Displaying publications 161 - 180 of 464 in total

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  1. Fulltext Ocular involvement in acute lymphoblastic leukaemia
    Tan AK, Azman A, Hoe TS, Rohana T
    Med J Malaysia, 1994 Dec;49(4):409-11.
    PMID: 7674978
    A six-year-old boy, a known case of acute lymphoblastic leukaemia (ALL) on remission since 1991 presented with leukocoria and poor vision of the left eye for two days' duration. Examination revealed endophthalmitis in the left eye with raised intraocular pressure. Anterior chamber paracentesis with vitreous biopsy confirmed a diagnosis of ocular involvement. Further investigation revealed that he also had bone marrow and central nervous system relapse. Clinical manifestation and treatment modalities of ocular involvement in leukaemia are discussed.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*
  2. Nutritional status and quality of life in patients with acute leukaemia prior to and after induction chemotherapy in three hospitals in Tehran, Iran: a prospective study
    Malihi Z, Kandiah M, Chan YM, Hosseinzadeh M, Sohanaki Azad M, Zarif Yeganeh M
    J Hum Nutr Diet, 2013 Jul;26 Suppl 1:123-31.
    PMID: 23627676 DOI: 10.1111/jhn.12043
    The primary objective of the present study was to assess changes in the nutritional status and quality of life in acute leukaemia patients, aged ≥15 years, who had undergone induction chemotherapy.
    Matched MeSH terms: Leukemia/complications*; Leukemia/drug therapy
  3. Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy
    Tan SY, Poh BK, Nadrah MH, Jannah NA, Rahman J, Ismail MN
    J Hum Nutr Diet, 2013 Jul;26 Suppl 1:23-33.
    PMID: 23701375 DOI: 10.1111/jhn.12074
    The assessment of nutritional status among paediatric patients is important for the planning and execution of nutritional strategies that strive to optimise the quality of life and growth among sick children. The present study aimed to evaluate the nutritional status and dietary intake among children with acute leukaemia.
    Matched MeSH terms: Leukemia, Myeloid/complications*; Leukemia, Myeloid/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  4. Fulltext Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry
    Moriyama T, Yang YL, Nishii R, Ariffin H, Liu C, Lin TN, et al.
    Blood, 2017 Sep 07;130(10):1209-1212.
    PMID: 28659275 DOI: 10.1182/blood-2017-05-782383
    Prolonged exposure to thiopurines (eg, mercaptopurine [MP]) is essential for curative therapy in acute lymphoblastic leukemia (ALL), but is also associated with frequent dose-limiting hematopoietic toxicities, which is partly explained by inherited genetic polymorphisms in drug metabolizing enzymes (eg, TPMT). Recently, our group and others identified germ line genetic variants in NUDT15 as another major cause of thiopurine-related myelosuppression, particularly in Asian and Hispanic people. In this article, we describe 3 novel NUDT15 coding variants (p.R34T, p.K35E, and p.G17_V18del) in 5 children with ALL enrolled in frontline protocols in Singapore, Taiwan, and at St. Jude Children's Research Hospital. Patients carrying these variants experienced significant toxicity and reduced tolerance to MP across treatment protocols. Functionally, all 3 variants led to partial to complete loss of NUDT15 nucleotide diphosphatase activity and negatively influenced protein stability. In particular, the p.G17_V18del variant protein showed extremely low thermostability and was completely void of catalytic activity, thus likely to confer a high risk of thiopurine intolerance. This in-frame deletion was only seen in African and European patients, and is the first NUDT15 risk variant identified in non-Asian, non-Hispanic populations. In conclusion, we discovered 3 novel loss-of-function variants in NUDT15 associated with MP toxicity, enabling more comprehensive pharmacogenetics-based thiopurine dose adjustments across diverse populations.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  5. Fulltext Noncytotoxic and Antitumour-Promoting Activities of Garcinia Acid Esters from Garcinia atroviridis Griff. ex T. Anders (Guttiferae)
    Mackeen MM, Mooi LY, Amran M, Mat N, Lajis NH, Ali AM
    Evid Based Complement Alternat Med, 2012;2012:829814.
