Biomedical subjects

Yang Li

Publications and source records attributed to Yang Li.

At least 37 records · Page 2Linked to original sources

PubMed2025

Analysis of genetic differences underlying chilling stress tolerance using whole genome Re-Sequencing in walnut (Juglans regia L.).

Walnut (Juglans regia L.) is prized worldwide for both its nutritional value and economic importance, yet it remains vulnerable to cold stress, with significant differences in tolerance among varieties. This study combined physiological analyses with whole-genome resequencing (WGS) to evaluate the cold stress responses of two varieties, ‘Qingxiang’ and ‘Liaoning No.8’. Under chilling stress (0 °C), we measured electrolyte leakage and antioxidant enzyme activity, applying both exogenous methyl jasmonate (MeJA) and the jasmonate inhibitor DIECA. Genomic variations were analyzed using WGS. Results showed that ‘Liaoning No.8’ exhibited superior cold tolerance. Application of MeJA reduced electrolyte leakage by 37% and MDA accumulation by 52% on average, whereas DIECA exacerbated stress-related damage. WGS achieved 16.24–16.26× coverage and identified 2.73–2.78 million SNPs, 378–382k InDels, 25–26k SVs, and 7.2–7.9k CNVs. Twenty genes containing sequence variants showed transcriptional responses under cold stress that were significantly correlated with mutation density (r = 0.62, P < 0.01). One gene, XM_018985465.2, which lacked SNPs in ‘Liaoning No.8’, was expressed 4.2 times more in this variety, suggesting cis-regulatory influence. These findings highlight the role of jasmonic acid signaling in enhancing cold tolerance in walnut and offer genomic insights into its underlying adaptive mechanisms.

Juglans↗

PubMed2025

Annexin A2 binds the 3'-UTR of H2AX mRNA and regulates histone-H2AX-derived hypoxia-inducible factor 1-alpha activation.

Annexin A2 (Anxa2), a multifunctional protein with RNA-binding capabilities, is frequently overexpressed in various tumors, and its expression is highly correlated with malignant progression. In this study, we demonstrate for the first time that Anxa2 was co-expressed with glycolytic genes, suggesting its potential role as a regulator of glycolysis. RNA-protein interaction assay revealed that Anxa2 interacted with 3'-UTR of H2AX mRNA and protected it from miRNA-mediated degradation. Up-regulated Histone-H2AX enhances the expression of glycolytic genes including GLUT1, HK2, PGK1, ENO1, PKM2, GAPDH and LDHA via stabilizing hypoxia-inducible factor 1-alpha (HIF1α), thereby accelerating lactic acid production and secretion. (20S) G-Rh2, a natural compound targeting Anxa2, significantly interfered the Anxa2-H2AX mRNA interaction, and inhibited subsequent glycolysis progression. We propose that Anxa2 acts as a novel regulator in glycolysis via enhancing H2AX expression, and (20S) G-Rh2 may exert its anti-cancer activity by targeting Anxa2-H2AX-HIF1α-glycolysis axis in human hepatoma HepG2 cells.

Humans↗

PubMed2025

Deep learning-based annotation of plant abiotic stress resistance genes for crops.

The declining costs of DNA sequencing have expanded genomic data, crucial for understanding plant abiotic stress responses and crop improvement. However, accurate gene annotation remains challenging. To address this limitation, we propose the PASRGA, a deep learning approach that leverages transfer learning and contrastive learning to annotate genes related to drought, salt, cold, and UV resistance. PASRGA achieves high F1-scores, area under the receiver operating characteristic (AUROC), area under the precision-recall curve (AUPRC), and Matthews correlation coefficient (MCC) in annotating stress resistance genes, significantly outperforming the general protein annotation model CLEAN, the plant phosphatase gene annotation model PF-NET, the top-ranked model in the CAFA5 challenge NetGO 4.0, and four traditional machine learning methods. Its effectiveness was further validated with a salt stress treatment experiment in Eutrema salsugineum. To facilitate crop breeding practices, we utilized PASRGA to annotate the genomes of 17 major crops. To improve accessibility and utility, we incorporated both manually curated and PASRGA-predicted gene data, together with the PASRGA tool, into the PlantASRG database (https://bioinfor.nefu.edu.cn/PlantASRG/). This comprehensive resource aims to support crop breeding initiatives and ensure food security.

