Displaying publications 1 - 20 of 22 in total

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  1. He S, Lai SL
    Geriatr Gerontol Int, 2023 Nov;23(11):817-829.
    PMID: 37822092 DOI: 10.1111/ggi.14688
    AIM: Functional disability is a widespread challenge faced by the older population in China, where those with functional disabilities demand greater healthcare and geriatric services. This study performs a longitudinal analysis examining the effects of physiological conditions, intra-, and extra-individual factors, and life-course socioeconomic status risk factors on the disability levels and change rates of functional disability trajectories in old age.

    METHODS: Data for this study came from the four waves of the China Health and Retirement Longitudinal Survey. A latent growth model was used to analyze the functional disability of 5044 older adults aged 60 and over in 2011 who survived to 2018.

    RESULTS: Pathologies are closely associated with functional disability trajectories, and higher numbers of comorbidities relate to more disabilities. Risk factors and intra- and extra-individual factors affect functional disability trajectories and work through independent and shared mechanisms. The effects of risk factors can be traced to childhood conditions, and higher childhood and adulthood socioeconomic status is related to fewer functional disabilities.

    CONCLUSION: Functional disability trajectories are dynamic processes related to pathologies, intra-, and extra-individual factors, and life-course risk factors, and thus prevention and control measures should focus on both childhood and adulthood. Promoting working in later life and improving childhood socioeconomic status deserve prompt attention. Geriatr Gerontol Int 2023; 23: 817-829.

  2. Tey NP, Lai SL
    ScientificWorldJournal, 2013;2013:423403.
    PMID: 24288482 DOI: 10.1155/2013/423403
    The high maternal and neonatal mortality rates in South Asia and Sub-Saharan Africa can be attributed to the lack of access and utilization of health services for delivery. Data from the Demographic and Health Surveys conducted in Bangladesh, India, Pakistan, Kenya, Nigeria, and Tanzania show that more than half of the births in these countries were delivered outside a health facility. Institutional delivery was closely associated with educational level, family wealth, place of residence, and women's media exposure status, but it was not influenced by women's work status and their roles in decision-making (with the exception of Nigeria). Controlling for other variables, higher parity and younger women were less likely to use a health facility for delivery. Within each country, the poorer, less educated and rural women had higher unmet need for maternal care services. Service related factors (accessibility in terms of cost and distance) and sociocultural factors (e.g., did not perceive the need for the services and objections from husband and family) also posed as barriers to institutional delivery. The paper concludes with some suggestions to increase institutional delivery.
  3. Lai SL, Tey NP
    Cult Health Sex, 2020 07;22(7):778-793.
    PMID: 32037969 DOI: 10.1080/13691058.2019.1685683
    In Cambodia, the growth of family planning services and socio-economic development have resulted in a spectacular rise in contraceptive prevalence rate and an equally remarkable reduction in contraceptive use differentials. With rising educational levels and increased participation in the modern labour market, Cambodian women are playing an increasingly pivotal role in household decision-making. This study used data from three rounds of Cambodia Demographic and Health Surveys to elucidate trends and patterns of contraceptive use. It then examined the determinants of contraceptive use through the use of logistic regression. The central hypothesis to be tested was whether or not women's involvement in household decision-making affected contraceptive use. Multivariate analysis showed that apart from the number of living children, women's work status and education of both men and women had a more significant impact on contraceptive use, as compared to women's power in household decision-making. More effort is needed to empower women in all aspects in order to reduce the socio-economic differentials in contraceptive use and improve their reproductive health, in line with the goal of the global agenda of the sustainable development goals (SDGs) to leave no one behind.
  4. Hoo KY, Lai SL
    Int J Health Serv, 2022 Oct 09.
    PMID: 36214188 DOI: 10.1177/00207314221131218
    This article analyzes the relationship between various forms of intimate partner violence (IPV) and unmet need for family planning (FP) in South Asia. The data were obtained from the latest wave of the Demographic and Health Survey in Afghanistan, India, Maldives, Nepal, and Pakistan. Binary logistic regression analyses show mixed results, with a significant association between at least one type of IPV and unmet need for FP in all countries under study, except Maldives. There were also contrasting findings on the IPV-unmet need nexus, with a positive sign in some but negative sign in others. Women who experienced physical violence were associated with a higher odds of having an unmet need in Pakistan, but the opposite was true in Afghanistan and Nepal. The odds of having an unmet need were higher among Indian women who experienced IPV (sexual and emotional). In Afghanistan, women who experienced IPV (physical and emotional) have lower odds of having an unmet need. However, the interaction analysis of IPV (physical and sexual) and partners' controlling behavior showed a positive association with unmet need. Policymakers need to develop policies and strategies to prevent IPV and reduce unmet need for FP, in line with the Sustainable Development Goals.
  5. Lai SL, Tey NP
    PMID: 34775805 DOI: 10.1177/10105395211058810
    The midwives play an important role in maternal and child health in developing countries, but they are rarely involved in providing family planning services, except in Indonesia. This article underscores the midwives' crucial role in supplying modern contraceptive methods in Indonesia. Data for this analysis came from 8 waves of the Indonesia Demographic and Health Survey (IDHS). The main analysis was confined to 17 216 current users of modern methods from the 2017 IDHS. The midwives delivered contraceptives to 53% of the modern-method users in Indonesia. Multinomial logistic regression shows that the odds of users obtaining their contraceptive supplies from the midwives was significantly associated with age, parity, urban-rural location, region, education, wealth, exposure to family planning, and method type. The midwives help to reduce the doctors' workload for them to focus on specialized services. Developing countries can learn from the Indonesian experience to ensure equitable access to family planning services.
  6. Lai SL, Mustafa MR, Wong PF
    Phytomedicine, 2018 Mar 15;42:144-151.
    PMID: 29655680 DOI: 10.1016/j.phymed.2018.03.027
    BACKGROUND: Targeting autophagy is emerging as a promising strategy in cancer therapeutics in recent years. Autophagy can be modulated to drive cancer cell deaths that are notoriously resistant to apoptotic-inducing drugs. In addition, autophagy has been implicated as a prosurvival mechanism in mediating cancer chemoresistance. Our previous study has demonstrated that Panduratin A (PA), a plant-derived active compound exploits ER-stress-mediated apoptosis as its cytotoxic mechanism on melanoma.

