Displaying publications 21 - 40 of 10191 in total

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  1. Farhadi A, Behzad-Behbahani A, Geramizadeh B, Sekawi Z, Rahsaz M, Sharifzadeh S
    J Med Virol, 2014 Jul;86(7):1134-44.
    PMID: 24700118 DOI: 10.1002/jmv.23945
    Limited data exist regarding whether a high-risk human papillomavirus (HR-HPV) infection increases the risk of developing renal cell carcinoma. The aim of this study was to investigate whether HPV infection has a role in the pathogenesis or development of a certain histological subtype of renal cell carcinoma. Formalin-fixed paraffin-embedded (FFPE) specimens of 122 patients with histopathologically proven renal cell carcinoma and their respective peritumoral tissues were examined. The presence of HPV-DNA was determined by a combination of MY/GP+ consensus primers and HPV-16/18 type specific nested PCRs followed by direct sequencing. Catalyzed signal-amplified colorimetric in situ hybridization (CSAC-ISH) technique was applied to determine the physical status of viral genome. The expression of p16INK4a and HPV L1 capsid proteins was evaluated using immunohistochemistry. HPV genome was detected in 37 (30.3%) tumor specimens and their four (4.1%) corresponding peritumoral tissues. HPV-18 was the most common viral type identified followed by HPV-16 and 58. Immunoexpression of p16INK4a was detected in 24 (20.3%) cases. Data analysis showed a significant correlation between p16INK4a expression and the presence of HR-HPV DNA (P 
    Matched MeSH terms: Sequence Analysis, DNA
  2. Hajrezaie M, Hassandarvish P, Moghadamtousi SZ, Gwaram NS, Golbabapour S, Najihussien A, et al.
    PLoS One, 2014;9(3):e91246.
    PMID: 24618844 DOI: 10.1371/journal.pone.0091246
    Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF).
    Matched MeSH terms: Blood Chemical Analysis
  3. Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Khosroushahi AY
    Anaerobe, 2014 Aug;28:29-36.
    PMID: 24818631 DOI: 10.1016/j.anaerobe.2014.04.012
    Lactobacillus acidophilus is categorized as a probiotic strain because of its beneficial effects in human health and prevention of disease transmission. This study is aimed to characterize the probiotic potential of L. acidophilus 36YL originally isolated from the vagina of healthy and fertile Iranian women. The L. acidophilus 36YL strain was identified using 16S rDNA gene sequencing and characterized by biochemical methodologies, such as antibiotics susceptibility, antimicrobial activity, and acid and bile resistance. The bioactivity of the secretion of this strain on four human cancer cell lines (AGS, HeLa, MCF-7, and HT-29) and one normal cell line (HUVEC) was evaluated by cytotoxicity assay and apoptosis analysis. This newly isolated strain was found to exhibit notable probiotic properties, such as admirable antibiotic susceptibility, good antimicrobial activity, and favorable resistance to acid and bile salt. The results of bioactivity assessment demonstrated acceptable anticancer effects on the four tested cancer cell lines and negligible side effects on the assayed normal cell line. Our findings revealed that the anticancer effect of L. acidophilus 36YL strain secretions depends on the induction of apoptosis in cancer cells. L. acidophilus 36YL strain is considered as a nutraceutical alternative or a topical medication with a potential therapeutic index because of the absence of cytotoxicity to normal cells, but effective toxicity to cancer cell lines.
    Matched MeSH terms: Sequence Analysis, DNA
  4. Abu Hassan H, Abd Aziz N, Hassan Y, Hassan F
    PMID: 24868154 DOI: 10.2147/COPD.S56637
    BACKGROUND: Lack of awareness among ex-smokers on the benefits of sustaining smoking cessation may be the main cause of their smoking relapse. This study explored health-related quality of life (HRQoL) and hospital admission amongst chronic obstructive pulmonary disease (COPD) patients according to the duration of smoking cessation.
