Displaying publications 61 - 80 of 415 in total

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  1. Kong CK, Roslani AC, Law CW, Law SC, Arumugam K
    Asian Pac J Cancer Prev, 2010;11(4):969-74.
    PMID: 21133609
    OBJECTIVE: Research over the past several decades has indicated that low socioeconomic class has a direct effect on health outcomes. In Malaysia, class distribution may differ with the region. The objective of this study was to compare the presentation and survival of colorectal cancer patients in two dissimilar cities, Kuala Lumpur and Kuching, Sarawak.

    METHODS: All patients diagnosed with a malignancy of the colon or rectum in Sarawak General Hospital and University of Malaya Medical Center from 1st Jan 2000-31st Dec 2006 were recruited. Data on presentation, socio-economic class and survival were obtained. The survival duration was categorized into more than three years or three years and less. Testing for significance was performed using the chi-square test, with p values less than 0.05 considered statistically significant.

    RESULTS: A total of 565 patients in UMMC and 642 patients in SGH had a new diagnosis of colorectal carcinoma. Patients in Kuching had a longer duration of symptoms and more advanced stage at presentation, but this was not statistically significant. Lower socio-economic class was a significant factor for late and more advanced stage at diagnosis, as well as poorer three and five year survival rates. However, survival was lower for patients in Kuching compared to Kuala Lumpur, even after matching for socio-economic class.

    CONCLUSION: There is near-zero awareness of colorectal cancer screening in Malaysia. These findings support reaching out to communities of lower socioeconomic backgrounds to improve the colorectal cancer survival rates.
    Matched MeSH terms: Colorectal Neoplasms/diagnosis*; Colorectal Neoplasms/mortality*; Colorectal Neoplasms/pathology
  2. Chong HY, Roslani AC, Law CW
    Med J Malaysia, 2013;68(1):30-3.
    PMID: 23466763 MyJurnal
    BACKGROUND: Screening for colorectal cancer (CRC) improves outcomes and reduces its incidence. However, population-based screening in Malaysia continues to be a challenge, in view of cost and limited availability of colonoscopic skills and facilities. Conventional qualitative faecal occult blood tests help to prioritize those who require earlier colonoscopies, but cannot distinguish between benign and malignant causes. Recently, quantitative immunochemical faecal occult blood tests (qFOBT) have demonstrated some discriminatory ability in distinguishing benign and malignant causes. We aim to assess feasibility of qFOBT as a tool for stratification of colonoscopic priority in asymptomatic patients.
    METHODS: A health awareness exhibition was held in a major shopping complex in Kuala Lumpur on 6 and 7 Feb 2010. All asymptomatic individuals> 40 years, and those < 40 with family history of CRC, were invited to participate. Eligible participants were given a questionnaire and screened using a qFOBT. A faecal haemoglobin level of 100 - 199 ng/mL was considered moderately positive, while a level of 200 ng/mL or more was strongly positive. Participants with a strongly positive qFOBT result were scheduled for a colonoscopy within the month, while those who were moderately positive were scheduled within 3 months.
    RESULTS: A total of 125 (82%) participants returned the qFOBT kit, of which 70 (56%) were male. The median age was 54 years. Majority of the participants were Chinese (60%), followed by Malay (25%), Indian (12%) and others (3%). Twelve (10%) participants were tested positive and were advised to undergo colonoscopy but 9 (75%) declined colonoscopy and further investigations citing lack of time as the reason. Of the 3 participants (all in the moderately positive group) who underwent colonoscopy, 2 had a family history of CRC. Colonoscopic findings revealed haemorrhoids in one participant and two participants had histologically proven benign sigmoid colonic polyps.
    CONCLUSION: The use of qFOBT as a tool to screen and prioritize asymptomatic patients for early colonoscopy in CRC screening is logistically feasible. However, in order for it to be effective, measures to improve compliance to colonoscopy need to be taken.
    Matched MeSH terms: Colorectal Neoplasms
  3. Abu Hassan MR, Ismail I, Mohd Suan MA, Ahmad F, Wan Khazim WK, Othman Z, et al.
    Epidemiol Health, 2016;38:e2016007.
    PMID: 26971697 DOI: 10.4178/epih.e2016007
    OBJECTIVES: This is the first study that estimates the incidence and mortality rate for colorectal cancer (CRC) patients in Malaysia by sex and ethnicity.

