In JoVE (1)

Other Publications (31)

Articles by Annalen Bleckmann in JoVE

Other articles by Annalen Bleckmann on PubMed

Identification of Metabotropic Glutamate Receptor Subtype 5 Potentiators Using Virtual High-Throughput Screening

ACS Chemical Neuroscience. Apr, 2010  |  Pubmed ID: 20414370

Selective potentiators of glutamate response at metabotropic glutamate receptor subtype 5 (mGluR5) have exciting potential for the development of novel treatment strategies for schizophrenia. A total of 1,382 compounds with positive allosteric modulation (PAM) of the mGluR5 glutamate response were identified through high-throughput screening (HTS) of a diverse library of 144,475 substances utilizing a functional assay measuring receptor-induced intracellular release of calcium. Primary hits were tested for concentration-dependent activity, and potency data (EC(50) values) were used for training artificial neural network (ANN) quantitative structure-activity relationship (QSAR) models that predict biological potency from the chemical structure. While all models were trained to predict EC(50), the quality of the models was assessed by using both continuous measures and binary classification. Numerical descriptors of chemical structure were used as input for the machine learning procedure and optimized in an iterative protocol. The ANN models achieved theoretical enrichment ratios of up to 38 for an independent data set not used in training the model. A database of approximately 450,000 commercially available drug-like compounds was targeted in a virtual screen. A set of 824 compounds was obtained for testing based on the highest predicted potency values. Biological testing found 28.2% (232/824) of these compounds with various activities at mGluR5 including 177 pure potentiators and 55 partial agonists. These results represent an enrichment factor of 23 for pure potentiation of the mGluR5 glutamate response and 30 for overall mGluR5 modulation activity when compared with those of the original mGluR5 experimental screening data (0.94% hit rate). The active compounds identified contained 72% close derivatives of previously identified PAMs as well as 28% nontrivial derivatives of known active compounds.

Thymidylate Synthase As a Prognostic Biomarker for Locally Advanced Rectal Cancer After Multimodal Treatment

Annals of Surgical Oncology. Sep, 2011  |  Pubmed ID: 21347782

For years, 5-fluorouracil (5-FU) has been the backbone of radiochemotherapy (RCT) of locally advanced rectal cancer. Its main target, thymidylate synthase (TS), is speculated to be an important biomarker for response prediction and long-term prognosis. In this study, we analyzed TS expression in the rectal cancer tissue of 208 patients to evaluate its predictive/prognostic potential.

YouTube, Dentistry, and Dental Education

Journal of Dental Education. Dec, 2011  |  Pubmed ID: 22184594

The objective of this study was to systematically assess the informational value, intention, source, and bias of videos related to dentistry available on the video-sharing Internet platform YouTube. YouTube (www.youtube.com) was searched for videos related to dentistry, using the system-generated sorts "by relevance" and "most viewed" and two categories (All and Education). Each of the first thirty results was rated by two assessors filling out a questionnaire for each (total: 120). The data were subjected to statistical analysis using Cohen's kappa, Pearson's correlation coefficient tau, Mann-Whitney U-tests, and a nonparametric three-way ANOVA, including an analysis of the interaction between the sorting and category effect, with an α-level of 5 percent. The scan produced 279,000 results in the category All and 5,050 in the category Education. The analysis revealed a wide variety of information about dentistry available on YouTube. The purpose of these videos includes entertainment, advertising, and education. The videos classified under Education have a higher degree of usefulness and informational value for laypersons, dental students, and dental professionals than those found in a broader search category. YouTube and similar social media websites offer new educational possibilities that are currently both underdeveloped and underestimated in terms of their potential value. Dentists and dental educators should also recognize the importance of these websites in shaping public opinion about their profession.

Effects of High-frequency Oscillatory Ventilation on Systemic and Cerebral Hemodynamics and Tissue Oxygenation: an Experimental Study in Pigs

Neurocritical Care. Oct, 2012  |  Pubmed ID: 21647845

In this study, we compare the effects of high frequency oscillatory ventilation (HFOV) with those of lung-protective volume-controlled ventilation (VCV) on cerebral perfusion, tissue oxygenation, and cardiac function with and without acute intracranial hypertension (AICH).

