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

Urothelial Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01993966
• Other study ID #: 201308047RIN
• Secondary ID: 103-002509
• Status: Not yet recruiting
• Phase: N/A
• First received: October 24, 2013
• Last updated: November 19, 2013
• Start date: January 2014
• Est. completion date: December 2016

Study information

• Verified date: November 2013
• Source: National Taiwan University Hospital
• Contact: Kuo-How Huang, M.D., Ph.D.
• Phone: 886-2-23123456
• Email: khhuang123[@]ntu.edu.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 25
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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 Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Locations

Country	Name	City	State
Taiwan	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.

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (5)

Hussain SA, James ND. The systemic treatment of advanced and metastatic bladder cancer. Lancet Oncol. 2003 Aug;4(8):489-97. Review. — View Citation

Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261-74. Review. — View Citation

Tachibana H. Molecular basis for cancer chemoprevention by green tea polyphenol EGCG. Forum Nutr. 2009;61:156-69. doi: 10.1159/000212748. Epub 2009 Apr 7. Review. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The IHC staining score	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	No