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Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells

Basar N, Oridupa OA, Ritchie KJ, Nahar L, Osman NM, Stafford A, et al.

Phytother Res, 2015 Jun;29(6):944-8.
PMID: 25779384 DOI: 10.1002/ptr.5329

Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is a well-known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet-tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra.

Matched MeSH terms: Liver Neoplasms/pathology
Inhibition of low-density lipoprotein oxidation and up-regulation of low-density lipoprotein receptor in HepG2 cells by tropical plant extracts

Salleh MN, Runnie I, Roach PD, Mohamed S, Abeywardena MY

J Agric Food Chem, 2002 Jun 19;50(13):3693-7.
PMID: 12059144

Twelve edible plant extracts rich in polyphenols were screened for their potential to inhibit oxidation of low-density lipoprotein (LDL) in vitro and to modulate LDL receptor (LDLr) activity in cultured HepG2 cells. The antioxidant activity (inhibition of LDL oxidation) was determined by measuring the formation of conjugated dienes (lag time) and thiobarbituric acid reagent substances (TBARS). Betel leaf (94%), cashew shoot (63%), Japanese mint (52%), semambu leaf (50%), palm frond (41%), sweet potato shoot, chilli fruit, papaya shoot, roselle calyx, and maman showed significantly increased lag time (>55 min, P < 0.05) and inhibition of TBARS formation (P < 0.05) compared to control. LDLr was significantly up-regulated (P < 0.05) by Japanese mint (67%), semambu (51%), cashew (50%), and noni (49%). Except for noni and betel leaf, most plant extracts studied demonstrated a positive association between antioxidant activity and the ability to up-regulate LDL receptor. Findings suggest that reported protective actions of plant polyphenols on lipoprotein metabolism might be exerted at different biochemical mechanisms.

Matched MeSH terms: Liver Neoplasms/metabolism
Fulltext Morphological Changes and Cellular Uptake of Functionalized Graphene Oxide Loaded with Protocatechuic Acid and Folic Acid in Hepatocellular Carcinoma Cancer Cell

Buskaran K, Hussein MZ, Mohd Moklas MA, Fakurazi S

Int J Mol Sci, 2020 Aug 16;21(16).
PMID: 32824281 DOI: 10.3390/ijms21165874

The development of nanocomposites has swiftly changed the horizon of drug delivery systems in defining a new platform. Major understanding of the interaction of nanocomposites with cells and how the interaction influences intracellular uptake is an important aspect to study in order to ensure successful utilisation of the nanocomposites. Studies have suggested that the nanocomposites' ability to permeate into biological cells is attributable to their well-defined physicochemical properties with nanoscale size, which is relevant to the nanoscale components of biology and cellular organelles. The functionalized graphene oxide coated with polyethylene glycol, loaded with protocatechuic acid and folic acid (GOP-PCA-FA) nanocomposite intracellular uptake was analysed using transmission electron microscope. The accumulation of fluorescent-labelled nanocomposites in the HepG2 cell was also analysed using a fluorescent microscope. In vitro cellular uptake showed that there was uptake of the drug from 24 h into the cells and the release study using fluorescently tagged nanocomposite demonstrated that release and accumulation were observed at 24 h and 48 h. Moreover, the migration ability of tumor cells is a key step in tumor progression which was observed 48 h after treatment. The GOP serves as a potential nanocarrier system which is capable of improving the therapeutic efficacy of drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated drugs. Nonetheless, it is essential to analyse the translocation of our newly developed GOP-PCA-FA, and its efficiency for drug delivery, effective cellular uptake, and abundant intracellular accumulation would be compromised by possible untoward side effects.

