Displaying publications 1 - 20 of 149 in total

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  1. Fulltext Laser-driven hot needle for tissue cauterization and percutaneous hyperthermia cancer therapy
    Abd Raziff H. H., Wong, Y. H., Lim, K. S., Yeong, Chai Hong
    Malaysian Journal of Medicine and Health Sciences, 2019;15(102):20-20.
    MyJurnal
    Introduction: Cancer has become a major economic and societal burden. The National Cancer Registry of Malaysia (NCR) estimates that one in four Malaysian (1:4) will develop cancer by the age of 75. This project aims to develop a prototype named “Laser ablation needle” for tissue cauterization and percutaneous hyperthermia cancer therapy. Our ultimate goal is to develop a highly flexible, operator-friendly and cost-effective laser ablation needle for tissue cauterization and hyperthermia cancer therapy, hence to improve the overall cancer survival rate and quality of life among the cancer patient population. Methods: The laser ablation needle is a closed loop opto-electronic control system, consists of a 2 mm Fiber Bragg Grating (FBG) – optical fiber temperature sensor, a laser driven hot needle and a micro-controller. Based on real-time temperature input from the FBG sensor, the micro-controller can perform a dynamic PID control on laser intensity for a safe hyperthermia treatment. In the fabrication, a medical grade optical fiber with a diameter of 800 μm was used for laser delivery. The optical fiber was embedded inside a biocompatible resin-made needle and connected to a 450 nm high power blue laser diode. The FBG temperature sensor was incorporated in the needle for real-time temperature monitoring and control. Focal hyperthermia produced by the laser-driven hot needle was conducted on ex-vivo bovine liver. Results: The rise in temperature was recorded by increasing laser power. The temperature profile was obtained at each depth. Irreversible thermal denaturation during irradiation was captured. Conclusion: These preliminary results suggest that this technique can be applied safely and effectively for cancer treatment. The developed prototype comprised of the diode laser showed that it can deliver its energy via simple optical fiber. This laser is cheaper and much smaller than the conventional high power lasers used in other studies.
  2. Fulltext 2 μm passively mode-locked thulium-doped fiber lasers with Ta2AlC-deposited tapered and side-polished fibers
    Ahmad H, Azri MFM, Ramli R, Samion MZ, Yusoff N, Lim KS
    Sci Rep, 2021 Oct 28;11(1):21278.
    PMID: 34711908 DOI: 10.1038/s41598-021-99928-z
    In this work, mode-locked thulium-doped fiber lasers operating in the 2 µm wavelength region were demonstrated using tantalum aluminum carbide (Ta2AlC)-based saturable absorbers (SAs) utilizing the evanescent wave interaction. The Ta2AlC MAX Phase was prepared by dissolving the Ta2AlC powder in isopropyl alcohol and then deposited onto three different evanescent field-based devices, which were the tapered fiber, side-polished fiber, and arc-shaped fiber. Flame-brushing and wheel-polishing techniques were used to fabricate the tapered and arc-shaped fibers, respectively, while the side-polished fiber was purchased commercially. All three SA devices generated stable mode-locked pulses at center wavelengths of 1937, 1931, and 1929 nm for the tapered, side-polished, and arc-shaped fibers. The frequency of the mode-locked pulses was 10.73 MHz for the tapered fiber, 9.58 MHz for the side-polished fiber, and 10.16 MHz for the arc-shaped fiber. The measured pulse widths were 1.678, 1.734, and 1.817 ps for each of the three SA devices. The long-term stability of the mode-locked lasers was tested for each configuration over a 2-h duration. The lasers also showed little to no fluctuations in the center wavelengths and the peak optical intensities, demonstrating a reliable, ultrafast laser system.
  3. Direct period measurement for fiber Bragg grating using an optical imaging technique
    Ali MM, Lim KS, Yang HZ, Chong WY, Lim WS, Ahmad H
    Appl Opt, 2013 Aug 1;52(22):5393-7.
