Displaying publications 41 - 60 of 514 in total

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  1. Sulaiman S, Shahril MR, Wafa SW, Shaharudin SH, Hussin SN
    Asian Pac. J. Cancer Prev., 2014;15(14):5959-64.
    PMID: 25081729
    BACKGROUND: Dietary carbohydrate, fiber and sugar intake has been shown to play a role in the etiology of breast cancer, but the findings have been inconsistent and limited to developed countries with higher cancer incidence.

    OBJECTIVE: To examine the association of premenopausal and postmenopausal breast cancer risk with dietary carbohydrate, fiber and sugar intake.

    MATERIALS AND METHODS: This population based case-control study was conducted in Malaysia with 382 breast cancer patients and 382 controls. Food intake pattern was assessed via an interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad range of potential confounders were included in analysis.

    RESULTS: A significant two fold increased risk of breast cancer among premenopausal (OR Q4 to Q1=1.93, 95%CI: 1.53-2.61, p-trend=0.001) and postmenopausal (OR Q4 to Q1=1.87, 95%CI: 1.03-2.61, p-trend=0.045) women was observed in the highest quartile of sugar. A higher intake of dietary fiber was associated with a significantly lower breast cancer risk among both premenopausal (OR Q4 to Q1=0.31, 95%CI: 0.12-0.79, p-trend=0.009) and postmenopausal (OR Q4 to Q1=0.23, 95%CI: 0.07-0.76, p-trend=0.031) women.

    CONCLUSIONS: Sugar and dietary fiber intake were independently related to pre- and postmenopausal breast cancer risk. However, no association was observed for dietary carbohydrate intake.

  2. Goh TB, Koh RY, Mordi MN, Mansor SM
    Asian Pac. J. Cancer Prev., 2014;15(14):5659-65.
    PMID: 25081682
    BACKGROUND: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro.

    MATERIALS AND METHODS: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively.

    RESULTS: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): 2.25±0.02 mmol trolox / mmol and 1.96±0.04 mmol trolox / mmol respectively) and DPPH (IC50=3.75±0.04 mg/mL and IC50=2.28±0.02 mg/mL respectively). Both MTG and SRM demonstrate equal potency (IC50=25.20±1.53 and IC50= 22.19±1.06 respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) (IC5024.40±1.26). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > 100 μM towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60).

    CONCLUSIONS: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.

  3. Juliana N, Shahar S, Chelliah KK, Ghazali AR, Osman F, Sahar MA
    Asian Pac. J. Cancer Prev., 2014;15(14):5759-65.
    PMID: 25081698
    Electrical impedance tomography (EIT) is a potential supplement for mammogram screening. This study aimed to evaluate and feasibility of EIT as opposed to mammography and to determine pain perception with both imaging methods. Women undergoing screening mammography at the Radiology Department of National University of Malaysia Medical Centre were randomly selected for EIT imaging. All women were requested to give a pain score after each imaging session. Two independent raters were chosen to define the image findings of EIT. A total of 164 women in the age range from 40 to 65-year-old participated and were divided into two groups; normal and abnormal. EIT sensitivity and specificity for rater 1 were 69.4% and 63.3, whereas for rater 2 they were 55.3% and 57.0% respectively. The reliability for each rater ranged between good to very good (p<0.05). Quantitative values of EIT showed there were significant differences in all values between groups (ANCOVA, p<0.05). Interestingly, EIT scored a median pain score of 1.51±0.75 whereas mammography scored 4.15±0.87 (Mann Whitney U test, p<0.05). From these quantitative values, EIT has the potential as a health discriminating index. Its ability to replace image findings from mammography needs further investigation.
  4. Athirajan V, Razak IA, Thurairajah N, Ghani WM, Ching HN, Yang YH, et al.
    Asian Pac. J. Cancer Prev., 2014;15(19):8183-9.
    PMID: 25339003
    BACKGROUND: A comparative cross-sectional study involving oral cancer patients and healthy individuals was designed to investigate associations between retinol, α-tocopherol and β-carotene with the risk of oral cancer.

    MATERIALS AND METHODS: This study included a total of 240 matched cases and controls where subjects were selected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol, α-tocopherol and β-carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and food frequency questionnaire (FFQ) respectively.

