Background & Aims: Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apo-ptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via ...Background & Aims: Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apo-ptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGFI, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer. Methods: Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements. Results: Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP- 3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95% CI: 1.0- 2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1- 3.3], Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2- 3.6], Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3- 6.2], Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0- 5.2], Ptrend = .04), and insulin (OR = 2.3 [95% CI: 1.1- 4.9], Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk. Conclusions: Levels of IGF-I, ratio of IGF-I/IGFBP - 3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.展开更多
Background and aim: Activating β-catenin mutations in exon 3 have been implicated in colorectal tumorigenesis. Although reports to the contrary exist, it has been suggested that β-catenin mutations occur more often ...Background and aim: Activating β-catenin mutations in exon 3 have been implicated in colorectal tumorigenesis. Although reports to the contrary exist, it has been suggested that β-catenin mutations occur more often in microsatellite unstable (MSI+) colorectal carcinomas, including hereditary non-polyposis colorectal cancer (HNPCC), as a consequence of defective DNA mismatch repair. We have analysed 337 colorectal carcinomas and adenomas, from both sporadic cases and HNPCC families, to provide an accurate assessment of β-catenin mutation frequency in each tumour type. Methods: Direct sequencing of exon 3 of β-catenin. Results: Mutations were rare in sporadic (1/83, 1.2%) and HNPCC adenomas (1/37, 2.7%). Most of the sporadic adenomas analysed (80%) were small (< 1 cm), and our data therefore differ from a previous report of a much higher mutation frequency in small adenomas. No oncogenic β-catenin mutations were identified in 34 MSI+and 78 microsatellite stable (MSI-) sporadic colorectal cancers but a raised mutation frequency (8/44, 18.2%) was found in HNPCC cancers; this frequency was significantly higher than that in HNPCC adenomas (p = 0.035) and in both MSI-(p< 0.0001) and MSI+(p = 0.008) sporadic cancers. Mutations were more common in higher stage (Dukes’stages C and D) cancers (p = 0.001). Conclusion: Exon 3 β-catenin mutations are associated specifically with malignant colorectal tumours in HNPCC; mutations appear not to result directly from deficient mismatch repair. Our data provide evidence that the genetic pathways of sporadic MSI+and HNPCC cancers may be divergent, and indicate that mutations in the HNPCC pathway of colorectal tumorigenesis may be determined by selection, not simply by hypermutation.展开更多
PURPOSE: Research data have recently emphasized an intrigu-ing association of JC polyoma virus with colon carcinogenesis. Tumorigenicity of JC virus is attributed to the T-antigen of its Mad-1 variant. Controversy aro...PURPOSE: Research data have recently emphasized an intrigu-ing association of JC polyoma virus with colon carcinogenesis. Tumorigenicity of JC virus is attributed to the T-antigen of its Mad-1 variant. Controversy arose when another research group did not confirm this association. The purpose of this study was to detect JC virus in a series of colon neoplasms from Greek patients. METHODS: A nested polymerase chain reaction assay was used to detect JC virus in 80 cancerous, 25 adenomatous specimens of large bowel, and 20 colonoscopic biopsy samples from normal patients without colorectal neoplasia. Quantitation of JC virus DNA was performed by real-time polymerase chain reaction. RESULTS: JC polyoma virus nucleotide sequence was detected in 61 percent of colon adenocarcinomas and in 60 percent of adenomas, at a viral load of 9 ×103 to 20 ×103 copies/μg DNA. Adjacent normal mucosa in 35 positive colon adenocarcinoma specimens, and normal mucosa from six patients of the control group, had low viral loads (50-450 copies/μg DNA). CONCLUSIONS: JC polyoma virus genome is present in colon neoplasms. JC virus detection in adenomas at comparable viral loads to malignant tumors suggests its implication at early steps of colonic carcinogenesis. Taking into consideration other published data, infection of colonic epithelium with JC virus might be a prime candidate for a role in chromosomal and genomic instability.展开更多
Objective: To evaluate the signs and symptoms associated with hyperprolactinemia and establish guidelines for a minimal serum PRL level for which pituitary imaging is indicated. Design: Retrospective study. Setting: R...Objective: To evaluate the signs and symptoms associated with hyperprolactinemia and establish guidelines for a minimal serum PRL level for which pituitary imaging is indicated. Design: Retrospective study. Setting: Reproductive endocrinology clinic in a university hospital. Patient(s): One hundred four consecutive patients with hyperprolactinemia, mean age 30 ± 6.5 (range 19- 44) years. Intervention(s): Classification of clinical symptoms, serum hormone measurements, and pituitary magnetic resonance imaging (MRI). Main Outcome Measure(s): Incidence of presenting symptoms, serum PRL levels, and pituitary tumor size. Result(s): Median (range)- PRL value was 82.6 ng/mL (25- 1,342). Reported symptoms from most to least common were infertility (48% ), headaches (39% ), oligoamenorrhea (29% ), galactorrhea (24% ), and visual changes (13% ). Hypothyroidism was diagnosed in 2 of 104 (1.9% ) patients. Of 86 patients who had pituitary imaging, 23 (26% ) had normal findings and 63 (74% ) had pituitary tumor; of these, 47 (55% of total imaged) had microadenomas and 16 (19% of total imaged) had macroadenomas. There was a statistically significant association between the tumor sizeand the PRL level. However, 11% of the patients with microadenomas had PRL levels >200 ng/mL, and 44% of the patients with macroadenomas had PRL levels between 25 and 200 ng/mL. Conclusion(s): The most common symptoms in the population studied were infertility and headaches. Coexisting thyroid disease was an uncommon finding. Most patients had a pituitary tumor on MRI. Although tumor size correlated with the serum PRL level, some macroadenomas were detected in women with only moderately elevated PRL values. On the basis of these findings, pituitary imaging should be obtained to identify pituitary tumors in all patients with persistently elevated PRL levels.展开更多
文摘Background & Aims: Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apo-ptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGFI, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer. Methods: Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements. Results: Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP- 3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95% CI: 1.0- 2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1- 3.3], Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2- 3.6], Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3- 6.2], Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0- 5.2], Ptrend = .04), and insulin (OR = 2.3 [95% CI: 1.1- 4.9], Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk. Conclusions: Levels of IGF-I, ratio of IGF-I/IGFBP - 3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.
