T1976 The Preventive Factors for Aspirin-Induced Peptic Ulcer
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pH values using a High K + /Nigericin calibration technique. Glands were acidified using an NH 4 Cl prepulse followed by a Na + -free solution. Alkalinization in Na + -free solution represents intracellular acid production and eliminates the possibility of contribution by the Na + / H + proteins. Studies were done in the presence or absence of indomethacin (100μM) or acetylsalicylic acid (ASA) (100-500μM). Results: In the presence of indomethacin, a rapid decrease in pH i is seen upon the removal of Na + , followed by an immediate rise in pH i , approaching pH of 7.0. In the absence of indomethacin, no alkalinization was observed until Na + was added back to the solution. In a separate series of experiments, a similar result was observed with ASA. In the presence of ASA, a rapid alkalinization was observed in the Na + -free solution, representing intracellular acid production. This effect was not seen in the absence of drug. Conclusions: This study suggests that indomethacin and ASA have a direct effect on activation of acid secretion in the parietal cell. This is a novel mechanism in which NSAID use may increase risk of PUD. The direct stimulatory effect on acid secretion provides evidence for a rapid onset of PUD via the decreased barrier function coupled with enhanced acid secretion that occurs in the absence of secretagogues. T1976 The Preventive Factors for Aspirin- Induced Peptic Ulcer Akiko Shiotani, Takashi Sakakibara, Yoshiyuki Yamanaka, Hiroshi Imamura, Minoru Fujita, Ken-ichi Tarumi, Noriaki Manabe, Tomoari Kamada, Jiro Hata, Ken Haruma Background: Interleukin-1β (IL-1β) polymorphisms are associated with peptic ulcer and atrophic gastritis. Aim: This study aimed to examine effects of corpus atrophy and the genotypes of genes related with peptic ulcer including IL-1β on risk of aspirin ulcer. Methods: 232 patients taking 100mg of aspirin for cardiovascular diseases, of whom 40 had peptic ulcer were enrolled. IL1β, interleukin-1 receptor antagonist (IL-1RN), tumor necrosis factor (TNF)-α , cyclooxygenase (COX)-1, cytochrome p450 2C9 (CYP2C9), UDP-glucuronosyl- transferase (UGT1A6) genotypes were determined, and serum pepsinogen levels were meas- ured. Results: The polymorphisms of IL-1β-511/-31 only were significantly associated with peptic ulcer, but other genotypes were not. Serum pepsinogen I and II levels and I/II ratio were significantly higher in the ulcer group than in the non-ulcer group. Taking PPI (OR, 0.10; 95% CI, 0.02-0.46), pepsinogen I of less than 50 ng/ml (OR, 0.26; 95% CI, 0.11- 0.64) and IL-1β-511 T carrier (OR, 0.36; 95% CI, 0.16-0.81) were significantly associated with peptic ulcer. Conclusions: Hypoacidity related with corpus atrophy as well as taking PPI seems to be preventively associated with development of peptic ulcer among low dose aspirin users. The detection of groups with a high risk for developing aspirin- induced ulcer by an assessment for the genotype of IL1β polymorphism or serum pepsinogen levels may serve to be a cost-effective prevention strategy. T1977 Rand Appropriateness Study with Development of Recommendations for NSAID Treatment Chris J. Hawkey, Angel Lanas, Carmelo Scarpignato, Herman Stoevelaar Background and rationale: Making appropriate treatment choices with non-steroidal anti- inflammatory drugs (NSAIDs) is increasingly complex. Physicians need to consider gastro- intestinal (GI) and cardiovascular (CV) safety issues of NSAIDs. Non-selective NSAIDs have gastro-toxicity which can be reduced by a proton pump inhibitor (PPI) or substitution of a selective cyclooxgenase (COX)-2 inhibitor. However, all NSAIDs may increase CV risks. It may be challenging to know best practice in particular patient profiles. We performed a RAND appropriateness study to support treatment choice in daily clinical practice. Methods: Using the RAND Appropriateness Method, an international, multi-disciplinary panel of 18 experts (in Rheumatology, Orthopaedics, Primary Care, Geriatrics, Gastroenterology and Cardiology) assessed the appropriateness of 5 NSAIDs (ibuprofen, diclofenac, naproxen, celecoxib and etoricoxib) both in mono-therapy and in combination with proton pump inhibitors. On an individual basis and by using a 9-point scale, the panel rated their appropriateness for different patient profiles (n = 144). These profiles were made up by a combination of several clinical variables, determined important in treatment choice, including age, history of upper gastro-intestinal events, cardiovascular risk, low-dose aspirin use, concomitant use of anti-coagulants, concomitant use of