    RESULTS: It was found that results from the two methods applied did not correlate, so that further analysis was done using the HPLC method utilising blood serum. Serum levels of retinol and α-tocopherol among cases (0.177±0.081, 1.649±1.670μg/ml) were significantly lower than in controls (0.264±0.137, 3.225±2.054μg/ml) (p<0.005). Although serum level of β-carotene among cases (0.106±0.159 μg/ml) were lower compared to controls (0.134±0.131μg/ml), statistical significance was not observed. Logistic regression analysis showed that high serum level of retinol (OR=0.501, 95% CI=0.254-0.992, p<0.05) and α-tocopherol (OR=0.184, 95% CI=0.091-0.370, p<0.05) was significantly related to lower risk of oral cancer, whereas no relationship was observed between β-carotene and oral cancer risk.

    CONCLUSIONS: High serum levels of retinol and α-tocopherol confer protection against oral cancer risk.

  5. Wan Abdul Rahman WF, Fauzi MH, Jaafar H
    Asian Pac. J. Cancer Prev., 2014;15(19):8441-5.
    PMID: 25339043
    BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2).

    METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH).

    RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).

    CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

  6. Woodward M
    Asian Pac. J. Cancer Prev., 2014;15(19):8521-6.
    PMID: 25339057
    In many countries of the Association of Southeast Asian Nations (ASEAN), cancer is an increasing problem due to ageing and a transition to Western lifestyles. Governments have been slow to react to the health consequences of these socioeconomic changes, leading to the risk of a cancer epidemic overwhelming the region. A major limitation to motivating change is the paucity of high-quality data on cancer, and its socioeconomic repercussions, in ASEAN. Two initiatives have been launched to address these issues. First, a study of over 9000 new cancer patients in ASEAN - the ACTION study - which records information on financial difficulties, as well as clinical outcomes, subsequent to the diagnosis. Second, a series of roundtable meetings of key stakeholders and experts, with the broad aim of producing advice for governments in ASEAN to take appropriate account of issues relating to cancer, as well as to generate knowledge and interest through engagement with the media. An important product of these roundtables has been the Jakarta Call to Action on Cancer Control. The growth and ageing of populations is a global challenge for cancer services. In the less developed parts of Asia, and elsewhere, these problems are compounded by the epidemiological transition to Western lifestyles and lack of awareness of cancer at the government level. For many years, health services in less developed countries have concentrated on infectious diseases and mother-and-child health; despite a recent wake-up call (United Nations, 2010), these health services have so far failed to allow for the huge increase in cancer cases to come. It has been estimated that, in Asia, the number of new cancer cases per year will grow from 6.1 million in 2008 to 10.6 million in 2030 (Sankaranarayanan et al., 2014). In the countries of the Association of Southeast Asian Nations (ASEAN), corresponding figures are 770 thousand in 2012 (Figure 1), rising to 1.3 million in 2030 (Ferlay et al., 2012). ASEAN consists of Brunei Darussalam, Cambodia, Indonesia, Lao, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Viet Nam. It, thus, includes low- and middle-income countries where the double whammy of infectious and chronic diseases will pose an enormous challenge in allocating limited resources to competing health issues. Cancer statistics, even at the sub-national level, only tell part of the story. Many individuals who contract cancer in poor countries have no medical insurance and no, or limited, expectation of public assistance. Whilst any person who has a family member with cancer can expect to bear some consequential burden of care or expense, in a poor family in a poor environment the burden will surely be greater. This additional burden from cancer is rarely considered, and even more rarely quantified, even in developed nations.
  7. Loh SY, Lee SY, Murray L
    Asian Pac. J. Cancer Prev., 2014;15(19):8127-34.
    PMID: 25338995
    BACKGROUND: Qigong is highly favoured among Asian breast cancer survivors for enhancing health. This study examined the hypothesis that quality of life (QoL) in the Qigong group is better than the placebo (aerobic) or usual care group.

    MATERIALS AND METHODS: A total of 197 participants were randomly assigned to either the 8-week Kuala Lumpur Qigong Trial or control groups in 2010-2011. Measurement taken at baseline and post- intervention included QoL, distress and fatigue. Analysis of covariance (ANCOVA) and Kruskal Wallis were used to examine for differences between groups in the measurements.

