We describe the direct identification of multiple cytochrome P450 (CYP) enzymes in healthy and cancerous tissue. CYPs in human liver colorectal metastases were compared with those in the surrounding liver using a mass spectrometry-based proteomic approach. Nano-scale reversed phase liquid chromatography combined with electrospray ionisation tandem mass spectrometry has been used to identify CYPs with no pre-selection of the proteins anticipated. Fourteen distinct CYP enzymes from the subfamilies 1A, 2A, 2B, 2C, 2D, 2E, 3A, 4A, 4F, 8B and 27A were positively identified; 13 in the liver samples and 12 in the tumour tissue. It was found that three of the colorectal metastases expressed essentially the same drug-metabolising pattern of CYPs as the surrounding liver, whilst three tumour samples from different individuals showed no CYP expression. This was likely in at least one case to be due to low sample mass. The CYP expression profile in an individual tumour is likely to be an important determinant in predicting the outcome of cancer chemotherapy.

The US private sector has indicated that the National Institute of Standards and Technology (NIST) has a role to play in facilitating the implementation of high throughput experimentation, e.g. using combinatorial methods. The Advanced Technology Program (ATP) is currently funding research projects in high throughput discovery of catalysts, electronic materials, and polymer coatings internally and externally to NIST. The NIST Measurement and Standards Laboratories (MSL) is actively pursuing research in electronic materials and organic polymers. This presentation presents details on these efforts at NIST.

The Advanced Technology Program (ATP), an agency within the U.S. Department of Commerce's Technology Administration and the National Institute of Standards and Technology, provides co-funding to industry for high-risk/high-payoff applied research. Companies of any size may apply, and universities or governmental research institutions may partner with industry in ATP projects. Since its inception, the ATP has participated in 468 projects, representing $3B of total industry/government investment. U.S. industry has indicated that ATP has a significant role to play in the area of high throughput R&D. ATP call catalyze the development of lower-cost hardware and software tools to bring leading-edge, generic technologies to more industries, and call facilitate the integration of hardware and software systems. The ATP is currently funding research projects in high throughput discovery of catalysts and polymer coatings, with FY199 project requests of $36.1M over five years. In addition to extramural funding, the ATP has internal funding of the NIST Measurement and Standards Laboratories (MSL). The MSL opportunity in high throughput screening is to develop measurement science to support new parallel methodologies and measurement tools tailored to specific industrial needs; to validate new and existing measurement methods and models using parallel or high throughput approaches; and to demonstrate application of HT methods to new materials and R&D problems; and to develop new standards addressing systems integration issues. The ATP is co-funding research at the NIST MSL in key areas.

This report is a collection point for non-proprietary business and technical information gleaned from industry input, for example as obtained at an Industry Probe Working Group Discussion held in March, 1998, public ATP Workshops held November 18, 1998 in Atlanta, GA, November 16, 1999 in San Jose, CA, as well as ATP's participation in many industrial forums in the last two years. Complete review articles can be found in the references.