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Developing simple and efficient nanotheranostic platforms with behavior responsive to the acid microenvironment of a tumor is of great significance for accurate tumor diagnosis and therapy. In this study, a smart 2D nanotheranostic platform has been successfully fabricated by doping functional ferrous ions into as-synthesized MgAl-layered double hydroxide (LDH) with doxurubicin (DOX) loading to form Fe-LDH/DOX NPs, which achieved magnetic resonance imaging (MRI)-guided synergistic chemo/photothermal therapy for breast cancer. The doping of ferrous ions into Fe-LDH/DOX enabled a strong photo-induced heating ability with a high photothermal conversion efficiency of 45.67%, which could be combined with the antitumor drug DOX to achieve the synergistic effect of photothermal therapy (PTT) and chemotherapy for killing tumor cells. Additionally, its in vitro pH-dependent degradation behavior and T2-weighted MRI effect revealed that the as-prepared Fe-LDH/DOX is sensitive to the tumor acid microenvironment. Most importantly, the growth rate of tumors in 4T1 bearing mice could be effectively inhibited after the synergistic treatment of PTT and chemotherapy by Fe-LDH/DOX. These results show that doping functional metal ions into LDH NPs may open a novel approach to fabricating an LDH NP-based nanotheranostics platform with advanced diagnostic and therapeutic performances.

Aims. Tripartite motif protein 36 (TRIM36) plays a tumor-suppressive role in prostate cancer. However, there is little information on the clinical relevance of TRIM36 expression in esophageal cancer (ESCA). Methods. TRIM36 expression was analyzed by using The Cancer Genome Atlas (TCGA) ESCA dataset as well as by quantitative real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) staining on samples from our hospital. Results. In the current study, the analysis of TCGA ESCA dataset suggested the decreased expression of TRIM36 in ESCA tissues. Further analyses on samples from our hospital demonstrated that TRIM36 was significantly downregulated in ESCA tissues than in the noncancerous controls at both the mRNA and protein levels. Moreover, gene set enrichment analysis on TCGA ESCA dataset suggested that TRIM36 expression was inversely correlated with the β-catenin pathway. IHC staining data showed that 66.25% (53/80) and 51.25% (41/80) of ESCA cases had a low expression of TRIM36 and a high expression of β-catenin, respectively. By Fisher’s exact test, we found that TRIM36 protein expression was significantly correlated with tumor size (P=0.0104), tumor stage (P=0.0169), lymph node metastasis (P=0.0021), vital status (P=0.0443), and β-catenin expression (P=0.0329). These findings suggest the potential clinical significance of TRIM36 in ESCA. Kaplan–Meier and log-rank test demonstrated that a low expression of TRIM6 and a high expression of β-catenin were associated with poor overall survival of ESCA patients. Conclusions. Our study provides evidence for the prognostic value of TRIM36 in ESCA.

Background Epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (EFEMP2), also known as fibulin-4, MBP1 and UPH1, is an extracellular matrix protein associated with a variety of tumors. The purpose of this study was to investigate the prognostic value and the function of EFEMP2 in lung cancer. Methods The mRNA and protein expression of EFEMP2 in lung normal and cancer tissues, lung cancer cell lines (A549, H460, H1299 and H1650) and normal epithelial cell line BEAS-2B were evaluated by immunohistochemistry, RT-qPCR and Western blotting. The Public databases (Oncomine and Kaplan-Meier plotter) were used to investigate the prognostic value of EFEMP2 in lung cancer. RNA interference (RNAi) and overexpression transfection were performed to detect the effects of EFEMP2 up- or down-regulation on lung normal and cancer cell proliferation, invasion and metastasis in vitro and in vivo. Results EFEMP2 was lowly expressed in lung cancer tissues and cells, and its low expression was associated with malignant phenotype and poor prognosis of lung cancer. The same conclusion had been drawn from the Public databases. EFEMP2 overexpression significantly inhibited the invasion of lung cancer cells, hampered the process of EMT, and decreased the expression and activity of MMP2 and MMP9, while EFEMP2 knockdown remarkably enhanced the invasion of lung cancer cells, promoted EMT, and increased the expression and activity of MMP2 and MMP9. Conclusion The low expression of EFEMP2 was detected in lung cancer and was positively correlated with the poor prognosis of patients. EFEMP2 was a tumor suppressor gene that inhibited the progress of lung cancer, which suggested a new research objective for the future studies.