    RESULTS: There were 95 consenting participants in this 8week trial. The adherence rates were 63% for Qigong and 65% for the placebo group. The Qigong group showed significant marginal improvement in Quality of life scores compared to placebo (mean difference=7.3 unit; p=0.036), compared to usual care (mean difference=6.7 unit; p=0.048) on Functional Assessment Cancer Therapy-Breast measure. There were no significant changes between the placebo and usual care groups in fatigue or distress at post intervention (8-week).

    CONCLUSIONS: Cancer survivors who participated in the Qigong intervention showed slightly better QOL. Follow up studies are greatly needed to evaluate which subgroups may best benefit from Qigong. With a steep rise of cancer survivors, there is an urgent need to explore and engage more cultural means of physical activity to fight side effects of treatment and for cancer control in developing countries.

  8. Hashim N, Jamalludin Z, Ung NM, Ho GF, Malik RA, Phua VC
    Asian Pac. J. Cancer Prev., 2014;15(13):5259-64.
    PMID: 25040985
    BACKGROUND: CT based brachytherapy allows 3-dimensional (3D) assessment of organs at risk (OAR) doses with dose volume histograms (DVHs). The purpose of this study was to compare computed tomography (CT) based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the cervix treated with high-dose-rate (HDR) intracavitary brachytherapy (ICBT).

    MATERIALS AND METHODS: Between March 2011 and May 2012, 20 patients were treated with 55 fractions of brachytherapy using tandem and ovoids and underwent post-implant CT scans. The external beam radiotherapy (EBRT) dose was 48.6 Gy in 27 fractions. HDR brachytherapy was delivered to a dose of 21 Gy in three fractions. The ICRU bladder and rectum point doses along with 4 additional rectal points were recorded. The maximum dose (DMax) to rectum was the highest recorded dose at one of these five points. Using the HDR plus 2.6 brachytherapy treatment planning system, the bladder and rectum were retrospectively contoured on the 55 CT datasets. The DVHs for rectum and bladder were calculated and the minimum doses to the highest irradiated 2cc area of rectum and bladder were recorded (D2cc) for all individual fractions. The mean D2cc of rectum was compared to the means of ICRU rectal point and rectal DMax using the Student's t-test. The mean D2cc of bladder was compared with the mean ICRU bladder point using the same statistical test .The total dose, combining EBRT and HDR brachytherapy, were biologically normalized to the conventional 2 Gy/fraction using the linear-quadratic model. (α/β value of 10 Gy for target, 3 Gy for organs at risk).

    RESULTS: The total prescribed dose was 77.5 Gy α/β10. The mean dose to the rectum was 4.58 ± 1.22 Gy for D 2cc, 3.76 ± 0.65 Gy at D ICRU and 4.75 ± 1.01 Gy at DMax. The mean rectal D 2cc dose differed significantly from the mean dose calculated at the ICRU reference point (p<0.005); the mean difference was 0.82 Gy (0.48 -1.19 Gy). The mean EQD2 was 68.52 ± 7.24 Gy α/β3 for D 2cc, 61.71 ± 2.77 Gy α/β3 at D ICRU and 69.24 ± 6.02 Gy α/β3 at DMax. The mean ratio of D 2cc rectum to D ICRU rectum was 1.25 and the mean ratio of D 2cc rectum to DMax rectum was 0.98 for all individual fractions. The mean dose to the bladder was 6.00 ± 1.90 Gy for D 2cc and 5.10 ± 2.03 Gy at D ICRU. However, the mean D 2cc dose did not differ significantly from the mean dose calculated at the ICRU reference point (p=0.307); the mean difference was 0.90 Gy (0.49-1.25 Gy). The mean EQD2 was 81.85 ± 13.03 Gy α/β3 for D 2cc and 74.11 ± 19.39 Gy α/β3 at D ICRU. The mean ratio of D 2cc bladder to D ICRU bladder was 1.24. In the majority of applications, the maximum dose point was not the ICRU point. On average, the rectum received 77% and bladder received 92% of the prescribed dose.

    CONCLUSIONS: OARs doses assessed by DVH criteria were higher than ICRU point doses. Our data suggest that the estimated dose to the ICRU bladder point may be a reasonable surrogate for the D 2cc and rectal DMax for D 2cc. However, the dose to the ICRU rectal point does not appear to be a reasonable surrogate for the D 2cc.

