Displaying publications 41 - 60 of 66 in total

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  1. Fulltext Diversity of Streptomyces spp. from mangrove forest of Sarawak (Malaysia) and screening of their antioxidant and cytotoxic activities
    Law JW, Chan KG, He YW, Khan TM, Ab Mutalib NS, Goh BH, et al.
    Sci Rep, 2019 12 03;9(1):15262.
    PMID: 31792235 DOI: 10.1038/s41598-019-51622-x
    Streptomycetes have been the center of attraction within scientific community owing to their capability to produce various bioactive compounds, for instance, with different antimicrobial, anticancer, and antioxidant properties. The search for novel Streptomyces spp. from underexplored area such as mangrove environment has been gaining attention since these microorganisms could produce pharmaceutically important metabolites. The aim of this study is to discover the diversity of Streptomyces spp. from mangrove in Sarawak and their bioactive potentials - in relation to antioxidant and cytotoxic activities. A total of 88 Streptomyces isolates were successfully recovered from the mangrove soil in Kuching, state of Sarawak, Malaysia. Phylogenetic analysis of all the isolates and their closely related type strains using 16S rRNA gene sequences resulted in 7 major clades in the phylogenetic tree reconstructed based on neighbour-joining algorithm. Of the 88 isolates, 18 isolates could be considered as potentially novel species according to the 16S rRNA gene sequence and phylogenetic analyses. Preliminary bioactivity screening conducted on the potential novel Streptomyces isolates revealed significant antioxidant activity and notable cytotoxic effect against tested colon cancer cell lines (HCT-116, HT-29, Caco-2, and SW480), with greater cytotoxicity towards SW480 and HT-29 cells. This study highlighted that the Sarawak mangrove environment is a rich reservoir containing streptomycetes that could produce novel secondary metabolites with antioxidant and cytotoxic activities.
  2. Identification of differentially expressed circular RNAs in chemoresistant colorectal cancer
    Abu N, Hon KW, Jeyaraman S, Yahaya A, Abdullah NM, Mustangin M, et al.
    Epigenomics, 2019 06;11(8):875-884.
    PMID: 31020847 DOI: 10.2217/epi-2019-0042
    Aim: Chemoresistance in colorectal cancer (CRC) has become a burden in treating the disease effectively. Circular RNAs (circRNAs) are a type of noncoding RNA that were found to be important in cellular homeostasis. The involvement of circRNAs in relation to chemoresistance in other types of cancers has also been reported. This study aims to identify the differentially expressed circRNAs between chemoresistant and chemosensitive CRC cells. Materials & methods: We developed a chemoresistant cell line model and profiled the circRNAs via microarray. We further validated the expression of two circRNAs in 25 formalin-fixed paraffin-embedded (FFPE) tissue specimens (13 nonresponders and 12 responders) via quantitative polymerase chain reaction (qPCR).  Results & conclusion: We found that there were 773 upregulated and 732 downregulated circRNAs between the chemoresistant and chemosensitive HCT-116 cells. We found that hsa_circ_32883 could be a promising biotarget.
  3. Fulltext Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis?
    Chew SS, Tan LT, Law JW, Pusparajah P, Goh BH, Ab Mutalib NS, et al.
    Cancers (Basel), 2020 Aug 13;12(8).
    PMID: 32823729 DOI: 10.3390/cancers12082272
    Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
  4. Fulltext Global metabolomics profiling of colorectal cancer in Malaysian patients
    Amir Hashim NA, Ab-Rahim S, Wan Ngah WZ, Nathan S, Ab Mutalib NS, Sagap I, et al.
    Bioimpacts, 2021;11(1):33-43.
    PMID: 33469506 DOI: 10.34172/bi.2021.05
    Introduction:
    The serum metabolomics approach has been used to identify metabolite biomarkers that can diagnose colorectal cancer (CRC) accurately and specifically. However, the biomarkers identified differ between studies suggesting that more studies need to be performed to understand the influence of genetic and environmental factors. Therefore, this study aimed to identify biomarkers and affected metabolic pathways in Malaysian CRC patients.
