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https://www.readbyqxmd.com/read/29324814/comprehensive-molecular-profiling-of-advanced-metastatic-olfactory-neuroblastomas
#1
Jasmina Topcagic, Rebecca Feldman, Anatole Ghazalpour, Jeffrey Swensen, Zoran Gatalica, Semir Vranic
Olfactory neuroblastoma (ONB) is a rare, locally aggressive, malignant neoplasm originating in the olfactory epithelium in the nasal vault. The recurrence rate of ONB remains high and there are no specific treatment guidelines for recurrent/metastatic ONBs. This study retrospectively evaluated 23 ONB samples profiled at Caris Life Sciences (Phoenix, Arizona) using DNA sequencing (Sanger/NGS [Illumina], n = 15) and gene fusions (Archer FusionPlex, n = 6), whole genome RNA microarray (HumanHT-12 v4 beadChip, Illumina, n = 4), gene copy number assays (chromogenic and fluorescent in situ hybridization), and immunohistochemistry...
2018: PloS One
https://www.readbyqxmd.com/read/29302031/a-non-cell-autonomous-role-for-pml-in-the-maintenance-of-leukemia-from-the-niche
#2
Jlenia Guarnerio, Lourdes Maria Mendez, Noboru Asada, Archita Venugopal Menon, Jacqueline Fung, Kelsey Berry, Paul S Frenette, Keisuke Ito, Pier Paolo Pandolfi
Disease recurrence after therapy, due to the persistence of resistant leukemic cells, represents a fundamental problem in the treatment of leukemia. Elucidating the mechanisms responsible for the maintenance of leukemic cells, before and after treatment, is therefore critical to identify curative modalities. It has become increasingly clear that cell-autonomous mechanisms are not solely responsible for leukemia maintenance. Here, we report a role for Pml in mesenchymal stem cells (MSCs) in supporting leukemic cells of both CML and AML...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29288729/extracellular-vesicles-or-free-circulating-dna-where-to-search-for-braf-and-ckit-mutations
#3
Jennifer Klump, Ulrike Philipp, Marie Follo, Anna Eremin, Hannes Lehmann, Sigrun Nestel, Nikolas von Bubnoff, Irina Nazarenko
Clinical evidence in oncology argues for the advantages of performing molecular analysis of blood biomarkers to provide information about systemic changes and tumor heterogeneity. Whereas the diagnostic value of cell-free circulating DNA (fcDNA) has successfully been demonstrated in several studies, DNA enclosed in extracellular vesicles (EV) has only recently been described, and its potential diagnostic value is unclear. We established a protocol for separation of EV and fc fractions and tested for presence of mutant BRAFV600E mediating resistance to Vemurafenib and cKITD816V mediating resistance to Imatinib in blood of patients with melanoma and mastocytosis...
December 27, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29282309/identification-of-a-multipotent-progenitor-population-in-the-spleen-that-is-regulated-by-nr4a1
#4
Melanie D Mumau, Ashley N Vanderbeck, Elizabeth D Lynch, Sophia B Golec, Stephen G Emerson, Jennifer A Punt
The developmental fate of hematopoietic stem and progenitor cells is influenced by their physiological context. Although most hematopoietic stem and progenitor cells are found in the bone marrow of the adult, some are found in other tissues, including the spleen. The extent to which the fate of stem cells is determined by the tissue in which they reside is not clear. In this study, we identify a new progenitor population, which is enriched in the mouse spleen, defined by cKit+CD71lowCD24high expression. This previously uncharacterized population generates exclusively myeloid lineage cells, including erythrocytes, platelets, monocytes, and neutrophils...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29241918/human-amniotic-fluid-stem-cells-have-better-potential-in-early-second-trimester-of-pregnancy-and-can-be-reprogramed-to-ips
#5
S W Steven Shaw, Po-Jen Cheng, Yao-Lung Chang, An-Shine Chao, Tzu-Hao Wang, Shuenn-Dyh Chang, T'sang-T'ang Hsieh, Kuo-Hsuan Chang
OBJECTIVE: To study the difference of amniotic fluid stem cell potential at different gestational age. MATERIALS AND METHODS: Second trimester amniocentesis was performed during 15 to 22nd week of gestational age in a single medical center from 2015 to 2016. Early second trimester amniotic fluid stem cells (E-AFS) and later one (L-AFS) were defined 15-18th week, and 19-22nd week, respectively. Cell characteristics, surface markers and ability to form induced pluripotent stem cells (iPS) were studied...