Matched MeSH terms: Liver Neoplasms/metabolism*
Cutaneous metastasis of hepatocellular carcinoma diagnosed by fine needle aspiration cytology and Hep Par 1 immunopositivity

Isa NM, Bong JJ, Ghani FA, Rose IM, Husain S, Azrif M

Diagn Cytopathol, 2012 Nov;40(11):1010-4.
PMID: 21563319 DOI: 10.1002/dc.21706

Cutaneous metastasis of hepatocellular carcinoma (HCC) is very rare, accounting for less than 0.8% of all known cutaneous metastases and occurring in 2.7-3.4% of HCCs. With less than 50 such cases reported worldwide, most of which were diagnosed histologically on excised lesions, it can only be expected that diagnosis made on cytological features alone would be challenging. We report a case of cutaneous metastasis of HCC diagnosed based on cytological features and confirmed by Hep Par 1 immunopositivity of the cell block material. An 81-year-old man, who was known to have unresectable HCC, presented with a 1-month history of painless, left nasal alae mass. The mass measured 1.5 cm in diameter, and was multilobulated with a central necrosis. Fine needle aspiration of the mass was done. Smears were cellular, comprising of malignant cells in loose clusters and aggregates as well as singly dispersed. The malignant cells displayed moderate nuclear pleomorphism, occasional prominent nucleoli, and intranuclear pseudoinclusion. Cell block material demonstrated the trabeculae pattern of the malignant cells and Hep Par 1 immunopositivity. The final diagnosis of a metastatic cutaneous HCC was made. In conclusion, cutaneous HCC metastasis is rare and should be considered in the differential diagnosis in patients with a history of HCC presenting with suspicious skin lesion. In the right clinical setting, a confident diagnosis can be made in such cases by using the fine needle aspiration technique aided with immunopositivity for Hep Par 1 antibody of the aspirated material.

Matched MeSH terms: Liver Neoplasms/pathology
Management of primary liver cell carcinoma

Balasegaram M

Am J Surg, 1975 Jul;130(1):33-7.
PMID: 50750

A review of 352 patients with primary liver cell carcinoma treated by the author is presented. The poor rate of resectability (7 per cent) has necessitated various forms of treatment over the years. These are described in detail. Based on this experience, the current form of treatment for nonresectable carcinoma is summarized. Although it is too early to assess this form of treatment, initial results appear to be promising. A second report in the near future is planned.

Matched MeSH terms: Liver Neoplasms/therapy*
Fulltext Multi-Target Approach to Metastatic Adrenal Cell Carcinoma

Wahab NA, Zainudin S, AbAziz A, Mustafa N, Sukor N, Kamaruddin NA

Arch Iran Med, 2016 Sep;19(9):671-3.
PMID: 27631184 DOI: 0161909/AIM.0012

Adrenal cell carcinoma is a rare tumor and more than 70% of patients present with advanced stages. Adrenal cell carcinoma is an aggressive tumor with a poor prognosis. Surgical intervention is the gold standard treatment and mitotane is the only drug approved for the treatment of adrenal cell carcinoma. Until recently in 2012, the etoposide, doxorubicin, cisplatin plus mitotane are approved as first-line therapy based on response rate and progression-free survival. This case illustrates a case of advanced adrenal cell carcinoma in a young girl who presented with huge adrenal mass with inferior vena cava thrombosis and pulmonary embolism. Multi-approach of therapy was used to control the tumor size and metastasis. Therefore, it may prolong her survival rate for up to 5 years and 4 months.

Matched MeSH terms: Liver Neoplasms/secondary*
Alpha-Fetoprotein levels in normal males from seven ethnic groups with different hepatocellular carcinoma risks

Sizaret P, Tuyns A, Martel N, Jouvenceaux A, Levin A, Ong YW, et al.

Ann N Y Acad Sci, 1975 Aug 22;259:136-55.
PMID: 54017

Alpha-Fetoprotein (AFP) levels of 1,335 males (15 years and older) of seven ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from Nairobi, forest, and the savanna region of the Ivory Coast) were determined by radioimmunoassay. A few elevated levels (up to 30 nanounits/ml) were detected in some normal individuals, especially in the older age-groups. In addition, there was a systematic age-dependency of AFP levels particularly evident in the groups from Singapore-Lyon, in which there was a 50% AFP increase between the ages of 20 and 40. Comparison between Africans on the one hand and people from Singapore-Lyon on the other hand revealed highly significant differences (p less than 0.001), especially in the younger groups, whereas Chinese, Malays, and Indians from Singapore had very similar AFP pattern; this suggests an important role for environmental factors in the regulation of AFP levels. The age dependency of the presumed effect of environmental factors is in keeping with experimental data showing that young animals respond more vigorously to AFP-stimulating factors. Although the incidence of hepatocellular carcinoma (HCC) differs in the three Singapore groups (the highest in Chinese and the lowest in Indians), no relationship was observed in this study between mean AFP level and HCC incidence in Singapore.

