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Leonardo Elia, Paolo Kunderfranco, Pierluigi Carullo, Marco Vacchiano, Floriana Maria Farina, Ignacio Fernando Hall, Stefano Mantero, Cristina Panico, Roberto Papait, Gianluigi Condorelli, Manuela Quintavalle
Adult vascular smooth muscle cells (VSMCs) possess the peculiar ability to de-differentiate in response to extracellular cues, such as vascular damage and inflammation. De-differentiated VSMCs are proliferative, migratory, and have decreased contractile capacity. VSMC dedifferentiation contributes not only to vascular repair, but also to cardiovascular pathologies, such as intimal hyperplasia/restenosis in coronary artery or peripheral vascular diseases and arterial aneurysm. We here demonstrate the role of ubiquitin-like, containing PHD and RING finger domains, 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity...
March 20, 2018: Journal of Clinical Investigation
Zuwei Li, Liang Zhou, Liwen Zhao, Peijie Chen, Yifeng Liu, Yu Ding, Shuolei Sun, Shangqi Yang, Yongqing Lai
Paratesticular liposarcoma is an infrequent tumor characterized by a growing, painless, inguinal or scrotal mass. Only about 200 cases have been reported as of yet in literature, however there are a few cases regarding giant paratesticular liposarcoma measuring over 10 cm. The disease may be commonly misdiagnosed prior to operation. Improper treatment tends to lead to local recurrence and distant metastasis. The current report presents a case of a 51-year-old patient with a large, painless right scrotum. Magnetic resonance imaging revealed a 7...
April 2018: Molecular and Clinical Oncology
Tiago D Serafim, Iliano V Coutinho-Abreu, Fabiano Oliveira, Claudio Meneses, Shaden Kamhawi, Jesus G Valenzuela
Sand flies, similar to most vectors, take multiple blood meals during their lifetime1-4 . The effect of subsequent blood meals on pathogens developing in the vector and their impact on disease transmission have never been examined. Here, we show that ingestion of a second uninfected blood meal by Leishmania-infected sand flies triggers dedifferentiation of metacyclic promastigotes, considered a terminally differentiated stage inside the vector5 , to a leptomonad-like stage, the retroleptomonad promastigote...
March 19, 2018: Nature Microbiology
Yuhua Chen, Lingling Meng, Haitao Shang, Qian Dou, Zhiwen Lu, Liping Liu, Zhijun Wang, Xingxing He, Yuhu Song
βII-Spectrin (β2SP), a Smad3/4 adaptor protein during transforming growth factor (TGF) β/Smad signal pathway, plays a critical role in suppressing hepatocarcinogenesis. Dedifferentiation is a distinctive feature of cancer progression. Therefore, we investigated whether the disruption of β2SP contributed to tumorigenesis of hepatocellular carcinoma (HCC) through the dedifferentiation. Down-regulation of β2SP in hepatocytes was observed in cirrhotic liver and HCC. The level of β2SP expression was closely associated with the differentiation status of hepatocytes in rat model of hepatocarcinogenesis and clinical specimens...
March 19, 2018: Cell Death & Disease
Wei-Dong Lü, Rui-Fang Sun, Ye-Rong Hu, Jan-Rong Lu, Lu Gu, Zhi-Gang Liu, Guang-Yan Lei, Zhun Qiang, Lin Cai
Acellular tumor extracellular matrices (ECMs) have limitations when employed as three-dimensional scaffolds for tumor engineering. In this work, methylene blue-mediated photooxidation was used to crosslink acellular tumor ECMs. Photooxidative crosslinking greatly increased the stiffness of acellular tumor ECM scaffolds but barely altered the Amide III band of the secondary structure of polypeptides and proteins. MCF-7, HepG2 and A549 cells cultured on photooxidatively crosslinked acellular tumor ECM scaffolds exhibited greater cell number per scaffold, more IL-8 and VEGF secretion, and increase migration and invasion abilities than cells cultured on uncrosslinked acellular tumor ECM scaffolds...
March 16, 2018: Acta Biomaterialia
L Rosato, L Panier Suffat, L Bertotti, P Perino, E Comello, G Mondini
BACKGROUND: Retroperitoneal or mesenteric primary liposarcoma is a malignant neoplasia whose prognosis depends on the biological variants, the radical resection surgery and the histological subtypes, as well as on local and remote recurrences. Liposarcoma is the most common variant of this tumour among tumours of soft retroperitoneal tissue. The purpose of this study is to evaluate whether the treatment of this disease, carried out at the Ivrea Hospital for urgent reasons, may be considered in line with the experience of high-volume Centres...
January 2018: Il Giornale di Chirurgia
Sara Touhami, Fanny Beguier, Sébastien Augustin, Hugo Charles-Messance, Lucile Vignaud, Emeline F Nandrot, Sacha Reichman, Valérie Forster, Thibaud Mathis, José-Alain Sahel, Bahram Bodaghi, Xavier Guillonneau, Florian Sennlaub
BACKGROUND: The retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE cell morphology and key functions in vitro. METHODS: Primary porcine RPE cells were exposed to TNFα (at 0...
