Shanqun Li

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.

Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered tissue damage. Receptor for advanced glycation end product (RAGE) and its ligand high mobility group box 1 (HMGB1) are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE), the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1) normal air (NA), (2) CIH, (3) CIH+sRAGE, and (4) NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6), apoptotic (Bcl-2/Bax), and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK) signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

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; p = 0.001) 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 p = 0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023) or disease-free survival (p = 0.027) as well as correlation between FLT1 and overall survival (p = 0.009). 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.

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.

Exhaled nitric oxide from the central airway and alveoli in OSAHS patients: the potential correlations and clinical implications.

BackgroundThe aim of the study was to evaluate exhaled nitric oxide (eNO) derived from different areas of airway in obstructive sleep apnea hypopnea syndrome (OSAHS) patients with NO exchange model and investigate the potential application and interpretation of eNO in clinical setting.MethodsThis study was divided into two parts. Firstly, we performed a case control study in 32 OSAHS patients and 27 non-OSAHS participants. Fractional eNO (FeNO) and eNO from the central airway (J’awNO) and from alveoli (CANO) were compared in OSAHS and control groups. Also, correlation of eNO to severity of OSAHS was analyzed. Secondly, a prospective study was conducted in 30 severe OSAHS patients who received a short-term nasal continuous positive airway pressure (nCPAP) treatment. We evaluated eNO, plasma ET-1 concentration, and echocardiography during the treatment process and explored the potential relationship among them.ResultsFeNO and J’awNO were higher in OSAHS and associated with disease severity, while CANO was relatively lower. After nCPAP treatment in severe OSAHS patients, FeNO and J’awNO decreased and CANO increased significantly. Substantial agreement was shown between the elevation of CANO and the decrease of plasma ET-1 concentration after nCPAP by Kappa analysis for consistency. Tei index, which is considered indicative of global right ventricular function, might be predicted by plasma ET-1 levels in severe OSAHS patients.ConclusionsNO exchange model provides us with more information of eNO derived from different areas. eNO is not only confirmed to be an effective method for airway inflammation evaluation in the follow-up of OSAHS, CANO may also serve as a useful marker in monitoring endothelial function, resistance of pulmonary circulation, and right ventricular function for clinical implication.