Displaying publications 541 - 560 of 660 in total

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  1. Yusof ZY, Netuveli G, Ramli AS, Sheiham A
    Oral Health Prev Dent, 2006;4(3):165-71.
    PMID: 16961024
    OBJECTIVES: To assess whether or not opportunistic oral cancer screening by dentists to detect pre-malignant or early cancer lesions is feasible. The objective was to analyse the patterns of dental attendance of a national representative sample over a period of 10 years to ascertain whether individuals at high-risk of oral cancer would be accessible for opportunistic oral cancer screening.

    METHODS: Secondary analysis of data extracted from the British Household Panel Survey, a national longitudinal survey (n=5547). Analysis to ascertain whether patterns of attendance for dental check-ups for a period of 10 years (1991-2001) were associated with risk factors for oral cancer such as age, sex, education, social class, smoking status and smoking intensity.

    RESULTS: Males, aged over 40 years, less educated manual workers and smokers were significantly less likely to attend for dental check-ups compared with females and younger, higher educated, higher socio-economic class non-smokers (p < 0.05). Throughout the 10-year period, young people, more than older people, had progressively lower odds ratios of attending. Those with more education used dental services more. Heavy smokers were infrequent attendees.

    CONCLUSIONS: This study suggests that opportunistic oral cancer screening by dentists is not feasible to include high-risk groups as they are not regular attendees over 10 years. Those who would be screened would be the low-risk groups. However, dentists should continue screening all patients as oral precancers are also found in regular attendees. More should be done to encourage the high-risk groups to visit their dentists.

    Matched MeSH terms: Mouth Neoplasms/diagnosis*
  2. Roberts R, Yee PTI, Mujawar S, Lahiri C, Poh CL, Gatherer D
    Sci Rep, 2019 04 01;9(1):5427.
    PMID: 30931960 DOI: 10.1038/s41598-019-41662-8
    Enterovirus A71 (EV-A71) is an emerging pathogen in the Enterovirus A species group. EV-A71 causes hand, foot and mouth disease (HFMD), with virulent variants exhibiting polio-like acute flaccid paralysis and other central nervous system manifestations. We analysed all enterovirus A71 complete genomes with collection dates from 2008 to mid-2018. All sub-genotypes exhibit a strong molecular clock with omega (dN/dS) suggesting strong purifying selection. In sub-genotypes B5 and C4, positive selection can be detected at two surface sites on the VP1 protein, also detected in positive selection studies performed prior to 2008. Toggling of a limited repertoire of amino acids at these positively selected residues over the last decade suggests that EV-A71 may be undergoing a sustained frequency-dependent selection process for immune evasion, raising issues for vaccine development. These same sites have also been previously implicated in virus-host binding and strain-associated severity of HFMD, suggesting that immune evasion may be an indirect driver for virulence (154 words).
    Matched MeSH terms: Hand, Foot and Mouth Disease/virology
  3. Yap YH, Say YH
    Cell Biol Int, 2012 Mar 1;36(3):273-7.
    PMID: 21980981 DOI: 10.1042/CBI20110088
    Since the discovery of PrPC (cellular prion protein), most studies have focused on its role in neurodegenerative diseases, whereas its function outside the nervous system remains obscure. We investigated the ability of PrPC in resisting TNFα (tumour necrosis factor α) apoptosis in three PrPC-transiently transfected cancer cell lines, renal adenocarcinoma ACHN, oral squamous cell carcinoma HSC-2 and colon adenocarcinoma LS174T. PrPC-expressing ACHN and LS174T cells had higher viabilities compared with the mock-transfected cells, while the transient overexpression of PrPC had minimal overall effect on HSC-2 cells due to its high endogenous PrPC expression. Cell cycles were also analysed, with both PrPC expressing ACHN and LS174T cells having a significantly higher proliferative index than mock-transfected cells. Flow cytometry analysis indicated a G1/S-phase cell cycle transition in both PrPC-expressing ACHN and LS174T cells. PrPC resists TNFα apoptosis due to a modest, but statistically significant, cell-specific cytoprotection compared with mock-transfected cells.
    Matched MeSH terms: Mouth Neoplasms/metabolism*
  4. Qamruddin I, Alam MK, Mahroof V, Karim M, Fida M, Khamis MF, et al.
    Pain Res Manag, 2021;2021:6624723.
    PMID: 34035871 DOI: 10.1155/2021/6624723
    Objective: Low-intensity pulsed ultrasound (LIPUS) is a noninvasive modality to stimulate bone remodeling (BR) and the healing of hard and soft tissues. This research evaluates the biostimulatory effect of LIPUS on the rate of orthodontic tooth movement (OTM) and associated pain, when applied at 3-week intervals.

