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Supplementary Table S1. Comparison of fold change of gene expression in ADAM9 knockdown and brain-metastatic cell sublines (Bm2 and Bm7) with parental cells.

The transmembrane cell adhesion protein ADAM9 has been implicated in cancer cell migration and lung cancer metastasis to the brain, but the underpinning mechanisms are unclear and clinical support has been lacking. Here, we demonstrate that ADAM9 enhances the ability of tissue plasminogen activator (tPA) to cleave and stimulate the function of the promigratory protein CDCP1 to promote lung metastasis. Blocking this mechanism of cancer cell migration prolonged survival in tumor-bearing mice and cooperated with dexamethasone and dasatinib (a dual Src/Abl kinase inhibitor) treatment to enhance cytotoxic treatment. In clinical specimens, high levels of ADAM9 and CDCP1 correlated with poor prognosis and high risk of mortality in patients with lung cancer. Moreover, ADAM9 levels in brain metastases derived from lung tumors were relatively higher than the levels observed in primary lung tumors. Our results show how ADAM9 regulates lung cancer metastasis to the brain by facilitating the tPA-mediated cleavage of CDCP1, with potential implications to target this network as a strategy to prevent or treat brain metastatic disease. Cancer Res; 74(18); 5229–43. ©2014 AACR.

Purpose: Lymphedema is common among breast cancer survivors (BCS) and negatively affects quality of life. There are modifiable factors to reduce lymphedema risk and exacerbation; it is unknown how aware survivors are of these factors. We hypothesized referral to lymphedema therapy (LT) to be associated with greater lymphedema knowledge.Methods: BCS at an NCI-designated cancer center between 2014-2015 were asked to complete an anonymous questionnaire. Eligibility criteria were the following: age ≥18, female sex, English-speaking, > 6 months post definitive breast cancer surgery, no cancer recurrence, and no prior or subsequent second cancer. The questionnaire included sociodemographics, clinical factors including LT referral, and 10 true/false questions assessing lymphedema knowledge. Multivariable logistic regressions assessed the relationship between prior LT referral and correctly answering questions about lymphedema misconceptions.Results: Of 209 participants, 53 (25%) had been referred to LT. Those who had sentinel lymph node dissection were less frequently referred to LT [15 (14%)] than those who had axillary lymph node dissection [38 (39%)]. Five of the true/false questions had a correct response rate of

Hypoxia and angiogenesis play key roles in the pathogenesis of esophageal squamous cell carcinoma (ESCC), but regulators linking these two pathways to drive tumor progression remain elusive. Here we provide evidence of ADAM9's novel function in ESCC progression. Increasing expression of ADAM9 was correlated with poor clinical outcomes in ESCC patients. Suppression of ADAM9 function diminished ESCC cell migration and in vivo metastasis in ESCC xenograft mouse models. Using cellular fractionation and imaging, we found a fraction of ADAM9 was present in the nucleus and was uniquely associated with gene loci known to be linked to the angiogenesis pathway demonstrated by genome-wide ChIP-seq. Mechanistically, nuclear ADAM9, triggered by hypoxia-induced translocation, functions as a transcriptional repressor by binding to promoters of genes involved in the negative regulation of angiogenesis, and thereby promotes tumor angiogenesis in plasminogen/plasmin pathway. Moreover, ADAM9 suppresses plasminogen activator inhibitor-1 gene transcription by interacting with its transcription factors at the promoter. Our findings uncover a novel regulatory mechanism of ADAM9 as a transcriptional regulator in angiogenesis and highlight ADAM9 as a promising therapeutic target for ESCC treatment.

