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TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of TP53 mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific TP53 mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. TP53 mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of TP53 mutations in our local datasets and publicly available datasets. The co‐occurring events of TP53 mutations in UrCa, along with their therapeutic indications, functional effects, and the tumor immune microenvironment, were also investigated. TP53 mutations were identified in 49.7% of the UrCa patients. Within this group, 25.1% of patients carried TP53Disruptive mutations, a genetic alteration correlated with a significantly poorer overall survival (OS) when compared to individuals with TP53Nondisruptive mutations and those with wild‐type TP53. Significantly, patients with TP53Disruptive mutations exhibit an increased probability of responding favorably to PD‐1/PD‐L1 blockade and chemoimmunotherapy. Meanwhile, there was no noteworthy distinction in OS among patients with varying TP53 mutation status who underwent chemotherapy. Samples with TP53Disruptive mutations showed an enriched APOBEC‐ and POLE‐related mutational signature, as well as an elevated tumor mutation burden. The sensitivity to immunotherapy in tumors carrying TP53Disruptive mutation may be attributed to the inflamed tumor microenvironment characterized by increased CD8+T cell infiltration and interferon‐gamma signaling activation. In conclusion, UrCa patients with TP53Disruptive mutations have shown reduced survival rates, yet they may respond well to PD‐1/PD‐L1 blockade therapy and chemoimmunotherapy. By distinguishing specific TP53 mutations, we can improve risk stratification and offer personalized genomics‐guided therapy to UrCa patients. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background: Luminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8+ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8+ T cells infiltration in MIBC. Methods: This study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8+ T cells and probed into the clinical implications of these subgroups in MIBC. Results: Among patients with Luminal-CD8+Thigh tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8+Tlow displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8+Tlow subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8+Thigh counterparts exhibited a heightened responsiveness to chemotherapy. Conclusions: We emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients. [ABSTRACT FROM AUTHOR]

Muscle‐invasive bladder cancer (MIBC) is a disease characterized by molecular and clinical heterogeneity, posing challenges in selecting the most appropriate treatment in clinical settings. Considering the significant role of CD4+ T cells, there is an emerging need to integrate CD4+ T cells with molecular subtypes to refine classification. We conducted a comprehensive study involving 895 MIBC patients from four independent cohorts. The Zhongshan Hospital (ZSHS) and The Cancer Genome Atlas (TCGA) cohorts were included to investigate chemotherapeutic response. The IMvigor210 cohort was included to assess the immunotherapeutic response. NCT03179943 was used to evaluate the clinical response to a combination of immune checkpoint blockade (ICB) and chemotherapy. Additionally, we evaluated genomic characteristics and the immune microenvironment to gain deeper insights into the distinctive features of each subtype. We unveiled four immune‐molecular subtypes, each exhibiting distinct clinical outcomes and molecular characteristics. These subtypes include luminal CD4+ Thigh, which demonstrated benefits from both immunotherapy and chemotherapy; luminal CD4+ Tlow, characterized by the highest level of fibroblast growth factor receptor 3 (FGFR3) mutation, thus indicating potential responsiveness to FGFR inhibitors; basal CD4+ Thigh, which could benefit from a combination of ICB and chemotherapy; and basal CD4+ Tlow, characterized by an immune suppression microenvironment and likely to benefit from transforming growth factor‐β (TGF‐β) inhibition. This immune‐molecular classification offers new possibilities for optimizing therapeutic interventions in MIBC. [ABSTRACT FROM AUTHOR]

Background: Though programmed cell death‐ligand 1 (PD‐L1) has been used in predicting the efficacy of immune checkpoint blockade (ICB), it is insufficient as a single biomarker. As a key effector of an intrinsically mutagenic microhomology‐mediated end joining (MMEJ) pathway, DNA polymerase theta (POLQ) was overexpressed in various malignancies, whose expression might have an influence on genomic stability, therefore altering the sensitivity to chemotherapy and immunotherapy. Methods: A total of 1304 patients with muscle‐invasive bladder cancer (MIBC) from six independent cohorts were included in this study. The Zhongshan Hospital (ZSHS) cohort (n = 134), The Cancer Genome Atlas (TCGA) cohort (n = 391), and the Neo‐cohort (n = 148) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n = 234) and the UNC‐108 cohort (n = 89) were used for the assessment of immunotherapeutic response. In addition, the relationship between POLQ and the immune microenvironment was assessed, and GSE32894 (n = 308) was used only for the evaluation of the immune microenvironment. Results: We identified POLQhigh PD‐L1high patients could benefit more from immunotherapy and platinum‐based chemotherapy. Further analysis revealed that high POLQ expression was linked to chromosome instability and higher tumor mutational burden (TMB), which might elicit the production of neoantigens. Further, high POLQ expression was associated with an active tumor immune microenvironment with abundant infiltration of immune effector cells and molecules. Conclusions: The study demonstrated that high POLQ expression was correlated with chromosome instability and antitumor immune microenvironment in MIBC, and the combination of POLQ and PD‐L1 could be used as a superior companion biomarker for predicting the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

Background and aims: In gastric cancer, the response rate of programmed cell death protein‐1 (PD‐1) inhibitor is far from satisfactory, indicating additional nonredundant pathways might hamper antitumour immunity. V‐domain immunoglobulin suppressor of T‐cell activation (VISTA) has been reported in several malignancies as a novel immune‐checkpoint. Nevertheless, the role of VISTA in gastric cancer still remains obscure. Our purpose is to explore the clinical significance and potential mechanism of VISTA in affecting gastric cancer patients' survival and immunotherapeutic responsiveness. Methods: Our study recruited eight independent cohorts with a total of 1403 gastric cancer patients. Immunohistochemistry, multiplex immunofluorescence, flow cytometry or intracellular flow cytometry, quantitative polymerase chain reaction, western blotting, fluorescence‐activated cell sorting, magnetic‐activated cell sorting, smart‐seq2, in vitro cell co‐culture and ex vivo tumour inhibition assays were applied to investigate the clinical significance and potential mechanism of VISTA in gastric cancer. Results: VISTA was predominantly expressed on tumour‐associated macrophages (TAMs), and indicated poor clinical outcomes and inferior immunotherapeutic responsiveness. VISTA+ TAMs showed a mixed phenotype. Co‐culture of TAMs and CD8+ T cells indicated that VISTA+ TAMs attenuated effective function of CD8+ T cells. Blockade of VISTA reprogrammed TAMs to a proinflammatory phenotype, reactivated CD8+ T cells and promoted apoptosis of tumour cells. Moreover, blockade of VISTA could also enhance the efficacy of PD‐1 inhibitor, suggesting that blockade of VISTA might synergise with PD‐1 inhibitor in gastric cancer. Conclusions: Our data revealed that VISTA was an immune‐checkpoint associated with immunotherapeutic resistance. Blockade of VISTA reprogrammed TAMs, promoted T‐cell‐mediated antitumour immunity, and enhanced efficacy of PD‐1 inhibitor, which might have implications in the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

