Displaying all 12 publications

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  1. Kasinathan G, Lee BS, Sathar J
    Clin Case Rep, 2021 Mar;9(3):1330-1333.
    PMID: 33768838 DOI: 10.1002/ccr3.3757
    Although the patient with very severe aplastic anemia might be a fit elderly receiving standard therapy, there are factors which contribute to an adverse outcome such as severity of pancytopenia, absence of minor paroxysmal nocturnal hemoglobinuria clone and infective complications of therapy.
  2. Lee BS, Sathar J, Sivapatham L, Lee LI
    Malays J Pathol, 2018 Aug;40(2):149-152.
    PMID: 30173232 MyJurnal
    INTRODUCTION: Non-transfusion dependent thalassaemia (NTDT) is a term used for thalassaemia patients who do not require lifelong regular transfusions for survival. Pregnancy in these women, whether spontaneous or through assisted reproductive technology, represents a challenge for the physician.
    MATERIALS AND METHODS: The maternal and foetal outcomes of patients with NTDT followed up in a tertiary haematology centre over 6 months period were studied. A total of 36 pregnancies in 26 pregnant women with NTDT were analysed.
    RESULTS: Among these women, all of the pregnancies resulted in successful delivery of singleton live-born neonates. There were four clinically distinct forms of NTDT among these women which include Hb E/β-thalassemia (mild and moderate forms), HbH disease, HbH-Constant Spring, and homozygous δβ-thalassemia. No blood transfusion was needed in 15 of the 36 pregnancies (41.6%). The lowest mean Hb level in which no blood transfusion was given was 8.21 g/dL. The mean of packed-cell units received during pregnancy was 6.95 units per pregnancy. There was no worsening of serum ferritin observed during pregnancy with mean serum ferritin pre- and post-pregnancy of 409.35 ug/L and 418.18 ug/L respectively. The mean gestational age at delivery was 38.6 weeks with no preterm delivery reported. The mean foetal birth weight was 2729 grams. There was no intrauterine growth restriction (IUGR) or congenital malformation. There was a case of small for gestational age (SGA) and a case of oligohydramnios.
    CONCLUSION: This study showed that pregnancy was possible, safe and has a favourable outcome in patients with NTDT with multidisciplinary care.
  3. Techatraisak K, Hestiantoro A, Soon R, Banal-Silao MJ, Kim MR, Seong SJ, et al.
    Reprod Sci, 2022 Feb 02.
    PMID: 35112299 DOI: 10.1007/s43032-021-00787-w
    Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (-28.9 ± 27.5 and - 34 ± 28.4) and control and powerlessness (-23.7 ± 28.2 and - 28.5 ± 26.2). Mean EAPP score change was -4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015.
  4. Cheng KK, Lee BS, Masuda T, Ito T, Ikeda K, Hirayama A, et al.
    Nat Commun, 2014;5:3233.
    PMID: 24481126 DOI: 10.1038/ncomms4233
    Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.
  5. Goh JJ, Ong HT, Lee BS, Teoh HK
    Malays J Pathol, 2023 Aug;45(2):247-259.
    PMID: 37658534
    INTRODUCTION: Mesenchymal stromal cells (MSCs) are promising vehicles for cancer therapy due to their homing ability and potency to be genetically manipulated through either viral or non-viral methods. Interleukin-12 (IL-12) is one of the key immunomodulatory cytokines which has anti-tumour effect. However, systemic administration of the cytokine at therapeutic dosage can cause serious toxicity in the host system due to the high systemic level of interferon-γ (IFN-γ) induced.

    OBJECTIVES: This study aimed to investigate the in vitro growth inhibition of genetically engineered human umbilical cord-derived mesenchymal stromal cells (hUCMSC) expressing IL-12 on H1975 human lung adenocarcinoma cells.

    MATERIALS AND METHODS: Both adenoviral method and electroporation which used to generate hUCMSC-IL12 were compared. The method with better outcome was selected to generate hUCMSC-IL12 for the co-culture experiment with H1975 or MRC-5 cells. Characterisation of hUCMSC and hUCMSC-IL12 was performed.

    RESULTS: Adenoviral method showed superior results in transfection efficiency (63.6%), post-transfection cell viability (82.6%) and hIL-12 protein expression (1.2 x 107 pg/ml) and thus was selected for the downstream experiments. Subsequently, hUCMSC-IL12 showed significant inhibition effect on H1975 cells after 5 days of co-culture. No significant difference was observed for all other co-culture groups, indicating that the inhibition effect was because of hIL-12. Lastly, the integrity of hUCMSC-IL12 remained unaffected by the transduction through examination of their surface markers and differentiation properties.

    CONCLUSION: This study provided proof of concept that hUCMSC can be genetically engineered to express hIL-12 which exerts direct growth inhibition effect on human lung adenocarcinoma cells.

  6. Techatraisak K, Hestiantoro A, Ruey S, Banal-Silao MJ, Kim MR, Seong SJ, et al.
    BMC Womens Health, 2019 05 16;19(1):68.
    PMID: 31096979 DOI: 10.1186/s12905-019-0758-6
    BACKGROUND: Dienogest has been shown to substantially improve endometriosis-associated symptoms such as debilitating chronic pelvic pain, and in turn, health-related quality of life (HRQoL). To date, there is no data on patient-reported outcomes reflecting the real-world practice in Asia where endometriosis is a relevant health, social and economic burden. This non-interventional, multi-center, prospective study aims to investigate the influence of dienogest on HRQoL.