Rationale: Brain metastasis in patients with lung cancer is life-threatening. However, the molecular mechanism for this catastrophic disease remains elusive, and few druggable targets are available. Therefore, this study aimed to identify and characterize proteins that could be used as therapeutic targets. Methods: Proteomic analyses were conducted to identify differentially expressed membrane proteins between brain metastatic lung cancer cells and primary lung cancer cells. A neuronal growth-associated protein, brain acid soluble protein 1 (BASP1), was chosen for further investigation. The clinical relevance of BASP1 in lung adenocarcinoma was first assessed. Tyrosine kinase activity assays and in vitro and in vivo functional assays were conducted to explore the oncogenic mechanisms of BASP1. Results: The protein levels of BASP1 were positively associated with tumor progression and poor prognosis in patients with lung adenocarcinoma. Membrane-bound BASP1 increased EGFR signaling and stabilized EGFR proteins by facilitating their escape from the ubiquitin-proteasome pathway. Reciprocally, activation of EGFR recruited more BASP1 to the plasma membrane, generating a positive feedback loop between BASP1 and EGFR. Moreover, the synergistic therapeutic effects of EGFR tyrosine kinase inhibitor and arsenic trioxide led to a reduction in the level of BASP1 protein observed in lung cancer cells with acquired resistance to EGFR inhibitors. Conclusions: The reciprocal interaction between BASP1 and EGFR facilitates EGFR signaling in brain metastatic lung cancer. Targeting the newly identified BASP1-EGFR interaction could open new venues for lung cancer treatment.

This study aimed to explore the relationship between self-esteem and mental adjustment and examine the directional effects in patients with breast cancer using path modeling. This was a cross-sectional, descriptive, and correlational study. A total of 128 patients with breast cancer were selected through convenience sampling at a medical center in northern Taiwan. They completed a basic characteristics questionnaire, the Memorial Symptom Assessment Scale short form, the Rosenberg Self-Esteem Scale, and the mini-Mental Adjustment to Cancer Scale. Descriptive statistics, regression analysis, and path analysis were used to analyze the data. The results showed that higher self-esteem was associated with better mental adjustment (β = 0.9, 95% confidence interval 0.6~1.3, p < 0.001). Age, religious beliefs, employment, cancer stage, and symptom distress were correlated with mental adjustment. Path modeling demonstrated that self-esteem, cancer stage, performance status, and symptom distress directly affected mental adjustment in patients with breast cancer. These findings suggest that health professionals should evaluate self-esteem, performance status, and symptom distress in patients with breast cancer immediately upon admission. This can facilitate early implementation of relevant nursing interventions and, consequently, improve self-esteem and symptom distress and increase mental adjustment in these patients.

Rationale: Lung adenocarcinoma (LUAD) is an aggressive disease with high propensity of metastasis. Among patients with early-stage disease, more than 30% of them may relapse or develop metastasis. There is an unmet medical need to stratify patients with early-stage LUAD according to their risk of relapse/metastasis to guide preventive or therapeutic approaches. In this study, we identified 4 genes that can serve both therapeutic and diagnostic (theranostic) purposes. Methods: Three independent datasets (GEO, TCGA, and KMPlotter) were used to evaluate gene expression profile of patients with LUAD by unbiased screening approach. Upon significant genes uncovered, functional enrichment analysis was carried out. The predictive power of their expression on patient prognosis were evaluated. Once confirmed their theranostic roles by integrated bioinformatics, we further conducted in vitro and in vivo validation. Results: We found that four genes (ADAM9, MTHFD2, RRM2, and SLC2A1) were associated with poor patient outcomes with an increased hazard ratio in LUAD. Knockdown of them, both separately and simultaneously, suppressed lung cancer cell proliferation and migration ability in vitro and prolonged survival time in metastatic tumor mouse models. Moreover, these four biomarkers were found to be overexpressed in tumor tissues from LUAD patients, and the total immunohistochemical staining scores correlated with poor prognosis. Conclusions: These results suggest that these four identified genes could be theranostic biomarkers for stratifying high-risk patients who develop relapse/metastasis in early-stage LUAD. Developing therapeutic approaches for the four biomarkers may benefit early-stage LUAD patients after surgery.

