Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been thought that squamous severe atypical metaplasia of the bronchus is reliably precancerous. The canine subcutaneous bronchial autograft model for studying the progression of epidermoid carcinogenesis (normal----regular squamous metaplasia----mild, moderate, and severe atypical metaplasia----squamous cell carcinoma) provides evidence that severe atypical metaplasia of the bronchial epithelium is reversible. Among 148 subcutaneous bronchial autografts that had serial sampling of the epithelium and exposure to implants of methylcholanthrene, severe atypical metaplasia was noted in 28 that received only a single implant. During the total carcinogen exposure (median 24.5 months), 9 of 28 (32%) developed squamous cell cancer, and 19 of 28 (68%) regressed toward normal. Severe atypical metaplasia was noted in 34 subcutaneous bronchial autografts that received two or more carcinogen implants: epidermoid cancer developed in 26 of 34 (76.5%), and regression toward or to normal occurred in 8 of 34 (23.5%). Severe atypical metaplasia was not detected in 53 subcutaneous bronchial autografts: 19 that received only a single implant and 34 that received two or more implants. Progression and regression occurred among these subcutaneous bronchial autografts in proportions similar to those found in subcutaneous bronchial autografts wherein severe atypical metaplasia was seen. Among 33 subcutaneous bronchial autografts initially studied after 6 months of exposure to carcinogen, progression to severe atypical metaplasia was seen 3 months later in 19 of 33 that had additional exposure; in the same interval regression of epithelial abnormalities occurred in 14 of 33 subcutaneous bronchial autografts that had no additional exposure (p less than 0.05). We have presented evidence that severe atypical metaplasia includes at least three cell populations: one committed to cancer without further stimulus, one that regresses despite further carcinogen exposure, and one that requires additional carcinogen to progress to cancer. At least in this model, severe atypical metaplasia is not inexorably precancerous. The subcutaneous bronchial autograft model is suitable for seeking biologic indicators of irreversibility.
J Thorac Cardiovasc Surg 1991 May
PMID:Variable regression of experimental bronchial preneoplasia during carcinogenesis. 202 36

The progression of preneoplasia into lung cancer can be serially studied in a new canine model that is simpler and more cost effective than previously reported methods of orthotopic endobronchial carcinogenesis. Short segments of bronchus, obtained by pneumonectomy, were placed on the back of 10 dogs in the form of subcutaneous bronchial autografts. These autografts (12 to 14 per dog) became vascularized and lined with normal respiratory epithelium. Four to 12 weeks after autograft implantation, 10% methylcholanthrene in crystalline form was put into 57 autografts and 10% methylcholanthrene in a silicone polymer sustained-release implant was placed into 54 autografts. Ten autografts without carcinogen (one per dog) served as controls. Serial samplings of each autograft during 9 to 97 weeks of carcinogen exposure showed the neoplastic progression from normal bronchial cells to invasive cancer through stages such as atypical squamous metaplasia and carcinoma in situ. To date, cancers have been histologically proved in 60 autografts; 36 were induced by implants and 24 by the crystalline form. Thirty-nine cancers were epidermoid, and the remainder were either adenocarcinomas (n = 3) or poorly differentiated spindle cell cancers (n = 18). The sustained-release implant method resulted in larger autografts with a greater tendency to progress to cancer than the crystalline carcinogens (p greater than 0.025). Therefore, the sustained-release implant is now considered the preferred method. Measurement of nuclear deoxyribonucleic acid by image analysis of nine histologic cancers demonstrated hyperploidy. Deoxyribonucleic acid from the L1 repeated sequence family was demonstrably hypomethylated in spindle cell tumors. Curettement of individual autografts yielded sheets of respiratory epithelium from which 43.5 to 409.5 micrograms of deoxyribonucleic acid was isolated. For the first time, deoxyribonucleic acid from each stage of the neoplastic progression in non-small cell lung cancer is available in adequate quantities for serial biochemical and therapeutic analysis.
J Thorac Cardiovasc Surg 1988 Apr
PMID:Non-small cell lung cancer in autogenous subcutaneous bronchial grafts in dogs. 283 61

