JMJD3 Is Required for Acute Pancreatitis and Pancreatitis-Associated Lung Injury.

Acute pancreatitis (AP) can be complicated by inflammatory disorders of remote organs, such as lung injury, in which Jumonji domain-containing protein 3 (JMJD3) plays a vital role in proinflammatory responses. Currently, we found that JMJD3 expression was upregulated in the pancreas and lung in an AP male mouse model, which was also confirmed in AP patients. Further experiments revealed that the upregulation of JMJD3 and proinflammatory effects were possibly exerted by mitochondrial DNA (mtDNA) or oxidized-mtDNA from tissue injury caused by AP. The release of mtDNA and oxidized-mtDNA contributed to the infiltration of inflammatory monocytes in lung injury through the stimulator of IFN genes (STING)/TLR9-NF-κB-JMJD3-TNF-α pathway. The inhibition of JMJD3 or utilization of Jmjd3-cKO mice significantly alleviated pulmonary inflammation induced by AP. Blocking mtDNA oxidation or knocking down the TLR9/STING pathway effectively alleviated inflammation. Therefore, inhibition of JMJD3 or STING/TLR9 pathway blockage might be a potential therapeutic strategy to treat AP and the associated lung injury.

Boosting Microwave Thermo-Dynamic Cancer Therapy of TiMOF via COF-Coating.

Microwave (MW) dynamic therapy (MDT) can efficiently eliminate tumor residue resulting from MW thermal therapy. However, MDT is currently in its infancy, and luck of effective MDT sensiters severely limits its clinical therapeutic effect. Herein, based on TiMOF (TM), a high-efficiency MW sensitizer is designed for MW thermo-dynamic therapy. TM can generate heat and cytotoxic reacyive oxygen species (ROS) under MW irradiation and has the potential to be used as an MW sensitizer, while the suboptimal MW dynamic sensitization effect of TM limits its application. Inorder to improve the MW dynamic sensitization performance, a covalent organic framework (COF) with good stability and a large conjugate system is used to cover TM, which is conductive to electron and energy transfer, thus increasing the ROS generation rate and prolonging the ROS lifetime. In addition, loading Ni NPs endow nanomaterials with magnetic resonance imaging capabilities. Therefore, this work develops an MW sensitizer based on TM for the first time, and the mechanism of COF coating to enhance the MW dynamic sensitization of TM is preliminarily explored, which provides a new idea for the further development of MW sensitizer with great potential.

A phase I clinical trial of sonodynamic therapy combined with temozolomide in the treatment of recurrent glioblastoma.

PURPOSE: The prognosis of recurrent glioblastoma (rGBM) is poor, and there is currently no effective treatment strategy. Sonodynamic therapy (SDT) is a new method for cancer treatment that uses a combination of low-frequency ultrasound and sonosensitisers to produce antitumor effects, which have shown good therapeutic effects in preclinical studies. Therefore, we initiated an open, prospective pilot study to evaluate the safety, tolerability, and efficacy of SDT for the treatment of rGBM. METHODS: Nine patients with rGBM were enrolled who had received multiple treatments, but the nidus continued to progress without additional standard treatments. After MRI localisation, porphyrin drugs were injected, and intermittent low-frequency ultrasound therapy was performed for five days. RESULTS: None of the nine patients in this clinical trial showed any clinical, neurological, haematological, or skin-targeted adverse effects associated with SDT. After the completion of the trial, one patient maintained stable disease, and eight patients experienced disease progression. Among the eight with progressive disease, the median progression-free survival time was 84 days. Four patients died, and the median overall survival duration after recurrence was 202.5 days. CONCLUSION: The number of patients in this study was small; therefore, a long-term survival benefit was not demonstrated. However, this study suggests that SDT has potential as a treatment for rGBM and warrants further exploration. Trial information: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ): ChiCTR2200065992. November 2, 2022, retrospectively registered.

Research progress of hyperthermia in tumor therapy by influencing metabolic reprogramming of tumor cells.