    Methods:
    Serum from 50 healthy controls and 50 CRC patients were collected at UKM Medical Centre. The samples were deproteinized with acetonitrile and untargeted metabolomics profile determined using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOFMS, Agilent USA). The data were analysed using Mass Profiler Professional (Agilent, USA) software. The panel of biomarkers determined were then used to identify CRC from a new set of 20 matched samples.
    Results:
    Eleven differential metabolites were identified whose levels were significantly different between CRC patients compared to normal controls. Based on the analysis of the area under the curve, 7 of these metabolites showed high sensitivity and specificity as biomarkers. The use of the 11 metabolites on a new set of samples was able to differentiate CRC from normal samples with 80% accuracy. These metabolites were hypoxanthine, acetylcarnitine, xanthine, uric acid, tyrosine, methionine, lysoPC, lysoPE, citric acid, 5-oxoproline, and pipercolic acid. The data also showed that the most perturbed pathways in CRC were purine, catecholamine, and amino acid metabolisms.
    Conclusion:
    Serum metabolomics profiling can be used to identify distinguishing biomarkers for CRC as well as to further our knowledge of its pathophysiological mechanisms.
  5. Draft Genome Sequence of Mangrove-Derived Streptomyces sp. MUSC 125 with Antioxidant Potential
    Ser HL, Tan WS, Ab Mutalib NS, Yin WF, Chan KG, Goh BH, et al.
    Front Microbiol, 2016;7:1470.
    PMID: 27695452
  6. Fulltext Author Correction: Streptomyces monashensis sp. nov., a novel mangrove soil actinobacterium from East Malaysia with antioxidative potential
    Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.
    Sci Rep, 2020 Jan 10;10(1):319.
    PMID: 31924829 DOI: 10.1038/s41598-019-55964-4
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  7. Fulltext Streptomyces monashensis sp. nov., a novel mangrove soil actinobacterium from East Malaysia with antioxidative potential
    Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.
    Sci Rep, 2019 02 28;9(1):3056.
    PMID: 30816228 DOI: 10.1038/s41598-019-39592-6
    A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name - Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA-DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03221T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.
  8. Fulltext Deep Transcriptome Sequencing of Pediatric Acute Myeloid Leukemia Patients at Diagnosis, Remission and Relapse: Experience in 3 Malaysian Children in a Single Center Study
    Osman SH, Abu N, Aziz H, Chow YP, Wan Mohamad Nazarie WF, Ab Mutalib NS, et al.
    Front Genet, 2020;11:66.
    PMID: 32174960 DOI: 10.3389/fgene.2020.00066
  9. Colorectal screening using the immunochemical faecal occult blood test kit among the Malaysian cohort participants
    Abdullah N, Abd Jalal N, Ismail N, Kamaruddin MA, Abd Mutalib NS, Alias MR, et al.
    Cancer Epidemiol, 2020 04;65:101656.
    PMID: 31923638 DOI: 10.1016/j.canep.2019.101656
    BACKGROUND: There has been a rapid increase in colorectal cancer (CRC) cases in Asian countries, including Malaysia. CRC is usually diagnosed at a late stage, and early detection of CRC is vital in improving survival. This study was conducted to determine the uptake rate of the immunochemical faecal occult blood test (iFOBT), the response rate to colonoscopy, and the CRC detection rate. We also wanted to identify the association between colorectal neoplasia and the Asia Pacific Colorectal Cancer Screening (APCS) scoring system.

    METHODS: We recruited 2264 individuals from The Malaysian Cohort participants aged 35-65 years who consented to colorectal screening using the iFOBT kit from July 2017 until January 2019.

    RESULTS: The response rate and positive iFOBT test rate of this study were 79.6% and 13.1% respectively. Among those with positive results, 125 individuals (52.7%) underwent colonoscopy; CRC was detected in six of them while 45 others (36.0%) had polyps. The overall CRC detection rate was 0.3% while the colorectal neoplasia detection rate (both colorectal cancer and colorectal polyps) was 2.3%. The APCS scoring indicated a significant association with colorectal neoplasia risk, with increasing trend by severity from moderate to high risk (3.46-11.14) compared to low risk. Most of the participants who were positive for iFOBT were those at high risk.