A canine model of squamous cell lung cancer has been developed through studies with 110 dogs exposed by 11 focal endobronchial regimens to chemical carcinogens: benzo(a)pyrene, nitrosomethylurea, methylcholanthrene, and dimethylbenzanthracene. A combination of nitrosomethylurea and benzo(a)pyrene caused the first invasive cancer after 5.5 years. Toxic side-effects resulted from either nitrosomethylurea or high-dose dimethylbenzanthracene given by bronchial submucosal injection and from adjuvant immunosuppression with azathioprine and corticosteroids. Four regimens in 58 dogs caused 31 cancers, including five T1-2 N0 M0 cancers, 17 metastasizing carcinomas, and nine carcinomas of lesser stages. The following regimens caused cancers: sequential benzo(a)pyrene, nitrosomethylurea, and yttrium 91; benzo(a)pyrene and topical nitrosomethylurea; low-dose dimethylbenzanthracene; high-dose methylcholanthrene. The most suitable regimen to date has been 30 mg of methylcholanthrene given by submucosal injection every 2 to 3 weeks; this produced cancers at preselected sites within 2 years of first exposure in eight of 10 dogs. The neoplastic continuum has followed a predictable, reproducible sequence that regularly began with epithelial hyperplasia. Squamous metaplasia occurred in 6 to 18 weeks; it was followed by progressive squamous atypia. The interval until invasive cancer developed varied with the regimen employed; it was about 20 months with methylcholanthrene. Serial cytologic specimens, studied by image analysis, revealed progressive increase in mean total cellular deoxyribonucleic acid content from diploid in normal cells to greater than tetraploid in cancer cells (p less than 0.01). We have recently been successful with serial passage of four canine lung cancers from four to twelve transplant generations in nude mice. There is now a predictable large animal model of squamous cell lung carcinoma at preselected site(s) that closely resembles human lung cancer. The preneoplastic period is short enough to be fiscally defensible, but long enough to permit study of the biologic changes during endobronchial carcinogenesis.
J Thorac Cardiovasc Surg 1986 Nov
PMID:Endobronchial carcinogenesis in dogs. 377 44

To investigate whether sex hormone receptors exist in the resected non-small-cell lung cancer in human beings and to determine a link between the pulmonary carcinogenesis and the sex receptor status of the lung cancer tissue, we reviewed the case histories of 64 patients who underwent resectional therapy for non-small-cell lung cancer between 1988 and 1990 (38 men and 26 women, mean age 65 years). Mouse monoclonal immunoglobulin G antibodies were used for immunohistochemical detection of estrogen receptors and progesterone receptors in the acetone-fixed specimen. The control group consisted of normal lung tissue from the patients with and without bronchogenic carcinoma and breast cancer tissue from the patients with estrogen and progesterone receptor immunoreactivity. No evidence of estrogen and progesterone receptor immunoreactivity was present in the normal lung tissue. All but two patients had immunoreactivity (97%) for estrogen receptors in the lung cancer tissue (p < 0.001). The differences for sex and for histologic subtypes were not statistically significant. Observed actuarial survival at 3 years was 83% for all patients with estrogen receptor immunoreactivity: 94% for women and 75% for men (p < 0.05). We found no correlation between the hormone receptor status and the type, clinical features, or prognosis of the non-small-cell lung cancer. We conclude that an abundance of estrogen receptors is hosted only in cancerous tissue, not in normal pulmonary tissue. Improved identification and definition of estrogen receptors in the nontarget lung cancer tissue offer a possibility of antiestrogen therapy for patients with advanced bronchogenic carcinoma.
J Thorac Cardiovasc Surg 1994 Jul
PMID:Sex hormone receptors in non-small-cell lung cancer in human beings. 802 59