    PMID: 23913056 DOI: 10.1364/AO.52.005393
    This paper proposes an approach based on an optical imaging technique for the period measurement of fiber Bragg gratings (FBG). The simple, direct technique involves a differential interface contrast (DIC) microscope and a high-resolution CCD camera. Image processing is performed on the microscope images to obtain low-noise grating profiles and then the grating periods. Adopting a large image sample size in the image processing can reduce uncertainty. During the investigation, FBGs of different grating periods are fabricated by prestraining the photosensitive fibers during the UV-writing process. A good linearity between the measured Bragg wavelengths and grating periods is observed and the measured strain-optics coefficient was found to be in agreement with reported literature.
  4. Periodic lateralized epileptiform discharges (PLEDs) in cerebral lupus correlated with white-matter lesions in brain MRI and reduced cerebral blood flow in SPECT
    Aye SM, Lim KS, Ramli NM, Tan CT
    Lupus, 2013 Apr;22(5):510-4.
    PMID: 23358870 DOI: 10.1177/0961203312474705
    This is a case report on an uncommon correlation between periodic lateralized epileptiform discharges (PLEDs) and white-matter lesions in cerebral lupus, and with a reduced cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). A 47-year-old woman with a long-term history of systemic lupus erythematosus (SLE) presented with a seizure followed by frontal lobe dysfunction clinically. An electroencephalogram (EEG) showed bilateral independent PLEDs in the frontal region. A magnetic resonance image of the brain showed white-matter changes in the frontal periventricular region. Cerebral angiogram did not reveal any evidence of vasculitis. A cerebral SPECT with tracer injected during the EEG showing PLEDs showed a reduction in CBF in the frontal regions. Clinical recovery was observed with intravenous immunoglobulin. This case shows that PLEDs can be seen with white-matter changes in SLE.
  5. Fulltext Synthesis of silver nanoparticle-decorated hydroxyapatite nanocomposite with combined bioactivity and antibacterial properties
    Bee SL, Bustami Y, Ul-Hamid A, Lim K, Abdul Hamid ZA
    J Mater Sci Mater Med, 2021 Aug 23;32(9):106.
    PMID: 34426879 DOI: 10.1007/s10856-021-06590-y
    Combination of bioactive material such as hydroxyapatite (HAp) with antibacterial agents would have great potential to be used as bone implant materials to avert possible bacterial infection that can lead to implant-associated diseases. The present study aimed to develop an antibacterial silver nanoparticle-decorated hydroxyapatite (HAp/AgNPs) nanocomposite using chemical reduction and thermal calcination approaches. In this work, natural HAp that was extracted from chicken bone wastes is used as support matrix for the deposition of silver nanoparticles (AgNPs) to produce HAp/AgNPs nanocomposite. XRD, FESEM-EDX, HRTEM, and XPS analyses confirmed that spherical AgNPs were successfully synthesized and deposited on the surface of HAp particles, and the amount of AgNPs adhered on the HAp surface increased with increasing AgNO3 concentration used. The synthesized HAp/AgNPs nanocomposites demonstrated strong antibacterial activity against Staphylococcus aureus bacteria, where the antibacterial efficiency is relied on the amount and size of deposited AgNPs. In addition, the in vitro bioactivity examination in Hank's balanced salt solution showed that more apatite were grown on the surface of HAp/AgNPs nanocomposite when AgNO3 concentration used >1 wt.%. Such nanocomposite with enhanced bioactivity and antibacterial properties emerged as a promising biomaterial to be applied for dentistry and orthopedic implantology.
  6. Antiepileptic-induced Psychosis as a Possible Predictor of Post-temporal Lobectomy Alternative Psychosis
    Benedict F, Lim KS, Jambunathan ST, Hashim AH
    East Asian Arch Psychiatry, 2016 Sep;26(3):109-11.
