Liyan Jiang

Primary Salivary Gland–Type Lung Cancer: Clinicopathological Analysis of 88 Cases from China

Introduction: Salivary gland–type cancers are rare lung neoplasms involving mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ACC), and epithelial–myoepithelial carcinoma (EMC). Their behavior and prognostic features are not clearly defined because of their low incidence. We retrospectively analyzed the clinicopathologic profiles of these tumors in a large series. Methods: Eighty-eight patients confirmed as having primary salivary gland–type lung cancer between May 2001 and January 2013 were included from the archives of two thoracic oncology center institutions in China and retrospectively evaluated. Results: Of the total 88 patients, 69 were MEC, 12 ACC, and seven EMC. Overall survival (OS) at 3, 5, and 10 years was 91.3%, 86%, and 80.6% in all cases, respectively, and disease-free survival (DFS) was 90.1%, 78.6%, and 55%, respectively. No significant difference was found among MEC, ACC, and EMC groups regarding OS (p = 0.518) and DFS (p = 0.082). Tumor-node-metastasis stage, lymph node involvement, intrathoracic invasion, and margin status were found to be related with OS (p = 0.000, 0.029, 0.000, 0.004) and DFS (p = 0.018, 0.042, 0.002, 0.002). Intrathoracic invasion was an independent predictor for OS (hazard ratio [HR], 1.129; p = 0.039) and DFS (HR, 1.071; p = 0.011). For patients with MEC, pathological grade also was an independent predictor of OS (HR, 0.045; p = 0.006) and DFS (HR, 0.067; p = 0.001). Conclusions: Salivary gland–type lung cancers are a group of low-aggressive entities with higher tendency to recurrence/metastasis. Intensive clinical, radiological, and pathological examinations are essential to estimation of the risk stratification and management.

Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor.

Non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR) are responsive to erlotinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of curcumin on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation was determined by MTT assay. Apoptosis was examined using TUNEL staining. Protein expression of genes was determined by Western blot. Tumor growth was assessed in a xenograft mouse model. Results showed that erlotinib had a stronger effect on the induction of apoptosis in erlotinib-sensitive PC-9 cells but showed a weaker effect on erlotinib-resistant H1975 and H1650 cells than cisplatin and curcumin. Furthermore, curcumin significantly increased the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, enhanced erlotinib-induced apoptosis, downregulated the expressions of EGFR, p-EGFR, and survivin, and inhibited the NF-κB activation in erlotinib-resistant NSCLC cells. The combination of curcumin and erlotinib exhibited the same effects on apoptosis as the combination of curcumin and cisplatin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of curcumin and erlotinib significantly inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that curcumin is a potential adjuvant for NSCLC patients during erlotinib treatment.

Chronic intermittent hypoxia leads to insulin resistance and impaired glucose tolerance through dysregulation of adipokines in non-obese rats

Background and objectivesThe aim of this study was to determine whether chronic intermittent hypoxia (CIH) could affect the secretion of adipokines, such as resistin, leptin, and adiponectin, in non-obese rats and to investigate the potential mechanisms.MethodsAn established rodent model of CIH was utilized, in which rats were exposed to varying oxygen levels (7–21 %) respectively over a period of 5 weeks. The area under the curve (AUCG) and the insulin resistance index (homeostasis model of assessment for insulin resistance index, HOMA-IR) were calculated. The levels of several secretory factors in the blood were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression in adipose tissues was measured by reverse transcription-polymerase chain reaction (RT-PCR).ResultsGlucose tolerance and the levels of adiponectin in non-obese rats were decreased in the CIH group both in the serum and adipose tissue compared with the controls, while the insulin resistance index and the levels of resistin and leptin were increased. Moreover, the expressions of hypoxia inducible factor-1α and lactate dehydrogenase A were significantly higher in chronic intermittent hypoxia rats than in control rats, suggesting the presence of adipose tissue hypoxia.ConclusionsThese results show that CIH leads to insulin resistance (IR) and impaired glucose tolerance (IGT) in a non-obese rodent model of obstructive sleep apnea-hypopnea syndrome, and these effects may be due to the dysregulation of adiponectin, resistin, and leptin.

MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression.

Introduction Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. Methods We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes. Results FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; pu200a=u200a0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and pu200a=u200a0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (pu200a=u200a0.023) or disease-free survival (pu200a=u200a0.027) as well as correlation between FLT1 and overall survival (pu200a=u200a0.009). Conclusions MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.

Adaptive servoventilation improves cardiac dysfunction and prognosis in heart failure patients with sleep-disordered breathing: a meta-analysis.

Adaptive servoventilation (ASV) is a new therapeutic modality to treat sleep‐disordered breathing (SDB) especially for central sleep apnoea associated with Cheyne–Stokes respiration, whereas the role of ASV in SDB patients with heart failure (HF) is controversial. The purpose of this study was to evaluate the effects of ASV on these patients through a meta‐analysis of published data.

