, , , , , , , , , , , , , . (2017), ¨Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma¨ (Xác định marker của tế bào gốc ung thư dạ dày kháng thuốc ở người), Clinical Cancer Research, 2017 Mar 15, 23(6), pp. 1586-1597. doi: 10.1158/1078-0432.CCR-15-2157.

Phu Hung Nguyen, Yann Touchefeu, Tony Durand, Philippe Aubert, Emilie Duchalais, Stanislas Bruley des Varannes, Christine Varon, Michel Neunlist and Tamara Matysiak-Budnik (2018), ¨Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type¨ (Acetylcholine cảm ứng các tế bào gốc ung thư dạ dày thể phân tán), Tumor Biology, September 2018, pp. 1–9, doi: 10.1177/1010428318799028. Scopus (Scimago, Q1).

Ngo Thu Ha, Le Thi Thanh Huong, La Thi Huyen, Nguyen Phu Hung (2017), ¨3D culture and analysis of the expression of cancer stem cell markers from gastric cancer cell line¨ (Nuôi cấy 3D và phân tích sự biểu hiện các marker tế bào gốc ung thư từ các dòng tế bào ung thư dạ dày ở người), Journal of Medical Research - Hanoi Medical University, JMR 111 E2 (2) – 2018, pp. 53-60.

Ngô Thu Hà, Lã Thị Huyền, Lê Thị Thanh Hương, Nguyễn Hữu Quân, Nguyễn Khắc Tấn, Nguyễn Phú Hùng (2017), ¨Xác định sự biểu hiện của marker tế bào gốc ung thư CD44 và ALDH của dòng tế bào ung thư dạ dày MKN45¨, Tạp chí Y học Việt Nam, tập 458, Số đặc biệt, tr.136-143.

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INFORMATION OF RESEARCH RESULTS

1. General information

• Project title: Isolation and evaluation of resistance characteristics of human gastric cancer stem cells.
• Code number: B2017-TNA-55
• Coordinator: Dr. Nguyen Phu Hung
• Implementing institution: Thai Nguyen University
• Duration: From January 2017- June 2019

2. Objectives

• Isolation and identification of cancer stem cell characteristics from human gastric cancer stem cells.
• Looking for a new marker of gastric cancer stem cells.
• Assessing the resistance properties of gastric cancer stem cells to the drugs being used in cancer treatments.
• Finding a specific marker for the resistance of gastric cancer stem cells.

3. Creativeness and innovativeness

Finding a new marker of gastric cancer stem cells, ALDH marker. It has also been experimentally proven that stem cells expressing this marker are resistant to anticancer drugs including Doxorubicin and 5-FU.

4. Researh results

1. 50 cancer specimens are collected from gastric cancer patients. Tissue samples are stained (HE) and analyzed some clinical, histopathological characteristics of the cancer samples studied.
2. Analyzed the expression of  9 potential stem cell markers of gastric cancer stem cells and showed that CD44 and ALDH are markers with lower expression level than other markers.  In particular, ALDH is expressed at low level in both cancer cell lines (less than 30%) and in stomach tumor cells isolated from patients.
3. The expression of ALDH is also determined by immunofluorescence on gastric cancer cell lines and by immunohistochemistry on gastric cancer tissues.
4. Has successfully separated the cell populations expressing ALDH as well as the cell populations not expressing ALDH by FACS technique. The seperated cell populations have a high purity (> 90%).
5. Cell populations after separation by FACS technique were cultured in 3D to assess the possibility of  tumorsphere formation. The results indicated that the ALDH-expressing population produced more tumorpheres than the ALSH-negative cell population..
6. Transplantation of cells separated by FACS technique in NSG mice showed that the ALDH-positive population was able to replicate tumors in vivo, while the ALDH negative cells failed to form in vivo tumors. This is the gold standard to indicates that ALDH is a marker of gastric cancer stem cells.
7. 7/. Cells expressing ALDH are resistant to current anti-cancer drugs including 5 Fluorouracil and Doxorubicin compared to ALDH-negative populations. The resistance has been shown to be related to the ABC complex proteins on cell membrane of gastric cancer stem cells.

5. Products

5.1. Sicientific products

5.1.1. Article

1. Article 1. Nguyen PH, Giraud J, Chambonnier L, Dubus P, Wittkop L, Belleannée G, Collet D, Soubeyran I, Evrard S, Rousseau B, Senant-Dugot N, Mégraud F, Mazurier F, Varon C. (2017 ), ¨Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma¨, Clinical Cancer Research, (IF = 10.199, Q1), 2017 Mar 15; 23 (6), pp. 1586-1597, wait: 10.1158 / 1078-0432.CCR-15-2157.
2. Article 2. Phu Hung Nguyen, Yann Touchefeu, Tony Durand, Philippe Aubert, Emilie Duchalais, Stanislas Bruley des Varannes, Christine Varon, Michel Neunlist and Tamara Matysiak-Budnik (2018), ¨Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type¨, Tumor Biology, September 2018, pp. 1–9, doi: 10.\1177 / 1010428318799028 (Scopus, Scimago Q1).
3. Article 3. Ngo Thu Ha, Le Thi Thanh Huong, La Thi Huyen, Nguyen Phu Hung (2017), ¨3D culture and analysis of the expression of cancer stem cell markers from gastric cancer cell line¨, Journal of Medical Research - Hanoi Medical University, JMR 111 E2 (2) - 2018, pp. 53-60.
4. Article 4. Ngo Thu Ha, La Thi Huyen, Le Thi Thanh Huong, Nguyen Huu Quan, Nguyen Khac Tan, Nguyen Phu Hung (2017), ¨Determine the expression of CD44 and ALDH cancer stem cell markers in the line gastric cancer cell MKN45¨, Vietnam Medical Journal, vol. 458, Special issue, pp.136-143.

5.1.2. Monographs

1. Nguyen Phu Hung (2019), Gastric cancer stem cell, Publishe, Thai Nguyen University (Publication Certificate).

5.1.3. Training products

1. Ngo Thu Ha, Master's Class K9 (2017), Analysis of the expression of ALDH and CD44 markers from gastric cancer cell line, Master's thesis in Applied Biology, Thai Nguyen University of Sciences, Successfully defended, rated Excellent.

6. Transfer alternatives, application institution, impacts and benefits of research results:

• This is a basic research project.
• Impact and benefits of the research results: The research results contribute to a new marker of gastric cancer stem cells, leading to new approaches to cancer treatment. On the other hand, identifying the resistance of stomach cancer stem cells will be particularly important in developing gastric cancer-targeted therapies.