March 16, 2018: Journal of Neuroinflammation
Paula V Monje
This chapter describes protocols to establish simplified in vitro assays of Schwann cell (SC) differentiation in the absence of neurons. The assays are based on the capacity of isolated primary SCs to increase or decrease the expression of myelination-associated genes in response to the presence or absence of cell permeable analogs of cyclic adenosine monophosphate (cAMP). No special conditions of media or substrates beyond the administration or removal of cAMP analogs are required to obtain a synchronous response on differentiation and dedifferentiation...
2018: Methods in Molecular Biology
Seyran Yiğit, Neşe Ekinci, Leyla Hayrullah, İrfan Öcal, İncim Bezircioğlu
OBJECTIVE: Dedifferentiated endometrioid adenocarcinoma is a recently defined uterine tumor composed of low grade endometrioid adenocarcinoma and undifferentiated carcinoma. Herein we present clinicopathologic, morphologic and immunohistochemical features of 5 dedifferentiated endometrioid adenocarcinoma cases. MATERIAL AND METHODS: All cases diagnosed as mixed endometrial adenocarcinoma (endometrioid + undifferentiated carcinoma) or dedifferentiated endometrioid adenocarcinoma between January 2008 and December 2014 were retrieved from the archives of our institution's pathology department...
March 16, 2018: Journal of the Turkish German Gynecological Association
Abraham Neelankal John, Ramesh Ram, Fang-Xu Jiang
Type 2 diabetes (T2D) is a global health issue and dedifferentiation plays underlying causes in the pathophysiology of T2D; however, there is a lack of understanding in the mechanism. Dedifferentiation results from the loss of function of pancreatic β-cells alongside a reduction in essential transcription factors under various physiological stressors. Our study aimed to establish db/db as an animal model for dedifferentiation by using RNA sequencing to compare the gene expression profile in islets isolated from wild-type, db/+ and db/db mice, and qPCR was performed to validate those significant genes...
March 14, 2018: Endocrine Pathology
Sopita Wongin, Saranatra Waikakul, Pojchong Chotiyarnwong, Wanwipa Siriwatwechakul, Masahiro Kino-Oka, Mee-Hae Kim, Kwanchanok Viravaidya-Pasuwat
BACKGROUND: Dedifferentiation of chondrocytes during cell expansion is one of the barriers in tissue construction for cartilage repair. To understand chondrocyte behavior and improve cell expansion in monolayer culture, this study investigated the effects of morphological changes and cellular aggregation on the maintenance of chondrogenic capacity by observing the expression patterns of chondrogenic (collagen type II and aggrecan) and dedifferentiation (collagen type I) markers. Primary human chondrocytes were cultured on either a polystyrene surface (PS) or a polyamidoamine dendrimer surface with a fifth-generation (G5) dendron structure to create a one-step process of cell expansion and the maintenance of chondrogenic activities prior to the construction of cell sheets...
March 14, 2018: BMC Biotechnology
Ze-Wei Tao, Mohamed Mohamed, Jeffrey G Jacot, Ravi K Birla
Bioengineering cardiac tissue constructs with adult cardiomyocytes may help treat adult heart defects and injury. In this study, we fabricated cardiac tissue constructs by seeding adult rat cardiomyocytes on a fibrin gel matrix and analyzed the electromechanical properties of the formed cardiac tissue constructs. Adult rat cardiomyocytes were isolated with a collagenase type II buffer using an optimized Langendorff perfusion system. Cardiac tissue constructs were fabricated using either indirect plating with cardiomyocytes that were cultured for 1 week and dedifferentiated or with freshly isolated cardiomyocytes...
March 13, 2018: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Jaime L Bernstein, Benjamin P Cohen, Alexandra Lin, Alice Harper, Lawrence J Bonassar, Jason A Spector
PURPOSE: The significant shortcomings associated with current autologous reconstructive options for auricular deformities have inspired great interest in a tissue engineering solution. A major obstacle in the engineering of human auricular cartilage is the availability of sufficient autologous human chondrocytes. A clinically obtainable amount of auricular cartilage tissue (ie, 1 g) only yields approximately 10 million cells, where 25 times this amount is needed for the fabrication of a full-scale pediatric ear...
March 13, 2018: Annals of Plastic Surgery
Katharine M Hinchcliff, Jessica Crockett, Steven W Thorpe, Christopher O Bayne
Long ischemia times adversely affect free flap survival, and large muscle flaps are particularly vulnerable. Hypothermic machine perfusion (HMP) is a well-established method of organ preservation, and recent literature has detailed the use of HMP to extend free flap ischemia times, predominantly in the laboratory setting. One limitation in the study and adoption of free flap HMP has been the availability of standardized perfusion machinery, as thus far institutions have built their own devices. We present a case of a 75-year-old woman with dedifferentiated chondrosarcoma of her right proximal femur...