Accuracy of Prehospital Diagnoses by Emergency Physicians: Comparison with Discharge Diagnosis

European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine. Oct, 2012  |  Pubmed ID: 21971293

A correct prehospital diagnosis of emergency patients is crucial as it determines initial treatment, admitting specialty, and subsequent treatment. We evaluated the diagnostic accuracy of emergency physicians.

Coordination of Tongue Activity During Swallowing in Mouth-breathing Children

Dysphagia. Sep, 2012  |  Pubmed ID: 22207245

Habitual mouth breathing is often accompanied by habitual anterior tongue thrust, instead of a lip closure, in order to create the anterior seal necessary for the initiation of physiological deglutition. We tested the null hypothesis of no significant influence of oral maneuver and the use of oral screens on tongue coordination and position during deglutition in 29 subjects (age = 6-16; mean = 9.69 years; 13/16 female/male) with habitual open-mouth posture using intraoral polysensography. The target parameters for swallowing were swallowing-associated nasal airflow interruption (NAI) and coordination of tongue-palate contact during NAI. Conventional myofunctional maneuvers could be facilitated and made more efficient, in terms of increasing the numbers of favorable early tongue-palate contacts typical of somatic swallowing, if accompanied by the application of an oral screen. Habitual open-mouth breathing does not necessarily coincide with distinctively pronounced proportions of late tongue-palate contact.

Predicting Restoration of Kidney Function During CRRT-free Intervals

Journal of Cardiothoracic Surgery. Jan, 2012  |  Pubmed ID: 22257468

Renal failure is common in critically ill patients and frequently requires continuous renal replacement therapy (CRRT). CRRT is discontinued at regular intervals for routine changes of the disposable equipment or for replacing clogged filter membrane assemblies. The present study was conducted to determine if the necessity to continue CRRT could be predicted during the CRRT-free period.

Effects of Pulmonary Acid Aspiration on the Lungs and Extra-pulmonary Organs: a Randomized Study in Pigs

Critical Care (London, England). Dec, 2012  |  Pubmed ID: 22380702

There is mounting evidence that injury to one organ causes indirect damage to other organ systems with increased morbidity and mortality. The aim of this study was to determine the effects of acid aspiration pneumonitis (AAP) on extrapulmonary organs and to test the hypothesis that these could be due to circulatory depression or hypoxemia.

Detection of Simultaneous Group Effects in MicroRNA Expression and Related Target Gene Sets

PloS One. 2012  |  Pubmed ID: 22723856

Expression levels of mRNAs are among other factors regulated by microRNAs. A particular microRNA can bind specifically to several target mRNAs and lead to their degradation. Expression levels of both, mRNAs and microRNAs, can be obtained by microarray experiments. In order to increase the power of detecting microRNAs that are differentially expressed between two different groups of samples, we incorporate expression levels of their related target gene sets. Group effects are determined individually for each microRNA, and by enrichment tests and global tests for target gene sets. The resulting lists of p-values from individual and set-wise testing are combined by means of meta analysis. We propose a new approach to connect microRNA-wise and gene set-wise information by means of p-value combination as often used in meta-analysis. In this context, we evaluate the usefulness of different approaches of gene set tests. In a simulation study we reveal that our combination approach is more powerful than microRNA-wise testing alone. Furthermore, we show that combining microRNA-wise results with 'competitive' gene set tests maintains a pre-specified false discovery rate. In contrast, a combination with 'self-contained' gene set tests can harm the false discovery rate, particularly when gene sets are not disjunct.

Potential of Surgery and Chemotherapy in Patients with Second Metastatic Recurrence After R0-resection of Colorectal Liver Metastases

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. Feb, 2012  |  Pubmed ID: 27983330

644 Background: Surgical resection is the standard of care for resectable colorectal metastases (CRM). Preoperative chemotherapy allows assessment of tumorbiology and has been shown to convert approximately 30% of unresectable patients into secondary resectability. In patients with second metastatic recurrence (SMR), complete (R0) resection of all metastases seems to be accompanied with a survival benefit. The role of chemotherapy is unclear.