    PMID: 22685487 DOI: 10.1155/2012/829814
    The in vitro antitumour-promoting, cytotoxic, and antioxidant activities of two ester derivatives of garcinia acid, that is, 2-(butoxycarbonylmethyl)-3-butoxycarbonyl-2-hydroxy-3-propanolide (1) and 1',1''-dibutyl methyl hydroxycitrate (2), that had been previously isolated from the fruits of Garcinia atroviridis Griff. ex T. Anders (Guttiferae), were examined. Based on the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation, compound 1 (IC(50): 70 μM) showed much higher (8-fold) antitumour-promoting activity than compound 2 (IC(50): 560 μM). In addition, both compounds were nontoxic towards CEM-SS (human T-lymphoblastic leukemia) cells (CD(50): >100 μM), Raji (human B-lymphoblastoid) cells (CD(50): >600 μM), and brine shrimp (LD(50): >300 μM). Although the antitumour-promoting activity of compound 1 is moderate compared with the known antitumour promoter genistein, its non-toxicity suggests the potential of compound 1 and related structures as chemopreventive agents. The weak antioxidant activity displayed by both compounds also suggested that the primary antitumour-promoting mechanism of compound 1 did not involve oxidative-stress quenching.
    Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
  6. Nonclonal Chromosomal Aberrations in Childhood Leukemia Survivors
    Chin TF, Ibrahim K, Thirunavakarasu T, Azanan MS, Oh L, Lum SH, et al.
    Fetal Pediatr Pathol, 2018 Aug;37(4):243-253.
    PMID: 30273079 DOI: 10.1080/15513815.2018.1492054
    BACKGROUND: Survivors of childhood cancer are at risk of developing a second malignancy. One possible mechanism for neoplastic transformation of cells is through induction of persistent genomic instability. This study aims to seek evidence of chromosomal instability in long-term childhood leukemia survivors (CLS) in one of the largest pediatric academic oncology centers in South East Asia.

    METHODS: 50 asymptomatic (subjects have remained leukemia-free since treatment cessation) CLS and 50 healthy controls were recruited in this cross-sectional study. Of 50 CLS, 44 had acute lymphoblastic leukemia and 6 had acute myeloid leukemia. G-banded karyotyping was performed on unstimulated peripheral blood leukocytes of all subjects.

    RESULTS: CLS had significantly higher occurrence of karyotypic abnormalities compared to controls. Five CLS harbored six nonclonal abnormalities (mostly aneuploidy) while none were found in controls.

    CONCLUSION: Subpopulations with nonclonal chromosomal aberrations were present in peripheral blood leukocytes of our cohort of childhood leukemia long-term survivors.

    Matched MeSH terms: Leukemia*
  7. Fulltext Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd
    Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, et al.
    Br J Haematol, 2017 10;179(2):219-228.
    PMID: 28699641 DOI: 10.1111/bjh.14829
    The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology
  8. Neutropenic enterocolitis treated by primary resection with anastomosis in a leukaemic patient receiving chemotherapy
    Anderson PE
    Aust N Z J Surg, 1993 Jan;63(1):74-6.
    PMID: 8466468
    Neutropenic enterocolitis is a complication of patients receiving chemotherapy for malignant disease. It has a characteristic presentation and may lead to gut perforation with consequent high mortality. It is best treated by early surgical intervention. Considerable mortality is inevitable in these gravely ill patients.
    Matched MeSH terms: Leukemia, Myeloid/complications*; Leukemia, Myeloid/drug therapy
  9. Fulltext Nephrotic syndrome in a patient with relapsed of chronic myeloid leukemia after peripheral blood stem cell transplantation
    Bee PC, Gan GG, Sangkar VJ, Haris AR
    Med J Malaysia, 2008 Mar;63(1):71-2.
    PMID: 18935742 MyJurnal
    Nephrotic syndrome (NS) is a well documented complication after allogeneic peripheral blood stem cell transplantation. It is usually due to autoimmune glomerulonephritis and thought to be a clinical manifestation of graft versus host disease. NS has also been reported to be associated with other hematological malignancies. We report a case of nephrotic syndrome in a patient who relapsed after allogeneic peripheral blood stem cell transplantation (PBSCT) for chronic myeloid leukemia (CML). The renal biopsy was suggestive of minimal change disease. There was no other evidence of graft versus host disease. He was treated with high dose prednisolone, with no response and finally succumbed to the underlying disease.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications*; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy*
  10. Nasal eschar: a warning sign of potentially fatal invasive fungal sinusitis in immunocompromised children
    Idris N, Lim LH
    J Pediatr Hematol Oncol, 2012 May;34(4):e134-6.
    PMID: 22430585 DOI: 10.1097/MPH.0b013e31824410e3
    Most invasive fungal sinusitis occurs in immunocompromised adult patients. We present the case study of a 12-year-old boy diagnosed with acute myeloblastic leukemia undergoing chemotherapy. He developed a progressive darkening discoloration over the dorsum of the nose that turned into an eschar. Nasal endoscopy revealed extensive necrotic tissue in the nasal cavity mucosa, inferior and middle turbinates, and septal cartilage that extended to the eschar of the skin over the nasal dorsum. Histopathology showed aspergillus invasive fungal rhinosinusitis.
