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Fulltext Comparative aspects of microRNA expression in canine and human cancers

Sahabi K, Selvarajah GT, Abdullah R, Cheah YK, Tan GC

J Vet Sci, 2018 Mar 31;19(2):162-171.
PMID: 28927253 DOI: 10.4142/jvs.2018.19.2.162

MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.
Fulltext Targeted inactivation of Salmonella Agona metabolic genes by group II introns and in vivo assessment of pathogenicity and anti-tumour activity in mouse model

Gwee CP, Khoo CH, Yeap SK, Tan GC, Cheah YK

PeerJ, 2019;7:e5989.
PMID: 30671294 DOI: 10.7717/peerj.5989

The fight against cancer has been a never-ending battle. Limitations of conventional therapies include lack of selectivity, poor penetration and highly toxic to the host. Using genetically modified bacteria as a tumour therapy agent has gained the interest of scientist from the past few decades. Low virulence and highly tolerability of Salmonella spp. in animals and humans make it as the most studied pathogen with regards to anti-tumour therapy. The present study aims to construct a genetically modified S. Agona auxotroph as an anti-tumour agent. LeuB and ArgD metabolic genes in ΔSopBΔSopD double knockout S. Agona were successfully knocked out using a Targetron gene knockout system. The knockout was confirmed by colony PCR and the strains were characterized in vitro and in vivo. The knockout of metabolic genes causes significant growth defect in M9 minimal media. Quadruple knockout ΔSopBΔSopDΔLeuBΔArgD (BDLA) exhibited lowest virulence among all of the strains in all parameters including bacterial load, immunity profile and histopathology studies. In vivo anti-tumour study on colorectal tumour bearing-BALB/c mice revealed that all strains of S. Agona were able to suppress the growth of the large solid tumour as compared with negative control and ΔLeuBΔArgD (LA) and BDLA auxotroph showed better efficacy. Interestingly, higher level of tumour growth suppression was noticed in large tumour. However, multiple administration of bacteria dosage did not increase the tumour suppression efficacy. In this study, the virulence of BDLA knockout strain was slightly reduced and tumour growth suppression efficacy was successfully enhanced, which provide a valuable starting point for the development of S. Agona as anti-tumour agent.
Fulltext Physiologically Relevant Alternative Carbon Sources Modulate Biofilm Formation, Cell Wall Architecture, and the Stress and Antifungal Resistance of Candida glabrata

Chew SY, Ho KL, Cheah YK, Sandai D, Brown AJP, Than LTL

Int J Mol Sci, 2019 Jun 28;20(13).
PMID: 31261727 DOI: 10.3390/ijms20133172

Flexibility in carbon metabolism is pivotal for the survival and propagation of many human fungal pathogens within host niches. Indeed, flexible carbon assimilation enhances pathogenicity and affects the immunogenicity of Candida albicans. Over the last decade, Candida glabrata has emerged as one of the most common and problematic causes of invasive candidiasis. Despite this, the links between carbon metabolism, fitness, and pathogenicity in C. glabrata are largely unexplored. Therefore, this study has investigated the impact of alternative carbon metabolism on the fitness and pathogenic attributes of C. glabrata. We confirm our previous observation that growth on carbon sources other than glucose, namely acetate, lactate, ethanol, or oleate, attenuates both the planktonic and biofilm growth of C. glabrata, but that biofilms are not significantly affected by growth on glycerol. We extend this by showing that C. glabrata cells grown on these alternative carbon sources undergo cell wall remodeling, which reduces the thickness of their β-glucan and chitin inner layer while increasing their outer mannan layer. Furthermore, alternative carbon sources modulated the oxidative stress resistance of C. glabrata as well as the resistance of C. glabrata to an antifungal drug. In short, key fitness and pathogenic attributes of C. glabrata are shown to be dependent on carbon source. This reaffirms the perspective that the nature of the carbon sources available within specific host niches is crucial for C. glabrata pathogenicity during infection.
Fulltext The Role of Breast Cancer Stem Cell-Related Biomarkers as Prognostic Factors

