METHODS: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method.
RESULTS: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer.
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METHODS: This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection.
RESULTS: In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity.
DISCUSSION: Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.
MATERIALS AND METHODS: Two hundred fifty-eight patients with primary liver tumors who underwent FDG-PET before LDLT were enrolled in this retrospective study. Unfavorable tumor histology was defined as primary liver tumor other than a well- or moderately differentiated HCC. Thirteen patients had unfavorable tumor histology, including 2 poorly differentiated HCC, 2 sarcomatoid HCC, 5 combined hepatocellular cholangiocarcinoma, 3 intrahepatic cholangiocarcinoma, and 1 hilar cholangiocarcinoma.
RESULTS: FDG-PET positivity was significantly associated with unfavorable tumor histology (P < 0.001). Both FDG-PET positivity and unfavorable tumor histology were significant independent predictors of tumor recurrence and overall survival. In a subgroup analysis of patients with FDG-PET-positive tumors, unfavorable tumor histology was a significant independent predictor of tumor recurrence and overall survival. High FDG uptake (tumor to non-tumor uptake ratio ≥ 2) was a significant predictor of unfavorable tumor histology. Patients with high FDG uptake and/or unfavorable tumors had significantly higher 3-year cumulative recurrence rate (70.8% versus 26.2%, P = 0.004) and worse 3-year overall survival (34.1% versus 70.8%, P = 0.012) compared to those with low FDG uptake favorable tumors.
CONCLUSIONS: The expression of FDG-PET is highly associated with histology of explanted HCC and predicts the recurrence. FDG-PET-positive tumors with high FDG uptake may be considered contraindication for LDLT due to high recurrence rate except when pathology proves favorable histology.
OBJECTIVE: The main objective of this study is to determine the potential anti-proliferative effect of KGM on cancer and normal human liver cell lines, HepG2 and WRL68, respectively.
METHOD: HepG2 and WRL68 cells were treated with KGM, D-mannose, KGM-D-mannose and 5-fluorouracil. The morphological changes in those treated cells were observed. Cytotoxic effect of the treatments on cell viability and proliferation, and apoptosis genes expression were assessed by cytotoxicity assay, flow cytometry and RT-PCR analyses.
RESULTS: The results show that KGM treatment resulted in reduced viability of HepG2 cells significantly, in line with the apoptosis-like morphological changes. Up-regulation of BAX and down-regulation of BCL2 genes as reflected by high Bax to Bcl 2 ratio suggests that the inhibitory effect of KGM on HepG2 cells most likely via Bcl2/Bax protein pathway. Despite the effectiveness of standard drug 5-FU in suppressing the viability and proliferation of HepG2 cells, it however, exhibited no selective inhibition of cancer cells as compared to KGM.
CONCLUSION: Current findings suggested that KGM is a potential anti-cancer compound/drug entity, which could be an alternative preventive agent against liver cancer.
METHODS: Male Wistar rats (200-250 g) were divided into 4 groups according to the diet given: control group (normal diet), ChV group with three different doses (50, 150 and 300 mg/kg body weight), liver cancer- induced group (choline deficient diet + 0.1% ethionine in drinking water or CDE group), and the treatment group (CDE group treated with three different doses of ChV). Rats were killed at 0, 4, 8 and 12 weeks of experiment and blood and tissue samples were taken from all groups for the determination of tumour markers expression alpha-fetoprotein (AFP), transforming growth factor-β (TGF-β), M2-pyruvate kinase (M2-PK) and specific antigen for oval cells (OV-6).
RESULTS: Serum level of TGF-β increased significantly (p < 0.05) in CDE rats. However, ChV at all doses managed to decrease (p < 0.05) its levels to control values. Expressions of liver tumour markers AFP, TGF-β, M2-PK and OV-6 were significantly higher (p < 0.05) in tissues of CDE rats when compared to control showing an increased number of cancer cells during hepatocarcinogenesis. ChV at all doses reduced their expressions significantly (p < 0.05).
CONCLUSIONS: Chlorella vulgaris has chemopreventive effect by downregulating the expression of tumour markers M2-PK, OV-6, AFP and TGF-β, in HCC-induced rats.
AIM OF STUDY: Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated.
MATERIALS AND METHODS: The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry.
RESULTS: The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50's ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50's ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additionally, by using annexin V-FITC/PI differential staining, 5 induced cells killing effect via the induction of apoptosis and necrosis in both HepG2 and HCT116 cells. Compound 3 produce necrosis and apoptosis only in HCT116 cells. On contrary, 6 induced apoptosis and necrosis in HepG2 cells and moderate necrosis in HCT116 cells.
CONCLUSION: Fourteen compounds were isolated from chloroform fraction of G. mangostana fruit hulls. Cytotoxic properties exhibited by the isolated xanthones from G. mangostana reinforce the avail of it as a natural cytotoxic agent against various cancers. These evidences could provide relevant bases for the scientific rationale of using G. mangostana in anti-cancer treatment.
METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).
RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).
CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.
MATERIALS AND METHODS: A retrospective cohort study of patients undergoing either treatment was carried out from January 2009 to December 2014. Tumour response to the procedures was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Kaplan-Meier analysis was used to assess and compare the overall survival in the two groups.
RESULTS: A total of 79 patients were analysed (34 had c-TACE, 45 had DEB-TACE) with a median follow-up of 11.8 months. A total of 20 patients in the c-TACE group (80%) and 12 patients in the DEB-TACE group (44%) died during the follow up period. The median survival durations in the c-TACE and DEB-TACE groups were 4.9 ± 3.2 months and 8.3 ± 2.0 months respectively (p=0.008). There was no statistically significant difference noted among the two groups with respect to mRECIST criteria.
CONCLUSIONS: DEB-TACE demonstrated a significant improvement in overall survival rates for patients with unresectable HCC when compared to c-TACE. It is a safe and promising approach and should potentially be considered as a standard of care in the management of unresectable HCC.
OBJECTIVE: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells.
MATERIALS AND METHODS: MTT assays, flow cytometry, comet assays and the reverse transcription- polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers.
RESULTS: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent.
CONCLUSIONS: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.