    Methods: Twenty-two patients (11 males and 11 females; mean age 19.18 ± 2.00 years) having Angle's Class II division 1 malocclusion needing bilateral extractions of maxillary first bicuspids were recruited for this split-mouth randomized clinical trial. After the initial stage of alignment and leveling with contemporary edgewise MBT (McLaughlin-Bennett-Trevisi) prescription brackets (Ortho Organizers, Carlsbad, Calif) of 22 mil, followed by extractions of premolars bilaterally, 6 mm nickel-titanium spring was used to retract the canines separately by applying 150 g force on 0.019 × 0.025-in stainless steel working archwires. LIPUS (1.1 MHz frequency and 30 mW/cm2 intensity output) was applied for 20 minutes extraorally and reapplied after 3 weeks for 2 more successive visits over the root of maxillary canine on the experimental side whereas the other side was placebo. A numerical rating scale- (NRS-) based questionnaire was given to the patients on each visit to record their weekly pain experience. Impressions were also made at each visit before the application of LIPUS (T1, T2, and T3). Models were scanned with a CAD/CAM scanner (Planmeca, Helsinki, Finland). Mann-Whitney U test was applied for comparison of canine movement and pain intensity between both the groups.

    Results: No significant difference in the rate of canine movement was found among the experimental (0.90 mm ± 0.33 mm) and placebo groups (0.81 mm ± 0.32 mm). There was no difference in pain reduction between experimental and placebo groups (p > 0.05).

    Conclusion: Single-dose application of LIPUS at 3-week intervals is ineffective in stimulating the OTM and reducing associated treatment pain.

    Matched MeSH terms: Mouth/physiopathology
  5. Raja NS, Karunakaran R, Ngeow YF, Awang R
    J Med Microbiol, 2005 Sep;54(Pt 9):901-903.
    PMID: 16091445 DOI: 10.1099/jmm.0.46169-0
    Vancomycin-resistant enterococci (VRE) are formidable organisms renowned for their ability to cause infections with limited treatment options and their potential for transferring resistance genes to other Gram-positive bacteria. Usually associated with nosocomial infections, VRE are rarely reported as a cause of community-acquired infection. Presented here is a case of community-acquired infection due to vancomycin-resistant Enterococcus faecium. The patient had been applying herbal leaves topically to his cheek to treat a buccal space abscess, resulting in a burn of the overlying skin. From pus aspirated via the skin a pure culture of E. faecium was grown that was resistant to vancomycin with a MIC of >256 microg ml-1 by the E test and resistant to teicoplanin by disc diffusion, consistent with the VanA phenotype. The organism was suspected of contaminating the leaf and infecting the patient via the burnt skin. This case highlights the need for further studies on the community prevalence of VRE among humans and animals to define unrecognized silent reservoirs for VRE, which may pose a threat to public health.
    Matched MeSH terms: Mouth Mucosa/microbiology
  6. Balasegaram M
    S Afr J Surg, 1972 Jun;10(2):79-87.
    PMID: 4546544
    Matched MeSH terms: Mouth Neoplasms/surgery
  7. Haron N, Zain RB, Nabillah WM, Saleh A, Kallarakkal TG, Ramanathan A, et al.
    Telemed J E Health, 2017 03;23(3):192-199.
    PMID: 27541205 DOI: 10.1089/tmj.2016.0128
    INTRODUCTION: This study examined the concordance in clinical diagnosis of high-risk lesions in the oral cavity and referral decisions between clinical oral examination (COE) and teledentistry.

