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

NCT ID: NCT01968928

Last Updated: 2013-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

25 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-01-31

Study Completion Date

2016-12-31

Brief Summary

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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.

Detailed Description

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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。

Conditions

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Bladder Urothelial Carcinoma

Keywords

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Bladder urothelial carcinoma (UC) pyruvate kinase drug resistance shikonin

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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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

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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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

Department of Urology, National Taiwan University Hospital, Taipei, Taiwan

Locations

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Department of Urology, National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Countries

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Taiwan

Central Contacts

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

Role: CONTACT

Phone: 886-2-23123456

Email: [email protected]

Chin-Ling Huang

Role: CONTACT

Phone: 886-2-23123456

Facility Contacts

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

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 19460998 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18337823 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21516121 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23791887 (View on PubMed)

Other Identifiers

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201308044RIN

Identifier Type: -

Identifier Source: org_study_id