Liver cancer is becoming one of the most lethal malignancies due to its high incidence and mortality. Accumulating studies have indicated that long non-coding RNAs (lncRNAs) are critical regulators of the tumorigenesis and development of various types of cancer, including liver cancer. LncRNA LOXL1-antisense RNA 1 (LOXL1-AS1) has been identified as an oncogene in some types of human cancer; however, its role in liver cancer remains obscure. Reverse transcription-quantitative PCR was used to measure LOXL1-AS1 expression in liver cancer tissues and cells. Western blot, MTT, colony formation, glucose uptake and wound healing assays were used to explore the biological function of LOXL1-AS1 in liver cancer cells. Bioinformatics analysis and RNA pull-down and luciferase reporter assays were used to explore the molecular mechanism of LOXL1-AS1 in liver cancer cells. Statistical analysis was used to compare the experimental results of different groups. In the present study, LOXL1-AS1 expression was significantly upregulated in liver cancer tissues and cells compared with in normal liver tissues and cells, respectively. High LOXL1-AS1 expression was associated with poor clinical outcomes in patients with liver cancer. Furthermore, LOXL1-AS1-knockdown suppressed glucose metabolism, proliferation, migration and epithelial-mesenchymal transition (EMT) of liver cancer cells. Subsequently, LOXL1-AS1 acted as a microRNA (miR)-377-3p sponge, and nuclear factor I B (NFIB) was confirmed as the downstream target of miR-377-3p in liver cancer cells. Additionally, rescue assays suggested that NFIB overexpression countervailed the inhibitory influence of LOXL1-AS1 silencing on liver cancer cellular processes. The present study demonstrated that LOXL1-AS1 promoted glucose metabolism, proliferation, migration and EMT of liver cancer cells by sponging miR-377-3p and modulating NFIB, which may provide a novel insight for the treatment of liver cancer.

/pdf/lncrna-loxl1-as1-promotes-liver-cancer-cell-proliferation-swougpe7bo.pdf

lncRNA LOXL1-AS1 promotes liver cancer cell proliferation and migration by regulating the miR-377-3p/NFIB axis.

Messenger RNA (mRNA) cancer vaccines are a new class of immunotherapies that can activate the immune system to recognize and destroy cancer cells. However, their effectiveness in treating colorectal cancer located on the mucosal surface of the gut is limited due to the insufficient activation of mucosal immune response and inadequate infiltration of cytotoxic T cells into tumors. To address this issue, a new mRNA cancer vaccine is developed that can stimulate mucosal immune responses in the gut by co-delivering all-trans-retinoic acid (ATRA) and mRNA using lipid nanoparticle (LNP). The incorporation of ATRA has not only improved the mRNA transfection efficiency of LNP but also induced high expression of gut-homing receptors on vaccine-activated T cells. Additionally, the use of LNP improves the aqueous solubility of ATRA, eliminating the need for toxic solvents to administer ATRA. Upon intramuscular injections, ATRA-adjuvanted mRNA-LNP significantly increase the infiltration of antigen-specific, cytotoxic T cells in the lamina propria of the intestine, mesenteric lymph nodes, and orthotopic colorectal tumors, resulting in significantly improved tumor inhibition and prolonged animal survival compared to conventional mRNA-LNP without ATRA. Overall, this study provides a promising approach for improving the therapeutic efficacy of mRNA cancer vaccines against colorectal cancer. 

All‐Trans‐Retinoic Acid‐Adjuvanted mRNA Vaccine Induces Mucosal Anti‐Tumor Immune Responses for Treating Colorectal Cancer

