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PTN Nghiên cứu và Ứng dụng Tế bào gốc

Category: Bài báo ngoài nước

  • Targeting breast cancer stem cells: Principle and Update

    Targeting breast cancer stem cells: Principle and update

    Phuc V Pham

    Abstract

    Breast cancer is a complicated problem. Many studies have been approaching to find out its cause and how to cure this disease. For 5-10 years ago many useful properties of breast cancer stem cells have been discovered and used as targets of new targeting strategies. There are some strategies that were used to target the breast cancer stem cells such as directly targeting on self renewal, indirectly targeting on microenvironment or directly killing breast cancer stem cells. Some chemical agents causing differentiation also were used to target breast cancer stem cells. Recently, immunotherapy as well as oncolytic virus also is two potential strategies in targeting breast cancer stem cells. In this review, we will review recent progress in the development of therapies to treat breast cancer using the breast cancer stem cell targeting strategy. This review helps us understand the development of targeting therapy in breast cancer treatment as well as which strategies can become novel therapies against breast cancer.

    References

    Full Text: PDF

  • Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells

    Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells

    • Trang Thi Maia, d,
    • JeongYong Moona, d,
    • YeonWoo Songa, d,
    • Pham Quoc Vietb, d,
    • Pham Van Phucb, d,
    • Jung Min Leec, d,
    • Tae-Hoo Yic, d,
    • Moonjae Chod,
    • Somi Kim Choa, d
    • a Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea
    • b Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh, Viet nam
    • c Department of Oriental Medicinal Materials and Processing, College of Life Science, Kyung Hee University, Gyeonggi 446-701, Republic of Korea
    • d Department of Medicine, Medical School, Jeju National University, Jeju 690-756, Republic of Korea

    Abstract

    Ginsenoside F2 (F2) was assessed for its antiproliferative activity against breast cancer stem cells (CSCs). F2 induced apoptosis in breast CSCs by activating the intrinsic apoptotic pathway and mitochondrial dysfunction. Concomitantly, F2 induced the formation of acidic vesicular organelles, recruitment of GFP-LC3-II to autophagosomes, and elevation of Atg-7 levels, suggesting that F2 initiates an autophagic progression in breast CSCs. Treatment with an inhibitor of autophagy enhanced F2-induced cell death. Our findings provide new insights into the anti-cancer activity of F2 and may contribute to the rational use and pharmacological study of F2.

    Keywords

    • Apoptosis;
    • Autophagy;
    • Breast cancer stem cells;
    • Ginsenoside F2

    http://www.sciencedirect.com/science/article/pii/S0304383512001000

    pubmed

     

  • Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

    Research

    Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

    Phuc V Pham, Nhan LC Phan, Nhung T Nguyen, Nhung H Truong, Thuy T Duong, Dong V Le, Kiet D Truong and Ngoc K Phan

    Journal of Translational Medicine 2011, 9:209 doi:10.1186/1479-5876-9-209

    Published: 7 December 2011

    Abstract

    Background

    Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs).

    Methods

    We isolated a breast cancer cell population (CD44+CD24- cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs.

    Results

    Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs.

    Conclusions

    Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.

    pubmed

  • ISOLATION OF CANCER CELL LINE FROM WOMAN BREAST TUMOR

    ISOLATION OF CANCER CELL LINE FROM WOMAN BREAST TUMOR

    Pham Van Phuc*, Le Thanh Trung, Truong Hai Nhung, Vuong Gia Tue, Duong Thanh Thuy, Phan Kim Ngoc

    University of Science, National University Hochiminh city

    SUMMARY

    Cancer cell lines have had important roles in anti-cancer drug screening research and development. Breast cancer cell lines contributed much in development of anti-cancer drugs. So that, many breast cancer cell lines have been established up to date. However, there is not breast cancer cell line from Vietnamese woman established today. The aim of this research was establishing the procedure to isolate breast cancer cell line from Vietnamese woman breast cancer tumor.  In this research, breast tumors in Phase IIIA were used to isolate candidate breast cancer cells by primary culture with specific medium. The cells isolated from primary culture were subcultured some times to propagate and enrich breast cancer cells. Cancer cell population was purified by sorting breast cancer cells based on CD90 negative-expression by flow cytometry. To confirm the tumor-creating capacity, purified breast cancer cell population was checked the expression of BRCA1 gene, CD24 marker and the potency creating tumor in vivo mice. The results showed that breast cancer cell lines had homogenous phormology with epithelial shape, expressed lowly BRCA1 gene and caused the tumor in mouse when injected more than 2 million cells.