    CONCLUSIONS: The awareness of CRC risk and iFOBT screening are important strategies for early detection of CRC. We showed a CRC detection rate of 0.3 % among those who volunteered to have the iFOBT screening.

  10. Fulltext Streptomyces sp.-A Treasure Trove of Weapons to Combat Methicillin-Resistant Staphylococcus aureus Biofilm Associated with Biomedical Devices
    Pusparajah P, Letchumanan V, Law JW, Ab Mutalib NS, Ong YS, Goh BH, et al.
    Int J Mol Sci, 2021 Aug 28;22(17).
    PMID: 34502269 DOI: 10.3390/ijms22179360
    Biofilms formed by methicillin-resistant S. aureus (MRSA) are among the most frequent causes of biomedical device-related infection, which are difficult to treat and are often persistent and recurrent. Thus, new and effective antibiofilm agents are urgently needed. In this article, we review the most relevant literature of the recent years reporting on promising anti-MRSA biofilm agents derived from the genus Streptomyces bacteria, and discuss the potential contribution of these newly reported antibiofilm compounds to the current strategies in preventing biofilm formation and eradicating pre-existing biofilms of the clinically important pathogen MRSA. Many efforts are evidenced to address biofilm-related infections, and some novel strategies have been developed and demonstrated encouraging results in preclinical studies. Nevertheless, more in vivo studies with appropriate biofilm models and well-designed multicenter clinical trials are needed to assess the prospects of these strategies.
  11. Fulltext Genome sequence of Streptomyces mangrovisoli MUSC 149T isolated from intertidal sediments
    Ser HL, Tan WS, Ab Mutalib NS, Yin WF, Chan KG, Goh BH, et al.
    Braz J Microbiol, 2017 09 06;49(1):13-15.
    PMID: 28927873 DOI: 10.1016/j.bjm.2017.01.013
    As the largest genus in Actinobacteria family, Streptomyces species have the ability to synthesize numerous compounds of diverse structures with bioactivities. Streptomyces mangrovisoli MUSC 149T was previously isolated as a novel streptomycete from mangrove forest in east coast of Peninsular Malaysia. The high quality draft genome of MUSC 149T comprises 9,165,825bp with G+C content of 72.5%. Through bioinformatics analysis, 21 gene clusters identified in the genome were associated with the production of bioactive secondary metabolites. The presence of these biosynthetic gene clusters in MUSC 149T suggests the potential exploitation of the strain for production of medically important compounds.
  12. Fulltext Anticancer Drug Discovery from Microbial Sources: The Unique Mangrove Streptomycetes
    Law JW, Law LN, Letchumanan V, Tan LT, Wong SH, Chan KG, et al.
    Molecules, 2020 Nov 17;25(22).
    PMID: 33212836 DOI: 10.3390/molecules25225365
    Worldwide cancer incidence and mortality have always been a concern to the community. The cancer mortality rate has generally declined over the years; however, there is still an increased mortality rate in poorer countries that receives considerable attention from healthcare professionals. This suggested the importance of the prompt detection, effective treatment, and prevention strategies. The genus Streptomyces has been documented as a prolific producer of biologically active secondary metabolites. Streptomycetes from mangrove environments attract researchers' attention due to their ability to synthesize diverse, interesting bioactive metabolites. The present review highlights research on mangrove-derived streptomycetes and the production of anticancer-related compounds from these microorganisms. Research studies conducted between 2008 and 2019, specifically mentioning the isolation of streptomycetes from mangrove areas and described the successful purification of compound(s) or generation of crude extracts with cytotoxic activity against human cancer cell lines, were compiled in this review. It is anticipated that there will be an increase in prospects for mangrove-derived streptomycetes as one of the natural resources for the isolation of chemotherapeutic agents.
  13. Fulltext Insights into Bacteriophage Application in Controlling Vibrio Species
    Letchumanan V, Chan KG, Pusparajah P, Saokaew S, Duangjai A, Goh BH, et al.
