Takenori Ochiai

Identification of Altered Protein Expression and Post-Translational Modifications in Primary Colorectal Cancer by Using Agarose Two-Dimensional Gel Electrophoresis

Purpose: Although numerous proteome studies have been performed recently to identify cancer-related changes in protein expression, only a limited display of relatively abundant proteins has been identified. The aim of this study is to identify novel proteins as potential tumor markers in primary colorectal cancer tissues using a high-resolution two-dimensional gel electrophoresis (2-DE). Experimental Design: 2-DE using an agarose gel for isoelectric focusing was used to compare protein profiling of 10 colorectal cancer tissues and adjacent normal mucosa. Altered expression and post-translational modification of several proteins were examined using Western blot analysis and immunohistochemistry. Results: Ninety-seven proteins of 107 spots (90.7%) that were differentially expressed between matched normal and tumor tissues were identified by mass spectrometry. Among them, 42 unique proteins (49 spots) significantly increased or decreased in the tumors. They include eukaryotic translation initiation factor 4H, inorganic pyrophosphatase, anterior gradient 2 homologue, aldolase A, and chloride intracellular channel 1, whose elevated expression in tumor tissues was confirmed by Western blot analysis and immunohistochemistry. Interestingly, only isoform 1 of two transcript variants of eukaryotic translation initiation factor 4H was greatly up-regulated in most of the tumor tissues. Moreover, post-translational modifications of the prolyl-4-hydroxylase β subunit and annexin A2 also were identified. Conclusions: We identified several novel proteins with altered expression in primary colorectal cancer using agarose 2-DE. This method is a powerful technique with which to search for not only quantitative but also qualitative changes in a biological process of interest and may contribute to the deeper understanding of underlying mechanisms of human cancer.

Reasonable Treatment for Pancreatic Cancer with Respect to Its Prognosis and Quality of Life of the Patients.

教室では, 膵癌に対し拡大りんぱ節郭清, isolation method+門脈合併切除を導入し, 拡大手術を推進してきた. 教室膵癌切除例99例を対象と予後, QOLからみた膵癌の至適治療につき検討した. 膵頭部癌切除例の検討ではD2郭清群はD1郭清群に比較し生存日数, 在宅生存日数の延長が得られた. 門脈合併切除により有意に局所再発率は低下した. しかしながら, stage IVb例では郭清度, 根治度に関わらず予後不良であった. 肝転移対策としてのisolation methodは肝転移抑制, 予後向上に寄与しなかった. 膵頭部癌に対する再建術式としては, 栄養状態, 膵機能の面でPDに比較しPpPDが優れていた. stage IVa以下の膵癌に対しては再建術式をPpPDとする積極的な拡大手術を, stage IVb症例では, QOLを考慮した治療法を選択すべきと考える.

Serum Sialyl Tn Antigen in the Patients with Gastric Cancer. Comparison with CEA, CA19-9 and TPA.

教室で経験した胃癌97例を対象として, 血清シアリルTn抗原 (STN) 測定の臨床的意義を検討した.カットオフ値を45U/mlとしたときの, 全体の陽性率は37.1%であり, 組織学的進行度が進むにつれて陽性率も高くなり, stage IVbでは72.7%であった.stage IVbのうち, 特に腹膜転移陽性例では陰性例に比べ陽性率.平均血清値ともに有意に高かった.それに対し, 血清CEA, CA19.9, TPAでは全くその傾向は見られなかった.肝転移の有無でSTNに差は見られなかった.また切除例においてリンパ節転移の有無でSTNの陽性率を比較するとリンパ節陽性例で有意に高かった.stage IVbでは, STNが高値のものほど予後が悪い傾向が見られた.以上より, 血清STN値は腹膜転移陽性例で特異的に高値をとり, 術前の腹膜転移診断に有用であり, また, 予後因子となりうることが示された.