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Fulltext Physical activity and body composition among cancer patients at Universiti Kebangsaan Malaysia Medical Center

Suhaina Sulaiman, Mohd Razif Shahril, Ahmad Zailani Hatta, Fuad Ismail

Malaysian Journal of Public Health Medicine, 2017;17(2):82-87.

Increasing physical activity level during and after treatment is recommended by the American Cancer Society because of the many benefits namely reducing fatigue and improves psychological distress which leads to an improvement in the quality of life. This study is aimed to compare physical activity level and body composition between oncology patients who are still undergoing treatment and those on medical follow-up. Patients were recruited based on convenience sampling from the Oncology Outpatient Clinics of Universiti Kebangsaan Malaysia Medical Center (UKMMC). Anthropometric measurements and body compositions were measured using calibrated tools while physical activity level were assessed using Global Physical Activity Questionnaire (GPAQ). Medical treatment history was obtained from patients medical records. A total of 53 patients (n=38 were undergoing treatment and n=15 was on follow-up) consisting of Malays (54.7%) and Chinese (45.3%) and with mean age of 55.3 ± 9.3 years. Most patients were previously diagnosed with ovarian cancer (39.6%) and colon cancer (18.9%) patients and they were at cancer stage III (18.8%). Body mass index (BMI) and percent fat mass were significantly different (p<0.05) between patients undergoing treatment (22.8 ± 2.7 kg/m2, 28.7 ± 7.2%) and on follow-up (26.2 ± 5.5 kg/m2, 37.1 ± 11.9%). Majority of the patients undergoing treatment were categorized under low physical activity compared to those on follow-up (p<0.05). Physical activity level measured as METS-minutes/week is also found to be significantly different (p<0.05) between patients on treatment and follow-up. As a conclusion, cancer patients undergoing treatment have low physical activity, with lower BMI and fat mass compared to those on follow-up. This is consistent with their nature of living where during treatment the patients will resting while coping with side effects of treatments.
Fulltext Villoglandular papillary adenocarcinoma of the uterine cervix with lymph node metastasis - a case report and review of the literature

Geok, Chin Tan, Mohd Sidik Shiran, Manickam Swaminathan, Ali Siti Aishah, M.D., Poo, Ling Ong, Mohd Dali Ahmad Zailani Hatta

Medicine & Health, 2006;1(1):85-90.
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Villoglandular papillary adenocarcinoma was first described by Young and Scully in 1989 as a distinct entity with the histological features of exophytic growth proliferation, villous and papillary architecture and mild to moderate nuclear atypia. We report one case of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix with lymph node metastasis and reviewed the clinicopathological features of six other cases reported in the literature. Our patient is the seventh similar reported cases. They ranged in age from 29 to 54 (mean, 41) years. Five had lymphovascular invasion. All except our patient were treated with radical hysterectomy and radiotherapy. She was followed-up for 7 months and unfortunately died due to chest infection.
Potential molecular signatures in epithelial ovarian cancer by genome wide expression profiling

Wong YL, Dali AZ, Mohamed Rose I, Jamal R, Mokhtar NM

Asia Pac J Clin Oncol, 2016 Jun;12(2):e259-68.
PMID: 24673814 DOI: 10.1111/ajco.12182

Ovarian cancer is the deadliest of all gynecologic cancers because of its late diagnosis and poor treatment outcomes. This study aimed to identify potential molecular signatures associated with biological processes that are implicated in epithelial ovarian cancer (EOC).
Gelsolin and ceruloplasmin as potential predictive biomarkers for cervical cancer by 2D-DIGE proteomics analysis

Lokamani I, Looi ML, Md Ali SA, Mohd Dali AZ, Ahmad Annuar MA, Jamal R

Pathol Oncol Res, 2014 Jan;20(1):119-29.
PMID: 23925487 DOI: 10.1007/s12253-013-9670-9

This study aimed to identify candidate proteins which may serve as potential biological markers for cervical cancer using 2D-DIGE. Serum samples of controls, patients with cervical intraepithelial neoplasia grade 3 (CIN 3), squamous cell carcinoma of early (SCC I and II) and late (SCC III and IV) stage were subjected to 2D-DIGE. Differentially expressed spots were identified by tandem mass spectrometry. Validation of candidate proteins in serum and tissue samples were then performed by ELISA and immunohistochemistry (IHC) analysis respectively. A total of 20 differentially expressed proteins were identified. These proteins were found to play key roles in the apoptosis pathway, complement system, various types of transportation such as hormones, fatty acids, lipid, vitamin E and drug transportation, coagulation cascade, regulation of iron and immunologic response. Based on their functional relevancy to the progression of various cancers, 4 proteins namely the complement factor H, CD5-like antigen, gelsolin and ceruloplasmin were chosen for further validation using ELISA. Biological network analysis showed that ceruloplasmin and gelsolin are closely interacted with the oncogene NF-κb. These two proteins were further validated using the IHC. Gelsolin and ceruloplasmin may serve as potential predictive biomarkers for the progression of high grade lesions.
Fulltext National HPV immunisation programme: knowledge and acceptance of mothers attending an obstetrics clinic at a teaching hospital, Kuala Lumpur

