Regulation and Function of CCL2 and N-Myc in Retinoic Acid-treated Neuroblastoma Cells.

Background/aim: Treatment with retinoic acid (RA) often promotes neuroblastoma differentiation and growth inhibition, including the suppression of the expression of the MYCN oncogene. However, RA also targets protumoral chemokines, such as CCL2, which may contribute to the development of resistance. The present study aimed to investigate the regulation and function of CCL2 and N-Myc in RA-treated neuroblastoma cells.

Enhancing Retinoic Acid-mediated Effects Through Inhibition of CYP26A1, CYP26B1 and HGF Signaling in Neuroblastoma Cells.

Background/aim: Retinoic acid (RA) induces tumor cell differentiation in diseases like acute promyelocytic leukemia or high-risk neuroblastoma. However, the formation of resistant cells, which results from dysregulation of different signaling pathways, limits therapy success. The present study aimed to characterize basic regulatory processes induced by the application of RA in human neuroblastoma cells, to identify therapeutic targets independent of the often amplified oncogene MYCN.

Molecular biomarkers of leukemia: convergence-based drug resistance mechanisms in chronic myeloid leukemia and myeloproliferative neoplasms.

Leukemia represents a diverse group of hematopoietic neoplasms that can be classified into different subtypes based on the molecular aberration in the affected cell population. Identification of these molecular classification is required to identify specific targeted therapeutic approaches for each leukemic subtype. In general, targeted therapy approaches achieve good responses in some leukemia subgroups, however, resistance against these targeted therapies is common.

Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity.

Background: The development of obesity-associated comorbidities such as type 2 diabetes (T2D) and hepatic steatosis has been linked to selected microRNAs in individual studies; however, an unbiased genome-wide approach to map T2D induced changes in the miRNAs landscape in human liver samples, and a subsequent robust identification and validation of target genes are still missing.

Methods: Liver biopsies from age- and gender-matched obese individuals with (n=20) or without (n=20) T2D were used for microRNA microarray analysis. The candidate microRNA and target genes were validated in 85 human liver samples, and subsequently mechanistically characterized in hepatic cells as well as by dietary interventions and hepatic overexpression in mice.

BTK acts as a modulator of the response to imatinib in chronic myeloid leukemia.

The use of tyrosine kinase inhibitors, such as imatinib, against the chronic myeloid leukemia (CML)-causing kinase BCR::ABL1 has become the model for successful targeted therapy. Nevertheless, drug resistance remains a clinical problem. Analysis of genome-wide expression and genetic aberrations of an imatinib-resistant CML cell line revealed downregulation of Bruton's tyrosine kinase (), predominantly associated with B cell malignancies, and a novel kinase domain variant in imatinib resistance.

Understanding the impact of ABCG2 polymorphisms on drug pharmacokinetics: focus on rosuvastatin and allopurinol.

Introduction: In addition to the well-established understanding of the pharmacogenetics of drug-metabolizing enzymes, there is growing data on the effects of genetic variation in drug transporters, particularly ATP-binding cassette (ABC) transporters. However, the evidence that these genetic variants can be used to predict drug effects and to adjust individual dosing to avoid adverse events is still limited.

Areas Covered: This review presents a summary of the current literature from the PubMed database as of February 2024 regarding the impact of genetic variants on ABCG2 function and their relevance to the clinical use of the HMG-CoA reductase inhibitor rosuvastatin and the xanthine oxidase inhibitor allopurinol.

Phenotype-Genotype Correlation Applying a Cocktail Approach and an Exome Chip Analysis Reveals Further Variants Contributing to Variation of Drug Metabolism.

Although great progress has been made in the fine-tuning of diplotypes, there is still a need to further improve the predictability of individual phenotypes of pharmacogenetically relevant enzymes. The aim of this study was to analyze the additional contribution of sex and variants identified by exome chip analysis to the metabolic ratio of five probe drugs. A cocktail study applying dextromethorphan, losartan, omeprazole, midazolam, and caffeine was conducted on 200 healthy volunteers.