// Kuo-Liang Chiu 1, 4, 5, * , Yu-Sen Lin 1, 8, * , Ting-Ting Kuo 7 , Chia-Chien Lo 7 , Yu-Kai Huang 7 , Hsien-Fang Chang 6 , Eric Y. Chuang 6 , Ching-Chan Lin 1, 9 , Wei-Chung Cheng 2, 3 , Yen-Nien Liu 10 , Liang-Chuan Lai 6, 11 and Yuh-Pyng Sher 1, 2, 7 1 Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan 2 Graduate Institute of BioMedical Sciences, China Medical University, Taichung 404, Taiwan 3 Research Center for Tumor Medical Science, China Medical University, Taichung 404, Taiwan 4 Division of Chest Medicine, Department of Internal Medicine, Taichung Tzu-Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan 5 School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 970, Taiwan 6 Bioinformatics and Biostatistics Core, Center of Genomic Medicine, National Taiwan University, Taipei 100, Taiwan 7 Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan 8 Division of Thoracic Surgery, China Medical University Hospital, Taichung 404, Taiwan 9 Division of Hematology and Oncology, China Medical University Hospital, Taichung 404, Taiwan 10 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan 11 Graduate Institute of Physiology, National Taiwan University, Taipei 106, Taiwan * These authors contributed equally to this work Correspondence to: Yuh-Pyng Sher, email: ypsher@mail.cmu.edu.tw Liang-Chuan Lai, email: llai@ntu.edu.tw Keywords: lung cancer, ADAM9, EGFR, miR-1, CDCP1 Received: November 30, 2016 Accepted: April 19, 2017 Published: May 07, 2017 ABSTRACT MicroRNAs (miRNAs), which are endogenous short noncoding RNAs, can regulate genes involved in important biological and pathological functions. Therefore, dysregulation of miRNAs plays a critical role in cancer progression. However, whether the aberrant expression of miRNAs is regulated by oncogenes remains unclear. We previously demonstrated that a disintegrin and metalloprotease domain 9 (ADAM9) promotes lung metastasis by enhancing the expression of a pro-migratory protein, CUB domain containing protein 1 (CDCP1). In this study, we found that this process occurred via miR-1 down-regulation. miR-1 expression was down-regulated in lung tumors, but increased in ADAM9 -knockdown lung cancer cells, and was negatively correlated with CDCP1 expression as well as the migration ability of lung cancer cells. Luciferase-based reporter assays showed that miR-1 directly bound to the 3′-untranslated region of CDCP1 and inhibited its translation. Treatment with a miR-1 inhibitor restored CDCP1 protein levels and enhanced tumor cell mobility. Overexpression of miR-1 decreased tumor metastases and increased the survival rate in mice. ADAM9 knockdown reduced EGFR signaling and increased miR-1 expression. These results revealed that ADAM9 down-regulates miR-1 via activating EGFR signaling pathways, which in turn enhances CDCP1 expression to promote lung cancer progression.

Metastasis is a crucial hallmark of cancer progression and remains the primary cause of patient deaths. Metastasis-associated proteases contribute to cancer progression by disrupting the extracellular matrix interaction to facilitate the spreading of cancer cells to other organs. ADAM9, a type of metalloprotease, has been reported to promote tumor biology and is associated with clinicopathological features such as poor outcome, therapy resistance, and metastasis formation. Targeting ADAM9 might serve as a putative therapeutic application; however, this option is currently unavailable. Resveratrol, a polyphenol from plants, has been shown to be promising for cancer treatment due to its wide variety of biological effects with few side effects. In this study, we demonstrated that resveratrol inhibits cancer cell migration and viability in lung and esophageal cancer cells through the regulation of ADAM9. Mechanistically, resveratrol inhibits ADAM9 protein expression in cancer cells through the ubiquitin-proteasome pathway. Moreover, resveratrol provides synergistic anticancer effects when combined with clinical chemotherapeutics. Our data suggests that resveratrol may inhibit human lung cancer and ESCC progression by inhibiting ADAM9 expression, thus providing a potential mechanism for the anticancer action of resveratrol.

ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developmental process, inflammation, and degenerative diseases. Recently, increasing evidence has shown that ADAM9 plays an important role in tumor biology. Overexpression of ADAM9 has been found in several cancer types and is correlated with tumor aggressiveness and poor prognosis. In addition, through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies. In this review, we summarize the current understanding of ADAM9 in biological function, pathophysiological diseases, and various cancers. Recent advances in therapeutic strategies using ADAM9-related pathways are presented as well.

This pilot, double-blind, randomized, placebo-controlled study is aimed at evaluating the effectiveness of low-level laser therapy (LLLT) as a complementary treatment to complete decongestive therapy (CDT) treating lymphedema among breast cancer patients for 12 months post-intervention. Study population was breast cancer patients who were diagnosed and referred to lymphedema clinic for CDT. Participants (n = 22) were randomized and assigned into either an active laser intervention group or an inactive laser placebo-control group. Active LLLT was administered to participants twice a week at the beginning of each CDT session. Outcome measures included lymphedema symptoms, symptom distress, and limb volume by an infrared perometer. Participants in the active and placebo laser groups were comparable in demographic and clinical predictors of lymphedema. In comparison with the placebo group (83.3%), significantly fewer participants in the active laser group (55.6%) reported more than one lymphedema symptom (p = 0.012) at 12 months post-intervention. Significantly, more patients in the active laser group (44.4%) reported less than two impaired limb mobility symptoms in comparison with the placebo group (33.3%) at 12 months post-intervention (p = 0.017). The active laser group had statistically significant improvements in symptom distress of sadness (p = 0.005) from 73 to 11% and self-perception (p = 0.030) from 36 to 0% over time from baseline to 12-months post-intervention. There was no significant reduction in limb volume. Findings of the trial demonstrated significant benefits of complementary LLLT for relieving symptoms and improvement of emotional distress in breast cancer patients with lymphedema.

Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo. Furthermore, simultaneous high expression of ADAM9 and VEGFA or of ADAM9 and ANGPT2 was correlated with poor prognosis in a clinical dataset. These findings suggest that ADAM9 promotes tumorigenesis through vascular remodeling, particularly by increasing the function of VEGFA, ANGPT2, and PLAT.

Background Suppression of cancer metastasis is an urgent therapeutic need because metastasis is a major cause of high mortality in different types of cancers including lung cancer. Overexpression of a disintegrin and metalloprotease 9 (ADAM9), a member of the ADAM family of type I transmembrane proteins, is observed in many cancers and correlates with lung cancer brain metastasis. Since it contributes to tumorigenesis due to its ability in cleaving and releasing a number of molecules that involves cancer progression, it would be a potential target for lung cancer treatment. Methods We have performed the genome-wide approach to explore ADAM9-regulated genes. Moreover, we have developed small compounds as ADAM9 inhibitors to target ADAM9’s catalytic domain using virtual screening and evaluated them by inhibiting ADAM9-mediated downstream pathways. Results Overexpression of ADAM9 in lung cancer cells promotes tumor metastasis. Several ADAM9-mediated pathways are investigated from RNA-seq analysis. In the other hand, we have validated the potency of developed small compounds in reducing ADAM9 protease activity, cancer cell growth, and cell migration. In tumor animal models, ADAM9 inhibitors exhibited high efficacy to reduce cancer progression in animals bearing lung tumors. Notably, no liver and kidney toxicity were detected, suggesting no severe toxicity after drug treatment. Conclusions We demonstrate inhibition of ADAM9 activity by potential ADAM9 inhibitor provide anti-lung tumor benefits in vitro and in vivo. Notably, ADAM9 inhibitor treatment has no systemically acute toxicity in mice. Thus, targeting ADAM9 provides a potential strategy for lung cancer treatment. Legal entity responsible for the study The authors. Funding The National Health Research Institutes, Taiwan. Disclosure All authors have declared no conflicts of interest.