Cellular metabolic reprogramming is an important feature of malignant tumors. Metabolic reprogramming causes changes in the levels or types of specific metabolites inside and outside the cell, which affects tumorigenesis and progression by influencing gene expression, the cellular state, and the tumor microenvironment. During tumorigenesis, a series of changes in the glucose metabolism, fatty acid metabolism, amino acid metabolism, and cholesterol metabolism of tumor cells occur, which are involved in the process of cellular carcinogenesis and constitute part of the underlying mechanisms of tumor formation. Hyperthermia, as one of the main therapeutic tools for malignant tumors, has obvious effects on tumor cell metabolism. In this paper, we will combine the latest research progress in the field of cellular metabolic reprogramming and focus on the current experimental research and clinical treatment of hyperthermia in cellular metabolic reprogramming to discuss the feasibility of cellular metabolic reprogramming-related mechanisms guiding hyperthermia in malignant tumor treatment, so as to provide more ideas for hyperthermia to treat malignant tumors through the direction of cellular metabolic reprogramming.

Hyperthermia inhibits growth of nasopharyngeal carcinoma through degradation of c-Myc.

BACKGROUND: Hyperthermia is a widely used adjunct treatment for different cancers including nasopharyngeal carcinoma (NPC). The protooncogene c-Myc is up-regulated in NPC and its expression is associated with poor prognosis. OBJECTIVE: We hypothesized that c-Myc constitutes an important hyperthermia treatment target, and we investigated its contribution to hyperthermia responses in NPC. METHODS: The growth of the human NPC cell lines CNE1 and CNE2 was analyzed using CCK-8 and clonogenicity assays after 43 °C hyperthermia, knockdown or overexpression of c-Myc. Flow cytometry measurements assessed cell cycle parameters and apoptosis, while levels of c-Myc together with key transcriptional targets were determined using qPCR and Western blotting. Parallel experiments were undertaken using NPC xenografts in nude mice and lastly, global transcriptomic changes were determined using 'RNAseq'. RESULTS: Hyperthermia increased the ubiquitination and proteasomal destruction of c-Myc, causing a rapid decline in c-Myc protein levels in NPC cells. Similar to c-Myc knockdown, NPC cells treated with hyperthermia showed growth inhibition associated with the downregulation of c-Myc target genes. Moreover, low levels of c-Myc could be sustainably repressed in NPC cells through repeated hyperthermia treatments. Importantly, the key findings of growth inhibition and decreased c-Myc protein levels were reproduced in NPC tumor xenografts. Bioinformatic analyses showed that downregulation of c-Myc constituted a central node in the hyperthermia response of NPC cells. CONCLUSION: Our study reveals that hyperthermia can readily destabilize c-Myc levels in NPC cells and inhibit tumor growth. This proposes new strategies for implementing hyperthermia to target c-Myc-driven cancers to improve therapeutic efficacy.

Prognostic Factors for Survival in Patients with Malignant Giant Cell Tumor of Bone: A Risk Nomogram Analysis Based on the Population.

BACKGROUND Malignant giant cell tumor of bone (MGCTB) is a rare histological type of malignant tumor that has a high tendency for local relapse and distant metastasis and ultimately leads to a poor prognosis. The purpose of this study was to describe the epidemiological features, identify the prognostic factors, and construct nomograms for patients with MGCTB. MATERIAL AND METHODS Patients with MGCTB that was histologically diagnosed between 1973 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database as a training set. Survival analysis, Lasso regression, and random forests were used to identify the prognostic variables and establish the nomograms for patients with MGCTB, while an external cohort of 37 patients from our own institution and an external cohort of 163 patients from the SEER database in 2016 were used to validate the generalization performance of the nomograms. RESULTS In total, univariate and multivariable analysis indicated that age, International Classification of Diseases for Oncology, historical stage, primary site, surgery information, radiotherapy, and chemotherapy were independent prognostic variables for overall survival or cause-specific survival. Nomograms based on the multivariable models were built to predict survival, and we achieved a higher C-index in subsequent multidimensional validation. CONCLUSIONS Age, historical stage, and chemotherapy were independent prognostic variables for overall survival and cause-specific survival of MGCTB patients, and radiotherapy and primary site were independent prognostic variables for overall survival. Nomograms based on significant clinicopathological features and clinical experience can be effective in predicting the probability of survival for MGCTB patients.

Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial cancer of the head and neck with high prevalence in southern China, which is accompanied by notable invasiveness and metastasis. Long noncoding RNAs (lncRNAs) participate in the progression of various cancers including NPC. Microarray-based analysis identified highly expressed lncRNA mothers against decapentaplegic homolog 5 (SMAD5)-antisense RNA 1 (AS1) related to NPC. Interestingly, it is found that SMAD5-AS1 competitively bound to microRNA (miR)-106a-5p to regulate SMAD5. Herein, the study aimed to clarify the role of SMAD5-AS1/miR-106a-5p/SMAD5 axis in the process of epithelial mesenchymal transition (EMT) in NPC. SMAD5-AS1 was highly expressed and miR-106a-5p was poorly expressed in NPC tissues and cell lines. The NPC cells were treated with a series of small interfering RNAs, mimics, or inhibitors to explore the effects of SMAD5-AS1, SMAD5, and miR-106a-5p on EMT, cell proliferation, migration, and invasion in NPC. Of note, SMAD5-AS1 silencing or miR-106a-5p overexpression reduced expression of N-cadherin, matrix metallopeptidase 9, Snail, and Vimentin while elevating E-cadherin expression, thus inhibiting EMT, cell proliferation, migration, and invasion in NPC by down-regulation of SMAD5. Moreover, SMAD5 silencing could reduce the ability of EMT induced by SMAD5-AS1 up-regulation. SMAD5-AS1 silencing or miR-106a-5p elevation inhibited tumorigenesis in nude mice. Taken together, SMAD5-AS1 silencing suppressed EMT, cell proliferation, migration, and invasion in NPC by elevating miR-106a-5p to down-regulate SMAD5, which provided a novel therapeutic target for NPC treatment.-Zheng, Y.-J., Zhao, J.-Y., Liang, T.-S., Wang, P., Wang, J., Yang, D.-K., Liu, Z.-S. Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.

Application of prophylactic cranial irradiation in limited-stage small-cell lung cancer: which patients could benefit?

AIM: To analyze the role of prophylactic cranial irradiation (PCI) on the survival for patients with limited-stage small-cell lung cancer (LS-SCLC). PATIENTS & METHODS: We screened patients from SEER database. Kaplan-Meier analysis and Cox proportional hazard model were used to evaluate factors influencing survival. RESULTS: LS-SCLC patients who receiving PCI were associated with better overall survival (OS; p < 0.001) and cancer-specific survival (CSS; p < 0.001). Multivariable Cox analysis revealed PCI was an independent prognostic factor for OS (p < 0.001) and CSS (p < 0.001). In subgroup analysis, there were no OS and CSS differences between PCI and no PCI groups in black patients and patient with a tumor size <5 cm (all p > 0.05). CONCLUSION: PCI remains an effective method for most LS-SCLC patients. However, caution should be taken in recommending PCI for black patients and patients with a tumor size <5 cm. Further clinical trials are necessary to validate our results and identify the most suitable patients for PCI in the modern era.

Enteral nutrition in esophageal cancer patients treated with radiotherapy: a Chinese expert consensus 2018.

Esophageal cancer (EC) patients receiving radiotherapy are at a high risk of malnutrition, which can increase the side effects of radiotherapy, reduce the accuracy and sensitivity of radiotherapy and decrease treatment effect. Therefore, timely and correct nutritional treatment is crucial. To date, however, neither consensus nor guidelines on enteral nutrition (EN) specifically for EC patients receiving radiotherapy exist. Accordingly, an expert consensus conference was held to establish consensus on the use of EN in EC patients receiving radiotherapy. It reflected the opinions of a multidisciplinary group of experts and a review of the current literature, and established common guidelines for nutritional screening and assessment, nutrition counseling, indication for EN, access and formulas of EN, effect evaluation, nutrition plan adjustment, and home enteral nutrition.

IL-1RN gene polymorphisms are associated with breast cancer risk in a Chinese Han population.

BACKGROUND: The interleukins (ILs) are a large family of endogenous cytokines that are crucial in the regulation of inflammation and immunological responses. The IL-1 receptor antagonist (IL-1RN) has been found to be associated with risk breast cancer (BC) in Korean and Indian women. However, little information is found about the polymorphisms of IL-1RN in Chinese Han BC patients. METHODS: We investigated the association between single-nucleotide polymorphisms (SNPs) in IL-1RN and BC risk in a case-control study that included 530 BC cases and 628 healthy controls. Six tag SNPs in IL-1RN were selected and genotyped using the Sequenom MassARRAY platform (Sequenom, San Diego, CA, USA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and sex. RESULTS: In the allele model, we found that the frequency of the 'T' allele of rs928940 was significantly lower in BC cases than in controls (OR = 0.776, 95% CI = 0.611-0.985, p = 0.037). In the genetic model analysis, five susceptibility SNPs were found to be associated with BC risk: the minor allele 'G' of rs315919, rs3181052 and rs452204 were associated with a decreased risk of BC under dominant model (p < 0.05), whereas the minor alleles 'T' and 'C' of rs928940 and rs4252019 were associated with a decreased risk of BC under both the codominant and dominant models (p < 0.05), which suggested these SNPs may play a protective role against BC risk. The haplotype 'TAGC' constructed by rs928940, rs3181052, rs452204 and rs4252019 was associated with a decreased risk of BC (OR = 0.33; 95% CI = 0.12-0.94; p = 0.038). CONCLUSIONS: The data obtained in the present study shed new light on the association between genetic polymorphisms of IL-1RN and BC susceptibility in the Chinese Han population.

