Bladder Urothelial CarcinomaNCT01968928
The Role of Pyruvate Kinase M2 in Growth, Invasion and Drug Resistance in Human Urothelial Carcinoma
An observational study of Bladder Urothelial Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
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. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Bladder Urothelial Carcinoma
- How many people
- 25 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2014to Dec 2016
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- patients with age between 20-80 years old and had taken Radical Cystectomy or nephrectomy between 2008-2012
Who cannot join
- patients with age not located in the interval of 20-80 years old.
Trial locations and contacts
1 site in 1 country.
Chin-Ling Huang contact
Taiwan1 site
Department of Urology, National Taiwan University Hospital
Taipei, 10002
Kuo-How Huang, M.D.,Ph.D., 886-2-23123456 ext. 65952, khhuang123@ntu.edu.tw
Kuo-How Huang, M.D.,Ph.D.
About this study
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.
Read the 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。
- Conditions
- Bladder Urothelial Carcinoma
- Keywords
- Bladder urothelial carcinoma (UC), pyruvate kinase, drug resistance, shikonin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| drug-resistant | specimens com from drug-resistant bladder urothelial carcinoma patients. | |
| normal | specimens come from normal bladder urothelial carcinoma patients. | |
| non-tumoral | specimens come from non-tumoral patients. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The IHC score
the IHC scores are acquired by IHC staining and the comparisons between each specimen are determined by IHC scores.
Measured: at the time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2013 (estimated)
- Study startJan 2014
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Bladder Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 25 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kuo-How Huang, M.D., Ph.D., Principal investigator, Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01968928
- Sponsor's protocol ID
- 201308044RIN
- Status last verified
- Oct 2013
- First submitted
- 21 Oct 2013
- Last updated
- 28 Oct 2013
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 19460998Christofk 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.
PubMed 18337823Chen 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.
PubMed 21516121Yang 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.
PubMed 23791887
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Pyruvate Kinase M2 in Growth, Invasion and Drug Resistance in Human Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT01968928
- Acronym / sponsor ID
- 201308044RIN
- Conditions
- Bladder Urothelial Carcinoma
- Keywords
- Bladder urothelial carcinoma (UC), pyruvate kinase, drug resistance, shikonin
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 24 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| drug-resistant | – | –specimens com from drug-resistant bladder urothelial carcinoma patients. |
| normal | – | –specimens come from normal bladder urothelial carcinoma patients. |
| non-tumoral | – | –specimens come from non-tumoral patients. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- patients with age between 20-80 years old and had taken Radical Cystectomy or nephrectomy between 2008-2012
Key exclusion criteria (1 listed)
- patients with age not located in the interval of 20-80 years old.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The IHC score
Time frame: at the time of surgery
the IHC scores are acquired by IHC staining and the comparisons between each specimen are determined by IHC scores.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2013.
- Background: PubMed 19460998Vander 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.
- Background: PubMed 18337823Christofk 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.
- Background: PubMed 21516121Chen 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.
- Background: PubMed 23791887Yang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chin-Ling Huang contact
Kuo-How Huang, M.D., Ph.D. principal investigator
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bladder Urothelial Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kuo-How Huang, M.D., Ph. D (886-2-23123456 ext. 65952, khhuang123@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The IHC score (time frame: at the time of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01968928, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2013.