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

Study Overview
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Brief Summary
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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
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(-)-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: To explore the anti-tumor effects of EGCG on human UC cells and elucidate the possible mechanisms. 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. 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. . To prove the in vitro findings and confirm the combinative efficacy of EGCG with chemotherapeutic agents in vivo by using the xenograft animal model. To establish a novel therapeutic strategy for treatment of UC.

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

Conditions
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Urothelial Carcinoma

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| drug-resistant<br>specimens com from drug-resistant bladder urothelial carcinoma patients | |
| normal<br>specimens come from normal bladder urothelial carcinoma patients | |
| non-tumoral<br>specimens come from non-tumoral patients | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urothelial carcinoma (UC),, (-)-epigallocatechin-3-gallate(EGCG),, chemotherapy,, cytotoxicity,, drug resistance,, xenograft.