Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/β-catenin signaling

Rationale: Antimicrobial peptides, such as cathelicidin LL-37/hCAP-18, are important effectors of the innate immune system with direct antibacterial activity. In addition, LL-37 is involved in the regulation of tumor cell growth. However, the molecular mechanisms underlying the functions of LL-37 in promoting lung cancer are not fully understood. Methods: The expression of LL-37 in the tissues and sera of patients with non-small cell lung cancer was determined through immunohistological, immunofluorescence analysis, and enzyme-linked immunosorbent assay. The animal model of wild-type and Cramp knockout mice was employed to evaluate the tumorigenic effect of LL-37 in non-small cell lung cancer. The mechanism of LL-37 involving in the promotion of lung tumor growth was evaluated via microarray analyses, recombinant protein treatment approaches in vitro, tumor immunohistochemical assays, and intervention studies in vivo. Results: LL-37 produced by myeloid cells was frequently upregulated in primary human lung cancer tissues. Moreover, its expression level correlated with poor clinical outcome. LL-37 activated Wnt/β-catenin signaling by inducing the phosphorylation of protein kinase B and subsequent phosphorylation of glycogen synthase kinase 3β mediated by the toll-like receptor-4 expressed in lung tumor cells. LL-37 treatment of tumor cells also decreased the levels of Axin2. In contrast, it elevated those of an RNA-binding protein (tristetraprolin), which may be involved in the mechanism through which LL-37 induces activation of Wnt/β-catenin. Conclusion: LL-37 may be a critical molecular link between tumor-supportive immune cells and tumors, facilitating the progression of lung cancer

Surgical Treatment for 11 Cases of Penile Verrucous Carcinoma

Penile verrucous carcinoma is a rare, well-differentiated and low-grade tumor. The surgeons are deficiently aware about the biological behavior and the clinicopathological characteristic of this disease, which raises difficulties during the treatment. In our present study, the clinical and pathological data of 11 patients with penile verrucous carcinoma, aged between 49 to 85 years was retrospectively analyzed. The tumors exhibited exophytic, papillary, caulifower-like or verrucose lesions of great dimensions measuring between 2 to 10 cm on the penises. The tumors were located at glans in 6 cases, invaded the coronoid sulcus in 4 cases and invaded the shaft of the penis in 1 case. Eight cases underwent partial penectomy, while the other 3 were treated with local excision. The diagnosis of penile verrucous carcinoma was confirmed by histopathologic examination of the specimens with the negative surgical margins in all the cases. Within the period of 12 to 60 months of follow-up, all the patients were disease-free with no case of recurrence and metastasis. The novel knowledge and experience of the treatment of penile verrucous carcinoma will be a useful clinical guide for surgeons in the future

Diagnostic Value of Methylated Septin9 for Colorectal Cancer Detection

BackgroundMethylated Septin9 (mSEPT9) has been suggested as a reliable biomarker in colorectal cancer (CRC) detection. We aimed to determine the diagnostic value of mSEPT9 for CRC detection in Chinese patients. In addition, we compared the diagnostic efficacy of mSEPT9 to traditional screening method [fecal occult blood test (FOBT)] and two biomarkers [carcinoembryonic antigen (CEA) and carbohydrate antigen-199 (Ca-199)].MethodsOverall 248 subjects including 123 patients with CRC and 125 controls were included. Plasma and fecal samples were collected for CEA, Ca-199, mSEPT9, and FOBT tests. Sensitivity and specificity were calculated to evaluate the diagnostic efficacy of each method; receiver operating characteristic (ROC) curve was plotted for the assessment of diagnostic accuracy, and comparisons among FOBT, mSEPT9, and the combination were assessed through area under the ROC curve (AUC).ResultsmSEPT9 achieved overall sensitivity and specificity of 61.8% [95% confidence interval (CI): 53.0–69.9%] and 89.6% (83.0–93.8%), respectively, with an AUC value of 0.757 (95% CI: 0.701–0.807), superior to FOBT [sensitivity: 61.4% (50.9–70.9%); specificity: 70.3% (59.1–79.5%); AUC: 0.658 (0.578–0.723)], CEA [sensitivity: 35.0% (27.1–43.7%); specificity: 62.6% (53.8–70.7%); AUC: 0.485 (0.411–0.559)], and Ca-199 [sensitivity: 17.9% (12.1–25.6%); specificity: 55.7% (48.9–64.1%); AUC: 0.353 (0.283–0.423)]. The combination of mSEPT9 and FOBT further improved sensitivity and AUC value of 84.1% (75.1–90.3%) and 0.807 (0.752–0.863), respectively, while specificity was declined to 62.2% (50.8–72.4%).ConclusionmSEPT9 demonstrated best diagnostic ability in CRC detection compared with FOBT, CEA, and Ca-199. The combination of mSEPT9 and FOBT further improved diagnostic sensitivity especially for early stage disease, which may provide a new approach for future CRC screening, though further investigations are warranted

