Abstract:
:The underlying mechanism leading to carcinogenesis involves genomic instability, likely related to aneuploidy. While p53 as a "guardian of the genome" is an appealing candidate as an initiator of genomic instability, its mutations or deletions usually occur late in the course of tumor progression. P53 may, however, become a target of events initiated by genomic instability. P53 is a transcription factor with multifaceted regulatory functions in the cell cycle, DNA repair and apoptosis. Inactivating p53 mutations have been described in some 50% of human cancers. These mutations are not only important in tumor progression but apparently also in the response of some tumors to chemotherapy and radiation treatment, thus to clinical outcome. P53 mutations are found in 14% of malignant thyroid tumors and are more frequent in poorly differentiated and anaplastic tumors. We have examined the mutation rates of p53 as a measure of genomic instability (hypermutability) of malignant thyroid tumors. We also wondered whether radiation enhances this tendency to genomic instability. To those ends we extracted all available entries from the p53 mutations database (http://www.perso@curies.fr), verified, extended where applicable, and supplemented that information from the original published reports. We were able to locate 100 entries. The distribution of the types of p53 aberrations in thyroid cancer was similar to those in the database as a whole. The silent mutation rate of 20%, not different from the expected 25%, is consistent with a random occurrence of these mutations. This silent mutation rate is 130 times that expected and is 7 times that of the p53 database. Moreover the distribution of p53 mutations is compatible with Poisson's distribution, which, when considered in the context of the silent mutation rates, indicates that p53 is particularly hypermutable in thyroid cancer. Epigenetic deamination of CpG dinucleotides at highly transforming DNA-contact residues is a feature of poorly differentiated tumors and thus associated with tumor progression. The rates of p53 mutations in radiation-related thyroid cancers (15.4%) are similar to those in spontaneously arising tumors, although there was a highly significant heterogeneity (p<0.0005) in the residues mutated in the two tumor sets. None of the residues mutated in radiation-related thyroid cancer involved CpG deamination. Based on the evidence of p53 hypermutability, thyroid cancer appears to exhibit remarkable genomic instability. Spontaneous epigenetic mutational events are involved in tumor progression. While thyroid cancer related to radiation exposure does not increase the rates of p53 mutation, they exhibit mutation at residues not involved in p53/DNA interface.
journal_name
J Endocrinol Investjournal_title
Journal of endocrinological investigationauthors
Farid NRdoi
10.1007/BF03343889keywords:
subject
Has Abstractpub_date
2001-07-01 00:00:00pages
536-45issue
7eissn
0391-4097issn
1720-8386journal_volume
24pub_type
杂志文章,评审abstract:BACKGROUND:In obese subjects it has been shown that cortisol (F) contributes to the reduction in insulin sensitivity, suggesting a role in the development of the metabolic syndrome (MS). AIM:The aim of this retrospective study was to evaluate the relationship between F and components of MS in 1,027 obese children and ...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/s40618-013-0014-0
更新日期:2014-01-01 00:00:00
abstract::The adrenomedullary response to stimuli is often elevated in poorly controlled insulin dependent diabetic patients, and it is controversial whether the adrenomedullary hyperactivity induces the suppression of the circadian rhythm of catecholamines. We have studied the urinary excretion of catecholamines in 11 diabetic...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03348628
更新日期:1990-07-01 00:00:00
abstract:PURPOSE:Aims of this study were to evaluate the agreement between the short and long versions of the International Physical Activity Questionnaire (IPAQ: Italian versions), their reproducibility (agreement and reliability) and construct validity (relative to pedometry) in a clinical population. METHODS:Ninety patients...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/s40618-017-0746-3
更新日期:2018-03-01 00:00:00
abstract::Osteoporosis is a multifactorial chronic disease that may become even more prevalent and more of a public health problem in the decades to come. Recent research has indicated that a number of macro- and micronutrients are involved in the development of bone health. In the past decade it became evident that vitamin K p...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章,评审
doi:
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The IGF-I system is deregulated in obese subjects in proportion to their degree of visceral adiposity. AIM:To e...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.3275/8511
更新日期:2012-11-01 00:00:00
