Displaying publications 41 - 53 of 53 in total

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  1. γ-Synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to the colon adenocarcinoma LS 174T cell line
    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/pathology*
  2. Fulltext Prognostic factors and the role of adjuvant chemotherapy in post-curative surgery for Dukes B and C colon cancers and survival outcomes: a Malaysian experience
    Hassan AS, Naicker M, Yusof KH, Wan Ishak WZ
    Asian Pac J Cancer Prev, 2015;16(6):2237-43.
    PMID: 25824744
    BACKGROUND: Adjuvant chemotherapy improves survival in Dukes C colon cancers post-curative resection. However, the evidence for a role with Dukes B lesions remains unproven despite frequent use for disease characterized by poor prognostic features. In view of limited Asia-specific data, this study aimed to determine survival outcomes and identify prognostic factors in a tertiary teaching hospital in Malaysia.

    MATERIALS AND METHODS: A total of 116 subjects who underwent curative surgery with and without adjuvant chemotherapy for Duke B and C primary colon adenocarcinomas diagnosed from 2004-2009 were recruited and data were collected retrospectively. Five-year overall survival (OS) and disease free survival (DFS) were analysed using Kaplan-Meier survival analysis and log-rank (Mantel-Cox) test. Prognostic factors were determined using Cox proportional hazards regression with both univariate and multivariate analyses.

    RESULTS: The survival analysis demonstrated a 5-year OS of 74.0% for all patients, with 74.9% for Dukes C subjects receiving chemotherapy compared to 28.6% in those not receiving chemotherapy (p=0.001). For Dukes B disease, the 5-year survival rate was 82.6% compared to 75.0% for subjects receiving and not receiving chemotherapy, respectively (p=0.17). Independent prognostic factors identified included a CEA level more than 3.5 ng/ml (hazard ratio (HR)=4.78; p=0.008), serosal involvement (HR=3.75; p=0.028) and completion of chemotherapy (HR= 0.20; p=0.007).

    CONCLUSIONS: In a regional context, this study supports current evidence from the West that adjuvant chemotherapy improves survival in Dukes C colon cancers post curative surgery. However, although a clear benefit has yet to be proven for Dukes B disease, our results suggest survival improvement in selected cases.
    Matched MeSH terms: Colonic Neoplasms/pathology
  3. Cancer of the colon and rectum in the first three decades of life
    Shahrudin MD, Noori SM
    Hepatogastroenterology, 1997;44(14):441-4.
    PMID: 9164516
    BACKGROUND/AIMS: Recently an increasing number of young colorectal carcinoma patients attending the University Hospital, Kuala Lumpur were noted. This report represents our experience with patients suffering from colorectal cancer aged 30 years or younger.
    MATERIALS AND METHODS: All cases of primary carcinoma of the colon and rectum admitted to the University Hospital during 1990 to 1994 were respectively reviewed. Inclusion criteria was that the patient had been 30 years or younger. Data collected included age, gender, race, site of tumour, presenting symptomatology, duration of symptoms, histology, extension of tumour and nodal involvement predisposing factors, treatment and follow-up.
    RESULTS: 21 patients were included, 5 patients (24%) were 30 years old at diagnosis, 12 (57%) patients were aged 20-29 years and 4 patients (19%) were less than 20 years old. Thirteen of the 21 patients were female, and 8 (38%) were male, 6 of the 21 patients (29%) were Malaysian, while 1 was Indian (4%). The remainder were Chinese, 14 patients (67%). Six patients (29%) had their primary tumour located in the rectosigmoid, 4 (19%) in the left colon, 1 (4%) in the splenic flexure, 2 in the transverse colon (9%), 1 in the hepatic flexure (4%) and 5 in the caecum 24(%). One patient had a tumour too diffuse to detect a primary site at the time of operation. One patient with a family history of polyps had his entire colon removed at age 14. He had 3 separate foci of tumour. The 5-year survival rate was 25%.
    DISCUSSION: Most patients with extensive disease and mucinous histology. Lesions are commonly seen beyond the transverse colon (57%). Presentation included most commonly abdominal pain, haematochezia or haemoccult positive stools.
    CONCLUSION: The symptoms above should alert surgeons to colorectal carcinoma as a differential diagnosis
    Matched MeSH terms: Colonic Neoplasms/pathology
  4. Bioengineered silver nanoparticles capped with bovine serum albumin and its anticancer and apoptotic activity against breast, bone and intestinal colon cancer cell lines
    Majeed S, Aripin FHB, Shoeb NSB, Danish M, Ibrahim MNM, Hashim R
    Mater Sci Eng C Mater Biol Appl, 2019 Sep;102:254-263.