Liang Li,1 Xue Yu,2 Guanqiang Ma,1 Zhiqi Ji,1 Shihao Bao,1 Xiaopeng He,1,3 Liang Song,1,3 Yang Yu,1,3 Mo Shi,1,3 Xiangyan Liu1,3 1Department of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Pediatrics, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 420100, People’s Republic of China; 3Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Mo Shi; Xiangyan LiuDepartment of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of ChinaEmail legendsm01@163.com; liuxiangyan1@163.comBackground: Early-stage lung squamous cell carcinoma (LUSC) progression is accompanied by changes in immune microenvironments and the expression of immune-related genes (IRGs). Identifying innate IRGs associated with prognosis may improve treatment and reveal new immunotherapeutic targets.Methods: Gene expression profiles and clinical data of early-stage LUSC patients were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases and IRGs from the InnateDB database. Univariate and multivariate Cox regression and LASSO regression analyses were performed to identify an innate IRG signature model prognostic in patients with early-stage LUSC. The predictive ability of this model was assessed by time-dependent receiver operator characteristic curve analysis, with the independence of the model-determined risk score assessed by univariate and multivariate Cox regression analyses. Overall survival (OS) in early-stage LUSC patients was assessed using a nomogram and decision curve analysis (DCA). Functional and biological pathways were determined by gene set enrichment analysis, and differences in biological functions and immune microenvironments between the high- and low-risk groups were assessed by ESTIMATE and the CIBERSORT algorithm.Results: A signature involving six IRGs (SREBF2, GP2, BMX, NR1H4, DDX41, and GOPC) was prognostic of OS. Samples were divided into high- and low-risk groups based on median risk scores. OS was significantly shorter in the high-risk than in the low-risk group in the training (P < 0.001), GEO validation (P = 0.00021) and TCGA validation (P = 0.034) cohorts. Multivariate Cox regression analysis showed that risk score was an independent risk factor for OS, with the combination of risk score and T stage being optimally predictive of clinical benefit. GSEA, ESTIMATE, and the CIBERSORT algorithm showed that immune cell infiltration was higher and immune-related pathways were more strongly expressed in the low-risk group.Conclusion: A signature that includes these six innate IRGs may predict prognosis in patients with early-stage LUSC.Keywords: early-stage lung squamous cell carcinoma, prognosis, risk score, gene signature, innate immune-related genes, immune cell infiltration

Esophageal squamous cell carcinoma (ESCC) is one of the most common devasting tumor around the world, characterized by persistent hypoxia. Hypoxia-inducible factor-2α (hif-2α) has been regarded as an oncogene in many kinds of cancers, exerting its function to promote tumor growth and metastasis. But the role of hif-2α in ESCC remains largely unknown. In this study, we discovered hif-2α was overexpressed in ESCC and could promote proliferation and metastasis in ESCC cells. Functionally, hif-2α facilitated EMT through Notch pathway in ESCC. Moreover, we identified hif-2α as an independent factor that predict poor prognosis in ESCC patients. These findings suggested that hif-2α is a key regulator of EMT and played a critical role in promoting ESCC progression.

Background DnaJ/Hsp40 homolog, subfamily B, member 6 (DNAJB6) is significantly down-regulated in esophageal squamous cell carcinoma (ESCC), while its complicated molecular mechanisms are still unknown. Aims To investigate the relationship between DNAJB6 and ESCC. Methods The expression of DNAJB6 was detected in ESCC patient by Western blot and immunohistochemistry. To overexpress DNAJB6a by lentivirus infection, colony-forming, CCK-8, transwell, mouse xenograft assays were utilized to verify the proliferous, invasive, and migratory role of DNAJB6a in ESCC cells. The MDA and GSH assays determine whether DNAJB6a participates in cell redox reaction. The variation of AKT and GPX4 was detected by Western blot. Results The correlation between DNAJB6 level and lymph node metastasis in ESCC patient was negative. Overexpressing DNAJB6a shows tumor-suppressive effects in vitro and in vivo. In addition, DNAJB6a overexpression was accompanied together with a remarkable reduction in the protein levels of GPX4 and phosphorylated AKT (p-AKT). Conclusion DNAJB6 plays an important anti-oncogenic role in ESCC evolvement via ferroptosis.

