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)

Recent epidemiologic evidence indicates that Helicobacter pylori infection increases the risk for gastric carcinoma. Infection with H. pylori leads to chronic gastritis, which usually persists for life unless treated with antimicrobial drugs. Because the great majority of gastritis patients never develop neoplasias, research concerning those who do may provide clues about carcinogenesis. In affluent populations, H. pylori infection leads to nonatrophic gastritis, predominantly involving diffusely the antrum (diffuse antral gastritis), the basic lesion seen in patients with duodenal ulcer, which has not been associated with increased risk for gastric carcinomas. In populations with high gastric cancer risk, H. pylori infection is associated with multifocal atrophic gastritis, which frequently advances to intestinal metaplasia, occasionally to dysplasia, and rarely to carcinoma. H. pylori infection increases the rate of proliferation of the gastric epithelial cells and decreases the gastric secretion of ascorbic acid, processes that may modulate the process of carcinogenesis. Infection with H. pylori is characterized by infiltration of lymphocytes, polymorphonuclear leukocytes, and macrophages in the gastric mucosa. There is considerable interest in investigating oxygen radicals originating in white blood cells and the possibility that they induce mutations with carcinogenic potential in the gastric epithelium.
 ...
PMID:Helicobacter pylori and gastric carcinogenesis. 776 38

Infections with high-risk strains of human papillomaviruses (HPVs) and with herpes simplex virus type 2 (HSV 2), as well as inactivation of the p53 tumor suppressor gene, are important cofactors in cervical carcinogenesis. We analyzed 41 paraffin-embedded cervical intraepithelial lesions, including 25 cases of low-grade cervical intraepithelia neoplasia (CIN), and 16 cases of high-grade CIN for the presence of HPV 16/18 and HSV 2 genomic sequences and for the nuclear accumulation of the p53 protein. HPV 16 DNA was detected in 24.% of low-grade CINs and in 43.7% of high-grade CINs. HPV 18 was found only in 8.% of low-grade CINs. None of the cases tested scored positive for HSV 2 DNA. Nuclear accumulation of p53 was found in 4% of low-grade CINs, and in 31.2% of high-grade CINs, including 57.1% of the lesions that were positive for HPV 16. These results indicate that HPV 16 infection was over sixfold more common than HPV 18 infection and that p53 overexpression was significantly associated with high-grade lesions.
 ...
PMID:p53 expression and genetic evidence for viral infection in intraepithelial neoplasia of the uterine cervix. 783 72

Infection of epithelial cells with human papillomavirus is an important early event in the development of cervical dysplasia. However, progression to overt malignancy appears dependent upon further genetic and/or epigenetic events. We have recently developed methodologies for the simultaneous analysis of loss of heterozygosity (LOH) at multiple PCR-based microsatellite loci using semiautomated fluorescent DNA sequencing technology to determine the locations of tumor suppressor genes which are inactivated during tumor progression. While examining 30 microsatellite loci for LOH on chromosomes 3p, 4, and 11q, we detected novel tumor-specific alleles indicative of microsatellite instability (MI). The methodology allowed rapid and accurate comparison of over 3000 genotypes from 89 primary tumors and 10 cervical carcinoma-derived cell lines and showed that five tumors (5.6%) and one human papillomavirus-negative cell line, C33A, had genetic features consistent with a replication error (RER+) phenotype as defined by MI at two or more loci. In each of the RER+ tumors, LOH was also observed at one or more loci on each of the three chromosomes examined. These findings suggest that defects in DNA repair-associated genes are rarely acquired and do not supersede allelic loss during cervical carcinogenesis. In addition, the semiautomated multiplex approach has proven unequivocal in the detection and interpretation of MI and should greatly accelerate the rapidity and accuracy of analysis of such defects in tumors. Moreover, the number of loci that can be relatively easily examined in this way will also allow a detailed statistical consideration of the importance of such events.
 ...
PMID:Analysis of replication error (RER+) phenotypes in cervical carcinoma. 864 Aug 35

