"Being a Good Parent" During Times of Illness as Defined by Chinese Children With Cancer, Their Parents, and Providers.

BACKGROUND: Identifying the definition of "being a good parent" facilitates the understanding of parents' personal beliefs and deeds regarding their ill child. OBJECTIVE: The aim of this study was to explore the concept of "being a good parent to my ill child" during pediatric cancer treatment from the perspective of Chinese children, parents, and providers. METHODS: A descriptive qualitative study was conducted with 6 children, 18 parents, 5 doctors, 19 nurses, and 3 social workers by semistructured interviews at 3 Chinese hospitals. RESULTS: Except for "letting the Lord lead," 7 themes from the original conceptual model were validated, for example, "being there for my child" (n = 51, 100.0%); "doing right by my child" (n = 38, 74.5%), "being an advocate for my child" (n = 27, 52.9%), "conveying love to my child" (n = 26, 51.0%), "making my child healthy" (n = 18, 35.3%), "being a good life example" (n = 13, 25.5%), and "not allowing suffering" (n = 13, 25.5%). A new theme, "rebuilding myself" (n = 39, 76.5%), emerged in the Chinese context. "Being a good parent to my ill child" is perceived differently among stakeholders. Healthcare professionals' facilitation to fulfill the concept included "recognizing the individualized good-parent definition," "providing best available care" and "establishing a supportive environment." CONCLUSION: "Being a good parent to my ill child" is meaningfully expressed by Chinese parents and recognized by children and providers during pediatric cancer treatment. IMPLICATIONS FOR PRACTICE: It is important to support parents in conveying their internal good parent definition and sharing it with stakeholders. Attention should be paid to related cultural influencers, a supportive family-friendly environment, and shared decision making involving the child's voice.

Thymol targeting interleukin 4 induced 1 expression reshapes the immune microenvironment to sensitize the immunotherapy in lung adenocarcinoma.

Immune checkpoint blockades are the most promising therapy in lung adenocarcinoma (LUAD). However, the response rate remains limited, underscoring the urgent need for effective sensitizers. Interleukin 4 induced 1 (IL4I1) is reported to have immunoinhibitory and tumor-promoting effects in several cancers. However, the targetable value of IL4I1 in sensitizing the immunotherapy is not clear, and there is a lack of effective small molecules that specifically target IL4I1. Here, we show that silencing IL4I1 significantly remodels the immune microenvironment via inhibiting aryl hydrocarbon receptor (AHR) signaling, thereby enhancing the efficacy of anti-PD-1 antibody in LUAD, which suggests that IL4I1 is a potential drug target for the combination immunotherapy. We then identify thymol as the first small molecule targeting IL4I1 transcription through a drug screening. Thymol inhibits the IL4I1 expression and blocks AHR signaling in LUAD cells. Thymol treatment restores the antitumor immune response and suppresses the progression of LUAD in an orthotopic mouse model. Strikingly, the combination treatment of thymol with anti-PD-1 antibody shows significant tumor regression in LUAD mice. Thus, we demonstrate that thymol is an effective small molecule to sensitize the PD-1 blockade in LUAD via targeting IL4I1, which provides a novel strategy for the immunotherapy of LUAD.

Case Report: ALK rearranged locally advanced lung adenocarcinoma showing inconsistent radiographic findings and pathological responses during neoadjuvant alectinib therapy.

Alectinib has been approved as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung carcinoma. Oncologists are also exploring the possibility of applying alectinib in the perioperative period. Here, we present a patient with locally advanced lung adenocarcinoma associated with EML4-ALK fusion mutation, who received neoadjuvant chemotherapy and alectinib treatment, and then underwent thoracoscopic left lower lung lobectomy. The patient initially received eight chemotherapy cycles and achieved partial remission. After eight cycles of chemotherapy, the lymph nodes in the hilar region again enlarged. The patient was then switched to 4 months of alectinib therapy, but no significant lesion changes were detected on imaging during this period. This raised the question of whether the patient developed alectinib resistance. The pathological findings of the postoperative lung lobe specimens indicated extensive necrosis in the tumor area with no residual tumor cells and massive chronic inflammatory cell infiltration around the tumor area, confirming inconsistency between the imaging findings and pathological results. Multi-point tumor specimen sampling was postoperatively performed. Tumor immune-related gene expression was detected in the sample with the help of the PanCancer IO360™ panel based on the nCounter platform. This is a rare case of a patient who was treated with neoadjuvant alectinib and had paradoxical radiographic findings and pathological responses. The possibility that intratumoral immune heterogeneity was responsible for this phenomenon has been discussed. Based on the findings, it is argued that the pathological response should be an important basis for assessing the effectiveness of neoadjuvant alectinib therapy.

Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Lung Adenocarcinoma.

Lung cancer is the leading cause of cancer-related deaths worldwide. Hypoxia is a crucial microenvironmental factor in lung adenocarcinoma (LUAD). However, the prognostic value based on hypoxia and immune in LUAD remains to be further clarified. The hypoxia-related genes (HRGs) and immune-related genes (IRGs) were downloaded from the public database. The RNA-seq expression and matched complete clinical data for LUAD were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to model construction. Hypoxia expression profiles, immune cell infiltration, functional enrichment analysis, Tumor Immune Dysfunction and Exclusion (TIDE) score and the somatic mutation status were analyzed and compared based on the model. Moreover, immunofluorescence (IF) staining in human LUAD cases to explore the expression of hypoxia marker and immune checkpoint. A prognostic model of 9 genes was established, which can divide patients into two subgroups. There were obvious differences in hypoxia and immune characteristics in the two groups, the group with high-risk score value showed significantly high expression of hypoxia genes and programmed death ligand-1 (PD-L1), and maybe more sensitive to immunotherapy. Patients in the high-risk group had shorter overall survival (OS). This model has a good predictive value for the prognosis of LUAD. We constructed a new HRGs and IRGs model for prognostic prediction of LUAD. This model may benefit future immunotherapy for LUAD.

Combining EGFR-TKI With SAHA Overcomes EGFR-TKI-Acquired Resistance by Reducing the Protective Autophagy in Non-Small Cell Lung Cancer.

Nowadays, lung cancer has the highest mortality worldwide. The emergence of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC) having EGFR-TKI-sensitive mutations. Unfortunately, acquired resistance happens for most patients. In the present research, we found that EGFR-TKIs (such as gefitinib and osimertinib) can induce autophagy in NSCLC cell lines. Compared with parental sensitive cells, drug-resistant cells have higher autophagy activity. The use of an autophagy inhibitor could enhance the toxicity of gefitinib and osimertinib, which indicates that the enhancement of protective autophagy might be one of the mechanisms of EGFR-TKI resistance in NSCLC. In addition, increased autophagy activity is associated with decreased enhancer of zeste homolog 2 (EZH2) expression. Knockdown of EZH2 or EZH2 inhibitor treatment could lead to increased autophagy in NSCLC cells, indicating that EZH2 is a negative regulator of autophagy. We revealed that the increase in autophagy caused by the reduction of EZH2 was reversed in vitro and in vivo when combining gefitinib or osimertinib with suberoylanilide hydroxamic acid (SAHA), a broad-spectrum histone deacetylase inhibitor (HDACi). In conclusion, our results indicated that the combination of EGFR-TKIs and SAHA may be a new strategy to overcome EGFR-TKIs acquired resistance.

DualMMP-GAN: Dual-scale multi-modality perceptual generative adversarial network for medical image segmentation.