Matched MeSH terms: Liver Neoplasms/blood*
Fulltext Genetic diversity of hepatitis B co-infection with hepatitis C, D and E viruses among Malaysian chronic hepatitis B patients

Hudu SA, Niazlin MT, Nordin SA, Tan SS, Omar H, Shahar H, et al.

Afr Health Sci, 2018 Dec;18(4):1117-1133.
PMID: 30766578 DOI: 10.4314/ahs.v18i4.33

Background: Hepatitis B virus co-infection with other strains of viral hepatitis is associated with increased risk of liver cirrhosis and hepatic decompensation.
Objectives: This is a prevalence study that assessed the genetic diversity of chronic hepatitis B patients and coinfection.
Methods: Chronic hepatitis B patients enrolled in this study were tested for antibodies of other hepatitis viruses using ELISA kits. Patient clinical profiles were collected and partial genes of HBV, HCV, and HEV were amplified, sequenced, and analyzed using phylogenetic analysis. The associations between variables were determined using the chi-squared test.
Results: Of the 82 patients recruited for this study, 53.7% were non-cirrhotic, 22.0% cirrhotic, 20.7% acute flare and 3.7% hepatocellular carcinoma. Majority (58%) of patients had a high level of ALT (≥34 U/L). Sequence analysis showed HBV (63.9%) belonged to genotype B, HEV belonged to genotype 4 while HCV belonged to genotype 3a and the genotypes were found to be significantly associated with the clinical stage of the patients (χ2=56.632; p<0.01). Similarly, Hepatitis B e antigen was also found to be significantly associated with the clinical stage of infection (χ2=51.952; p<0.01).
Conclusion: This study revealed that genetic diversity was found to have a significant impact on the severity of infection.

Matched MeSH terms: Liver Neoplasms/epidemiology
Hepatitis markers in Malaysians with hepatocellular carcinoma

Lopez JB, Thambyrajah V, Balasegaram M, Satgunasingam N

Br J Biomed Sci, 1994 Jun;51(2):177-80.
PMID: 7519505

Sera from 80 Malaysians with confirmed hepatocellular carcinoma were tested for five markers of the hepatitis B virus, anti-HCV and anti-HDV by enzyme immunoassay, and alpha fetoprotein (AFP) was measured by radioimmunoassay. Of the patients, 98.8% had evidence of HBV infection and 75% were positive for HBsAg--which latter correlated with AFP raised above cut-off values of 500 ng/ml (P = 0.0001) and 200 ng/ml (P = 0.005). Males correlated significantly with the presence of HBsAg (P = 0.002). Thirty-one per cent of HBsAg positive patients were also positive for HBeAg and 74% for anti-HBe. Twenty per cent of the cases were concurrently positive for both HBsAg and anti-HBs. Six of 70 (8.6%) patients were positive for anti-HCV, of whom four were also positive for HBsAg. None of 67 patients tested for anti-HDV were positive. The results strongly indicate an important aetiological role for hepatitis B virus in causation of hepatocellular carcinoma among Malaysians.