Abstract Background In recent years, the research on the relationship between sarcopenia before and after the treatment of esophageal cancer, as well as its impact on prognosis of esophageal cancer, has increased rapidly, which has aroused people’s attention to the disease of patients with esophageal cancer complicated with sarcopenia. This review examines the prevalence of sarcopenia in patients with esophageal cancer, as well as the relationship between sarcopenia (before and after surgery or chemotherapy) and prognosis in patients with esophageal cancer. Moreover, we summarized the potential pathogenesis of sarcopenia and pharmacologic and non-pharmacologic therapies. Methods A narrative review was performed in PubMed and Web of Science using the keywords (“esophageal cancer” or “esophageal neoplasm” or “neoplasm, esophageal” or “esophagus neoplasm” or “esophagus neoplasms” or “neoplasm, esophagus” or “neoplasms, esophagus” or “neoplasms, esophageal” or “cancer of esophagus” or “cancer of the esophagus” or “esophagus cancer” or “cancer, esophagus” or “cancers, esophagus” or “esophagus cancers” or “esophageal cancer” or “cancer, esophageal” or “cancers, esophageal” or “esophageal cancers”) and (“sarcopenia” or “muscular atrophy” or “aging” or “senescence” or “biological aging” or “aging, biological” or “atrophies, muscular” or “atrophy, muscular” or “muscular atrophies” or “atrophy, muscle” or “atrophies, muscle” or “muscle atrophies”). Studies reporting relationship between sarcopenia and esophageal cancer were analyzed. Results The results of the review suggest that the average prevalence of sarcopenia in esophageal cancer was 46.3% ± 19.6% ranging from 14.4 to 81% and sarcopenia can be an important predictor of poor prognosis in patients with esophageal cancer. Patients with esophageal cancer can suffer from sarcopenia due to their nutritional deficiencies, reduced physical activity, chemotherapy, and the effects of certain inflammatory factors and pathways. When classic diagnostic values for sarcopenia such as skeletal muscle index (SMI) are not available clinically, it is also feasible to predict esophageal cancer prognosis using simpler metrics, such as calf circumference (CC), five-count sit-up test (5-CST), and six-minute walk distance (6MWD). Conclusions Identifying the potential mechanism of sarcopenia in patients with esophageal cancer and implementing appropriate interventions may hold the key to improving the prognosis of these patients. 

Correlation between sarcopenia and esophageal cancer: a narrative review

Radical surgery is the most commonly used treatment for hepatocellular carcinoma (HCC). However, the surgical effect remains not ideal, and prognostic

Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer

Purpose This study aims to assess the prognostic value of inflammatory markers and clinical features in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients receiving anti-programmed death 1 (PD-1) treatment. Methods Based on receiver operating characteristic curve (ROC) analysis, Youden’s indexes were applied to determine the cut-off values for inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocye ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Wilcoxon test was conducted to evaluate the changes in above inflammatory markers. Kaplan-Meier method was utilized to estimate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used to compare the different survival between groups. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of inflammatory markers and clinical features. Results 162 advanced or metastatic ESCC patients receiving anti-PD-1 treatment were enrolled in this retrospective study. The cut-off values of NLR, dNLR, MLR, PLR, and SII were 4.748, 2.214, 0.309, 250.505, and 887.895, respectively. NLR, dNLR, PLR, and SII declined significantly among the partial response (PR) (P<0.001, P<0.001, P=0.036, P<0.001), objective response rate (ORR) (P<0.001, P<0.001, P=0.036, P<0.001), and disease control rate (DCR) (P<0.001, P<0.001, P=0.038, P<0.001) groups, respectively. Significant increases were found in NLR (P<0.001), dNLR (P<0.001), MLR (P=0.001), and SII (P=0.024) when anti-PD-1 treatment failed. Multivariate Cox regression analysis indicated that NLR (P<0.001, P=0.002), lymph node metastasis (P=0.013, P=0.001), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (P=0.008, P=0.002), and treatment lines (P=0.037, P=0.048) were significant prognostic indicators of PFS and OS. Additionally, SII (P=0.016) was also significantly related to OS in ESCC patients. The risk score model showed that low risk patients prolonged PFS and OS than those with middle or high risk (P<0.001, P<0.001). Conclusion Inflammatory markers can reflect short-term outcomes of anti-PD-1 treatment for ESCC patients. NLR, lymph node metastases, ECOG PS, and treatment lines are significant prognostic indicators for PFS and OS. And the risk score model constructed based on the above factors has favourable prognostic predictive value.

