To investigate the effects of LncRNA SNHG20 on epithelial mesenchymal transition (EMT) and microtubule formation in human oral squamous cell carcinoma (OSCC) cells through targeted regulation of the miR-520c-3p/RAB22A pathway.

To explore the function of LIM and calponin homology domains 1 (LIMCH1) in the development and progression of oral squamous cell carcinoma (OSCC), along with their potential clinical applications.

Objective: To analyze the clinical significance of molecular classification and hereditary phenotype in endometrial carcinoma (EC) based on high throughput sequencing (NGS). Methods: 97 EC samples were collected retrospectively from December 2019 to October 2022 in China-Japan Friendship Hospital. NGS technique was used to analyze the molecular classification, POLE hypermutation, microsatellite high Instability/mismatch repair dysfunction (MSI-H/MMRd), P53 protein abnormality (P53 abn), and non-specific molecular profile (NSMP). Lynch syndrome related genes and BRCA1/2 genes were detected by NGS and their genetic characteristics were analyzed. Results: Of the 97 EC cases, 77 were endometrial adenocarcinoma and 20 were other pathological subtypes. The proportions of the four molecular subtypes were 9.3% (9/97) POLE hypermutation, 16.5% (16/97) MSI-H, 17.5% (17/97) P53 abn and 56.7% (55/97) NSMP, respectively. There were significant differences in age, histological type, lymph node metastasis, pathological stage and other parameters among the four molecular types (P＜0.05). 8.2% (8/97) were multiple molecular typing and four multiple molecular typings detected, including POLEmut-MSI-H, POLEmut-P53abn, MSI-H-P53abn, P53abn-P53abn, which accounted for 1.0% (1/97), 3.1% (3/97), 1.0% (1/97) and 3.1% (3/97), respectively. The consistent rate of MSI-H and MMR protein expression was 92.9% (Kappa=0.818, P＜0.001). The coincidence rate between TP53 gene sequencing and P53 protein expression was 88.9% (Kappa=0.661, P＜0.001). In MSI-H type, 25.0% (4/16) were diagnosed as Lynch syndrome, and 75.0% (12/16) were diagnosed as Lynch like syndrome. 7.2% (7/97) BRCA2 somatic variation was detected, while BRCA1/2 germline variation was not detected in 97 cases. Conclusions: EC molecular classification has feasibility and clinical value. High throughput sequencing can detect low frequency mutations of TP53 gene, suggesting that it can provide more accurate molecular information and more accurate molecular typing effect. It is suggested to further detect Lynch syndrome related genes in patients with MSI-H, so as to carry out genetic management for patients and their families and achieve better therapeutic effect.

Non-small cell lung cancer(NSCLC) is one of the major histopathological types of lung cancer, accounting for about 85 percent of all lung cancers. The human epidermal growth factor receptor 2 (HER-2) alteration in NSCLC include gene mutations, gene amplifications, and protein overexpression, and is one of the important driving target. Currently, the treatment options for HER-2 altered NSCLC are still relatively limited, and more effective drugs are urgently needed. Antibody-drug conjugates (ADCs) are a highly efficient combination of targeted monoclonal antibodies and cytotoxic drugs that enable precision therapy for tumors. This paper discusses the current status of treating HER-2 variant NSCLC and the research progress of ADCs in HER-2 variant NSCLC, as well as their development prospects in NSCLC.

To investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL) in children.

To investigate the association of NUF2 expression with tumor prognosis and its regulatory role in tumor microenvironment.

To analyze the association of CHMP2B expression level of with clinicopathological characteristics and prognosis of clear cell renal cell carcinoma (CRCC) and the possible role of CHMP2B in tumorigenesis and progression of CRCC.

Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16 (CXCL16) in cancer correlates with poor prognosis, as well as tumor cell proliferation, migration, and invasion. While CXCL16 can serve as a tumor biomarker, the underlying mechanism in modulating head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, the aimed was to investigate the CXCL16 expression in HNSCC and to uncover the potential underlying mechanism. Hereby, we determined the high expression of CXCL16 in The Cancer Genome Atlas (TCGA) database, as well as in tissue samples from patients with HNSCC at our central hospital and from HNSCC cell lines. The results showed that CXCL16 knockdown inhibited the proliferation, migration, and invasion of HNSCC cells. Mechanistically, transcriptome sequencing revealed that CXCL16 may affect HNSCC cell growth by regulating the antioxidant pathway of glutathione peroxidase 1 (GPX1). The reactive oxygen species (ROS) levels were elevated in small interfering CXCL16 (si-CXCL16) cells, which may contribute to the inhibition of cell proliferation, migration, and invasion. Moreover, treatment of cells with the GPX1 inhibitor eldecalcitol (ED-71) revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group. In conclusion, CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway. Thus, targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC.

