Tislelizumab in previously treated, locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors.

Objective: The open-label, phase II RATIONALE-209 study evaluated tislelizumab (anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) tumors. Methods: Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate (ORR; primary endpoint), duration of response (DoR), and progression-free survival (PFS) were assessed by independent review committee (Response Evaluation Criteria in Solid Tumors v1.1). Results: Eighty patients were enrolled and treated; 75 (93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease (n=79; 98.8%). At primary analysis (data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval (95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal (n=46): 39.1% (95% CI, 25.1-54.6); gastric/gastroesophageal junction (n=9): 55.6% (95% CI, 21.2-86.3); others (n=20): 60.0% (95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five (6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up (data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs. Conclusions: Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

Spectral broadening scheme for suppressing SBS effects based on time-domain optimized chirp-like signals.

We propose a novel (to our knowledge) driving scheme to suppress the stimulated Brillouin scattering (SBS) effect in master oscillator power amplification (MOPA) systems based on an external high-order phase modulation. Since seed sources with the linear chirp can uniformly broaden the SBS gain spectrum with a high SBS threshold, a chirp-like signal was designed by applying further editing and processing to the piecewise parabolic signal. Compared with the traditional piecewise parabolic signal, the chirp-like signal has similar linear chirp characteristics and can reduce the driving power and sampling rate requirements, enabling more efficient spectral spreading. The SBS threshold model is constructed theoretically based on the three-wave coupling equation. The spectrum modulated by the chirp-like signal is compared with the flat-top and Gaussian spectra in terms of the SBS threshold and the bandwidth-distribution normalized threshold, and a considerable improvement is demonstrated. Meanwhile, the experimental validation is carried out in a watt-class amplifier based on the MOPA structure. At a 3 dB bandwidth of ∼10 GHz, the SBS threshold of the seed source modulated by the chirp-like signal is improved by 35% compared to the flat-top spectrum and 18% compared to the Gaussian spectrum, respectively, and the normalized threshold is also the highest among them. Our study shows that the SBS suppression effect is not only related to the power distribution of the spectrum but also can be improved by the time domain design, which provides a new idea for analyzing and improving the SBS threshold of narrow-linewidth fiber lasers.

Signal-to-noise ratio degradation analysis for optoelectronic feedback-based chaotic optical communication systems.

Chaotic optical communication encrypts transmitted signals through physical noise; this ensures high security while causing a certain decrease in the signal-to-noise ratio (SNR). Thus, it is necessary to analyze the SNR degradation of decrypted signals after chaotic encryption and the minimum requirements for the SNR of the fiber channel to meet the required bit error rate (BER) performance. Accordingly, an SNR model of decrypted signals for optoelectronic feedback-based chaotic optical communication systems is proposed. Under different channel SNRs, the SNR degradation of 40 Gbit/s phase chaos and intensity chaos models is investigated by simulation and experiment, respectively, with a 15 GHz wideband chaotic carrier. Comparing decrypted signals with original signals, the simulation results show that there is a 2.9 dB SNR degradation for both intensity chaos and phase chaos. Further, in experiments, SNR degradation from 4.5 dB to 5.6 dB, with various channel SNRs for intensity chaos, is analyzed, while there is an SNR degradation from 7.1 dB to 8.3 dB for phase chaos. The simulation and experimental results provide guidance for long-distance transmission chaotic optical communication systems.

[Distribution of memory B cell subsets in peripheral blood of children with frequently relapsing nephrotic syndrome]. / é¢‘å¤å‘è‚¾ç— ç»¼åˆå¾æ‚£å„¿å¤–å‘¨è¡€è®°å¿†B细胞亚群分布变化.

OBJECTIVES: To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease. METHODS: A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed. RESULTS: Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05). CONCLUSIONS: Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.

High-power narrow-linewidth fiber lasers using optical spectrum broadening based on high-order phase modulation of inversion probability-tuning sequence.

Continuous fiber laser with ultra-high power and narrow linewidth is one of the key devices in the field of high-precision industrial processing, beam combining, and nonlinear frequency conversion. Under the premise of ensuring the signal quality, continuously increasing the output power is the focus of high-power narrow-linewidth fiber lasers. Driven by the white noise or pseudo-random binary sequence (PRBS), using cascaded phase modulations to broaden the spectrum of the seed source to suppress the stimulated Brillouin scattering (SBS) effect in the master oscillator power amplifier (MOPA) structure is an effective solution to increase the output power. However, this type of optical spectrum needs to be optimized, and the randomness of the driving signal causes a self-pulsing effect, which limits the further increase of the output power. In this paper, the influence of the frequency interval and randomness of the driving signal on the SBS effect in the laser system is analyzed. The modulated spectral type can be simply adjusted through changing the bit rate and inversion probability. Combining with high-order phase modulation, an approximate rectangular spectral broadening of the seed source with a tunable bandwidth up to 30 GHz is achieved. Compared with the cascaded white noise case, the output power of this scheme is increased by 600 W under the extended bandwidth of 27 GHz. It is fully verified that the seed source spectrum with high in-band flatness and low randomness can effectively suppress the SBS effect in the fiber laser and increase the output power.