    MATERIALS AND METHODS: This study recruited COPD patients from a chest clinic who agreed to participate in a medication therapy-adherence program from January to June 2013. They were interviewed during their visits to obtain information regarding their smoking history and HRQoL. They were divided into three groups according to smoking status (sustained quitters, quit ≥5 years; quitters, quit <5 years; and smokers, smoking at least one cigarette/day). The effects of the duration of cessation on HRQoL and hospital admission were analyzed using a multinomial logistic model.
    RESULTS: A total of 117 participants with moderate COPD met the inclusion criteria, who were comprised of 41 sustained quitters, 40 quitters, and 36 smokers. Several features were similar across the groups. Most of them were married elderly men (aged >64 years) with low-to-middle level of education, who smoked more than 33 cigarettes per day and had high levels of adherence to the medication regimen. The results showed that sustained quitters were less likely to have respiratory symptoms (cough, phlegm and dyspnea) than smokers (odds ratio 0.02, confidence interval 0-0.12; P<0.001). The hospital admission rate per year was increased in quitters compared to smokers (odds ratio 4.5, confidence interval 1.91-10.59; P<0.005).
    CONCLUSION: A longer duration of quitting smoking will increase the benefits to COPD patients, even if they experience increased episodic respiratory symptoms in the early period of the cessation. Thus, the findings of this study show the benefits of early smoking cessation.
    KEYWORDS: HRQoL; chronic obstructive pulmonary disease (COPD); hospital admission and hospital stay
    Study site: Chest Clinic, Hospital Melaka, Malaysia
    Matched MeSH terms: Multivariate Analysis
  5. Abdulameer SA, Syed Sulaiman SA, Hassali MA, Sahib MN, Subramaniam K
    Int J Rheum Dis, 2014 Jan;17(1):93-105.
    PMID: 24472272 DOI: 10.1111/1756-185X.12104
    The aims of this study were to translate and examine the psychometric properties of the Malaysian version of the Osteoporosis Health Belief Scale (OHBS-M) among type 2 diabetes patients (T2DM) and to assess the correlation between osteoporosis knowledge, health belief and self-efficacy scales, as well as assess the osteoporosis risk in the sample population using quantitative ultrasound measurement (QUS).
    Matched MeSH terms: Factor Analysis, Statistical
  6. Kong C, Yehye WA, Abd Rahman N, Tan MW, Nathan S
    PMID: 24393217 DOI: 10.1186/1472-6882-14-4
    The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.
    Matched MeSH terms: Survival Analysis
  7. Ho CS, Yap SH, Phuah NH, In LL, Hasima N
    Lung Cancer, 2014 Feb;83(2):154-62.
    PMID: 24360396 DOI: 10.1016/j.lungcan.2013.11.024
    Dysregulation in miRNA expression contributes towards the initiation and progression of metastasis by regulating multiple target genes. In this study, variations in miRNA expression profiles were investigated between high and low invasive NSCLC cell lines followed by identification of miRNAs with targets governing NSCLC's metastatic potential.
    Matched MeSH terms: Microarray Analysis
  8. Chia PL, Earnest A, Lee R, Lim J, Wong CP, Chia YW, et al.
    Ann Acad Med Singap, 2013 Sep;42(9):432-6.
    PMID: 24162317
    INTRODUCTION: In Singapore, the age-standardised event rates of myocardial infarction (MI) are 2- and 3-fold higher for Malays and Indians respectively compared to the Chinese. The objectives of this study were to determine the prevalence and quantity of coronary artery calcification (CAC) and non-calcified plaques across these 3 ethnic groups.

