Objective To investigate whether PLCB1 expression leads to gastric adenocarcinoma metastasis and poor prognosis, and to preliminarily analyze its mechanism. Methods 122 gastric adenocarcinoma patients and their adjacent non-cancerous tissues were selected, and tissue microarray technology was used to detect the expression levels of PLCB1, epithelial cadherin(E-cadherin), vimentin and CD8+ T cells by immunohistochemistry, and scored by two pathologists. According to the immunohistochemical score of PLCB1, the patients were divided into PLCB1 high expression group (IHC>90) and PLCB1 low expression group (IHC≤90). The clinical pathological characteristics, epithelial mesenchymal transition(EMT)-related proteins and CD8+ T cells expression differences between the two groups were compared. The overall survival of the patients was collected, and COX regression analysis and Kaplan-Meier curve were used to evaluate the relationship between PLCB1 expression level and prognosis. Results PLCB1 was highly expressed in 55 cases of gastric adenocarcinoma tissues, while only 12 cases in adjacent non-cancerous tissues. The tumor invasion depth, lymph node metastasis degree and TNM stage of the PLCB1 high expression group were higher than those of the PLCB1 low expression group. Chi-square test showed that PLCB1 expression level was negatively correlated with E-cadherin (r=-0.339), positively correlated with vimentin (r=0.211), and negatively correlated with CD8+ T cells (r=-0.343). Kaplan-Meier curve analysis showed that the overall survival and disease-free survival of gastric adenocarcinoma patients with high PLCB1 expression were significantly reduced. Multivariate COX regression analysis showed that except for lymph node metastasis, tumor invasion depth, TNM stage, E-cadherin and vimentin were also independent prognostic factors for gastric adenocarcinoma patients. Conclusion PLCB1 is highly expressed in gastric adenocarcinoma, and is closely related to tumor aggressiveness and prognosis. PLCB1 may induce EMT and inhibit CD8+ T cell infiltration to affect gastric adenocarcinoma metastasis and immune response.

Objective To investigate the effect of resveratrol on the tumor microenvironment in osteosarcoma. Methods A C57BL/6 xenograft mouse model was established and treated with resveratrol. Single-cell sequencing was performed to analyze changes in the tumor microenvironment. Immunohistochemistry was used to assess immune cell infiltration, while Western blotting was conducted to examine alterations in cellular signaling pathways. Results Resveratrol significantly inhibited the proliferation of LM8 osteosarcoma cells in C57BL/6 mice compared to the control group. Additionally, CD8+ T cell recruitment was enhanced. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was notably downregulated in LM8 osteosarcoma cells following resveratrol treatment. Conclusion Resveratrol promotes CD8+ T cell infiltration by inhibiting the JAK2/STAT3 signaling pathway, suggesting its potential as a therapeutic agent in osteosarcoma treatment.

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335fl/fl FOXP3creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4+ T cells, CD8+ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4+ and CD8+ T cells, along with their respective effector cells, was significantly higher in the Zfp335CKO group than in the WT group. The proportions of CD4+ and CD8+ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335CKO group compared to that of the WT group. In addition, the percentage of CD8+ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)+ Treg in the Zfp335CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.

To explore the association of the expression of WW domain-containing ubiquitin E3 ligase 1 (WWP1) with immune infiltration in tumor microenvironment (TME) of ovarian cancer.

To investigate the mechanism by which circ_EPHB4 regulates temozolomide (TMZ) sensitivity of glioma cells through the miR-424-5p/Wnt3 signal axis.

Non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths worldwide, remains a significant clinical challenge despite advances in immune checkpoint inhibitors therapy, with drug resistance persisting as a major obstacle. Palmitoylation, a critical post-translational modification (PTM) primarily catalyzed by palmitoyltransferases of the zinc finger DHHC-type (ZDHHC), has recently demonstrated important implications in NSCLC. This review aims to elucidate the mechanisms and clinical potential of ZDHHC-mediated protein palmitoylation in NSCLC progression and immune escape.
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Lung cancer is one of the malignant cancers with the highest incidence rate, and it is important to identify the factors contributing to lung cancer carcinogenesis for prevention. Lifestyle and genetic factors play important roles in cancer development, however the impact of dietary factors, such as soy product intake, on lung cancer risk remains inadequately understood. This study aims to explore the associations between soy product intake, genetic risk, and lung cancer incidence, and validate the consistent effects of soy product intake in European populations, thereby providing new insights for lung cancer prevention.

Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM.

Lung adenocarcinoma (LUAD) is the predominant subtype of non-small cell lung cancer (NSCLC). Damage-specific DNA binding protein 1 (DDB1), as a core protein of the CUL4-DDB1 ubiquitin ligase complex, is involved in the regulation of DNA damage repair, epigenetic modification, and cell cycle checkpoint activation. While the involvement of DDB1 in tumour progression through DNA repair and RNA transcriptional regulation has been reported, its expression and role in LUAD remain to be elucidated. This study aims to investigate the expression and role of DDB1 in LUAD.

Objective: To explore the association between human kallikrein 10 (KLK10) gene methylation levels in female breast tumor tissues and risk of invasive breast cancer. Methods: A case-control study was conducted. The clinical data and paraffin-embedded breast tissue samples of female patients with invasive breast cancer and benign breast diseases admitted to Huai'an Hospital Affiliated to Xuzhou Medical University from 2017 to 2020 and to the Affiliated Hospital of Nantong University from 2020 to 2021 were retrospectively collected, and the methylation levels of each CpG site of the KLK10 gene in the tissues were detected. The methylation levels of KLK10 gene were compared between benign breast diseases and invasive breast cancer (including different pathological types and molecular subtypes), and the multivariate logistic regression model was used to analyze the correlation between the methylation level of KLK10 gene CpG site and the risk of invasive breast cancer. The OR value was expressed as the relative risk of invasive breast cancer for each 10% increase in methylation level. Results: A total of 462 cases of invasive breast cancer aged 52 (46, 58) years and 517 benign breast disease controls aged 45 (41, 50) years were collected. The methylation levels of KLK10_CpG_1 [0.41 (0.26, 0.59) vs 0.36 (0.24, 0.50)], KLK10_CpG_3 [0.38 (0.18, 0.61) vs 0.32 (0.19, 0.49)], and KLK10_CpG_4 [0.52 (0.39, 0.65) vs 0.30 (0.22, 0.38] in the invasive breast cancer group were higher than those in the benign control group (all P<0.05). There were significant differences in the methylation levels of KLK10_CpG_1, KLK10_CpG_3 and KLK10_CpG_4 between the benign control group and various pathological types and molecular subtypes of invasive breast cancer (all P<0.05). The methylation levels of KLK10_CpG_4 in all different pathological types and molecular subtypes of breast cancer were higher than those in the control group (all P<0.05). The methylation levels of the overall KLK10_CpG_1 (OR=1.10, 95%CI: 1.03-1.17), KLK10_CpG_3 (OR=1.11, 95%CI: 1.05-1.18), and KLK10_CpG_4 (OR=1.77, 95%CI: 1.61-1.95) sites were positively correlated with invasive breast cancer (all P<0.05). In breast cancer patients aged≤50 years, the methylation levels of KLK10_CpG_1 (OR=1.14, 95%CI: 1.05-1.24), KLK10_CpG_3 (OR=1.12, 95%CI: 1.04-1.21) and KLK10_CpG_4 (OR=1.90, 95%CI: 1.68-2.15) sites were positively correlated with invasive breast cancer (all P<0.05). In breast cancer patients aged>50 years, the high methylation levels of KLK10_CpG_3 (OR=1.13, 95%CI: 1.03-1.25) and KLK10_CpG_4 (OR=1.60, 95%CI: 1.37-1.86) sites were positively correlated with invasive breast cancer (all P<0.05). Conclusion: Hypermethylation of the KLK10 gene in female breast tumor tissue is associated with the risk of invasive breast cancer.

