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Association of The IDH1 C.395G>A (R132H) Mutation with Histological Type in Malay Brain Tumors

Mohamed Yusoff AA, Zulfakhar FN, Sul’ain MD, Idris Z, Abdullah JM

Asian Pac J Cancer Prev, 2016 12 01;17(12):5195-5201.
PMID: 28125199

Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.
Artificial Light at Night and Cancer: Global Study

Al-Naggar RA, Anil Sh

Asian Pac J Cancer Prev, 2016 10 01;17(10):4661-4664.
PMID: 27892680

Background: Artificial light at night (ALAN) has been linked to increased risk of cancers in body sites like the breast
and colorectum. However exposure of ALAN as an environmental risk factor and its relation to cancers in humans has
never been studied in detail. Objective: To explore the association of ALAN with all forms of cancers in 158 countries.
Materials and Methods: An ecological study encompassing global data was conducted from January to June 2015,
with age-standardized rates (ASR) of cancers as the outcome measure. ALAN, in the protected areas, as the exposure
variable, was measured with reference to the Protected Area Light Pollution Indicator (PALI) and the Protected Area
Human Influence Indicator (PAHI). Pearson’s correlations were calculated for PALI and PAHI with ASR of cancers for
158 countries, adjusted for country populations, electricity consumption, air pollution, and total area covered by forest.
Stratified analysis was conducted according to the country income levels. Linear regression was applied to measure the
variation in cancers explained by PALI and PAHI. Results: PALI and PAHI were positively associated with ASR of all
forms of cancer, and also the four most common cancers (p < 0.05). These positive correlations remained statistically
significant for PAHI with all forms of cancer, lung, breast, and colorectal cancer after adjusting for confounders. Positive
associations of PALI and PAHI with cancers varied with income level of the individual countries. Variation in all forms
of cancers, and the four most common cancers explained by PALI and PAHI, ranged from 3.3 – 35.5%. Conclusion:
Artificial light at night is significantly correlated for all forms of cancer as well as lung, breast, colorectal, and prostate
cancers individually. Immediate measures should be taken to limit artificial light at night in the main cities around the
world and also inside houses.
Fulltext Exophytic Verrucous Hyperplasia of the Oral Cavity – Application of Standardized Criteria for Diagnosis from a Consensus Report

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.
Cost Analysis of Using a Closed-System Transfer Device (CSTD) for Antineoplastic Drug preparation in a Malaysian Government-Funded Hospital

Chan HK, Lim YM

Asian Pac J Cancer Prev, 2016 11 01;17(11):4951-4957.
PMID: 28032722

Background: Apart from reducing occupational exposure to cytotoxic hazards, the PhaSeal® closed-system transfer device (CSTD) can extend the beyond-use dates (BUDs) of unfinished vials of antineoplastic drugs for up to 168 hours (seven days). In this study, the total material cost incurred by its use in a Malaysian government-funded hospital was calculated. Methods: A list of vial stability following initial needle punctures of 29 commonly-used antineoplastic drugs was compiled. The amount of the materials used, including drugs, infusion bottles, the PhaSeal® CSTD and other consumables, was recorded on a daily basis for three months in 2015. The total cost was calculated based on the actual acquisition costs, and was compared with that of a hypothetical scenario, whereby conventional syringe-needle sets were used for the same amounts of preparations. Results: The use of the PhaSeal® CSTD incurred a cost of MYR 383,634.52 (USD 92,072.28) in three months, representing an average of MYR 170.5 (USD 40.92) per preparation or an estimated annual cost of MYR 1,534,538.08 (USD 368,289.14). Compared with conventional syringe-needle approach, it is estimated to lead to an additional spending of MYR 148,627.68 (USD 35,670.64) yearly. Conclusion: Although there was a reduction of drug wastage achieved by extending BUDs of unfinished vials using the PhaSeal® CSTD, cost saving was not observed, likely attributable to the wide use of lower-priced generic drugs in Malaysia. Future studies should further evaluate the possibility of cost saving, especially in health settings where branded and high-cost antineoplastic drugs are more commonly used.
Anti-Proliferative Effects of Dendrophthoe pentandra Methanol Extract on BCR/ABL-Positive and Imatinib-Resistant Leukemia Cell Lines