    MATERIALS AND METHODS: This was a retrospective descriptive study. We identified 1041 patients (810 Chinese, 139 Malays, 92 Indians) without previous history of cardiovascular disease who underwent cardiac computed tomography for atypical chest pain evaluation. A cardiologist, who was blinded to the patients' clinical demographics, reviewed all scans. We retrospectively analysed all their case records.

    RESULTS: Overall, Malays were most likely to be active smokers (P = 0.02), Indians had the highest prevalence of diabetes mellitus (P = 0.01) and Chinese had the highest mean age (P <0.0001). The overall prevalence of patients with non-calcified plaques as the only manifestation of sub-clinical coronary artery disease was 2.1%. There was no significant difference in the prevalence of CAC, mean CAC score or prevalence of non-calcified plaques among the 3 ethnic groups. Active smoking, age and hypertension were independent predictors of CAC. Non-calcified plaques were positively associated with male gender, age, dyslipidaemia and diabetes mellitus.

    CONCLUSION: The higher MI rates in Malays and Indians in Singapore cannot be explained by any difference in CAC or non-calcified plaque. More research with prospective follow-up of larger patient populations is necessary to establish if ethnic-specific calibration of CAC measures is needed to adjust for differences among ethnic groups.

    Matched MeSH terms: Analysis of Variance
  9. Ong LY, Razak SN, Lee YM, Sri La Sri Ponnampalavanar S, Syed Omar SF, Azwa RI, et al.
    J Med Virol, 2014 Jan;86(1):38-44.
    PMID: 24127302 DOI: 10.1002/jmv.23772
    Expansion of antiretroviral treatment programs have led to the growing concern for the development of antiretroviral drug resistance. The aims were to assess the prevalence of drug resistant HIV-1 variants and to identify circulating subtypes among HAART-naïve patients. Plasma specimens from N = 100 HIV+ HAART-naïve adult were collected between March 2008 and August 2010 and viral RNA were extracted for nested PCR and sequenced. PR-RT sequences were protein aligned and checked for transmitted drug resistance mutations. Phylogenetic reconstruction and recombination analysis were performed to determine the genotypes. Based on the WHO consensus guidelines, none of the recruited patients had any transmitted drug resistance mutations. When analyzed against the Stanford guidelines, 35% of patients had at least one reported mutation that may reduce drug susceptibility to PI (24%), NRTI (5%), and NNRTI (14%). The commonly detected mutation that may affect current first line therapy was V179D (3%), which may lead to reduced susceptibility to NNRTI. The predominant circulating HIV-1 genotypes were CRF01_AE (51%) and CRF33_01B (17%). The prevalence of unique recombinant forms (URF) was 7%; five distinct recombinant structures involving CRF01_AE and subtype B' were observed, among them a cluster of three isolates that could form a novel circulating recombinant form (CRF) candidate. Transmitted drug resistance prevalence among HAART-naïve patients was low in this cohort of patients in Kuala Lumpur despite introduction of HAART 5 years ago. Owing to the high genetic diversity, continued molecular surveillance can identify the persistent emergence of HIV-1 URF and novel CRF with significant epidemiological impact.
    Matched MeSH terms: Sequence Analysis, DNA
  10. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF
    Int J Dermatol, 2014 Jun;53(6):676-84.
    PMID: 23967807 DOI: 10.1111/ijd.12070
    BACKGROUND: Generalized pustular psoriasis (GPP) is a severe but rare variant of psoriasis. Our objective is to review the clinical profile, comorbidities, and outcome of patients with GPP.
    MATERIALS AND METHODS: A retrospective note review of all patients with adult-onset GPP.
    RESULTS: A total of 102 patients with adult-onset GPP were diagnosed between 1989 and November 2011, with a female to male ratio of 2 : 1. The mean age at onset of GPP was 40.9 years (range: 21-81 years). Acute GPP was the most common variant seen (95 cases), followed by four localized variants of GPP and three with annular pustular psoriasis. Fever and painful skin were present in 89% of patients, arthritis in 34.7%, and leukocytosis in 78.4%. Common triggers were systemic steroids (45 cases), pregnancy (17 cases), and upper respiratory tract infections (16 cases). A positive family history of psoriasis and GPP was present in 29% and 11%, respectively. Comorbidities included obesity (42.9%), hypertension (25.7%), hyperlipidemia (25.7%), and diabetes mellitus (23.7%). The mean duration of admission and pustular flare for acute GPP was 10.3 days (range: 3-44 days) and 16 days (range: 7-60 days), respectively. Fifty-four patients responded to systemic retinoid, 21 to methotrexate, eight to cyclosporine, and one to adalimumab, but recurrences were common.
    CONCLUSIONS: Our study confirms the poor response of GPP to currently available anti-psoriatic agents, with frequent flare-ups. There is a need for a more effective targeted therapy for this condition.
    Matched MeSH terms: Analysis of Variance
  11. Jan Mohamed HJ, Mitra AK, Zainuddin LR, Leng SK, Wan Muda WM
    Women Health, 2013;53(4):335-48.
    PMID: 23751089 DOI: 10.1080/03630242.2013.788120
    Metabolic syndrome has been associated with an increased risk of cardiovascular disease and diabetes mellitus. The objective of this study was to determine gender differences in the prevalence and factors associated with metabolic syndrome in a rural Malay population. This cross-sectional study, conducted in Bachok, Kelantan, involved 306 respondents aged 18 to 70 years. The survey used a structured questionnaire to collect information on demographics, lifestyle, and medical history. Anthropometric measurements, such as weight, height, body mass index, waist and hip circumference, and blood pressure were measured. Venous blood samples were taken by a doctor or nurses and analyzed for lipid profile and fasting glucose. The overall prevalence of metabolic syndrome was 37.5% and was higher among females (42.9%). Being unemployed or a housewife and being of older age were independently associated with metabolic syndrome in a multivariate analysis. Weight management and preventive community-based programs involving housewives, the unemployed, and adults of poor education must be reinforced to prevent and manage metabolic syndrome effectively in adults.
    Matched MeSH terms: Regression Analysis
  12. Huri HZ, Makmor-Bakry M, Hashim R, Mustafa N, Wan Ngah WZ
    Int J Clin Pharm, 2012 Dec;34(6):863-70.
    PMID: 22869200 DOI: 10.1007/s11096-012-9682-7
    BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are frequently admitted to the hospital with severe or acute hyperglycaemia secondary to an acute illness or disease. Uncontrolled glycaemia is a significant problem during severe or acute hyperglycaemia.

