Comparing the benefits of postoperative adjuvant chemotherapy vs. observation for stage IB non-small cell lung cancer: a meta-analysis.

BACKGROUND: The aim of this meta-analysis was to compare the benefits of postoperative adjuvant chemotherapy vs. observation for stage IB non-small cell lung cancer (NSCLC). METHODS: A literature search was performed in PubMed, Embase, and Cochrane Library databases, and stage IB NSCLC patients were assigned to the postoperative adjuvant chemotherapy and observation groups. The 5-year overall survival (OS), 5-year disease-free survival (DFS), local recurrence, and distant metastasis were then assessed. In addition, statistical analysis was conducted using Review Manager 5.3 software. RESULTS: The meta-analysis involved nine articles and included 1,645 stage IB patients. There was no significance in the 5-year OS [relative risk (RR) =1.05; 95% confidence interval (CI): 0.98-1.13; P=0.14] and 5-year DFS (RR =1.29; 95% CI: 0.97-1.72; P=0.08) between the postoperative adjuvant chemotherapy and observation groups. However, there was a significant difference in local recurrence (RR =0.43; 95% CI: 0.23-0.80; P=0.007) and distant metastasis (RR =0.68; 95% CI: 0.48-0.97; P=0.03) between the two groups. CONCLUSIONS: Adjuvant chemotherapy might not be recommended for stage IB NSCLC.

Tip60-siRNA regulates ABCE1 acetylation to suppress lung cancer growth via activation of the apoptotic signaling pathway.

Lung cancer is a leading cause of cancer-associated mortality and morbidity worldwide. Previous studies have suggested that ATP-binding cassette transporter E1 (ABCE1) acetylation is upregulated in the tissues and cells of lung cancer and is associated with the prognosis of patients with lung cancer. The aim of the present study was to investigate the association between Tat interactive protein 60 kDa (Tip60) expression and ABCE1 acetylation, and the effect of Tip60 on the biological functions of A549 lung carcinoma cells. The expression levels of Tip60 and ABCE1 acetylation were examined using western blot and co-immunoprecipitation (Co-IP) assays in normal bronchial epithelial (HBE) and human lung cancer (A549) cells. The expression of Tip60 then was downregulated in A549 cells using small interfering RNA. Wound healing and Transwell assays were used to assess cell invasion and migration. The biological effects of Tip60 in lung cancer cells were investigated using MTT and flow cytometric assays. Subsequently, tumor xenografts were established to observe the effect of Tip60 on lung cancer in vivo. Western blot and Co-IP assays were performed to investigate the mechanism of Tip60 in A549 cells. Tip60 expression and ABCE1 acetylation were upregulated in the lung cancer cells compared with the normal bronchial epithelial cells. Downregulation of Tip60 decreased the acetylation of ABCE1 and inhibited cell proliferation, invasion and migration. Furthermore, the downregulation of Tip60 activated the apoptotic pathway in order to achieve its suppressive function. In the xenografts, the tumor weight and volume were notably reduced due to the downregulation of Tip60 expression. The results of the present study strongly suggest that Tip60 is a novel target in the prevention and treatment of lung cancer.

The expression and correlation between chemokine CCL7 and ABCE1 in non-small cell lung cancer.

Lung cancer is a malignant disease, and has the highest incidence and mortality worldwide. Lung cancer is also a popular subject in the field of cancer research. The molecular mechanisms of lung cancer development, invasion and metastasis need to be determined to prolong survival times and improve the quality of life. Recent studies have demonstrated that ATP-binding cassette sub-family E member 1 (ABCE1) is one of the factors that contributes to the development and metastasis of lung cancer, but the specific mechanism of this phenomenon remains unclear. A polymerase chain reaction microarray was used in the present study to screen for chemokine (C-C motif) ligand 7 (CCL7) expression in cell lines that highly expressed ABCE1, and the results showed that CCL7 was highly expressed in H1299 cells (P<0.01). The expression of CCL7 and ABCE1 in lung cancer tissues obtained from 30 patients with non-small cell lung cancer (NSCLC) was higher than that in adjacent normal lung tissues (P<0.01), and a positive correlation between the expression levels of the two genes in NSCLC was observed. These findings indicate that ABCE1 is involved in the development and progression of lung cancer through the CCL7 signaling pathway.

Elevation of the Chemokine Pair CXCL10/CXCR3 Initiates Sequential Glial Activation and Crosstalk During the Development of Bimodal Inflammatory Pain after Spinal Cord Ischemia Reperfusion.