Zamani A, Mat Jusoh SA, Al-Jamal HA, Sul'ain MD, Johan MF

Asian Pac J Cancer Prev, 2016 11 01;17(11):4857-4861.
PMID: 28030911

Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R (IC50= 192 μg/mL) compared to K562 (500 μg/ mL) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.
Fulltext Potential role of E4 protein in human papillomavirus screening: a review

Yajid AI, Zakariah MA, Mat Zin AA, Othman NH

Asian Pac J Cancer Prev, 2017 02 01;18(2):315-319.
PMID: 28345325

In 2006, cervical cancer was reported as the second most common cancer in women of Malaysia. This type of cancer has been shown to correlate with persistent high risk human papillomavirus (HPV) infection. Although HPV is well known to induce cervical cancer, knowledge of pathways that link the latent stage of the viral replication cycle to precancerous and cancerous stages remains incomplete. However, it is interesting to note that the virus can be isolated from tissues ranging from normal to low-grade squamous intraepithelial lesions as well as high-grade intraepithelial lesions (HSILs), thus prompting scientists to develop HPV detection methods for screening. Detection of HPV using viral proteins such as L1 and E1 is proposed to be very useful in assisting the management of high risk infection and cervical cancer. These tests however can lead to false positive results, largely due to the exisstence of asymptomatic or transient HPV infections within any given individual. Somes observation indicate that use of HPV proteins such as E6 and E7 might lead to false positive results. However, one particular HPV protein, E4 shows potential as an accurate marker of the tissue state following HPV infection. E4 expression has been shown to correlate with the levels of HPV DNA incorporation by the host. Thus, it is possible that E4 could serve as a useful marker to define stages of viral carcinogenesis.
Comparative Cost-Effectiveness Analysis of Two Different Two-Dose Human Papillomavirus Vaccines in Malaysia

Van Kriekinge G, Sohn WY, Aljunid SM, Soon R, Yong CM, Chen J, et al.

Asian Pac J Cancer Prev, 2018 Apr 25;19(4):933-940.
PMID: 29693347

Purpose: To comparatively evaluate the results of a 2-dose human papillomavirus (HPV) vaccination programme
with the AS04-adjuvanted HPV16/18 vaccine (AS04-HPV-16/18v) or HPV-6/11/16/18 vaccine (4vHPVv), in addition
to cervical cancer (CC) screening, in Malaysia. Methods: A lifetime Markov model replicating the natural history of
HPV in 13-year-old girls was adapted to Malaysia to assess the impact of vaccination on pre-cancerous lesions, genital
warts and CC cases, CC deaths, quality-adjusted life years (QALYs), and costs from the perspective of the Malaysian
Ministry of Health. Vaccine effectiveness was based on efficacy and HPV type distribution. Both vaccines were assumed
to have equal efficacy against vaccine-type HPV but differed for protection against non-vaccine types. Vaccine price
parity was used and health and cost outcomes were discounted at 3%/annum. Sensitivity analyses tested the robustness
of the results. Results: The model predicted that AS04-HPV-16/18v would result in 361 fewer CC cases and 115 fewer
CC deaths than 4vHPVv, whereas 4vHPVv averted 4,241 cases of genital warts over the cohort’s lifetime. Discounted
total costs showed savings of 18.50 million Malaysian Ringgits and 246 QALYs in favour of AS04-HPV-16/18v. In
one-way sensitivity analyses, the discount rate was the most influential variable for costs and QALYs, but AS04-HPV-
16/18v remained dominant throughout. A two-way sensitivity analysis to assess the longevity of cross-protection for both
vaccines confirmed the base-case. Conclusions: In Malaysia, the use of AS04-HPV-16/18v, in addition to screening,
was modelled to be dominant over 4vHPVv, with greater estimated CC benefits and lower costs.
Clausenidin Induces Caspase 8-Dependent Apoptosis and Suppresses Production of VEGF in Liver Cancer Cells

Waziri PM, Abdullah R, Rosli R, Omar AR, Abdul AB, Kassim NK, et al.

