Displaying publications 1 - 20 of 418 in total

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  1. Li CMY, Briggs MT, Lee YR, Tin T, Young C, Pierides J, et al.
    Clin Exp Med, 2024 Mar 16;24(1):53.
    PMID: 38492056 DOI: 10.1007/s10238-024-01311-5
    Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.
    Matched MeSH terms: Colorectal Neoplasms*
  2. Saadh MJ, Mohamed AH, Almoyad MAA, Allela OQB, Amin AH, Malquisto AA, et al.
    Cell Biochem Funct, 2024 Mar;42(2):e3962.
    PMID: 38491792 DOI: 10.1002/cbf.3962
    Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC.
    Matched MeSH terms: Colorectal Neoplasms*
  3. Fareez IM, Lim SM, Ramasamy K
    Probiotics Antimicrob Proteins, 2024 Feb;16(1):99-112.
    PMID: 36508139 DOI: 10.1007/s12602-022-10020-y
    The pathogenesis of colorectal cancer (CRC) is associated with gut dysbiosis that is attributed to unhealthy lifestyles and dietary habits. Consumption of microencapsulated probiotics may potentially restore the gut microbiota in favour of prevention against CRC. This study determined the fate of microencapsulated Lactiplantibacillus plantarum (formerly known as Lactobacillus plantarum) LAB12 in the gastrointestinal tract (GIT) and assessed the chemopreventive effect of microencapsulated L. plantarum LAB12 in vivo. The targeted release of L. plantarum LAB12 from Alg-based microcapsules at the stomach, ileum, caecum and colon of Sprague-Dawley rats was examined by confocal microscopy and qPCR. Microcapsules loaded with L. plantarum LAB12 remained intact in the stomach. Free L. plantarum LAB12 were present in abundance (> 7 log CFU) only in the intestines. Subsequently, the chemopreventive properties of microencapsulated L. plantarum LAB12 were validated against NU/NU nude mice bearing orthotopic transplanted CT-26 CRC (12 female mice; 4-6 weeks old; 20-22 g; n = 6/group). Orthotopic mice pre-supplemented with microencapsulated L. plantarum LAB12 (10 log CFU kg-1 BW for 11 weeks) were presented with significantly (p 
    Matched MeSH terms: Colorectal Neoplasms*
  4. Lin G, Dong L, Cheng KK, Xu X, Wang Y, Deng L, et al.
    Anal Chem, 2023 Aug 22;95(33):12505-12513.
    PMID: 37557184 DOI: 10.1021/acs.analchem.3c02246
    Metabolic pathways are regarded as functional and basic components of the biological system. In metabolomics, metabolite set enrichment analysis (MSEA) is often used to identify the altered metabolic pathways (metabolite sets) associated with phenotypes of interest (POI), e.g., disease. However, in most studies, MSEA suffers from the limitation of low metabolite coverage. Random walk (RW)-based algorithms can be used to propagate the perturbation of detected metabolites to the undetected metabolites through a metabolite network model prior to MSEA. Nevertheless, most of the existing RW-based algorithms run on a general metabolite network constructed based on public databases, such as KEGG, without taking into consideration the potential influence of POI on the metabolite network, which may reduce the phenotypic specificities of the MSEA results. To solve this problem, a novel pathway analysis strategy, namely, differential correlation-informed MSEA (dci-MSEA), is proposed in this paper. Statistically, differential correlations between metabolites are used to evaluate the influence of POI on the metabolite network, so that a phenotype-specific metabolite network is constructed for RW-based propagation. The experimental results show that dci-MSEA outperforms the conventional RW-based MSEA in identifying the altered metabolic pathways associated with colorectal cancer. In addition, by incorporating the individual-specific metabolite network, the dci-MSEA strategy is easily extended to disease heterogeneity analysis. Here, dci-MSEA was used to decipher the heterogeneity of colorectal cancer. The present results highlight the clustering of colorectal cancer samples with their cluster-specific selection of differential pathways and demonstrate the feasibility of dci-MSEA in heterogeneity analysis. Taken together, the proposed dci-MSEA may provide insights into disease mechanisms and determination of disease heterogeneity.
    Matched MeSH terms: Colorectal Neoplasms*
  5. Ng PY, Nafi SNM, Jalil NAC, Kueh YC, Lee YY, Zin AAM
    Croat Med J, 2023 Feb 28;64(1):29-36.
    PMID: 36864816
    AIM: To assess the association of the expression of apolipoprotein B (apoB) and 4-hydroxynonenal (4HNE) with the clinicopathological data of patients with colorectal cancer (CRC).

