Background: The sinus tarsi syndrome (STS) is a common foot and ankle disease with controversial pathogenesis and treatment procedures. This long-term study aimed to analyze the effect of a staged surgical strategy for STS.
The small, heavily glycosylated protein CD24 is primarily expressed by many immune cells and is highly expressed mostly in cancer cells. As one of the most crucial biomarkers of cancers, CD24 is frequently highly expressed in solid tumors, while tumor-associated macrophages express Siglec-10 at high levels, Siglec-10 and CD24 can interact on innate immune cells to lessen inflammatory responses to a variety of disorders. Inhibiting inflammation brought on by SHP-1 and/or SHP-2 phosphatases as well as cell phagocytosis by macrophages, the binding of CD24 to Siglec-10 can prevent toll-like receptor-mediated inflammation. Targeted immunotherapy with immune checkpoint inhibitors (ICI) has lately gained popularity as one of the best ways to treat different tumors. CD24 is a prominent innate immune checkpoint that may be a useful target for cancer immunotherapy. In recent years, numerous CD24/Siglec-10-related research studies have made tremendous progress. This study discusses the characteristics and workings of CD24/Siglec-10-targeted immunotherapy and offers a summary of current advances in CD24/Siglec-10-related immunotherapy research for cancer. We then suggested potential directions for CD24-targeted immunotherapy, basing our speculation mostly on the results of recent preclinical and clinical trials.
Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC. Methods: Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by using in vitro and in vivo experiments. Immunoprecipitation and in vivo ubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14. Results: Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results of in vitro and in vivo assays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer. Conclusion: Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.
Abstract Background Only few studies have been evaluated the clinical characteristics and prognosis of hepatocellular carcinoma in young patients. The purpose of this study is to identify prognostic factors and develop an efficient and practical nomogram to predict cancer-specific survival in young patients with hepatocellular carcinoma. Methods Four-hundred-and-forty-one young patients with hepatocellular carcinoma who had undergone surgery from 2004-2015 were selected from the Surveillance, Epidemiology, and End Results database. The competing risk model, Lasso and Cox regression were used to screen prognostic factors for cancer-specific survival, and a prognostic nomogram was established using these factors. Thirty-nine young patients with hepatocellular carcinoma from the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Science were used to validate our model. To further evaluate the predictive performance of our model, the concordance index was calculated and the calibration curves were drawn. The clinical usefulness was evaluated by decision curve analysis(DCA). Finally, all patients were grouped by our nomogram. The survival of different risk groups was analyzed using the Kaplan-Meier method, and the differences among survival curves were compared by the log-rank test. Results The median survival times of the Surveillance, Epidemiology, and End Results training group and the external National Cancer Center validation group were 41 and 52 months, respectively. Histological grade, tumor size, Alpha-fetoprotein, T stage, and M stage were selected as independent factors for cancer-specific survival, and a prognostic nomogram was established. The concordance indices of the training and external validation groups were 0.76 (95% CI, 0.72 to 0.80) and 0.92 (se=0.085), respectively. The calibration plots showed good agreement. Decision curve analysis revealed that our nomogram resulted in a better clinical net benefit than the AJCC 7th edition and Barcelona Clinic Liver Cancer staging systems. Patients were divided into two risk groups according to the cut-off value of 125 of the total points from our nomogram. Kaplan-Meier plots for cancer-specific survival were performed using the log-rank test, the p-value of which was <0.001. Conclusions The practical nomogram resulted in a more-accurate prognostic prediction for young hepatocellular carcinoma patients after curative liver resection.
