Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022.

Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity. Methods: Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection. Results: A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer" was the top reference with the most citations, Lung Cancer was the core journal, and "serum tumor marker" experienced a citation burst over the past 5 years. Conclusion: This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.

Prognostic significance of elevated pretreatment serum levels of CEA and CA-125 in epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer is a highly lethal gynecological malignancy. Accurate and cost-effective predictive tools to estimate the prognosis of patients with epithelial ovarian cancer before treatment are currently lacking. OBJECTIVE: The purpose of this study was to evaluate the prognostic significance of pretreatment serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen-125 (CA-125) in primary epithelial ovarian cancer. METHODS: Between 2008 and 2016, 326 patients with a diagnosis of primary epithelial ovarian cancer were retrospectively reviewed. We attempted to identify an optimal cut-off value of CEA to predict survival using ROC curve analysis. Cox regression univariate and multivariate analyses were used to evaluate prognostic factors. RESULTS: The optimal cut-off value of CEA was 2.6 ng/mL. In univariate and multivariate analyses, FIGO stage and pretreatment CA-125 and CEA levels significantly predicted progression-free and overall survival. The 5-year progression-free survival rate for patients with both a CEA level < 2.6 ng/mL and CA-125 level < 35 U/mL was 84%, compared to only 33% for the patients with higher levels of both markers (p< 0.001). The 5-year cancer specific survival rate was 94% in those with a CEA level < 2.6 ng/mL and CA-125 level < 35 U/mL, and only 39% for those with higher levels of both markers (p< 0.001). CONCLUSIONS: In addition to traditional prognostic factors, a pretreatment serum CEA level ⩾ 2.6 ng/mL and CA-125 level ⩾ 35 U/mL were also independent prognostic factors for epithelial ovarian cancer. Patients with an elevated CEA and/or CA-125 level before treatment should be considered to be at high-risk of recurrence and death.

Effects of Gegen Dingxuan Capsule on behavior, X-Ray Signs of the Cervical Spine, and Humoral Factor Levels in a Rat Model of Cervical Vertigo.

OBJECTIVE: To investigate the effects of Gegen Dingxuan capsule on behavior, X-ray signs of the cervical spine, and levels of norepinephrine (NE), nitric oxide (NO), endothelin (ET-1), and calcitonin gene-related peptide (CGRP) in the plasma of a rat model of cervical vertigo and additionally to clarify the underlying mechanisms of action. METHOD: A total of 40 male SPF Sprague-Dawley rats were randomly assigned to blank control, model, Sibelium, and Gegen Dingxuan capsule groups, with 10 rats in each group. A rat model of cervical vertigo was produced by physically damaging the cervical spine, thereby perturbing its stability. After cervical spine surgery, rats in the Sibelium and Gegen Dingxuan capsule groups were administered Sibelium and Gegen Dingxuan capsule, respectively. After 4 and 8 weeks of administration, balance beam test was used to assess behavior, lateral X-ray images of the cervical spine were taken and scored, and the plasma levels of NE, NO, ET-1, and CGRP were measured. RESULTS: After 4 and 8 weeks of drug administration, the balance beam test scores in the Gegen Dingxuan capsule group were significantly higher than those in the Sibelium group. The radiographic scores were significantly lower in the Gegen Dingxuan capsule group than those in the Sibelium group at 8 weeks. Plasma NE, NO, ET-1 levels, and ET-1/CGRP ratio were significantly decreased in the Gegen Dingxuan capsule group compared with the model group. No significant difference was found between the Sibelium and Gegen Dingxuan capsule groups. Plasma CGRP levels were significantly increased in the Gegen Dingxuan capsule group compared with the model group and were significantly decreased compared with the Sibelium group. CONCLUSIONS: Gegen Dingxuan capsule improves behavior, radiographic scores, reduces plasma levels of NE, NO, ET-1, and the ET-1/CGRP ratio, and increases plasma CGRP levels. Gegen Dingxuan capsule may improve outcome in the rat model of cervical vertigo by ameliorating cervical facet joint disorder, relieving cervical muscle spasm and vasospasm, increasing blood supply, and regulating humoral factor levels.

Effects of Chailong Jieyu Pill on Behavior, Monoamine Neurotransmitters, and Corticosteroid Receptors in a Rat Model of Anxiety Disorder.

