bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract TMEM-039: THE ROLE OF SNAIL IN CELL DIFFERENTIATION STATUS: EPITHELIAL-MESENCHYMAL TRANSITION AND CANCER STEM CELLS
Authors: Wang Hanmin , Huisken-Hill Alyse , Chirshev Evgeny , Unternaehrer-Hamm Juli 
Published: June 2017

Abstract
PURPOSE: The epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and become mesenchymal cells with migratory and invasive properties. EMT is essential for numerous developmental processes such as gastrulation, and is involved in the initiation of metastasis for cancer progression.
Cancer cells that undergo EMT are enabled to metastasize to form secondary tumors. One characteristic of advanced tumors is a low expression level of let-7, a miRNA known to be vital in both maintenances of cellular differentiation and tumor suppression. There is a gap in the literature concerning the mechanism of let-7 downregulation. Our purpose in this study is to present data that shows Snail, an EMT inducer, directly represses let-7, hence inducing cancer stem cells.
EXPERIMENTAL PROCEDURES: Ovarian, pancreatic and breast cancer cell lines treated with TGFβ or EGF, inducers of EMT, were studied in our experiments. Expression of several markers at protein level was visualized with immunofluorescence and quantified with flow cytometry. Gene expression of mesenchymal, epithelial and pluripotency factors and miRNAs was detected by q-RT-PCR. Chromatin immunoprecipitation of Snail was performed in ovarian cancer lines. Let-7i promoter luciferase with and without Snail were co-transfected into OVSAHO and 293T cell lines and followed by luciferase assays for detection of bioluminescence. Snail was knocked down by lentiviral small hairpin RNA. Snail was overexpressed by estrogen receptor fusion protein. Orthotopic xenografts of patient-derived ovarian cancer cells were used to test the effect of Snail knockdown on tumor burden.
RESULTS: In selected ovarian cancer lines, levels of Snail expression correlated directly with Nanog, and indirectly with let-7 expression. Snail bound promoters of let-7 in cell lines tested. Luciferase assays demonstrated direct repression of let-7 transcription by Snail. Metastatic burden was significantly reduced in cell line xenografts in which Snail was knocked down.
CONCLUSIONS: Let-7 is confirmed to be negatively related to Snail. Our preliminary data also shows Snail directly represses let-7, therefore induces properties of stemness in cancer cells. Cell line and patient-derived data support the relationship between Snail expression, let-7 downregulation, and the induction of cancer stem cells. Snail knockdown appears to disrupt the cancer stem cell state and reduces disease progression.
Citation Format: Hanmin Wang, Alyse Huisken-Hill, Evgeny Chirshev, Juli Unternaehrer-Hamm. THE ROLE OF SNAIL IN CELL DIFFERENTIATION STATUS: EPITHELIAL-MESENCHYMAL TRANSITION AND CANCER STEM CELLS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-039.
Abstract TMEM-042: MALIGNANT EXTRACELLULAR VESICLES CAUSE MESOTHELIAL CELL DAMAGE TOWARD PERITONEAL DISSEMINATION IN OVARIAN CANCER
Authors: Yokoi Akira , Ochiya Takahiro 
Published: June 2017

