Displaying publications 81 - 100 of 286 in total

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  1. Hoe SL, Lee ES, Khoo AS, Peh SC
    Pathology, 2009;41(6):561-5.
    PMID: 19900105
    AIMS: Nasopharyngeal carcinoma (NPC) is a common malignancy among men in Malaysia. To determine the role of p53 in NPC, we screened for p53 mutations and evaluated the protein expression levels in samples from local patients with NPC.

    METHODS: Fifty-three formalin-fixed, paraffin-embedded nasopharyngeal carcinoma tissue blocks were chosen for this study. The presence of Epstein-Barr virus (EBV) was determined by in situ hybridisation using an EBER probe. p53 protein expression was detected using immunohistochemistry. Simultaneously, amplifications by PCR were performed for p53 exons 5 to 8, followed by mutation screening via single strand conformation polymorphism (SSCP). Sequencing of all the four exons was performed in five samples with mobility shift. To rule out false negative results by SSCP, 13 samples with p53 overexpression and five samples with low p53 expression were randomly selected and sequenced.

    RESULTS: There was no mutation found in exons 5 to 8 in all the samples despite 46 (87%) of them having high p53 levels. EBV was detected in 51 (96%) out of 53 samples. There was no statistically significant association between p53 expression level and EBV presence.

    CONCLUSIONS: High-intensity staining for p53 by immunohistochemistry was common in our series of NPC tissue samples but was not associated with 'hot spot' mutations of exons 5-8 of the gene. We did not find a significant relationship between the expression level of p53 and presence of EBV. Our study confirms that mutation of the DNA-binding domain of p53 is rare in NPC.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  2. Hong SK, Gul YA, Ithnin H, Talib A, Seow HF
    Asian J Surg, 2004 Jan;27(1):10-7.
    PMID: 14719508
    BACKGROUND: Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS.

    METHODS: A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral.

    RESULTS: COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores.