    PMID: 27703099
    We present a patient with topiramate-induced psychosis who developed alternative psychosis following temporal lobectomy. The number of surgical candidates for temporal lobectomy is increasing as is the frequency of psychiatric co-morbidities. Preoperative planning should take account of these psychiatric co-morbidities. In particular, precautions should be taken when antiepileptic drug-induced psychosis occurs, as this could predict the occurrence of alternative psychosis following lobectomy.
  7. Amino acid composition of Ascaris lumbricoides, A. suum and Toxocara canis
    Bisseru B, Lim KG
    Med J Malaya, 1968 Mar;22(3):236.
    PMID: 4234371
  8. Fulltext Malaysian mothers' knowledge & practices on care of neonatal jaundice
    Boo NY, Gan CY, Gian YW, Lim KS, Lim MW, Krishna-Kumar H
    Med J Malaysia, 2011 Aug;66(3):239-43.
    PMID: 22111448
    This study aimed to determine the gaps of knowledge and practices of care of neonatal jaundice among Malaysian mothers. It was a cross sectional study of 400 mothers who attended the obstetric clinics or were admitted to the obstetric wards of a general hospital. They were surveyed with a structured set of questionnaire. The results showed that a majority (93.8%) of them knew about neonatal jaundice, and 71.7% knew that jaundice lasting more than 2 weeks was abnormal. However, only 34.3% of them were aware that jaundice appearing during the first 36 hours of life was abnormal. Less than 20% knew about glucose-6-phosphate dehydrogenase deficiency and that fetal-maternal blood group differences could cause jaundice. Although 71.7% and 69.7%, respectively, of the mothers knew that severe jaundice could cause death and brain damage, only 38.4% of them were aware that severe jaundice could result in hearing impairment. A very low proportion (27.1%) of them was aware that putting jaundiced infants under the direct sun could result in dehydration and worsening of jaundice. Out of a maximum score of 15, the mean maternal knowledge score was 7.4 (95% confidence intervals: 7.1, 7.7). Majority (83.1%) of the multiparous mothers with a past history of having children developing neonatal jaundice (n = 154) practiced placing their infants under the direct sun. This study revealed that there was a wide knowledge gap among Malaysian mothers on care of neonatal jaundice. Placing infants under the direct sun was still a common practice.
    Study site: Obstetric clinic, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia
  9. Leptospirosis in Malaysia: a common cause of short-term fever
    Brown GW, Lee CK, Huxsoll DL, Ng TS, Lim KJ, Wan HS, et al.
    Southeast Asian J. Trop. Med. Public Health, 1976 Sep;7(3):380-3.
    PMID: 1030842
    A study of 1,437 unselected febrile patients in rural Malaysia yielded a diagnosis of leptospirosis in 86 (6.0%). The clinical syndrome was mild to moderate in all cases, jaundice was observed in only 2 (2.3%) and no deaths were documented. The diagnosis was not clinically obvious in most cases, and it is apparent that many infections must be going unnoticed at present.
  10. Scrub typhus: a common cause of illness in indigenous populations
    Brown GW, Robinson DM, Huxsoll DL, Ng TS, Lim KJ
    Trans R Soc Trop Med Hyg, 1976;70(5-6):444-8.
    PMID: 402722
    An explanation was sought for the disparity between the low reported incidence of scrub typhus and the high prevalence of antibody to Rickettsia tsutsugamushi in the rural population of Malaysia. A combination of isolation of the organism, titration of antibody by indirect immunofluorescence, and the Weil-Felix test was used to confirm infections. Scrub typhus was found to be very common, causing 23% of all febrile illnesses at one hospital. The infection was particularly prevalent in oil-palm workers, causing an estimated 400 cases annually in a population of 10,000 people living on one plantation. The clinical syndrome, whether mild or severe, was difficult to distinguish from that due to other infections. Eschars, rashes and adenopathy were uncommon. When used to examine early sera, the Weil-Felix test failed to confirm the diagnosis in most infections.20
  11. Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population
    Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung WH, et al.
    Pharmacogenomics J, 2017 03;17(2):170-173.