Abstract
PURPOSE: To elucidate novel mechanisms of peritoneal dissemination by focusing on extracellular vesicles
BACKGROUNDS AND SUMMARY: Metastasis to the abdominal cavity is frequently observed in ovarian cancer patients and is one of the reasons for the unfavorable outcomes. Extracellular vesicles (EVs), including exosomes and microvesicles, are small membrane vesicles that contain various bioactive molecules, such as microRNAs, mRNAs and proteins, and they are released from all cell types and play key physiological roles in intercellular communication. Recent evidence has demonstrated that cancer cells secrete EVs to both proximal surrounding cells and distal sites, thereby enabling the development of a cancer microenvironment that in turn promotes cancer metastasis.
We established orthotopic mouse models by using 4 ovarian carcinoma cell lines with different metastatic traits and investigated the functions of cancer-derived EVs. The EVs from highly metastatic cells strongly induced metastatic behavior in moderately metastatic tumors. Notably, the metastatic cancer EVs efficiently induced apoptotic cell death in mesothelial cells in vitro and in vivo, thus resulting in the destruction of the peritoneal mesothelium barrier. Whole transcriptome analysis showed that MMP1 was significantly elevated in mesothelial cells treated with highly metastatic cancer EVs, and intact MMP1 mRNAs were selectively packaged in the EVs. Importantly, MMP1 expression in ovarian cancer is tightly correlated with a poor prognosis, particularly in stage I patients. Moreover, we found MMP1 mRNA-carrying EVs in the ascites of cancer patients, and these EVs also induced apoptosis in mesothelial cells.
CONCLUSIONS: Our findings provide a promise for the understanding of a previously unknown mechanism for peritoneal dissemination that is associated with cancer-derived EVs, and which may be novel biomarkers for prognosis and can provide a new therapeutic strategy for inhibiting metastasis by disrupting the EVs.
Citation Format: Akira Yokoi and Takahiro Ochiya. MALIGNANT EXTRACELLULAR VESICLES CAUSE MESOTHELIAL CELL DAMAGE TOWARD PERITONEAL DISSEMINATION IN OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-042.
SCN5A
Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome
Authors: Makarawate Pattarapong , Chaosuwannakit Narumol , Vannaprasaht Suda , Sahasthas Dujdao , Koo Seok Hwee , Lee Edmund Jon Deoon , Tassaneeyakul Wichittra , Barajas‐Martinez Hector , Hu Dan , Sawanyawisuth Kittisak 
Published: June 2017

Background

Brugada syndrome (BrS) is an inherited primary arrhythmia disorder leading to sudden cardiac arrest.

SCN
5A

, encoding the α‐subunit of the cardiac sodium channel (Nav1.5), is the most common pathogenic gene of BrS. An implantable cardioverter defibrillator (
ICD
) is the standard treatment for secondary prevention. This study aimed to evaluate association of the

SCN
5A

variant with this cardiac conduction disturbance and appropriate
ICD
shock therapy in Thai symptomatic BrS patients with
ICD
implants.

Methods and Results

Symptomatic BrS patients diagnosed at university hospital were enrolled from 2008 to 2011. The primary outcome of the study was an appropriate
ICD
shock defined as having non‐pacing‐associated
ICD
shock after the occurrence of ventricular tachycardia or ventricular fibrillation. Associations between

SCN
5A

polymorphisms, cardiac conduction disturbance, and potential confounding factors associated with appropriate
ICD
shock therapy were analyzed. All 40 symptomatic BrS patients (median age, 43 years) with
ICD
implantations were followed for 24 months. There were 16 patients (40%) who had the appropriate
ICD
shock therapy after
ICD
treatment. An independent factor associated with appropriate
ICD
shock therapy was

SCN
5A‐

R1193Q with an adjusted hazard ratio of 10.550 (95%
CI
, 1.631–68.232).

Conclusions

SCN
5A‐

R1193Q is associated with cardiac conduction disturbances. It may be a genetic marker associated with ventricular arrhythmia leading to appropriate
ICD
shock therapy in symptomatic BrS patients with
ICD
treatment. Because of the small sample size of study population and the appropriate
ICD
shock outcome, further large studies are needed to confirm the results of this study.
Protein kinase C epsilon delays latency until anoxic depolarization through arc expression and GluR2 internalization
Authors: Cohan Charles H , Stradecki-Cohan Holly M , Morris-Blanco Kahlilia C , Khoury Nathalie , Koronowski Kevin B , Youbi Mehdi , Wright Clinton B , Perez-Pinzon Miguel A 
Published: June 2017