    PURPOSE: Our previous proteomics analysis revealed that treatment with PA resulted in the upregulation of an autophagy marker, LC3B in melanoma cells. Therefore, the present study sought to investigate the role of PA-induced autophagy in melanoma cells.

    METHODS: Transmission electron microscopy was performed for examination of autophagic ultra-structures in PA-treated A375 cells. Cytoplasmic LC3B and p62/SQSMT1 punctate structures were detected using immunofluorescene staining. Expression levels of LC3B II, p62/SQSMT1, ATG 12, Beclin 1, phospho S6 (ser235/236), phospho AMPK (Thr172) and cleaved PARP were evaluated by western blotting.

    RESULTS: Autophagosomes, autolysosomes and punctuates of LC3 proteins could be observed in PA-treated A375 cells. PA-induced autophagy in A375 melanoma cells was found to be mediated through the inhibition of mTOR signaling and activation of AMPK pathway. Furthermore, we showed that PA-induced apoptosis was increased in the presence of an autophagy inhibitor, signifying the cytoprotective effect of PA-induced autophagy in melanoma cells.

    CONCLUSION: Taken together, results from the present study suggest that the inhibition of autophagy by targeting mTOR and AMPK could potentiate the cytotoxicity effects of PA on melanoma cells.

  7. Tey NP, Lai SL, Ng ST
    J Biosoc Sci, 2019 01;51(1):77-94.
    PMID: 29352813 DOI: 10.1017/S0021932017000682
    There has been a secular decline in age at menarche since the 19th century. Early-maturing women are more likely to have their sexual debut at a younger age, which in turn gives rise to a host of reproductive health and social problems. This study used data from five waves of National Demographic and Health Surveys conducted in the Philippines between 1993 and 2013 to examine the trends and socioeconomic differentials in age at menarche and sexual debut. The changing trend in age at menarche and sexual debut was examined across birth cohorts, and logistic regressions were used to identify the determinants of early sexual debut. In the Philippines, the mean and median ages at menarche declined from 13.2 years and 12.6 years, respectively, among young women born in 1973-1977, to 12.9 years and 12.3 years, respectively, among those born in 1993-1997. The proportion who had their sexual debut by age 20 increased from 41.2% for the 1968-1972 birth cohort to 53.4% for the 1988-1992 birth cohort. Filipino women with low education, from poor families and living in rural areas were more likely to have earlier sexual debut despite attaining menarche at a later age as compared with their higher educated counterparts, and those from wealthier families and urban areas. Logistic regression analysis showed that, besides marital status, women's education and age at menarche were important determinants of early sexual debut. However, ethnicity, place of residence and family wealth had no significant effects on age at menarche. An increasing proportion of young women were found to be having unprotected sexual debut and at a younger age, with health and social ramifications. Hence, apart from increasing the enrolment of girls in schools and discouraging teenage marriage, there is a need for social and health agencies to implement appropriate adolescent sexual and reproductive health programmes such as counselling and educational campaigns, as well as support services, to address sexual problems among the youth.
  8. Huang X, Tey NP, Lai SL
    Asia Pac J Public Health, 2024 May;36(4):352-357.
    PMID: 38590147 DOI: 10.1177/10105395241244960
    China's aging population has witnessed a surge in widowed older adults, raising concerns about their mental health. Losing a spouse is a profoundly distressing experience with enduring effects on well-being. Despite the proverbial belief in time's healing power, existing studies often neglect the potential decline in depressive symptoms during widowhood. Drawing data from the 2015 and 2018 China Health and Retirement Longitudinal Study, this study delved into the impact of widowhood duration on depression among 8370 older adults and uncovered significantly higher depression scores among widowed individuals, particularly in the initial three years. This study revealed that widowhood contributes to heightened depression levels even after accounting for sociodemographic factors. Although the depressive impact lessens over time, it persists beyond three years, underscoring the need for heightened awareness and support for this vulnerable population.
  9. Lai SL, Tey NP, Mahmud A, Ismail N
    Int Q Community Health Educ, 2021 Jul;41(4):395-403.
    PMID: 33167794 DOI: 10.1177/0272684X20972864
    BACKGROUND: The private sector is playing an increasingly important role in family planning services globally. The active participation of private providers is associated with a higher contraceptive prevalence rate.

    OBJECTIVES: To examine the differentials and determinants of the utilization of private providers for family planning services.

    METHOD: This study used the 2014 Malaysian Population and Family Survey data. Cross-tabulations and logistic regression were performed on 1,817 current users of modern methods.

    RESULTS: Overall, 26% of modern method users obtained their supplies from private clinics/pharmacies and 15.2% from other sources, such as drug stores and sundry shops. The odds of utilizing the private sector for family planning services differ significantly across regions and socio-economic groups. The odds of obtaining supply from the private clinics/pharmacies were higher among the Chinese and urban women (AOR > 1), and it was lower among those from the eastern region (AOR = 0.47, 95% CI = 0.30-0.73). Non-Bumiputera, urban, higher educated, and working women, and those whose husbands decided on family planning had higher odds of obtaining the supply from the other sources (AOR > 1).

    CONCLUSION: The private sector complements and supplements the public sector in providing family planning services to the public.

  10. Tey NP, Lai SL, Teh JK
    Maturitas, 2016 Dec;94:39-45.
    PMID: 27823743 DOI: 10.1016/j.maturitas.2016.08.016
    OBJECTIVES: The aims of this study were to assess the current sharp rise in chronic diseases and disabilities with advancing age, and to examine the debilitating effects of chronic diseases among the oldest old in China.

    STUDY DESIGN AND OUTCOME VARIABLES: This study used data from four waves of the Chinese Longitudinal Health and Longevity Survey (CLHLS) conducted in 2002, 2005, 2008 and 2011. The sample comprised 2137 older adults who were interviewed in 2002 and re-interviewed in the following waves. Cross-tabulations were run to show the rise in chronic disease and disability with age. Ordinal logistic regression was run to examine the debilitating effects of these diseases in terms of the ability of the oldest old to perform activities of daily living.

