Primary pulmonary meningioma and minute pulmonary meningothelial-like nodules: Rare pulmonary nodular lesions requiring more awareness in clinical practice.

In this editorial, we comment on an article by Ruan et al published in a recent issue of the World Journal of Clinical Case. Pulmonary meningothelial proliferative lesions, including primary pulmonary meningiomas, minute pulmonary meningothelial-like nodules, and metastatic pulmonary meningiomas are rare pulmonary lesions. These lesions are difficult to differentiate from lung cancers based on clinical and imaging manifestations. Herein, we briefly introduce the clinical, imaging, and pathological characteristics of these lesions and discuss their pathogenesis to strengthen the current understanding of pulmonary meningothelial proliferative lesions in clinical diagnosis and therapy.

PHLDA3 promotes lung adenocarcinoma cell proliferation and invasion via activation of the Wnt signaling pathway.

The PHLDA3 gene encodes a small 127 amino acid protein with a pleckstrin homology (PH)-only domain. The expression and significance of PHLDA3 in lung cancer remain unclear. Here, we investigated the role of PHLDA3 in tumor proliferation and invasion in lung adenocarcinoma. Immunohistochemistry and immunoblotting analyses were used to assess PHLDA3 expression in lung cancer tissues, and its correlation with clinicopathological factors in lung cancer. Plasmids encoding PHLDA3 and small interfering RNA against PHLDA3 were used to regulate the expression of PHLDA3 in lung cancer cells. Furthermore, the effects of PHLDA3 on lung cancer cell proliferation and invasion were investigated using the MTS, colony formation, Matrigel invasion, and wound healing assays. Co-immunoprecipitation analysis and inhibitors of both the Wnt signaling pathway and GSK3ß were used to explore the regulatory mechanisms underlying the role of PHLDA3 in lung cancer cells. PHLDA3 was found to be overexpressed in lung cancer tissues, and its expression was correlated with poor outcomes in lung adenocarcinoma patients. PHLDA3 expression promoted the proliferation, invasion, and migration of lung cancer cells. Overexpression of PHLDA3 activated the Wnt signaling pathway and facilitated epithelial-mesenchymal transition. Inhibition of Wnt signaling pathway activity, using XAV-939, reversed the effects of PHLDA3 overexpression in lung cancer cells; moreover, PHLDA3 could bind to GSK3ß. Inhibition of GSK3ß activity, using CHIR-99021, restored the proliferative and invasive abilities of PHLDA3 knockdown cells. Our findings demonstrate that PHLDA3 is highly expressed in lung adenocarcinomas and is correlated with poor outcomes. Furthermore, it promotes the proliferation and invasion of lung cancer cells by activating the Wnt signaling pathway.

DEK is highly expressed in breast cancer and is associated with malignant phenotype and progression.

DEK proto-oncogene (DEK) has been demonstrated as an oncogene and is associated with the development of many types of tumor; however, the expression and role of DEK in breast cancer remain unknown. The present study aimed to determine the role of DEK in the progression of breast cancer. The expression of DEK in 110 breast cancer tissues and 50 adjacent normal breast tissues was examined using immunohistochemistry. Furthermore, DEK expression was upregulated by DEK transfection or downregulated by DEK shRNA interference in MCF7 cells. Proliferative and invasive abilities were examined in MCF7 cells using MTT assay, colony-formation assay and transwell invasion assays. The results demonstrated that DEK expression level was significantly increased in breast cancer tissues compared with normal breast tissues. Furthermore, high DEK expression was associated with high histological grade, lymph node metastasis, advanced Tumor-Node-Metastasis stage and high Ki-67 index; however, DEK expression was not associated with the expression level of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. High DEK expression indicated poor prognosis in patients with breast cancer. DEK overexpression upregulated the protein expression of ß-catenin and Wnt and increased the proliferative and invasive abilities of breast cancer cells. DEK downregulation had the opposite effect. Taken together, the results from the present study demonstrated that high expression of DEK was common in patients with breast cancer and was associated with progression of the disease and poor prognosis, and that DEK overexpression promoted the proliferative and invasive abilities of breast cancer cells.

