1998 Fiscal Year Annual Research Report

がんの個性に応じた合理的な遺伝子診療法の開発〜治療抵抗性癌の効果的治療法開発,予後予測,第2癌発症予測

Research Project

Project/Area Number	10557116
Research Institution	Tohoku University
Principal Investigator	小針雅男東北大学, 医学部, 助教授 (30170369)
Co-Investigator(Kenkyū-buntansha)	武田和憲東北大学, 医学部, 講師 (20171639) 渋谷和彦東北大学, 医学部・附属病院, 助手 (70260429) 古川徹東北大学, 医学部, 助手 (30282122) 砂村真琴東北大学, 医学部・附属病院, 助手 (10201584) 堀井明東北大学, 医学部, 教授 (40249983)
Keywords	膵癌 / 発癌メカニズム / 遺伝子診療 / 遺伝子異常 / LOH / マイクロサテライト不安定性 / DNAミスマッチ修復 / 治療抵抗性
Research Abstract	1.手術症例のうち,胃癌150例,大腸癌200例,膵癌100例,子宮体癌130例から抽出した腫瘍のDNAを用いて,各染色体のマイクロサテライトマーカーを用いたPCR法によりLOHとマイクロサテライト不安定性(MSI)を検出した結果,癌の発生臓器に特異的な染色体欠失を認めた.特に,大腸癌では1P32-q36,胃癌は16q24,膵癌は6q及び12qの複数の領域,子宮内膜癌は10q25-q26など,既知の遺伝子異常が検出されていない領域の異常を明らかにすることができた. 2.DNAミスマッチ修復(MMR)異常をMSIを指標として検討し,大腸癌18,6%,胃癌19%,膵癌16.7%,子宮内膜癌26%でMMRの異常を認めた.この結果から,癌の発生臓器によりMSI(+)に大きな違いがあることと,遺伝性非腺腫症性大腸癌(HNPCC)にしばしば合併する癌においてMSI(+)の頻度が高いことがわかった. 3.MMRの標的遺伝子,すなわちTGFβレセプターII型遺伝子,IGF II レセプター遺伝子,BAX遺伝子,PTEN遺伝子などのMMRの下流に位置する遺伝子の解析を行い,大腸癌,胃癌,子宮内膜癌において高頻度の遺伝子異常が認められたが,膵癌においてはこれらの遺伝子異常は全く検出されなかった. 4.以上の検討結果から,発癌には複数の経路が関わっており,発癌メカニズムの違いが臨床における腫瘍の多様性や治療抵抗性などに反映すると考えられた.今後は上記の遺伝子異常を多数の臨床データと照らし合わせて総合的に評価して,術前のスクリーニングから癌の個性を把握するための遺伝子診療法を開発する予定である.

Research Products

(22 results)

All Other

All Publications (22 results)

[Publications] Kimura,M.: "Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer." Cancer Research. 58. 2456-2460 (1998)
[Publications] Fukushige,S.: "Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis." Cancer Research. 58. 4220-4226 (1998)
[Publications] Lozonschi,L.: "Controlling tumor angiogenesis and metastasis of C26 murin colon adenocarcino-ma by a new matrix metalloproteinase inhibitor,KB-R7785,in two tumor models." Cancer Research. (in press).
[Publications] Kobari,M.: "Staging systems for pancreatic cancer.Differences between the Japanese and UICC systems." J Hep Bil Pancr Surg. 5. 121-127 (1998)
[Publications] Sunamura,M.: "Intraoperative radiotherapy for patients with advanced pancreatic adenocarcinoma." J Hep Bil Pancr Surg. 5. 151-157 (1998)
[Publications] Abe,T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer." Genes Chromosomes Cancer. (in press).
[Publications] Okusaka,T.: "Tumor markers in walnating the response to radiotherapy in unresectable pancreatic cancer." Hepato Gastroenterology. 45. 872-876 (1998)
[Publications] Sunamura,M.: "The anti-angiogenic effect of IL-12 on early growth of human pancreatic cancer in SCID mice." Microcirculation annual. 14. 143-144 (1998)
[Publications] Lozonschi,L.: "The anti-angiogenic and anti-metastatic properties of a new matrix metalloproteinase inhibitor,KB-R7785." Microcirculation annual. 14. 145-146 (1998)
[Publications] Matsumoto,G.: "Adjuvant immunotherapy using genetically engineered interleukin 12 secreting fibroblasts prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model." Surgery. in press.
[Publications] Furukawa,T.: "Genomic analysis of DUSP6,a dual specificity MAP kinase phosphatase,in pancreatic cancer." Cytogenet.Cell Genet.82. 156-159 (1998)
[Publications] Ouyang,H.: "The BAX gene,the promoter of apoptosis, is mutated in genetically unstable cancers of the colorectum,stomach,and endometrium." Clinical Cancer Research. 4. 1071-1076 (1998)
[Publications] Orikasa,K: "Identification of a 700-kb region of common allelic loss in chromosome bands 3p14.3-p21.1 in human renal cell carcinoma." Cancer Genet.Cytogen.104. 104-110 (1998)
[Publications] Yatsuoka,T.: "Genomic analysis of the thymine-DNA glycosylase(TDG)gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma." International Journal of Pancreatology. (in press).
[Publications] Yoshinaga,K.: "The PTEN,BAX,and IGFIIR genes are mutated in endometrial atypical hyperplasia." Japanese Journal of Cancer Research. 89. 985-990 (1998)
[Publications] Matsuzaki,M.: "Detailed deletion mapping on chromosome 1p32-p36 in human colorectal cancer.Identification of three distinct regions of common allelic loss." International Journal of Oncology. 13. 1229-1233 (1998)
[Publications] Sato,M.: "The H-cadherin(CDHI3)gene is inactivated in human lung cancer." Hum.Genet.103. 96-101 (1998)
[Publications] Han,S.: "Infrequent somatic mutations of the p73 gene in various human cancers." European Journal of Surgical Oncology. (in press).
[Publications] Orikasa,K: "Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer." J.Hum.Genet.43. 228-230 (1998)
[Publications] Yamakawa,H: "Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer." Genes Chromosomes Cancer. 23. 74-77 (1998)
[Publications] Sato,M.: "Identification of a 910-kb region of common allelic loss in chromosome bands 16q24.1-q24.2 in human lung cancer." Genes Chromosomes Cancer. 22. 1-8 (1998)
[Publications] Mori,Y.: "Chromosome band 16q24 is frequently deleted in human gastric cancer." Br.J.Cancer. (in press).

