Psoas muscle mass index and peak expiratory flow as measures of sarcopenia: relation to outcomes of elderly patients with resectable esophageal cancer.

Objectives: The objective of this study is to investigate whether the evaluation of postoperative outcomes or overall survival in patients who undergo surgery for esophageal cancer can be achieved by assessing sarcopenia using psoas muscle mass index and peak expiratory flow. Methods: This retrospective study analyzed the clinical data of 356 elderly patients (≥ 65 years) who had undergone radical surgery for esophageal cancer. Muscle mass and muscle strength were assessed by psoas muscle mass index (bilateral psoas area/height2) and peak expiratory flow, using preoperative computed tomography and spirometry, respectively. Sarcopenia is defined as a condition where both the psoas muscle mass index and peak expiratory flow fall below their gender-specific cutoff values. Survival and postoperative complications were compared between patients with and without sarcopenia. Results: Out of the 356 elderly individuals diagnosed with esophageal cancer, 84 patients (23.6%) were found to have sarcopenia. The group with sarcopenia showed a notably higher occurrence of postoperative pneumonia (29.8% vs 16.9%, P < 0.001) and anastomotic leak (9.5% vs 3.7%, P < 0.05) compared to those without sarcopenia. Additionally, a multivariate analysis concluded that sarcopenia independently acted as a risk factor for postoperative pneumonia, possessing an odds ratio of 1.90 (P < 0.05). The survival rate after 3 years for individuals with sarcopenia was considerably lower than those without sarcopenia (57.8% vs 70.2%, P < 0.05). Sarcopenia was identified as an unfavorable prognostic factor for overall survival, with a hazard ratio of 1.51 (P < 0.05). Conclusions: Preoperative sarcopenia diagnosed by psoas muscle mass index and peak expiratory flow is associated with reduced overall survival and adverse postoperative outcomes among elderly individuals suffering from esophageal cancer.

Long noncoding RNA MIAT promotes non-small cell lung cancer progression by sponging miR-149-5p and regulating FOXM1 expression.

BACKGROUND: Long non-coding RNAs (lncRNAs) are a class of endogenous non-coding RNAs of longer than 200 bp that play crucial roles in cancer biology. Here, we assessed the tumorigenic properties of a long noncoding RNA, MIAT, in non-small cell lung cancer (NSCLC). METHODS: Survival and clinicopathological analyses were done in a cohort of 80 patients with NSCLC. MIAT expression level were determined by real-time quantitative reverse transcriptase PCR (qRT-PCR). Dual luciferase reporter assays were employed to test the interaction between MIAT and miR-149-5p. Ectopic overexpression and shRNA-mediated knockdown of MIAT, CCK-8 and colony formation assays, Transwell migration and invasion in vitro, and in vivo tumorigenesis experiment were used to evaluate the function of MIAT. RESULTS: MIAT was significantly up-regulated in NSCLC tissues and cell lines, and was closely associated with advanced pathological stage and poor overall survival. Gain- and loss-of-function experiments in cell lines and mouse xenograft models showed that MIAT promoted the proliferation, migration, and invasion of NSCLC cells in vitro and accelerated tumor growth in vivo. Luciferase assay, western blotting, qRT-PCR, and rescue experiments showed that, mechanistically, MIAT could directly bind to miR-149-5p, and subsequently served as a sponge to increase the expression level of Forkhead box M1 (FOXM1). CONCLUSIONS: Our study reveals that MIAT acts as an oncogene in NSCLC via a novel MIAT/miR-149/FOXM1 axis, thus providing potential biomarkers and therapeutic targets for the management of NSCLC.

Juglanin inhibits lung cancer by regulation of apoptosis, ROS and autophagy induction.

Juglanin (Jug) is obtained from the crude extract of Polygonum aviculare, exerting suppressive activity against cancer cell progression in vitro and in vivo. Juglanin administration causes apoptosis and reactive oxygen species (ROS) in different types of cells through regulating various signaling pathways. In our study, the effects of juglanin on non-small cell lung cancer were investigated. A significant role of juglanin in suppressing lung cancer growth was observed. Juglanin promoted apoptosis in lung cancer cells through increasing Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, which is regulated by TNF-related apoptosis-inducing ligand/Death receptors (TRAIL/DRs) relied on p53 activation. Anti-apoptotic members Bcl-2 and Bcl-xl were reduced, and pro-apoptotic members Bax and Bad were enhanced in cells and animals receiving juglanin. Additionally, nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) activation were inhibited by juglanin. Further, juglanin improved ROS and induced autophagy. ROS inhibitor N-acetyl-l-cysteine (NAC) reversed apoptosis induced by juglanin in cancer cells. The formation of autophagic vacoules and LC3/autophagy gene7 (ATG7)/Beclin1 (ATG6) over-expression were observed in juglanin-treated cells. Also, juglanin administration to mouse xenograft models inhibited lung cancer progression. Our study demonstrated that juglanin could be a promising candidate against human lung cancer progression.