The activation of Toll-like receptors (TLRs) is involved in the innate immune response and the acute inflammatory response following sepsis-induced acute lung injury (ALI). Increasing evidence has demonstrated that sepsis-induced ALI may be closely associated with several abnormal TLRs, activated by components of microorganisms. However, the number of TLRs involved in this process and the extent of their involvement has not been fully elucidated. The current study examined the simultaneous activation of four TLRs closely associated with sepsis-induced ALI. The results demonstrated that in contrast to the sham-operated group, the mRNA and protein expression levels of TLR2/4/9 were significantly increased in the cecal ligation and puncture (CLP)-operated group. In addition, TLR2-/-, TLR3-/-, TLR4-/- and TLR9-/- C57BL/6 mice were used to establish a CLP-induced ALI animal model and measure the expression levels of TNF-α and IL-6 in plasma and lung tissue samples. The expression of both TNF-α and IL-6 were significantly decreased in TLR2-/-, TLR4-/- and TLR9-/- mice compared with WT mice. In addition, the results revealed that knockdown of TLR2, 4 or 9 decreased immune cell infiltration and therefore may attenuate lung injury. Furthermore, the overall survival was significantly increased in TLR2-/-, 4-/- and 9-/- CLP-induced ALI mice compared with the WT CLP-induced ALI mice. However, there was no statistical significance between TLR3-/- CLP-induced ALI and WT CLP-induced ALI in the current study. Taken together, these results suggest that in the sepsis-induced ALI model, several TLRs are upregulated and participate in the inflammatory response. Therefore, inhibition of multiple TLRs including TLR2, 9, and especially TLR4 simultaneously, but not TLR3, may be a potential therapeutic target for the treatment of sepsis-induced ALI.

BACKGROUND The FGFR family can be activated by FGFs and plays important roles in regulating cell growth, differentiation, migration, and angiogenesis. Recent studies have suggested that FGFR4 could regulate several processes, including tumor progression. Esophageal squamous cell carcinoma (ESCC) is a malignancy with high global occurrence. However, the molecule mechanism and the potential roles of FGFR4 in ESCC remain unknown. METHODS Immunohistochemistry and Western blotting were used to detect FGFR4 expression in ESCC samples and cell lines. Cell counting kit-8, and clonogenic, transwell, flow cytometric, and tumor xenograft in nude mice assays were utilized to determine the effect of blocking FGFR4 in proliferation, invasion, migration, and apoptosis of ESCC cells. RESULTS FGFR4 is frequently overexpressed in ESCC tissue and cell lines. in vitro assays have shown that blocking FGFR4 by a specific blocker, H3B-6527, significantly decreases proliferation, invasion, and migration, and alters epithelial-mesenchymal transition markers in ESCC cells. In addition, FGFR4 blockade is associated with the induction of apoptosis and affects PI3K/Akt and MAPK/ERK pathways. Moreover, FGFR4 blockade could significantly inhibit the growth of xenograft tumors in vivo. CONCLUSION Our findings suggest that blocking FGFR4 significantly suppresses the malignant behaviors of ESCC and indicate that FGFR4 is a potential target for the treatment of ESCC.

BACKGROUND Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in several malignancies. Here, we define the correlation between STAT3 expression and lymph node micrometastasis of early-stage non-small cell lung cancer. Then we highlight some possibilities associated with developing a way to detect tumor micrometastasis and an anticancer drug that might therapeutically inhibit the STAT3 signaling pathway. METHODS The samples were collected from 50 patients with early-stage non-small cell lung cancer and 50 patients with benign lung tumors. Mucin 1 mRNA expression was evaluated to determine lymph node micrometastasis status. STAT3 mRNA, STAT3 protein, and phosphorylated STAT3 protein expression were evaluated through reverse transcription polymerase chain reaction, western blot, and immunohistochemistry, respectively. Measurement data was represented as mean ± standard deviation, and the t-rest or F-test were used. The χ2 -test was used in enumeration data. Logistic regression analysis was carried out to determine the independent risk factors influencing lymph node micrometastasis. RESULTS STAT3 mRNA and proteins expression were correlated with lymph node micrometastasis (P

