Displaying publications 1 - 20 of 41 in total

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  1. Chung KH, Othman Z, Lee JS
    J Food Sci Technol, 2015 Oct;52(10):6218-29.
    PMID: 26396368 DOI: 10.1007/s13197-014-1700-4
    Corn starches with different amylose-to-amylopectin ratio (waxy, normal, Hylon V, and Hylon VII) were treated with five doses of gamma irradiation (1, 5, 10, 25, and 50 kGy). The effects of gamma irradiation on the physicochemical properties of starch samples were investigated. Waxy samples showed an increase of amylose-like fractions when irradiated at 10 kGy. The reduction in apparent amylose content increased with amylose content when underwent irradiation at 25 and 50 kGy. Low amylose starches lost their pasting ability when irradiated at 25 and 50 kGy. Results from thermal behavior and pasting profile suggested that low level of cross-linking occurred in Hylon VII samples irradiated at 5 kGy. Severe reduction in pasting properties, gelatinization temperatures and relative crystallinity with increasing irradiation intensity revealed that waxy samples were affected more by gamma irradiation; this also indicated amylopectin was the starch fraction most affected by gamma irradiation. Alteration level was portrayed differently when different kind of physicochemical properties were investigated, in which the pasting properties and crystallinity of starches were more immensely influenced by gamma irradiation while thermal behavior was less affected. Despite the irradiation level, the morphology and crystal pattern of starch granules were found remain unchanged by irradiation.
  2. Chiu MT, Tham HJ, Lee JS
    J Food Sci Technol, 2017 Sep;54(10):3327-3337.
    PMID: 28974818 DOI: 10.1007/s13197-017-2785-3
    This study was designed to determine the effect of osmotic dehydration (OD) process temperature (35-55 °C), sucrose concentration (40-60% w/w) and immersion time (90-210 min) on the water loss (WL), solid gain (SG), DPPH radical scavenging activity, ferric reducing antioxidant power (FRAP) and sensory quality of the dehydrated Terung Asam slices. Response Surface Methodology with Central Composite Design was applied to investigate the influence of these variables on the aforementioned responses. The increase in the levels of these processing parameters increased the WL and SG. The antioxidant activities also increased with sugar concentration, but reduced with immersion time and temperature elevation. About 36-80% of IC50 and 47-72% of FRAP were depleted after osmotic process. The loss of antioxidants was predominantly due to leaching during osmotic treatment rather than hot air drying. Despite the losses of these compounds, osmotic pretreatment was able to improve the sensory quality of the product. The optimum OD process condition was predicted as process temperature 38.1 °C, sucrose concentration 55.6% and osmotic duration 126.3 min.
  3. Lee JS, Bukhari SN, Fauzi NM
    Drug Des Devel Ther, 2015;9:4761-78.
    PMID: 26316713 DOI: 10.2147/DDDT.S86242
    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells.
  4. Lee JS, Ee ML, Chung KH, Othman Z
    Carbohydr Polym, 2013 Sep 12;97(2):614-7.
    PMID: 23911492 DOI: 10.1016/j.carbpol.2013.05.047
    The effect of gamma-irradiation on formation of resistant starch (RS) in corn starch with different amylose content was examined. Normal corn starch, waxy corn starch, and high amylose corn starch (Hylon V and Hylon VII) were irradiated at 5, 10, 25 and 50 kGy. Gamma-irradiation at 5 kGy increased the amylose-like molecules in starches and thus significantly enhanced the RS content (p<0.05). Highest RS content was produced by 50 kGy irradiated in all the starch samples (p<0.05). The irradiation-induced RS was more evident in waxy corn starch, followed by high amylose corn starch and normal corn starch.
  5. Phua MH, Tsuyuki S, Furuya N, Lee JS
    J Environ Manage, 2008 Sep;88(4):784-95.
    PMID: 17629393
    Tropical deforestation is occurring at an alarming rate, threatening the ecological integrity of protected areas. This makes it vital to regularly assess protected areas to confirm the efficacy of measures that protect that area from clearing. Satellite remote sensing offers a systematic and objective means for detecting and monitoring deforestation. This paper examines a spectral change approach to detect deforestation using pattern decomposition (PD) coefficients from multitemporal Landsat data. Our results show that the PD coefficients for soil and vegetation can be used to detect deforestation using change vector analysis (CVA). CVA analysis demonstrates that deforestation in the Kinabalu area, Sabah, Malaysia has significantly slowed from 1.2% in period 1 (1973 and 1991) to 0.1% in period 2 (1991 and 1996). A comparison of deforestation both inside and outside Kinabalu Park has highlighted the effectiveness of the park in protecting the tropical forest against clearing. However, the park is still facing pressure from the area immediately surrounding the park (the 1 km buffer zone) where the deforestation rate has remained unchanged.
  6. Harris H, Ooi YBH, Lee JS, Matanjun P
    BMC Public Health, 2019 Jun 13;19(Suppl 4):554.
    PMID: 31196012 DOI: 10.1186/s12889-019-6854-6
    BACKGROUND: Rural coastal communities in Sabah are still overly represented in the hardcore poor economic status. The aim of this study was to determine the prevalence of hypertension, diabetes mellitus and hypercholesterolemia among adults, in relation to economic status.

