Multiscale network analysis reveals molecular mechanisms and key regulators of the tumor microenvironment in gastric cancer.

Gastric cancer (GC) is the third leading cause of cancer deaths and the fourth most prevalent malignancy worldwide. The high incidence and mortality rates of gastric cancer result from multiple factors such as ineffective screening, diagnosis, and limited treatment options. In our study, we sought to systematically identify predictive molecular networks and key regulators to elucidate complex interacting signaling pathways in GC. We performed an integrative network analysis of the transcriptomic data in The Cancer Genome Atlas (TCGA) gastric cancer cohort and then comprehensively characterized the predictive subnetworks and key regulators by the matched genetic and epigenetic data. We identified 221 gene subnetworks (modules) in GC. The most prognostic subnetworks captured multiple aspects of the tumor microenvironment in GC involving interactions among stromal, epithelial and immune cells. We revealed the genetic and epigenetic underpinnings of those subnetworks and their key transcriptional regulators. We computationally predicted and experimentally validated specific mechanisms of anticancer effects of GKN2 in gastric cancer proliferation and invasion in vitro. The network models and the key regulators of the tumor microenvironment in GC identified here pave a way for developing novel therapeutic strategies for GC.

Nomogram to Predict Overall Survival for Thoracic Esophageal Squamous Cell Carcinoma Patients After Radical Esophagectomy.

BACKGROUND: Effective tools evaluating the prognosis for patients with esophageal cancer undergoing surgery is lacking. The current study aimed to develop a nomogram to predict overall survival (OS) and provide evidence for adjuvant therapy for patients with esophageal carcinoma after esophagectomy. METHODS: The study retrospectively reviewed patients with pathologic T1N +/T2-4aN0-3, M0 thoracic esophageal squamous cell carcinoma after radical esophagectomy, with or without adjuvant therapy, in one institution as the training cohort (n = 2281). A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS, which were validated in an independent validation cohort (n = 1437). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate prognostic efficacy. RESULTS: In the training cohort, the median OS was 50.46 months, and the 5-year OS rate was 47.08%. Adjuvant therapy, sex, tumor location, grade, lymphovascular invasion, removed lymph nodes, and T and N categories were identified as predictive factors for OS. The nomogram showed favorable prognostic efficacy in the training and validation cohorts (5-year OS AUC: 0.685 and 0.744, respectively), which was significantly higher than that of the American Joint Committee on Cancer (AJCC) staging system. The nomogram distinguished OS rates among six risk groups, whereas AJCC could not separate the OS of 2A and 1B, 3C and 3B, or 3A and 2B. Patients with a nomogram score of 72 to 227 were predicted to achieve a 5-year OS increase of 10% or more from adjuvant therapy. CONCLUSION: The nomogram could effectively predict OS and aided decision making in adjuvant therapy for patients with thoracic esophageal squamous cell carcinoma after esophagectomy.

Prediction of three lipid derivatives for postoperative gastric cancer mortality: the Fujian prospective investigation of cancer (FIESTA) study.