As a typical ecological fragile zone and an area with a high intensity of human activities, the Loess Plateau (LP) of China has significantly altered its ecosystem and the corresponding services under the influence of urbanization processes. However, most existing studies focus on the spatial and temporal changes of ecosystem services (ESs) and their interrelationships under the influence of ecological restoration works in the LP, leaving limited research on the impacts of urbanization on ESs. Therefore, this study constructed a research framework for exploring the spatio-temporal dynamics and interactions of ESs under the influence of urbanization based on time series data from 2000 to 2020. The results showed that: (1) based on the comprehensive urbanization level (CUL), developed and developing areas accounted for 5.63% of the total area; (2) for the whole LP, all ESs except Habitat Quality (HQ) showed an increased trend. HQ showed a trade-off with the other services, while there was a clear synergy between the other three types of services; (3) in terms of processes of urbanization, Carbon Sequestration, Water Yield and HQ gradually decreased with increased levels of urbanization, and Soil Conservation increased the least in developing areas. The trade-off between HQ and the other three services decreased with increasing urbanization, while the synergy between the other three services strengthened as urbanization deepened. These findings suggest that urbanization significantly impacts ESs. It is necessary to implement appropriate measures (e.g., sponge city construction, urban green space, etc.) to address the impacts of urbanization on ESs. [ABSTRACT FROM AUTHOR]

Restoration action is critical to ensure a safe environment for humans. Reasonable planning is essential to optimize the efficiency of ecological restoration inputs and outputs when implementing restoration measures. In this study, a method that combines human activity intensity assessment and multi-criteria decision analysis to determine ecological restoration priority (ERP) areas was developed to identify priority and feasible areas for ecological restoration in Shaanxi Province in 2020. The results showed that the total area involved in restoration feasibility assessment in Shaanxi is 10.89 × 104 km2. Among them, the percentage of regions with low feasibility (less than 0.2) is 68.86%, mainly located in Qinling area. High feasibility areas (more than 0.6) accounted for 2.47%, mainly located in the Loess Plateau area of northern Shaanxi. The spatial distribution of the human activity intensity is concentrated in urban areas and extended with the distribution of roads. In total, 10.69% of the regions showed high and very high intensity of human activity, including the Guanzhong urban agglomeration region. This study identified 6078 km2 and 671 km2 of medium and high ecological restoration priority areas, which are more concentrated in the north of the study area. The need for ecological restoration work is even more urgent in northern Shaanxi. In general, the framework in this study has spatially located the priority and feasible areas for restoration, and may provide a useful reference for landscape-scale spatial conservation planning. [ABSTRACT FROM AUTHOR]

Although the Internet and social media provide people with a range of opportunities and benefits in a variety of ways, the proliferation of fake news has negatively affected society and individuals. Many efforts have been invested to detect the fake news. However, to learn the representation of fake news by context information, it has brought many challenges for fake news detection due to the feature sparsity and ineffectively capturing the non-consecutive and long-range context. In this paper, we have proposed Intra-graph and Inter-graph Joint Information Propagation Network (abbreviated as IIJIPN) with Third-order Text Graph Tensor for fake news detection. Specifically, data augmentation is firstly utilized to solve the data imbalance and strengthen the small corpus. In the stage of feature extraction, Third-order Text Graph Tensor with sequential, syntactic, and semantic features is proposed to describe contextual information at different language properties. After constructing the text graphs for each text feature, Intra-graph and Inter-graph Joint Information Propagation is used for encoding the text: intra-graph information propagation is performed in each graph to realize homogeneous information interaction, and high-order homogeneous information interaction in each graph can be achieved by stacking propagation layer; inter-graph information propagation is performed among text graphs to realize heterogeneous information interaction by connecting the nodes across the graphs. Finally, news representations are generated by attention mechanism consisting of graph-level attention and node-level attention mechanism, and then news representations are fed into a fake news classifier. The experimental results on four public datasets indicate that our model has outperformed state-of-the-art methods. Our source code is available at https://github.com/cuibenkuan/IIJIPN. [ABSTRACT FROM AUTHOR]

Background: V domain Immunoglobulin suppressor of T cell activation (VISTA) has been proved to be a novel immune checkpoint molecule that positively regulates T cell infiltration in several malignancies. However, the clinical impact of VISTA on muscle-invasive bladder cancer (MIBC) patients remains relatively obscure. Methods: This study enrolled 135 MIBC patients from Zhongshan Hospital (ZSHS) and 391 patients from The Cancer Genome Atlas (TCGA) to examine the VISTA expression and immune contexture based on immunohistochemistry (IHC) staining and CIBERSORT algorithm. Additionally, IMvigor210 Cohort included 195 bladder-derived urothelial carcinoma patients to evaluate the efficacy of immunotherapy. Kaplan-Meier curve and Cox regression analyses were conducted to assess clinical outcomes. Results: MIBC patients with high VISTA+ immune cells (ICs) possessed poor overall survival and inferior therapeutic responsiveness to adjuvant chemotherapy (ACT), but superior responsiveness to PD-L1 inhibitor. VISTA+ ICs infiltration shaped an immunoevasive context featured by regulatory T cells (Tregs), M2 macrophages, mast cells and exhausted CD8+ T cells infiltration, with increased interleukin 10 (IL-10), transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ), but also elevated T-cell immunoglobulin mucin-3 (TIM-3), lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and ITIM domain (TIGIT), which was also mainly presented in basal-squamous and luminal-infiltrated subtypes of MIBC. Conclusion: VISTA+ ICs infiltration could be an independent predictor to identify poor prognosis and therapeutic responses (PD-L1 blockade and ACT) in MIBC patients, which was associated with immunoevasive contexture. The novel immune checkpoint VISTA might be utilized as a candidate treatment biomarker in MIBC patients. [ABSTRACT FROM AUTHOR]