Ko CCH, Chia WK, Selvarajah GT, Cheah YK, Wong YP, Tan GC

Diagnostics (Basel), 2020 Sep 19;10(9).
PMID: 32961774 DOI: 10.3390/diagnostics10090721

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide, and its incidence is on the rise. A small fraction of cancer stem cells was identified within the tumour bulk, which are regarded as cancer-initiating cells, possess self-renewal and propagation potential, and a key driver for tumour heterogeneity and disease progression. Cancer heterogeneity reduces the overall efficacy of chemotherapy and contributes to treatment failure and relapse. The cell-surface and subcellular biomarkers related to breast cancer stem cell (BCSC) phenotypes are increasingly being recognised. These biomarkers are useful for the isolation of BCSCs and can serve as potential therapeutic targets and prognostic tools to monitor treatment responses. Recently, the role of noncoding microRNAs (miRNAs) has extensively been explored as novel biomarker molecules for breast cancer diagnosis and prognosis with high specificity and sensitivity. An in-depth understanding of the biological roles of miRNA in breast carcinogenesis provides insights into the pathways of cancer development and its utility for disease prognostication. This review gives an overview of stem cells, highlights the biomarkers expressed in BCSCs and describes their potential role as prognostic indicators.
Fulltext Cellular Metabolic Profiling of CrFK Cells Infected with Feline Infectious Peritonitis Virus Using Phenotype Microarrays

Ng SW, Selvarajah GT, Cheah YK, Mustaffa Kamal F, Omar AR

Pathogens, 2020 May 25;9(5).
PMID: 32466289 DOI: 10.3390/pathogens9050412

Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis.
METHODS: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray™ plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells.
RESULTS: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells.
CONCLUSION: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection.
Fulltext Identification of Potential Chemical Substrates as Fuel for Hypoxic Tumors That May Be Linked to Invadopodium Formation in Hypoxia-Induced MDA-MB-231 Breast-Cancer Cell Line

Hamad HA, Enezei HH, Alrawas A, Zakuan NM, Abdullah NA, Cheah YK, et al.

Molecules, 2020 Aug 26;25(17).
PMID: 32858793 DOI: 10.3390/molecules25173876

Hypoxia plays a significant role in solid tumors by the increased expression of hypoxia-inducible factor-1α (HIF-1α), which is known to promote cancer invasion and metastasis. Cancer-cell invasion dynamically begins with the degradation of the extracellular matrix (ECM) via invadopodia formation. The chemical substrates that are utilized by hypoxic cells as fuel to drive invadopodia formation are still not fully understood. Therefore, the aim of the study was to maintain MDA-MB-231 cells under hypoxia conditions to allow cells to form a large number of invadopodia as a model, followed by identifying their nutrient utilization. The results of the study revealed an increase in the number of cells forming invadopodia under hypoxia conditions. Moreover, Western blot analysis confirmed that essential proteins for hypoxia and invadopodia, including HIF-1α, vascular endothelial growth factor (VEGF), metallopeptidase-2 (MMP-2), and Rho guanine nucleotide exchange factor 7 (β-PIX), significantly increased under hypoxia. Interestingly, phenotype microarray showed that only 11 chemical substrates from 367 types of substrates were significantly metabolized in hypoxia compared to in normoxia. This is thought to be fuel for hypoxia to drive the invasion process. In conclusion, we found 11 chemical substrates that could have potential energy sources for hypoxia-induced invadopodia formation of these cells. This may in part be a target in the hypoxic tumor and invadopodia formation. Additionally, these findings can be used as potential carrier targets in cancer-drug discovery, such as the usage of dextrin.
Fulltext Landmark-based homologous multi-point warping approach to 3D facial recognition using multiple datasets