    RESULTS: The prevalence of chronic diseases rose sharply with age. The prevalence rate of six major diseases increased between 38% (respiratory diseases) and 533% (neurological disorder) among respondents who were re-interviewed nine years later. Cardiovascular diseases were the most common. Neurological disorder and cancer were less common, but had the most debilitating effects on patients. Overall, 10.0%, 3.1% and 3.1% of the respondents were disabled by cardiovascular, musculoskeletal and sensorial diseases, respectively. Ordinal logistic regression showed that neurological disorder had the strongest debilitating effects, followed by musculoskeletal and cardiovascular diseases among 2137 older persons who had survived and were followed up from the base year (2002) through 2011.

    CONCLUSION: The rapid rise in chronic diseases has resulted in an increased burden of disability among the oldest old in China. There is a need to improve health care systems for the prevention and management of chronic diseases.

  11. Lai SL, Wong PF, Lim TK, Lin Q, Mustafa MR
    Proteomics, 2015 May;15(9):1608-21.
    PMID: 25594392 DOI: 10.1002/pmic.201400039
    Melanoma is a lethal form of skin cancer with rising global incidence. However, limited treatment options are available for advanced melanoma and this is further compounded by the development of resistance toward existing drugs. Panduratin A (PA), a cyclohexanyl chalcone found in Boesenbergia rotunda, was investigated for its cytotoxic potentials against human malignant melanoma A375 cells. Our initial findings revealed that mitochondrion is the primary acting site of PA on A375 cancer cells and the cytotoxic mechanisms of PA were further investigated using a temporal quantitative proteomics approach by iTRAQ 2D-LC-MS/MS. Comprehensive proteomics analysis identified 296 proteins that were significantly deregulated in PA-treated A375 cells and revealed the involvement of mitochondrial oxidative phosphorylation, secretory and ER stress pathway, and apoptosis. We further confirmed that the PA-induced apoptosis was mediated by prolonged ER stress at least in part via the PERK/eIF2α/ATF4/CHOP pathway. Pretreatment with cycloheximide, an ER stress inhibitor rescued PA-induced cell death, which was accompanied by the suppression of ER-stress-related HSPA5 and CHOP proteins. The present study provides comprehensive mechanistic insights into the cytotoxic mechanisms of PA.
  12. Lai SL, Wong PF, Lim TK, Lin Q, Mustafa MR
    Phytomedicine, 2015 Jan 15;22(1):203-12.
    PMID: 25636890 DOI: 10.1016/j.phymed.2014.11.016
    Panduratin A (PA), a cyclohexanyl chalcone from Boesenbergia rotunda (L.) Mansf. was shown to possess anti-angiogenic effects in our previous study. In the present study, the molecular targets and anti-angiogenic mechanisms of PA on human umbilical vein endothelial cells (HUVECs) were identified using an iTRAQ-based quantitative proteomics approach. A total of 263 proteins were found to be differentially regulated in response to treatment with PA. Ingenuity Pathway Analysis revealed that cellular growth and proliferation, protein synthesis, RNA post-transcriptional modification, cellular assembly and organization and cell-to-cell signaling and interaction were the most significantly deregulated molecular and cellular functions in PA-treated HUVECs. PA inhibited the expressions of ARPC2 and CTNND1 that are associated with the formation of actin cytoskeleton, focal adhesion and cellular protrusions. In addition, PA down-regulated CD63, GRB-2, ICAM-2 and STAB-1 that are implicated in adhesion, migration and tube formation of endothelial cells. The differential expressions of three targets, namely, ARPC2, CDK4, and GRB-2 were validated by western blot analyses. Furthermore, PA inhibited G1-S progression, and resulted in G0/G1 arrest in HUVECs. The blockage in cell cycle