Displaying publications 81 - 100 of 169 in total

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  1. Mishra RK, Ramasamy K, Ahmad NA, Eshak Z, Majeed AB
    J Mater Sci Mater Med, 2014 Apr;25(4):999-1012.
    PMID: 24398912 DOI: 10.1007/s10856-013-5132-x
    Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.
    Matched MeSH terms: Colonic Neoplasms/drug therapy*; Colonic Neoplasms/metabolism; Colonic Neoplasms/pathology
  2. Joshi SC, Pant I, Shukla AN, Anshari MA
    J Cancer Res Ther, 2008 8 9;4(2):99-101.
    PMID: 18688130
    Follow-up of colorectal carcinoma after therapy is based on symptoms, tumor markers, and imaging studies. Clinicians sometimes face diagnostic dilemmas because of unusual presentations on the imaging modalities coupled with rising serum markers. We report a case of colorectal carcinoma that presented with gastrointestinal symptoms 14 months after completion of treatment. Investigations showed rise in carcinoembryonic antigen (CEA). Suspecting disease recurrence, complete radioimaging workup was performed; the only abnormality detected was a smooth, hypodense area in the posterior third of the spleen on contrast-enhanced computed tomography abdomen. In view of the previous diagnosis of carcinoma colon, the symptoms reported by the patient, the elevated CEA, and the atypical CECT appearance, a diagnosis of splenic metastasis was made. The patient was subjected to splenectomy as a curative treatment. However, the histopathological report revealed it to be a splenic infarct. The present case reemphasizes the limitations of radiological studies in the follow-up of carcinoma colon.
    Matched MeSH terms: Colonic Neoplasms/diagnosis; Colonic Neoplasms/pathology*; Colonic Neoplasms/surgery
  3. Goh KL, Quek KF, Yeo GT, Hilmi IN, Lee CK, Hasnida N, et al.
    Aliment Pharmacol Ther, 2005 Nov 1;22(9):859-64.
    PMID: 16225496
    Colorectal cancer is one of the most common forms of gastrointestinal cancer in the world today. In the Asia-Pacific area, it is the fastest emerging gastrointestinal cancer.
    Matched MeSH terms: Colonic Neoplasms/ethnology; Colonic Neoplasms/epidemiology; Colonic Neoplasms/therapy
  4. Phang CW, Karsani SA, Sethi G, Abd Malek SN
    PLoS One, 2016;11(2):e0148775.
    PMID: 26859847 DOI: 10.1371/journal.pone.0148775
    Flavokawain C (FKC) is a naturally occurring chalcone which can be found in Kava (Piper methysticum Forst) root. The present study evaluated the effect of FKC on the growth of various human cancer cell lines and the underlying associated mechanisms. FKC showed higher cytotoxic activity against HCT 116 cells in a time- and dose-dependent manner in comparison to other cell lines (MCF-7, HT-29, A549 and CaSki), with minimal toxicity on normal human colon cells. The apoptosis-inducing capability of FKC on HCT 116 cells was evidenced by cell shrinkage, chromatin condensation, DNA fragmentation and increased phosphatidylserine externalization. FKC was found to disrupt mitochondrial membrane potential, resulting in the release of Smac/DIABLO, AIF and cytochrome c into the cytoplasm. Our results also revealed that FKC induced intrinsic and extrinsic apoptosis via upregulation of the levels of pro-apoptotic proteins (Bak) and death receptors (DR5), while downregulation of the levels of anti-apoptotic proteins (XIAP, cIAP-1, c-FlipL, Bcl-xL and survivin), resulting in the activation of caspase-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase (PARP). FKC was also found to cause endoplasmic reticulum (ER) stress, as suggested by the elevation of GADD153 protein after FKC treatment. After the cells were exposed to FKC (60μM) over 18hrs, there was a substantial increase in the phosphorylation of ERK 1/2. The expression of phosphorylated Akt was also reduced. FKC also caused cell cycle arrest in the S phase in HCT 116 cells in a time- and dose-dependent manner and with accumulation of cells in the sub-G1 phase. This was accompanied by the downregulation of cyclin-dependent kinases (CDK2 and CDK4), consistent with the upregulation of CDK inhibitors (p21Cip1 and p27Kip1), and hypophosphorylation of Rb.
    Matched MeSH terms: Colonic Neoplasms/drug therapy*; Colonic Neoplasms/metabolism; Colonic Neoplasms/pathology
  5. Koh KS, Telisinghe PU, Bickle I, Abdullah MS, Chong CF, Chong VH
    Asian Pac J Cancer Prev, 2015;16(8):3279-83.
    PMID: 25921132
    BACKGROUND: Colorectal cancer (CRC) is the most common gastrointestinal cancer and the incidence is increasing. CRC is more common with increasing age, but a proportion occurs in young adults, termed young CRC. This study assessed the incidence and the demographic of young CRC in Brunei Darussalam.