Agbolade O, Nazri A, Yaakob R, Ghani AAA, Cheah YK

PeerJ Comput Sci, 2020;6:e249.
PMID: 33816901 DOI: 10.7717/peerj-cs.249

Over the years, neuroscientists and psychophysicists have been asking whether data acquisition for facial analysis should be performed holistically or with local feature analysis. This has led to various advanced methods of face recognition being proposed, and especially techniques using facial landmarks. The current facial landmark methods in 3D involve a mathematically complex and time-consuming workflow involving semi-landmark sliding tasks. This paper proposes a homologous multi-point warping for 3D facial landmarking, which is verified experimentally on each of the target objects in a given dataset using 500 landmarks (16 anatomical fixed points and 484 sliding semi-landmarks). This is achieved by building a template mesh as a reference object and applying this template to each of the targets in three datasets using an artificial deformation approach. The semi-landmarks are subjected to sliding along tangents to the curves or surfaces until the bending energy between a template and a target form is minimal. The results indicate that our method can be used to investigate shape variation for multiple datasets when implemented on three databases (Stirling, FRGC and Bosphorus).
Multiple microRNA signature panel as promising potential for diagnosis and prognosis of head and neck cancer

Subha ST, Chin JW, Cheah YK, Mohtarrudin N, Saidi HI

Mol Biol Rep, 2022 Feb;49(2):1501-1511.
PMID: 34837627 DOI: 10.1007/s11033-021-06954-1

MicroRNAs are small non-coding RNA that regulate gene expressions of human body. To date, numerous studies have reported that microRNAs possess great diagnostic and prognostic power in head and neck cancer and had governed a lot of attention. The factor for the successfulness of miRNAs in these aspects is due to cancer being fundamentally tied to genetic changes, which are regulated by these miRNAs. Head and neck cancer, leading the world record for cancer as number sixth, is caused by multiple risk factors such as tobacco consumption, alcohol consumption, dietary factors, ethnicity, family history, and human papilloma virus. It derives at locations such as oral cavity, pharynx, larynx, paranasal sinus and salivary gland and have high rate of mortality with high recurrence rate. Besides, head and neck cancer is also usually having poor prognosis due to its asymptomatic nature. However, this diagnostic and prognostic power can be further improved by using multiple panels of miRNA as a signature or even combined with TNM staging system to obtain even more remarkable results. This is due to multiple factors such as tumour heterogeneity and components of the tumour which may affect the composition of miRNAs. This review covers the examples of such miRNA signatures, compare their diagnostic and prognostic powers, discuss some controversial roles of unreported miRNAs, and the molecular mechanisms of the miRNAs in gene targeting and pathways.
Fulltext Epidermal growth factor receptor mutations in lung adenocarcinoma in Malaysian patients

Liam CK, Wahid MI, Rajadurai P, Cheah YK, Ng TS

J Thorac Oncol, 2013 Jun;8(6):766-72.
PMID: 23575413 DOI: 10.1097/JTO.0b013e31828b5228

Despite available data from other Asian countries, the prevalence of epidermal growth factor receptor (EGFR) mutations among lung adenocarcinoma patients has not been reported in Malaysia. This study sought to determine the frequency of EGFR mutations among multiethnic Malaysian patients diagnosed with lung adenocarcinoma.
Fulltext Detection of epidermal growth factor receptor mutations in formalin fixed paraffin embedded biopsies in Malaysian non-small cell lung cancer patients

Shi Yeen TN, Pathmanathan R, Shiran MS, Ahmad Zaid FA, Cheah YK

J Biomed Sci, 2013 Apr 16;20:22.
PMID: 23590575 DOI: 10.1186/1423-0127-20-22

BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) are reportedly associated with various responses in non-small cell lung cancer (NSCLC) patients receiving the anti-EGFR agents. Detection of the mutation therefore plays an important role in therapeutic decision making. The aim of this study was to detect EGFR mutations in formalin fixed paraffin embedded (FFPE) samples using both Scorpion ARMS and high resolution melt (HRM) assay, and to compare the sensitivity of these methods.
RESULTS: All of the mutations were found in adenocarcinoma, except one that was in squamous cell carcinoma. The mutation rate was 45.7% (221/484). Complex mutations were also observed, wherein 8 tumours carried 2 mutations and 1 tumour carried 3 mutations.
CONCLUSIONS: Both methods detected EGFR mutations in FFPE samples. HRM assays gave more EGFR positive results compared to Scorpion ARMS.
Discrimination of probiotic Lactobacillus strains for poultry by repetitive sequenced-based PCR fingerprinting