    Keywords: Breast tumor, breast cancer cell line, CD24 marker, cancer cell

    Fulltext: Journal of Biotechnology 8(4): 1775-1783, 2010

    * Author for correspondence: Tel: 84-8-38397719; Fax: 84-8-38967365; E-mail: pvphuc@hcmuns.edu.vn


  • ISOLATION AND COMPARISON OF TUMORIGENICITY OF DIFFERENT CELL POPULATIONS IN MCF-7 BREAST CANCER CELL

    ISOLATION AND COMPARISON OF TUMORIGENICITY OF DIFFERENT CELL POPULATIONS IN MCF-7 BREAST CANCER CELL LINE BASED ON CD44 AND CD24 MARKERS

    Pham Van Phuc1, Siah Chia Keng2, Nguyen Thi Minh Nguyet1, Duong Thanh Thuy1, Phan Kim Ngoc1

    1University of Science, Vietnam National University HCM city

    2Temasek Polytechnic, Singapore

    SUMMARY

    Breast cancer stem cells are the origin of breast tumour. Cells expressing marker CD44+CD24-/dim were considered breast cancer stem cells in human being. The aims of this study is to isolate potential candidate breast cancer stem cell from the MCF-7 cell line to find out whether it is possible to isolate cancer stem cells using two cell surface markers: CD44 and CD24. Stem-like properties were studied in vivo by observing the tumorigenicity of different cell populations in immunosuppressed mouse models. MCF-7 cells were subculture for several passages and were sorted out into 3 different cell populations by 2 specific antibodies which bind to CD44 and CD24, using flow cytometry. Cell sub-populations: CD44+, CD44+/CD24+ and CD44+/CD24-/dim were further cultured and were then analysed using flow cytometry again to determine the purity of the population. Different cell sub-populations were then harvested and injected into mouse models at two specific doses, 103 and 106 cells. Tumour formation in the mice was monitored closely and the percentages of mice which have tumour were recorded as results. The results showed that the capacity of causing tumour in mouse was highest in CD44+CD24-/dim cell population and lowest in CD44+ cell population. These results confirmed CD44+CD24-/dim cells were the strongest cell population causing tumour in breast cancer cells MCF-7.

    Keywords: Breast cancer cells, MCF-7 cell line, Breast cancer stem cells, Tumorigenicity

    Fulltext: Journal of Biotechnology 8(4): 1-7, 2010

    * Author for correspondence: Tel: 84-8-38397719; Fax: 84-8-38967365; E-mail: pvphuc@hcmuns.edu.vn


  • Research on in vitro culture and inducing nacre crystal formation of freshwater pearl mussel…

    Pham Van Phuc, Pham Quoc Viet, Nguyen Minh Hoang, Nguyen Thanh Tam and Phan Kim Ngoc (2011). Research on in vitro culture and inducing nacre crystal formation of freshwater pearl mussel mantle epithelial cell Sinohyriopsis cumingii. International Journal of Fisheries and Aquaculture 3(6):104- 112.

    International Journal of Fisheries and Aquaculture Vol. 3(6), pp.105- 113, June 2011

    ISSN 2006-9839 ©2011 Academic Journals

     

    Full Length Research Paper

     

    Research on in vitro culture and inducing nacre crystal formation of freshwater pearl mussel mantle epithelial cell Sinohyriopsis cumingii

    Pham Van Phuc*, Pham Quoc Viet, Nguyen Minh Hoang, Nguyen Thanh Tam and Phan Kim Ngoc

     

    Laboratory of Stem Cell Research and Application University of Science, Vietnam National University, Ho Chi Minh, Vietnam.

     

    *Corresponding author: E-mail: pvphuc@hcmuns.edu.vn.

     

    Accepted 28 March, 2011

    Abstract

    The foundation of natural pearl formation by mussels is calcium carbonate in the form of aragonite crystals, secreted essentially by the epithelial cells of mantle tissue as nacre. The in vitro explant culture of nacre secreting pallial mantle explants of freshwater pearl mussel was a vital step in the approach to the establishment of quality of pearl mussel species, by screening pearl mussel species that are able to form pearls with high efficiency. Moreover, the results of this research provide knowledge for the future in vitro colored pearl production. The aims of this research were to culture freshwater pearl mussel mantle epithelial cells and to investigate the capacity of their nacre-secretion when they were induced by some specific factors such as Ca2+, FGF-2 and EGF. In this research, mantle epithelial cells were cultured in four different kinds of medium (DMEM/F12, L15-M199, IMDM, TCM) and temperature [(4, 24°C and room temperature (28°C)] to select the suitable environment for pearl mussel mantle epithelial cell culture for at least one month. After that, old medium was changed by fresh medium supplemented with three inducers (Ca2+, FGF, EGF). Nacre secretion of these cells was evaluated via the nacre formation in culture medium. The results showed that the mantle epithelial cells may be cultured in vitro and secrete nacre in DMEM/F12 medium supplemented with 10% FBS, but the efficiency of secretion was independent with different inducers investigated. DMEM/F12 medium is the best for growing of mantle epithelial cells while IMDM medium is suitable for heamocyte –like cells.

