Exploring the Kinh Vietnamese genomic database for the polymorphisms of the P450 genes towards precision public health.

BACKGROUND: Human cytochrome P450 (CYPs) genes are essential in metabolising drugs. Due to their high polymorphism, population-specific studies are of great interest. AIM: This research examined the six CYP genes, including CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, and CYP4F2 in the Kinh Vietnamese (KHV) for population-scale precision medicine. SUBJECTS AND METHODS: We processed data from a genomics database of 206 healthy and unrelated KHV individuals to calculate CYP allele frequencies. First, we compared the CYP genes of the KHV to six other populations retrieved from the 1000 Genomes Project. Second, we searched the PharmGBK database for drug-CYP interaction data to compile a drug dosage recommendation for the KHV. RESULTS: We observed the diverging trends in genetic variations of CYP2B6, CYP2D6, and CYP3A5 in the KHV. Regarding phenotypic drug responses in the KHV, CYP2C19 exhibited all metabolic phenotypes at a non-trivial frequency. In addition, CYP3A5 metabolised drugs at a lower rate compared to the other five CYPs. CONCLUSION: This is the first large-scale study to investigate multiple CYP genes in the KHV for precision medicine from a public health perspective. Differences found in the distributions of metabolizers for the KHV suggest careful prescriptions for CYP2C19 and CYP3A5-metabolised drugs.

Vγ9γδ T Cell Induction by Human Umbilical Cord Blood Monocytes-Derived, Interferon-α-Stimulated Dendritic Cells.

Dendritic cells (DC) are professional antigen-presenting cells that activate T cells to kill cancer cells. The extracellular products of DCs have also been reported to perform the same function. In this study, we examined the in vitro differentiation of umbilical cord blood monocytes into DCs in the presence of GM-CSF, and interferon (IFN)-α. The resulting DC population (called IFN-DCs) were then matured in the presence of TNF-α, and pulsed with total protein extracted from A549 cancer cell line. The pulsed DCs and their conditioned medium were then used to stimulate allogeneic lymphocytes (alloLym). The proliferation and cytotoxicity of alloLym were then determined. The results showed that after 5 days of differentiation, the stimulated monocytes had the typical morphology and characteristic surface markers of DCs. Both unpulsed and pulsed IFN-DCs can induce the proliferation of alloLym, especially Vγ9γδ T cells. The conditioned medium from pulsed and unpulsed IFN-DCs culture also prompted the growth of Vγ9γδ T cells. Moreover, alloLym stimulated with pulsed DCs and their conditioned medium had a greater cytotoxic effect on A549 cells than the ones that were not stimulated. Our results indicated that IFN-DCs and their conditioned medium could induce the anti-tumor immunity in vitro, providing evidence for application of cord blood monocytes-derived, interferon-α- stimulated dendritic cells and their extracellular products in anti-cancer therapy.

Phase I Clinical Trial Using Autologous Ex Vivo Expanded NK Cells and Cytotoxic T Lymphocytes for Cancer Treatment in Vietnam.

(1) Background: Immune cell therapy recently attracted enormous attention among scientists as a cancer treatment, but, so far, it has been poorly studied and applied in Vietnam. The aim of this study was to assess the safety of autologous immune cell therapy for treating lung, liver, and colon cancers-three prevalent cancers in Vietnam. (2) Method: This was an open-label, single-group clinical trial that included 10 patients with confirmed diagnosis of colon, liver, or lung cancer, conducted between March 2016 and December 2017. (3) Results: After 20-21 days of culture, the average number of cytotoxic T lymphocytes (CTLs) increased 488.5-fold and the average cell viability was 96.3%. The average number of natural killer cells (NKs) increased 542.5-fold, with an average viability of 95%. Most patients exhibited improved quality of life, with the majority of patients presenting a score of 1 to 2 in the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG/PS) scale, a decrease in symptoms on fatigue scales, and an increase in the mean survival time to 18.7 months at the end of the study. (4) Conclusion: This method of immune cell expansion met the requirements for clinical applications in cancer treatment and demonstrated the safety of this therapy for the cancer patients in Vietnam.

Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies.