December 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29239034/succinate-dehydrogenase-sdh-deficient-neoplasia
#6
REVIEW
Anthony J Gill
The succinate dehydrogenase (SDH) complex is a key respiratory enzyme composed of four subunits: SDHA, SDHB, SDHC and SDHD. Remarkably, immunohistochemistry for SDHB becomes negative whenever there is bi-alleic inactivation of any component of SDH, which is very rare in the absence of syndromic disease. Therefore, loss of SDHB immunohistochemistry serves as a marker of syndromic disease, usually germline mutation of one of the SDH subunits. Tumours which show loss of SDHB expression are termed succinate dehydrogenase-deficient...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29184677/cell-free-dna-analysis-by-sire%C3%A2-next-generation-sequencing-panel-in-non-small-cell-lung-cancer-patients-focus-on-basal-setting
#7
Pasquale Pisapia, Francesco Pepe, Riccardo Smeraglio, Maria Russo, Danilo Rocco, Roberta Sgariglia, Mariantonia Nacchio, Caterina De Luca, Elena Vigliar, Claudio Bellevicine, Giancarlo Troncone, Umberto Malapelle
Background: Non small cell lung cancer (NSCLC) is diagnosed in most cases on small tissue samples, such as cytological preparations and histological biopsies; these limited tissue specimens may be not always sufficient for testing epidermal growth factor receptor (EGFR) mutations and other relevant predictive biomarkers. Cell-free DNA (cfDNA) can be used as a surrogate for EGFR mutational testing, whenever tissue is unavailable. However, the detection of gene mutations on cfDNA is challenging; in fact, the extremely low concentration of circulating tumor DNA requires the implementation of highly sensitive and validated next generation techniques...
October 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29147018/enforced-gfi1-expression-impedes-human-and-murine-leukemic-cell-growth
#8
Judith M Hönes, Aniththa Thivakaran, Lacramioara Botezatu, Pradeep Patnana, Symone Vitoriano da Conceição Castro, Yahya S Al-Matary, Judith Schütte, Karen B I Fischer, Lothar Vassen, André Görgens, Ulrich Dührsen, Bernd Giebel, Cyrus Khandanpour
The differentiation of haematopoietic cells is regulated by a plethora of so-called transcription factors (TFs). Mutations in genes encoding TFs or graded reduction in their expression levels can induce the development of various malignant diseases such as acute myeloid leukaemia (AML). Growth Factor Independence 1 (GFI1) is a transcriptional repressor with key roles in haematopoiesis, including regulating self-renewal of haematopoietic stem cells (HSCs) as well as myeloid and lymphoid differentiation. Analysis of AML patients and different AML mouse models with reduced GFI1 gene expression levels revealed a direct link between low GFI1 protein level and accelerated AML development and inferior prognosis...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29124822/advanced-cell-culture-models-for-diamond-blackfan-anemia-and-other-erythroid-disorders
#9
REVIEW
Anna Rita Migliaccio, Lilian Varricchio
In vitro surrogate models of human erythropoiesis made many contributions to our understanding of the extrinsic and intrinsic regulation of this process in vivo and how they are altered in erythroid disorders. In the past, variability among the levels of hemoglobin F produced by adult erythroblasts generated in vitro by different laboratories identified stage of maturation, fetal bovine serum and accessory cells as "confounding factors", i.e. parameters intrinsically wired in the experimental approach that bias the results observed...
November 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/29113963/gain-of-function-of-asxl1-truncating-protein-in-the-pathogenesis-of-myeloid-malignancies
#10
Hui Yang, Stefan Kurtenbach, Ying Guo, Ines Lohse, Michael A Durante, Jianping Li, Zhaomin Li, Hassan Al-Ali, Lingxiao Li, Zizhen Chen, Matthew G Field, Peng Zhang, Shi Chen, Shohei Yamamoto, Zhuo Li, Yuan Zhou, Stephen D Nimer, J William Harbour, Claes Wahlestedt, Mingjiang Xu, Feng-Chun Yang
Additional Sex Combs-Like 1 (ASXL1) is mutated at a high frequency in all forms of myeloid malignancies associated with poor prognosis. We generated a Vav1 promoter driven Flag-Asxl1Y588X transgenic mouse model, Asxl1Y588X Tg, to express a truncated FLAG-ASXL1aa1-587 protein in the hematopoietic system. The Asxl1Y588X Tg mice had an enlarged hematopoietic stem cell (HSC) pool, shortened survival, and predisposition to a spectrum of myeloid malignancies, thereby recapitulating the characteristics of myeloid malignancy patients with ASXL1 mutations...