BACKGROUND: As we previously reported, the presence of preoperative metabolic syndrome can predict the significant risk of gastric cancer mortality. As a further extension, we evaluated the prediction of three lipid derivatives generated from triglycerides (TG), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDLC and LDLC) at baseline for postoperative gastric cancer mortality by prospectively analysing 3012 patients. The three lipid derivatives included the ratio of TC minus HDLC to HDLC known as atherogenic index (AI), the ratio of TG to HDLC abbreviated as THR and the ratio of LDLC to HDLC abbreviated as LHR. METHODS: Gastric cancer patients who received gastrectomy between January 2000 and December 2010 were consecutively recruited from Fujian Cancer Hospital. Follow-up assessment was implemented annually before December 2015. RESULTS: Finally, there were 1331 deaths from gastric cancer and 1681 survivors, with a median follow-up time of 44.05 months. 3012 patients were evenly randomized into the derivation group and the validation group, and both groups were well balanced at baseline. Overall adjusted estimates in the derivation group were statistically significant for three lipid derivatives (hazard ratio [HR]: 1.20, 1.17 and 1.19 for AI, THR and LHR, respectively, all P < 0.001), and were reproducible in the validation group. The risk prediction of three lipid derivatives was more obvious in males than females, in patients with tumor-node-metastasis stage I-II than stage III-IV, in patients with intestinal-type than diffuse-type gastric cancer, in patients with normal weight than obesity, and in patients without hypertension than with hypertension, especially for AI and LHR, and all results were reproducible. Calibration and discrimination statistics showed good reclassification performance and predictive accuracy when separately adding three lipid derivatives to baseline risk model. A prognostic nomogram was accordingly built based on significant attributes to facilitate risk assessment, with a good prediction capability. CONCLUSIONS: Our results indicate that preoperative lipid derivatives, especially AI and LHR, are powerful predictors of postoperative gastric cancer mortality, with more obvious prediction in patients of male gender or with tumor-node-metastasis stage I-II or intestinal-type gastric cancer, and in the absence of obesity or hypertension before gastrectomy.

Geometric Accuracy Evaluation of High-Resolution Satellite Images Based on Xianning Test Field.

The evaluation of geometric accuracy of high-resolution satellite images (HRSIs) has been increasingly recognized in recent years. The traditional approach is to verify each satellite individually. It is difficult to directly compare the difference in their accuracy. In order to evaluate geometric accuracy for multiple satellite images based on the same ground control benchmark, a reliable test field in Xianning (China) was utilized for geometric accuracy validation of HRSIs. Our research team has obtained multiple HRSIs in the Xianning test field, such as SPOT-6, Pleaides, ALOS, ZY-3 and TH-1. In addition, ground control points (GCPs) were acquired with GPS by field surveying, which were used to select the significant feature area on the images. We assess the orientation accuracy of the HRSIs with the single image and stereo models. Within this study, the geometrical performance of multiple HRSIs was analyzed in detail, and the results of orientation are shown and discussed. As a result, it is feasible and necessary to establish such a geometric verification field to evaluate the geometric quality of multiple HRSIs.

Preoperative metabolic syndrome and prognosis after radical resection for colorectal cancer: The Fujian prospective investigation of cancer (FIESTA) study.

This prospective study sought to investigate the prediction of preoperative metabolic syndrome and its components for the risk of colorectal cancer (CRC) mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. In total, 1,318 CRC patients who received radical resection were consecutively enrolled between January 2000 and December 2008. The median follow-up time was 58.6 months, with 412 deaths from CRC. The CRC patients with metabolic syndrome had significantly shorter median survival time (MST) than those without (50.9 vs. 170.3 months, p < 0.001). Among four components of metabolic syndrome, hyperglycemia was the strongest predictor and its presence was associated with shorter MST than its absence (44.4 vs. 170.3 months, p < 0.001). Moreover, the complication of metabolic syndrome in CRC patients was associated with a 2.98-fold increased risk of CRC mortality (hazard ratio [HR] = 2.98, 95% confidence interval [CI]: 2.40-3.69, p < 0.001) after adjusting for confounding factors. The magnitude of this association was especially potentiated in CRC patients with tumor-node-metastasis stage I/II (HR = 3.94, 95% CI: 2.65-5.85, p < 0.001), invasion depth T1/T2 (HR = 5.41, 95% CI: 2.54-11.50, p < 0.001), regional lymph node metastasis N0 (HR = 4.06, 95% CI: 2.85-5.80, p < 0.001) and negative distant metastasis (HR = 3.23, 95% CI: 2.53-4.12, p < 0.001). Further survival tree analysis reinforced the prognostic capability of fasting blood glucose in CRC survival. Our findings convincingly demonstrated that preoperative metabolic syndrome, especially hyperglycemia, was a robust predictor for CRC mortality, and the protection was more obvious in patients with Stage I/II.

Elevated Preoperative Platelet to Lymphocyte Ratio Indicates Poor Survival in Patients with Resected High-grade Serous Ovarian Carcinoma.

