Thymomas and thymic carcinomas (TC) are malignant thymic epithelial tumors (TETs) with poor outcome, if non-resectable. Metabolic signatures of TETs have not yet been studied and may offer new therapeutic options. Metabolic profiles of snap-frozen thymomas (WHO types A, AB, B1, B2, B3, n = 12) and TCs (n = 3) were determined by high resolution magic angle spinning 1H nuclear magnetic resonance (HRMAS 1H-NMR) spectroscopy. Metabolite-based prediction of active KEGG metabolic pathways was achieved with MetPA. In relation to metabolite-based metabolic pathways, gene expression signatures of TETs (n = 115) were investigated in the public “The Cancer Genome Atlas” (TCGA) dataset using gene set enrichment analysis. Overall, thirty-seven metabolites were quantified in TETs, including acetylcholine that was not previously detected in other non-endocrine cancers. Metabolite-based cluster analysis distinguished clinically indolent (A, AB, B1) and aggressive TETs (B2, B3, TCs). Using MetPA, six KEGG metabolic pathways were predicted to be activated, including proline/arginine, glycolysis and glutathione pathways. The activated pathways as predicted by metabolite-profiling were generally enriched transcriptionally in the independent TCGA dataset. Shared high lactic acid and glutamine levels, together with associated gene expression signatures suggested a strong “Warburg effect”, glutaminolysis and redox homeostasis as potential vulnerabilities that need validation in a large, independent cohort of aggressive TETs. If confirmed, targeting metabolic pathways may eventually prove as adjunct therapeutic options in TETs, since the metabolic features identified here are known to confer resistance to cisplatin-based chemotherapy, kinase inhibitors and immune checkpoint blockers, i.e., currently used therapies for non-resectable TETs.
Cancer is a disorder characterized by an uncontrollable overgrowth and a fast-moving spread of cells from a localized tissue to multiple organs of the body, reaching a metastatic state. Throughout years, complexity of cancer progression and invasion, high prevalence and incidence, as well as the high rise in treatment failure cases leading to a poor patient prognosis accounted for continuous experimental investigations on animals and cellular models, mainly with 2D- and 3D-cell culture. Nowadays, these research models are considered a main asset to reflect the physiological events in many cancer types in terms of cellular characteristics and features, replication and metastatic mechanisms, metabolic pathways, biomarkers expression, and chemotherapeutic agent resistance. In practice, based on research perspective and hypothesis, scientists aim to choose the best model to approach their understanding and to prove their hypothesis. Recently, 3D-cell models are seen to be highly incorporated as a crucial tool for reflecting the true cancer cell microenvironment in pharmacokinetic and pharmacodynamics studies, in addition to the intensity of anticancer drug response in pharmacogenomics trials. Hence, in this review, we shed light on the unique characteristics of 3D cells favoring its promising usage through a comparative approach with other research models, specifically 2D-cell culture. Plus, we will discuss the importance of 3D models as a direct reflector of the intrinsic cancer cell environment with the newest multiple methods and types available for 3D-cells implementation.
Benzofuran is a heterocyclic compound found naturally in plants and it can also be obtained through synthetic reactions. Multiple physicochemical characteristics and versatile features distinguish benzofuran, and its chemical structure is composed of fused benzene and furan rings. Benzofuran derivatives are essential compounds that hold vital biological activities to design novel therapies with enhanced efficacy compared to conventional treatments. Therefore, medicinal chemists used its core to synthesize new derivatives that can be applied to a variety of disorders. Benzofuran exhibited potential effectiveness in chronic diseases such as hypertension, neurodegenerative and oxidative conditions, and dyslipidemia. In acute infections, benzofuran revealed anti-infective properties against microorganisms like viruses, bacteria, and parasites. In recent years, the complex nature and the number of acquired or resistant cancer cases have been largely increasing. Benzofuran derivatives revealed potential anticancer activity with lower incidence or severity of adverse events normally encountered during chemotherapeutic treatments. This review discusses the structure–activity relationship (SAR) of several benzofuran derivatives in order to elucidate the possible substitution alternatives and structural requirements for a highly potent and selective anticancer activity.
This article aims to describe the conjoint analysis (CA) method and its application in healthcare settings, and to provide researchers with a brief guide to conduct a conjoint study. CA is a method for eliciting patients’ preferences that offers choices similar to those in the real world and allows researchers to quantify these preferences. To identify literature related to conjoint analysis, a comprehensive search of PubMed (MEDLINE), EMBASE, Web of Science, and Google Scholar was conducted without language or date restrictions. To identify the trend of publications and citations in conjoint analysis, an online search of all databases indexed in the Web of Science Core Collection was conducted on the 8th of December 2021 without time restriction. Searching key terms covered a wide range of synonyms related to conjoint analysis. The search field was limited to the title, and no language or date limitations were applied. The number of published documents related to CA was nearly 900 during the year 2021 and the total number of citations for CA documents was approximately 20,000 citations, which certainly shows that the popularity of CA is increasing, especially in the healthcare sciences services discipline, which is in the top five fields publishing CA documents. However, there are some limitations regarding the appropriate sample size, quality assessment tool, and external validity of CA.
Objective: To assess the feasibility of using adaptive choice-based conjoint (ACBC) analysis to elicit patients’ preferences for pharmacological treatment of osteoarthritis (OA), patients’ satisfaction with completing the ACBC questionnaire, and factors associated with questionnaire completion time. Methods: Adult patients aged 18 years and older with a medical diagnosis of OA, experiencing joint pain in the past 12 months, and living in the Northeast of England participated in the study. The participants completed a web-based ACBC questionnaire about their preferences regarding pharmaceutical treatment for OA using a touchscreen laptop independently, and accordingly, the questionnaire completion time was measured. Moreover, the participants completed a pen-and-paper feedback form about their experience in completing the ACBC questionnaire. Results: Twenty participants aged 40 years and older, 65% females, 75% had knee OA, and suffering from OA for more than 5 years participated in the study. About 60% of participants reported completing a computerized questionnaire in the past. About 85% of participants believed that the ACBC task helped them in making decisions regarding their OA medications, and 95% agreed or strongly agreed that they would be happy to complete a similar ACBC questionnaire in the future. The average questionnaire completion time was 16 min (range 10–24 min). The main factors associated with longer questionnaire completion time were older age, never using a computer in the past, and no previous experience in completing a questionnaire. Conclusions: The ACBC analysis is a feasible and efficient method to elicit patients’ preferences for pharmacological treatment of OA, which could be used in clinical settings to facilitate shared decision-making and patient-centered care. The ACBC questionnaire completion consumes a significantly longer time for elderly participants, who never used a computer, and never completed any questionnaire previously. Therefore, the contribution of patients and public involvement (PPI) group in the development of the ACBC questionnaire could facilitate participants’ understanding and satisfaction with the task. Future research including patients with different chronic conditions may provide more useful information about the efficiency of ACBC analysis in eliciting patients’ preferences for osteoarthritis treatment.
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