Background Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide and is characterized by activation of epithelial-mesenchymal transition (EMT). EPB41L5 is regarded as a key factor in the progression of EMT and metastasis in various kinds of cancers, although the role and mechanism of EPB41L5 in ESCC have not yet been elucidated. In addition, tumor cells can acquire enhanced aggressiveness and a mesenchymal phenotype through phosphorylation of MAPK signaling pathway components. Here, we intend to explore whether EPB41L5 can regulate the EMT process in ESCC and reveal whether the MAPK signaling pathway is involved. Methods We compared the expression level of EPB41L5 with the prognostic characteristics of 100 ESCC patients to hypothesize the role of EPB41L5 in the progression of ESCC. Furthermore, in vivo and in vitro experiments were conducted to verify the conclusions from the analysis of clinical specimens and investigate the underlying mechanism by which EPB41L5 contributes to ESCC. Results We discovered that EPB41L5 was overexpressed in ESCC and that higher EPB41L5 expression was related to higher TNM stage, a higher incidence of lymphatic metastasis and worse prognosis. Moreover, using ESCC cells and nude mouse models, we found that EPB41L5 promoted EMT, proliferation, migration and invasion in ESCC. Mechanistically, activation of phosphorylation in the ERK/p38 MAPK signaling pathway was involved in the EPB41L5-mediated regulation of EMT. Conclusion In conclusion, our findings suggest that EPB41L5 plays a critical role in the regulation of EMT and the progression of ESCC.

Recent studies have demonstrated that deregulated microRNA (miRNA/miR) expression has a profound impact on biological and pathological processes; abnormal miR-1469 expression was detected in several human malignancies. In the present study, the clinicopathological and prognostic significance of miR-1469 was assessed in 129 patients with esophageal squamous cell cancer (ESCC) who successfully underwent esophagectomy and esophagogastrostomy. Low miR-1469 expression was identified to be significantly associated with tumor invasion depth (P=0.026), lymph node metastasis status (P

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to high lymphatic metastatic recurrence rates after Ivor Lewis esophagectomy. We sought to investigate the correlation between tumor necrosis factor alpha-induced protein 8 (TNFAIP8) expression and postoperative lymphatic recurrence in patients with pN0 ESCC. One hundred twenty-two patients with pN0 ESCC undergoing Ivor Lewis esophagectomy were enrolled in this study. TNFAIP8 overexpression was found in 73 (59.8 %) tumor specimens. The 3-year lymphatic metastatic recurrence rate among TNFAIP8-overexpressing patients was significantly higher than in TNFAIP8-negative patients (p = 0.003). Multivariate Cox regression identified TNFAIP8 overexpression as an independent risk factor for lymphatic recurrence (p = 0.048). TNFAIP8 messenger RNA (mRNA) levels were significantly higher in patients with lymphatic recurrence than in patients without tumor recurrence (p = 0.019). Stable silencing of TNFAIP8 expression in ESCC-derived cells (Eca109) reduced proliferation, motility, and invasion and induced apoptosis. In addition, transient silencing of TNFAIP8 expression decreased cell motility and invasion and increased apoptosis in a second ESCC-derived cell line (KYSE150). Taken together, these findings suggest that TNFAIP8 overexpression is a potential biomarker to identify pN0 ESCC patients at higher risk of lymphatic recurrence who may benefit from adjuvant therapy.

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive tumors worldwide. The Mucin 1 (MUC1) heterodimeric protein has been confirmed that is overexpressed in ESCC and induced adverse outcomes. However, the detailed mechanism(s) remained challenging. So, we investigated the relationship between MUC1‐C and metabolism in ESCC cells. In the results, TP53‐induced glycolysis and apoptosis regulator (TIGAR) was overexpressed and correlative with MUC1‐C positively in ESCC tissue. Targeting MUC1‐C inhibits AKT–mTORC–S6K1 signaling and blocks TIGAR translation. We found that the inhibitory effect of GO‐203 on TIGAR was mediated by inhibition of AKT–mTOR–S6K1 pathway. The findings also demonstrated that the suppressive effect of GO‐203 on TIGAR is related to the decrease of glutathione level, the increase of reactive oxygen species and the loss of mitochondrial transmembrane membrane potential. In xenograft tissues, GO‐203 inhibited the growth of ESCC cells and lead to the low expression of transmembrane C‐terminal subunit (MUC1‐C) and TIGAR. This evidence supports the contention that MUC1‐C is significant for metabolism in ESCC and indicated that MUC1‐C is a potential target for the treatment of ESCC.