This study primarily investigated the mechanism of Astragalus polysaccharides(APS), a Chinese medicinal material, in regulating the Nrf2/SLC7A11/GPX4 signaling pathway to induce ferroptosis in ovarian cancer cells(Caov-3 and SKOV3 cells). Caov-3 and SKOV3 cells were divided into control(Vehicle) group, APS group, glutathione peroxidase 4 inhibitor(RSL3) group, and APS+RSL3 group. After 48 h of intervention, the activity and morphology of the cells in each group were observed. The cell counting kit-8(CCK-8) method was used to determine the half-maximal inhibitory concentration(IC_(50)), while colony formation and EdU assays were conducted to assess cell proliferation. Biochemical reagents were used to detect lipid reactive oxygen species(L-ROS), malondialdehyde(MDA), divalent iron ions(Fe~(2+)), and glutathione(GSH) in Caov-3 cells. Transmission electron microscopy was employed to observe the morphological changes of mitochondria in Caov-3 cells. Bioinformatics analysis were used to screen potential target genes of APS in ovarian cancer cells. Western blot and RT-PCR were applied to measure the protein and mRNA expression of Nrf2, SLC7A11, and GPX4. The results revealed that APS effectively inhibited the activity and proliferation of ovarian cancer cells, significantly increased the expression levels of L-ROS, MDA, and Fe~(2+)(P<0.001), and significantly reduced the expression level of GSH(P<0.001). Under electron microscopy, the mitochondria of Caov-3 cells appeared significantly smaller, with a marked increase in the density of the bilayer membrane, disappearance of mitochondrial cristae, and rupture of the outer mitochondrial membrane. These effects were more pronounced when APS was combined with RSL3. Bioinformatics screening identified Nrf2, SLC7A11, and GPX4 as potential target genes for APS in ovarian cancer cells. APS was shown to reduce the protein and mRNA expression of Nrf2, SLC7A11, and GPX4(P<0.01), with the APS+RSL3 showing even more significant effects(P<0.001). In conclusion, APS can induce ferroptosis in ovarian cancer cells, and its mechanism may be related to the regulation of the Nrf2/SLC7A11/GPX4 signaling pathway, providing an experimental basis for the use of APS injections in the treatment of ovarian cancer.

Based on the focal adhesion kinase(FAK)/steroid receptor coactivator(Src)/extracellular regulated protein kinase(ERK) pathway, this study explored the effects of Xihuang Pills on angiogenesis, invasion, and metastasis in prostate cancer. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to analyze and identify the active ingredients of Xihuang Pills. Bioinformatics techniques, including R language and Perl programs, were employed to analyze the interactions between prostate cancer-related targets and the potential targets of Xihuang Pills. A subcutaneous transplantation tumor model of prostate cancer was established in nude mice using PC3 cells to verify the efficacy and molecular mechanisms of Xihuang Pills. In vitro cellular experiments, including cell proliferation assays(CCK-8), Transwell assays, scratch assays, real-time quantitative reverse transcription PCR, and Western blot, were used to detect the effects of Xihuang Pills on the proliferation, invasion, and migration of prostate cancer cells, as well as on FAK/Src/ERK pathway-related targets. LC-MS/MS identified 99 active ingredients in Xihuang Pills, including gallic acid, gentisic acid, artemisinin, corilagin, phenylbutazone-glucoside, thujic acid, and arecoic acid B. Network pharmacological analysis of the active ingredients in Xihuang Pills revealed that the FAK/Src/ERK signaling pathway was a key pathway in its anti-prostate cancer effects. In vivo and in vitro experiments confirmed that Xihuang Pills significantly inhibited the proliferation, invasion, and migration of PC3 and LNCaP cells, suppressed the growth of PC3 subcutaneous tumors, and reduced the protein expression levels related to the FAK/Src/ERK signaling pathway. In conclusion, the inhibition of angiogenesis, invasion, and metastasis by regulating the FAK/Src/ERK pathway is one of the mechanisms by which Xihuang Pills exert anti-prostate cancer effects.

