Displaying publications 81 - 98 of 98 in total

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  1. Tan BS, Tiong KH, Muruhadas A, Randhawa N, Choo HL, Bradshaw TD, et al.
    Mol. Cancer Ther., 2011 Oct;10(10):1982-92.
    PMID: 21831963 DOI: 10.1158/1535-7163.MCT-11-0391
    Both 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F-203; NSC 703786) and 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (GW-610; NSC 721648) are antitumor agents with novel mechanism(s). Previous studies have indicated that cytochrome (CYP) P450 1A1 is crucial for 5F-203 activity. In the present study, we investigated the functional role of 2 newly identified CYP P450 enzymes, CYP2S1 and CYP2W1, in mediating antitumor activity of benzothiazole compounds. We generated isogenic breast cancer (MDA-MB-468, MCF-7) and colorectal cancer (CRC; KM12 and HCC2998) cell lines depleted for CYP1A1, CYP2S1, or CYP2W1. The sensitivity of these cells to 5F-203 and GW-610 was then compared with vector control cells. 5F-203 exhibited potent activity against breast cancer cells, whereas GW-610 was effective against both breast and colorectal cancer cells. CYP1A1 was induced in both breast cancer and CRC cells, while CYP2S1 and CYP2W1 were selectively induced in breast cancer cells only following treatment with 5F-203 or GW-610. Depletion of CYP1A1 abrogated the sensitivity of breast cancer and CRC cells to 5F-203 and GW-610. Although depletion of CYP2S1 sensitized both breast cancer and CRC cells toward 5F-203 and GW-610, CYP2W1 knockdown caused marked resistance to GW-610 in CRC cells. Our results indicate that CYP-P450 isoforms, with the exception of CYP1A1, play an important role in mediating benzothiazole activity. CYP2S1 appears to be involved in deactivation of benzothiazoles, whereas CYP2W1 is important for bioactivation of GW-610 in CRC cells. Because CYP2W1 is highly expressed in colorectal tumors, GW-610 represents a promising agent for CRC therapy.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  2. Kaur G, Masoud A, Raihan N, Radzi M, Khamizar W, Kam LS
    Indian J Med Res, 2011 Aug;134:186-92.
    PMID: 21911971
    DNA mismatch repair gene (MMR) abnormalities are seen in 95 per cent of hereditary nonpolyposis colorectal cancer (HNPCC) and 10-15 per cent of sporadic colorectal cancers. There are no data on MMR abnormalities in Malaysian colorectal cancer patients. This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  3. Norlida AO, Phang KS
    Malays J Pathol, 2010 Dec;32(2):111-6.
    PMID: 21329182 MyJurnal
    Colorectal carcinogenesis is a complex multistep process that includes changes in histomorphological appearance of the colonic mucosa and changes at molecular level. Aberrant crypt foci (ACF) was first described by Bird in 1987 on examination of methylene-blue-stained colonic mucosa of azoxymethane-treated mice under light microscopy. Since then ACF was considered as the earliest preneoplastic change that can be seen in the colonic mucosa. The aim of this study was to look at the histomorphology and distribution of ACF in colorectal carcinoma. 50 formalin-fixed archival colectomy specimens for colorectal carcinoma were examined under light microscopy after staining with 0.2% methylene blue. ACF was identified by larger and darker crypts with thickened epithelium, and often elevated from adjacent normal mucosa. ACF was found in 41 of 50 colectomy specimens examined. There were 328 ACF consisting of 36 (11.0%) ACF without hyperplasia or dysplasia, 263 (80.2%) ACF with hyperplasia and 29 (8.8%) ACF with dysplasia. Of these 29 ACF with dysplasia, 25 showed low grade dysplasia and four high grade dysplasia. The density of ACF was higher in the left colon, those older than 65 years of age and among males but these findings were statistically not significant. The crypt multiplicity of hyperplastic ACF (30.149, SD 28.395) was larger than dysplastic ACF (20.613, SD 40.128). The spectrum of histological changes observed probably represent the evolution of ACF in colorectal carcinogenesis.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  4. Ghazali AK, Musa KI, Naing NN, Mahmood Z
    Asian J Surg, 2010 Jul;33(3):127-33.
    PMID: 21163410 DOI: 10.1016/S1015-9584(10)60022-X
    To determine the 5-year survival rate and prognostic factors for survival in patients with colorectal cancer treated at the Surgical Unit, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  5. Yeoh LC, Loh CK, Gooi BH, Singh M, Gam LH
    World J Gastroenterol, 2010 Jun 14;16(22):2754-63.
    PMID: 20533595
    AIM: To identify differentially expressed hydrophobic proteins in colorectal cancer.