    MATERIALS AND METHODS: All histologically proven CRC between 1986 and 2014 registered with the Department of Pathology cancer registry were reviewed and data extracted for analyses. Young CRC was defined as cancer in patients aged less than 45 years. The various population groups were categorized into locals (Malays, Chinese and Indigenous) and expatriates.

    RESULTS: Over the study period, there were 1,126 histologically proven CRC (mean age 59.1 ± 14.7 years, Male 58.0%, Locals 91.8% and 8.2% expatriates). Young CRC accounted for 15.1% with the proportion declining over the years, from 29% (1986-1990) to 13.2% (2011-2014). The proportion of young CRC was highest among the indigenous (30.8%), followed by the expatriates (29.3%), Malays (14.3%) and lowest among the Chinese (10.8%). The mean age of young CRC was 35.9 ± 6.2; lowest among the indigenous (33.5 ± 6.7), expatriate (34.9 ± 6.0) groupd and the Malays (35.6 ± 6.5) compared to the Chinese (38.6 ± 4.6), a similar trend being observed in the non-young CRC groups. There were no difference between the genders and tumor locations (rectum or colon) between the young and the non-young CRC cases. Female young CRC was significantly younger than male (p<0.05) without any significant variation between the various population groups (p>0.05).

    CONCLUSIONS: Our study showed that the young CRC accounted for 15.1% of all CRC with declining trend observed over recent years. Young CRC was more common among indigenous, expatriates and Malays and least common among the Chinese. There were no differences in the gender and tumor locations.
    Matched MeSH terms: Colonic Neoplasms/ethnology; Colonic Neoplasms/epidemiology; Colonic Neoplasms/pathology
  6. Goh KW, Say YH
    Tumour Biol., 2015 Sep;36(10):7947-60.
    PMID: 25956278 DOI: 10.1007/s13277-015-3455-6
    γ-synuclein, a neuronal protein of the synuclein family, is involved in carcinogenesis. To investigate its role in colorectal cancer carcinogenesis, we overexpressed γ-synuclein in LS 174T colon adenocarcinoma cell line (termed LS 174T-γsyn). When compared with untransfected/mock transfectants, LS 174T-γsyn had higher mobility in scratch wound assay, tend to scatter more in cell-scattering assay, and had enhanced lamellipodia and filopodia formation in cell-spreading assay. Enhanced adhesion of LS 174T-γsyn to fibronectin and collagen and significantly higher proliferation rate showed that γ-synuclein was able to increase extracellular matrix interaction and promoted proliferation of LS 174T. Higher invasiveness of LS 174T-γsyn was evidenced by enhanced invasion to the bottom of the basement membrane in Boyden chamber assay. However, LS 174T-γsyn were significantly more vulnerable to doxorubicin, vincristine and hydrogen peroxide insults, via apoptotic cell death. LS 174T-γsyn also had reduced anchorage-independent growth as shown by reduced colony formation and reduced anoikis resistance. We found that overexpression of γ-synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to LS 174T, where the former was mediated through enhanced cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation, while the latter involved hepatocyte growth factor (HGF) downregulation and subsequent downstream signalling pathways possibly involving extracellular signal-regulated kinases (ERK)1/2, p38α, c-Jun N-terminal kinase (JNK) pan and Signal Transducers and Activators of Transcription (STATs). This unexpected contrasting finding as compared to other similar studies on colon cancer cell lines might be correlated with the degree of tumour advancement from which the cell lines were derived from.