文摘Background and aim: Activating β-catenin mutations in exon 3 have been implicated in colorectal tumorigenesis. Although reports to the contrary exist, it has been suggested that β-catenin mutations occur more often in microsatellite unstable (MSI+) colorectal carcinomas, including hereditary non-polyposis colorectal cancer (HNPCC), as a consequence of defective DNA mismatch repair. We have analysed 337 colorectal carcinomas and adenomas, from both sporadic cases and HNPCC families, to provide an accurate assessment of β-catenin mutation frequency in each tumour type. Methods: Direct sequencing of exon 3 of β-catenin. Results: Mutations were rare in sporadic (1/83, 1.2%) and HNPCC adenomas (1/37, 2.7%). Most of the sporadic adenomas analysed (80%) were small (< 1 cm), and our data therefore differ from a previous report of a much higher mutation frequency in small adenomas. No oncogenic β-catenin mutations were identified in 34 MSI+and 78 microsatellite stable (MSI-) sporadic colorectal cancers but a raised mutation frequency (8/44, 18.2%) was found in HNPCC cancers; this frequency was significantly higher than that in HNPCC adenomas (p = 0.035) and in both MSI-(p< 0.0001) and MSI+(p = 0.008) sporadic cancers. Mutations were more common in higher stage (Dukes’stages C and D) cancers (p = 0.001). Conclusion: Exon 3 β-catenin mutations are associated specifically with malignant colorectal tumours in HNPCC; mutations appear not to result directly from deficient mismatch repair. Our data provide evidence that the genetic pathways of sporadic MSI+and HNPCC cancers may be divergent, and indicate that mutations in the HNPCC pathway of colorectal tumorigenesis may be determined by selection, not simply by hypermutation.
文摘PURPOSE: Research data have recently emphasized an intrigu-ing association of JC polyoma virus with colon carcinogenesis. Tumorigenicity of JC virus is attributed to the T-antigen of its Mad-1 variant. Controversy arose when another research group did not confirm this association. The purpose of this study was to detect JC virus in a series of colon neoplasms from Greek patients. METHODS: A nested polymerase chain reaction assay was used to detect JC virus in 80 cancerous, 25 adenomatous specimens of large bowel, and 20 colonoscopic biopsy samples from normal patients without colorectal neoplasia. Quantitation of JC virus DNA was performed by real-time polymerase chain reaction. RESULTS: JC polyoma virus nucleotide sequence was detected in 61 percent of colon adenocarcinomas and in 60 percent of adenomas, at a viral load of 9 ×103 to 20 ×103 copies/μg DNA. Adjacent normal mucosa in 35 positive colon adenocarcinoma specimens, and normal mucosa from six patients of the control group, had low viral loads (50-450 copies/μg DNA). CONCLUSIONS: JC polyoma virus genome is present in colon neoplasms. JC virus detection in adenomas at comparable viral loads to malignant tumors suggests its implication at early steps of colonic carcinogenesis. Taking into consideration other published data, infection of colonic epithelium with JC virus might be a prime candidate for a role in chromosomal and genomic instability.
文摘Objective: To evaluate the signs and symptoms associated with hyperprolactinemia and establish guidelines for a minimal serum PRL level for which pituitary imaging is indicated. Design: Retrospective study. Setting: Reproductive endocrinology clinic in a university hospital. Patient(s): One hundred four consecutive patients with hyperprolactinemia, mean age 30 ± 6.5 (range 19- 44) years. Intervention(s): Classification of clinical symptoms, serum hormone measurements, and pituitary magnetic resonance imaging (MRI). Main Outcome Measure(s): Incidence of presenting symptoms, serum PRL levels, and pituitary tumor size. Result(s): Median (range)- PRL value was 82.6 ng/mL (25- 1,342). Reported symptoms from most to least common were infertility (48% ), headaches (39% ), oligoamenorrhea (29% ), galactorrhea (24% ), and visual changes (13% ). Hypothyroidism was diagnosed in 2 of 104 (1.9% ) patients. Of 86 patients who had pituitary imaging, 23 (26% ) had normal findings and 63 (74% ) had pituitary tumor; of these, 47 (55% of total imaged) had microadenomas and 16 (19% of total imaged) had macroadenomas. There was a statistically significant association between the tumor sizeand the PRL level. However, 11% of the patients with microadenomas had PRL levels >200 ng/mL, and 44% of the patients with macroadenomas had PRL levels between 25 and 200 ng/mL. Conclusion(s): The most common symptoms in the population studied were infertility and headaches. Coexisting thyroid disease was an uncommon finding. Most patients had a pituitary tumor on MRI. Although tumor size correlated with the serum PRL level, some macroadenomas were detected in women with only moderately elevated PRL values. On the basis of these findings, pituitary imaging should be obtained to identify pituitary tumors in all patients with persistently elevated PRL levels.
