Future Directions

The majority of evidence appears to indicate that the preservation of immune function after an operative procedure confers advantages to the patient in terms of recovery and oncological outcome. It consequently seems likely that the deliberate stimulation of the immune system perioperatively may be a way to avoid the detrimental effects of surgery and upregulation of this nature may also result in improved cancer control. The early postoperative period may be an ideal time for induction of immune-based anticancer therapy, as tumor burden is at its lowest. Perioperative tumor vaccines may also be effective means of establishing specific immune responses against the tumor before resection (90). These concepts are being actively tested in experimental settings although they are yet to enter the clinical mainstream. It is likely that future basic science and clinical trials will identify specific areas of immune modulation in this challenging area.

Traditional methods of studying and manipulating the immune response have numerous shortcomings. They study individual components of the immune system rather than a collective "systems" response (6). The human genome project has made the "systems" approach to disease a reality. Simultaneous publication of draft versions of the genome in February 2001 in Nature and Science were important milestones and introduced major changes in medicine (91,92). Powerful tools for accurately deciphering biological information are now available. Emphasis is steadily shifting from structural genomics to functional genomics and proteomics. As a result, 21st century molecular biology in urology looks rather different and new and more effective preventive and therapeutic strategies are emerging (93,94). We urologists are getting familiar with acronyms like (expressed sequence tag—a short piece of di-oxy ribose nucleic acid sequence corresponding to a fragment of cdi-oxy ribose nucleic acid), (serial analysis of gene expression—a method that produces very short sequence tags used for gene identification), and SNP (single nucleotide polymorhisms—variations in single nucleotides between people, which may determine susceptibility and resistance to disease among different individuals), which were previously thought to be of little relevance.

High throughput tools are already providing us valuable information about important urological cancers. Like cancer, immune dysfunction is a "systems disease" and it is now obvious that the traditional method of searching for isolated genetic alterations is no longer useful. Microarray technology (95,96) allows a number of genes and genomic alterations to be studied at the same time. Some of these utilize high-speed robots such as Q-Bot. Bioinformatics is vital to make sense of this large amounts of genetic data. Such technology will allow us to better define and compare the immunological changes after laparoscopy and open surgery. An example would be to study genetic changes associated with the T-cell receptor (Fig. 12). It would be possible to create oligonucleotide arrays that interrogate the expression patterns of each of these genes during T-cell development and their alterations after laparoscopic procedures. Commercially available signalling pathway gene arrays contain genes important to signal transduction that mediate the immune response and inflammation. These genes encode adhesion molecules, receptors, ligands, adaptors, kinases, regulators, transcription factors, and downstream effector proteins for each of these pathways. Signal transduction plays essential roles in immune cell activation, proliferation, differentiation, and apoptosis. Immune arrays that could prove useful in the field of laparoscopy are dendritic, antigen presenting cell arrays, and toll-like receptor signalling pathway arrays. These are available on chips of the size of a fingernail.

Combinatorial chemistry is an important tool where the idea is to synthesize a string of information using a combination of basic letters. For example, a combination of various molecules would lead to the creation of different three-dimensional shapes. Combinatorial chemistry can be used to facilitate the design and synthesis of new immunological targets in a rapid fashion.

Finally the most important tool for deciphering biological information is based on computational sciences. These are designed to collect, store, analyze, and ultimately distribute various types of biological information. A good example of this is the dissemination of collective information regarding the human genome project through GenBank and the Internet. This approach can only succeed through collaboration between computer scientists, applied mathematicians, biologists, and physicians (6,98).

Over the next few years, the systems' approach to immunology will become popular and this will certainly have an impact on the expanding field of minimally invasive urology.

FIGURE 12 ■ Location and complexity of genomic sequence of the human beta T-cell receptor. Source: From Ref. 97.

FIGURE 12 ■ Location and complexity of genomic sequence of the human beta T-cell receptor. Source: From Ref. 97.

The Receptor The Urology
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