Inactivation of Patched1 in Mice Leads to Development of Gastrointestinal Stromal-like Tumors That Express Pdgfrα but Not Kit

Gastroenterology. Jan, 2013  |  Pubmed ID: 23041331

A fraction of gastrointestinal stromal tumor (GIST) cells overexpress the platelet-derived growth factor receptor (PDGFR)A, although most overexpress KIT. It is not known if this is because these receptor tyrosine kinases have complementary oncogenic potential, or because of heterogeneity in the cellular origin of GIST. Little also is known about why Hedgehog (HH) signaling is activated in some GIST. HH binds to and inactivates the receptor protein patched homolog (PTCH).

RBiopaxParser--an R Package to Parse, Modify and Visualize BioPAX Data

Bioinformatics (Oxford, England). Feb, 2013  |  Pubmed ID: 23274212

Biological pathway data, stored in structured databases, is a useful source of knowledge for a wide range of bioinformatics algorithms and tools. The Biological Pathway Exchange (BioPAX) language has been established as a standard to store and annotate pathway information. However, use of these data within statistical analyses can be tedious. On the other hand, the statistical computing environment R has become the standard for bioinformatics analysis of large-scale genomics data. With this package, we hope to enable R users to work with BioPAX data and make use of the always increasing amount of biological pathway knowledge within data analysis methods.

Carcinoma Cells Misuse the Host Tissue Damage Response to Invade the Brain

Glia. Aug, 2013  |  Pubmed ID: 23832647

The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis.

Relaxins Enhance Growth of Spontaneous Murine Breast Cancers As Well As Metastatic Colonization of the Brain

Clinical & Experimental Metastasis. Aug, 2013  |  Pubmed ID: 23963762

Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as elevated expression of the respective receptors and the relaxin receptor RXFP1 in the tumour tissue. It is also associated with enhanced infiltration by tumour-associated macrophages which are known to promote tumour progression. Additionally, we show in an ex vivo model of metastatic brain colonization that porcine relaxin as well as human brain-specific relaxin-3 promotes invasion into the brain tissue and enhance interaction of breast cancer cells with the resident brain macrophages, the microglia. Relaxin signaling is mediated via RXFP1, since R 3/I5, a specific agonist of the relaxin-3 receptor RXFP3 in the brain, does not significantly enhance invasion. Taken together, these findings strongly support a role of relaxins in the progression of breast cancer where they foster primary tumour growth as well as metastatic colonization by direct and indirect means.

Zoledronic Acid Inhibits Macrophage/microglia-assisted Breast Cancer Cell Invasion

Oncotarget. Aug, 2013  |  Pubmed ID: 24036536

The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether thisis due to directtoxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis.

Melusin Protects from Cardiac Rupture and Improves Functional Remodelling After Myocardial Infarction

Cardiovascular Research. Jan, 2014  |  Pubmed ID: 24130190

Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach.

Failure of Acute Procedural Success Predicts Adverse Outcome After Percutaneous Edge-to-edge Mitral Valve Repair with MitraClip

EuroIntervention : Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2014  |  Pubmed ID: 24972141

MitraClip implantation is evolving as a potential alternative treatment to conventional surgery in high-risk patients with significant mitral regurgitation (MR). However, outcome predictors are under-investigated. The aim of this study was to identify predictors of midterm mortality and heart failure rehospitalisation after percutaneous mitral valve repair with MitraClip.

Impact of Frailty on Short- and Long-term Morbidity and Mortality After Transcatheter Aortic Valve Implantation: Risk Assessment by Katz Index of Activities of Daily Living

EuroIntervention : Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. Sep, 2014  |  Pubmed ID: 25136880

Transcatheter aortic valve implantation (TAVI) represents a less invasive treatment option for elderly patients. Therefore, we aimed to determine the impact of frailty measured by the Katz Index of activities of daily living (ADL) on short- and long-term mortality after TAVI.