Background: AT-rich interaction domain 1A (ARID1A) encodes a vital component of switch/sucrose non-fermentable chromatin-remodeling complex. Given its association with genomic instability, we conducted this study to determine whether ARID1A mutation status had an impact on therapeutic responsiveness in gastric cancer (GC), especially combinatory chemo-immunotherapy. Methods: We retrospectively enrolled a total of 1162 patients from five independent cohorts. ZSHS Cohort and TCGA Cohort were designed to inform chemotherapeutic relevance and immunobiology of ARID1A-mutant GC based on tissue samples and sequencing data, respectively. MSKCC Cohort, mGC Cohort, and Melanoma Cohort were utilized to interrogate the predictive efficacy of ARID1A mutation to programmed cell death protein 1 (PD-1) blockade. Results: ARID1A mutation was enriched in EBV-positive, hypermutated-single nucleotide variant and microsatellite-unstable subtype GC, and was predictive of responsiveness to both fluorouracil-based chemotherapy and PD-1 blockade. Specifically, ARID1A mutation score was a highly sensitive indicator (91%) of response to pembrolizumab. Mechanistically, ARID1A mutation correlated with extensive DNA damage repair deficiency and immunogenic tumor microenvironment (TME) featured by elevated activated subsets of CD8+ T cells, CD4+ T cells, and NK cells. Type 17T helper cells were typically abundant in ARID1A-mutant GC and might be a precondition for chemosensitivity conferred by ARID1A mutation. Furthermore, ARID1A mutation indicated elevated expression of VEGFA and CLDN18, as well as over-representation of ERBB2 and FGFR2 signaling pathway. Conclusions: ARID1A-mutant GC displayed immunogenic TME and might be a candidate for both monotherapy and the combination of frontline chemotherapy and PD-1 blockade. [ABSTRACT FROM AUTHOR]

Fake news detection mainly relies on the extraction of article content features with neural networks. However, it has brought some challenges to reduce the noisy data and redundant features, and learn the long-distance dependencies. To solve the above problems, Dual-channel Convolutional Neural Networks with Attention-pooling for Fake News Detection (abbreviated as DC-CNN) is proposed. This model benefits from Skip-Gram and Fasttext. It can effectively reduce noisy data and improve the learning ability of the model for non-derived words. A parallel dual-channel pooling layer was proposed to replace the traditional CNN pooling layer in DC-CNN. The Max-pooling layer, as one of the channels, maintains the advantages in learning local information between adjacent words. The Attention-pooling layer with multi-head attention mechanism serves as another pooling channel to enhance the learning of context semantics and global dependencies. This model benefits from the learning advantages of the two channels and solves the problem that pooling layer is easy to lose local-global feature correlation. This model is tested on two different COVID-19 fake news datasets, and the experimental results show that our model has the optimal performance in dealing with noisy data and balancing the correlation between local features and global features. [ABSTRACT FROM AUTHOR]

A graph G is called triangle-free if G does not contain a triangle as an induced subgraph. Let H n be the set of triangle-free graphs of order n with six non-zero eigenvalues. In this paper, we find 19 graphs of H n , and we show that the other graphs of H n can be constructed from these 19 graphs by adding some congruent vertices. Hence we completely characterize the triangle-free graphs with six non-zero eigenvalues. [ABSTRACT FROM AUTHOR]

Background: CD39, a rate-limiting enzyme to convert extracellular ATP (eATP) to adenosine, has been reported to be a key modulator of immune response, but its correlation with therapeutic sensitivity remains obscure. We conducted this study to determine whether the integration of CD39 and traditional biomarkers could improve the prediction of responsiveness to PD-L1 blockade and platinum-based chemotherapy.Methods: We retrospectively enrolled a total of 760 patients from IMvigor210 trial, TCGA database and Zhongshan Hospital in this study. We constructed the CPT scoring system based on CD39, PD-L1 and tumour mutation burden (TMB) and validated its efficacy in predicting therapeutic responsiveness in MIBC patients. Kaplan-Meier survival and Cox regression analyses were applied to assess clinical outcomes of patients.Results: The CPT scoring system could predict the response to PD-L1 blockade and platinum-based chemotherapy. The CPT score was positively correlated with APOBEC mutational signature and SNV neoantigens enrichment, antigen presentation, and TCR signalling. High CPT score also indicated the inflamed immune phenotype and basal/squamous molecular subtype.Conclusions: CD39 expression is closely correlated with the immunogenic contexture of MIBC. Integrating CD39 with PD-L1 and TMB could stratify the sensitivity of patients with MIBC to PD-L1 blockade and platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Exosomes-related microRNAs (miRNAs) have been considered to be the significant biomarkers contributing to the development of atrial fibrillation (AF). We observed the implicit mechanism of exosomes-miR-148a derived from bone marrow mesenchymal stem cells (BMSCs) in AF. The AF cell and mice models were established firstly. QRT-PCR and Western blot analysis were applied to detect the expression of miR-148a, SPARC-associated modular calcium-binding protein 2 (SMOC2), Bcl-2, Bax, and caspase-3. BMSCs were separated from healthy mice and exosomes were obtained from BMSCs. BMSCs were transfected with mimics and inhibitor, and HL-1 cells were treated with mimics and pcDNA3.1. MTT assay were used to detect cell viability of cells. Flow cytometric analysis and TUNEL analysis were used for detecting cell apoptosis of cells. In our study, exosomes derived from BMSCs inhibited the development of AF, and miR-148a acted a vital role in this segment. SMOC2 was a target gene of miR-148a and promoted apoptosis of HL-1 cells. Additionally, miR-148a mimics decreased cellular apoptosis, eliminated SMOC2 expression, and elevated Bcl-2 expression in AF-treated cells. Collectively, miR-148a overexpressed in BMSC-exosomes restrained cardiomyocytes apoptosis by inhibiting SMOC2. [ABSTRACT FROM AUTHOR]

Spatio-temporal dynamic monitoring of soil moisture is highly important to management of agricultural and vegetation ecosystems. The temperature-vegetation dryness index based on the triangle or trapezoid method has been used widely in previous studies. However, most existing studies simply used linear regression to construct empirical models to fit the edges of the feature space. This requires extensive data from a vast study area, and may lead to subjective results. In this study, a Modified Temperature-Vegetation Dryness Index (MTVDI) was used to monitor surface soil moisture status using MODIS (Moderate-resolution Imaging Spectroradiometer) remote sensing data, in which the dry edge conditions were determined at the pixel scale based on surface energy balance. The MTVDI was validated by field measurements at 30 sites for 10 d and compared with the Temperature-Vegetation Dryness Index (TVDI). The results showed that the R2 for MTVDI and soil moisture obviously improved (0.45 for TVDI, 0.69 for MTVDI). As for spatial changes, MTVDI can also better reflect the actual soil moisture condition than TVDI. As a result, MTVDI can be considered an effective method to monitor the spatio-temporal changes in surface soil moisture on a regional scale. [ABSTRACT FROM AUTHOR]