Infection with the liver fluke, Opisthorchis viverrini, is a causative agent of cholangiocarcinoma. One possible contributing factor in this carcinogenesis is the chronic, local generation of nitric oxide by inflammatory cells expressing inducible nitric oxide synthase and the production of N-nitroso compounds via the reaction between amines and nitrosating agents derived from nitric oxide. Our previous studies provided evidence that nitric oxide synthesis is elevated during human liver fluke infection. Here we present data on the same sample of men which definitively demonstrates increased nitrosation of proline and thioproline (thiazolidine-4-carboxylic acid) among infected men compared to uninfected control subjects on a low nitrate diet. This difference was specifically abolished by co-administration of ascorbic acid with proline and by elimination of parasites by praziquantel treatment. Multivariate statistical models demonstrate the importance of salivary thiocyanate levels to variation in the nitrosation of proline among uninfected individuals, but not among those with current fluke infection. This suggests that considerable generation of nitrosating agents (N203/N204) in infected people may be occurring via oxidation of arginine by nitric oxide synthase in inflamed tissue which is thiocyanate insensitive. Analyses revealed positive associations between N-nitrosoproline excretion and nitrate/nitrite levels in urine, plasma and saliva and with usual alcohol intake; with variation in these trends between groups. In conclusion, we have confirmed the relationship between O.viverrini infection and enhanced endogenous nitrosation, showing evidence of its extragastric site. New information is also provided on the determinants of N-nitrosamino acid excretion in men on a controlled low nitrate diet without smoking, conditions which reduce exogenous sources of nitrosating agents.
Carcinogenesis 1996 May
PMID:Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection. 864 Sep 16

Infection with HPV 16 is believed to be a major risk factor for cervical cancer. To correlate HPV 16 infection and carcinogenesis in the cervix, we examined by ELISA 326 sera from healthy females and patients with cervical cancer, cervical intraepithelial neoplasia, or dysplasia, for the presence of IgG antibodies against HPV 16 virion protein L2 expressed in Escherichia coli. Whereas 2 of 208 were positive in the healthy females, 4 of 23 and 6 of 90 were positive in the patients with cervical cancer and dysplasia, respectively. The findings indicate that infection with HPV 16 is related to cancer and dysplasia of the cervix. The anti-L2 antibody did not occur coincidentally with the antibodies against the HPV 16 early proteins E4 and E7, which are specifically but independently associated with patients with cervical cancer.
 ...
PMID:Occurrence of the antibody against human papillomavirus type 16 virion protein L2 in patients with cervical cancer and dysplasia. 868 15

Helicobacter pylori is firmly established as a human pathogen; it fulfils all of Koch's postulates as the infectious agent causing chronic, active (type B) gastritis. Infection is strongly associated with duodenal and gastric ulcer. Recently, gastric mucosal-associated lymphoid tissue lymphoma has been successfully treated by curing H. pylori infection. Because of the evidence that the organism causes chronic gastritis and an increased risk of gastric cancer, it has been classified as a category 1 carcinogen by the World Health Organization. However, the overwhelming majority of people infected have no symptoms. Current eradication therapy is not ideal; there are treatment failures and substantial side effects. As a result, therapy should be reserved for people with clinical symptoms and complications. The infection, if present, should be treated in patients who have endoscopic evidence of mucosal ulcers in the stomach or duodenum. Current evidence does not support treating the infection to prevent gastric carcinogenesis or to alleviate symptoms of abdominal discomfort in the absence of peptic ulcers.
 ...
PMID:Why guidelines are required for the treatment of Helicobacter pylori infection in children. 888 75

Infection with hepadnaviruses and exposure to aflatoxin B1 (AFB1) are considered major risk factors in the development of hepatocellular carcinoma (HCC) in humans and in animals. A high rate of mutations in the p53 tumor suppressor gene in hepatocellular carcinomas of predominantly hepatitis B virus (HBV) carrier patients has been recently related to dietary aflatoxin. Another member of the hepadnavirus family, the woodchuck hepatitis virus (WHV), infects woodchucks in a manner similar to that of HBV in humans. Therefore, it was of particular interest to determine whether the p53 gene in woodchuck HCCs associated with hepadnavirus infection and with exposure to AFB1 is affected in the same manner as in human HCCs. By direct PCR-sequencing, we analyzed exons 4-9 of the p53 gene in 13 HCCs from 12 woodchucks (two uninfected, ten WHV carriers). Six WHV carrier and two uninfected woodchucks were treated with AFB1. None of the analyzed HCC samples exhibited mutations, either in p53 gene exons 4-9, or in splicing donor-acceptor sites. The present data are consistent with our previous study that indicated a low rate of p53 mutations in HCCs of AFB1-treated ground squirrels, either infected or not infected with ground squirrel hepatitis virus, and in WHV carrier woodchucks not exposed to AFB1. Overall, our findings indicate that in woodchucks and in ground squirrels exposure to aflatoxin may affect the development of p53 mutations less than in humans.
Carcinogenesis 1996 Dec
PMID:Absence of mutations in the p53 tumor suppressor gene in woodchuck hepatocellular carcinomas associated with hepadnavirus infection and intake of aflatoxin B1. 900 7