BACKGROUND: Platelet to lymphocyte ratio (PLR) is widely used as an inflammation-related cancer biomarker. However, since its prognostic importance in resected high-grade serous ovarian carcinoma (HGSC) is still unknown, we investigated the association between PLR and the prognosis in resected HGSC in this study. METHODS: Details of 103 patients with HGSC who underwent ovarian resection were collected in this retrospective study. Preoperative PLR was calculated based on platelet and lymphocyte count values. A χ2 test was used to analyze the relationship between PLR and clinical variables, a Kaplan-Meier curve and log rank analysis was used to evaluate overall survival, and multivariable analysis was used to analyze the prognostic factors. RESULTS: The preoperative PLR median value (188.8) was used to divide patients into two groups: the high PLR group (PLR > 188.8) and low PLR group (PLR ≤ 188.8). A high PLR was significantly associated with a higher death rate (81.6% vs. 59.3%, p = 0.013) and a shorter median overall survival time (37 months vs. 58 months, p = 0.035) during follow-up (median length = 43 months). Multivariable data further demonstrated that a high PLR was related to a two-fold increase in risk of death (hazard ratio [HR]: 2.19, 95% confidence interval (CI): 1.30 - 3.68, p = 0.003). In addition, the risk of a CA125 of > 640.0 U/mL was significantly greater in the high PLR group (odds ratio [OR]: 2.72, 95% CI: 1.18 - 6.27, p = 0.019). Multivariable analysis suggests that PLR was an independent prognostic factor for resected HGSC. CONCLUSIONS: PLR has potential as a prognostic biomarker for predicting the survival of patients with resected HGSC.

Stage-dependent changes of preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in colorectal cancer.

This study aims to assess the association of the preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with tumor stage in colorectal cancer (CRC) patients. A retrospective study was performed in 336 CRC patients. Preoperative whole blood counts, serum levels of carcinoembryonic antigen (CEA), and clinicopathologic data were collected. The correlations between laboratory parameters and the tumor, node, and metastasis (TNM) stages were analyzed. The clinicopathologic TNM stages among CRC patients were 12.8 % at stage I, 32.4 % at stage II, 44.6 % at stage III, and 10.1 % at stage IV. NLR, PLR, and CEA levels were higher in CRC patients compared to healthy controls (all P < 0.0001). Both NLR and PLR showed an early elevation as compared to CEA, with a higher area under curve (AUC) value (0.71 vs. 0.62) in predicting the presence of the tumor with stage I/II. Accordingly, significant elevations of NLR (P = 0.0018) and PLR (P < 0.0001) were firstly detected in stage I and stage II, respectively. In addition, NLR exhibited a second phase elevation in stage IV, with a significant higher level in M1 subgroup compared to M0 subgroup (P = 0.022). While PLR showed a T stage-dependent increase (P = 0.0003) and was identified as an independent factor for the T grade development (P < 0.0001). Our data indicated that both neutrophil- and platelet-mediated inflammatory reactions are predominantly involved in the different stages of CRC development. Determination of pretreatment levels of NLR and PLR might provide useful information for the early diagnosis or the therapeutic choices in CRC patients.

Cervical lymph node metastasis classified as regional nodal staging in thoracic esophageal squamous cell carcinoma after radical esophagectomy and three-field lymph node dissection.