November 7, 2017: Blood
https://www.readbyqxmd.com/read/29074532/identity-crisis-for-regenerative-cardiac-ckit-cells
#11
Onur Kanisicak, Ronald J Vagnozzi, Jeffery D Molkentin
No abstract text is available yet for this article.
October 27, 2017: Circulation Research
https://www.readbyqxmd.com/read/29050203/loss-of-egr1-a-human-del5q-gene-accelerates-bcr-abl-driven-chronic-myelogenous-leukemia
#12
Silvia Maifrede, Andrew Magimaidas, Xiaojin Sha, Kaushiki Mukherjee, Dan A Liebermann, Barbara Hoffman
There is substantial evidence that early growth response-1 (Egr1) gene, a zinc-finger transcription factor, behaves as a tumor suppressor in leukemia. This includes reports from this laboratory that constitutive Egr1 overrides leukemia conferred by deregulated c-Myc or E2F-1 in the M1 myeloid leukemic cell line by promoting differentiation. To investigate the effect of Egr1 on the initiation and progression of Chronic Myelogenous Leukemia (CML), lethally irradiated syngeneic wild type mice were reconstituted with bone marrow (BM) from either wild type or Egr1 null mice transduced with a 210-kD BCR-ABL-expressing MSCV-retrovirus (bone marrow transplantation {BMT})...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029632/fatal-haemorrhage-and-neoplastic-thrombosis-in-a-captive-african-lion-panthera-leo-with-metastatic-testicular-sex-cord-stromal-tumour
#13
Omar Antonio Gonzales-Viera, Angélica María Sánchez-Sarmiento, Natália Coelho Couto de Azevedo Fernandes, Juliana Mariotti Guerra, Rodrigo Albergaria Ressio, José Luiz Catão-Dias
BACKGROUND: The study of neoplasia in wildlife species contributes to the understanding of cancer biology, management practices, and comparative pathology. Higher frequencies of neoplasms among captive non-domestic felids have been reported most commonly in aging individuals. However, testicular tumours have rarely been reported. This report describes a metastatic testicular sex cord-stromal tumour leading to fatal haemorrhage and thrombosis in a captive African lion (Panthera leo). CASE PRESENTATION: During necropsy of a 16-year-old male African lion, the left testicle and spermatic cord were found to be intra-abdominal (cryptorchid), semi-hard and grossly enlarged with multiple pale-yellow masses...
October 13, 2017: Acta Veterinaria Scandinavica
https://www.readbyqxmd.com/read/28931604/sublethal-total-body-irradiation-causes-long-term-deficits-in-thymus-function-by-reducing-lymphoid-progenitors
#14
Shiyun Xiao, Ivo D Shterev, Wen Zhang, Lauren Young, Jae-Hung Shieh, Malcolm Moore, Marcel van den Brink, Gregory D Sempowski, Nancy R Manley
Total body irradiation (TBI) damages hematopoietic cells in the bone marrow and thymus; however, the long-term effects of irradiation with aging remain unclear. In this study, we found that the impact of radiation on thymopoiesis in mice varied by sex and dose but, overall, thymopoiesis remained suppressed for ≥12 mo after a single exposure. Male and female mice showed a long-term dose-dependent reduction in thymic cKit(+) lymphoid progenitors that was maintained throughout life. Damage to hematopoietic stem cells (HSCs) in the bone marrow was dose dependent, with as little as 0...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28895052/the-effects-of-periostin-in-a-rat-model-of-isoproterenol-mediated-cardiotoxicity
#15
Mahmut Sözmen, Alparslan K Devrim, Yonca B Kabak, Tuba Devrim, Mert Sudagidan
Periostin is an extracellular matrix protein from fasciclin family, and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The present study was designed to investigate cardioprotective effects of the recombinant murine periostin peptide administration in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague Dawley rats in 4 groups (n = 21): control group (1), periostin-treated group (2), ISO-treated group (3), and ISO + periostin-treated group (4)...