    Front Microbiol, 2016;7:1114.
    PMID: 27486446 DOI: 10.3389/fmicb.2016.01114
    Bacterial infections from various organisms including Vibrio sp. pose a serious hazard to humans in many forms from clinical infection to affecting the yield of agriculture and aquaculture via infection of livestock. Vibrio sp. is one of the main foodborne pathogens causing human infection and is also a common cause of losses in the aquaculture industry. Prophylactic and therapeutic usage of antibiotics has become the mainstay of managing this problem, however, this in turn led to the emergence of multidrug resistant strains of bacteria in the environment; which has raised awareness of the critical need for alternative non-antibiotic based methods of preventing and treating bacterial infections. Bacteriophages - viruses that infect and result in the death of bacteria - are currently of great interest as a highly viable alternative to antibiotics. This article provides an insight into bacteriophage application in controlling Vibrio species as well underlining the advantages and drawbacks of phage therapy.
  14. Fulltext Targeted Next-Generation Sequencing Identifies Actionable Targets in Estrogen Receptor Positive and Estrogen Receptor Negative Endometriod Endometrial Cancer
    Suhaimi SS, Ab Mutalib NS, Khor SS, Zain RRM, Syafruddin SE, Abu N, et al.
    Front Pharmacol, 2018;9:750.
    PMID: 30057548 DOI: 10.3389/fphar.2018.00750
    Endometrioid endometrial cancer (EEC) is the commonest form of endometrial cancer and can be divided into estrogen receptor (ER) positive and negative subtypes. The mutational profiles of EEC have been shown to aid in tailoring treatment; however, little is known about the differences between the gene mutation profiles between these two subtypes. This study aims to investigate the gene mutation profile in ER positive and negative EEC, and to further elucidate the role of WHSC1 mutations in this cancer. EEC and normal endometrial tissues were obtained from 29 patients and subjected to next-generation sequencing (NGS) using Ion Ampliseq Comprehensive Cancer PanelTM targeting 409 cancer related. A total of 741 non-synonymous alterations were identified from 272 genes in ER positive subtype while 448 non-synonymous variants were identified from 221 genes in ER negative subtype. PTEN is the most frequently altered gene in ER positive subtype (64%, 7/11) while ARID1A is the most frequently altered gene in ER negative subtype (50%, 4/8). We also identified alterations in ERRB3 (36%, 4/11), GNAS (36%, 4/11), and WHSC1 (27%, 3/11) in the ER positive subtype. WHSC1 R1126H and L1268P were shown to significantly increase cell viability, proliferation, migration, and survival. In addition, reduction in ER expression sensitized EEC-1 cell with WHSC1 L1268P mutant to Fulvestrant treatment. We revealed the mutational spectra of ER positive and ER negative EEC that could lead to better understanding of the biological mechanisms of endometrial cancer and may ultimately result in improvement of treatment options and patient prognosis.
  15. Detection of dynorphin 1-17 biotransformation fragments in human nasal polyps by UPLC-QTOF-MS
    Ballouze R, Ismail MN, Abu Kassim NS, Salhimi SM, Mohamad I, Abd Mutalib NS, et al.
    Anal Bioanal Chem, 2024 Jan;416(2):545-557.