systemic corticosteroids and pattern of use. Based on the median score and the extent of agreement, a panel recommendation was calculated for each treatment option: “inappropriate”, “appropriate”, or “uncertain”. Results: Agreement was reached in 26% of the cases (n=1440), while most ratings were indeterminate (62%). In more than 85% of the cases non-selective NSAIDs without PPI were found inappropriate. Regression analysis showed that of all variables, a history of upper GI events showed the highest impact on the predicted appropriateness scores for all medications, irrespective of CV risk level. In patients with a previous uncomplicated or complicated GI event, neither intermittent nor continuous use of non-selective NSAIDs alone was rated appropriate. Conclusion: It is useful to determine from different perspectives the appropriateness of NSAIDs in relation to several patient-specific clinical conditions. Since approaches were identified that would never be appropriate, recommendations were gener- ated for safer NSAID prescribing for patients with different levels of GI and CV risks. T1978 Impact of Upper Gasrtointestinal Mucosal Damage Associated with Continuous Use of Low-Dose Aspirin in Japan Takashi Kawai, Akira Yamashina, Kenji Yagi, Tetsuya Yamagishi, Fuminori Moriyasu Introduction: Low-dose aspirin is standard treatment for prevention of cardiovascular events in at-risk patients. However, long-term administration of low-dose aspirin is associated with a greater risk of adverse events, including gastrointestinal injury. In Japan there were only few reports according to upper gastrointestinal bleeding, no date of peptic ulcer and erosive esophagitis. In this study we evaluate the risk of esophageal lesions, gastric ulcer and duodenal ulcer in patients receiving continuous low-dose aspirin. Methods: The subjects were 101 patients who received low-dose aspirin more than 3 months. Mean age was A-613 AGA Abstracts 67.5±7.69. The presence of reflex esophagitis, esophageal ulcer, gastric ulcer, and duodenal ulcer was assessed by Esophagogastroduodenoscopy (EGD).We classified reflex esophagitis (R.E.) reference to LA classification: A, B, C, D, and peptic ulcer were measured ulcer size. H. pylori infection was also examined using 13C UBT. GI symptom were assessed by GSRS. Result: R.E.s was recognized in 6.9% (7/101) patients (LA-A: 1, LA-B: 3, LA-C 2, and LA- D: 1). Esophageal ulcer was recognized in 1 patient. Gastric ulcer was recognized 11.9% (12/101) patients and ulcer size was 6.42+/- 3.19mm. Duodenal ulcer was recognized 4% (4/101) patients and ulcer size was 6.25+/- 3.41 mm. H. pylori infection positive:negative ratio was 7:5 in gastric ulcer, 1:4 in duodenal ulcer. GSRS scores (reflex, abdominal pain, indigestion, diarrhea, constipation) were 1.42, 1.33,1.74, 1.28 in R.E., 1.45,1.40, 1.49, 1.37, 1.69 in gastric ulcer, 1.35, 1.35, 2.9, 1.83, 3.1 in duodenal ulcer, 1.36, 1.32, 1.65, 1.40, 1,98 in no R.E. and ulcers. Conclusion: In patients with low-dose aspirin, peptic ulcer was recognized 15.8%, but majority of ulcer was shallow type. Reflex esophagitis was also recognized, 3 cases were severe type (LA-C,D). Most are asymptomatic. Low-dose aspirin cause the damage of gastroduodenal mucosa, but also of esophagus. T1979 Pepsinogen II As Marker of Inflammation in H.P Infection and in NSAIDs Damage Francesco Di Mario, Loredana Guida, Andrea Iori, Lucas G. Cavallaro, Margherita Curlo, Ester Morana, Marino Venerito, Peter Malfertheiner, Carmelo Scarpignato, Massimo Rugge, Angelo Franzè BACKGROUND: H.p infection and NSAIDs are claimed to be independent risk factors for gastritis. Serum pepsinogen II (PGII) significantly increase in presence of H. pylori related gastritis. AIM: to evaluate the effect of differents NSAIDs and H. pylori on PGII levels and gastric histology. METHODS: 81 reumatological patients treated with NSAIDs, of whom 34 pts ( F19, mean age 58, range 27-66) treated with Celecoxib 200 mg (group 1); 28 pts (F 21, mean age 53, range 26-72) treated with ibuprofen 1,200 mg (group 2); 19 pts (11 F, mean age 54, range 29-69) treated with Diclofenac 100 mg (group 3) entered in the study. A blood sample was taken from each subject to evaluate serological levels of PGII and antibodies IgG anti H. pylori (EIA, biohit, Helsinki, Finland) were perfomed. H.p status has been investigated by means of histology, UBT and H.psA (at least two) RESULTS: Group 1: H.p positive 16/34 pts (F11, mean age 59, range 30-66); group 2: H.p +, 14/28 pts (F9, mean age 55, range 26-70); group 3, H.p +, 9/19 pts (F5, mean age 55, range 31-69); the mean PGII levels in the Group 1 was 12+or-5 in overall, 14+or-6 in H.p positive pts; in the group 2 PGII