    PMID: 31146998 DOI: 10.1016/j.msec.2019.04.041
    The aim of the current study was to biosynthesize the silver nanoparticles (AgNPs) from the bacterial strain of Bacillus cereus (ATCC 14579) extracellularly. When bacterial extract was challenged with 1 mM silver nitrate (AgNO3) the color of the extract changed into brown confirms the formation of nanoparticles. These nanoparticles were capped with bovine serum albumin (BSA). UV- visible spectroscopy showed the absorption peak at 420 nm indicates the formation of AgNPs. Fourier Infra -red (FTIR) attenuated total reflection (ATR) spectroscopy showed amide and amine group associated with AgNPs that stabilizes the nanoparticles. Energy dispersive x-ray spectroscopy (EDX) showed a strong peak of silver confirms the presence of silver. Thermo gravimetric analysis (TGA) analysis was used to determine the protein degradation showed less protein degradation at higher temperature confirms the stability of nanoparticles. Transmission electron microscopy (TEM) showed the AgNPs are well dispersed and spherical, and 5.37 nm to 17.19 whereas albumin coated nanoparticles are size ranges from 11.26 nm to 23.85 nm. The anticancer effect of capped AgNPs (cAgNPs) showed the IC50 value against breast cancer MCF-7 at 80 μg/mL, intestinal colon cancer HCT- 116 60 μg/mL, and bone cancer osteosarcoma MG-63 cell line80 μg/mL while against normal fibroblast cells 3T3 cells showed the IC50 value at 140 μg/mL. Lactate dehydrogenase assay (LDH) showed higher toxicity on MCF-7, HCT-116, and MG-63 cells. The apoptotic study clearly showed the blebbing of membrane, chromatin condensation due to the production of reactive oxygen species (ROS) by ethidium bromide and acridine orange dual staining method. The DNA analysis showed the complete fragmentation of the DNA of treated cells when compared with control cells.
    Matched MeSH terms: Colonic Neoplasms/pathology
  5. Lignans and Polyphenols of Phyllanthus amarus Schumach and Thonn Induce Apoptosis in HCT116 Human Colon Cancer Cells through Caspases-Dependent Pathway
    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/pathology
  6. Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC 6H 4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination
    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/pathology
  7. 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ)
    Tan BS, Kang O, Mai CW, Tiong KH, Khoo AS, Pichika MR, et al.
    Cancer Lett, 2013 Aug 9;336(1):127-39.
    PMID: 23612072 DOI: 10.1016/j.canlet.2013.04.014
    6-Shogaol has been shown to possess many antitumor properties including inhibition of cancer cell growth, inhibition of cancer metastasis, induction of apoptosis in cancer cells and induction of cancer cell differentiation. Despite its prominent antitumor effects, the direct molecular target of 6-shogaol has remained elusive. To identify the direct targets of 6-shogaol, a comprehensive antitumor profile of 6-shogaol (NSC752389) was tested in the NCI-60 cell line in an in vitro screen. The results show that 6-shogaol is COMPARE negative suggesting that it functions via a mechanism of action distinct from existing classes of therapeutic agents. Further analysis using microarray gene profiling and Connectivity Map analysis showed that MCF-7 cells treated with 6-shogaol display gene expression signatures characteristic of peroxisome proliferator activated receptor γ (PPARγ) agonists, suggesting that 6-shogaol may activate the PPARγ signaling pathway for its antitumor effects. Indeed, treatment of MCF-7 and HT29 cells with 6-shogaol induced PPARγ transcriptional activity, suppressed NFκB activity, and induced apoptosis in breast and colon cancer cells in a PPARγ-dependent manner. Furthermore, 6-shogaol is capable of binding to PPARγ with a binding affinity comparable to 15-delta prostaglandin J2, a natural ligand for PPARγ. Together, our findings suggest that the antitumor effects of 6-shogaol are mediated through activation of PPARγ and imply that activation of PPARγ might be beneficial for breast and colon cancer treatment.
    Matched MeSH terms: Colonic Neoplasms/pathology
  8. Inducing G2/M Cell Cycle Arrest and Apoptosis through Generation Reactive Oxygen Species (ROS)-Mediated Mitochondria Pathway in HT-29 Cells by Dentatin (DEN) and Dentatin Incorporated in Hydroxypropyl-β-Cyclodextrin (DEN-HPβCD)
    Ashwaq AS, Al-Qubaisi MS, Rasedee A, Abdul AB, Taufiq-Yap YH, Yeap SK
    Int J Mol Sci, 2016 Oct 18;17(10).
