Increased pretreatment triglyceride glucose-body mass index associated with poor prognosis in patients with advanced non-small cell lung cancer.

BACKGROUND: The association between the triglyceride glucose-body mass index (TyG-BMI) and various health outcomes has been postulated. Nonetheless, the application of TyG-BMI in predicting the prognosis of non-small cell lung cancer (NSCLC) remains poorly understood. Our objective was to explore the association between TyG-BMI and both progression-free survival (PFS) and overall survival (OS) in patients with advanced NSCLC. METHODS: A retrospective study was conducted on the data of 426 patients diagnosed with advanced NSCLC between 2018 and 2022. The TyG-BMI values were derived from the serum triglyceride, fasting plasma glucose, and BMI measurements obtained at the time of diagnosis. Cox proportional hazards regression models were applied to examine the impact of TyG-BMI on both progression-free survival (PFS) and overall survival (OS) in advanced NSCLC. RESULTS: The median duration of follow-up was 899 days, with an interquartile range of 256-1486 days. In comparison to the lowest tertile of TyG-BMI, the highest tertile model demonstrated a significant association with worse OS (hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.21-2.80; P = 0.001) and PFS (HR: 2.10; 95% CI: 1.40-3.10; P < 0.001). Each standard deviation increase in TyG-BMI corresponded to a 10% reduction in OS (95% CI: 1%-24%) and a 14% reduction in PFS (95% CI: 2%-27%). Subgroup analyses indicated that cigarette smokers and individuals with elevated C-reactive protein (CRP) levels exhibited a notably unfavorable prognosis in relation to TyG-BMI-associated advanced NSCLC, as evident in both OS (P for interaction: 0.046 for smoking) and PFS (P for interaction: 0.033 for smoking and 0.049 for CRP). CONCLUSION: Our data revealed a causal relationship between TyG-BMI and an unfavorable prognosis in patients with advanced NSCLC. Furthermore, this independent association exhibits greater significance in individuals who are smokers and exhibit higher levels of CRP.

APOC1 predicts a worse prognosis for esophageal squamous cell carcinoma and is associated with tumor immune infiltration during tumorigenesis.

Background: Esophageal carcinoma (ESCA), a common malignant tumor of the digestive tract with insidious onset, is a serious threat to human health. Despite multiple treatment modalities for patients with ESCA, the overall prognosis remains poor. Apolipoprotein C1 (APOC1) is involved in tumorigenesis as an inflammation-related molecule, and its role in esophageal cancer is still unknown. Methods: We downloaded documents and clinical data using The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. We also conducted bioinformatics studies on the diagnostic value, prognostic value, and correlation between APOC1 and immune infiltrating cells in ESCA through STRING (https://cn.string-db.org/), the TISIDB (http://cis.hku.hk/TISIDB/) website, and various other analysis tools. Results: In patients with ESCA, APOC1 was significantly more highly expressed in tumor tissues than in normal tissues (p < 0.001). APOC1 could diagnose ESCA more accurately and determine the TNM stage and disease classification with high accuracy (area under the curve, AUC≥0.807). The results of the Kaplan-Meier curve analysis showed that APOC1 has prognostic value for esophageal squamous carcinoma (ESCC) (p = 0.043). Univariate analysis showed that high APOC1 expression in ESCC was significantly associated with worse overall survival (OS) (p = 0.043), and multivariate analysis shows that high APOC1 expression was an independent risk factor for the OS of patients with ESCC (p = 0.030). In addition, the GO (gene ontology)/KEGG (Kyoto encyclopedia of genes and genomes) analysis showed a concentration of gene enrichment in the regulation of T-cell activation, cornification, cytolysis, external side of the plasma membrane, MHC protein complex, MHC class II protein complex, serine-type peptidase activity, serine-type endopeptidase activity, Staphylococcus aureus infection, antigen processing and presentation, and graft-versus-host disease (all p < 0.001). GSEA (gene set enrichment analysis) showed that enrichment pathways such as immunoregulatory-interactions between a lymphoid and non-lymphoid cell (NES = 1.493, p. adj = 0.023, FDR = 0.017) and FCERI-mediated NF-KB activation (NES = 1.437, p. adj = 0.023, FDR = 0.017) were significantly enriched in APOC1-related phenotypes. In addition, APOC1 was significantly associated with tumor immune infiltrating cells and immune chemokines. Conclusion: APOC1 can be used as a prognostic biomarker for esophageal cancer. Furthermore, as a novel prognostic marker for patients with ESCC, it may have potential value for further investigation regarding the diagnosis and treatment of this group of patients.