was 13+ or- 7 in overall, 15+or-3 in H.p + pts; in the Group 3 was 18+ or-9 in overall, 19+or-8 in the H.p + pts. Statistically significant differences: Group 1 vs Group 3, p=0.05; H.p + pts Group 1 and Group 2 vs H.p+ pts group 3, p=0.05; CONCLU- SION: Celecoxib showed association with lowest levels of PGII. H.p infection is associated with higher levels of PGII in all the three groups. T1980 Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Colorectal Cancer (CRC) Cellular Proliferation via Several Intracellular Pathways Priti Bijpuria, Joseph D. Feuerstein, Daniel Prabakaran, M. Michael Wolfe Background: Numerous epidemiologic studies have reported that rates of colorectal cancer (CRC) and other GI malignancies are increased in obese individuals. In addition to mediating the enteroinsular axis and functioning as an efficiency hormone, GIP may play a critical role in the pathogenesis of obesity. The ever-increasing prevalence of obesity emphasizes the importance of conducting a detailed characterization of the relationship between obesity and cancer, as well as the mechanisms that may be involved. Aim: To assess the possibility that enhanced GIP expression, which occurs in obesity, might contribute to the pathogenesis of obesity-related carcinogenesis, and to investigate the intracellular mechanisms that might mediate GIP-induced CRC tumor growth. Methods: MC-26 cells (mouse CRC cell line) and DLD-1 cells (human CRC cell line), both of which express GIP receptors, were incubated in the presence of GIP (1-200 nM) for various times. Cell proliferation was measured by MTS assay, and cellular protein was extracted and assessed by Western analysis using specific antibodies to measure the expression of cyclooxygenase-2 (COX-2), β-catenin, Akt, ERK kinase, and mTor pathway components. Results: The inclusion of GIP in the incubation medium significantly increased CRC cell proliferation in a concentration- and time-dependent manner. COX-2, which is overexpressed in colonic neoplasms, plays an integral role in tumorigenesis and neoplastic proliferation, and β-catenin, which normally plays a major role in cell-cell adhesion, is also overexpressed in CRC, and thereby stimulates uncontrolled cellular proliferation. GIP treatment significantly increased the expression of COX-2 (3-fold) and β-catenin (2-fold) in a time-dependent manner, and the increments in COX-2 and β- catenin levels were both attenuated by pre-incubation with 1 μM NS-398, a selective COX- 2 inhibitor. Moreover, GIP (0.1-100 nM) induced the activation of Akt and ERK in a concentration-dependent manner. GIP also activated the phosphorylation of p70S6K, a component of mTOR pathway, which was abolished in the presence of rapamycin, a known mTOR inhibitor. Summary and Conclusion: The results of these studies suggest that GIP- stimulated CRC cell growth may be mediated in part through intracellular pathways involving COX-2 and β-catenin, as well as through the activation of Akt, ERK, and mTOR pathways. These studies indicate that the presence of receptors to this important efficiency hormone in CRC may enable ligand binding and, in so doing, stimulate cell proliferation. The overexpression of GIP, which occurs in obesity, might thereby contribute to the enhanced rate of CRC observed in obesity. AGA Abstracts
Transcript of T1976 The Preventive Factors for Aspirin-Induced Peptic Ulcer
pH values using a High K+/Nigericin calibration technique. Glands were acidified using anNH4Cl prepulse followed by a Na+-free solution. Alkalinization in Na+-free solution representsintracellular acid production and eliminates the possibility of contribution by the Na+/H+ proteins. Studies were done in the presence or absence of indomethacin (100μM) oracetylsalicylic acid (ASA) (100-500μM). Results: In the presence of indomethacin, a rapiddecrease in pHi is seen upon the removal of Na+, followed by an immediate rise in pHi,approaching pH of 7.0. In the absence of indomethacin, no alkalinization was observeduntil Na+ was added back to the solution. In a separate series of experiments, a similarresult was observed with ASA. In the presence of ASA, a rapid alkalinization was observedin the Na+-free solution, representing intracellular acid production. This effect was not seenin the absence of drug. Conclusions: This study suggests that indomethacin and ASA havea direct effect on activation of acid secretion in the parietal cell. This is a novel mechanismin which NSAID use may increase risk of PUD. The direct stimulatory effect on acid secretionprovides evidence for a rapid onset of PUD via the decreased barrier function coupled withenhanced acid secretion that occurs in the absence of secretagogues.