Matched MeSH terms: Liver Neoplasms/microbiology*
Fulltext Hepatitis C--the Malaysian story

Sinniah M, Ooi BG

Singapore Med J, 1993 Apr;34(2):132-4.
PMID: 8266152

We studied the presence of Hepatitis C Virus (HCV) antibodies in a defined Malaysian population and examined the association, if any, between HCV and the Hepatitis B Virus (HBV), using sensitive recombinant DNA second generation Enzyme Immunoassay (EIA) test kits. This sero-prevalence study comprised 1,434 sera from eleven distinct groups comprising intravenous drug users (IVDU), haemophiliacs, male homosexuals, female prostitutes, healthy blood donors, staff of dialysis unit and laboratory personnel, chronic renal failure patients undergoing dialysis (CRFD), patients with liver cirrhosis, chronic active hepatitis, chronic persistent hepatitis and primary liver cancer. Except in laboratory personnel and dialysis staff, HCV antibodies were detected in each group of patients ranging from 3% in blood donors to 85% in IVDU. The main modes of HCV transmission identified were parenteral drug use, transfusion and/or dialysis related. The HBV was found to be the major viral etiological agent in 75% of chronic liver disease (CLD); while in 10% of cases both HCV and HBV were detected. HCV was implicated as the sole viral agent in only a small proportion (1.5%) of patients with chronic liver disease.

Matched MeSH terms: Liver Neoplasms/microbiology
Fulltext Release of a liver anticancer drug, sorafenib from its PVA/LDH- and PEG/LDH-coated iron oxide nanoparticles for drug delivery applications

Ebadi M, Bullo S, Buskara K, Hussein MZ, Fakurazi S, Pastorin G

Sci Rep, 2020 Dec 09;10(1):21521.
PMID: 33298980 DOI: 10.1038/s41598-020-76504-5

The use of nanocarriers composed of polyethylene glycol- and polyvinyl alcohol-coated vesicles encapsulating active molecules in place of conventional chemotherapy drugs can reduce many of the chemotherapy-associated challenges because of the increased drug concentration at the diseased area in the body. The present study investigated the structure and magnetic properties of iron oxide nanoparticles in the presence of polyvinyl alcohol and polyethylene glycol as the basic surface coating agents. We used superparamagnetic iron oxide nanoparticles (FNPs) as the core and studied their effectiveness when two polymers, namely polyvinyl alcohol (PVA) and polyethylene glycol (PEG), were used as the coating agents together with magnesium-aluminum-layered double hydroxide (MLDH) as the nanocarrier. In addition, the anticancer drug sorafenib (SO), was loaded on MLDH and coated onto the surface of the nanoparticles, to best exploit this nano-drug delivery system for biomedical applications. Samples were prepared by the co-precipitation method, and the resulting formation of the nanoparticles was confirmed by X-ray, FTIR, TEM, SEM, DLS, HPLC, UV-Vis, TGA and VSM. The X-ray diffraction results indicated that all the as-synthesized samples contained highly crystalline and pure Fe3O4. Transmission electron microscopy analysis showed that the shape of FPEGSO-MLDH nanoparticles was generally spherical, with a mean diameter of 17 nm, compared to 19 nm for FPVASO-MLDH. Fourier transform infrared spectroscopy confirmed the presence of nanocarriers with polymer-coating on the surface of iron oxide nanoparticles and the existence of loaded active drug consisting of sorafenib. Thermogravimetric analyses demonstrated the thermal stability of the nanoparticles, which displayed enhanced anticancer effect after coating. Vibrating sample magnetometer (VSM) curves of both produced samples showed superparamagnetic behavior with the high saturation magnetization of 57 emu/g for FPEGSO-MLDH and 49 emu/g for FPVASO-MLDH. The scanning electron microscopy (SEM) images showed a narrow size distribution of both final samples. The SO drug loading and the release behavior from FPEGSO-MLDH and FPVASO-MLDH were assessed by ultraviolet-visible spectroscopy. This evaluation showed around 85% drug release within 72 h, while 74% of sorafenib was released in phosphate buffer solution at pH 4.8. The release profiles of sorafenib from the two designed samples were found to be sustained according to pseudo-second-order kinetics. The cytotoxicity studies confirmed the anti-cancer activity of the coated nanoparticles loaded with SO against liver cancer cells, HepG2. Conversely, the drug delivery system was less toxic than the pure drug towards fibroblast-type 3T3 cells.