    METHODS: The 4,501 patients were selected from National Cancer Patient Registry-Colorectal Cancer data. Patient survival status was cross-checked with the National Registration Department. The age-standardised rate (ASR) was calculated as the proportion of CRC cases (incidence) and deaths (mortality) from 2008 to 2013, weighted by the age structure of the population, as determined by the Department of Statistics Malaysia and the World Health Organization world standard population distribution.

    RESULTS: The overall incidence rate for CRC was 21.32 cases per 100,000. Those of Chinese ethnicity had the highest CRC incidence (27.35), followed by the Malay (18.95), and Indian (17.55) ethnicities. The ASR incidence rate of CRC was 1.33 times higher among males than females (24.16 and 18.14 per 100,000, respectively). The 2011 (44.7%) CRC deaths were recorded. The overall ASR of mortality was 9.79 cases, with 11.85 among the Chinese, followed by 9.56 among the Malays and 7.08 among the Indians. The ASR of mortality was 1.42 times higher among males (11.46) than females (8.05).

    CONCLUSIONS: CRC incidence and mortality is higher in males than females. Individuals of Chinese ethnicity have the highest incidence of CRC, followed by the Malay and Indian ethnicities. The same trends were observed for the age-standardised mortality rate.

    Matched MeSH terms: Colorectal Neoplasms/ethnology; Colorectal Neoplasms/mortality; Colorectal Neoplasms/epidemiology*
  4. Tan BL, Norhaizan ME, Pandurangan AK, Hazilawati H, Roselina K
    Pak J Pharm Sci, 2016 Jan;29(1):205-12.
    PMID: 26826813
    Brewers' rice is one of abundant agricultural waste products in the rice industry. The present study is designed to investigate the potential of brewers' rice to inhibit the development of aberrant crypt foci (ACF) in colon of azoxymethane (AOM)-treated rats. The effects on the attenuation of hepatic toxicity and kidney function enzymes were also evaluated. Male Sprague-Dawley rats were randomly divided into five groups: (G1) normal; (G2) AOM alone; and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of brewers' rice, respectively. The rats in group 2-5 were injected intraperitoneally with AOM (15 mg/kg body weight) once weekly for two weeks. After 8 weeks of treatment,the total number of ACF/colon and the number of ACF in the distal and middle colon were significantly reduced in all treatment groups compared to G2 (p<0.05). Brewers' rice decreased the number of ACF with dysplastic morphology in a dose-dependent manner. Alkaline phosphatase (ALP) level in G5 was significantly lower compared to the G2 (p<0.05). In conclusion, this study found the potential value of brewers' rice in reducing the risk of cancer susceptibility in colon.
    Matched MeSH terms: Colorectal Neoplasms/chemically induced; Colorectal Neoplasms/pathology; Colorectal Neoplasms/prevention & control*
  5. Magaji BA, Moy FM, Roslani AC, Law CW, Raduan F, Sagap I
    Asian Pac J Cancer Prev, 2015;16(18):8101-5.
    PMID: 26745045
    BACKGROUND: This study examined the psychometric properties of the Bahasa Malaysia (BM) version of the European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer-specific Quality Of Life Questionnaire (QLQ-CR29).

    MATERIALS AND METHODS: We studied 93 patients recruited from University Malaya and Universiti Kebangsaan Medical Centers, Kuala Lumpur, Malaysia using a self-administered method. Tools included QLQ-C30, QLQ-CR29 and Karnofsky Performance Scales (KPS). Statistical analyses included Cronbach's alpha, test-retest correlations, multi-traits scaling and known-groups comparisons. A p value ≤ 0.05 was considered significant.