progression was accompanied with the suppression of mTOR signaling. Treatment of HUVECs with PA resulted in decreased phosphorylation of ribosomal S6 and 4EBP1 proteins, the two downstream effectors of mTOR signaling. We further showed that PA is able to inhibit mTOR signaling induced by VEGF, a potent inducer of angiogenesis. Taken together, by integrating quantitative proteomic approach, we identified protein targets in which PA mediates its anti-angiogenic effects. The present study thus provides mechanistic evidence to the previously reported multifaceted anti-angiogenic effects of PA. Our study further identified mTOR signaling as an important target of PA, and therefore highlights the potential of PA for therapeutic intervention against angiogenesis-related pathogenesis, particularly, metastatic malignancy.
  13. Cheah SC, Lai SL, Lee ST, Hadi AH, Mustafa MR
    Molecules, 2013 Jul 24;18(8):8764-78.
    PMID: 23887718 DOI: 10.3390/molecules18088764
    In the present study, we investigated the effects of panduratin A (PA), isolated from Boesenbergia rotunda, on apoptosis and chemoinvasion in A549 human non-small cell lung cancer cells. Activation of the executioner procaspase-3 by PA was found to be dose-dependent. Caspase-3 activity was significantly elevated at the 5 µg/mL level of PA treatment and progressed to a maximal level. However, no significant elevated level was detected on procaspase-8. These findings suggest that PA activated caspase-3 but not caspase-8. Numerous nuclei of PA treated A549 cells stained brightly by anti-cleaved PARP antibody through High Content Screening. This result further confirmed that PA induced apoptotic cell death was mediated through activation of caspase-3 and eventually led to PARP cleavage. Treatment of A549 cells with PA resulted in a strong inhibition of NF-κB activation, which was consistent with a decrease in nuclear levels of NF-κB/p65 and NF-κB/p50 and the elevation of p53 and p21. Besides that, we also showed that PA significantly inhibited the invasion of A549 cells in a dose-dependent manner through reducing the secretion of MMP-2 of A549 cells gelatin zymography assay. Our findings not only provide the effects of PA, but may also be important in the design of therapeutic protocols that involve targeting of either p53 or NF-κB.
  14. Wong PF, Tong KL, Jamal J, Khor ES, Lai SL, Mustafa MR
    EXCLI J, 2019;18:764-776.
    PMID: 31611757 DOI: 10.17179/excli2019-1505
    Accumulation of senescent endothelial cells can cause endothelium dysfunction which eventually leads to age-related vascular disorders. The senescent-associated secretory phenotype (SASP) cells secrete a plethora of soluble factors that negatively influence the surrounding tissue microenvironment. The present study sought to investigate the effects of exosomes, which are nano-sized extracellular vesicles known for intercellular communications secreted by SASP cells on young endothelial cells. Exosomes were isolated from the condition media of senescent human umbilical vein endothelial cells (HUVECs) and then confirmed by the detection of exosome specific CD63 and CD9 expressions, electron microscopy and acetylcholinesterase assay. The purified exosomes were used to treat young HUVECs. Exposure to exosomes repressed the expression of adherens junction proteins including vascular endothelial (VE)-cadherin and beta-catenin, decreased cell growth kinetics and impaired endothelial migration potential of young endothelial cells. These findings suggest that senescent HUVECs-secreted exosomes could disrupt barrier integrity that underpins endothelial barrier dysfunction in healthy young endothelial cells.
  15. Lai SL, Cheah SC, Wong PF, Noor SM, Mustafa MR
    PLoS One, 2012;7(5):e38103.
    PMID: 22666456 DOI: 10.1371/journal.pone.0038103
    BACKGROUND: Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays.

