Wednesday, October 18, 2006 12:12:45 AM
CEGE needs to get going.
This looks pretty good.
>>This combination therapy regimen induced complete tumor regression and generated antitumor immunity in 75% of tumor-bearing mice.<<
>>Cell, Tumor, and Stem Cell Biology
Low-Dose Etoposide Enhances Telomerase-Dependent Adenovirus-Mediated Cytosine Deaminase Gene Therapy through Augmentation of Adenoviral Infection and Transgene Expression in a Syngeneic Bladder Tumor Model
Gia-Shing Shieh1,5, Ai-Li Shiau1,2, Yi-Te Yo2, Pey-Ru Lin2, Chao-Ching Chang3, Tzong-Shin Tzai4 and Chao-Liang Wu1,3
1 Institute of Clinical Medicine and Departments of 2 Microbiology and Immunology, 3 Biochemistry and Molecular Biology, and 4 Urology, National Cheng Kung University Medical College, Tainan, Taiwan; and 5 Tainan Hospital, Department of Health, Executive Yuan, Taiwan
Requests for reprints: Chao-Liang Wu, Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, 1 Dashiue Road, Tainan 70101, Taiwan. Phone: 886-6-2353535, ext. 5536; Fax: 886-6-2741694; E-mail: wumolbio@mail.ncku.edu.tw or Tzong-Shin Tzai, Department of Urology, National Cheng Kung University Medical College, Tainan 70101, Taiwan. Phone: 886-6-2353535, ext. 5253; Fax: 886-6-2383678; E-mail: TTS777@mail.ncku.edu.tw.
The human telomerase reverse transcriptase (hTERT) promoter can selectively drive transgene expression in many telomerase-positive human cancer cells. Here we evaluated combination therapy of adenoviral vector Ad-hTERT-CD encoding E. coli cytosine deaminase (CD) driven by the hTERT promoter and low-dose etoposide (0.1 µg/mL) for treating bladder cancer. Ad-hTERT-CD conferred sensitivity to 5-fluorocytosine (5-FC) in bladder cancer cells, which could be enhanced by etoposide treatment, but not in normal cells. Such effect was correlated with up-regulation of hypoxia-inducible factor (HIF)-1 expression. By contrast, etoposide activated p53 and down-regulated hTERT promoter activity in normal cells. Etoposide also increased adenoviral infection via enhancement of coxsackie-adenovirus receptor expression on bladder cancer and normal cells. Combination index analysis revealed that combined therapy of Ad-hTERT-CD (109 plaque-forming units)/5-FC (200 mg/kg) with etoposide (2 mg/kg) synergistically suppressed tumor growth and prolonged survival in mice bearing syngeneic MBT-2 bladder tumors. This combination therapy regimen induced complete tumor regression and generated antitumor immunity in 75% of tumor-bearing mice. Furthermore, increased infiltrating CD4+ and CD8+ T cells and necrosis within tumors were found in mice receiving combination therapy of Ad-hTERT-CD and etoposide compared with those treated with either treatment alone. Thus, the potential high therapeutic index of the combination therapy may be an appealing therapeutic intervention for bladder cancer. Furthermore, because a majority of human tumors exhibit high telomerase activity, adenovirus-mediated CD gene therapy driven by the hTERT promoter in combination with low-dose etoposide may be applicable to a broad spectrum of cancers. (Cancer Res 2006; 66(20): 9957-66)<<
Recent GERN News
- Geron Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) • Business Wire • 06/20/2024 08:30:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/12/2024 08:05:08 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/12/2024 08:05:04 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/10/2024 09:53:19 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/10/2024 04:30:13 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:08 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:06 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:06 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:05 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:03 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:03 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 06/07/2024 08:03:44 PM
- Geron Announces FDA Approval of RYTELO™ (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia • Business Wire • 06/07/2024 01:58:00 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/05/2024 08:05:20 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/04/2024 09:02:18 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 05/17/2024 08:05:30 PM
- Geron Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) • Business Wire • 05/16/2024 08:30:00 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 05/15/2024 08:07:34 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/13/2024 08:05:15 PM
- Geron Corporation Reports First Quarter 2024 Financial Results and Business Highlights • Business Wire • 05/02/2024 11:00:00 AM
- Geron to Announce First Quarter 2024 Financial Results on May 2, 2024 • Business Wire • 04/25/2024 08:30:00 PM
- Geron Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) • Business Wire • 04/18/2024 08:30:00 PM
- Geron to Participate at Upcoming Investor Conferences in April • Business Wire • 04/03/2024 08:30:00 PM
- Geron Corporation Announces Pricing of $150 Million Underwritten Offering of Common Stock and Pre-Funded Warrants • Business Wire • 03/19/2024 01:07:00 PM
- Geron Announces FDA Oncologic Drugs Advisory Committee Votes in Favor of the Clinical Benefit/Risk Profile of Imetelstat for the Treatment of Transfusion-Dependent Anemia in Patients with Lower-Risk MDS • Business Wire • 03/14/2024 07:54:00 PM
Mass Megawatts Announces $220,500 Debt Cancellation Agreement to Improve Financing and Sales of a New Product to be Announced on July 11 • MMMW • Jun 28, 2024 7:30 AM
VAYK Exited Caribbean Investments for $320,000 Profit • VAYK • Jun 27, 2024 9:00 AM
North Bay Resources Announces Successful Flotation Cell Test at Bishop Gold Mill, Inyo County, California • NBRI • Jun 27, 2024 9:00 AM
Branded Legacy, Inc. and Hemp Emu Announce Strategic Partnership to Enhance CBD Product Manufacturing • BLEG • Jun 27, 2024 8:30 AM
POET Wins "Best Optical AI Solution" in 2024 AI Breakthrough Awards Program • POET • Jun 26, 2024 10:09 AM
HealthLynked Promotes Bill Crupi to Chief Operating Officer • HLYK • Jun 26, 2024 8:00 AM