Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A digital cell image processor was used to compute 15 parameters on Feulgen-stained thyroid nuclei from 238 archival, i.e., formalin-fixed, paraffin-embedded thyroid lesions. The morphonuclear parameters were related to morphometric (nuclear area), densitometric (nuclear DNA content), and textural (chromatin pattern characteristics) features. With respect to development of a malignant condition, their variations were compared with the World Health Organization's International Histological Classification of thyroid tumors. The relationship between morphonuclear parameter assessments and tumor size and the presence or absence of metastasis at the time of diagnosis was also investigated: no relationship with respect to cytomorphonuclear assessments was found. Nuclear area and nuclear DNA content discriminated between simple multinodular goiters and multinodular goiters with adenomatous hyperplasia. In the same way, the mean parameter values describing the chromatin pattern of multinodular goiters were significantly distinct from those describing the chromatin pattern of adenomas and carcinomas. Furthermore, chromatin pattern descriptions made it possible to discriminate between cell nuclei from papillary carcinomas and follicular carcinomas, and further between follicular carcinomas and follicular adenomas. A marked variation was observed within individual cases of multinodular goiters, adenomas, and carcinomas, a feature suggesting that morphonuclear assessment is of limited value for the diagnosis of individual clinical cases. In contrast, these results show that morphometric, densitometric, and textural nuclear assessments are useful aids for thyroid tumor typing, adding interesting results with respect to thyroid tumor progression. Indeed, the primary findings demonstrate that nodules with adenomatous hyperplasia from multinodular goiter lesions and microvesicular adenomas more closely resemble follicular carcinomas than do simple multinodular goiters and normomacrovesicular adenomas. Such data might reflect a biologic progression from benign to malignant follicular thyroid lesions.
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PMID:Relationship between histopathologic typing and morphonuclear assessments of 238 thyroid lesions. Digital cell image analysis performed on Feulgen-stained nuclei from formalin-fixed, paraffin-embedded materials. 137 4

Recent evidence has emphasized the importance of programmed cell death, or apoptosis, in the maintenance of tissue homeostasis and pathogenesis of tumors. This study analyzed the significance of apoptosis in relation to the expression of p53 and bcl-2 proteins, tissue proliferation defined by Ki-67 expression, and tissue histology in thyroid tissue. Extent of apoptosis was defined by morphological criteria and the terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate (dUTP) biotin nick end labeling (TUNEL) assay. Immunocytochemistry was performed for p53, bcl-2, and Ki-67 expression. There was good correlation between TUNEL-reactive cells and morphological evaluation criteria for apoptosis. The extent of apoptosis was significantly associated with the type of thyroid lesion (r = 0.66990, p = 0.000012), both proliferative (namely multinodular goiter) and neoplastic (benign and malignant). A higher extent of apoptosis was evident in medullary and anaplastic carcinomas. Apoptosis also correlated to p53 protein accumulation (r = 0.485, p = 0.00041) and Ki-67 immunoreactivity (r = 0.435, p = 0.001). An inverse correlation was observed between bcl-2 expression and the extent of apoptosis (r = -0.33369, p = 0.01912). A direct correlation was also observed between p53 expression and Ki-67 immunoreactivity (r = 0.623, p = 0.0002). By inhibiting apoptosis, bcl-2, may cause a shift in tissue kinetics toward the preservation of genetically aberrant cells, thereby facilitating tumor progression. These results imply that rapidly proliferating tumors appear to have a high cell turnover state in which there may be increased chance of apoptosis among the proliferating cells. The ability of apoptosis to occur in the presence of a possibly mutant p53 protein suggest the existence of at least two p53 dependent apoptotic pathways, one requiring activation of specific target genes and the other independent of it. However, keeping in mind the limited number of subjects studied in each subgroup and the rather low correlation coefficients, these possibilities would have to be substantiated in a larger study population.
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PMID:In situ apoptosis in the thyroid. 1071 47

Millions of people worldwide suffer goiter, a proliferative disease of the follicular cells of the thyroid that may become neoplastic. Thyroid neoplasms have low proliferative index, low apoptotic index and a high incidence of metastasis. TGF-beta is overexpressed in thyroid follicular tumor cells. To investigate the role of TGF-beta in thyroid tumor progression, we established cultures of human thyrocytes from different proliferative pathologies (Grave's disease, multinodular goiter, follicular adenoma, papillary carcinoma), lymph node metastasis, and a normal thyroid sample. All cultures maintained the thyrocyte phenotype. TGF-beta induced cell-cycle arrest in all cultures, in contrast with results reported for other epithelial tumors. In deprived medium, TGF-beta induced apoptosis in normal thyrocyte cultures and all neoplastic cultures except the metastatic cultures. This apoptosis was mediated by a reduction in p27kip1 levels, inducing cell-cycle initiation. Antisense p27 expression induced apoptosis in the absence of TGF-beta. By contrast, in cells in which p27 was overexpressed, TGF-beta had a survival effect. In growth medium, a net survival effect occurs in neoplastic thyrocytes only, not normal thyrocytes, due to activation of the NF-kappaB survival program. Together, these findings suggest that (a) thyroid neoplasms are due to reduced apoptosis, not increased division, in line with the low proliferative index of these pathologies, and (b) TGF-beta induces apoptosis in normal thyrocytes via p27 reduction, but that in neoplastic thyrocytes this effect is overridden by activation of the NF-kappaB program.
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PMID:TGF-beta-induced apoptosis in human thyrocytes is mediated by p27kip1 reduction and is overridden in neoplastic thyrocytes by NF-kappaB activation. 1458 8

Gene expression profiling (GEP) of normal thyroid tissue from 43 patients with thyroid carcinoma, 6 with thyroid adenoma, 42 with multinodular goiter, and 6 with Graves-Basedow disease was carried out with the aim of achieving a better understanding of the genetic mechanisms underlying the role of normal cells surrounding the tumor in the thyroid cancer progression. Unsupervised and supervised analyses were performed to compare samples from neoplastic and non-neoplastic diseases. GEP and subsequent RT-PCR analysis identified 28 differentially expressed genes. Functional assessment revealed that they are involved in tumorigenesis and cancer progression. The distinct GEP is likely to reflect the onset and/or progression of thyroid cancer, its molecular classification, and the identification of new potential prognostic factors, thus allowing to pinpoint selective gene targets with the aim of realizing more precise preoperative diagnostic procedures and novel therapeutic approaches.This study is focused on the gene expression profiling analysis followed by RT-PCR of normal thyroid tissues from patients with neoplastic and non-neoplastic thyroid diseases. Twenty-eight genes were found to be differentially expressed in normal cells surrounding the tumor in the thyroid cancer. The genes dysregulated in normal tissue samples from patients with thyroid tumors may represent new molecular markers, useful for their diagnostic, prognostic and possibly therapeutic implications.
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PMID:Gene expression profiling of normal thyroid tissue from patients with thyroid carcinoma. 2710 34