September 11, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28868184/multiple-endocrine-neoplasia-2b-differential-increase-in-enteric-nerve-subgroups-in-muscle-and-mucosa
#16
John M Hutson, Pam J Farmer, Cristal J Peck, Chung W Chow, Bridget R Southwell
Multiple endocrine neoplasia 2B (MEN2B) is a rare syndrome caused by an activating mutation of the RET gene, leading to enteric gangliomatosis. This child presented with constipation at 1-mo old, was diagnosed with MEN2B by rectal biopsy at 4 mo, had thyroidectomy at 9 mo and a colectomy at 4 years. We studied the extent of neuronal and nerve fibre proliferation and which classes of enteric nerves are affected by examining the colon with multiple neuronal antibodies. Resected transverse colon was fixed, frozen, sectioned and processed for fluorescence immunohistochemistry labelling with antibodies against TUJ1, Hu, ChAT, NOS, VIP, SP and CGRP and cKit...
August 15, 2017: World Journal of Gastrointestinal Pathophysiology
https://www.readbyqxmd.com/read/28859475/identification-of-slirp-as-a-g-quadruplex-binding-protein
#17
Preston Williams, Lin Li, Xiaoli Dong, Yinsheng Wang
The guanine quadruplex (G4) structure in DNA is a secondary structure motif that plays important roles in DNA replication, transcriptional regulation, and maintenance of genomic stability. Here, we employed a quantitative mass spectrometry-based approach to profile the interaction proteomes of three well-defined G4 structures derived from the human telomere and the promoters of cMYC and cKIT genes. We identified SLIRP as a novel G4-interacting protein. We also demonstrated that the protein could bind directly with G4 DNA with Kd values in the low nanomolar range and revealed that the robust binding of the protein toward G4 DNA requires its RRM domain...
September 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28782271/comparison-of-nitrergic-signaling-in-circular-and-longitudinal-smooth-muscle-of-murine-ileum
#18
B Voussen, K Beck, N Mauro, J Keppler, A Friebe
BACKGROUND: Gastrointestinal (GI) motility originates from coordinated movements of circular (CM) and longitudinal (LM) smooth muscle. How the two muscle layers react individually to nitrergic input and how they integrate nitrergic signaling is not thoroughly understood. METHODS: We used immunohistochemistry to unveil expression of NO-sensitive guanylyl cyclase (NO-GC) in the ileum. For functional analyses, we measured tone of ileal CM and spontaneous contractions in both ileal muscle layers from mice lacking NO-GC globally (GCKO) and specifically in smooth muscle cells (SMC-GCKO)...
August 7, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28774773/degradation-of-extracellular-dna-by-dnase1-significantly-reduces-testicular-damage-after-testicular-torsion-in-rats
#19
Michael Boettcher, Dennis Meier, Miguel Jiménez-Alcázar, Georg Eschenburg, Stefan Mietzsch, Deirdre Vincent, Michaela Klinke, Magdalena Trochimiuk, Birgit Appl, Bastian Tiemann, Robert Bergholz, Konrad Reinshagen, Tobias A Fuchs
OBJECTIVE: To examine the effects of DNase1 treatment on testicular damage after testicular torsion (TT). It has been demonstrated that TT induces thrombus formation and that anticoagulation significantly reduces testicular damage after TT. It was hypothesized that these thrombi are dependent on neutrophil extracellular traps (NETs) and thus NETs disintegration would reduce testicular cell damage. METHODS: A sham operation was performed in 10 rats. Thirty-four rats underwent induction of iatrogenic TT for 3 hours...
November 2017: Urology
https://www.readbyqxmd.com/read/28736634/gastrointestinal-stromal-tumors-gists-point-mutations-matter-in-management-a-review
#20
REVIEW
Peter J Oppelt, Angela C Hirbe, Brian A Van Tine
The therapeutic implications of the genomic alterations seen within the drivers of gastrointestinal stromal tumors (GIST) are among the best understood in all of solid tumors. Sequencing of cKIT and PDGFRα should be considered standard practice for the treatment of GIST patients. In this article, we will review the common mutations and how they are utilized in clinical management. In addition, we will review the rare D842V PDGFRα mutation and the diverse molecular group that lacks a mutation in either cKIT or PDGFRα (wild-type GIST) which are best treated on clinical trial...
June 2017: Journal of Gastrointestinal Oncology
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