Global cerebral ischemia is a debilitating injury that damages the CA1 region of the hippocampus, an area important for learning and memory. Protein kinase C epsilon (PKCɛ) activation is a critical component of many neuroprotective treatments. The ability of PKCɛ activation to regulate AMPA receptors (AMPARs) remains unexplored despite the role of AMPARs in excitotoxicity after brain ischemia. We determined that PKCɛ activation increased expression of a protein linked to learning and memory, activity-regulated cytoskeleton-associated protein (arc). Also, arc is necessary for neuroprotection and confers protection through decreasing AMPAR currents via GluR2 internalization. In vivo, activation of PKCɛ increased arc expression through a BDNF/TrkB pathway, and decreased GluR2 mRNA levels. In hippocampal cultured slices, PKCɛ activation decreased AMPAR current amplitudes in an arc- and GluR2-dependent manner. Additionally, PKCɛ activation triggered an arc- and GluR2 internalization-dependent delay in latency until anoxic depolarization. Inhibiting arc also blocked PKCɛ-mediated neuroprotection against lethal oxygen and glucose deprivation. These data characterize a novel PKCɛ-dependent mechanism that for the first time defines a role for arc and AMPAR internalization in conferring neuroprotection.
Atelocollagen Enhances the Healing of Rotator Cuff Tendon in Rabbit Model
Authors: Suh Dong-Sam , Lee Jun-Keun , Yoo Ji-Chul , Woo Sang-Hun , Kim Ga-Ram , Kim Ju-Won , Choi Nam-Yong , Kim Yongdeok , Song Hyun-Seok 
Published: June 2017

Background: Failure of rotator cuff healing is a common complication despite the rapid development of surgical repair techniques for the torn rotator cuff. Purpose: To verify the effect of atelocollagen on tendon-to-bone healing in the rabbit supraspinatus tendon compared with conventional cuff repair. Study Design: Controlled laboratory study. Methods: A tear of the supraspinatus tendon was created and repaired in 46 New Zealand White rabbits. They were then randomly allocated into 2 groups (23 rabbits per group; 15 for histological and 8 for biomechanical test). In the experimental group, patch-type atelocollagen was implanted between bone and tendon during repair; in the control group, the torn tendon was repaired without atelocollagen. Each opposite shoulder served as a sham (tendon was exposed only). Histological evaluation was performed at 4, 8, and 12 weeks. Biomechanical tensile strength was tested 12 weeks after surgery. Results: Histological evaluation scores of the experimental group (4.0 ± 1.0) were significantly superior to those of the control group (7.7 ± 2.7) at 12 weeks ( P = .005). The load to failure was significantly higher in the experimental group (51.4 ± 3.9 N) than in the control group (36.4 ± 5.9 N) ( P = .001). Conclusion: Histological and biomechanical studies demonstrated better results in the experimental group using atelocollagen in a rabbit model of the supraspinatus tendon tear. Clinical Relevance: Atelocollagen patch could be used in the cuff repair site to enhance healing.
Does Participation in Sports Affect Osteoarthritic Progression After Periacetabular Osteotomy?
Authors: Hara Daisuke , Hamai Satoshi , Fukushi Jun-ichi , Kawaguchi Ken-ichi , Motomura Goro , Ikemura Satoshi , Komiyama Keisuke , Nakashima Yasuharu 
Published: June 2017