miR-181a-5p restrains non-small cell lung cancer cell invasion and migration by regulating the GTSE1/p53/NF-κB axis.

microRNAs (miRNAs) are relevant to metastasis and invasion of non-small cell lung cancer (NSCLC). This study investigated the role of miR-181a-5p in lung cancer. Expression patterns of miR-181a-5p and GTSE1 in the human NSCLC cell line A549 and normal lung epithelial cell line BASE-2B were detected. miR-181a-5p mimic was delivered into A549 cells utilizing Lipofectamine 2000 to overexpress miR-181a-5p, followed by analysis of cell viability, proliferation, apoptosis, invasion, and migration. GTSE1 (G2 and S phase-expressed-1) was predicted as the downstream target gene of miR-181a-5p using bioinformatics analysis software. Targeting relationship between miR-181a-5p and GTSE1 was validated via dual-luciferase assay, RIP assay, and RNA pull-down. Activation of the p53/NF-κB pathway was determined. miR-181a-5p was weakly-expressed in NSCLC cells relative to normal lung epithelial cells. miR-181a-5p overexpression prevented NSCLC cell proliferation, migration, and invasion. Mechanically, miR-181a-5p targeted GTSE1. GTSE1 overexpression partly annulled repression of miR-181a-5p overexpression on NSCLC cell malignant behavior. miR-181a-5p activated the p53 pathway and inhibited the NF-κB pathway by targeting GTSE1. Overall, this study for the first time validated that miR-181a-5p impeded NSCLC cell invasion and migration through activation of the p53 pathway and inhibition of the NF-κB pathway by targeting GTSE1, which may provide a potential novel insight into NSCLC treatment.

Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR.

Non-small cell lung cancer (NSCLC) is a malignant tumor. Serum exosomal miR-27b is related to tumor diagnosis. We explored the roles of serum exosomal miR-27b in NSCLC. NSCLC patients were assigned to NSCLC-early/terminal groups, with healthy subjects as controls. miR-27b expression was assessed using reverse transcription-quantitative polymerase chain reaction, and its diagnostic efficiency was analyzed using the receiver operating characteristic curve. The correlation between serum exosomal miR-27b expression and tumor markers carcinoembryonic antigen 125 (CA125), carcinoembryonic antigen (CEA), and cytokeratin 19-soluble fragment (CYFRA21-1) was analyzed using the Pearson analysis. The downstream target genes were predicted. Epidermal growth factor receptor (EGFR) level was assessed using enzyme-linked immunosorbent assay. Correlations of miR-27b expression with serum EGFR level and CA125, CEA, and CYFRA21-1 levels were analyzed using the Pearson analysis. Serum exosomal miR-27b was diminished in NSCLC and was further decreased in the NSCLS-terminal group. The sensitivity of miR-27b < 0.8150 for NSCLC diagnosis was 76.64%, and the specificity was 83.33%. Serum exosomal miR-27b was negatively correlated with CA125, CEA, and CYFRA21-1. miR-27b targeted EGFR. Serum EGFR was raised in NSCLC and was further elevated in the NSCLS-terminal group. miR-27b expression was negatively correlated with EGFR level. EGFR level was positively correlated with CA125, CEA, and CYFRA21-1 levels. Collectively, low expression of miR-27b assisted NSCLC diagnosis, and miR-27b exerted effects on NSCLC through EGFR.

Daidzein-rich isoflavones aglycone inhibits lung cancer growth through inhibition of NF-κB signaling pathway.

