Displaying publications 1 - 20 of 63 in total

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  1. Sawai S, Mohktar MS, Safwani WKZW, Ramasamy TS
    Anticancer Agents Med Chem, 2018;18(9):1258-1266.
    PMID: 29521251 DOI: 10.2174/1871520618666180307143229
    BACKGROUND: Konjac Glucomannan (KGM) is a water-soluble dietary fibre extracted from Amorphophallus konjac K. Koch (Araceae). Konjac fibre has been clinically proven as an effective antioxidant agent in weight control but its traditionally known tumour suppression property remains to be explored.

    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.

    Matched MeSH terms: Liver Neoplasms/pathology
  2. Handayani T, Sakinah S, Nallappan M, Pihie AH
    Anticancer Res, 2007 Mar-Apr;27(2):965-71.
    PMID: 17465228
    Xanthorrhizol is a sesquiterpenoid compound extracted from the rhizome of Curcuma xanthorrhiza. This study investigated the antiproliferative effect and the mechanism of action of xanthorrhizol on human hepatoma cells, HepG2, and the mode of cell death. An antiproliferative assay using methylene blue staining revealed that xanthorrhizol inhibited the proliferation of the HepG2 cells with a 50% inhibition of cell growth (IC50) value of 4.17 +/- 0.053 microg/ml. The antiproliferative activity of xanthorrhizol was due to apoptosis induced in the HepG2 cells and not necrosis, which was confirmed by the Tdt-mediated dUTP nick end labeling (TUNEL) assay. The xanthorrhizol-treated HepG2 cells showed typical apoptotic morphology such as DNA fragmentation, cell shrinkage and elongated lamellipodia. The apoptosis mediated by xanthorrhizol in the HepG2 cells was associated with the activation of tumor suppressor p53 and down-regulation of antiapoptotic Bcl-2 protein expression, but not Bax. The levels of Bcl-2 protein expression decreased 24-h after treatment with xanthorrhizol and remained lower than controls throughout the experiment, resulting in a shift in the Bax to Bcl-2 ratio thus favouring apoptosis. The processing of the initiator procaspase-9 was detected. Caspase-3 was also found to be activated, but not caspase-7. Xanthorrhizol exerts antiproliferative effects on HepG2 cells by inducing apoptosis via the mitochondrial pathway.
    Matched MeSH terms: Liver Neoplasms/pathology
  3. Khaw KY, Kumar P, Yusof SR, Ramanathan S, Murugaiyah V
    Arch Pharm (Weinheim), 2020 Nov;353(11):e2000156.
    PMID: 32716578 DOI: 10.1002/ardp.202000156
    α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 µM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50 : AChE, 2.48 µM; BChE, 5.87 µM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
    Matched MeSH terms: Liver Neoplasms/pathology
  4. Li L, Zhang W, Desikan Seshadri VD, Cao G
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):3029-3036.
    PMID: 31328556 DOI: 10.1080/21691401.2019.1642902
    Nowadays, the synthesis and characterization of gold nanoparticles (AuNPs) from plant based extracts and effects of their anticancer have concerned an important interest. Marsdenia tenacissima (MT), a conventional Chinese herbal medicine, has long been used for thousands of years to treat tracheitis, asthma, rheumatism, etc. In this present study, we optimize the reaction of parameters to manage the nanoparticle size, which was categorized by high-resolution transmission electron microscopy (HR-TEM). A different characterization method, for example, UV-visible spectroscopy (UV-vis), fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) were performed to consider the synthesized AuNPs getting from the MT leaf extract. The MT-AuNPs were analyzed for their cytotoxicity property against HepG2 cells by MTT analysis. The apoptosis was evaluated by using reactive oxygen species (ROS), migration assay, mitochondrial membrane potential (MMP) and apoptotic protein expression. Interestingly, the findings of our study observed the cytotoxicity effect of synthesized MT-AuNPs at a concentration of 59.62 ± 4.37 μg after 24 hrs treatment. Apoptosis was induced by the MT-AuNPs with enhanced ROS, changed MMP and inhibit the migration assay. Finally, the apoptosis was confirmed by the considerable up-regulation of Bax, caspase-9 and caspase-3, while the anti-apoptotic protein expressions of Bcl-2 and Bcl-XL were down-regulated. Although, in this studies, we evaluated the characterization, synthesis and anticancer action of gold nanoparticles from MT (MT-AuNPS) helpful for liver cancer therapeutics.
    Matched MeSH terms: Liver Neoplasms/pathology*
  5. Azlin AH, Looi LM, Cheah PL
    Asian Pac J Cancer Prev, 2014;15(9):3959-63.
    PMID: 24935581
    The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.
    Matched MeSH terms: Liver Neoplasms/pathology
  6. Norsa'adah B, Nurhazalini-Zayani CG
    Asian Pac J Cancer Prev, 2013;14(11):6955-9.
    PMID: 24377632
    The incidence of hepatocellular carcinoma (HCC) is relatively high in Southeast Asia. Globally, HCC has a high fatality rate and short survival. The objectives of this retrospective cohort study were to review the epidemiology and survival of HCC patients at a tertiary centre in north-east of Peninsular Malaysia. Subjects were adult HCC patients diagnosed by histopathology or radio-imaging. Secondary liver carcinoma was excluded. Kaplan Meier and multiple Cox proportional hazard survival analyses were used. Only 210 HCC cases from years 1987-2008, were included in the final analysis. The number of cases was increasing annually. The mean age was 55.0 (SD 13.9) years with male:female ratio of 3.7:1. Approximately 57.6% had positive hepatitis B virus, 2.4% hepatitis C virus, 20% liver cirrhosis and 8.1% chronic liver disease. Only 2.9% had family history and 9.0% had frequently consumed alcohol. Most patients presented with abdominal pain or discomfort and had hepatomegaly, 47.9% had an elevated α-fetoprotein level of 800 IU/ml or more, 51.9% had multiple tumors and 44.8% involved multiple liver lobes. Approximately 63.3% were in stage 3 and 23.4% in stage 4, and 82.9% did not receive any treatment. The overall median survival time was 1.9 months (95% confidence interval (CI): 1.5, 2.3). The 1-month, 6-month, 1-year and 2-year survival rates were 71.8%, 23.3%, 13.0% and 7.3% respectively. Significant prognostic factors were Malay ethnicity [Adjusted hazard ratio (AHR) 1.6; 95%CI: 1.0, 2.5; p=0.030], no chemotherapy [AHR 1.7; 95%CI: 1.1, 2.5; p=0.017] and Child-Pugh class C [AHR 2.6; 95%CI: 1.4, 4.9; p=0.002]. HCC in our study affected a wide age range, mostly male, in advanced stage of disease, with no treatment and very low survival rates. Primary prevention should be advocated in view of late presentation and difficulty of treatment. Vaccination of hepatitis virus and avoidance of liver toxins are to be encouraged.
    Matched MeSH terms: Liver Neoplasms/pathology
  7. Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A, Eshak Z
    Asian Pac J Cancer Prev, 2015;16(14):6047-53.
    PMID: 26320494
    BACKGROUND: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability.