    METHODOLOGY/PRINCIPAL FINDINGS: PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.

    CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy.

  16. Ting Pao Lin I, Ghazali NI, Teo Y, Lai SL, Bakhtiar MF, Tang MM
    Indian J Dermatol, 2024;69(5):406-410.
    PMID: 39649968 DOI: 10.4103/ijd.ijd_172_24
    Autohemotherapy is a commonly used treatment for recalcitrant chronic urticaria in some countries. Herein we report our experience using autologous serum therapy in eight patients with recalcitrant chronic spontaneous urticaria. Autologous serum therapy was initiated weekly for nine weeks followed by every fortnightly. Urticaria Activity Score (UAS) 7, Dermatology Life Quality Index (DLQI), and reduction of antihistamine usage were used to assess the treatment response. Eight patients (age range: 25-76 years old; four females and four males) had one to ten years of duration of recalcitrant chronic spontaneous urticaria. All failed to respond to high doses of second-generation antihistamines and five to immune-modulating agents. Three did not respond to omalizumab. At week nine, the reduction of UAS7 ranged from 76.2% to 100%. There was more than an 80% improvement in DLQI in all patients. The number of wheals seemed to be reduced first followed by pruritus. Three patients had stopped antihistamines by week eight of treatment. No adverse events were reported in all eight patients. Autologous serum therapy may serve as an alternative treatment for recalcitrant chronic spontaneous urticaria. Apart from the practicality, which requires frequent clinic visits, venipuncture, and centrifugation, it is cheap and effective with minimal adverse events.
  17. Tey NP, Yew SY, Low WY, Su'ut L, Renjhen P, Huang MS, et al.
    PLoS One, 2012;7(12):e52116.
    PMID: 23300600 DOI: 10.1371/journal.pone.0052116
    Abortion is a serious public health issue, and it poses high risks to the health and life of women. Yet safe abortion services are not readily available because few doctors are trained to provide such services. Many doctors are unaware of laws pertaining to abortion. This article reports survey findings on Malaysian medical students' attitudes toward abortion education and presents a case for including abortion education in medical schools.
  18. Yap LF, Lai SL, Rhodes A, Sathasivam HP, Abdullah MA, Pua KC, et al.
    Infect Agent Cancer, 2018;13:21.
    PMID: 29942347 DOI: 10.1186/s13027-018-0193-6
    Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising in Western countries and this has been attributed to human papillomavirus (HPV) infection. p16 expression is a marker for HPV infection and p16 positive OPSCC is now recognized as a separate disease entity. There are only limited data available regarding HPV-related OPSCC in Asian countries and no data from Malaysia.

