ORCID Profile
0000-0002-3436-4369
Current Organisations
University of Medicine and Pharmacy at Ho Chi Minh city
,
Flinders University
,
Binh Dan Hospital
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Publisher: American Association for Cancer Research (AACR)
Date: 12-2017
DOI: 10.1158/1535-7163.MCT-17-0074
Abstract: We investigated the potential of combining the hypoglycemic drug metformin (MET) and the antiepileptic drug valproic acid (VPA), which act via different biochemical pathways, to provide enhanced antitumor responses in prostate cancer. Prostate cancer cell lines (LNCaP and PC-3), normal prostate epithelial cells (PrEC), and patient-derived prostate tumor explants were treated with MET and/or VPA. Proliferation and apoptosis were assessed. The role of p53 in response to MET + VPA was assessed in cell lines using RNAi in LNCaP (p53+) and ectopic expression of p53 in PC-3 (p53−). The role of the androgen receptor (AR) was investigated using the AR antagonist enzalutamide. The combination of MET and VPA synergistically inhibited proliferation in LNCaP and PC-3, with no significant effect in PrEC. LNCaP, but not PC-3, demonstrated synergistic intrinsic apoptosis in response to MET + VPA. Knockdown of p53 in LNCaP (p53+, AR+) reduced the synergistic apoptotic response as did inhibition of AR. Ectopic expression of p53 in PC-3 (p53−, AR−) increased apoptosis in response to MET + VPA. In patient-derived prostate tumor explants, MET + VPA also induced a significant decrease in proliferation and an increase in apoptosis in tumor cells. In conclusion, we demonstrate that MET + VPA can synergistically kill more prostate cancer cells than either drug alone. The response is dependent on the presence of p53 and AR signaling, which have critical roles in prostate carcinogenesis. Further in vivo/ex vivo preclinical studies are required to determine the relative efficacy of MET + VPA as a potential treatment for prostate cancer. Mol Cancer Ther 16(12) 2689–700. ©2017 AACR.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.UROLONC.2009.12.008
Abstract: Although prostate cancer (CaP) is the most common male cancer in developed countries, the incidence of CaP in Vietnam remains unknown and the patients often seek treatment at a late stage in their illness. The mass screening of CaP, which has been performed since Jan 2008 in Binh Dan hospital (Ho Chi Minh City) aims to evaluate the effect of CaP mass screening in Vietnam. The details of CaP treatment from 1999 to now in Ho Chi Minh City (HCMC) were also used for evaluation and comparison. From the first quarter of 2008, we started a free CaP screening program in HCMC. There were 408 cases during first round of results. When inspecting CaP treatment, all papers and studies of CaP at Binh Dan hospital from 1999 were analyzed, including 1,775 CaPs treated. A total of 408 subjects were screened during the CaP program. Prostate biopsies were carried out on 87 men (21.3%) based on PSA values and DRE results. Ten of these biopsied men (2.5%) were diagnosed with CaP, mostly with Gleason's scores of 5 to 7 and in an early clinical stage. In reviewing CaP treatment from 1999 to 2009, complete androgen blockade/maximal androgen blockade (MAB/CAB) was widely used, while chemotherapy and radiotherapy were not routinely used. Open and laparoscopic total prostatectomy remarkably increased due to the many efforts of CaP screening. The number of CaP cases has now reached and overtaken the number of bladder cancer cases in our hospital. Similarly, early diagnosis rates have increased in parallel with radical treatment. Our initial outcomes reflected a low prevalence of CaP in general (2,5%), but a high occurrence of medium grade lesions (Gleason 7) among patients who tested positive for CaP. On one hand, this observation highlights the value of the CaP screening programs in alerting doctors eople and detecting more cases in the early stages of development. On the other hand, the benefit of a mass screening program for CaP is not proven. Meanwhile, selective CaP screening takes advantage of diagnosis and treatment in our country.
Location: Viet Nam
Start Date: 2016
End Date: 2016
Funder: South Australian Health and Medical Research Institute
View Funded ActivityStart Date: 2013
End Date: 2017
Funder: Australia Awards
View Funded ActivityStart Date: 2017
End Date: 2017
Funder: Flinders University
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Flinders Medical Centre Foundation
View Funded Activity