Infection of the human cervix with certain papillomavirus subtypes is associated with the development of neoplastic squamous lesions that can progress to overt cervical malignancies. Recently, multistage squamous carcinogenesis has been achieved in K14-HPV16 transgenic mice, wherein expression of the human papillomavirus (HPV) type 16 early genes is targeted to basal squamous epithelial cells by regulatory elements of the human keratin-14 (K14) promoter. Immunostaining of the endothelial marker vWf revealed a parallel upregulation of angiogenesis during the early neoplastic stages in both human cervix and the epidermis of K14-HPV16 transgenic mice. Moreover, high-grade premalignant lesions and cancers in humans and transgenic mice were characterized by an additional increment in the number of new capillaries and close apposition of the microvasculature to the overlying neoplastic epithelium. Expression of the potent angiogenic factor VEGF was progressively up-regulated during carcinogenesis in both species, correlating with the increased density and altered distribution of the microvasculature. Thus, angiogenesis occurs during the premalignant stages of squamous carcinogenesis in both human cervical disease and a relevant transgenic model and may be controlled by similar molecular mechanisms in both species. These results validate the use of the transgenic model to elucidate the role of angiogenesis during HPV-associated neoplastic progression.
 ...
PMID:Cross-species comparison of angiogenesis during the premalignant stages of squamous carcinogenesis in the human cervix and K14-HPV16 transgenic mice. 910 16

Recent advances in molecular biology have demonstrated that multistep genetic alterations are involved in the carcinogenesis of human colorectal cancer and that alteration of the p53 gene by mutation, deletion, or rearrangement is a major factor in this process. Human gene therapy has become a reality with the development of effective techniques for delivering the gene to the target cells. The efficacy of gene therapy for various types of genetic disease now being evaluated in clinical trials. These findings led us to develop a novel gene therapeutic strategy for human colorectal cancer that could replace the abnormal p53 gene using a recombinant, replication-defective adenoviral vector (termed Adp53). Infection with Adp53 induced rapid apoptotic cell death in DLD-1 and LoVo human colorectal cancer cell lines differing in their p53 status. Treatment with cisplatin following infection with Adp53 significantly suppressed the growth of WiDr colorectal cancer cells compared to single treatments alone. Thus restoration of wild-type p53 function exhibited an antitumor effect by inducing apoptosis as well as by markedly enhancing the effect of common chemotherapeutic agents in human colorectal cancer cells. In addition, Adp53 infection was antiangiogenic in SW620 human colorectal cancer cells. The application of this technology to human cancer therapy is now in progress. The article reviews recent highlights in this rapidly evolving field.
 ...
PMID:[Molecular surgery for human colorectal cancer with tumor suppressor p53 gene transfer]. 974 29

Genetic and epigenetic alterations in oncogenes, tumor suppressor genes, cell adhesion molecules, telomere and telomerase activity as well as genetic instability at several microsatellite foci are responsible for multistep process of human stomach carcinogenesis. The scenario of these alterations found in gastric cancer differs depending on the two histological types, indicating that different genetic pathways exist for well differentiated or intestinal type and poorly differentiated or diffuse type gastric cancers, even though both types of gastric cancer may arise from epithelial "stem cells" which express human telomerase reverse transcriptase (hTRT) and telomerase activity. Infection with Helicobacter pylori, which evidently causes the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS), may be a strong trigger for "stem cell" hyperplasia in intestinal metaplasia, followed by telomere reduction and increase telomerase activity as well as hTRT overexpression. They may precede DNA replication error, DNA hypermethylation, CD44 abnormal transcript and p53 mutations, all of which occur in at least 30% of intestinal metaplasia as early events of multistep pathogenesis of well differentiated type gastric cancer.
 ...
PMID:Molecular mechanism of human stomach carcinogenesis implicated in Helicobacter pylori infection. 978 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>