BACKGROUND/AIMS: Spinal microglia and astrocytes are the main responders to the inflammatory cascade and process pain through various neural interactions. CXCL10 is a late-phase protein that accelerates arteriogenesis during reperfusion through CXCR3. However, the early-phase expression (within 72 h postoperatively) of CXCL10 and CXCR3 during the development of ischemia-reperfusion (IR)-induced inflammatory pain remains unclear. We investigated whether this chemokine pair participates in glial interactions during early-phase IR injury. METHODS: A rat model was induced by an 8-min occlusion of the aortic arch. Temporal assessments of mechanical and thermal allodynia and the protein levels of CXCL10 and CXCR3 were determined through measurements of paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) and Western blotting assays. The co-localization of various cells with glial cells was detected by double immunofluorescence. The effects of CXCL10/CXCR3 on glial interactions were explored by intrathecal treatment with specific inhibitors (AMD487, minocycline and fluorocitrate) and recombinant CXCL10, and subsequent release of cytokines was assessed by ELISAs. RESULTS: The IR injury initiated bimodal allodynia within 72 h of reperfusion, as illustrated by two W-shape trends in the PWTs and PWLs with two minima at 12 and 48 h post-IR. Allodynia was highly correlated with overexpression of CXCL10 and CXCR3, which were expressed in microglia at the early stage and in both microglia and astrocytes at the late stage, as shown by increased CXCL10 and CXCR3 immunoreactivities and double-labeled cells. AMD487 and minocycline injections exerted comparable inhibitory effects on CXCR3 and Iba-1 and on GFAP immunoreactivity at 12 and 48 h post-IR, and these inhibitory effects were only observed at 48 h following fluorocitrate injection. The levels of TNF-α and IL-6 showed variations in concert with the changes in Iba-1 and GFAP immunoreactivities. Recombinant CXCL10 injection reversed the abovementioned effects. CONCLUSION: The results showed that CXCL10/CXCR3 are involved in bimodal inflammatory pain during early-phase IR injury. The sequential activation of and crosstalk between microglia and astrocytes mediated through CXCR3 upregulation suggested that treatments targeting specific cell types are important in post-IR allodynia.

Serum Fork-Head Box D3 (FOXD3) Expression Is Down-Regulated in and Associated with Diagnosis of Patients with Non-Small Cell Lung Cancer.

BACKGROUND The aim of this study was to detect the expression of fork-head box D3 (FOXD3) and investigate its diagnostic value in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS The relative expression of FOXD3 at mRNA and protein levels was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analysis, respectively. Chi-square test was used to explore the relevance of FOXD3 expression with clinical features of NSCLC patients. A receiver operating characteristic (ROC) curve was built to estimate the diagnostic value of FOXD3 in distinguishing NSCLC patients from healthy controls. RESULTS Serum FOXD3 expression was weakly expressed in NSCLC patients compared to the controls at mRNA and protein levels (P<0.001) and low FOXD3 expression was positively correlated with TNM stage, lymph node metastasis, and differentiation. The ROC curve indicated that FOXD3 acts as a diagnostic bio-marker for NSCLC patients, with an AUC of 0.826 corresponding to a sensitivity of 77.1% and a specificity of 74.6%, and an optimal cutoff point of 2.38. CONCLUSIONS Decreased expression of serum FOXD3 was observed in NSCLC patients, and it was found to be a potential molecular marker for the diagnosis of NSCLC.

Deficiency of Functional Iron-Sulfur Domains in ABCE1 Inhibits the Proliferation and Migration of Lung Adenocarcinomas By Regulating the Biogenesis of Beta-Actin In Vitro.

BACKGROUND/AIMS: ATP-binding cassette transporter E1 (ABCE1), a unique ABC superfamily member that bears two Fe-S clusters, is essential for metastatic progression in lung cancer. Fe-S clusters within ABCE1 are crucial for ribosome dissociation and translation reinitiation; however, whether these clusters promote tumor proliferation and migration is unclear. METHODS: The interaction between ABCE1 and ß-actin was confirmed using GST pull-down. The lung adenocarcinoma (LUAD) cell line A549 was transduced with lentiviral packaging vectors overexpressing either wild-type ABCE1 or ABCE1 with Fe-S cluster deletions (ΔABCE1). The role of Fe-S clusters in the viability and migration of cancer cells was evaluated using clonogenic, MTT, Transwell and wound healing assays. Cytoskeletal rearrangement was determined using immunofluorescent techniques. RESULTS: Fe-S clusters were the key domains in ABCE1 involved in binding to ß-actin. The proliferative and migratory capacity increased in cells overexpressing ABCE1. However, the absence of Fe-S clusters reversed these effects. A549 cells overexpressing ABCE1 exhibited irregular morphology and increased levels of cytoskeletal polymerization as indicated by the immunofluorescence images. In contrast, cells expressing the Fe-S cluster deletion mutant presented opposing effects. CONCLUSION: These results demonstrate the indispensable role of Fe-S clusters when ABCE1 participates in the proliferation and migration of LUADs by interacting with ß-actin. The Fe-S clusters of ABCE1 may be potential targets for the prevention of lung cancer metastasis.

