To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It wa...To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibrted basal and growth hormone releasing hormone (GRH)stimulated GH secretion in 87. 5 % and 100. 0 % of the GH adenomas . respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor ,postreceptor Ca2+ channel and Ca2+GH secreting coupling in 6 (66. 6%) and 5 (55. 5 % ) cases of 9 GH adenomas respectively. Among them,the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.展开更多
AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp ...AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related "epigenetic clock" genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes.展开更多
Among pituitary tumors, prolactin (PRL)-secreting pituitary adenomas are by far the most frequent ones. The development of symptomatic hydrocephalus due to a pituitary adenoma is an exceptional event. The authors desc...Among pituitary tumors, prolactin (PRL)-secreting pituitary adenomas are by far the most frequent ones. The development of symptomatic hydrocephalus due to a pituitary adenoma is an exceptional event. The authors describe a 37-year-old man who had a pituitary adenoma associated with obstructive hydrocephalus that was managed by endoscopic transnasal transsphenoidal surgery. Postoperative CT and MRI scans showed resolution of the obstructive hydrocephalus and the foramen of Monro was open. Postoperatively, the patient had visual and headache improvement. Subsequently, the patient is a candidate for cranial surgery or medical therapy to complete the treatment. The present case highlights the fact that pituitary adenomas with obstructive hydrocephalus should be distinguished from other tumors especially colloid cysts.展开更多
Background： Thyrotropin-secreting pituitary adenomas （TSHomas） are a rare cause of hyperthyroidism. Somatostatin （SST） analogs work by interacting with somatostatin receptors （SSTRs）. This study aimed to evalua...Background： Thyrotropin-secreting pituitary adenomas （TSHomas） are a rare cause of hyperthyroidism. Somatostatin （SST） analogs work by interacting with somatostatin receptors （SSTRs）. This study aimed to evaluate short-term preoperative octreotide （OCT） use in TSHoma patients and to investigate SSTR2 and SSTR5 expression and observe structural changes in tumor tissue. Methods： We reviewed records and samples from eight TSHoma patients treated between July 2012 and July 2015. We tested immunohistochemically for SSTR2/5 expression and examined TSHoma cells for morphological changes. Signed rank sum test was used to compare the efficacy of short-term preoperative OCT treatment. Results： OCT treatment （median time： 7.9 days, range： 3-16 days; median total dose： 1.8 mg, range： 0.94.2 mg） led to significant decrease in all patients＇ thyroid hormone levels （FT3 [nmol/L]： 8.33 [7.02, 12.29] to 4.67 [3.52, 5.37] [P = 0.008]; FT4 [pmol/L]： 25.36 [21.34, 28.99] to 16.66 [14.88, 21.49] [P = 0.016]; and TSH [gU/ml]： 5.80 [4.37, 6.78] to 0.57 [0.19, 1.24] [P = 0.008]）. All the eight tumor specimens expressed high SSTR2 protein levels; 5/8 expressed high SSTRS, but 3/8 that expressed low SSTR5 presented a significantly higher TS H suppression rate （P = 0.036）. Electron microscopy showed subcellular level impairments, including clumped nuclear chromatin and reduced cytoplasmic volume. Golgi complexes were observed in the OCT-treated TSHoma specimens. Conclusions： OCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.展开更多
Animal model bearing pituitary prolactin-secreting adenomas (prolactinoma) induced by 17-β-estradiol (E2) in both eutopic pituitary and ectopic pituitary grafted under the renal capsule was generated. Northern blotti...Animal model bearing pituitary prolactin-secreting adenomas (prolactinoma) induced by 17-β-estradiol (E2) in both eutopic pituitary and ectopic pituitary grafted under the renal capsule was generated. Northern blotting assay indicated that PRL mRNA level in eutopic prolactinomas was higher than that in normal pituitaries and ectopic prolactinomas (P【0.05 - 0.01). By polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, a point mutation from C to A occurring at -36 nt in proximal promoter of rat PRL (rPRL) gene was found only in eutopic prolactinomas. No base change was detected in ectopic prolactinomas. Fusion gene transfection assay in vitro exhibited increased activity of the mutant promoter derived from eutopic prolactinoma (P【0.01). These data suggested that the base change in the proximal promoter of rPRL gene may be associated with hyperexpression of rPRL gene in eutopic prolactinomas. The pathogenesis of eutopic and ectopic prolactinomas展开更多
文摘To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibrted basal and growth hormone releasing hormone (GRH)stimulated GH secretion in 87. 5 % and 100. 0 % of the GH adenomas . respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor ,postreceptor Ca2+ channel and Ca2+GH secreting coupling in 6 (66. 6%) and 5 (55. 5 % ) cases of 9 GH adenomas respectively. Among them,the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.