Lee CM, Sieo CC, Cheah YK, Abdullah N, Ho YW

J Sci Food Agric, 2012 Feb;92(3):660-6.
PMID: 21919004 DOI: 10.1002/jsfa.4627

Four repetitive element sequence-based polymerase chain reaction (rep-PCR) methods, namely repetitive extragenic palindromic PCR (REP-PCR), enterobacterial repetitive intergenic consensus PCR (ERIC-PCR), polytrinucleotide (GTG)₅ -PCR and BOX-PCR, were evaluated for the molecular differentiation of 12 probiotic Lactobacillus strains previously isolated from the gastrointestinal tract of chickens and used as a multistrain probiotic. This study represents the first analysis of the comparative efficacy of these four rep-PCR methods and their combination (composite rep-PCR) in the molecular typing of Lactobacillus strains based on a discriminatory index (D).
Fulltext Evaluation of DNA and RNA extraction methods

Edwin Shiaw CS, Shiran MS, Cheah YK, Tan GC, Sabariah AR

Med J Malaysia, 2010 Jun;65(2):133-7.
PMID: 23756798 MyJurnal

This study was done to evaluate various DNA and RNA extractions from archival FFPE tissues. A total of 30 FFPE blocks from the years of 2004 to 2006 were assessed with each modified and adapted method. Extraction protocols evaluated include the modified enzymatic extraction method (Method A), Chelex-100 extraction method (Method B), heat-induced retrieval in alkaline solution extraction method (Methods C and D) and one commercial FFPE DNA Extraction kit (Qiagen, Crawley, UK). For RNA extraction, 2 extraction protocols were evaluated including the enzymatic extraction method (Method 1), and Chelex-100 RNA extraction method (Method 2). Results show that the modified enzymatic extraction method (Method A) is an efficient DNA extraction protocol, while for RNA extraction, the enzymatic method (Method 1) and the Chelex-100 RNA extraction method (Method 2) are equally efficient RNA extraction protocols.
Synthesis of a DNA-targeting nickel (II) complex with testosterone thiosemicarbazone which exhibits selective cytotoxicity towards human prostate cancer cells (LNCaP)

Heng MP, Sinniah SK, Teoh WY, Sim KS, Ng SW, Cheah YK, et al.

Spectrochim Acta A Mol Biomol Spectrosc, 2015 Nov 5;150:360-72.
PMID: 26057090 DOI: 10.1016/j.saa.2015.05.095

Testosterone thiosemicarbazone, L and its nickel (II) complex 1 were synthesized and characterized by using FTIR, CHN, (1)H NMR, and X-ray crystallography. X-ray diffraction study confirmed the formation of L from condensation of testosterone and thiosemicarbazide. Mononuclear complex 1 is coordinated to two Schiff base ligands via two imine nitrogens and two tautomeric thiol sulfurs. The cytotoxicity of both compounds was investigated via MTT assay with cisplatin as positive reference standard. L is more potent towards androgen-dependent LNCaP (prostate) and HCT 116 (colon). On the other hand, complex 1, which is in a distorted square planar environment with L acting as a bidentate NS-donor ligand, is capable of inhibiting the growth of all the cancer cell lines tested, including PC-3 (prostate). It is noteworthy that both compounds are less toxic towards human colon cell CCD-18Co. The intrinsic DNA binding constant (Kb) of both compounds were evaluated via UV-Vis spectrophotometry. Both compounds showed Kb values which are comparable to the reported Kb value of typical classical intercalator such as ethidium bromide. The binding constant of the complex is almost double compared with ligand L. Both compounds were unable to inhibit the action topoisomerase I, which is the common target in cancer treatment (especially colon cancer). This suggest a topoisomerase I independent-cell death mechanism.
In vitro modulation of probiotic bacteria on the biofilm of Candida glabrata

