Glycolysis, the sweet appetite of the tumor microenvironment.

Cancer cells display an altered metabolic phenotype, characterised by increased glycolysis and lactate production, even in the presence of sufficient oxygen - a phenomenon known as the Warburg effect. This metabolic reprogramming is a crucial adaptation that enables cancer cells to meet their elevated energy and biosynthetic demands. Importantly, the tumor microenvironment plays a pivotal role in shaping and sustaining this metabolic shift in cancer cells. This review explores the intricate relationship between the tumor microenvironment and the Warburg effect, highlighting how communication within this niche regulates cancer cell metabolism and impacts tumor progression and therapeutic resistance. We discuss the potential of targeting the Warburg effect as a promising therapeutic strategy, with the aim of disrupting the metabolic advantage of cancer cells and enhancing our understanding of this complex interplay within the tumor microenvironment.

Cluster effect for SNP-SNP interaction pairs for predicting complex traits.

Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP-SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP-SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP-SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP-SNP interaction detection accuracy.

RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations.

N6-methyladenosine (m6A) methylation, a prevalent epitranscriptomic modification, plays a crucial role in regulating mRNA expression, stability, and translation in mammals. M6A regulators have gained attention for their potential implications in tumorigenesis and clinical applications, such as cancer diagnosis and therapeutics. The existing literature predominantly addresses m6A regulators in the context of primary prostate cancer (PCa). However, a notable gap in the knowledge emerges regarding the dynamic expression patterns of these regulators as PCa progresses towards the castration-resistant stage (CRPC). Employing sequential window acquisition of all theoretical mass spectra (SWATH-MS) and RNAseq analysis, we comprehensively profiled the expression of 27 m6A regulators in hormone/androgen-dependent and -independent PCa cell lines, revealing distinct clustering between tumor and adjacent normal prostate tissues. High-grade PCa tumors demonstrated the upregulation of METTL3, RBM15B, and HNRNAPA2B1 and the downregulation of ZC3H13, NUDT21, and FTO. Notably, we identified six m6A regulators associated with PCa survival. Additionally, association analysis of the PCa-associated risk loci in the cancer genome atlas program (TCGA) data unveiled genetic variations near the WTAP, HNRNPA2B1, and FTO genes as significant expression quantitative trait loci. In summary, our study unraveled abnormalities in m6A regulator expression in PCa progression, elucidating their association with PCa risk loci. Considering the heterogeneity within the PCa phenotypes and treatment responses, our findings suggest that prognostic stratification based on m6A regulator expression could enhance PCa diagnosis and prognosis.

G-Protein Signaling Modulator 2 as a Potential Biomarker in Colorectal Cancer: Integrative Analysis Using Genetic Profiling and Pan-Cancer Studies.

Colorectal cancer (CRC) imposes a significant healthcare burden globally, prompting the quest for innovative biomarkers to enhance diagnostic and therapeutic strategies. This study investigates the G-protein signaling modulator (GPSM) family across several cancers and presents a comprehensive pan-cancer analysis of the GPSM2 gene across several gastrointestinal (GI) cancers. Leveraging bioinformatics methodologies, we investigated GPSM2 expression patterns, protein interactions, functional enrichments, prognostic implications, genetic alterations, and immune infiltration associations. Furthermore, the expression of the GPSM2 gene was analyzed using real-time analysis. Our findings reveal a consistent upregulation of GPSM2 expression in all GI cancer datasets analyzed, suggesting its potential as a universal biomarker in GI cancers. Functional enrichment analysis underscores the involvement of GPSM2 in vital pathways, indicating its role in tumor progression. The prognostic assessment indicates that elevated GPSM2 expression correlates with adverse overall and disease-free survival outcomes across multiple GI cancer types. Genetic alteration analysis highlights the prevalence of mutations, particularly missense mutations, in GPSM2. Furthermore, significant correlations between GPSM2 expression and immune cell infiltration are observed, suggesting its involvement in tumor immune evasion mechanisms. Collectively, our study underscores the multifaceted role of GPSM2 in GI cancers, particularly in CRC, emphasizing its potential as a promising biomarker for prognosis and therapeutic targeting. Further functional investigations are warranted to elucidate its clinical utility and therapeutic implications in CRC management.

Pegylated nanoliposomal cisplatin ameliorates chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model. METHODS: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests. RESULTS: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group. CONCLUSIONS: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice.