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1998 Fiscal Year Final Research Report Summary

FUNDAMENTAL RESEARCH OF GENE THERAPY FOR CERVICAL CANCER BY ANTISENSE STRATEGY TARGETING IGF-1 RECEPTOR

Research Project

Project/Area Number 09671684
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

OKUDA Mitsuo  OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (50261235)

Co-Investigator(Kenkyū-buntansha) KODAMA Junichi  OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (90263582)
KAMIMURA Shigehito  OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (90281154)
OKUDA Hiroyuki  OKAYAMA UNIVERSITY MEDICAL SCHOOL ASSOCIATE PROFESSOR, 医学部, 助教授 (30033286)
HONGO Atsusi  OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (10301293)
MIYAGI Yasunari  OKAYAMA UNIVERSITY MEDICAL SCHOOL HOSPITAL ASSISTANT, 医学部・附属病院, 助手 (10273989)
Project Period (FY) 1997 – 1998
KeywordsIGF-1 / antisense / cervical cancer / HPV
Research Abstract

The Insulin-like growth factor I receptor (IGF-IR) plays an essential role in the establishment and maintenance of transformed phenotype, and interference with the IGF-IR pathway by antisense or dominant negative mutants causes reversal of the transformed phenotype in many rodent and human tumor cell lines. We stably transfected IGF-IR antisense mRNA expression plasmid into human papillomavirus (HPV) negative C33a cell line, HPV-16 positive SiHa cell line, and HPV-18 positive HeLa S3 cell line to determine whether the IGF-IR could be a target for cervical cancer cells especially in the presence of HPV. Approximately 30-80% downregulation of IGF-IR expression was observed by western blot in antisense transfected clones. There was a little inhibition in monolayer growth in all cell lines. In C33a cells, wild type and sense clones formed 92-146 colonies in soft agar after 3 weeks, antisense clones formed less than 12 colonies. In SiHa cells, wild type and sense clones formed about 60 colonies after 5 weeks, antisense clones formed 0-3 colonies. In HeLa S3 cells, wild type and sense clones formed 218-291 colonies in soft agar after 2 weeks, antisense clones formed 14-160 colonies. There was a good correlation between IGF-IR downreguration level and inhibition of transformation in soft agar. Tumorigenesis in nude mice was strongly inhibited in HeLa S3 and SiHa clones transfected with the antisense. These results indicate that downregulation of IGF-IR by antisense RNA can reverse the transformed phenotype of human cervical cancer cells even when harboring malignant type HPVs.