Cerebral ischemia/reperfusion injury induces airway mucus hypersecretion in rats and activates IL­13­associated inflammatory mechanisms.

The majority of patients that suffer a stroke have excessive sputum, which accelerates the development of pulmonary complications. However, it is unclear whether cerebral ischemia and reperfusion (I/R) injury induces mucus hypersecretion, and the potential role of inflammation remains unknown. In the present study, the reversible middle cerebral artery occlusion model was applied in rats to induce cerebral I/R injury. The rats were grouped according to the duration of reperfusion (6, 12, 24, 48 and 72 h). Neurological dysfunction was evaluated by Longa scoring and lung dry­to­wet weight (dw/ww) ratios were determined to reflect the degree of mucus secretion. Inflammatory factor interleukin­13 (IL­13) and tumor necrosis factor­α (TNF­α) levels in serum and bronchoalveolar lavage fluid (BALF) were determined by enzyme­linked immunosorbent assay. Pulmonary levels of mucin 5AC (MUC5AC) and key molecules involved in nuclear factor­κB (NF­κB) signaling were determined by western blotting and immunohistochemistry. Rats with cerebral I/R had impaired neurological function, which was associated with the length of reperfusion time. In addition, the dw/ww lung ratio decreased and the pulmonary expression of MUC5AC increased with the increase in severity of neurological dysfunction, indicating that cerebral I/R may induce mucus hypersecretion in a reperfusion time­dependent manner. IL­13 and TNF­α levels in serum and BALF, as well as the nuclear translocation of NF­κB p65 in pulmonary tissues, significantly increased following cerebral I/R, which suggests that the activation of IL­13 and NF­κB inflammatory pathways may be involved. The present study concluded that cerebral I/R injury may induce airway mucus hypersecretion by activating IL­13 and NF­κB inflammatory pathways.

MiR-372-3p promotes cell growth and metastasis by targeting FGF9 in lung squamous cell carcinoma.

The aim of this study was to study the role of miR-372-3p in lung squamous cell carcinoma (LSCC) cell proliferation and invasion by suppressing FGF9. RT-PCR was used to determine miR-372-3p and FGF9 mRNA expression in tissues and cells. Western blot was used to determine FGF9 expression in tissues and NCI-H520 cell line. Dual luciferase reporter gene assay was conducted to confirm that FGF9 can be directly targeted by miR-372-3p. MTT, colony formation assays were conducted to investigate the effects of ectopic miR-372-3p and FGF9 expression on NCI-H520 cell growth. Flow cytometry was used to analyze the influence of miR-372-3p and FGF9 expression on cell cycle distribution and apoptosis. Transwell assay was also conducted to see the effects of miR-372-3p and FGF9 expression on NCI-H520 cell invasiveness. MiR-372-3p was found significantly overexpressed in both LSCC tissues and cell lines, whereas FGF9 mRNA was found underexpressed in LSCC tissues. MiR-372-3p directly bound to wild-type FGF9 mRNA 3'UTR, therefore led to the reduction in FGF9 expression. The upregulation of FGF9 or the downregulation of miR-372-3p substantially retarded LSCC cell growth, mitosis, and invasion. MiR-372-3p enhanced LSCC cell proliferation and invasion through inhibiting FGF9.

Pharmacokinetic evaluation of Shenfu Injection in beagle dogs after intravenous drip administration.

Shenfu Injection (SFI) is a well-defined Chinese herbal formulation that is obtained from red ginseng and processed aconite root. The main active constituents in SFI are ginsenosides and aconitum alkaloids. In this work, ginsenosides (ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rc) and aconitum alkaloids (benzoylmesaconine and fuziline) were used as the index components to explore the pharmacokinetic behavior of SFI. A selective and sensitive HPLC-MS/MS method was developed for the quantification of ginsenosides and aconitum alkaloids in dog plasma and was used to characterize the pharmacokinetics of the five index components after intravenous drip of three different dosages of SFI in beagle dogs. The pharmacokinetic properties of the index components were linear over the dose range of 2-8 mL/kg.