Matched MeSH terms: Liver Neoplasms/drug therapy
Effects of tocotrienols on cell viability and apoptosis in normal murine liver cells (BNL CL.2) and liver cancer cells (BNL 1ME A.7R.1), in vitro

Har CH, Keong CK

Asia Pac J Clin Nutr, 2005;14(4):374-80.
PMID: 16326644

The effects of tocotrienols on murine liver cell viability and their apoptotic events were studied over a dose range of 0-32 microg mL(-1). Normal murine liver cells (BNL CL.2) and murine liver cancer cells (BNL 1ME A.7R.1) were treated with tocotrienols (T(3)), alpha tocopherol (alpha-T) and the chemo drug, Doxorubicin (Doxo, as a positive control). Cell viability assay showed that T(3) significantly (P < or = 0.05) lowered the percentage of BNL 1ME A.7R.1 cell viability in a dose-responsive manner (8-16 microg mL(-1)), whereas T did not show any significant (P>0.05) inhibition in cell viability with increasing treatment doses of 0-16 microg mL(-1). The IC(50) for tocotrienols were 9.8, 8.9, 8.1, 9.7, 8.1 and 9.3 microg mL(-1) at 12, 24, 36, 48, 60 and 72 hours respectively. Early apoptosis was detected 6 hours following T(3) treatment of BNL 1ME A.7R.1 liver cancer cells, using Annexin V-FITC fluorescence microscopy assay for apoptosis, but none were observed for the non-treated liver cancer cells at the average IC(50) of 8.98 microg mL(-1) tocotrienols for liver cancer cells. Several apoptotic bodies were detected in BNL 1ME A.7R.1 liver cancer cells at 6 hours post-treatment with tocotrienols (8.98 microg mL(-1)) using Acridine Orange/Propidium Iodide fluorescence assay. However, only a couple of apoptotic bodies were seen in the non-treated liver cancer cells and the BNL CL.2 normal liver cells. Some mitotic bodies were also observed in the T(3)-treated BNL 1ME A.7R.1 liver cancer cells but were not seen in the untreated BNL 1ME A.7R.1 cells and the BNL CL.2 liver cells. Following T(3)-treatment (8.98 microg mL(-1)) of the BNL 1ME A.7R.1 liver cancer cells, 24.62%, 25.53% and 44.90% of the cells showed elevated active caspase 3 activity at 9, 12 and 24 hours treatment period, respectively. DNA laddering studies indicated DNA fragmentation occurred in the T(3)-treated liver cancer cells, BNL 1ME A.7R.1 but not in non-treated liver cancer cells and the T(3)-treated and non-treated normal liver cells. These results suggest that tocotrienols were able to reduce the cell viability in the murine liver cancer cells at a dose of 8-32 microg mL(-1) and that this decrease in percentage cell viability may be due to apoptosis.

Matched MeSH terms: Liver Neoplasms, Experimental/pathology*
Adaptation of international guidelines for metastatic colorectal cancer: an asian consensus

Cheng AL, Li J, Vaid AK, Ma BB, Teh C, Ahn JB, et al.

Clin Colorectal Cancer, 2014 Sep;13(3):145-55.
PMID: 25209093 DOI: 10.1016/j.clcc.2014.06.004

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Matched MeSH terms: Liver Neoplasms/genetics; Liver Neoplasms/secondary; Liver Neoplasms/therapy*
Fulltext Diagnosis and management of ruptured hepatoma: single center experience over 10 years