Predictive value of PD-L1 and TMB for short-term efficacy prognosis in non-small cell lung cancer and construction of prediction models.

Objective: To investigate the correlation between programmed death ligand 1(PD-L1), tumor mutation burden (TMB) and the short-term efficacy and clinical characteristics of anti-PD-1 immune checkpoint inhibitor combination chemotherapy in NSCLC patients. The efficacy of the prediction model was evaluated. Methods: A total of 220 NSCLC patients receiving first-line treatment with anti-PD-1 immune checkpoint inhibitor combined with chemotherapy were retrospectively collected. The primary endpoint was short-term efficacy ORR. The correlation between short-term efficacy, PD-L1, TMB, and clinical characteristics using χ2 test or t-test was evaluated. Screen the independent prognostic factors using univariate and multivariate logistic regression analyses, and construct a nomogram prediction model using the "rms" package in R software. Using receiver operating characteristic (ROC) curve analysis to evaluate the independent Prognostic factors and the prediction model. Using decision curve analysis (DCA) to verify the superiority of the prediction model. Results: The mean values of PD-L1, TMB, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, and albumin were the highest in the ORR group, PD-L1 expression and TMB correlated with epidermal growth factor receptor expression. Multivariate analyses showed that PD-L1, TMB, and neutrophil were independent prognostic factors for ORR. The area under the ROC curve (AUC) values of the ROC constructed based on these three indicators were 0.7104, 0.7139, and 0.7131, respectively. The AUC value under the ROC of the nomogram model was 0.813. The DCA of the model showed that all three indicators used together to build the prediction model of the net return were higher than those of the single indicator prediction model. Conclusion: PD-L1, TMB, and neutrophils are independent prognostic factors for short-term efficacy. The nomogram prediction model constructed using these three indicators can further improve predictive efficacy of ICIs in patients with NSCLC.

The role of extracellular vesicles in the development of nasopharyngeal carcinoma and potential clinical applications.

BACKGROUND: Extracellular vesicles (EVs) can be secreted by a wide variety of cells, including tumor cells, and contain some bioactive molecules from the source cells. Therefore, they can potentially be used as biomarkers for early diagnosis of tumors and for tumor therapy. In addition, EVs can affect the features of target cells and participate in regulating the development process of tumors. METHODS: A literature review was conducted to elucidate the role of extracellular vesicles in the progression and treatment of nasopharyngeal carcinoma. RESULTS: In this review, we discuss the molecular mechanisms of cell proliferation, angiogenesis, epithelial-mesenchymal transformation and metastasis, immune response, and chemo-radiotherapy resistance that are induced by EVs. We also reviewed the potential applications of EVs as biomarkers, therapeutic agents, and carriers so as to determine new directions for the early diagnosis and targeted therapy of nasopharyngeal carcinoma. The application limitations have also been discussed in this review, further work is needed to ensure optimal outcomes for patients. CONCLUSION: Although the roles of extracellular vesicles in the progression of nasopharyngeal carcinoma have been summarized, some aspects are still unclear and need to be further studied. In addition, the applications of extracellular vesicles in the treatment of nasopharyngeal carcinoma still need to optimize conditions to produce better therapeutic outcomes for patients with nasopharyngeal carcinoma.

CircMAN1A2 contributes to nasopharyngeal carcinoma progression via enhancing the ubiquitination of ATMIN through miR-135a-3p/UBR5 axis.

