Displaying publications 1 - 20 of 30 in total

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  1. Falavigna A, Quadros FW, Teles AR, Wong CC, Barbagallo G, Brodke D, et al.
    Global Spine J, 2018 May;8(3):303-310.
    PMID: 29796379 DOI: 10.1177/2192568217735804
    Study Design: Cross-sectional study.

    Objectives: To continue the line of a previous publication using steroid for acute spinal cord injury (SCI) by spine surgeons from Latin America (LA) and assess the current status of methylprednisolone (MP) prescription in Europe (EU), Asia Pacific (AP), North America (NA), and Middle East (ME) to determine targets for educational activities suitable for each region.

    Methods: The English version of a previously published questionnaire was used to evaluate opinions about MP administration in acute SCI in LA, EU, AP, NA, and ME. This Internet-based survey was conducted by members of AOSpine. The questionnaire asked about demographic features, background with management of spine trauma patients, routine administration of MP in acute SCI, and reasons for MP administration.

    Results: A total of 2659 responses were obtained for the electronic questionnaire from LA, EU, AP, NA, and ME. The number of spine surgeons that treat SCI was 2206 (83%). The steroid was used by 1198 (52.9%) surgeons. The uses of MP were based predominantly on the National Acute Spinal Cord Injury Study III study (n = 595, 50%). The answers were most frequently given by spine surgeons from AP, ME, and LA. These regions presented a statistically significant difference from North America (P < .001). The number of SCI patients treated per year inversely influenced the use of MP. The higher the number of patients treated, the lower the administration rates of MP observed.

    Conclusions: The study identified potential targets for educational campaigns, aiming to reduce inappropriate practices of MP administration.

  2. Sureisen M, Achannan R, Chong KC, Wong CC
    BMJ Case Rep, 2015 Oct 27;2015.
    PMID: 26508120 DOI: 10.1136/bcr-2015-212748
    Congenital spinal fusion of an odontoid process to an atlantal hemiarch is very rare. The unfamiliarity of the medical fraternity with this congenital malformation can easily be mistaken for an acute fracture, chronic infection or inflammatory disease. We present our experience of managing an adult who presented with neck pain after a motor vehicle accident. Radiological investigation revealed congenital fusion of the odontoid process to the atlantal hemiarch. The prevalence, embryology and clinical significance of this anomaly are discussed. As the natural progression of this anomaly is not well documented, we suggest periodic follow-up to monitor the progression of degenerative changes and instability of the occipitoatlantal junction.
  3. Shetty AP, Rajavelu R, Viswanathan VK, Watanabe K, Chhabra HS, Kanna RM, et al.
    Asian Spine J, 2020 Aug;14(4):475-488.
    PMID: 32493003 DOI: 10.31616/asj.2020.0014
    STUDY DESIGN: Multicenter validation study.

    PURPOSE: To evaluate the inter-rater reliability of Rajasekaran's kyphosis classification through a multicenter validation study.

    OVERVIEW OF LITERATURE: The classification of kyphosis, developed by Rajasekaran, incorporates factors related to curve characteristics, including column deficiency, disc mobility, curve magnitude, and osteotomy requirements. Although the classification offers significant benefits in determining prognosis and management decisions, it has not been subjected to multicenter validation.

    METHODS: A total of 30 sets of images, including plain radiographs, computed tomography scans, and magnetic resonance imaging scans, were randomly selected from our hospital patient database. All patients had undergone deformity correction surgery for kyphosis. Twelve spine surgeons from the Asia-Pacific region (six different countries) independently evaluated and classified the deformity types and proposed their surgical recommendations. This information was then compared with standard deformity classification and surgical recommendations.

    RESULTS: The kappa coefficients for the classification were as follows: 0.88 for type 1A, 0.78 for type 1B, 0.50 for type 2B, 0.40 for type 3A, 0.63 for type 3B, and 0.86 for type 3C deformities. The overall kappa coefficient for the classification was 0.68. Regarding the repeatability of osteotomy recommendations, kappa values were the highest for Ponte's (Schwab type 2) osteotomy (kappa 0.8). Kappa values for other osteotomy recommendations were 0.52 for pedicle subtraction/disc-bone osteotomy (Schwab type 3/4), 0.42 for vertebral column resection (VCR, type 5), and 0.30 for multilevel VCRs (type 6).