BACKGROUND: Lymph node metastasis (LNM) is most common in esophageal squamous cell carcinoma (SCC). The bi-directional spread is a key feature of LNM in patients with thoracic esophageal SCC (TE-SCC). The purpose of this study was to analyze the prognostic factors of survival in patients with TE-SCC with cervical lymph node metastasis (CLM) and validate the staging system of the current American Joint Committee on Cancer (AJCC) in a cohort of Chinese patients. METHODS: Of 1715 patients with TE-SCC who underwent radical esophagectomy plus three-field lymph node dissection at a single hospital between January 1993 and March 2007, 547 patients who had pathologically confirmed CLM (296 had surgery only and 251 had surgery + postoperative radiotherapy) were included in this study. The locations of the lymph nodes (LNs) were classified based on the guidelines of the Japanese Society for Esophageal Diseases. RESULTS: The rate of CLM was 31.9% for all patients and was 44.2%, 31.5%, and 14.4% for patients with upper, middle, and lower TE-SCC, respectively (P < 0.0001). The rates of metastasis to 101 (paraesophageal lymph nodes), 104 (supraclavicular lymph nodes), 102 (deep cervical lymph nodes) and 103 (retropharyngeal lymph nodes) areas were 89.0%, 25.6%, 3.7% and 0.5%, respectively. The 5-year overall survival (OS) rate with CLM was 27.7% (median survival, 27.5 months). The 5-year OS rates were 21.3% versus 34.2% (median survival, 21.9 months versus 35.4 months) for after surgery only versus surgery + postoperative radiotherapy, respectively (P < 0.0001 for both). Multivariate analysis showed that the independent prognostic factors for survival were sex, pT stage, pN stage, number of fields with positive LNs, and treatment modality. In surgery only group, the 5-year OS rates were 24.1%, 16.2% and 11.7%, respectively, when there was metastasis to 101 LN alone, 104 LN alone or both 101 LN and 104 LN. The 5-year OS rates were 17.7%, 22.5% and 31.7%, for patients with upper, middle and lower TE-SCC , respectively (P = 0.112). The 5-year OS rates were 43.0%, 25.5%, 10.2% in patients with 1 field (cervical LNs), 2 fields (cervical + mediastinal, and/or cervical + abdominal LNs), and 3 fields (cervical + mediastinal + abdominal LNs) positive LNs, respectively (P < 0.0001). The number of fields of positive LNs did not impact the OS according to different pN stage (all P > 0.05). CONCLUSION: Patients with TE-SCC with CLM have better prognosis, which supports the current AJCC staging system for esophageal SCC.

[Prognostic analysis of cervical lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma].

OBJECTIVE: To analyze the prognostic factors of cervical lymph node metastasis (CLN) in thoracic esophageal squamous cell carcinoma (TESCC), and to probe and verify the esophageal carcinoma staging of the 7th edition of American Joint Committee on Cancer (AJCC) TNM staging system. METHODS: A total of 1 715 TESCC patients underwent radical esophagectomy plus three-field lymph node dissection at Fujian Provincial Cancer Hospital between January 1993 and March 2007. 547 patients had pathological metastasis of CLN, and 296 patients received surgery only (S group) and 251 patients received postoperative radiotherapy (S+R group). The prognostic factors were analyzed and the pattern of recurrence and metastases was studied according to the esophageal carcinoma staging criteria of the 7th edition of AJCC TNM staging system. RESULTS: The metastasis rate of CLN was 31.9% for the entire group, 44.2%, 31.5% and 14.4% for the upper, middle and lower TESCC, respectively (P < 0.001). The 5-year overall survival rate of the patients with metastatic CLN was 27.7%, and the median overall survival time was 27.5 months. The 5-year survival rate was 21.3% in the S group and 34.2% in the S+R group, and the median survival time was 21.9 months in the S group and 35.4 months in the S+R group (P < 0.001). Multivariate analysis showed that gender, lesion length in X-ray, N stage, AJCC stage and treatment modality were independent prognostic factors of CLN metastasis in TESCC. Independent prognostic factors for S group included the primary tumor site, pT stage, N stage and AJCC stage, and N stage was an independent prognostic factor for the S+R group. CONCLUSIONS: TESCC with CLN metastasis have a better prognosis after surgery. It supports that cervical lymph nodes belong to regional lymph nodes classified in the 7th edition of AJCC TNM staging system.

[Methylation of Runx3 promoter in different breast lesions].