Background: Periacetabular osteotomy (PAO) is an effective treatment for symptomatic acetabular dysplasia. However, whether postoperative participation in sports leads to progression of the Kellgren-Lawrence (KL) grade of osteoarthritis (OA) in these patients is unclear. Purpose: To investigate (1) participation in sports before and after PAO and (2) whether postoperative participation in sports leads to progression of the KL grade. Study Design: Case-control study; Level of evidence, 3. Methods: The authors retrospectively reviewed data on 161 patients (183 hips) who underwent PAO for symptomatic acetabular dysplasia with preoperative KL grade 1 or 2 between 1998 and 2011. The mean age at the time of surgery was 42.0 ± 10.9 years (range, 12-64 years), and the mean follow-up duration was 100 months (range, 13-180 months). Data included participation in sports, the University of California, Los Angeles (UCLA) activity scale score, age at the time of surgery, body mass index, follow-up duration, history of treatment for developmental hip dislocations, Merle d’Aubigné-Postel score, Oxford Hip Score, center-edge angle, and KL grade. Univariate and multivariate analyses were applied to determine which factors were associated with progression to KL grade 3 or 4 after PAO. Results: The number of patients who participated in sports significantly increased from 50 (31.1%) preoperatively to 89 (55.3%) postoperatively. The mean UCLA score significantly increased from 4.7 ± 2.1 preoperatively to 5.5 ± 2.0 postoperatively. The KL grade progressed to grade 3 or 4 in 16 hips, including 4 hips that underwent conversion to total hip arthroplasty. No significant differences were found in postoperative participation in sports (89 hips [53.3%] vs 11 hips [68.8%], respectively; P = .24) and the UCLA score (5.6 ± 2.0 vs 5.1 ± 2.0, respectively; P = .30) between hips with KL grade 1 or 2 and KL grade 3 or 4. A multivariate analysis revealed that no factors, including postoperative participation in sports, were significantly associated with progression to KL grade 3 or 4. Conclusion: Postoperative participation in sports after PAO did not significantly and negatively influence progression of the KL grade at midterm follow-up.
A Simple Method for 2-D In Vivo Dosimetry by Portal Imaging
Authors: Peca Stefano , Brown Derek Wilson , Smith Wendy Lani 
Published: June 2017

Purpose: To improve patient safety and treatment quality, verification of dose delivery in radiotherapy is desirable. We present a simple, easy-to-implement, open-source method for in vivo planar dosimetry of conformal radiotherapy by electronic portal imaging device (EPID). Methods: Correlation ratios, which relate dose in the mid-depth of slab phantoms to transit EPID signal, were determined for multiple phantom thicknesses and field sizes. Off-axis dose is corrected for by means of model-based convolution. We tested efficacy of dose reconstruction through measurements with off-reference values of attenuator thickness, field size, and monitor units. We quantified the dose calculation error in the presence of thickness changes to simulate anatomical or setup variations. An example of dose calculation on patient data is provided. Results: With varying phantom thickness, field size, and monitor units, dose reconstruction was almost always within 3% of planned dose. In the presence of thickness changes from planning CT, the dose discrepancy is exaggerated by up to approximately 1.5% for 1 cm changes upstream of the isocenter plane and 4% for 1 cm changes downstream. Conclusion: Our novel electronic portal imaging device in vivo dosimetry allows clinically accurate 2-dimensional reconstruction of dose inside a phantom/patient at isocenter depth. Due to its simplicity, commissioning can be performed in a few hours per energy and may be modified to the user’s needs. It may provide useful dose delivery information to detect harmful errors, guide adaptive radiotherapy, and assure quality of treatment.
In vitro psoriasis models with focus on reconstructed skin models as promising tools in psoriasis research
Authors: Desmet Eline , Ramadhas Anesh , Lambert Jo , Van Gele Mireille 
Published: June 2017

Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder. Recent advances in and optimization of three-dimensional skin equivalent models have made them attractive and promising alternatives to the simplistic monolayer cultures, immunological different in vivo models and scarce ex vivo skin explants. Moreover, human skin equivalents are increasing in complexity level to match human biology as closely as possible. Here, we critically review the different types of three-dimensional skin models of psoriasis with relevance to their application potential and advantages over other models. This will guide researchers in choosing the most suitable psoriasis skin model for therapeutic drug testing (including gene therapy via siRNA molecules), or to examine biological features contributing to the pathology of psoriasis. However, the addition of T cells (as recently applied to a de-epidermized dermis-based psoriatic skin model) or other immune cells would make them even more attractive models and broaden their application potential. Eventually, the ultimate goal would be to substitute animal models by three-dimensional psoriatic skin models in the pre-clinical phases of anti-psoriasis candidate drugs. Impact statement The continuous development of novel in vitro models mimicking the psoriasis phenotype is important in the field of psoriasis research, as currently no model exists that completely matches the in vivo psoriasis skin or the disease pathology. This work provides a complete overview of the different available in vitro psoriasis models and suggests improvements for future models. Moreover, a focus was given to psoriatic skin equivalent models, as they offer several advantages over the other models, including commercial availability and validity. The potential and reported applicability of these models in psoriasis pre-clinical research is extensively discussed. As such, this work offers a guide to researchers in their choice of pre-clinical psoriasis model depending on their type of research question.
Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries?
Authors: Baillieul S , Chacaroun S , Doutreleau S , Detante O , Pépin JL , Verges S 
Published: June 2017

