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論文
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Honda, Masao ; Sakai, Yoshio ; Yamashita, Taro ; Yamashita, Tatsuya ; Sakai, Akito ; Mizukoshi, Eishiro ; Nakamoto, Yasunari ; Tatsumi, Isamu ; Miyazaki, Yoshitaka ; Tanno, Hiroshi ; Kaneko, Shuichi ; Hokuriku Liver Study Group
概要:
金沢大学医薬保健研究域医学系<br />To develop a non-invasive and sensitive diagnostic test for cancer using peripheral blood, we evalua
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ted gene expression profiling of blood obtained from patients with cancer of the digestive system and normal subjects. The expression profiles of blood-derived total RNA obtained from 39 cancer patients (11 colon cancer, 14 gastric cancer, and 14 pancreatic cancer) was clearly different from those obtained from 15 normal subjects. By comparing the gene expression profiles of cancer patients and normal subjects, 25 cancer-differentiating genes (p<5.0×10-6 and fold differences >3) were identified and an " expression index" deduced from the expression values of these genes differentiated the validation cohort (11 colon cancer, 8 gastric cancer, 18 pancreatic cancer, and 15 normal subjects) into cancer patients and normal subjects with 100% (37/37) and 87% (13/15) accuracy, respectively. Although, the expression profiles were not clearly different between the cancer patients, some characteristic genes were identified according to the stage and species of the cancer. Interestingly, many immune-related genes such as antigen presenting, cell cycle accelerating, and apoptosis- and stress-inducing genes were up-regulated in cancer patients, reflecting the active turnover of immune regulatory cells in cancer patients. These results showed the potential relevance of peripheral blood gene expression profiling for the development of new diagnostic examination tools for cancer patients. © 2010 Elsevier Inc.
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| 2.
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Matsuo, Shinro ; Nakajima, Kenichi ; Kinuya, Seigo ; Yamagishi, Masakazu
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Objective: Takotsubo cardiomyopathy is a cardiac syndrome with an acute onset defined by chest symptoms and ST segment e
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levation on electrocardiograms. Takotsubo cardiomyopathy is sometimes misdiagnosed as acute myocardial infarction (AMI). Therefore a non-invasive diagnostic method is needed to be established for setting up appropriate strategies. The purpose of this study was to detect myocardial metabolic abnormalities and to determine the diagnostic usefulness of 123I-beta-methy-iodophenyl pentadecanoic acid (123I-BMIPP) imaging in patients with takotsubo cardiomyopathy. Methods and results: We examined 16 patients with takotsubo cardiomyopathy and 12 with AMI in the left anterior descending artery. All patients were studied with resting 123I-BMIPP imaging. Total defect score (TDS) of 123I-BMIPP and perfusion were semi-quantitatively determined with single-photon emission computed tomography (SPECT) imaging using a 17-segment 5-point model. TDS of 123I-BMIPP were 4.8 ± 2.7 in patients with Takotsubo cardiomyopathy and 22.4 ± 10.7 in AMI. The ratio of summed BMIPP defect score of non-apical to apical segments in Takotsubo cardiomyopathy was smaller than that of the patients with AMI (0.1 ± 0.1 vs. 1.1 ± 0.7, p < 0.0001), indicating that 123I-BMIPP abnormalities were exclusively observed the in apical area. The ratio of summed perfusion defect scores of non-apical to apical segments in takotsubo cardiomyopathy did not differ significantly from that of AMI (0.52 ± 0.6 vs. 0.57 ± 0.3, p = NS). Summed BMIPP defect score in the apical area of takotsubo cardiomyopathy was larger than that of perfusion defect score (3.9 ± 2.7 vs. 1.8 ± 1.8, p = 0.04). Conclusion: Impaired metabolic metabolism exclusively in the apical region was observed by 123I-BMIPP SPECT images in takotsubo cardiomyopathy. These typical metabolic SPECT features of the disease can be utilized on differential diagnosis of takotsubo cardiomyopathy. © 2013.<br />This is the author's version of a work accepted for publication by Japanese College of Cardiology. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. The definitive version has been published in Journal of Cardiology, 64 (1), pp. 49-56,2014 July, 10.1016/j.jjcc.2013.10.019
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| 3.
