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https://www.readbyqxmd.com/read/29151133/treatment-of-relapsed-aml-and-mds-after-allogeneic-stem-cell-transplantation-with-decitabine-and-dli-a-retrospective-multicenter-analysis-on-behalf-of-the-german-cooperative-transplant-study-group
#1
Thomas Schroeder, Christina Rautenberg, William Krüger, Uwe Platzbecker, Gesine Bug, Juliane Steinmann, Stefan Klein, Olaf Hopfer, Kathrin Nachtkamp, Mustafa Kondakci, Stefanie Geyh, Rainer Haas, Ulrich Germing, Martin Bornhäuser, Guido Kobbe
In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11)...
November 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29150295/paternal-transmission-of-early-life-traumatization-through-epigenetics-do-fathers-play-a-role
#2
Enrique d'Harcourt Rowold, Lara Schulze, Sandra Van der Auwera, Hans Jörgen Grabe
Traumatizing events are known to have consequences for the victim which may lead to the development of several well-known mental disorders. Recent research has shown that traumatic events may affect not only the victims' lives, but also that of their progeny. It is generally accepted that this transmission of trauma occurs through parental behavior; however as has been recently discovered, the effects of trauma may also be inherited due to induced alterations in gene expression. These changes, so called epigenetic modifications, illuminate the interaction between genes and the environment...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150092/generation-of-integration-free-induced-pluripotent-stem-cell-lines-derived-from-two-patients-with-x-linked-alport-syndrome-xlas
#3
Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, Angel Raya
Skin biopsies were obtained from two male patients with X-linked Alport syndrome (XLAS) with hemizygous COL4A5 mutations in exon 41 or exon 46. Dermal fibroblasts were extracted and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53 shRNA. The generated induced Pluripotent Stem Cell (iPSC) lines AS-FiPS2-Ep6F-28 and AS-FiPS3-Ep6F-9 were free of genomically integrated reprogramming genes, had the specific mutations, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro...
September 9, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29149760/patterns-of-relapse-in-poor-prognosis-germ-cell-tumours-in-the-getug-13-trial-implications-for-assessment-of-brain-metastases
#4
Y Loriot, L Pagliaro, A Fléchon, J Mardiak, L Geoffrois, P Kerbrat, C Chevreau, R Delva, F Rolland, C Theodore, G Roubaud, G Gravis, J C Eymard, J P Malhaire, C Linassier, M Habibian, A L Martin, F Journeau, M Reckova, C Logothetis, A Laplanche, G Le Teuff, S Culine, K Fizazi
BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain...
November 14, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29148973/the-somatically-generated-portion-of-the-t-cell-receptor-cdr3%C3%AE-contributes-to-the-mhc-allele-specificity-of-the-t-cell-receptor
#5
Philippa Marrack, Sai Harsha Krovi, Daniel Silberman, Janice White, Eleanor Kushnir, Maki Nakayama, James Crooks, Thomas Danhorn, Sonia Leach, Randy Anselment, James Scott-Browne, Laurent Gapin, John Kappler
Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29148101/homeobox-protein-msx-1-inhibits-expression-of-bone-morphogenetic-protein-2-bone-morphogenetic-protein-4-and-lymphoid-enhancer-binding-factor-1-via-wnt-%C3%AE-catenin-signaling-to-prevent-differentiation-of-dental-mesenchymal-cells-during-the-late-bell-stage
#6
Xiao-Yu Feng, Xiao-Shan Wu, Jin-Song Wang, Chun-Mei Zhang, Song-Lin Wang
Homeobox protein MSX-1 (hereafter referred to as MSX-1) is essential for early tooth-germ development. Tooth-germ development is arrested at bud stage in Msx1 knockout mice, which prompted us to study the functions of MSX-1 beyond this stage. Here, we investigated the roles of MSX-1 during late bell stage. Mesenchymal cells of the mandibular first molar were isolated from mice at embryonic day (E)17.5 and cultured in vitro. We determined the expression levels of β-catenin, bone morphogenetic protein 2 (Bmp2), Bmp4, and lymphoid enhancer-binding factor 1 (Lef1) after knockdown or overexpression of Msx1...
November 17, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/29147855/phase-ii-study-of-palonosetron-aprepitant-and-dexamethasone-to-prevent-nausea-and-vomiting-induced-by-multiple-day-emetogenic-chemotherapy
#7
Takeshi Ioroi, Junya Furukawa, Manabu Kume, Sachi Hirata, Yuko Utsubo, Naomi Mizuta, Hideaki Miyake, Masato Fujisawa, Midori Hirai
PURPOSE: This study aimed to determine the antiemetic efficacy and safety of palonosetron, aprepitant and dexamethasone in patients with testicular germ cell tumours (TGCTs) receiving 5-day cisplatin-based combination chemotherapy. METHODS: In this open-label, single-arm, single-centre study, the antiemetic therapy consisted of palonosetron 0.75 mg on day 1, aprepitant 125 mg on day 1 and 80 mg on days 2-7 and dexamethasone 6.6 mg on days 1-7. The primary endpoint was complete response (CR; no vomiting/retching or rescue medication) in the overall period (0-240 h), and secondary endpoints included complete protection (CP; defined as CR and no more than mild nausea) and total control (TC; defined as CR and no nausea)...