Multi-modality magnetic resonance imaging (MRI) can reveal distinct patterns of tissue in the human body and is crucial to clinical diagnosis. But it still remains a challenge to obtain diverse and plausible multi-modality MR images due to expense, noise, and artifacts. For the same lesion, different modalities of MRI have big differences in context information, coarse location, and fine structure. In order to achieve better generation and segmentation performance, a dual-scale multi-modality perceptual generative adversarial network (DualMMP-GAN) is proposed based on cycle-consistent generative adversarial networks (CycleGAN). Dilated residual blocks are introduced to increase the receptive field, preserving structure and context information of images. A dual-scale discriminator is constructed. The generator is optimized by discriminating patches to represent lesions with different sizes. The perceptual consistency loss is introduced to learn the mapping between the generated and target modality at different semantic levels. Moreover, generative multi-modality segmentation (GMMS) combining given modalities with generated modalities is proposed for brain tumor segmentation. Experimental results show that the DualMMP-GAN outperforms the CycleGAN and some state-of-the-art methods in terms of PSNR, SSMI, and RMSE in most tasks. In addition, dice, sensitivity, specificity, and Hausdorff95 obtained from segmentation by GMMS are all higher than those from a single modality. The objective index obtained by the proposed methods are close to upper bounds obtained from real multiple modalities, indicating that GMMS can achieve similar effects as multi-modality. Overall, the proposed methods can serve as an effective method in clinical brain tumor diagnosis with promising application potential.

Pyroptosis-Related LncRNA Signatures Correlate With Lung Adenocarcinoma Prognosis.

Background: Pyroptosis is a new type of programmed cell death, accompanied by an intense inflammatory response. Previous studies have shown that pyroptosis can modify long-chain non-coding RNA (lncRNA), thereby affecting the occurrence and progression of tumors. However, the underlying role of pyroptosis-related lncRNA in lung adenocarcinoma (LUAD) remains to be elucidated. Therefore, the purpose of our study was to evaluate the prognostic value of pyrolysis-related lncRNA in patients with LUAD. Methods: A total of 454 LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) database. Pearson's correlation coefficient was used to identify the pyroptosis-related lncRNAs. Unsupervised consensus clustering was used to identify the various LUAD molecular subtypes. A least absolute shrinkage and selection operator (LASSO) analysis was conducted to construct a prognostic signature. Results: An 11-lncRNA prognostic signature out of 19 identified pyroptosis-related prognostic lncRNAs was constructed. The patients with LUAD were divided into low-risk and high-risk groups. Patients in the high-risk group had higher score values and mortality. The immune score, stromal score, and estimate score were lower in the high-risk group. The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR > 1, p < 0.01). BTLA, PD-1, PD-L1, CTLA, and CD47 were lower expressed in the high-risk group. Conclusions: Our study identified an 11-pyroptosis-related lncRNA signature. These findings could further clarify the role of pyroptosis in LUAD and guide the prognosis and individualized treatment of patients.

Construction of a circular RNA-microRNA-messenger RNA regulatory network of hsa_circ_0043256 in lung cancer by integrated analysis.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) are diagnosed in advanced stages and with a poor 5-year survival rate. There is a critical need to identify novel biomarkers to improve the therapy and overall prognosis of this disease. METHODS: Differentially expressed genes (DEGs) were identified from three profiles of GSE101586, GSE101684 and GSE112214 using Venn diagrams. hsa_circ_0043256 were validated using quantitative real-time polymerase chain reaction (RT-qPCR). The circular RNA-microRNA-messenger RNA (circRNA-miRNA-mRNA) regulatory network was constructed with Cytoscape 3.7.0. Hub genes were identified with protein interaction (PPI) and validated with the Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA) databases, and immunohistochemistry. Survival analyses were also performed using a Kaplan-Meier (KM) plotter. The effects of hsa_circ_0043256 on cell proliferation and cell cycles were evaluated by EdU staining and flow cytometry, respectively. RESULTS: hsa_circ_0043256, hsa_circ_0029426 and hsa_circ_0049271 were obtained. Following RT-qPCR validation, hsa_circ_0043256 was selected for further analysis. In addition, functional experiment results indicated that hsa_circ_0043256 could inhibit cell proliferation and cell-cycle progression of NSCLC cells in vitro. Prediction by three online databases and combining with DEGs identified from The Cancer Genome Atlas (TCGA), a network containing one circRNAs, three miRNAs, and 209 mRNAs was developed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated DEGs might be associated with lung cancer onset and progression. A PPI network based on the 209 genes was established, and five hub genes (BIRC5, SHCBP1, CCNA2, SKA3, and GINS1) were determined. Following verification of five hub genes using GEPIA database, HPA database, and immunohistochemistry. High expression of all five hub genes led to poor overall survival. CONCLUSION: Our study constructed a circRNA-miRNA-mRNA network of hsa_circ_0043256. hsa_circ_0043256 may be a potential therapeutic target for lung cancer.