  9. Osman HA, Hasan H, Suppian R, Bahar N, Hussin NS, Rahim AA, et al.
    Asian Pac. J. Cancer Prev., 2014;15(13):5245-7.
    PMID: 25040982
    BACKGROUND: Helicobacter pylori (H. pylori) is one of the most important causes of dyspepsia and gastric cancer and diagnosis can be made by invasive or non-invasive methods. The Atlas Helicobacter pylori antigen test is a new rapid non-invasive method which is simple to conduct. The aim of this study was to determine its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy.

    MATERIALS AND METHODS: This prospective study was conducted between July 2012 and December 2013. Stool samples of 59 dyspeptic patients who underwent upper endoscopy were evaluated for H. pylori stool antigen.

    RESULTS: From the 59 patients who participated in this study, there were 36 (61%) males and 23 (39%) females. H. pylori was diagnosed in 24 (40.7%) gastric biopsies, 22 (91.7 %) of these being positive for the Atlas H. pylori antigen test. The sensitivity, specificity, PPV, NPV and accuracy were 91.7%, 100%, 100%, 94.6% and 96.6% respectively.

    CONCLUSIONS: The Atlas H. pylori antigen test is a new non-invasive method which is simple to perform and avails reliable results in a few minutes. Thus it can be the best option for the diagnosis of H. pylori infection due to its high sensitivity and specificity.

  10. Rashid RM, Ramli S, John J, Dahlui M
    Asian Pac. J. Cancer Prev., 2014;15(13):5143-7.
    PMID: 25040965
    Cervical cancer screening in Malaysia is by opportunistic Pap smear which contributes to the low uptake rate. To overcome this, a pilot project called the SIPPS program (translated as information system of Pap smear program) had been introduced whereby women aged 20-65 years old are invited for Pap smear and receive recall to repeat the test. This study aimed at determining which recall method is most cost-effective in getting women to repeat Pap smear. A randomised control trial was conducted where one thousand women were recalled for repeat smear either by registered letter, phone messages, phone call or the usual postal letter. The total cost applied for cost-effectiveness analysis includes the cost of sending letter for first invitation, cost of the recall method and cost of two Pap smears. Cost-effective analysis (CEA) of Pap smear uptake by each recall method was then performed. The uptake of Pap smear by postal letter, registered letters, SMS and phone calls were 18.8%, 20.0%, 21.6% and 34.4%, respectively (p<0.05). The CER for the recall method was lowest by phone call compared to other interventions; RM 69.18 (SD RM 0.14) compared to RM 106.53 (SD RM 0.13), RM 134.02 (SD RM 0.15) and RM 136.38 (SD RM 0.11) for SMS, registered letter and letter, respectively. ICER showed that it is most cost saving if the usual method of recall by postal letter be changed to recall by phone call. The possibility of letter as a recall for repeat Pap smear to reach the women is higher compared to sending SMS or making phone call. However, getting women to do repeat Pap smear is better with phone call which allows direct communication. Despite the high cost of the phone call as a recall method for repeat Pap smear, it is the most cost-effective method compared to others.
  11. Chan HK, Ismail S
    Asian Pac. J. Cancer Prev., 2014;15(13):5305-9.
    PMID: 25040993
    BACKGROUND: This study aimed to assess the most common physical side effects experienced by local chemotherapy patients. Their perceptions of these side effects and informational needs from clinical pharmacists were also evaluated.

    MATERIALS AND METHODS: This was a single-center, cross-sectional study. A face-to-face interview guided by a structured questionnaire with cancer patients admitted to receive repeated cycles of chemotherapy was conducted. Information collected included chemotherapy-related side effects after last chemotherapy experience, the most worrisome side effects, the side effects overlooked by healthcare professionals and the preferred method, amount and source of receiving related information.

    RESULTS: Of 99 patients recruited, 90 participated in this survey (response rate: 90.9%). The majority were in the age range of 45-64 years (73.3%) and female (93.3%). Seventy-five (83.3%) and seventy-one (78.9%) experienced nausea and vomiting, respectively. Both symptoms were selected as two of the most worrisome side effects (16.7% vs. 33.3%). Other common and worrisome side effects were hair loss and loss of appetite. Symptoms caused by peripheral neuropathies were perceived as the major symptoms being overlooked (6.7%). Most patients demanded information about side effects (60.0%) and they would like to receive as much information as possible (86.7%). Oral conversation (83.3%) remained as the preferred method and the clinical pharmacist was preferred by 46.7% of patients as the educator in this aspect.