    Matched MeSH terms: Colonic Neoplasms/drug therapy; Colonic Neoplasms/metabolism; Colonic Neoplasms/pathology*
  7. Al-Shibli SM, Harun N, Ashour AE, Mohd Kasmuri MHB, Mizan S
    PeerJ, 2019;7:e7624.
    PMID: 31592340 DOI: 10.7717/peerj.7624
    Obesity is demonstrated to be a risk factor in the development of cancers of various organs, such as colon, prostate, pancreas and so on. Leptine (LEP) is the most renowned of the adipokines. As a hormone, it mediates its effect through leptin receptor (LEPR), which is widely expressed in various tissues including colon mucosa. In this study, we have investigated the degree of expression of LEP and LEPR in colorectal cancer (CRC). We collected 44 surgically resected colon cancer tissues along with normal adjacent colon tissue (NACT) from a sample of CRC patients from the Malaysian population and looked for leptin and leptin receptors using immunohistochemistry (IHC). All the samples showed low presence of both LEP and LEPR in NACT, while both LEP and LEPR were present at high intensity in the cancerous tissues with 100% and 97.7% prevalence, respectively. Both were sparsed in the cytoplasm and were concentrated beneath the cell membrane. However, we did not find any significant correlation between their expression and pathological parameters like grade, tumor size, and lymph node involvement. Our study further emphasizes the possible causal role of LEP and LEPR with CRC, and also the prospect of using LEPR as a possible therapeutic target.
    Matched MeSH terms: Colonic Neoplasms
  8. Subramani B, Pullai CR, Krishnan K, Sugadan SD, Deng X, Hiroshi T, et al.
    Biomed Rep, 2014 Jul;2(4):505-508.
    PMID: 24944796
    Immune cell-based therapies using natural killer (NK) cells and cytotoxic T cells are under constant scrutiny, with the aim to design an effective and reduced-toxicity therapy, which will benefit patients via improved quality of life and improved prognosis. Four patients with stage IV colon cancer were administered 1, 3, 5 and 6 effector cell intravenous infusions, respectively. Peripheral blood was collected from the patients and the ex vivo activation and expansion of NK and T cells was performed in Good Manufacturing Practice-certified clean rooms for ~12-15 days. Immunophenotypic analysis of the peripheral blood mononuclear cells (PBMCs) and expanded NK and T cells was conducted using flow cytometry and the patients were followed up. On average, 4.8×107 initial PBMCs and 2.7×109 total expanded cells were obtained. The intravenous infusions of the expanded cells were not accompanied by adverse reactions. Improved prognosis, reflected by a considerable decrease in the cancer markers, accompanied by an improved quality of life in the patients were observed. In conclusion, potential strategies are currently under development for the large-scale production of effectors cells; therefore, autologous immune enhancement therapy (AIET) may be considered as a viable approach to cancer treatment.
    Matched MeSH terms: Colonic Neoplasms
  9. Venkatachalam K, Vinayagam R, Arokia Vijaya Anand M, Isa NM, Ponnaiyan R
    Toxicol Res (Camb), 2020 Feb;9(1):2-18.
    PMID: 32440334 DOI: 10.1093/toxres/tfaa004
    1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.
    Matched MeSH terms: Colonic Neoplasms
  10. Mohamed SIA, Jantan I, Nafiah MA, Seyed MA, Chan KM
    Curr Pharm Biotechnol, 2021;22(2):262-273.
    PMID: 32532192 DOI: 10.2174/1389201021666200612173029
    BACKGROUND: The anticancer effects of Phyllanthus amarus extract on various cancer cells have been investigated, however, the effects of its major constituents on HCT116 human colorectal cancer cells have not been reported.