    METHODS: A cross-sectional study using stratified random sampling was conducted in seven coastal villages in Semporna, Sabah: Kabogan Laut, Salimbangun, Pekalangan, Pokas, Tampi-Tampi Timbayan, Sum Sum and Selinggit. Socio-demographic data were obtained via interviewer administered questionnaires in Sabah Malay creole. Anthropometric measurements, blood pressure, fasting blood glucose and blood lipids were obtained.

    RESULTS: A total of 330 adults (133 males, 197 females) completed the study. Mean age was 43.7 ± 15.8 years. Most participants (87%) were living below the Poverty Line Income. Median per capita household income was RM83.33/month (≈ USD20/month). The number of newly diagnosed cases of hypercholesterolemia was 40.6%, diabetes mellitus was 5.8%, and hypertension was 24.5%. Adults from the hardcore poor economic status (household income ≤RM760/month (≈USD183/month) were the most represented in those who did not have a blood pressure, blood sugar and blood lipids check in the 12 months preceding the study (Χ2, p 

  7. Lee JS, Choi SJ, Kim L, Park IS, Han JY, Kim JM, et al.
    Malays J Pathol, 2019 Aug;41(2):213-222.
    PMID: 31427559
    INTRODUCTION: Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with a non-common pattern can be diagnostic challenging. Pathologists can be unavoidably and unintentionally blind to non-descript tumor cells in a lymphohistiocytic- (LH) or small-cell (SC)-pattern. We report a case of primary systemic ALK+ ALCL with a SC pattern that presented as secondary gastric lesions with a mixed LH and SC pattern that was masqueraded as inflammatory lesions.

    CASE REPORT: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered.

    DISCUSSION: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.