Green algae are able to convert solar energy to H 2 via the photosynthetic electron transport pathway under certain conditions. Algal hydrogenase (HydA, encoded by HYDA ) is in charge of catalyzing the reaction: 2H + + 2e − ↔ H 2 but usually inhibited by O 2 , a byproduct of photosynthesis. The aim of this study was to knockdown PsbO (encoded by psbO ), a subunit concerned with O 2 evolution, so that it would lead to HydA induction. The alga, Chlorella sp. DT, was then transformed with short interference RNA antisense- psbO ( siRNA-psbO ) fragments. The algal mutants were selected by checking for the existence of siRNA-psbO fragments in their genomes and the low amount of PsbO proteins. The HYDA transcription and the HydA expression were observed in the PsbO-knockdown mutants. Under semi-aerobic condition, PsbO-knockdown mutants could photobiologically produce H 2 which increased by as much as 10-fold in comparison to the wild type.

Background: A majority of lung cancer patients are diagnosed at late stages due to early metastasis. We conducted studies to demonstrate MicroRNA(miR)-218 is associated with over expression of ADAM9, CDCP1, and hence could play a role of lung cancer metastasis. Materials and Methods: We used lung cancer cells with suppression and overexpression of miR-218, and measured ADAM9, and CDCP1 expression with the correlation of lung cancer cell migration and survival. Mutation of 39-UTR of CDCP1 mRNA was performed to test the binding point of miR-218. Transfection of cancer cells in mice was also used to demonstrate in vitro effects. Results: Several lung cancer cell lines showed decreased expression of miR-218, and overexpression in ADAM9 and CDCP1. Suppression of miR-218 was associated with overexpression of ADAM9 and CDCP1, hence, increased cancer cell migration. Overexpression of miR-218, in contrast, suppressed expression of ADAM9 and CDCP1, hence, decreasing not only migration, but also anoikis resistance of cancer cells. Suppression of CDCP1 by miR-218 was inhibited after mutation of 39-UTR of CDCP1 mRNA. Over expression of miR-218 reduced tumor growth in mice. Conclusions: Suppression of miR-218 in lung cancer cells is associated with increased cell migration due to overexpiression of ADAM9 and CDCP1. Restoration of miR-218 inhibits tumour cell mobility, anchorage-free survival and tumor sphere formation, moreover, reduces tumor growth in mice.

Green algae are able to convert solar energy into biological hydrogen (solar-to-H2) from H+ via chloroplast hydrogenase (HydA), which can accept electrons directly from ferredoxin and generates H2. HydA is nuclear-encoded by the hydA gene, and its transcription and activity can only be observed under anaerobic or sulfur-deprived conditions. In this study we attempted to homologously overexpress hydA to enhance H2 production in Chlorella sp. DT (DT) under aerobic and S-supplied (+S) conditions. The nucleotides of partial genomic DNA and cDNA of DT hydA were sequenced and cloned. The engineered coding region of the hydA gene (hydAc) was constructed into plasmids and driven by the promoters that can function under aerobic conditions. The DT cells were transformed with the constructed plasmids and the resultant transgenics were verified as containing homologous hydAc fragments in their genomic DNAs. Under aerobic and +S conditions, the RNA transcription of hyAc and the protein expression of HyA in the alga DT transgenics could be observed. The H2 production of the DT transgenics with homologously overexpressed HydA increased by as much as 7 to 10-fold in comparison to the DT wild type under the same conditions.

Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression. Suppression of miR-218 was associated with high migration ability in lung cancer cells. Direct interaction between miR-218 and the 3′-UTR of CDCP1 mRNAs was detected in luciferase-based transcription reporter assays. CDCP1 protein levels decreased as expression levels of miR-218 increased and increased in cells treated with miR-218 antagomirs. Induction of miR-218 inhibited tumor cell mobility, anchorage-free survival and tumor-initiating cell formation in vitro and delayed tumor metastases in mice. Our findings revealed an integrative tumor suppressor function of miR-218 in lung carcinogenesis and metastasis.