    RESULTS: The internal consistency coefficients for body image, urinary frequency, blood and mucus and stool frequency scales were acceptable (Cronbach's alpha α ≥ 0.65). However, the coefficients were low for the blood and mucus and stool frequency scales in patients with a stoma bag (α = 0.46). Test-retest correlation coefficients were moderate to high (range: r = 0.51 to 1.00) for most of the scales except anxiety, urinary frequency, buttock pain, hair loss, stoma care related problems, and dyspareunia (r ≤ 0.49). Convergent and discriminant validities were achieved in all scales. Patients with a stoma reported significantly higher symptoms of blood and mucus in the stool, flatulence, faecal incontinence, sore skin, and embarrassment due to the frequent need to change the stoma bag (p < 0.05) compared to patients without stoma. None of the scales distinguished between patients based on the KPS scores. There were no overlaps between scales in the QLQ-C30 and QLQ-CR29 (r < 0.40).

    CONCLUSIONS: the BM version of the QLQ-CR29 indicated acceptable psychometric properties in most of the scales similar to original validation study. This questionnaire could be used to complement the QLQ-C30 in assessing HRQOL among BM speaking population with colorectal cancer.

    Matched MeSH terms: Colorectal Neoplasms/psychology*; Colorectal Neoplasms/rehabilitation*; Colorectal Neoplasms/therapy
  6. Lau TP, Lian LH, Cheah PL, Looi LM, Roslani AC, Goh KL, et al.
    Eur J Cancer Prev, 2017 11;26(6):506-510.
    PMID: 28059856 DOI: 10.1097/CEJ.0000000000000336
    X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations. In view of the conflicting findings generated, we aimed to investigate the association between XRCC1 and genetic predisposition to CRC among Malaysians. The present case-control association study was conducted on 130 CRC patients and 212 age-matched healthy controls. The genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln single nucleotide polymorphisms was performed with allele-specific real-time PCR approach. This was followed by basic statistical analysis on the single nucleotide polymorphisms and haplotype data obtained. No significant difference in the allele and genotype frequencies was observed between CRC patients and healthy controls (P>0.05). There was also no association observed between XRCC1 haplotypes and CRC (P>0.05). In conclusion, a positive association between XRCC1 gene polymorphisms and CRC risk was not established in our Malaysian population.
    Matched MeSH terms: Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/genetics*; Colorectal Neoplasms/epidemiology*
  7. Rus Bakarurraini NAA, Ab Mutalib NS, Jamal R, Abu N
    Vaccines (Basel), 2020 Jul 10;8(3).
    PMID: 32664247 DOI: 10.3390/vaccines8030371
    Over the last few decades, major efforts in cancer research and treatment have intensified. Apart from standard chemotherapy approaches, immunotherapy has gained substantial traction. Personalized immunotherapy has become an important tool for cancer therapy with the discovery of immune checkpoint inhibitors. Traditionally, tumor-associated antigens are used in immunotherapy-based treatments. Nevertheless, these antigens lack specificity and may have increased toxicity. With the advent of next-generation technologies, the identification of new tumor-specific antigens is becoming more important. In colorectal cancer, several tumor-specific antigens were identified and functionally validated. Multiple clinical trials from vaccine-based and adoptive cell therapy utilizing tumor-specific antigens have commenced. Herein, we will summarize the current landscape of tumor-specific antigens particularly in colorectal cancer.
    Matched MeSH terms: Colorectal Neoplasms
  8. Wan Ibrahim NR, Chan HK, Soelar SA, Azmi AN, Mohd Said R, Abu Hassan MR
    Asian Pac J Cancer Prev, 2020 Apr 01;21(4):1057-1061.
    PMID: 32334470 DOI: 10.31557/APJCP.2020.21.4.1057
    BACKGROUND: While the world witnesses an increasing trend of young-onset colorectal cancer (CRC), the information regarding the impact of age on CRC is limited in Malaysia. This study aimed to compare the incidence, clinic-demographic profiles and survival rates of CRC between patients above and under 50 years of age in northern Malaysia.