November 16, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29147574/generational-comparisons-f1-versus-f3-of-vinclozolin-induced-epigenetic-transgenerational-inheritance-of-sperm-differential-dna-methylation-regions-epimutations-using-medip-seq
#8
Daniel Beck, Ingrid Sadler-Riggleman, Michael K Skinner
Environmentally induced epigenetic transgenerational inheritance of disease and phenotypic variation has been shown to involve DNA methylation alterations in the germline (e.g. sperm). These differential DNA methylation regions (DMRs) are termed epimutations and in part transmit the transgenerational phenotypes. The agricultural fungicide vinclozolin exposure of a gestating female rat has previously been shown to promote transgenerational disease and epimutations in F3 generation (great-grand-offspring) animals...
July 2017: Environmental Epigenetics
https://www.readbyqxmd.com/read/29146461/resveratrol-supports-and-alpha-naphthoflavone-disrupts-growth-of-human-ovarian-follicles-in-an-in-vitro-tissue-culture-model
#9
Jie Hao, Astrud R Tuck, Marcus O D Sjödin, Johan Lindberg, Anna Sand, Boel Niklasson, Maria Argyraki, Outi Hovatta, Pauliina Damdimopoulou
Infertility is a global health problem with an estimated incidence of 15%. Exposure to chemicals is a potential causal factor, and there is a lack of studies examining the effects on female germ cells. Here, we have studied the impact of different aryl hydrocarbon receptor (AHR) modulators on human ovarian follicles using a human ovarian tissue culture model. Expression of AHR was analyzed in tissue samples, and effects of the selected ligands resveratrol (RSVL), 6-formylindolo(3,2-b)carbazole (FICZ), and alpha-naphthoflavone (aNF) on AHR transactivation studied in a granulosa cell tumor line...
November 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29146413/ct-fluoroscopy-guided-core-needle-biopsy-of-anterior-mediastinal-masses
#10
T Iguchi, T Hiraki, Y Matsui, H Fujiwara, J Sakurai, Y Masaoka, M Uka, T Tanaka, H Gobara, S Kanazawa
OBJECTIVE: To retrospectively evaluate the safety, diagnostic yield, and risk factors of diagnostic failure of computed tomography (CT) fluoroscopy-guided biopsies of anterior mediastinal masses. MATERIALS AND METHODS: Biopsy procedures and results of anterior mediastinal masses in 71 patients (32 women/39 men; mean [±standard deviation] age, 53.8±20.0years; range, 14-88years) were analyzed. Final diagnoses were based on surgical outcomes, imaging findings, or clinical follow-up findings...
November 13, 2017: Diagnostic and Interventional Imaging
https://www.readbyqxmd.com/read/29145898/making-gametes-from-alternate-sources-of-stem-cells-past-present-and-future
#11
REVIEW
Deepa Bhartiya, Sandhya Anand, Hiren Patel, Seema Parte
Infertile couples including cancer survivors stand to benefit from gametes differentiated from embryonic or induced pluripotent stem (ES/iPS) cells. It remains challenging to convert human ES/iPS cells into primordial germ-like cells (PGCLCs) en route to obtaining gametes. Considerable success was achieved in 2016 to obtain fertile offspring starting with mouse ES/iPS cells, however the specification of human ES/iPS cells into PGCLCs in vitro is still not achieved. Human ES cells will not yield patient-specific gametes unless and until hES cells are derived by somatic cell nuclear transfer (therapeutic cloning) whereas iPS cells retain the residual epigenetic memory of the somatic cells from which they are derived and also harbor genomic and mitochondrial DNA mutations...