  8. Chiou CF, Wang BC, Caldwell R, Furnback W, Lee JS, Kothandaraman N, et al.
    Neuropsychiatr Dis Treat, 2015;11:1989-94.
    PMID: 26346330 DOI: 10.2147/NDT.S86722
    Schizophrenia results in substantial health care utilization costs. Much of these costs can be attributed to health care use resulting from nonadherence to treatment, relapse, and hospitalization.
  9. Lee SY, Park ME, Kim RH, Ko MK, Lee KN, Kim SM, et al.
    Vaccine, 2015 Jan 29;33(5):664-9.
    PMID: 25528521 DOI: 10.1016/j.vaccine.2014.12.007
    Of the seven known serotypes of foot-and-mouth disease virus (FMDV), type A has the most diverse variations. Genetic variations also occur frequently at VP1, VP2, VP3, and VP4 because these proteins constitute the viral capsid. The structural proteins of FMDV, which are closely related to immunologic correlations, are the most easily analyzed because they have highly accessible information. In this study we analyzed the type A vaccine viruses by alignment of available sequences in order to find appropriate vaccine strains. The matching rate of ASIA topotype-specific sites (20 amino acids) located on the viral surface, which are mainly VP1 and VP2, was highly related to immunologic reactivity. Among the available vaccines analyzed in this study, we suggest that A Malaysia 97 could be used as a vaccine virus as it has the highest genetic similarity and immunologic aspects to field strains originating in East Asia.
  10. Petz LN, Turell MJ, Padilla S, Long LS, Reinbold-Wasson DD, Smith DR, et al.
    Am J Trop Med Hyg, 2014 Oct;91(4):666-71.
    PMID: 25114013 DOI: 10.4269/ajtmh.13-0218
    Tembusu virus (TMUV) is an important emerging arthropod-borne virus that may cause encephalitis in humans and has been isolated in regions of southeast Asia, including Malaysia, Thailand, and China. Currently, detection and identification of TMUV are limited to research laboratories, because quantitative rapid diagnostic assays for the virus do not exist. We describe the development of sensitive and specific conventional and real-time quantitative reverse transcription polymerase chain reaction assays for detecting TMUV RNA in infected cell culture supernatant and Culex tarsalis mosquitoes. We used this assay to document the replication of TMUV in Cx. tarsalis, where titers increased 1,000-fold 5 days after inoculation. These assays resulted in the detection of virus-specific RNA in the presence of copurified mosquito nucleic acids. The use of these rapid diagnostic assays may have future applications for field pathogen surveillance and may assist in early detection, diagnosis, and control of the associated arthropod-borne pathogens.
  11. Loh LC, Ong CK, Koo HJ, Lee SM, Lee JS, Oh YM, et al.
    PMID: 30174423 DOI: 10.2147/COPD.S165898
    Background: COPD-associated mortality was examined using a novel approach of phenotyping COPD based on computed tomography (CT)-emphysema index from quantitative CT (QCT) and post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) in a local Malaysian cohort.

    Patients and methods: Prospectively collected data of 112 eligible COPD subjects (mean age, 67 years; male, 93%; mean post-BD FEV1, 45.7%) was available for mortality analysis. Median follow-up time was 1,000 days (range, 60-1,400). QCT and clinicodemographic data were collected at study entry. Based on CT-emphysema index and post-BD FEV1% predicted, subjects were categorized into "emphysema-dominant," "airway-dominant," "mild mixed airway-emphysema," and "severe mixed airway-emphysema" diseases.

    Results: Sixteen patients (14.2%) died of COPD-associated causes. There were 29 (25.9%) "mild mixed," 23 (20.5%) "airway-dominant," 15 (13.4%) "emphysema-dominant," and 45 (40.2%) "severe mixed" cases. "Mild mixed" disease was proportionately more in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Group A, while "severe mixed" disease was proportionately more in GOLD Groups B and D. Kaplan-Meier survival estimates showed increased mortality risk with "severe mixed" disease (log rank test, p=0.03) but not with GOLD groups (p=0.08). Univariate Cox proportionate hazard analysis showed that age, body mass index, long-term oxygen therapy, FEV1, forced volume capacity, COPD Assessment Test score, modified Medical Research Council score, St Georges' Respiratory Questionnaire score, CT-emphysema index, and "severe mixed" disease (vs "mild mixed" disease) were associated with mortality. Multivariate Cox analysis showed that age, body mass index, and COPD Assessment Test score remain independently associated with mortality.