Brillouin-based dual-frequency microwave signals generation using polarization-multiplexing modulation.

Dual-frequency microwave signals have potential applications in radar and communication systems to improve system integration and signal conversion convenience. Flexible frequency tunability and low phase noise are important factors for dual-frequency microwave signals. This research focuses on improving frequency tunability of dual-frequency microwave signals meanwhile maintaining low phase noise and high spectrum purity. The outputs of two optical injection-locked slave lasers as Brillouin pump signals are employed combining with an integrated polarization-multiplexing modulator to realize orthogonal polarization multiplexing. Stable dual-frequency microwave signals are obtained in an optoelectronic oscillation loop simultaneously. The obtained microwave signals inherit the flexible frequency tunability of Brillouin effect and low phase noise of the optoelectronic oscillator at the same time.

Generation and phase noise analysis of a wide optoelectronic oscillator with ultra-high resolution based on stimulated Brillouin scattering.

Microwave signals with broadband tunable frequencies and low phase noise can be widely used in communication systems and radar systems. Optoelectronic oscillators (OEOs) with high Q value have the potential to generate the signals meeting the above requirements. In this paper, we present a simple scheme to realize a widely tunable OEO with ultra-high tuning resolution based on stimulated Brillouin scattering (SBS), meanwhile maintaining the low phase noise for all the generated frequencies. By choosing different high-order sideband of the phase-modulated signal as the SBS pump, the frequency of the generated signal can be widely tuned. The accurate frequency tuning can be achieved by changing the drive signal frequency of the phase modulator. As a result, the obtained signal of the OEO with the frequency tuning range up to 40 GHz, and the tuning resolution as accurate as 10 MHz can be obtained. The influence of the SBS gain and the drive signal on the signal phase noise is analyzed theoretically. The effects of the drive signal and the electrical amplifier on the phase noise of the obtained signal are analyzed experimentally. The results show that the noise figure of the amplifier directly affects the phase noise quality of the acquired signal. And the phase noise of the generated signals is lower than -120 dBc/Hz at 100 kHz offset frequency, which has no relation with the drive signal, or the order of the modulation sideband.

Mechanisms of action of natural products on type 2 diabetes.

Over the past several decades, type 2 diabetes mellitus (T2DM) has been considered a global public health concern. Currently, various therapeutic modalities are available for T2DM management, including dietary modifications, moderate exercise, and use of hypoglycemic agents and lipid-lowering medications. Although the curative effect of most drugs on T2DM is significant, they also exert some adverse side effects. Biologically active substances found in natural medicines are important for T2DM treatment. Several recent studies have reported that active ingredients derived from traditional medicines or foods exert a therapeutic effect on T2DM. This review compiled important articles regarding the therapeutic effects of natural products and their active ingredients on islet ß cell function, adipose tissue inflammation, and insulin resistance. Additionally, this review provided an in-depth understanding of the multiple regulatory effects on different targets and signaling pathways of natural medicines in the treatment of T2DM as well as a theoretical basis for clinical effective application.

Strategies to improve the effect of mesenchymal stem cell therapy on inflammatory bowel disease.

Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis and is an idiopathic, chronic inflammatory disease of the colonic mucosa. The occurrence of IBD, causes irreversible damage to the colon and increases the risk of carcinoma. The routine clinical treatment of IBD includes drug treatment, endoscopic treatment and surgery. The vast majority of patients are treated with drugs and biological agents, but the complete cure of IBD is difficult. Mesenchymal stem cells (MSCs) have become a new type of cell therapy for the treatment of IBD due to their immunomodulatory and nutritional functions, which have been confirmed in many clinical trials. This review discusses some potential mechanisms of MSCs in the treatment of IBD, summarizes the experimental results, and provides new insights to enhance the therapeutic effects of MSCs in future applications.

Tiny NaOH Assisted Facile Preparation of Silk Nanofibers and Their Nanotube-Compositing Strong, Flexible, and Conductive Films.