    METHODS: We obtained 80 CRC histopathological specimens sent to the Pathology Laboratory of Hospital Universiti Sains Malaysia from 2015 to 2019. Data on demographic factors, body mass index (BMI), and clinicopathological characteristics were also collected. Formalin-fixed paraffin-embedded tissues were stained by using an optimized immunohistochemical protocol.

    RESULTS: Patients were mostly older than 50 years, male, Malay, and overweight or obese. A high apoB expression was observed in 87.5% CRC samples (70/80), while a high 4HNE expression was observed in only 17.5% (14/80) of CRCs. The expression of apoB was significantly associated with the sigmoid and rectosigmoid tumor sites (p =0.001) and tumor size 3-5 cm (p =0.005). 4HNE expression was significantly associated with tumor size 3-5 cm (p =0.045). Other variables were not significantly associated with the expression of either marker.

    CONCLUSION: ApoB and 4HNE proteins may play a role in promoting CRC carcinogenesis.

    Matched MeSH terms: Colorectal Neoplasms*
  6. Ramizah MS, Tee SC, Muhammad SJ, Abdul AH, Shahabuddin NH, Saiyidah Adila A
    Med J Malaysia, 2023 Jan;78(1):39-45.
    PMID: 36715190
    INTRODUCTION: Several risk factors found to be associated with postoperative complications and cancer surgery, which carry a significant morbidity risk to cancer patients. Therefore, prehabilitation is necessary to improve the functional capability and nutritional status of a patient prior to surgery, so that the patient can withstand any postoperative activity and associated deterioration. Thus, this study aims to assess the effectiveness of prehabilitation interventions on the functional status of patients with gastric and oesophageal cancer who underwent esophagectomy and gastrectomy.

    MATERIAL AND METHODS: An interventional study was carried out among oesophageal and gastric cancer patients who had undergone surgery at the National Cancer Institute of Malaysia. The prehabilitation process took a maximum of two weeks, depending on the patient's optimisation before surgery. The prehabilitation is based on functional capacity (ECOG performance status), muscle function (handgrip strength), cardio-respiratory function (peak flow meter) and nutritional status (calorie and protein). Postoperative outcomes are measured based on the length of hospital stay, complications, and Clavien-Dindo Classification.

    RESULTS: Thirty-one patients were recruited to undergo a prehabilitation intervention prior to gastrectomy (n=21) and esophagectomy (n=10). Demographically, most of the cancer patients were males (67.7%) with an ideal mean of BMI (23.5±6.0). Physically, the majority of them had physical class (ASA grade) Grade 2 (67.7%), ECOG performance status of 1 (61.3%) and SGA grade B (51.6%). The functional capacity and nutritional status showed a significant improvement after one week of prehabilitation interventions: peak expiratory flow meter (p<0.001), handgrip (p<0.001), ECOG performance (p<0.001), walking distance (p<0.001), incentive spirometry (p<0.001), total body calorie (p<0.001) and total body protein (p=0.004). However, those patients who required two weeks of prehabilitation for optimization showed only significant improvement in peak expiratory flow meter (p<0.001), handgrip (p<0.001), and incentive spirometry (p<0.001). Prehabilitation is significantly associated postoperatively with the length of hospital stay (p=0.028), complications (p=0.011) and Clavien-Dindo Classification (p=0.029).

    CONCLUSION: Prehabilitation interventions significantly increase the functional capacity and nutritional status of cancer patients preoperatively; concurrently reducing hospital stays and complications postoperatively. However, certain cancer patients might require over two weeks of prehabilitation to improve the patient's functional capacity and reduce complications postoperatively.