The study investigated the effect of casticin on the proliferation of non-small cell lung cancer(NSCLC) H322 cells and explored its molecular mechanism. Firstly, the cell counting kit-8(CCK-8) assay, colony formation assay, and EdU assay were used to detect the effect of casticin on the proliferation capacity of H322 cells under different concentrations and treatment durations. Then, glucose uptake, lactate production, extracellular pH, and oxygen consumption of H322 cells were measured before and after casticin treatment to analyze its impact on glycolysis in NSCLC H322 cells. Finally, real-time fluorescence quantitative PCR(RT-qPCR) and Western blot assays were performed to explore glycolysis-related molecules affected by casticin. The experiments showed that casticin inhibited the proliferation of NSCLC H322 cells in a dose-and time-dependent manner, with half-maximal inhibitory concentrations(IC_(50)) of 28.64 and 19.41 μmol·L~(-1) after 48 and 72 hours of treatment, respectively. Casticin also inhibited glucose uptake and lactate production in H322 cells, while increasing extracellular pH and oxygen consumption. Further investigation revealed that casticin inhibited the expression of glycolysis-related molecules, including glucose transporter 1(GLUT1), hexokinase 2(HK2), aldolase A(ALDOA), pyruvate kinase M2(PKM2), and hypoxia-inducible factor-1α(HIF-1α). Overexpression of HIF-1α was found to reverse the inhibitory effects of casticin on H322 cell proliferation and glycolysis. These findings suggest that casticin may regulate cellular glycolysis by inhibiting the expression of HIF-1α, thereby inhibiting the proliferation of NSCLC H322 cells. This study identifies a potential drug for the treatment of NSCLC and provides a direction for further research.

This study aims to investigate the mechanism of tanshinone Ⅱ_A(Tan Ⅱ_A) in protecting mice from diethylinitrosamine(DEN)/carbon tetrachloride(CCl_4)/ethanol(C_2H_5OH)-induced hepatocellular carcinoma(HCC) and HepG2 cells from hydrogen peroxide(H_2O_2)-induced oxidative damage via the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) and nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) signaling pathways. Sixty male C57BL/6J mice were grouped as follows: control, model, low, medium, and high-dose(10, 20, 40 mg·kg~(-1), respectively) Tan Ⅱ_A, and colchicine(0.2 mg·kg~(-1)), with 10 mice in each group. The HCC model was established with DEN/CCl_4/C_2H_5OH for 20 weeks, and the mice were then euthanized for collection of blood and liver specimens. A protein-protein interaction(PPI) network of the targets of Tan Ⅱ_A in the prevention of HCC was constructed. HepG2 cells were treated with 150 μmol·L~(-1) H_2O_2 for the modeling of oxidative stress. The cell counting kit-8(CCK-8) was used to assess the effects of different concentrations(1, 2, 4 μmol·L~(-1)) of Tan Ⅱ_A on the relative viability of cells. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the liver tissue, and an automatic biochemical analyzer was used to measure the levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the mice serum. Relevant assay kits were used to measure the levels of reactive oxygen species(ROS), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), and glutathione peroxidase(GSH-Px) in the liver and cells. Immunohistochemistry, immunofluorescence assay, and Western blot were employed to determine the expression of phosphorylated PI3K(p-PI3K), PI3K, phosphorylated Akt(p-Akt), Akt, Nrf2, and HO-1. Compared with the control group, the model group exhibited typical pathological manifestations of liver cancer in the liver tissue, with elevated levels of ALT and AST in the serum, risen levels of ROS and MDA in the liver, and lowered levels of SOD and GSH in the liver. Compared with the control group, the HepG2 cells treated with H_2O_2 showed significantly decreased activities of SOD and GSH-Px and increased ROS and MDA levels. In the liver tissue and HepG2 cells, the modeling up-regulated the expression of p-PI3K and p-Akt while down-regulating the expression of Nrf2 and HO-1. Compared with the model group, different doses of Tan Ⅱ_A reduced the levels of ALT and AST in the serum, elevated the levels of SOD, GSH, and GSH-Px in the liver tissue and cells, and lowered the ROS and MDA levels, which indicated significant alleviation of oxidative stress. The PPI network showed that Akt was a core target of the PI3K/Akt and Nrf2/HO-1 signaling pathways. Western blot, immunohistochemistry, and immunofluorescence assay results indicated that Tan Ⅱ_A promoted the expression of Nrf2 and HO-1 while inhibiting the phosphorylation of PI3K and Akt. In conclusion, Tan Ⅱ_A may delay the progression of HCC by inhibiting oxidative stress via the PI3K/Akt and Nrf2/HO-1 signaling pathways.