Abstract Diabetes is closely related to the occurrence of endometrial cancer (EC) and its poor prognosis. However, there is no effective clinical treatment for EC patients with diabetes (patient EC+/dia+ ). To explore new therapeutic targets, Ishikawa is cultured with high glucose (Ishikawa HG ) mimicking hyperglycemia in patient EC+/dia+ . Subsequently, it is discovered that Ishikawa HG exhibits glucose metabolic reprogramming characterized by increased glycolysis and decreased oxidative phosphorylation. Further, pyruvate dehydrogenase kinase 1 (PDK1) is identified to promote glycolysis of Ishikawa HG by proteomics. Most importantly, JX06, a novel PDK1 inhibitor combined metformin (Met) significantly inhibits Ishikawa HG proliferation though Ishikawa HG is resistant to Met. Furthermore, a reduction‐sensitive biodegradable polymer is adopted to encapsulate JX06 to form nanoparticles (JX06‐NPs) for drug delivery. It is found that in vitro JX06‐NPs have better inhibitory effect on the growth of Ishikawa HG as well as patient‐derived EC cells (PDC) than JX06. Additionally, it is found that JX06‐NPs can accumulate to the tumor of EC‐bearing mouse with diabetes (mice EC+/dia+ ) after intravenous injection, and JX06‐NPs combined Met can significantly inhibit tumor growth of mice EC+/dia+ . Taken together, the study demonstrates that the combination of JX06‐NPs and Met can target the cancer metabolism plasticity, which significantly inhibits the growth of EC, thereby provides a new adjuvant therapy for patients EC+/dia+ .
Abstract Background Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. Methods We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. Results Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828–0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05). Conclusion We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment.
Abstract Background: Glycolysis is the primary mechanism of energy metabolism in tumor cells. The purpose of this study is to develop a glycolysis-related risk signature for endometrial cancer and analyze its relationship with immune function. Methods: The mRNA expression profiling and clinical information of endometrial cancer were downloaded from TCGA database. GSEA was performed to screen out gene sets related to glycolysis, and the R software was used to screen DEGs. Univariate Cox and LASSO regression analyses were used to construct a glycolysis-related prognostic signature for endometrial cancer. WGCNA were performed to identify the potential mechanisms associated with the prognostic signature. Immune scores, stromal scores and ESTIMATE scores were calculated based on the R “ESTIMATE” algorithm. The “CIBERSORT” algorithm was used to evaluate the infiltration of immune cells. ROC curve, nomogram, gene alteration, coexpression analyses and PPIs were also performed. Results: We identified a glycolysis-related gene signature (PFKM, PSMC4, NUP85, PDHA1, CDK1, CLDN9, CENPA, GPI, NUP155 and GPCI) for predicting the prognosis of endometrial cancer. Based on this gene signature, the patients were divided into high- and low-risk subgroups. The overall survival of patients in the high-risk subgroup was significantly lower than that of the low-risk group. Multivariate Cox regression analysis results showed that the ten-gene signature was an independent prognostic factor for endometrial cancer. The ROC curve confirmed the accuracy of the prognostic signature (AUC=0.730). The immune scores and ESTIMATE scores of patients in the high-risk subgroup were lower than those of the low-risk subgroup, while the low immune score and ESTIMATE scores were closely related to the poor prognosis of patients. The high-risk group was associated with lower cellular immune infiltration of resting dendritic cells, resting memory T cells and Tregs, while the overall survival rate of resting dendritic cells and Tregs in the low-proportion group was significantly lower than that in the high-proportion group. Conclusions: we constructed a glycolysis-related ten-gene signature to predict the survival and prognosis of endometrial cancer. Our findings may help to elucidate the mechanism of glycolysis and provide new ideas for targeted therapy and prognosis of endometrial cancer.
Objective The International Federation of Gynecology and Obstetrics (FIGO) released a new staging for endometrial cancer (EC), which revised the FIGO2009 staging to include histopathological and molecular features. The purpose of this study was to validate the prognostic accuracy of the new staging and discuss its clinical applicability. Methods In this single-centre retrospective study, 540 patients with primary surgically treated early-stage EC were enrolled and staged according to FIGO2009/2023. Kaplan-Meier survival analysis was used to compare for prognostic differentiation. Cox regression was used to identify potential prognostic indicators. Results A total of 81 patients underwent staging shifts, all stage elevation. The prognosis difference between new stages I and II was more significant. The new staging was more predictive of death postoperatively. Lesion maximum diameter (LMD) was one of the independent risk factors associated with prognosis. Taking LMD=5.70 cm as the cut-off value could further differentiate patients with divergent prognoses within FIGO2023 stage IIC. Conclusion FIGO2023 staging demonstrated greater prognostic accuracy. In addition, LMD may be another critical factor affecting prognosis.
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