    Matched MeSH terms: Colorectal Neoplasms*
  7. Pramanik A, Xu Z, Shamsuddin SH, Khaled YS, Ingram N, Maisey T, et al.
    ACS Appl Mater Interfaces, 2022 Mar 09;14(9):11078-11091.
    PMID: 35196008 DOI: 10.1021/acsami.1c21655
    Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior in vivo is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group Im3m that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells. Unlike nontargeted cubosomes, Affimer tagged cubosomes showed preferential accumulation in cancer cells compared to normal cells not only in vitro (2D monolayer cell culture and 3D spheroid models) but also in vivo in colorectal cancer mouse xenografts, while exhibiting low nonspecific absorption and toxicity in other vital organs. Cancerous spheroids had maximum cell death compared to noncancerous cells upon targeted delivery. Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  8. 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*
  9. Chan MW, Chean KY, Kader Maideen SF, Kow FP
    Asian Pac J Cancer Prev, 2021 Nov 01;22(11):3475-3482.
    PMID: 34837902 DOI: 10.31557/APJCP.2021.22.11.3475
    Colorectal cancer (CRC) is the most common cancer in men and the second most common cancer in women in Malaysia. A major challenge for CRC screening programs is to improve the screening participation rates. In Malaysia, the most critical barrier to the uptake of CRC screening is the lack of patient awareness. This study aimed to determine the intention and the uptake of CRC screening, and to explore the related motivators and barriers after raising awareness with a brief health education.

    METHODS: An analytical cross-sectional study was conducted in a government health clinic of Penang from March to August 2019. Asymptomatic clinic attendees aged 50-75 years who had no prior awareness of CRC screening were recruited by systematic random sampling technique. Participants first received a standardised one to one health education, followed by an interview using a standardised questionnaire to assess their CRC screening intention and the relevant motivators and barriers. A submission of a sample for immunochemical faecal occult blood test (iFOBT) was considered as an uptake of the CRC screening.

    RESULTS: A total of 546 participants participated in this study. The mean age of the participants was 62.8 (SD=6.36). Majority of them were females (57.3%), Chinese (78.6%), who had attained primary or higher education (92.0%) and had comorbidities (87.0%).  After a brief health education, 231 participants (42.3%) agreed to undergo iFOBT. The actual screening uptake rate in this study was 28%. Perceived benefit of the test (84.4%) was the most common motivators, while self-perceived non-vulnerability was the biggest impediment to CRC screening intention. Physicians' recommendation was the perceived most effective way in raising CRC awareness.

    CONCLUSION: Participants prefer physicians to provide health education. Standardised brief health education is inadequate to stimulate CRC screening adherence. Future interventions will require in-depth understanding of patients' beliefs, risk perception, and affective responses.

    Matched MeSH terms: Colorectal Neoplasms/diagnosis*
  10. Tan YJ, Lee YT, Mancera RL, Oon CE
    Life Sci, 2021 Nov 01;284:119747.
    PMID: 34171380 DOI: 10.1016/j.lfs.2021.119747
    BZD9L1 was previously described as a SIRT1/2 inhibitor with anti-cancer activities in colorectal cancer (CRC), either as a standalone chemotherapy or in combination with 5-fluorouracil. BZD9L1 was reported to induce apoptosis in CRC cells; however, the network of intracellular pathways and crosstalk between molecular players mediated by BZD9L1 is not fully understood. This study aimed to uncover the mechanisms involved in BZD9L1-mediated cytotoxicity based on previous and new findings for the prediction and identification of related pathways and key molecular players. BZD9L1-regulated candidate targets (RCTs) were identified using a range of molecular, cell-based and biochemical techniques on the HCT 116 cell line. BZD9L1 regulated major cancer pathways including Notch, p53, cell cycle, NFκB, Myc/MAX, and MAPK/ERK signalling pathways. BZD9L1 also induced reactive oxygen species (ROS), regulated apoptosis-related proteins, and altered cell polarity and adhesion profiles. In silico analyses revealed that most RCTs were interconnected, and were involved in the modulation of catalytic activity, metabolism and transcription regulation, response to cytokines, and apoptosis signalling pathways. These RCTs were implicated in p53-dependent apoptosis pathway. This study provides the first assessment of possible associations of molecular players underlying the cytotoxic activity of BZD9L1, and establishes the links between RCTs and apoptosis through the p53 pathway.
    Matched MeSH terms: Colorectal Neoplasms/metabolism; Colorectal Neoplasms/pathology*
  11. Schliemann D, Ramanathan K, Matovu N, O'Neill C, Kee F, Su TT, et al.
    BMC Cancer, 2021 Oct 19;21(1):1125.
    PMID: 34666704 DOI: 10.1186/s12885-021-08809-1
    BACKGROUND: Low- and middle-income countries (LMICs) experienced increasing rates of colorectal cancer (CRC) incidence in the last decade and lower 5-year survival rates compared to high-income countries (HICs) where the implementation of screening and treatment services have advanced. This review scoped and mapped the literature regarding the content, implementation and uptake of CRC screening interventions as well as opportunities and challenges for the implementation of CRC screening interventions in LMICs.