In recent years, microRNAs, also called as miRNAs, play an important role in carcinogenesis, and the dysregulation of miRNAs is closely associated with cancer progression. Till now, little has been known about the role of miRNA-146a in the esophageal squamous cell carcinomas (ESCC). In the present study, we used in vitro assays to investigate the mechanisms of miRNA-146a in ESCC cell lines and 60 ESCC tissues. Here, we found that miRNA-146a expression is downregulated in both ESCC cell lines and tissues and obviously associated with pathological indicators, such as metastasis and stage of ESCC. In addition, the overexpression of miRNA-146a suppressed EC109 and TE8 cell proliferation and invasion. Meanwhile, miRNA-146a overexpression extremely inhibited the protein expression of insulin receptor substrate 2 (IRS2). Notably, the enforced expression of IRS2 in EC109 cells with miRNA-146a overexpression attenuated the inhibitory effects of miRNA-146a. In conclusion, our findings suggest that miRNA-146a may function as a useful clinical tool in the treatment and diagnosis of ESCC, and its overexpression suppressed cell growth through inhibition of IRS2. Thus, miRNA-146a pathway may be recommended as potential makers for drug design.

The poor prognosis of esophageal squamous cell carcinoma (ESCC) is mainly attributed to higher lymphatic-related metastatic ability. Whether the loss of expression of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is associated with lymphatic-related metastasis needs elucidation. In the present study, we assessed the mRNA and protein level of PTEN in ESCC by qRT-PCR and immunohistochemistry. The results showed PTEN mRNA level in tumors was significantly lower than that in corresponding non-tumor esophageal epitheliums (p

Aberrant activation of the signal transducer and activator of transcription 3 (STAT3) occurs in many human tumors. Many studies have provided compelling evidence for the critical role of aberrant STAT3 activity in malignant transformation and tumor progression. But few of them provided data on whether activated STAT3 overexpression correlated with patients’ prognosis. Here, we define the relationship between phosphorylated STAT3 (pSTAT3) function and prognosis of non-small cell lung cancer (NSCLC). Immunohistochemical analyses were carried out on 82 surgically resected NSCLC tissues to evaluate the expression level of pSTAT3. The Kaplan–Meier method was used to calculate the survival rate, and the log-rank test was performed to compare the survival difference. Cox regression analysis was performed to identify prognostic risk factors. All statistic analyses were performed with SPSS11.5 statistical software. Differences were considered significant when the P value was

Whether promoter hypermethylation of phosphatase and tensin homologue deleted from chromosome 10 (PTEN) is associated with loss of PTEN expression was not yet elucidated in esophageal squamous cell carcinoma (ESCC). The methylation status of PTEN gene was evaluated in 74 ESCC specimens and four esophageal cancer cell lines. Its association with clinicopathological factors or the prognosis was investigated by statistical analysis. We further measured messenger RNA (mRNA) and protein level of PTEN by quantitative RT-PCR and immunohistochemistry and studied the role of PTEN hypermethylation in loss of PTEN expression in clinical samples. Next, demethylation of PTEN gene with 5-azaC in EC9706 was performed to confirm the clinical findings. PTEN methylation was only found in 14 (18.9 %) of 74 ESCC tumor samples and one (EC9706) of four esophageal cancer cell lines. PTEN methylation was not statistically associated with clinicopathological factors and the prognosis (p > 0.05). In addition, 41 patients (55.4 %) and 38 patients (51.4 %) showed reduced mRNA level of PTEN and negative expression of PTEN protein in ESCC tumors, respectively. Detailed analysis indicated that PTEN methylation was a possible mechanism of loss of PTEN expression in ESCC, and further 5-azaC demethylation revealed inversed methylation status and increased mRNA or protein level of PTEN in EC9706. However, the role of PTEN methylation in loss of PTEN expression was still limited due to low frequency of methylation in ESCC. PTEN hypermethylation is a rare event and did not play an important role in the prognosis and loss of PTEN expression in ESCC.

Upregulation of miR-21 (microRNA-21) and downregulation of miR-34b/c have been found in breast cancer (BC). However, their regulation mechanism and function roles in BC have not been fully addressed. Here, we report that miR-21 levels were inversely correlated with miR-34b/c levels in BC. MiR-21 upregulation contributes to PTEN downregulation, which is beneficial for the activation of PI3K/AKT signaling. The activation of AKT phosphorylates FOXO3a, triggering relocalization of FOXO3a proteins from the nucleus to the cytoplasm. FOXO3a is a newly identified transcription factor responsible for miR-34b/c expression. Downregulation of nuclear FOXO3a decreased the expression levels of miR-34b and miR-34c in breast cancer cells, in which p53 was mutated. We also found upregulation of circulating miR-21 and downregulation of circulating miR-34b/c in BC patients’ serum. More importantly, we showed that systemic delivery of miR-34b/c or with anti-miR-21 significantly inhibited breast tumor growth in vivo. These results suggest that high circulating levels of miR-21 and low levels of miR-34b/c may provide potential biomarkers for BC diagnosis, and systemic delivery of miR-34b/c has potential as a therapeutic option for BC treatment.