    CONCLUSIONS: Excellent accuracy was found for types 1A, 1B, and 3C deformities (ends of spectrum). There was more variation among surgeons in differentiating between one-column (types 2A and 2B) and two-column (types 3A and 3B) deficiencies, as surgeons often failed to recognize the radiological signs of posterior column failure. This failure to identify column deficiencies can potentially alter kyphosis management. There was excellent consensus among surgeons in the recommendation of type 2 osteotomy; however, some variation was observed in their choice for other osteotomies.

  4. Faruk NA, Mohd-Amin MZ, Awang-Ojep DN, Teo YY, Wong CC
    Malays Orthop J, 2018 Nov;12(3):50-52.
    PMID: 30555648 MyJurnal DOI: 10.5704/MOJ.1811.013
    Giant cell tumour (GCT) is a benign tumour but can be locally aggressive and with the potential to metastasise especially to the lungs. Successful treatments have been reported for long bone lesions; however, optimal surgical and medical treatment for spinal and sacral lesions are not well established. In treating spinal GCTs, the aim is to achieve complete tumour excision, restore spinal stability and decompress the neural tissues. The ideal surgical procedure is an en bloc spondylectomy or vertebrectomy, where all tumour cells are removed as recurrence is closely related to the extent of initial surgical excision. However, such a surgery has a high complication rate, such as dura tear and massive blood loss. We report a patient with a missed pathological fracture of T12 treated initially with a posterior subtraction osteotomy, who had recurrence three years after the index surgery and subsequently underwent a three level vertebrectomy and posterior spinal fusion.
  5. Kopansky-Giles D, Johnson CD, Haldeman S, Chou R, Côté P, Green BN, et al.
    Eur Spine J, 2018 09;27(Suppl 6):915-924.
    PMID: 30151804 DOI: 10.1007/s00586-018-5725-7
    PURPOSE: The purpose of this report is to describe the development of a list of resources necessary to implement a model of care for the management of spine-related concerns anywhere in the world, but especially in underserved communities and low- and middle-income countries.

    METHODS: Contents from the Global Spine Care Initiative (GSCI) Classification System and GSCI care pathway papers provided a foundation for the resources list. A seed document was developed that included resources for spine care that could be delivered in primary, secondary and tertiary settings, as well as resources needed for self-care and community-based settings for a wide variety of spine concerns (e.g., back and neck pain, deformity, spine injury, neurological conditions, pathology and spinal diseases). An iterative expert consensus process was used using electronic surveys.

    RESULTS: Thirty-five experts completed the process. An iterative consensus process was used through an electronic survey. A consensus was reached after two rounds. The checklist of resources included the following categories: healthcare provider knowledge and skills, materials and equipment, human resources, facilities and infrastructure. The list identifies resources needed to implement a spine care program in any community, which are based upon spine care needs.

    CONCLUSION: To our knowledge, this is the first international and interprofessional attempt to develop a list of resources needed to deliver care in an evidence-based care pathway for the management of people presenting with spine-related concerns. This resource list needs to be field tested in a variety of communities with different resource capacities to verify its utility. These slides can be retrieved under Electronic Supplementary Material.

  6. Johnson CD, Haldeman S, Chou R, Nordin M, Green BN, Côté P, et al.
    Eur Spine J, 2018 09;27(Suppl 6):925-945.
    PMID: 30151805 DOI: 10.1007/s00586-018-5720-z
    PURPOSE: Spine-related disorders are a leading cause of global disability and are a burden on society and to public health. Currently, there is no comprehensive, evidence-based model of care for spine-related disorders, which includes back and neck pain, deformity, spine injury, neurological conditions, spinal diseases, and pathology, that could be applied in global health care settings. The purposes of this paper are to propose: (1) principles to transform the delivery of spine care; (2) an evidence-based model that could be applied globally; and (3) implementation suggestions.

    METHODS: The Global Spine Care Initiative (GSCI) meetings and literature reviews were synthesized into a seed document and distributed to spine care experts. After three rounds of a modified Delphi process, all participants reached consensus on the final model of care and implementation steps.