/pdf/prognostic-value-of-inflammatory-markers-and-clinical-2p4mnjw7.pdf

Prognostic value of inflammatory markers and clinical features for survival in advanced or metastatic esophageal squamous cell carcinoma patients receiving anti-programmed death 1 treatment

Objective To investigate the expression of long noncoding RNA lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) in hepatocellular carcinoma tissues and its effect on cell proliferation, migration, and invasion. Methods Quantitative real-time PCR was used to analyze the expression of LOXL1-AS1 RNA in tumor tissues, adjacent normal tissues, and cell lines. MTT assay, colony formation assay, flow cytometry analysis, transwell assays, and lentivirus-mediated RNA interference (RNAi) technology were used to evaluate cell proliferation and migration. Results In the present study, we observed that the expression level of LOXL1-AS1 in hepatocellular carcinoma tissue was significantly higher than that in adjacent nontumor tissues, and its expression in three hepatic carcinoma cell lines was obviously higher than that in a normal cell line. In addition, in the Hep-G2 cell line, LOXL1-AS1 downregulation significantly inhibited cell proliferation in the light of the MTT and colony formation assays in vitro, which was consistent with animal experiment in vivo. What is more, cell migration was also inhibited in vitro in Matrigel Transwell Assay by LOXL1-AS1 knockdown, which might be partly attributed to the reduction of MMP-2 and MMP-9 protein expressions. Finally, cell cycle analysis revealed that knockdown of LOXL1-AS1 induced significantly a G0/G1 phase cell cycle arrest, which might be partly attributed to the downregulation of Cdc2, Cdc25A, and cyclin B1 protein expression. Conclusion In conclusion, we demonstrated that reduced LOXL1-AS1 expression could inhibit hepatocellular carcinoma cell proliferation, migration, and invasion. The application of RNAi targeting LOXL1-AS1 might be a potential treatment strategy in advanced cases.

/pdf/the-long-noncoding-rna-loxl1-as1-promotes-the-proliferation-1yyqvw7vsg.pdf

The Long Noncoding RNA LOXL1-AS1 Promotes the Proliferation, Migration, and Invasion in Hepatocellular Carcinoma.

Objective Systemic inflammatory factors are independent risk factors in the formation and progression of various solid tumors. However, whether systemic inflammatory factors are associated with effect and prognosis of esophageal squamous cell carcinoma patients treated with immunotherapy remains unknown. The aim of this study is to assess the value of systemic inflammatory factors in the efficacy of camrelizumab for patients with advanced, metastatic esophageal squamous cell carcinoma. Methods We conducted a retrospective analysis of 90 patients with advanced, metastatic esophageal squamous cell carcinoma who received treatment with camrelizumab in Xinghua People’s Hospital between August 2019 and October 2021. The optimal cut-off values of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) for predicting efficacy and prognosis were identified based on the receiver operating characteristic (ROC) curve. Progression free survival (PFS) and overall survival (OS) were evaluated using the Kaplan–Meier method, and differences in PFS or OS between groups were compared by the Log rank test. Univariate and multivariate Cox proportional hazards regression models were performed to analyze prognostic values of each variable. Results The optimal cutoff values of PLR, NLR and SII predicted survival outcomes were 157.7, 3.84 and 750.8, respectively. Higher PLR, NLR and SII were associated with shorter PFS (HR for PLR = 2.899, P = 0.001; HR for NLR = 3.629, P < 0.001; HR for SII = 10.251, P < 0.001) and OS (HR for PLR = 4.583, P < 0.001; HR for NLR = 3.921, P < 0.001; HR for SII = 38.606, P < 0.001). Multivariate Cox regression analysis revealed that high PLR, NLR and SII were independent risk factors of PFS and OS in the advanced, metastatic esophageal squamous cell carcinoma patients receiving camrelizumab. Conclusion PLR, NLR and SII are potentially effective prognostic predictors in advanced, metastatic esophageal squamous cell carcinoma patients treated with camrelizumab.