Bronchoalveolar Lavage Fluid-Derived Exosomes: A Novel Role Contributing to Lung Cancer Growth

Exosomes are nanovesicles produced by a number of different cell types and regarded as important mediators of cell-to-cell communication. Although bronchoalveolar lavage fluid (BALF) has been shown to be involved in the development of tumors, its role in lung cancer (LC) remains unclear. In this article, we systemically studied BALF-derived exosomes in LC. C57BL/6 mice were injected with Lewis lung carcinoma cells and exposed to non-typeable Haemophilus influenza (NTHi) lysate. The analysis showed that the growth of lung tumors in these mice was significantly enhanced compared with the control cohort (only exposure to air). Characterization of the exosomes derived from mouse BALF demonstrated elevated levels of tumor necrosis factor alpha and interleukin-6 in mice exposed to NTHi lysates. Furthermore, abnormal BALF-derived exosomes facilitated the development of LC in vitro and in vivo. The internalization of the BALF-derived exosomes contributed to the development of LC tumors. Collectively, our data demonstrated that exosomes in BALF are a key factor involved in the growth and progression of lung cancer

Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 4 (TLR4) is expressed on immune cells as a sensor that recognizes lipopolysaccharide (LPS), a microbial conserved component. It has recently been determined that the expression of TLR4 is also found in various types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral squamous cell carcinoma (OSCC) treatment. However, the mechanisms responsible for cisplatin resistance are not well understood.</p> <p>Results</p> <p>The present study was designed to elucidate the role of TLR4 expression in human OSCC regarding immune escape and apoptotic resistance to cisplatin. TLR4 and the myeloid differentiation primary response gene 88 (MyD88) were highly expressed in OSCC cell lines. Upon LPS stimulation both NF-κB and p38 MAPK pathways were activated in OSCC cell lines, followed by the production of large quantities of IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells (HIOECs). OSCC cell lines were found to be resistant to cisplatin-mediated apoptosis after pretreatment with LPS.</p> <p>Conclusions</p> <p>Our results suggested that TLR4 was functionally expressed in human OSCC cells and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might thus elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC.</p

Mechanical Behaviors and Acoustic Emission Fractal Characteristics of Bump-Prone Coal under Different Loading Rates

Coal and rock dynamic disasters occur frequently in deep coal mining. The loading rate affects the mechanical properties and behaviors. Uniaxial compression acoustic emission (AE) tests of bump-prone coal under various loading rates were carried out, and the mechanical properties, AE spatiotemporal evolution, and spatial fractal characteristics were analyzed. The experimental results indicate that the uniaxial compressive strength is positively related to the loading rate, and the elastic modulus increases before decreasing with the loading rate. The failure strain is positively related to the loading rate, and the percentage of the compaction phase relative to the pre-peak phase decreases with the loading rate. The hit rate, absolute energy, AE events, and amplitude evolution of coal samples under various loading rates are the same, and the maximum of AE absolute energy and hit rate is positively related to the loading rate. The spatial evolution of AE events of coal samples under various loading rates is the same, showing a “slow increase → slow increase → fast increase → rapid increase → slow increase” trend. The spatial fractal dimension ranges from 2.1 to 2.9, and the evolution of coal samples under various loading rates is the same, exhibiting a downward trend

<it>In vitro</it> and <it>in vivo</it> anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma

Abstract Background Metformin, which is widely used as an antidiabetic agent, has recently been reported to reduce cancer risk and improve prognosis in certain malignancies. However, the specific mechanisms underlying the effect of metformin on the development and progression of several cancers including oral squamous cell carcinoma (OSCC) remain unclear. In the present study, we investigated the effects of metformin on OSCC cells in vitro and in vivo. Methods OSCC cells treated with or without metformin were counted using a hemocytometer. The clonogenic ability of OSCC cells after metformin treatment was determined by colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the activation of related signaling pathways was examined by immunoblotting. The in vivo anti-tumor effect of metformin was examined using a xenograft mouse model. Immunohistochemistry and TUNEL staining were used to determine the expression of cyclin D1 and the presence of apoptotic cells in tumors from mice treated with or without metformin. Results Metformin inhibited proliferation in the OSCC cell lines CAL27, WSU-HN6 and SCC25 in a time- and dose-dependent manner, and significantly reduced the colony formation of OSCC cells in vitro. Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase. Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells. In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax. Metformin also markedly reduced the expression of cyclin D1 and increased the numbers of apoptotic cells in vivo, thus inhibiting the growth of OSCC xenografts. Conclusions Our data suggested that metformin could be a potential candidate for the development of new treatment strategies for human OSCC.</p

Eu3+ DOPED SILICA FILM AS LUMINESCENT DOWN-SHIFTING LAYER FOR CRYSTALLINE Si SOLAR CELLS

Eu3+ doped silica films have been prepared by sol–gel method and employed as luminescent down-shifting layer on the front side of a crystalline Si solar cell to improve their conversion efficiency. Measurements under standard test conditions (AM1.5, 100 mW/cm2) show the conversion efficiency of Si solar cell with silica film containing Eu3+ is improved 9.5% maximally as compared to the Si solar cell with pure silica film. However, high Eu3+ concentration is not encouraged because concentration quenching effect will decrease the efficiency of the solar cell.Solar cell, conversion efficiency, Eu3+, sol–gel method

Plasma versican and plasma exosomal versican as potential diagnostic markers for non-small cell lung cancer

Abstract Background and aims This study aimed to investigate the expression of plasma versican and plasma exosomal versican in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological features, and to evaluate its diagnostic performance in NSCLC and its predictive function for NSCLC incidence and metastasis risk. Materials and methods There were 110 instances of NSCLC, 42 cases of benign lung disease, and 55 healthy controls from September 2018 to October 2020 at Tongji Hospital Affiliated to Tongji University. Blood was collected and plasma was separated before surgery, and plasma exosomes were extracted by ExoQuick kit. Morphological and molecular phenotype identification of exosomes was performed by transmission electron microscopy, Nanosight particle tracking analysis, and western blotting. Plasma versican and plasma exosomal versican were detected in all subjects to assess their expression levels and diagnostic value in NSCLC. Clinicopathological data were collected to explore correlations between abnormal plasma versican and plasma exosomal versican expression and clinicopathological parameters. Receiver operating characteristic (ROC) curve was used to judge its diagnostic performance in NSCLC, and binary logistic regression analysis was used to predict the risk of NSCLC incidence and metastasis. Results Plasma versican and plasma exosomal versican expression in NSCLC patients was significantly upregulated and was significantly higher in T3 + T4 patients compared with T1 + T2 patients (P < 0.05); the levels of plasma versican and plasma exosomal versican were positively correlated with lymph node metastasis, distant metastases (e.g., brain, bone), and mutation(e.g., EGFR,ALK)in NSCLC patients (all P < 0.05). Furthermore, ROC curve analysis showed that plasma versican and plasma exosomal versican had higher AUC values than NSE, CYFRA21-1, and SCC, and better diagnostic performance in NSCLC patients. However, the AUC and diagnostic performances of plasma versican and plasma exosomal versican in advanced-stage NSCLC patients were not shown to be significantly better than CEA. The results of binary logistic regression analysis showed that high levels of plasma exosomal versican had higher predictive value for lung cancer incidence, while high levels of plasma versican had higher predictive value for lung cancer metastasis. Conclusion Our findings showed that plasma versican and plasma exosomal versican might be potential diagnostic markers for NSCLC. High plasma exosomal versican expression can be used as a predictor of NSCLC risk and high plasma versican expression can be used as a predictor of NSCLC metastasis risk