T1976
The Preventive Factors for Aspirin- Induced Peptic UlcerAkiko Shiotani, Takashi Sakakibara, Yoshiyuki Yamanaka, Hiroshi Imamura, MinoruFujita, Ken-ichi Tarumi, Noriaki Manabe, Tomoari Kamada, Jiro Hata, Ken Haruma
Background: Interleukin-1β (IL-1β) polymorphisms are associated with peptic ulcer andatrophic gastritis. Aim: This study aimed to examine effects of corpus atrophy and thegenotypes of genes related with peptic ulcer including IL-1β on risk of aspirin ulcer. Methods:232 patients taking 100mg of aspirin for cardiovascular diseases, of whom 40 had pepticulcer were enrolled. IL1β, interleukin-1 receptor antagonist (IL-1RN), tumor necrosis factor(TNF)-α , cyclooxygenase (COX)-1, cytochrome p450 2C9 (CYP2C9), UDP-glucuronosyl-transferase (UGT1A6) genotypes were determined, and serum pepsinogen levels were meas-ured. Results: The polymorphisms of IL-1β-511/-31 only were significantly associated withpeptic ulcer, but other genotypes were not. Serum pepsinogen I and II levels and I/II ratiowere significantly higher in the ulcer group than in the non-ulcer group. Taking PPI (OR,0.10; 95% CI, 0.02-0.46), pepsinogen I of less than 50 ng/ml (OR, 0.26; 95% CI, 0.11-0.64) and IL-1β-511 T carrier (OR, 0.36; 95% CI, 0.16-0.81) were significantly associatedwith peptic ulcer. Conclusions: Hypoacidity related with corpus atrophy as well as takingPPI seems to be preventively associated with development of peptic ulcer among low doseaspirin users. The detection of groups with a high risk for developing aspirin- induced ulcerby an assessment for the genotype of IL1β polymorphism or serum pepsinogen levels mayserve to be a cost-effective prevention strategy.