  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] 吉野内光夫: "骨盤リンパ節でのHPV DNA 検出による子宮頚癌微小転移の予知"産婦の世界. 50(7). 461-468 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉野内光夫: "IGF-Iレセプター・アンチセンス法による子宮頚癌遺伝子治療の基礎的検討"山陽放送学術文化財団リポート. 42. 39-44 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉野内光夫: "子宮頸癌術後再発の予知"産婦人科治療. 77(4). 436-440 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 宮木康成: "子宮頸部腺癌の臨床像"日臨細胞岡山会誌. 17. 1-2 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 児玉順一: "進行子宮頚癌に対するNeoadjuvant Chemotherapy - Pilot Study -"癌と化学療法. 26(1). 89-92 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Tokumo: "CD44 exon v6 is not implicated in the progression and metastasis of endometrial cancer"Cancer Lett.. 125. 221-225 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kobayashi: "Presence of human papilloma virus DNA in pelvic lymph nodes can predict unexpected recurrence of cervical cancer in patients with histologically negative lymph nodes"Clin.Cancer Res.. 4(4). 979-983 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Tokumo: "CD44exon v6 Correlates with Cellular Differentiation but not with progression and metastasis of Cervical Cancer"Eur.J.Cancer. 34(13. 2107-2111 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Kodama: "Vascular Endothelial Growth Factor Is Implicated in Early Invasion in Cervical Cancer"Eur.J.Cancer. 35. 485-489 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Kodama: "Angiogenesis and Platelet-derived Endotherical Growth Factor/thymidine phosphorylase Expression in Cervical Cancer"Int.J.Oncol.. 15(1). 149-154 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Kodama: "Angiogenesis and Platelet-derived Endothelial Cell Growth Factor/thymidine Phosphorylase Expression in Endometrial"Oncology Reports. 6. 617-620 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Seki: "Platelet-derived Endotherial Growth Factor Is Not Implicated in progression of Cervical Cancer"Int.J.Oncol.. 15(4). 781-786 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Yoshinouchi: "Analysis by Multiplex PCR of the Physical Status of Human Papilloma Virus type 16 DNA in Cervical Cancers"J.Clin.Microbiol.. 37(11). 3514-3517 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Seki: "Vascular Endothelial Growth Factor and Platelet-derived Endothelial Cell Growth Expression Are Implicated in the Angiogenesis of Endometrial Cancer."Eur.J.Cancer.. 36. 68-73 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Nakamura: "Down-regulation of the Insulin-like Growth Factor I Receptor by Antisense RNA Can Reverse the Transformed Phenotype of Human Cervical Cancer Cell Lines."Cancer Res.. 60(3). 760-765 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Yoshinouchi: "Alteration of the CDKN2/p16Gene Is Not Required for HPV- positive Uterine Cervical Cancer Cell Lines."Int.J.Oncol.. 16(3). 537-541 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Yoshinouchi: "Presence of Human Papilloma virus DNA in Pelvic Lymph Nodes can Predict Micro metastasis in Histologically Negative Lymph Nodes"Sannfujinnka no Sekai. 50(7). 461-468 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Yoshinouchi: "Fundamental Research of Gene Therapy for Cervical Cancer by Antisense Strategy Targeting IGF-1 Receptor"Sanyou Housou Bunkazaidan Reports. 42. 39-44 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Yoshinouchi: "Prediction of Recurrence of Cervical Cancer Patients post Surgery"Sannfujinnka Tiryou. 77(4). 436-440 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Miyagi: "Clinical Characteristics of The Uterine Cervix. Adenocarcinoma"Nihon Rinshou Saibou Gakkai Okayama Shibukaishi. 17. 1-2 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Kodama: "Neoadjuvant Chemotherapy for Advanced Cervical Cancer. -Pilot Study-"Cancer and Chemotherapy. 26(1). 89-92 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Tokumo: "CD44 exon v6 is not implicated in the progression and metastasis of endometrial cancer"Cancer Lett.. 125. 221-225 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Kobayashi: "Presence of human papilloma virus DNA in pelvic lymph nodes can predict unexpected recurrence of cervical cancer in patients with histologically negative lymph nodes"Clin. Cancer Res.. 4(4). 979-983 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Tokumo: "CD44 exon v6 Correlates with Cellular Differentiation but not with progression and metastasis of Cervical Cancer"Eur. J. Cancer. 34(13). 2107-2111 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Kodama: "Vascular Endothelial Growth Factor Is Implicated in Early Invasion in Cervical Cancer"Eur. J. Cancer. 35. 485-489 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Kodama: "Angiogenesis and Platelet-derived Endotherial Growth Factor / thymidine phosphorylase Expression in Cervical Cancer"Int. J. Oncol.. 15(1). 149-154 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Kodama: "Platelet-derived Endotherial Growth Factor Is Not Implicated in progression of Cervical Cancer"Oncology Reports. 6. 617-620 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Seki: "Angiogenesis and Platelet-derived Endothelial Cell Growth Factor / thymidine Phosphorylase Expression in Endometrial Cancer"Int. J. Oncol.. 15(4). 781-786 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Yoshinouchi: "Analysis by Multiplex PCR of the Physical Status of Human Papilloma Virus type 16 DNA in Cervical Cancers"J. Clin. Microbiol.. 37(11). 3514-3517 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Seki: "Vascular Endothelial Growth Factor and Platelet-derived Endothelial Cell Growth Expression Are Implicated in the Angiogenesis of Endometrial Cancer"Eur. J. Cancer. 36. 68-73 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Nakamura: "Down-regulation of the Insulin-like Growth Factor I Receptor by Antisense RNA Can Reverse the Transformed Phenotype of Human Cervical Cancer Cell Lines"Cancer Res.. 60(3). 760-765 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Yoshinouchi: "Alteration of the CDKN2/p16 Gene Is Not Required for HPV-positive Uterine Cervical Cancer Cell Lines"Int. J. Oncol.. 16(3). 537-541 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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