    PMID: 38040942 DOI: 10.1007/s00216-023-05061-3
    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammation of the sinonasal mucosa. CRSwNP treatments are associated with inconsistent efficacy and recurrence of symptoms. Dynorphin 1-17 (DYN 1-17) and its fragments have been shown to modulate the immune response in various inflammatory conditions. This study aimed to investigate the effect of different pH and degrees of inflammation on DYN 1-17 metabolism in human CRSwNP tissues. DYN 1-17 was incubated with grade 3 and grade 4 inflamed tissues of CRSwNP patients at pH 5.5 and pH 7.4 over a range of incubation periods. The resulting fragments were identified using an ultra-performance liquid chromatography (UPLC) system coupled to quadrupole-time of flight (QTOF) mass spectrometry based on their accurate mass. The rate of DYN 1-17 fragmentation was slower at pH 5.5 in comparison to pH 7.4. The extent and rate of metabolism of DYN 1-17 were much lower in grade 3 inflamed tissue (31-32 fragments) than in grade 4 (34-41 fragments). N-Terminal fragments (DYN 1-15, 1-11, 1-10, and 1-6) were metabolized slower at pH 5.5 as compared to pH 7.4. DYN 1-12, 1-8, 2-10, 4-10, 5-10, and 8-14 were only observed under the inflammatory pH while DYN 5-17 and 6-17 were only identified upon incubation with grade 4 CRSwNP tissues. DYN 1-17 metabolism was significantly affected by the pH level and the severity of the inflammation of CRSwNP tissues, indicating the potential roles of DYN 1-17 and its fragments in modulating the inflammatory response and their avenue as therapeutics in future studies.
  16. Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer
    Soh JE, Abu N, Sagap I, Mazlan L, Yahaya A, Mustangin M, et al.
    Immunotherapy, 2019 10;11(14):1205-1219.
    PMID: 31478431 DOI: 10.2217/imt-2019-0073
    Colorectal cancer is the third commonest malignancy in Asia including Malaysia. The immunogenic cancer-testis antigens, which are expressed in a variety of cancers but with limited expression in normal tissues except the testis, represent an attractive approach to improve treatment options for colorectal cancer. We aimed to validate four PASD1 peptides as the immunotherapeutic targets in colorectal cancer. First, PASD1 mRNA and protein expression were determined via real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. The PASD1 peptides specific to HLA-A*24:02 were investigated using IFN-y-ELISpot assay, followed by the cytolytic and granzyme-B-ELISpot assays to analyze the cytolytic effects of CD8+ T cells. Gene and protein expressions of PASD1 were detected in 20% and 17.3% of colorectal cancer samples, respectively. PASD1(4) peptide was shown to be immunogenic in colorectal cancer samples. CD8+ T cells raised against PASD1(4) peptide were able to lyze HLA-A*24:02+ PASD1+ cells. Our results reveal that PASD1(4) peptide represents a potential target for colorectal cancer.
  17. Fulltext Vibrio vulnificus: An Environmental and Clinical Burden
    Heng SP, Letchumanan V, Deng CY, Ab Mutalib NS, Khan TM, Chuah LH, et al.
    Front Microbiol, 2017;8:997.
    PMID: 28620366 DOI: 10.3389/fmicb.2017.00997
    Vibrio vulnificus is a Gram negative, rod shaped bacterium that belongs to the family Vibrionaceae. It is a deadly, opportunistic human pathogen which is responsible for the majority of seafood-associated deaths worldwide. V. vulnificus infection can be fatal as it may cause severe wound infections potentially requiring amputation or lead to sepsis in susceptible individuals. Treatment is increasingly challenging as V. vulnificus has begun to develop resistance against certain antibiotics due to their indiscriminate use. This article aims to provide insight into the antibiotic resistance of V. vulnificus in different parts of the world as well as an overall review of its clinical manifestations, treatment, and prevention. Understanding the organism's antibiotic resistance profile is vital in order to select appropriate treatment and initiate appropriate prevention measures to treat and control V. vulnificus infections, which should eventually help lower the mortality rate associated with this pathogen worldwide.
  18. Fulltext Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer
    Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Mazlan L, Raja Ali RA, et al.
    Sci Rep, 2021 02 03;11(1):2925.
    PMID: 33536501 DOI: 10.1038/s41598-021-82465-0
    Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.
  19. Fulltext Molecular Characterization of Somatic Alterations in Dukes' B and C Colorectal Cancers by Targeted Sequencing
    Abdul SN, Ab Mutalib NS, Sean KS, Syafruddin SE, Ishak M, Sagap I, et al.
    Front Pharmacol, 2017;8:465.