Recently, the dysregulation of circRNAs has been increasingly implicated in the pathogenesis of nasopharyngeal carcinoma (NPC). Among these circRNAs, circMAN1A2 has been highlighted for the up-regulated expression in NPC, whereas the underlying mechanisms have not been clearly established. Thus, the aim of this study was to delineate the tumor-supporting role of circMAN1A2 in the oncogenesis and metastases of NPC. We validated through qRT-PCR that circMAN1A2 was highly expressed in NPC tissues and NPC cells. Survival analysis through Kaplan-Meier method showed that the overall survival, disease-free survival, and distant metastasis-free survival of patients was negatively correlated with the expression of circMAN1A2. Then, gain- and loss-of function assays demonstrated that circMAN1A2 knockdown could impede the proliferation, migration, invasion, and EMT in NPC cells. Further, we conducted dual luciferase reporter gene, RIP, and RNA pull down assays, unveiling that circMAN1A2 functioned as a sponge of miR-135a-3p, and miR-135a-3p targeted UBR5. Additionally, UBR5 interacted with ATMIN to foster the ubiquitination of ATMIN, thereby expediting the malignant behaviors of NPC cells as well as the lung and inguinal lymph node metastases of NPC tumors in vivo. Together, our study uncovered the tumor-initiating and pro-metastatic role of circMAN1A2-miR-135a-3p-UBR5-ATMIN axis in NPC regulation that may be a potential therapeutic target for human NPC.

[Influence of Pre-treatment Lymphocyte/Monocyte Ratio and Neutrophil/Lymphocyte Ratio on the Prognosis of Patients with Extranodal NK/T-Cell Lymphoma].

OBJECTIVE: To explore the influence of lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of 203 patients with ENKTL admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were retrospectively analyzed. The ROC curve determined the limit values of LMR and NLR; Categorical variables were compared using a chi-square test, expressed as frequency and percentage (n,%). Continuous variables were expressed as medians and extremes and compared with the Mann-Whitney U test; Progression-free survival (PFS) and overall survival (OS) of different grouped LMR and NLR patients were analyzed using Kaplan-Meier curves and compared with log-rank tests. The COX proportional risk regression model was used to perform one-factor and multi-factor analysis of PFS and OS. RESULTS: The optimal critical values of LMR and NLR were determined by the ROC curve, which were 2.60 and 3.40, respectively. LMR≤2.60 was more likely to occur in patients with bone marrow invasion (P=0.029) and higher LDH (P=0.036), while NLR≥3.40 was more likely to occur in patients with higher ECOG scores (P=0.002), higher LDH (P=0.008), higher blood glucose (P=0.024), and lower PLT (P=0.010). Kaplan-Meier survival analysis showed that PFS and OS of patients in the high LMR group were significantly better than the low LMR group, while PFS and OS in the low NLR group were significantly better than the high NLR group. The results of multivariate COX analysis showed that EBV-DNA positive (P=0.047), LMR≤2.60 (P=0.014), NLR≥3.40 (P=0.023) were independent risk factors affecting PFS in patients with ENKTL. LMR≤2.60 (P<0.001), NLR≥3.40 (P=0.048), and high ß2-MG (P=0.013) were independent risk factors affecting OS in patients with ENKTL. CONCLUSION: Low LMR and high NLR before treatment are associated with poor prognosis in patients with ENKTL, which also can be used as an easily testable, inexpensive, and practical prognostic indicator in the clinic.

Transcription Factor GLI1 Induces IL-6-Mediated Inflammatory Response and Facilitates the Progression of Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is a neuroendocrine tumor whose pathogenesis remains unclear. This study investigated the role of glioma-associated oncogene family zinc finger 1 (GLI1), a transcription factor in the sonic hedgehog (SHH) signaling pathway, in ACP. We discovered that GLI1 regulates the expression of IL-6, thereby triggering inflammatory responses in ACP and influencing the tumor's progression. Analyzing the Gene Expression Omnibus (GEO) database chip GSE68015, we found that GLI1 is overexpressed in ACP, correlating positively with the spite of ACP and inflammation markers. Knockdown of GLI1 significantly inhibited the levels of tumor necrosis factor α, interleukin-6 (IL-6), and IL-1ß in ACP cells, as well as cell proliferation and migration. We further identified a binding site between GLI1 and the promoter region of IL-6, demonstrating that GLI1 can enhance the expression of IL-6. These findings were verified in vivo, where activation of the SHH pathway significantly promoted GLI1 and IL-6 expressions in nude mice, inducing inflammation and tumor growth. Conversely, GLI1 knockdown markedly suppressed these processes. Our study uncovers a potential molecular mechanism for the occurrence of inflammatory responses and tumor progression in ACP.

Logic gate controlled theranostic nanoagents for in situ microwave thermal therapeutic efficacy evaluation.

