Displaying publications 1 - 20 of 127 in total

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  1. Zulkapli R, Abdul Razak F, Zain RB
    Integr Cancer Ther, 2017 09;16(3):414-425.
    PMID: 28818030 DOI: 10.1177/1534735416675950
    Cancers involving the oral cavity, head, and neck regions are often treated with cisplatin. In cancer therapy, the main target is to eliminate unwanted cancerous cells. However, reports on the nonselective nature of this drug have raised few concerns. Incorrect nutritional habits and lifestyle practices have been directly linked to cancer incidence. Nutrients with antioxidant activity inhibit cancer cells development, destroying them through oxidative stress and apoptosis. α-tocopherol, the potent antioxidant form of vitamin E is a known scavenger of free radicals. In vitro study exhibited effective antitumor activity of α-tocopherol on ORL-48 at 2.5 ± 0.42 µg/mL. Cisplatin exhibited stronger activity at 1.0 ± 0.15 µg/mL, but unlike α-tocopherol it exhibited cytotoxicity on normal human epidermal keratinocytes at very low concentration (<0.1 µg/mL). Despite the lower potency of α-tocopherol, signs of apoptosis such as the shrinkage of cells and appearance of apoptotic bodies were observed much earlier than cisplatin in time lapse microscopy. No apoptotic vesicles were formed with cisplatin, instead an increased population of cells in the holoclone form which may suggest different induction mechanisms between both agents. High accumulation of cells in the G0/G1 phase were observed through TUNEL and annexin V-biotin assays, while the exhibition of ultrastructural changes of the cellular structures verified the apoptotic mode of cell death by both agents. Both cisplatin and α-tocopherol displayed cell cycle arrest at the Sub G0 phase. α-tocopherol thus, showed potential as an antitumour agent for the treatment of oral cancer and merits further research.
  2. 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.
  3. Zanaruddin SN, Yee PS, Hor SY, Kong YH, Ghani WM, Mustafa WM, et al.
    PLoS One, 2013;8(11):e80229.
    PMID: 24224046 DOI: 10.1371/journal.pone.0080229
    OBJECTIVES: The frequency of common oncogenic mutations and TP53 was determined in Asian oral squamous cell carcinoma (OSCC).

    MATERIALS AND METHODS: The OncoCarta(™) panel v1.0 assay was used to characterize oncogenic mutations. In addition, exons 4-11 of the TP53 gene were sequenced. Statistical analyses were conducted to identify associations between mutations and selected clinico-pathological characteristics and risk habits.

    RESULTS: Oncogenic mutations were detected in PIK3CA (5.7%) and HRAS (2.4%). Mutations in TP53 were observed in 27.7% (31/112) of the OSCC specimens. Oncogenic mutations were found more frequently in non-smokers (p = 0.049) and TP53 truncating mutations were more common in patients with no risk habits (p = 0.019). Patients with mutations had worse overall survival compared to those with absence of mutations; and patients who harbored DNA binding domain (DBD) and L2/L3/LSH mutations showed a worse survival probability compared to those patients with wild type TP53. The majority of the oncogenic and TP53 mutations were G:C > A:T and A:T > G:C base transitions, regardless of the different risk habits.

    CONCLUSION: Hotspot oncogenic mutations which are frequently present in common solid tumors are exceedingly rare in OSCC. Despite differences in risk habit exposure, the mutation frequency of PIK3CA and HRAS in Asian OSCC were similar to that reported in OSCC among Caucasians, whereas TP53 mutations rates were significantly lower. The lack of actionable hotspot mutations argue strongly for the need to comprehensively characterize gene mutations associated with OSCC for the development of new diagnostic and therapeutic tools.

  4. Zain RB, Athirajan V, Ghani WM, Razak IA, Raja Latifah RJ, Ismail SM, et al.
    Cell Tissue Bank, 2013 Mar;14(1):45-52.
