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https://www.readbyqxmd.com/read/29346763/derepression-of-the-iroquois-homeodomain-transcription-factor-gene-irx3-confers-differentiation-block-in-acute-leukemia
#1
Tim D D Somerville, Fabrizio Simeoni, John A Chadwick, Emma L Williams, Gary J Spencer, Katalin Boros, Christopher Wirth, Eleni Tholouli, Richard J Byers, Tim C P Somervaille
The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML), ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346562/scaffold-free-trachea-regeneration-by-tissue-engineering-with-bio-3d-printing
#2
Daisuke Taniguchi, Keitaro Matsumoto, Tomoshi Tsuchiya, Ryusuke Machino, Yosuke Takeoka, Abdelmotagaly Elgalad, Kiyofumi Gunge, Katsunori Takagi, Yasuaki Taura, Go Hatachi, Naoto Matsuo, Naoya Yamasaki, Koichi Nakayama, Takeshi Nagayasu
OBJECTIVES: Currently, most of the artificial airway organs still require scaffolds; however, such scaffolds exhibit several limitations. Alternatively, the use of an autologous artificial trachea without foreign materials and immunosuppressants may solve these issues and constitute a preferred tool. The rationale of this study was to develop a new scaffold-free approach for an artificial trachea using bio-3D printing technology. Here, we assessed the circumferential tracheal replacement using scaffold-free trachea-like grafts generated from isolated cells in an inbred animal model...
January 15, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29345968/mature-gastric-chief-cells-are-not-required-for-the-development-of-metaplasia
#3
Hiroto Kinoshita, Yoku Hayakawa, Zhengchuan Niu, Mitsuru Konishi, Masahiro Hata, Mayo Tsuboi, Yuki Hayata, Yohko Hikiba, Sozaburo Ihara, Hayato Nakagawa, Yoshihiro Hirata, Timothy C Wang, K Koike
During human gastric carcinogenesis, intestinal metaplasia (IM) is frequently seen in the atrophic stomach. In mice, a distinct type of metaplasia known as spasmolytic polypeptide-expressing metaplasia (SPEM) is found in several inflammatory and genetically engineered models. Given the diversity of long- and short-term models of mouse SPEM, it remains unclear whether all models have a shared or distinct molecular mechanism. The origin of SPEM in mice is currently under debate. It is postulated that stem or progenitor cells acquire genetic alterations that then supply metaplastic cell clones, while the possibility of transdifferentiation or dedifferentiation from mature gastric chief cells has also been suggested...
January 18, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29345518/bacterial-pathogenesis-and-interleukin-17-interconnecting-mechanisms-of-immune-regulation-host-genetics-and-microbial-virulence-that-influence-severity-of-infection
#4
Michelle N Chamoun, Antje Blumenthal, Matthew J Sullivan, Mark A Schembri, Glen C Ulett
Interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the control of many different disorders, including autoimmune, oncogenic, and diverse infectious diseases. In the context of infectious diseases, IL-17 protects the host against various classes of microorganisms but, intriguingly, can also exacerbate the severity of some infections. The regulation of IL-17 expression stems, in part, from the activity of Interleukin-23 (IL-23), which drives the maturation of different classes of IL-17-producing cells that can alter the course of infection...
January 18, 2018: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/29345353/hipop-mesenchymal-population-has-high-potential-for-repairing-injured-peripheral-nerves
#5
Yukako Yamauchi, Shousaku Itoh, Haruna Naruse, Yuki Itoh, Makoto Abe, Takumi Kagioka, Mikako Hayashi
Bone marrow stromal cells (BMSCs) are reportedly a heterogeneous population of mesenchymal stem cells (MSCs). Recently, we developed a simple strategy for the enrichment of MSCs with the capacity to differentiate into osteoblasts, chondrocytes, and adipocytes. On transplantation, the progenitor-enriched fractions can regenerate the bone with multiple lineages of donor origin and are thus called "highly purified osteoprogenitors" (HipOPs). Although our previous studies have demonstrated that HipOPs are enriched with MSCs and exhibit a higher potential to differentiate into osteoblasts, adipocytes, and chondrocytes than BMSCs, their potential to differentiate into neural cells has not been clarified...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345101/a-pdgf-ccreert2-knock-in-mouse-model-for-tracing-pdgf-c-cell-lineages-during-development
#6
Xiaoli Wu, Wenjun Liu, Hao Ding
PDGF-C, a member of the platelet-derived growth factor (PDGF) family, plays important roles in the development of craniofacial structures, the neural system, the vascular system and tumors. PDGF-C could also be required for the regulation of certain types of stem or progenitor cells as suggested by its expression in the regions where these cells are located. To further characterize the role of PDGF-C in development, we generated a Pdgf-cCreERT2 mouse strain, in which a tamoxifen-inducible Cre (CreERT2) cDNA was specifically targeted into the Pdgf-c genomic locus and controlled by the endogenous Pdgf-c regulatory elements...