Crops, Agricultural↗

PubMed2024

PSEUDO-RESPONSE REGULATOR 3b and transcription factor ABF3 modulate abscisic acid-dependent drought stress response in soybean.

The circadian system plays a pivotal role in facilitating the ability of crop plants to respond and adapt to fluctuations in their immediate environment effectively. Despite the increasing comprehension of PSEUDO-RESPONSE REGULATORs and their involvement in the regulation of diverse biological processes, including circadian rhythms, photoperiodic control of flowering, and responses to abiotic stress, the transcriptional networks associated with these factors in soybean (Glycine max (L.) Merr.) remain incompletely characterized. In this study, we provide empirical evidence highlighting the significance of GmPRR3b as a crucial mediator in regulating the circadian clock, drought stress response, and abscisic acid (ABA) signaling pathway in soybeans. A comprehensive analysis of DNA affinity purification sequencing and transcriptome data identified 795 putative target genes directly regulated by GmPRR3b. Among them, a total of 570 exhibited a significant correlation with the response to drought, and eight genes were involved in both the biosynthesis and signaling pathways of ABA. Notably, GmPRR3b played a pivotal role in the negative regulation of the drought response in soybeans by suppressing the expression of abscisic acid-responsive element-binding factor 3 (GmABF3). Additionally, the overexpression of GmABF3 exhibited an increased ability to tolerate drought conditions, and it also restored the hypersensitive phenotype of the GmPRR3b overexpressor. Consistently, studies on the manipulation of GmPRR3b gene expression and genome editing in plants revealed contrasting reactions to drought stress. The findings of our study collectively provide compelling evidence that emphasizes the significant contribution of the GmPRR3b-GmABF3 module in enhancing drought tolerance in soybean plants. Moreover, the transcriptional network of GmPRR3b provides valuable insights into the intricate interactions between this gene and the fundamental biological processes associated with plant adaptation to diverse environmental conditions.

Glycine max↗

PubMed2007

Discovering potassium channel blockers from synthetic compound database by using structure-based virtual screening in conjunction with electrophysiological assay.

Potassium ion (K+) channels are attractive targets for drug discovery because of the essential roles played in biological systems. However, high-throughput screening (HTS) cannot be used to screen K+ channel blockers. To overcome this disadvantage of HTS, we have developed a virtual screening approach for discovering novel blockers of K+ channels. On the basis of a three-dimensional model of the eukaryotic K+ channels, molecular docking-based virtual screening was employed to search the chemical database MDL Available Chemicals Directory (ACD). Compounds were ranked according to their relative binding energy, favorable shape complementarity, and potential to form hydrogen bonds with the outer mouth of the K+ channel model. Twenty candidate compounds selected from the virtual screening were examined using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. Among them, six compounds (5, 6, 8, 18-20) potently blocked both the delayed rectifier (IK) and fast transient K+ currents (IA). When applied externally, these six compounds preferentially blocked IK with potencies 2- to 500-fold higher than that of tetraethylammonium chloride. Intracellular application of the six compounds had no effect on both K+ currents. In addition, the interaction models and binding free energy calculations demonstrated that hydrophobic interaction and solvent effects play important roles in the inhibitory activities of these compounds. The results demonstrated that structure-based computer screening strategy could be used to identify novel, structurally diverse compounds targeting the pore binding pocket of the outer mouth of voltage-gated K+ channels. This study provides an alternative way of finding new blockers of voltage-gated K+ channels, while the techniques for high-throughput screening of K+ channel drugs remain in development.

Animals↗

PubMed2007

The effects of histone deacetylase inhibitors on the induction of differentiation in chondrosarcoma cells.