    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.

    Matched MeSH terms: Liver Neoplasms/pathology*
  8. Rahman FA, Naidu J, Ngiu CS, Yaakob Y, Mohamed Z, Othman H, et al.
    Asian Pac J Cancer Prev, 2016;17(8):4037-41.
    PMID: 27644658
    BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer that is frequently diagnosed at an advanced stage. Transarterial chemoembolisation (TACE) is an effective palliative treatment for patients who are not eligible for curative treatment. The two main methods for performing TACE are conventional (c-TACE) or with drug eluting beads (DEB-TACE). We sought to compare survival rates and tumour response between patients undergoing c-TACE and DEB-TACE at our centre.

    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.

    Matched MeSH terms: Liver Neoplasms/pathology
  9. Waziri PM, Abdullah R, Rosli R, Omar AR, Abdul AB, Kassim NK, et al.
    Asian Pac J Cancer Prev, 2018 Apr 25;19(4):917-922.
    PMID: 29693341
    Clausena excavata Burm f. is used by traditional healers to treat cancer patients in South East Asia. The use of the
    plant and its compounds is based on Asian folklore with little or no scientific evidence supporting the therapeutic efficacy
    The current study aimed to determine the effect of pure clausenidin isolated from C. excavata on caspase-8-induced cell
    death as well as angiogenesis in the HepG2 hepatocellular carcinoma cell line. Caspase-8 and extrinsic death receptor
    protein expression was determined using spectrophotometry and protein profile arrays, respectively. Ultrastructural
    analysis of clausenidin-treated cells was conducted using transmission electron microscopy. In addition, anti-angiogenic
    effects of clausenidin were investigated by Western blot analysis. Clausenidin significantly (p<0.05) increased the
    activity of caspase-8 and expression of protein components of the death inducing signaling complex (DISC) in HepG2
    cells. Ultrastructural analysis of the clausenidin-treated HepG2 cells revealed morphological abnormalities typical of
    apoptosis. Furthermore, clausenidin significantly (p<0.05) decreased the expression of vascular endothelial growth
    factor (VEGF). Therefore, clausenidin is a potential anti-angiogenic agent which may induce apoptosis of hepatocellular
    carcinoma cells.
    Matched MeSH terms: Liver Neoplasms/pathology
  10. Chaudhry GE, Sohimi NKA, Mohamad H, Zafar MN, Ahmed A, Sung YY, et al.
    Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):17-24.
    PMID: 33576208 DOI: 10.31557/APJCP.2021.22.S1.17
    OBJECTIVE: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line.