Brain-specific metastasis is one of the primary causes of recurrence following complete resection of non-small cell lung cancer (NSCLC) and the underlying mechanism remains unclear. The present study was designed to investigate the correlation between C-X-C chemokine receptor type 4 (CXCR4) expression and brain-specific metastasis of NSCLC. Lung cancer tissues from 105 patients who underwent complete tumor resection between January 1998 and June 2008 (sample group, 34 with brain metastasis during the follow-up period; control group 1, 34 without metastasis during the follow-up period; and control group 2, 37 with other organ metastasis, excluding brain metastasis, during the follow-up period) were examined by immunohistochemistry to detect the expression of CXCR4 protein. The differences in CXCR4 expression were compared using McNemar’s χ2 test. Estimation of survival was calculated with the Kaplan-Meier method and the statistical differences were analyzed with the log-rank test. Overexpression of CXCR4 protein was observed in 31 (91.2%) NSCLC patients with brain metastasis, which was greater than that observed in the NSCLC patients with other organ metastases (73.0%; P=0.048) and without metastases (14.7%; P

Targeted therapy has greatly improved the treatment for adenocarcinoma of the lung, but not squamous cell carcinoma (SCC) of the lung. The current paper describes the abnormalities of receptor tyrosine kinases (RTK) in lung SCC in a hope to stimulate the development of therapeutics that can have clinical impact.We reviewed both clinical and preclinical studies published in English regarding RTK abnormalities and/ or RTK-targeting treatment for SCC of the lung.RTK alterations have been demonstrated as biological signature for SCC of the lung. A number of clinical trials of RTK-targeting therapy have been carried out or are ongoing, with encouraging results.SCC of the lung should be treated as an independent disease with unique treatment options based on molecular changes, particularly RTK.

Lung cancer is one of the most common types of malignant tumor worldwide. The etiology of lung cancer is complex and, although significant progress has been made in previous investigations, the molecular mechanism responsible for lung cancer remains to be fully elucidated. In the present study, the association between lung cancer and transmembrane 7 superfamily member 4 (TM7SF4) was investigated. Reverse transcription‑quantitative polymerase chain reaction technology was used to detect the expression of TM7SF4, and it was expressed at a high level in lung cancer. Furthermore, by overexpressing and inhibiting the expression of TM7SF4, the present study compared cell proliferation and migration rates. It was confirmed that TM7SF4 promoted lung cancer cell proliferation and migration. TM7SF4 was also confirmed to promote cancer cell migration and invasion by modulating the activation of the phosphatidylinositol 3‑kinase/Akt pathway in the A549 cells. Correspondingly, the inhibition of TM7SF4 decreased the expression of proteins associated with AKT, whereas the overexpression of TM7SF4 promoted the expression of the relevant proteins. Therefore, the present study confirmed that TM7SF4 was involved in the progression of lung cancer via regulating the activation of AKT. These findings suggested that TM7SF4 may be involved in the progression of lung cancer and may be a novel therapeutic target for this disease.

Background CCR7 and MUC1 are correlated with lymph node metastasis in ESCC, but the role of MUC1 in the CCR7-induced lymphatic metastasis and the underlying molecular mechanism is still unclear. Methods The expression of CCR7 and MUC1 was detected in the ESCC samples by IHC, and the clinical significance of CCR7 and MUC1 in ESCC was analyzed. The expression of CCR7 and MUC1 in ESCC cell lines was detected by qRT-PCR and western blot. The effect of CCL21 on the migration and invasion of ESCC cells was determined by transwell assay. The activity of MUC1 promoter was determined by luciferase reporter assay. The activation of Erk, Akt and Sp1 was detected by western blot and the binding of Sp1 to the MUC1 promoter was determined by ChIP. Results The co-expression of CCR7 and MUC1 was detected in 153 ESCC samples by IHC, and both were correlated with lymph node metastasis, regional lymphatic recurrence and poor prognosis. Correspondingly, increasing levels of MUC1 mRNA and protein were detected in the ESCC cell lines KYSE410 and Eca9706 after treatment with CCL21 in a time- and dose-dependent manner. Furthermore, silencing MUC1 could remarkably suppress the invasion and migration of ESCC cells induced by CCL21. Moreover, heterologous CCR7 promoted the invasion and migration of KYSE150 and up-regulated MUC1 expression. Increasing levels of activated ERK1/2 and Akt were detected in KYSE410 after treating the cells with CCL21, and inhibiting the activation of ERK1/2 but not Akt caused the increased transcription of MUC1. Finally, the phosphorylation of Sp1 induced by ERK1/2 and subsequent increases in the binding of Sp1 to the muc1 promoter at −99/−90 were confirmed to cause the up-regulation of MUC1 induced by CCL21-CCR7. Conclusions Our findings suggested that MUC1 plays an important role in CCL21-CCR7-induced lymphatic metastasis and may serve as a therapeutic target in ESCC.