PURPOSE: Histologically, chondrosarcomas represent the degree of chondrogenic differentiation, which is associated with the prognosis of the disease. Histone acetylation and deacetylation play key roles in the regulation of chondrocytic differentiation. Here, we describe the antitumor effects of histone deacetylase (HDAC) inhibitors as differentiating reagents on chondrosarcomas. EXPERIMENTAL DESIGN: We examined the effects of a HDAC inhibitor, depsipeptide, on the growth of chondrosarcoma cell lines. We also investigated the modulation of the expression levels of extracellular matrix genes and the induction of phenotypic change in chondrosarcoma cells treated with depsipeptide. Finally, we examined the antitumor effect of depsipeptide on chondrosarcoma in vivo. RESULTS: Depsipeptide inhibited the growth of chondrosarcoma cells by inducing cell cycle arrest and/or apoptosis. HDAC inhibitors increased the expression of the alpha1 chain of type II collagen (COL2A1) gene due to the enhanced histone acetylation in the promoter and enhancer. Depsipeptide also up-regulated the expressions of aggrecan and the alpha2 chain of type XI collagen (COL11A2) mRNA in a dose-dependent manner. Moreover, long-term treatment with a low dose of depsipeptide resulted in the induction of differentiation into hypertrophic phenotype, as shown by the increment of the alpha1 chain of type X collagen (COL10A1) expression in chondrosarcoma cells. In vivo studies and histologic analyses confirmed that depsipeptide significantly inhibited tumor growth and induced differentiation into the hypertrophic and mineralized state in chondrosarcoma cells. CONCLUSIONS: These results strongly suggest that HDAC inhibitors may be promising reagents for use as a differentiating chemotherapy against chondrosarcomas.

Apoptosis↗

PubMed2006

Mapping determinants of gene expression plasticity by genetical genomics in C. elegans.

Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 degrees C and 24 degrees C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 degrees C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity.

Animals↗

PubMed2006

Synthesis of primary arylselenoamides by reaction of aryl nitriles with Woollins' reagent.

[Structure: see text] The reaction of aryl nitriles with Woollins' reagent followed by water affords a variety of primary arylselenoamides in 60-100% yield. The first crystal structures of two primary selenoamides are reported.

Molecular Structure↗

PubMed2006

PLD-assisted VLS growth of aligned ferrite nanorods, nanowires, and nanobelts-synthesis, and properties.

We report here a systematic synthesis and characterization of aligned alpha-Fe2O3 (hematite), epsilon-Fe2O3, and Fe3O4 (magnetite) nanorods, nanobelts, and nanowires on alumina substrates using a pulsed laser deposition (PLD) method. The presence of spherical gold catalyst particles at the tips of the nanostructures indicates selective growth via the vapor-liquid-solid (VLS) mechanism. Through a series of experiments, we have produced a primitive "phase diagram" for growing these structures based on several designed pressure and temperature parameters. Transmission electron microscopy (TEM) analysis has shown that the rods, wires, and belts are single-crystalline and grow along <111>m or <110>h directions. X-ray diffraction (XRD) measurements confirm phase and structural analysis. Superconducting quantum interference device (SQUID) measurements show that the iron oxide structures exhibit interesting magnetic behavior, particularly at room temperature. This work is the first known report of magnetite 1D nanostructure growth via the vapor-liquid-solid (VLS) mechanism without using a template, as well as the first known synthesis of long epsilon-Fe2O3 nanobelts and nanowires.

Journal Article↗

PubMed2006

Efficacy and antivascular effects of EphA2 reduction with an agonistic antibody in ovarian cancer.