    OBJECTIVE: This study sought to identify demographic, clinical, and genetic factors that may contribute to increased insulin resistance or worsening of glycaemic control in patients with T2DM.

    SETTING: This prospective cohort study included 156 patients with T2DM and severe or acute hyperglycaemia who were treated with insulin at any medical ward of the National University of Malaysia Medical Centre.

    METHOD: Insulin resistance was determined using the homeostatic model assessment-insulin resistance index. Glycaemic control during the episode of hyperglycaemia was assessed as the degree to which the patient achieved the target glucose levels. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify polymorphisms in insulin receptor substrate (IRS) genes.

    MAIN OUTCOME MEASURE: Identification of possible predictors (demographic, clinical, or genetic) for insulin resistance and glycaemic control during severe/acute hyperglycaemia.

    RESULTS: A polymorphism in IRS1, r.2963 G>A (p.Gly972Arg), was a significant predictor of both insulin resistance [odds ratios (OR) 4.48; 95 % confidence interval (CI) 1.2-16.7; P = 0.03) and worsening of glycaemic control (OR 6.04; 95 % CI 0.6-64.6; P = 0.02). The use of loop diuretics (P < 0.05) and antibiotics (P < 0.05) may indirectly predict worsening of insulin resistance or glycaemic control in patients with severe/acute hyperglycaemia.

    CONCLUSION: Clinical and genetic factors contribute to worsening of insulin resistance and glycaemic control during severe/acute hyperglycaemia in patients with T2DM. Early identification of factors that may influence insulin resistance and glycaemic control may help to achieve optimal glycaemic control during severe/acute hyperglycaemia.