Chew SY, Cheah YK, Seow HF, Sandai D, Than LT

Anaerobe, 2015 Aug;34:132-8.
PMID: 26028405 DOI: 10.1016/j.anaerobe.2015.05.009

A conspicuous new concept of pathogens living as the microbial societies in the human host rather than free planktonic cells has raised considerable concerns among scientists and clinicians. Fungal biofilms are communities of cells that possess distinct characteristic such as increased resistance to the immune defence and antimycotic agents in comparison to their planktonic cells counterpart. Therefore, inhibition of the biofilm may represent a new paradigm for antifungal development. In this study, we aim to evaluate the in vitro modulation of vulvovaginal candidiasis (VVC)-causing Candida glabrata biofilms using probiotic lactobacilli strains. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 were shown to have completely inhibited C. glabrata biofilms and the results were corroborated by scanning electron microscopy (SEM), which revealed scanty structures of the mixed biofilms of C. glabrata and probiotic lactobacilli strains. In addition, biofilm-related C. glabrata genes EPA6 and YAK1 were downregulated in response to the probiotic lactobacilli challenges. The present study suggested that probiotic L. rhamnosus GR-1 and L. reuteri RC-14 strains inhibited C. glabrata biofilm by partially impeding the adherence of yeast cells and the effect might be contributed by the secretory compounds produced by these probiotic lactobacilli strains. Further investigations are required to examine and identify the biofilm inhibitory compounds and the mechanism of probiotic actions of these lactobacilli strains.
Fulltext High genetic diversity of Enterococcus faecium and Enterococcus faecalis clinical isolates by pulsed-field gel electrophoresis and multilocus sequence typing from a hospital in Malaysia

Weng PL, Ramli R, Shamsudin MN, Cheah YK, Hamat RA

Biomed Res Int, 2013;2013:938937.
PMID: 23819125 DOI: 10.1155/2013/938937

Little is known on the genetic relatedness and potential dissemination of particular enterococcal clones in Malaysia. We studied the antibiotic susceptibility profiles of Enterococcus faecium and Enterococcus faecalis and subjected them to pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). E. faecium and E. faecalis displayed 27 and 30 pulsotypes, respectively, and 10 representative E. faecium and E. faecalis isolates (five each) yielded few different sequence types (STs): ST17 (2 isolates), ST78, ST203, and ST601 for E. faecium, and ST6, ST16, ST28, ST179, and ST399 for E. faecalis. Resistance to tazobactam-piperacillin and ampicillin amongst E. faecium isolates was highly observed as compared to E. faecalis isolates. All of the isolates were sensitive to vancomycin and teicoplanin. The presence of epidemic and nosocomial strains of selected E. faecium STs: 17, 78, and 203 and E. faecalis ST6 as well as high rates of resistance to multiple antibiotics amongst E. faecium isolates is of a particular concern.
Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple-negative breast cancer cells

Foo JB, Saiful Yazan L, Tor YS, Wibowo A, Ismail N, Armania N, et al.

J Ethnopharmacol, 2016 Jul 1;187:195-204.
PMID: 27131434 DOI: 10.1016/j.jep.2016.04.048

Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia.
Fulltext Whole genome sequence data of an Antarctic bacterium, Arthrobacter sp. ES1 from the Schirmacher Oasis, East Antarctica

Teoh CP, Yusof NA, Budiman C, Cheah YK, Wong CMVL

Data Brief, 2023 Jun;48:109052.
PMID: 36942092 DOI: 10.1016/j.dib.2023.109052

Arthrobacter is a coryneform bacterium in the family of Micrococcaceae. Arthrobacter species isolated from hostile environments are capable of producing interesting bioactive compounds, some of which may be a new class of antibiotics. Here, we present the complete genome sequence of Arthrobacter sp. ES1 isolated from Schirmacher Oasis in East Antarctica. Genomic DNA sequencing was performed using the Illumina MiSeq sequencer. Arthrobacter sp. ES1 has a genome size of 3,964,927 bp and a GC content of 65.73%. The raw genome sequences have been deposited in the NCBI Sequence Read Archive database under the accession number, SRR20664316.
Fulltext Evaluating the roles of microRNAs associated with nonalcoholic fatty liver disease in hepatocellular carcinoma tumorigenesis: a systematic review and network analysis

Peng Q, Zhu X, Jiang Y, Peng M, Zheng D, Wang X, et al.