    OBJECTIVE: In the present study, we investigated the cytotoxic effect of 80% ethanol extract of P. amarus and its marker constituents (phyllanthin, hypophyllanthin, gallic acid, niranthin, greraniin, phyltetralin, isolintetralin, corilagin and ellagic acid) on HCT116 and their underlying mechanisms of action.

    METHODS: Their antiproliferative and apoptotic effects on HCT 116 were performed using MTT assay and flow cytometric analysis, respectively, while caspases 3/7, 8 and 9 activities were examined using the colorimetric method. The expression of cleaved poly ADP ribose polymerase enzyme (PARP) and cytochrome c proteins was investigated by the immune-blot technique.

    RESULTS AND DISCUSSION: HPLC and LC-MS/MS analyses demonstrated that the extract contained mainly lignans and polyphenols. The plant samples markedly suppressed the growth and expansion of HCT116 cells in a concentration- and time-dependent manner with no toxicity against normal human fibroblast CCD18 Co. P. amarus extract, phyllanthin and gallic acid induced mode of cell death primarily through apoptosis as confirmed by the exteriorization of phosphatidylserine. Caspases 3/7, 8, and 9 activities increased in a concentration-dependent manner following 24h treatment. The expressions of cleaved PARP (Asp 214) and cytochrome c were markedly upregulated.

    CONCLUSION: P. amarus extract, phyllanthin and gallic acid exhibited an apoptotic effect on HCT116 cells through the caspases-dependent pathway.

    Matched MeSH terms: Colonic Neoplasms/drug therapy; Colonic Neoplasms/enzymology*; Colonic Neoplasms/pathology
  11. Ooi KK, Yeo CI, Ang KP, Akim AM, Cheah YK, Halim SN, et al.
    J Biol Inorg Chem, 2015 Jul;20(5):855-73.
    PMID: 26003312 DOI: 10.1007/s00775-015-1271-5
    The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P-Au-S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 1-3 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 1-3. Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 1-3 and these are able to inhibit cell invasion and to suppress the activity of TrxR.
    Matched MeSH terms: Colonic Neoplasms/drug therapy*; Colonic Neoplasms/metabolism; Colonic Neoplasms/pathology
  12. Appalanaido GK, Bahajjaj SIBZ, Shukor SA, Ahmad MZ, Francis HCH
    Oxf Med Case Reports, 2021 Apr;2021(4):omab016.
    PMID: 33948189 DOI: 10.1093/omcr/omab016
    Liver is the most common site for metastasis from colorectal cancer (CRC). Non-surgical treatment options for oligometastatic CRC confined to the liver which represents an intermediate state in the metastatic cascade are fast expanding. Currently, several liver-directed local therapeutic options are available, such as hepatic arterial infusion (HAI) therapy, radio-frequency ablation (RFA), transarterial chemoembolization (TACE), stereotactic body radiotherapy and high dose rate brachytherapy (HDRBT). Many factors such as patient's fitness, liver function (LF), tumour size, location of the tumour in the liver and scheduling of systemic therapy need to be considered when selecting patients for surgery or local liver-directed therapy. This case report illustrates a successful local treatment with staged HDRBT for a large and unresectable, liver only oligometastatic disease from CRC. This patient underwent 4 cycles of chemotherapy (FOLFOX 4) followed by primary tumour resection and first stage of HDRBT to liver for a residual 14 cm tumour after the chemotherapy. After completing a further 4 cycles of chemotherapy with the same regimen, the tumour remained stable at 8 cm. She underwent a second stage of HDRBT to the same lesion and a repeat PET-CT scan done 8 weeks after the second HDRBT showed complete metabolic response. To our knowledge, this is the largest CRC metastatic liver lesion that has been successfully treated with HDRB.
    Matched MeSH terms: Colonic Neoplasms
  13. Tan HCL, Tan JH, Nur Dzainuddin NA, Chan KK
    Ann Coloproctol, 2020 Apr;36(2):94-101.
    PMID: 32178501 DOI: 10.3393/ac.2019.05.10
    PURPOSE: The purpose of this study was to demonstrate the feasibility and safety of laparoscopic-assisted anterior resection (LAAR) for colorectal cancer in a local Asian population.