    Matched MeSH terms: Amplified Fragment Length Polymorphism Analysis
  13. Chew BH, Mastura I, Shariff-Ghazali S, Lee PY, Cheong AT, Ahmad Z, et al.
    Cardiovasc Diabetol, 2012;11:54.
    PMID: 22607105 DOI: 10.1186/1475-2840-11-54
    BACKGROUND: Uncontrolled blood pressure (BP) is a significant contributor of morbidity and even mortality in type 2 diabetes (T2D) patients. This study was done to determine the significant determinants of uncontrolled blood pressure in T2D patients in Malaysia.
    METHODS: Between 1st January 2009 to 31st December 2009, data from 70 889 patients with Type 2 diabetes was obtained from the Adult Diabetes Control and Management Registry for analysis; 303 centers participated in the study. Their demographic characteristics, the nature of their diabetes, their state of hypertension, treatment modalities, risk factors, and complications are described. Based on their most recent BP values, subjects were divided into controlled BP and uncontrolled BP and their clinical determinants compared. Independent determinants were identified using multivariate logistic regression.
    RESULTS: The mean age of patients at diagnosis of diabetes was 52.3 +/- 11.1 years old. Most were women (59.0 %) and of Malay ethnicity (61.9 %). The mean duration of diabetes was 5.9 +/- 5.6 years. A total of 57.4 % were hypertensive. Of the 56 503 blood pressure (BP) measured, 13 280 (23.5 %) patients had BP <130/80 mmHg. Eighteen percent was on > two anti-hypertensive agents. Health clinics without doctor, older age (>/= 50 years old), shorter duration of diabetes (< 5 years), Malay, overweight were determinants for uncontrolled blood pressure (BP >/=130/80 mmHg). Patients who were on anti-hypertensive agent/s were 2.7 times more likely to have BP >/=130/80 mmHg. Type 2 diabetes patients who had ischaemic heart disease or nephropathy were about 20 % and 15 % more likely to have their blood pressure treated to target respectively.
    CONCLUSIONS: Major independent determinants of uncontrolled BP in our group of T2D patients were Malay ethnicity, older age, recent diagnosis of diabetes, overweight and follow-up at health clinics without a doctor and possibly the improper use of anti hypertensive agent. More effort, education and resources, especially in the primary health care centres are needed to improve hypertensive care among our patients with diabetes.
    Matched MeSH terms: Multivariate Analysis
  14. Wu YL, Kim JH, Park K, Zaatar A, Klingelschmitt G, Ng C
    Lung Cancer, 2012 Aug;77(2):339-45.
    PMID: 22494567 DOI: 10.1016/j.lungcan.2012.03.012
    Maintenance therapy, commenced immediately after the completion of first-line chemotherapy, is a promising strategy for improving treatment outcomes in patients with non-small-cell lung cancer (NSCLC). The global phase III SequentiAl Tarceva in UnResectable NSCLC (SATURN) study evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib as maintenance treatment in NSCLC patients without progression after first-line chemotherapy. We report a retrospective subanalysis of Asian patients enrolled in SATURN. Patients with advanced NSCLC with no evidence of progression after four cycles of chemotherapy were randomized to receive erlotinib 150 mg/day or placebo, until progressive disease or limiting toxicity. The co-primary endpoints of SATURN were progression-free survival (PFS) in all patients and in those with positive EGFR immunohistochemistry (IHC) status. Secondary endpoints included overall survival (OS), disease control rate, safety, quality of life (QoL) and biomarker analyses. In total, 126 patients from East and South-East Asian centers were randomized (14% of the intent-to-treat population): 88 from Korea, 28 from China and 10 from Malaysia; one patient was excluded from this analysis due to Indian ethnicity. PFS was significantly prolonged in the erlotinib treatment arm, both overall (hazard ratio [HR]: 0.57; p=0.0067) and in patients with EGFR IHC-positive disease (HR=0.50; p=0.0057). There was a trend towards an increase in OS, which reached statistical significance in the EGFR IHC-positive subgroup (p=0.0233). The overall response rate was significantly higher with erlotinib compared with placebo (24% versus 5%; p=0.0025). Erlotinib was generally well tolerated and had no negative impact on QoL in this subpopulation. The most common treatment-related adverse events were rash, diarrhea and pruritus. Erlotinib was effective and well tolerated in Asian patients, producing benefits consistent with those observed in the overall SATURN population. Maintenance treatment with erlotinib appears to be a useful option for the management of Asian patients with advanced NSCLC without progression after first-line chemotherapy.
    Matched MeSH terms: Survival Analysis
  15. Zamri HF, Shamsudin MN, Rahim RA, Neela V
    Vaccine, 2012 May 2;30(21):3231-8.
    PMID: 22426330 DOI: 10.1016/j.vaccine.2012.02.012