Thymic adenocarcinoma accompanied by type A thymoma and pulmonary minimally invasive adenocarcinoma and harboring distinct gene alterations: A case report.

RATIONALE: Thymic adenocarcinoma is an extremely rare thymic carcinoma. The exact genetic alteration associated with thymic adenocarcinoma is unclear. Here, we report a case of thymic adenocarcinoma accompanied by type A thymoma and pulmonary minimally invasive adenocarcinoma (MIA). PATIENT CONCERNS: A 53-year-old woman presented with multiple nodules in the mediastinum and lung. Thoracic computed tomography revealed nodules in the anterior superior mediastinum and anterior mediastinum near the right pericardium and ground-glass opacity (GGO) in the right superior lobe of the lung. DIAGNOSIS: The tumor in the anterior superior mediastinum was diagnosed as primary thymic papillary adenocarcinoma. The tumor in the anterior mediastinum near the right pericardium was diagnosed as type A thymoma. The GGO of the right superior lobe of the lung was diagnosed as a MIA. INTERVENTION: The patient underwent thoracoscopic mediastinal tumor resection and partial lobectomy in our hospital. OUTCOMES: The postoperative course was uneventful. The patient is alive and free of the disease for 22 months after diagnosis. LESSONS: Thyroid transcription factor 1 (TTF-1) was positive in this case of thymic adenocarcinoma, which indicated that a thymic adenocarcinoma with TTF-1-positive may not necessarily be a metastasis of lung or thyroid adenocarcinoma. The positive staining of CD5 and CD117 can help us to confirm the thymic origin. Molecular genetic analysis indicated that these tumors harbored different mutations. The thymic adenocarcinoma and type A thymoma both had the mutation of KMT2A, but the mutation sites were different. KMT2A mutation may be a common genetic change in thymic tumorigenesis. The genetic alterations disclosed in this study will help expand the understanding of thymic tumors.

TRIP13 promotes the proliferation and invasion of lung cancer cells via the Wnt signaling pathway and epithelial-mesenchymal transition.

Thyroid hormone receptor interactor 13 (TRIP13) is an ATPase that has been found to be overexpressed in many tumors. The aim of this study was to investigate the role of TRIP13 and its mechanism of action in lung cancer. The expression of TRIP13 was examined in lung cancer tissues and corresponding normal lung tissues by western blotting. TRIP13 was overexpressed or knocked down by transient transfection or siRNA interference in lung cancer cells, respectively. The expression of key proteins associated with the Wnt signaling pathway and epithelial-mesenchymal transition (EMT) was assessed. The interaction between TRIP13 and low-density lipoprotein receptor-related protein 6 (LRP6) was examined by co-immunoprecipitation and laser confocal immunofluorescence. Moreover, this study determined the proliferative and invasive ability of cells through colony formation, cell proliferation, and Matrigel invasion assays. The expression of TRIP13 was higher in lung cancer tissues than in normal lung tissues (p = 0.002), and this correlated with poor patient prognosis (p < 0.001). In addition, overexpression of TRIP13 enhanced the levels of active ß-catenin and target proteins of the Wnt signaling pathways (p < 0.05). This study found that TRIP13 can co-localize and bind with LRP6. Furthermore, overexpression of TRIP13 caused the upregulation of N-cadherin, Snail, and vimentin, and the downregulation of E-cadherin (p < 0.05). The aforementioned results were reversed after knocking down the expression of TRIP13 (p < 0.05). TRIP13 is highly expressed in lung cancers, indicating poor prognosis. overexpression of TRIP13 promotes the proliferative and invasive ability of lung cancer cells via the activation of Wnt signaling pathway and EMT.

FAM83A Promotes Lung Cancer Progression by Regulating the Wnt and Hippo Signaling Pathways and Indicates Poor Prognosis.

