44 research outputs found

    An analysis on nature of limited liability partnerships in Malaysia

    No full text
    Limited Liability Partnership (LLP) is an additional form of business entity available for an entrepreneur who decides to carry on a business in Malaysia. The Companies Commission of Malaysia introduces this business entity under the Limited Liability Partnership Act (LLPA) in 2012. This paper looks into the history of the legislation of LLPA in Malaysia while using the doctrinal approach in analyzing the nature of LLP. The conceptual understanding of LLP and a valid definition of LLP is presented by referring to provisions of LLPA. Evaluation of the best features of LLP is provided, and the important provisions of LLPA are included and discussed in detail. This paper also reviews the relevant authorities and their responsibilities in monitoring LLP in Malaysia. By doing so, a clear exposure in the application of LLP can be provided. Finally, a recommendation for future research and a conclusion are provided at the end of the paper

    DNA Vaccines Targeting Novel Cancer-Associated Antigens Frequently Expressed in Head and Neck Cancer Enhance the Efficacy of Checkpoint Inhibitor

    No full text
    HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs). Converting TILlow tumors to TILhigh tumors is thus critical to improve clinical outcome. Here we describe a novel DNA vaccines to facilitate the T-cell infiltration and control tumor growth. We evaluated the expression of target antigens and their respective immunogenicity in HNSCC patients. The efficacy of DNA vaccines targeting two novel antigens were evaluated with or without CPI using a syngeneic model. Most HNSCC patients (43/44) co-expressed MAGED4B and FJX1 and their respective tetramer-specific T cells were in the range of 0.06-0.12%. In a preclinical model, antigen-specific T cells were induced by DNA vaccines and increased T cell infiltration into the tumor, but not MDSC or regulatory T cells. The vaccines inhibited tumor growth and improved the outcome alone and upon combination with anti-PD1 and resulted in tumor clearance in approximately 75% of mice. Pre-existence of MAGED4B and FJX1-reactive T cells in HNSCC patients suggests that these widely expressed antigens are highly immunogenic and could be further expanded by vaccination. The DNA vaccines targeting these antigens induced robust T cell responses and with the anti-PD1 antibody conferring excellent tumor control. This opens up an opportunity for combination immunotherapy that might benefit a wider population of HNSCC patients in an antigen-specific manner

    Analysis of complications following multidisciplinary functional intervention in paediatric craniomaxillofacial deformities

    No full text
    Paediatric craniomaxillofacial (CMF) surgery requires a multidisciplinary team approach to ensure the optimal and holistic management of children with craniofacial deformities. The aim of this retrospective study was to analyse the complications following functional interventions among 34 CMF deformity patients in a single multidisciplinary craniofacial centre. Electronic data including patient demographic characteristics and clinical entry were analysed. Inclusion criteria were all paediatric patients with CMF deformities who underwent various functional interventions. A total of 64 interventions (48 intermediate and 16 definitive) were conducted. Based on the Sharma classification of complications, 20.3% were type I, 4.7% were type II, 1.6% were type III, and 4.7% were type IV . Most complications were type I, which included local infection (3.1%) and premature opening of tarsorrhaphy (3.1%). More serious complications (types III and IV) included temporary visual loss (1.6%) and intraoperative haemorrhage (1.6%). Although a low complication rate was observed in intermediate interventions, a higher complication rate was observed in more complex definitive interventions such as monobloc distraction osteogenesis. Although most complications were manageable, effective prevention remains mandatory, as serious complications may lead to permanent damage and mortality. This analysis highlights the importance of a multidisciplinary team approach to optimize the outcomes in CMF patient management

    Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models

    No full text
    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. © 2019, Springer Nature Switzerland AG

    Determining the Accuracy of the Mandibular Canal Region in 3D Biomodels Fabricated from CBCT Scanned Data: A Cadaveric Study