The transmembrane cell adhesion protein ADAM9 has been implicated in cancer cell migration and lung cancer metastasis to the brain, but the underpinning mechanisms are unclear and clinical support has been lacking. Here, we demonstrate that ADAM9 enhances the ability of tissue plasminogen activator (tPA) to cleave and stimulate the function of the promigratory protein CDCP1 to promote lung metastasis. Blocking this mechanism of cancer cell migration prolonged survival in tumor-bearing mice and cooperated with dexamethasone and dasatinib (a dual Src/Abl kinase inhibitor) treatment to enhance cytotoxic treatment. In clinical specimens, high levels of ADAM9 and CDCP1 correlated with poor prognosis and high risk of mortality in patients with lung cancer. Moreover, ADAM9 levels in brain metastases derived from lung tumors were relatively higher than the levels observed in primary lung tumors. Our results show how ADAM9 regulates lung cancer metastasis to the brain by facilitating the tPA-mediated cleavage of CDCP1, with potential implications to target this network as a strategy to prevent or treat brain metastatic disease. Cancer Res; 74(18); 5229–43. ©2014 AACR.

Objectives Rapamycin inhibits products of molecular pathways in esophageal squamous cell carcinoma and limits tumor cell growth by targeting 4E-BP1- and eIF4E-dependent gene translation. In this study, we investigate the influence of 4E-BP1-to-eIF4E ratio on rapamycin response in esophageal squamous cell carcinoma cells, and the underlying mechanism is discussed. Methods The response to rapamycin treatment was examined in 6 esophageal cancer cell lines. Adjustment of the 4E-BP1/eIF4E ratio was carried out by knockdown or overexpression of 4E-BP1 and eIF4E. The relationship between Egr-1 and 4E-BP1 expression in esophageal cancer cells was also studied. Results The 4E-BP1/eIF4E ratio was adjusted to evaluate the response to rapamycin treatment in TE1 and TE2 esophageal cancer cells. TE2 cells are sensitized to rapamycin treatment after overexpression of 4E-BP1 or knockdown of eIF4E; TE1 cells become resistant to rapamycin after knockdown of 4E-BP1 or overexpression of eIF4E. These data suggest that the 4E-BP1/eIF4E ratio is a determinant for the response of TE1 and TE2 cells to rapamycin treatment. Egr-1 expression was higher in TE2 cells compared with other esophageal cancer cell lines, and its knockdown increased 4E-BP1 expression in TE2 cells, which became sensitive to rapamycin treatment. Conclusions The 4E-BP1/eIF4E ratio is a determinant of the response of rapamycin treatment in esophageal cancer cells. Egr-1 can reduce 4E-BP1 gene expression and render esophageal squamous cell carcinoma cells resistant to rapamycin with a relatively low 4E-BP1/eIF4E ratio. Thus, the 4E-BP1/eIF4E ratio may represent a therapeutic index for the prediction of clinical outcome of rapamycin treatment in patients with esophageal squamous cell carcinoma.

Lung cancer is the leading cause of cancer death worldwide, and brain metastasis is a major cause of morbidity and mortality in lung cancer. CDH2 (N-cadherin, a mesenchymal marker of the epithelial-mesenchymal transition) and ADAM9 (a type I transmembrane protein) are related to lung cancer brain metastasis; however, it is unclear how they interact to mediate this metastasis. Because microRNAs regulate many biological functions and disease processes (e.g., cancer) by down-regulating their target genes, microRNA microarrays were used to identify ADAM9-regulated miRNAs that target CDH2 in aggressive lung cancer cells. Luciferase assays and western blot analysis showed that CDH2 is a target gene of miR-218. MiR-218 was generated from pri-mir-218-1, which is located in SLIT2, in non-invasive lung adenocarcinoma cells, whereas its expression was inhibited in aggressive lung adenocarcinoma. The down-regulation of ADAM9 up-regulated SLIT2 and miR-218, thus down-regulating CDH2 expression. This study revealed that ADAM9 activates CDH2 through the release of miR-218 inhibition on CDH2 in lung adenocarcinoma.