T1977
Rand Appropriateness Study with Development of Recommendations forNSAID TreatmentChris J. Hawkey, Angel Lanas, Carmelo Scarpignato, Herman Stoevelaar
Background and rationale: Making appropriate treatment choices with non-steroidal anti-inflammatory drugs (NSAIDs) is increasingly complex. Physicians need to consider gastro-intestinal (GI) and cardiovascular (CV) safety issues of NSAIDs. Non-selective NSAIDs havegastro-toxicity which can be reduced by a proton pump inhibitor (PPI) or substitution ofa selective cyclooxgenase (COX)-2 inhibitor. However, all NSAIDs may increase CV risks.It may be challenging to know best practice in particular patient profiles. We performed aRAND appropriateness study to support treatment choice in daily clinical practice. Methods:Using the RAND Appropriateness Method, an international, multi-disciplinary panel of 18experts (in Rheumatology, Orthopaedics, Primary Care, Geriatrics, Gastroenterology andCardiology) assessed the appropriateness of 5 NSAIDs (ibuprofen, diclofenac, naproxen,celecoxib and etoricoxib) both in mono-therapy and in combination with proton pumpinhibitors. On an individual basis and by using a 9-point scale, the panel rated theirappropriateness for different patient profiles (n = 144). These profiles were made up by acombination of several clinical variables, determined important in treatment choice, includingage, history of upper gastro-intestinal events, cardiovascular risk, low-dose aspirin use,concomitant use of anti-coagulants, concomitant use of systemic corticosteroids and patternof use. Based on the median score and the extent of agreement, a panel recommendationwas calculated for each treatment option: “inappropriate”, “appropriate”, or “uncertain”.Results: Agreement was reached in 26% of the cases (n=1440), while most ratings wereindeterminate (62%). In more than 85% of the cases non-selective NSAIDs without PPIwere found inappropriate. Regression analysis showed that of all variables, a history ofupper GI events showed the highest impact on the predicted appropriateness scores for allmedications, irrespective of CV risk level. In patients with a previous uncomplicated orcomplicated GI event, neither intermittent nor continuous use of non-selective NSAIDs alonewas rated appropriate. Conclusion: It is useful to determine from different perspectives theappropriateness of NSAIDs in relation to several patient-specific clinical conditions. Sinceapproaches were identified that would never be appropriate, recommendations were gener-ated for safer NSAID prescribing for patients with different levels of GI and CV risks.
T1978
Impact of Upper Gasrtointestinal Mucosal Damage Associated withContinuous Use of Low-Dose Aspirin in JapanTakashi Kawai, Akira Yamashina, Kenji Yagi, Tetsuya Yamagishi, Fuminori Moriyasu
Introduction: Low-dose aspirin is standard treatment for prevention of cardiovascular eventsin at-risk patients. However, long-term administration of low-dose aspirin is associated witha greater risk of adverse events, including gastrointestinal injury. In Japan there were onlyfew reports according to upper gastrointestinal bleeding, no date of peptic ulcer and erosiveesophagitis. In this study we evaluate the risk of esophageal lesions, gastric ulcer andduodenal ulcer in patients receiving continuous low-dose aspirin. Methods: The subjectswere 101 patients who received low-dose aspirin more than 3 months. Mean age was
A-613 AGA Abstracts
67.5±7.69. The presence of reflex esophagitis, esophageal ulcer, gastric ulcer, and duodenalulcer was assessed by Esophagogastroduodenoscopy (EGD).We classified reflex esophagitis(R.E.) reference to LA classification: A, B, C, D, and peptic ulcer were measured ulcer size.H. pylori infection was also examined using 13C UBT. GI symptom were assessed by GSRS.Result: R.E.s was recognized in 6.9% (7/101) patients (LA-A: 1, LA-B: 3, LA-C 2, and LA-D: 1). Esophageal ulcer was recognized in 1 patient. Gastric ulcer was recognized 11.9%(12/101) patients and ulcer size was 6.42+/- 3.19mm. Duodenal ulcer was recognized 4%(4/101) patients and ulcer size was 6.25+/- 3.41 mm. H. pylori infection positive:negativeratio was 7:5 in gastric ulcer, 1:4 in duodenal ulcer. GSRS scores (reflex, abdominal pain,indigestion, diarrhea, constipation) were 1.42, 1.33,1.74, 1.28 in R.E., 1.45,1.40, 1.49,1.37, 1.69 in gastric ulcer, 1.35, 1.35, 2.9, 1.83, 3.1 in duodenal ulcer, 1.36, 1.32, 1.65,1.40, 1,98 in no R.E. and ulcers. Conclusion: In patients with low-dose aspirin, peptic ulcerwas recognized 15.8%, but majority of ulcer was shallow type. Reflex esophagitis was alsorecognized, 3 cases were severe type (LA-C,D). Most are asymptomatic. Low-dose aspirincause the damage of gastroduodenal mucosa, but also of esophagus.