    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.
    .

    Matched MeSH terms: Liver Neoplasms/pathology*
  11. Zakaria KN, Amid A, Zakaria Z, Jamal P, Ismail A
    Asian Pac J Cancer Prev, 2019 Feb 26;20(2):563-567.
    PMID: 30803221
    Problem statement: Clinicanthus nutans has been used by Malaysian since long time ago. It is used to treat many diseases including cancer. Many studies carried out on its crude extract but no clear report on the specific secondary metabolites responsible for its nature in treating selected diseases. Objective: This study aims to confirm the practice carried out by many people on the usage of Clinicanthus nutans in treating cancer. Methods: C. nutans leaves were extracted by methanol. Thin layer chromatography was used to identify the suitable solvent for fractions separation. The fractions were then separated at larger volume using gravity column chromatography. Each fraction was tested on its anti-proliferative activity on Hep-G2 liver cancer cells by MTT assay. The phytochemical screening was carried out to identify the bioactive compound based on qualitative analysis. Results: The fraction 2 (F2) of C. nutans showed the lowest IC50 value of 1.73 μg/ml against Hep-G2 cancer cells, and it is identified as triterpenes. Conclusion: The fraction F2 identified as triterpenes isolated from C. nutans has potential as an anti-proliferative agent against liver cancer.
    Matched MeSH terms: Liver Neoplasms/pathology*
  12. Tajul Arifin K, Sulaiman S, Md Saad S, Ahmad Damanhuri H, Wan Ngah WZ, Mohd Yusof YA
    BMC Cancer, 2017 12 21;17(1):879.
    PMID: 29268718 DOI: 10.1186/s12885-017-3883-3
    BACKGROUND: Chlorella vulgaris (ChV), a unicellular green algae has been reported to have anticancer and antioxidant effects. The aim of this study was to determine the chemopreventive effect of ChV on liver cancer induced rats by determining the level and expression of several liver tumour markers.

    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.

    Matched MeSH terms: Liver Neoplasms/pathology
  13. Kadir FA, Kassim NM, Abdulla MA, Yehye WA
    PMID: 24305067 DOI: 10.1186/1472-6882-13-343
    Hepatocellular carcinoma is a common type of tumour worldwide with a high mortality rate and with low response to current cytotoxic and chemotherapeutic drugs. The prediction of activity spectra for the substances (PASS) software, which predicted that more than 300 pharmacological effects, biological and biochemical mechanisms based on the structural formula of the substance was efficiently used in this study to reveal new multitalented actions for Vitex negundo (VN) constituents.
    Matched MeSH terms: Liver Neoplasms/pathology
  14. Qi Qi C, Ajit Singh V
    BMJ Case Rep, 2012;2012.
    PMID: 22892228 DOI: 10.1136/bcr.01.2012.5518
    The authors present an interesting case under our follow-up who has had five different forms of tumours with different pathologies throughout his lifetime. He started off with hepatoma, followed by pleomorphic sarcoma of the thigh, adenocarcinoma of the prostate, meningioma and finally schwanoma. He is still alive to this date.
    Matched MeSH terms: Liver Neoplasms/pathology*
  15. Cheah PL, Looi LM, Lin HP, Yap SF
    Cancer, 1990 Jan 1;65(1):174-6.
    PMID: 2152851
    In the 7-year period between 1980 and 1987, six cases of childhood primary hepatocellular carcinoma (PHC) were confirmed histologically in our institution. Hepatitis B surface antigen (HBsAg) seropositivity was confirmed in five of the cases, and tissue HBsAg was shown in four of these using the Shikata's orcein stain. An associated maternal HBsAg seropositivity was shown in two of the seropositive children. The youngest seropositive patient who developed PHC was 7 years old. The mother of this patient was also seropositive. These observations support a causal relation between childhood Hepatitis B virus infection and PHC. The importance of vertical or perinatal transmission of HBV in the causation of childhood PHC and the prophylactic role of childhood vaccination is emphasized. Attention is also drawn to the relative short malignant transformation time seen in some of these patients.
    Matched MeSH terms: Liver Neoplasms/pathology
  16. Sumithran E, Looi LM
    Cancer, 1985 Sep 1;56(5):1124-7.
    PMID: 2990666
    In West Malaysia, hepatocellular carcinoma (HCC) is common in the Chinese and in the members of the Senoi aboriginal tribe, two racial groups with diametrically opposite life-styles. Certain fundamental differences exist between the liver tumors in the two races. In the Senoi, the tumor occurs in a younger age group and there is a greater male preponderance than in the Chinese. There is also a very close relationship between hepatitis B virus infection, chronic active hepatitis, cirrhosis, liver cell dysplasia, and HCC in the Senoi and the tumors generally present as multiple nodules studding both lobes of the liver. In the Chinese, although a relationship between hepatitis B virus infection, HCC, and cirrhosis exists, this association is not as strong as in the Senoi and the tumors are generally large and solitary. The data suggest that, although the hepatitis B virus is probably an important oncogenic agent in both racial groups, there may be a difference in the pathogenesis of HCC in the two races.
    Matched MeSH terms: Liver Neoplasms/pathology*
  17. Sumithran E, Prathap K
    Cancer, 1977 Oct;40(4):1618-20.
    PMID: 198100
    Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer.
    Matched MeSH terms: Liver Neoplasms/pathology
  18. Stepien M, Fedirko V, Duarte-Salles T, Ferrari P, Freisling H, Trepo E, et al.
    Cancer Epidemiol, 2016 Feb;40:179-87.
    PMID: 26773278 DOI: 10.1016/j.canep.2016.01.002
    INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.

