Objective: To investigate the value of multimodal ultrasound imaging indicators in evaluating the efficacy of neoadjuvant chemotherapy for breast cancer, and to establish a multivariate Logistic regression model for evaluating neoadjuvant chemotherapy for breast cancer. Methods: A retrospective analysis of 38 breast cancer patients who underwent surgery after neoadjuvant chemotherapy was divided into pathologically ineffective (NMHR) and pathologically effective (MHR) according to Miller & Payne grading method. The image characteristics of conventional ultrasound, elastography, and contrast-enhanced ultrasound parameters were compared between the two groups. Univariate and multivariate Logistic analyses were used to analyze factors affecting the efficacy of neoadjuvant chemotherapy. The receiver operating curve (ROC) of each factor was drawn, and the area under the ROC curve and evaluation indicators such as sensitivity and specificity were calculated. Results: After neoadjuvant chemotherapy in the effective group (MHR), the tumor's longest diameter reduction rate (ΔD), morphology, margin, posterior echo attenuation, calcification, resistance index (RI), peak systole velocity (peak systole velocity, PSV), strain ratio (SR), elasticity score, peak intensity (PI) and time to peak (TTP) were the factors affecting the efficacy of neoadjuvant chemotherapy (P<0.05). The factor Logistic regression model showed that the longest tumor diameter reduction rate, PSV, SR, PI, TTP were reliable factors for the efficacy of neoadjuvant chemotherapy in breast cancer. The area under the ROC curve of the multivariate logistic regression model was 0.911, and the sensitivity and specificity were 94.7% and 68.4%, respectively, which had higher accuracy than the single-factor model. Conclusion: The multivariate regression model of multimodal ultrasound imaging technology can evaluate the efficacy of neoadjuvant chemotherapy and improve the diagnostic coincidence rate and efficacy.
N6-methyladenosine (m6A) modifications are the most abundant internal modifications of mRNA and have a significant role in various cancers; however, the m6A methylome profile of oral squamous cell carcinoma (OSCC) in the mRNA-wide remains unknown. In this study, we examined the relationship between m6A and OSCC. Four pairs of OSCC and adjacent normal tissues were compared by Methylated RNA immunoprecipitation sequencing (MeRIP-seq). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) analyses were used to further analyze the MeRIP-seq data. A total of 2,348 different m6A peaks were identified in the OSCC group, including 85 m6A upregulated peaks and 2,263 m6A downregulated peaks. Differentially methylated m6A binding sites were enriched in the coding sequence in proximity to the stop codon of both groups. KEGG analysis revealed genes with upregulated m6A-modified sites in the OSCC group, which were prominently associated with the forkhead box O (FOXO) signaling pathway. Genes containing downregulated m6A-modified sites were significantly correlated with the PI3K/Akt signaling pathway, spliceosome, protein processing in the endoplasmic reticulum, and endocytosis. IPA analysis indicated that several genes with differential methylation peaks form networks with m6A regulators. Overall, this study established the mRNA-wide m6A map for human OSCC and indicated the potential links between OSCC and N6-methyladenosine modification.
Aberrant expression of transcription factor AP-2α has been functionally associated with various cancers, but its clinical significance and molecular mechanisms in human glioma are largely elusive. Methods: AP-2α expression was analyzed in human glioma tissues by immunohistochemistry (IHC) and in glioma cell lines by Western blot. The effects of AP-2α on glioma cell proliferation, migration, invasion and tumor formation were evaluated by the 3-(4,5-dimethyNCthiazol-2-yl)-25-diphenyltetrazolium bromide (MTT) and transwell assays in vitro and in nude mouse models in vivo. The influence of AP-2α on glioma cell stemness was analyzed by sphere-formation, self-renewal and limiting dilution assays in vitro and in intracranial mouse models in vivo. The effects of AP-2α on temozolomide (TMZ) resistance were detected by the MTT assay, cell apoptosis, real-time PCR analysis, western blotting and mouse experiments. The correlation between AP-2α expression and the expression of miR-26a, Nanog was determined by luciferase reporter assays, electrophoretic mobility shift assay (EMSA) and expression analysis. Results: AP-2α expression was downregulated in 58.5% of glioma tissues and in 4 glioma cell lines. AP-2α overexpression not only reduced the proliferation, migration and invasion of glioma cell lines but also suppressed the sphere-formation and self-renewal abilities of glioma stem cells in vitro. Moreover, AP-2α overexpression inhibited subcutaneous and intracranial xenograft tumor growth in vivo. Furthermore, AP-2α enhanced the sensitivity of glioma cells to TMZ. Finally, AP-2α directly bound to the regulatory region of the Nanog gene, reduced Nanog, Sox2 and CD133 expression. Meanwhile, AP-2α indirectly downregulated Nanog expression by inhibiting the interleukin 6/janus kinase 2/signal transducer and activator of transcription 3 (IL6/JAK2/STAT3) signaling pathway, consequently decreasing O6-methylguanine methyltransferase (MGMT) and programmed death-ligand 1 (PD-L1) expression. In addition, miR-26a decreased AP-2α expression by binding to the 3' untranslated region (UTR) of AP-2α and reversed the tumor suppressive role of AP-2α in glioma, which was rescued by a miR-26a inhibitor. TMZ and the miR-26a inhibitor synergistically suppressed intracranial GSC growth. Conclusion: These results suggest that AP-2α reduces the stemness and TMZ resistance of glioma by inhibiting the Nanog/Sox2/CD133 axis and IL6/STAT3 signaling pathways. Therefore, AP-2α and miR-26a inhibition might represent a new target for developing new therapeutic strategies in TMZ resistance and recurrent glioma patients.
