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Dedifferentiation

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https://www.readbyqxmd.com/read/28529632/imaging-of-chemokine-receptor-4-expression-in-neuroendocrine-tumors-a-triple-tracer-comparative-approach
#1
Rudolf A Werner, Alexander Weich, Takahiro Higuchi, Jan S Schmid, Andreas Schirbel, Michael Lassmann, Vanessa Wild, Martina Rudelius, Theodor Kudlich, Ken Herrmann, Michael Scheurlen, Andreas K Buck, Saskia Kropf, Hans-Jürgen Wester, Constantin Lapa
C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [(68)Ga]Pentixafor in comparison to (68)Ga-DOTA-D-Phe-Tyr3-octreotide ([(68)Ga]DOTATOC) and (18)F-fluorodeoxyglucose ([(18)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [(68)Ga]DOTATOC, [(18)F]FDG, and [(68)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management...
2017: Theranostics
https://www.readbyqxmd.com/read/28524745/actin-cytoskeleton-regulates-functional-anchorage-migration-switch-during-t-cadherin-induced-phenotype-modulation-of-vascular-smooth-muscle-cells
#2
Agne Frismantiene, Emmanouil Kyriakakis, Boris Dasen, Paul Erne, Therese J Resink, Maria Philippova
Vascular smooth muscle cell (SMC) switching between differentiated and dedifferentiated phenotypes is reversible and accompanied by morphological and functional alterations that require reconfiguration of cell-cell and cell-matrix adhesion networks. Studies attempting to explore changes in overall composition of the adhesion nexus during SMC phenotype transition are lacking. We have previously demonstrated that T-cadherin knockdown enforces SMC differentiation, whereas T-cadherin upregulation promotes SMC dedifferentiation...
May 19, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28513981/exposure-to-fermentation-supernatant-of-staphylococcus-aureus-accelerated-dedifferentiation-of-chondrocytes-and-production-of-antimicrobial-peptides
#3
Shuaijun Li, Yun Zhang, Yidan Sun, Weigang Cao, Lei Cui
Staphylococcus aureus is the most popular pathogen found in septic arthritis. Despite bacteria was eradicated from joint cavity during acute infection, destruction of articular cartilage often continues for years, leading to permanent joint damage. The mechanism responsible for this consistent catabolic reaction in septic arthritis remains unclear. Here, we found that fermentation supernatant (FS) of Staphylococcus aureus accelerated dedifferentiation of chondrocytes and induced expression of catabolic factors including A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs 5, NO synthase 2, matrix metalloproteinase -3, -13...
May 17, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28506962/pair-feeding-but-not-insulin-phloridzin-or-rosiglitazone-treatment-curtails-markers-of-beta-cell-dedifferentiation-in-db-db-mice
#4
Emi Ishida, Ja Young Kim-Muller, Domenico Accili
Beta cell failure is a hallmark of type 2 diabetes. Among several cellular biological mechanisms of cellular dysfunction, we and others have recently proposed that dedifferentiation of beta cells can explain the slowly progressive onset and partial reversibility of beta-cell failure. Accordingly, we provided evidence of such processes in humans and experimental animal models of insulin-resistant diabetes. In this study, we asked whether beta cell dedifferentiation can be prevented with diet or pharmacological treatment of diabetes...
May 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28504705/wounding-induces-dedifferentiation-of-epidermal-gata6-cells-and-acquisition-of-stem-cell-properties
#5
Giacomo Donati, Emanuel Rognoni, Toru Hiratsuka, Kifayathullah Liakath-Ali, Esther Hoste, Gozde Kar, Melis Kayikci, Roslin Russell, Kai Kretzschmar, Klaas W Mulder, Sarah A Teichmann, Fiona M Watt
The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6(+) cells migrate from the SD into the interfollicular epidermis and dedifferentiate, acquiring the ability to undergo long-term self-renewal and differentiate into a much wider range of epidermal lineages than in undamaged tissue...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28504617/opportunities-and-challenges-in-the-wider-adoption-of-liver-and-interconnected-microphysiological-systems
#6
David J Hughes, Tomasz Kostrzewski, Emma L Sceats
Liver disease represents a growing global health burden. The development of in vitro liver models which allow the study of disease and the prediction of metabolism and drug-induced liver injury in humans remains a challenge. The maintenance of functional primary hepatocytes cultures, the parenchymal cell of the liver, has historically been difficult with dedifferentiation and the consequent loss of hepatic function limiting utility. The desire for longer term functional liver cultures sparked the development of numerous systems, including collagen sandwiches, spheroids, micropatterned co-cultures and liver microphysiological systems...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28499369/characterization-of-a-splice-site-mutation-in-the-tumor-suppressor-gene-flcn-associated-with-renal-cancer
#7
Malte P Bartram, Tripti Mishra, Nadine Reintjes, Francesca Fabretti, Hakam Gharbi, Alexander C Adam, Heike Göbel, Mareike Franke, Bernhard Schermer, Stefan Haneder, Thomas Benzing, Bodo B Beck, Roman-Ulrich Müller
BACKGROUND: Renal cell carcinoma is among the most prevalent malignancies. It is generally sporadic. However, genetic studies of rare familial forms have led to the identification of mutations in causative genes such as VHL and FLCN. Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors. METHODS: Using Sanger sequencing we identify a heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient suffering from renal cell carcinoma...