    METHODS: We systematically followed a five-step scoping review framework to identify and review relevant literature about CRC screening in LMICs, written in the English language before February 2020. We searched Medline, Embase, Web of Science and Google Scholar for studies targeting the general, asymptomatic, at-risk adult population. The TIDieR tool and an implementation checklist were used to extract data from empirical studies; and we extracted data-informed insights from policy reviews and commentaries.

    RESULTS: CRC screening interventions (n = 24 studies) were implemented in nine middle-income countries. Population-based screening programmes (n = 11) as well as small-scale screening interventions (n = 13) utilised various recruitment strategies. Interventions that recruited participants face-to-face (alone or in combination with other recruitment strategies) (10/15), opportunistic clinic-based screening interventions (5/6) and educational interventions combined with screening (3/4), seemed to be the strategies that consistently achieved an uptake of > 65% in LMICs. FOBT/FIT and colonoscopy uptake ranged between 14 and 100%. The most commonly reported implementation indicator was 'uptake/reach'. There was an absence of detail regarding implementation indicators and there is a need to improve reporting practice in order to disseminate learning about how to implement programmes.

    CONCLUSION: Opportunities and challenges for the implementation of CRC screening programmes were related to the reporting of CRC cases and screening, cost-effective screening methods, knowledge about CRC and screening, staff resources and training, infrastructure of the health care system, financial resources, public health campaigns, policy commitment from governments, patient navigation, planning of screening programmes and quality assurance.

    Matched MeSH terms: Colorectal Neoplasms/diagnosis*
  12. Dahham SS, Tabana Y, Asif M, Ahmed M, Babu D, Hassan LE, et al.
    Int J Mol Sci, 2021 Sep 29;22(19).
    PMID: 34638895 DOI: 10.3390/ijms221910550
    Beta-Caryophyllene (BCP), a naturally occurring sesquiterpene abundantly found in cloves, hops, and cannabis, is the active candidate of a relatively new group of vascular-inhibiting compounds that aim to block existing tumor blood vessels. Previously, we have reported the anti-cancer properties of BCP by utilizing a series of in-vitro anti-tumor-related assays using human colorectal carcinoma cells. The present study aimed to investigate the effects of BCP on in-vitro, ex-vivo, and in-vivo models of anti-angiogenic assays and evaluate its anti-cancer activity in xenograft tumor (both ectopic and orthotopic) mice models of human colorectal cancer. Computational structural analysis and an apoptosis antibody array were also performed to understand the molecular players underlying this effect. BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of rat aorta microvessels. BCP has a probable binding at Site#0 on the surface of VEGFR2. Moreover, BCP significantly deformed the vascularization architecture compared to the negative control in a chick embryo chorioallantoic membrane assay. BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively. The histological analysis of the tumor from BCP-treated mice revealed a clear reduction of the density of vascularization. In addition, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions. These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.
    Matched MeSH terms: Colorectal Neoplasms/blood supply; Colorectal Neoplasms/prevention & control*
  13. Juhari WKW, Ahmad Amin Noordin KB, Zakaria AD, Rahman WFWA, Mokhter WMMWM, Hassan MRA, et al.
    Genes (Basel), 2021 09 20;12(9).
    PMID: 34573430 DOI: 10.3390/genes12091448
    BACKGROUND: This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression.

    METHOD: Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms.

