Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies demonstrate that some colon cancers possess receptors for various gastrointestinal hormones or neurotransmitters, the occupation of which can affect growth. These results are limited because frequently only a small number of tumors are studied, only 1 or 2 receptors are sought, and the effect on cell function is not investigated. In the present study, 10 recently characterized human colon cancer cell lines were studied to determine whether they possess receptors for any of 12 different gastrointestinal hormones or neurotransmitters and to determine whether these receptors mediate changes in cellular function. Each of the cell lines exhibited receptors for at least one radioligand. Receptors for vasoactive intestinal peptide (VIP) and muscarinic cholinergic agents occurred on 60%, bombesin and gastrin on 30%, beta-adrenergic agents and gastrin-releasing peptide (GRP) on 20%, and somatostatin, opiates, neuromedin B, and substance P on 10%. Analysis of [3H]N-methylscopolamine binding revealed a Kd of 0.2 nM for N-methylscopolamine with a binding capacity of 2500 sites/cell. With the agonist carbamylcholine, the receptor exhibited 2 classes of binding sites: one of high affinity (Kd 55 microM) representing 75% of the binding sites and one of low affinity (Kd 0.3 mM) representing 25% of the binding sites. Analysis of 125I-[Tyr4]bombesin binding revealed a receptor of high affinity (Kd 2.1 microM) with a binding capacity of 3300 sites/cell. Inhibition of binding by agonists revealed relative potencies of 125I-[Tyr4]bombesin greater than GRP much greater than neuromedin B, and two recently described antagonists were similar in potency to GRP. Analysis of 125I-VIP binding revealed a receptor having 2 classes of binding sites: one of high affinity (Kd 3.6 nM) and one of low affinity (Kd 1.7 microM) which represented the majority of the 5.5 x 10(6) binding sites/cell. The relative potencies of agonists were VIP greater than helodermin greater than peptide histidine methionine greater than secretin. Evaluation of biological activity mediated by the muscarinic cholinergic and bombesin receptors revealed an increase of intracellular calcium and of inositol triphosphate by specific receptor agonists. The presence or absence of receptors detected by binding correlated closely with the ability of selective receptor agonists to alter cell function. These results demonstrate the presence of several different receptors for gastrointestinal hormones or neurotransmitters, some described for the first time, on human colon cancer cell lines, including bombesin-related peptides, VIP, somatostatin, substance P, beta-adrenergic agents, calcitonin gene-related peptide, gastrin, muscarinic cholinergic agents, and opiates.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Characterization of functional receptors for gastrointestinal hormones on human colon cancer cells. 131 Jun 40

Several somatostatin analogs with recently synthesized acetylated N terminus were assayed in vivo for their effects on sodium pentobarbital-stimulated growth hormone (GH) levels in fed male rats and gastrin-releasing peptide (14-27)-stimulated gastrin levels in fasted male rats. The binding characteristics of these analogs to somatostatin receptors were also examined in various human tumors and normal tissues. The analog RC-101-I, injected at a dose of 0.1 micrograms/100 g body wt, significantly suppressed GH release (P less than 0.01) for at least 2 hr. Analog RC-160-II caused the longest inhibition of GH release, greater than that induced by nonacetylated parent analog RC-160, with GH levels showing significant suppression (P less than 0.01) for more than 3 hr. Analogs RC-160-II and RC-101-I and RC-160, injected at a dose of 1.0 micrograms/100 g body wt, significantly (P less than 0.01) suppressed gastrin-releasing peptide (14-27)-stimulated serum gastrin. Analog RC-101-I was active in this test at a dose of 0.1 micrograms/100 g body wt. RC-160-II showed significant binding to somatostatin-14 receptors in all investigated tissues (human colon, human colon cancer, breast cancer, human pancreas and pancreatic cancer, human prostate and prostate cancer, and rat cerebral cortex), but there were marked variations in binding affinities among various normal and cancerous tissues. The highest affinity was found in membranes of colon cancer (Ka = 18.4 nM-1) and breast cancer (Ka = 12.46 nM-1). The binding affinity of RC-160-II to somatostatin receptors in membranes of the breast cancer was similar to that of RC-160. RC-101-I showed higher binding affinity to somatostatin-14 receptors than RC-160 in human breast, pancreatic, and prostate cancer. With the exception of breast cancer tissue, the binding affinity of RC-101-I was significantly lower than that of RC-160-II in membranes of all investigated tissues. It can be concluded that acetylated somatostatin analogs RC-101-I and RC-160-II possess prolonged and enhanced biological activities in suppressing serum GH and gastrin in rats. Significant variations in binding affinities for these analogs in different tissues and various tumors suggest that differences may exist between somatostatin receptors in normal versus malignant tissues. This raises the possibility that some of these analogs could be used more selectively in the treatment of various neoplasms.
 ...
PMID:Biological activity and receptor binding characteristics to various human tumors of acetylated somatostatin analogs. 134 89

