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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between aging and cancer is complex because the intrication takes place at the cell, the organism and the environment levels. On the other hand, carcinogenesis is a multi-step process, and different mechanisms may be involved in each step. For example, oxidants and antioxidants may play a different role depending upon the phase considered. Tumors in older patients are generally described as slow growing. The difference in tumor aggressiveness between young and older patients is especially obvious in breast cancer patients. The age specificity of some breast risk factors suggests that breast cancer which has been diagnosed in an aged woman was induced late in her life. We address the question whether the characteristics of a senescent organism with regards to oxidant-antioxidant status could be causally related to the slow evolution of tumors in old patients.
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PMID:Aging and cancer: plasma antioxidants and lipid peroxidation in young and aged breast cancer patients. 145 May 89

The field of experimental head and neck oncology continues to expand in both scope and meaningful observations. During the past year, research has focused intensively on factors responsible for disease development, genetic alterations that contribute to cancer progression, tumor growth factors and their modulation, and the biologic and clinical significance of cell-surface antigen expression. In the field of carcinogenesis, various dietary components that either promote or inhibit head and neck cancer development have been identified. Clinical trials that utilize various vitamins and their precursors such as beta-carotene have been reported. Genetic studies have demonstrated that head and neck cancers are heterogeneous in their oncogene expression; potentially, a reflection of the differential effect of various environmental carcinogenic exposures. Finally, the relationship between modulation of normally occurring cell-surface antigens and tumor aggressiveness has been demonstrated by several investigators throughout the past year. Significantly, animal models and human clinical trials have demonstrated that modulation of cell surface components by biologic agents alters the behavior of head and neck cancer and its relationship to the host.
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PMID:Experimental head and neck oncology. 149 56

For therapeutic decisions it is essential to have an evaluation of the tumor volume and the grade of dedifferentiation. Measurement of PSA gives a good additional guide to the tumor volume and to dissemination of the disease. Investigation of the DNA ploidy values can offer further important information on the aggressiveness of the tumor and be helpful for our understanding of the process of tumor propagation. However, DNA studies can still not be regarded as being standard in the clinical work-up of these patients. They are optional but they have a definite place in the research on prostatic cancer. The various methods to study tumor growth by analysis of the S phase fraction are interesting new contributions but still belong to the research laboratories. When we consider prognostic indicators we have to take into account the biologic character of carcinogenesis. Modern research has shown that the development and the progression of cancer is not an instantaneous and solitary reaction. It is a series of events and a net-work reaction between growth-regulating factors, stimulating and inhibiting, a step-wise alteration of the genome. We must recognize that what we are observing is the condition at the present time, and, of course, the observation must be evaluated together with the whole clinical scenario, the man's age, his general condition etc. But still the series of diagnostic procedures presented here will give a rather solid ground for both our therapeutic decisions and for evaluation of the results of treatment.
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PMID:Prognostic indicators in prostatic cancer. 150 80

Pro-cathepsin D is overexpressed in breast cancer cells compared to normal mammary epithelial cells. Moreover, its processing and maturation are altered resulting in increased secretion. In estrogen-responsive breast cancer cell lines such as MCF7 cells and ZR75-1 cells, the 2.2-kb cathepsin D mRNA is accumulated specifically by estrogens and growth factors. Estrogen regulation is mostly transcriptional, while growth factors stabilize the mRNA and act indirectly. In estrogen-receptor-negative cell lines, there is a constitutive high production of cathepsin D mRNA. Moreover in uterine cells, progesterone is the inducer rather than estrogen, indicating the complexity of regulation by steroids, depending on the tissue. The increased production of cathepsin D appears to be correlated with the aggressiveness of the tumour, as shown by retrospective clinical studies, suggesting a role in mammary carcinogenesis.
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PMID:Overexpression and hormonal regulation of pro-cathepsin D in mammary and endometrial cancer. 262 16