    MATERIALS AND METHODS: Sixteen individuals with a range of oral potentially malignant disorders (OPMD) and normal oral mucosa were included. Five areas of the oral cavity were photographed by three dentists using mobile phone cameras with 5 MP-13 MP resolutions. On the same day, the patients were given COE by two oral medicine specialists (OMS) and 3 weeks later, they reviewed the images taken using the phone, and concordance was examined between the two by Kappa statistics. The sensitivity and specificity of clinical diagnosis using the phone images were also measured. Pre- and post-program questionnaires were answered by both the dentists and the OMS to determine the feasibility of integrating teledentistry in their clinical practice.

    RESULTS: The Kappa values in determining the presence of lesion, category of lesion (OPMD or not), and making referral decision were moderate to strong (0.64-1.00). The overall sensitivity was more than 70% and specificity was 100%. The false negative rate decreased as the camera resolution increased. All dentists agreed that the process could facilitate early detection of oral mucosal lesion, and was easy to use in the clinic.

    CONCLUSIONS: This study provides evidence that teledentistry can be used for communication between primary care and OMS and could be readily integrated into clinical setting for patient management.

    Matched MeSH terms: Mouth Neoplasms/diagnosis*
  8. Fahmy O, Schubert T, Khairul-Asri MG, Stenzl A, Gakis G
    Int J Urol, 2017 04;24(4):320-323.
    PMID: 28208217 DOI: 10.1111/iju.13307
    The surgical treatment of a long proximal ureteral stricture is a challenging situation for reconstructive surgeons. Despite the underlying morbidities, ileal interposition and autotransplantation are the options available to treat complex cases of long segment ureteral stricture. Buccal mucosa has shown excellent results in urethroplasty. However, its use in ureteral reconstruction is infrequent. We report on a 64-year-old female patient with multiple comorbidities and prior abdominal surgeries for Crohn's disease who underwent a successful total substitution of a long segment of the proximal ureter using buccal mucosa. Regular postoperative isotope scans showed improvement in renal function. Based on the pleasant outcome of this case and review of the literature, buccal mucosa might be a viable option with low morbidity in selected cases.
    Matched MeSH terms: Mouth Mucosa/transplantation*
  9. Eachempati P, Aggarwal H, Shenoy VK, Baliga M
    J Coll Physicians Surg Pak, 2018 Sep;28(9):S187-S189.
    PMID: 30173693 DOI: 10.29271/jcpsp.2018.09.S187
    Oral mucosal melanoma is rare and more aggressive than cutaneous melanoma. Hard palate and maxillary alveolar crest are most commonly involved. Multidisciplinary team approach is necessary for successful management of this tumor. The main treatment modality is surgical resection, which usually results in impaired mastication, deglutition, speech, oral competence and significant cosmetic deformity. Here, a rare case of oral mucosal melanoma of mandibular gingiva in a 44-year man is reported, who was treated by en-block mandibular resection followed by adjuvant therapy with high dose interferons (IFN) - 2b. Following two weeks of healing period, prosthetic rehabilitation of the patient was done with an interim removable denture prosthesis, which effectively limited the unfavourable effects of surgery and helped him in resocialisation.
    Matched MeSH terms: Mouth Mucosa/pathology*
  10. Kim JY, Kim J, Bandara BMR, Tilakaratne WM, Kim D
    BMC Complement Med Ther, 2022 Jan 25;22(1):20.
    PMID: 35078428 DOI: 10.1186/s12906-022-03505-4
    BACKGROUND: Osbeckia octandra is a plant endemic to Sri Lanka and is used in ethnomedicine for treating various diseases. However, the anti-cancer properties of O. octandra are yet to be fully investigated. In the present study, we evaluated the anti-cancer effects of O. octandra on oral cancer cells.

    METHODS: Human oral cancer cell lines (HSC2, YD10B, YD38, YD9, and YD32) were used in this study. BrdU incorporation, cell cycle and annexin-V/PI staining were all evaluated using flow cytometry to determine the extent to which O. octandra leaf extract inhibits cell proliferation and induces apoptosis. Cell viability and reactive oxygen species (ROS) were also measured in order to investigate the anti-cancer effects of O. octandra extracts. Western blotting was performed to detect cell cycle related protein such as cyclin d1 and cdk4, and to detect apoptosis-related proteins such as Bcl-2, Bcl-XL, Bax, Caspase-9, Cleaved caspase-3, Fas, Caspase-8, and Bid.