May 12, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28498808/restoration-of-p53-using-the-novel-mdm2-p53-antagonist-apg115-suppresses-dedifferentiated-papillary-thyroid-cancer-cells
#8
Haibo Chen, Dingyuan Luo, Lin Zhang, Xiaofeng Lin, Qiuyun Luo, Hanjie Yi, Jing Wang, Xianglei Yan, Baoxia Li, Yuelei Chen, Xingguang Liu, Hong Zhang, Sheng Liu, Miaozhen Qiu, Dajun Yang, Ningyi Jiang
Dedifferentiated papillary thyroid cancer (DePTC) is characterized by aggressive growth, recurrence, distant metastasis, and resistance to radioactive iodine (RAI) therapy. DePTC is also accompanied by poor prognosis and high early-mortality. Nevertheless, most DePTC cells show intact p53 downstream functionality. In cells with wild-type p53, the murine double minute2 (MDM2) protein interacts with p53 and abrogates its activity. Inhibition of the MDM2-p53 interaction restores p53 activity and leads to cell cycle arrest and apoptosis...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498284/undifferentiated-and-dedifferentiated-endometrial-carcinomas-with-pole-exonuclease-domain-mutations-have-a-favorable-prognosis
#9
Iñigo Espinosa, Cheng-Han Lee, Emanuela D'Angelo, José Palacios, Jaime Prat
POLE exonuclease domain mutations have recently been described in undifferentiated endometrial carcinoma but, because of the rarity of this aggressive type of endometrial cancer, their prognostic significance is unknown. We have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, β-catenin, and SMARCB1) and mutational status (POLE, PIK3CA, and PTEN) of 21 undifferentiated carcinomas (8 undifferentiated and 13 dedifferentiated carcinomas). Loss of ARID1A expression was observed in 9 of 19 cases (47%), loss of expression of at least 1 DNA mismatch repair protein in 7 (7/21; 33%), and p53 immunoreaction was aberrant (mutated/inactivated) in 11 cases (11/21; 52%)...
May 11, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28491177/incidentally-discovered-well-differentiated-retroperitoneal-liposarcoma-with-inguinal-canal-herniation-report-of-2-cases
#10
Valeria Fiaschetti, Francesca Castellani, Giusy Croce, Mariateresa Mondillo, Andrea Amico, Adriano De Majo, Valentina Girardi, Roberta Di Trapano, Roberto Floris
Well-differentiated retroperitoneal liposarcomas are slow growing and low-grade tumors, reaching usually huge size before being symptomatic and so diagnosed, therefore with increase of the surgical risk and of the probability of dedifferentiation. Inguinal location of these tumors is unusual and rarely diagnosed.
June 2017: Radiology case reports
https://www.readbyqxmd.com/read/28487881/whole-genome-sequencing-identifies-homozygous-brca2-deletion-guiding-treatment-in-dedifferentiated-prostate-cancer
#11
Karin Purshouse, Anna Schuh, Benjamin P Fairfax, Sam Knight, Pavlos Antoniou, Helene Dreau, Niko Popitsch, Kevin Gatter, Ian Roberts, Lisa Browning, Zoe Traill, David Kerr, Clare Verrill, Mark Tuthill, Jenny C Taylor, Andrew Protheroe
Whole-genome sequencing (WGS) has transformed the understanding of the genetic drivers of cancer and is increasingly being used in cancer medicine to identify personalized therapies. Here we describe a case in which the application of WGS identified a tumoral BRCA2 deletion in a patient with aggressive dedifferentiated prostate cancer that was repeat-biopsied after disease progression. This would not have been detected by standard BRCA testing, and it led to additional treatment with a maintenance poly ADP ribose polymerase (PARP) inhibitor following platinum-based chemotherapy...