The rapid progress in molecular biology has allowed investigators to define some of the basic mechanisms of carcinogenesis. At the molecular level, cellular transformation results from the occurrence of two or three distinct genetic events that uncouple the cell from its normal regulatory mechanisms. One family of genes, the oncogenes, may be particularly important in the process. The aberrant expression of oncogenes, either by mutation or simply by increased transcription, may result in cellular transformation. The genes usually code for growth factors, growth factor receptors or for proteins involved in the transduction of growth signals into the nucleus. Genetic activation causes the cell to continuously sense a message to undergo mitosis, and the cell no longer responds to its normal regulatory signals. The concepts are rapidly moving into the clinical realm as the genetic mechanisms of particular neoplasms have been investigated. The neuroblastoma is the first tumor system in which the biologic characteristics of the tumor were found to be related to a known oncogene; the amplification of the myc gene is an independent marker of the aggressiveness of the tumor. In addition, much progress has been made in defining the specific genetic lesions responsible for retinoblastomas, Wilms' tumors and carcinomas of the colon that arise in patients with familial polyposis coli. As more knowledge accumulates regarding the exact mechanisms through which the proteins encoded by oncogenes affect these carcinomas and others, it may become possible to design pharmacologic agents rationally to hinder their growth selectively.
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PMID:The emerging genetics of cancer. 264 25

The effect of chemical carcinogen N-nitrosodiethylamine (NDEA) was studied in white noninbred male rats in a series of experiments. The animals treated with dopamine receptor agonist (apomorphine) showed statistically significant inhibition of carcinogenesis. Dopamine receptor antagonist (haloperidol) showed a tendency to stimulate the carcinogenesis. Also, the modifying effect of NDEA on behavior stereotypy and aggressiveness of experimental animals was found following apomorphine injection at various dosages. The data obtained are discussed from the point of view of the leading role of ANS in homeostatic regulation of the organism and in carcinogenesis.
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PMID:The role of central dopaminergic processes in chemical carcinogenesis. 653 38

The overview of apoptosis presented here emphasizes cell deletion in the immune system, with particular reference to T- and B-lymphocyte development, and the in vivo and in vitro senescence of human neutrophils. Some biochemical criteria that are used to identify apoptotic cells are described. Pitfalls in using agarose gel electrophoresis as the sole method for the identification of apoptotic cells are discussed. There are multiple modes of cell death that can be identified at the morphologic level. Thus the central role of microscopic methods, and in particular, electron microscopy, as an important tool in the study of cell death mechanisms, is presented. Apoptosis has a protective role against disease and could, a priori, have an important role in either the initiation or progression of cancer. Two paradoxes concerning the relationship of tumor aggressiveness at the clinical level to mitotic activity have been explained by an evaluation of apoptotic index. In the first case, basal cell carcinomas grow slowly but show a high rate of mitosis. Here, the apoptotic rate is quite high, but just below the mitotic rate, thereby accounting for the slow rate of growth. A second instance is follicular lymphoma, which has a low rate of mitosis that is less than that described for reactive germinal centers. However, apoptosis is markedly reduced in follicular lymphomas compared with that seen in reactive germinal centers, thus providing an explanation for the progressive growth of the follicle. We present a brief description of recent work from our laboratory that indicates that apoptosis may play an important role in colon carcinogenesis. We have shown that sodium deoxycholate, the particular bile salt present in highest concentration in the colon, induces apoptosis in the goblet cells of the human colonic mucosa in an in vitro assay. The intriguing finding is that cells of the normal-appearing mucosa of colon cancer patients are resistant to bile salt-induced apoptosis. This suggests a novel hypothesis about the etiologic role of bile salts in colon cancer. The chronic presence of bile salts that accompany a high-fat diet could select for apoptosis-resistant epithelial cells in the colon over time. Thus, a resistance-to-apoptosis bioassay may prove useful as an intermediate biomarker for determining which individuals are at high risk for colon cancer.
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PMID:Role of apoptosis in biology and pathology: resistance to apoptosis in colon carcinogenesis. 757 Oct 81