ARID1A, ARID1B, and ARID2 Mutations Serve as Potential Biomarkers for Immune Checkpoint Blockade in Patients With Non-Small Cell Lung Cancer.

Worldwide, non-small cell lung cancer (NSCLC) has the highest morbidity and mortality of all malignancies. The lack of responsiveness to checkpoint inhibitors is a central problem in the modern era of cancer immunotherapy, with the rapid development of immune checkpoint inhibitors (ICIs) in recent years. The human switch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex has been reported to be recurrently mutated in patients with cancer, and those with SWI/SNF mutations have been reported to be sensitive to ICIs. Six reported cohorts, a total of 3416 patients, were used to analyze the mutation status of ARID1A, ARID1B, ARID2 and SMARCA4 in patients with NSCLC and the effect of mutations on prognosis after ICIs. Finally, a nomogram was established to guide the clinical use of ICIs. The results show that patients with NSCLC who have ARID1A, ARID1B, and ARID2 mutations of the SWI/SNF complex were more likely to benefit from ICI therapy.

HOTAIR promotes gefitinib resistance through modification of EZH2 and silencing p16 and p21 in non-small cell lung cancer.

The long non-coding RNA Hox transcript antisense intergenic RNA (HOTAIR) plays a critical role in tumorigenesis as well as drug resistance in various cancers. However, the molecular mechanism by which HOTAIR induces gefitinib resistance in non-small cell lung cancer is to date unclear. In the present study, we revealed that HOTAIR is upregulated in gefitinib-resistant lung cancer cells and over-expression of HOTAIR enhances gefitinib resistance in lung cancer cells. In addition, the overexpression of HOTAIR promotes cell cycle progression through epigenetic regulation of EZH2/H3K27. Silencing of EZH2 by either siRNA or inhibitors sensitized the lung cancer cells to gefitinib. Inhibition of EZH2 induces expression of p16 and p21, whereas levels of CDK4, cyclinD1, E2F1, and LSD1 are significantly decreased in PC-9 cells overexpressing HOTAIR. ChIP-PCR experiments indicate that HOTAIR increases H3K27me3 recruitment to the promoter of p16 and p21 in PC-9 lung cancer cells overexpressing HOTAIR. In xenograft mouse models, overexpressing HOTAIR in lung cancer tissues decreased p16 and p21 proteins. Taken together, these data suggest that HOTAIR contributes to gefitinib resistance by regulating EZH2 and p16 and p21. Targeting HOTAIR may be a novel therapeutic strategy for treating gefitinib-resistance in non-small cell lung cancer.

EML4-ALK-mediated activation of the JAK2-STAT pathway is critical for non-small cell lung cancer transformation.

BACKGROUND: The echinoderm microtubule-associated protein-like-4 anaplastic lymphoma kinase (EML4-ALK) fusion gene was identified in a subset of non-small cell lung cancer (NSCLC) patients. They responded positively to ALK inhibitors. This study aimed to characterize the mechanisms triggered by EML4-ALK to induce NSCLC transformation. METHODS: HEK293 and NIH3T3 cells were transfected with EML4-ALK variant 3 or pcDNA3.1-NC. H2228 cells were transfected with siRNA-EML4-ALK or siRNA-NC. Cell viability and proliferation were measured by the CCK-8 and EdU methods, respectively. Flow cytometry revealed apoptosis. Gene expression profiles were generated from a signaling pathway screen in EML4-ALK-regulated lung cancer cells and verified by qPCR and Western blotting. The co-immunoprecipitation and immunohistochemistry/ immunofluorescence determined the interaction and colocalization of JAK2-STAT pathway components with EML4-ALK. RESULTS: Microarray identified several genes involved in the JAK2-STAT pathway. JAK2 and STAT6 were constitutively phosphorylated in H2228 cells. EML4-ALK silencing downregulated phosphorylation of STAT6. Expression of EML4-ALK in HEK293 and NIH3T3 cells activated JAK2, STAT1, STAT3, STAT5, and STAT6. In EML4-ALK-transfected HEK293 cells and EML4-ALK-positive H2228 cells, activated STAT6 and JAK2 colocalized with ALK. STAT3 and STAT6 were phosphorylated and translocated to the nucleus of H2228 cells following IL4 or IL6 treatment. Apoptosis increased, while cell proliferation and DNA replication decreased in H2228 cells following EML4-ALK knockdown. In contrast, HEK293 cell viability increased following EML4-ALK overexpression, while H2228 cell viability significantly decreased after treatment with ALK or JAK-STAT pathway inhibitors. CONCLUSIONS: Our data suggest that the aberrant expression of EML4-ALK leads to JAK2-STAT signaling pathway activation, which is essential for the development of non-small cell lung cancer.

