BIOMAT Database Logo BIOMAT Database Logo

Successful adenovirus-mediated wild-type p53 gene transfer in patients with bladder cancer by intravesical vector instillation. 2002

Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
Department of Medicine III, Johannes Gutenberg University, Mainz, Germany.

OBJECTIVE To study safety, feasibility, and biologic activity of adenovirus-mediated p53 gene transfer in patients with bladder cancer. METHODS Twelve patients with histologically confirmed bladder cancer scheduled for cystectomy were treated on day 1 with a single intratumoral injection of SCH 58500 (rAd/p53) at cystoscopy at one dose level (7.5 x 10(11) particles) or a single intravesical instillation of SCH 58500 with a transduction-enhancing agent (Big CHAP) at three dose levels (7.5 x 10(11) to 7.5 x 10(13) particles). Cystectomies were performed in 11 patients on day 3, and transgene expression, vector distribution, and biologic markers of transgene activity were assessed by molecular and immunohistochemical methods in tumors and normal bladder samples. RESULTS Specific transgene expression was detected in tissues from seven of eight assessable patients treated with intravesical instillation of SCH 58500 but in none of three assessable patients treated with intratumoral injection of SCH 58500. Induction of RNA and protein expression of the p53 target gene p21/WAF1 was demonstrated in samples from patients treated with SCH 58500 instillation at higher dose levels. Distribution studies after intravesical instillation of SCH 58500 revealed both high transduction efficacy and vector penetration throughout the whole urothelium and into submucosal tumor cells. No dose-limiting toxicity was observed, and side effects were local and of transient nature. CONCLUSIONS Intravesical instillation of SCH 58500 combined with a transduction-enhancing agent is safe, feasible, and biologically active in patients with bladder cancer. Studies to evaluate the clinical efficacy of this treatment in patients with localized high-risk bladder cancer are warranted.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D001749 Urinary Bladder Neoplasms Tumors or cancer of the URINARY BLADDER. Bladder Cancer,Bladder Neoplasms,Cancer of Bladder,Bladder Tumors,Cancer of the Bladder,Malignant Tumor of Urinary Bladder,Neoplasms, Bladder,Urinary Bladder Cancer,Bladder Cancers,Bladder Neoplasm,Bladder Tumor,Cancer, Bladder,Cancer, Urinary Bladder,Neoplasm, Bladder,Neoplasm, Urinary Bladder,Tumor, Bladder,Tumors, Bladder,Urinary Bladder Neoplasm
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005822 Genetic Vectors DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition. Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000256 Adenoviridae A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases. Adenoviruses,Ichtadenovirus,Adenovirus,Ichtadenoviruses
D000283 Administration, Intravesical The instillation or other administration of drugs into the bladder, usually to treat local disease, including neoplasms. Bladder Drug Administration,Drug Administration, Bladder,Instillation, Bladder,Intravesical Drug Administration,Administration, Intravesical Drug,Injections, Intravesical,Intravesical Administration,Intravesical Injection,Intravesical Instillation,Administration, Bladder Drug,Administrations, Bladder Drug,Administrations, Intravesical,Administrations, Intravesical Drug,Bladder Drug Administrations,Bladder Instillation,Bladder Instillations,Drug Administration, Intravesical,Drug Administrations, Bladder,Drug Administrations, Intravesical,Injection, Intravesical,Instillation, Intravesical,Instillations, Bladder,Instillations, Intravesical,Intravesical Administrations,Intravesical Drug Administrations,Intravesical Injections,Intravesical Instillations
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

Related Publications

Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
Adenovirus-Mediated Wild-Type p53 Gene Transfer into Head and Neck Cancers.
January 2000, Methods in molecular medicine,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
[Therapeutic effect of adenovirus-mediated transfer of the wild-type p53 gene with cisplatin].
July 1996, Gan to kagaku ryoho. Cancer & chemotherapy,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
Adenovirus-mediated transfer of a wild-type p53 gene and induction of apoptosis in cervical cancer.
July 1996, Cancer research,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
p53 Mutation in bladder cancer patients in Japan and inhibition of growth by in vitro adenovirus-mediated wild-type p53 transduction in bladder cancer cells.
January 2001, Molecular urology,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.
September 1996, Nature medicine,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer.
September 1998, Human gene therapy,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene.
May 1994, Cancer research,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
Alteration of drug chemosensitivity caused by the adenovirus-mediated transfer of the wild-type p53 gene in human lung cancer cells.
February 2000, Cancer gene therapy,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
High-efficiency gene transfer and high-level expression of wild-type p53 in human lung cancer cells mediated by recombinant adenovirus.
March 1994, Cancer gene therapy,
Jürgen Kuball, and Shu Fen Wen, and Joachim Leissner, and Derek Atkins, and Patricia Meinhardt, and Erlinda Quijano, and Heidrun Engler, and Beth Hutchins, and Daniel C Maneval, and Michael J Grace, and Mary Ann Fritz, and Stefan Störkel, and Joachim W Thüroff, and Christoph Huber, and Martin Schuler
Molecular determinants of cell death induction following adenovirus-mediated gene transfer of wild-type p53 in prostate cancer cells.
January 2001, International journal of cancer,
Copied contents to your clipboard!