    PMID: 26927288 DOI: 10.1038/tpj.2016.10
    Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.
  12. Optimal waist circumference cut-off values for predicting cardiovascular risk factors in a multi-ethnic Malaysian population
    Cheong KC, Ghazali SM, Hock LK, Yusoff AF, Selvarajah S, Haniff J, et al.
    Obes Res Clin Pract, 2014 Mar-Apr;8(2):e154-62.
    PMID: 24743011 DOI: 10.1016/j.orcp.2013.03.004
    INTRODUCTION: Previous studies have proposed the lower waist circumference (WC) cutoffs be used for defining abdominal obesity in Asian populations.
    OBJECTIVE: To determine the optimal cut-offs of waist circumference (WC) in predicting cardiovascular (CV) risk factors in the multi-ethnic Malaysian population.
    METHODS: We analysed data from 32,703 respondents (14,980 men and 17,723 women) aged 18 years and above who participated in the Third National Health and Morbidity Survey in 2006. Gender-specific logistic regression analyses were used to examine associations between WC and three CV risk factors (diabetes mellitus, hypertension, and hypercholesterolemia). The Receiver Operating Characteristic (ROC) curves were used to determine the cut-off values of WC with optimum sensitivity and specificity for detecting these CV risk factors.
    RESULTS: The odds ratio for having diabetes mellitus, hypertension, and hypercholesterolemia, or at least one of these risks, increased significantly as the WC cut-off point increased. Optimal WC cut-off values for predicting the presence of diabetes mellitus, hypertension, hypercholesterolemia and at least one of the three CV risk factors varied from 81.4 to 85.5 cm for men and 79.8 to 80.7 cm for women.
    CONCLUSIONS: Our findings indicate that WC cut-offs of 81 cm for men and 80 cm for women are appropriate for defining abdominal obesity and for recommendation to undergo cardiovascular risk screening and weight management in the Malaysian adult population.
    Study name: National Health and Morbidity Survey (NHMS-2006)
  13. Note: Fabrication of tapered fibre tip using mechanical polishing method
    Cheong YK, Lim KS, Lim WH, Chong WY, Zakaria R, Ahmad H
    Rev Sci Instrum, 2011 Aug;82(8):086115.
    PMID: 21895293 DOI: 10.1063/1.3627374
    Tapered fibre tips fabricated using mechanical polishing method is studied. The fibre tips are formed by sequential polishing flat-ended single mode fibres with decreasing aluminium oxide polishing film grit size. Based on the proposed technique, tapered fibre tips with cone angle ranging from 30° to 130° are fabricated by controlling the polishing angle. Besides the variety of cone angle, considerable smoothness of the fibre tip surface may assist in good metal coating and hence a well-defined aperture can be obtained. In addition, this paper presents a two-step hybrid fabrication method combining the proposed polishing method with chemical etching method to increase the possible fibre tip cone angles achievable by chemical etching method.
  14. PesTrapp mobile app: A trap setting application for real-time entomological field and laboratory study
    Cheong YL, Rosilawati R, Mohd-Khairuddin CI, Siti-Futri FF, Nur-Ayuni N, Lim KH, et al.
    Trop Biomed, 2021 Jun 01;38(2):171-179.
    PMID: 34172707 DOI: 10.47665/tb.38.2.054
    Diseases such as malaria, dengue, Zika and chikungunya remain endemic in many countries. Setting and deploying traps to capture the host/vector species are fundamental to understand their density and distributions. Human effort to manage the trap data accurately and timely is an exhaustive endeavour when the study area expands and period prolongs. One stop mobile app to manage and monitor the process of targeted species trapping, from field to laboratory level is still scarce. Toward this end, we developed a new mobile app named "PesTrapp" to acquire the vector density index based on the mobile updates of ovitraps and species information in field and laboratory. This study aimed to highlight the mobile app's development and design, elucidate the practical user experiences of using the app and evaluate the preliminary user assessment of the mobile app. The mobile app was developed using mobile framework and database. User evaluation of the mobile app was based on the adjusted Mobile App Rating Scale and Standardized User Experience Percentile Rank Questionnaire. The process flows of system design and detailed screen layouts were described. The user experiences with and without the app in a project to study Aedes surveillance in six study sites in Selangor, Malaysia were elucidated. The overall mean user evaluation score of the mobile app was 4.0 out of 5 (SD=0.6), reflects its acceptability of the users. The PesTrapp, a one-stop solution, is anticipated to improve the entomological surveillance work processes. This new mobile app can contribute as a tool in the vector control countermeasure strategies.