    PMID: 22373599 DOI: 10.1007/s10561-012-9298-0
    Identification of diagnostic markers for early detection and development of novel and therapeutic agents for effective patient management are the main motivation for cancer research. Biological specimens from large cohort and case-control studies which are crucial in providing successful research outcomes are often the limiting factor that hinders research efforts, especially in developing countries. Therefore, the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS) were established to systematically collect large number of samples with comprehensive sociodemographic, clinicopathological, management strategies, quality of life and associated patient follow-up data to facilitate oral cancer research in Malaysia. The MOCDTBS also promotes sharing among researchers and the development of a multidisciplinary research team. The following article aims to describe the process of setting-up and managing the MOCDTBS.
  5. Zain RB, Ghani WM, Razak IA, Latifah RJ, Samsuddin AR, Cheong SC, et al.
    Asian Pac J Cancer Prev, 2009 Jul-Sep;10(3):513-8.
    PMID: 19640201
    BACKGROUND: The rising burden of cancer in the developing world calls for a re-evaluation of the treatment strategies employed to improve patient management, early detection and understanding of the disease. There is thus an increasing demand for interdisciplinary research that integrates two or more disciplines of what may seemed to be highly unrelated and yet very much needed as strategies for success in research. This paper presents the processes and barriers faced in building partnerships in oral cancer research in a developing country.

    METHODS: A case study was undertaken in a developing country (Malaysia) to assess the strengths and weaknesses of the situation leading to the formation of a multidisciplinary research partnership in oral cancer. Following the formalization of the partnership, further evaluation was undertaken to identify measures that can assist in sustaining the partnership.

    RESULTS: The group identifies its strength as the existence of academia, research-intensive NGOs and good networking of clinicians via the existence of the government's network of healthcare provider system who are the policy makers. The major weaknesses identified are the competing interest between academia and NGOs to justify their existence due to the lack of funding sources and well trained human resources.

    CONCLUSIONS: With the growing partnership, the collaborative group recognizes the need to develop standard operating procedures (SOPs) and guidelines for the sharing and usage of resources in order to safeguard the interest of the original partners while also attending to the needs of the new partners.
  6. Zain RB
    Oral Oncol, 2001 Apr;37(3):205-10.
    PMID: 11287272
    This is an update on cultural and dietary risk factors for oral precancer and cancer. It is an overview on ethnic differences (where possible) and socio-cultural risk factors (tobacco/areca nut/betel quid, alcohol use and dietary factors) in relation to oral precancer and cancer. While studies were from Western countries, India and China, this update also attempts to include and highlight some studies conducted in the Asia-Pacific region.
  7. Zain RB
    J Oral Sci, 2000 Mar;42(1):15-9.
    PMID: 10808270
    One of the objectives of this short communication was to add to the literature on the prevalence of oral recurrent aphthous stomatitis (ORAS). This research is based on a total of 11,697 randomly selected Malaysian subjects with an age range of 25-115 years and a mean age of 44.5 +/- 13.9 years who were examined for oral mucosal lesions (ORAS). The prevalence of ORAS detected during the oral examination (average point prevalence) was found to be 0.5% (64 subjects). ORAS formed 5.7% of all lesions detected during the survey. The average point prevalence of ORAS was highest in the indigenous people of Sabah and Sarawak (1.2%), followed by the Chinese (0.7%), the Malays (0.5%) and the Indians (0.1%). This difference was statistically significant (p < 0.001). A review of the English literature on the prevalence of ORAS revealed different prevalence types used by different researchers, namely average point prevalence (APP), self reported life-time prevalence (SLP) and self reported two-year prevalence (STP). The other objective of this paper was to present the different types of prevalence that have been reported in the literature and to discuss the usefulness of such prevalence types in relation to using epidemiology in deriving certain possible etiological associations.
  8. Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Shrestha P, et al.
    J Oral Pathol Med, 1999 Jan;28(1):1-4.