November 16, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29145655/paternal-exposure-to-environmental-chemical-stress-affectsmale-offspring-s-hepatic-mitochondria
#12
Roger Godschalk, Alex Remels, Camiel Hoogendoorn, Jan van Benthem, Mirjam Luijten, Nur Duale, Gunnar Brunborg, Ann-Karin Olsen, Freek G Bouwman, Armelle Munnia, Marco Peluso, Edwin Mariman, Frederik Jan van Schooten
Pre-conceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3x per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29145128/microgravity-simulation-activates-cdc42-via-rap1gds1-to-promote-vascular-branch-morphogenesis-during-vasculogenesis
#13
Shouli Wang, Zhao Yin, Bei Zhao, Yanmei Qi, Jie Liu, Saum A Rahimi, Leonard Y Lee, Shaohua Li
Gravity plays an important role in normal tissue maintenance. The ability of stem cells to repair tissue loss in space through regeneration and differentiation remains largely unknown. To investigate the impact of microgravity on blood vessel formation from pluripotent stem cells, we employed the embryoid body (EB) model for vasculogenesis and simulated microgravity by clinorotation. We first differentiated mouse embryonic stem cells into cystic EBs containing two germ layers and then analyzed vessel formation under clinorotation...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29144948/re-the-world-health-organization-2016-classification-of-testicular-germ-cell-tumours-a-review-and-update-from-the-international-society-of-urological-pathology-testis-consultation-panel
#14
https://www.readbyqxmd.com/read/29143989/nanos2-promotes-differentiation-of-chicken-gallus-gallus-embryonic-stem-cells-to-male-germ-cells
#15
Zhang Wenhui, Bi Yulin, Wang Yingjie, Li Dong, He Nana, Wang Man, Jin Jing, Zuo Qisheng, Zhang Yani, Li Bichun
Nanos2 is an evolutionarily conserved RNA-binding protein containing 2 CCHC-type zinc finger motives. Here, we report that Nanos2 is strongly expressed in the testis compared to other tissues in chicken (Gallus gallus). Overexpression and knockout plasmid vectors were constructed, and in-vitro Cas9/gRNA digestion and T7 endonuclease I (T7E1) assay indicated that Nanos2-g1 possessed the highest knockout activity. In vitro and in vivo, Nanos2 overexpression accelerated the production of embryoid bodies (EBs) and SSC-like cells and promoted cvh, c-kit and integrin α6 expression...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29143560/induced-pluripotent-stem-cells-derived-from-human-amnion-in-chemically-defined-conditions
#16
Jaroslav Slamecka, Steven McClellan, Anna Wilk, Javier Laurini, Elizabeth Manci, Simon P Hoerstrup, Benedikt Weber, Laurie Owen
Fetal stem cells are a unique type of adult stem cells that have been suggested to be broadly multipotent with some features of pluripotency. Their clinical potential has been documented but their upgrade to full pluripotency could open up a wide range of cell-based therapies particularly suited for pediatric tissue engineering, longitudinal studies or disease modeling. Here we describe episomal reprogramming of mesenchymal stem cells from the human amnion to pluripotency (AM-iPSC) in chemically defined conditions...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29143282/hypomethylating-agents-for-treatment-and-prevention-of-relapse-after-allogeneic-blood-stem-cell-transplantation
#17
REVIEW
Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe
Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT...
November 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29142409/reversible-testicular-toxicity-of-piperine-on-male-albino-rats
#18
Gopichand Chinta, Mohane Selvaraj Coumar, Latha Periyasamy
Background: Piperine was widely used in traditional medicine for inducing sterility and abortion. Objective: To evaluate the effect of the piperine on testis of male albino rats. Materials and Methods: Adult male rats were divided into four groups (n = 12). Group I (control): Rats were given vehicle p.o. i.e. 0.5% carboxymethyl cellulose in normal saline daily for 60 days, Group II (ED): Rats received piperine at a dose of 10 mg/kg body weight (b...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142301/alteration-of-the-intestinal-microbiome-characterizes-preclinical-inflammatory-arthritis-in-mice-and-its-modulation-attenuates-established-arthritis
#19
Rebecca Rogier, Heather Evans-Marin, Julia Manasson, Peter M van der Kraan, Birgitte Walgreen, Monique M Helsen, Liduine A van den Bersselaar, Fons A van de Loo, Peter L van Lent, Steven B Abramson, Wim B van den Berg, Marije I Koenders, Jose U Scher, Shahla Abdollahi-Roodsaz
Perturbations of the intestinal microbiome have been observed in patients with new-onset and chronic autoimmune inflammatory arthritis. However, it is currently unknown whether these alterations precede the development of arthritis or are rather a consequence of disease. Modulation of intestinal microbiota by oral antibiotics or germ-free condition can prevent arthritis in mice. Yet, the therapeutic potential of modulation of the microbiota after the onset of arthritis is not well characterized. We here show that the intestinal microbial community undergoes marked changes in the preclinical phase of collagen induced arthritis (CIA)...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142208/transient-increases-in-intracellular-calcium-and-reactive-oxygen-species-levels-in-tcam-2-cells-exposed-to-microgravity
#20
C Morabito, S Guarnieri, A Catizone, C Schiraldi, G Ricci, M A Mariggiò
The effects of microgravity on functions of the human body are well described, including alterations in the male and female reproductive systems. In the present study, TCam-2 cells, which are considered a good model of mitotically active male germ cells, were used to investigate intracellular signalling and cell metabolism during exposure to simulated microgravity, a condition that affects cell shape and cytoskeletal architecture. After a 24 hour exposure to simulated microgravity, TCam-2 cells showed 1) a decreased proliferation rate and a delay in cell cycle progression, 2) increased anaerobic metabolism accompanied by increased levels of intracellular Ca(2+), reactive oxygen species and superoxide anion and modifications in mitochondrial morphology...
November 15, 2017: Scientific Reports
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