    METHODS: Asian women received dienogest (2 mg/daily) and were followed for 24 months. The effectiveness of dienogest to improve HRQoL and endometriosis-associated pelvic pain (EAPP) was assessed by patient-reported outcomes. HRQoL, especially the "pain" domain as primary endpoint, was evaluated with the Endometriosis Health Profile-30 (EHP-30) questionnaire. The numeric rating scale served to determine changes in the severity of EAPP. Within the presented interim analysis (data cut-off: 2017-11-27), the mean changes in EHP-30 and EAPP scores from baseline to 6 months upon availability of the data were evaluated. Treatment-emergent adverse events (TEAEs) and bleeding profiles were documented.

    RESULTS: Dienogest therapy decreased EHP-30 scores in all assessed domains (score 0-100, lower scores indicate better HRQoL). Primarily, the "pain" domain was improved in 78.4% of patients. EAPP was reduced (score 0-10, lower scores reflect less pain), highlighted by a mean reduction of the pain score by - 4.5 points. Patients with a higher EAPP score at baseline had an increased response to dienogest (- 6.2 points mean change) compared to patients with low baseline EAPP severity (- 1.4 points mean change). Both surgically and clinically diagnosed patients described comparable pain reduction, as well as women with or without prior treatment. Drug-related TEAEs were documented for 31.5% of patients, with amenorrhoea (5.9%) and metrorrhagia (5.1%) being the most common events. The bleeding pattern was changed upon dienogest, characterized by decreased normal bleeding (84.2 to 28.8%) and increased amenorrhea (3.2 to 42.9%) at 6 months.

    CONCLUSION: The data indicate an amelioration of HRQoL and EAPP upon dienogest therapy. No new safety signals were observed. Therefore, its use as first-line therapy for long-term management of debilitating and chronic endometriosis-associated pain represents an interesting option that remains to be further investigated.

    TRIAL REGISTRATION: Name of registry: Clinical Trials Clinicaltrials.gov registration number: NCT02425462 Registration date: 2015-04-24. Registration timing: prospective.

  7. Leong HY, Su CA, Lee BS, Lan JC, Law CL, Chang JS, et al.
    Bioresour Technol, 2019 Jan;271:30-36.
    PMID: 30261334 DOI: 10.1016/j.biortech.2018.09.093
    Microalgae biorefinery is presently receiving a lot of attention as driven by its production of high value-added products. In this study, an oleaginous microalga Aurantiochytrium limacinum SR21 was cultured for docosahexaenoic acid (DHA) production using 20% (w/v) of K2HPO4-waste feedstock to replace 0.005% (w/v) of KH2PO4 in the flask culture. DHA is an essential nutrient for human's brain functionalities. Collectively, the K2HPO4-waste feedstock with working concentration of 0.005% (w/v) in the cultivation prompted a higher lipid content (8.29%) and DHA production (128.81 mg.L-1). Moreover, natural plant pigment products containing stabilised betacyanins were utilised as natural red colourants for hard candy production. This study develops microalgal cultivation using salt-rich waste feedstock for a higher lipid and DHA content as well as application of natural colouring agents in food products.
  8. Kasinathan G, Lee BS
    Clin Case Rep, 2021 Jun;9(6):e04156.
    PMID: 34194755 DOI: 10.1002/ccr3.4156
    Coexistent myelodysplastic syndrome and acute megakaryoblastic leukemia is an aggressive disease which often do not respond to standard chemotherapy due to the various molecular and cytogenetic abnormalities. Understanding of the molecular pathogenesis may lead to better therapeutic modalities as current conventional therapies are largely ineffective.
  9. Fann RJ, D'Silv EC, Tanusha K, Wong TK, Lee BS, Sathar J, et al.
    Med J Malaysia, 2023 Jul;78(4):429-436.
    PMID: 37518908
    INTRODUCTION: Most evidence about the management of cancer and hematological malignancy in pregnancy are derived from retrospective observational studies with a small sample size. Availability of sufficiently large data has enabled evidence-based decision-making in this clinical dilemma.

    MATERIALS AND METHODS: Retrospective study looking into patients diagnosed with acute leukemia or lymphoma in pregnancy from 1st January 2014 to 1st January 2020 in Ampang General Hospital including newly or previously diagnosed and relapsed disease RESULTS: 37 cases of acute leukemia or lymphoma in pregnancy occurred in 34 patients. Majority of acute leukemia or lymphoma in pregnancy diagnosed in 1st trimester or in the setting of previously established or relapsed disease was therapeutically terminated. Thirteen pregnancies treated with antenatal chemotherapy resulted in livebirths except one stillbirth. More adverse obstetric outcomes are observed in pregnancies that did not receive antenatal chemotherapy, but association did not reach statistical significance. There was no significant difference in fetal outcome between cohort with and without antenatal chemotherapy. No treatment related mortality was observed in pregnancies with antenatal chemotherapy. Overall survival for newly diagnosed acute leukemia in pregnancy is significantly better with antenatal chemotherapy versus no antenatal chemotherapy.

    CONCLUSION: Treatment with chemotherapy in 2nd trimester of pregnancy onwards appears to have tolerable risks with favorable obstetric and fetal outcome. Deferment of treatment for acute leukemia in pregnancy to after delivery may cause increased risk of maternal and fetal adverse outcome.

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