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  1. Baradaran A, Yusoff K, Shafee N, Rahim RA
    J Cancer, 2016;7(4):462-6.
    PMID: 26918060 DOI: 10.7150/jca.13566
    The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) with its immunotherapeutic activities and sialic acid binding abilities is a promising cancer adjuvant. The HN was surfaced displayed on Lactococcus lactis and its cancer targeting ability was investigated via attachment to the MDA-MB231 breast cancers. To surface display the HN protein on the bacterial cell wall, HN was fused to N-acetylmuraminidase (AcmA) anchoring motif of L. lactis and expressed in Chinese hamster ovary cells. The expressed recombinant fusion proteins were purified and mixed with a culture of L. lactis and Lactobacillus plantarum. Immunofluorescence assay showed the binding of the recombinant HN-AcmA protein on the surface of the bacterial cells. The bacterial cells carrying the HN-AcmA protein interacted with the MDA-MB231 breast cancer cells. Direct and fluorescent microscopy confirmed that L. lactis and Lb. plantarum surface displaying the recombinant HN were attached to the breast cancer MDA-MB231 cells, providing evidence for the potential ability of HN in targeting to cancer cells.
  2. Zhu CZ, Ting HN, Ng KH, Ong TA
    J Cancer, 2019;10(17):4038-4044.
    PMID: 31417648 DOI: 10.7150/jca.28989
    Background and purpose: Bladder cancer is the most common malignant tumour in the urinary system, with a high incidence and recurrence rate. While the incidence of bladder cancer has been rising in recent years, the prevalence of bladder carcinoma is showing an increasing tendency in the younger age group. There are several methods to detect bladder cancer, but different methods have varying degrees of accuracy which intrinsically depends on the method's sensitivity and specificity. Our aim was to comprehensively summarize the current detection methods for bladder cancer based on the available literature, and at the same time, to find the best combination of different effective methods which can produce a high degree of accuracy in detecting the presence of cancerous cells in the bladder. Materials and Methods: We used key word retrieval method for searching related references in English that had been indexed in PubMed and Medline. Results and Discussion: This paper discussed the different detection methods and their sensitivities/specificities as well as the advantages and disadvantages. We summarized the best identified cancer cell detection methods with higher sensitivity/specificity. Conclusion: The results of this review can positively help to identify accurate methods for detecting bladder cancer and highlight areas to be further improved for future research work.
  3. Abu Halim NH, Zakaria N, Theva Das K, Lin J, Lim MN, Fakiruddin KS, et al.
    J Cancer, 2021;12(12):3468-3485.
    PMID: 33995625 DOI: 10.7150/jca.50793
    Retinoic acid receptor beta is a nuclear receptor protein that binds to retinoic acid (RA) to mediate cellular signalling in embryogenic morphogenesis, cell growth, and differentiation. However, the function of RARβ in cancer stem cells (CSCs) has yet to be determined. This study aimed to understand the role of RARβ in regulating cell growth and differentiation of lung cancer stem cells. Based on the clonogenic assay, spheroid assay, mRNA levels of stem cell transcription factors, and cell cycle being arrested at the G0/G1 phase, the suppression of RARβ resulted in significant inhibition of A549 parental cell growth. This finding was contradictory to the results seen in CSCs, where RARβ inhibition enhanced the cell growth of putative and non-putative CSCs. These results suggest that RARβ suppression may act as an essential regulator in A549 parental cells, but not in the CSCs population. The findings in this study demonstrated that the loss of RARβ promotes tumorigenicity in CSCs. Microarray analysis revealed that various cancer pathways were significantly activated following the suppression of RARβ. The changes seen might compensate for the loss of RARβ function, CSCs population's aggressiveness, which led to the CSCs population's aggressiveness. Thus, understanding the role of RARβ in regulating the stemness of CSCs may lead to targeted therapy for lung CSCs.
  4. Zhang WJ, Chen C, Zhou ZH, Gao ST, Tee TJ, Yang LQ, et al.
    J Cancer, 2017;8(10):1818-1825.
    PMID: 28819379 DOI: 10.7150/jca.19057
    Background: Hypoxia was a common feature for accelerating tumor metastasis by both inducting epithelial-mesenchymal transition (EMT) of tumor cells and polarization of tumor-associated macrophages (TAMs). The association and roles between hypoxia, EMT and TAMs in the biological behavior of gastric cancer (GC) for the time being recurrence is unclear. Material and methods: hypoixa by expression of hypoxia-inducible factor-1 alpha (HIF-1α), polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68 and CD163, and the expression of E-cadherin as EMT property had been evaluated in 236 patients consecutive with histologically confirmed GC. Clinical significance was assessed for all these patients. Results: High expression of HIF-1α was found in patients with aggressive features, especially for recurrent patients. High infiltration of TAMs and abnormal expression of EMT-marker were also related to aggressive characteristics and predicted poor prognosis in GC. Meanwwhile, there existed a significant correlation among expression of HIF-1α, infiltration of TAMs and EMT marker in GC tissues. Multivariate Cox analysis revealed that high expression of HIF-1α combined TAMs infiltration were independent prognostic factors for disease-specific survival rate. Conclusion: HIF-1α is an unfavorable indicator for prognosis, may promote tumor progression through the induction of EMT and establishment of a pro-tumor immunosuppressive microenvironment. Further investigation into the therapeutic effects of blocking hypoxia is possible a potential strategy for GC treatment.
