Establishment of cancer cell line originating from a patient with high-grade serous ovarian carcinoma.

Aim: Ovarian cancer is a serious malignancy with high prevalence and mortality. Methods: We isolated and characterized an ovarian high-grade serous cancer cell line (M4) from a tumor of a Vietnamese patient with ovarian carcinoma. Results: The M4 cancer cell line showed good proliferation and stability in culture. Morphologically, the M4 cells showed similar characteristics to tumor cells such as a polyhedral shape, large irregular nuclei, high nuclear/cytoplasmic ratio, high nuclear density and expressing cancer markers like CA125, p53 and Ki67 markers. Conclusion: We have successfully isolated and characterized the M4 cell line from a Vietnamese patient with ovarian carcinoma.

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.

SOCS3 genetic variants and promoter hypermethylation in patients with chronic hepatitis B.

The clinical manifestations of hepatitis B viral infection (HBV) include chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The contribution of negative regulator suppressor of cytokine signaling-3 (SOCS3) promoter variants in HBV disease and SOCS3 hypermethylation in tumor tissues were investigated. The SOCS3 promoter region was screened for polymorphisms in 878 HBV patients and in 272 healthy individuals. SOCS3 promoter methylation was examined by bisulfite sequencing. SOCS3 mRNA expression was quantified in 37 tumor and adjacent non-tumor liver tissue specimens. The minor allele rs12953258A was associated with increased susceptibility to HBV infection (OR=1.3, 95%CI=1.1-1.6, adjusted P=0.03). The minor allele rs111033850C and rs12953258A were observed in increased frequencies in HCC and LC patients compared to CHB patients (HCC: OR=1.7, 95%CI=1.1-2.9, adjusted P=0.046; LC: OR=1.4, 95%CI=1.1-1.9, adjusted P=0.017, respectively). HBV patients with rs111033850CC major genotype had decreased viral load (P=0.034), whereas the rs12953258AA major genotype contributed towards increased viral load (P=0.029). Tumor tissues revealed increased hypermethylation compared to adjacent non-tumor tissues (OR=5.4; 95%CI= 1.9-17.1; P=0.001). Increased SOCS3 expression was observed in HBV infested tumor tissues than non-HBV related tumor tissues (P=0.0048). SOCS3 promoter hypermethylation was associated with relatively low mRNA expression in tumor tissues (P=0.0023). In conclusion, SOCS3 promoter variants are associated with HBV susceptibility and SOCS3 hypermethylation stimulates HCC development.

Gamma-Secretase Inhibitor IX (GSI) Impairs Concomitant Activation of Notch and Wnt-Beta-Catenin Pathways in CD44+ Gastric Cancer Stem Cells.

Cancer stem cells (CSC) are associated with tumor resistance and are characterized in gastric cancer (GC). Studies have indicated that Notch and wnt-beta-catenin pathways are crucial for CSC development. Using CD44+ CSCs, we investigated the role of these pathways in GC carcinogenesis. We performed cell proliferation, wound healing, invasion, tumorsphere, and apoptosis assays. Immunoblot analysis of downstream signaling targets of Notch and wnt-beta-catenin were tested after gamma-secretase inhibitor IX (GSI) treatment. Immunohistochemistry, immunofluorescence, and Fluorescence activated cell sorting (FACS) were used to determine CD44 and Hairy enhancer of split-1 (Hes1) expression in human GC tissues. CD44+ CSCs were subcutaneously injected into NMR-nu/nu mice and treated with vehicle or GSI. GC patients with expression of CD44 and Hes1 showed overall reduced survival. CD44+ CSCs showed high expression of Hes1. GSI treatment showed effective inhibition of cell proliferation, migration, invasion, tumor sphere formation of CD44+ CSCs, and induced apoptosis. Importanly, Notch1 was found to be important in mediating a crosstalk between Notch and wnt-beta-catenin in CD44+ CSCs. Our study highlights a crosstalk between Notch and wnt-beta-catenin in gastric CD44+ CSCs. Expression of CD44 and Hes1 is associated with patient overall survival. GSI could be an alternative drug to treat GC. Stem Cells Translational Medicine 2017;6:819-829.

Soluble MICB protein levels and platelet counts during hepatitis B virus infection and response to hepatocellular carcinoma treatment.

BACKGROUND: The human major histocompatibility complex class I polypeptide-related sequence B (MICB) is a protein that modulates the NK and T cell activation through the NKG2D receptor and is related to several diseases including cancer. METHODS: The study investigated the prognostic role of soluble MICB (sMICB) protein in the progression of HBV-related liver diseases and to HBV-related HCC treatment. The sMICB serum levels were measured in 266 chronic HBV-infected Vietnamese patients and in healthy controls, and correlated with clinical and laboratory parameters and with therapeutic interventions for HBV-related HCC. RESULTS: Significant differences in both clinical and laboratory parameters were observed among the patient groups with different stages of hepatitis. The platelet counts were significantly decreased with disease progression (P < 0.001). The sMICB serum levels were significantly increased in HBV patients compared to healthy controls (P < 0.0001). Among the patients with different stages of hepatitis, asymptomatic individuals (ASYM) revealed higher sMICB serum levels while liver cirrhosis (LC) patients revealed lower sMICB serum levels (P < 0.0001) compared to other patient groups. Notably, the sMICB serum levels were decreased in treated HCC patient group compared to not-treated HCC patient group (P = 0.05). Additionally, the sMICB levels were significantly correlated with platelet counts in ASYM and HCC patients (r = -0.37, P = 0.009; and r = 0.22, P = 0.025, respectively). CONCLUSIONS: Our results demonstrate a potential role of sMICB serum levels and platelet counts during immune response to the HBV infection, liver disease progression and response to the HCC treatment.

Combination of vaccine-strain measles and mumps virus synergistically kills a wide range of human hematological cancer cells: Special focus on acute myeloid leukemia.

Through combining vaccine-derived measles and mumps viruses (MM), we efficiently targeted a wide range of hematopoietic cancer cell lines. MM synergistically killed many cell lines including acute myeloid leukemia (AML) cell lines. Further investigation suggested that enhanced oncolytic effect of MM was due to increased apoptosis induction. In an U937 xenograft AML mouse model, MM displayed greater tumor suppression and prolonged survival. Furthermore, MM efficiently killed blasts from 16 out of 20 AML patients and elicited more efficient killing effect on 11 patients when co-administered with Ara-C. Our results demonstrate that MM is a promising therapeutic candidate for hematological malignancies.