BACKGROUND: EphA2 is an oncoprotein and tyrosine kinase receptor that is overexpressed in ovarian and many other cancers. We investigated the effects of reduced EphA2 levels on tumor growth and the tumor microenvironment in an orthotopic ovarian cancer model. METHODS: The effect of the EphA2-agonistic monoclonal antibody EA5, alone or in combination with paclitaxel, on the growth of ovarian cancer cells (SKOV3ip1, HeyA8, and HeyA8MDR [taxane-platinum resistant]) was determined in vitro and in vivo by immunoblotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and immunohistochemical analysis. Expression of EphA2 and markers of angiogenesis (CD31, vascular endothelial growth factor [VEGF], and basic fibroblast growth factor), proliferation (proliferating cell nuclear antigen), and endothelial cell apoptosis (CD31-terminal deoxynucleotidyl transferase biotin-deoxyuridine triphosphate nick-end labeling colocalization) and phosphorylation of Src were analyzed by immunoblotting, immunohistochemistry, immunofluorescence, and in situ hybridization in tumors from treated mice. Statistical tests were two-sided. RESULTS: EA5 antibody treatment led to a more than 90% reduction in EphA2 expression in HeyA8 tumors in vivo. In mice bearing orthotopic SKOV3ip1 or HeyA8 tumors, 4 weeks of EA5 treatment resulted in tumors that weighed 31% and 45% less, respectively, than those in control (IgG-treated) mice (95% confidence interval [CI] = -0.09% to 71% and 20% to 70%, P = .27 and .01, respectively). Combination therapy with EA5 and paclitaxel reduced tumor weight by 77% and 80% (95% CI = 63% to 91% and 68% to 91%), respectively, compared with paclitaxel alone and by 92% and 88% (95% CI = 87% to 97% and 80% to 94%), respectively, compared with IgG alone. Combination therapy also reduced the weight of HeyA8MDR tumors by 47% (95% CI = 24% to 72%) compared with paclitaxel. Mice bearing SKOV3ip1 or HeyA8 tumors that were treated with combination therapy survived longer than those treated with paclitaxel alone (median survival = 144 versus 69 days and 46 versus 37 days, respectively). EA5-treated tumors had reduced microvascular density, proliferation, and VEGF protein and mRNA levels, with increased endothelial cell apoptosis. EphA2 was associated with Src, which was rapidly dephosphorylated after EA5 treatment. CONCLUSIONS: EA5 in combination with paclitaxel decreased tumor growth in an orthotopic ovarian cancer mouse model through antiangiogenic mechanisms associated with reduced levels of VEGF and phosphorylated Src. Humanized antibody constructs against EphA2 are worthy of future study.

Analysis of Variance↗

PubMed2006

Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells.

Recent studies using ovarian cancer cells have shown that the catecholamine hormones norepinephrine (norepi) and epinephrine (epi) may influence cancer progression by modulating the expression of matrix metalloproteinases (MMP) and vascular endothelial growth factor (VEGF). The purpose of this study is to determine if the stress hormone norepi can influence the expression of MMP-2, MMP-9, and VEGF in nasopharyngeal carcinoma (NPC) tumors by using three NPC tumor cell lines. The NPC cell lines HONE-1, HNE-1, and CNE-1 were treated with norepi. The effects of norepi on MMP-2, MMP-9, and VEGF synthesis were measured by ELISA; functional MMP activity was measured by the invasive potential of the cells using a membrane invasion culture system whereas functional activity of VEGF was analyzed using a human umbilical vein endothelial cell tube formation assay. Norepi treatment increased MMP-2, MMP-9, and VEGF levels in culture supernatants of HONE-1 cells, which could be inhibited by the beta-blocker propranolol. Norepi induced the invasiveness of all NPC cell lines in a dose-dependent manner, which was blocked by CMT-3, an MMP inhibitor, and propranolol. Norepi stimulated the release of functional angiogenic VEGF by HONE-1 cells as well. Finally, HONE-1 cells were shown to express beta-adrenergic receptors as did seven of seven NPC biopsies examined. The data suggest that catecholamine hormones produced by the sympathetic-adrenal medullary axis may affect NPC tumor progression, in part, through modulation of key angiogenic cytokines.

Biopsy↗

PubMed2006

Self-assembly and cytotoxicity study of waterwheel-like dinuclear metal complexes: the first metal complexes appended with multiple free hydroxamic acid groups.