Front Med (Lausanne), 2024;11:1462513.
PMID: 39618816 DOI: 10.3389/fmed.2024.1462513

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with high morbidity and mortality. The rapidly increasing incidence of NAFLD is becoming an essential precursor of HCC globally. MicroRNAs (miRNAs) are involved in the progression of NAFLD and HCC.
METHOD: Potential miRNAs associated with NAFLD in HCC tumorigenesis were identified through a systematic review, and their roles were evaluated by data mining analysis. The biological function of the potential miRNA and its target genes in NAFLD and HCC were evaluated by bioinformatic analysis.
RESULT: MIR122 was identified as the potential miRNA associated with NAFLD and HCC. Then, MIR122 expression was significantly lower in HCC patients, and higher MIR122 levels were associated with significantly better overall survival. Next, the biological functions of MIR122 and target genes were predicted to be involved in inflammation, fibrosis, cell proliferation, invasion, metastasis, and apoptosis. In particular, the FOXO signaling pathway may regulate the above biological functions.
CONCLUSION: MIR122 was suggested to be involved in progressing from NAFLD to HCC through the PI3K/AKT/FOXO pathway.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier: CRD 42024517940.
Fulltext MicroRNA-155 as Biomarker and Its Diagnostic Value in Breast Cancer: A Systematic Review

Yeo BS, Lee WX, Mahmud R, Tan GC, Wahid MIA, Cheah YK

World J Oncol, 2025 Feb;16(1):1-15.
PMID: 39850528 DOI: 10.14740/wjon1955

The investigation of microRNAs (miRNAs) for the purpose of identifying biomarkers and new treatments for breast cancer has been gaining traction from scientists in recent years. Of all the miRNAs, miR-155 has been reportedly involved in breast cancer development as it regulates various cellular processes such as glucose uptake, proliferation, metastasis, and migration. Various efforts have been done towards researching miR-155 as a biomarker in breast cancer; however, the results were varied. The objective of the current systematic review is to compile and summarize information regarding miR-155 as a potential diagnostic biomarker for breast cancer. All eligible studies were found from SCOPUS and PubMed databases. Out of the 376 potential eligible records, only 26 original articles were selected for further assessment according to inclusion and exclusion criteria. The expressions of miR-155 in serum, plasma, biopsy, urine, nipple aspirate fluid, serum exosomes, and peripheral blood mononuclear cells were recorded and analyzed. Besides that, the expression of miR-155 was also correlated to clinicopathological features in breast cancer patients. The area under the curve (AUC) values from receiver operating characteristic (ROC) analysis used to evaluate diagnostic sensitivity and specificity of miR-155 as a diagnostic biomarker were also recorded. The limitations such as the small sampling size, the unemployment of internal controls for quantitative real-time polymerase chain reaction (RT-qPCR), and inconsistency of sensitivity as well as specificity values of miR-155 as a biomarker have been discussed. The present study proposed that miR-155 is a good diagnostic biomarker for breast cancer; however, further clinical research is required to assess the validity of miR-155 as a potential biomarker to translate the research outcomes into clinical practice.
G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh], R=Me, Et, and iPr, during zebrafish development

Ooi KK, Yeo CI, Mahandaran T, Ang KP, Akim AM, Cheah YK, et al.

J Inorg Biochem, 2017 01;166:173-181.
PMID: 27865929 DOI: 10.1016/j.jinorgbio.2016.11.008

Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17-22% cf. untreated cells. LC50values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.

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