The Predictive Value of Systemic Inflammatory Factors in Advanced, Metastatic Esophageal Squamous Cell Carcinoma Patients Treated with Camrelizumab

Limited benefit population of immunotherapy makes it urgent to select effective biomarkers for screening appropriate treatment population. Herein, we have investigated the predictive values of circulating CD8+ T cells and CD8+T/CD4+T cell ratio in advanced gastric cancer patients receiving immunotherapy.A retrospective cohort analysis of 187 advanced gastric cancer patients receiving sintilimab combined with oxaliplatin and capecitabine therapy in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University between December 2019 and February 2023 was conducted. The corresponding clinical outcomes of the variables were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier methods and Cox proportional hazards regression models.The optimal cutoff values for percentages of CD8+ T cells, naive CD8+ T cells (CD8+ Tn) and memory CD8+ T cells (CD8+ Tm) expressing programmed cell death -1(PD-1) as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were 21.0, 21.5, 64.3 and 0.669, respectively. It was found that the mean percentages of CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). We also observed this correlation in programmed cell death-ligand 1(PD-L1) combined positive score (CPS) ≥ 5 subgroups. Univariate and multivariate Cox regression analyses demonstrated that lower CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were independent risk factors in advanced gastric cancer patients receiving immunotherapy plus chemotherapy.The circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio revealed high predictive values for response and prolonged survival outcomes in advanced gastric cancer patients receiving immunotherapy. Memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio might be effective for screening benefit population of immunotherapy in advanced gastric cancer patients based on this preliminary evidence. 

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Nutritional indicators have been implicated in the survival outcomes of various malignant tumors. However, there are few studies on the association between nutritional indicators and immunotherapy for esophageal cancer. The present study aimed to explore the value of nutritional indicators with regard to the survival outcomes in patients with metastatic esophageal squamous cell carcinoma (ESCC) treated with camrelizumab. A retrospective cohort analysis of 158 metastatic ESCC patients treated with camrelizumab in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University (Xinghua, China) between September 2019 and July 2022 was conducted. A receiver operating characteristic curve was used to determine the optimal cut-off values of prognostic nutritional index (PNI) and albumin (ALB). The cut-off value for body mass index (BMI) was set at the normal lower limit (18.5 kg/m2). Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and the differences in PFS or OS between groups were compared using the log-rank test. The prognostic value of each variable was analyzed based on the univariate and multivariate Cox proportional hazards regression models. The optimal cutoff values of PNI, ALB and BMI were 41.35, 36.8 g/l and 18.5 kg/m2, respectively. Lower PNI, ALB and BMI were closely associated with shorter PFS [hazard ratio (HR) for PNI, 3.599; P<0.001; HR for ALB, 4.148; P<0.001; HR for BMI, 5.623; P<0.001) and OS (HR for PNI, 7.605; P<0.001; HR for ALB, 7.852; P<0.001; HR for BMI, 7.915; P<0.001) times. Univariate and multivariate Cox regression analyses indicated that lower PNI, ALB and BMI were independent risk factors of PFS and OS in patients with metastatic ESCC receiving camrelizumab treatment. In conclusion, PNI, ALB and BMI are promising predictive indicators to assess the survival outcomes in patients with metastatic ESCC treated with camrelizumab. Moreover, PNI, ALB and BMI may have prognostic significance in these patients.

/pdf/predictive-value-of-nutritional-indicators-with-regard-to-3iwuxwbq.pdf

Predictive value of nutritional indicators with regard to the survival outcomes in patients with metastatic esophageal squamous cell carcinoma treated with camrelizumab

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The Long Noncoding RNA LOXL1-AS1 Promotes the Proliferation, Migration, and Invasion in Hepatocellular Carcinoma.

The Predictive Value of Systemic Inflammatory Factors in Advanced, Metastatic Esophageal Squamous Cell Carcinoma Patients Treated with Camrelizumab

Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients

Predictive value of nutritional indicators with regard to the survival outcomes in patients with metastatic esophageal squamous cell carcinoma treated with camrelizumab