    CONCLUSIONS: the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  3. Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  4. Hor YZ, Salvamani S, Gunasekaran B, Yian KR
    Yale J Biol Med, 2023 Dec;96(4):511-526.
    PMID: 38161583 DOI: 10.59249/VHYE2306
    Colorectal Neoplasia Differentially Expressed (CRNDE), a long non-coding RNA that was initially identified as aberrantly expressed in colorectal cancer (CRC) has also been observed to exhibit elevated expression in various other human malignancies. Recent research has accumulated substantial evidence implicating CRNDE as an oncogenic player, exerting influence over critical cellular processes linked to cancer progression. Particularly, its regulatory interactions with microRNAs and proteins have been shown to modulate pathways that contribute to carcinogenesis and tumorigenesis. This review will comprehensively outline the roles of CRNDE in colorectal, liver, glioma, lung, cervical, gastric and prostate cancer, elucidating the mechanisms involved in modulating proliferation, apoptosis, migration, invasion, angiogenesis, and radio/chemoresistance. Furthermore, the review highlights CRNDE's potential as a multifaceted biomarker, owing to its presence in diverse biological samples and stable properties, thereby underscoring its diagnostic, therapeutic, and prognostic applications. This review aims to provide comprehensive insights of CRNDE-mediated oncogenesis and identify CRNDE as a promising target for future clinical interventions.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/genetics
  5. Horne HN, Beena Devi CR, Sung H, Tang TS, Rosenberg PS, Hewitt SM, et al.
    Breast Cancer Res Treat, 2015 Jan;149(1):285-91.
    PMID: 25537643 DOI: 10.1007/s10549-014-3243-9
    Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We, therefore, used two unique population-based resources with molecular data to compare incidence rates for the 'intrinsic' breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the National Cancer Institute's surveillance, epidemiology, and end results 18 registries database (SEER 18). The intrinsic breast cancer subtypes were recapitulated with the joint expression of the HRs (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor-2 (HER2). Invasive breast cancer incidence rates overall were fivefold greater in SEER 18 than in Malaysia. The majority of breast cancers were HR-positive in SEER 18 and HR-negative in Malaysia. Notwithstanding the greater relative distribution for HR-negative cancers in Malaysia, there was a greater absolute risk for all subtypes in SEER 18; incidence rates were nearly 7-fold higher for HR-positive and 2-fold higher for HR-negative cancers in SEER 18. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US than Malaysia. Additional analytical studies are sorely needed to determine the factors responsible for the elevated risk of all subtypes of breast cancer in high-risk countries like the United States.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/genetics
  6. Htwe TT, Karim N, Wong J, Jahanfar S, Mansur MA
    Singapore Med J, 2010 Nov;51(11):856-9.
    PMID: 21140111
    INTRODUCTION: Galectin-3 is a member of the beta-galactoside-binding protein family that plays an important role in cell-to-cell adhesion and in cell-to-matrix interaction. Cellular expression of galectin-3 is correlated with cancer aggressiveness and metastasis.
    METHODS: We examined the differential expression of galectin-3 in a collection of 142 cases of thyroid lesions, including 108 cases of papillary thyroid carcinoma (PTC) and 34 cases of follicular carcinoma (FCA). An immunohistochemical method was applied and semiquantitative scoring was performed on the staining intensity of the positive tissue. Scoring was done on cells at the central portion of the tumour foci and on cells at the periphery that were adjacent to the neighbouring normal thyroid tissue matrix.
    RESULTS: A significantly higher expression (p is 0.001) of galectin-3 was observed in the advancing peripheral thyroid cancer cells compared to the centrally located cells that were not in close contact with the neighbouring stromal tissue in cases with PTC compared to those with FCA.
    CONCLUSION: This finding supported the role of galectin-3 in its cell-to-cell adhesion and cell-to-matrix interaction. Galectin-3 is a potential tumour marker for indicating local and distance metastasis, especially in cases with PTC.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  7. Huang D, Guo W, Gao J, Chen J, Olatunji JO
    Molecules, 2015;20(9):17405-28.
    PMID: 26393569 DOI: 10.3390/molecules200917405