T1979
Pepsinogen II As Marker of Inflammation in H.P Infection and in NSAIDsDamageFrancesco Di Mario, Loredana Guida, Andrea Iori, Lucas G. Cavallaro, Margherita Curlo,Ester Morana, Marino Venerito, Peter Malfertheiner, Carmelo Scarpignato, MassimoRugge, Angelo Franzè
BACKGROUND: H.p infection and NSAIDs are claimed to be independent risk factors forgastritis. Serum pepsinogen II (PGII) significantly increase in presence of H. pylori relatedgastritis. AIM: to evaluate the effect of differents NSAIDs and H. pylori on PGII levels andgastric histology. METHODS: 81 reumatological patients treated with NSAIDs, of whom 34pts ( F19, mean age 58, range 27-66) treated with Celecoxib 200 mg (group 1); 28 pts (F21, mean age 53, range 26-72) treated with ibuprofen 1,200 mg (group 2); 19 pts (11 F,mean age 54, range 29-69) treated with Diclofenac 100 mg (group 3) entered in the study.A blood sample was taken from each subject to evaluate serological levels of PGII andantibodies IgG anti H. pylori (EIA, biohit, Helsinki, Finland) were perfomed. H.p status hasbeen investigated by means of histology, UBT and H.psA (at least two) RESULTS: Group1: H.p positive 16/34 pts (F11, mean age 59, range 30-66); group 2: H.p +, 14/28 pts (F9,mean age 55, range 26-70); group 3, H.p +, 9/19 pts (F5, mean age 55, range 31-69); themean PGII levels in the Group 1 was 12+or-5 in overall, 14+or-6 in H.p positive pts; inthe group 2 PGII was 13+ or- 7 in overall, 15+or-3 in H.p + pts; in the Group 3 was 18+or-9 in overall, 19+or-8 in the H.p + pts. Statistically significant differences: Group 1 vsGroup 3, p=0.05; H.p + pts Group 1 and Group 2 vs H.p+ pts group 3, p=0.05; CONCLU-SION: Celecoxib showed association with lowest levels of PGII. H.p infection is associatedwith higher levels of PGII in all the three groups.
T1980
Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates ColorectalCancer (CRC) Cellular Proliferation via Several Intracellular PathwaysPriti Bijpuria, Joseph D. Feuerstein, Daniel Prabakaran, M. Michael Wolfe
Background: Numerous epidemiologic studies have reported that rates of colorectal cancer(CRC) and other GI malignancies are increased in obese individuals. In addition to mediatingthe enteroinsular axis and functioning as an efficiency hormone, GIP may play a criticalrole in the pathogenesis of obesity. The ever-increasing prevalence of obesity emphasizesthe importance of conducting a detailed characterization of the relationship between obesityand cancer, as well as the mechanisms that may be involved. Aim: To assess the possibilitythat enhanced GIP expression, which occurs in obesity, might contribute to the pathogenesisof obesity-related carcinogenesis, and to investigate the intracellular mechanisms that mightmediate GIP-induced CRC tumor growth. Methods: MC-26 cells (mouse CRC cell line) andDLD-1 cells (human CRC cell line), both of which express GIP receptors, were incubatedin the presence of GIP (1-200 nM) for various times. Cell proliferation was measured byMTS assay, and cellular protein was extracted and assessed by Western analysis using specificantibodies to measure the expression of cyclooxygenase-2 (COX-2), β-catenin, Akt, ERKkinase, and mTor pathway components. Results: The inclusion of GIP in the incubationmedium significantly increased CRC cell proliferation in a concentration- and time-dependentmanner. COX-2, which is overexpressed in colonic neoplasms, plays an integral role intumorigenesis and neoplastic proliferation, and β-catenin, which normally plays a majorrole in cell-cell adhesion, is also overexpressed in CRC, and thereby stimulates uncontrolledcellular proliferation. GIP treatment significantly increased the expression of COX-2 (3-fold)and β-catenin (2-fold) in a time-dependent manner, and the increments in COX-2 and β-catenin levels were both attenuated by pre-incubation with 1 μM NS-398, a selective COX-2 inhibitor. Moreover, GIP (0.1-100 nM) induced the activation of Akt and ERK in aconcentration-dependent manner. GIP also activated the phosphorylation of p70S6K, acomponent of mTOR pathway, which was abolished in the presence of rapamycin, a knownmTOR inhibitor. Summary and Conclusion: The results of these studies suggest that GIP-stimulated CRC cell growth may be mediated in part through intracellular pathways involvingCOX-2 and β-catenin, as well as through the activation of Akt, ERK, and mTOR pathways.These studies indicate that the presence of receptors to this important efficiency hormonein CRC may enable ligand binding and, in so doing, stimulate cell proliferation. Theoverexpression of GIP, which occurs in obesity, might thereby contribute to the enhancedrate of CRC observed in obesity.
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