Letchumanan VP, Lim KF, Mohamad AB

Med J Malaysia, 2013 Oct;68(5):405-9.
PMID: 24632870 MyJurnal

INTRODUCTION: Spontaneous rupture is a dramatic presentation of HCC and it carries high mortality rate. To study the outcomes of ruptured HCC patients managed at a tertiary referral centre in Malaysia.
METHODS: A retrospective review of all ruptured HCC patients managed as inpatient at the Department of Hepatobiliary Surgery, Hospital Selayang between January 2001 and December 2010. Data was retrieved from the hospital electronic medical records, Powerchart (Cerner Corporation Inc., USA) and supplemented with registry from Interventional Radiology record of chemoembolization and registry from hepatobiliary operative surgery records.
RESULTS: There were 22 patients admitted with confirmed diagnosis of ruptured HCC over 10 years period. The common clinical findings on presentation were abdominal pain and presence of shock (36.4%). The mortality rate was 81.8% with only four patients noted to be alive during the follow up. One year overall survival for ER and DR are 40.0% and 72.7% respectively and the median survival in patients treated with DR was 433.3 days whereas it was 212.5 days in ER group.
CONCLUSIONS: This study supports the clinical practice of TAE should be the first line treatment followed by staged surgery in suitable candidates with ruptured HCC.

Matched MeSH terms: Liver Neoplasms
Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update

Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, et al.

Hepatol Int, 2012 Jun;6(3):531-61.
PMID: 26201469 DOI: 10.1007/s12072-012-9365-4

Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was discussed and debated. The earlier "Asian-Pacific consensus statement on the management of chronic hepatitis B" was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.

Matched MeSH terms: Liver Neoplasms
Fulltext Radionuclide therapy of hepatocellular carcinoma

Sundram F

Biomed Imaging Interv J, 2006 Jul;2(3):e40.
PMID: 21614248 MyJurnal DOI: 10.2349/biij.2.3.e40

Hepatocellular carcinoma (HCC) is a malignant tumour of the hepatocyte. It is a common malignancy worldwide and causes almost half a million deaths annually. Asia is a high risk area. Although surgery (hepatectomy or liver transplantation) is the main form of curative treatment, the majority of patients are not eligible for surgery due to extent of tumour and dysfunction of liver. Radiopharmaceuticals used for transarterial treatment of HCC were Yttrium-90 microspheres, Iodine-131 lipiodol, Rhenium-188 lipiodol, and Holmium-166 Chitosan complex. Yittrium-90 microspheres are glass or resin microspheres of mean sphere diameter of 20 to 30 micrometre. The activity administered was about 4 GBq. Reported response rate was about 20%, and median survival was 54 weeks. On inoperable tumours, reported objective response of I-131 lipiodol was 40 to 70%, and median survival was six to nine months. It showed efficacy similar to TACE. In adjuvant treatment following curative resection of HCC, reported three year survival was 86% compared with 46% for the control group. The administered activity in both adjuvant and inoperable HCC was about 2 GBq (55 mCi). Rhenium-188 lipiodol is a new radioconjugate, and using it we treated 70 patients with inoperable HCC. This treatment was a part of a multi-centre trial sponsored by the International Atomic Energy Agency. Partial response was obtained in 17% of cases, while 49% had stable disease at three months, and 34% showed disease progression. In terms of survival, 19% survived one year, 60% for six months, and 90% for three months. The mean activity was about 4.6 GBq (124 mCi). This method was safe and free from adverse effects.

Matched MeSH terms: Liver Neoplasms
Fulltext Social determinants of Hepatitis C virus infection among people who inject drug in Negeri Sembilan

Azline Abdilah,, Sri Ganesh Muthiah, Hayati Kadir Shahar

Malaysian Journal of Medicine and Health Sciences, 2019;15(104):62-62.
MyJurnal

Introduction: Hepatitis C virus (HCV) infection is a major leading cause of morbidity and mortality worldwide. Per-sistent HCV infection is associated with major liver complications such as liver failure, liver cancer and fatality. It is estimated that 5.6 million people who inject drugs (PWID) were chronically infected with HCV globally, meanwhile, 59% of those diagnosed as HCV in Malaysia were PWID. The objective of this study was to determine the social determinants of HCV infection among PWID in Negeri Sembilan, Malaysia. Methods: A cross-sectional study was conducted based on stratified proportionate to size sampling among registered Methadone Maintenance Therapy (MMT) clients with PWID attending health clinics in Negeri Sembilan from February 2018 to July 2018. All eligi-ble respondents were randomly selected. Data were collected using an interviewer-guided questionnaire and was analysed using Statistical Package of IBM SPSS version 23. Independent T test and Chi-square test (χ2) were used to determine the associations between the variables. Results: Majority of the respondents in this study were between 20 and 63 years of age, Malay (90.1%) and infected with HCV (89%). There was a significant association between the respondent’s age (p