The BCL9-2 Proto-oncogene Governs Estrogen Receptor Alpha Expression in Breast Tumorigenesis

Oncotarget. Aug, 2014  |  Pubmed ID: 25149534

The majority of human breast cancers express estrogen receptor alpha (ER), which is important for therapy with anti-estrogens. Here we describe the role of BCL9-2, a proto-oncogene previously characterized as co-activator of Wnt/ß-catenin signaling, for mammary tumorigenesis in mice and human. ER positive human breast cancers showed overexpression of BCL9-2 and tamoxifen treated patients with high BCL9-2 demonstrated a better survival. BCL9-2 was upregulated during puberty and pregnancy in normal mammary epithelia, but downregulated in the involuted gland. BCL9-2 overexpression in vivo delayed the mammary involution and induced alveolar hyperplasia. Moreover, aged BCL9-2 transgenic mice developed ductal-like mammary tumors with high nuclear ER expression. We found, that primary cell cultures of BCL9-2 breast tumors responded to tamoxifen treatment. Moreover, BCL9-2 regulated the expression of ER and the proliferation of human breast cancer cells independently of ß-catenin. Finally, we describe a novel mechanism, how BCL9-2 regulates ER transcription by interaction with Sp1 through the proximal ESR1 gene promoter. In summary, BCL9-2 induces ER positive breast cancers in vivo, regulates ER expression by a novel ß-catenin independent mechanism in breast cancer cells, and might predict the therapy response to tamoxifen treatment.

Integrated MiRNA and MRNA Profiling of Tumor-educated Macrophages Identifies Prognostic Subgroups in Estrogen Receptor-positive Breast Cancer

Molecular Oncology. Jan, 2015  |  Pubmed ID: 25205039

Various studies have identified aberrantly expressed miRNAs in breast cancer and demonstrated an association between distinct miRNAs and malignant progression as well as metastasis. Even though tumor-associated macrophages (TAM) are known mediators of these processes, little is known regarding their miRNA expression upon education by malignant cells in vivo.

Tumor-derived Microvesicles Mediate Human Breast Cancer Invasion Through Differentially Glycosylated EMMPRIN

Journal of Molecular Cell Biology. Apr, 2015  |  Pubmed ID: 25503107

Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologous and heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN.

Anti-CSF-1 Treatment is Effective to Prevent Carcinoma Invasion Induced by Monocyte-derived Cells but Scarcely by Microglia

Oncotarget. Jun, 2015  |  Pubmed ID: 26098772

The mononuclear phagocytic system is categorized in three major groups: monocyte-derived cells (MCs), dendritic cells and resident macrophages. During breast cancer progression the colony stimulating factor 1 (CSF-1) can reprogram MCs into tumor-promoting macrophages in the primary tumor. However, the effect of CSF-1 during colonization of the brain parenchyma is largely unknown. Thus, we analyzed the outcome of anti-CSF-1 treatment on the resident macrophage population of the brain, the microglia, in comparison to MCs, alone and in different in vitro co-culture models. Our results underline the addiction of MCs to CSF-1 while surprisingly, microglia were not affected. Furthermore, in contrast to the brain, the bone marrow did not express the alternative ligand, IL-34. Yet treatment with IL-34 and co-culture with carcinoma cells partially rescued the anti-CSF-1 effects on MCs. Further, MC-induced invasion was significantly reduced by anti-CSF-1 treatment while microglia-induced invasion was reduced to a lower extend. Moreover, analysis of lung and breast cancer brain metastasis revealed significant differences of CSF-1 and CSF-1R expression. Taken together, our findings demonstrate not only differences of anti-CSF-1 treatment on MCs and microglia but also in the CSF-1 receptor and ligand expression in brain and bone marrow as well as in brain metastasis.

The Metastatic Infiltration at the Metastasis/brain Parenchyma-interface is Very Heterogeneous and Has a Significant Impact on Survival in a Prospective Study

Oncotarget. Oct, 2015  |  Pubmed ID: 26299612

The current approach to brain metastases resection is macroscopic removal of metastasis until reaching the glial pseudo-capsule (gross total resection (GTR)). However, autopsy studies demonstrated infiltrating metastatic cells into the parenchyma at the metastasis/brain parenchyma (M/BP)-interface.

Comparative Study on Gene Set and Pathway Topology-based Enrichment Methods

BMC Bioinformatics. Oct, 2015  |  Pubmed ID: 26489510

Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis.

