Background: Studies on serum one-carbon metabolism factors (folate, B6, B12, homocysteine, and methionine) with lung cancer (LC) risk have produced inconsistent results. We aimed to systematically evaluate the association between them.Methods: This study was reported in accordance with the PRISMA Statement and was registered with PROSPERO (no. CRD42018086654). Relevant studies were searched in PubMed, Embase, MEDLINE, and CNKI up to February 2018. Random-effects models were used to estimate the pooled standardized mean differences (SMD) or odds ratios (OR), as well as their 95% confidence interval (CI). Sensitivity and subgroup analysis were performed to identify the source of heterogeneity. Publication bias was also assessed.Results: A total of 14 articles (8,097 patients) were included. The concentration of serum folate and vitamin B6 of LC patients were lower than the controls [SMD −0.53, 95% CI (−0.70, −0.35), p = 0.001 and SMD −0.28, 95%CI (−0.53, −0.02), p = 0.001, respectively]. While the concentration of homocysteine of the cases was higher than the controls [SMD 0.41, 95% CI (0.24, 0.59), p = 0.001]. However, there were no significant differences between LC patients and the controls in terms of vitamin B12 and methionine [SMD −0.09, 95% CI (−0.27, 0.09), p = 0.202 and SMD −0.13, 95% CI (−0.36, 0.10), p = 0.001]. Subgroup analysis showed that these results were more significant in Europe, Asia, former and current smokers, and the male population (p-value < 0.05).Conclusions: Serum folate and vitamin B6 might be protective factors against lung carcinogenesis and homocysteine could contribute to LC risk.
BackgroundTo evaluate the effect of qi-nourishing essence-replenishing Chinese herbal medicine combined with chemotherapy in survival of advanced non-small-cell lung cancer(NSCLC) patients with essence and qi deficiency.MethodsA prospective multi-centered randomized controlled study was conducted, and 266 advanced NSCLC patients were enrolled. 126 patients in control group received Vinorelbine plus cisplatin(NP) chemotherapy combined with symptom-oriented Chinese herbs medication(without qi-nourishing essence-replenishing herbs);140 patients in experimental group received NP chemotherapy combined with qi-nourishing essence-replenishing Chinese herbal medication(Kangliu Zengxiao Decoction and modified Feiyanning Decoction, during and after chemotherapy respectively).ResultsOne patient in control and 2 in experimental group were excluded for failure to complete two cycles of chemotherapy. During follow-up, 17 and 7 patients in control and experimental group were excluded respectively(4 and 4 for taking Gefetinib after disease progression, 4 and 2 for receiving other chemotherapeutic regimens, 9 and 1 for lost to follow-up). 239 patients were included in the final analysis (131 in experimental group and 108 in control). Median overall survival in experimental group was significantly longer than control group (14.87vs.12.97 months,P = 0.027). In experimental and control group, 1-year, 3-year, 5-year, 7-year, and 9-year survival rates were 57% vs. 53%, 17% vs. 8%, 10% vs. 2%, 6% vs. 0%, and 6% vs. 0%, respectively.ConclusionQi-nourishing essence-replenishing Chinese herbal medicine combined with chemotherapy improves survival of advanced NSCLC patients with essence and qi deficiency.
Cinobufagin is used as a traditional Chinese medicine for cancer therapy. However, it has some disadvantages, such as poor water solubility, short circulating half-life, and low bioavailability. In the present study, a targeted delivery and smart responsive polydopamine (PDA)-based nanomedicine for delivering cinobufagin was rationally designed to improve the anticancer efficacy of the compound for the treatment of lung cancer. The modification of the nanomedicine using folic acid first mediated tumor targeting via the interaction between folic acid and its receptors on tumor cells. After lysosomes escape, the PDA nanomedicine was triggered by the low pH and released its cargo into the tumor microenvironment. The nanomedicine had a better therapeutic effect against lung cancer when used in combination with photothermal therapy. Compared with other nanomedicines used with photothermal therapy, this nanocarrier was not only sensitive to biologically low pH levels for on-demand drug release, but was also biodegradable, breaking down into biocompatible terminal products. Therefore, the proposed drug delivery system with targeted delivery and smart release demonstrated potential as a multifunctional nanoplatform that can enhance the bioavailability and reduce the side effects of chemotherapeutic agents.
Background The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear. Methods Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 and GSE112214) were identified by utilizing R package (Limma). Circinteractome and StarBase databases were used to predict circRNA associated-miRNAs and mRNAs, respectively. Then, protein–protein interaction (PPI) network of hub genes and ceRNA network were constructed by STRING and Cytoscape. Also, analyses of functional enrichment, genomic mutation and diagnostic ROC were performed. TIMER database was used to analyze the association between immune infiltration and target genes. Kaplan–Meier analysis, cox regression and the nomogram prediction model were used to evaluate the prognostic value of target genes. Finally, the expression of potential circRNAs and target genes was validated in cell lines and tissues by quantitative real-time PCR (qRT-PCR) and Human Protein Atlas (HPA) database. Results In this study, 15 DECs were identified between NSCLC tissues and adjacent-normal tissues in two GEO datasets. Following the qRT-PCR corroboration, 7 DECs (hsa_circ_0002017, hsa_circ_0069244, hsa_circ_026337, hsa_circ_0002346, hsa_circ_0007386, hsa_circ_0008234, hsa_circ_0006857) were dramatically downregulated in A549 and SK-MES-1 compared with HFL-1 cells. Then, 12 circRNA-sponged miRNAs were screened by Circinteractome and StarBase, especially, hsa-miR-767-3p and hsa-miR-767-5p were significantly up-regulated and relevant to the prognosis. Utilizing the miRDB and Cytoscape, 12 miRNA-target genes were found. Functional enrichment, genomic mutation and diagnostic analyses were also performed. Among them, FNBP1, AKT3, HERC1, COL4A1, TOLLIP, ARRB1, FZD4 and PIK3R1 were related to the immune infiltration via TIMER database. The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram. Furthermore, the hub-mRNAs were validated in cell lines and tissues. Conclusion We constructed the circRNA-miRNA-mRNA network that might provide novel insights into the pathogenesis of NSCLC and reveal promising immune infiltration and prognostic biomarkers.
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