    Matched MeSH terms: Leukemia, Myeloid, Acute/drug therapy*; Leukemia, Myeloid, Acute/immunology; Leukemia, Myeloid, Acute/microbiology; Leukemia, Myeloid, Acute/pathology
  11. Fulltext N-Ethyl-n-Nitrosourea Induced Leukaemia in a Mouse Model through Upregulation of Vascular Endothelial Growth Factor and Evading Apoptosis
    Aliyu A, Shaari MR, Ahmad Sayuti NS, Reduan MFH, Sithambaram S, Noordin MM, et al.
    Cancers (Basel), 2020 Mar 13;12(3).
    PMID: 32183192 DOI: 10.3390/cancers12030678
    Chemical carcinogens are commonly used to investigate the biology and prognoses of various cancers. This study investigated the mechanism of leukaemogenic effects of n-ethyl-n-nitrosourea (ENU) in a mouse model. A total of 14 3-week-old male Institute of Cancer Research (ICR)-mice were used for the study. The mice were divided into groups A and B with seven mice each. Group A served as the control while group B received intraperitoneal (IP) injections of 80 mg/kg ENU twice with a one-week interval and were monitored monthly for 3 months for the development of leukaemia via blood smear examination. The mice were sacrificed humanely using a CO2 chamber. Blood, spleen, lymph nodes, liver, kidney and lung samples were collected for blood smear examination and histopathological evaluation. The expression of angiogenic protein (VEGF), and pro and anti-apoptotic proteins (BCL2 and BAX), was detected and quantified using Western blot technique. Leukaemia was confirmed by the presence of numerous blast cells in the peripheral blood smear in group B. Similarly, the VEGF and BCL2 proteins were significantly (p < 0.05) upregulated in group B compared to A. It is concluded that IP administration of 80 mg/kg ENU induced leukaemia in ICR-mice 12 weeks post administration through upregulation of angiogenic and anti-apoptotic proteins: VEGF and BCL2.
    Matched MeSH terms: Leukemia
  12. Myeloid Sarcoma of Temporal Bone: A Rare Manifestation of Relapse Acute Myeloid Leukemia
    Goh BS, Tang CL, Tan GC
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 2):1023-1026.
    PMID: 31750119 DOI: 10.1007/s12070-015-0930-8
    Myeloid sarcoma is a rare malignant extramedullary neoplasm of myeloid precursor cells. This disorder may occur in concomitance with or precede development of acute or chronic myeloid leukemia. Sometimes, it is the initial manifestation of relapse in a previously treated acute myeloid leukemia. We report a case of 11 years old boy with acute myeloid leukemia in remission state, presented with short history of right otalgia associated with facial nerve palsy. Diagnosis of right acute mastoiditis with facial nerve palsy as complication of acute otitis media was made initially. Patient underwent simple cortical mastoidectomy but histopathology from soft tissue that was sent revealed diagnosis of myeloid sarcoma. A leukemic relapse was confirmed by paediatric oncologist through bone marrow biopsy. Chemotherapy was commenced but patient responded poorly to the treatment.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute
  13. Mycobacterium abscessus Gastric Band Infection Complicated by Immune Reconstitution Inflammatory Syndrome and Cured in the Context of Allogeneic Hematopoietic Stem Cell Transplantation
    An N, Purtill D, Boan P
    Open Forum Infect Dis, 2021 Feb;8(2):ofaa637.
    PMID: 33553476 DOI: 10.1093/ofid/ofaa637
    We present a case of abdominal gastric band-associated Mycobacterium abscessus infection, manifesting after the onset of acute myeloid leukemia, complicated by immune reconstitution inflammatory syndrome (IRIS), and cured while receiving an allogeneic hematopoietic stem cell transplant. IRIS should be considered in less classical situations where there is unexplained clinical deterioration.
    Matched MeSH terms: Leukemia, Myeloid, Acute
  14. Fulltext Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients
    Akhter A, Mughal MK, Elyamany G, Sinclair G, Azma RZ, Masir N, et al.
    Diagn Pathol, 2016 Sep 15;11(1):89.
    PMID: 27632978 DOI: 10.1186/s13000-016-0541-z
    The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL.
    Matched MeSH terms: Leukemia, Myeloid, Acute/diagnosis; Leukemia, Myeloid, Acute/genetics*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
  15. Multiclass Benchmarking Framework for Automated Acute Leukaemia Detection and Classification Based on BWM and Group-VIKOR
    Alsalem MA, Zaidan AA, Zaidan BB, Albahri OS, Alamoodi AH, Albahri AS, et al.