Natural silk nanofibers (SNFs) can not only be used as good building blocks for two- or three-dimensional biomaterials but also provide a clue for understanding the theory of structure-function relationships. Nevertheless, it is still difficult to directly extract SNFs from natural silk fibers due to their high crystallinity and recalcitrant complex structures. In the present study, a dilute alkali-assisted separation of high-yield SNFs is proposed. The degummed silk was first treated with a tiny amount of alkali at a mild temperature, followed by high-pressure homogenization. Under the optimized conditions (2% sodium hydroxide, 0 °C, 48 h), SNFs with diameters of 8-42 nm and lengths of 0.9 ± 0.3 µm were prepared with yields higher than 75%, which retained the natural structures at the nanoscale and some inherent properties of silk fibers. Interestingly, SNFs can be used as a stabilizing matrix to assist carbon nanotubes (CNTs) to disperse, aiming to form a uniform and stable CNT/SNF dispersion. Thereafter, a strong and flexible conductive composite film was fabricated with good mechanical properties. The composite film showed good piezoelectric properties and electric thermal response, which has promising application prospects for SNFs, such as in optical devices, nanoelectronics, and biosensors.

Top-down extraction of surface carboxylated-silk nanocrystals and application in hydrogel preparation.

Bionanomaterial based hydrogels originated from natural biopolymer have drawn much attention for advanced applications. However, nanosilk-based hydrogels derived from top-down approaches remain in their infancy. First, nanosilks based on existing methods fail to prepare hydrogels; second, both nanosilk extraction and surface modification remain a challenge due to high crystallinity and sophisticated hierarchical structures. To produce nanosilk-based hydrogels, pretreatment and oxidation are necessary. In this work, pretreatments were conducted first to loosen the sophisticated structures of natural silk fibers, NaClO oxidation was utilized in succession to introduce carboxyl groups onto silk fibroin. Combined with moderate mechanical disintegration, silk nanocrystals with additional carboxyl groups were prepared facilely. Finally, silk nanocrystal-based hydrogels were prepared successfully through gas phase coagulation. An optimization of pretreatment approaches and oxidation conditions was carried out. The morphologies, chemical and crystalline structures of original, pretreated and oxidized silk fibroin as well as nanofibrillated silk were investigated. In addition, the silk nanocrystal-based hydrogel exhibited outstanding mechanical properties compared to those of dissolved and regenerated silk fibroin-based hydrogels. Moreover, silk nanocrystal-based aerogels present highly porous, interconnected, and crisscrossed network nanostructures, which are ideal candidates for tissue regeneration and provide new prospects as porous scaffolds for bioengineering applications.

Estimation of soil organic carbon storage based on digital soil mapping technique.

Accurate spatial distribution information of soil properties would be helpful for improving the accuracy of soil organic carbon storage estimation. In this study, terrain factors were used as predictors, and the fuzzy C-means (FCM) clustering method was used to make digital soil prediction mapping for soil organic carbon content, soil bulk density, soil depth, and soil gravel content in Nanshan forest farm in Jiyuan City of Henan Province. Based on the digital mapping results, the prediction mapping of soil organic carbon density and the estimation of soil organic carbon storage were realized. The results showed that the average soil organic carbon density in the study area based on the digital soil mapping method was 4.24 kg·m-2, the mean error (ME), mean absolute error (MAE) and root mean square error (RMSE) of the prediction map were 0.08, 2.80 and 5.03 kg·m-2, respectively. The accuracy, stability and reliability of the prediction results were higher than the tradiation methods. The soil organic carbon storage in the study area was estimated to be 3.08×108 kg. Based on the digital soil mapping technology, only a small number of soil samples could be used to map and estimate the soil organic carbon density with high accuracy, which could characterize the spatial distribution characteristics of soil organic carbon density. This study provided a new way to estimate soil organic carbon storage, which would help to improve the accuracy and efficiency of soil organic carbon storage estimation.

PPARγ/SOD2 Protects Against Mitochondrial ROS-Dependent Apoptosis via Inhibiting ATG4D-Mediated Mitophagy to Promote Pancreatic Cancer Proliferation.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognosis. Our previous study found that peroxisome proliferator activated receptor gamma (PPARγ) was capable of enhancing glycolysis in PDAC cells. However, whether PPARγ could promote PDAC progression remains unclear. In our present study, PPARγ was positively associated with tumor size and poor prognosis in PDAC patients. Functional assays demonstrated that PPARγ could promote the proliferation of pancreatic cancer cells in vitro and in vivo. Additionally, flow cytometry results showed that PPARγ decreased mitochondrial reactive oxygen species (mitochondrial ROS) production, stabilized mitochondrial membrane potential (MMP) and inhibited cell apoptosis via up-regulating superoxide dismutase 2 (SOD2), followed by the inhibition of ATG4D-mediated mitophagy. Meanwhile, the activation of PPARγ might reduce pancreatic cancer cell stemness to improve PDAC chemosensitivity via down-regulating ATG4D. Thus, these results revealed that PPARγ/SOD2 might protect against mitochondrial ROS-dependent apoptosis via inhibiting ATG4D-mediated mitophagy to promote pancreatic cancer proliferation, further improving PDAC chemosensitivity.

Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner.

BACKGROUND: Hypoxia is a characteristic of the tumor microenvironments within pancreatic cancer (PC), which has been linked to its malignancy. Recently, hypoxia has been reported to regulate the activity of important carcinogenic pathways by changing the status of histone modification. NOX4, a member of NADPH oxidase (NOX), has been found to be activated by hypoxia and promote cancer progression in several cancers. But whether it is involved in the epigenetic changes of tumor cells induced by hypoxia is still unclear, and its biological roles in PC also need to be explored. METHODS: A hypoxic-related gene signature and its associated pathways in PC were identified by analyzing the pancreatic cancer gene expression data from GEO and TCGA database. Candidate downstream gene (NOX4), responding to hypoxia, was validated by RT-PCR and western blot. Then, we evaluated the relationship between NOX4 expression and clinicopathologic parameters in 56 PC patients from our center. In vitro and in vivo assays were preformed to explore the phenotype of NOX4 in PC. Immunofluorescence, western blot and chromatin immunoprecipitation assays were further applied to search for a detailed mechanism. RESULTS: We quantified hypoxia and developed a hypoxia signature, which was associated with worse prognosis and elevated malignant potential in PC. Furthermore, we found that NADPH oxidase 4 (NOX4), which was induced by hypoxia and upregulated in PC in a HIF1A-independent manner, caused inactivation of lysine demethylase 5A (KDM5A), increased the methylation modification of histone H3 and regulated the transcription of EMT-associated gene_ snail family transcriptional repressor 1 (SNAIL1). This served to promote the invasion and metastasis of PC. NOX4 deficiency repressed hypoxia-induced EMT, reduced expression of H3K4ME3 and impaired the invasion and metastasis of PC cells; however, knockdown of KDM5A reversed the poor expression of H3KEME3 induced by NOX4 deficiency, thereby promoting EMT. CONCLUSIONS: This study highlights the prognostic role of hypoxia-related genes in PC and strong correlation with EMT pathway. Our results also creatively discovered that NOX4 was an essential mediator for hypoxia-induced histone methylation modification and EMT in PC cells.

ALDH1A3 Accelerates Pancreatic Cancer Metastasis by Promoting Glucose Metabolism.

Background: The aldehyde dehydrogenase 1 family member A3 (ALDH1A3) is a key enzyme associated with a variety of metabolic processes, including glucose metabolism. We recently uncovered that glucose metabolism played an essential role in promoting metastasis of pancreatic ductal adenocarcinoma (PDAC). As ALDH1A3 labels an aggressive subtype of PDAC, we hypothesized that ALDH1A3 functionally promoted PDAC metastasis via its metabolic effect on glucose metabolism. Methods: Expression of ALDH1A3 was detected in human PDAC tissues by immunohistochemistry. ALDH1A3 was knocked down or overexpressed in PDAC cells by either shRNA or overexpression vector. The functional roles of ALDH1A3 were characterized in vitro and in vivo. Transcriptional profiling via RNA-sequencing was used to explore the possible underlying molecular mechanisms. Glucose uptake, extracellular lactate, and ATP production were measured to access the metabolic influence of ALDH1A3 on PDAC cells. Results: ALDH1A3 was associated with poor prognosis in PDAC patients. Functionally, ALDH1A3 promoted PDAC metastasis in vitro and in vivo. Further studies revealed that ALDH1A3 activated PI3K/AKT/mTOR signaling pathway and its downstream target-PPARγ (peroxisome proliferator-activated receptor gamma). This led to increase the expression of HK2 (hexokinase 2), which subsequently enhanced the glycolysis in PDAC cells. Additionally, the pharmacological inhibition of PPARγ activity in ALDH1A3-positive cells impaired glycolytic genes expression, PI3K/AKT/mTOR activity and cellular glycolysis. Conclusions: ALDH1A3 promotes PDAC metastasis via its metabolic influence on glucose metabolism. PPARγ and its downstream PI3K/AKT/mTOR signaling pathway maybe involved in this process.

Elevated FAM3C promotes cell epithelial- mesenchymal transition and cell migration in gastric cancer.