January 18, 2018: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29344995/activation-of-human-cd141-and-cd1c-dendritic-cells-in-vivo-with-combined-tlr-3-and-tlr-7-8-ligation
#7
Frances E Pearson, Karshing Chang, Yoshihito Minoda, Ingrid M Leal Rojas, Oscar L Haigh, Ghazal Daraj, Kirsteen M Tullett, Kristen J Radford
Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+ cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+ /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte (CTL) responses, making them attractive targets to exploit for the development of new cancer immunotherapies...
January 18, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29344417/the-effect-of-traditional-chinese-medicine-on-neural-stem-cell-proliferation-and-differentiation
#8
REVIEW
Wei Qin, Shiya Chen, Shasha Yang, Qian Xu, Chuanshan Xu, Jing Cai
Neural stem cells (NSCs) are special types of cells with the potential for self-renewal and multi-directional differentiation. NSCs are regulated by multiple pathways and pathway related transcription factors during the process of proliferation and differentiation. Numerous studies have shown that the compound medicinal preparations, single herbs, and herb extracts in traditional Chinese medicine (TCM) have specific roles in regulating the proliferation and differentiation of NSCs. In this study, we investigate the markers of NSCs in various stages of differentiation, the related pathways regulating the proliferation and differentiation, and the corresponding transcription factors in the pathways...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29344309/adult-stem-cells-in-vascular-remodeling
#9
REVIEW
Dong Wang, LeeAnn K Li, Tiffany Dai, Aijun Wang, Song Li
Understanding the contribution of vascular cells to blood vessel remodeling is critical for the development of new therapeutic approaches to cure cardiovascular diseases (CVDs) and regenerate blood vessels. Recent findings suggest that neointimal formation and atherosclerotic lesions involve not only inflammatory cells, endothelial cells, and smooth muscle cells, but also several types of stem cells or progenitors in arterial walls and the circulation. Some of these stem cells also participate in the remodeling of vascular grafts, microvessel regeneration, and formation of fibrotic tissue around biomaterial implants...
2018: Theranostics
https://www.readbyqxmd.com/read/29344263/thalidomide-inhibits-proliferation-and-epithelial-mesenchymal-transition-by-modulating-cd133-expression-in-pancreatic-cancer-cells
#10
Congying Chen, Ge Yu, Wenqin Xiao, Miao Xing, Jianbo Ni, Rong Wan, Guoyong Hu
Pancreatic cancer is a solid malignancy with a high mortality rate, on account of the high incidence of metastasis at the time of detection. The aggressiveness of pancreatic cancer may be partly driven by cancer stem cells (CSCs), which are characterized by the ability to self-renew and recapitulate tumors in the ectopic setting. However, although a number of drugs targeting CSCs are currently under clinical investigation, few effective drugs have been developed. The present study demonstrated that thalidomide inhibited cell proliferation and metastasis in pancreatic cancer cell lines through the inhibition of epithelial mesenchymal transition...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344217/aleukemic-extramedullary-t-lymphoid-myeloid-bilineage-hematopoietic-and-lymphoid-malignancy-with-progression-to-bilineage-leukemia-at-relapse-a-case-report
#11
Mengyao Wu, Xiaoqiu Li, Feng Tang, Ping Zhu, Tianling Ding, Yan Yuan, Tong Chen
Bilineage T lymphoid and myeloid (T/My) neoplasms are rare entities among the hematopoietic and lymphoid malignancies. The majority of patients present with leukemic symptoms in which blasts are observed in the peripheral blood (PB) or bone marrow (BM) at a percentage of >20% of nucleated cells. Only a minimal number of cases of T/My bilineage hematopoietic and lymphoid malignancy have been reported with extramedullary infiltration as the initial symptom. The origin of the neoplastic cells in T/My bilineage malignancy has been documented as the hematopoietic stem cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344178/long-non-coding-rna-lnctcf7-activates-the-wnt-%C3%AE-catenin-pathway-to-promote-metastasis-and-invasion-in-colorectal-cancer
#12
Tengyu Li, Jing Zhu, Xin Wang, Guowei Chen, Lie Sun, Shuai Zuo, Junling Zhang, Shanwen Chen, Ju Ma, Zihao Yao, Youwen Zheng, Zeyang Chen, Yucun Liu, Pengyuan Wang
Long non-coding RNA (Lnc)TCF7 is a novel lncRNA that is involved in tumorigenesis. Previous studies have revealed that lncTCF7 serves an essential role in maintaining cancer stem cell self-renewal; however, the functions of lncTCF7 in colorectal cancer (CRC) remain unknown. Therefore, the present study aimed to investigate the role of lncTCF7 in CRC. LncTCF7 was upregulated in 52/58 CRC tissues, and its expression correlated with tumor size, lymph metastasis and tumor-node-metastasis stage in CRC. Knocking down lncTCF7 in colon cancer cell lines decreased cell proliferation, migration and invasion, while lncTCF7 overexpression showed opposite changes...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344017/global-registration-identifier-for-donors-grid-of-hematopoietic-stem-cells-road-to-automation-and-safety
#13
REVIEW
Joachim Klaus Neller, Paul Ashford, Caroline van Veen, Andreas Humpe
Once a cohort exceeds a certain size, it becomes mandatory to assign an identifier (ID) for each individual to ensure a secure, reliable, and unambiguous assignment. In the field of hematopoietic stem cell transplantation, with a still growing number of voluntary unrelated donors, it was recognized that a system needs to be developed to uniquely identify potential donors on a global scale to facilitate communication and to prevent errors in identification of donors. Efforts in this respect resulted in establishment of the GRID, with a defined structure and allocated rules...