    Key words: DMEM/F12, Ca2+, EGF, FGF, Freshwater mussel, mantle epithelial cells, nacre secretion.

  • Regeneration of Pancreatic B Cells of Type 1 Diabetic Mouse by Stem Cell Transplatation

    Pham Van Phuc, Pham Le Buu Truc, Duong Thanh Thuy, Truong Hai Nhung and Doan Chinh Chung, Phan Kim Ngoc. Regeneration of Pancreatic B Cells of Type 1 Diabetic Mouse by Stem Cell Transplatation. IFMBE Proceedings, 1, Volume 27, The Third International Conference on the Development of Biomedical Engineering in Vietnam, Part 5, Pages 163-166.

    IFMBE Proceedings, 2010, Volume 27, Part 5, 163-166, DOI: 10.1007/978-3-642-12020-6_40

    Regeneration of Pancreatic B Cells of Type 1 Diabetic Mouse by Stem Cell Transplatation

    Pham Van Phuc, Pham Le Buu Truc, Duong Thanh Thuy, Truong Hai Nhung, Doan Chinh Chung, Nguyen Khac Toan, Ma Kien Phuc and Phan Kim Ngoc

    Abstract

    Type 1 diabetes is the result of an autoimmune attack against the insulin-producing β cells of the pancreas. Current treatment for patients with type 1 diabetes typically involves a rigorous and invasive regimen of testing blood glucose levels many times a day along with injections of recombinant insulin. Islet transplantation is still not indicated for pediatric patients. Many recent researches have shown that stem cell therapy can be the best choice for treatment this disease. The aims of this research were investigating regeneration of pancreatic β cells of type 1 diabetic mouse after stem cell transplantation. Diabetic mice were induced by streptozocin. Some different kinds of stem cell such as mesenchymal stem cells and nucleated cells derived from human umbilical cord blood; mesenchymal stem cells and hematopoietic stem cells and mononuclear cells derived from murine bone marrow; insulin-secreting cells differentiated from mesenchymal stem cells were used to transplant into diabetic mice. Each diabetic mouse was transplanted with 5×106 cells by one of two ways: inject into pancreas or inject into tail portal vein. Regeneration of β cells was confirmed by decreasing blood glucose level, increasing insulin concentration in blood, body weight and the number of islets of Langerhans in the pancreas. The results showed that transplanting different kinds of stem cells as well as injection methods would give different results for regeneration of β cells. The best result achieved when transplanting insulin producing cells derived from mesenchymal stem cells into diabetic mice by directly injecting into pancreas.

    Keywords diabetic mouse – mesenchymal stem cell – bone marrow – stem cell therapy – type 1 diabetes

    * Author for correspondence: Tel: 84-8-38397719; Fax: 84-8-38967365; E-mail: pvphuc@hcmuns.edu.vn

  • Results of Curing Some Diseases by Stem Cell Transplantation at Stem Cell R&D Laboratory

    Phan Kim Ngoc and Pham Van Phuc. Results of Curing Some Diseases by Stem Cell Transplantation at Stem Cell R&D Laboratory. IFMBE Proceedings, 1, Volume 27, The Third International Conference on the Development of Biomedical Engineering in Vietnam, Part 5, Pages 167-170.

    IFMBE Proceedings, 2010, Volume 27, Part 5, 167-170, DOI: 10.1007/978-3-642-12020-6_41

    Results of Curing Some Diseases by Stem Cell Transplantation at Stem Cell R&D Laboratory

    Phan Kim Ngoc and Pham Van Phuc

    Stem cell therapy in curing dangerous diseases usually is main target of many researches about stem cells. In the world, researching and applying stem cells to cure diseases got some great achievements while there is a few in Viet Nam. In recently years, Laboratory of Stem cell R&D, University of Science, VNU HCM city carried out some researches about preclinical treatment diseases using stem cell therapy. We used some different kinds of stem cells such as mesenchymal stem cells derived from umbilical cord blood to cure bone marrow failure syndrome and bone broken. The results showed that efficiency of cure was different when various methods and kinds of stem cell were applied. These results were bases for developing novel approaches and applying clinical treatment.

    * Author for correspondence: Tel: 84-8-38397719; Fax: 84-8-38967365; E-mail: pvphuc@hcmuns.edu.vn

  • Isolation and characterization of breast cancer stem cells from malignant tumours in Vietnamese…

    Pham Van Phuc, Tran Thi Thanh Khuong, Le Van Dong, Truong Dinh Kiet, Tran Tung Giang and Phan Kim Ngoc (2010). Isolation and characterization of breast cancer stem cells from malignant tumours in Vietnamese women. Journal of Cell and Animal Biology 4(12):163–16.