  15. Achalasia cardia: A five-year review in Hospital Tuanku Ja'afar, Seremban
    Chin DHJ, Lim KG, Peh HS, Burud IAS, Tata MD, Zakaria J
    Med J Malaysia, 2022 Jan;77(1):41-46.
    PMID: 35086993
    INTRODUCTION: Achalasia cardia is an oesophageal motility disorder that affects various age groups. This study focused on the epidemiological features of achalasia, its risk factors, treatment modalities offered and the clinical outcomes in a tertiary hospital.

    MATERIALS AND METHODS: A retrospective search was carried out on all patients with a diagnosis of achalasia cardia in Hospital Tuanku Ja'afar (HTJ), Seremban, Malaysia between 2014 and 2018. Demographic data, patient symptomatology, and definitive management options were determined from the records. Telephone interviews were conducted to evaluate patient satisfaction with the outcome of treatment.

    RESULTS: There were 30 patients with a newly diagnosed achalasia cardia in that 5-year period, with an equal incidence among men and women. The mean age of presentation was 44.63 ± 18.21 years. Malays formed the largest group. The mean weight and body mass index were 46.8 ± 10.4 kg and 18.0 ± 4.4 kg/m2 respectively. There was a wide range of duration of symptoms at presentation with a mean of 30.11 ± 35.29 months. Almost all patients presented with dysphagia (96.7%) while 70% also noted loss of weight. All patients underwent oesophagogastroduodenoscopy (OGDS) and 26 patients (86.7%) had barium swallow as part of diagnostic workup. A total of 18 patients underwent a laparoscopic Heller myotomy with or without Dor Fundoplication and/or cruroplasty while two patients (6.7%) underwent pneumatic dilatation as first treatment. Iatrogenic mucosal perforations were detected in 8 patients who underwent myotomy and fundoplication and were repaired intraoperatively. Of the patients who underwent myotomy and fundoplication, the mean weight increase was 15.6kg, increasing from 43.0 ± 8.4 kg to 58.6 ± 13.7 kg. All the patients who underwent treatment were satisfied with their treatment outcomes.

    CONCLUSION: Most patients with achalasia cardia deemed suitable for surgery and counselled accordingly accept surgery resulting in high levels of satisfaction and weight gain in almost all these patients. A small minority who opt for pneumatic dilatation may also achieve satisfactory outcomes comparable to surgery in the short term. Although rare, clinicians should be able to recognise this disease early as early intervention often leads to satisfactory longterm outcomes.

  16. Spreading profile of evaporative liquid drops in thin porous layer
    Chong WY, Lim KS, Lim WH, Harun SW, Adikan FR, Ahmad H
    Phys Rev E Stat Nonlin Soft Matter Phys, 2012 Jan;85(1 Pt 2):016314.
    PMID: 22400665
    Spreading of evaporative liquid drops in a thin porous layer has been studied. The entire spreading process can be divided into three distinct phases according to the change of the wetted porous region size. The first phase is characterized by the expansion of the wetted porous region and shrinking of the liquid drop. Contact line pinning is observed in the wetted porous region in the second phase even with the liquid drop totally absorbed into the porous layer. The third phase sees the shrinkage of the wetted porous region until it is not observable. Based on these observations, a model is devised to simulate the spreading of a liquid drop under the studied conditions. Partial differential equations are used to describe the relation between liquid drop volume and other important parameters of a fluid flow, including maximum wetted region diameter achieved, time taken to reach each spreading process phase, and evaporation rate. Calculated results are in good agreement with the experimental data.