    RESULTS: Sixty-six experts representing 24 countries participated. The GSCI model of care has eight core principles: person-centered, people-centered, biopsychosocial, proactive, evidence-based, integrative, collaborative, and self-sustaining. The model of care includes a classification system and care pathway, levels of care, and a focus on the patient's journey. The six steps for implementation are initiation and preparation; assessment of the current situation; planning and designing solutions; implementation; assessment and evaluation of program; and sustain program and scale up.

    CONCLUSION: The GSCI proposes an evidence-based, practical, sustainable, and scalable model of care representing eight core principles with a six-step implementation plan. The aim of this model is to help transform spine care globally, especially in low- and middle-income countries and underserved communities. These slides can be retrieved under Electronic Supplementary Material.

  7. Johnson CD, Haldeman S, Nordin M, Chou R, Côté P, Hurwitz EL, et al.
    Eur Spine J, 2018 09;27(Suppl 6):786-795.
    PMID: 30151808 DOI: 10.1007/s00586-018-5723-9
    PURPOSE: The purpose of this report is to describe the Global Spine Care Initiative (GSCI) contributors, disclosures, and methods for reporting transparency on the development of the recommendations.

    METHODS: World Spine Care convened the GSCI to develop an evidence-based, practical, and sustainable healthcare model for spinal care. The initiative aims to improve the management, prevention, and public health for spine-related disorders worldwide; thus, global representation was essential. A series of meetings established the initiative's mission and goals. Electronic surveys collected contributorship and demographic information, and experiences with spinal conditions to better understand perceptions and potential biases that were contributing to the model of care.

    RESULTS: Sixty-eight clinicians and scientists participated in the deliberations and are authors of one or more of the GSCI articles. Of these experts, 57 reported providing spine care in 34 countries, (i.e., low-, middle-, and high-income countries, as well as underserved communities in high-income countries.) The majority reported personally experiencing or having a close family member with one or more spinal concerns including: spine-related trauma or injury, spinal problems that required emergency or surgical intervention, spinal pain referred from non-spine sources, spinal deformity, spinal pathology or disease, neurological problems, and/or mild, moderate, or severe back or neck pain. There were no substantial reported conflicts of interest.

    CONCLUSION: The GSCI participants have broad professional experience and wide international distribution with no discipline dominating the deliberations. The GSCI believes this set of papers has the potential to inform and improve spine care globally. These slides can be retrieved under Electronic Supplementary Material.

  8. Haldeman S, Johnson CD, Chou R, Nordin M, Côté P, Hurwitz EL, et al.
    Eur Spine J, 2018 09;27(Suppl 6):901-914.
    PMID: 30151811 DOI: 10.1007/s00586-018-5721-y
    PURPOSE: The purpose of this report is to describe the development of an evidence-based care pathway that can be implemented globally.

    METHODS: The Global Spine Care Initiative (GSCI) care pathway development team extracted interventions recommended for the management of spinal disorders from six GSCI articles that synthesized the available evidence from guidelines and relevant literature. Sixty-eight international and interprofessional clinicians and scientists with expertise in spine-related conditions were invited to participate. An iterative consensus process was used.

    RESULTS: After three rounds of review, 46 experts from 16 countries reached consensus for the care pathway that includes five decision steps: awareness, initial triage, provider assessment, interventions (e.g., non-invasive treatment; invasive treatment; psychological and social intervention; prevention and public health; specialty care and interprofessional management), and outcomes. The care pathway can be used to guide the management of patients with any spine-related concern (e.g., back and neck pain, deformity, spinal injury, neurological conditions, pathology, spinal diseases). The pathway is simple and can be incorporated into educational tools, decision-making trees, and electronic medical records.

    CONCLUSION: A care pathway for the management of individuals presenting with spine-related concerns includes evidence-based recommendations to guide health care providers in the management of common spinal disorders. The proposed pathway is person-centered and evidence-based. The acceptability and utility of this care pathway will need to be evaluated in various communities, especially in low- and middle-income countries, with different cultural background and resources. These slides can be retrieved under Electronic Supplementary Material.