    PMID: 27763535
    Dentatin (DEN), purified from the roots of Clausena excavata Burm f., has poor aqueous solubility that reduces its therapeutic application. The aim of this study was to assess the effects of DEN-HPβCD (hydroxypropyl-β-cyclodextrin) complex as an anticancer agent in HT29 cancer cell line and compare with a crystal DEN in dimethyl sulfoxide (DMSO). The exposure of the cancer cells to DEN or DEN-HPβCD complex leads to cell growth inhibition as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To analyze the mechanism, in which DEN or DEN-HPβCD complex causes the death in human colon HT29 cancer cells, was evaluated by the enzyme-linked immunosorbent assay (ELIZA)-based assays for caspase-3, 8, 9, and reactive oxygen species (ROS). The findings showed that an anti-proliferative effect of DEN or DEN-HPβCD complex were via cell cycle arrest at the G2/M phase and eventually induced apoptosis through both mitochondrial and extrinsic pathways. The down-regulation of poly(ADP-ribose) polymerase (PARP) which leaded to apoptosis upon treatment, was investigated by Western-blotting. Hence, complexation between DEN and HPβCD did not diminish or eliminate the effective properties of DEN as anticancer agent. Therefore, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents in the future.
    Matched MeSH terms: Colonic Neoplasms/pathology
  9. Fulltext Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G(1) arrest and apoptosis
    Jada SR, Matthews C, Saad MS, Hamzah AS, Lajis NH, Stevens MF, et al.
    Br J Pharmacol, 2008 Nov;155(5):641-54.
    PMID: 18806812 DOI: 10.1038/bjp.2008.368
    BACKGROUND AND PURPOSE: Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death.
    EXPERIMENTAL APPROACH: Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry.
    KEY RESULTS: Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF-7 (breast) and HCT-116 (colon) cancer cells. In the NCI screen, 3,19-(2-bromobenzylidene) andrographolide (SRJ09) and 3,19-(3-chloro-4-fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G(1) arrest and apoptosis in MCF-7 and HCT-116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF-7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT-116 cells was confirmed by annexin V-FITC/PI flow cytometry analysis.
    CONCLUSION AND IMPLICATIONS: The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G(1) phase cell cycle arrest, coupled with induction of apoptosis.
    Matched MeSH terms: Colonic Neoplasms/pathology
  10. Fulltext 1-(2,6-dihydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl) ethanone-induced cell cycle arrest in G₁/G₀ in HT-29 cells human colon adenocarcinoma cells
    Lay MM, Karsani SA, Malek SN
    Int J Mol Sci, 2014 Jan 02;15(1):468-83.
    PMID: 24451128 DOI: 10.3390/ijms15010468
    1-(2,6-Dihydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl) ethanone (DMHE) was isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff.) Boerl fruits and the structure confirmed by GC-MS (gas chromatography-mass spectrometry) and NMR (nuclear magnetic resonance) analysis. This compound was tested on the HT-29 human colon adenocarcinoma cell line using MTT (method of transcriptional and translational) cell proliferation assay. The results of MTT assay showed that DMHE exhibited good cytotoxic effect on HT-29 cells in a dose- and time-dependent manner but no cytotoxic effect on the MRC-5 cell line after 72 h incubation. Morphological features of apoptotic cells upon treatment by DMHE, e.g., cell shrinkage and membrane blebbing, were examined by an inverted and phase microscope. Other features, such as chromatin condension and nuclear fragmentation were studied using acridine orange and propidium iodide staining under the fluorescence microscope. Future evidence of apoptosis/necrosis was provided by result fromannexin V-FITC/PI (fluorescein-isothiocyanate/propidium iodide) staining revealed the percentage of early apoptotic, late apoptotic, necrotic and live cells in a dose- and time-dependent manner using flow cytometry. Cell cycle analysis showed G0/G1 arrest in a time-dependent manner. A western blot analysis indicated that cell death might be associated with the up-regulation of the pro-apoptotic proteins Bax PUMA. However, the anit-apotptic proteins Bcl-2, Bcl-xL, and Mcl-1 were also found to increase in a time-dependent manner. The expression of the pro-apoptotic protein Bak was not observed.
    Matched MeSH terms: Colonic Neoplasms/pathology
  11. Adaptation of international guidelines for metastatic colorectal cancer: an asian consensus
    Cheng AL, Li J, Vaid AK, Ma BB, Teh C, Ahn JB, et al.
    Clin Colorectal Cancer, 2014 Sep;13(3):145-55.
    PMID: 25209093 DOI: 10.1016/j.clcc.2014.06.004
    Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.
    Matched MeSH terms: Colonic Neoplasms/pathology
  12. Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment
    Bose A, Elyagoby A, Wong TW
    Int J Pharm, 2014 Jul 1;468(1-2):178-86.
    PMID: 24709212 DOI: 10.1016/j.ijpharm.2014.04.006
    In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.
    Matched MeSH terms: Colonic Neoplasms/pathology
  13. Fulltext Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells
    Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA
    Nutr J, 2015;14:31.
    PMID: 25889965 DOI: 10.1186/s12937-015-0015-2
    The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29.
    Matched MeSH terms: Colonic Neoplasms/pathology
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