Displaying all 3 publications

Abstract:
Sort:
  1. Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models
    Yee PS, Zainal NS, Gan CP, Lee BKB, Mun KS, Abraham MT, et al.
    Target Oncol, 2019 04;14(2):223-235.
    PMID: 30806895 DOI: 10.1007/s11523-019-00626-8
    BACKGROUND: Given that aberrant activation of epidermal growth factor receptor family receptors (ErbB) is a common event in oral squamous cell carcinoma, and that high expression of these receptor proteins is often associated with poor prognosis, this rationalizes the approach of targeting ErbB signaling pathways to improve the survival of patients with oral squamous cell carcinoma. However, monotherapy with the ErbB blocker afatinib has shown limited survival benefits.

    OBJECTIVES: This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma.

    METHODS: We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models.

    RESULTS: In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models.

    CONCLUSIONS: Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.

  2. Fulltext The Glaciozyma antarctica genome reveals an array of systems that provide sustained responses towards temperature variations in a persistently cold habitat
    Firdaus-Raih M, Hashim NHF, Bharudin I, Abu Bakar MF, Huang KK, Alias H, et al.
    PLoS One, 2018;13(1):e0189947.
    PMID: 29385175 DOI: 10.1371/journal.pone.0189947
    Extremely low temperatures present various challenges to life that include ice formation and effects on metabolic capacity. Psyhcrophilic microorganisms typically have an array of mechanisms to enable survival in cold temperatures. In this study, we sequenced and analysed the genome of a psychrophilic yeast isolated in the Antarctic region, Glaciozyma antarctica. The genome annotation identified 7857 protein coding sequences. From the genome sequence analysis we were able to identify genes that encoded for proteins known to be associated with cold survival, in addition to annotating genes that are unique to G. antarctica. For genes that are known to be involved in cold adaptation such as anti-freeze proteins (AFPs), our gene expression analysis revealed that they were differentially transcribed over time and in response to different temperatures. This indicated the presence of an array of adaptation systems that can respond to a changing but persistent cold environment. We were also able to validate the activity of all the AFPs annotated where the recombinant AFPs demonstrated anti-freeze capacity. This work is an important foundation for further collective exploration into psychrophilic microbiology where among other potential, the genes unique to this species may represent a pool of novel mechanisms for cold survival.
  3. Fulltext Southeast Asia Strategic Multilateral Dialogue on Biosecurity
    Cicero A, Meyer D, Shearer MP, AbuBakar S, Bernard K, Carus WS, et al.
    Emerg Infect Dis, 2019 May;25(5).
    PMID: 31002062 DOI: 10.3201/eid2505.181659
    A strategic multilateral dialogue related to biosecurity risks in Southeast Asia, established in 2014, now includes participants from Singapore, Malaysia, Indonesia, Thailand, Philippines, and the United States. This dialogue is conducted at the nonministerial level, enabling participants to engage without the constraints of operating in their official capacities. Participants reflect on mechanisms to detect, mitigate, and respond to biosecurity risks and highlight biosecurity issues for national leadership. Participants have also identified factors to improve regional and global biosecurity, including improved engagement and collaboration across relevant ministries and agencies, sustainable funding for biosecurity programs, enhanced information sharing for communicable diseases, and increased engagement in international biosecurity forums.
Related Terms
    Try searching for something
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links