In vivo monitoring of treatment response is of great significance for tumor therapy in clinical trials, but it remains a formidable challenge. Herein, we demonstrate a logic AND gate theranostic nanoagent that responds to the coexistence of endogenous and exogenous stimuli, namely HAuCl4@1-Tetradecanol@Gd-based metal-organic framework@SiO2 nanocomposites (APGS NCs). Upon microwave (MW) irradiation, HAuCl4 in the inner part of APGS NCs reacts with the tumor-associated glutathione (GSH). Subsequently, it transforms into an active luminescent form of Au@1-Tetradecanol@Gd-MOF@SiO2 nanocomposites (AuPGS NCs). The intensity of generated fluorescence is correlated with the tumor thermal-injury status. Thus, the generation of AuPGS NCs with high intensity fluorescence under the co-activation of MW and GSH can visualize the treatment effects during MW thermal therapy and instantly modulate the irradiation time and range for optimal outcomes. Hence, this logic gate controlled APGS NCs makes MW thermal therapy eliminate tumor cells completely. This research offers an effective strategy for the design and preparation of activatable theranostic nanoagents for precise tumor imaging and therapy.

Long non-coding RNA ZNF667-AS1 retards the development of esophageal squamous cell carcinoma via modulation of microRNA-1290-mediated PRUNE2.

Abnormal long non-coding RNAs (lncRNAs) have been detected in esophageal squamous cell carcinoma (ESCC). Here, we focused on lncRNA ZNF667-AS1 and its downstream mechanism in ESCC progression. Differentially expressed lncRNAs in ESCC were predicted by bioinformatics analysis. ZNF667-AS1, microRNA-1290 (miR-1290), and prune homolog 2 with BCH domain (PRUNE2) expression was determined with their relationship in cell biological processes analyzed also by means of gain- and loss-of-function assays. Xenograft mouse models were performed to re-produce the in vitro findings. We found a decline in ZNF667-AS1 expression in ESCC tissues and cell lines. ZNF667-AS1 overexpression indicated a favorable prognosis of ESCC sufferers. ZNF667-AS1 overexpression suppressed ESCC cell malignant potentials. ZNF667-AS1 reduced miR-1290 to result in upregulation of the miR-1290 target gene PRUNE2. The inhibiting property of ZNF667-AS1 on the malignant characteristics of ESCC cells was achieved by disrupting the miR-1290-mediated downregulation of PRUNE2. ZNF667-AS1 suppressed the tumorigenesis of ESCC in vivo. Collectively, our study demonstrates that ZNF667-AS1 can function as a tumor suppressor in ESCC by upregulating PRUNE2 and downregulating miR-1290.

Effects of Enteral Nutrition on Patients With Oesophageal Carcinoma Treated With Concurrent Chemoradiotherapy: A Prospective, Multicentre, Randomised, Controlled Study.

Background: The oesophageal carcinoma patients show high incidence of malnutrition, which negatively affects their therapy outcome. Moreover, benefits of enteral nutrition remain to be studied in details in these patients. Therefore, we set to assess the effects of enteral nutrition on the nutritional status, treatment toxicities and survival in the oesophageal carcinoma patients treated with concurrent chemoradiotherapy (CCRT). Materials and Methods: Eligible patients were randomly assigned to either the experimental or control group. The patients in the experimental group were treated with a whole-course enteral nutrition management, while the control group were provided a unsystematic nutrition without setting intake goals for energy and protein. The primary endpoint was a change in body weight, while the secondary endpoints included nutrition-related haematological indicators, toxicities, completion rate of treatment and survival. Results: A total of 222 patients were randomised to either the experimental (n=148) or control (n=74) group. Patients in the experimental group showed significantly less decrease in body weight, serum albumin and haemoglobin levels, a lower incidence rates of grade ≥3 myelosuppression and infection, and a higher completion rate of CCRT than those in the control group. While analyses of the 2 and 3 year overall survival (OS) and progression-free survival (PFS) did not reveal differences between these groups, we observed a significantly higher OS at 1 year (83.6% vs. 70.0%). In the subgroup analysis, patients with patient-generated subjective global assessment (PG-SGA)=C were likely to have better OS and PFS with enteral nutrition. Conclusions: In EC patients treated with CCRT, enteral nutrition conferred positive effects on the nutritional status, treatment toxicities and prognosis, which mandate its inclusion in clinical practice. Clinical Trial Registration: This prospective trial has been registered with www.clinicaltrials.gov as NCT02399306.

The role of toll-like receptors (TLRs) in pan-cancer.

BACKGROUND: Toll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study's goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis. METHODS: The expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data. RESULTS: Our multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research. CONCLUSION: TLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators. Key MessagesToll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.