With the rapid development of epidermal growth factor receptor (EGFR) gene testing of lung adenocarcinoma patients has been routinely carried out, EGFR mutations are also possible for some small samples of non-smoking female lung squamous cell carcinoma patients. This increases the opportunity for targeted therapy for this group of patients. However, drug resistance in patients with lung squamous cell carcinoma during targeted therapy is an important factor affecting subsequent treatment. There are multiple mechanisms of acquired drug resistance in targeted therapy, and the alteration of mesenchymal-epithelial transition factor (MET) signaling pathway is one of the common mechanisms of drug resistance. At present, some selective tyrosine kinase inhibitors (TKIs) of MET has been approved for non-small cell lung cancer with MET gene 14 exon skipping mutation, such as Glumetinib, Savolitinib, Tepotinib, Capmatinib, etc. Drugs that target secondary MET amplification are still in clinical trials. This paper retrospectively analyzed the clinical data of a female patient with EGFR-TKIs resistant secondary MET amplified squamous cell lung cancer, and reviewed relevant literature to explore how to optimize the treatment of lung squamous cell carcinoma patients with EGFR mutation, so as to provide clinical reference for the diagnosis and treatment of such patients.
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Mesenchymal-epithelial transition factor (MET) gene mutation is a large class of mutations commonly seen in non-small cell lung cancer (NSCLC). MET mutation includes subtypes such as MET exon 14 skipping mutation (METex14m) and MET amplification (METamp). For advanced NSCLC with METex14m, Savolitinib has a high sensitivity as a member of tyrosine kinase inhibitors (TKIs). METamp is a relatively rare genetic mutation type which can serve as a driver gene to mediate primary and later acquired drug resistance of epidermal growth factor receptor (EGFR)-TKIs. For advanced NSCLC with secondary METamp, EGFR-TKIs combined with MET-TKIs are usually used in clinical treatment, while the optimal treatment strategy for advanced NSCLC with primary METamp has not yet been determined. For locally advanced NSCLC patients with positive driver gene mutations such as EGFR, anaplastic lymphoma kinase (ALK) fusion and METex14m, there have been relevant cases reported that neoadjuvant targeted therapy could achieve a good prognosis, but there have been no cases of neoadjuvant targeted therapy for locally advanced NSCLC patients with METamp. This report describes a case of a locally advanced NSCLC patient with dual driver gene mutations (EGFR L858R combined with primary METamp), the tumor did not shrink after 1 month of Gefitinib monotherapy, but significantly subsided after 4 months of Savolitinib monotherapy. After radical surgery, the pathological results proved pathological complete response (pCR) of the tumor, and the patient had a good response to postoperative continual Savolitinib treatment, with no recurrence nor metastasis observed to date. This case reports the feasibility and effectiveness of neoadjuvant targeted therapy for locally advanced NSCLC with primary METamp, aiming to provide effective reference for perioperative treatment of locally advanced NSCLC with primary METamp.
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Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer-related death worldwide, with anaplastic lymphoma kinase (ALK) fusion mutations accounting for approximately 4%-9% of cases. In recent years, there are increasing clinical evidences suggesting that the combination of ALK inhibitors with surgical treatment holds significant potential for clinical application in resectable early and locally advanced non-small cell lung cancer (NSCLC) patients. This review aims to summarize the advances in neoadjuvant targeted therapy for ALK fusion positive NSCLC and discuss its advantages and challenges in clinical practice.
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Lung cancer is one of the malignant tumors with the highest morbidity and mortality rates worldwide, seriously threatening human health. Non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancer cases. STMN1 is a microtubule depolymerizing protein widely present in the cytoplasm and its expression level is associated with the prognosis of NSCLC patients. Through meta-analysis, this study aimed to investigate the predictive value of the expression level of STMN1 for the prognosis of lung cancer and screen for tumor markers with high sensitivity and specificity to optimize the whole-process management of lung cancer patients.