Matched MeSH terms: Liver Neoplasms
Fulltext Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma

Buskaran K, Bullo S, Hussein MZ, Masarudin MJ, Mohd Moklas MA, Fakurazi S

Materials (Basel), 2021 Feb 09;14(4).
PMID: 33572054 DOI: 10.3390/ma14040817

Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites' physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. Finally, the proteomic profiling array and quantitative reverse transcription polymerase chain reaction revealed the expression of pro-apoptotic and anti-apoptotic proteins induced by graphene oxide conjugated PEG loaded with protocatechuic acid drug folic acid coated nanocomposite (GOP-PCA-FA) in HepG2 cells. In conclusion, GOP-PCA-FA nanocomposites treated HepG2 cells exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid and GOP-PCA nanocomposites, due to the utilization of a folic acid-targeting nanodrug delivery system.

Matched MeSH terms: Liver Neoplasms
Hepatocellular carcinoma: A local registry on risk factors, imaging patterns, treatment strategies and overall survival

Raja M, Yaacob Y, Wong Z, Chik I

Med J Malaysia, 2021 03;76(2):151-156.
PMID: 33742621

INTRODUCTION: Hepatocellular carcinoma (HCC) is among the common death-causing cancers worldwide. This liver malignancy is primarily diagnosed using radiological imaging techniques. Most of the patients in Malaysia present late and were diagnosed at an intermediate or advanced stage of Barcelona Clinic of Liver Cancer (BCLC). This causes a limitation on the treatment options for the patients.
MATERIALS AND METHODS: We performed a retrospective crosssectional study of HCC cases within a five-year period in our center with data collected from Hospital Canselor Tunku Mukhriz (HCTM). This study examines the HCC risk factors, the pattern of diagnosis, treatment options and overall survival.
RESULTS: The findings from this study showed that viral hepatitis was the highest risk factor in which most of the patients were elderly males who presented with abdominal distension. In addition, given the high prevalence of metabolic diseases Malaysia, it is predicted that the number of non-alcoholic steatohepatosis (NASH)-related HCC cases might increase. Alpha-fetoprotein (AFP) proved to have no significant role in the detection of the disease. The number of patients detected at early BCLC was minimal, resulting in limited options of treatment. Overall survival of our HCC patients was poor at 17 months.
CONCLUSION: We conclude that HCC patients in HCTM mostly presented at late stage to hospital, hence limiting the treatment options and resulted in poor survival rate. Disease awareness should be implemented at primary care level to detect HCC at its early stage. Subsequently, a multidisciplinary hospital team is required to manage the disease at its different stages of presentation.

Matched MeSH terms: Liver Neoplasms
Fulltext Predictors and association of Hepatitis C virus infections among people who injects drug in Negeri Sembilan

Azline Abdilah, Sri Ganesh Muthiah, Hayati Kadir

Malaysian Journal of Medicine and Health Sciences, 2020;16(1):261-269.
MyJurnal

Introduction: Hepatitis C virus (HCV) infection is known as contributing to high morbidity and mortality globally. Major liver complications such as liver failure and liver cancer which can lead to fatality have been associated with persistent HCV infection. Globally, it is estimated that 5.6 million chronically infected HCV are among people who inject drugs (PWID). Malaysia has estimated that 59% HCV infections were among PWID. The aim of this study is to determine the prevalence of HCV infection and its predictors among PWID in Negeri Sembilan. Methods: A cross-sectional study based on random proportion to size sampling was conducted among 212 out of 1414 regis- tered Methadone Maintenance Therapy (MMT) clients with PWID attending health clinics in Negeri Sembilan from February 2018 to July 2018. Data were collected using questionnaires administered through face-to-face interviews. Data were analyzed using Statistical Package of IBM SPSS Statistics Version 23 and p-value of

Matched MeSH terms: Liver Neoplasms

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