FAM83A (family with sequence similarity 83, member A) has been found to be highly expressed in cancers. The purpose of this study was to clarify the role and mechanism of FAM83A in lung cancers. The expression of FAM83A in lung cancer cells was enhanced by gene transfection or knocked down by small interfering RNA interference. The key proteins of the Wnt signaling pathway, the Hippo signaling pathway, and epithelial-mesenchymal transition (EMT) were examined using Western blot. The proliferation and invasion of lung cancer cells were examined using cell proliferation, colony formation, and invasion assays. The expression of FAM83A in lung cancer tissues was significantly increased and was correlated with advanced tumor-node-metastasis (TNM) stage and poor prognosis. Overexpression of FAM83A enhanced the proliferation, colony formation, and invasion of lung cancer cells. Meanwhile, FAM83A overexpression increased the expression of active ß-catenin and Wnt target genes and the activity of EMT. Furthermore, in FAM83A-overexpressed cells, the activity of Hippo pathway was downregulated, whereas the expression of yes-associated protein (YAP) and its downstream targets cyclin E and CTGF were upregulated. The inhibitor of the Wnt signaling pathway, XAV-939, reversed the promoting effect of FAM83A on YAP, cyclin E, and CTGF. On knocking down the expression of FAM83A, we obtained the opposite results. However, the inhibitor of GSK3ß, CHIR-99021, restored the expression of YAP, cyclin E, and CTGF after FAM83A was knocked down. FAM83A is highly expressed in lung cancers and correlated with advanced TNM stage and poor prognosis. FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process.

DEK promotes the proliferation and invasion of lung cancers and indicates poor prognosis in lung adenocarcinomas.

DEK has been revealed to be overexpressed in many cancers and associated with cancer progression. The aim of the present study was to elucidate the role of DEK with a specific focus on its underlying mechanism in lung cancers. DEK expression in lung cancers and normal lung tissues and the correlations between DEK expression and clinicopathological parameters of lung cancers were investigated using the data from The Cancer Genome Atlas (TCGA). DEK expression was upregulated by DEK transfection or downregulated by DEK shRNA interference in A549 and H1299 cells. The effects of DEK on the Wnt signaling pathway and epithelial­mesenchymal transition (EMT) were examined using western blotting. Proliferative and invasive abilities were observed in A549 and H1299 cells treated with DEK using an MTT assay, colony formation assay, and Transwell migration and invasion assays. The expression of DEK was higher in lung cancer tissues than that in normal lung tissues. DEK expression was positively correlated with the expression of epidermal growth factor receptor (EGFR) and KRAS in lung adenocarcinomas. High expression of DEK indicated poor prognosis in lung adenocarcinomas (P=0.018). Enhanced expression of DEK upregulated the levels of active­ß­catenin and Wnt target genes, such as cyclin D1, c­Myc and MMP7 and increased the proliferative and invasive abilities of lung cancer cells. Enhanced expression of DEK in A549 and H1299 cells also increased the levels of EGFR, KRAS, vimentin, Snail, and N­cadherin, and decreased the level of E­cadherin. The opposite results were obtained with knockdown of DEK expression. DEK was highly expressed in lung cancers and indicated poor prognosis in lung adenocarcinomas. DEK expression activated the Wnt signaling pathway and EMT process and promoted the proliferation and invasion of lung cancers.

Overexpression of KRT17 promotes proliferation and invasion of non-small cell lung cancer and indicates poor prognosis.