Mutations in the structural domain of the epidermal growth factor receptor (EGFR) kinase represent a critical pathogenetic factor in non-small cell lung cancer (NSCLC). Small-molecule EGFR-tyrosine kinase inhibitors (TKIs) serve as first-line therapeutic agents for the treatment of EGFR-mutated NSCLC. But the resistance mutations of EGFR restrict the clinical application of EGFR-TKIs. In this study, we constructed a clinically relevant PC-9 EGFRD19/T790M/C797S cellular model featuring the mutation type within the EGFRD19/T790M/C797S. This model aims to investigate the inhibitory effects of small-molecule EGFR-TKIs and to provide a cellular platform for developing a new generation of innovative drugs that target resistance associated with EGFR mutations.

The early stages of tumor bone metastasis are closely associated with changes in the vascular niche of the bone microenvironment, and abnormal angiogenesis accelerates tumor metastasis and progression. However, the effects of lung adenocarcinoma (LUAD) cells reprogrammed by the bone microenvironment on the vascular niche within the bone microenvironment and the underlying mechanisms remain unclear. This study investigates the effects and mechanisms of LUAD cells reprogrammed by the bone microenvironment on endothelial cells and angiogenesis, providing insights into the influence of tumor cells on the vascular niche within the bone microenvironment.

B and T lymphocyte attenuator (BTLA) is an inhibitory immune checkpoint, which typically interacts with herpesvirus entry mediator (HVEM) and plays a crucial role in regulating immune balance. BTLA interacts with its ligand HVEM in a cis manner on the surface of the same immune cell to maintain immune tolerance, while trans interactions on the surface of different immune cells mediate immunosuppressive effects. Dysregulation of the BTLA/HVEM axis can impair the functions of immune cells, particularly T lymphocytes, promoting immune escape of tumor cells and ultimately leading to tumor progression. Researchers have found that BTLA and HVEM are abnormally expressed in various tumors and are associated with prognosis, suggesting that they may be potential targets for tumor immunotherapy. This review summarizes the molecular structures of BTLA and HVEM, immunomodulatory mechanisms, recent advances in hematologic malignancies, potential inhibitors of BTLA/HVEM interaction, and their applications in immunotherapy for hematologic malignancies.

Objective To investigate the effect of basic helix-loop-helix family member E40 (BHLHE40) on the invasion and migration of osteosarcoma (OS) cells, and to explore the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the biological behavior of OS mediated by BHLHE40, providing a scientific basis for targeted therapy of OS. Methods On the basis of clinical OS samples and OS cell lines, the expression differences of BHLHE40 between OS and adjacent tissues, as well as those between OS cells and normal osteoblast cell lines, were analyzed. BHLHE40 knockdown OS cells were obtained through shRNA transfection. The effects of BHLHE40 on OS cell proliferation, migration, and invasion were examined using CCK-8, EdU staining, wound healing, and Transwell assays. The involvement of the PI3K/AKT signaling pathway was assessed by Western blotting. Further validation was conducted in vivo experiments. Results The expression of BHLHE40 was significantly higher in OS tissues compared to adjacent tissues. In OS cell lines, BHLHE40 protein expression levels were increased compared to normal osteoblasts, and the cell line with the highest BHLHE40 expression was selected for subsequent knockdown experiments. Compared with the knockdown control group, the BHLHE40 knockdown group exhibited reduced cell viability, EdU-positive cell count, colony number, cell migration, and invasion abilities, along with downregulation of phosphorylated PI3K(p-PI3K)/PI3K and p-AKT/AKT protein expression. The aforementioned functions of BHLHE40 were also reproduced in in vivo experiments. Conclusion BHLHE40 is highly expressed in OS tissues, and its knockdown can significantly inhibit OS cell proliferation, migration, and invasion, while reducing PI3K/AKT signaling pathway activity. This suggests that BHLHE40 could serve as a novel therapeutic target for OS.