DPA Contest is a world-famous side-channel competition aiming at analyzing and evaluating the implementing security of some latest countermeasures. Improved Rotating S-box Masking Scheme (RSM2.0) is one of the most popular countermeasures designed during DPA Contest V4.2, which arms with both Low Entropy Masking Schemes and shuffling strategy to ensure the software security of AES-128, particularly the non-profiled security. Up to now, conducting high efficient non-profiled attacking scheme with low resource costs is still a challenge. In this paper, we first propose general and non-profiled leakage fingerprint attacks (named NP-LFA) for secret cracking and make use of it to crack RSM2.0 random masks with almost 100% accuracy. Further, we analyze the hidden vulnerabilities embedded in RSM2.0 implementation, and utilize them to bypass the shuffling defense and perform the master key recovery. Official evaluation results show that NP-LFA is capable of compromising RSM2.0 within 14 traces, each of which only costs 60 ms processing time. Such result validates the high efficiency and light-weighted characteristics of our attacking scheme, which has ranked the first in the official website till now. In addition, we discuss and put forward some possible strategies to mitigate our NP-LFA threats. [ABSTRACT FROM AUTHOR]

The discovery of circular RNAs and exploration of their biological functions are increasingly attracting attention in cell bio-sciences. Owing to their unique characteristics of being highly conserved, having a relatively longer half-life, and involvement in RNA maturation, transportation, epigenetic regulation, and transcription of genes, it has been accepted that circRNAs play critical roles in the variety of cellular processes. One of the critical importance of these circRNAs is the presence of small open reading frames that enable them to encode peptides/proteins. In particular, these encoded peptides/proteins mediate essential cellular activities such as proliferation, invasion, epithelial–mesenchymal transition, and apoptosis and develop an association with the development and progression of cancers by modulating diverse signaling pathways. In addition, these peptides have potential roles as biomarkers for the prognosis of cancer and are being used as drug targets against tumorigenesis. In the present review, we thoroughly discussed the biogenesis of circRNAs and their functional mechanisms along with a special emphasis on the reported chimeric peptides/proteins encoded by circRNAs. Additionally, this review provides a perspective regarding the opportunities and challenges to the potential use of circRNAs in cancer diagnosis and therapeutic targets in clinics. [ABSTRACT FROM AUTHOR]

Background: Foxp3+RORγt+ T cells possess both characteristics of regulatory T cells and T helper 17 cells and show significant immunoregulatory functions in autoimmune diseases. However, the role and clinical significance of Foxp3+RORγt+ T cells in gastric cancer remains unclear. Methods: We enrolled 452 gastric cancer tissue microarray samples and 60 fresh tumor tissue samples from Zhongshan Hospital. The infiltration of Foxp3+RORγt+ T cells and immune contexture were examined by immunohistochemistry and flow cytometry. Survival analyses of patient subgroups were conducted by Kaplan–Meier curves, log-rank test and Cox proportional model. Results: High infiltration of Foxp3+RORγt+ T cells predicted poor overall survival (P = 0.0222 and 0.0110) and inferior therapeutic response (P = 0.003 for interaction) in gastric cancer. Foxp3+RORγt+ T cells were associated with impaired effective function of CD8+ T cells featured by decreased interferon-γ, granzyme B and CD107a expression. Co-evaluation of Foxp3+RORγt+ T cells and CD8+ T cells could predict survival outcomes and chemotherapeutic responsiveness more precisely. Conclusions: We found that Foxp3+RORγt+ T cells could potentially attenuate effective functions of CD8+ T cells and led to adverse survival outcomes and inferior chemotherapeutic responsiveness. Moreover, the novel co-evaluation system might be useful for prognosis prediction for appropriate treatment in gastric cancer. Novelty and impact statements: Clinical significance of Foxp3+RORγts+ T cells has not been studied in gastric cancer. Herein, we investigated the prognostic value of Foxp3+RORγt+ T cells in 452 patients. We demonstrated that intratumoral Foxp3+RORγt+ T cell infiltration was a prognostic biomarker for overall survival and the identification of patients might benefit from post-gastrectomy 5-fluorouracil. These findings allow a more precise stratification upon the co-evaluation with CD8+ T cells to better clinical management for patients who would benefit from 5-fluorouracil. [ABSTRACT FROM AUTHOR]

Purpose: In recent years, less options are available for treating carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa. The present study investigates the susceptibility rates to imipenem/relebactam for the treatment of intra-abdominal infections (IAIs), respiratory tract infections (RTIs) and urinary tract infections (UTIs) caused by A. baumannii and P. aeruginosa in China. Patients and Methods: A total of 1886 P. aeruginosa and 1889 A. baumannii isolates were collected in 21 centers (7 regions) as a part of the global SMART surveillance program between 2015 and 2018. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) recommendations using the broth microdilution methodology at Peking Union Medical College Hospital. Results: For P. aeruginosa, overall susceptibility rates to imipenem/relebactam were 84.2% at a CLSI breakpoint of ≤ 2 mg/L compared to 55.7% for imipenem. Susceptibility rates of imipenem-non-susceptible P. aeruginosa to imipenem/relebactam were 64.4% and for multidrug-resistance (MDR) P. aeruginosa susceptibility rates were increased from 25.2% for imipenem to 65.8% for imipenem/relebactam. The susceptibilities of imipenem-non-susceptible and MDR P. aeruginosa strains were similarly restored by imipenem/relebactam in non-ICU and ICU wards. The rate of imipenem-non-susceptibilities A. baumannii isolates was 79.0%, whereas the MDR rate was 81.9%. Relebactam did not change the susceptibilities of imipenem-non susceptible or MDR A. baumannii isolates. Conclusion: Imipenem/relebactam provides a therapy option to treat infections caused by MDR or imipenem-non-susceptible P. aeruginosa but not A. baumannii infections in China. [ABSTRACT FROM AUTHOR]