Chronic osteomyelitis is a bone infection that results in hypertrophic scarring of the soft tissue surrounding the infected bone. This scarring can create functional problems and its treatment is challenging. The aim of the present study was to evaluate the efficacy of decorin in treating scar formation in osteomyelitis and the underlying mechanism of its action. A rat osteomyelitis model was used, and animals were divided into three groups, as follows: Group A (control), group B (osteomyelitis model) and group C (decorin-treated). X-ray scans, hematoxylin and eosin (H&E) staining and Masson's trichrome staining were performed to observe changes in femur and muscle tissue. In order to assess the role of the transforming growth factor β1 (TGF-β1)/Smad signaling pathway in scar formation in osteomyelitis, alterations in muscle tissue morphology and in the activation of key members of the TGF-β1/Smad signaling pathway were investigated in groups A and B. According to the results of H&E staining, evident fibrosis in muscle tissue were observed at days 14 and 28 in group B. Simultaneously, the expression levels of key members of the TGF-β1/Smad signaling pathway were increased. Subsequent to treatment with decorin in group C, scarring was reduced, and significant downregulation of collagen I, TGF-β1, phosphorylated (p)Smad2 and pSmad3 protein expression levels was observed at days 14 and 28 compared with the osteomyelitis group. In conclusion, these results suggest that activation of TGF-β1 may serve an important role in the formation of scars in osteomyelitis and that decorin can reduce scar formation in an osteomyelitis rat model through inhibition of the TGF-β1/Smad signaling pathway.

The objective of this paper is to study the treatment outcome of postoperative adjuvant radiation therapy in Ivor Lewis esophagectomy with two-field lymphadenectomy (2FL) and evaluate whether the method can replace three-field lymphadenectomy (3FL). We collected a consecutive series of 503 patients who had undergone Ivor Lewis esophagectomy with 2FL over a seven-year period in our department and evaluated the therapeutic efficacy of postoperative adjuvant radiation therapy. Recurrence and survival rates were calculated with the Kaplan-Meier method, and the differences were compared by the log-rank test. Logistic regression analysis was used to test risk factors for postoperative lymph node metastasis. Cox regression analysis was used to identify prognostic risk factors. The overall 3- and 5-year survival rates were 62.8 and 34.4 %, respectively. There was a significant difference in 5-year survival rate between patients received adjuvant radiation therapy and did not receive radiation therapy. Postoperative adjuvant radiation therapy for patients who underwent Ivor Lewis esophagectomy with 2FL may offer the patients significant survival benefits and reduces the incidence of recurrence in cervical and superior mediastinal lymph nodes.

Lung cancer is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) is the most common pathological type of lung cancer, divided into squamous cell carcinoma and adenocarcinoma. Despite better techniques of surgery and improvement in adjuvant and neoadjuvant therapy, the median survival of advanced NSCLC is only 8-10 months. With increased understanding of molecular alternations in NSCLC, considerable efforts have focused on the development of personalized molecular-targeted therapies. The PI3K/AKT/mTOR pathway regulates tumor development, growth, and proliferation of NSCLC. Various novel inhibitors targeting this pathway have been identified in preclinical studies or clinical trials. Some genetic alternations may be considered sensitive or resistant biomarkers to these inhibitors. Sometimes, upregulation of RTK and the downstream PI3K pathway or upregulation of the ERK pathway by compensatory feedback reactivation in response to these inhibitors also lead to drug resistance. Therefore, combination therapy of these inhibitors and other targeted inhibitors such as EGFR-TKI or MEK inhibitors according to genetic status and categories of inhibitors is required to enhance the efficacy of these inhibitors. Here, we reviewed the genetic status of the PI3K/AKT/mTOR pathway in NSCLC and the novel inhibitors targeting this pathway in preclinical or clinical studies, exploring the possible genetic alternations related to different inhibitors and the means to enhance the antitumor effect in NSCLC.