    J Med Syst, 2019 Jun 01;43(7):212.
    PMID: 31154550 DOI: 10.1007/s10916-019-1338-x
    This paper aims to assist the administration departments of medical organisations in making the right decision on selecting a suitable multiclass classification model for acute leukaemia. In this paper, we proposed a framework that will aid these departments in evaluating, benchmarking and ranking available multiclass classification models for the selection of the best one. Medical organisations have continuously faced evaluation and benchmarking challenges in such endeavour, especially when no single model is superior. Moreover, the improper selection of multiclass classification for acute leukaemia model may be costly for medical organisations. For example, when a patient dies, one such organisation will be legally or financially sued for incidents in which the model fails to fulfil its desired outcome. With regard to evaluation and benchmarking, multiclass classification models are challenging processes due to multiple evaluation and conflicting criteria. This study structured a decision matrix (DM) based on the crossover of 2 groups of multi-evaluation criteria and 22 multiclass classification models. The matrix was then evaluated with datasets comprising 72 samples of acute leukaemia, which include 5327 gens. Subsequently, multi-criteria decision-making (MCDM) techniques are used in the benchmarking and ranking of multiclass classification models. The MCDM used techniques that include the integrated BWM and VIKOR. BWM has been applied for the weight calculations of evaluation criteria, whereas VIKOR has been used to benchmark and rank classification models. VIKOR has also been employed in two decision-making contexts: individual and group decision making and internal and external group aggregation. Results showed the following: (1) the integration of BWM and VIKOR is effective at solving the benchmarking/selection problems of multiclass classification models. (2) The ranks of classification models obtained from internal and external VIKOR group decision making were almost the same, and the best multiclass classification model based on the two was 'Bayes. Naive Byes Updateable' and the worst one was 'Trees.LMT'. (3) Among the scores of groups in the objective validation, significant differences were identified, which indicated that the ranking results of internal and external VIKOR group decision making were valid.
    Matched MeSH terms: Leukemia, Myeloid, Acute/diagnosis*; Leukemia, Myeloid, Acute/pathology*
  16. Mucigerin, a new coumarin from Calophyllum mucigerum (Guttiferae)
    Ee GC, Ng KN, Taufiq-Yap YH, Rahmani M, Ali AM, Muse R
    Nat Prod Res, 2004 Apr;18(2):123-8.
    PMID: 14984084
    Our recent studies on the stem bark of Calophyllum mucigerum (Guttiferae) have yielded a new coumarin mucigerin, a prenylated xanthone cudraxanthone C and the common steroidal triterpenes friedelin and stigmasterol. Structural elucidations of these compounds were achieved using 1H NMR, 13C NMR, DEPT, COSY, HETCOR and HMBC experiments while MS gave the molecular masses. Cytotoxic assays using CEM-SS cell line (T-lymphoblastic leukemia) on the crude extracts of the stem bark indicated some activity. The crude extracts were also found to be moderately toxic against the larvae of Aedes aegypti. This article reports the isolation and identification of mucigerin as well as bioassay data.
    Matched MeSH terms: Leukemia-Lymphoma, Adult T-Cell/pathology
  17. Fulltext Molecular responses during chemotherapy in acute myeloid leukemias in predicting poor-response to standard chemotherapy
    Maha A, Cheong SK, Leong CF, Seow HF
    Malays J Pathol, 2009 Dec;31(2):81-91.
    PMID: 20514850 MyJurnal
    Signal transduction pathways are constitutively expressed in leukaemic cells resulting in aberrant survival of the cells. It is postulated that in cells of chemo-sensitive patients, chemotherapy induces apoptotic signals leading to cell death while survival signals are maintained in cells of chemo-resistant patients. There is very little information currently, on the expression of these mediators in patients immediately after chemotherapy initiation. We examined the expression pattern of proinflammatory cytokines, signaling molecules of the PI3K and MAPK pathways molecules and death receptor, DR5 on paired samples at diagnosis and during chemotherapy in acute myeloid leukaemia patients treated with cytosine arabinoside and daunorubicin. The results were correlated with remission status one month after chemotherapy. We found that in chemo-sensitive patients, chemotherapy significantly increased the percentage of cases expressing TNF-alpha (p = 0.025, n = 9) and IL-6 (p = 0.002, n = 11) compared to chemo-resistant cases. We also observed an increased percentage of chemo-sensitive cases expressing DR5 and phosphorylated p38, and Jnk. Thus, expression of TNF-alpha, IL-6, DR5, phospho-p38 and phospho-Jnk may regulate cell death in chemo-sensitive cases. In contrast, a significantly higher percentage of chemo-resistant cases expressed phospho-Bad (p = 0.027, n = 9). IL-beta and IL-18 were also found to be higher in chemo-resistant cases at diagnosis and during chemotherapy. Thus, expression of various cellular molecules in leukaemic blasts during chemotherapy may be useful in predicting treatment outcome. These cellular molecules may also be potential targets for alternative therapy.