e23002Background: A majority of lung cancer patients are diagnosed at late stage due to early metastasis. We conducted studies to demonstrate MicroRNA(miR)-218 is associated with overexpression of ...

This article explores the application of Watson's Caring Theory to a child suffering from minor burns injury and his mother. After the nursing process, their physical and social-psychological needs were met. A trauma accident always affects the child and the caregiver, especially the mother. Burn injury brings physical injury, pain, and loss of control to the child and makes the mother feel very guilty and lose her confidence in her ability to take care of the child. After the caring behaviors had been practiced, relationships of mutual trust were developed between the child, his mother and the primary nurse. In the child, the medical treatments were accomplished, the pain was relieved, and he resumed his communication mode. Finally, abilities to deal with burn injury were also built between the child and his mother. This experience could serve as a reference in the emergency nursing of trauma children. The focus of emergency care is not only applying scientific knowledge in the physical area, but also using the caring behaviors to meet the individual's social-psychological needs.

The purpose of this study is to understand the correlation of symptom distresses and coping strategies of patients with lung cancer. Seventy-three patients with non-small cell lung cancer from the cancer center or ward in the two medical centers located in northern Taiwan participated. The instruments used in this study were the Symptom Distress Scale and Coping Strategies Scale. The results of the study showed that the degree of symptom distress during the therapeutic period was mild to moderate. When patients were confronted with symptom distress, they combined problem- and emotion-focused coping strategies. Participants with higher physical symptom distress had higher psychological distress and emotion-focused coping strategy frequency. It was also found that the distress of tension-anxiety and age explained 39.4% of variance in physical symptom distresses. The physical symptom distresses and the frequency of emotion-focused coping strategy frequency explained 48.8% of variance in the psychologic symptom distresses. Finally, it is recommend that a support group be established to enable sharing of experiences and emotional support among patients.

Lung cancer is the leading cause of cancer death worldwide, and brain metastasis is a major cause of morbidity and mortality in lung cancer. Currently, it is not clear which molecules or what mechanisms mediate lung cancer brain metastasis. To explore this question, we compared our established brain-metastatic lung cancer sublines with their parental cancer cells, and identified ADAM9 (a disintegrin and metalloprotease 9) was overexpressed in metastatic sublines. Knocking down ADAM9 expression in lung cancer cells also showed significant reduction of lung cancer brain metastasis in vitro and in vivo. Furthermore, using a genome-wide approach to screen ADAM9-related mRNAs and microRNAs involved in brain metastasis, we identified that CDH2, encoding N-cadherin, was up-regulated by ADAM9 in brain-metastatic lung cancer sublines, and the 3′UTR of CDH2 contains the predicted binding sites of several microRNAs that were down-regulated in ADAM9-overexpressed cancer cells. Luciferase assays and western blot analysis showed that CDH2 is a target gene of microRNAs. The up-regulation of microRNAs, in turn, reduced the expression of its target gene and further inhibited the migration ability of aggressive lung adenocarcinoma cells. This study revealed that ADAM9 activates CDH2 through the release of microRNA inhibition of CDH2 in lung adenocarcinoma and plays a role in lung cancer metastasis. Citation Format: Yuh-Pyng Sher, Li-Ju Wang, Mong-Hsun Tsai, Ting-Ting Kuo, Eric Y. Chuang, Liang-Chuan Lai. ADAM9 regulates microRNAs expression for lung cancer metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3533. doi:10.1158/1538-7445.AM2014-3533