Chailong Jieyu Pill (CJP) is composed of Radix Bupleuri, Radix Scutellariae, Rhizoma Pinelliae Preparata, Radix Codonopsis, Radix Glycyrrhizae preparata, keel, Concha Ostreae, Concha Margaritifera Usta, Rhizoma Zingiberis Recens, and Fructus Jujubae. CJP has shown good clinical effects on improving anxiety disorders. However, as the mechanism underlying such benefits remains unclear, the aim of this study was to investigate the mechanism of action for CJP on anxiety-related behaviors in a rat model of anxiety disorder. After establishing a rat model of anxiety disorder using uncertain empty bottle stimulation, rats were divided into control, model, citalopram, low-dose CJP, and high-dose CJP groups. After 1 month of administration, effects of treatments on rat appearance, body weight, and open-field test scores were observed. In addition, hippocampal monoamine neurotransmitter (5-hydroxytryptamine, dopamine, and norepinephrine) contents were measured with an enzyme-linked immunosorbent assay, and mRNA expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) were measured with reverse transcription-polymerase chain reaction. CJP increased rat weight, and this effect was increased in the high-dose CJP group compared with the citalopram group (P < 0.05). CJP also elevated open-field test scores compared with the citalopram group (P < 0.05). While CJP decreased monoamine neurotransmitter contents in rat hippocampus, the regulatory effect of CJP on 5-hydroxytryptamine was reduced compared with citalopram (P < 0.01). CJP upregulated GR mRNA expression in both low-dose (P < 0.05) and high-dose (P < 0.01) CJP groups, but only the latter significantly downregulated MR mRNA expression and showed enhanced effects compared with citalopram (P < 0.05). Thus, CJP likely exerted its significant antianxiety effect by diminishing monoamine neurotransmitters and regulating mRNA expression of MR and GR in the hippocampus of our rat model of anxiety disorder.

Isokotomolide A, a new butanolide extracted from the leaves of Cinnamomum kotoense, arrests cell cycle progression and induces apoptosis through the induction of p53/p21 and the initiation of mitochondrial system in human non-small cell lung cancer A549 cells.

This study is the first to investigate isokotomolide A (IKA), a butanolide compound isolated from the leaves of Cinnamomum kotoense Kanehira & Sasaki (Lauraceaee), which exhibits an anti-proliferative activity in human non-small cell lung cancer A549 cells. The results show that IKA inhibits the proliferation of A549 by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. Blockade of cell cycle was associated with increased p21/WAF1 levels and reduced amounts of cyclin D1, cyclin E, Cdk2, Cdk4, and Cdk6 in a p53-mediated manner. IKA treatment also increased p53 phosphorylation (Ser15) and decreased the interaction of p53-MDM2. IKA treatment triggered the mitochondrial apoptotic pathway, indicated by changing Bax/Bcl-2 ratios, cytochrome c release and caspase-9 activation. In addition, pre-treatment of cells with caspase-9 inhibitor inhibited IKA-induced apoptosis, indicating that caspase-9 activation was involved in A549 cells' apoptosis induced by IKA. Our study reports here for the first time that the induction of p53/p21 and the initiation of the mitochondrial apoptotic system may participate in the anti-proliferative activity of IKA in human non-small cell lung cancer cells.

Rugosin E, an ellagitannin, inhibits MDA-MB-231 human breast cancer cell proliferation and induces apoptosis by inhibiting nuclear factor-kappaB signaling pathway.

In this study, we first report the chemopreventive effect of rugosin E in human breast cancer cell line, MDA-MB-231. Treatment with rugosin E decreased the cell proliferation of MDA-MB-231 cells in a dose-dependent manner. Rugosin E treatment arrested MDA-MB-231 cells at G0/G1 phase. This effect was strongly associated with concomitant decrease in the level of cyclin D1, cyclin D2, cyclin E, cdk2, cdk4, and cdk6, and increase of p21/WAF1. In addition, rugosin E also induced apoptotic cell death. Rugosin E increased in the expression of Bax, Bak, and Bcl-Xs, but decreased the levels of Bcl-2 and Bcl-X(L), and subsequently triggered mitochondria apoptotic pathway (release of cytochrome c, activation of caspase-9, and caspase-3). In addition, pre-treatment of cells with caspase-9 inhibitor blocked rugosin E-induced cell proliferation and apoptosis, indicating caspase-9 activation was involved in rugosin E-mediated MDA-MB-231 cells apoptosis. Rugosin E inhibited the constitutively activated and inducible NF-kappaB in both its DNA-binding activity and transcriptional activity. Furthermore, rugosin E also inhibited the TNF-alpha-activated NF-kappaB-dependent reporter gene expression of cyclin D1, c-Myc, XIAP, Bcl-2, and Bcl-X(L) were all downregulated by rugosin E. Our results indicated that rugosin E inhibits the activation of NF-kappaB, and this may provide a molecular basis for drug development in the prevention and treatment of cancer by rugosin E.