    Conclusion: "Severe mixed airway-emphysema" disease may predict COPD-associated mortality. Age, body mass index, and COPD Assessment Test score remain as key mortality risk factors in our cohort.
  12. Jahurul MHA, Zaidul ISM, Beh L, Sharifudin MS, Siddiquee S, Hasmadi M, et al.
    Food Res Int, 2019 01;115:105-115.
    PMID: 30599921 DOI: 10.1016/j.foodres.2018.08.017
    Fruits are important food commodities that can be consumed either raw or processed and are valued for their taste, nutrients, and healthy compounds. Mangifera pajang Kosterm (bambangan) is an underutilized fruit found in Malaysia (Sabah and Sarawak), Brunei, and Indonesia (Kalimantan). It is highly fibrous and juicy with an aromatic flavour and strong smell. In recent years, bambangan fruit has been gaining more attention due to its high fibre, carotenoid content, antioxidant properties, phytochemicals, and medicinal usages. Therefore, the production, trade, and consumption of bambangan fruit could be increased significantly, both domestically and internationally, because of its nutritional value. The identification and quantification of bioactive compounds in bambangan fruit has led to considerable interest among scientists. Bambangan fruit and its waste, especially its seeds and peels, are considered cheap sources of valuable food and are considered nutraceutical ingredients that could be used to prevent various diseases. The use of bambangan fruit waste co-products for the production of bioactive components is an important step towards sustainable development. This is an updated report on the nutritional composition and health-promoting phytochemicals of bambangan fruit and its co-products that explores their potential utilization. This review reveals that bambangan fruit and its co-products could be used as ingredients of dietary fibre powder or could be incorporated into food products (biscuits and macaroni) to enhance their nutraceutical properties.
  13. Kim G, Chen E, Tay AY, Lee JS, Phua JN, Shabbir A, et al.
    Jpn J Clin Oncol, 2017 02 26;47(2):179-184.
    PMID: 28173154 DOI: 10.1093/jjco/hyw153
    Peritoneal recurrence after gastrectomy for gastric cancer is common and the prognosis is dismal. Recent evidence suggests that extensive peritoneal lavage with large volume of normal saline after surgery before abdominal closure can reduce the risk of peritoneal recurrence and improve overall survival. This study aims to evaluate the benefit of extensive intraoperative peritoneal lavage. This is a prospective, open-label, multicentre randomised controlled trial involving 15 international centres in China, Korea, Japan, Malaysia and Singapore. Patients with cT3/4 stomach cancer undergoing curative resection are randomised to either extensive peritoneal lavage (10 l of saline) or standard lavage (≤2 l of saline). The primary outcome is overall survival and secondary outcomes include disease-free survival and peritoneal recurrence. The minimum sample size is 600 subjects with 300 per arm completing 3 years follow-up. The data will be analysed on an intention-to-treat basis, assuming a two-sided test with a 5% level of significance.
  14. Nguyen DH, Lee JS, Park KD, Ching YC, Nguyen XT, Phan VHG, et al.
    Nanomaterials (Basel), 2020 Mar 17;10(3).
    PMID: 32192177 DOI: 10.3390/nano10030542
    Phytoconstituents presenting in herbal plant broths are the biocompatible, regenerative, and cost-effective sources that can be utilized for green synthesis of silver nanoparticles. Different plant extracts can form nanoparticles with specific sizes, shapes, and properties. In the study, we prepared silver nanoparticles (P.uri.AgNPs, P.zey.AgNPs, and S.dul.AgNPs) based on three kinds of leaf extracts (Phyllanthus urinaria, Pouzolzia zeylanica, and Scoparia dulcis, respectively) and demonstrated the antifungal capacity. The silver nanoparticles were simply formed by adding silver nitrate to leaf extracts without using any reducing agents or stabilizers. Formation and physicochemical properties of these silver nanoparticles were characterized by UV-vis, Fourier transforms infrared spectroscopy, scanning electron microscope, transmission electron microscope, and energy dispersive X-ray spectroscopy. P.uri.AgNPs were 28.3 nm and spherical. P.zey.AgNPs were 26.7 nm with hexagon or triangle morphologies. Spherical S.dul.AgNPs were formed and they were relatively smaller than others. P.uri.AgNPs, P.zey.AgNPs and S.dul.AgNPs exhibited the antifungal ability effective against Aspergillus niger, Aspergillus flavus, and Fusarium oxysporum, demonstrating their potentials as fungicides in the biomedical and agricultural applications.
  15. Higuchi T, Ishigooka J, Iyo M, Yeh CB, Ebenezer EG, Liang KY, et al.
    Asia Pac Psychiatry, 2019 Jun;11(2):e12352.
    PMID: 30950208 DOI: 10.1111/appy.12352
    INTRODUCTION: To evaluate efficacy and safety of lurasidone for the treatment of Asian patients with schizophrenia.