Two waterwheel-like dinuclear complexes [M(2)(PHA)(4)(H(2)O)(2)] (M = Cu(II) (1), Zn(II) (2); HPHA = phthal-hydroxamic acid) appended with four free hydroxamic acid groups, namely, free hydroxamic acid metal complexes (FHAMCs) have been synthesized and characterized. The crystal structure of complex 1 was determined by single crystal X-ray diffraction, which adopts the paddlewheel motif with four bidentate carboxylate ligands joining two Cu(II) ions. The relative cytotoxicities of compounds 1 and 2 against SMMC-7721 and HO-8910 cell lines are similar and more predominant than HPHA (IC(50): Cu(II)>Zn(II)>>HPHA). The synergic effect of the bound water molecules, multiple free hydroxamic acid groups and dimetal active sites with bridging carboxylate may have significant impacts on their pharmacological activity. As the prototype for a new class of hydroxamic acid derivatives, the self-assembly of FHAMCs presents a promising new strategy in designing multiple hydroxamic acids with remarkable bioactivities.

Antineoplastic Agents↗

PubMed2006

Fluoride ion-triggered dual fluorescence switch based on naphthalimides winged zinc porphyrin.

A novel fluoride ion-triggered dual fluorescence molecular switch based on naphthalimides winged zinc porphyrin (1) was designed and prepared. The fluorescence of the zinc porphyrin unit could be regulated "ON-OFF" on the excitation of 365 nm and "OFF-ON" on the excitation of 504 nm, respectively, in the presence of fluoride ion. The obvious color changes induced by the intermolecular proton transfer on N-H fragments are clearly visible to the naked eye.

Journal Article↗

PubMed2006

Oxidative modification of M-type K(+) channels as a mechanism of cytoprotective neuronal silencing.

Voltage-gated K(+) channels of the Kv7 family underlie the neuronal M current that regulates action potential firing. Suppression of M current increases excitability and its enhancement can silence neurons. We here show that three of five Kv7 channels undergo strong enhancement of their activity by oxidative modification induced by physiological concentrations of hydrogen peroxide. A triple cysteine pocket in the channel S2-S3 linker is critical for this effect. Oxidation-induced enhancement of M current produced a hyperpolarization and a dramatic reduction of action potential firing frequency in rat sympathetic neurons. As hydrogen peroxide is robustly produced during hypoxia-induced oxidative stress, we used an oxygen/glucose deprivation neurodegeneration model that showed neuronal death to be severely accelerated by M current blockade. Such blockade had no effect on survival of normoxic neurons. This work describes a novel pathway of M-channel regulation and suggests a role for M channels in protective neuronal silencing during oxidative stress.

Animals↗

PubMed2006

Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of K+ channels.

MthK is a prokaryotic Ca(2+)-gated K(+) channel that, like other ligand-gated channels, converts the chemical energy of ligand binding to the mechanical force of channel opening. The channel's eight ligand-binding domains, the RCK domains, form an octameric gating ring in which Ca(2+) binding induces conformational changes that open the channel. Here we present the crystal structures of the MthK gating ring in closed and partially open states at 2.8 A, both obtained from the same crystal grown in the absence of Ca(2+). Furthermore, our biochemical and electrophysiological analyses demonstrate that MthK is regulated by both Ca(2+) and pH. Ca(2+) regulates the channel by changing the equilibrium of the gating ring between closed and open states, while pH regulates channel gating by affecting gating-ring stability. Our findings, along with the previously determined open MthK structure, allow us to elucidate the ligand gating mechanism of RCK-regulated K(+) channels.

Allosteric Regulation↗

PubMed2006

Cloning, expression, and identification of genes involved in the conversion of DL-2-amino-Delta2-thiazoline-4-carboxylic acid to L-cysteine via S-carbamyl-L-cysteine pathway in Pseudomonas sp. TS1138.