    CONCLUSIONS: The high prevalence of chemotherapy-related side effects among local patients is of concern. Findings of their perceptions and informational needs may serve as a valuable guide for clinical pharmacists to help in side effect management in Malaysia.

  12. Azmawati MN, Najibah E, Hatta MD, Norfazilah A
    Asian Pac. J. Cancer Prev., 2014;15(13):5283-6.
    PMID: 25040989
    Stage of cervical cancer may adversely affect the quality of life (QOL) among patients. The objective of this study was to predict the QOL among cervical cancer patients by the stage of their cancer. A cross-sectional study from September 2012 until January 2013 was conducted among cervical cancer patients who completed treatment. All patients completed a interviewer-guided questionnaire comprising four sections: (A) socio- demographic data, (B) medical history, (C) QOL measured by general health status questionnaire (QLQ-30) and (D) cervical cancer specific module CX-24 (EORTC) was used to measured patient's functional, symptom scale and their global health status. Results showed that global health status, emotional functioning and pain score were higher in stage III cervical cancer patients while role functioning was higher in stage I cervical cancer patients. Patients with stage IV cancer have a lower mean score in global health status (adjusted b-22.0, 95 CI% -35.6, -8.49) and emotional functioning (adjusted b -22.5, 95 CI% -38.1, -6.69) while stage III had lower mean score in role functioning (adjusted b -14.3, 95 CI% -25.4, -3.21) but higher mean score in pain (adjusted b 22.1, 95 CI% 8.56, 35.7). In conclusion, stage III and IV cervical cancers mainly affect the QOL of cervical cancer patients. Focus should be given to these subgroups to help in improving the QOL.
  13. Yusof A, Chia YC, Hasni YM
    Asian Pac. J. Cancer Prev., 2014;15(19):8095-9.
    PMID: 25338990
    BACKGROUND: Worldwide, over half a million women died of breast cancer in 2011 alone. Mammography screening is associated with a reduction of 20 to 35% in breast cancer mortality. The aim of this study was to determine the awareness and practice of mammography screening and predictors of its uptake in Malaysian women attending a primary care clinic.

    MATERIALS AND METHODS: A cross-sectional study was carried out among women aged 40 to 74 years attending a primary care clinic in Selangor, Malaysia. An assisted structured questionnaire included questions on socio-demography, source of information and level of knowledge. An adapted version of the revised Champion Health Belief Model Scale plus other associated factors for mammography screening up-take were also included as part of the questionnaire. Predictors for mammography screening uptake were only determined in those who were aware about mammography screening. Significant predictors were determined by logistic regression.

    RESULTS: 447 women were recruited for this study; 99.1% of them (n: 411) were aware about breast cancer. Only 50.1% (n: 206) had knowledge about mammography screening. Prevalence of clinical breast-examination (CBE) was 23.3% (n: 104) and mammography screening up-take was 13.2% (n: 59). The predictors for the latter were those who have had clinical breast-examination (aOR=17.58, 95%CI: 7.68-39.82) and those aged between 50 to 59 years (aOR=3.94, 95%CI: 1.61-9.66) as well as those aged 60 years and above (aOR=6.91, 95%CI: 2.28-20.94). Good knowledge and positive beliefs about mammography screening were not associated with mammography screening uptake.

    CONCLUSIONS: Half of our Malaysian women were aware about mammography screening. However, the uptake of mammography was low. Previous CBE and older age were significant predictors of mammography screening uptake. Increasing CBE services may increase compliance with guidelines.
  14. Yankuzo HM, Emilia ST, Shaari R, Yaacob NS
    Asian Pac. J. Cancer Prev., 2014;15(16):6721-6.
    PMID: 25169515
    BACKGROUND: The aim of this preliminary study was to address variations of responses observed with different starting tumor sizes of 10 and 15 mm, and the effects of different doses of tamoxifen (TAM) on experimental rat mammary tumors.

    MATERIALS AND METHODS: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and 500 μg/day) groups of six animals each, and another group (n=6) treated with TAM 100 μg/day at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice.