Expression of ATP binding cassette E1 enhances viability and invasiveness of lung adenocarcinoma cells in vitro.

ATP binding cassette E1 (ABCE1), a member of the family of ATP binding cassette transporters, has initially emerged as an RNase L inhibitor. As a highly conserved protein, it is involved in capsid assembly and translation processes of the human immunodeficiency virus as well as in tumor development and progression. Studies have shown that ABCE1 protein was overexpressed in lung carcinoma tissues and metastatic lymph nodes compared to normal lung tissues. However, little is known about the roles of ABCE1 in lung cancer. The present study investigated the biological effects of vector-mediated ABCE1 overexpression in lung cancer cells in vitro and examined the underlying molecular mechanisms. Overexpression of ABCE1 in the LTEP­a-2 lung adenocarcinoma cell line was achieved by transfection with a plasmid containing full­length ABCE1 cDNA. The ectopic expression of ABCE1 was shown to promote the viability and invasive capacity of lung cancer cells, and to in reduce p27 expression. However, overexpression of ABCE1 did not significantly affect the cell cycle distribution. In conclusion, the present study suggested that ABCE1 promotes the growth, invasion and metastasis of lung adenocarcinoma cells and may represent a potential biomarker and therapeutic target for lung cancer.

MicroRNA-376c suppresses non-small-cell lung cancer cell growth and invasion by targeting LRH-1-mediated Wnt signaling pathway.

MicroRNAs (miRNAs) that negatively regulate gene expression have emerged as novel therapeutic tools for cancer treatment. In this study, we investigated the potential role of Liver receptor homolog-1 (LRH-1), a novel oncogene, in non-small-cell lung cancer (NSCLC), and examined the regulation of LRH-1 by miRNAs. We found that LRH-1 was highly overexpressed in NSCLC cell lines. Knockdown of LRH-1 by small interfering RNA significantly inhibited NSCLC cell growth and invasion. miR-376c directly targeted the 3'-untranslated region (UTR) of LRH-1 and negatively regulated LRH-1 expression, as detected by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction and Western blot analysis. Further data showed that miR-376c expression was inversely correlated with LRH-1 expression in clinical cancer samples. Overexpression of miR-376c could inhibit NSCLC cell growth and invasion as well as Wnt signaling. In contrast, depletion of miR-376c exhibited the opposite effects. Moreover, these effects of miR-376c overexpression were partially abrogated by overexpression of LRH-1. Taken together, these results indicate that LRH-1 is involved in regulating the growth and invasion of NSCLC cells and that miR-376c inhibits NSCLC cell growth and invasion by targeting LRH-1, providing a novel insight into the potential for development of anti-cancer drugs for NSCLC.

Tumor metastatic promoter ABCE1 interacts with the cytoskeleton protein actin and increases cell motility.

ABCE1, a member of the ATP-binding cassette (ABC) family, is a candidate tumor metastatic promoter in lung cancer. Overexpression of ABCE1 is correlated with aggressive growth and metastasis in lung cancer cells. However, the exact mechanism remains unclear. In the present study, GST pull-down assay provided evidence of the possible interaction between ABCE1 and ß-actin using GST-ABCE1 as a bait protein. Co-immunoprecipitation manifested ABCE1 formed complexes with ß-actin in vivo. ABCE1 overexpression significantly increased the migration of lung cancer cells which may be attributed to the promotion of F-actin rearrangements. Taken together, these data suggest that overexpression of ABCE1 produces an obvious effect on the motility of lung cancer cells through cytoskeleton rearrangement.

ABCE1 plays an essential role in lung cancer progression and metastasis.

ATP-binding cassette E1 (ABCE1) is a member of the ATP-binding cassette transporters and regulates a broad range of biological functions including viral infection, cell proliferation, and anti-apoptosis. We have previously shown that ABCE1 is a prognostic indicator for lung cancer, although the underlying mechanisms remain unclear. To investigate whether the ABCE1 gene contributes to the malignancy of lung tumors, we introduced ABCE1 into LTEP-a-2 lung adenocarcinoma cells. Ectopic ABCE1 expression promoted clonogenicity and anchorage-independent growth of LTEP-a-2 cells, while in a mouse xenograft tumor model, it had an augmentative effect on tumor growth and metastasis and reduced the expression of the tumor-suppressor gene growth arrest and DNA damage-inducible 45α (GADD45α). Moreover, apoptosis was not significantly influenced by ABCE1 in vitro. In summary, we have provided evidence that ABCE1 plays an essential role in the progression and metastasis of lung cancers and may represent a valuable therapeutic target for the management of lung tumor.