Capture-Based Targeted Ultradeep Sequencing in Paired Tissue and Plasma Samples Demonstrates Differential Subclonal ctDNA-Releasing Capability in Advanced Lung Cancer.

Introduction Circulating tumor DNA (ctDNA), which represents an unbiased way to assess tumor genetic profile noninvasively, facilitates studying intratumor heterogeneity. Although intratumor heterogeneity has been elucidated substantially in a few cancer types, including NSCLC, how it influences the ability of tumor cells harboring different genetic abnormalities in releasing their DNA remains elusive. We designed a capture‐based panel targeting NSCLC to detect and quantify genetic alterations from plasma samples by using deep sequencing. By applying the panel to paired biopsy and plasma samples, we imputed and compared the ctDNA‐releasing efficiency in subclones harboring distinct genetic variants. Methods We collected 40 pairs of matched biopsy and plasma samples from patients with advanced lung cancer and applied capture‐based sequencing using our LungPlasma panel, which consists of critical exons and introns of 168 genes. We derived a normalized relative allelic fraction score (NRAFS) to reflect ctDNA‐releasing efficiency. Results By using mutations detected in biopsy samples as a reference, we achieved 87.2% by‐variant sensitivity, including for single‐nucleotide variants, insertions or deletions, and gene fusions. Furthermore, the by‐variant sensitivity for the seven most critical and actionable genes was 96.2%. The average NRAFS for subclones carrying mutations from seven actionable genes was 0.877; in contrast, the average NRAFS for other mutations was 0.658. Mutations from four genes involved in cell cycle pathways had a particularly low NRAFS (0.480) compared with the other two groups (p = 0.07). Conclusions We have demonstrated that subclones carrying driver mutations are more prone to release DNA. We have also demonstrated the quantitative ability of capture‐based sequencing, paving its way for routine utilization in clinical settings.

Association between XPA gene rs1800975 polymorphism and susceptibility to lung cancer: a meta-analysis.

Xeroderma pigmentosum complementation group A (XPA) gene is a key member of nucleotide excision repair pathway. It was reported that XPA rs1800975 polymorphism was associated with susceptibility to lung cancer. However, the conclusions were controversial.

STAT4 knockout protects LPS-induced lung injury by increasing of MDSC and promoting of macrophage differentiation.

The disruption of signal transducer and activator of transcription 4 (STAT4) signal can inhibit the inflammation and protect organs from injury during severe bacterial infection. However, the mechanism of STAT4 signal in lung injury remains poor understood. Here we report that STAT4 deficiency decreased the lethality and protein leakage in STAT4(-/-) mice and protected lipopolysaccharid (LPS)-induced lung injury with ameliorated edema, inflammatory infiltration and hemorrhage. The expression of CD11b(+)Gr-1(+) myeloid derived suppressor cells (MDSCs) markedly increased in the circulation of STAT4(-/-) mice after LPS stimuli, accompanying with increased macrophages infiltration in inflamed lung tissue. In addition, the levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 decreased while anti-inflammatory cytokine (IL-10) increased in the bronchoalveolar lavage fluid of STAT4(-/-) mice. Thus, these results indicate that the accumulation of MDSCs and macrophages play a critical role in LPS-induced lung injury. Targeting MDSCs and macrophages polarization through a STAT4 dependent signaling pathway might help to reduce the inflammation and damage of lung tissue.

A meta-analysis: is low-dose computed tomography a superior method for risky lung cancers screening population?

Low‐dose computed tomography (LDCT) has been proposed to be a new screening method to discover lung cancers in an early stage, especially those patients who are in a high risk of lung cancer. The primary objective of this meta‐analysis is to systematically review the effect of LDCT on screening for lung cancers among the risky population who are older than 49 years old and with smoking exposure.

Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone‐marrow‐derived mesenchymal stem cells (BMSCs) on combined acid plus small non‐acidified particle (CASP)‐induced aspiration lung injury. Enhanced green fluorescent protein (EGFP+) or EGFP− BMSCs or 15d‐PGJ2 were injected via the tail vein into rats immediately after CASP‐induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone‐marrow‐derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP‐induced lung injury. Bone‐marrow‐derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor‐α and Cytokine‐induced neutrophil chemoattractant (CINC)‐1 and the expression of p‐p65 and increased the levels of interleukin‐10 and 15d‐PGJ2 and the expression of peroxisome proliferator‐activated receptor (PPAR)‐γ in the lung tissue in CASP‐induced rats. Tumour necrosis factor‐α stimulated BMSCs to secrete 15d‐PGJ2. A tracking experiment showed that EGFP+ BMSCs were able to migrate to local lung tissues. Treatment with 15d‐PGJ2 also significantly inhibited CASP‐induced lung inflammation and the production of pro‐inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC‐derived 15d‐PGJ2 activation of the PPAR‐γ receptor, reducing the production of proinflammatory cytokines.