    METHODS: This was a registry-based, cross-sectional study. All the CRC cases reported by 18 hospitals to the National Cancer Patient Registry - Colorectal Cancer (NCPR-CC) between January 2007 and December 2017 were included in the analysis. The patients were categorized by age into the above-50 and under-50 groups. The changes in the age-standardized incidence and mortality rates of both the age groups were determined using the time-series analysis, and the impact of age on the mortality risk was assessed using the Cox regression analysis.

    RESULTS: Of the 6,172 CRC patients enrolled in the NCPR-CC, 893 (14.5%) were in the under-50 group. As compared with their older counterparts, the patients in the under-50 group were more likely to be female, be of Malay ethnicity, be non-smokers, have a family history of CRC, and present late for treatment. The age-standardized incidence and mortality rates of CRC in the under-50 group remained stable over the years, while a decreasing trend was clearly seen in the mortality rates of CRC in the above-50 group (p=0.003). Nevertheless, the two age groups also did not differ in the mortality risk (adjusted hazards ratio: 1.10; 95% CI: 0.90, 1.36).

    CONCLUSION: Young-onset CRC constituted a considerable proportion of CRC cases in Malaysia. However, in contrast with the findings of most studies, it demonstrated neither an uptrend in age-standardized incidence rates nor a higher mortality risk. Our findings suggest the need to upscale and lower the recommended age for CRC screening in Malaysia.

    Matched MeSH terms: Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/mortality*; Colorectal Neoplasms/epidemiology*
  9. Mustapha MA, Shahpudin SN, Aziz AA, Ankathil R
    World J Gastroenterol, 2012 Jun 7;18(21):2668-73.
    PMID: 22690076 DOI: 10.3748/wjg.v18.i21.2668
    To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8 -251T>A polymorphism on colorectal cancer (CRC) susceptibility risk.
    Matched MeSH terms: Colorectal Neoplasms/diagnosis*; Colorectal Neoplasms/ethnology; Colorectal Neoplasms/genetics*
  10. Teh LK, Hamzah S, Hashim H, Bannur Z, Zakaria ZA, Hasbullani Z, et al.
    Ther Drug Monit, 2013 Oct;35(5):624-30.
    PMID: 23942539 DOI: 10.1097/FTD.0b013e318290acd2
    Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine.
    Matched MeSH terms: Colorectal Neoplasms/blood; Colorectal Neoplasms/drug therapy*; Colorectal Neoplasms/genetics*
  11. Faidzal, O., Azmi, M.N., Kalavathi, R.
    MyJurnal
    Squamous cell carcinoma of the rectum is a very rare malignancy. In the literature, the incidence has been reported as 0.25 to 0.1 per 10000 colorectal carcinomas. Due to its rarity, the treatment and behavior of this tumor have only been discussed in case reports. As a result, several theories regarding their pathogenesis have been proposed. We will describe our experience in managing this rare malignancy in a 69-year-old man who presented with altered bowel habit. Surgery remains the mainstay of treatment. Issues regarding additional treatment have been presented in the literature. The rarity of this tumour also raises issues regarding criteria for diagnosis which we will try to highlight and discuss.
    Matched MeSH terms: Colorectal Neoplasms
  12. Magaji BA, Moy FM, Roslani AC, Law CW
    BMC Cancer, 2017 05 18;17(1):339.
    PMID: 28521746 DOI: 10.1186/s12885-017-3336-z
    BACKGROUND: Colorectal cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death globally. It is the second most common cancer among both males and females in Malaysia. The economic burden of colorectal cancer is likely to increase over time owing to its current trend and aging population. Cancer survival analysis is an essential indicator for early detection and improvement in cancer treatment. However, there was a scarcity of studies concerning survival of colorectal cancer patients as well as its predictors. Therefore, we aimed to determine the 1-, 3- and 5-year survival rates, compare survival rates among ethnic groups and determine the predictors of survival among colorectal cancer patients.
    METHODS: This was an ambidirectional cohort study conducted at the University Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia. All Malaysian citizens or permanent residents with histologically confirmed diagnosis of colorectal cancer seen at UMMC from 1 January 2001 to 31 December 2010 were included in the study. Demographic and clinical characteristics were extracted from the medical records. Patients were followed-up until death or censored at the end of the study (31st December 2010). Censored patients' vital status (whether alive or dead) were cross checked with the National Registration Department. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Log-rank test was used to compare the survival rates, while Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival.
    RESULTS: Among 1212 patients, the median survival for colorectal, colon and rectal cancers were 42.0, 42.0 and 41.0 months respectively; while the 1-, 3-, and 5-year relative survival rates ranged from 73.8 to 76.0%, 52.1 to 53.7% and 40.4 to 45.4% respectively. The Chinese patients had the lowest 5-year survival compared to Malay and Indian patients. Based on the 814 patients with data on their Duke's staging, independent predictors of poor colorectal cancer (5-year) survival were male sex (Hazard Ratio [HR]: 1.41; 95% CI: 1.12, 1.76), Chinese ethnicity (HR: 1.41; 95% CI: 1.07,1.85), elevated (≥ 5.1 ng/ml) pre-operative carcino-embryonic antigen (CEA) level (HR: 2.13; 95% CI: 1.60, 2.83), Duke's stage C (HR: 1.68; 95% CI: 1.28, 2.21), Duke's stage D (HR: 4.61; 95% CI: 3.39, 6.28) and emergency surgery (HR: 1.52; 95% CI: 1.07, 2.15).
    CONCLUSIONS: The survival rates of colorectal cancer among our patients were comparable with those of some Asian countries but lower than those found in more developed countries. Males and patients from the Chinese ethnic group had lower survival rates compared to their counterparts. More advanced staging and late presentation were important predictors of colorectal cancer survival. Health education programs targeting high risk groups and emphasizing the importance of screening and early diagnosis, as well as the recognition of symptoms and risk factors should be implemented. A nationwide colorectal cancer screening program should be designed and implemented to increase early detection and improve survival outcomes.
    Matched MeSH terms: Colorectal Neoplasms/mortality*; Colorectal Neoplasms/pathology; Colorectal Neoplasms/therapy
  13. Tan YJ, Lee YT, Yeong KY, Petersen SH, Kono K, Tan SC, et al.
    Future Med Chem, 2018 Sep 01;10(17):2039-2057.
    PMID: 30066578 DOI: 10.4155/fmc-2018-0052
    AIM: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

