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

NCT ID: NCT01993966

Last Updated: 2013-11-25

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 25 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2016-12-31

Brief Summary

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.

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.

Conditions

Urothelial Carcinoma

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

drug-resistant

specimens com from drug-resistant bladder urothelial carcinoma patients

No interventions assigned to this group

normal

specimens come from normal bladder urothelial carcinoma patients

No interventions assigned to this group

non-tumoral

specimens come from non-tumoral patients

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kuo-How Huang, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

No. 7, Chung Shans. Rd., Taipei, Taiwan

Locations

Department of Urology, National Taiwan University Hospital

Taipei, No. 7, Chung Shans. Rd.,, Taiwan

Department of Urology, National Taiwan University Hospital

Taipei, No. 7, Chung Shans. Rd., Taiwan

Countries

Taiwan

Central Contacts

Kuo-How Huang, M.D., Ph.D.

Role: CONTACT

khhuang123@ntu.edu.tw

886-2-23123456 ext. 65952

Chin-Ling Huang

Role: CONTACT

886-2-23123456 ext. 65233

Facility Contacts

Kuo-How Huang, M.D.,Ph.D.

Role: primary

886-2-23123456

Chin-Ling Huang

Role: backup

d95447004@ntu.edu.tw

886-2-23123456 ext. 65233

Kuo-How Huang, M.D.,Ph.D.

Role: primary

khhuang123@ntu.edu.tw

886-2-23123456 ext. 65952

References

Hussain SA, James ND. The systemic treatment of advanced and metastatic bladder cancer. Lancet Oncol. 2003 Aug;4(8):489-97. doi: 10.1016/s1470-2045(03)01168-9.

Reference Type: BACKGROUND

PMID: 12901963 (View on PubMed)

Ueki O, Hisazumi H, Uchibayashi T, Naito K, Tajiri S, Takemae K, Kawaguchi K, Kameda K, Nishino A, Nango C, et al. Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced urothelial cancer. Cancer Chemother Pharmacol. 1992;30 Suppl:S72-6. doi: 10.1007/BF00686947.

Reference Type: BACKGROUND

PMID: 1394823 (View on PubMed)

Tachibana H. Molecular basis for cancer chemoprevention by green tea polyphenol EGCG. Forum Nutr. 2009;61:156-169. doi: 10.1159/000212748. Epub 2009 Apr 7.

Reference Type: BACKGROUND

PMID: 19367120 (View on PubMed)

Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009 Jun;9(6):429-39. doi: 10.1038/nrc2641.

Reference Type: BACKGROUND

PMID: 19472429 (View on PubMed)

Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261-74. doi: 10.1016/j.cell.2007.06.009.

Reference Type: BACKGROUND

PMID: 17604717 (View on PubMed)

Other Identifiers

103-002509

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

201308047RIN

Identifier Type: -

Identifier Source: org_study_id