    A gene associated with lipopolysaccharide (LPS) transport was cloned from a local clinical Vibrio cholerae O1 strain of the Ogawa serotype by using the Lactococcus lactis nisin-controlled expression (NICE) system. The V. cholerae wzm gene, which codes for an integral membrane transporter protein, was expressed and targeted to the cytoplasmic membrane, and was crudely isolated through simple centrifugation and SDS solubilization. To examine seroreactivity of this construct, rabbits were orally fed with 10(9) cfu/ml of live, recombinant L. lactis carrying the wzm gene, induced with nisin prior to administration. Recombinant plasmids were retrieved from L. lactis cultured directly from stool samples of inoculated rabbits. Reverse-transcriptase PCR of wzm using the retrieved plasmids confirmed transcription of this gene, indicating viability and stability of the recombinants in vivo. The L. lactis-Wzm construct elicited substantial levels of IgG and sIgA, and challenge with virulent V. cholerae O1 evoked severe diarrhoea in the naive, non-immunised control group, but not in those fed with either recombinant or non-recombinant L. lactis. Oral administration with recombinant L. lactis expressing the V. cholerae wzm gene increases both systemic and mucosal immunity, whereas L. lactis itself appears capable of protecting against the diarrhoeal symptoms caused by V. cholerae. Wzm is a conserved membrane protein associated with the LPS endotoxin, and together with the food-grade L. lactis, represent an attractive target for the development of a safer, live anti-infective therapy against V. cholerae.
    Matched MeSH terms: Sequence Analysis, DNA
  16. Chew BH, Ismail M, Lee PY, Taher SW, Haniff J, Mustapha FI, et al.
    Diabetes Res Clin Pract, 2012 Jun;96(3):339-47.
    PMID: 22305940 DOI: 10.1016/j.diabres.2012.01.017
    Numerous studies with compelling evidence had shown a clear relationship between dyslipidaemia and cardiovascular (CV) events in patients with diabetes mellitus. This was an observational study based on secondary data from the online registry database Adult Diabetes Control and Management (ADCM) looking into the determinants of uncontrolled dyslipidaemia in type 2 diabetes mellitus patients. Independent predictors were identified using multivariate logistic regression. A total of 303 centres (289 health clinics, 14 hospitals) contributed a total of 70,889 patients (1972 or 2.8% patients were from hospital). About thirty eight percent were reported to have dyslipidaemia. There were 40.7% patients on lipid-lowering agents and of those above age 40 years old, only 38.1% of them were on a statin. Malay ethnicity and younger age groups (<50 years old) were two major determinants of uncontrolled LDL-C, TG and HDL-C. Female gender and uncontrolled blood pressure were determinants of uncontrolled LDL-C, and poor glycaemic control was related independently to high TG. This study has highlighted the suboptimal management of diabetic dyslipidaemia in Malaysia. Pharmacological treatment of dyslipidaemia could be more effective. Healthcare stakeholders in this country, especially in the primary care, have to recognize these shortfalls and take immediate remedial measures.
    Matched MeSH terms: Multivariate Analysis
  17. Rahman MN, Rani MR, Rohani JM
    Work, 2012;43(4):507-14.
    PMID: 22927603 DOI: 10.3233/WOR-2012-1404
    The aim of this study was to investigate the work-related musculoskeletal disorders (WMSDs) among workers in wall plastering jobs within the construction industry.
    Matched MeSH terms: Task Performance and Analysis
  18. Alfizah H, Ramelah M, Rizal AM, Anwar AS, Isa MR
    Helicobacter, 2012 Oct;17(5):340-9.
    PMID: 22967117 DOI: 10.1111/j.1523-5378.2012.00956.x
    Polymorphisms of Helicobacter pylori cagA and vacA genes do exist and may contribute to differences in H. pylori infection and gastroduodenal diseases among races in the Malaysian population. This study was conducted to characterize the polymorphisms in H. pylori cagA and vacA in Malaysian population.
    Matched MeSH terms: Sequence Analysis, DNA
  19. Mohan S, Abdelwahab SI, Kamalidehghan B, Syam S, May KS, Harmal NS, et al.
    Phytomedicine, 2012 Aug 15;19(11):1007-15.
    PMID: 22739412 DOI: 10.1016/j.phymed.2012.05.012
    The plant Artocarpus obtusus is a tropical plant that belongs to the family Moraceae. In the present study a xanthone compound Pyranocycloartobiloxanthone A (PA) was isolated from this plant and the apoptosis mechanism was investigated. PA induced cytotoxicity was observed using MTT assay. High content screening (HCS) was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and cytochrome c release. Reactive oxygen species formation was investigated on treated cells by using fluorescent analysis. Human apoptosis proteome profiler assays were performed to investigate the mechanism of cell death. In addition mRNA levels of Bax and Bcl2 were also checked using RT-PCR. Caspase 3/7, 8 and 9 were measured for their induction while treatment. The involvement of NF-κB was analyzed using HCS assay. The results showed that PA possesses the characteristics of selectively inducing cell death of tumor cells as no inhibition was observed in non-tumorigenic cells even at 30 μg/ml. Treatment of MCF7 cells with PA induced apoptosis with cell death-transducing signals, that regulate the MMP by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol. The release of cytochrome c triggered the activation of caspases-9, then activates downstream executioner caspase-3/7 and consequently cleaved specific substrates leading to apoptotic changes. This form of apoptosis was found closely associated with the extrinsic pathway caspase (caspase-8) and inhibition of translocation of NF-κB from cytoplasm to nucleus. The results demonstrated that PA induced apoptosis of MCF7 cells through NF-κB and Bcl2/Bax signaling pathways with the involvement of caspases.
    Matched MeSH terms: Protein Array Analysis
  20. Zanaruddin SN, Saleh A, Yang YH, Hamid S, Mustafa WM, Khairul Bariah AA, et al.
    Hum Pathol, 2013 Mar;44(3):417-26.
    PMID: 23026198 DOI: 10.1016/j.humpath.2012.06.007
    The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC.
    Matched MeSH terms: Cluster Analysis
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