    RESULTS: An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes-IFNE, PTCH2 and SEMA3D-which were predicted to affect protein function, were identified in three Malay CRC patients. In addition, 19 candidate genes-ANKDD1B, CENPM, CLDN5, MAGEB16, MAP3K14, MOB3C, MS4A12, MUC19, OR2L8, OR51Q1, OR51AR1, PDE4DIP, PKD1L3, PRIM2, PRM3, SEC22B, TPTE, USP29 and ZNF117-harbouring nonsense variants were prioritised. These genes are suggested to play a role in cancer predisposition and to be associated with cancer risk. Pathway enrichment analysis indicated significant enrichment in the olfactory signalling pathway.

    CONCLUSION: This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients.

    Matched MeSH terms: Colorectal Neoplasms/genetics*; Colorectal Neoplasms/pathology
  14. Loh SY, Sapihis M, Danaee M, Chua YP
    Disabil Rehabil, 2021 09;43(19):2729-2738.
    PMID: 31962056 DOI: 10.1080/09638288.2020.1715492
    PURPOSE: This novel study aims to explore the relationship between occupational participation, meaningful activity, and the health-related quality of life of people living with a diagnosis of colorectal cancer.

    METHODS: A cross-sectional study design with 113 colorectal cancer survivors (from two large public hospitals in Malaysia) was conducted. Data collection tools included the Occupational Participation Questionnaire, Engagement in Meaningful-activities, and the European Organization for Research and Treatment in Cancer Quality of Life (QOL) Questionnaire. Data analyses were conducted using SmartPLS to examine path analyses between the three measures.

    RESULTS: There were independent significant relationships between (1) occupational participation, and (2) meaningful activity engagements on the dependent variable of QOL in this cohort of cancer survivors. More importantly, the result showed that "meaningful-activity" positively and significantly mediates the path between occupational participation and quality of life [β = 0.250 (0.46*0.59), ρ 

    Matched MeSH terms: Colorectal Neoplasms*
  15. Ishak NIM, Mohamed S, Madzuki IN, Mustapha NM, Esa NM
    Naunyn Schmiedebergs Arch Pharmacol, 2021 09;394(9):1907-1915.
    PMID: 34009457 DOI: 10.1007/s00210-021-02101-6
    Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Male Balb/c mice were randomly assorted into three groups (n = 6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced + 50 mg limonin/kg body weight. The CRC developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin E2, and histopathology inflammation scores, while increasing reduced glutathione (GSH) in CRC-induced mice. Limonin significantly (p 
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*; Colorectal Neoplasms/pathology
  16. Chok KC, Koh RY, Ng MG, Ng PY, Chye SM
    Molecules, 2021 Aug 20;26(16).
    PMID: 34443626 DOI: 10.3390/molecules26165038
    Even though an increasing number of anticancer treatments have been discovered, the mortality rates of colorectal cancer (CRC) have still been high in the past few years. It has been discovered that melatonin has pro-apoptotic properties and counteracts inflammation, proliferation, angiogenesis, cell invasion, and cell migration. In previous studies, melatonin has been shown to have an anticancer effect in multiple tumors, including CRC, but the underlying mechanisms of melatonin action on CRC have not been fully explored. Thus, in this study, we investigated the role of autophagy pathways in CRC cells treated with melatonin. In vitro CRC cell models, HT-29, SW48, and Caco-2, were treated with melatonin. CRC cell death, oxidative stress, and autophagic vacuoles formation were induced by melatonin in a dose-dependent manner. Several autophagy pathways were examined, including the endoplasmic reticulum (ER) stress, 5'-adenosine monophosphate-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (Akt), and mammalian target of rapamycin (mTOR) signaling pathways. Our results showed that melatonin significantly induced autophagy via the ER stress pathway in CRC cells. In conclusion, melatonin demonstrated a potential as an anticancer drug for CRC.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*; Colorectal Neoplasms/metabolism
  17. Noman E, Al-Shaibani MM, Bakhrebah MA, Almoheer R, Al-Sahari M, Al-Gheethi A, et al.
    J Fungi (Basel), 2021 May 30;7(6).
    PMID: 34070936 DOI: 10.3390/jof7060436
    The promising feature of the fungi from the marine environment as a source for anticancer agents belongs to the fungal ability to produce several compounds and enzymes which contribute effectively against the cancer cells growth. L-asparaginase acts by degrading the asparagine which is the main substance of cancer cells. Moreover, the compounds produced during the secondary metabolic process acts by changing the cell morphology and DNA fragmentation leading to apoptosis of the cancer cells. The current review has analyed the available information on the anticancer activity of the fungi based on the data extracted from the Scopus database. The systematic and bibliometric analysis revealed many of the properties available for the fungi to be the best candidate as a source of anticancer drugs. Doxorubicin, actinomycin, and flavonoids are among the primary chemical drug used for cancer treatment. In comparison, the most anticancer compounds producing fungi are Aspergillusniger, A.fumigatusA.oryzae, A.flavus, A. versicolor, A.terreus,Penicilliumcitrinum, P.chrysogenum, and P.polonicum and have been used for investigating the anticancer activity against the uterine cervix, pancreatic cancer, ovary, breast, colon, and colorectal cancer.
    Matched MeSH terms: Colorectal Neoplasms
  18. Kumar M, Tata MD, Sahid Nik Lah NA
    Ann Med Surg (Lond), 2021 May;65:102353.
    PMID: 34007446 DOI: 10.1016/j.amsu.2021.102353
    Introduction: Signet cell carcinoma (SRCC)of the rectum is a rare subtype of the rectum cancer which accounts for only 0.8% of colorectal cancer in adolescents and young adults (AYAs) which spread aggressively to other organs and peritoneum.