    RESULTS: Leaf extract of O. octandra reduced oral squamous cell carcinoma (OSCC) cell viability in a dose-dependent manner. Leaf extract of O. octandra has non-toxic in normal keratinocytes. Also, O. octandra extract interrupted the DNA replication via G1 phase arrests, and this effect was independent of ROS generation. In the apoptosis-related experiments, the population of annexin V-positive cells increased upon treatment with O. octandra extract. Furthermore, the expression of anti-apoptotic protein (Bcl-2 and Bcl-xL) was decreased, whereas the expression of cleaved caspase-3 protein was increased in O. octandra-treated OSCC cells.

    CONCLUSIONS: The results suggest that a leaf extract of O. octandra inhibited the proliferation of OSCC cells through G1 phase arrest and interrupting DNA replication. The leaf extract of O. octandra could trigger the apoptotic response via caspase 3 activation in OSCC cells. These results suggest that O. octandra has the potential to be developed as an alternative medicine for treating OSCC.

    Matched MeSH terms: Mouth Neoplasms/drug therapy*
  11. Rajandram RK, Ramli R, Karim F, Rahman RA, Fun LC
    N Z Med J, 2007;120(1256):U2590.
    PMID: 17589558
    Agranulocytosis is a rare complication of ticlopidine and can be life-threatening. We report a case of ticlopidine-induced agranulocytosis and neutropenia (neutrophil count of 0.1 x 10(9)/L) with necrotizing gingivitis in a 54-year-old Malaysian-Chinese female. She was started on ticlopidine 250 mg twice daily 3 weeks prior to this hospital admission. We started her on intravenous metronidazole and amoxicillin and clavulanic acid (Augmentin) and concurrently stopped ticlopidine. A series of clinical and laboratory investigations were carried out and a final diagnosis of necrotizing gingivitis possibly secondary to agranulocytosis was made. The patient was discharged home after 2 weeks of hospitalisation.
    Matched MeSH terms: Mouth Mucosa/pathology
  12. Zanaruddin SN, Yee PS, Hor SY, Kong YH, Ghani WM, Mustafa WM, et al.
    PLoS One, 2013;8(11):e80229.
    PMID: 24224046 DOI: 10.1371/journal.pone.0080229
    OBJECTIVES: The frequency of common oncogenic mutations and TP53 was determined in Asian oral squamous cell carcinoma (OSCC).

    MATERIALS AND METHODS: The OncoCarta(™) panel v1.0 assay was used to characterize oncogenic mutations. In addition, exons 4-11 of the TP53 gene were sequenced. Statistical analyses were conducted to identify associations between mutations and selected clinico-pathological characteristics and risk habits.

    RESULTS: Oncogenic mutations were detected in PIK3CA (5.7%) and HRAS (2.4%). Mutations in TP53 were observed in 27.7% (31/112) of the OSCC specimens. Oncogenic mutations were found more frequently in non-smokers (p = 0.049) and TP53 truncating mutations were more common in patients with no risk habits (p = 0.019). Patients with mutations had worse overall survival compared to those with absence of mutations; and patients who harbored DNA binding domain (DBD) and L2/L3/LSH mutations showed a worse survival probability compared to those patients with wild type TP53. The majority of the oncogenic and TP53 mutations were G:C > A:T and A:T > G:C base transitions, regardless of the different risk habits.

    CONCLUSION: Hotspot oncogenic mutations which are frequently present in common solid tumors are exceedingly rare in OSCC. Despite differences in risk habit exposure, the mutation frequency of PIK3CA and HRAS in Asian OSCC were similar to that reported in OSCC among Caucasians, whereas TP53 mutations rates were significantly lower. The lack of actionable hotspot mutations argue strongly for the need to comprehensively characterize gene mutations associated with OSCC for the development of new diagnostic and therapeutic tools.