[Immune Microenvironment Comparation Study between EGFR Mutant and EGFR Wild Type Lung Adenocarcinoma Patients Based on TCGA Database].

BACKGROUND: Lung cancer is a malignant with high incidence and mortality and adenocarcinoma is among the most popular subtypes. Epidermal growth factor receptor (EGFR) mutation is one of the most important driver mutations for lung adenocarcinoma and EGFR-tyrosine kinase inhibitor (TKI) will benefit those patients with sensitive EGFR mutations. Recently, immune checkpoint inhibitor (ICI) therapy, provide a new breakthrough treatment for lung cancer patients. Whereas immunotherapy as an emerging treatment does not benefit patients with EGFR mutations, for which mechanistic studies are poorly defined and focused on the link of EGFR mutations and programmed cell death-ligand 1 (PD-L1) expression, we speculate that the different immune microenvironment associated with the two classes of patients. METHODS: Lung adenocarcinoma datasets were collected from the Cancer Genome Atlas (TCGA) database, and clinical information and gene expression profiles were downloaded. The immune related lymphocyte infiltration in TCGA database were generated through timer 2.0 GSEA was used to analyze the difference of pathway expression between EGFR mutant patients and wild type patients. RESULTS: EGFR mutation was more frequently among women and never smokers. Immunoinfiltration analysis showed that patients with EGFR mutation tends to have more tumor associated fibroblasts, common myeloid progenitor cells, hematopoietic stem cells, effector CD4⁺ T cells and natural killer T cells infiltration, and less memory B cells, naïve B cells, plasma B cells, plasmacytoid dendritic cells, memory CD4⁺ T cells, CD4⁺ helper T cells 2, naive CD8⁺ T cells, CD8⁺ T cells and central memory CD8⁺ T cells infiltration. Moreover, patients with more infiltration of CD8⁺ T cells, natural killer T cells, memory B cells and hematopoietic stem cells, tends have better prognosis (Log-rank test, P=0.017, 0.0093, 0.018, 0.016). However, the patients with more CD4⁺ T th2 infiltration in the tumor tends to have worse prognosis (Log-rank test, P=0.016). Furthermore, the results of gene set enrichment analysis showed that compared with the lung adenocarcinoma patients with EGFR wild type, the three pathways positive regulation of natural killer (NK) cell-mediated immune response to tumor cells, NK cell activation involved in immune response, and NK cell-mediated immune response to tumor cells related to natural killer cells in patients with EGFR mutation were down regulated, while the pathway the positive regulation of cytokine secretion involved in immune response was up-regulated in EGFR mutation patients. CONCLUSIONS: The tumour microenvironment of patients with EGFR mutations lacks potent tumour killing effector cells and appears dysfunctional with effector cells. This may be a potential reason for the poor efficacy of immunotherapy in patients with EGFR mutations.

Identification of small proline-rich protein 1B (SPRR1B) as a prognostically predictive biomarker for lung adenocarcinoma by integrative bioinformatic analysis.