    Methods: We identified 60 Malaysian patients with OPSCC over a 12-year period (2004-2015) from four different hospitals in two major cities, Kuala Lumpur and Penang. The detection of HPV was carried out using p16 immunohistochemistry and high risk HPV DNA in situ hybridisation.

    Results: Overall, 15 (25%) tumours were p16 positive by immunohistochemistry, 10 of which were also positive for high risk HPV DNA by in situ hybridisation. By comparison, a matched cohort of UK patients had a p16 positive rate of 49%. However, between 2009 and 2015, where cases were available from all four hospitals, 13 of 37 (35%) cases were p16 positive. In our Malaysian cohort, 53% of patients were of Chinese ethnicity and 80% of the p16 positive cases were found in these patients; no Indian patients had p16 positive disease, despite representing 35% of the total cohort.

    Conclusion: The proportion of OPSCCs associated with HPV in Malaysia appears to be lower than in European and American cohorts and could possibly be more prevalent amongst Malaysians of Chinese ethnicity. Further, our data suggests that the burden of HPV-related OPSCC could be increasing in Malaysia. Larger cross-sectional studies of Malaysian patients are required to determine the public health implications of these preliminary findings.

  19. Ismail AI, Hyder Ali IA, Wong CK, Ban AY, Mz Zahrah F, Lem LK, et al.
    Pulm Ther, 2025 Mar;11(1):25-40.
    PMID: 39520649 DOI: 10.1007/s41030-024-00278-8
    INTRODUCTION: The MERIT study in Malaysia is a real-world retrospective, observational, multicenter study that evaluated asthma control in patients with uncontrolled asthma who were switched from as-needed (pro re nata [PRN]) budesonide/formoterol or inhaled corticosteroid (ICS) whenever a short-acting beta-agonist (SABA) was taken, to proactive regular dosing of fluticasone propionate/salmeterol (FP/SAL PRD).

    METHODS: Data from the medical records of patients who were stepped up to FP/SAL PRD were extracted retrospectively at baseline and follow-up (between 3 and 6 months after stepping up to FP/SAL PRD). The primary endpoint was the percentage of patients with improvement in asthma control assessed via the Asthma Control Test (ACT). Secondary endpoints included safety and the percentage of patients with moderate and severe exacerbations. Additionally, patient-reported use of reliever medication, systemic corticosteroids, emergency department visits, or hospitalization was also analyzed.

    RESULTS: One hundred twenty patients with uncontrolled asthma who were stepped up to FP/SAL PRD were enrolled in the study. Of these, 76 (63.3%) patients were on prior budesonide/formoterol PRN, and 44 (36.7%) were on prior ICS with SABA PRN treatment. After stepping up to FP/SAL PRD with a mean follow-up of 5.8 months, 110 (91.7%) patients achieved asthma control at the follow-up visit (p 

  20. Patmanathan SN, Johnson SP, Lai SL, Panja Bernam S, Lopes V, Wei W, et al.
    Sci Rep, 2016 05 10;6:25650.
    PMID: 27160553 DOI: 10.1038/srep25650
    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.
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