OBJECTIVE: To investigate the methylation status of Runx3 promoter and Runx3 expression in breast lesion tissues. METHODS: One hundred and fourteen breast lesions, including 35 cases of fibroadenoma, 39 cases of intraductal carcinoma, 40 cases of invasive ductal carcinoma, and 33 cases of normal breast tissue from Fabruary 2010 to August 2012 were included in this study. Runx3 protein expression was assessed by immunohistochemical SP method; whereas methylation of Runx3 promoter was assessed by high resolution melting (HRM) analysis. RESULTS: Runx3 protein was mainly expressed in the cytoplasm of ductal epithelial cells. The expression rates of Runx3 in normal breast tissue, fibroadenoma, ductal carcinoma in situ, invasive ductal carcinoma were 87.9% (29/33), 85.7% (30/35), 53.8% (21/39), and 40.0% (16/40) respectively. The methylation rates of Runx3 promoter were 12.1% (4/33), 20.0% (7/35), 46.2% (18/39), and 57.5% (23/40), respectively. Correlation analysis between promoter methylation and protein expression of Runx3 in different breast tissue showed the r value in normal breast tissue, fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma was -0.431 (P = 0.012), -0.408 (P = 0.015), -0.589 (P = 0.000) and -0.743 (P = 0.000) respectively. CONCLUSIONS: Runx3 protein expression shows a downward trend in ductal carcinoma in situ and invasive ductal carcinoma, meanwhile its promoter methylation increases significantly. The methylation of Runx3 promoter may be one of the important factors in the occurrence and development of breast cancer.

Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X(HBX) gene- transfected hepatic stellate cells. / é€šè¿‡æœºæ¢°åŠ›åˆºæ¿€ä¹™åž‹è‚ç‚Žç— æ¯’XåŸºå› (HBX)转染的肝星状细胞制备血液透析用双层仿生血管.

Artificial vascular graft (AVG) fistula is widely used for hemodialysis treatment in patients with renal failure. However, it has poor elasticity and compliance, leading to stenosis and thrombosis. The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery, which is primarily maintained by collagen in the extracellular matrix (ECM) of arterial cells. Studies have revealed that in hepatitis B virus (HBV)-induced liver fibrosis, hepatic stellate cells (HSCs) become hyperactive and produce excessive ECM fibers. Furthermore, mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure. Based on the above factors, we transfected HSCs with the hepatitis B viral X (HBX) gene for simulating the process of HBV infection. Subsequently, these HBX-HSCs were implanted into a polycaprolactone-polyurethane (PCL-PU) bilayer scaffold in which the inner layer is dense and the outer layer consists of pores, which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold. We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization. Then, the vessel scaffold was implanted into a rabbit's neck arteriovenous fistula model. It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit's body. Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels, providing a novel approach for creating clinical vascular access for dialysis.

Identification of common variants in BRCA2 and MAP2K4 for susceptibility to sporadic pancreatic cancer.

Germline mutations in genes that cause hereditary syndromes are highly predisposed to familial pancreatic cancer. However, genetic susceptibility to sporadic pancreatic cancer is largely uncovered. We conducted a two-stage association study on pancreatic cancer that included 981 cases and 1991 controls in the first stage followed by a second stage (2603 cases and 2877 controls). Using an approach based on candidate genes whose roles in pancreatic cancer have been well known, we identified two new susceptibility loci. rs11571836 located in the BRCA2 3'-untranslated region was significantly associated with lower expression of BRCA2 transcript and increased pancreatic cancer risk [odds ratio = 1.30, 95% confidence interval = 1.14-1.47, P = 7.64 × 10(-5)] in a recessive manner. rs12939944 located in the MAP2K4 intron was associated with decreased risk (odds ratio = 0.82, 95% confidence interval = 0.74-0.91, P = 0.0001) in a dominant manner. Our results demonstrate for the first time that common variants in BRCA2 and MAP2K4 are susceptibility to sporadic pancreatic cancer.

Nuclear TK1 expression is an independent prognostic factor for survival in pre-malignant and malignant lesions of the cervix.