Background: CD47 has been identified as an innate immune checkpoint and found to be associated with inferior survival in various types of cancer. However, the critical role of CD47 in gastric cancer and its association with tumor associated macrophages remain unclear. Methods: Tumor tissues of gastric cancer from Zhongshan Hospital and data from GSE62254, GSE84437 and TCGA datasets were analyzed. Immunohistochemistry was performed to detect the expression of CD47, CD11c, CD163 and CD68 in gastric cancer tissues. Kaplan–Meier curves and Cox model were used for comparing the clinical outcomes of patients belonging to different subgroups. Results: Gastric cancer patients with high CD47 expression exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT). A positive correlation was found between M1-polarized macrophage infiltration and CD47 expression in gastric cancer; however, the prognostic value of M1-polarized macrophages was attenuated in CD47-high gastric cancer patients. Moreover, we found that CD47 mRNA level was enriched in microsatellite-instable (MSI) subtype of gastric cancer and associated with ARID1A mutation and FGFR2 signaling pathway activation. Conclusions: Aberrant CD47 expression represented an independent predictor for adverse survival outcome and ACT resistance in gastric cancer. Targeting CD47 might be a promising strategy for gastric cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39+CD8+ T cells are abundant, but their function remains obscure. We aim to assess clinical value of CD39+CD8+ T cells and seek a potential therapeutic target in ccRCC. Experimental design: We immunohistochemically evaluated clinical value of CD39+CD8+ T cells in a retrospective Zhongshan Hospital cohort of 243 ccRCC patients. Fresh tumor samples (n = 48), non-tumor tissues and peripheral blood for flow cytometry analyses were collected to analyze immune cell functions from Zhongshan Hospital. The survival benefit of tyrosine kinase inhibitors (TKIs) in this subpopulation was evaluated. Kaplan–Meier analysis and COX regression model were applied for survival analyses. Bioinformatics analysis performed in TCGA KIRC cohort and the scRNA-seq cohort. Results: We found that accumulation of CD39+CD8+ T cells indicated poor prognosis (p < 0.0001) and indicated therapeutic benefit of TKIs therapy (p = 0.015). CD39+CD8+ T cells showed decreased TNF-α and IFN-γ with elevated PD-1 and TIM-3 expression. Further analysis of tumor-infiltrating immune cell landscape in the ccRCC revealed the positive correlation between CD39+CD8+ T cells and Tregs (p = 0.037) and M2-polarized macrophages (p < 0.0001). Finally, inhibition of CD39 partially restores the anti-tumor function of CD8+ T cells. Conclusions: High CD39+CD8+ T cells indicated poor prognosis in ccRCC, due to impaired anti-tumor function of CD39+CD8+ T cells and indicated therapeutic benefit of TKIs therapy. [ABSTRACT FROM AUTHOR]

With dichotomous etiology and pathogenesis, intestinal type and diffuse type gastric cancers vary in their clinical and molecular features to the point of representing distinct entities. However, the differences of tumor-infiltrating immune cells within the two types of gastric cancer have not been well researched. This study was aimed to evaluate the functional impact of Lauren classification on immune contexture in gastric cancer patients. Tumor tissues of gastric cancer patients from Zhongshan Hospital and gastric cancer data from The Cancer Genome Atlas (TCGA) cohort were analyzed. By immunohistochemistry and flow cytometry, we found that intratumoral CD8+ T cells were more abundant but less functional in diffuse type as compared with those in intestinal type tumor tissues. Survival analysis indicated that CD8+ T cells yielded favorable prognosis only in intestinal type patients other than diffuse type cancer patients. Moreover, such diffuse type-associated CD8+ T cell dysfunction was featured by elevated expression of immunosuppressive factors including interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1) and indoleamine 2,3-dioxygenase 1 (IDO1). In summary, we found that the density, prognostic significance and functional status of intratumoral CD8+ T cells varied with Lauren subtypes in gastric cancer. These results further indicated Lauren classification might be a potential therapeutic marker, and should be considered in therapeutic decisions, especially immunotherapeutic eligibility. [ABSTRACT FROM AUTHOR]

Background: Meconium peritonitis (MP) is a rare fetal disease that needs to be urgently identified for surgical intervention. We report a series of 35 patients diagnosed prenatally with MP by magnetic resonance imaging (MRI), illustrate the imaging findings and investigate the predictive value of these findings for postpartum management. Method: A consecutive cohort of patients diagnosed with MP who were born at our institution from 2013 to 2018 was enrolled retrospectively. The prenatal ultrasound and MRI findings were analyzed. Fisher's exact probability test was used to evaluate the predictive value of MRI for surgical intervention between the operative group and the nonoperative group. Results: Ascites (30/35) and distended bowel loops (27/35) were two of the most common prenatal MP-related findings on fetal MRI. Of the 35 infants, 26 received surgical intervention. All fetuses with MRI scans showing bowel dilatation (14/26, p = 0.048) and micro-colorectum (13/26, p = 0.013) required surgery. There were no significant differences in the number of fetuses with meconium pseudocysts and peritoneal calcifications between the two groups. Conclusion: Fetuses with bowel dilatation and micro-colorectum on MRI may need postpartum surgical intervention. Infants with only a small amount of ascites and slight bowel distention were likely to receive conservative treatment. [ABSTRACT FROM AUTHOR]

Background: Intratumoural CD103+CD8+ T cells have been linked to prolonged survival in several malignancies. However, the clinical significance of CD103+CD8+ T cells in gastric cancer remains unexplored.Methods: Gastric cancer tissues from Zhongshan Hospital and data from Gene Expression Omnibus were obtained and analysed. Immunohistochemistry and flow cytometry were performed to detect the number and phenotypical characteristics of CD103+CD8+ T cells. The effect of programmed cell death protein-1 (PD-1) blockade on CD103+CD8+ T cells was evaluated with the use of an in vitro study based on fresh tumour tissues.Results: CD103+CD8+ T cells predicted superior overall survival and provided better prognostic power than total CD8+ T cells in gastric cancer. Patients with high CD103+CD8+ T cell infiltration also gained more benefit from adjuvant chemotherapy. Flow cytometry analysis showed that CD103+CD8+ T cells exerted superior anti-tumour effects with stronger retention capacity and cytotoxicity. Moreover, an in vitro study showed that CD103+CD8+ T cells were more functionally restored after PD-1 blockade than CD103-CD8+ T cells.Conclusions: CD103+CD8+ T cells might be a useful marker to predict prognosis and therapeutic efficacy for gastric cancer patients. Efforts to increase intratumoural CD103+CD8+ T cell frequency might be a novel therapeutic strategy in gastric cancer. [ABSTRACT FROM AUTHOR]

