Tumor metabolism has been deeply investigated for cancer therapeutics. Here, we demonstrate that glutamine deficiency alone could not completely inhibit cancer cell growth and that many potent kidney-type glutaminase (KGA) inhibitors did not show satisfying in vivo efficacy. The potent KGA allosteric inhibitor, CB-839, resulted in up to 80% growth inhibition of all tested cell lines, whereas Hexylselen (CPD-3B), a KGA/glutamate dehydrogenase (GDH) inhibitor, showed essentially no toxicity to normal cells up to a 10 μM concentration and could completely inhibit the growth of many aggressive cell lines. Further analyses showed that CPD-3B targets not only KGA and GDH but also thioredoxin reductase (TrxR) and amidotransferase (GatCAB), which results in corresponding regulation of Akt/Erk/caspase-9 signaling pathways. In an aggressive liver cancer xenograft model, CPD-3B significantly reduced tumor size, caused massive tumor tissue damage, and prolonged survival rate. These provide important information for furthering the drug design of an effective anticancer KGA allosteric inhibitor.

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The cell is the basic structural and functional unit of all living organisms. As the smallest unit and building blocks of life, cells differ in size, shape, metabolism, reproduction, and growth requirements. Cells reproduce through cell division involving a four-phase (G1, S, G2, M) cell cycle, which is tightly regulated at multiple checkpoints. The resulting growth curve demonstrates that cell population increases in three sequential steps: incubation, exponential hyperplasia, and stagnation/death phases. Cell growth is subject to changes in disease state and/or environmental conditions. This chapter will focus on methods for cell growth measurement, which are grouped into five sections: cell cycle, apoptosis, growth curve, druginduced proliferation (DIP), and continuous assays. Among the continuous assays, the EZMTT dye allows for long-term tracking of cell growth under various conditions and shows promise in precision medicine by early detection of drug resistance.

Background. The incentive spirometer (IS) is a mechanical device that promotes lung expansion and can be used to prevent and treat postoperative pulmonary complications. In this study, the preventive effect of pulmonary function training with IS on the improvement of pulmonary function and pulmonary complications was observed. Methods. From May 2019 to April 2021, 69 scoliosis patients with impaired moderate and severe lung function were divided into the traditional pulmonary training group (n = 32) and IS-enhanced pulmonary training group (n = 35). The patient underwent lung function testing after admission and one week after the start of training and chest CT on the third day after surgery. Results. The average age was 13.47 and 15.66, respectively ( p  = 0.223). The Cobb angles were 83.84 and 83.97 ( p  = 0.756), respectively, and no statistical difference between the parameters of lung function was detected. After 1 week of respiratory function training, significant improvement in lung function testing parameters including VC%, FVC%, FEV1%, FEV1/FVC, FEV1/VC, and MVV% was found in both groups. Analysis of covariance showed more significant improvement in IS-enhanced group compared to the conventional training group ( p  < 0.05). The incidence of postoperative pulmonary atelectasis was lower in IS-enhanced group than in traditional groups (2.9% vs. 21.9%, p  = 0.043) with no difference in the overall incidence of pulmonary complications ( p  = 0.164) and shorter preoperative and total hospitalization in the IS-enhanced group. Conclusion. Compared to traditional pulmonary function training, IS-enhanced training can significantly accelerate the improvement of pulmonary function testing parameters, shorten the preoperative pulmonary function training time, reduce the incidence of postoperative pulmonary tension complications, and accelerate postoperative rehabilitation.