    METHODS: This is a retrospective review of all patients with colorectal cancer operated from November 2017 to October 2018. Main variables of interest were demography, type and surgery, length of stay (LOS), and the involvement of proximal and distal doughnut. Postoperative complications were analysed using chi-square or Fisher exact and Mann-Whitney tests.

    RESULTS: There were 23 patients with a mean age of 62.5 ± 12.2 years. The mean time from diagnosis to surgery was 97.1 ± 154.84 days. There were 12 patients in the LAAR group and 11 in the open anterior resection (OAR) group. Duration of surgery was shorter in OAR (129.58 ± 51.38 minutes) compared to LAAR (147.91 ± 39.37 minutes). Mean LOS was shorter in the LAAR group with 5±1.5 days compared to the OAR group of 7.42 ± 4.25 days. However, there was no significant P-value for both duration of surgery (P = 0.322) or LOS (P = 0.87). A total of 3 complications were recorded after OAR and 2 after LAAR. Both groups had clear proximal and distal margins with 16 (12-18.5) harvested lymph nodes in LAAR and 18 (16-22) in OAR, which were equal (P = 0.155).

    CONCLUSION: This study reports a shorter LOS in the minimally invasive group of 2 days with similar oncologic resection outcomes. This shows that LAAR is feasible in Malaysia and has potential outcome benefits.