    Clinacanthans nutans (Burm. f.) Lindau is a popular medicinal vegetable in Southern Asia, and its extracts have displayed significant anti-proliferative effects on cancer cells in vitro. However, the underlying mechanism for this effect has yet to be established. This study investigated the antitumor and immunomodulatory activity of C. nutans (Burm. f.) Lindau 30% ethanol extract (CN30) in vivo. CN30 was prepared and its main components were identified using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS/MS). CN30 had a significant inhibitory effect on tumor volume and weight. Hematoxylin and eosin (H & E) staining and TUNEL assay revealed that hepatoma cells underwent significant apoptosis with CN30 treatment, while expression levels of proliferation markers PCNA and p-AKT were significantly decreased when treated with low or high doses of CN30 treatment. Western blot analysis of PAPR, caspase-3, BAX, and Bcl2 also showed that CN30 induced apoptosis in hepatoma cells. Furthermore, intracellular staining analysis showed that CN30 treatment increased the number of IFN-γ⁺ T cells and decreased the number of IL-4⁺ T cells. Serum IFN-γ and interleukin-2 levels also significantly improved. Our findings indicated that CN30 demonstrated antitumor properties by up-regulating the immune response, and warrants further evaluation as a potential therapeutic agent for the treatment and prevention of cancers.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  8. Hung TH, Hsu SC, Cheng CY, Choo KB, Tseng CP, Chen TC, et al.
    Oncotarget, 2014 Dec 15;5(23):12273-90.
    PMID: 25401518
    Multidrug resistance in cancer cells arises from altered drug permeability of the cell. We previously reported activation of the Wnt pathway in ABCB1-overexpressed human uterus sarcoma drug-resistant MES-SA/Dx5 cells through active β-catenin and associated transactivation activities, and upregulation of Wnt-targeting genes. In this study, Wnt5A was found to be significantly upregulated in MES-SA/Dx5 and MCF7/ADR2 cells, suggesting an important role for the Wnt5A signaling pathway in cancer drug resistance. Higher cAMP response elements and Tcf/Lef transcription activities were shown in the drug-resistant cancer cells. However, expression of Wnt target genes and CRE activities was downregulated in Wnt5A shRNA stably-transfected MES-SA/Dx5 cells. Cell viability of the drug-resistant cancer cells was also reduced by doxorubicin treatment and Wnt5A shRNA transfection, or by Wnt5A depletion. The in vitro data were supported by immunohistochemical analysis of 24 paired breast cancer biopsies obtained pre- and post-chemotherapeutic treatment. Wnt5A, VEGF and/or ABCB1 were significantly overexpressed after treatment, consistent with clinical chemoresistance. Taken together, the Wnt5A signaling pathway was shown to contribute to regulating the drug-resistance protein ABCB1 and β-catenin-related genes in antagonizing the toxic effects of doxorubicin in the MDR cell lines and in clinical breast cancer samples.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  9. Hung TH, Chen CM, Tseng CP, Shen CJ, Wang HL, Choo KB, et al.
    Int J Biochem Cell Biol, 2014 Aug;53:55-65.
    PMID: 24814288 DOI: 10.1016/j.biocel.2014.04.011
    Multidrug-resistant (MDR) cancer is a major clinical problem in chemotherapy of cancer patients. We have noted inappropriate PKCδ hypomethylation and overexpression of genes in the PKCδ/AP-1 pathway in the human uterus sarcoma drug-resistant cell line, MES-SA/Dx5 cells, which also overexpress p-glycoprotein (ABCB1). Recent studies have indicated that FZD1 is overexpressed in both multidrug-resistant cancer cell lines and in clinical tumor samples. These data have led us to hypothesize that the FZD1-mediated PKCδ signal-transduction pathway may play an important role in drug resistance in MES-SA/Dx5 cells. In this work, the PKCδ inhibitor Rottlerin was found to reduce ABCB1 expression and to inhibit the MDR drug pumping ability in the MES-SA/Dx5 cells when compared with the doxorubicin-sensitive parental cell line, MES-SA. PKCδ was up-regulated with concurrent up-regulation of the mRNA levels of the AP-1-related factors, c-JUN and c-FOS. Activation of AP-1 also correlated with up-regulation of the AP-1 downstream genes HGF and EGR1. Furthermore, AP-1 activities were reduced and the AP-1 downstream genes were down-regulated in Rottlerin-treated or PKCδ shRNA-transfected cells. MES-SA/Dx5 cells were resensitized to doxorubicin-induced toxicity by co-treatment with doxorubicin and Rottlerin or PKCδ shRNA. In addition, cell viability and drug pump-out ability were significantly reduced in the FZD1 inhibitor curcumin-treated and FZD1 shRNA-knockdown MES-SA/Dx5 cells, indicating involvement of PKCδ in FZD1-modulated ABCB1 expression pathway. Taken together, our data demonstrate that FZD1 regulates PKCδ, and the PKCδ/AP-1 signalling transduction pathway plays an important role in drug resistance in MES-SA/Dx5 cells.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  10. Huq AM, Wai LK, Rullah K, Mohd Aluwi MFF, Stanslas J, Jamal JA
    Chem Biol Drug Des, 2019 03;93(3):222-231.
    PMID: 30251480 DOI: 10.1111/cbdd.13404
    Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson-Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1 μM) and PGR (13.9-fold at 0.01 μM) genes. ERα-mimosine binding energy was -49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  11. Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A, Eshak Z
    Asian Pac J Cancer Prev, 2015;16(14):6047-53.
    PMID: 26320494
    BACKGROUND: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability.