BACKGROUND: With the ongoing development of targeted therapy and immunotherapy in recent years, the overall five-year survival rate of NSCLC patients has not improved, and the search for novel diagnostic and prognostic markers for lung adenocarcinoma continues. METHODS: Lung adenocarcinoma (LUAD) gene expression data and relevant clinical information were obtained from the TCGA. Hub genes were identified with weighted gene co-expression network analysis (WGCNA) and protein-protein interaction network (PPI). Survival analyses were also performed using GEPIA. The 536 LUAD patients were divided into two groups according to the SPRR1B expression level and analyzed by gene set enrichment analysis (GSEA) and verified by immunoblotting. The effects of SPRR1B on cell proliferation and cell metastasis and apoptosis were evaluated by 5-ethynyl-2'-deoxyuridine (EdU) staining, colony formation assay, transwell migration and invasion assay, and flow cytometry, respectively. RESULTS: A total of 2269 DEGs were analyzed by WGCNA and five hub genes (CCK, FETUB, PCSK9, SPRR1B, and SPRR2D) were identified. Among them, SPRR1B was selected as one of the most significant prognostic genes in LUAD. SPRR1B was found to be highly expressed in lung adenocarcinoma cells compared with that in normal bronchial epithelial cells. In addition, silencing of SPRR1B could inhibit the cell proliferation, invasion, and migration of lung adenocarcinoma cells, but induced cell apoptosis and G2/M phase arrest in vitro. The result of GSEA and immunoblotting revealed that SPRR1B activated the MAPK signaling pathway involved in the proliferation and metastasis of lung cancer. CONCLUSIONS: Our findings demonstrate that SPRR1B may function as a prognosis predictor in lung adenocarcinoma.

EZH2 inhibitors reverse resistance to gefitinib in primary EGFR wild-type lung cancer cells.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. In traditional anti-cancer therapy, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) have been proven to be beneficial for patients with EGFR mutations. However, patients with EGFR wild-type NSCLC were usually not respond to EGFR-TKIs. Enhancer of zeste homolog 2 (EZH2) is a key molecular in the PRC2 complex and plays an important role in epigenetic regulation and is overexpressed in variant tumors. EZH2 inhibitors have been reported to sensitize variant tumor cells to anticancer drugs. This study aimed to investigate whether the EZH2 inhibitors, GSK343 and DZNep when combined with gefitinib can reverse EGFR-TKIs resistance in EGFR wild-type NSCLC cells. METHODS: The RNA-sequencing data of patients with NSCLC [502 patients with lung squamous cell carcinoma, including 49 paracancerous lung tissues and 513 patients with lung adenocarcinoma (LUAD), including 59 paracancerous lung tissues] from the Cancer Genome Atlas (TCGA), were analyzed for EZH2 expression. EZH2 expression was verified in 40 NSCLC tissue cancer samples and their corresponding paracancerous tissues from our institute (TJMUGH) via RT-PCR. A549 and H1299 cells treated with siRNA or EZH2 inhibitors were subjected to cell viability and apoptosis analyses as well to EGFR pathway proteins expression analyses via western blotting. RESULTS: EZH2 was upregulated in human NSCLC tissues and correlated with poor prognosis in patients with LUAD based on data from both TCGA and TJMUGH. Both GSK343 and DZNep sensitized EGFR wild-type LUAD cells (A549 and H1299) to gefitinib and suppressed cell viability and proliferation in vitro by downregulating the phosphorylation of EGFR and AKT and by inducing cell apoptosis. Co-administration of EZH2 inhibitors (GSK343 or DZNep) with gefitinib exerted a stronger inhibitory effect on tumor activity, cell proliferation and cell migration than single drug administration in vitro and in vivo. CONCLUSIONS: These data suggest that the combination of EZH2 inhibitors with EGFR-TKIs may be an effective method for treating NSCLC-patients with EGFR-wild type, who do not want to undergo traditional treatment with chemotherapy.

[Apatinib Combined with CCI-779 Inhibits the Proliferation and Migration of Small Cell Lung Cancer NCI-H446 Cells In Vitro].

