Rapid advances in diagnostic and therapeutic techniques have greatly improved cancer prognosis. How ever, even at present, it is difficult to predict cancer metastasis, and the elucidation of the mechanism of can cer metastasis and its therapeutic application have just begun. Cancer progresses as a complex phenome non involving various life phenomena such as the abnormal proliferation of cells, their acquisition of motility,degradation of extracellular matrices, and changes in intercellular adhesiveness. The interaction of a very wide diversity of molecules acting inside and outside the cells controls the complex behaviors of cancer cells. In particular, molecules acting outside the cells are thought to directly specify the malignant characteristics of cancer cells; therefore, investigators are attempting to prevent cancer cell invasion and metastasis by inhibit ing their functions. The extracellularly acting molecules include a group of molecules, such as fibronectin and laminin, which interact with each other or with other molecules to form matrices and regulate tissue formation and cell functions. In general, extracellular matrix molecules such as collagen are thought to block the inva sion and metastasis of cancer cells. Conversely, hyaluronan, which is another matrix component and large sugar chain molecule, is synthesized, formed into matrices in many cancer tissues such as breast and colon cancers and gliomas, and is closely related to cancer progression. This paper focuses on hyaluronan and its matrix formation, gives an overview of studies aimed at elucidating tumor progression, and refers to recent trends towards blocking cancer invasion and metastasis by targeting the biosynthesis of hyaluronan.

食道癌の遺伝子発現の解析を培養細胞系から臨床サンプルに展開し，評価した。 食道癌においてtight junctionに関係するconnexin43遺伝子の発現が認められないか低発現の細胞株や症例を認めた。DNAマイクロアレイを用いた解析により，In vitroのconnexin43遺伝子導入した高発現株はプロテア－ゼ，細胞接着因子や薬剤排出の膜蛋白遺伝子の発現が低く，プロテア－ゼ阻害因子，Topoisomerase IIα遺伝子等の発現が高かった。In vivoでは，connexin43遺伝子発現を認めない食道癌はconnexin26, 30遺伝子も共に発現が低下していた。 connexin43遺伝子の発現が認められない食道癌があり，高発現させることにより抗癌剤感受性規定因子や転移・浸潤関連因子群の遺伝子発現に変化が認められた。

BAC DNAをプリントしたDNAチップを使用しCGH-array法による大腸癌肝転移巣の解析をおこなった。7p, 7q, 8q, 9p22, 9q31, 11q23.1, 13q, 16q21-22, 20p, 20qのamplificationと4p, 4q, 5q11-q34, 8p23-p12, 11q13, 14q, 15q, 17p, 17q21, 17q24, 18p, 18q, 22qのdeletionが40%以上の症例に認められ、特に8p21-p23（−）, 18q11-q23（−）, 11q23.1（＋） , 20q12-q13（＋）は80％であった。異常を示した既存の遺伝子としてAIB1, CAS , PTPN1, AVR2/BTAK, BCLXにamplificationを、deletionとしてはPRLTS, DPC4/Smad4 , DCC , BCL2が80%以上を示した。今後転移や予後に関しても研究をおこないgenomic markerを同定できれば診療の一助になると思われる。

Various types of chromosomal abnormalities occur in tumor cells. Chromosomal translocation is one of the most popular abnormalities in hematopoietic tumor or many other tumors. It is known that specific chromosomal translocations, e.g. t(9,22) in chronic myeloid leukemia or t(11,22) in Ewing sarcoma, occur frequently and generate chimeric gene products providing oncogenic stimuli. Although the juxtaposition of two loci of genes in the nucleus is recently suggested to be an important factor for the cancer type-specific translocations, the mechanism have not been elucidated yet. If the three-dimensional relative positions among many kinds of genes or chromosome domains are simultaneously identified in the interphase nuclei, the important parts of the mechanism of chromosomal translocation can be discovered. In order to demonstrate this approach,the multi-color and 3-dimentional fluorescence microscopic system is required. However, only several different fluorescent dyes can be detected simultaneously by the conventional confocal laser microscopy because of overlapping fluorescent spectra. Therefore, we developed a novel imaging system composed of the nipkow-disk confocal scanner and spectral analyzer, that enables multi-color FISH analysis on the optical sections of the interphase nuclei. In this study, we focused on confirming the possibility to observe the optically sectioned images of various fluorescent specimens by way of our 3-D spectral analyzing technology.

薬剤の毒性を検査する方法としては，従来マウスの骨髄有核赤血球を使用した小核試験が行われてきた。これらin vivo に対して，in vitro の試験を確立するために，ヒト由来培養細胞を利用した小核試験を行い，有効性を検討した。ヒト肺癌細胞A549に抗がん剤3種を種々の濃度で持続接触させた後，ギムザ染色を行い，小核発現率を測定した。vindesine，cisplatinでは有意に発現率が上昇したが，doxorubicinでは有意な上昇はみられなかった。ヒト肺癌培養細胞を用いた小核試験は抗癌剤毒性試験として有効である可能性が示唆された。

Recently almost the entire sequence of the human genome was determined. Now, genome function analysis is being actively investigated. DNA chips are useful tools for sequencing and SNP analyses. DNA chips consist of surfaces on which probes of DNA sub-sequences of short length (4-10b) and all combinations of DNA of a specific length are printed without any particular design. To determine DNA sequences longer than 1000 bases, a DNA chip with probes longer than 10 bases is desirable, but this may be result in a huge and prohibitively expensive chip. Therefore, to reduce the size of DNA chips, chip design is considered to be important. We applied Self Organizing Maps (SOM) to select a adequate set of probes to represent actual DNA sequences on a DNA chip. SOM is particularly well suited because it can organize the generic feature of DNA sequence by learning DNA sequences. Furthermore, it will be possible to design the 2-dimentional layout of the probes on DNA chip. We improved the SOM algorithm so that it could learn the discrete values for 'A','T','G',C' symbols and adjust the length of probes automatically. We examined the selected probes by testing for DNA polymorphism on a computer simulation to evaluate the adequacy of the selected sets of probes.

ProteinChip technology provides a way to rapidly analyze proteins. Its application covers many research areas including protein profiling, protein-protein interaction, protein purification, and protein identification. This review shows current contribution of ProteinChip technology in these researches.