Our previous researches have identified immunoevasive subtype muscle‐invasive bladder cancer (MIBC) characterized with immune cells infiltration patterns. Our study explored the clinical significance, immunoregulatory role and therapeutic value of intratumoral IL22‐producing cells in MIBC. Two hundred and fifty‐nine formalin‐fixed paraffin‐embedded MIBC samples and 83 freshly resected MIBC tissues and 391 TCGA MIBC samples were retrospectively evaluated. Immunohistochemistry and flow cytometry were applied to identify immune cell infiltration and functional status. In vitro intervention studies were to test the therapeutic and predictive potential of IL22+ cells. Our data revealed patients with high IL22+ cells infiltration suffered poor overall survival and recurrence‐free survival in both training and validation cohorts. Only pT2 patients of combined cohort with low IL22+ cells infiltration gained survival benefits from adjuvant chemotherapy (ACT) significantly. Besides, immune contexture featured with increased pro‐tumor cells and immunosuppressive cytokines was identified in patients with high IL22+ cells density. The expression pattern of exhausted and effector markers in CD8+ T cells from high IL22+ cells subgroup indicated their dysfunctional status. Importantly, nivolumab showed tumor‐killing efficacy in tumors with high IL22+ cells infiltration, and immunosuppressive contexture with CD8+ T cells exhaustion was abrogated in tumors treated with anti‐IL22 antibody. In summary, IL22+ cells infiltration determined immunosuppressive contexture with CD8+ T cell dysfunction. Tumor‐infiltrating IL22+ cells could be used as an independent marker to predict prognosis and ACT responses. IL22+ cells infiltration possessed the potential to be a favorable predictor for nivolumab application and IL22 blockade could be a novel therapeutic strategy in MIBC. What's new? IL22 was reported to promote tumor cell growth, angiogenesis, and chemotherapeutic resistance. However, few studies have investigated the role of this cytokine in the development of immunosuppressive microenvironment. Our study found that IL22+ cells infiltration was an independent indicator of overall survival, recurrence‐free survival, and adjuvant chemotherapy benefit in muscle‐invasive bladder cancer (MIBC). The results also revealed the immunoregulatory role of IL22+ cells in the immunoevasive subtype of MIBC with CD8+ T cells exhaustion. The results supported IL22+ cells infiltration as a potential predictor for responsiveness to PD‐1 blockade and identified IL22 blockade as a novel immunotherapeutic strategy in MIBC. [ABSTRACT FROM AUTHOR]

Interleukin-9 (IL-9) is a T cell cytokine that is associated with inflammation and allergy, but the expression level of IL-9 in gastric cancer and its clinical significance are less well established. Our study aims to uncover the critical role of IL-9 in the progression of gastric cancer. Here, a total of 453 patients with gastric cancer undergoing curative resection were enrolled for immunohistochemical analyses, and Kaplan-Meier analysis was conducted to compare overall survival of patients in different subgroups. We further investigated the correlation between IL-9 expression and functional status of intratumoral CD8+ T cells by means of Flow cytometry. Moreover, in vitro study was preformed to further explore the influence of IL-9 on anti-tumor immunity. Results indicated that gastric cancer patients with high IL-9 expression showed improved overall survival and gained more benefit from 5-fluorouracil-based adjuvant chemotherapy (ACT). High IL-9 expression was associated with increased numbers and elevated function of intratumoral CD8+ T cells. In vitro study revealed that recombinant human IL-9 (rhIL-9) exhibit anti-tumor activity via enhancing the function of intratumoral CD8+ T cells. Moreover, we found rhIL-9 could augment the efficacy of Pembrolizumab in gastric cancer. In summary, these results suggest that IL-9 expression could act as an independent predictor for overall survival and ACT response and enhancing IL-9 signaling might represent an important therapeutic strategy in gastric cancer. [ABSTRACT FROM AUTHOR]

Our previous study has identified intratumoral CD103+CD8+ T cells as a favorable prognostic factor in gastric cancer. However, the significance of CD103+CD4+ T cells in gastric cancer hasn't yet been elucidated. Here, we aimed to investigate the clinical significance and phenotype characteristics of intratumoral CD103+CD4+ T cells in gastric cancer. In our study, 469 formalin-fixed and paraffin-embedded samples and 24 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital were included. We manifested that intratumoral CD103+CD4+ T cells in gastric cancer predicted poor overall survival and inferior responsiveness to fluorouracil-based ACT. The density and phenotypic characteristics of CD103+CD4+ T cells in gastric cancer were detected by immunohistochemistry and flow cytometry, which showed that CD103+CD4+ T cells exhibited an immunosuppressive phenotype and higher retention capacity in tumor tissues. Furthermore, increased CD103+CD4+ T cells contributed to CD8+T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Overall, this study revealed that intratumoral CD103+CD4+T cell infiltration defined immunoevasive contexture and predicted poor prognosis and inferior responsiveness to fluorouracil-based ACT. Therefore, we recommended that CD103+CD4+ T cells might be a potential immunotherapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]

Bladder cancer is the ninth most frequent-diagnosed disease worldwide, bearing high morbidity and mortality rates. Studies have shown that a particular population of CXCR5+CD8+ T cells was associated with superior prognosis in various tumor types, and yet its role in muscle-invasive bladder cancer (MIBC) remains unclear. In this study, 662 MIBC patients from 3 cohorts (Zhongshan Hospital, n = 141; Shanghai Cancer Center, n = 108; The Cancer Genome Atlas, n = 403) were analyzed retrospectively. 11 fresh resected samples of MIBC were examined to characterize the phenotype of CXCR5+CD8+ T cells and 402 MIBC patients from TCGA were applied for bioinformatics analysis. It was explored that the abundance of intratumoral CXCR5+CD8+ T cells indicated superior overall survival and disease-free survival. Patients with a higher infiltration of CXCR5+CD8+ T cells in tumor tissue benefit more from adjuvant chemotherapy (ACT). Intratumoral CXCR5+CD8+ T cells displayed cytolytic and self-renewal features. Remarkably, CXCR5+CD8+ T cells were mainly presented in the basal and stromal-rich subtypes of MIBC and tumors with enriched CXCR5+CD8+ T cells showed limited FGFR3 signaling signature and activated immunotherapeutic and EGFR associated pathway. In conclusion, we identified an excellent prognosis and ACT sensitive subtype of MIBC with intratumoral CXCR5+CD8+ T cell abundance. Tumors with high density of CXCR5+CD8+ T cells possessed potential sensitivity to immunotherapy and EGFR-targeted therapy. CXCR5+CD8+ T cells provide a new potential biomarker as well as a therapeutic target in MIBC. [ABSTRACT FROM AUTHOR]