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.
 ...
PMID:Post-translational processing of gastrin in neoplastic human colonic tissues. 147 26

Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with a [D-Trp6] agonist of luteinizing hormone releasing hormone (LH-RH), somatostatin analogue (RC-160), and bombesin/gastrin releasing peptide antagonist (RC-3095). Some inhibitory effect of [D-Trp6] LH-RH microcapsules releasing 25 micrograms/day on tumor growth was observed that could be due to sex steroid deprivation, but the inhibition was not statistically significant. Microcapsules of RC-160, releasing 50 micrograms/day, significantly reduced tumor volume after 21 and 24 days of treatment, but at the end of the experiment the inhibition in tumor volume and weight was not significant. Bombesin/gastrin releasing peptide antagonist RC-3095, at a dose of 20 micrograms/day administered by daily s.c. injections or by continuous infusion using Alzet osmotic minipumps, had the greatest inhibitory effect on tumor growth. Tumor volume, percentage change in tumor volume, and tumor weights were significantly decreased in both groups treated with RC-3095. This is the first report on inhibition of human colon cancer growth in vivo by bombesin antagonists.
 ...
PMID:Inhibition of growth of HT-29 human colon cancer xenografts in nude mice by treatment with bombesin/gastrin releasing peptide antagonist (RC-3095). 168 40

The effect of a long-acting somatostatin analogue SMS 201.995 (SMS; Sandoz) on basal and gastrin-stimulated growth of 4 human colon cancer lines was studied in vitro and in vivo. Proliferation assay was done with overnight [75Se]selenomethionine uptake after 5 days of incubation. Gastrin concentrations used were 5e-10 M and 1e-7 M. SMS concentrations were from 2e-12 M to 2e-7 M. Cell lines LIM 1215, LIM 2405, and LIM 2412 were inhibited dose-dependently in both basal and gastrin-stimulated groups. LIM 1863 was slightly stimulated. Based on in vivo growth characteristics, LIM 2412 and LIM 2405 were selected for xenograft study. The dose of 50 micrograms/kg/day was arrived at after a preliminary experiment showed it to be safe and effective. The LIM 2412 xenografts in the SMS-treated animals were 473.3 +/- 99.9 (SD) versus 838.1 +/- 111.3 mm3 in control (P less than 0.05) after 20 days. The LIM 2405 tumors were also significantly inhibited (81.2 +/- 30.0 versus 245.7 +/- 48.3 mm3, P less than 0.01). The effect of SMS appeared to be reversible. Oral SMS at 200 micrograms/kg/day was not absorbed. This study suggests that SMS may have direct antitumor effects in human colon cancer.
 ...
PMID:SMS 201.995 inhibits in vitro and in vivo growth of human colon cancer. 173 55

Gastrin is trophic to colon cancers that possess gastrin receptors. Whether fasting serum gastrin concentrations are high in patients with colon cancer is controversial. We therefore studied the effect of food on serum gastrin concentrations in patients with colon cancer and control subjects. Fasting serum gastrin was greater, though not significantly so, in patients with colon cancer before surgery (mean (SD) 17.4 (3.6) pmol/l, n = 16) compared with control subjects (12.6 (1.9) pmol/l, n = 14). Postprandial increases in serum gastrin were significantly and persistently higher than normal in the cancer patients. These increases were due to a subset of six patients with serum gastrin concentrations greater than the control mean + 2 SD at 20 and 40 minutes (62 pmol/l-146 pmol/l). Four of the six patients had intra-abdominal metastases. The extent of the increase may well correlate with that of the disease. Surgical resection of the tumour resulted in a fall in serum gastrin values and probably reflects the cause of the hypergastrinaemia. Hypergastrinaemia may, therefore, be an important aetiological factor in colon carcinogenesis.
 ...
PMID:Postprandial hypergastrinaemia in patients with colorectal cancer. 175 67

We studied the effects of dietary calcium, fat and fiber on serum gastrin in Fischer-344 rats in a full factorial experiment as part of a larger study of diet and colon cancer risk factors. Nine- to 10-wk-old male rats were fed standard or experimental diets for 4 wk. Wheat bran was the sole source of fiber. Wheat bran levels were 0, 2.5, 10 and 20%; fat levels were 1, 5 and 10%; calcium levels were 0.18, 0.52 and 1.04% of diet weight. On d 29 serum was collected and stored at -80 degrees C until analyzed. There was a significant (P less than 0.0001) dose-dependent increase in serum gastrin from 102 to 173 ng/L, with increasing calcium. No other significant changes in serum gastrin were noted with the dietary changes. A long-term change in the level of serum gastrin, caused by dietary modification, will influence the trophic effect that gastrin has on colonic mucosa as well as on colon carcinomas. We speculate that calcium supplementation, although slowing colonic proliferation, might have an undesirable effect on the growth of early undetected colonic tumors.
 ...
PMID:Serum gastrin increases with increasing dietary calcium but not with increasing dietary fat or fiber in Fischer-344 rats. 185 25

