon-like or trabecular arrangement. Neuroendocrine carcinomas consisted of 5 cases in which tumor cells with prominent nuclear atypism were arranged in a ribbon-like or trabecular fashion and formed gland-like structures. There were also small round tumor cells resembling lymphocytes. The prognosis of neuroendocrine carcinomas is very poor with marked tumor invasion of lymphatics and veins resulting in liver metastases and death within one year after operation. Thirty cases out of the 32 showed a positive argyrophil reaction, while immunohistochemistry of 29 cases revealed more than one peptide hormone in 23 cases. The most common hormone was somatostatin being present in 18 of the 23 tumors and glucagon in 16 of the 23 tumors. Gastrin/CCK and calcitonin were proven in 6 of the 23 tumors and in 4 of the 23 tumors, respectively. On the other hand, more than two hormones was present in 15 of the 23 tumors examined. Histologically, neuroendocrine tumors have a very wide spectrum. Histogenetically, typical carcinoids and neuroendocrine carcinomas are considered to be of the same origin with the former showing morphological and functional differentiation to endocrine cells and the latter being more undifferentiated.

Topics: Adult; Aged; Calcitonin; Carcinoid Tumor; Cholecystokinin; Female; Gastrins; Glucagon; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Rectal Neoplasms; Somatostatin

This study was designed to determine the effect of gastrin on colorectal neoplasms in the rat. Multiple colon and rectal cancers were induced in each of 57 rats with methylazoxymethanol. Animals were randomly assigned to groups: (1) antral exclusion, (2) antrectomy, (3) sham, or (4) sham with subsequent pentagastrin injections. Resulting tumors were analyzed for concentration and synthesis of DNA, RNA, and protein. The number of tumors per rat and distribution of tumors within the colons did not vary among groups. Antrectomy did not alter the gastrin level, and tumors developing in these animals did not differ from those of sham controls. Antral exclusion markedly raised serum gastrin levels. Both chronic endogenous hypergastrinemia and administration of exogenous pentagastrin significantly increased tumor synthesis and concentration of DNA, RNA, and protein. We conclude that gastrin exerts a trophic effect on colorectal neoplasms in rats. This biological phenomenon suggests a tumor regulatory role for the hormone.

Topics: Animals; Colonic Neoplasms; DNA; Gastrectomy; Gastrins; Male; Neoplasms, Experimental; Pentagastrin; Proteins; Rats; Rectal Neoplasms; RNA