BACKGROUND: Lung cancer is the most common malignancy world-wide. Small cell lung cancer is the deadliest subtype of lung cancer, which features such as rapid growth, early metastasis, and high vascularization. Apatinib is a vascular endothelial growth factor receptor 2 inhibitor independently developed in China, which has a significant inhibition in a variety of solid tumors. The purpose of this study is to investigate the effects of Apatinib alone or Apatinib combined with mammalian target of rapamycin (mTOR) inhibitor, CCI-779, on small cell lung cancer cell line NCI-H446 in vitro. METHODS: The small cell lung cancer cell line NCI-H446 was grew in vitro. The effects of Apatinib alone or Apatinib combined with CCI-779 on proliferation, apoptosis, cell cycle and migration of NCI-H446 small cell lung cancer cells were detected by CCK8; FACS and transwell assays were also carried out; Western blot assays were used to detect vascular endothelial growth factor and cell cycle related protein expression. RESULTS: CCK8 assays showed that high concentration of Apatinib could inhibit the proliferation of NCI-H446 cells. Apoptosis assays showed that high concentration of Apatinib could induce NCI-H446 cell apoptosis. Transwell assays showed that high concentration of Apatinib could inhibit NCI-H446 cell migration. After combined with mTOR inhibitor CCI-779, low concentration of Apatinib could inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells and induce apoptosis. CONCLUSIONS: Apatinib has a concentration-dependent effect on the small cell lung cancer cell line NCI-H446. High concentration of Apatinib can inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells, induce apoptosis. Apatinib combined with the mTOR inhibitor CCI-779 can sensitize the NCI-H446 cells to Apatinib.

Resection of anterior mediastinal ectopic pancreas by right thoracoscopy: A case report.

Ectopic pancreas is uncommon in the anterior mediastinum. Herein, a 32-year-old woman presented to our institution for investigation of an abnormal mediastinal shadow on chest computed tomography. The patient underwent complete surgical resection of the anterior mediastinal mass by right thoracoscopy, and the postoperative pathology examination confirmed the diagnosis of ectopic pancreas. There were no clinical signs of pancreatitis. No recurrence or metastasis was observed during a follow-up period of 3 years. English language medical literature was also searched in order to identify other case reports describing this rare condition and identified 17 papers describing 20 cases of anterior mediastinal ectopic pancreas, which were all confirmed at surgery. All clinical characteristics in these cases were reviewed.

Dietary fresh fish and processed fish intake and the risk of glioma: A meta-analysis of observational studies.

The current study was to evaluate the predicted role of dietary fresh fish and processed fish intake for risk of glioma. Databases of Web of Science, PubMed, and Wan Fang Med Online were retrieved up to Jan 31th, 2018. Eligible studies were identified based on defined inclusion criteria. Summarized results of relative risk (RR) with corresponding 95% confidence intervals (CI) were calculated using a random effects model. Sensitivity analysis and publication bias were also performed. The final analysis in this report included a total of 9 articles. The summarized RR and 95%CI from 8 studies for dietary fresh fish intake and glioma risk was 0.823 (95%CI= 0.698-0.970), with no evidence of significant between-study heterogeneity (I2=43.6%, P=0.088). Moreover, positive associations were also found both in Caucasian populations and Asia populations. Seven studies were used to assess the relationship between dietary processed fish intake and the risk of glioma. Significantly increased risk of glioma was found for the highest category of dietary processed fish intake [summarized RR= 1.554, 95%CI= 1.169-2.066, I2= 72.1%, P= 0.001], especially among Caucasian populations. No publication bias was found. In summary, findings from this meta-analysis concluded that dietary fresh fish intake could reduce the risk of glioma. However, very high processed fish intake had a significant association with increased glioma risk.

miR-182 suppresses invadopodia formation and metastasis in non-small cell lung cancer by targeting cortactin gene.

