EGCG Modulate the Cytotoxic Effects of Chemotherapeutic Agents in Human Urothelial Carcinoma Cells

November 19, 2013 updated by: National Taiwan University Hospital

Mechanism of (-)-Epigallocatechin -3-gallate (EGCG) to Modulate the Cytotoxic Effects of Chemotherapeutic Agents in Human Urothelial Carcinoma Cells

Urothelial carcinoma (UC) is the most common cancer of urinary tract. Patients with metastatic UC are usually treated with systemic chemotherapy. There still existed 30% to 50% of advanced UC not responsive to cisplatin-based chemotherapy; the prognosis for patients with metastatic UC remains poor.

Study Overview

Status

Unknown

Conditions

Detailed Description

(-)-epigallocatechin -3-gallate (EGCG) is the most abundant polyphenol compound from green tea, representing ~16.5% of the water-extractable fraction. EGCG have various bioactivities and can bind and regulate a wide range of molecular involved in cell cycle, signal transduction, and protein degradation. However, the anticancer effects of EGCG on UC have not been thoroughly explored. Our preliminary data show that EGCG alone can inhibit cell proliferation and induce apoptosis with the activation of caspases and PARP in a time dependent manner. Moreover, EGCG can enhance the cytotoxicity of several chemotherapeutic drugs in vitro. The underlying mechanism seems to be associated with Akt and ERK pathway. We will also check the Akt and ERK protein level by immunohistochemical staining in clinically chemoreistant bladder urothelial carcinoma specimens to further prove our in vitro findings. We will further confirm the effect of chemotherapeutic drugs combined with EGCG on UC in vivo via xenograft model.

The specific aims of the study are:

  1. To explore the anti-tumor effects of EGCG on human UC cells and elucidate the possible mechanisms.
  2. To study the combinative cytotoxic effect of EGCG with other chemotherapeutic agents such as cisplatin, doxorubicin and gemcitabine on UC cells; moreover, to investigate the underlying mechanisms.
  3. To investigate the expression level of phospho-Akt and phospho-ERK in clinically chemoreistant bladder urothelial carcinoma specimens to further confirm our finding in clinical events. .
  4. To prove the in vitro findings and confirm the combinative efficacy of EGCG with chemotherapeutic agents in vivo by using the xenograft animal model.
  5. To establish a novel therapeutic strategy for treatment of UC.

Study Type

Observational

Enrollment (Anticipated)

25

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
    • No. 7, Chung Shans. Rd.
      • Taipei, No. 7, Chung Shans. Rd., Taiwan, 100
        • Department of Urology, National Taiwan University Hospital
    • No. 7, Chung Shans. Rd.,
      • Taipei, No. 7, Chung Shans. Rd.,, Taiwan, 100
        • Department of Urology, National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

patients with age between 20-80 years old and had taken Radical Cystectomy or nephrectomy between 2008-2012 were chosen as study population

Description

Inclusion Criteria:

  • In January 2008 to December 2012 at the National Taiwan University Hospital for surgery (radical resection of kidney and ureter or bladder removal) of urothelial carcinoma histopathology specimens of patients willing to participate in this study and the subjects described in the consent Book signer.

Exclusion Criteria:

  • In January 2008 to December 2012 at the National Taiwan University Hospital for surgery (radical resection of kidney and ureter or bladder removal) of urothelial carcinoma histopathology specimens of patients are reluctant to join the researcher

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
drug-resistant
specimens com from drug-resistant bladder urothelial carcinoma patients
normal
specimens come from normal bladder urothelial carcinoma patients
non-tumoral
specimens come from non-tumoral patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The IHC staining score
Time Frame: at the time of surgery
the IHC staining scores are acquired by IHC staining and assessed by pathologist. The comparisons between each specimen are determined by IHC scores.
at the time of surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

  • Principal Investigator: Kuo-How Huang, M.D.,Ph.D., No. 7, Chung Shans. Rd., Taipei, Taiwan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

October 24, 2013

First Submitted That Met QC Criteria

November 19, 2013

First Posted (Estimate)

November 25, 2013

Study Record Updates

Last Update Posted (Estimate)

November 25, 2013

Last Update Submitted That Met QC Criteria

November 19, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201308047RIN
  • 103-002509 (Other Grant/Funding Number: National Taiwan University Hospital)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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