    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.

    Matched MeSH terms: Liver Neoplasms/pathology
  19. Ban KC, Singh H, Krishnan R, Seow HF
    Cancer Lett, 2003 Sep 25;199(2):201-8.
    PMID: 12969793
    The aim of this study is to investigate the potential correlation between the expression of phosphorylated glycogen synthase kinase-3beta (phospho-GSK-3beta) and beta-catenin, and the mutations of beta-catenin gene at the consensus GSK-3beta phosphorylation site. The reason for this approach is to gain a better understanding of the molecular mechanisms of hepatocarcinogenesis in Malaysia. The expression of phospho-GSK-3beta and beta-catenin by immunohistochemistry and the mutations of beta-catenin were studied in 23 hepatocellular carcinoma (HCC) and surrounding tissues. Overexpression of phospho-GSK-3beta and beta-catenin was found in 12/23 (52.2%) and 13/23 (56.5%) in HCC tissues, 6/23 (26.1%) and 9/23 (39.1%) in surrounding tissues, respectively. Overexpression of beta-catenin in HCC tissues compared to the surrounding liver tissue was found to be higher in HCC tissues (p=0.015). In addition, we found that the expression of phospho-GSK-3beta was related with the accumulation of beta-catenin in surrounding tissues (p<0.05). The expression of phospho-GSK-3beta and its association with the development of HCC is reported for the first time. In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues. This result differed from HCC in geographical areas with high aflatoxin exposure.
    Matched MeSH terms: Liver Neoplasms/pathology
  20. Taha MM, Abdul AB, Abdullah R, Ibrahim TA, Abdelwahab SI, Mohan S
    Chem Biol Interact, 2010 Aug 05;186(3):295-305.
    PMID: 20452335 DOI: 10.1016/j.cbi.2010.04.029
    Zerumbone (ZER), a monosesquiterpene found in the subtropical ginger (Zingiber zerumbet Smith), possesses antiproliferative properties to several cancer cells lines, including the cervical, skin and colon cancers. In this study, the antitumourigenic effects of ZER were assessed in rats induced to develop liver cancer with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and dietary 2-acetylaminofluorene (AAF) (0.02%). The rats also received intraperitoneal ZER injections at 15, 30 or 60 mg/kg body wt. twice a week for 11 weeks, beginning week four post-DEN injection. The hepatocytes of positive control (DEN/AAF) rats were smaller with larger hyperchromatic nuclei than normal, showing cytoplasmic granulation and intracytoplasmic violaceous material, which were characteristics of hepatocarcinogenesis. Histopathological evaluations showed that ZER protects the rat liver from the carcinogenic effects of DEN and AAF. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and alpha-fetoprotein (AFP) were significantly lower (P<0.05) in ZER-treated than untreated rats with liver cancer. The liver malondialdehyde (MDA) concentrations significantly (P<0.05) increased in the untreated DEN/AAF rats indicating hepatic lipid peroxidation. There was also significant (P<0.05) reduction in the hepatic tissue glutathione (GSH) concentrations. The liver sections of untreated DEN/AAF rats also showed abundant proliferating cell nuclear antigen (PCNA), while in ZER-treated rats the expression of this antigen was significantly (P<0.05) lowered. By the TUNEL assay, there were significantly (P<0.05) higher numbers of apoptotic cells in DEN/AAF rats treated with ZER than those untreated. Zerumbone treatment had also increased Bax and decreased Bcl-2 protein expression in the livers of DEN/AAF rats, which suggested increased apoptosis. Even after 11 weeks of ZER treatment, there was no evidence of abnormality in the liver of normal rats. This study suggests that ZER reduces oxidative stress, inhibits proliferation, induces mitochondria-regulated apoptosis, thus minimising DEN/AAF-induced carcinogenesis in rat liver. Therefore, ZER has great potential in the treatment of liver cancers.
    Matched MeSH terms: Liver Neoplasms/pathology
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