Iron oxide magnetic nanoparticles combined with actein suppress non-small-cell lung cancer growth in a p53-dependent manner.

Actein (AT) is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida that has been investigated for its antitumor effects. AT treatment leads to apoptosis in various cell types, including breast cancer cells, by regulating different signaling pathways. Iron oxide (Fe3O4) magnetic nanoparticles (MNPs) are nanomaterials with biocompatible activity and low toxicity. In the present study, the possible benefits of AT in combination with MNPs on non-small-cell lung cancer (NSCLC) were explored in in vitro and in vivo studies. AT-MNP treatment contributed to apoptosis in NSCLC cells, as evidenced by activation of the caspase 3-signaling pathway, which was accompanied by downregulation of the antiapoptotic proteins Bcl2 and BclXL, and upregulation of the proapoptotic signals Bax and Bad. The death receptors of TRAIL were also elevated following AT-MNP treatment in a p53-dependent manner. Furthermore, a mouse xenograft model in vivo revealed that AT-MNP treatment exhibited no toxicity and suppressed NSCLC growth compared to either AT or MNP monotherapies. In conclusion, this study suggests a novel therapy to induce apoptosis in suppressing NSCLC growth in a p53-dependent manner by combining AT with Fe3O4 MNPs.

An upregulation of CD8+CD25+Foxp3+ T cells with suppressive function through interleukin 2 pathway in pulmonary arterial hypertension.

Accumulating evidence suggests that abnormal inflammation plays a critical role in the pathogenesis of pulmonary arterial hypertension (PAH). CD8+CD25+Foxp3+ T cell is a novel cell subtype, and its role in PAH is not yet investigated. Here, we observed that PAH patients presented a significant upregulation of CD8+CD25+Foxp3+ T cells and a downregulation of CD4+CD25+Foxp3+ T cells compared to healthy controls. Regardless, the total number of CD25+Foxp3+ T cells in PAH patients was still smaller than that in healthy controls. Compared to CD8+CD25- T cells, CD8+CD25+ T cells presented higher Foxp3 expression, lower interferon (IFN)-γ expression and higher transforming growth factor (TGF)-ß expression, in both healthy and PAH individuals. The CD8+CD25+ T cells in PAH patients also demonstrated regulatory function by suppressing the proliferation of CD4+CD25- and CD8+CD25- effector T cells, albeit at lower efficiency than CD4+CD25+ T cells from PAH patients and healthy volunteers. CD8+CD25+ T cells from PAH responded to interleukin (IL)-2 supplement by expansion and upregulating Foxp3 expression. In PAH patients, IL-2-treated CD8+CD25+ T cells were more potent at inhibiting CD4+CD25- effector T cell proliferation than IL-2-untreated CD8+CD25+ T cells. Together, we found an upregulation of CD8+CD25+Foxp3+ T cells in PAH patients, and this T cell population presented suppressive activity that could be enhanced by IL-2 treatment.

The pseudogene-derived long noncoding RNA SFTA1P is down-regulated and suppresses cell migration and invasion in lung adenocarcinoma.

Pseudogenes were once considered to be genomic fossils without biological function. Interestingly, recent evidence showed that a lot of pseudogenes are transcribed in human cancers, and their alterations contribute to multiple cancer development and progression. It is apparent that many pseudogenes transcribe noncoding RNAs and contribute to the role noncoding genome plays in human cancers. On this basis, some pseudogene transcripts are currently ranked among the classes of long noncoding RNAs. In this study, we identified a new pseudogene-derived long noncoding RNA termed SFTA1P by analyzing the microarray data of non-small cell lung cancer from Gene Expression Omnibus datasets. We found that SFTA1P expression was significantly decreased in non-small cell lung cancer tissues compared with normal tissues in non-small cell lung cancer microarray data. Moreover, decreased SFTA1P expression is only correlated with lung adenocarcinoma patients' poor survival time but not with lung squamous cell carcinoma patients' survival. In addition, gain-of-function studies including growth curves, migration, invasion assays, and in vivo studies were performed to verify the tumor suppressor role of SFTA1P in non-small cell lung cancer. Finally, the potential underlying pathways involved in SFTA1P were investigated by analyzing the SFTA1P-correlated genes in The Cancer Genome Atlas lung adenocarcinoma and normal tissues RNA sequencing data. Taken together, these findings demonstrate that pseudogene-derived long noncoding RNA SFTA1P exerts the tumor suppressor functions in human lung adenocarcinoma. Our investigation reveals the novel roles of pseudogene in lung adenocarcinoma, which may serve as a new target for lung adenocarcinoma diagnosis and therapy.