    METHODS: Patients with schizophrenia from Japan, South Korea, Malaysia, and Taiwan were randomly assigned to 6 weeks of double-blind treatment with 40 or 80 mg/d of lurasidone or placebo. The primary efficacy measure was change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total score. Efficacy was evaluated using a mixed-model repeated-measures (MMRM) analysis in the modified intention-to-treat (mITT) population.

    RESULTS: On the basis of the analysis for the mITT population, the estimated difference score for lurasidone 40 and 80 mg/d vs placebo was -4.8 (P = 0.050) and -4.2 (P = 0.080). For the full intention-to-treat (ITT) population, the difference score for lurasidone 40 and 80 mg/d vs placebo was -5.8 (P = 0.017) and -4.2 (P = 0.043). The most frequent adverse events in the lurasidone 40 and 80 mg/d and placebo groups, respectively, were akathisia (7.3%, 10.4%, 3.3%), somnolence (6.0%, 2.6%, 0.7%), and vomiting (6.0%, 5.8%, 2.0%). The proportion of patients experiencing clinically significant weight gain (≥7%) was 5.3% for lurasidone 40 mg/d, 1.3% for 80 mg/d, and 1.4% for placebo. End point changes in metabolic parameters and prolactin were comparable for both lurasidone groups and placebo.

    CONCLUSIONS: In the ITT (but not the mITT) population, treatment with lurasidone was associated with significant improvement in the PANSS total score in patients with schizophrenia. Lurasidone was generally well tolerated with minimal impact on weight and metabolic parameters.

  16. Cho BC, Chewaskulyong B, Lee KH, Dechaphunkul A, Sriuranpong V, Imamura F, et al.
    J Thorac Oncol, 2019 01;14(1):99-106.
    PMID: 30240852 DOI: 10.1016/j.jtho.2018.09.004
    INTRODUCTION: Here we report efficacy and safety data of an Asian subset of the phase III FLAURA trial (NCT02296125), which compares osimertinib with standard of care (SoC) EGFR tyrosine kinase inhibitors (TKIs) in patients with previously untreated advanced NSCLC with tumors harboring exon 19 deletion (Ex19del)/L858R EGFR TKI-sensitizing mutations.

    METHODS: Eligible Asian patients (enrolled at Asian sites) who were at least 18 years of age (≥20 years in Japan) and had untreated EGFR-mutated advanced NSCLC were randomized 1:1 to receive osimertinib (80 mg, orally once daily) or an SoC EGFR TKI (gefitinib, 250 mg, or erlotinib, 150 mg, orally once daily). The primary end point was investigator-assessed progression-free survival (PFS). The key secondary end points were overall survival, objective response rate, central nervous system efficacy, and safety.

    RESULTS: The median PFS was 16.5 versus 11.0 months for the osimertinib and SoC EGFR TKI groups, respectively (hazard ratio = 0.54, 95% confidence interval: 0.41-0.72, p < 0.0001). The overall survival data were immature (24% maturity). The objective response rates were 80% for osimertinib and 75% for an SoC EGFR TKI. The median central nervous system PFS was not calculable for the osimertinib group and was 13.8 months for the SoC EGFR TKI group (hazard ratio = 0.55, 95% confidence interval: 0.25-1.17, p = 0.118). Fewer adverse events of grade 3 or higher (40% versus 48%) and fewer adverse events leading to treatment discontinuation (15% versus 21%) were reported with osimertinib versus with an SoC EGFR TKI, respectively.