    PMID: 9890449
    A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.
  9. Zain RB, Khoo SP, Yeo JF
    Singapore Dent J, 1995 Jul;20(1):8-10.
    PMID: 9582682
    A clinical analysis of 304 cases of pyogenic granuloma (excluding pregnancy tumour) were obtained from the clinical evaluations submitted by clinicians while sending specimens for biopsy. The average age of the patients with pyogenic granuloma was 28.9 years with a peak age incidence in the second decade. More female patients were affected and the lesions present mainly in the Chinese. The majority of the lesions were ulcerated and pedunculated. The lesions had a mean diameter of 10.8 mm with a mean lesion duration of 6.0 months. The gingiva was the prevalent site for these lesions with a greater number being located in the maxilla. The recurrence rate was found to be 14.1%.
  10. Zain RB, Ikeda N, Razak IA, Axéll T, Majid ZA, Gupta PC, et al.
    Community Dent Oral Epidemiol, 1997 Oct;25(5):377-83.
    PMID: 9355776
    The prevalence of oral mucosal lesions in Malaysia was determined by examining a representative sample of 11,707 subjects aged 25 years and above throughout the 14 states over a period of 5 months during 1993/1994. A two-stage stratified random sampling was undertaken. A predetermined number of enumeration blocks, the smallest population unit in the census publication, was selected from each state. With the selected enumeration block, a systematic sample of living quarters was chosen with a random start. The survey instrument included a questionnaire on sociodemographic characteristics and a clinical examination. The clinical examination was carried out by 16 specially trained dental public health officers and the diagnosis calibrated with a final concordance rate of 92%. The age in the sample ranged from 25 to 115 years with a mean of 44.5+/-14.0. The sample comprised 40.2% males and 59.8% females; 55.8% were Malays, 29.4% Chinese, 10.0% Indians and 1.2% other ethnic groups. Oral mucosal lesions were detected in 1131 (9.7%) subjects, 5 (0.04%) had oral cancer, 165 (1.4%) had lesions or conditions that may be precancerous (leukoplakia, erythroplakia, submucous fibrosis and lichen planus) and 187 (1.6%) had betel chewer's mucosa. The prevalence of oral precancer was highest amongst Indians (4.0%) and other Bumiputras (the indigenous people of Sabah and Sarawak) (2.5%) while the lowest prevalence was amongst the Chinese (0.5%).
  11. Zain RB, Sakamoto F, Shrestha P, Mori M
    Malays J Pathol, 1995 Jun;17(1):23-30.
    PMID: 8907001
    Proliferating cell nuclear antigen (PCNA) is a well known marker for cell proliferation. It tends to accumulate in the late G1 and S-phase of the cell cycle. A monoclonal antibody (MoAb) against PCNA is now available and it can react with paraffin-embedded specimens. In the present study, PCNA immunohistochemical staining of 36 cases of oral cancer specimens obtained from surgery were investigated. The results showed differing nuclear staining patterns for PCNA in normal, hyperplastic and dysplastic epithelium, early cancer and 3 levels of differentiation for squamous cell carcinoma of the oral cavity. It appears that PCNA can be a useful marker in delineating normal epithelium and hyperplastic epithelium from dysplasia in the oral cavity. The use of PCNA staining may further emphasize the conventional histopathological grading of well-differentiated, moderately-differentiated and poorly-differentiated oral squamous cell carcinoma but is still dependent on basic criteria as observed without immunostaining. PCNA expression for all grades of squamous cell carcinoma are present at the deep, infiltrative margins.
  12. Zain RB, Koh LS
    Dent J Malays, 1988 Nov;10(2):37-40.
    PMID: 3271126
    A study has been conducted on 198 employees of a steel-mill industry. These participants were examined for mucosal lesions in the oral cavity and including the commissures and vermillion borders of the lips. The prevalences of 16 types of lesions are reported.