BACKGROUND: Metastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Invadopodia, which are cancer-specific protrusive structures, play a crucial role in the metastatic cascade through degradation of the basement membrane and surrounding stroma. Cortactin, a critical component of invadopodia, frequently used as an invadopodia marker, a universally important player in invadopodia function, and is frequently overexpressed in cancer, but the exact mechanism of regulation is not yet fully understood. METHODS: The expression level of CTTN in human non-small cell lung cancer (NSCLC) tissues was detected by qRT-PCR. Cell migration, invasion and invadopodia formation were assessed in vitro by wound-healing, transwell assay and immunofluorescence, respectively. The dual-luciferase reporter assay was used to identify the direct target of miR-182. RESULTS: Hepatocyte growth factor (HGF) and phorbol 12,13-dibutyrate (PDBu) can induce CTTN expression, motility, and invasion ability, as well as invadopodia formation in non-small cell lung cancer (NSCLC). Moreover, miR-182 suppressed metastasis and invadopodia formation by targeting CTTN in NSCLC. Our qRT-PCR results showed that CTTN expression was inversely correlated with miR-182 expression that suppressed invadopodia formation via suppression of the Cdc42/N-WASP pathway. Furthermore, miR-182 negatively regulated invadopodia function, and suppressed extracellular matrix(ECM) degradation in lung cancer cells by inhibiting cortactin. CONCLUSION: Collectively, our results demonstrated that miR-182 targeted CTTN gene in NSCLC and suppressed lung cancer invadopodia formation, and thus suppressed lung cancer metastasis. This suggests a therapeutic application of miR-182 in NSCLC.

Molecular features of giant-cell carcinoma of the lung: a case report and literature review.

Giant-cell carcinoma of the lung (GCCL) is a rare histological form of poorly differentiated non-small-cell lung cancer, which is classified as a subtype of pulmonary sarcomatoid carcinomas. In this case report, we describe the case of a 50-year-old Chinese male who presented with a pulmonary nodule in the right upper lobe of his lung. After thoracoscopic lobectomy, a histopathologic diagnosis of GCCL was made. He did well postoperatively, showing no local recurrence or distal disease in a 7-year follow-up period. Furthermore, for this case, we also analyzed 295 tumor-related driver genes with high-throughput sequencing technology. We found that treatment using MEK inhibitor, CDK 4/6 inhibitor, and TP53 inhibitor may provide a new therapeutic direction for GCCL. Therefore, complete tumor excision is the best choice of treatment strategy at the early stage of GCCL and gene target therapy may be a new therapeutic option for this disease.

Nationwide cross-sectional adherence to mammography screening guidelines: national behavioral risk factor surveillance system survey results.

PURPOSE: Varying recommendations about breast cancer screening have generated much confusion about when and how often to undergo mammography screening, yet there is limited population-based data about the extent to which patients adhere to various mammographic screening guidelines in practice. Our purpose was to evaluate population-based adherence to mammographic screening using criteria from major guideline-producing organizations. METHODS: Women aged 40-74 in the 2014 Behavioral Risk Factor Surveillance System survey were included. Self-reported mammographic screening within 1 or 2 years, according to major guideline-producing organizations (American Cancer Society [ACS], US Preventative Services Task Force [USPSTF], American College of Radiology [ACR], American College of Obstetricians and Gynecologists [ACOG]) was calculated with logistic regression, adjusting for demographics and indices of access to health care. RESULTS: 159,123 women were included. By age category, cross-sectional adherence to USPSTF guidelines ranged from 76 to 81%, ACS (55-81%) and ACR/ACOG (45-64%) with increasing age being associated improved adherence. The highest proportions of women undergoing mammographic screening were seen in women ages 65-69 (66% within last year, 81% within last 2 years). Statistically significant predictors of adherence to mammography screening included increased income category (OR 1.08, 1.07-1.09), higher education category (OR 1.13, 1.11-1.16), and increased access to health care (OR 2.25, 1.94-2.60), adjusted for age categories. CONCLUSIONS: Adherence to mammography screening was closest to USPSTF guidelines with 76-81% cross-sectional adherence. Frequency of screening increases with age with highest screening proportions in women ages 65-69 (66% within last year, 81% within last 2 years). For all screening guidelines, adherence to mammography screening remains poor in women with limited access to health insurance with less than half of women obtaining recommended screening.