Asian Pac J Cancer Prev, 2018 Apr 25;19(4):917-922.
PMID: 29693341

Clausena excavata Burm f. is used by traditional healers to treat cancer patients in South East Asia. The use of the
plant and its compounds is based on Asian folklore with little or no scientific evidence supporting the therapeutic efficacy
The current study aimed to determine the effect of pure clausenidin isolated from C. excavata on caspase-8-induced cell
death as well as angiogenesis in the HepG2 hepatocellular carcinoma cell line. Caspase-8 and extrinsic death receptor
protein expression was determined using spectrophotometry and protein profile arrays, respectively. Ultrastructural
analysis of clausenidin-treated cells was conducted using transmission electron microscopy. In addition, anti-angiogenic
effects of clausenidin were investigated by Western blot analysis. Clausenidin significantly (p<0.05) increased the
activity of caspase-8 and expression of protein components of the death inducing signaling complex (DISC) in HepG2
cells. Ultrastructural analysis of the clausenidin-treated HepG2 cells revealed morphological abnormalities typical of
apoptosis. Furthermore, clausenidin significantly (p<0.05) decreased the expression of vascular endothelial growth
factor (VEGF). Therefore, clausenidin is a potential anti-angiogenic agent which may induce apoptosis of hepatocellular
carcinoma cells.
Prevalence and Pattern of Antibiotic Resistant Strains of Helicobacter Pylori Infection in ASEAN

Vilaichone RK, Quach DT, Yamaoka Y, Sugano K, Mahachai V

Asian Pac J Cancer Prev, 2018 May 26;19(5):1411-1413.
PMID: 29802708

Objective: Antibiotic resistance has significantly impact on eradication rates for H. pylori infection and remains
important cause of treatment failure worldwide including ASEAN countries. The aim of this study was to survey
the prevalence and antibiotic resistant pattern of H. pylori infection in ASEAN. Methods: This study was a survey among
26 experts from 9 ASEAN countries including Thailand, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines,
Singapore and Vietnam whom attended a meeting to develop the ASEAN consensus on H. pylori management in Bangkok
in November 2015. A questionnaire was sent to each member of the consensus meeting. The detail of the questionnaire
included information about prevalence of H. pylori infection, facilities to perform H. pylori culture, molecular testing
for antibiotic resistance and antibiotic resistance rate in their countries. Results: H. pylori infection remain common
in ASEAN ranging from 20% in Malaysia, 21-54% in Thailand and 69% in Myanmar. Most of ASEAN countries
can perform H. pylori cultures and antibiotic susceptibility tests except Laos and Cambodia. In ASEAN countries,
metronidazole resistant H pylori is quite common whereas amoxicillin resistance remain rare. Clarithromycin resistance
results in a significant decrease in H. pylori eradication rate with clarithromycin-containing regimens. The prevalence of
clarithromycin resistance varies in ASEAN countries being high in Vietnam (30%) and Cambodia (43%), moderate to high
in Singapore (17%) and low in Malaysia (6.8%), Philippine (2%) and Myanmar (0%). In Thailand, clarithromycin
resistance tends to higher in large cities (14%) than in rural areas (~3.7%). Conclusion: ASEAN countries should
develop a standard protocol for regular susceptibility testing of H. pylori so that clinicians would be better able to
choose reliably effective empiric therapies. The wide range of antibiotic resistance in ASEAN countries suggests that
the preferred first line regimen should be depend on the local antibiotic resistance other than single recommendation.
Fulltext Factors affecting uptake of cervical cancer screening among African women in Klang Valley, Malaysia

Nwabichie CC, Manaf RA, Ismail SB

Asian Pac J Cancer Prev, 2018 Mar 27;19(3):825-831.
PMID: 29582641

Introduction: Cervical cancer is a health concern among women worldwide, presently ranking as the second to fourth common cancer type among women in different parts of the world. Human papillomaviruses (HPV) 16 and 18 are the main causative agents of cervical cancer. However, prevention is possible with early and regular cervical cancer screening.
Objective: This study aimed to identify the cervical cancer screening practices and factors affecting the screening status of African immigrant women attending selected church services in Klang Valley, Malaysia.
Methodology: A cross-sectional study among 320 randomly selected respondents between ages 18-69 was conducted in three different churches with high numbers of African participants. A self-administered questionnaire was distributed among the respondents. To ensure a good understanding, the questionnaire was written and self-explained in English language, because English is the general spoken language among the study population. Three levels of analysis were conducted using SPSS 21, involving descriptive analysis, chi square and multiple logistic regression.
Results: The response rate was 98.2%, the majority (68.1%) of the respondents being aged 31-50 years and married. The prevalence of screening among the respondents over the past 3 years was 27.2%. Using a p-value of 0.05 as the significance level, the final model showed that marital status (p=0.004), knowledge (p=0.035), perceived barriers (p=0.003), and having a regular health care provider (p<0.001) were the only significant predicting factors of uptake of cervical screening among African immigrant women in Klang Valley, Malaysia.
Conclusion: The findings revealed that the uptake of cervical cancer screening among the African women was very low. Marital status, knowledge, perceived barriers and having a regular health care provider were the predictive factors. Specific awareness programs to increase uptake should be designed and implemented by the relevant authorities.
Understanding and Challenges in Taking Tyrosine Kinase Inhibitors among Malaysian Chronic Myeloid Leukemia Patients: A Qualitative Study