    METHODS: Eighteen pairs of colorectal cancerous tissues in addition to tissues from normal mucosa were analysed. Hydrophobic proteins were extracted from the tissues, separated using 2-D gel electrophoresis and analysed using Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS). Statistical analysis of the proteins was carried out in order to determine the significance of each protein to colorectal cancer (CRC) and also their relation to CRC stages, grades and patients' gender.

    RESULTS: Thirteen differentially expressed proteins which were expressed abundantly in either cancerous or normal tissues were identified. A number of these proteins were found to relate strongly with a particular stage or grade of CRC. In addition, the association of these proteins with patient gender also appeared to be significant.

    CONCLUSION: Stomatin-like protein 2 was found to be a promising biomarker for CRC, especially in female patients. The differentially expressed proteins identified were associated with CRC and may act as drug target candidates.

    Matched MeSH terms: Colorectal Neoplasms/pathology*
  6. 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/pathology
  7. Naik VR, Jaafar H, Seng CE
    Indian J Pathol Microbiol, 2010 Jan-Mar;53(1):12-4.
    PMID: 20090214 DOI: 10.4103/0377-4929.59175
    The purpose of this study was to count the number of lymphatic channels present in colorectal adenocarcinoma and correlate it with site, size, and stage of tumor, lymph node metastasis.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  8. Ho K, Yazan LS, Ismail N, Ismail M
    Cancer Epidemiol, 2009 Aug;33(2):155-60.
    PMID: 19679064 DOI: 10.1016/j.canep.2009.06.003
    Vanillin is responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies showed that vanillin could enhance the repair of mutations and thus function as an anti-mutagen. However, its role in cancer, a disease that is closely related to mutation has not yet been fully elucidated.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  9. Mahadeva S, Rembacken BJ
    Surg Endosc, 2009 Feb;23(2):417-22.
    PMID: 18806938 DOI: 10.1007/s00464-008-9983-z
    BACKGROUND: Standard polypectomy techniques may be contributing to ineffective eradication of colonic superficial neoplasia, an increasing number of which are nonpolypoid. We aimed to demonstrate the practicality and efficacy of the "inject and cut" endoscopic mucosal resection (EMR) technique in routine clinical practice.

    METHODS: Colonic EMRs performed for polypoid and nonpolypoid lesions at a tertiary institution were prospectively collected and analyzed for efficacy, and short and long-term complications.

    RESULTS: 224 colonic neoplasms (143 flat, 65 sessile and 16 subpedunculated) were excised by the standard inject-and-cut method, with standard accessories. The median size of all lesions was 10 mm (range 2-50 mm) and 110 (49.2%) lesions were located in the proximal colon. Histological completeness of resection was achieved in 87% of cases. Of the lesions 77.2% were dysplastic, with 5 cases of carcinoma in situ and 18 severely dysplastic adenomas. Complications included bleeding in five cases (2.2 %) and a single case of perforation (0.4%). All complications were managed endoscopically. Median follow up at 24 +/- 16 months (range 12-84 months) revealed a 7.2% local recurrence rate, all of which were subsequently eradicated by repeat EMR.

    CONCLUSIONS: Standard inject-and-cut colonic EMR is practical and effective in the eradication of superficial colonic neoplasia.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  10. Chandramathi S, Suresh K, Anita ZB, Kuppusamy UR
    J Cancer Res Clin Oncol, 2009 Feb;135(2):319-23.
    PMID: 18758816 DOI: 10.1007/s00432-008-0462-7
    PURPOSE: This study aimed to use non-invasive methods to assess and compare the levels of oxidative indices and non-enzymatic antioxidants in breast and colorectal cancer (CRC) patients. Various studies have reported on lipid peroxidation, hydrogen peroxide (H(2)O(2)) and ferric-reducing antioxidant power (FRAP) levels in the serum of cancer patients but this is the first report that highlights the significance of urinary-advanced oxidative protein product (AOPP) in cancer patients.
    METHODS: The levels of advanced oxidative protein product (AOPP), hydrogen peroxide (H(2)O(2)), malondialdehyde (MDA) which is a marker for lipid peroxidation and ferric-reducing antioxidant power (FRAP) were measured in urine samples of breast (n = 101) and colorectal cancer (n = 49) patients attending the Oncology Clinic, University Malaya Medical Centre, Kuala Lumpur and were compared with 95 age-matched healthy individuals.
    RESULTS: AOPP, H(2)O(2) and MDA levels in the urine were significantly higher in the CRC patients compared to the control subjects and breast cancer patients. In breast cancer patients, only AOPP level was elevated. FRAP level did not differ between breast and colorectal cancer patients but the levels were significantly lower compared to control subjects.
    CONCLUSION: Urinary oxidative indices such as AOPP, H(2)O(2), and MDA as well as FRAP could serve as useful non-invasive oxidative stress markers in colorectal cancer but only AOPP serves as a useful urinary oxidative biomarker in breast cancer.
    Study site: Oncology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
    Matched MeSH terms: Colorectal Neoplasms/pathology
  11. Rashid MR, Aziz AF, Ahmad S, Shah SA, Sagap I
    Asian Pac J Cancer Prev, 2009;10(6):1163-6.
    PMID: 20192604
    BACKGROUND: Colorectal cancer (CRC) is one of the major malignancies in the world. In Malaysia, CRC is fast becoming the commonest cause of cancer death. Its etiology is complex, involving both environmental and genetic factors. This study looked at the profile and outcome of five-year follow-up of patients with CRC.