  13. Zain RB
    PMID: 2609215
    The prevalence of clinically observed oral lichenoid reaction in 186 Malay army personnel using Fansidar for 9 weeks was found to be 4.8%. The prevalence was found to be 0.5% in 186 army personnel who had stopped using Fansidar for 2 months and 0% in 143 army personnel (control group) who had not used Fansidar for at least 4 months. The lesion showed a higher prevalence for the gingiva. There was no correlation between cigarette smoking and the occurrence of these lesions in each group.
  14. Zain RB, Roswati N, Ismail K
    Singapore Dent J, 1989 Dec;14(1):29-32.
    PMID: 2487471
    Many studies have been reported on radiographic lesion sizes of periapical lesions. However no studies have been reported on prevalences of subjective radiographic features in these lesions except for the early assumption that a periapical cyst usually exhibit a radiopaque cortex. This study is conducted to evaluate the prevalences of several subjective radiographic features of periapical cysts and granulomas in the hope to identify features that maybe suggestive of either diagnosis. The results showed that a regular (circular or semi-circular) radiographic outline is likely to be a periapical cyst while an irregular radiographic outline is not indicative of either a cyst or a granuloma. The association between the regular/irregular radiographic outline and the type of periapical lesion was found to be statistically significant (p less than 0.001). The associations of two other radiographic features and the type of periapical lesion were found to be just statistically significant (p less than 0.01). These features are the symmetry/asymmetry of the radiolucency in relation to the apex and the funnel-shaped/angular-shaped extension of the radiolucency. The widely accepted criteria that the possession of a radiopaque cortex surrounding the radiolucency can discriminate between a periapical cyst and granuloma cannot be statistically supported in this study.
  15. Zain RB, Razak IA
    Community Dent Oral Epidemiol, 1989 Jun;17(3):148-9.
    PMID: 2786793
    The association between cigarette smoking and the prevalence of oral mucosal lesions was examined in 495 Malaysian army personnel. No associations between cigarette smoking and recurrent aphthous ulcerations, pre-leukoplakia and frictional keratosis could be obtained in this study. Positive associations were found between cigarette smoking and leukoedema as well as denture stomatitis. There was a negative association between cigarette smoking and the presence of coated tongue.
  16. Zain RB, Fei YJ
    Oral Surg. Oral Med. Oral Pathol., 1990 Oct;70(4):466-70.
    PMID: 2120653
    Two hundred four cases of fibrous lesions of the gingiva were studied histologically for the presence of calcified tissue, the nature of the connective tissue, the type of keratinization, and the degree of epithelial thickness. Initially these lesions were subcategorized into four specific entities, namely fibrous epulis, fibroepithelial polyp, calcifying fibroblastic granuloma, and ossifying fibrous epulis. It was found that 46.5% of the lesions contained calcifications. The connective tissue was represented predominantly by either the collagenous type (50.5%) or the mixed (cellular and collagenous) type (44.6%). It was also found that 36% of the lesions were ulcerated, and, of these, 79.5% were associated with the cellular type of connective tissue and calcifications. In an attempt to subcategorize the fibrous lesions into specific entities, it was found that 32 cases (15.7%) had mixed features. This fact supports the suggestion that these lesions are stages in the spectrum of a single disease process and should collectively be termed fibroblastic gingival lesions. However, it is also suggested that the two terms, namely peripheral fibroma and fibrous epulis with and without ossification, should be retained whereas the usage of other terminologies should be avoided.
  17. Zain RB, Fei YJ
    Odontostomatol Trop, 1990 Sep;13(3):94-6.
    PMID: 2075149
    Peripheral fibroma/fibrous epulis accounts for the great majority of localised gingival swellings as was substantiated by various reports in the literature. A study was undertaken to investigate the clinical features of a series of 204 localised fibrous gingival swellings received by the Histopathology Laboratory, Department of Oral Surgery, National University of Singapore. The female patients were more affected than the male patients and the lesions occurred predominantly among the Chinese. The lesions were mainly pedunculated and most commonly occurred in anterior maxilla. The recurrence rate was about 10.3%. In conclusion the results obtained in this study were overall in agreement with those of other authors.