Lim YM, Eng WL, Chan HK

Asian Pac J Cancer Prev, 2017 07 27;18(7):1925-1930.
PMID: 28749622

Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has long been delivered under the
Malaysian Patient Assistance Program (MYPAP), but research on identifying factors contributing to non-adherence to
tyrosine kinase inhibitors (TKIs) is still limited. The current study explored understanding and challenges of Malaysian
CML patients in taking imatinib and nilotinib. Methods: Semi-structured, face-to-face interviews were conducted
with 13 CML patients receiving treatment at a public tertiary care center, and were analyzed using the content analysis
approach. Results: The patients generally demonstrated inadequate knowledge, particularly of the natural history and
staging of CML, the function of TKIs, and the methods used for monitoring the effectiveness of treatment. A number of
them also had experiences of withholding, skipping or altering the treatment, mainly due to the life-disturbing adverse
drug effects (ADRs), forgetfulness, and religious and social issues. Besides, most of them were found having limited
skills in managing the ADRs, and not using prompts as reminders to take the medications. Furthermore, even though
nilotinib was generally perceived as better tolerated as compared with imatinib, the inconvenience caused by the need
to take it twice daily and on an empty stomach was constantly highlighted by the patients. Conclusion: While TKIs
are widely used for CML treatment in Malaysia, the findings have revealed a lack of patient education and awareness,
which warrants an integrated plan to reinforce medication adherence.
Serum Procalcitonin Predicts Anastomotic Leaks in Colorectal Surgery

Hayati F, Mohd Azman ZA, Nasuruddin DN, Mazlan L, Zakaria AD, Sagap I

Asian Pac J Cancer Prev, 2017 07 27;18(7):1821-1825.
PMID: 28749112

Background: Anastomotic leaks in colorectal surgery results in a high morbidity and mortality rate. Serum procalcitonin levels is known as a sensitive and specific marker of sepsis and could be use as a marker for early detection of a leak allowing early intervention. It may help a clinician decide to perform a CT scan even earlier especially when the diagnosis of a leak is uncertain. The aim of this study is to determine whether serum procalcitonin is a good predictor of anastomotic leak in colorectal surgery. Methodology: Between July 2014 until October 2015, 70 patients undergoing colorectal surgery were prospectively analyzed in a single-center tertiary teaching hospital. Demographic and surgical data were obtained. Serum procalcitonin was taken before surgery and at day 3 (72 hours) postoperatively. During the postoperative period, the patients were observed in the ward for features of anastomotic leak and if present, it was managed accordingly. The primary outcome was to prospectively determine an association between serum procalcitonin levels and an anastomotic leak in patients who underwent colorectal surgery with a primary anastomosis. Result: The rate of anastomotic leak was 4.5% (3 patients) with a mortality rate of 4.3% (3 patients). A rise in serum procalcitonin was statistically significant among patients with anastomotic leak. The optimal procalcitonin cut-off level at postoperative day 3 was 5.27 ng/mL, resulting in 100% sensitivity, 85% specificity, 23% positive predictive value and 100% negative predictive value. Nevertheless, none of the variables showed statistical significance with an anastomotic leak. Conclusion: Procalcitonin is a reliable biochemical marker to help diagnose anastomotic leak in colorectal surgery. Our study has shown that a level of 5 times beyond normal is statistically significant and a value of more than 5.27 ng/mL is confirmatory of a leak.
Radiation Exposure in Patients with Inflammatory Bowel Disease: a Fourteen-Year Review at a Tertiary Care Centre in Malaysia

Naidu J, Wong Zh, Palaniappan Sh, Ngiu ChS, Yaacob NY, Abdul Hamid H, et al.

