Ironi Dalam Bahasa Kiasan Punjabi : Analisis Semantik Inkuisitif

Bahasa merupakan satu medium penyampaian pelbagai hasrat yang berkesan. Kajian ini mengkaji bahasa kiasan Punjabi yang digunakan oleh masyarakat Sikh di Malaysia. Objektif kajian adalah untuk mengenal pasti unsur haiwan dalam bahasa kiasan Punjabi. Kajian ini berbentuk kualitatif. Lima bahasa kiasan yang berunsurkan haiwan yang dikutip melalui kaedah temu bual dianalisis berdasarkan pendekatan semantik inkuisitif Nor Hashimah Jalaluddin (2014). Hasil kajian mendapati bahawa ada beberapa nasihat melalui bahasa kiasan yang memasukkan unsur haiwan dalam ujarannya. Didapati makna pada peringkat permukaan semantik, cuma memaparkan makna selapis sahaja. Dengan pendekatan semantik inkuisitif, dapatan kajian menunjukkan penyebutan unsur haiwan dalam ujaran bahasa kiasan masyarakat Punjabi berbaur ironi dan mempunyai falsafah kehidupan masyarakat ini. Setiap bahasa kiasan yang dianalisis memaparkan makna berlapis yang perlu dikupas dengan mengaitkan makna selapis berkenaan dengan kehidupan masyarakat Punjabi secara keseluruhan yang merangkumi aspek norma dan pemikiran mereka serta tindak tanduk kehidupan yang mereka harungi seharian. Kajian juga mendapati bahawa ujaran kiasan ini dicipta berdasarkan pengamatan terhadap persekitaran dan alam pemikiran mereka yang berbentuk abstrak dan memerlukan pengamatan teliti. Akhirnya, didapati bahawa pendekatan semantik inkuisitif yang menggabungjalinkan data, teori, kognitif, falsafah dan akal budi sesebuah masyarakat dapat memaparkan makna sebenar yang hendak disampaikan menerusi bahasa kiasan ini. Dengan kaedah semantik skrip, makna selapis mudah diketahui. Kemudian dengan semantik resonans, pemetaan makna selapis ini dikaitkan dengan kognitif penutur dan akhirnya dengan analisis semantik inkuisitif, makna yang lebih deskriptif dapat dijelmakan. Kaitan makna dapat dikonstruk satu per satu dengan tiga peringkat analisis dalam semantik inkuisitif. Makna yang diperoleh lebih tinggi kesahannya

Deciphering the Multifaceted Relationship between Oncolytic Viruses and Natural Killer Cells

Despite active research in virotherapy, this apparently safe modality has not achieved widespread success. The immune response to viral infection appears to be an essential factor that determines the efficacy of oncolytic viral therapy. The challenge is determining whether the viral-elicited immune response is a hindrance or a tool for viral treatment. NK cells are a key component of innate immunity that mediates antiviral immunity while also coordinating tumor clearance. Various reports have suggested that the NK response to oncolytic viral therapy is a critical factor in premature viral clearance while also mediating downstream antitumor immunity. As a result, particular attention should be given to the NK cell response to various oncolytic viral vectors and how their antiviral properties can be suppressed while maintaining tumor clearance. In this review we discuss the current literature on the NK response to oncolytic viral infection and how future studies clarify this intricate response

Gene expression profiling of the anti-glioma effect of Cilengitide

Cilengitide (EMD121974), an inhibitor of the adhesive function of integrins, demonstrated preclinical efficacy against malignant glioma. It is speculated that cilengitide can inhibit tumor growth, invasion, and angiogenesis. However, the effects of cilengitide on these processes have not been sufficiently examined. In this study, we investigated the anti-glioma effect of cilengitide using DNA microarray analysis. U87ΔEGFR cells (human malignant glioma cell line) were used for this experiment. The cells were harvested after 16 h of cilengitide treatment, and mRNA was extracted. Gene expression and pathway analyses were performed using a DNA microarray (CodeLink™Human Whole Genome Bioarray). The expression of 265 genes was changed with cilengitide treatment. The expression of 214 genes was up-regulated by more than 4-fold and the expression of 51 genes was down-regulated by more than 4-fold compared to the controls. In pathway analysis, "apoptotic cleavage of cellular proteins" and "TNF receptor signaling pathway" were over-represented. Apoptotic-associated genes such as caspase 8 were up-regulated. Gene expression profiling revealed more detailed mechanism of the anti-glioma effect of cilengitide. Genes associated with apoptosis were over-represented following cilengitide treatment

RNA Nanoparticle as a Vector for Targeted siRNA Delivery into Glioblastoma Mouse Model