Ezat SW, Hod R, Mustafa J, Mohd Dali AZ, Sulaiman AS, Azman A

Asian Pac J Cancer Prev, 2013;14(5):2991-9.
PMID: 23803068

BACKGROUND: Introduction of the HPV vaccine is a forefront primary prevention method in reducing the incidence of carcinogenic human papillomavirus (HPV) and cervical cancer. The Malaysia government has implemented the National HPV immunisation programme since 2010, supplying HPV vaccine free to targeted 13 year olds. This study aimed to explore the level of knowledge among mothers on cervical cancer, HPV, HPV vaccine and National HPV (NHPV) immunisation programme since its' implementation. It also assessed acceptance of mothers towards HPV vaccine being administered to their daughter, son or themselves.
MATERIALS AND METHODS: A cross sectional study was conducted on 155 respondents using self-administered questionnaires; conducted in December 2012 at the Obstetrics and Gynaecology Clinic in a teaching hospital in Kuala Lumpur. Respondents were selected using a multistage sampling technique.
RESULTS: A response rate of 100% was obtained. Overall, 51.0% of mothers had good knowledge, with 55% having good knowledge of cervical cancer, 54.2% for both HPV and the National HPV immunisation programme and 51.0% for the HPV vaccine. Regression analyses showed that ethnicity was associated with knowledge on cervical cancer (p=0.003) while education was associated with knowledge on HPV (p=0.049). Three factors are associated with knowledge of the National HPV immunisation programme; ethnicity (p=0.017), mothers' education (p=0.0005) and number of children (p=0.020). The acceptance of HPV vaccine to be administered among daughter was the highest at 87.1%, followed by for mothers themselves at 73.5%, and the least is for sons 62.6%.
CONCLUSIONS: This study found that the overall level of knowledge was moderate. Adequate information on cervical cancer, HPV, HPV vaccination and the National HPV immunisation programme should be provided to mothers in order to increase acceptance of the HPV vaccine which can reduce the disease burden in the future.
Study site: O&G clinic, Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
Fulltext Molecular markers associated with nonepithelial ovarian cancer in formalin-fixed, paraffin-embedded specimens by genome wide expression profiling

Vui-Kee K, Mohd Dali AZ, Mohamed Rose I, Ghazali R, Jamal R, Mokhtar NM

Kaohsiung J. Med. Sci., 2012 May;28(5):243-50.
PMID: 22531302 DOI: 10.1016/j.kjms.2011.11.007

Nonepithelial ovarian cancer (NEOC) is a rare cancer that is often misdiagnosed as other malignant tumors. Research on this cancer using fresh tissues is nearly impossible because of its limited number of samples within a limited time provided. The study is to identify potential genes and their molecular pathways related to NEOC using formalin-fixed paraffin embedded samples. Total RNA was extracted from eight archived NEOCs and seven normal ovaries. The RNA samples with RNA integrity number >2.0, purity >1.7 and cycle count value <28 cycles were hybridized to the Illumina Whole-Genome DASL assay (cDNA-mediated annealing, selection, extension, and ligation). We analyzed the results using the GeneSpring GX11.0 and FlexArray software to determine the differentially expressed genes. Microarray results were validated using an immunohistochemistry method. Statistical analysis identified 804 differentially expressed genes with 443 and 361 genes as overexpressed and underexpressed in cancer, respectively. Consistent findings were documented for the overexpression of eukaryotic translation elongation factor 1 alpha 1, E2F transcription factor 2, and fibroblast growth factor receptor 3, except for the down-regulated gene, early growth response 1 (EGR1). The immunopositivity staining for EGR1 was found in the majority of cancer tissues. This finding suggested that the mRNA level of a transcript did not always match with the protein expression in tissues. The current gene profile can be the platform for further exploration of the molecular mechanism of NEOC.
Clusterin as a potential marker in distinguishing cervical neoplasia

Lokamani I, Looi ML, Ali SA, Dali AZ, Jamal R

Anal. Quant. Cytol. Histol., 2011 Aug;33(4):223-8.
PMID: 21980627

To assess the immunoexpression of clusterin (CLU) in the progression of cervical neoplasia.
Gene expression profiling and cancer-related pathways in type I endometrial carcinoma