    PMID: 28769798 DOI: 10.3389/fphar.2017.00465
    Despite global progress in research, improved screening and refined treatment strategies, colorectal cancer (CRC) remains as the third most common malignancy. As each type of cancer is different and exhibits unique alteration patterns, identifying and characterizing gene alterations in CRC that may serve as biomarkers might help to improve diagnosis, prognosis and predict potential response to therapy. With the emergence of next generation sequencing technologies (NGS), it is now possible to extensively and rapidly identify the gene profile of individual tumors. In this study, we aimed to identify actionable somatic alterations in Dukes' B and C in CRC via NGS. Targeted sequencing of 409 cancer-related genes using the Ion Ampliseq(TM) Comprehensive Cancer Panel was performed on genomic DNA obtained from paired fresh frozen tissues, cancer and normal, of Dukes' B (n = 10) and Dukes' C (n = 9) CRC. The sequencing results were analyzed using Torrent Suite, annotated using ANNOVAR and validated using Sanger sequencing. A total of 141 somatic non-synonymous sequence variations were identified in 86 genes. Among these, 64 variants (45%) were predicted to be deleterious, 38 variants (27%) possibly deleterious while the other 39 variants (28%) have low or neutral protein impact. Seventeen genes have alterations with frequencies of ≥10% in the patient cohort and with 14 overlapped genes in both Dukes' B and C. The adenomatous polyposis coli gene (APC) was the most frequently altered gene in both groups (n = 6 in Dukes' B and C). In addition, TP53 was more frequently altered in Dukes' C (n = 7) compared to Dukes' B (n = 4). Ten variants in APC, namely p.R283(∗), p.N778fs, p.R805(∗), p.Y935fs, p.E941fs, p.E1057(∗), p.I1401fs, p.Q1378(∗), p.E1379(∗), and p.A1485fs were predicted to be driver variants. APC remains as the most frequently altered gene in the intermediate stages of CRC. Wnt signaling pathway is the major affected pathway followed by P53, RAS, TGF-β, and PI3K signaling. We reported the alteration profiles in each of the patient which has the potential to affect the clinical decision. We believe that this study will add further to the understanding of CRC molecular landscape.
  20. Fulltext Streptomyces colonosanans sp. nov., A Novel Actinobacterium Isolated from Malaysia Mangrove Soil Exhibiting Antioxidative Activity and Cytotoxic Potential against Human Colon Cancer Cell Lines
    Law JW, Ser HL, Duangjai A, Saokaew S, Bukhari SI, Khan TM, et al.
    Front Microbiol, 2017;8:877.
    PMID: 28559892 DOI: 10.3389/fmicb.2017.00877
    Streptomyces colonosanans MUSC 93JT, a novel strain isolated from mangrove forest soil located at Sarawak, Malaysia. The bacterium was noted to be Gram-positive and to form light yellow aerial and vivid yellow substrate mycelium on ISP 2 agar. The polyphasic approach was used to determine the taxonomy of strain MUSC 93JT and the strain showed a range of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. Phylogenetic and 16S rRNA gene sequence analysis indicated that closely related strains include Streptomyces malachitofuscus NBRC 13059T (99.2% sequence similarity), Streptomyces misionensis NBRC 13063T (99.1%), and Streptomyces phaeoluteichromatogenes NRRL 5799T (99.1%). The DNA-DNA relatedness values between MUSC 93JT and closely related type strains ranged from 14.4 ± 0.1 to 46.2 ± 0.4%. The comparison of BOX-PCR fingerprints indicated MUSC 93JT exhibits a unique DNA profile. The genome of MUSC 93JT consists of 7,015,076 bp. The DNA G + C content was determined to be 69.90 mol%. The extract of strain MUSC 93JT was demonstrated to exhibit potent antioxidant activity via ABTS, metal chelating, and SOD assays. This extract also exhibited anticancer activity against human colon cancer cell lines without significant cytotoxic effect against human normal colon cells. Furthermore, the chemical analysis of the extract further emphasizes the strain is producing chemo-preventive related metabolites. Based on this polyphasic study of MUSC 93JT, it is concluded that this strain represents a novel species, for which the name Streptomyces colonosanans sp. nov. is proposed. The type strain is MUSC 93JT (= DSM 102042T = MCCC 1K02298T).
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