Objective: We aimed to investigate the relationship between CYP2D6*10 gene polymorphisms and adverse reactions associated with tamoxifen treatment in breast cancer patients, and assess the value of CYP2D6*10 gene polymorphism testing in guiding the use of medications in endocrine therapy for breast cancer. Methods: 177 breast cancer patients with HR-positive and postoperative tamoxifen were admitted to the First Affiliated Hospital of Nanjing Medical University from November 2012 to December 2021. Their clinicopathologic data were collected for follow-up observation of adverse reactions related to tamoxifen treatment. After two years of tamoxifen treatment, finger blood of these patients was taken for CYP2D6 gene polymorphism detection. Moreover, databases including RNAfold, QTLbase, 3DSNP v2.0, RegulomeDB 2.2, and HaploReg v4.2 were used to predict the annotation of proximal and distal interactions of CYP2D6 polymorphic sites between genes and regulatory elements. Results: Genotyping analysis revealed 40 patients (22.6%) with the CC genotype, 79 (44.6%) with the CT genotype, and 58 (32.8%) with the TT genotype. Common adverse reactions to tamoxifen included abnormal liver function (58), fatty liver (81), uterine fibroids (12), and endometrial surgery for endometrial thickening (17). Univariate and multivariate logistic regression analyses showed that there were no significant statistical differences between the CC and CT+TT genotypes in terms of liver damage, new-onset fatty liver, uterine fibroids, or tumor recurrence and metastasis (P＞0.05). Notably, endometrial thickening was more significant in patients with the CT+TT genotype (4.37±3.82 mm) than in those with the CC genotype (2.43±2.96 mm), with a statistically significant difference between them (P＜0.01). Bioinformatic analysis suggested that in breast tissues, the CYP2D6*10 polymorphic locus had a significant expression quantitative trait locus (eQTL) effect with CYP2D6, and its genetic variations could affect the binding of CYP2D6 to transcription factors, which might modulate the expression of CYP2D6 through changes in secondary structure and chromatin modifications, etc., and thus affect the tamoxifen drug sensitivity. Further eQTL analysis showed significant correlation between CYP2D6 expression levels with different genotypes of the CYP2D6 rs1065852 polymorphism in breast tissues (P＜0.01). Conclusion: Tamoxifen remains a primary therapeutic agent for premenopausal HR-positive breast cancer patients, and its efficacy is influenced by polymorphisms in the CYP2D6*10. It is recommended that for breast cancer patients carrying the CYP2D6 CT and TT genotypes, endometrial monitoring should be strengthened during treatment with tamoxifen, and the medication should be adjusted in a timely manner.

N6-methyladenosine (m6A) modification, as a widespread and high-profile type of epigenetic modification, can dynamically and reversibly regulate the whole process of RNA metabolism. This modification governs RNA stability, splicing, and translation via m6A regulators, which are categorized as Writers, Erasers, and Readers. m6A modification also plays a critical role in the development of tumors. Disruptions in the homeostasis of m6A modification levels lead to dysregulation of m6A regulators. Consequently, these dysregulated regulators modulate the proliferation, migration, and invasion of tumor cells and interfere with the normal functions of suppressor genes and oncogenes. This article aims to comprehensively elucidate the specific regulatory impacts of m6A modification on tumor-related gene expression. It focuses on the regulatory mechanisms of m6A modification on mRNA stability. Additionally, it explores the influence of m6A on the molecular translation of key signaling pathways. Moreover, it investigates the indirect regulatory effects mediated by non-coding RNAs (ncRNAs), etc. The intention is to offer a novel analysis of the pathogenesis of cancer at a new level, and also provide a theoretical basis for finding new effective treatment methods.

Objective: To systematically investigate the association and regulatory mechanism between genetic variants in the binding region of pancreatic and duodenal homeobox 1 (PDX1) and pancreatic cancer susceptibility in the Chinese population. Methods: Chromatin immunoprecipitation sequencing (ChIP-seq) was performed using the human pancreatic cancer cell line BxPC-3 to identify and annotate genetic variants within the PDX1 binding region. A two-center case-control study was conducted, and logistic regression models were employed to analyze the association between PDX1-related variants and pancreatic cancer susceptibility. Functional experiments were performed to elucidate the molecular mechanisms of these genetic variants. Results: ChIP-seq analysis identified 1 608 PDX1 binding regions. SNPs within these regions were significantly enriched in susceptible areas of pancreatic cancer (P<0.001). The common variant rs154659, located within the most significant PDX1 binding peak, was further investigated. The multivariate logistic regression model showed that compared with individuals with TT genotype, individuals with CC genotype had a reduced risk of pancreatic cancer by 29.2% (OR=0.708, 95%CI: 0.589-0.850). Functional studies demonstrated that the rs154659[C] allele displayed higher relative luciferase activity than the rs154659[T] allele. Knockdown of PDX1 significantly attenuated the relative luciferase differences between the two alleles. Conclusion: Genetic variants in the PDX1 binding region are associated with pancreatic cancer risk. The rs154659 modulates pancreatic cancer susceptibility by specifically altering PDX1 binding activity.

To explore the genetic testing outcomes of a fetal family with Thyroid dyshormonogenesis type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations.