Asian Pac J Cancer Prev, 2017 04 01;18(4):933-939.
PMID: 28545190

Background and Aims: Patients with inflammatory bowel disease (IBD) are subjected to a large amount of ionizing
radiation during the course of their illness. This may increase their risk of malignancy to a greater level than that due
to the disease itself. In Caucasian patients with Crohn’s disease, this has been well documented and recommendations
are in place to avoid high radiation imaging protocols. However, there are limited data available on radiation exposure
in Asian IBD patients.We therefore sought to identify total radiation exposure and any differences between ethnically
diverse ulcerative colitis (UC) and Crohn’s disease (CD) patients at our centre along with determining factors that may
contribute to any variation. Methods: The cumulative effective dose (CED) was calculated retrospectively from 2000
to 2014 using data from our online radiology database and patients’ medical records. Total CED in the IBD population
was measured. High exposure was defined as a radiation dose of greater than 0.2mSv (equivalent to slightly less than
½ a year of background radiation). Results: A total of 112 cases of IBD (36 CD and 76 UC) were reviewed. Our CD
patients were diagnosed at an earlier age than our UC cases (mean age 26.1 vs 45.7). The total CED in our IBD population
was 8.53 (95% CI: 4.53-12.52). Patients with CD were exposed to significantly higher radiation compared to those
with UC. The mean CED was 18.6 (7.30-29.87) and 3.65 (1.74-5.56, p=0.01) for CD and UC patients respectively. 2
patients were diagnosed as having a malignancy during follow up with respective CED values of 1.76mSv and 10mSv.
Conclusions: CD patients, particularly those with complicated disease, received a higher frequency of diagnostic
imaging over a shorter period when compared to UC patients. Usage of low radiation imaging protocols should be
encouraged in IBD patients to reduce their risk of consequent malignancy.
Re-Expression of Bone Marrow Proteoglycan-2 by 5-Azacytidine is associated with STAT3 Inactivation and Sensitivity Response to Imatinib in Resistant CML Cells

Al-Jamal HAN, Johan MF, Mat Jusoh SA, Ismail I, Wan Taib WR

Asian Pac J Cancer Prev, 2018 Jun 25;19(6):1585-1590.
PMID: 29936783

Background: Epigenetic silencing of tumor suppressor genes (TSG) is involved in development and
progression of cancers. Re-expression of TSG is inversely proportionate with STAT3 signaling pathways.
Demethylation of DNA by 5-Azacytidine (5-Aza) results in re-expression of silenced TSG. Forced expression of
PRG2 by 5-Aza induced apoptosis in cancer cells. Imatinib is a tyrosine kinase inhibitor that potently inhibits BCR/
ABL tyrosine kinase resulting in hematological remission in CML patients. However, majority of CML patients treated
with imatinib would develop resistance under prolonged therapy. Methods: CML cells resistant to imatinib were
treated with 5-Aza and cytotoxicity of imatinib and apoptosis were determined by MTS and annexin-V, respectively.
Gene expression analysis was detected by real time-PCR, STATs activity examined using Western blot and methylation
status of PRG2 was determined by pyrosequencing analysis. Result: Expression of PRG2 was significantly higher in
K562-R+5-Aza cells compared to K562 and K562-R (p=0.001). Methylation of PRG2 gene was significantly decreased
in K562-R+5-Aza cells compared to other cells (p=0.021). STAT3 was inactivated in K562-R+5-Aza cells which showed
higher sensitivity to imatinib. Conclusion: PRG2 gene is a TSG and its overexpression might induce sensitivity to
imatinib. However, further studies are required to evaluate the negative regulations of PRG2 on STAT3 signaling.
Knowledge, Decision-Making and Acceptance of Human Papilloma Virus Vaccination among Parents of Primary School Students in Kota Bharu, Kelantan, Malaysia