Purpose: Tumor-associated macrophages (TAMs) exist as heterogeneous subsets and have dichotomous roles in cancer-immune evasion. This study aims to assess the clinical effects of Galectin-9+ tumor-associated macrophages (Gal-9+TAMs) in muscle-invasive bladder cancer (MIBC). Experimental design: We identified Gal-9+TAMs by immunohistochemistry (IHC) analysis of a tumor microarray (TMA) (n = 141) from the Zhongshan Hospital and by flow cytometric analysis of tumor specimens (n = 20) from the Shanghai Cancer Center. The survival benefit of platinum-based chemotherapy in this subpopulation was evaluated. The effect of the tumor-immune microenvironment with different percentages of Gal-9+TAMs was explored. Results: The frequency of Gal-9+TAMs increased with tumor stage and grade. Gal-9+TAMs predicted poor overall survival (OS) and recurrence-free survival (RFS) and were better than Gal-9−TAMs and TAMs to discriminate prognostic groups. In univariate and multivariate Cox regression analyses, patients with high percentages of Gal-9+TAMs showed the prominent survival benefit after receiving adjuvant chemotherapy (ACT). High Gal-9+TAM infiltration correlated with increasing numbers of regulatory T cells (Tregs) and mast cells and decreasing numbers of CD8+T and dendritic cells (DCs). Dense infiltration of Gal-9+TAMs was related to reduced cytotoxic molecules, enhanced immune checkpoints or immunosuppressive cytokines expressed by immune cells, as well as active proliferation of tumor cells. Additionally, the subpopulation accumulated was strongly associated with PD-1+TIM-3+CD8+T cells. Conclusions: Gal-9+TAMs predicted OS and RFS and response to ACT in MIBC patients. High Gal-9+TAMs were associated with a pro-tumor immune contexture concomitant with T cell exhaustion. [ABSTRACT FROM AUTHOR]

Purpose: Hypoxia-inducible factor 2α (HIF-2α) overexpression leads to activation of angiogenic pathways. However, little is known about the association between HIF-2α expression and anti-tumor immunity in clear cell renal cell carcinoma (ccRCC). We aimed to explore how HIF-2α influenced the microenvironment and the underlying mechanisms. Experimental design: We immunohistochemically evaluated immune cells infiltrations and prognostic value of HIF-2α expression in a retrospective Zhongshan Hospital cohort of 280 ccRCC patients. Fresh tumor samples, non-tumor tissues and autologous peripheral blood for RT-PCR, ELISA and flow cytometry analyses were collected from patients who underwent nephrectomy in Zhongshan Hospital from September 2017 to April 2018. The TCGA KIRC cohort and SATO cohort were assessed to support our findings. Results: We demonstrated that ccRCC patients with HIF-2αhigh tumors exhibited reduced overall survival (p = 0.025) and recurrence-free survival (p < 0.001). Functions of CD8+ T cells were impaired in HIF-2αhigh patients. In ccRCC patients, HIF-2α induced the expression of stem cell factor (SCF), which served as chemoattractant for mast cells. Tumor infiltrating mast cells impaired anti-tumor immunity partly by secreting IL-10 and TGF-β. HIF-2α mRNA level adversely associated with immunostimulatory genes expression in KIRC and SATO cohorts. Conclusions: HIF-2α contributed to evasion of anti-tumor immunity via SCF secretion and subsequent recruitment of mast cells in ccRCC patients. [ABSTRACT FROM AUTHOR]

Purpose: CD19+ tumor-infiltrating B-cells (CD19+ TIB) play a crucial role in tumorigenesis, but their clinical relevance in muscle-invasive bladder cancer (MIBC) remains unknown. This study aimed to investigate the prognostic value of CD19+ TIB for post-surgery survival and adjuvant chemotherapy response in MIBC.Experimental design: We assessed TIB by immunohistochemical staining of CD19 in 246 MIBC patients from Zhongshan Hospital and Shanghai Cancer Center. We evaluated the survival benefit of platinum-based chemotherapy according to CD19+ TIB. The mechanism underlying CD19+ TIB antitumor immunity was explored through the Cancer Genome Atlas (TCGA) dataset analysis and an in vitro Ag presentation assay.Results: CD19+ TIB extensively infiltrated into the tumor stroma of MIBC. Adjuvant chemotherapy (ACT) led to a significantly increased benefit in the high CD19+ TIB MIBC patients (P = 0.003). In multivariate analysis, high CD19+ TIB MIBC patients had significantly longer OS with ACT in the discovery set (HR = 0.487, P = 0.038). TCGA gene expression analyses showed enrichment of adaptive immunity, T-cell-mediated immunity, and antigen-presentation signaling pathways in high CD19+ TIB MIBC patients. Moreover, CD19+ TIB co-localized with activated CD4+ TIT and expressed surface markers characteristic of antigen-presenting cells. Finally, an antigen-presentation assay demonstrated the antigen-presentation function of CD19+ TIB.Conclusion: CD19+ TIB was identified as an independent prognostic factor, which could predict for post-surgery survival and platinum-based ACT benefits in MIBC. CD19+ TIB serve as antigen-presenting cells (APCs) to activate CD4+ TIT in the tumor environment of MIBC. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Medicine & Health is the property of Journal of Modern Medicine & Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PTEN is a tumour suppressor that is frequently mutated in a variety of cancers. Hence, PTEN has significant potential as a therapeutic molecule. PTEN-long is an alternative translation variant, with an additional 173 amino acids added to the N-terminal of the canonical PTEN when CUG of the mRNA is utilized as the start codon. PTEN-long is secreted into serum and can re-enter cells throughout the body. One of the major barriers for gene therapy is to efficiently and specifically deliver DNA or RNA material to target cells. As an alternative approach, if a therapeutic protein can be directly delivered to target cell of interest, it should theoretically function well within the cells, particularly for genes that are deficiently expressed in vivo. Most therapeutic proteins are incapable of efficiently permeating the cell membrane. In this study, we have employed CRISPR/Cas9 gene editing tool combined with single-stranded template to edit CTG of PTEN-long to ATG in the genome. Two guide RNAs close to CTG site were found to have similar efficiency in driving PTEN-long expression. Furthermore, we detected PTEN-long expression in transfected whole-cell lysate and in concentrated culture media in Western blot. Interestingly, the culture media of PTEN-long expression can reduce Akt phosphorylation level and repress U87 cell proliferation compared to wild-type U87 or control media. Taken together, PTEN-long driven by CRISPR/Cas9 imports and exports cells and represses nearby cell proliferation, indicating the PTEN-long generated by CRISPR/Cas9 has potential to be an alternative strategy for PTEN gene therapy. [ABSTRACT FROM AUTHOR]