Central nervous system diseases are among the most disabling in the world. Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation as pharmacology treatments are often insufficiently effective. Conditioning the central nervous system has been proposed as a potential non-pharmacological neuro-therapeutic. Conditioning refers to a procedure by which a potentially deleterious stimulus is applied near to but below the threshold of damage to the organism to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic conditioning has been investigated in several cellular and preclinical models and is now recognized as inducing endogenous mechanisms of neuroprotection. Ischemic, traumatic, or chronic neurodegenerative diseases can benefit from hypoxic conditioning strategies aiming at preventing the deleterious consequences or reducing the severity of the pathological condition (preconditioning) or aiming at inducing neuroplasticity and recovery (postconditioning) following central nervous system injury. Hypoxic conditioning can consist in single (sustained) or cyclical (intermittent, interspersed by short period of normoxia) hypoxia stimuli which duration range from few minutes to several hours and that can be repeated over several days or weeks. This mini-review addresses the existing evidence regarding the use of hypoxic conditioning as a potential innovating neuro-therapeutic modality to induce neuroprotection, neuroplasticity and brain recovery. This mini-review also emphasizes issues which remain to be clarified and future researches to be performed in the field.Impact statementNeuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation. Hypoxic conditioning may represent a harmless and efficient non-pharmacological new therapeutic modality in the field of neuroprotection and neuroplasticity, as supported by many preclinical data. Animal studies provide clear evidence for neuroprotection and neuroplasticity induced by hypoxic conditioning in several models of neurological disorders. These studies show improved functional outcomes when hypoxic conditioning is applied and provides important information to translate this intervention to clinical practice. Some studies in humans provide encouraging data regarding the tolerance and therapeutic effects of hypoxic conditioning strategies. The main issues to address in future research include the definition of the appropriate hypoxic dose and pattern of exposure, the determination of relevant physiological biomarkers to assess the effects of the treatment and the evaluation of combined strategies involving hypoxic conditioning and other pharmacological or non-pharmacological treatments.
Metal artefacts severely hamper magnetic resonance imaging of the rotator cuff tendons after rotator cuff repair with titanium suture anchors
Authors: Schröder Femke F. , Huis in’t Veld Rianne , den Otter Lydia A. , van Raak Sjoerd M. , ten Haken Bennie , Vochteloo Anne J. H. 
Published: June 2017

Background The rate of retear after rotator cuff surgery is 17%. Magnetic resonance imaging (MRI) scans are used for confirmative diagnosis of retear. However, because of the presence of titanium suture anchors, metal artefacts on the MRI are common. The present study evaluated the diagnostic value of MRI after rotator cuff tendon surgery with respect to assessing the integrity as well as the degeneration and atrophy of the rotator cuff tendons when titanium anchors are in place. Methods Twenty patients who underwent revision surgery of the rotator cuff as a result of a clinically suspected retear between 2013 and 2015 were included. The MRI scans of these patients were retrospectively analyzed by four specialized shoulder surgeons and compared with intra-operative findings (gold standard). Sensitivity and interobserver agreement among the surgeons in assessing retears as well as the Goutallier and Warner classification were examined. Results In 36% (range 15% to 50%) of the pre-operative MRI scans, the observers could not review the rotator cuff tendons. When the rotator cuff tendons were assessable, a diagnostic accuracy with a mean sensitivity of 0.84 (0.70 to 1.0) across the surgeons was found, with poor interobserver agreement (kappa = 0.12). Conclusions Metal artefacts prevented accurate diagnosis from MRI scans of rotator cuff retear in 36% of the patients studied.