Mohd Sopian M, Shaaban J, Mohd Yusoff SS, Wan Mohamad WMZ

Asian Pac J Cancer Prev, 2018 Jun 25;19(6):1509-1514.
PMID: 29936724

Background: The incidence of cervical cancer in younger women remains high. This is worrisome as it affects
future generations. Therefore Malaysia implements human papilloma virus (HPV) vaccination as a national vaccination
program. Parents play an important role in determining the success of this HPV vaccination program among schoolaged
girls by their compliance. Objective: To assess parental knowledge, decision-making and acceptance of HPV
vaccination. Methods: This cross sectional study was conducted among 280 randomly selected parents of primary
school students aged 11 in Kota Bharu using a pre-validated self-administered questionnaire to assess knowledge and
decision-making with regard to HPV vaccination. Results: Most parents (62%) were shown to have poor knowledge
while most decision-making was shared. Age of respondents (adjusted odds ratio ‘AOR’= 1.09; 95% confidence interval
‘CI’= 1.04-1.14; p <0.001) and good knowledge of HPV vaccination (AOR= 16.32; 95% CI= 7.32-36.4; p <0.001) were
significantly associated with HPV vaccine acceptance. Conclusion: The majority of parents exhibited poor knowledge
which may affect their decision-making and uptake of HPV vaccination among their children. This highlights the need
to better educate parents on HPV vaccination.
SelfSampling Versus Physicians' Sampling for Cervical Cancer Screening Agreement of Cytological Diagnoses

Othman NH, Zaki FH, Hussain NH, Yusoff WZ, Ismail P

Asian Pac J Cancer Prev, 2016;17(7):3489-94.
PMID: 27509997

BACKGROUND: A major problem with cervical cancer screening in countries which have no organized national screening program for cervical cancer is suboptimal participation. Implementation of selfsampling method may increase the coverage.
OBJECTIVE: We determined the agreement of cytological diagnoses made on samples collected by women themselves (selfsampling) versus samples collected by physicians (Physician sampling).
MATERIALS AND METHODS: We invited women volunteers to undergo two procedures; cervical selfsampling using the Evalyn brush and physician sampling using a Cervex brush. The women were shown a video presentation on how to take their own cervical samples before the procedure. The samples taken by physicians were taken as per routine testing (Gold Standard). All samples were subjected to Thin Prep monolayer smears. The diagnoses made were according to the Bethesda classification. The results from these two sampling methods were analysed and compared.
RESULTS: A total of 367 women were recruited into the study, ranging from 22 to 65 years age. There was a significant good agreement of the cytological diagnoses made on the samples from the two sampling methods with the Kappa value of 0.568 (p=0.040). Using the cytological smears taken by physicians as the gold standard, the sensitivity of selfsampling was 71.9% (95% CI:70.972.8), the specificity was 86.6% (95% CI:85.7 87.5), the positive predictive value was 74.2% (95% CI:73.375.1) and the negative predictive value was 85.1% (95% CI: 84.286.0). Selfsampling smears (22.9%) allowed detection of microorganisms better than physicians samples (18.5%).
CONCLUSIONS: This study shows that samples taken by women themselves (selfsampling) and physicians have good diagnostic agreement. Selfsampling could be the method of choice in countries in which the coverage of women attending clinics for screening for cervical cancer is poor.
Roles of MicroRNA21 and MicroRNA29a in Regulating Cell Adhesion Related Genes in Bone Metastasis Secondary to Prostate Cancer

Mohamad M, Wahab NA, Yunus R, Murad NA, Zainuddin ZM, Sundaram M, et al.

Asian Pac J Cancer Prev, 2016;17(7):3437-45.
PMID: 27509989

BACKGROUND: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be downregulated in clinical samples, most likely due to the posttranscriptional modification by microRNAs. Targeted genes would be upregulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors.
MATERIALS AND METHODS: MicroRNA software predicted that miR21 targets VCL while miR29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalinfixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels.
RESULTS: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down regulated while CX3CL1 was upregulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly up regulated while CX3CL1 mRNA was significantly downregulated compared to the RWPE1 case.
CONCLUSIONS: The downregulation of VCL in FFPE specimens is most likely regulated by miR21 based on the in vitro evidence but the exact mechanism of how miR21 can regulate VCL is unclear. Upregulated in CaP, CX3CL1 was found not regulated by miR29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNAmRNA interactions may provide additional knowledge for individualized study of cancers.
Fulltext Bone mineral density and breast cancer risk factors among premenopausal and postmenopausal women: A systematic review

Zain NM, Seriramulu VP, Chelliah KK

Asian Pac J Cancer Prev, 2016;17(7):3229-34.
PMID: 27509955

BACKGROUND: Bone mineral density (BMD) is a lifetime marker of estrogen in a woman's body and has been associated with increased breast cancer risk. Nonetheless the actual association is still debatable. Furthermore, estrogen is very crucial in maintaining human bone density and gradually decreases over age. A systematic search was conducted to assess any association of BMD with breast cancer risk factors among premenopausal and postmenopausal women.