To develop anti-tumor agents for lung cancer, we aim to characterize a herbal compound, daidzein-rich isoflavones aglycone (DRIA), in inhibiting the proliferation and NF-κB signaling pathway of lung cancer. MTT and colony formation assays were used to analyze the proliferation of lung cancer cells in presence of DRIA treatment, which showed that DRIA dose-dependently inhibited the proliferation and colony formation of lung cancer cells. Enzyme-linked immunosorbent assay revealed that interleukin-6 (IL6) and interleukin-8 (IL-8) levels were reduced by DRIA. p65-NFκB expression and activation, which was enhanced by TNF-α and C/EBPß treatment, were attenuated by DRIA. Exogenous tumor necrosis factor-α (TNF-α) and CCAAT/enhancer binding protein (C/EBPß) were used to enhance NF-κB signaling in cells, and the effects of DRIA in attenuating NF-κB signaling were assessed by analyzing p65-NFκB expression in mRNA and protein levels, using quantitative real-time PCR (qRT-PCR), western blot and immunofluorescence staining. immunohistochemical staining revealed that Ki-67 and p65-NF-κB levels in A594 tumor xenografts of A594 tumors were also reduced by DRIA treatment in mice. Our data indicates that DRIA is effective in inhibiting the proliferation and NFκB signaling of lung cancer both in vitro and in vivo.

[Study of pancreases ß-cell function in first-degree relatives of type 2 diabetes patients].

AIM: To investig the pancreases ß-cell function in no-diabetic first-degree relatives of type 2 diabetes mellitus( FDR) patients. METHODS: Collect T2DM first-degree relatives, and divided them into three groups:no-diabetes group with normal sugar tolerance (NGT); no-diabetes with abnormal sugar tolerance (IGT); new-confirmed T2DM. apart from that three group patients, 30 normal people with no-related disease risks were also collected as normal control (NC). All four groups of patients were experienced with intravenous glucose tolerance test (IVGTT) and counting the first phase of pancreases function by statistic AIR35 and insulin sensitive index (ISI). RESULTS: New-confirmed T2DM patients with the significantly abnormal statistic results about AIR3.5 and ISI, while NGT patients had the abnormal results compared with normal control group but better than T2DM patients. CONCLUSION: Compared with normal group patients, NGT group appeared decrease of pancreases first phase secretes and insulin resistance but not aggravate enough to induce type 2 diabetes.

Madecassoside reduces ischemia-reperfusion injury on regional ischemia induced heart infarction in rat.

Madecassoside (MA), one of the principle terpenoids in Centella asiatica, has shown protect effect on isolated rat hearts and isolated cardiomyocytes against reperfusion injury in our previous studies. The aim of this study is to investigate if MA also protected against myocardial ischemia-reperfusion injury in vivo. The ischemia infarction model was established in rats. Left ventricular function was monitored during the ischemia-reperfusion period by a multi-channel recorder. After the ischemia-reperfusion process the infarcted areas were assessed. The levels of lactate dehydrogenase (LDH), creatinephosphokinase (CK), malondialdehyde (MDA), super-oxide dismutase (SOD) and C-reactive protein (CRP) in serum were determined. Cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. Pre-treatment with MA (50, 10 mg/kg) attenuated myocardial damage characteristic of decreasing infarct size, decreasing LDH and CK release. Activities of SOD were increased and MDA level increased obviously in control group whereas pretreatment with MA blunted the decrease of SOD activity, markedly reduced the level of MDA and the activity of CRP, and relieved myocardial cell apoptosis. These results suggest that MA has the protective effect on myocardial ischemia-reperfusion injury. This protection ability possibly due to its anti-lipid peroxidation, anti-inflammation and anti-apoptosis function and the enhancement of SOD activity.

Radioimmunotherapy of carcinoma of colon with [131I]-labeled recombinant chimeric monoclonal antibodies to carcinoembryonic antigen.