  18. Zain RB, Pateel DGS, Ramanathan A, Kallarakkal TG, Wong GR, Yang YH, et al.
    J Cancer Educ, 2020 Aug 21.
    PMID: 32821988 DOI: 10.1007/s13187-020-01814-1
    Early diagnosis of oral cancer results in less aggressive treatment and improves the quality of life and overall 5-year survival rate. Well-trained dental professionals can play a crucial role in the early detection of oral cancers. The present study aims to determine the effectiveness of the training program "OralDETECT", a spaced repetitive, test-enhanced learning tool with a corrective feedback mechanism for early detection of oral cancer. Thirty-two dentists and 259 dental students from three Malaysian dental schools were involved in this study. All participants were trained and calibrated to recognize oral potentially malignant disorders (OPMD) and oral cancer using "OralDETECT", which is comprised of a series of pre-test, lecture, post-tests and review sessions. The percentage of correct answers (scores) for each test given by the participants was calculated and analysed using a paired t test. It was found that the overall percentage of diagnostic accuracy for both dental professionals and student groups increased to above 80% from the pre-tests to the final post-tests. There was a significant improvement in overall scores between the pre-tests and all three post-tests for the dental professional groups and the student groups. The diagnostic accuracy for individual OPMD and lesions suspicious of oral cancer also increased to above 80% for both groups. The results of our study demonstrate that the "OralDETECT" is an efficient and effective competency tool which can be used to train dental professionals and students for the early detection of OPMD and oral cancer.
  19. Zain RB, Kallarakkal TG, Ramanathan A, Kim J, Tilakaratne WM, Takata T, et al.
    Asian Pac J Cancer Prev, 2016 01 09;17(9):4491.
    PMID: 27865210 DOI: 10.7314/APJCP.2016.17.(9).4491
    Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions
    including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous
    leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a
    viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or
    by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as
    verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary
    squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC)
    need to be further clarified for better understanding of their predictable biologic behavior and appropriate
    treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to
    the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous
    hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical
    features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a
    PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of
    the ‘First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral
    Cavity’ held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named
    ‘Exophytic Verrucous Hyperplasia’. Previously described clinical features of OVH such as the ‘blunt’ or ‘sharp’
    variants; and the ‘mass’ or ‘plaque’ variants can now collectively fall under this newly described entity. This paper
    discusses in detail the application of the standardized criteria guidelines of ‘Exophytic Verrucous Hyperplasia’
    as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool
    of OVH cases and facilitate a better understanding of OVH malignant potential.
  20. Yong ZW, Zaini ZM, Kallarakkal TG, Karen-Ng LP, Rahman ZA, Ismail SM, et al.
    Sci Rep, 2014;4:6073.
    PMID: 25123227 DOI: 10.1038/srep06073
    The clinical relevance of DNA copy number alterations in chromosome 8 were investigated in oral cancers. The copy numbers of 30 selected genes in 33 OSCC patients were detected using the multiplex ligation-dependent probe amplification (MLPA) technique. Amplifications of the EIF3E gene were found in 27.3% of the patients, MYC in 18.2%, RECQL4 in 15.2% and MYBL1 in 12.1% of patients. The most frequent gene losses found were the GATA4 gene (24.2%), FGFR1 gene (24.2%), MSRA (21.2) and CSGALNACT1 (12.1%). The co-amplification of EIF3E and RECQL4 was found in 9% of patients and showed significant association with alcohol drinkers. There was a significant association between the amplification of EIF3E gene with non-betel quid chewers and the negative lymph node status. EIF3E amplifications did not show prognostic significance on survival. Our results suggest that EIF3E may have a role in the carcinogenesis of OSCC in non-betel quid chewers.
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