    OBJECTIVE: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells.

    MATERIALS AND METHODS: MTT assays, flow cytometry, comet assays and the reverse transcription- polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers.

    RESULTS: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent.

    CONCLUSIONS: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*
  12. Ibrahim K, Abdul Murad NA, Harun R, Jamal R
    Int J Mol Med, 2020 Aug;46(2):685-699.
    PMID: 32468002 DOI: 10.3892/ijmm.2020.4619
    Glioblastoma multiforme (GBM) is an aggressive type of brain tumour that commonly exhibits resistance to treatment. The tumour is highly heterogenous and complex kinomic alterations have been reported leading to dysregulation of signalling pathways. The present study aimed to investigate the novel kinome pathways and to identify potential therapeutic targets in GBM. Meta‑analysis using Oncomine identified 113 upregulated kinases in GBM. RNAi screening was performed on identified kinases using ON‑TARGETplus siRNA library on LN18 and U87MG. Tousled‑like kinase 1 (TLK1), which is a serine/threonine kinase was identified as a potential hit. In vitro functional validation was performed as the role of TLK1 in GBM is unknown. TLK1 knockdown in GBM cells significantly decreased cell viability, clonogenicity, proliferation and induced apoptosis. TLK1 knockdown also chemosensitised the GBM cells to the sublethal dose of temozolomide. The downstream pathways of TLK1 were examined using microarray analysis, which identified the involvement of DNA replication, cell cycle and focal adhesion signalling pathways. In vivo validation of the subcutaneous xenografts of stably transfected sh‑TLK1 U87MG cells demonstrated significantly decreased tumour growth in female BALB/c nude mice. Together, these results suggested that TLK1 may serve a role in GBM survival and may serve as a potential target for glioma.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/genetics; Gene Expression Regulation, Neoplastic/physiology
  13. Ibrahim N, Nazimi AJ, Ajura AJ, Nordin R, Latiff ZA, Ramli R
    J Craniofac Surg, 2016 Jul;27(5):1361-6.
    PMID: 27391504 DOI: 10.1097/SCS.0000000000002792
    The aim of this study was to describe the clinical features and expression of bcl-2, cyclin D1, p53, and proliferating cell nuclear antigen (PCNA) antibodies in syndromic (nevoid basal cell carcinoma syndrome [NBCCS]) and nonsyndromic patients diagnosed with keratocystic odontogenic tumor (KCOT).

    METHODS: This descriptive study comprised 5 patients of KCOT associated with NBCCS and 8 patients of nonsyndromic type treated in the Department of Oral Maxillofacial Surgery, Universiti Kebangsaan Malaysia Medical Centre between years 1998 and 2011. The clinical features (site, size, treatment, and recurrence), demographic characteristics, and immunohistochemistry results using antibodies of bcl-2, cyclin D1, p53, and PCNA were examined. The association of the antibody expression and the type of KCOT was analyzed using Fisher exact test.

    RESULTS: Altogether there were 13 patients, 5 with syndromic KCOT (1 patient met 3 major criteria of NBCCS) and 8 with sporadic KCOT. The age range for syndromic KCT was 11 to 21 years (mean 16.00 years, SD 4.36) and 10 to 54 years (median 24.50 years, interquartile range 19.00) for the nonsyndromic KCOT. Tumor recurrence occurred in 3 patients (7.7%); 1 patient from the syndromic and 2 patients from the nonsyndromic. The most positive expression was observed in PCNA for both the syndromic and nonsyndromic samples and the least positive expression involved the p53.