  9. Haldeman S, Nordin M, Chou R, Côté P, Hurwitz EL, Johnson CD, et al.
    Eur Spine J, 2018 09;27(Suppl 6):776-785.
    PMID: 30151809 DOI: 10.1007/s00586-018-5722-x
    PURPOSE: Spinal disorders, including back and neck pain, are major causes of disability, economic hardship, and morbidity, especially in underserved communities and low- and middle-income countries. Currently, there is no model of care to address this issue. This paper provides an overview of the papers from the Global Spine Care Initiative (GSCI), which was convened to develop an evidence-based, practical, and sustainable, spinal healthcare model for communities around the world with various levels of resources.

    METHODS: Leading spine clinicians and scientists around the world were invited to participate. The interprofessional, international team consisted of 68 members from 24 countries, representing most disciplines that study or care for patients with spinal symptoms, including family physicians, spine surgeons, rheumatologists, chiropractors, physical therapists, epidemiologists, research methodologists, and other stakeholders.

    RESULTS: Literature reviews on the burden of spinal disorders and six categories of evidence-based interventions for spinal disorders (assessment, public health, psychosocial, noninvasive, invasive, and the management of osteoporosis) were completed. In addition, participants developed a stratification system for surgical intervention, a classification system for spinal disorders, an evidence-based care pathway, and lists of resources and recommendations to implement the GSCI model of care.

    CONCLUSION: The GSCI proposes an evidence-based model that is consistent with recent calls for action to reduce the global burden of spinal disorders. The model requires testing to determine feasibility. If it proves to be implementable, this model holds great promise to reduce the tremendous global burden of spinal disorders. These slides can be retrieved under Electronic Supplementary Material.

  10. Abduljabbar FH, Teles AR, Ouellet JA, Ferland CE, Wong CC, Barbagallo G, et al.
    Spine (Phila Pa 1976), 2021 Oct 15;46(20):1418-1927.
    PMID: 34559753 DOI: 10.1097/BRS.0000000000004038
    STUDY DESIGN: Cross-sectional survey study.

    OBJECTIVE: To evaluate the prevalence of burnout, assess the personal and professional characteristics associated with burnout in spine surgeons and determine their quality of life.

    SUMMARY OF BACKGROUND DATA: Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and decreased sense of accomplishment that leads to decreased effectiveness at work. To date, there has been a lack of information on the prevalence of burnout among spine surgeons worldwide and the risk factors associated with this condition.

    METHODS: An electronic survey with members of AO Spine was performed in May 2018. The survey evaluated demographic variables, practice characteristics, burnout, and quality of life. Maslach Burnout Inventory (MBI) and EuroQol 5-dimensions (EQ5D) were used to evaluate burnout and quality of life, respectively.

    RESULTS: A total of 818 surgeons from 86 countries completed the survey. The prevalence of burnout was 30.6%. In the multiple linear model, emotional fatigue was independently associated with younger age (B = -0.17, CI95% = -0.26 to -0.07, P 

  11. Chen CK, Wong CC, Teo YY, Phui VE
    Int J Spine Surg, 2021 Dec;15(6):1180-1188.
    PMID: 35078892 DOI: 10.14444/8151
    BACKGROUND: Cervical facet joint pain is an important cause of chronic neck pain. The recommended treatment for this condition is radiofrequency (RF) neurotomy of the medial branch of dorsal rami. There have been attempts to find safe and effective ways to perform this procedure. The objective of this study is to describe the single entry posterior parasagittal approach and to evaluate the efficacy and safety of this approach compared to the conventional posterolateral approach of RF neurotomy of cervical medial branch.

    METHODS: The record of all patients with cervical facet pain who were treated with RF neurotomy medial branch of dorsal rami between January 2016 and December 2019 were reviewed retrospectively. Comparisons were made between patients who underwent RF neurotomy with multiple skin entry posterolateral approach and those who underwent RF neurotomy with single entry posterior parasagittal approach. The primary outcome was measured as the mean changes in numerical rating scale (NRS), and the secondary outcomes were duration and complications related to both approaches.