abstract::There is increasing evidence that androgen therapy in men may be effectively applied in several conditions to improve well being and health. Classical indications for androgen therapy in males are represented by primary or secondary hypogonadism, delayed puberty, aplastic anemia and that secondary to chronic renal fai...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章,评审
doi:10.1007/BF03343707
更新日期:2000-03-01 00:00:00
abstract::The unlimited availability of GH obtained by recombinant DNA technology has allowed optimization of treatment in GH-deficient (GHD) children. At the same time it has prompted a number of studies in conditions not characterized by GHD such as Turner syndrome, intrauterine growth retardation, chronic renal failure and o...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章,评审
doi:10.1007/BF03345367
更新日期:2005-02-01 00:00:00
abstract::Among the several antigens involved in autoimmune thyroid diseases, the microsomal antigen has been recently identified as the human thyroid peroxidase (TPO). The availability of highly purified TPO and anti-TPO monoclonal antibody (mAb) allowed us to study in more details anti-TPO autoimmune antibodies (aAb) and thei...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03348084
更新日期:1986-04-01 00:00:00
abstract:PURPOSE:Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. METHODS:In this retrospective study, patients with primary hyperparathyroidi...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/s40618-020-01369-4
更新日期:2020-07-29 00:00:00
abstract::GH may exert direct growth-promoting and metabolic actions on target tissues, but most of its effects are mediated by circulating (endocrine) or local (auto-/paracrine) IGF-I. The GH/IGF-I system has an important role in cardiac development and in maintaining the structure and function of the heart. A subgroup of chil...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03345590
更新日期:2008-03-01 00:00:00
abstract::Obesity is associated with a number of serious diseases and with a degree of motor disability, but the extent of the risk and functional derangement within the obese population is not yet completely defined. The study aims to evaluate the combined effect of degree of adiposity, body fat distribution and age on selecte...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03349195
更新日期:2006-11-01 00:00:00
abstract::Final height was evaluated in 47 patients with classical 21-hydroxylase treated since diagnosis, and in 29 patients with nonclassical (NC) 21-hydroxylase deficiency who had never been treated before reaching final adult height. Classical patients achieved final heights consistently below the mean for the general popul...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Sleep-related breathing disorders are recognized as major health problems in obesity. They are involved in both hypertension and Type 2 diabetes, through mechanisms possibly related to increased sympathetic tone. We studied the association of habitual snoring with diabetes, hypertension, weight cycling and physical ac...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03346260
更新日期:2004-02-01 00:00:00
abstract::Signals that determine skeletal cell fate, function and apoptosis are critical to normal bone remodeling. Skeletal cells synthesize growth factors; some regulate cell replication, others regulate osteoblastic differentiation. Bone morphogenetic proteins (BMP) and Wnts induce the differentiation of mesenchymal cells to...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章,评审
doi:
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Levothyroxine (L-T4) treatment aims to minimize the risk of differentiated thyroid cancer (DTC) recurrence and should be tailored to patient risk stratification and potential morbidity from adverse effects. AIM:To evaluate the effectiveness of current recommendations on L-T4 treatment of DTC patients in cli...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.3275/8369
更新日期:2012-11-01 00:00:00
abstract::Type 2 diabetes (T2D) and obesity are the major public health problems. Substantial efforts have been made to define loci and variants contributing to the individual risk of these disorders. However, the overall risk explained by genetic variation is very modest. Epigenetics is one of the fastest growing research area...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章,评审
doi:10.1007/s40618-016-0473-1
更新日期:2016-10-01 00:00:00
abstract::Aromatase activity for androstenedione was measured in stromal cells of human uterine endometrium throughout the menstrual cycle. The effect of progestogen on aromatase activity was also examined in the endometrial stromal cells. Aromatase activity tended to be high in the proliferative cells compared to the secretory...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03349962
更新日期:1989-03-01 00:00:00
abstract:BACKGROUND:Adipose tissue has been suggested to influence bone density and metabolism through the effect of some adipokines. However, whether adiponectin and visfatin may correlate with bone metabolism is still unclear. AIM:The aim of this study was to investigate the relationship of adiponectin and visfatin with bone...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03346703
更新日期:2011-01-01 00:00:00