    MATERIALS AND METHODS: Retrospective case review study done on CRC patients at University Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, Malaysia. Patientsandapos; socio-demographic characteristics, modalities of treatment, cancer characteristics and outcome at 5-year follow up were extracted from the case records.

    RESULTS: A total of 107 case records of patients were analyzed. Peak age of CRC presentation was 40-69 years (71.1%). Male to female ratio was 1.2:1 with Chinese predominance (52.3%). Anaemia and its related symptoms including per rectal bleeding was the commonest clinical presentation. The median duration of clinical presentation was 13 weeks (IQR 21.8). More than two-thirds presented as non-emergency cases (69.2%). Most patients presented with Dukes C stage (40.2%). The overall 5-year survival rate was 40% with local recurrence rate of 19.6%. Metastasis after curative-intend treatment (surgery with adjuvant therapy) developed in 26% of patients. Lower recurrence (p = 0.016, OR = 0.205) and metastatic disease (p = 0.02, OR = 0.24) found among the Chinese patients. Almost half of the patients defaulted follow up care (43%), most often within the first year of treatment (22.4%) and the Chinese were the least likely to default (p= 0.04, OR = 0.45).

    CONCLUSION: Socio-demographic profile of CRC patients in UKMMC is comparable to Asia pacific region. Apparent delay in seeking treatment gives rise to poor overall survival and local recurrence rates.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  12. bin Sabir Husin Athar PP, bte Ahmad Norhan N, bin Saim L, bin Md Rose I, bte Ramli R
    Ann Acad Med Singap, 2008 Sep;37(9):788-3.
    PMID: 18989497
    INTRODUCTION: Metastatic adenocarcinoma from the gastrointestinal tract to the sinonasal tract is rare. The histological morphology of this lesion is indistinguishable from the colonic variant of primary sinus adenocarcinoma or intestinal-type adenocarcinoma (ITAC).

    CLINICAL PICTURE: This is a report of a case of metastatic adenocarcinoma of colorectal origin to the paranasal sinuses in a 52-year-old female who was previously treated for adenocarcinoma of the sigmoid colon. A histologic study of the surgical specimen from the sinonasal cavity demonstrated a tumour identical to the patient's prior primary tumour of the colon. The sinonasal neoplastic tissue showed marked positivity for carcinoembryonic antigen and expressed cytokeratin 20, which differentiates metastatic colonic adenocarcinoma from ITAC.

    TREATMENT/OUTCOME: The patient received palliative radiation but died 3 months after the diagnosis.

    CONCLUSION: Distinguishing metastatic adenocarcinoma from gastrointestinal tract from ITAC can be difficult. In view of the resemblance, immunohistochemical staining can help in differentiating them. It is important to recognise these as metastatic lesions as the treatment is mainly palliative.

    Matched MeSH terms: Colorectal Neoplasms/pathology*
  13. Chan SH, Ng C, Looi LM
    ANZ J Surg, 2008 Sep;78(9):775-9.
    PMID: 18844907 DOI: 10.1111/j.1445-2197.2008.04648.x
    Isosulfan blue is not available for clinical use in Malaysia. This study describes the use of methylene blue as an alternative to isosulfan blue in colorectal sentinel node mapping.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
  14. Yaacob NS, Darus HM, Norazmi MN
    Exp. Toxicol. Pathol., 2008 Sep;60(6):505-12.
    PMID: 18579355 DOI: 10.1016/j.etp.2008.05.006
    Studies have shown that ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) can induce differentiation and inhibit proliferation of several cancer cells. The present study was performed to investigate the effects of the PPARgamma ligand, ciglitazone, and the involvement of PPARgamma in modulating the growth of human colorectal cancer cells. Lactate dehydrogenase release assay showed that ciglitazone potently inhibited HT-29 (well-differentiated) and COLO-205 (poorly differentiated) colorectal adenocarcinoma cell growth. Measurement of apoptosis by flow cytometry using a fluorescein-conjugated monoclonal antibody against cytokeratin 18 revealed a high induction of apoptosis by ciglitazone in a time-dependent fashion. The expression of PPARgamma1 but not PPARgamma2 mRNA was significantly downregulated as measured by real-time quantitative PCR, and the PPARgamma protein levels were decreased as determined by Western blot analysis. We conclude that ciglitazone treatment suppressed colon cancer cell growth via induction of apoptosis. However, the anticancer effects of ciglitazone may not depend solely on PPARgamma activation.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  15. Khor TO, Gul YA, Ithnin H, Seow HF
    Int J Colorectal Dis, 2006 May;21(4):291-300.
    PMID: 16041507
    BACKGROUND AND AIMS: It is well accepted that activation of Wnt signalling occurs in colorectal carcinoma (CRC), but the correlation amongst the various proteins involved in primary tumours are still unclear. The expression of the inducer of this pathway, Wnt-1, and the downstream effectors, WISP-1, cyclin-D1 and survivin proteins, was compared in a series of CRC tissues with the apparently normal adjacent tissues to determine the relationship of these proteins.

    PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tissue samples of 47 CRCs surgically resected at the Kuala Lumpur Hospital (KLH) between 1999 and 2000 were used. Immunohistochemical staining with monoclonal antibodies against cyclin-D1 and survivin and polyclonal antibodies against Wnt-1 and WISP-1 was performed. Results of immunohistochemistry were analysed for correlation between biomolecules and histopathological data of the patients.

    RESULTS: Of the 47 CRCs, 26 (55.3%), 15 (31.9%), 5 (10.6%) and 28 (59.6%) of the tumours exhibited positivity for Wnt-1, WISP-1, cyclin D1 and survivin, respectively. A lower percentage of the 40 apparently normal adjacent tissues were found to be positive for Wnt-1 (7, 17.5%), WISP-1 (+/-5, 12.5%) and survivin (13, 32.5%), but cyclin D1 was not detected in any of them. Interestingly, the total scores of Wnt-1, WISP-1 and survivin were significantly higher in CRC tissues (p=0.001, 0.034 and 0.044, respectively). Using the Spearman rank correlation test, a positive linear relationship was found between total Wnt-1 score with total WISP-1 score (rho=0.319, p=0.003) and total survivin score (rho=0.609, p=or<0.001). The expression of WISP-1 in the CRC tissues was found to be positively correlated with patients older than 60 years old (p=0.011). In addition, nuclear cyclin-D1 expression was found to be associated with poorly differentiated CRC tissues (p<0.001, Table 5) and right-sided CRC tumour (p=0.019, Table 6). Total WISP-1 score was associated with well-differentiated CRC tissues (p=0.029).

    CONCLUSIONS: Overexpression and interplay between Wnt-1, WISP-1, survivin and cyclin-D1 may play a role in tumorigenesis, possibly by promoting cell cycle checkpoint progression, accelerating cell growth and inhibiting apoptosis. Our data may provide useful information towards the search for potent therapeutic targets towards the development of novel treatment strategies for CRC.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  16. Rajendra S, Ho JJ, Arokiasamy J
    J Gastroenterol Hepatol, 2005 Jan;20(1):51-5.
    PMID: 15610446
    Ethnic differences have been reported for colorectal polyps and large bowel cancer; although the supporting data is weak and insufficient to draw firm conclusions.
    Matched MeSH terms: Colorectal Neoplasms/pathology
  17. Hong SK, Gul YA, Ithnin H, Talib A, Seow HF
    Asian J Surg, 2004 Jan;27(1):10-7.
    PMID: 14719508
    BACKGROUND: Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS.

    METHODS: A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral.

    RESULTS: COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores.

    CONCLUSIONS: the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  18. Cheong KL, Roohi S, Jarmin R, Sagap I, Tong SHY, Qureshi A
    Med J Malaysia, 2000 Dec;55(4):464-6.
    PMID: 11221158
    Colonoscopy is an integral part of the clinician armamentarium in the diagnosis of colorectal cancer and its precursor, the adenoma. Polypoid lesions when identified can be excised at colonoscopy and in turn reduce the risk of colorectal cancer. We prospectively evaluated the yield of colorectal cancer and adenomatous polyps by indication for colonoscopy over a one-year period. A total of 375 colonoscopies were carried out. The more common indications of colonoscopy were rectal bleeding, abdominal pain, surveillance of colorectal cancer and altered bowel habit. The highest yield for cancer was for rectal bleeding with 12.5% while surveillance of patients with a history of polyps yielded the highest percentage of new polyps. We conclude that rectal bleeding as an indication for colonoscopy yielded the highest number of cancers.
    Matched MeSH terms: Colorectal Neoplasms/pathology*
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