    No full text
    Objective: To validate the accuracy of the mandibular canal region in 3D biomodel produced by using data obtained from Cone-Beam Computed Tomography (CBCT) of cadaveric mandibles. Methods: Six hemi-mandible samples were scanned using the i-CAT CBCT system. The scanned data was transferred to the OsiriX software for measurement protocol and subsequently into Mimics software to fabricate customized cutting jigs and 3D biomodels based on rapid prototyping technology. The hemi-mandibles were segmented into 5 dentoalveolar blocks using the customized jigs. Digital calliper was used to measure six distances surrounding the mandibular canal on each section. The same distances were measured on the corresponding cross-sectional OsiriX images and the 3D biomodels of each dentoalveolar block. Results: Statistically no significant difference was found when measurements from OsiriX images and 3D biomodels were compared to the “gold standard” -direct digital calliper measurement of the cadaveric dentoalveolar blocks. Moreover, the mean value difference of the various measurements between the different study components was also minimal. Conclusion: Various distances surrounding the mandibular canal from 3D biomodels produced from the CBCT scanned data was similar to that of direct digital calliper measurements of the cadaveric specimens. © 2019 Bentham Science Publishers

    Hypernasality in singing among children with cleft palate: a preliminary study

    No full text
    The aim of this study was to document differences in hypernasality during speaking and singing among children with cleft palate and to compare nasality score ratings of trained and untrained listeners. Twenty subjects with cleft palate aged between 7 and 12 years participated in this study. Audio recordings were made of the children reading a passage and singing a common local song, both in the Malay language. The degree of hypernasality was judged through perceptual assessment. Three trained listeners (a speech therapist, a classical singer, and a linguistic expert – all academicians) and two untrained listeners (a cleft volunteer worker and a national high school teacher) assessed the recordings using a visual analogue scale (VAS). Inter-rater and intra-rater reliability for hypernasality in both speaking and singing were verified using the intra-class correlation coefficient (ICC). A significant reduction in hypernasality was observed during singing as compared to speaking, indicating that hypernasality reduces when a child with cleft palate sings. The act of singing significantly reduces hypernasality. The outcome of this study suggests that children with cleft palate would benefit from singing exercises to ultimately reduce hypernasality. However, future research is needed to objectively measure nasality in singing compared to speaking. © 2019 International Association of Oral and Maxillofacial Surgeon

    In vitro evaluation of dual-antigenic PV1 peptide vaccine in head and neck cancer patients

    No full text
    Peptide vaccines derived from tumour-associated antigens have been used as an immunotherapeutic approach to induce specific cytotoxic immune response against tumour. We previously identified that MAGED4B and FJX1 proteins are overexpressed in HNSCC patients; and further demonstrated that two HLA-A2-restricted 9–11 amino acid peptides derived from these proteins were able to induce anti-tumour immune responses in vitro independently using PBMCs isolated from these patients. In this study, we evaluated the immunogenicity and efficacy of a dual-antigenic peptide vaccine (PV1), comprised of MAGED4B and FJX1 peptides in HNSCC patients. We first demonstrated that 94.8% of HNSCC patients expressed MAGED4B and/or FJX1 by immunohistochemistry, suggesting that PV1 could benefit the majority of HNSCC patients. The presence of pre-existing MAGED4B and FJX1-specific T-cells was detected using a HLA-A2 dimer assay and efficacy of PV1 to induce T-cell to secrete cytotoxic cytokine was evaluated using ELISPOT assay. Pre-existing PV1-specific T-cells were detected in all patients. Notably, we demonstrated that patients’ T-cells were able to secrete cytotoxic cytokines upon exposure to target cells expressing the respective antigen post PV1 stimulation. Furthermore, patients with high expression of MAGED4B and FJX1 in their tumours were more responsive to PV1 stimulation, demonstrating the specificity of the PV1 peptide vaccine. Additionally, we also demonstrated the expression of MAGED4B and FJX1 in breast, lung, colon, prostate and rectal cancer suggesting the potential use of PV1 in these cancers. In summary, PV1 could be a good vaccine candidate for the treatment of HNSCC patients and other cancers expressing these antigens

    Effects of palbociclib in oral squamous cell carcinoma and the role of PIK3CA in conferring resistance