MATERIALS AND METHODS: Review identification was performed through databases searching on MEDLINE, CINAHL and SCOPUS and 19 qualified studies were elected. The keywords used were "bone mineral density", "breast cancer", and "breast density".

RESULTS: A total of 19 articles showed variation with the majority of the studies focused on postmenopausal and a few focused on premenopausal women. Overall there was no concensus on effects.

CONCLUSIONS: An enormous effort is being undertaken by researchers to prove that BMD might be one of the significant risk factors for breast cancer.
Fulltext Pioneering Annual Colorectal Cancer Screening and Treatment Targeting Low Income Communities in Malaysia (20102015)

Tze CN, Fitzgerald H, Qureshi A, Tan HJ, Low ML

Asian Pac J Cancer Prev, 2016;17(7):3179-83.
PMID: 27509948

The aim of this study was to assess the rate of uptake of a customised annual Colorectal Cancer Awareness, Screening and Treatment Project (CCASTP) using faecal immunohistochemical test (FIT) kits in low income communities in Malaysia. The immediate objectives were (1) to evaluate the level of adherence of CRC screening among lowincome groups, (2) to assess the knowledge and awareness of the screened population and (3) to assess the accuracy of FIT kits. A total of 1,581 FIT kits were distributed between years 2010 to 2015 to healthy asymptomatic participants of the annual CCASTP organized by Empowered the Cancer Advocacy Society of Malaysia. Data for sociodemographic characteristics, critical health and lifestyle information of the registered subjects were collected. Findings for use of the FIT kits were collected when they were returned for stool analyses. Those testingd positive were invited to undergo a colonoscopy examination. A total of 1,436 (90.8%) of the subjects retuned the FITkits, showing high compliance. Among the 129 subjects with positive FIT results, 92 (71.3%) underwent colonoscopy. Six cases (6.5%) of CRC were found. Based on the data collected, the level of awareness of stool examination and knowledge about CRC was poor amongst the participants. Gender, age group, ethnicity and risk factors (i.e. smoking, lack of exercise and low consumption of fresh fruits) were associated with positive FITkit results. In conclusion, CRC screening can be performed in the community with a single FITkit. Although CRC knowledge and awareness is poor in lowincome communities, the average return rate of the FIT kits and rate of colonoscopy examination were 91.2% and 70.3%, respectively.
35Year Research History of Cytotoxicity and Cancer: a Quantitative and Qualitative Analysis

Farghadani R, Haerian BS, Ebrahim NA, Muniandy S

Asian Pac J Cancer Prev, 2016;17(7):3139-45.
PMID: 27509942

Cancer is the leading cause of morbidity and mortality worldwide, characterized by irregular cell growth. Cytotoxicity or killing tumor cells that divide rapidly is the basic function of chemotherapeutic drugs. However, these agents can damage normal dividing cells, leading to adverse effects in the body. In view of great advances in cancer therapy, which are increasingly reported each year, we quantitatively and qualitatively evaluated the papers published between 1981 and December 2015, with a closer look at the highly cited papers (HCPs), for a better understanding of literature related to cytotoxicity in cancer therapy. Online documents in the Web of Science (WOS) database were analyzed based on the publication year, the number of times they were cited, research area, source, language, document type, countries, organizationenhanced and funding agencies. A total of 3,473 publications relevant to the target key words were found in the WOS database over 35 years and 86% of them (n=2,993) were published between 20002015. These papers had been cited 54,330 times without self citation from 1981 to 2015. Of the 3,473 publications, 17 (3,557citations) were the most frequently cited ones between 2005 and 2015. The topmost HCP was about generating a comprehensive preclinical database (CCLE) with 825 (23.2%) citations. One third of the remaining HCPs had focused on drug discovery through improving conventional therapeutic agents such as metformin and ginseng. Another 33% of the HCPs concerned engineered nanoparticles (NPs) such as polyamidoamine (PAMAM) dendritic polymers, PTX/SPIOloaded PLGAs and cell derived NPs to increase drug effectiveness and decrease drug toxicity in cancer therapy. The remaining HCPs reported novel factors such as miR205, Nrf2 and p27 suggesting their interference with development of cancer in targeted cancer therapy. In conclusion, analysis of 35year publications and HCPs on cytotoxicity in cancer in the present report provides opportunities for a better understanding the extent of topics published and may help future research in this area.

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