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)

Colorectal cancer is the third most incident cancer in the United States and is second only to lung cancer as a cause of cancer-related mortality. Colorectal cancer develops through a multistep process characterized by histopathological precursor lesions and molecular genetic alterations. This sequential process of tumorigenesis provides opportunities for the development and testing of both primary and secondary prevention strategies. This review focuses on chemoprevention, which is defined as the use of natural or synthetic agents to reverse the process of carcinogenesis. Epidemiological studies have consistently shown that chronic intake of nonsteroidal anti-inflammatory drugs (NSAIDs), principally aspirin, can reduce the incidence of colorectal adenomas and carcinomas. Evaluation of NSAIDs, including newer selective cyclo-oxygenase-2 inhibitors, in carcinogen-induced and genetically manipulated animal models of colorectal cancer demonstrates that these drugs are effective chemopreventive agents. In humans, the NSAID sulindac has been studied in familial adenomatous polyposis patients and was found to regress colorectal adenomas in a placebo-controlled trial. More recently, the selective cyclo-oxygenase-2 inhibitor Celebrex was also shown to be effective in familial adenomatous polyposis and was approved by the Food and Drug Administration as a adjuct to usual care in these patients. NSAIDs, as well as other chemopreventive agents, are currently being studied in patients at increased risk of colorectal cancer, including those with sporadic adenomas. The outcome of these studies has the potential to impact patient management practices. However, chemopreventive agents cannot be recommeded at present for average-risk individuals or for those with sporadic colorectal neoplasia. In addition to demonstrating efficacy, chemopreventive agents must be safe and well tolerated for chronic administration and should be relatively cost-effective. Although still in its infancy, the field of chemoprevention is an exciting and rapidly advancing area of investigation. Chemopreventive strategies, if effective, offer the promise of producing a paradigm shift in our current approach to colorectal cancer.
 ...
PMID:Chemoprevention of colorectal cancer. 1180 36

The multistep process of carcinogenesis, which can take many years, provides many opportunities for intervention to inhibit disease progression. Effective chemoprevention agents may reduce the risk of cancer by inhibiting the initiation stage of carcinoma through induction of apoptosis or DNA repair in cells harboring mutations, or they may act to prevent promotion of tumor growth. Similarly, chemoprevention may entail blocking cancer progression to an invasive phenotype. Over the past decade, in vitro, preclinical, and clinical data have supported the hypothesis that cyclooxygenase (COX)-2 plays a central role in oncogenesis and that treatment with COX-2 inhibitors offers an effective chemoprevention strategy, as exemplified by the activity of celecoxib (Celebrex) in familial adenomatous polyposis. These COX-2 data have contributed to initiation of clinical trials testing COX-2 inhibitors for the chemoprevention of a wide variety of cancers that overexpress COX-2.
 ...
PMID:Current application of selective COX-2 inhibitors in cancer prevention and treatment. 1210 79

Selective inhibition of eicosanoid synthesis is thought to have effects on carcinogenesis in lung and colon cancer. However, it is still unknown whether pancreatic cancer might also be influenced. Therefore we evaluated the impact of selective cyclooxygenase-2 inhibitor Celebrex and selective 5-lipoxygenase inhibitor Zyflo on liver metastasis in a solid model of pancreatic adenocarcinoma in Syrian hamster. In week 33, the animals were sacrificed and incidence of pancreatic carcinomas and number and size of liver metastases were determined. Activities of antioxidative enzymes (GSHPX/SOD) and concentrations of products of lipidperoxidation were measured in liver metastases and non-metastatic hepatic tissue. The incidence (54.5 vs. 100%), number (3.17 +/- 0.98 vs. 6.75 +/- 0.71) and size (2.67 +/- 1.97 vs. 11.75 +/- 1.98 mm2) of liver metastases were decreased by combined therapy of Zyflo and Celebrex (P < 0.05). Furthermore, activities of GSHPX ([73.77 +/- 5.67]*10(5) vs. [15.49 +/- 4.02]*10(5) U/mg prot.; P < 0.05) and SOD (474.92 +/- 108.8 vs. 127.89 +/- 38.75 U/mg prot.; P < 0.05) were increased, while lipidperoxidation (0.31 +/- 0.08 nmol/mg prot. vs. 1.54 +/- 0.55 nmol/mg prot.; P < 0.05) was decreased by combination therapy, in non-metastatic hepatic tissue. Moreover, combined therapy increased lipidperoxidation in liver metastases (0.47 +/- 0.09 vs. 1.95 +/- 0.12 nmol/mg prot.; P < 0.05). Thus, a combination of Celebrex and Zyflo might be a new concept to decrease tumour growth in liver metastases in advanced pancreatic cancer.
 ...
PMID:Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters. 1255 73