We had previously identified p53 mutations in Barrett's esophagus and therefore began a multiinstitutional study to determine their significance as a marker for malignancy. Ninety-eight patients from four institutions were studied. Forty-eight patients (37 men and 11 women, mean age 56.2 years) had Barrett's esophagus with metaplasia or dysplasia but no evidence of malignancy at a mean follow-up of 2.2 years. Barrett's esophagus was classified as metaplasia with no evidence of dysplasia in 32 patients, as low-grade dysplasia in 13, and as high-grade dysplasia in three. The other 50 patients (46 men and four women, mean age 60.2 years) had adenocarcinoma arising in Barrett's esophagus. Tissues from normal stomach or esophagus, tumor, and Barrett's esophagus were obtained for deoxyribonucleic acid analysis by endoscopic biopsy from patients with Barrett's esophagus or cancer or during operations on some patients with Barrett's cancer. Exons 5 through 9 of the p53 gene were studied for mutations by single-strand conformational polymorphism analysis after polymerase chain reaction amplification. Mutations detected by single-strand conformational polymorphism analysis were confirmed by deoxyribonucleic acid sequencing. None of the tissue samples from patients with Barrett's esophagus alone and no dysplasia or low-grade dysplasia had any p53 mutations, but one of the three patients with high-grade dysplasia and no evidence of invasive malignancy did have a p53 mutation. Of the 50 patients with Barrett's cancer, however, 23 (46%) had p53 mutations in Barrett's epithelium, tumors, or both. Twenty of these patients had p53 mutations in the tumor only (n = 16) or in both tumor and Barrett's epithelium (n = 4), suggesting that the mutation plays a direct role in carcinogenesis. Mutations in Barrett's epithelium were found in one patient in the group without malignancy and in seven patients with cancer (one with no dysplasia, two with low-grade dysplasia, and five with high-grade dysplasia). In three patients with cancer, mutations occurred only in Barrett's epithelium, suggesting that such mutations may also be a marker for genomic instability. Mutations were predominantly found in exons 5, 7, and 8, and transitions from guanine to adenine were the most frequent changes. Mutations of p53 are clearly involved in the pathogenesis of Barrett's cancer for a subset of patients (46%), and the fact that we could detect mutations in premalignant Barrett's epithelium supports the hypothesis that p53 mutations may be a useful marker for patients at increased risk for development of invasive cancer.
J Thorac Cardiovasc Surg 1996 Feb
PMID:Mutations of p53 in Barrett's esophagus and Barrett's cancer: a prospective study of ninety-eight cases. 858 5

The preclinical evidence for a potential influence of calcium channel blockers (CCBs) on carcinogenesis is discussed in the light of a broad database from rodent carcinogenicity studies as well as literature data. In all bioassays performed in rats and mice on the dihydropyridine CCBs--nifedipine, nimodipine, nisoldipine, and nitrendipine--no evidence was found for a carcinogenic potential of these compounds. Calcium is an essential intracellular signal for cell proliferation and apoptosis. The crucial role of increased cell proliferation in all stages of carcinogenesis is well documented. Some indirect experimental evidence also points to a role of defective apoptosis in tumor promotion. CCBs uniformly inhibit cell proliferation, whereas the influence of CCBs on apoptosis is inconsistent, resulting in an inhibition or increase in apoptosis dependent on cell type. Accordingly, antitumorigenic effects of CCBs have been reported based on their antiproliferative action. A tumor-promoting effect of CCBs based on inhibition of apoptosis, however, remains purely speculative and, in fact, can be denied based on the results of in vivo bioassays. It is therefore concluded that there is no preclinical evidence that should give rise to concern over the carcinogenic potential of dihydropyridine-type CCBs.
Cardiovasc Drugs Ther 1998 May
PMID:Calcium channel blockers and the risk of cancer: a preclinical assessment. 965 74

Prebiotics is a recent novel food concept that includes food ingredients that are not digested in the human upper intestinal tract and hence arrive in the colon where they are selectively fermented by a limited number of colonic bacteria. Amongst these are bifidobacteria and lactobacilli, which are considered indicators of a well-balanced intestinal flora. Probiotics are bacteria that, while passing through the intestine, may exert specific beneficial effects on the host's physiology. In general, probiotics are members of the group of the lactic acid-producing bacteria. By means of a variety of experimental models it was demonstrated that prebiotic carbohydrates and probiotics consistently reduced processes of carcinogenesis and tumorigenesis. Synergistic chemopreventive actions were observed with combinations of the two, which together are called synbiotics. One of the most important causes of death in the ageing western population is colon cancer, which is typically associated with a western-style diet. On the basis of the available experimental data, an EU-funded research project (the SYNCAN project QLK1-1999-00346) was set up to evaluate whether synbiotics and prebiotics can be added to food without detriment to (and hopefully eventually improving) organoleptic properties. They are, as such, a good vector for importing nutritionally interesting properties into our diet.
Nutr Metab Cardiovasc Dis 2001 Aug
PMID:Evaluation in human volunteers of the potential anticarcinogenic activities of novel nutritional concepts: prebiotics, probiotics and synbiotics (the SYNCAN project QLK1-1999-00346). 1189 62