Objective: To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL. Methods: Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL. Results: NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing (r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively (P>0.05) . Conclusions: Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Objective: To investigate the key genetic mutations during the progressive disease (PD) /leukemic transformation (LT) course in MDS by analyzing the dynamic changes of genetic mutations in patients with myelodysplastic neoplasms (MDS) with or without PD/LT. Methods: This study enrolled 84 patients with sequential MDS from May 2019 to August 2023 at ZhongDa Hospital Southeast University and used the next generation sequencing to detect gene mutations. The dynamic changes of genetic mutations in patients with MDS with or without PD/LT were retrospectively analyzed. Results: ①This study analyzed data from 84 patients diagnosed with MDS with a median age of 63 (range: 31-95) years and consisting of 51 males and 33 females. Participants were distributed to the PD cohort (n=20), LT cohort (n=13), and non-PD/LT cohort (n=51). Patients from the PD/LT cohorts demonstrated a higher proportion of bone marrow blasts than the non-PD/LT cohort at the first sequencing (1.6% vs. 0.4%, P=0.013). ②The most frequently mutated genes that were detected at first sequencing were ASXL1 (n=21, 25.0%), TP53 (n=17, 20.2%), TET2 (n=12, 14.3%), DNMT3A (n=11, 13.1%), and U2AF1 (n=11, 13.1%). Further, patients from the PD/LT cohorts exhibited a higher median number of mutated genes than the non-PD/LT cohort (2 vs.1, P=0.014) at first sequencing. TET2 (27.3% vs. 5.9%, P=0.010), SETBP1 (15.2% vs.2.0%, P=0.033), and RUNX1 (18.2% vs. 2.0%, P=0.013) mutations were enriched in the PD/LT cohorts than in the non-PD/LT cohort. ③The most frequently detected acquired mutations (Ⅰ mutations) and clonally expanded mutations (Ⅱ mutations) were TP53 (n=9, 10.7%), TET2 (n=7, 8.3%), ASXL1 (n=7, 8.3%), and RAS pathway (n=7, 8.3%). Furthermore, patients from the PD/LT cohorts showed a higher median number of Ⅰ/Ⅱ genes than the non-PD/LT cohort (2 vs. 0, P<0.001), and Ⅰ/Ⅱ RAS pathway (21.2% vs. 0, P=0.001), TP53 (27.3% vs. 0, P<0.001), and TET2 (18.2% vs. 2.0%, P=0.013) mutations were enriched in PD/LT cohorts than in the non-PD/LT cohorts. ④Most of the TP53 mutations (9/12, 75.0%) in PD/LT cohorts were Ⅰ/Ⅱ mutations, whereas all of the TP53 mutations in non-PD/LT cohort were clone-decrease mutations (Ⅲ mutations) (5/8, 62.5%) or clone-stable mutations (Ⅳ mutations) (3/8, 37.5%). Most of the RAS pathway mutations (7/8,87.5%) in the PD/LT cohorts were Ⅰ/Ⅱ mutations, whereas only one patient in the non-PD/LT cohort demonstrated RAS pathway mutations, which belonged to Ⅳ mutations. Conclusion: Patients from the PD/LT cohorts demonstrated a higher proportion of bone marrow blasts and a higher median number of mutations than the non-PD/LT cohort at first sequencing; TET2, SETBP1, and RUNX1 mutations were enriched in the PD/LT cohorts than in the non-PD/LT cohort at first sequencing. Patients from the PD/LT cohorts exhibited a higher number of Ⅰ/Ⅱ mutations than the non-PD/LT cohort. Further, Ⅰ/Ⅱ TP53, RAS pathway, and TET2 mutations were enriched in the PD/LT cohorts, and Ⅰ/Ⅱ TP53 and RAS pathway mutations may contribute to the PD/LT.