Microsatellite instability characterizes a sub-set of sporadic colorectal cancers (CRCs) as well as CRCs from patients with hereditary non-polyposis colorectal cancer (HNPCC). In order to clarify when the cells acquire a replication-error phenotype (RER) during colorectal-tumor progression, we examined the incidence of RER in 80 primary tumors and 36 liver metastases at 8 microsatellite loci; 1 mono-, 5 di-, 1 tetra- and 1 pentanucleotide. RER were detected in 20.1% (17/80) of primary tumors, including 5 tumors showing RER at 2 or more loci (RER2), while the incidence of RER in liver metastases (22.2%, 8/36) was almost the same as that in primary tumors, and there was only one RER2 case in metastases. There were 3 cases in which both primary tumors and liver metastases had the same type of RER at the same locus, and there were 2 cases that showed RER in primary tumors but not in liver metastases. In contrast, there was no case in which RER was detected in a metastasis but not in the corresponding primary tumor. The RER phenotype did not show correlation with any clinicopathological parameters of cancer-cell aggressiveness, such as clinical staging, histological grade and survival. These results indicate that a sub-set of CRCs acquire the RER phenotype in the relatively early stages of colorectal carcinogenesis, and that the RER phenotype is not associated with aggressiveness of CRCs.
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PMID:Microsatellite instability in primary and metastatic colorectal cancers. 762 2

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.
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PMID:Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa. 782 4

The recent advances in molecular biology have led to a concept that carcinomas arise from the accumulation of a series of genetic alterations involving activation of protooncogenes and inactivation of tumor suppressor genes. The present study was designed to elucidate that such processes take place in the tumorigenesis of the uterine endometrium as well. The incidence of ras gene mutation, which were mostly composed of the point mutations of k-ras codons 12 and 13, was higher in carcinomas (31%) than atypical hyperplasias (15%), with marginal significance, but has not been associated with aggressiveness of the carcinomas. Thus, k-ras activations may occur as an early event in tumorigenesis. Mutations of tumor suppressor gene, p53, were detected in 24% of carcinomas and 8% of atypical hyperplasia, while they are not statistically different. The p53 mutations were associated with poorly differentiated adenocarcinomas. The most common pattern of the base change detected in endometrial carcinomas was the transition from G:C to A:T. The p53 mutations at CpG sites were frequent, especially at codon 248. Loss of heterozygosity (LOH) was more frequently detected than the mutations and most cases with LOH harbored the mutations, suggesting that allelic loss may precede the mutation in the tumorigenesis of endometrium. Expression of p53 was well correlated with type of the p53 mutation and its overexpression is associated with aggressive clinical behavior, suggesting the possible application of p53 as a prognostic indicator. The other tumor suppressor genes, Retinoblastoma gene (RB) and DCC gene, were also involved in the endometrial carcinogenesis. LOH and abnormal m-RNA of RB were detected in 15% and 33% of carcinomas, respectively, and associated with advanced clinical stage and poorly differentiated adenocarcinomas. LOH of DCC was also detected in some cases while that of APC was not detected. Thus, tumor suppressor genes may also play an important role as later events in carcinogenesis by inactivation mechanism consisting of the loss of one chromosomal allele and/or mutation of the gene in the remaining allele. Human papillomavirus (HPV) DNA type 16 was curiously detected in 5% of cases by both Southern blot and in situ hybridization analyses. Consequently, two third of endometrial carcinomas examined in the present study for ras, p53, RB, DCC, APC and HPV showed abnormality of at least one of these genes. The abnormality of multiple genes may contribute as an etiologic role to multisteps in carcinogenesis of the endometrium.
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PMID:[Genetic alterations and transformations in development and establishment of uterine endometrial carcinomas]. 837 Oct 6


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