    RESULTS: Thirty-one patients who underwent RF neurotomy via posterolateral approach were compared with 40 patients who underwent the procedure via posterior parasagittal approach. Both approaches showed a significant decrease in the NRS from baseline values. However, the differences in the NRS lowering effect at 3 and 12 months between these 2 approaches were not statistically significant. The duration of the procedure was significantly shorter with posterior parasagittal approach (44.13 ± 4.72 minutes vs 54.68 ± 7.39 minutes; P < 0.001). There were no serious complications encountered in both approaches.

    CONCLUSIONS: With comparable efficacy and safety profile between the posterior parasagittal and the conventional posterolateral approaches, the former single skin entry approach offers the added advantage of being less time-consuming. Further randomized prospective studies are necessary to validate these findings.

  12. Wong HC, Wong CC, Sagineedu SR, Loke SC, Lajis NH, Stanslas J
    Cell Biol Toxicol, 2014 Oct;30(5):269-88.
    PMID: 25070834 DOI: 10.1007/s10565-014-9282-5
    3,19-(3-Chloro-4-fluorobenzylidene)andrographolide (SRJ23), a new semisynthetic derivative of andrographolide (AGP), exhibited selectivity against prostate cancer cells in the US National Cancer Institute (NCI) in vitro anti-cancer screen. Herein, we report the in vitro growth inhibition and mechanisms of cell cycle arrest and apoptosis induced by SRJ23.
  13. Wong CC, Lim SH, Sagineedu SR, Lajis NH, Stanslas J
    Pharmacol Res, 2016 05;107:66-78.
    PMID: 26940565 DOI: 10.1016/j.phrs.2016.02.024
    SRJ09 (3,19-(2-bromobenzylidene)andrographolide), a semisynthetic andrographolide (AGP) derivative, was shown to induce G1 cell cycle arrest and eventually apoptosis in breast and colon cancer cell lines. The present investigation was carried out to elucidate the mechanisms cell cycle arrest and apoptosis and evaluate the in vivo antitumor activity of SRJ09. The in vitro growth inhibitory properties of compounds were assessed in colon (HCT-116) and breast (MCF-7) cancer cell lines. Immunoblotting was utilized to quantitate the protein levels in cells. The gene expressions were determined using reverse transcriptase PCR (RT-PCR). Pharmacokinetic investigation was carried out by determining SRJ09 levels in plasma of Balb/C mice using HPLC. In vivo antitumor activity was evaluated in athymic mice carrying HCT-116 colon tumor xenografts. SRJ09 displayed improved in vitro activity when compared with AGP by producing rapid cell killing effect in vitro. Its activity was not compromised in MES-SA/Dx5 multidrug resistant (MDR) cells expressing p-glycoprotein. Cells treated with SRJ09 (0.1-10μM) displayed increased p21 protein level, which corresponded with gene expression. Whereas CDK4 protein level and gene expression was suppressed. The treatment did not affect cyclin D1. Changes of these proteins paralleled G1 cell cycle arrest in both cell lines as determined by flow cytometry. Induction of apoptosis by SRJ09 in HCT-116 cells which occurred independent of p53 and bcl-2 was inhibited in the presence of caspase 8 inhibitor, implicating the extrinsic apoptotic pathway. A single dose (100mg/kg, i.p) of SRJ09 produced a plasma concentration range of 12-30.4μM. At 400mg/kg (q4dX3), it significantly retarded growth of tumor xenografts. The antitumor activity of SRJ09 is suggested mediated via the induction of p21 expression and suppression of CDK-4 expression without affecting cyclin D1 to trigger G1 arrest leading to apoptosis.
  14. Abdul Latip AF, Hussein MZ, Stanslas J, Wong CC, Adnan R
    Chem Cent J, 2013;7:119.
    PMID: 23849189 DOI: 10.1186/1752-153X-7-119
    Layered hydroxides salts (LHS), a layered inorganic compound is gaining attention in a wide range of applications, particularly due to its unique anion exchange properties. In this work, layered zinc hydroxide nitrate (LZH), a family member of LHS was intercalated with anionic ciprofloxacin (CFX), a broad spectrum antibiotic via ion exchange in a mixture solution of water:ethanol.
  15. Sia U, Tan BB, Teo YY, Wong CC
    Malays Orthop J, 2019 Mar;13(1):14-19.
    PMID: 31001378 DOI: 10.5704/MOJ.1903.002