    Case presentation: We present a case of 15-year-old boy from rural area, presented with chronic diarrhea and per rectal bleeding for 3 months. The diagnosis was determined by colonoscope which revealed a fungating mass identified at 10cm from anal verge. Histological examination confirmed diagnosis of signet ring cell adenocarcinoma. CT scan of the abdomen showed thickening involving the recto-sigmoid colon and rectal mass, without evidence of distant metastatic disease. The patient's carcinoembryonic antigen level was within the normal range. He underwent a colostomy and was subjected to neoadjuvant CCRT and surgery.

    Discussion: This CASE highlights the importance and challenges in achieving early diagnosis and surgical intervention of signet-ring cell carcinoma in adolescents, as most cases are detected at an advanced stage coupled with the scarcity of information on these rarer subtypes which leads to a poor prognosis.

    Conclusion: In managing Signet cell carcinoma of the colorectal, physician have to know that it has a poor prognosis in patients of any age. However, in young teenagers delayed diagnosis and treatment option are narrowed to palliative management. Genetic profiling of family members and similar environment population may be a key to early detection.

    Matched MeSH terms: Colorectal Neoplasms
  19. Che Jalil NA, Rama Chandran P, Samsudin AHZ, Yahya MM, Wan Abdul Rahman WF
    Malays J Pathol, 2021 Apr;43(1):69-73.
    PMID: 33903308
    Cancer metastasis to the thyroid gland from non-thyroid sites is a rare presentation in clinical practice. The most frequent primary cancers that metastasise to the thyroid are renal cell carcinoma, followed by colorectal, lung and breast. We report a case of a 64-year-old Malay lady who presented with anterior neck swelling 4 years after an initial diagnosis of uterine leiomyosarcoma. She had undergone a hysterectomy procedure four years ago. Fine needle aspiration cytology of the thyroid mass suggested undifferentiated thyroid carcinoma. After multi-disciplinary discussion, the patient underwent thyroidectomy and the final histopathological diagnosis was metastatic leiomyosarcoma of the thyroid. The diagnosis was aided by an immunohistochemistry panel of positive myogenic markers, negative epithelial markers as well as the previous medical history of uterine leiomyosarcoma. Metastatic leiomyosarcoma of the thyroid may mimic primary undifferentiated (anaplastic) thyroid carcinoma (UTC) with a sarcomatoid pattern, medullary thyroid carcinoma (MTC) with spindle cells morphology and spindle cell tumour with thymus-like differentiation (SETTLE). Hence, a multidisciplinary approach must be practised by pathologists, surgeons and radiologists to consider metastatic lesions of the thyroid gland, especially when a previous history of cancer exists or is suspected.
    Matched MeSH terms: Colorectal Neoplasms
  20. 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: Colorectal Neoplasms
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