BACKGROUND: Thymidine kinase 1 (TK1) is a proliferation biomarker that has been found useful for prognostication in cancer patients. Here we investigate for the first time the use of TK1 expression as a prognostic factor for patients with premalignant and malignant lesions of the uterine cervix. METHODS: TK1 expression was determined by immunohistochemistry in cervical lesions (cervical intraepithelial neoplasia (CIN), n = 216; invasive cervical carcinoma, n = 84). TK1 and Ki-67 expressions and pathological/FIGO stages and age were correlated with 5-year survival by Kaplan-Meier, log rank and COX hazard uni- and multivariate analyses. RESULTS: TK1 labeling index (LI) was significantly correlated with CIN grades and invasive cervical carcinoma stages, while TK1 labeling intensity was only correlated to CIN grades. TK1 LI was significantly higher compared with Ki-67 LI. TK1 LI correlated significantly to 5-year survival in patients with invasive cervical carcinoma, particularly nuclear TK1 LI. In a multivariate analysis, nuclear TK1 expression was independent prognostic factor in patients with in situ/invasive cervical carcinoma or in invasive cervical carcinoma alone. Interestingly, in invasive cervical carcinoma patients with advanced tumors, nuclear TK1 expression could identify patients with significantly better survival rates (80%), while Ki-67 could not. CONCLUSIONS: Nuclear TK1 expression in early grade CIN predicts risk for progression to malignancy. Nuclear TK1 expression is also a prognostic factor for treatment outcome, particularly in patients with advanced cervical carcinomas. Nuclear TK1 expression is more useful than Ki-67 and pathological/FIGO stages.

Prediction of presurgical metabolic syndrome for gastric cancer-specific mortality is more evident in smokers: The FIESTA study.

BACKGROUNDS: We aimed to test whether the prediction of presurgical metabolic syndrome for postsurgical survival outcomes of gastric cancer hinges upon cigarette smoking status. METHODS: This study is a part of the ongoing Fujian prospective investigation of cancer (FIESTA) study. Patients with gastric cancer received radical resection of primary gastric cancer between January 2000 and December 2010, with the latest follow-up ended in December 2015. The 1:1 propensity score matching analysis was adopted to balance confounders between smokers and never-smokers. Effect-size estimates are expressed as hazard ratio (HR) with 95% confidence interval (CI). Model performance was evaluated using the Hosmer and Lemeshow test and 10-fold cross-validated area under the receiver operating characteristic curve (AUROC). Statistical analyses were completed with SAS software (v9.4). RESULTS: Total 2779 patients with gastric cancer were analyzed, including 2223 smokers and 556 never-smokers. Median follow-up time was 45.6 months. Cigarette smoking was not associated with postsurgical survival differences. Presurgical metabolic syndrome complication was significantly associated with increased gastric cancer-specific mortality in smokers (HR [95% CI]: 2.73 [1.53-4.89], p < 0.001), but not in never-smokers. Relative excess risk due to interaction was estimated to be 2.43 (95% CI: 0.40-4.45). After constructing a risk assessment score, one unit increment was associated with 10% reduced risk of gastric cancer-specific mortality (HR [95% CI]: 0.90 [0.88-0.91], p < 0.001), with 10-fold cross-validated AUROC being 0.82 (95% CI: 0.74-0.92). CONCLUSIONS: Our findings showed that the prediction of presurgical metabolic syndrome for gastric cancer-specific mortality was more evident in smokers. Practically, this study provides evidence base for future personalized prediction and helped risk-stratify gastric cancer patients who might experience serious postsurgical consequences.

Intelligent Nanoplatform Integrating Macrophage and Cancer Cell Membrane for Synergistic Chemodynamic/Immunotherapy/Photothermal Therapy of Breast Cancer.

