1.
Does nab-paclitaxel have a higher incidence of peripheral neuropathy than solvent-based paclitaxel? Evidence from a systematic review and meta-analysis.
Guo, X, Sun, H, Dong, J, Feng, Y, Li, H, Zhuang, R, Wang, P, Cai, W, Zhou, Y
Critical reviews in oncology/hematology. 2019;:16-23
Abstract
Paclitaxel-induced peripheral neuropathy is a common reason for dose reduction or early cessation of therapy. Nab-paclitaxel was developed to provide additional clinical benefits and overcome the safety drawbacks of solvent-based paclitaxel. However, the incidence of peripheral neuropathy induced by nab-paclitaxel was reported higher than solvent-based paclitaxel but evidence remains inconsistent. Therefore, we conducted a meta-analysis to compare the incidence and severity of peripheral neuropathy between nab-paclitaxel and solvent-based paclitaxel mono-chemotherapy. In total, 24 articles were included in this meta-analysis. Results revealed the incidence of peripheral neuropathy induced by nab-paclitaxel was higher than solvent-based paclitaxel. The dosage and assessment method could influence the comparison of the incidence and severity of peripheral neuropathy between nab-paclitaxel and solvent-based paclitaxel. Current evidence suggests the incidence of peripheral neuropathy induced by nab-paclitaxel was higher than solvent-based paclitaxel among cancer patients received mono-chemotherapy. When received nab-paclitaxel, more attention should be paid to peripheral neuropathy.
2.
Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations.
Li, D, Du, X, Guo, X, Zhan, L, Li, X, Yin, C, Chen, C, Li, M, Li, B, Yang, H, et al
Journal of experimental & clinical cancer research : CR. 2017;(1):168
Abstract
BACKGROUND Previous studies have indicated that tumor mitochondrial DNA (mtDNA) mutations are primarily shaped by relaxed negative selection, which is contradictory to the critical roles of mtDNA mutations in tumorigenesis. Therefore, we hypothesized that site-specific selection may influence tumor mtDNA mutations. METHODS To test our hypothesis, we developed the largest collection of tumor mtDNA mutations to date and evaluated how natural selection shaped mtDNA mutation patterns. RESULTS Our data demonstrated that both positive and negative selections acted on specific positions or functional units of tumor mtDNAs, although the landscape of these mutations was consistent with the relaxation of negative selection. In particular, mutation rate (mutation number in a region/region bp length) in complex V and tRNA coding regions, especially in ATP8 within complex V and in loop and variable regions within tRNA, were significantly lower than those in other regions. While the mutation rate of most codons and amino acids were consistent with the expectation under neutrality, several codons and amino acids had significantly different rates. Moreover, the mutations under selection were enriched for changes that are predicted to be deleterious, further supporting the evolutionary constraints on these regions. CONCLUSION These results indicate the existence of site-specific selection and imply the important role of the mtDNA mutations at some specific sites in tumor development.