Gene Expression Profiles Distinguish the Carcinogenic Effects of Aristolochic Acid in Target (Kidney) and Non-target (Liver) Tissues in Rats

BACKGROUND: Aristolochic acid (AA) is the active component of herbal drugs derived from Aristolochia species that have been used for medicinal purposes since antiquity. AA, however, induced nephropathy and urothelial cancer in people and malignant tumors in the kidney and urinary tract of rodents. Although AA is bioactivated in both kidney and liver, it only induces tumors in kidney. To evaluate whether microarray analysis can be used for distinguishing the tissue-specific carcinogenicity of AA, we examined gene expression profiles in kidney and liver of rats treated with carcinogenic doses of AA. RESULTS: Microarray analysis was performed using the Rat Genome Survey Microarray and data analysis was carried out within ArrayTrack software. Principal components analysis and hierarchical cluster analysis of the expression profiles showed that samples were grouped together according to the tissues and treatments. The gene expression profiles were significantly altered by AA treatment in both kidney and liver (p < 0.01; fold change > 1.5). Functional analysis with Ingenuity Pathways Analysis showed that there were many more significantly altered genes involved in cancer-related pathways in kidney than in liver. Also, analysis with Gene Ontology for Functional Analysis (GOFFA) software indicated that the biological processes related to defense response, apoptosis and immune response were significantly altered by AA exposure in kidney, but not in liver. CONCLUSION: Our results suggest that microarray analysis is a useful tool for detecting AA exposure; that analysis of the gene expression profiles can define the differential responses to toxicity and carcinogenicity of AA from kidney and liver; and that significant alteration of genes associated with defense response, apoptosis and immune response in kidney, but not in liver, may be responsible for the tissue-specific toxicity and carcinogenicity of AA

Complications of traditional Chinese/herbal medicines (TCM)—a guide for perplexed oncologists and other cancer caregivers

Introduction: Cancer patients often seek complementary or alternative medicines to supplement or replace treatments prescribed by licensed medical practitioners. Traditional Chinese/herbal medicine (TCM) is a popular complementary intervention among cancer patients of Asian ethnicity, many of whom take it during their conventional treatment. Few of these patients inform their doctors, however, creating a risk of unexpected sequelae arising from either pharmacologic toxicity, unsuitable dosing, interactions with anti-cancer drugs or other medications, adulteration, or idiosyncratic reactions. If unrecognized, these problems may be misattributed to conventional treatment toxicity or disease progression, and remedial action may be inappropriate or delayed. Goals of work: The purpose of this review is to help oncologists recognize the common presentations of TCM-related problems in cancer patients-such as abnormal liver function tests, unexpectedly severe myelosuppression, hemostatic defects, renal functional impairment, or suspected drug interactions-and to teach strategies by which these problems can be anticipated, prevented, or managed. Conclusion: Through sensitive understanding of the reasons favoring TCM usage, oncologists can gain the trust and respect of their TCM-using patients while ensuring the safety and efficacy of conventional anticancer treatments. © 2008 Springer-Verlag.link_to_subscribed_fulltex