AIM: To study the distribution of [(131)I]-labeled anti-CEA MoAbs and its therapeutic effect on the human colonic cancer model in nude mice. METHODS: A nude mice model of human colonic cancer was established. [(131)I]-labeled anti-CEA MoAbs were injected intravenously into mice. The distribution of the MoAbs was then determined and the effect of RIT on human colonic cancer was observed. RESULTS: The [(131)I]-labeled anti-CEA MoAbs had a specific distribution after injection. Tumor/non-tumor ratios for [(131)I]-labeled anti-CEA MoAbs were 10-20 times higher than [(131)I]-labeled IgG 96 h after injection. Thirty days after injection, significant inhibition of the volume and weight of tumor was observed in the treated mice compared with the control. The tumor growth inhibition rate of 3.1 mCi/kg CEA MoAbs group (LS180, LS174T, SW1116) was 47.8%-64.0%. This was 69.6%-78.6% in the 6.25 mCi/kg CEA MoAbs group, and 81.8%-86.2% in the 12.5 mCi/kg [(131)I]-labeled anti-CEA MoAbs group. The plasma CEA level was also lower in treated mice. CONCLUSION: The results indicate that [(131)I]-labeled anti-CEA MoAbs can be effective in RIT on colonic cancers.

Safety evaluation of recombinant staphylokinase in rhesus monkeys.

Recombinant staphylokinase (rSTAR) is a profibrinolytic agent of bacterial origin. The objective of this study was to assess the toxicity of rSTAR administered with bolus intravenous infusion in rhesus monkeys (2/sex/group) at the dosages of 0, 4, 14, and 49 mg/kg/day for 2 weeks. The clinical signs were thickening of the skin in all animals and mild hematoma formation in three dosage groups at the injection sites. There were no effects on body weight, absolute or relative organ weights, ophthalmology, or electrocardiogram. Urinalysis indicated that 2 monkeys in 14 or 49 mg/kg/day group developed proteinuria and mild hematuria. Increases in serum BUN levels (14 and 49 mg/kg/day), ALT activity, and bilirubin levels (49 mg/kg/day), and decreases in red blood cell counts, hemoglobin concentrations and Hct values (49 mg/kg/day) were observed at week 2. Significant prolongtion of APTT, PT, and TT (14 and 49 mg/kg/day), and decreases in circulating plasminogen levels (3 treatment groups) were noted. Dose-dependent increases in the titers of anti-rSTAR antibodies and neutralizing rSTAR activity were observed in the three treated groups. Increased neutralizing rSTAR activity diminished the phamacologic effects of rSTAR (ie, prolonged APTT, PT, and TT approaching baseline levels at week 2). Histopathological findings included hemorrhage, and perivascular inflammatory cell infiltration at the injection sites, heptocellular degeneration characterized as cytoplasmic eosinophilia, vacuolation and condensed nuclei (49 mg/kg/day), effusion of RBCs and plasma within some Bowman's capsules and hyaline casts within the lumen of some renal tubules in the kidneys (14 and 49 mg/day/kg), and mild to moderate megakaryocyte hypoplasia with varying levels of pyknotic nuclei at all dose levels. Immune deposits in glomeruli in the kidneys from the three treated groups were detected. These changes were reversible following a 4-week recovery period. In the present preclinical evaluation of toxicity in monkeys, rSTAR is well toleratte at doses up to 49 mg/kg/day. The toxic target organs are the liver, kidney, and bone marrow.

[Therapeutic Effect of rhIL-11 on Thrombocytopenia Induced by Carboplatin in Rhesus Monkeys]

The effectiveness of rhIL-11 on thrombocytopenia induced by carboplatin in rhesus monkeys was investigated. Thrombocytopenia was induced in monkeys by i.v. administration of carboplatin at a dose of 15 mg/kg(-1)/d(-1) for three consecutive days. rhIL-11 (50 or 100 micro g/kg(-1)/d(-1)) or Neumega (100 micro g/kg(-1)/d(-1)) were administered s.c. for 14 days beginning one day following the final dose of carboplatin. The results showed that rhIL-11 significantly improved mean platelet nadirs and shortened the mean duration of platelet counts less than 50% of pre-treatment values. Administration of rhIL-11 also resulted in moderate increase of the reticulated platelet, leukocyte and reticulocyte counts in peripheral blood and megakaryocytic and erythroid progenitors in bone marrow. rhIL-11 did not enhance ADP-induced platelet aggregation. These results indicate that rhIL-11 has a potent thrombopoietic effect in vivo and could be an important agent to reduce the severity and duration of thrombocytopenia following chemotherapy.