March 14, 2018: Microsurgery
Kyle T Householder, Danielle M DiPerna, Eugene P Chung, Anne Rosa Luning, Duong T Nguyen, Sarah E Stabenfeldt, Shwetal Mehta, Rachael W Sirianni
Histone deacetylases (HDACs) are known to be key enzymes in cancer development and progression through their modulation of chromatin structure and the expression and post-translational modification of numerous proteins. Aggressive dedifferentiated tumors, like glioblastoma, frequently overexpress HDACs, while HDAC inhibition can lead to cell cycle arrest, promote cellular differentiation and induce apoptosis. Although multiple HDAC inhibitors, such as quisinostat, are of interest in oncology due to their potent in vitro efficacy, their failure in the clinic as monotherapies against solid tumors has been attributed to poor delivery...
February 24, 2018: Colloids and Surfaces. B, Biointerfaces
Elena Maryamchik, Kirill A Lyapichev, Bradford Halliday, Andrew E Rosenberg
We report a first case of paraneoplastic human chorionic gonadotropin (HCG) production in a dedifferentiated liposarcoma with rhabdosarcomatous differentiation in an 83-year-old man with a retroperitoneal mass, unilateral scrotal enlargement, and a serum HCG level of 843 IU/L. Core biopsy of the retroperitoneal mass revealed rhabdomyosarcoma. Orchiectomy revealed a paratesticular dedifferentiated liposarcoma with rhabdosarcomatous differentiation. Fluorescence in situ hybridization analysis performed on both the retroperitoneal and paratesticular masses revealed amplification of MDM2...
March 1, 2018: International Journal of Surgical Pathology
Sucharita Boddu, Peter W Hashim, John K Nia, Rebecca Horowitz, Aaron Farberg, Gary Goldenberg
Stem cell therapies are at the forefront of regenerative aesthetic medicine. Multipotent stem cells and induced pluripotent stem cells (iPSCs), progenitor cells that result from the dedifferentiation of specialized adult cells, have demonstrated promise in tissue regeneration for a wide range of dermatologic conditions and aesthetic applications. Herein, we review the potential of stem cells as a new frontier in aesthetic dermatology.
January 2018: Cutis; Cutaneous Medicine for the Practitioner
Vittoria Poli, Luca Fagnocchi, Alessandra Fasciani, Alessandro Cherubini, Stefania Mazzoleni, Sara Ferrillo, Annarita Miluzio, Gabriella Gaudioso, Valentina Vaira, Alice Turdo, Miriam Giaggianesi, Aurora Chinnici, Elisa Lipari, Silvio Bicciato, Silvano Bosari, Matilde Todaro, Alessio Zippo
Breast cancer consists of highly heterogeneous tumors, whose cell of origin and driver oncogenes are difficult to be uniquely defined. Here we report that MYC acts as tumor reprogramming factor in mammary epithelial cells by inducing an alternative epigenetic program, which triggers loss of cell identity and activation of oncogenic pathways. Overexpression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. MYC-driven dedifferentiation supports the onset of a stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways...
March 9, 2018: Nature Communications
Jingwen Liao, Yanyan Zhang, Ying Wu, Fanxing Zeng, Lijun Shi
AIMS: This study investigated whether long-term exercise can influence vascular smooth muscle cells (VSMCs) phenotypic switching in mesenteric arteries of hypertensive rats, with a focus on the modulation of protein kinase B (PKB/Akt) signaling by microRNA-145 (miR-145). MAIN METHODS: In the exercise intervention experiment, mesenteric arteries from 3-month-old spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were isolated for histological observation, phenotypic marker analysis, Akt phosphorylation quantification, and miR-145 evaluation after being subjected to moderate-intensity treadmill training (E) or being sedentary (C) for 8 weeks...
March 6, 2018: Life Sciences
Bo Hu, Megan Mccollum, Vignesh Ravi, Sezgi Arpag, Daniel Moiseev, Ryan Castoro, Bret C Mobley, Bryan W Burnette, Carly Siskind, John W Day, Robin Yawn, Shawna Feely, Yuebing Li, Qing Yan, Michael E Shy, Jun Li
OBJECTIVE: Charcot-Marie-Tooth type 4J (CMT4J) is a rare autosomal recessive neuropathy caused by mutations in FIG4 that result in loss of FIG4 protein. This study investigates the natural history and mechanisms of segmental demyelination in CMT4J. METHODS: Over the past 9 years, we have enrolled and studied a cohort of 12 CMT4J patients, including 6 novel FIG4 mutations. We evaluated these patients and related mouse models using morphological, electrophysiological and biochemical approaches...
March 8, 2018: Annals of Neurology
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