    Matched MeSH terms: Colonic Neoplasms
  14. Al-Khdhairawi AAQ, Low YY, Manshoor N, Arya A, Jelecki M, Alshawsh MA, et al.
    J Nat Prod, 2020 12 24;83(12):3564-3570.
    PMID: 33305943 DOI: 10.1021/acs.jnatprod.0c00618
    Two new diterpene pyrones, asperginols A (1) and B (2), and four known analogues (3-6) were isolated from the endophytic fungus Aspergillus sp. HAB10R12. The structures and absolute configurations of these compounds were elucidated based on the analysis of their NMR, MS, and X-ray diffraction data. The revision of the absolute configurations at C-10, C-11, and C-14 of the known diterpene pyrones (3-6) and the determination of the configuration at the polyene side chain for compounds (4-6) were made using chemical methods and vibrational circular dichroism analysis. This group of diterpene pyrone compounds showed unique structural features including a 7/6/6 tricyclic diterpene moiety with an unusual trans-syn-trans stereochemical arrangement. Compound 6 showed moderate activity against the HT-29 colon cancer cell line.
    Matched MeSH terms: Colonic Neoplasms
  15. Rida Tajau, Siti Farhana Fathy, Mek Zah Salleh, Nor Azowa Ibrahim, Maznah Ismail, Kamaruddin Hashim
    MyJurnal
    The acrylated palm oil (APO) nanoparticle is a potential product that can be used as carriers in
    medical field. The main focus of the present study was to study the potential of the APO
    nanoparticles for used in a controlled drug delivery system. The microemulsion system is used as a
    medium to incorporate an active substance such as Thymoquinone (TQ) into the APO polymeric
    micelle and then the radiation technique is used as a tool for the synthesis of TQ-loaded APO
    nanoparticle. The nano-size TQ-loaded APO particles resulted the particle size of less than 150 nm
    with spherical in shape. The TQ release profile was carried out in potassium buffer saline (PBS)
    solutions (pH 7.4) at 37
    oC. And, the zero-order model has been used to determine the mechanism
    of the drug release from the corresponding nanoparticles, respectively. The TQ release was found
    to be sustained and controlled in pH 7.4. At pH 7.4, the release of TQ followed the zero-order
    model. The in-vitro drug release study showed a good prospect of the APO nanoparticle on being a
    potential drug carrier as there are toxic against colon cancer cells and not toxic towards normal
    cells. This suggested that the APO product produce using this radiation technique can be
    developed into different type of carrier systems for controlled drug release applications.
    Matched MeSH terms: Colonic Neoplasms
  16. Al-Naggar RA, Anil Sh
    Asian Pac J Cancer Prev, 2016 10 01;17(10):4661-4664.
    PMID: 27892680
    Background: Artificial light at night (ALAN) has been linked to increased risk of cancers in body sites like the breast
    and colorectum. However exposure of ALAN as an environmental risk factor and its relation to cancers in humans has
    never been studied in detail. Objective: To explore the association of ALAN with all forms of cancers in 158 countries.
    Materials and Methods: An ecological study encompassing global data was conducted from January to June 2015,
    with age-standardized rates (ASR) of cancers as the outcome measure. ALAN, in the protected areas, as the exposure
    variable, was measured with reference to the Protected Area Light Pollution Indicator (PALI) and the Protected Area
    Human Influence Indicator (PAHI). Pearson’s correlations were calculated for PALI and PAHI with ASR of cancers for
    158 countries, adjusted for country populations, electricity consumption, air pollution, and total area covered by forest.
    Stratified analysis was conducted according to the country income levels. Linear regression was applied to measure the
    variation in cancers explained by PALI and PAHI. Results: PALI and PAHI were positively associated with ASR of all
    forms of cancer, and also the four most common cancers (p < 0.05). These positive correlations remained statistically
    significant for PAHI with all forms of cancer, lung, breast, and colorectal cancer after adjusting for confounders. Positive
    associations of PALI and PAHI with cancers varied with income level of the individual countries. Variation in all forms
    of cancers, and the four most common cancers explained by PALI and PAHI, ranged from 3.3 – 35.5%. Conclusion:
    Artificial light at night is significantly correlated for all forms of cancer as well as lung, breast, colorectal, and prostate
    cancers individually. Immediate measures should be taken to limit artificial light at night in the main cities around the
    world and also inside houses.
    Matched MeSH terms: Colonic Neoplasms
  17. Lau MF, Vellasamy S, Chua KH, Sabaratnam V, Kuppusamy UR
    EXCLI J, 2018;17:186-199.
    PMID: 29743857 DOI: 10.17179/excli2018-1011