Two novel genes (tsB, tsC) involved in the conversion of DL-2-amino-Delta2-thiazoline-4-carboxylic acid (DL-ATC) to L-cysteine through S-carbamyl-L-cysteine (L-SCC) pathway were cloned from the genomic DNA library of Pseudomonas sp. TS1138. The recombinant proteins of these two genes were expressed in Escherichia coli BL21, and their enzymatic activity assays were performed in vitro. It was found that the tsB gene encoded an L-ATC hydrolase, which catalyzed the conversion of L-ATC to L-SCC, while the tsC gene encoded an L-SCC amidohydrolase, which showed the catalytic ability to convert L-SCC to L-cysteine. These results suggest that tsB and tsC play important roles in the L-SCC pathway and L-cysteine biosynthesis in Pseudomonas sp. TS1138, and that they have potential applications in the industrial production of L-cysteine.

Base Sequence↗

PubMed2006

Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE-65 in a mouse model of retinal pigment epithelium damage.

Stem cell regeneration of damaged tissue has recently been reported in many different organs. Since the loss of retinal pigment epithelium (RPE) in the eye is associated with a major cause of visual loss - specifically, age-related macular degeneration - we investigated whether hematopoietic stem cells (HSC) given systemically can home to the damaged subretinal space and express markers of RPE lineage. Green fluorescent protein (GFP) cells of bone marrow origin were used in a sodium iodate (NaIO(3)) model of RPE damage in the mouse. The optimal time for adoptive transfer of bone marrow-derived stem cells relative to the time of injury and the optimal cell type [whole bone marrow, mobilized peripheral blood, HSC, facilitating cells (FC)] were determined by counting the number of GFP(+) cells in whole eye flat mounts. Immunocytochemistry was performed to identify the bone marrow origin of the cells in the RPE using antibodies for CD45, Sca-1, and c-kit, as well as the expression of the RPE-specific marker, RPE-65. The time at which bone marrow-derived cells were adoptively transferred relative to the time of NaIO(3) injection did not significantly influence the number of cells that homed to the subretinal space. At both one and two weeks after intravenous (i.v.) injection, GFP(+) cells of bone marrow origin were observed in the damaged subretinal space, at sites of RPE loss, but not in the normal subretinal space. The combined transplantation of HSC+FC cells appeared to favor the survival of the homed stem cells at two weeks, and RPE-65 was expressed by adoptively transferred HSC by four weeks. We have shown that systemically injected HSC homed to the subretinal space in the presence of RPE damage and that FC promoted survival of these cells. Furthermore, the RPE-specific marker RPE-65 was expressed on adoptively transferred HSC in the denuded areas.

Animals↗

PubMed2006

Inducible resistance of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand receptor 2-mediated apoptosis by generation of a blockade at the death domain function.

Induction of tumor cell resistance to therapeutics has been a major obstacle in cancer therapy. Targeting of the death receptors by a natural ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or agonistic monoclonal antibodies against TRAIL receptor 1 (TRAIL-R1) or TRAIL receptor 2 (TRAIL-R2) has been thought to be a promising cancer therapy. To determine whether tumor cells are able to generate a resistance to apoptosis induced by an anti-TRAIL-R2 antibody, TRA-8, we examined the apoptotic response of human breast and ovarian cancer cell lines after treatment with TRA-8. Our results show that tumor cell resistance to TRA-8 can be induced by repeated treatment of tumor cells with low, non-apoptosis-inducing doses of TRA-8. Interestingly, the induced resistance to apoptosis was not due to a global apoptotic defect in tumor cells but rather a selective defect in the TRAIL-R2 signaling pathway. Whereas TRA-8-treated tumor cells developed a selective resistance to TRAIL-R2-mediated apoptosis, the apoptotic responses induced by TRAIL, an anti-TRAIL-R1 antibody (2E12), and other apoptotic stimuli were not impaired. The expression levels of cell surface TRAIL-R2 were not altered and mutations of TRAIL-R2 were not found in the resistant cells. The induced TRA-8 resistance was due to a selective blockade at the level of the death domain and could be reversed by a wide array of chemotherapeutic agents. Proteomic analysis of death-inducing signaling complex formation during TRA-8 treatment shows that the translocation of TRAIL-R2-associated apoptotic proteins was significantly altered. Our results suggest that the prevention of tumor cell resistance to therapeutic agents that target the death receptors must be taken into consideration.

Apoptosis↗