PURPOSE: Keratin 17 (KRT17) is a 48 KDa type I intermediate filament, which is mainly expressed in epithelial basal cells. KRT17 has been shown to be overexpressed in many malignant tumors and play an important role in the occurrence and development of tumors. Therefore, this study explored the role and underlying mechanism of KRT17 in non-small cell lung cancers (NSCLC). METHODS: KRT17 expression and its correlations with clinicopathological factors were examined in lung cancer tissues by immunohistochemistry. The prognosis value of KRT17 in NSCLCs was retrieved from The Cancer Genome Atlas (TCGA) online databases. The expression level of KRT17 was increased or decreased by KRT17 gene transfection or small RNA interference in lung cancer cells, respectively. Further, proliferation and invasiveness of lung cancer cells were determined by cell proliferation and invasion assays, respectively. Finally, expression levels of proteins related to Wnt signaling pathways and epithelial mesenchymal transition (EMT) were detected by Western blot. RESULTS: The expression level of KRT17 in NSCLCs was significantly higher than normal lung tissues. High expression of KRT17 predicted poor prognosis of patients with NSCLCs, especially lung adenocarcinomas, and was correlated with poor differentiation and lymphatic metastasis. Overexpression of KRT17 enhanced, while KRT17 knockdown inhibited, the proliferation and invasiveness of lung cancer cells. Overexpression of KRT17 up-regulated ß-catenin activity and levels of Wnt target genes, such as cyclin D1, c-Myc, and MMP7. Moreover, KRT17 promoted EMT by up-regulating Vimentin, MMP-9, and Snail expression and down-regulating E-cadherin expression. CONCLUSION: Overexpression of KRT17 is common in NSCLCs and indicates poor prognosis. Overexpression of KRT17 enhances the proliferation and invasiveness of NSCLC cells by activating the Wnt signaling pathway and EMT process. KRT17 is a potential indicator of NSCLC progression and poor survival.

PRDM16 functions as a suppressor of lung adenocarcinoma metastasis.

BACKGROUND: The transcription factor PR domain containing 16 (PRDM16) is known to play a significant role in the determination and function of brown and beige fat. However, the role of PRDM16 in tumor biology has not been well addressed. Here we investigated the impact of PRDM16 on tumor growth and metastasis in lung cancer. METHODS: UALCAN database, immunoblotting and immunohistochemistry analysis were used to assess PRDM16 expression in lung cancer patients. Kaplan-Meier plotter database was used to analyze the overall survival of patients with lung cancer stratified by PRDM16 expression. PRDM16 overexpression and knockdown experiments were conducted to assess the effects of PRDM16 on growth and metastasis in vitro and in vivo, and its molecular mechanism was investigated in lung adenocarcinoma cells by chromatin immunoprecipitation-sequencing (ChIP-Seq), real time-quantitative PCR (RT-qPCR), luciferase assay, xenograft models and rescue experiments. RESULTS: PRDM16 was downregulated in lung adenocarcinomas, and its expression level correlated with key pathological characteristics and prognoses of lung adenocarcinoma patients. Overexpressing PRDM16 inhibited the epithelial-to-mesenchymal transition (EMT) of cancer cells both in vivo and in vitro by repressing the transcription of Mucin-4 (MUC4), one of the regulators of EMT in lung adenocarcinomas. Furthermore, deleting the PR domain from PRDM16 increased the transcriptional repression of MUC4 by exhibiting significant differences in histone modifications on its promoter. CONCLUSIONS: Our findings demonstrate a critical interplay between transcriptional and epigenetic modifications during lung adenocarcinoma progression involving EMT of cancer cells and suggest that PRDM16 is a metastasis suppressor and potential therapeutic target for lung adenocarcinomas.

Overexpression of Nemo-like Kinase Promotes the Proliferation and Invasion of Lung Cancer Cells and Indicates Poor Prognosis.

BACKGROUND: Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinaserelated kinase involved in the pathogenesis of several human cancers. OBJECTIVE: The aim of this study was to investigate the expression and role of NLK in lung cancers, and its underlying mechanisms. METHODS: We examined the expression of NLK in lung cancer tissues through western blot analysis. We enhanced or knocked down NLK expression by gene transfection or RNA interference, respectively, in lung cancer cells, and examined expression alterations of key proteins in the Wnt signaling pathway and in epithelial-mesenchymal transition (EMT). We also examined the roles of NLK in the proliferation and invasiveness of lung cancer cells by cell proliferation, colony formation, and Matrigel invasion assays. RESULTS: NLK expression was found to be significantly higher in lung cancer tissue samples than in corresponding healthy lung tissue samples. Overexpression of NLK correlated with poor prognosis of patients with lung cancer. Overexpression of NLK upregulated ß-catenin, TCF4, and Wnt target genes such as cyclin D1, c-Myc, and MMP7. N-cadherin and TWIST, the key proteins in EMT, were upregulated, while E-cadherin expression was reduced. Additionally, proliferation, colony formation, and invasion turned out to be enhanced in NLK-overexpressing cells. After NLK knockdown in lung cancer cells, we obtained the opposite results. CONCLUSION: NLK is overexpressed in lung cancers and indicates poor prognosis. Overexpression of NLK activates the Wnt signaling pathway and EMT and promotes the proliferation and invasiveness of lung cancer cells.