    CONCLUSION: PCNA, bcl-2 protein, and cyclin D1 expressions could be useful in evaluating the proliferative activity of the tumor and the aggressiveness of the clinical presentation; however, the authors would propose for larger sample size research for more definitive results.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  14. In LL, Azmi MN, Ibrahim H, Awang K, Nagoor NH
    Anticancer Drugs, 2011 Jun;22(5):424-34.
    PMID: 21346553 DOI: 10.1097/CAD.0b013e328343cbe6
    In this study, the apoptotic mechanism and combinatorial chemotherapeutic effects of the cytotoxic phenylpropanoid compound 1'S-1'-acetoxyeugenol acetate (AEA), extracted from rhizomes of the Malaysian ethnomedicinal plant Alpinia conchigera Griff. (Zingiberaceae), on MCF-7 human breast cancer cells were investigated for the first time. Data from cytotoxic and apoptotic assays such as live and dead and poly-(ADP-ribose) polymerase cleavage assays indicated that AEA was able to induce apoptosis in MCF-7 cells, but not in normal human mammary epithelial cells. A microarray global gene expression analysis of MCF-7 cells, treated with AEA, suggested that the induction of tumor cell death through apoptosis was modulated through dysregulation of the nuclear factor-kappaB (NF-κB) pathway, as shown by the reduced expression of various κB-regulated gene targets. Consequent to this, western blot analysis of proteins corresponding to the NF-κB pathway indicated that AEA inhibited phosphorylation levels of the inhibitor of κB-kinase complex, resulting in the elimination of apoptotic resistance originating from NF-κB activation. This AEA-based apoptotic modulation was elucidated for the first time in this study, and gave rise to the proposal of an NF-κB model termed the 'Switching/Alternating Model.' In addition to this, AEA was also found to synergistically enhance the proapoptotic effects of paclitaxel, when used in combination with MCF-7 cells, presumably by a chemosensitizing role. Therefore, it was concluded that AEA isolated from the Malaysian tropical ginger (A. conchigera) served as a very promising candidate for further in-vivo development in animal models and in subsequent clinical trials involving patients with breast-related malignancies.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  15. Ismail AF, Oskay Halacli S, Babteen N, De Piano M, Martin TA, Jiang WG, et al.
    Biochem. J., 2017 Mar 24;474(8):1333-1346.
    PMID: 28232500 DOI: 10.1042/BCJ20160875
    Urothelial bladder cancer is a major cause of morbidity and mortality worldwide, causing an estimated 150 000 deaths per year. Whilst non-muscle-invasive bladder tumours can be effectively treated, with high survival rates, many tumours recur, and some will progress to muscle-invasive disease with a much poorer long-term prognosis. Thus, there is a pressing need to understand the molecular transitions occurring within the progression of bladder cancer to an invasive disease. Tumour invasion is often associated with a down-regulation of E-cadherin expression concomitant with a suppression of cell:cell junctions, and decreased levels of E-cadherin expression have been reported in higher grade urothelial bladder tumours. We find that expression of E-cadherin in a panel of bladder cancer cell lines correlated with the presence of cell:cell junctions and the level of PAK5 expression. Interestingly, exogenous PAK5 has recently been described to be associated with cell:cell junctions and we now find that endogenous PAK5 is localised to cell junctions and interacts with an E-cadherin complex. Moreover, depletion of PAK5 expression significantly reduced junctional integrity. These data suggest a role for PAK5 in maintaining junctional stability and we find that, in both our own patient samples and a commercially available dataset, PAK5mRNA levels are reduced in human bladder cancer compared with normal controls. Taken together, the present study proposes that PAK5 expression levels could be used as a novel prognostic marker for bladder cancer progression.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  16. Ismail NI, Othman I, Abas F, H Lajis N, Naidu R
    Int J Mol Sci, 2019 May 17;20(10).
    PMID: 31108984 DOI: 10.3390/ijms20102454
    Colorectal cancer (CRC) is among the top three cancer with higher incident and mortality rate worldwide. It is estimated that about over than 1.1 million of death and 2.2 million new cases by the year 2030. The current treatment modalities with the usage of chemo drugs such as FOLFOX and FOLFIRI, surgery and radiotherapy, which are usually accompanied with major side effects, are rarely cured along with poor survival rate and at higher recurrence outcome. This trigger the needs of exploring new natural compounds with anti-cancer properties which possess fewer side effects. Curcumin, a common spice used in ancient medicine was found to induce apoptosis by targeting various molecules and signaling pathways involved in CRC. Disruption of the homeostatic balance between cell proliferation and apoptosis could be one of the promoting factors in colorectal cancer progression. In this review, we describe the current knowledge of apoptosis regulation by curcumin in CRC with regard to molecular targets and associated signaling pathways.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  17. Jafarlou M, Baradaran B, Shanehbandi D, Saedi TA, Jafarlou V, Ismail P, et al.
    Cell Mol Biol (Noisy-le-grand), 2016 May 30;62(6):44-9.
    PMID: 27262801
    Acute myeloid leukemia (AML) is one of the most frequent types of leukemia which mostly affects adult people. Resistance to therapeutic drugs is considered as a major clinical concern resulting in a weaker response to chemotherapy, disease relapse and decreased survival rate. Survivin, a member of Inhibitor of Apoptosis Proteins (IAPs), is associated with drug resistance and inhibition of apoptotic mechanisms in numerous hematological malignancies. In the present study, we examined the combined effect of etoposide and siRNA-mediated silencing of survivin on U-937 acute myeloid leukemia cells. The AML cells were transfected with survivin specific siRNA and gene knockdown was confirmed by quantitative real time PCR and western blotting. Subsequently, U-937 cells were assessed for response to etoposide treatment and apoptosis rate was measured with flowcytometery. The cytotoxic effects in siRNA-etoposide group were measured and compared to etoposide single therapy group. Survivin siRNA effectively knocked down the mRNA and protein levels of survivin, which led to lower cell proliferation and enhanced apoptosis. Furthermore, combined treatment of etoposide and survivin siRNA synergistically increased the cell toxic effects of etoposide and its ability to induce apoptosis.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  18. Jahidin AH, Stewart TA, Thompson EW, Roberts-Thomson SJ, Monteith GR
    Biochem Biophys Res Commun, 2016 Sep 02;477(4):731-736.
    PMID: 27353380 DOI: 10.1016/j.bbrc.2016.06.127
    Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca(2+). These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  19. Jeon AJ, Teo YY, Sekar K, Chong SL, Wu L, Chew SC, et al.
    BMC Cancer, 2023 Feb 03;23(1):118.
    PMID: 36737737 DOI: 10.1186/s12885-022-10444-3
    BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).

    METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples.

    RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate.

    DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  20. Jusoh AR, Mohan SV, Lu Ping T, Tengku Din TADAAB, Haron J, Romli RC, et al.
    Asian Pac J Cancer Prev, 2021 May 01;22(5):1375-1381.
    PMID: 34048164 DOI: 10.31557/APJCP.2021.22.5.1375
    OBJECTIVE: This study aimed to characterize the miRNA expression profiles from plasma samples of our local breast cancer patients in comparison to healthy control by using miRNA PCR Array.

    METHODS: In this study, plasma miRNA profiles from eight early-stage breast cancer patients and nine age-matched (± 2 years) healthy controls were characterized by miRNA array-based approach, followed by differential gene expression analysis, Independent T-test and construction of Receiver Operating Characteristic (ROC) curve to determine the capability of the assays to discriminate between breast cancer and the healthy control.

    RESULTS: Based on the 372-miRNAs microarray profiling, a set of 40 differential miRNAs was extracted regarding to the fold change value at 2 and above. We further sub grouped 40 miRNAs of breast cancer patients that were significantly expressed at 2-fold change and higher. In this set, we discovered that 24 miRNAs were significantly upregulated and 16 miRNAs were significantly downregulated in breast cancer patients, as compared to the miRNA expression of healthy subjects. ROC curve analysis revealed that seven miRNAs (miR-125b-5p, miR-142-3p, miR-145-5p, miR-193a-5p, miR-27b-3p, miR-22-5p and miR-423-5p) had area under curve (AUC) value > 0.7 (AUC p-value < 0.05). Overlapping findings from differential gene expression analysis, ROC analysis, and Independent T-Test resulted in three miRNAs (miR-27b-3p, miR-22-5p, miR-145-5p). Cohen's effect size for these three miRNAs was large with d value are more than 0.95.

    CONCLUSION: miR-27b-3p, miR-22-5p, miR-145-5p could be potential biomarkers to distinguish breast cancer patients from healthy controls. A validation study for these three miRNAs in an external set of samples is ongoing.
    .

    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
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