Saghir FS, Rose IM, Dali AZ, Shamsuddin Z, Jamal AR, Mokhtar NM

Int. J. Gynecol. Cancer, 2010 Jul;20(5):724-31.
PMID: 20973258

INTRODUCTION: Malignant transformation of type I endometrium involves alteration in gene expression with subsequent uncontrolled proliferation of altered cells.
OBJECTIVE: The main objective of the present study was to identify the cancer-related genes and gene pathways in the endometrium of healthy and cancer patients.
MATERIALS AND METHODS: Thirty endometrial tissues from healthy and type I EC patients were subjected to total RNA isolation. The RNA samples with good integrity number were hybridized to a new version of Affymetrix Human Genome GeneChip 1.0 ST array. We analyzed the results using the GeneSpring 9.0 GX and the Pathway Studio 6.1 software. For validation assay, quantitative real-time polymerase chain reaction was used to analyze 4 selected genes in normal and EC tissue.
RESULTS: Of the 28,869 genes profiled, we identified 621 differentially expressed genes (2-fold) in the normal tissue and the tumor. Among these genes, 146 were up-regulated and 476 were down-regulated in the tumor as compared with the normal tissue (P < 0.001). Up-regulated genes included the v-erb-a erythroblastic leukemia viral oncogene homolog 3 (ErbB3), ErbB4, E74-like factor 3 (ELF3), and chemokine ligand 17 (CXCL17). The down-regulated genes included signal transducer and activator transcription 5B (STAT5b), transforming growth factor A receptor III (TGFA3), caveolin 1 (CAV1), and protein kinase C alpha (PKCA). The gene set enrichment analysis showed 10 significant gene sets with related genes (P < 0.05). The quantitative polymerase chain reaction of 4 selected genes using similar RNA confirmed the microarray results (P < 0.05).
CONCLUSIONS: Identification of molecular pathways with their genes related to type I EC contribute to the understanding of pathophysiology of this cancer, probably leading to identifying potential biomarkers of the cancer.
Expression of p53, bcl-2 and Ki-67 in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix

Looi ML, Dali AZ, Ali SA, Ngah WZ, Yusof YA

Anal. Quant. Cytol. Histol., 2008 Apr;30(2):63-70.
PMID: 18561741

To assess the expression of p53, bcl-2 and Ki-67 in the progression of cervical neoplasia.
Oxidative damage and antioxidant status in patients with cervical intraepithelial neoplasia and carcinoma of the cervix

Looi ML, Mohd Dali AZ, Md Ali SA, Wan Ngah WZ, Mohd Yusof YA

Eur J Cancer Prev, 2008 Nov;17(6):555-60.
PMID: 18941377 DOI: 10.1097/CEJ.0b013e328305a10b

Free radicals that induced lipid peroxidation and DNA damage have been implicated in many diseases including cancer. Cellular antioxidant defense plays an important role in neoplastic disease to counteract oxidative damage. This study aims to investigate the status of oxidative damage by measuring plasma malondialdehyde (MDA) level and urinary 8-hydroxydeoxyguanosine (8-OHdG), and the level of antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase in patients with cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC) of the cervix. Urinary 8-OHdG was measured by an enzyme-linked immunosorbent assay kit. MDA and antioxidant enzyme activities were determined by high-performance liquid chromatography and spectrophotometry, respectively. Eighty patients with CIN and SCC of the cervix were recruited and compared with normal controls. Urinary 8-OHdG/creatinine ratio did not show any significant changes in any disease status studied as compared with controls (P=0.803). Plasma MDA was found to be increased in CIN and SCC patients when compared with controls (P=0.002). Glutathione peroxidase activity was increased (P=0.0001) whereas superoxide dismutase and catalase activity was decreased (P=0.019 and 0.0001, respectively) in both CIN and SCC patients when compared with controls. Urinary 8-OHdG may not be a good marker for enhanced oxidative stress in cervical cancer. Oxidative damage as demonstrated by the level of MDA is markedly increased in CIN and SCC patients with changes of enzymatic antioxidants observed.
Fulltext Molecular characterization of serous ovarian carcinoma using a multigene next generation sequencing cancer panel approach

Ab Mutalib NS, Syafruddin SE, Md Zain RR, Mohd Dali AZ, Mohd Yunos RI, Saidin S, et al.

BMC Res Notes, 2014;7:805.
PMID: 25404506 DOI: 10.1186/1756-0500-7-805

High grade serous ovarian cancer is one of the poorly characterized malignancies. This study aimed to elucidate the mutational events in Malaysian patients with high grade serous ovarian cancer by performing targeted sequencing on 50 cancer hotspot genes.
Plasma proteome analysis of cervical intraepithelial neoplasia and cervical squamous cell carcinoma

Looi ML, Karsani SA, Rahman MA, Dali AZ, Ali SA, Ngah WZ, et al.