Oncolytic measles and mumps viruses (MeV, MuV) have a potential for anti-cancer treatment. We examined the anti-tumor activity of MeV, MuV, and MeV-MuV combination (MM) against human solid malignancies (HSM). MeV, MuV, and MM targeted and significantly killed various cancer cell lines of HSM but not normal cells. MM demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer xenograft tumor model compared to MeV and MuV. MeV, MuV, and MM significantly induced the expression of immunogenic cell death markers and enhanced spleen-infiltrating immune cells. In conclusion, MM combination significantly improves the treatment of human solid malignancies.

Development of Fe3O4/Ag core/shell-based multifunctional immunomagnetic nanoparticles for isolation and detection of CD34+ stem cells.

Fe3O4/Ag core/shell nanoparticles functionalized with the free amino (NH2) functional groups (Fe3O4/Ag-NH2) were conjugated with fluorescent electron coupled dye (ECD)-antiCD34 antibody using the 1-ethyl-3-(3'-dimethyl-aminopropyl) carbodiimide (EDC) catalyst (ECD - Electron Coupled Dye or R Phycoerythrin-Texas Red is a fluorescent organic dye attached to the antibody). The characteristic fluorescence of ECD in the antibody was investigated and was used as a good indicator for estimating the percentage of the antibodies that were successfully conjugated with the nanoparticles. The conjugation efficiency was found to increase depending on the VNP:VAB ratio, where VNP and VAB are the volumes of the nanoparticle solution (concentration of 50 ppm) and the as-purchased antibody solution, respectively. The conjugation efficiency rapidly increased from approximately 18% to approximately 70% when VNP:VAB was increased from 2:1 to 100:1, and it gradually reached the saturated state at an efficiency of 95%, as the VNP:VAB was equal to 300:1. The bioactivity of the abovementioned conjugation product (denoted by Fe3O4/Ag-antiCD34) was evaluated in an experiment for the collection of stem cells from bone marrow samples.

Ex vivo expansion of human peripheral blood natural killer cells and cytotoxic T lymphocytes from lung cancer patients.

Lung cancer is the most common type of cancer with the highest cancer-associated mortality rates worldwide, as well as in Vietnam. Numerous studies have demonstrated that higher numbers and higher rate of activity of infiltrating natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) in the tumor are closely correlated with positive prognosis, tumor size decrease and longer survival of lung cancer patients. In the present study, the effectiveness of BINKIT® kit in the ex vivo expansion of NK cells and CTLs in the peripheral blood of 7 patients aged between 30 and 84 years with metastatic lung cancer was evaluated. After 21 days of culture, the average number of CTLs (CD3+CD8+) increased by 742.3-fold in the CTL culture, accounting for 72.2% of the cultured cell population, and the mean cell viability was 95.7%. In the NK cell culture, the average number of NK cells (CD3-CD56+) increased by 637.5-fold, accounting for 84.3% of the cultured cell population, with an average viability of 94.7%. The percentage of active NK cells (CD3-CD56+ bright) was 82.1%, which increased by 408.9-fold. Notably, a close correlation was identified between the numbers of cytokine-induced killer (CD3+CD56+) and NK (CD3-CD56+) cells in the NK cell culture (P<0.05). In the two culture conditions (namely NK cell and CTL cultures), no clear correlation was identified between the rate of initial immune cells in the peripheral blood and the corresponding number following ex vivo expansion (P>0.05). These results revealed that the method of expansion and activation of NK cells and CTLs from peripheral blood was successfully applied using BINKIT, and reached the requirements for clinical applications in cancer treatment in Vietnam.

Cytotoxic and anti-tumor activities of lignans from the seeds of Vietnamese nutmeg Myristica fragrans.

Four lignans, meso-dihydroguaiaretic acid (DHGA), macelignan, fragransin A2 and nectandrin B, were isolated from the seeds of Myristica fragrans (Vietnamese nutmeg) and investigated for their cytotoxic activity against eight cancer cell lines. Of these, DHGA exhibited potent cytotoxicity against H358 with IC50 value of 10.1 µM. In addition, DHGA showed antitumor activity in allogeneic tumor-bearing mice model.