Cell membrane-coated nanoplatforms for drug delivery have garnered significant attention due to their inherent cellular properties, such as immune evasion and homing abilities, making them a subject of widespread interest. The coating of mixed membranes from different cell types onto the surface of nanoparticles offers a way to harness natural cell functions, enhancing biocompatibility and improving therapeutic efficacy. In this study, we merged membranes from murine-derived 4T1 breast cancer cells with RAW264.7 (RAW) membranes, creating a hybrid biomimetic coating referred to as TRM. Subsequently, we fabricated hybrid TRM-coated Fe3O4 nanoparticles loaded with indocyanine green (ICG) and imiquimod (R837) for combination therapy in breast cancer. Comprehensive characterization of the RIFe@TRM nanoplatform revealed the inherent properties of both cell types. Compared to bare Fe3O4 nanoparticles, RIFe@TRM nanoparticles exhibited remarkable cell-specific self-recognition for 4T1 cells in vitro, leading to significantly prolonged circulation life span and enhanced in vivo targeting capabilities. Furthermore, the biomimetic RIFe@TRM nanoplatform induced tumor necrosis through the Fenton reaction and photothermal effects, while R837 facilitated enhanced uptake of tumor-associated antigens, further activating CD8+ cytotoxic T cells to strengthen antitumor immunotherapy. Hence, RIFe@TRM nanoplatform demonstrated outstanding synergy in chemodynamic/immunotherapy/photothermal therapies, displaying significant inhibition of breast tumor growth. In summary, this study presents a promising biomimetic nanoplatform for effective treatment of breast cancer.

RNU12 inhibits gastric cancer progression via sponging miR-575 and targeting BLID.

Gastric cancer (GC) is one of the major causes of cancer deaths with 5-year survival ratio of 20%. RNU12 is one of long noncoding RNAs (lncRNAs) regulating the tumor progression. However, how RNU12 affecting GC is not clear. qRT-PCR was utilized for determining the RNU12 expression in cell lines, 113 cases of paired gastric cancer (GC) and their adjacent normal gastric tissues. The biofunction alterations of RNU12 were assessed by its overexpression or knockdown in GC cells. MTT and cloning assay were assayed for the cell proliferation, the flow cytometry for the detection of cell cycle and the wound healing assay (WHA) and transwell invasion assay (TIA) for examining the migration and invasion of cells. The expressions of a set of genes related proliferation and migration were investigated with the Western Blotting (WB). RNA immunoprecipitation (RIP), biotinylated RNA pull-down and dual luciferase reporter tests were used to detect the interactions of RNU12 with miR-575/BLID. The in vivo proliferation and migration ability of RNU12 infected cells were determined in zebrafish system. This study revealed that RNU12 inhibited proliferation, invasion and metastasis by sponging of miR-575 and regulating the downstream BLID and modulated EMT of GC cells. The RNU12/miR-575/BLID axis is likely to be the prognosis biomarkers and drug targets of GC.

Identification of potential therapeutic drugs targeting core genes for systemic lupus erythematosus (SLE) and coexisting COVID-19: Insights from bioinformatic analyses.

OBJECTIVE: Systemic lupus erythematosus (SLE) patients are at risk during the COVID-19 pandemic, yet the underlying molecular mechanisms remain incompletely understood. This study sought to analyze the potential molecular connections between COVID-19 and SLE, employing a bioinformatics approach to identify effective drugs for both conditions. METHODS: The data sets GSE100163 and GSE183071 were utilized to determine share differentially expressed genes (DEGs). These DEGs were later analyzed by various bioinformatic methods, including functional enrichment, protein-protein interaction (PPI) network analysis, regulatory network construction, and gene-drug interaction construction. RESULTS: A total of 50 common DEGs were found between COVID-19 and SLE. Gene ontology (GO) functional annotation revealed that "immune response," "innate immune response," "plasma membrane," and "protein binding" were most enriched in. Additionally, the pathways that were enriched include "Th1 and Th2 cell differentiation." The study identified 48 genes/nodes enriched with 292 edges in the PPI network, of which the top 10 hub genes were CD4, IL7R, CD3E, CD5, CD247, KLRB1, CD40LG, CD7, CR2, and GZMK. Furthermore, the study found 48 transcription factors and 8 microRNAs regulating these hub genes. Finally, four drugs namely ibalizumab (targeted to CD4), blinatumomab (targeted to CD3E), muromonab-CD3 (targeted to CD3E), and catumaxomab (targeted to CD3E) were found in gene-drug interaction. CONCLUSION: Four possible drugs that targeted two specific genes, which may be beneficial for COVID-19 patients with SLE.