    MATERIALS & METHODS: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

    RESULTS & CONCLUSION: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

    Matched MeSH terms: Colorectal Neoplasms/drug therapy*; Colorectal Neoplasms/metabolism; Colorectal Neoplasms/pathology
  14. 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.
    Matched MeSH terms: Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/economics; Colorectal Neoplasms/prevention & control*
  15. Veettil SK, Lim KG, Chaiyakunapruk N, Ching SM, Abu Hassan MR
    Asian J Surg, 2017 Nov;40(6):481-489.
    PMID: 27492344 DOI: 10.1016/j.asjsur.2016.07.005
    BACKGROUND: This study aims to provide an analytical overview of the changing burden of colorectal cancer and highlight the implementable control measures that can help reduce the future burden of colorectal cancer in Malaysia.

    METHODS: We performed a MEDLINE search via OVID with the ​Medical Subject Headings (MeSH) terms "Colorectal Neoplasms"[Mesh] and "Malaysia"[Mesh], and PubMed with the key words "colorectal cancer" and "Malaysia" from 1990 to 2015 for studies reporting any clinical, societal, and economical findings associated with colorectal cancer in Malaysia. Incidence and mortality data were retrieved from population-based cancer registries/databases.

    RESULTS: In Malaysia, colorectal cancer is the second most common cancer in males and the third most common cancer in females. The economic burden of colorectal cancer is substantial and is likely to increase over time in Malaysia owing to the current trend in colorectal cancer incidence. In Malaysia, most patients with colorectal cancer have been diagnosed at a late stage, with the 5-year relative survival by stage being lower than that in developed Asian countries. Public awareness of the rising incidence of colorectal cancer and the participation rates for colorectal cancer screening are low.

