IC50: an unsuitable measure for large-sized prostate cancer spheroids in drug sensitivity evaluation

Preclinical models of tumors have the potential to become valuable tools for commercial drug research and development, and 3D culture systems are gaining traction in this area, particularly in prostate cancer (PCa) research. However, nearly all 3D drug design and screening assessments are based on 2D experiments, suggesting limitations of 3D drug testing. To simulate the natural response of human cells to the drug, we detected the half-maximal inhibitory concentration (IC50) changes of 2D/3D LNCaP cells in the drug docetaxel, as well as the sensitivity of different morphologies of 2D/3D LNCaP to docetaxel treatment. In contrast to 2D LNCaP cells, the evaluation of LNCaP spheroids’ susceptibility to treatment was more complicated; the fitness of IC50 curves of 2D and 3D tumor cell preclinical models differs significantly. IC50 curves were unsuitable for large-sized LNCaP spheroids. More evaluation indexes (such as max inhibition) and experiments (such as spheroids formation) should be explored and performed to evaluate the susceptibility systematically

A prognostic index model for assessing the prognosis of ccRCC patients by using the mRNA expression profiles of AIF1L, SERPINC1 and CES1

Background: Kidney carcinoma is a major cause of carcinoma-related death, with the prognosis for advanced or metastatic renal cell carcinoma still very poor. The aim of this study was to investigate feasible prognostic biomarkers that can be used to construct a prognostic index model for clear cell renal cell carcinoma (ccRCC) patients. Methods: The mRNA expression profiles of ccRCC samples were downloaded from the The Cancer Genome Atlas (TCGA) dataset and the correlation of AIF1L with malignancy, tumor stage and prognosis were evaluated. Differentially expressed genes (DEGs) between AIF1L-low and AIF1L-high expression groups were selected. Those with prognostic value as determined by univariate and multivariate Cox regression analysis were then used to construct a prognostic index model capable of predicting the outcome of ccRCC patients. Results: The expression level of AIF1L was lower in ccRCC samples than in normal kidney samples. AIF1L expression showed an inverse correlation with tumor stage and a positive association with better prognosis. ccRCC samples were divided into high- and low-expression groups according to the median value of AIF1L expression. In the AIF1L-high expression group, 165 up-regulated DEGs and 601 down-regulated DEGs were identified. Three genes (AIF1L, SERPINC1 and CES1) were selected following univariate and multivariate Cox regression analysis. The hazard ratio (HR) and 95% confidence intervals (CI) for these genes were: AIF1L (HR = 0.83, 95% CI: 0.76–0.91), SERPINC1 (HR = 1.33, 95% CI: 1.12–1.58), and CES1 (HR = 0.87, 95% CI: 0.78–0.97). A prognostic index model based on the expression level of the three genes showed good performance in predicting ccRCC patient outcome, with an area under the ROC curve (AUC) of 0.671. Conclusion: This research provides a better understanding of the correlation between AIF1L expression and ccRCC. We propose a novel prognostic index model comprising AIF1L, SERPINC1 and CES1 expression that may assist physicians in determining the prognosis of ccRCC patients

Geographical Isolation, Buried Depth, and Physicochemical Traits Drive the Variation of Species Diversity and Prokaryotic Community in Three Typical Hypersaline Environments

The prokaryotic community composition, species diversity and the distribution patterns at various taxonomic levels in a salt lake (Chaka salt lake), solar salterns (Taipei saltworks and Dongfang saltworks), and salt mines (Yuanyongjing salt mine, Xiangyan salt mine, and Dinyuan salt mine) were investigated using clone library or Illumina MiSeq sequencing. The clone library approach revealed that the salt lake harbors low species diversity (H’ = 0.98) as compared to the solar saltern (H’ = 4.36) and salt mine (H’ = 3.57). The dominant group in the salt lake is a species from the genus Haloparvum which constitutes about 85% of the total sequences analyzed. The species diversities in salt salterns and salt mines are richer than in the salt lake, and the dominant group is less significant in terms of total percentage. High-throughput sequencing showed that geographical isolation greatly impacted on the microbial community (phyla level) and species diversity (operational taxonomic units (OTUs) level) of salt mines. Species of the genus Natronomonas are found in all three types of environments investigated. In addition, the microbial community and species diversity of different stratums of the salt mine are very similar. Furthermore, species of the genus Halorubrum flourish in the newest stratum of salt mine and have become the dominant group. This study provides some new knowledge on the species diversity and prokaryotic community composition of three typical hypersaline environments