Drug Interactions of Tetrahydrocannabinol and Cannabidiol in Cannabinoid Drugs.

Background: Cannabinoid drugs containing tetrahydrocannabinol (THC), or its structural analogues, as monotherapeutic agents or as extracts or botanical preparations with or without cannabidiol (CBD) are often prescribed to multimorbid patients who are taking multiple drugs. This raises the question of the risk of drug interactions.

Methods: This review of the pharmacokinetics and pharmacodynamics of interactions with cannabinoid drugs and their potential effects is based on pertinent publications retrieved by a selective literature search.

Clonal evolution in tyrosine kinase inhibitor-resistance: lessons from -models.

Introduction: Resistance in anti-cancer treatment is a result of clonal evolution and clonal selection. In chronic myeloid leukemia (CML), the hematopoietic neoplasm is predominantly caused by the formation of the BCR::ABL1 kinase. Evidently, treatment with tyrosine kinase inhibitors (TKIs) is tremendously successful.

PSMA-617 inhibits proliferation and potentiates the Lu-PSMA-617-induced death of human prostate cancer cells.

The human prostate-specific membrane antigen (PSMA) is substantially up-regulated in metastatic prostate cancer (PCa) cells. PSMA can be targeted by Lu conjugated to PSMA-617, a high-affinity ligand for the PSMA. The binding of the radioligand, Lu-PSMA-617, results in its internalisation and delivery of β-radiation into the cancer cells.

Pharmacogenomics in practice: a review and implementation guide.

Considerable efforts have been exerted to implement Pharmacogenomics (PGx), the study of interindividual variations in DNA sequence related to drug response, into routine clinical practice. In this article, we first briefly describe PGx and its role in improving treatment outcomes. We then propose an approach to initiate clinical PGx in the hospital setting.

Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.

The hematopoietic neoplasm chronic myeloid leukemia (CML) is a rare disease caused by chromosomal reciprocal translocation t(9;22)(q34:q11) with subsequent formation of the BCR-ABL1 fusion gene. This fusion gene encodes a constitutively active tyrosine kinase, which results in malignant transformation of the cells. Since 2001, CML can be effectively treated using tyrosine kinase inhibitors (TKIs) such as imatinib, which prevent phosphorylation of downstream targets by blockade of the BCR-ABL kinase.

CRISPR/Cas9-induced knockout reveals the role of ABCB1 in the response to temozolomide, carmustine and lomustine in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor with limited therapeutic options. Besides surgery, chemotherapy using temozolomide, carmustine or lomustine is the main pillar of therapy. However, therapy success is limited and prognosis still is very poor.

Genome‑wide expression and methylation analyses reveal aberrant cell adhesion signaling in tyrosine kinase inhibitor‑resistant CML cells.

Although chronic myeloid leukemia (CML) can be effectively treated using BCR‑ABL1 kinase inhibitors, resistance due to kinase alterations or to BCR‑ABL1 independent mechanisms remain a therapeutic challenge. For the latter, the underlying mechanisms are widely discussed; for instance, gene expression changes, epigenetic factors and alternative signaling pathway activation. In the present study, ‑CML cell models of resistance against the tyrosine kinase inhibitors (TKIs) imatinib (0.

Dietary induction of obesity and insulin resistance is associated with changes in Fgf21 DNA methylation in liver of mice.

DNA methylation is dynamically regulated in metabolic diseases, but it remains unclear whether the changes are causal or consequential. Therefore, we used a longitudinal approach to refine the onset of metabolic and DNA methylation changes at high temporal resolution. Male C57BL/6N mice were fed with 60 % high-fat diet (HFD) for up to 12 weeks and metabolically characterized weekly.

Pharmacogenomics of Impaired Tyrosine Kinase Inhibitor Response: Lessons Learned From Chronic Myelogenous Leukemia.

The use of small molecules became one key cornerstone of targeted anti-cancer therapy. Among them, tyrosine kinase inhibitors (TKIs) are especially important, as they were the first molecules to proof the concept of targeted anti-cancer treatment. Since 2001, TKIs can be successfully used to treat chronic myelogenous leukemia (CML).