    Introduction: Post-implantation rod deformation is anticipated in scoliosis surgery but the difference in rod deformation between titanium and cobalt chrome rod has not been elucidated. This study aims to compare the difference in rod deformation between two groups. Materials and Methods: Twenty-one adolescent idiopathic scoliosis (AIS) patients were recruited from a single center. The over-contoured concave rods were traced prior to insertion. Post-operative sagittal rod shape was determined from lateral radiographs. Rod deformation was determined using maximal rod deflection and angle of the tangents to rod end points. The differences between pre- and post-operative rod contour were analysed statistically. Rod deformation and thoracic kyphosis between two types of implants were analysed. Results: Both rods exhibited significant change of rod angle and deflection post-operatively. Curvature of the titanium rod and cobalt chrome rod decreased from 60.5° to 37°, and 51° to 28° respectively. Deflection of titanium rod and cobalt chrome rod reduced from 28mm to 23.5mm and 30mm to 17mm respectively. There was no significant difference between titanium and cobalt chrome groups with regard to rod angle (p=0.173) and deflection (p=0.654). Thoracic kyphosis was increased from 20° to 26° in titanium group but a reduction from 25° to 23° was noticed in cobalt chrome group, but these findings were not statistically significant. Conclusion: There was no statistical difference in rod deformation between the two groups. Thus, the use of titanium rod in correction of sagittal profile is not inferior in outcome compared with cobalt chrome but with lower cost.
  16. Wong CC, Sagineedu SR, Sumon SH, Sidik SM, Phillips R, Lajis NH, et al.
    Environ Toxicol Pharmacol, 2014 Sep;38(2):489-501.
    PMID: 25168151 DOI: 10.1016/j.etap.2014.07.016
    Andrographolide (AGP) is the main bioactive constituent isolated from the traditional medicinal, Andrographis paniculata which contributes towards its various biological activities, including anticancer property. In this study, a series of new AGP derivatives were semi-synthesised and screened against the NCI in vitro 60 cell lines. From the screening results, we had identified SRS07 as the most potent AGP derivative, against breast and colon cancer cell lines. Subsequently, SRS07 was tested for its capability to induce cell cycle arrest and apoptosis in MCF-7 and HCT116 cancer cells. SRS07 effectively induced G1 cell cycle arrest in both cell lines and ultimately apoptosis by inducing DNA fragmentation in HCT116 cells. The apoptotic cell death induced by SRS07 was confirmed via FITC Annexin-V double staining. Western blot analysis of SRS07-treated HCT116 cells revealed that the compound induced apoptosis be activating caspase 8 which in turn cleaved Bid to t-Bid to initiate cell death cascade. Prediction of the possible mode of action of SRS07 by utilising NCI COMPARE analysis failed to reveal a distinct mechanism category. Hence, it is speculated that SRS07 possesses novel mechanism of action. In conclusion, SRS07 demonstrated superior in vitro anticancer profiles and emerged as a potential lead anticancer candidate.
  17. Wong C, Phang H, Cheong M, Ramiah R
    Malays Orthop J, 2012 Nov;6(3):54-6.
    PMID: 25279060 MyJurnal DOI: 10.5704/MOJ.1207.007
    We present the case of a patient with multiple atraumatic osteoporotic vertebral fractures in an adolescent with suprasellar germinoma and also review of relevant literature. The patient suffered from a rare adolescent brain tumour with common complications which are often overlooked and give rise to significant morbidity. Suprasellar germinoma is an intracranial neoplasm, that in addition to its rarity, has variable clinical presentation. Despite appropriate treatment and good outcome, tumour related morbidity is still of concern for these patients.
  18. Quah SY, Wong CC, Wong HC, Ho KL, Abdul Manan N, Deb PK, et al.
    Toxicol Appl Pharmacol, 2021 08 15;425:115605.
    PMID: 34087331 DOI: 10.1016/j.taap.2021.115605