The inactivation of RUNX3 in various cancers has been reported while the expression of RUNX3 on protein level in esophageal squamous cell carcinoma (ESCC) and its relationship with pathological parameters and prognosis still remained unclear. In this study, we examined the expression of RUNX3 in 158 ESCC samples and 20 normal esophageal mucosa samples by immunohistochemistry and qRT-PCR. The IHC result showed that RUNX3 was detected mainly in the nuclei of basal layer cells in 18 of 20 normal mucosa samples while in 158 ESCC samples, there were 46 with RUNX3 nuclei expression, 37 RUNX3 cytoplasmic expression, and 75 negative expression. The qRT-PCR confirmed the downregulation of RUNX3 mRNA in the RUNX3 protein negative group than in the RUNX3 nuclei and cytoplasmic expression group (P

Objective To investigate the association between v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue ( KRAS) gene mutations and levels of human leucocyte antigen (HLA) class I antigen in primary lung tumours and metastatic lymph nodes of patients with non-small cell lung cancer (NSCLC). Methods Patients with NSCLC undergoing tumour resection were enrolled. KRAS codon 12 mutations were analysed in normal lung and lymph node tissue, primary lung tumours and metastatic lymph nodes using polymerase chain reaction–restriction fragment length polymorphism analysis. HLA class I antigen immunostaining was examined using flow cytometry. Results A total of 65 patients participated in the study. All normal lung tissues had positive HLA class I antigen immunostaining. The majority of primary lung tumours (56/65) and all of the metastatic lymph nodes (31/31) had downregulated HLA class I antigen immunostaining. There was a positive correlation between downregulated HLA class I antigen in primary tumours and metastatic lymph nodes. There was a negative correlation between KRAS codon 12 mutations and the level of HLA class I antigen in primary and metastatic tumours. Conclusions KRAS codon 12 mutations appear to be important in the downregulation of HLA class I antigen in NSCLC. Abnormal activation of the oncogenic KRAS pathway might provide a new treatment target for NSCLC.

Aims and background To study the inhibitory effect of p21WAF1/CIP1 activation by saRNA on the growth of human pancreatic cancer cells PANC-1 in vitro and in vivo. Methods and study design A dsRNA (dsP21) targeting the p21WAF1/CIP1 gene promoter at position-322 relative to the transcription start site was transfected into PANC-1 cells. Expression of mRNA and protein was evaluated by semiquantitative RT-PCR and Western blotting. Proliferation of PANC-1 cells was measured by the MTT method, and the apoptosis rate was detected by flow cytometry. PANC-1 cells were transplanted subcutaneously in nude mice, and the inhibitory effect of dsP21 on tumor growth was observed. Results The introduction of dsP21 was shown to efficiently up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells according to the results of RT-PCR and Western blotting (P Conclusions dsP21 targeting the p21WAF1/CIP1 gene promoter can specifically up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells. It therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo and can be used as a new method and material for the gene therapy of pancreatic cancer.

Endocan plays a role in tumour angiogenesis and tumour growth. The aim of this study was to detect the expression of endocan in hepatocellular carcinoma (HCC) tumour-associated endothelial cells and to correlate endocan expression with clinicopathological parameters and tumour angiogenesis. Tumour tissues and surrounding non-cancerous hepatic parenchyma from 42 primary HCC patients were studied. Endothelial cells were isolated using magnetic microbeads conjugated with anti-CD31 and endocan expression was evaluated by real-time reverse transcription-polymerase chain reaction, Western blotting and immunohistochemistry. Endocan was significantly over-expressed in endothelial cells isolated from HCC tumours compared with corresponding non-cancerous liver tissues. In addition, the endocan mRNA level was significantly correlated with the serum α-fetoprotein level, intra-tumoural microvessel density, vascular endothelial growth factor mRNA, and vascular and venous invasion. The over-expression of endocan in tumour endothelial cells was closely related to the process of angiogenesis and pathogenesis in HCC, and suggests that endocan might be a useful marker for HCC progression.