The study investigated the specific mechanism by which oxocrebanine, the anti-hepatic cancer active ingredient in Stephania hainanensis, inhibits the proliferation of hepatic cancer cells. Firstly, methyl thiazolyl tetrazolium(MTT) assay, 5-bromodeoxyuridine(BrdU) labeling, and colony formation assay were employed to investigate whether oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells. Propidium iodide(PI) staining was used to observe the oxocrebanine-induced apoptosis of HepG2 and Hep3B2.1-7 cells. Western blot was employed to verify whether apoptotic effector proteins, such as cleaved cysteinyl aspartate-specific protease 3(c-caspase-3), poly(ADP-ribose) polymerase 1(PARP1), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Bcl-2 homologous killer(Bak), and myeloid cell leukemia-1(Mcl-1) were involved in apoptosis. Secondly, HepG2 cells were simultaneously treated with oxocrebanine and the autophagy inhibitor 3-methyladenine(3-MA), and the changes in the autophagy marker LC3 and autophagy-related proteins [eukaryotic translation initiation factor 4E-binding protein 1(4EBP1), phosphorylated 4EBP1(p-4EBP1), 70-kDa ribosomal protein S6 kinase(P70S6K), and phosphorylated P70S6K(p-P70S6K)] were determined. The results of MTT assay, BrdU labeling, and colony formation assay showed that oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells in a dose-dependent manner. The results of flow cytometry suggested that the apoptosis rate of HepG2 and Hep3B2.1-7 cells increased after treatment with oxocrebanine. Western blot results showed that the protein levels of c-caspase-3, Bax, and Bak were up-regulated and those of PARP1, Bcl-2, and Mcl-1 were down-regulated in the HepG2 cells treated with oxocrebanine. The results indicated that oxocrebanine induced apoptosis, thereby inhibiting the proliferation of hepatic cancer cells. The inhibition of HepG2 cell proliferation by oxocrebanine may be related to the induction of protective autophagy in hepatocellular carcinoma cells. Oxocrebanine still promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, reduced the phosphorylation levels of 4EBP1 and P70S6K, which can be reversed by the autophagy inhibitor 3-MA. It is prompted that oxocrebanine can inhibit the proliferation of hepatic cancer cells by inducing autophagy. In conclusion, oxocrebanine inhibits the proliferation of hepatic cancer cells by inducing apoptosis and autophagy.

This study aims to investigate the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung carcinoma-bearing mice via the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2α(eIF2α)/activated transcription factor 4(ATF4)/C/EBP homologous protein(CHOP) signaling pathway. Sixty SPF-grade male C57BL/6 mice were selected and assigned into a blank group and a modeling group by the random number table method. After modeling of the Lewis lung carcinoma, the mice in the modeling group were randomized into model, cisplatin(5 mg·kg~(-1), once a week), and low-, medium-, and high-dose(1.7, 3.5, and 7.05 g·kg~(-1), respectively, once a day) Guiqi Yiyuan Ointment+cisplatin(5 mg·kg~(-1)) groups(n=10). After 14 days of continuous intervention, the spleen, thymus, and tumor samples of the mice were collected, weighed, and recorded, and the spleen index, thymus index, and tumor suppression rate were calculated. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes in the tumor tissue. The morphological changes of the endoplasmic reticulum of tumor cells were observed by transmission electron microscopy. The positive expression of phosphorylated eIF2α(p-eIF2α) and ATF4 in the tumor tissue was detected by immunofluorescence. Western blot was employed to determine the protein levels of phosphorylated PERK(p-PERK), p-eIF2α, ATF4, CHOP, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinase inhibitor 1A(p21), and cyclinD1 in the tumor tissue. Real-time fluorescent quantitative PCR was employed to determine the mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, Bcl-2, p21, and cyclinD1 in the tumor tissue. Compared with the blank group, the model group showed decreases in spleen index and thymus index(P&lt;0.05). Compared with the model group, the cisplatin group showed decreases in spleen index and thymus index(P&lt;0.05), and the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups presented increases in spleen index and thymus index(P&lt;0.05). In addition, the treatment groups all showed decreased tumor mass(P&lt;0.05), increased tumor cell lysis and nuclear rupture, widened gap between rough endoplasmic reticulum, enhanced average fluorescence intensity of p-eIF2α and ATF4(P&lt;0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P&lt;0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P&lt;0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P&lt;0.05). Compared with the cisplatin group, the combination groups showed increases in spleen index and thymus index(P&lt;0.05) as well as mean optical density(P&lt;0.05), and the high-dose Guiqi Yiyuan Ointment+cisplatin group showed decreased tumor mass(P&lt;0.05). In addition, the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups showcased enhanced average fluorescence intensity of p-eIF2α and ATF4(P&lt;0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P&lt;0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P&lt;0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P&lt;0.05). In conclusion, Guiqi Yiyuan Ointment combined with cisplatin can effectively inhibit the growth of Lewis lung carcinoma in mice by regulating the expression of proteins related to the PERK/eIF2α/ATF4/CHOP signaling pathway and promoting cell cycle arrest and apoptosis.

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.