Ternary NaO-FeO-PO (NFP) glasses with varying NaO/FeO, NaO/PO, and FeO/PO ratios were prepared. The properties and crystallization tendencies were systemically investigated. It is shown that both density and chemical stability of the glass increase with FeO. In contrast the NaO/PO ratio has little effect on the glass properties for a fixed FeO content. The crystallization behavior of the glasses was analyzed by DTA and XRD. Unlike LiO-FeO-PO glasses NFP glasses were found to be stable against crystallization. 15NaO-27FeO-58PO glass was found to have the highest chemical stability among the studied NFP samples; the influence of TiO, ZrO on crystallization in this composition was studied. It is found that addition of 3.4 mol% TiO or 2.2 mol% ZrO had little effect on the crystallization behavior of this glass. However, when the amounts of TiO or ZrO were increased to 8.4 or 5.5 mol% respectively the glass readily devitrified. Furthermore the addition of fluorine (introduced by replacing NaCO with NaF in the glass batch) leads to amorphous glasses which could be crystallized to form NaFePO upon controlled thermal treatment. With increasing NaF additions the activation emergy for crystallization decreased from 428 to 381 kJ/mol. [ABSTRACT FROM AUTHOR]

A novel turn-on fluorescent 8-amino BODIPY-based probe carrying a thiourea unit as the mercury ion recognition unit has been developed. Due to the cascade reaction processes, consecutive color changes reflecting the electronic absorption and emission responses were observed upon addition of increased concentrations of mercury(ii) ions. The likely sensing mechanism was proposed as mercury ion-promoted cyclization and subsequent hydrolysis. The probe displayed a selective response to mercury ions over other metal ions. Additionally, experiments with living Human Hepatoma SMMC-7721 cells to visualize intracellular mercury ions in biological systems were carried out with the probe. [ABSTRACT FROM AUTHOR]

The expression of sialic acid-binding Ig-like lectin (Siglec) family has been detected in many malignant tumors and correlated with patient outcomes. The present study aims to investigate the prognostic value of Siglec-8 expression and refine current risk stratification system in patients with gastric cancer. Two independent sets of patients ( n = 78; n = 356, respectively) with gastric cancer from Zhongshan Hospital were enrolled into this study. The expression of Siglec-8 was detected by immunohistochemistry. Cox regression analysis was used to assess the prognostic value of Siglec-8 expression and clinical outcomes. A novel molecular prognostic stratification system combining intratumoral Siglec-8 expression with TNM stage was determined by means of receiver operating characteristic analysis. Multivariate Cox regression analysis identified that intratumoral Siglec-8 low expression was an independent prognostic factor for dismal overall survival of patients with gastric cancer. Incorporating intratumoral Siglec-8 expression into the current TNM staging system showed more accuracy for predicting prognosis of patients with gastric cancer. Our study suggested that intratumoral Siglec-8 expression was an independent prognostic factor for overall survival of patients with gastric cancer. Incorporating Siglec-8 expression level into current TNM staging system might add more comprehensive prognostic information for patients with gastric cancer and lead to a more precise risk stratification system for predicting clinical outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the potential prognostic significance of interleukin-33 (IL-33) in patients with clear-cell renal cell carcinoma (ccRCC) after surgical resection. In this retrospective research, we enrolled 203 patients with ccRCC undergoing nephrectomy between 2003 and 2004 in a single institution. We recorded clinicopathologic features, overall survival (OS), and recurrence-free survival (RFS) and assessed IL-33 expression by immunohistochemical staining. On such bases, the correlations between IL-33 expression and clinicopathologic features and prognosis were evaluated. A high expression of IL-33 was significantly associated with advanced TNM stage and Fuhrman grade ( p = 0.017 and p < 0.001, respectively) in patients with ccRCC. Moreover, multivariate analysis identified IL-33 as an independent prognostic factor of OS for patients with ccRCC after surgery (hazard ratio = 2.050; 95 % CI 1.223-3.447; p = 0.006). The incorporation of IL-33 into the TNM stage and Fuhrman grade might help to refine individual risk stratification. The IL-33 expression may serve as an independent negative predictor of survival for patients with ccRCC after surgery. [ABSTRACT FROM AUTHOR]

Copyright of Leather & Footwear Journal / Revista de Pielarie Incaltaminte is the property of INCDTP and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Colony-stimulating factor 1 receptor (CSF-1R), a single-pass type III transmembrane tyrosine-protein kinase, is mainly involved in inflammation and immune regulation to facilitate the progression of solid tumors. This study aimed to evaluate the impact of CSF-1R expression on clinical outcome of patients with clear cell renal cell carcinoma (ccRCC) after surgery. Methods: We retrospectively enrolled 268 patients with ccRCC undergoing nephrectomy between 2001 and 2004. Clinicopathologic features and cancer-specific survival (CSS) were collected. Western blot analysis was performed in the pairwise comparisons of CSF-1R expression in peritumor and tumor tissues of patients with ccRCC. Immunohistochemistry was conducted to determine CSF-1R expression level in tumor specimens. Survival analysis was performed by the Kaplan-Meier method. Cox regression models were used to evaluate the impact of prognostic factors on CSS. A concordance index was calculated to measure prognostic accuracy. A prognostic nomogram was constructed on the basis of the identified independent prognostic factors. Results: CSF-1R expression in tumor tissues was higher than in peritumor tissues in 71.4 % (5 of 7) patients. CSF-1R expression of tumor tissues was positively associated with metastasis, tumor, node, metastasis classification system (TNM) stage, Eastern Cooperative Oncology Group performance status score and poor CSS. CSF-1R expression was determined as an independent prognostic factor for CSS in patients with ccRCC. Furthermore, extension of the well-established prognostic models with CSF-1R expression presented significantly improved prognostic accuracy. An efficient prognostic nomogram was constructed on the basis of the independent prognostic factors. Conclusions: High CSF-1R expression is a potential independent adverse prognostic factor for CSS in patients with ccRCC. [ABSTRACT FROM AUTHOR]

Background: Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time.Methods: We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models.Results: The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL-6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ-confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years.Conclusions: Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients. [ABSTRACT FROM AUTHOR]