METHODS: A mixed survey questionnaire with open- and closed-ended questions relating to HTA governance, HTA infrastructure, supply and demand of HTA and global HTA networking opportunities in each country was administered electronically to representatives of HTA nodal agencies of all ASEAN members. In-person meetings or email correspondence were used to clarify or validate any unclear responses. Results were collated and presented quantitatively.
RESULTS: Responses from eight out of ten member countries were analysed. The results illustrate that countries in the ASEAN region are at different stages of HTA institutionalization. While Malaysia, Singapore and Thailand have well-established processes and methods for priority setting through HTA, other countries, such as Cambodia, Indonesia, Lao PDR, Myanmar, the Philippines and Vietnam, have begun to develop HTA systems in their countries by establishing nodal agencies or conducting ad-hoc activities.
DISCUSSION AND CONCLUSION: The study provides a general overview of the HTA landscape in ASEAN countries. Systematic efforts to mitigate the gaps between the demand and supply of HTA in each country are required while ensuring adequate participation from stakeholders so that decisions for resource allocation are made in a fair, legitimate and transparent manner and are relevant to each local context.
DESIGN: The role of matrix stiffness in several cancers including oral cancer was reviewed with a tailored search strategy using relevant keywords as per the Medline format. The role of molecular mediators, Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) was weighed in the context of OSF along two distinct pathways.
RESULTS: Increased matrix stiffness activates the transcriptional coactivators, YAP and TAZ shuttling between the nucleus and cytoplasm. YAP and TAZ, serve as mechanical transducers in promoting cell migration, invasion and epithelial-mesenchymal transition (EMT). The hypoxic microenvironment in the advanced stage of OSF promotes the migratory phenotype through mechanical memory.
CONCLUSIONS: Reprogramming of a stiff matrix has the potential to restore the Hippo-YAP/TAZ tumor suppressor pathway and reverse fibrosis-associated tumor development.
METHODS: A review of the literature was conducted with a tailored search strategy to unravel the novel pathways and mechanisms of nicotine-induced oral carcinogenesis.
RESULTS: Nicotine and NDNs act on nicotinic Acetylcholine Receptors (nAChRs) as agonists. Nicotine facilitates cravings through α4β2nAChR and α7nAChR, via enhanced brain dopamine release. Nicotine binding to nAChR promotes proliferation, migration, invasion, chemoresistance, radioresistance, and metastasis of oral cancer cells. Nicotine binding to α7nAChR on keratinocytes triggers Ras/Raf-1/MEK1/ERK cascade promoting anti-apoptosis and pro-proliferative effects. Furthermore, the nicotine-enhanced metastasis is subdued on nAChR blockade through reduced nuclear localization of p-EGFR.
CONCLUSION: Protracted exposure to nicotine/NDN augments cancer-stimulatory α7nAChR and desensitizes cancer inhibitory α4β2nAChR. Since nAChRs dictate both addictive and carcinogenic effects of nicotine, it seems counterintuitive to designate nicotine just as an addictive agent devoid of any carcinogenicity.