- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01968928
The Role of Pyruvate Kinase M2 in Growth, Invasion and Drug Resistance in Human Urothelial Carcinoma
October 24, 2013 updated by: National Taiwan University Hospital
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.
Study Overview
Status
Unknown
Conditions
Detailed 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:
- 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.
- 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.
- 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?
- To further prove the in vitro findings in the nude mice xenograft model。
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
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Taipei, Taiwan, 10002
- Department of Urology, National Taiwan University Hospital
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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:
- 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 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
- Observational Models: Case-Only
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
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drug-resistant
specimens com from drug-resistant bladder urothelial carcinoma patients.
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normal
specimens come from normal bladder urothelial carcinoma patients.
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non-tumoral
specimens come from non-tumoral patients.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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The IHC score
Time Frame: at the time of surgery
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the IHC scores are acquired by IHC staining and the comparisons between each specimen are determined by IHC scores.
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at the time of surgery
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Kuo-How Huang, M.D., Ph.D., Department of Urology, National Taiwan University Hospital, 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
- 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.
- 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.
- 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.
- 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.
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 21, 2013
First Submitted That Met QC Criteria
October 21, 2013
First Posted (Estimate)
October 24, 2013
Study Record Updates
Last Update Posted (Estimate)
October 28, 2013
Last Update Submitted That Met QC Criteria
October 24, 2013
Last Verified
October 1, 2013
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201308044RIN
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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