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Summary: Multiple myeloma (MM) is the second most common malignant haematological disease with a poor prognosis. The limit therapeutic progress has been made in MM patients with cancer relapse, necessitating deeper research into the molecular mechanisms underlying its occurrence and development. A genome‐wide CRISPR‐Cas9 loss‐of‐function screening was utilized to identify potential therapeutic targets in our research. We revealed that COQ2 plays a crucial role in regulating MM cell proliferation and lipid peroxidation (LPO). Knockout of COQ2 inhibited cell proliferation, induced cell cycle arrest and reduced tumour growth in vivo. Mechanistically, COQ2 promoted the activation of the MEK/ERK cascade, which in turn stabilized and activated MYC protein. Moreover, we found that COQ2‐deficient MM cells increased sensitivity to the LPO activator, RSL3. Using an inhibitor targeting COQ2 by 4‐CBA enhanced the sensitivity to RSL3 in primary CD138+ myeloma cells and in a xenograft mouse model. Nevertheless, co‐treatment of 4‐CBA and RSL3 induced cell death in bortezomib‐resistant MM cells. Together, our findings suggest that COQ2 promotes cell proliferation and tumour growth through the activation of the MEK/ERK/MYC axis and targeting COQ2 could enhance the sensitivity to ferroptosis in MM cells, which may be a promising therapeutic strategy for the treatment of MM patients. [ABSTRACT FROM AUTHOR]

Anthracyclines remain the cornerstone of numerous chemotherapeutic protocols, with beneficial effects against haematological malignancies and solid tumours. Unfortunately, the clinical usefulness of anthracyclines is compromised by the development of cardiotoxic side effects, leading to dose limitations or treatment discontinuation. There is no absolute linear correlation between the incidence of cardiotoxicity and the threshold dose, suggesting that genetic factors may modify the association between anthracyclines and cardiotoxicity risk. And the majority of single nucleotide polymorphisms (SNPs) associated with anthracycline pharmacogenomics were identified in the ATP‐binding cassette (ABC) and solute carrier (SLC) transporters, generating increasing interest in the pharmacogenetic implications of their genetic variations for anthracycline‐induced cardiotoxicity (AIC). This review focuses on the influence of SLC and ABC polymorphisms on AIC and highlights the prospects and clinical significance of pharmacogenetics for individualised preventive approaches. [ABSTRACT FROM AUTHOR]

Summary: Multiple myeloma (MM) is the second most common haematological malignancy. Despite the development of new drugs and treatments in recent years, the therapeutic outcomes of patients are not satisfactory. It is necessary to further investigate the molecular mechanism underlying MM progression. Herein, we found that high E2F2 expression was correlated with poor overall survival and advanced clinical stages in MM patients. Gain‐ and loss‐of‐function studies showed that E2F2 inhibited cell adhesion and consequently activated cell epithelial‐to‐mesenchymal transition (EMT) and migration. Further experiments revealed that E2F2 interacted with the PECAM1 promoter to suppress its transcriptional activity. The E2F2‐knockdown‐mediated promotion of cell adhesion was significantly reversed by the repression of PECAM1 expression. Finally, we observed that silencing E2F2 significantly inhibited viability and tumour progression in MM cell models and xenograft mouse models respectively. This study demonstrates that E2F2 plays a vital role as a tumour accelerator by inhibiting PECAM1‐dependent cell adhesion and accelerating MM cell proliferation. Therefore, E2F2 may serve as a potential independent prognostic marker and therapeutic target for MM. [ABSTRACT FROM AUTHOR]

Aim: This study assessed the efficacy and safety of tigecycline in children with life-threatening infections.Methods: We retrospectively reviewed the clinical records of patients treated with tigecycline from June 2012 to May 2014 in a Chinese tertiary centre.Results: The study comprised 24 patients (14 male) with a median age of four years (range, 50 days-12 years). The most frequently isolated microorganism, most common isolation site and type of infection were Acinetobacter baumannii, tracheal aspirate fluid and ventilator-associated pneumonia, respectively. Tigecycline was administered at a loading dose of 1.5 or 2.0 mg/kg and 1.0 mg/kg every 12 hours after that. The average duration of treatment was 11.6 ± 5.8 days. The clinical response and microbiological eradication rate were 37.5% and 29.2%, respectively. Six of the patients we studied (25.0%) died, and three of these deaths were considered to be infection related. Adverse drug reactions were identified in four patients (16.7%) during the treatment, including abnormal liver function, prolonged prothrombin time and diarrhoea.Conclusion: Our findings suggest that tigecycline may be an option for children with severe infections. However, more prospective, controlled trials are required to objectively evaluate the efficacy and safety of tigecycline in children. [ABSTRACT FROM AUTHOR]

Background: Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal tumor. However, the molecular mechanisms of KIRC pathogenesis remain little known. The purpose of our study was to identify potential key genes related to the occurrence and prognosis of KIRC, which could serve as novel diagnostic and prognostic biomarkers for KIRC. Methods: Three gene expression profiles from gene expression omnibus database were integrated to identify differential expressed genes (DEGs) using limma package. Enrichment analysis and PPI construction for these DEGs were performed by bioinformatics tools. We used Gene Expression Profiling Interactive Analysis (GEPIA) database to further analyze the expression and prognostic values of hub genes. The GEPIA database was used to further validate the bioinformatics results. The Connectivity Map was used to identify candidate small molecules that could reverse the gene expression of KIRC. Results: A total of 503 DEGs were obtained. The PPI network with 417 nodes and 1912 interactions was constructed. Go and KEGG pathway analysis revealed that these DEGs were most significantly enriched in excretion and valine, leucine, and isoleucine degradation, respectively. Six DEGs with high degree of connectivity (ACAA1, ACADSB, ALDH6A1, AUH, HADH,and PCCA) were selected as hub genes, which significantly associated with worse survival of patients. Finally, we identified the top 20 most significant small molecules and pipemidic acid was the most promising small molecule to reverse the KIRC gene expression. Conclusions: This study first uncovered six key genes in KIRC which contributed to improving our understanding of the molecular mechanisms of KIRC pathogenesis. ACAA1, ACADSB, ALDH6A1, AUH, HADH,and PCCA could serve as the promising novel biomarkers for KIRC diagnosis, prognosis, and treatment. [ABSTRACT FROM AUTHOR]