    Chemoresistance poses a major hurdle to cancer treatments. Andrographolide-derived SRJ09 and SRJ23 were reported to exhibit potent, selective inhibitory activities against colon and prostate cancer cells, respectively. In this study, previously developed resistant colon (HCT-116rst09) and prostate (PC-3rst23) cancer cell lines were used to elucidate the molecular mechanisms contributing to chemoresistance. Cytotoxic effects of SRJ09 and SRJ23 on both parental and resistant cells were investigated. Cell cycle distributions in HCT-116rst09 cells following SRJ09 treatment were analysed using flow cytometry. Whole-genome microarray analysis was performed on both parental and resistant cells to obtain differential gene expression profiles. Microarray data were subjected to protein-protein interaction network, functional enrichment, and pathway analyses. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the changes in expression levels of selected genes. Besides morphological changes, HCT-116rst09 cells showed 7.0-fold resistance to SRJ09 while PC-3rst23 cells displayed a 5.5-fold resistance to SRJ23, as compared with their respective parental cells. G0/G1-phase cell cycle arrest was observed in HCT-116rst09 cells upon SRJ09 treatment. Collectively, 77 and 21 genes were found differentially modulated in HCT-116rst09 and PC-3rst23 cells, respectively. Subsequent bioinformatics analysis revealed several genes associated with FGFR4 and PI3K pathways, and cancer stemness, were chemoresistance mediators in HCT-116rst09 cells. RT-PCR confirmed the HMOX1 upregulation and ATG12 downregulation protected the PC-3rst23 cells from SRJ23 cytotoxicity. In conclusion, acquired chemoresistance to SRJ09 and SRJ23 in colon and prostate cancer cells, respectively, could be attributed to the alterations in the expression of genes such as those related to PI3K and autophagy pathways.
  19. Pan KL, Ting SS, Mohamad AWK, Lee WG, Wong CC, Rasit AH
    Med J Malaysia, 2003 Dec;58(5):752-7.
    PMID: 15190663
    Improvements in the overall treatment of patients with aggressive, large tumours involving the bone have made it possible to preserve and salvage limbs instead of amputating them. Each patient is unique in his clinical presentation and social circumstance. The different reconstructive options available allow us to choose the most appropriate method suited to the particular patient and with minimal delay, even when resources are limited. The patient and the relatives actively participate in the choice. The early experience of the different techniques for reconstructing these bone defects at our hospital are presented in this paper.
  20. Wong CC, Periasamy N, Sagineedu SR, Sidik S, Sumon SH, Loadman P, et al.
    Invest New Drugs, 2014 Oct;32(5):806-14.
    PMID: 24875131 DOI: 10.1007/s10637-014-0105-6
    Limited tumor penetrability of anti-cancer drugs is recognized as one of the major factors that lead to poor anti-tumor activity. SRJ09 (3,19-(2-bromobenzylidene) andrographolide) has been identified as a lead anti-cancer agent for colon cancer. Recently, this compound was shown by us to be a mutant K-Ras binder. In this present study, the penetrability of SRJ09 through the DLD-1 colon cancer multicell layer (MCL) was evaluated. The amount of SRJ09 that penetrated through the MCL was quantitated by utilizing high performance liquid chromatography (HPLC). Histopathological staining was used to visualize the morphology of MCL. A chemosensitivity assay was performed to assess the anti-cancer activity of SRJ09 in DLD-1 cells. SRJ09 was able to penetrate through DLD-1 MCL and is inversely proportional with the MCL thickness. The flow rates for SRJ09 through MCL were 0.90 ± 0.20 μM/min/cm(2) and 0.56 ± 0.06 μM/min/cm(2) for days 1 and 5, respectively, which are better than doxorubicin. Histopathological examination revealed that the integrity of the DLD-1 MCL was retained and no visible damage was inflicted on the cell membrane, confirming the penetration of SRJ09 was by diffusion. Short term exposure (1 h) in DLD-1 cells demonstrated SRJ09 had IC50 of 41 μM which was approximately 4-folds lower than andrographolide, the parent compound of SRJ09. In conclusion, SRJ09 successfully penetrated through DLD-1 MCL by diffusion and emerged as a potential candidate to be developed as a clinically viable anti-colon cancer drug.
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