    Get PDF
    Objective: Lack of effective therapies remains a problem in the treatment of oral squamous cell carcinoma (OSCC), especially in patients with advanced tumors. OSCC development is driven by multiple aberrancies within the cell cycle pathway, including amplification of cyclin D1 and loss of p16. Hence, cell cycle inhibitors of the CDK4/6-cyclin D axis are appealing targets for OSCC treatment. Here, we determined the potency of palbociclib and identified genetic features that are associated with the response of palbociclib in OSCC. Methods: The effect of palbociclib was evaluated in a panel of well-characterized OSCC cell lines by cell proliferation assays and further confirmed by in vivo evaluation in xenograft models. PIK3CA-mutant isogenic cell lines were used to investigate the effect of PIK3CA mutation towards palbociclib response. Results: We demonstrated that 80% of OSCC cell lines are sensitive to palbociclib at sub-micromolar concentrations. Consistently, palbociclib was effective in controlling tumor growth in mice. We identified that palbociclib-resistant cells harbored mutations in PIK3CA. Using isogenic cell lines, we showed that PIK3CA mutant cells are less responsive to palbociclib as compared to wild-type cells with concurrent upregulation of CDK2 and cyclin El protein levels. We further demonstrated that the combination of a PI3K/mTOR inhibitor (PF-04691502) and palbociclib completely controlled tumor growth in mice. Conclusions: This study demonstrated the potency of palbociclib in OSCC models and provides a rationale for the inclusion of PIK3CA testing in the clinical evaluation of CDK4/6 inhibitors and suggests combination approaches for further clinical studies

    An in vitro three-dimensional co-culture system for ameloblastoma modelling

    Get PDF
    Ameloblastoma, the most clinically significant odontogenic epithelial tumor, is a locally-invasive and destructive lesion in the jawbones. However, the nature of this infiltrativeness and destructive behavior remains ill-understood. To address this, we established an in vitro three-dimensional (3D) co-culture system to simulate an amelobastoma disease model aimed at investigating the interactions between tumor cells and osteoblasts. Osteoblastic cell lines (KUSA/A1 and MC3T3-E1) and one stromal cell line (ST2) were separately co-seeded with ameloblastoma-derived cell line (AM-1) in a collagen scaffold (representing the extracellular bone matrix) and incubated with mineralization medium. Immunohistochemistry, double immunofluorescence and mineralization assay were performed. Only AM-1/KUSA-A1 co-culture showed a significant increase in AM-1 cell count, suggesting that heterotypic cell-cell interaction promotes tumoral cell growth, while formation of visible AM-1 epithelial nest-like structures resembling ameloblastoma cells in their native state, suggest morphodifferentiation. A RANK-high, RANKL-low and osteoprotegerin-low immunoprofile in co-culture AM-1 cells implies deregulated osteoclastogenesis. Mineralization assays showed diminished calcification in AM-1/KUSA-A1 co-culture extracellular matrix suggesting an altered local bone metabolism. In contrast, KUSA/A1 monocultures showed abundant extracellular matrix calcification. Taken together, these results suggest that a 3D co-culture system as an amelobastoma disease model provides insights that bidirectional ameloblastoma-osteoblastic interactions might play a role in modulating tumor growth and osteoclastogenesis

    Metal organic chemical vapor deposition of m-plane GaN epi-layer using a three-step approach towards enhanced surface morphology

    No full text
    Specular m-plane (101¯0) gallium nitride (m-GaN) epi-layer are grown on m-plane (101¯0) sapphire substrates by metal organic chemical vapor deposition using a three-step approach. A two-step approach was used to grow m-GaN buffer layer (BL), while a three-step approach was applied to improve the surface morphology of the top m-GaN epi-layer at high temperature. The three-step approach started with growing m-aluminum nitride nucleation layer with an optimized ammonia flux during the growth of aluminum nitride. Then the temperature was ramped up during the recrystallization step before the m-GaN BL deposition at low-temperature and the growth of m-GaN layer at high-temperature for the final step. Unexpectedly, when ammonia flow was intentionally halted during the recrystallization step, the surface morphology of the BL drastically changed from three- to two- dimensional with an abrupt cross-sectional structure. This in turn facilitated the complete coalescence of the m-GaN layer as revealed by field emission scanning electron microscopy. The three-step technique was found to affect the quality of m-GaN epi-layer as the samples exhibit improved crystallinity with X-ray diffraction rocking curves widths of 4680 and 1980 arcsec along the azimuth, perpendicular and parallel to [101¯0] directions, respectively
    corecore