    CONCLUSION: The efficiency of different screening approaches must be assessed, and an organized national screening program should be developed in a phased manner. It is essential to maintain a balanced investment in awareness programs targeting general population and primary care providers, focused on increasing the knowledge on symptoms and risk factors of colorectal cancer, awareness on benefits of screening, and promotion of healthy life styles to prevent this important disease.

    Matched MeSH terms: Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/ethnology*; Colorectal Neoplasms/surgery
  16. Lim LC, Lim YM
    Proteomics, 2018 02;18(3-4).
    PMID: 29316255 DOI: 10.1002/pmic.201700169
    Tumor heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumor subtypes. Recent publications in the past 10 years have revealed proteome heterogeneity between different colorectal tumors and within the same tumor site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumor (intratumor heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumor heterogeneity). The potential use of proteome heterogeneity in precision medicine and its implications in biomarker discovery and therapeutic outcomes will be discussed. Identification of the unique proteome landscape between and within individual tumors is imperative for understanding cancer biology and the management of CRC patients.
    Matched MeSH terms: Colorectal Neoplasms
  17. Hasbullah HH, Musa M
    Int J Mol Sci, 2021 Nov 03;22(21).
    PMID: 34769370 DOI: 10.3390/ijms222111941
    Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and is responsible as one of the main causes of mortality in both men and women. Despite massive efforts to raise public awareness on early screening and significant advancements in the treatment for CRC, the majority of cases are still being diagnosed at the advanced stage. This contributes to low survivability due to this cancer. CRC patients present various genetic changes and epigenetic modifications. The most common genetic alterations associated with CRC are p53 and KRAS mutations. Gene therapy targeting defect genes such as TP53 (tumor suppressor gene encodes for p53) and KRAS (oncogene) in CRC potentially serves as an alternative treatment avenue for the disease in addition to the standard therapy. For the last decade, significant developments have been seen in gene therapy for translational purposes in treating various cancers. This includes the development of vectors as delivery vehicles. Despite the optimism revolving around targeted gene therapy for cancer treatment, it also has various limitations, such as a lack of availability of related technology, high cost of the involved procedures, and ethical issues. This article will provide a review on the potentials and challenges of gene therapy targeting p53 and KRAS for the treatment of CRC.
    Matched MeSH terms: Colorectal Neoplasms/genetics; Colorectal Neoplasms/pathology; Colorectal Neoplasms/therapy*
  18. Leong SW, Chia SL, Abas F, Yusoff K
    Molecules, 2020 Aug 26;25(17).
    PMID: 32858795 DOI: 10.3390/molecules25173877
    In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure-activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*; Colorectal Neoplasms/metabolism; Colorectal Neoplasms/pathology
  19. Butt J, Jenab M, Willhauck-Fleckenstein M, Michel A, Pawlita M, Kyrø C, et al.
    Int J Cancer, 2018 Jul 15;143(2):245-252.
    PMID: 29377173 DOI: 10.1002/ijc.31283
    The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case-control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44-3.27). In this prospective nested case-control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification.
    Matched MeSH terms: Colorectal Neoplasms/immunology; Colorectal Neoplasms/microbiology*; Colorectal Neoplasms/epidemiology
  20. Murphy N, Ward HA, Jenab M, Rothwell JA, Boutron-Ruault MC, Carbonnel F, et al.
    Clin Gastroenterol Hepatol, 2019 Jun;17(7):1323-1331.e6.
    PMID: 30056182 DOI: 10.1016/j.cgh.2018.07.030
    BACKGROUND & AIMS: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision.

    METHODS: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests.

    RESULTS: After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors.

    CONCLUSIONS: The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.

    Matched MeSH terms: Colorectal Neoplasms/diagnosis; Colorectal Neoplasms/etiology*; Colorectal Neoplasms/epidemiology
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