Cancer databases

Bardou, V.-J., Arpino, G., Elledge, R.M., Osborne, C.K., and Clark, G.M. 2003. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J. Clin. Oncol. 21, 1973-1979. 

Peltomaki P, Vasen HF, and the ICG-HNPCC. Mutations predisposing to hereditary nonpolyposis colorectal cancer database and results of a collaborative study. Gastroenterology 1997 113 1146-58. 

Cancer Database cancer information/pdq/ screening and detection, prevention, treatment, genetics, and supportive care information. 

GAC US NIH/NIEHS Genetic Alterations in Cancer database Quantitatively described mutations found in the tumors indueed by the compounds present in the environment http //www.niehs.nih.gov/research/resourees/databases/gae/ index.efm... 

The National Cancer Institute (NCI) database is a collection of more than half a million structures, assembled by NCI s Developmental Therapeutics Program (DTP) or its predecessors in the course of NCTs anti-cancer screening efforts that started in the late 1950s (plus the more recent anti-HIV screening) [37-39]. Approximately half of this database is publicly available without any usage restrictions, and is therefore called the "Open NCI Database. For each of these structures (more than 250 000) the DTP record contains at least the chemical structure as a coimection table and an NCI accession number, the NSC number. 

Structure and Nomenclature Search System. This system links the collection of chemical databases found in the Chemical Information System (CIS), one of the first interactive systems for stmcture and substmcture searching. References from the separate files can be retrieved by SANSS using CAS Registry Numbers, and the database of stmctures may be searched for stmctures or substmctures. An adaptation of the SANSS software for substmcture searching has been incorporated in the Dmg Information System of the National Cancer Institute for its own use (54). 

Today, 3D databases, which provide the means for storing and searching for 3D information of compounds, are proven to be useful tools in drug discovery programs. This is well exemplified with the recent discovery of novel nonpeptide HIV-1 protease inhibitors using pharmacophore searches of the National Cancer Institute 3D structural database [13-15]. 

Patient databases with genetic profiles, e.g. for cardiovascular diseases, diabetes, cancer, etc. may play an important role in the future for individual health care, by integrating personal genetic profile into diagnosis, despite obvious ethical problems. The goal is to analyse a patient s individual genetic profile and compare it with a collection of reference profiles and other related information. This may improve individual diagnosis, prophylaxis, and therapy. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-efifect level (NOAEL-from animal and human studies) by a consistent application of uncertainty factors that reflect various types of data used to estimate RfDs and an additional modifying factor, which is based on a professional judgment of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects such as cancer. 

Figure 8.2 Example of a 2D substructure search. The search is for the diphenyl ether query substructure at the top of the figure, below which are shown five of the hits resulting from a search of the National Cancer Institute database of molecules that have been tested in the US government anticancer program (see URL http //dtp.nci. nih.gov/). This database is also used for the search outputs shown in Figures 8.3 and 8.4.

Rabow AA, Shoemaker RH, Sausville EA, Coveil DG. Mining the National Cancer Institute s tumor-screening database identification of compounds with similar cellular activities. J Med Chem 2002 45 818-40. 

Bcl-2 is one of the many factors that control apoptosis, and overexpression of Bcl-2 has been observed in many different cancers. A homology model of Bcl-2 was derived from the NMR 3D structure of the Bcl-XL complex with a Bak BH3 peptide. This model served to search the NCI 3D database of 206,876 organic compounds for potential Bcl-2 inhibitors, which bind to the Bak BH3 binding site of Bcl-2. Full conformational flexibility of the ligands was taken into account in the program DOCK. Thirty-five potential inhibitors were tested, and seven of them had IC50 values from 1.6 to W.OpM. One of... 

Scherf U, Ross DT, Waltham M, Smith LH, Lee JK, Tanabe L et al. A gene expression database for the molecular biology of cancer. Nat Genet 2000 24 236-44. 

An inverse correlation between thyroid cancer risk and phytoestrogens was recently proposed as a result of a multi-ethnic population-based case control study conducted in the San Francisco Bay Area (Hom-Ross et al., 2002). In this study, dietary habits and phytoestrogen consumption were assessed by a food-frequency questionnaire and by a nutrient database. The outcome of the study was that soy-based foods and alfalfa sprouts were associated with a reduction of thyroid cancer risk, whereas a Western diet did not influence cancer risk. No difference was observed between American and Asian women or between pre- and postmenopausal women. Furthermore, among the few compounds examined, the isoflavones genistein and daidzein and the lignan secoisolariciresinol were the phytoestrogens most frequently associated with risk reduction (Horn-Ross et al., 2002). 

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