    Journal of Cell and Animal Biology Vol. 4(12), pp. 163–169, December 2010

    ISSN 1996-0867 ©2010 Academic Journals

    Full Length Research Paper

    Isolation and characterization of breast cancer stem cells from malignant tumours in Vietnamese women


    Pham Van Phuc1*, Tran Thi Thanh Khuong1, Le Van Dong2, Truong Dinh Kiet3, Tran Tung Giang4 and Phan Kim Ngoc1


    1Laboratory of Stem cell Research and Application, University of Science, VNU-HCM, Vietnam.

    2Military Medical University, Ha Noi, Vietnam.

    3University of Medicine – Pharmacy, HCM city, Vietnam.

    4The University of New South Wales, Sydney, Australia.


    *Corresponding author. E-mail: pvphuc@hcmuns.edu.vn,  phamvanphuc2308@gmail.com. Tel: (84.8)38397719. Fax: (84.8) 38350096.


    Accepted 17 November, 2010


    Abstract

    Cancer stem cells are the origin of tumors and have been isolated successfully from different kinds of tumors. Breast cancer stem cells have been recently identified in breast carcinoma with markers CD44+/CD24-/dim. This population can cause tumor and display stem cell-like properties. However, direct evidences that breast cancer stem cells can be propagated in vitro is still lacking. This research was carried out to isolate and propagate in vitro breast cancer stem cells from tumor biopsy. Breast tumor biopsy was used to isolate breast cancer cells by primary tissue culture. As such, breast cancer stem cells were isolated from breast cancer cells by catcher-tube based cell sorter on flow cytometter machine. These cells were propagated by an in vitro culture in a free serum specific medium. The results showed that the CD44+CD24-/dim cell population that were maintained, were capable of self-renewal and extensive proliferation as clonal non-adherent spherical clusters. Interestingly, cultured cells were CD44+CD24-/dim expressed by the putative stem cell marker Oct-4, resistant with verapamil at 50 µg/ml, and gave rise to new tumors when as few as 1000 cells were injected into the mammary fat pad of immune-deficient mice. This population was a suitable in vitro model to study breast cancer stem cells and develop therapeutic strategies to treat breast cancer.


    Key words: Breast cancer, breast tumor, cancer stem cell, CD44+CD24-/dim

  • Effects of breast cancer stem cell extract primed dendritic cell transplantation on breast cancer…

    Pham Van Phuc, Chi Jee Hou, Nguyen Thi Minh Nguyet, Duong Thanh Thuy, Le Van Dong, Truong Dinh Kiet and Phan Kim Ngoc. Effects of breast cancer stem cell extract primed dendritic cell transplantation on breast cancer tumor murine models. Annual Review & Research in Biology 1(1):1-13, 2011.

    Annual Review & Research in Biology, ISSN: 2231-4776


    Research Paper



    Effects of Breast Cancer Stem Cell Extract Primed Dendritic Cell Transplantation on Breast Cancer Tumor Murine Models


    Pham Van Phuc1*, Chi Jee Hou1, Nguyen Thi Minh Nguyet1, Duong Thanh Thuy1, Le Van Dong2, Truong Dinh Kiet1 and Phan Kim Ngoc1

    1Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam;
    2Military Medical University, Ha Noi, Vietnam;

    Abstract

    Cancer stem cells are considered as an origin of cancer. Cancer stem cells can cause tumors in mice models. Recent studies proved the efficacy of some promising therapies to treat cancers. Dendritic cell (DC) therapy is one of the best promising therapies to treat cancer. In recent years, DC therapy is performed by using primed cancer cell antigens of DC to immune organism body. This research aims to combine DC therapy with cancer stem cell antigen for treating breast cancer in murine models. DCs were derived from mouse bone marrow monocytes. Then they were primed with the breast cancer cell antigen prior to employ into the tumor mice model. This was performed to determine whether the DCs would capture and eventually migrate, be present in the spleen and present the cancer antigens to autologous CD8 T cells; induce the activation of the CTL response. The existence of tumors in mice was evaluated after 15-60 days from transplantation. The results showed that 40% mice of the experimental group, with injected breast cancer stem cell antigen loaded DCs, got tumors after 18 transplantation days. But in control group 100% mice got tumors after 15 transplantation days. It is also noticed that transplanted DCs could migrate into spleen, stimulate CD8 T cells and CD45 T cells proliferation. Specially, the ratio of CD8 T cells strongly increased in comparison to control or normal mice. These results are important and provides most required initial platform to do further experiment. Results of this study also established a promising novel targeting therapy for cancer, especially for breast cancer.

     

    Keywords : Breast cancer stem cell, cancer stem cell, dendritic cell, dendritic cell therapy, immunotherapy;

    * Author for correspondence: Tel: 84-8-38397719; Fax: 84-8-38967365; E-mail: pvphuc@hcmuns.edu.vn