Functional Food Ingredients Against Colorectal Cancer is one of the first European Union funded Research Projects at the cross-road of functional genomics [comprising transcriptomics, the measurement of the expression of all messengers RNA (mRNAs) and proteomics, the measurement of expression/state of all proteins], nutrition and human health. The goal of Functional Food Ingredients Against Colorectal Cancer is to develop a colon epithelial cell line-based screening assay for nutrients with presumed anti-colorectal carcinogenic properties. Genes involved in colon carcinogenesis are identified at the RNA and protein level, using a variety of methods (subtractive hybridisation, DNA microarray, proteomics) in combination with models for colorectal cancer development (human biopsies, rat model for colorectal carcinogenesis, colorectal cancer epithelial cell lines). Secondly, colorectal cancer epithelial cell lines are selected, in terms of their capacity to undergo gene/protein expression changes representing different phases in the colorectal carcinogenesis. Thirdly, these cell lines are used to determine the effects of nutrients with presumed anti-carcinogenic properties (e.g. resveratrol, flavonoids) on functional genomics-derived endpoints. Once validated against the effects of these nutrients in in vivo animal models and classical biomarkers for colorectal carcinogenesis, these cell line models combined with functional genomics represent useful tools to study colorectal carcinogenesis and screen for nutrients with anti-carcinogenic properties.
Nutr Metab Cardiovasc Dis 2001 Aug
PMID:Functional food ingredients against colorectal cancer. An example project integrating functional genomics, nutrition and health. 1189 63

A 69-year-old Japanese man undergoing total gastrectomy for multiple gastric ulcers at age 46 was found endoacopically to have multiple esophageal cancers in the upper, mid, and lower esophagus. Esophageal mucosa associated with tumors was replaced with columnar epithelium. He underwent total esophagectomy combined with laryngectomy, pharyngectomy, and lymph node dissection using the large bowel for reconstruction. The resected esophagus had multiple cancers, including well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and small-cell carcinoma. Barrett's mucosa consisted mainly of specialized columnar epithelium while both junctional and fundic Barrett's epithelium was observed partially but not clearly. This case is indicative of the high and totipotential carcinogenetic risk of Barrett's epithelium and the relationship between duodenal content reflux and esophageal carcinogenesis after total gastrectomy.
Jpn J Thorac Cardiovasc Surg 2003 Jun
PMID:Coexistent multiple adenocarcinomas arising in Barrett's esophagus 23 years after total gastrectomy and esophageal small cell carcinoma. 1283 Dec 43

Lung cancer is the leading cause of cancer-related death in the world. Tobacco is an addictive agent producing carcinogenic effects that have been extremely difficult to prevent or detect in a curable stage. Important randomized controlled studies have been published in "healthy" smokers (primary prevention); patients with early lesions, such as mucosal dysplasia/metaplasia (secondary prevention); and those who have already had definitive treatment for their first tobacco-related malignancy (tertiary prevention). To date, the results have been generally disappointing. It is critical to remember that lung cancer is usually diagnosed decades after the patient has begun or even stopped smoking. We must intervene with more effective agents or combinations of agents and do it earlier in the process of carcinogenesis. Approximately 10% of patients with lung cancer either never smoked or only were "passive" smokers due to their environment, workplace. These "never-smokers" may actually benefit from retinoids, while current smokers have not benefited from alpha-tocopherol, retinal, N-acetylcysteine, or isotretinoin. Smokers are actually harmed by the concurrent use of beta-carotene. We now have unprecedented knowledge regarding the control of cellular growth and senescence. New diagnostic tools also allow detection of smaller lesions. We must use all our knowledge of the cancer biology, new risk models, more refined intermediate markers, and modern detection tools to focus more clearly on the pathology of lung cancer and design research to ask more probing and relevant questions so we can begin to put an end to the worldwide scourge of this terrible killer.
Semin Thorac Cardiovasc Surg 2003 Oct
PMID:Nonsmall-cell lung cancer: chemoprevention studies. 1471 Mar 83


1 2 3 Next >>