    Matched MeSH terms: Leukemia, Myeloid, Acute/drug therapy*; Leukemia, Myeloid, Acute/genetics; Leukemia, Myeloid, Acute/pathology
  18. Fulltext Molecular rearrangements of chromosome 22 in chronic myeloid leukemia in a multi-ethnic Malaysian population
    Bosco JJ, Dyck JA
    Singapore Med J, 1989 Aug;30(4):363-7.
    PMID: 2814539
    Rearrangements in the DNA of chronic myelogenous leukemia patients of Chinese, Malay and Indian origin were detected in the breakpoint cluster region of chromosome 22 using molecular techniques. The DNA of fifty patients was examined using a 1.2 kb DNA probe. Rearrangements were detected in 46/50 patients. Karyotypic data were available in nine patients, all of whom were Philadelphia chromosome positive and exhibited DNA rearrangement. Detection of the Philadelphia translocation by molecular methods, at this institution, where cytogenetics is not routinely performed, confirms its diagnostic value. The rearrangement data obtained in this study is consistent with molecular features of chronic myelogenous leukemia patients of Western countries.
    Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/ethnology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics*
  19. Molecular identification of Candida orthopsilosis isolated from blood culture
    Yong PV, Chong PP, Lau LY, Yeoh RS, Jamal F
    Mycopathologia, 2008 Feb;165(2):81-7.
    PMID: 18266075 DOI: 10.1007/s11046-007-9086-8
    The incidence of candidemia and invasive candidiasis have increased markedly due to the increasing number of immunocompromised patients. There are five major medically important species of Candida with their frequency of isolation in the diminishing order namely Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei. In addition, there are numerous other species of Candida which differ in their genetic makeup, virulence properties, drug susceptibilities and sugar assimilation capabilities. In this report, an unusual Candida species was isolated from the blood of two leukaemic patients. Conventional culture and biochemical tests identified the Candida species as C. parapsilosis. Using fungal-specific oligonucleotide primers ITS1 and ITS4, we managed to amplify the ribosomal RNA gene and its internal transcribed spacer region from the genomic DNA of these isolates. The PCR products were then purified and subjected to automated DNA sequencing using BLAST and CLUSTAL sequence analysis identified these isolates to be Candida orthopsilosis. Candida orthopsilosis is a new species recently identified in 2005, being morphologically indistinguishable from C. parapsilosis and was previously classified as a subspecies of C. parapsilosis. This report highlights the importance of complementing traditional culture and biochemical-based identification methods with DNA-based molecular assays such as PCR as the latter is more superior in terms of its discriminatory power and speed.
    Matched MeSH terms: Leukemia/microbiology
  20. Molecular docking studies of bioactive compounds from Annona muricata Linn as potential inhibitors for Bcl-2, Bcl-w and Mcl-1 antiapoptotic proteins
    Mohamad Rosdi MN, Mohd Arif S, Abu Bakar MH, Razali SA, Mohamed Zulkifli R, Ya'akob H
    Apoptosis, 2018 01;23(1):27-40.
    PMID: 29204721 DOI: 10.1007/s10495-017-1434-7
    Annona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies. A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless, the binding mode and the molecular interactions of the plant's bioactive constituents have not yet been unveiled for most of these mechanisms. In the current study, we aim to elucidate the binding interaction of ten bioactive phytochemicals of A. muricata L. to three Bcl-2 family of antiapoptotic proteins viz. Bcl-2, Bcl-w and Mcl-1 using an in silico molecular docking analysis software, Autodock 4.2. The stability of the complex with highest affinity was evaluated using MD simulation. We compared the docking analysis of these substances with pre-clinical Bcl-2 inhibitor namely obatoclax. The study identified the potential chemopreventive agent among the bioactive compounds. We also characterized the important interacting residues of protein targets which involve in the binding interaction. Results displayed that anonaine, a benzylisoquinoline alkaloid, showed a high affinity towards the Bcl-2, thus indicating that this compound is a potent inhibitor of the Bcl-2 antiapoptotic family of proteins.
    Matched MeSH terms: Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors*; Myeloid Cell Leukemia Sequence 1 Protein/genetics; Myeloid Cell Leukemia Sequence 1 Protein/metabolism; Myeloid Cell Leukemia Sequence 1 Protein/chemistry
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