Long non-coding RNA BANCR promotes proliferation and migration of lung carcinoma via MAPK pathways.

Lung carcinoma (LC) is one of the most mortal malignant tumors, and is becoming one of most lethal threat to human health and life. LncRNAs, emerging non-coding RNAs but poorly understood, are involved in the proliferation, metastasis, infiltration and apoptosis of LC. In this study, an lncRNA BANCR in LC cells was chosen to investigate the effect on LC cells, and clarify the possible mechanism. The results showed that BANCR levels were downregulated in LC cells. When BANCR expression was improved by tranfection with pcDNA-BANCR vector, tumor growth was suppressed. Vise versa, when BANCR was knockdown by si-BANCR, cell proliferation and migration of LC were remarkably promoted. We further found that MAPK pathways were involved in the BANCR-mediated cell proliferation and migration of LC. Moreover, BANCR was found to regulate LC proliferation and migration via not ERK MAPK, but p38 MAPK and JNK inactivations. These findings not only suggested that BANCR may be a new target for LC chemotherapy in future, but also will help us to fully understand the oncogenesis of LC.

[Research and practice about risk control of shenfu injection].

Shenfu injection is developed by improving dosage form of ancient prescription "Shenfu Tang" and is mainly derived from extracts of both traditional Chinese medicine red ginseng and prepared lateral root of monkshood with polysorbate 80 as auxiliary material. Shenfu injection may be administered through intramuscular injection, intravenous drip or intravenous injection. It produces good effects in restoring Yang and rescuing patients from collapse, tonifying Qi and preventing exhaustion. It is mainly used to treat not only syncope and prostration resulting from sudden Yang collapse (infectious, hemorrhagic and water depletion shock etc), but also pavor, palpitation, dyspnea with cough, stomachache, diarrhea and arthralgia etc caused by deficiency of Yang (deficiency of vital energy). Research group has audited the monitored hospitals and has carried out postmarketing study of Shenfu solution from many aspects including literature review, spontaneous reporting system (SRS) and hospital information system (HIS) data analysis etc. A summary is shown below.

Overexpression of RNF146 in non-small cell lung cancer enhances proliferation and invasion of tumors through the Wnt/ß-catenin signaling pathway.

Studies have suggested a possible correlation between the newly identified E3 ubiquitin ligase ring finger protein 146 (RNF146) and tumor development. However, until now, studies on RNF146 have been restricted to poly(ADP-ribosyl)ation and ubiquitin ligation, whereas the role of RNF146 in tumor biology has rarely been reported. In the present study, the role of RNF146 in non-small cell lung cancer (NSCLC) was investigated. The results showed that the expression of RNF146 was increased in clinical lung cancer samples and cell lines. RNF146 expression correlated with tumor size, differentiation level, lymphatic metastasis, pTNM staging, and prognosis of patients in stage I. RNF146 expression was negatively correlated with Axin expression but positively correlated with the nuclear expression of ß-catenin in NSCLC tissues. RNF146 downregulated the expression of Axin in lung cancer cell lines and induced the expression and nuclear distribution of ß-catenin. Overexpression of RNF146 in NSCLC cell lines increased the levels of cyclinD1, cyclinE, and CDK4, promoted cell cycle G0/G1-S transitions, and regulated cell proliferation. Overexpression of RNF146 led to upregulated levels of matrix metalloproteinases 2 and 7 and enhanced lung cancer cell invasiveness, events that were mediated by the classical Wnt/ß-catenin signaling pathway. In summary, the data in the present study indicate that RNF146 regulated the development and progression of NSCLC by enhancing cell growth, invasion, and survival, suggesting that RNF146 may be a potential treatment target in NSCLC.

PRKACB is downregulated in non-small cell lung cancer and exogenous PRKACB inhibits proliferation and invasion of LTEP-A2 cells.

