New Abstracts 4/01/02 - 4/14/02

New Abstracts of interest from a MEDLINE search (colon OR colorectal OR chemoprevention) AND cancer.

COX-2

4/16/02 NSAID inhibition of GI cancer growth: clinical implications and molecular mechanisms of action Am J Gastroenterol 2002 Mar;97(3):542-53 PMID: 11922545 The precise mechanisms by which NSAIDs exert their chemopreventive effects are not fully explained, but likely involve inhibition of cyclo-oxygenase, the enzyme that converts arachidonic acid to prostaglandins. Two isoforms of this enzyme, cyclo-oxygenase 1 (COX-1) and COX-2, have been identified. COX-2 is absent in normal mucosa but is overexpressed in colonic, gastric, and esophageal cancers, as well as their precursor lesions. The inhibition of COX-2 through either pharmacological agents or gene deletion results in suppression of colonic polyp formation. NSAIDs reduce colonic, gastric, and esophageal cancer cell growth, in part, by inducing apoptosis. However, the antineoplastic effects of NSAIDs may be partly independent of their ability to inhibit COX-2. The mechanisms involved in the antineoplastic actions of NSAIDs include inhibition of angiogenesis (essential for delivery of oxygen and nutrients to a growing tumor), induction of apoptosis (which is usually reduced in cancer cells) by stimulation of proapoptotic genes, and direct inhibition of cancer cell growth by blocking signal transduction pathways responsible for cell proliferation

4/16/02 New Strategies for Colorectal Cancer Prevention and Treatment. World J Surg 2002 Apr 15;26(7) PMID: 11948369 Emerging data have implicated cyclooxygenase-2 (COX-2) and prostanoid production in the pathogenesis of colorectal carcinoma. Several reports indicate a close relation between the intake of nonsteroidal antiinflammatory drugs (NSAIDs) and a decreased risk for developing colorectal cancer. Epidemiologic studies indicate a 40% to 50% reduction in mortality due to colorectal cancer in individuals taking NSAIDs (e.g., aspirin). Epigenetic factors including age, diet, angiogenesis, and immune responses also appear to contribute to the development of CRC.

4/16/02 The role of cyclooxygenase inhibitors in cancer prevention Curr Pharm Des 2002;8(12):1035-62 PMID: 11945150 Ideally, chemopreventive agents should be low in toxicity, morbidity, and cost. Several individual agents and agent combinations are currently under evaluation in the U.S. National Cancer Institute s (NCI) chemoprevention agent development program. Nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (COX) -1 and -2 are among the most promising classes of agents for targeted molecular prevention.

4/16/02 Colon cancer prevention with NO-releasing NSAIDs Prostaglandins Other Lipid Mediat 2002 Feb;67(2):107-20 PMID: 11936617 A seminal advance in the prevention of colon cancer has been the observation that nonsteroidal antiinflammatory drugs (NSAIDs) reduce the incidence of and mortality from colon cancer by about half. Among current efforts to overcome the side effects of NSAIDs, an important limitation for their application as chemopreventive agents, is the synthesis of nitric oxide-releasing NSAIDs. These novel compounds may display greater safety and greater efficacy compared to their parent traditional NSAIDs and thus hold significant promise as chemopreventive agents against human colon cancer

Garlic

4/16/02 Diallyl Disulfide (DADS) Induces the Antitumorigenic NSAID-Activated Gene (NAG-1) by a p53-Dependent Mechanism in Human Colorectal HCT 116 Cells J Nutr 2002 Apr;132(4):773-778 PMID: 11925476 Garlic is appealing as an anti-carcinogenic agent due to its ability to induce apoptosis in vitro and inhibit the formation and growth of tumors in animals in vivo. Diallyl disulfide (DADS) is a constituent of garlic that suppresses neoplastic cell growth and induces apoptosis... Thus, DADS-induced apoptosis and NAG-1 protein expression appear to occur via p53.

Intra-Arterial Chemotherapy

4/16/02 Downstaging of hepatocellular carcinoma and liver metastases from colorectal cancer by selective intra-arterial chemotherapy Surgery 2002 Apr;131(4):433-442 PMID: 11935134 Conclusions. About one third of patients with unresectable liver tumors can be successfully treated by neoadjuvant intra-arterial chemotherapy followed by curative resection. This strategy appears particularly promising in patients with large HCC. This approach should be investigated further.