Odd-skipped related 1 inhibits lung cancer proliferation and invasion by reducing Wnt signaling through the suppression of SOX9 and ß-catenin.

The odd-skipped related 1 (OSR1) gene encodes a zinc-finger transcription factor. The expression and significance of OSR1 in human tumors remains unclear. We found that OSR1 was downregulated in lung cancers, and its expression was correlated with poor differentiation. Overexpression of OSR1 by OSR1 gene transfection into H1299 cells (H1299-OSR1) inhibited the proliferation and invasion of lung cancer cells. Knockdown of OSR1 with small interfering (si)RNA against OSR1 in A549 cells (A549-siOSR1) enhanced the proliferation and invasion of lung cancer cells. Western blot analysis showed that the expression level of GSK3ß increased, while that of p-GSK3ß, nuclear ß-catenin, cyclin D1, c-Myc and matrix metallopeptidase 7 significantly decreased in the H1299-OSR1 cells, and this pattern was reversed in the A549-siOSR1 cells compared to that in the control cells. Furthermore, upregulation of sex-determining region Y-box 9 (SOX9) by SOX9 gene transfection increased the expression of ß-catenin, which was inhibited by OSR1. The mRNA and protein expression levels of SOX9 and ß-catenin were reduced in H1299-OSR1 cells and increased in A549-siOSR1 cells. In conclusion, the expression of OSR1 was more reduced in lung cancer tissues than in normal lung tissues, and was correlated with poor differentiation. OSR1 downregulated the activity of the Wnt signaling pathway by suppressing the expression of SOX9 and ß-catenin.

Thyroid cancer 1 (C8orf4) shows high expression, no mutation and reduced methylation level in lung cancers, and its expression correlates with ß-catenin and DNMT1 expression and poor prognosis.

Thyroid cancer 1 (TC1, C8orf4) plays important roles in tumors. The aim of this study was to examine the protein expression levels, methylation status, and mutational status of TC1 (C8orf4) in lung cancers, and investigate the correlation between TC1, other members of the Wnt signaling pathway, and lung cancer. TC1 expression levels were assessed via immunohistochemical staining in 179 cases of lung cancer. ß-catenin, TCF4, Axin, Disabled-2, Chibby, and DNA methyltransferase-1 (DNMT1) expressions were also examined. Bisulfite sequencing PCR analysis was used to examine the methylation status of the C8orf4 locus, while PCR analysis and direct sequencing were used to determine its mutational status. We found high TC1 expression correlated with poor differentiation, advanced TNM stage, lymphatic metastasis, and poor prognosis in lung cancer patients. TC1 expression also correlated with ß-catenin and DNMT1 expressions. No mutations in C8orf4 were detected. However, methylation levels of C8orf4 in lung cancers were lower than in corresponding normal lung tissues. In conclusion, high TC1 expression is implicated in lung cancer progression and correlates with poor prognosis in lung cancer. Reduced methylation levels might be responsible for the elevated TC1 expression levels. TC1, ß-catenin, and DNMT1 can synergistically activate Wnt/ß-catenin signaling in lung cancers.

Benzene C-H Etherification via Photocatalytic Hydrogen-Evolution Cross-Coupling Reaction.

Aryl ethers can be constructed from the direct coupling between the benzene C-H bond and the alcohol O-H bond with the evolution of hydrogen via the synergistic merger of photocatalysis and cobalt catalysis. Utilizing the dual catalyst system consisting of 3-cyano-1-methylquinolinum photocatalyst and cobaloxime, intermolecular etherification of arenes with various alcohols and intramolecular alkoxylation of 3-phenylpropanols with formation of chromanes are accomplished. These reactions proceed at remarkably mild conditions, and the sole byproduct is equivalent hydrogen gas.

Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H Amination and Hydroxylation.

We present a blueprint for aromatic C-H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities.

Caveolae Restrict Tiger Frog Virus Release in HepG2 cells and Caveolae-Associated Proteins Incorporated into Virus Particles.

Caveolae are flask-shaped invaginations of the plasma membrane. Caveolae play important roles in the process of viruses entry into host cells, but the roles of caveolae at the late stage of virus infection were not completely understood. Tiger frog virus (TFV) has been isolated from the diseased tadpoles of the frog, Rana tigrina rugulosa, and causes high mortality of tiger frog tadpoles cultured in Southern China. In the present study, the roles of caveolae at the late stage of TFV infection were investigated. We showed that TFV virions were localized with the caveolae at the late stage of infection in HepG2 cells. Disruption of caveolae by methyl-ß-cyclodextrin/nystatin or knockdown of caveolin-1 significantly increase the release of TFV. Moreover, the interaction between caveolin-1 and TFV major capsid protein was detected by co-immunoprecipitation. Those results suggested that caveolae restricted TFV release from the HepG2 cells. Caveolae-associated proteins (caveolin-1, caveolin-2, cavin-1, and cavin-2) were selectively incorporated into TFV virions. Different combinations of proteolytic and/or detergent treatments with virions showed that caveolae-associated proteins were located in viral capsid of TFV virons. Taken together, caveolae might be a restriction factor that affects virus release and caveolae-associated proteins were incorporated in TFV virions.

[Trans-areola single port endoscopic thoracic sympathectomy for the treatment of palmar hyperhidrosis: a new surgical approach].

OBJECTIVE: To evaluate the cosmetic effects and safety profiles of trans-areola single port endoscopic thoracic sympathectomy. METHODS: A retrospective study was conducted for 45 males and 7 females with palmar hyperhidrosis undergoing trans-areola single port endoscopic thoracic bilateral sympathectomy during April and June 2011. RESULTS: All operations were successfully performed without severe morbidity and mortality. No conversion to open technique was necessary. The mean unilateral operative duration was 6 minutes (range: 5 - 8). The time was calculated from the time of skin incision to that of dressing application over wound. The mean hospitalization duration was 2.2 days (range: 2 - 3). The mean follow-up period was 2.8 months (range: 1 - 7). All patients achieved excellent cosmetic effects. No incision scar was found. CONCLUSION: Trans-areola single port endoscopic thoracic sympathectomy is a safe and effective therapeutic procedure for primary palmar hyperhidrosis. The incision is undetectable with excellent cosmetic effects. The trans-areola route is a new ideal and promising approach for endoscopic thoracic sympathectomy.

[Establishment of rat integrated discrete multiple organ cell culture (IdMOC) model].

OBJECTIVE: To establish the integrated discrete multiple organ cell culture (IdMOC) system. METHODS: Rat primary cell of hepatocyte, nephrocyte, cardiomyocytes, alveolar macrophage, dermal fibroblasts were isolated by collagenase digestion, separation of bronchial lavage, two-step digestion method and cultured respectively, with monolayer culture. To establish the integrated discrete multiple organ cell culture (IdMOC) system, glass slides of five different cells were used to the same dish with 10% FBS DMEM medium cultured 7d, using MTT comparison primary cells cultured alone and cocultured when growth. RESULTS: Established rat hepatocytes, renal cell, cardiomyocyte, alveolar macrophages, dermal fibroblasts separation method was stable, cell separation survival rate was about 90.0%. Hepatocytes separation survival rate 90.3% ,renal cell separation survival rate 91.9%, cardiomyocyte separation survival rate 93.0% and beating rate indifference curve among 3d-15d, alveolar macrophages cell separation survival rate 90.8%, dermal fibroblasts cell separation survival rate 92.7%. Five primary cells multiple organ cells coculture showed cocultured cell growth proliferation well, cultured alone and cocultured cells growth curve basic coincide. CONCLUSION: Established rat multiple organ cell co-culture is successful.