May 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28481029/loss-of-h2b-monoubiquitination-is-associated-with-poor-differentiation-and-enhanced-malignancy-of-lung-adenocarcinoma
#12
Keqiang Zhang, Jinhui Wang, Tommy R Tong, Xiwei Wu, Rebecca Nelson, Yate-Ching Yuan, Theresa Reno, Zheng Liu, Xinwei Yun, Jae Y Kim, Ravi Salgia, Dan J Raz
Deregulated monoubiquitination of histone H2B (H2Bub1), mainly catalyzed by E3 ubiquitin-protein ligase RNF20/RNF40 complex, may play an important role in cancer. Here we investigate potential roles of H2Bub1 and the underlying mechanisms through which it contributes to cancer development and progression in lung adenocarcinoma. We show that downregulation of H2Bub1 through RNF20 knockdown dramatically decreases H3K79 and H3K4 trimethylation in both normal and malignant lung epithelial cell lines. Concurrently, global transcriptional profiling analysis reveals that multiple tumor-associated genes such as CCND3, E2F1/2, HOXA1, Bcl2 modifying factor (BMF), Met, and Myc; and signaling pathways of cellular dedifferentiation, proliferation, adhesion, survival including p53, cadherin, Myc, and anti-apoptotic pathways are differentially expressed or significantly altered in these lung epithelial cells upon downregulation of H2Bub1...
May 8, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28477272/hif-1%C3%AE-mdm2-cdk4-and-p16-expression-in-ischemic-fasciitis-focusing-on-its-ischemic-condition
#13
Yuichi Yamada, Izumi Kinoshita, Kenichi Kohashi, Hidetaka Yamamoto, Yuki Kuma, Takamichi Ito, Kenji Koda, Atsushi Kisanuki, Manabu Kurosawa, Michiko Yoshimura, Masutaka Furue, Yoshinao Oda
Ischemic fasciitis is a benign myofibroblastic lesion, occurring in the sacral region or proximal thigh of elderly or bedridden individuals. The pathogenesis of ischemic fasciitis is thought to be based on ischemic condition; however, it has never been demonstrated. In this study, we examined the expression of ischemia-associated proteins in ischemic fasciitis by immunohistochemical and genetic methods. Specifically, this study aimed to reveal the expression of HIF-1α, MDM2, CDK4, p16, and gene amplification of MDM2 gene...
May 6, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28476380/claudin-6-expression-is-useful-to-distinguish-myxofibrosarcomas-from-other-myxoid-soft-tissue-tumors
#14
Hirofumi Bekki, Hidetaka Yamamoto, Katsumi Takizawa, Takeshi Iwasaki, Hiroshi Otsuka, Yuichi Yamada, Kenichi Kohashi, Katsumi Harimaya, Yukihide Iwamoto, Yoshinao Oda
Myxofibrosarcoma (MFS) is characterized by abundant myxoid stroma, a wide spectrum of cytological atypia, and frequent local recurrence. Some soft tissue tumors with myxoid stroma can histologically mimic MFS, but have different biological behaviors. Here we sought to identify a useful diagnostic marker for MFS. After our analysis of the gene expression dataset from the Gene Expression Omnibus database, we focused on claudin 6 (CLDN 6). The status of CLDN 6 was assessed by immunohistochemistry in 61 samples of MFS and other (benign) myxoid soft tissue tumors (28 myxoma samples, 12 nodular fasciitis samples), 18 low-grade fibromyxoid sarcoma, 30 myxoid liposarcoma, 29 extraskeletal myxoid chondrosarcoma and 27 dedifferentiated liposarcoma with myxoid feature samples...
December 5, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28473229/atypical-flat-lesions-derive-from-pancreatic-acinar-cells
#15
Guido von Figura, Leonie Fahrenkrog-Petersen, Ana Hidalgo-Sastre, Daniel Hartmann, Norbert Hüser, Roland M Schmid, Matthias Hebrok, Nilotpal Roy, Irene Esposito
OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is thought to derive from different precursor lesions including the recently identified atypical flat lesions (AFL). While all precursor lesions and PDAC share ductal characteristics, there is an ongoing debate about the cellular origin of the different PDAC precursor lesions. In particular, pancreatic acinar cells have previously been shown to display a remarkable plasticity being able to undergo ductal dedifferentiation in the context of oncogenic stimuli...