Surgery

4/16/02 Pulmonary resection for metastases from colorectal adenocarcinomas Zhonghua Yi Xue Za Zhi (Taipei) 2002 Jan;65(1):15-22 PMID: 11939670 CONCLUSIONS: We concluded that lung metastasectomy for colorectal cancer is safe and effective to improve the survival. Since there were no significant factors influencing the survival, there should be no absolute contraindication against resectable pulmonary metastasis after primary lesions were adequately controlled

RF Ablation

4/16/02 Hepatic radiofrequency ablation Arch Surg 2002 Apr;137(4):422-7 PMID: 11926946 CONCLUSIONS: Hepatic RFA is an effective treatment option for patients with unresectable hepatic malignancies. Careful patient selection based on tumor size, location, and number and on patient clinical status should determine the choice of treatment. Further controlled trials are needed to determine the effect of hepatic RFA on long-term survival.

Thalidomide

4/16/02 Thalidomide in cancer treatment: a potential role in the elderly? Drugs Aging 2002;19(2):85-100 PMID: 11950376 In addition, the antitumour effects of the conventional cytotoxic drug cyclophosphamide and the tumour necrosis factor inducer 5,6-dimethylxanthenone-4-acetic acid (DMXAA) were found to be potentiated by thalidomide in mice bearing colon 38 adenocarcinoma tumours. Further studies have revealed that thalidomide upregulates intratumoral production of tumour necrosis factor-alpha 10-fold over that induced by DMXAA alone. Coadministration of thalidomide also significantly reduced the plasma clearance of DMXAA and cyclophosphamide. All these effects of thalidomide may contribute to the enhanced antitumour activity. Recent clinical trials of thalidomide have indicated that it has minimal anticancer activity for most patients with solid tumours when used as a single agent, although it was well tolerated.

Prognostic Indicators

4/16/02 CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer Hepatogastroenterology 2002 Jan-Feb;49(43):160-4 PMID: 11941943 CONCLUSIONS: The data from our study indicate that serum CA19-9 level is the most significant prognostic indicator of patients with metastatic colorectal cancer. It is recommended that stratification for further clinical trials for patients with metastatic colorectal cancer should be carried out according to serum CA19-9 levels.

Chemoprevention

4/16/02 Prevention and chemoprevention of colorectal neoplasms Dig Liver Dis 2002 Jan;34(1):59-69 PMID: 11926575 Available evidence does not support the contention that a more appropriate diet can be of great help in the prevention of these neoplasms, either because the scientific evidence is poor and highly controversial, or because changes in diet are difficult to implement, at least in many Western countries. Similarly, a preventive approach based on the modification of lifestyle remains improbable, either in the short --or in the long period of time. Secondary prevention--i.e., the systematic removal of adenomatous polyps--can hardly be applied in the general population, with the exception of individuals at risk because members of families with Adenomatosis coli or Lynch syndrome, or affected by inflammatory bowel diseases. Finally, chemoprevention (i.e., the attempt to prevent tumour development through the administration of drugs or natural compounds that interfere with various phases of carcinogenesis) is still in its infancy Though attractive, this approach requires well-designed studies which should be carried out for years before being evaluated and interpreted; so far most of these investigations gave inconsistent or controversial results. In conclusion, both primary and secondary prevention of colorectal malignancies appear difficult to apply in the general population, and chemoprevention is still at the beginning of a (presumably] long story

Miscellaneous

4/16/02 Antitumor Effects of Miconazole on Human Colon Carcinoma Xenografts in Nude Mice through Induction of Apoptosis and G0/G1 Cell Cycle Arrest Toxicol Appl Pharmacol 2002 Apr 1;180(1):22-35 PMID: 11922774 Miconazole (MIC), a promising oral antifungal agent, has been used worldwide in the treatment of superficial mycosis. In this study, we demonstrated that MIC dose dependently arrested various human cancer cells at the G0/G1 phase of the cell cycle. The protein levels of p53, p21/Cip1, and p27/Kip1 were significantly elevated by MIC treatment in COLO 205 cells... Our study provides the novel mechanisms of antitumor effects of MIC and such results may have significant applications for cancer chemotherapy

4/16/02 Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ 2002 Apr 6;324(7341):813 PMID: 11934773 Conclusions: Intensive follow up after curative resection for colorectal cancer improves survival. Large trials are required to identify which components of intensive follow up are most beneficial

4/16/02 Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug-resistant colon carcinoma cells (LoVo) than on their wild-type counterparts Int J Cancer 2002 May 1;99(1):43-52 PMID: 11948490 Our results support the hypothesis that mitochondrial functionality affects the sensitivity of cells to the cytotoxic enzymatic oxidation products of spermine, which might be promising anticancer agents, mainly against drug-resistant tumor cells.

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