abstract::To characterize natriuretic peptide receptor (NPr) gene expression in human tissues, we cloned portions of the cDNAs codifying for NPr with guanylyl cyclase activity (NPr-A and NPr-B) and without guanylyl cyclase activity (NPr-C). Total RNA was extracted from samples taken at surgery from normal human tissues. NPr-A a...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03349021
更新日期:1996-10-01 00:00:00
abstract::Antithyroid drugs may be proposed as the firstline therapy for hyperthyroidism due to Graves' disease since some patients undergo prolonged remission after drug withdrawal. On the other hand, some studies, though controversial, indicated that methimazole (MMI) has some immunomodulating activity. We retrospectively ana...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03346433
更新日期:2008-10-01 00:00:00
abstract::The aim of the study was to determine the main metabolic parameters of 11-beta-hydroxy-androstenedione (11 OHAD) in man. Seven normal subjects were investigated at 1-3 months interval by 2 types of isotope dilution techniques using a tritiated tracer: constant infusion and bolus iv injection. 3H-11 OHAD and 3H-11-beta...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03349485
更新日期:1984-12-01 00:00:00
abstract::A longitudinal study was carried out in an area of endemic goiter of north-eastern Sicily. Three different surveys (in 1977, 1983 and 1994) evaluated the epidemiological prevalence of goiter in schoolchildren of the endemic area (towns of Bronte, Troina and Maniaci) in comparison to an iodine sufficient control area (...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03349031
更新日期:1996-10-01 00:00:00
abstract::Male to female sex reversal results from failure of testis development. Mutations in the SRY gene or in other genes involved in the sexual differentiation pathway are considered to cause XY gonadal dysgenesis. The majority of the mutations in the SRY described so far are located within the SRY coding region, mainly in...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03347266
更新日期:2005-07-01 00:00:00
abstract:PURPOSE:Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder companied with neuroendocrine and metabolic disorders. Gut microbiota has been implicated to play a key role in metabolic diseases and the production of neurotransmitters. Previous studies have reported the alterations in the gut micr...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/s40618-020-01481-5
更新日期:2021-01-02 00:00:00
abstract::A strong relationship was previously described between the nocturnal oscillations of plasma renin activity (PRA) and the sleep cycles, with levels of PRA that increase during non rapid eye movement sleep and decrease during rapid eye movement sleep. This study was designed to determine whether ritanserin, a 5-hydroxyt...
journal_title:Journal of endocrinological investigation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF03349016
更新日期:1996-09-01 00:00:00
abstract::We experienced an unusual combination of painless thyroiditis and Sheehan's syndrome in a single patient. A 29-year-old postpartum woman was referred to us for suspected Sheehan's syndrome. Endocrine tests confirmed the diagnosis, but, unexpectedly, her thyroid hormone levels in the plasma were elevated. Based on the ...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03350313
更新日期:1997-06-01 00:00:00
abstract::Not only thyroid adenomas and carcinomas, but also the majority of single and well delimited goiter nodules, even if morphologically heterogeneous, are of clonal origin. However, it is still unknown whether the nodules of rapidly growing, recurrent goiters are clonal or polyclonal. We investigated by PCR-based analysi...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03350774
更新日期:1998-06-01 00:00:00
abstract::We studied the possibility of an association between serum somatomedin-C (Sm-C) and thyroid hormone concentrations. For this purpose 34 hyperthyroid patients, 39 patients with primary hypothyroidism, 36 patients with severe nonthyroidal illnesses (NTI), and 63 euthyroid healthy control subjects were examined. The mean...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章
doi:10.1007/BF03349528
更新日期:1990-02-01 00:00:00
abstract::Eighteen patients affected by laparoscopically confirmed endometriosis were randomly assigned to three different schedules of treatment with gonadotropin-releasing hormone agonist (GnRH-a) (goserelin depot formulation 3.6 mg) every 28 days for 6 months. Six women received the first implant in early follicular phase, 4...
journal_title:Journal of endocrinological investigation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF03348925
更新日期:1993-11-01 00:00:00
abstract::Somatostatin and its derivatives have been predominantly studied and succesfully used in endocrinological diseases. This article reviews the rationale of the use of somatostatin and its derivatives in ophthalmology based on current understanding of its action in the eye and summarizes previously published controlled s...
journal_title:Journal of endocrinological investigation
pub_type: 杂志文章,评审
doi:
更新日期:2005-01-01 00:00:00