Overexpression of cyclooxygenase-2 (COX-2) is frequently present in lung cancer and may play a significant role in carcinogenesis, invasion, and metastasis. It has been associated with shortened survival in patients with resected early-stage adenocarcinoma of the lung. COX-2 inhibition decreases tumor cell proliferation in vivo and has been shown to enhance tumor radiosensitivity. Additionally, COX-2 inhibition may protect normal pulmonary tissue from radiation fibrosis. Clinical studies are under way to assess the potential benefits and risks of COX-2 inhibition in the treatment of lung cancer. The rationale for COX-2 inhibitors in the treatment of lung cancer will be reviewed. The results of a phase II study assessing the acute toxicity of concurrent celecoxib (Celebrex) and thoracic irradiation in patients with non-small-cell lung cancer (NSCLC) are reported, and an ongoing Radiation Therapy Oncology Group study using celecoxib and concurrent radiation therapy for NSCLC in patients with intermediate prognostic factors is reviewed.
 ...
PMID:Celecoxib and radiation therapy in non-small-cell lung cancer. 1568 27

Selective inhibition of eicosanoid synthesis seems to decrease carcinogenesis, however, the effect on liver metastasis in pancreatic cancer is still unknown. Ductal pancreatic adenocarcinoma was chemically induced by weekly injection of N-nitrosobis-2-oxopropylamine (BOP) in Syrian hamster. Animals received selective inhibition of cyclooxygenase-2 (Celebrex) and 5-lipoxygenase (Zyflo). In week 33, hamsters were sacrificed and incidence of pancreatic carcinomas as well as liver metastases were examined. Furthermore, size and number of liver metastases per animal were determined and concentration of PGF1alpha, PGE2 and leukotrienes was measured in hepatic and pancreatic tissue. Combined therapy (Celebrex+Zyflo) significantly decreased incidence, number and size of liver metastases. Furthermore extra- and intrametastatic concentration of PGE2 was reduced by this treatment in hepatic tissue. Single Cox-2-inhibition (Celebrex) decreased intrametastatic hepatic PGF1alpha and PGE2 concentration while PGF1alpha concentration was reduced in non-metastatic liver (nml). Moreover 5-LOX-inhibition (Zyflo) decreased intrametastatic PGE2 concentration as well as PGF1alpha and PGE2 in nml. In pancreatic carcinomas highest LT-concentration was found after combined treatment and this therapy group was the only one revealing a significantly higher amount of LTs in carcinomas compared to tumour-free tissue. Hepatic LT-concentration was significantly lower in the control groups than in nml of the tumour groups. Combination of Cox-2-inhibition and 5-Lox-inhibition might be a suitable adjuvant therapy to prevent liver metastasis in human ductal pancreatic adenocarcinoma.
 ...
PMID:Effects of selective COX-2 and 5-LOX inhibition on prostaglandin and leukotriene synthesis in ductal pancreatic cancer in Syrian hamster. 1596 50

The present experiment aims to evaluate tumor suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2) celecoxib (Celebrex, Pfizer) administered alone and in combination with melatonin in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley female rats. Celecoxib was administered daily at a concentration of 1.666 g/kg diet to two groups during 20 weeks (starting a week before first NMU application). A combination of celecoxib and melatonin applied in drinking water (20 microg/ml drinking water), daily from 15:00 to 08:00 hours was administered to the second group. The anticarcinogenic effects of chemopreventive drugs were compared with control (NMU) animals. Celecoxib administration decreased mammary tumor incidence (by 24%), while combination of celecoxib and melatonin decreased tumor incidence even more significantly (-30%). Significant decrease in tumor frequency per group was recorded in both groups with chemoprevention: celecoxib alone (-54%) and combination of celecoxib and melatonin (-64%). Celecoxib significantly influenced tumor frequency per animal in the group with combination of both protective substances (-52%). Celecoxib administration resulted in prolonged latency by 3%, and by 13% in the group with combination of both protective substances. These results confirm preventive effects of celecoxib in induced rat mammary carcinogenesis. The administration of isolated MEL had only lesser effect, but in the combination with CELE revealed some potentiating influence in mammary carcinogenesis inhibition. The present study is the first to prove efficacy of the above-mentioned celecoxib and melatonin intake. Our results point to the need for a deeper analysis of coxib efficacy in human carcinogenesis.
 ...
PMID:Celecoxib and melatonin in prevention of female rat mammary carcinogenesis. 1930 29