April 25, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28469300/bladder-cancer-micro-rnas-as-biomolecules-for-prognostication-and-surveillance
#16
REVIEW
Nilay Mitash, Swasti Tiwari, Shalini Agnihotri, Anil Mandhani
INTRODUCTION: Bladder cancer (BC) has varied clinical behavior in terms of recurrence and progression. Current pathological characteristics are insufficient to prognosticate the outcome of a given treatment. Cellular metabolic regulatory molecules, such as micro RNA (miRNA), could be a potential biomarker to prognosticate the treatment outcomes. MATERIALS AND METHODS: PubMed and Google Scholar databases were searched for publications from 1990 to 2016, related to miRNA biogenesis, its function, and role in the pathogenesis of bladder as well as other cancers...
April 2017: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/28468914/rig-i-resists-hypoxia-induced-immunosuppression-and-dedifferentiation
#17
Christina Engel, Grethe Brügmann, Silke Lambing, Larissa H Mühlenbeck, Samira Marx, Christian Hagen, Dorottya Horváth, Marion Goldeck, Janos Ludwig, Anna-Maria Herzner, Jan W Drijfhout, Daniela Wenzel, Christoph Coch, Thomas Tüting, Martin Schlee, Veit Hornung, Gunther Hartmann, Jasper G Van den Boorn
A hypoxic tumor microenvironment is linked to poor prognosis. It promotes tumor cell dedifferentiation and metastasis and desensitizes tumor cells to type-I interferon (IFN), chemotherapy, and irradiation. The cytoplasmic immunoreceptor retinoic acid-inducible gene-I (RIG-I) is ubiquitously expressed in tumor cells and upon activation by 5'-triphosphate RNA (3pRNA) drives the induction of type I IFN and immunogenic cell death. Here, we analyzed the impact of hypoxia on the expression of RIG-I in various human and murine tumor and nonmalignant cell types and further investigated its function in hypoxic murine melanoma...
May 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28468615/epithelial-ciliated-beating-cells-essential-for-ex-vivo-ali-culture-growth
#18
Delphine Gras, Aurélie Petit, Jérémy Charriot, Lucie Knabe, Khuder Alagha, Anne Sophie Gamez, Céline Garulli, Arnaud Bourdin, Pascal Chanez, Nicolas Molinari, Isabelle Vachier
BACKGROUND: Bronchial epithelium plays a key role in orchestrating innate and adaptive immunity. The fate of ex vivo airway epithelial cultures growing at the air liquid interface (ALI) derived from human endobronchial biopsies or brushings is not easy to predict. Calibrating and differentiating these cells is a long and expensive process requiring rigorous expertise. Pinpointing factors associated with ALI culture success would help researchers gain further insight into epithelial progenitor behavior...
May 3, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28467804/androgen-receptor-status-predicts-development-of-brain-metastases-in-ovarian-cancers
#19
Gloria Mittica, Rebecca Senetta, Giulia Scotto, Massimo Aglietta, Furio Maggiorotto, Eleonora Ghisoni, Sofia Genta, Renzo Boldorini, Claudia Manini, Isabella Morra, Roberta Buosi, Anna Sapino, Paola Cassoni, Giorgio Valabrega
Brain metastases are uncommon localizations in epithelial ovarian cancer (EOC), their reported incidence is increasing and no predictive biomarkers have been identified yet. Goals of this study were: i) to define a possible association between Estrogen Receptor (ER), Progesterone Receptor (PR), Androgen Receptor (AR),human EGF receptor 2 (HER2) and brain progression in EOC patients, and ii) to identify differences in ER, PR, AR and HER2 protein expression from primary EOC and its matched resected brain metastasis...
April 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466810/oleanolic-acid-oa-regulates-inflammation-and-cellular-dedifferentiation-of-chondrocytes-via-mapk-signaling-pathways
#20
A-R Phull, S-H Eo, S J Kim
Oleanolic acid (OA) is a bioactive triterpenoid in medicinal plants. It possesses various pharmacological properties, including analgesic, anti-inflammatory, and antitumor effects. The effects of OA in chondrocytes, however, are not well characterized. Here, we used rabbit articular chondrocytes as a cellular model to investigate the effects and regulatory mechanisms of OA on dedifferentiation and pro-inflammation. OA promoted dedifferentiation of chondrocytes by inhibiting type II collagen and pro-inflammatory activity by increasing cyclooxygenase-2 (COX-2) expression...
March 31, 2017: Cellular and Molecular Biology
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