Recent progress in cancer research revealed that gut hormones have the activity to regulate the cellular growth of cancer cells. Gastrin, cholecystokinin and vasoactive intestinal peptide were demonstrated to stimulate the growth of gastric cancer cells, pancreatic cancer cells and colon cancer cells, respectively. Accordingly, it is possible to assume that these gut hormones may play an important role in the progression of these cancers. Further studies will be required to clarify the role of gut hormones as physiological growth factors in gastrointestinal tissues. The other aspect of gut hormones related with cellular growth is their role as autocrine growth factors. Gastrin-releasing peptide (GRP) is classified as a gut hormone with the structural similarity with amphibian bombesin. Several reported findings indicate that GRP functions as an autocrine growth factor for human small cell lung carcinoma; a monoclonal antibody for GRP is now applied for the therapy of this cancer. It is important to find out other gut hormones functioning as autocrine growth factors.
 ...
PMID:[Gut hormones with activity to modulate cellular growth]. 208 20

We have previously demonstrated trophic effects of gastrin on mouse colon cancer (MC-26) cells, in vivo, and demonstrated the presence of gastrin receptors (GR) on these cells. The cellular and intracellular mechanism by which gastrin expresses trophic effects on colon cancer cells is, however, as yet unknown. For us to start investigating the possible mechanisms involved, it was important that we first develop an in vitro model, in which gastrin expresses its trophic effects directly on the MC-26 cells. The growth-promoting effects of gastrin on the MC-26 cells were examined in various in vitro culture models, in terms of [3H]thymidine incorporation and cell number. A significant trophic effect of gastrin could be demonstrated on quiescent cells in culture, in the absence of serum. The optimal cell-culture conditions for observing trophic effects of gastrin were defined and included a 24-h period of rapid growth of MC-26 cells in serum-supplemented normal growth medium, followed by a 24-h period of culture in serum-free medium containing an optimal dose (1.0 mM) of thymidine, to achieve growth-arrest of the cells. Addition of gastrin (0.5 to 25 nM) to the quiescent, growth-arrested cells resulted in significant dose-dependent increases in both the incorporation of [3H]thymidine uptake by the cells, and a significant increase in cell number. The concentration of GR on the growth-arrested quiescent MC-26 cells in culture was significantly increased compared to the GR concentration on the control, asynchronized cells. The increased presence of GR on the growth-arrested, synchronized MC-26 cells may have allowed us to observe a significant trophic effect of gastrin on the MC-26 cells, in vitro itself. To determine if gastrin was functioning as an autocrine growth factor for MC-26 cells, we examined the effect of gastrin antibodies on the growth of MC-26 cells; no significant effect of the antigastrin IgG on the growth of MC-26 cells was observed.
 ...
PMID:Growth-promoting effects of gastrin on mouse colon cancer cells in vitro: absence of autocrine effects. 222 4

The effects of gastrin, proglumide (a gastrin receptor antagonist), and somatostatin on growth of human colon adenocarcinoma cell lines CX1, X56, and HT29 were examined in two experimental models. Nude mice bearing xenografts of colon cancer CX1 or X56 were treated for 14-25 days subcutaneously with saline, pentagastrin (0.5 or 1.0 mg/kg), proglumide (250 or 500 mg/kg), or somatostatin 14 (33, 100, or 300 micrograms/kg) twice daily. Tumor volume, weight, protein, and deoxyribonucleic acid were measured. HT29 cells were grown in vitro and the effects of gastrin 17, proglumide, and somatostatin on growth were evaluated by cell counts or [3H]thymidine incorporation. The larger dose of pentagastrin significantly increased tumor growth in the nude mouse (p less than 0.005) and gastrin induced a biphasic effect on deoxyribonucleic acid synthesis in tissue culture with significant increases of up to 39% (p less than 0.025). Somatostatin alone significantly inhibited tumor growth in two of the cell lines and also inhibited the gastrin-induced growth. Proglumide had no effect by itself but significantly inhibited gastrin-stimulated growth. These findings suggest that growth of some human colon cancers may be hormone-dependent.
 ...
PMID:Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer. 290 11


1 2 3 4 5 6 7 8 9 Next >>