    RESULTS: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups.

    CONCLUSIONS: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.

  15. Tan HK, Moad AI, Tan ML
    Asian Pac. J. Cancer Prev., 2014;15(16):6463-75.
    PMID: 25169472
    The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.
  16. Akhtari-Zavare M, Ghanbari-Baghestan A, Latiff LA, Matinnia N, Hoseini M
    Asian Pac. J. Cancer Prev., 2014;15(16):6531-4.
    PMID: 25169482
    BACKGROUND: In Iran, breast cancer is the most prevalent cancer in women and a major public health problem.

    METHODS: A cross sectional study was carried out to determine knowledge on breast cancer and breast self- examination (BSE) practices of 384 females living in the city of Hamadan, Iran. A purposive sampling method was adopted and data were collected via face-to-face interviews based on a validated questionnaire developed for this study.

    RESULTS: Among respondents 268 (69.8%) were married and 144 (37.5%) of the respondents reported having a family history of breast cancer. One hundred respondents (26.0%) claimed they practiced BSE. Level of breast cancer knowledge was significantly associated with BSE practice (p=0.000). There was no association with demographic details (p<0.05).

    CONCLUSION: The findings showed that Iranian women's knowledge regarding breast cancer and the practice of BSE is inadequate. Targeted education should be implemented to improve early detection of breast cancer.

  17. Al-Jamal HA, Jusoh SA, Yong AC, Asan JM, Hassan R, Johan MF
    Asian Pac. J. Cancer Prev., 2014;15(11):4555-61.
    PMID: 24969884
    BACKGROUND: Silencing due to methylation of suppressor of cytokine signaling-3 (SOCS-3), a negative regulator gene for the JAK/STAT signaling pathway has been reported to play important roles in leukemogenesis. Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets the BCR-ABL protein and induces hematological remission in patients with chronic myeloid leukemia (CML). Unfortunately, the majority of CML patients treated with imatinib develop resistance under prolonged therapy. We here investigated the methylation profile of SOCS-3 gene and its downstream effects in a BCR-ABL positive CML cells resistant to imatinib.

    MATERIALS AND METHODS: BCR-ABL positive CML cells resistant to imatinib (K562-R) were developed by overexposure of K562 cell lines to the drug. Cytotoxicity was determined by MTS assays and IC50 values calculated. Apoptosis assays were performed using annexin V-FITC binding assays and analyzed by flow cytometry. Methylation profiles were investigated using methylation specific PCR and sequencing analysis of SOCS-1 and SOCS-3 genes. Gene expression was assessed by quantitative real-time PCR, and protein expression and phosphorylation of STAT1, 2 and 3 were examined by Western blotting.

    RESULTS: The IC50 for imatinib on K562 was 362 nM compared to 3,952 nM for K562-R (p=0.001). Percentage of apoptotic cells in K562 increased upto 50% by increasing the concentration of imatinib, in contrast to only 20% in K562-R (p<0.001). A change from non-methylation of the SOCS-3 gene in K562 to complete methylation in K562-R was observed. Gene expression revealed down- regulation of both SOCS-1 and SOCS-3 genes in resistant cells. STAT3 was phosphorylated in K562-R but not K562.

    CONCLUSIONS: Development of cells resistant to imatinib is feasible by overexposure of the drug to the cells. Activation of STAT3 protein leads to uncontrolled cell proliferation in imatinib resistant BCR-ABL due to DNA methylation of the SOCS-3 gene. Thus SOCS-3 provides a suitable candidate for mechanisms underlying the development of imatinib resistant in CML patients.

  18. Hakim L, Alias E, Makpol S, Ngah WZ, Morad NA, Yusof YA
    Asian Pac. J. Cancer Prev., 2014;15(11):4651-7.
    PMID: 24969899
    The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75 mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75 mg/mL Gelam honey) synergistically lowered the IC50 of Gelam honey to 22 mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose- dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.
  19. Hooshmand S, Ghaderi A, Yusoff K, Thilakavathy K, Rosli R, Mojtahedi Z
    Asian Pac. J. Cancer Prev., 2014;15(7):3311-7.
    PMID: 24815488
    BACKGROUND: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest.

    MATERIALS AND METHODS: ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα.

    RESULTS: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells.

    CONCLUSIONS: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

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