Vaccination Knowledge, Attitudes, Perceptions, and Educational Needs of Pharmacists in Singapore: A Cross-Sectional Study.

Background: Singapore's adult vaccination coverage is suboptimal, and this can be attributed to a lack of vaccination recommendations and misconceptions. Studies have explored pharmacists' vaccination knowledge, attitudes, and practice behaviour overseas but limited information about pharmacists in Singapore is available. This study aims to investigate pharmacists' vaccination knowledge, attitudes towards providing vaccination services, and their educational needs.

Celastrol in cancer therapy: Recent developments, challenges and prospects.

Cancer is one of the world's biggest healthcare burdens and despite the current advancements made in treatment plans, the outcomes for oncology patients have yet to reach their full potential. Hence, there is a pressing need to develop novel anti-cancer drugs. A popular drug class for research are natural compounds, due to their multi-targeting potential and enhanced safety profile.

Resveratrol for cancer therapy: Challenges and future perspectives.

Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been expected to ameliorate cancer and foster breakthroughs in cancer therapy. Despite thousands of preclinical studies on the anticancer activity of resveratrol, little progress has been made in translational research and clinical trials. Most studies have focused on its anticancer effects, cellular mechanisms, and signal transduction pathways in vitro and in vivo.

User Preferences and Persona Design for an mHealth Intervention to Support Adherence to Cardiovascular Disease Medication in Singapore: A Multi-Method Study.

Background: The use of mobile health (mHealth) has gained popularity globally, including for its use in a variety of health interventions, particularly through short message service (SMS) text messaging. However, there are challenges to the use of mHealth, particularly among older users who have a large heterogeneity in usability and accessibility barriers when using technology.

Objective: In order to better understand and conceptualize the diversity of users and give insight into their particular needs, we turned to persona creation.

Perspectives on Acceptance and Use of a Mobile Health Intervention for the Prevention of Atherosclerotic Cardiovascular Disease in Singapore: Mixed-Methods Study.

Background: Cardiovascular disease, including atherosclerotic cardiovascular disease (ASCVD), is a growing public health threat globally and many individuals remain undiagnosed, untreated, and uncontrolled. Simultaneously, mobile health (mHealth) interventions using short messaging service (SMS) have gained popularity globally. There is an opportunity for innovative approaches such as mHealth to encourage and enable adherence to medications for ASCVD and its risk factors.

Access and adherence to medications for the primary and secondary prevention of atherosclerotic cardiovascular disease in Singapore: a qualitative study.

Background: Atherosclerotic cardiovascular disease (ASCVD) is a growing public health threat globally, and many individuals remain undiagnosed, untreated, and their condition remains uncontrolled. The key to effective ASCVD management is adherence to pharmacotherapy, and non-adherence has been associated with an increased risk of cardiovascular events and complications such as stroke, further impacting a patient's ability to be adherent. Our qualitative study aimed to explore factors influencing medication adherence in the primary and secondary prevention of ASCVD in Singapore.

A Review on Liquid Chromatography-Tandem Mass Spectrometry Methods for Rapid Quantification of Oncology Drugs.

In the last decade, the tremendous improvement in the sensitivity and also affordability of liquid chromatography-tandem mass spectrometry (LC-MS/MS) has revolutionized its application in pharmaceutical analysis, resulting in widespread employment of LC-MS/MS in determining pharmaceutical compounds, including anticancer drugs in pharmaceutical research and also industries. Currently, LC-MS/MS has been widely used to quantify small molecule oncology drugs in various biological matrices to support preclinical and clinical pharmacokinetic studies in R&D of oncology drugs. This mini-review article will describe the state-of-the-art LC-MS/MS and its application in rapid quantification of small molecule anticancer drugs.

Quantification of desoxyrhapontigenin (4-methoxyresveratrol) in rat plasma by LC-MS/MS: Application to pre-clinical pharmacokinetic study.