  17. Fulltext Phenothiazine deposits in corneo and lens
    Choong YY, Lim KS
    Med J Malaysia, 2001 Mar;56(1):92-4.
    PMID: 11503304
    Phenothiazines have been associated with various ocular adverse effects, in particular cataract and corneal deposits. Several effects are vision threatening. Awareness of these effects, in particular by Psychiatrists and Ophthalmologist, is essential for prompt diagnosis and appropriate treatment. We report two patients presented to us with corneal deposits and lenticular opacities following long term use of Phenothiazines.
  18. SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma
    Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, et al.
    J Clin Oncol, 2018 07 01;36(19):1913-1921.
    PMID: 29498924 DOI: 10.1200/JCO.2017.76.0892
    Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.
  19. Fulltext Traditional medicine and food supplements in rheumatic diseases
    Chow SK, Yeap SS, Goh EML, Veerapen K, Lim KKT
    Med J Malaysia, 2002 Sep;57(3):283-91.
    PMID: 12440267
    This was a prospective survey using a standard questionnaire to determine the prevalence of use of oral traditional medicine and food supplements among patients with rheumatic diseases. Among the 141 patients surveyed, we found that 69% of the patients were consuming food supplements, 35% were using traditional medicine and 45% had used traditional medicine at some time or other. Females were more likely to use food supplements (P < 0017); especially among those with higher education (p < 0.036). There was no statistical difference between those who had ever consumed compared to those who never used traditional medicines. The Chinese were more likely than others to be using traditional medicine (p < 0.007). Vitamin C and B were the most commonly used food supplements. More than two thirds of the patients obtained their traditional medicine from non-medical personnel. More than half of them used 2 or more types of traditional medicine for more than two months. Spending on traditional medicine was noted to be modest with 73% spending less than one hundred ringgit a month for their traditional treatment. Doctors need to be aware of the possible interactions between these 'self-medications' and the conventionally prescribed medication.
  20. Cancer-associated fibroblasts regulate keratinocyte cell-cell adhesion via TGF-β-dependent pathways in genotype-specific oral cancer
    Cirillo N, Hassona Y, Celentano A, Lim KP, Manchella S, Parkinson EK, et al.
    Carcinogenesis, 2017 01;38(1):76-85.
    PMID: 27803052 DOI: 10.1093/carcin/bgw113
    The interrelationship between malignant epithelium and the underlying stroma is of fundamental importance in tumour development and progression. In the present study, we used cancer-associated fibroblasts (CAFs) derived from genetically unstable oral squamous cell carcinomas (GU-OSCC), tumours that are characterized by the loss of genes such as TP53 and p16INK4A and with extensive loss of heterozygosity, together with CAFs from their more genetically stable (GS) counterparts that have wild-type TP53 and p16INK4A and minimal loss of heterozygosity (GS-OSCC). Using a systems biology approach to interpret the genome-wide transcriptional profile of the CAFs, we show that transforming growth factor-β (TGF-β) family members not only had biological relevance in silico but also distinguished GU-OSCC-derived CAFs from GS-OSCC CAFs and fibroblasts from normal oral mucosa. In view of the close association between TGF-β family members, we examined the expression of TGF-β1 and TGF-β2 in the different fibroblast subtypes and showed increased levels of active TGF-β1 and TGF-β2 in CAFs from GU-OSCC. CAFs from GU-OSCC, but not GS-OSCC or normal fibroblasts, induced epithelial-mesenchymal transition and down-regulated a broad spectrum of cell adhesion molecules resulting in epithelial dis-cohesion and invasion of target keratinocytes in vitro in a TGF-β-dependent manner. The results demonstrate that the TGF-β family of cytokines secreted by CAFs derived from genotype-specific oral cancer (GU-OSCC) promote, at least in part, the malignant phenotype by weakening intercellular epithelial adhesion.
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