The Role of Pyruvate Kinase M2 in Growth, Invasion and Drug Resistance in Human Urothelial Carcinoma

Bladder Urothelial Carcinoma Clinical Trial

Official title:

The Role of Pyruvate Kinase M2 in Growth, Invasion and Drug Resistance in Human Urothelial Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01968928
• Other study ID #: 201308044RIN
• Status: Not yet recruiting
• Phase: N/A
• First received: October 21, 2013
• Last updated: October 24, 2013
• Start date: January 2014
• Est. completion date: December 2016

Study information

• Verified date: October 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

Bladder urothelial carcinoma (UC) is a common malignancy and the incidence is increasing by years in Taiwan. Chemoresistance was inevitable in treatment of metastatic disease and lead to the ominous outcomes. To develop novel therapeutic strategies to overcome chemoresistance is imperative. Cancer cells uptake glucose at higher rates than normal tissue but use most of glucose for glycolysis even under normoxia condition, which is known as the Warburg effect. Pyruvate kinase (PK) catalyzes the last step in the process of glycolysis, and one of it isoform--PKM2 has been reported to be associated with tumor progression and some specific tissues and promotes the Warburg effect in cancer cells.

Description:

Regulation of PKM2 can be a novel target of cancer therapy. Meanwhile, PKM2 may play a critical role in the development of drug resistance and can be a promising target to overcome drug resistance.

In this study, our specific aims are as follows:

1. To prove the differentia expression levels of PKM2 in UC cells and drug-resistant UC cells, as well as in human UC tissues and drug-resistant UC tissues.

2. To examine the effect of PKM2 regulations（PKM2 siRNA and shikonin）on invasiveness and metastatic ability of UC cells and clarify the role of PKM2 in human UC cells.

3. To investigate the combinatory effect of PKM2 regulations（PKM2 siRNA and shikonin）and currently used chemotherapeutic agents (cisplatin，gemcitabine ,doxorubicin). Do PKM2 regulations enhance the cytotoxic effect of chemotherapy and overcome the chemoresistance？

4. To further prove the in vitro findings in the nude mice xenograft model。

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:

• patients with age between 20-80 years old and had taken Radical Cystectomy or nephrectomy between 2008-2012

Exclusion Criteria:

• patients with age not located in the interval of 20-80 years old.

Study Design

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

Related Conditions & MeSH terms

• Bladder Urothelial Carcinoma
• Carcinoma
• Carcinoma, Transitional Cell

Locations

Country	Name	City	State
Taiwan	Department of Urology, National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (4)

Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene. 2011 Oct 20;30(42):4297-306. doi: 10.1038/onc.2011.137. Epub 2011 Apr 25. — View Citation

Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008 Mar 13;452(7184):230-3. doi: 10.1038/nature06734. — View Citation

Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009 May 22;324(5930):1029-33. doi: 10.1126/science.1160809. Review. — View Citation

Yang W, Lu Z. Regulation and function of pyruvate kinase M2 in cancer. Cancer Lett. 2013 Oct 10;339(2):153-8. doi: 10.1016/j.canlet.2013.06.008. Epub 2013 Jun 18. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The IHC score	the IHC scores are acquired by IHC staining and the comparisons between each specimen are determined by IHC scores.	at the time of surgery	No