Polyaluminocarbosilanes(PACS)with different Al contents were synthesized by reacting liquid polycarbosilane(LPCS)with aluminum acetylacetonate[Al(AcAc)3].Compared with those reported in literatures,this route is considered to be more convenient and safer since no circulating reflux is needed.It was shown that the composition and structure of LPCS heated and kept at the synthesis temperature of PACS remained fairly stable.The chemical elemental analysis results of PACS indicated that through this route the Al contents were almost fully introduced into PACS from Al(AcAc)3,and with the increasing of Al contents,the O contents also increased.Furthermore,the formation of AlO4,AlO5 and AlO6 was confirmed by 27Al MAS NMR results.On the base of the structure analysis it was suggested that LPCS reacted with Al(AcAc)3 by consuming Si_H bonds.Then Si_O_Al crosslinking bonds were formed,leading to the increases of the number average molecular weight and the polydispersion index in molecular weight with the increase of Al contents in PACS.
Objective Tristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes. Methods Eighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR). Results Serum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05). Conclusion These results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.
Purpose This study aims to evaluate the efficacy of immune checkpoint inhibitors (ICIs) combined with concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with locally advanced esophageal squamous cell carcinoma. Materials and methods This retrospective cohort study included patients diagnosed with locally advanced esophageal squamous cell carcinoma who received either CCRT alone or CCRT combined with ICIs from April 2019 to February 2023. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS). Results A total of 101 patients were enrolled, with 58 undergoing CCRT alone and 43 receiving CCRT+ICI. The CCRT+ICI group demonstrated a higher complete response rate compared to the CCRT alone group (11.6% vs. 1.7%, P = 0.037). However, no significant difference was observed in 1-year PFS (58.9% vs. 55.2%; hazard ratio [HR] = 1.26, 95% confidence interval [CI]: 0.70-2.26; P = 0.445) or 1-year OS (70.8% vs. 75.9%; HR = 1.21, 95% CI: 0.58-2.53; P = 0.613) between CCRT+ICI and CCRT alone groups. The CCRT alone group experienced a higher incidence of leukopenia of any grade (93.1% vs. 76.7%, P = 0.039) but a lower incidence of pneumonitis of any grade (36.2% vs. 65.1%, P = 0.008). Conclusion CCRT+ICI may not lead to improved survival outcomes compared to CCRT alone in patients with locally advanced esophageal squamous cell carcinoma. These findings indicate the need for further investigation into this treatment approach.
Poly(ethylene glycol) (PEG) is applied extensively in biomedical fields because of its nontoxic, nonimmunogenic, and protein resistance properties. However, the strong hydrophilicity of PEG prevents it from self-assembling into an amphiphilic micelle in water, making it a challenge to fabricate a full-PEG carrier to deliver hydrophobic anticancer drugs. Herein, a paclitaxel (PTX)-loaded nanodrug was readily prepared through self-assembly of PTX and an amphiphilic PEG derivative, which was synthesized via melt polycondensation of two PEG diols (i.e., PEG200 and PEG10k) and mercaptosuccinic acid. The full PEG component endows the nanocarrier with good biocompatibility. Furthermore, because of the core cross-linked structure via the oxidation of mercapto groups, the nanodrug can be selectively disassociated under an intratumor reductive microenvironment through the reduction of disulfide bonds to release the loaded PTX and kill the cancer cells while maintaining high stability under the extratumor physiological condition. Additionally, it was confirmed that the nanodrug not only prolongs the biocirculation time of PTX but also possesses excellent in vivo antitumor efficacy while avoiding side effects of free PTX, for example, liver damage, which is promising for delivering clinical hydrophobic drugs to treat a variety of malignant tumors.
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