    Colorectal cancer (CRC) is the third most leading cause of morbidity and mortality throughout the world. 5-fluorouracil (5-FU), which is often administrated to disrupt carcinogenesis, was found to elevate blood glucose level among CRC patients. Thus, this study was conducted to evaluate the influence of rosiglitazone on antiproliferative effect of 5-FU using cellular model. Two human colonic carcinoma cell lines (HCT 116 and HT 29) were cultured in the presence of 5-FU, rosiglitazone or in combination under normal and high glucose concentration. The drug cytotoxicity was evaluated using the MTT assay whereas the assessment of cell cycle was carried out using the flow cytometry technique. Combination index (CI) method was used to determine the drug interaction between rosiglitazone and 5-FU. High glucose diminished the cytotoxic effect of 5-FU but at a high drug dosage, this effect could be overcome. Cell cycle analysis demonstrated that 5-FU and rosiglitazone caused G1-phase arrest and S-phase arrest, respectively. CI values indicated that rosiglitazone exerted synergistic effect on 5-FU regardless of glucose levels. This study is the first to demonstrate the influence of rosiglitazone on cytotoxicity of 5-FU under normal or high glucose level. Rosiglitazone may be a promising drug for enhancing the efficacy of 5-FU in the treatment of CRC associated with hyperglycemia.
    Matched MeSH terms: Colonic Neoplasms
  18. Zainal Abidin SA, Rajadurai P, Chowdhury MEH, Ahmad Rusmili MR, Othman I, Naidu R
    Basic Clin Pharmacol Toxicol, 2018 Nov;123(5):577-588.
    PMID: 29908095 DOI: 10.1111/bcpt.13060
    The aim of this study was to investigate the cytotoxic, antiproliferative activity and the induction of apoptosis by L-amino acid oxidase isolated from Calloselasma rhodostoma crude venom (CR-LAAO) on human colon cancer cells. CR-LAAO was purified using three chromatographic steps: molecular exclusion using G-50 gel filtration resin, ion-exchange by MonoQ column and desalted on a G25 column. The purity and identity of the isolated CR-LAAO was confirmed by SDS-PAGE and LC-MS/MS. CR-LAAO demonstrated time- and dose-dependent cytotoxic activity on SW480 (primary human colon cancer cells) and SW620 (metastatic human colon cancer cells) with an EC50 values of 6 μg/ml and 7 μg/ml at 48 hr, respectively. Quantification of apoptotic cells based on morphological features demonstrated significant increase in apoptotic cell population in both SW480 and SW620 cells which peaked at 48 hr. Significant increase in caspase-3 activity and reduction in Bcl-2 levels were demonstrated following CR-LAAO treatment. These data provide evidence on the potential anticancer activity of CR-LAAO from the venom of C. rhodostoma for therapeutic intervention of human colon cancer.
    Matched MeSH terms: Colonic Neoplasms
  19. Saifullah B, Buskaran K, Shaikh RB, Barahuie F, Fakurazi S, Mohd Moklas MA, et al.
    Nanomaterials (Basel), 2018 Oct 11;8(10).
    PMID: 30314340 DOI: 10.3390/nano8100820
    The treatment of cancer through chemotherapy is limited by its toxicity to healthy tissues and organs, and its inability to target the cancer site. In this study, we have designed an anticancer nanocomposite delivery system for protocatechuic acid (PCA) using graphene oxide⁻polyethylene glycol as the nanocarrier, and coated with folic acid (GO⁻PEG⁻PCA⁻FA) for targeting the cancer cells. The designed anticancer delivery system was found to show much better anticancer activity than the free drug PCA against liver cancer HEP-G2 cells and human colon cancer HT-29 cells; at same time, it was found to be less toxic to normal fibroblast 3T3 cells. The folate-coated anticancer delivery system was found to show better activity then the free drug and the uncoated anticancer delivery system. The in vitro release of the PCA was found to be sustained in human physiological pHs, i.e., blood pH 7.4 and intracellular lysosomal pH 4.8. These in vitro findings are highly encouraging for further in vivo evaluation studies.
    Matched MeSH terms: Colonic Neoplasms
  20. Asmariah Ahmad, Safura Salik, Yap Wei Boon, Ahmad Rohi Ghazali, Noorhisham Tan Kofli
    Jurnal Sains Kesihatan Malaysia, 2018;16(101):23-26.
    MyJurnal
    Mutagenic and antimutagenic activities of lactic acid bacteria (LAB) Lactobacillus plantarum isolated from the local fermented durian (tempoyak) was determined by Ames test (Salmonella/microsome mutagenicity assay). Our study also involved pre-incubation assay against Salmonella typhimurium TA 98 and TA 100 bacterial strain in the presence and absence of metabolic activator S9 system. It was found that the L. plantarum showed no mutagenic activity on both S. typhimurium strain TA 98 and TA 100 in the presence and absence of metabolic activator. Significant antimutagenic activity (p < 0.05) was observed in both cell-free supernatant and bacterial cell suspension of L. plantarum as compared to the mutagenicity induced by 2-Aminoanthracene in the presence of metabolic activator. Meanwhile, in the absence of metabolic activator, only the bacterial cells of L. plantarum showed antimutagenicity acitivity against Sodium Azide and 2-Nitrofluorene. In conclusion, L. plantarum could play a vital role as chemopreventive agent by binding to mutagens and suppressing mutagenesis. Thus, L. plantarum could be consider as a good candidate for functional food development as a supplement product to prevent development of colon cancer.
    Matched MeSH terms: Colonic Neoplasms
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