Desoxyrhapontigenin (DRG, 4-methoxyresveratrol or trans-3,5-dihydroxy-4'-methoxystilbene) is a naturally occurring resveratrol (RES) derivative with a variety of biological activities. To facilitate its further medicinal exploration, a reliable LC-MS/MS method was developed and validated for the quantification of DRG in rat plasma using heavy isotope labelled RES as an internal standard. The ESI was operated in its negative ion mode while DRG and RES were determined by multiple reaction monitoring (MRM) using precursor-to-product ion transitions of m/z 241.

Pan-HDAC inhibition by panobinostat mediates chemosensitization to carboplatin in non-small cell lung cancer via attenuation of EGFR signaling.

Accumulating evidence has implicated the aberrant regulation of histone deacetylases (HDACs) as a nexus for multiple cancer hallmarks and in mediating tumor adaptation and resistance to genotoxic chemotherapy, suggesting a rational pairing of HDAC inhibitors with DNA damaging chemotherapeutic agents in the treatment of human malignancies. Here we report that panobinostat (LBH589), a potent pan-HDAC inhibitor, effectively curbed the proliferation of non-small cell lung cancer (NSCLC) cell lines A549, Calu-1, H226, H460, H838 and SKMES-1 at IC concentrations between 4 and 31 nmol/L via pleiotropic mechanisms, including crosstalk with EGFR signal transduction cascades. Combination therapy with carboplatin elicited rapid tumor cell kill and effectively restrained anchorage-independent clonogenic survival to a considerably greater extent over either monotherapy.

Synergistic disruption of ERα/HER2 crosstalk by endoxifen and lapatinib in breast cancer cells.

Background: Despite decades of clinical success, tamoxifen therapy is complicated by inter-individual variability due to CYP450 polymorphism and resistance attributed to ERα/HER2 crosstalk. Direct administration of endoxifen shows promise in circumventing obligatory CYP450 bioactivation while maintaining efficacy. Separately, disruption of the crosstalk using probe antagonists against ERα (tamoxifen) and HER2 (e.

Judicious Toggling of mTOR Activity to Combat Insulin Resistance and Cancer: Current Evidence and Perspectives.

The mechanistic target of rapamycin (mTOR), via its two distinct multiprotein complexes, mTORC1, and mTORC2, plays a central role in the regulation of cellular growth, metabolism, and migration. A dysregulation of the mTOR pathway has in turn been implicated in several pathological conditions including insulin resistance and cancer. Overactivation of mTORC1 and disruption of mTORC2 function have been reported to induce insulin resistance.

A novel combinatorial strategy using Seliciclib(®) and Belinostat(®) for eradication of non-small cell lung cancer via apoptosis induction and BID activation.

With conventional anticancer agents for non-small cell lung cancer (NSCLC) reaching therapeutic ceiling, the novel combination using histone deacetylase inhibitor, PXD101 (Belinostat(®)), and CDK inhibitor, CYC202 (Seliciclib(®)), was investigated as an alternative anticancer strategy. At clinically achievable concentration of CYC202 (15 µM), combination therapy resulted in significant reduction in cell proliferation (IC50 = 3.67 ± 0.

Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development.

Nimbolide is one of the main components in the leaf extract of Azadirachta indica (A. indica). Accumulating evidence from various in vitro and in vivo studies indicates that nimbolide possesses potent anticancer activity against several types of cancer and also shows potential chemopreventive activity in animal models.

Quantification of the resveratrol analogs trans-2,3-dimethoxy-stilbene and trans-3,4-dimethoxystilbene in rat plasma: application to pre-clinical pharmacokinetic studies.

trans-2,3-Dimethoxystilbene (2,3-DMS) and trans-3,4-dimethoxystilbene (3,4-DMS) are two synthetic resveratrol (trans-3,5,4'-trihydroxystilbene) analogs. In this study, a simple HPLC method was developed and validated to determine 2,3-DMS and 3,4-DMS in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column through a 12.

A miniaturized flow-through cell to evaluate skin permeation of endoxifen.