BACKGROUND: Tumor metastasis is an important factor in treatment failure for advanced gastric cancer. Family with sequence similarity 3 member C (FAM3C) is known to play a critical role in inducing epithelial-mesenchymal transition in several cancer types, while its role in gastric cancer is unidentified. The aim of this study was to investigate the role of FAM3C in gastric cancer and provide new information on the receptor tyrosine-kinase pathway and cytokine-based therapies. METHODS: FAM3C expression was tested in human gastric cancer tissue and adjacent normal mucosa, and the prognostic effect of FAM3C was analyzed in data from the Cancer Genome Atlas (TCGA). The role of FAM3C in gastric cancer proliferation and metastasis was investigated in vitro and in vivo. Western blot analysis and immunofluorescence were used to detect the underlying mechanisms. RESULTS: FAM3C expression was increased in gastric cancer tissue and showed cytoplasmic distribution. Gastric cancer patients with FAM3C overexpression had significantly worse prognoses based on TCGA data. In the gastric cancer cell lines MKN45 and AGS, knockdown of FAM3C dramatically attenuated cell migration, but had almost no influence on proliferation, while exogenous FAM3C promoted cell migration in a cell line with low FAM3C expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of TCGA data showed that FAM3C was mainly associated with genes involved in focal adhesion, extracellular matrix-receptor interactions and the PI3K-Akt signaling pathway. Knockdown of FAM3C in gastric cancer cell lines significantly suppressed epithelial-mesenchymal transition, as demonstrated by increased expression of E-cadherin and decreased expression of Snail and Slug. Furthermore, knockdown of FAM3C strongly suppressed activation of the PI3K-Akt signaling pathway. Finally, we confirmed that FAM3C knockdown significantly decreased metastatic lesions in vivo. CONCLUSION: Our study demonstrated that FAM3C can promote gastric cancer metastasis both in vitro and in vivo. FAM3C should be taken into consideration for gastric cancer treatments involving inhibition of the ligands and downstream pathways of receptor tyrosine kinases.

Protective role of ABCG2 against oxidative stress in colorectal cancer and its potential underlying mechanism.

Colorectal cancer (CRC), one of the most common cancer types worldwide, is associated with a high mortality rate, and oxidative stress and inflammation play a vital role in this malignancy. A previous study by our group indicated that ATP binding cassette subfamily G member 2 (ABCG2) was capable of protecting cells from reactive oxygen species (ROS)­mediated cell damage and death. In the present study, the role of ABCG2 in CRC was investigated by using clinical samples and cell lines. The levels of oxidative stress markers and inflammatory factors were increased, while the levels of antioxidants were decreased in CRC tissues or the serum of patients. Notably, high expression of ABCG2 in CRC tissues which may be the feedback of over-oxidative reaction, was associated with a poor prognosis. Further in vitro study indicated that the downregulation of ABCG2 induced ROS generation and inflammatory reactions, and inhibited the production of antioxidants. The nuclear factor (NF)-κB signaling pathway was activated under oxidative stress induced by ABCG2 knockdown. In conclusion, the present results indicated that ABCG2 may relieve oxidative stress and inflammatory response by inhibiting the NF-κB signaling pathway in cell models, and may thus play a potential protective role in CRC. This information may provide novel theoretical mechanisms and future targets for CRC therapy.

Increased Glutamine Consumption in Cisplatin-Resistant Cells Has a Negative Impact on Cell Growth.

The emergence of drug-resistant subclones remains the primary reason for tumor treatment failure. Some theories suggest that drug-resistant cell growth can be suppressed by drug-sensitive cells because resistant cells are less fit than sensitive cells in the absence of drug. We investigated fitness differences and their underlying mechanisms in cisplatin (ddp)-resistant cells and parental cells. We found that glutamine (Gln) consumption was substantially higher in ddp-resistant cells than that in sensitive cells, indicating that significantly fewer ddp-resistant cells than sensitive cells could be generated under the same Gln conditions. Interestingly, the antioxidant capacity of ddp-resistant cells was also significantly enhanced and was directly related to the presence of Gln. Then, we found that enhanced antioxidant capacity was sustained by accelerated Gln catabolism in resistant cells through oncogenic KRAS. Further analysis indicated that rapid Gln catabolism directly mediated ddp resistance through enhanced antioxidant capacity, but the maximum number of resistant cells that could be produced with the same amount of Gln was significantly reduced due to increased Gln catabolism. Collectively, our study revealed that rapid Gln catabolism provided ddp-resistant cells with the ability to tolerate cytotoxic treatment but also hindered the growth of ddp-resistant cells due to excessive Gln consumption.