    Matched MeSH terms: Mouth Neoplasms/genetics*
  13. Aw-Yong KL, Sam IC, Koh MT, Chan YF
    PLoS One, 2016;11(11):e0165659.
    PMID: 27806091 DOI: 10.1371/journal.pone.0165659
    Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD). Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4), and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142-156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41-55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates.
    Matched MeSH terms: Hand, Foot and Mouth Disease/immunology*
  14. Tan le V, Tuyen NT, Thanh TT, Ngan TT, Van HM, Sabanathan S, et al.
    J Virol Methods, 2015 Apr;215-216:30-6.
    PMID: 25704598 DOI: 10.1016/j.jviromet.2015.02.011
    Enterovirus A71 (EV-A71) has emerged as the most important cause of large outbreaks of severe and sometimes fatal hand, foot and mouth disease (HFMD) across the Asia-Pacific region. EV-A71 outbreaks have been associated with (sub)genogroup switches, sometimes accompanied by recombination events. Understanding EV-A71 population dynamics is therefore essential for understanding this emerging infection, and may provide pivotal information for vaccine development. Despite the public health burden of EV-A71, relatively few EV-A71 complete-genome sequences are available for analysis and from limited geographical localities. The availability of an efficient procedure for whole-genome sequencing would stimulate effort to generate more viral sequence data. Herein, we report for the first time the development of a next-generation sequencing based protocol for whole-genome sequencing of EV-A71 directly from clinical specimens. We were able to sequence viruses of subgenogroup C4 and B5, while RNA from culture materials of diverse EV-A71 subgenogroups belonging to both genogroup B and C was successfully amplified. The nature of intra-host genetic diversity was explored in 22 clinical samples, revealing 107 positions carrying minor variants (ranging from 0 to 15 variants per sample). Our analysis of EV-A71 strains sampled in 2013 showed that they all belonged to subgenogroup B5, representing the first report of this subgenogroup in Vietnam. In conclusion, we have successfully developed a high-throughput next-generation sequencing-based assay for whole-genome sequencing of EV-A71 from clinical samples.
    Matched MeSH terms: Hand, Foot and Mouth Disease/virology*
  15. Vincent-Chong VK, Ismail SM, Rahman ZA, Sharifah NA, Anwar A, Pradeep PJ, et al.
    Oral Dis, 2012 Jul;18(5):469-76.
    PMID: 22251088 DOI: 10.1111/j.1601-0825.2011.01894.x
    Multistep pathways and mechanisms are involved in the development of oral cancer. Chromosomal alterations are one of such key mechanisms implicated oral carcinogenesis. Therefore, this study aims to determine the genomic copy number alterations (CNAs) in oral squamous cell carcinoma (OSCC) using array comparative genomic hybridization (aCGH) and in addition attempt to correlate CNAs with modified gene expression.
    Matched MeSH terms: Mouth Neoplasms/genetics*; Mouth Neoplasms/metabolism
  16. Alabsi AM, Lim KL, Paterson IC, Ali-Saeed R, Muharram BA
    Biomed Res Int, 2016;2016:4904016.
    PMID: 27123447 DOI: 10.1155/2016/4904016
    Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome c enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.
    Matched MeSH terms: Mouth Neoplasms/metabolism; Mouth Neoplasms/pathology*
  17. Sosroseno W, Bird PS, Gemmell E, Seymour GJ
    Oral Microbiol. Immunol., 2003 Oct;18(5):318-22.
    PMID: 12930525
    Mucosal presentation of Actinomyces viscosus results in antigen-specific systemic immune suppression, known as oral tolerance. The aim of the present study was to determine the mechanism by which this oral tolerance is induced. DBA/2 mice were gastrically immunized with A. viscosus. Serum, Peyer's patch (PP) and spleen cells were transferred to syngeneic recipients which were then systemically challenged with the sameiA. viscosus strain. To determine antigen-specificity of cells from gastrically immunized mice, recipients which received immune spleen cells were also challenged with Porphyromonas gingivalis. One week after the last systemic challenge, the delayed type hypersensitivity (DTH) response was determined by footpad swelling and the level of serum IgG, IgA and IgM antibodies to A. viscosus or P. gingivalis measured by an ELISA. No suppression of DTH response or of specific serum antibodies was found in recipients which received serum from gastrically immunized mice. Systemic immune suppression to A. viscosus was observed in recipients which had been transferred with PP cells obtained 2 days but not 4 and 6 days after gastric immunization with A. viscosus. Conversely, suppressed immune response could be seen in recipients transferred with spleen cells obtained 6 days after gastric immunization. The immune response to P. gingivalis remained unaltered in mice transferred with A. viscosus-gastrically immunized cells. The results of the present study suggest that oral tolerance induced by A. viscosus may be mediated by antigen-specific suppressor cells which originate in the PP and then migrate to the spleen.
    Matched MeSH terms: Mouth Mucosa/immunology*; Mouth Mucosa/microbiology
  18. Chan YF, Wee KL, Chiam CW, Khor CS, Chan SY, Amalina W MZ, et al.
    Trop Biomed, 2012 Sep;29(3):451-66.
    PMID: 23018509 MyJurnal
    Three genomic regions, VP4 capsid, VP1 capsid and 3D RNA polymerase of human enterovirus 71 (EV-71) and coxsackievirus A16 (CV-A16) were sequenced to understand the evolution of these viruses in Malaysia. A total of 42 EV-71 and 36 CV-A16 isolates from 1997- 2008 were sequenced. Despite the presence of many EV-71 subgenotypes worldwide, only subgenotypes B3, B4, B5, C1 and C2 were present in Malaysia. Importation of other subgenotypes such as C3, C4/D and C5 from other countries was infrequent. For CV-A16, the earlier subgenotype B1 was replaced by subgenotypes B2a and the recent B2c. Subgenotype B2a was present throughout the study while B2c only emerged in 2005. No genetic signatures could be attributed to viral virulence suggesting that host factors have a major role in determining the outcome of infection. Only three EV-71 B3 isolates showed non-consistent phylogeny in the 3D RNA polymerase region which indicated occurrence of recombination in EV-71. High genetic diversity was observed in the Malaysian EV-71 but Malaysian CV-A16 showed low genetic diversity in the three genomic regions sequenced. EV-71 showed strong purifying selection, but that occurred to a lesser extent in CV-A16.
    Matched MeSH terms: Hand, Foot and Mouth Disease/epidemiology; Hand, Foot and Mouth Disease/virology*
  19. Lee HM, Patel V, Shyur LF, Lee WL
    Phytomedicine, 2016 Nov 15;23(12):1535-1544.
    PMID: 27765374 DOI: 10.1016/j.phymed.2016.09.005
    BACKGROUND: Oral cancer is the sixth most common cancer worldwide and 90% of oral malignancies are caused by oral squamous cell carcinoma (OSCC). Curcumin, a phytocompound derived from turmeric (Curcuma longa) was observed to have anti-cancer activity which can be developed as an alternative treatment option for OSCC. However, OSCC cells with various clinical-pathological features respond differentially to curcumin treatment.