Systemic siRNA administration to target and treat glioblastoma, one of the most deadly cancers, requires robust and efficient delivery platform without immunogenicity. Here we report newly emerged multivalent naked RNA nanoparticle (RNP) based on pRNA 3-way-junction (3WJ) from bacteriophage phi29 to target glioblastoma cells with folate (FA) ligand and deliver siRNA for gene silencing. Systemically injected FA-pRNA-3WJ RNPs successfully targeted and delivered siRNA into brain tumor cells in mice, and efficiently reduced luciferase reporter gene expression (4-fold lower than control). The FA-pRNA-3WJ RNP also can target human patient-derived glioblastoma stem cells, thought to be responsible for tumor initiation and deadly recurrence, without accumulation in adjacent normal brain cells, nor other major internal organs. This study provides possible application of pRNA-3WJ RNP for specific delivery of therapeutics such as siRNA, microRNA and/or chemotherapeutic drugs into glioblastoma cells without inflicting collateral damage to healthy tissues

Oncolytic HSV Vectors and Anti-Tumor Immunity

The therapeutic promise of oncolytic viruses (OVs) rests on their ability to both selectively kill tumor cells and induce anti-tumor immunity. The potential of tumors to be recognized and eliminated by an effective anti-tumor immune response has been spurred on by the discovery that immune checkpoint inhibition can overcome tumor-specific cytotoxic T cell (CTL) exhaustion and provide durable responses in multiple tumor indications. OV-mediated tumor destruction is now recognized as a powerful means to assist in the development of anti-tumor immunity for two important reasons: (i) OVs, through the elicitation of an anti-viral response and the production of type I interferon, are potent stimulators of inflammation and can be armed with transgenes to further enhance anti-tumor immune responses; and (ii) lytic activity can promote the release of tumor-associated antigens (TAAs) and tumor neoantigens that function as in situ tumor-specific vaccines to elicit adaptive immunity. Oncolytic herpes simplex viruses (oHSVs) are among the most widely studied OVs for the treatment of solid malignancies, and Amgen's oHSV Imlygic® for the treatment of melanoma is the only OV approved in major markets. Here we describe important biological features of HSV that make it an attractive OV, clinical experience with HSV-based vectors, and strategies to increase applicability to cancer treatment

White paper on microbial anti-cancer therapy and prevention

In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting (‘Microbial Based Cancer Therapy’) at the US National Cancer Institute in the summer of 2017. Here, we define ‘Microbial Therapy’ to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care

HOX and PBX gene dysregulation as a therapeutic target in glioblastoma multiforme

Background: Glioblastoma multiforme (GBM) is the most common high-grade malignant brain tumour in adults and arises from the glial cells in the brain. The prognosis of treated GBM remains very poor with 5-year survival rates of 5%, a figure which has not improved over the last few decades. Currently, there is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. HOX gene dysregulation is now a widely recognised feature of many malignancies. Methods: In this study we have focused on HOX gene dysregulation in GBM as a potential therapeutic target in a disease with high unmet need. Results: We show significant dysregulation of these developmentally crucial genes and specifically that HOX genes A9, A10, C4 and D9 are strong candidates for biomarkers and treatment targets for GBM and GBM cancer stem cells. We evaluated a next generation therapeutic peptide, HTL-001, capable of targeting HOX gene over-expression in GBM by disrupting the interaction between HOX proteins and their co-factor, PBX. HTL-001 induced both caspase-dependent and -independent apoptosis in GBM cell lines. Conclusion: In vivo biodistribution studies confirmed that the peptide was able to cross the blood brain barrier. Systemic delivery of HTL-001 resulted in improved control of subcutaneous murine and human xenograft tumours and improved survival in a murine orthotopic model

UNSUR IRONI DALAM BAHASA KIASAN PUNJABI: ANALISIS SEMANTIK INKUISITIF

Bahasa merupakan satu medium penyampaian yang berkesan dan sering digunakan oleh semua masyarakat. Dalam kajian ini bahasa yang difokuskan oleh pengkaji ialah bahasa Punjabi yang digunakan oleh masyarakat Sikh di Malaysia. Kajian ini bertujuan mengenal pasti unsur haiwan dalam bahasa kiasan Punjabi melalui kacamata semantik inkuisitif dalam memperlihatkan akal budi orang Punjabi. Tumpuan analisis ini ialah pada kiasan yang menunjukkan unsur haiwan dengan memperlihatkan makna ironi di sebalik kiasan tersebut. Kajian berbentuk kualitatif iaitu kajian bersifat deskriptif ini mengaplikasikan teori semantik dengan kaedah inkuisitif yang merupakan gabungan di antara pemikiran kognitif dengan maklumat baru, akal budaya masyarakat Punjabi. Data kiasan Punjabi dikumpul melalui kaedah temu bual yang dijalankan oleh pengkaji kerana kiasan Punjabi belum lagi didokumentasikan. Hasil kajian mendapati budaya dan akal Punjabi dapat dikaitkan dengan kiasan tersebut. Ketersiratan makna kiasan yang mempunyai unsur haiwan jelas memperlihatkan falsafah masyarakat Punjabi. Kajian ini juga dapat membuktikan hubungan bahasa, masyarakat dan pemikiran dalam kiasan Punjabi berdasarkan pendekatan yang digunakan. Akal budi Punjabi dapat dilihat dengan jelas, pencungkilan makna dilakukan dengan kaedah yang sistematik dan saintifik