  5. Dorasamy MS, Choudhary B, Nellore K, Subramanya H, Wong PF
    J Cancer, 2017;8(15):3086-3098.
    PMID: 28928900 DOI: 10.7150/jca.14835
    Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme in the de novo biosynthesis pathway of pyrimidines. Inhibition of this enzyme impedes cancer cell proliferation but the exact mechanisms of action of these inhibitors in cancer cells are poorly understood. In this study, we showed that cancer cells, namely melanoma, myeloma and lymphoma overexpressed DHODH protein and treatment with A771726 and Brequinar sodium resulted in cell cycle arrest at S-phase. Transfection with DHODH shRNA depleted DHODH protein expression and impeded the proliferation of melanoma cells. shRNA knockdown of DHODH in combination with DHODH inhibitors further reduced the cancer cell proliferation, suggesting that knockdown of DHODH had sensitized the cells to DHODH inhibitors. Cell cycle regulatory proteins, c-Myc and its transcriptional target, p21 were found down- and up-regulated, respectively, following treatment with DHODH inhibitors in melanoma, myeloma and lymphoma cells. Interestingly, knockdown of DHODH by shRNA had also similarly affected the expression of c-Myc and p21 proteins. Our findings suggest that DHODH inhibitors induce cell cycle arrest in cancer cells via additional DHODH-independent pathway that is associated with p21 up-regulation and c-Myc down-regulation. Hence, DHODH inhibitors can be explored as potential therapeutic agents in cancer therapy.
  6. Ho CS, Noor SM, Nagoor NH
    J Cancer, 2018;9(2):331-345.
    PMID: 29344280 DOI: 10.7150/jca.18188
    MicroRNAs (miRNAs) have been extensively studied over the decades and have been proposed as potential molecular targets for cancer treatment. Studies have shown that miR-378 participates in numerous biological processes in various cancers; whereas miR-1827 has only been reported in pediatric glioma. The mechanism of how miRNAs modulate lung cancer metastasis remains unclear. Our previous study demonstrated that miR-378 is up-regulated while miR-1827 is down-regulated in high invasive lung cancer sub-cell lines, and their biological functions have been described. Here, we report that miR-378 and miR-1827 modulate lung cancer cell invasion and migration via epithelial-mesenchymal transition (EMT). We also demonstrated that cells treated with miR-378 inhibitors or miR-1827 mimics had reduced number of metastases and ectopic vessels in the zebrafish embryo model. We then showed that miR-378 promoted invasion and miR-1827 suppressed migration by targeting RBX1 and CRKL, respectively. Restored protein expression in miRNA-overexpressed/ miRNA-suppressed cells attenuated the inhibitory/ inducing effect of the miRNA on lung cancer cells. Collectively, our findings highlight that miR-378 and miR-1827 could serve as novel therapeutic targets in lung cancer.
  7. Salam DSDA, Thit EE, Teoh SH, Tan SY, Peh SC, Cheah SC
    J Cancer, 2020;11(1):190-198.
    PMID: 31892985 DOI: 10.7150/jca.36954
    C-MYC, BCL2 and BCL6 genes are the most commonly oncogenes involved in B-Cell lymphomas. Translocations of these oncogenes are associated with an aggressive clinical course. This study aims to elucidate the patterns of BCL6, BCL2 and C-MYC gene aberrations among Malaysian B-cell Non-Hodgkin Lymphoma (NHL) using fluorescence in situ hybridization (FISH). Eighty-one B-cell NHL tissue blocks were retrieved between the year 2011 to 2015 and investigated using immunohistochemistry and interphase FISH dual colour break-apart probes of BCL2, BCL6, C-MYC and IgH. A significant difference was detected between the nodal and extranodal sites in all the BCL2 (p=0.01), C-MYC (p=0.03) and IgH (p=0.006) cases except for BCL6 (p=0.2). Our study showed that BCL6 had the highest gene translocation while BCL2/BCL6 had the most mixed aberrations of gain copies and translocation, however no mixed aberrations of gain copies and translocation was found in C-MYC. None of the mixed gain copies and translocation was found in any of the germinal centre B-cell (GCB) subtype of Diffuse Large B-cell Lymphoma, however, five were found in BCL6 and IgH gene in the non-GCB subtype; while mixed gain copies and translocation cases of BCL2 gene was found in the Follicular Lymphoma cases only. The study found interesting findings of BCL2, C-MYC and IgH gene aberrations between nodal and extranodal sites. This information might benefit future study in predicting prognosis and determine effective therapeutic strategies in the multi-ethnic populations of Malaysia as well as the Asian population.
  8. Goh KW, Stephen A, Wu YS, Sim MS, Batumalaie K, Gopinath SCB, et al.
    J Cancer, 2023;14(13):2491-2516.
    PMID: 37670975 DOI: 10.7150/jca.85260
    Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.
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