Protein kinase cAMP-dependent catalytic ß (PRKACB) is a member of the Ser/Thr protein kinase family and a key effector of the cAMP/PKA-induced signal transduction involved in numerous cellular process, including cell proliferation, apoptosis, gene transcription, metabolism and differentiation. In the present study, the expression pattern of PRKACB in non-small cell lung cancer (NSCLC) and the effect of PRKACB upregulation on cell proliferation, apoptosis and invasion were investigated. PRKACB mRNA and protein expression was analyzed in the NSCLC tissue and corresponding normal tissues of 30 cases, using quantitative RT-PCR and western blot analysis. A plasmid containing full-length PRKACB was transfected into LTEP-A2 cells to further investigate the effects of PRKACB overexpression on proliferation, apoptosis and invasion of the transfected cells, which were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and Transwell assays. The results revealed that the NSCLC tissues exhibited much lower levels of PRKACB mRNA and protein compared with their corresponding normal tissues. The upregulation of PRKACB decreased the numbers of proliferative, colony and invasive cells, while the apoptotic rates of transfected cells were increased. These data indicate that PRKACB is downregulated in NSCLC tissues and that upregulation of PRKACB may be an effective way to prevent the progression of NSCLC.

Prognostic significance of twist and N-cadherin expression in NSCLC.

BACKGROUND: Metastasis is the most common cause of disease failure and mortality for non-small cell lung cancer after surgical resection. Twist has been recently identified as a putative oncogene and a key regulator of carcinoma metastasis. N-cadherin is associated with a more aggressive behavior of cell lines and tumors. The aim of this study was to evaluate the clinical relevance of Twist and N-cadherin expression in NSCLC, and the effects of Twist1 knockdown on lung cancer cells. METHODS: We examined the expressions of Twist and N-cadherin by immunohistochemistry in 120 cases of non-small cell lung cancer (including 68 cases with follow-up records). We also analyzed Twist1 and N-cadherin mRNA expression in 30 non-small cell lung cancer tissues using quantitative reverse transcription polymerase chain reaction. The functional roles of Twist1 in lung cancer cell lines were evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell apoptosis and invasion. RESULTS: In lung cancer tissues, the overexpression rate of Twist was 38.3% in lung cancer tissues. Overexpression of N-cadherin was shown in 40.83% of primary tumors. Moreover, Twist1 mRNA expression levels correlated with N-cadherin mRNA levels. Furthermore, overexpression of Twist1 or N-cadherin in primary non-small cell lung cancers was associated with a shorter overall survival (P<0.01, P<0.01, respectively). Depleting Twist expression inhibited cell invasion and increased apoptosis in lung cancer cell lines. CONCLUSIONS: The overexpression of Twist and N-cadherin could be considered as useful biomarkers for predicting the prognosis of NSCLC. Twist1 could inhibit apoptosis and promote the invasion of lung cancer cells, and depletion of Twist1 in lung cancer cells led to inhibition of N-cadherin expression.

Expression of p114RhoGEF predicts lymph node metastasis and poor survival of squamous-cell lung carcinoma patients.

The Rho-specific guanine nucleotide exchanging factor p114RhoGEF is involved in RhoA activation and cell motility. Previous studies suggest that altered expression of p114RhoGEF could contribute to cancer progression. We investigated an association of p114RhoGEF expression with progression and prognosis of non-small cell lung cancer (NSCLC). Immunohistochemistry was performed to detect p114RhoGEF expression in 105 NSCLC (34 adenocarcinoma and 71 squamous-cell carcinoma) and 32 normal lung tissues. We found that p114RhoGEF expression was upregulated in squamous-cell lung carcinoma and that p114RhoGEF expression was significantly higher in squamous-cell carcinoma than in adenocarcinoma or normal tissues (P<0.05, both). Expression of p114RhoGEF protein was significantly associated with lymph node metastasis of lung cancer (P<0.05), but not with patients' age, gender, tumor size, differentiation, or stage. Expression of p114RhoGEF protein was also associated with poor overall and event-free survival of squamous-cell lung carcinoma patients (P<0.05). Taken together, p114RhoGEF expression may be useful in predicting progression and survival of squamous-cell lung carcinoma patients. A future study will investigate whether p114RhoGEF can serve as a novel therapeutic target in squamous-cell lung cancer.

The biological regulation of ABCE1.

ATP binding cassette E1 (ABCE1) protein, also named RLI or HP68, is one member of ATP binding cassette superfamily. By forming a heterodimer with RNase L, ABCE1 protein inhibits the IFN-depended 2-5A/RNase L system and regulates a broad range of biological functions including viral infection, tumor cell proliferation, and antiapoptosis. As a highly conserved protein, recent studies have mainly focused that ABCE1 protein is involving in the fields of HIV virus capsids assembly and important roles in translation. Our manuscript will review the studies which revealed the biological regulation of ABCE1.