基金Supported by the National Research,Development and Innovation Office,No.KMR-12-1-2012-0216the Hungarian Scientific Research Fund,No.OTKA-K111743
文摘AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related "epigenetic clock" genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes.
文摘Among pituitary tumors, prolactin (PRL)-secreting pituitary adenomas are by far the most frequent ones. The development of symptomatic hydrocephalus due to a pituitary adenoma is an exceptional event. The authors describe a 37-year-old man who had a pituitary adenoma associated with obstructive hydrocephalus that was managed by endoscopic transnasal transsphenoidal surgery. Postoperative CT and MRI scans showed resolution of the obstructive hydrocephalus and the foramen of Monro was open. Postoperatively, the patient had visual and headache improvement. Subsequently, the patient is a candidate for cranial surgery or medical therapy to complete the treatment. The present case highlights the fact that pituitary adenomas with obstructive hydrocephalus should be distinguished from other tumors especially colloid cysts.
文摘Background： Thyrotropin-secreting pituitary adenomas （TSHomas） are a rare cause of hyperthyroidism. Somatostatin （SST） analogs work by interacting with somatostatin receptors （SSTRs）. This study aimed to evaluate short-term preoperative octreotide （OCT） use in TSHoma patients and to investigate SSTR2 and SSTR5 expression and observe structural changes in tumor tissue. Methods： We reviewed records and samples from eight TSHoma patients treated between July 2012 and July 2015. We tested immunohistochemically for SSTR2/5 expression and examined TSHoma cells for morphological changes. Signed rank sum test was used to compare the efficacy of short-term preoperative OCT treatment. Results： OCT treatment （median time： 7.9 days, range： 3-16 days; median total dose： 1.8 mg, range： 0.94.2 mg） led to significant decrease in all patients＇ thyroid hormone levels （FT3 [nmol/L]： 8.33 [7.02, 12.29] to 4.67 [3.52, 5.37] [P = 0.008]; FT4 [pmol/L]： 25.36 [21.34, 28.99] to 16.66 [14.88, 21.49] [P = 0.016]; and TSH [gU/ml]： 5.80 [4.37, 6.78] to 0.57 [0.19, 1.24] [P = 0.008]）. All the eight tumor specimens expressed high SSTR2 protein levels; 5/8 expressed high SSTRS, but 3/8 that expressed low SSTR5 presented a significantly higher TS H suppression rate （P = 0.036）. Electron microscopy showed subcellular level impairments, including clumped nuclear chromatin and reduced cytoplasmic volume. Golgi complexes were observed in the OCT-treated TSHoma specimens. Conclusions： OCT can control hormone levels and damage the ultrastructure of tumor cells and organelles. Short-term response to OCT may be related to SSTR5 expression. Preoperative SST analog treatment for TSHoma could be considered as a combination therapy.
文摘Animal model bearing pituitary prolactin-secreting adenomas (prolactinoma) induced by 17-β-estradiol (E2) in both eutopic pituitary and ectopic pituitary grafted under the renal capsule was generated. Northern blotting assay indicated that PRL mRNA level in eutopic prolactinomas was higher than that in normal pituitaries and ectopic prolactinomas (P【0.05 - 0.01). By polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, a point mutation from C to A occurring at -36 nt in proximal promoter of rat PRL (rPRL) gene was found only in eutopic prolactinomas. No base change was detected in ectopic prolactinomas. Fusion gene transfection assay in vitro exhibited increased activity of the mutant promoter derived from eutopic prolactinoma (P【0.01). These data suggested that the base change in the proximal promoter of rPRL gene may be associated with hyperexpression of rPRL gene in eutopic prolactinomas. The pathogenesis of eutopic and ectopic prolactinomas