Endoxifen, an anti-estrogenic agent, has been recently implicated in the use of breast cancer. Its physicochemical properties make it a good candidate for transdermal delivery. However, as an investigative drug, its limited supply makes it difficult to conduct extensive pre-formulation studies.

Quantification of trans-2,6-difluoro-4'-N,N-dimethylaminostilbene in rat plasma: application to a pharmacokinetic study.

trans-2,6-Difluoro-4'-N,N-dimethylaminostilbene (DFS), a synthetic stilbene, displayed potent pre-clinical anti-cancer activities exceeding that observed for naturally occurring resveratrol. In this study, a simple and sensitive HPLC method was developed and validated to quantify DFS in rat plasma. The lower limit of quantification (LLOQ) was 5 ng/ml.

Clinical therapeutics for phenylketonuria.

Phenylketonuria was amongst the first of the metabolic disorders to be characterised, exhibiting an inborn error in phenylalanine metabolism due to a functional deficit of the enzyme phenylalanine hydroxylase. It affects around 700,000 people around the globe. Mutations in the gene coding for hepatic phenylalanine hydroxylase cause this deficiency resulting in elevated plasma phenylalanine concentrations, leading to cognitive impairment, neuromotor disorders and related behavioural symptoms.

Association of eleven common, low-penetrance colorectal cancer susceptibility genetic variants at six risk loci with clinical outcome.

Background: Low-penetrance genetic variants have been increasingly recognized to influence the risk of tumor development. Risk variants for colorectal cancer (CRC) have been mapped to chromosome positions 8q23.3, 8q24, 9p24.

Synergistic effects of suberoylanilide hydroxamic acid combined with cisplatin causing cell cycle arrest independent apoptosis in platinum-resistant ovarian cancer cells.

Histone deacetylase inhibitors (HDACIs) belong to an emerging class of anticancer compounds. It is increasingly recognized that their unique and complementary mode of action make HDACIs valuable agents in augmenting the cytotoxicity of conventional chemotherapeutics. We examined the potential for combined use of an approved HDACI, suberoylanilide hydroxamic acid (SAHA), with cisplatin (Cddp) in platinum-resistant ovarian cancer cells, OVCAR-3 and SKOV-3.

Microarray analysis revealed dysregulation of multiple genes associated with chemoresistance to As(2)O(3) and increased tumor aggressiveness in a newly established arsenic-resistant ovarian cancer cell line, OVCAR-3/AsR.

The potential of arsenic trioxide (As(2)O(3)) for use as a novel therapy for ovarian cancer treatment has been increasingly recognized. In this study, we developed an arsenic-resistant OVCAR-3 subline (OVCAR-3/AsR) and aimed to identify the molecular mechanisms and signaling pathways contributing to the development of acquired arsenic chemoresistance in ovarian cancer. OVCAR-3/AsR cells were obtained following continual exposure of parental OVCAR-3 cells to low dose As(2)O(3) for 12months.

Differential augmentative effects of buthionine sulfoximine and ascorbic acid in As2O3-induced ovarian cancer cell death: oxidative stress-independent and -dependent cytotoxic potentiation.

The potential of arsenic trioxide (As2O3) as a novel therapy against ovarian cancer has been progressively recognized. Its prospective usefulness for treatment of this malignancy either alone or in combination with other chemotherapeutic agents has been increasingly explored. In this study, we attempted to enhance the cytotoxicity of As2O3 in ovarian cancer cells through manipulation of cellular glutathione (GSH) levels using either buthionine sulfoximine (BSO) or ascorbic acid (AA).

Current trends in modern pharmaceutical analysis for drug discovery.

Traditionally, pharmaceutical analysis referred to the chemical analysis of drug molecules. However, over the years, modern pharmaceutical analysis has evolved beyond this to encompass combination techniques, high-throughput technologies, chemometrics, microdosing studies, miniaturization and nanotechnology. These analytical advances are now being employed in all stages of drug discovery and the focus of this review will be on how these technologies are being employed within this process.