J Biosci, 2009 Dec;34(6):917-25.
PMID: 20093745

Although cervical cancer is preventable with early detection, it remains the second most common malignancy among women. An understanding of how proteins change in their expression during a particular diseased state such as cervical cancer will contribute to an understanding of how the disease develops and progresses. Potentially, it may also lead to the ability to predict the occurrence of the disease. With this in mind, we aimed to identify differentially expressed proteins in the plasma of cervical cancer patients. Plasma from control, cervical intraepithelial neoplasia (CIN) grade 3 and squamous cell carcinoma (SCC) stage IV subjects was resolved by two-dimensional gel electrophoresis and the resulting proteome profiles compared. Differentially expressed protein spots were then identified by mass spectrometry. Eighteen proteins were found to be differentially expressed in the plasma of CIN 3 and SCC stage IV samples when compared with that of controls. Competitive ELISA further validated the expression of cytokeratin 19 and tetranectin. Functional analyses of these differentially expressed proteins will provide further insight into their potential role(s) in cervical cancer-specific monitoring and therapeutics.
Fulltext Targeted Next-Generation Sequencing Identifies Actionable Targets in Estrogen Receptor Positive and Estrogen Receptor Negative Endometriod Endometrial Cancer

Suhaimi SS, Ab Mutalib NS, Khor SS, Zain RRM, Syafruddin SE, Abu N, et al.

Front Pharmacol, 2018;9:750.
PMID: 30057548 DOI: 10.3389/fphar.2018.00750

Endometrioid endometrial cancer (EEC) is the commonest form of endometrial cancer and can be divided into estrogen receptor (ER) positive and negative subtypes. The mutational profiles of EEC have been shown to aid in tailoring treatment; however, little is known about the differences between the gene mutation profiles between these two subtypes. This study aims to investigate the gene mutation profile in ER positive and negative EEC, and to further elucidate the role of WHSC1 mutations in this cancer. EEC and normal endometrial tissues were obtained from 29 patients and subjected to next-generation sequencing (NGS) using Ion Ampliseq Comprehensive Cancer PanelTM targeting 409 cancer related. A total of 741 non-synonymous alterations were identified from 272 genes in ER positive subtype while 448 non-synonymous variants were identified from 221 genes in ER negative subtype. PTEN is the most frequently altered gene in ER positive subtype (64%, 7/11) while ARID1A is the most frequently altered gene in ER negative subtype (50%, 4/8). We also identified alterations in ERRB3 (36%, 4/11), GNAS (36%, 4/11), and WHSC1 (27%, 3/11) in the ER positive subtype. WHSC1 R1126H and L1268P were shown to significantly increase cell viability, proliferation, migration, and survival. In addition, reduction in ER expression sensitized EEC-1 cell with WHSC1 L1268P mutant to Fulvestrant treatment. We revealed the mutational spectra of ER positive and ER negative EEC that could lead to better understanding of the biological mechanisms of endometrial cancer and may ultimately result in improvement of treatment options and patient prognosis.
Does palm oil vitamin E reduce the risk of pregnancy induced hypertension?

Mahdy ZA, Siraj HH, Khaza'ai H, Mutalib MS, Azwar MH, Wahab MA, et al.

Acta Medica (Hradec Kralove), 2013;56(3):104-9.
PMID: 24592747

In view of the high anti-oxidative potential oftocotrienol, the role of the tocotrienol-rich fraction (TRF) of palm oil in preventing pregnancy induced hypertension (PIH) was explored in a randomized double-blind placebo-controlled clinical trial in an urban teaching hospital. Healthy primigravidae were randomized to receive either oral TRF 100 mg daily or placebo, from early second trimester until delivery. Out of 299 women, 151 were randomized into the TRF arm and 148 into the placebo arm. A total of 15 (5.0%) developed PIH. Although there was no statistically significant difference in the incidence of PIH (4/151 or 2.6% in the TRF arm vs. 11/148 or 7.4% in the placebo arm, p = 0.058) between the two arms, there was a tendency towards a lower incidence of PIH in the TRF arm compared to the placebo arm. With TRF supplementation, the relative risk (RR) of PIH was 0.36 (95% CI 0.12-1.09). In conclusion, although TRF from palm oil does not statistically significantly reduce the risk of development of PIH in the population studied, the 64% reduction in incidence of PIH is substantial. The findings warrant further clinical trials, particularly in high risk populations.

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