Discrimination of gastric cancer from normal by serum RNA based on surface-enhanced Raman spectroscopy (SERS) and multivariate analysis.

PURPOSE: Here, the authors explore the feasibility of discriminating cancer patients from healthy controls by serum RNA detection based on surface-enhanced Raman spectroscopy (SERS) and multivariate analysis. METHODS: MgSO(4)-aggregated silver nanoparticles (Ag NP) as the SERS-active substrate presented strong SERS signals to RNA. SERS measurements were performed on two groups of serum RNA samples: one group from patients (n = 31) with gastric cancer and the other group from healthy volunteers (n = 34). RESULTS: Tentative assignments of the Raman bands in the normalized SERS spectra demonstrated that there are differential expressions of circulating RNA between the gastric cancer group and the control group. Principal component analysis (PCA) combined with linear discriminate analysis (LDA) was introduced to differentiate gastric cancer from normal and achieved sensitivity of 100% and specificity of 94.1%. CONCLUSIONS: This exploratory study demonstrated potential for developing serum RNA SERS analysis into a useful clinical tool for noninvasive screening and detection of cancer.

KRAS mutation and NF-κB activation indicates tolerance of chemotherapy and poor prognosis in colorectal cancer.

BACKGROUND: Evidence shows a strong relationship between KRAS mutations and the NF-κB signaling pathway. In colorectal cancer, however, the study of this subject has been very limited and results are inconsistent. AIMS: To examine the relationship between KRAS mutations and NF-κB activation and their effect on chemotherapy response and survival of colorectal cancer patients. MATERIALS AND METHODS: NF-κB activation was analyzed by immunohistochemistry in 167 primary colorectal cancer specimens in which the KRAS mutation status was confirmed. Clinical and pathologic data were extracted from the medical records and reviewed. RESULTS: Of 167 tumors screened, 63 (37.7 %) had NF-κB activation, 59 (35.3 %) had KRAS mutations, and 30 (18.0 %) had both NF-κB activation and KRAS mutations. The frequency of NF-κB activation in tumors with KRAS mutations was significantly higher than in tumors with wild type KRAS; 50.8 versus 30.6 %, P = 0.012. Patients with both KRAS mutations and NF-κB activation had a lower objective response to first-line chemotherapy than patients with other tumors, 23.8 versus 49.4 % (P = 0.035). Compared to patients with both KRAS mutations and NF-κB activation, overall survival of patients in other groups was significantly higher; median overall survival was 28.4 months (95 % CI 21.0-35.8) versus 46.3 months (95 % CI 39.4-53.2), hazard ratio 0.259 (95 % CI 0.125-0.538), P = 0.005. CONCLUSIONS: NF-κB activation was associated with KRAS mutation, and both KRAS mutation and NF-κB activation were indicative of high tolerance of chemotherapy and poor prognosis for colorectal cancer patients. Tumors with KRAS mutations and NF-κB activation may be a unique subtype of colorectal cancer.

Epithelioid angiosarcoma arising in schwannoma: report of three Chinese cases with review of the literature.

Angiosarcoma arising in a schwannoma is extremely rare with only eleven cases having been reported in the English literature. We describe here three further cases occurring in adult males with a pre-existing longstanding schwannoma. The tumor arose each from the vagus, ischiadic and adrenergic nerve respectively. None of the patients had von Recklinghausen's disease. Microscopically, the tumor was composed of a mixture of a benign schwannoma and an epithelioid angiosarcoma. The two components changed abruptly within the tumor. The endothelial cell differentiation was confirmed by immunohistochemistry. A review of published reports, including the present cases, suggests a poor prognosis with a high rate of local recurrence, distant metastasis and mortality.