1998 Fiscal Year Annual Research Report

がんの個性に応じた合理的な遺伝子診療法の開発〜治療抵抗性癌の効果的治療法開発,予後予測,第2癌発症予測

Principal Investigator

小針 雅男 東北大学, 医学部, 助教授 (30170369)

Research Products

[Publications] Kimura,M.: "Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer." Cancer Research. 58. 2456-2460 (1998)

[Publications] Fukushige,S.: "Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis." Cancer Research. 58. 4220-4226 (1998)

[Publications] Lozonschi,L.: "Controlling tumor angiogenesis and metastasis of C26 murin colon adenocarcino-ma by a new matrix metalloproteinase inhibitor,KB-R7785,in two tumor models." Cancer Research. (in press).

[Publications] Kobari,M.: "Staging systems for pancreatic cancer.Differences between the Japanese and UICC systems." J Hep Bil Pancr Surg. 5. 121-127 (1998)

[Publications] Sunamura,M.: "Intraoperative radiotherapy for patients with advanced pancreatic adenocarcinoma." J Hep Bil Pancr Surg. 5. 151-157 (1998)

[Publications] Abe,T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer." Genes Chromosomes Cancer. (in press).

[Publications] Okusaka,T.: "Tumor markers in walnating the response to radiotherapy in unresectable pancreatic cancer." Hepato Gastroenterology. 45. 872-876 (1998)

[Publications] Sunamura,M.: "The anti-angiogenic effect of IL-12 on early growth of human pancreatic cancer in SCID mice." Microcirculation annual. 14. 143-144 (1998)

[Publications] Lozonschi,L.: "The anti-angiogenic and anti-metastatic properties of a new matrix metalloproteinase inhibitor,KB-R7785." Microcirculation annual. 14. 145-146 (1998)

[Publications] Matsumoto,G.: "Adjuvant immunotherapy using genetically engineered interleukin 12 secreting fibroblasts prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model." Surgery. in press.

[Publications] Furukawa,T.: "Genomic analysis of DUSP6,a dual specificity MAP kinase phosphatase,in pancreatic cancer." Cytogenet.Cell Genet.82. 156-159 (1998)

[Publications] Ouyang,H.: "The BAX gene,the promoter of apoptosis, is mutated in genetically unstable cancers of the colorectum,stomach,and endometrium." Clinical Cancer Research. 4. 1071-1076 (1998)

[Publications] Orikasa,K: "Identification of a 700-kb region of common allelic loss in chromosome bands 3p14.3-p21.1 in human renal cell carcinoma." Cancer Genet.Cytogen.104. 104-110 (1998)

[Publications] Yatsuoka,T.: "Genomic analysis of the thymine-DNA glycosylase(TDG)gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma." International Journal of Pancreatology. (in press).

[Publications] Yoshinaga,K.: "The PTEN,BAX,and IGFIIR genes are mutated in endometrial atypical hyperplasia." Japanese Journal of Cancer Research. 89. 985-990 (1998)

[Publications] Matsuzaki,M.: "Detailed deletion mapping on chromosome 1p32-p36 in human colorectal cancer.Identification of three distinct regions of common allelic loss." International Journal of Oncology. 13. 1229-1233 (1998)

[Publications] Sato,M.: "The H-cadherin(CDHI3)gene is inactivated in human lung cancer." Hum.Genet.103. 96-101 (1998)

[Publications] Han,S.: "Infrequent somatic mutations of the p73 gene in various human cancers." European Journal of Surgical Oncology. (in press).

[Publications] Orikasa,K: "Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer." J.Hum.Genet.43. 228-230 (1998)

[Publications] Yamakawa,H: "Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer." Genes Chromosomes Cancer. 23. 74-77 (1998)

[Publications] Sato,M.: "Identification of a 910-kb region of common allelic loss in chromosome bands 16q24.1-q24.2 in human lung cancer." Genes Chromosomes Cancer. 22. 1-8 (1998)

[Publications] Mori,Y.: "Chromosome band 16q24 is frequently deleted in human gastric cancer." Br.J.Cancer. (in press).

小針雅男東北大学, 医学部, 助教授 (30170369)