    HYPOTHESIS: Intracellular copper levels have been reported to correlate with tumor pathogenesis and affect the sensitivity of cancer cells to cytotoxic chemotherapy. We hypothesized that intracellular copper levels may affect the sensitivity of oral cancer cells to curcumin.

    METHODS: We analysed the correlation between intracellular copper levels and response to curcumin treatment in a panel of OSCC cell lines derived from oral cancer patients. Exogenous copper was supplemented in curcumin insensitive cell lines to observe the effect of copper on curcumin-mediated inhibition of cell viability and migration, as well as induction of oxidative stress and apoptosis. Protein markers of cell migration and oxidative stress were also analysed using Western blotting.

    RESULTS: Concentrations of curcumin which inhibited 50% OSCC cell viability (IC50) was reduced up to 5 times in the presence of 250 µM copper. Increased copper level in curcumin-treated OSCC cells was accompanied by the induction of intracellular ROS and increased level of Nrf2 which regulates oxidative stress responses in cells. Supplemental copper also inhibited migration of curcumin-treated cells with enhanced level of E-cadherin and decreased vimentin, indications of suppressed epithelial-mesenchymal transition. Early apoptosis was observed in combined treatment but not in treatment with curcumin or copper alone.

    CONCLUSION: Supplement of copper significantly enhanced the inhibitory effect of curcumin treatment on migration and viability of oral cancer cells. Together, these findings provide molecular insight into the role of copper in overcoming insensitivity of oral cancer cells to curcumin treatment, suggesting a new strategy for cancer therapy.

    Matched MeSH terms: Mouth Neoplasms/drug therapy*; Mouth Neoplasms/metabolism
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