    CONCLUSION: In this Asian population, first-line osimertinib demonstrated a clinically meaningful improvement in PFS over an SoC EGFR TKI, with a safety profile consistent with that for the overall FLAURA study population.

  17. Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al.
    J Am Med Dir Assoc, 2014 Feb;15(2):95-101.
    PMID: 24461239 DOI: 10.1016/j.jamda.2013.11.025
    Sarcopenia, a newly recognized geriatric syndrome, is characterized by age-related decline of skeletal muscle plus low muscle strength and/or physical performance. Previous studies have confirmed the association of sarcopenia and adverse health outcomes, such as falls, disability, hospital admission, long term care placement, poorer quality of life, and mortality, which denotes the importance of sarcopenia in the health care for older people. Despite the clinical significance of sarcopenia, the operational definition of sarcopenia and standardized intervention programs are still lacking. It is generally agreed by the different working groups for sarcopenia in the world that sarcopenia should be defined through a combined approach of muscle mass and muscle quality, however, selecting appropriate diagnostic cutoff values for all the measurements in Asian populations is challenging. Asia is a rapidly aging region with a huge population, so the impact of sarcopenia to this region is estimated to be huge as well. Asian Working Group for Sarcopenia (AWGS) aimed to promote sarcopenia research in Asia, and we collected the best available evidences of sarcopenia researches from Asian countries to establish the consensus for sarcopenia diagnosis. AWGS has agreed with the previous reports that sarcopenia should be described as low muscle mass plus low muscle strength and/or low physical performance, and we also recommend outcome indicators for further researches, as well as the conditions that sarcopenia should be assessed. In addition to sarcopenia screening for community-dwelling older people, AWGS recommends sarcopenia assessment in certain clinical conditions and healthcare settings to facilitate implementing sarcopenia in clinical practice. Moreover, we also recommend cutoff values for muscle mass measurements (7.0 kg/m(2) for men and 5.4 kg/m(2) for women by using dual X-ray absorptiometry, and 7.0 kg/m(2) for men and 5.7 kg/m(2) for women by using bioimpedance analysis), handgrip strength (<26 kg for men and <18 kg for women), and usual gait speed (<0.8 m/s). However, a number of challenges remained to be solved in the future. Asia is made up of a great number of ethnicities. The majority of currently available studies have been published from eastern Asia, therefore, more studies of sarcopenia in south, southeastern, and western Asia should be promoted. On the other hand, most Asian studies have been conducted in a cross-sectional design and few longitudinal studies have not necessarily collected the commonly used outcome indicators as other reports from Western countries. Nevertheless, the AWGS consensus report is believed to promote more Asian sarcopenia research, and most important of all, to focus on sarcopenia intervention studies and the implementation of sarcopenia in clinical practice to improve health care outcomes of older people in the communities and the healthcare settings in Asia.
  18. Kim WJ, Gupta V, Nishimura M, Makita H, Idolor L, Roa C, et al.
    Int. J. Tuberc. Lung Dis., 2018 07 01;22(7):820-826.
    PMID: 29914609 DOI: 10.5588/ijtld.17.0524
    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment.

    OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup.

    METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis.

    RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score.

    CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

  19. Tak WY, Lin SM, Wang Y, Zheng J, Vecchione A, Park SY, et al.
    Clin. Cancer Res., 2018 01 01;24(1):73-83.
    PMID: 29018051 DOI: 10.1158/1078-0432.CCR-16-2433
    Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73-83. ©2017 AACR.
  20. Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, et al.
    Clin. Cancer Res., 2019 11 15;25(22):6644-6652.
    PMID: 31439584 DOI: 10.1158/1078-0432.CCR-19-1126
    PURPOSE: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non-small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125).

    EXPERIMENTAL DESIGN: Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test.

    RESULTS: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed EGFRm positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79% [95% confidence interval (CI), 74-84] and 68% (95% CI, 61-75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months).

    CONCLUSIONS: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.

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