Newly Constructed Network Models of Different WNT Signaling Cascades Applied to Breast Cancer Expression Data

PloS One. 2015  |  Pubmed ID: 26632845

WNT signaling is a complex process comprising multiple pathways: the canonical β-catenin-dependent pathway and several alternative non-canonical pathways that act in a β-catenin-independent manner. Representing these intricate signaling mechanisms through bioinformatic approaches is challenging. Nevertheless, a simplified but reliable bioinformatic WNT pathway model is needed, which can be further utilized to decipher specific WNT activation states within e.g. high-throughput data.

β-catenin-independent WNT Signaling and Ki67 in Contrast to the Estrogen Receptor Status Are Prognostic and Associated with Poor Prognosis in Breast Cancer Liver Metastases

Clinical & Experimental Metastasis. Apr, 2016  |  Pubmed ID: 26862065

Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, β-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01-0.56) and high Ki67 (HR 3.68, 95 % CI 1.12-12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11-5.44). Additionally, the β-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02-4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed β-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis.

Osteolytic Lesions Occur Rarely in Patients with B-CLL and May Respond Well to Ibrutinib

Leukemia & Lymphoma. Oct, 2016  |  Pubmed ID: 26916814

Computational Identification of Key Regulators in Two Different Colorectal Cancer Cell Lines

Frontiers in Genetics. 2016  |  Pubmed ID: 27092172

Transcription factors (TFs) are gene regulatory proteins that are essential for an effective regulation of the transcriptional machinery. Today, it is known that their expression plays an important role in several types of cancer. Computational identification of key players in specific cancer cell lines is still an open challenge in cancer research. In this study, we present a systematic approach which combines colorectal cancer (CRC) cell lines, namely 1638N-T1 and CMT-93, and well-established computational methods in order to compare these cell lines on the level of transcriptional regulation as well as on a pathway level, i.e., the cancer cell-intrinsic pathway repertoire. For this purpose, we firstly applied the Trinity platform to detect signature genes, and then applied analyses of the geneXplain platform to these for detection of upstream transcriptional regulators and their regulatory networks. We created a CRC-specific position weight matrix (PWM) library based on the TRANSFAC database (release 2014.1) to minimize the rate of false predictions in the promoter analyses. Using our proposed workflow, we specifically focused on revealing the similarities and differences in transcriptional regulation between the two CRC cell lines, and report a number of well-known, cancer-associated TFs with significantly enriched binding sites in the promoter regions of the signature genes. We show that, although the signature genes of both cell lines show no overlap, they may still be regulated by common TFs in CRC. Based on our findings, we suggest that canonical Wnt signaling is activated in 1638N-T1, but inhibited in CMT-93 through cross-talks of Wnt signaling with the VDR signaling pathway and/or LXR-related pathways. Furthermore, our findings provide indication of several master regulators being present such as MLK3 and Mapk1 (ERK2) which might be important in cell proliferation, migration, and invasion of 1638N-T1 and CMT-93, respectively. Taken together, we provide new insights into the invasive potential of these cell lines, which can be used for development of effective cancer therapy.

Use of the Impella Device for Acute Coronary Syndrome Complicated by Cardiogenic Shock - Experience From a Single Heart Center With Analysis of Long-term Mortality

The Journal of Invasive Cardiology. Dec, 2016  |  Pubmed ID: 27529657

Impella is a microaxial rotary pump that is placed across the aortic valve to expel aspirated blood from the left ventricle into the ascending aorta; it can be used in cardiogenic shock. While previous studies have evaluated the efficacy and safety of the Impella device, more clinically relevant data are necessary, especially with regard to outcomes.

A Comparison Between the GlideScope® Classic and GlideScope® Direct Video Laryngoscopes and Direct Laryngoscopy for Nasotracheal Intubation

Journal of Clinical Anesthesia. Sep, 2016  |  Pubmed ID: 27555188

Prospective, randomized, clinical trial.

Ror2 Signaling is Required for Local Upregulation of GDF6 and Activation of BMP Signaling at the Neural Plate Border

Development (Cambridge, England). Sep, 2016  |  Pubmed ID: 27578181

The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction.

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