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論文
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京, 哲 ; Kyo, Satoru
概要:
金沢大学大学院・医学系研究科<br />血液中の微量癌細胞をテロメレース活性を示標に同定することを目的として実験を行った。上皮細胞特異的抗体を吸着させたビーズを用いて患者血液から採取した単核球分画より上皮細胞を選択的に濃縮回収した。この回収
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物より細胞抽出液を得て、TRAP法によりテロメレース活性を測定した。予備実験として癌細胞株を血液5ccに様々な細胞数で混ぜ合わせ、同様の方法でテロメレース活性を測定したところ、血液5cc中に1000個の癌細胞が存在すれば検出可能な感度であった。なお正常ボランティア40名より得た検体のテロメレース活性も同時に測定し、これよりカットオフ値を設定したところ進行婦人科癌患者21例のうち4例にテロメレース活性陽性例を認めた。これらはいずれも3期あるいは4期の子宮癌および卵巣癌患者であった。さらにこれらの患者のうち2例は治療により腫瘍マーカーの陰性化を認めたが、治療後の血液細胞中のテロメレース活性もカットオフ値以下に減少し、病勢を反映している可能性が示唆された。今後さらに症例数を増やして検討して行く予定である。さらに子宮内膜細胞診材料よりテロメレース活性測定法(TRAP法)を用いて内膜癌細胞の検出も試み、感度80%以上の良好な診断率を得た。特に、細胞診陰性の見逃し例のなかに、TRAP法で陽性となる症例があり、細胞診との併用により診断率が向上することが期待される。<br />To examine the possibility of novel tumor markers, telomerase activity was measured by the TRAP assay using blood samples from patients with various gynecologic tumors. To purify the epithelial components in blood samples, beads-based method was used, in which blood cells were incubated with beads that were conjugated with specific anti-epithelial antigen. Approximately, 20% of patients exhibited telomerase activity in this method, all of them had advanced gynecologic tumors, such as cervical and ovarian cancers, while none of 40 normal healthy volunteers showed no telomerase activity. Interestingly, telomerase activity observed in these patients decreased after initial treatment, such as chemotherapy and radiotherapy, suggesting that it might reflect disease progression.We also examined the possibility of telomerase-based screening method for endometrial cancers using exfoliated endometrial scarping samples. We could achieved more than 80% of sensitivity to detect endometrial cancers using TRAP assay with endometrial scarping samples. Combination of this method with classical cytologic smear test may improve sensitivity and specificity to screen endometrial cancers.<br />研究課題/領域番号:13671702, 研究期間(年度):2001 – 2002<br />出典：「テロメレース活性を利用した婦人科癌の新たな遺伝子診断および遺伝子治療の開発」研究成果報告書 課題番号13671702（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-13671702/136717022002kenkyu_seika_hokoku_gaiyo/)を加工して作成
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論文
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京, 哲 ; Kyo, Satoru
概要:
金沢大学医学部・附属病院<br />テロメレースは染色体DNAの末端構造であるテロメアを伸長させる酵素で、ほとんど全ての癌においてテロメレースの活性化が知られている。これに対して正常細胞ではテロメレース活性は認められていない。よってテロメレ
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ースの活性化は細胞の不死化や癌化に重要なステップであると考えられている。我々は癌特異的に認められるテロメレースの活性を利用して、これを癌の診断に応用することを目指し研究を進めてきた。特にテロメレースの活性中心であるhTERTの発現を同定することで、婦人科癌診断への応用が可能か否かについて検討した。テロメレーステロメレース活性を規定する因子であるhuman telomerase reverse transcriptase(hTERT)の発現は我々の研究により癌に特異的に認められ、テロメレース活性とも非常によく相関していた。RT-PCR法によるhTERT mRNAの検出は極めて高感度で、テロメレース活性を測定するのと同等以上に高い感受性および特異性を持ち、卵巣癌、内膜癌、子宮頚癌などで診断価値があることを見いだした。またスクリーニングの方法としても利用価値が高く、子宮頚部の擦過細胞からRNAを抽出してRT-PCRを施行し、hTERTの発現の有無を検討したところ、子宮頚部異形成にも一部に発現が認められ、子宮頚癌では高率に発現が確認された。我々はさらに子宮内膜細胞診においてもhTERT発現を検討し、通常の閉経後の正常人にはほとんど発現が認められないのに対し、内膜癌患者では80%以上に発現が認められ、内膜癌のスクリーニングにも有用であることを明らかにした。以上の結果よりテロメレース活性、特にhTERT mRNAの発現が新たな癌診断のためのマーカーとなり得ることが確認され、今後臨床応用に向けたさらなる研究が期待される。<br />Telomerase is a cellular reverse transcriptase which catalyzes the synthesis and extension of telomeric DNA.This enzyme is specifically activated in most malignant tumors, but is usually inactive in normal somatic cells, and within which telomeres therefore progressively shorten with cell division. A mechanism to maintain telomere stability is required for the cells to overcome replicative senescence, and telomerase activation may therefore be a rate-limiting or critical step in cellular immortality and oncogenesis. Human telomerase reverse transcriptase (hTERT) is a catalytic subunit protein of telomerase and is a critical determinant of its enzymatic activity.In the present study, we examined the utility of detecting telomerase activity and hTERT mRNA expression for the diagnosis and screening of gynecologyc tumors. We found that most gynecologic cancers express telomerase activity while the corresponding normal tissues do not. Cervical and endometrial exfoliated cells were collected from the patients with or without cervical or endometrial lesions and telomerase activity and hTERT mRNA expression were detected by the TRAP assays or RT-PCR assays. Approximately 90% of the patients with cervical or endometrial cancer were positive for telomerase activity or hTERT mRNA expression, while less than 10% of those without any lesions were so. 50 to 60% of the patients with premalignant lesions, such as suqamous intraepithelial lesions (SIL) expressed telomerase activity or hTERT mRNA.These findings suggest that detection of telomerase activity or hTERT mRNA expression may be an useful tool for cancer diagnosis and screening.<br />研究課題/領域番号:11671604, 研究期間(年度):1999 – 2000<br />出典：「テロメレース活性および活性中にサブュニットの検出による婦人科癌診断への応用」研究成果報告書 課題番号11671604（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （ https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-11671604/ ）を加工して作成
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