November 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/29343975/spotlight-on-midostaurin-in-the-treatment-of-flt3-mutated-acute-myeloid-leukemia-and-systemic-mastocytosis-design-development-and-potential-place-in-therapy
#14
REVIEW
Ellen Weisberg, Martin Sattler, Paul W Manley, James D Griffin
The Fms-like tyrosine kinase-3 (FLT3; fetal liver kinase-2; human stem cell tyrosine kinase-1; CD135) is a class III receptor tyrosine kinase that is normally involved in regulating the proliferation, differentiation, and survival of both hematopoietic cells and dendritic cells. Mutations leading it to be constitutively activated make it an oncogenic driver in ~30% of acute myeloid leukemia (AML) patients where it is associated with poor prognosis. The prevalence of oncogenic FLT3 and the dependency on its constitutively activated kinase activity for leukemia growth make this protein an attractive target for therapeutic intervention...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29343865/targeting-murine-leukemic-stem-cells-by-antibody-functionalized-mesoporous-silica-nanoparticles
#15
Tamoghna Mandal, Michaela Beck, Nicole Kirsten, Mika Lindén, Christian Buske
Acute leukemia is initiated and maintained by leukemia stem cells (LSCs) and therefore there is great interest to develop innovative therapeutic approaches which target LSCs. Here we show that mesoporous silica nanoparticles (MSNs) functionalized with succinic anhydride, tagged with an anti-B220 antibody and loaded with the anthracycline daunorubicin are efficiently incorporated into murine B220-positive AML LSCs and preferentially kill these cells in comparison to B220-negative AML LSCs in vitro. Furthermore, short - term treatment of the AML LSCs with these MSNs before transplant significantly delayed leukemia development in recipient mice...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343849/mutant-p53-gain-of-function-underlies-high-expression-levels-of-colorectal-cancer-stem-cells-markers
#16
Hilla Solomon, Nathan Dinowitz, Ioannis S Pateras, Tomer Cooks, Yoav Shetzer, Alina Molchadsky, Meital Charni, Stav Rabani, Gabriela Koifman, Ohad Tarcic, Ziv Porat, Ira Kogan-Sakin, Naomi Goldfinger, Moshe Oren, Curtis C Harris, Vassilis G Gorgoulis, Varda Rotter
Emerging notion in carcinogenesis ascribes tumor initiation and aggressiveness to cancer stem cells (CSCs). Specifically, colorectal cancer (CRC) development was shown to be compatible with CSCs hypothesis. Mutations in p53 are highly frequent in CRC, and are known to facilitate tumor development and aggressiveness. Yet, the link between mutant p53 and colorectal CSCs is not well-established. In the present study, we set to examine whether oncogenic mutant p53 proteins may augment colorectal CSCs phenotype...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29343653/establishment-of-a-screening-system-to-identify-novel-gata-2-transcriptional-regulators
#17
Keiichi Ohashi, Tohru Fujiwara, Koichi Onodera, Yo Saito, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is essential for cell proliferation and differentiation. Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia and acute myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which is associated with increased susceptibility to viral infections...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29343646/role-of-boundary-conditions-in-determining-cell-alignment-in-response-to-stretch
#18
Kellen Chen, Andrea Vigliotti, Mattia Bacca, Robert M McMeeking, Vikram S Deshpande, Jeffrey W Holmes
The ability of cells to orient in response to mechanical stimuli is essential to embryonic development, cell migration, mechanotransduction, and other critical physiologic functions in a range of organs. Endothelial cells, fibroblasts, mesenchymal stem cells, and osteoblasts all orient perpendicular to an applied cyclic stretch when plated on stretchable elastic substrates, suggesting a common underlying mechanism. However, many of these same cells orient parallel to stretch in vivo and in 3D culture, and a compelling explanation for the different orientation responses in 2D and 3D has remained elusive...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343582/hiv-replication-and-latency-in-a-humanized-nsg-mouse-model-during-suppressive-oral-combinational-art
#19
Sangeetha Satheesan, Haitang Li, John C Burnett, Mayumi Takahashi, Shasha Li, Shiny Xiaqin Wu, Timothy W Synold, John J Rossi, Jiehua Zhou
Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, they cannot accurately represent the quiescent cellular environment of primary latently infected cells in vivo...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343483/nr4a1-and-nr4a3-restrict-hsc-proliferation-via-reciprocal-regulation-of-c-ebp%C3%AE-and-inflammatory-signaling
#20
Pablo R Freire, Orla M Conneely
Members of the NR4A subfamily of nuclear receptors have complex, overlapping roles during hematopoietic cell development and also function as tumor suppressors of hematological malignancies. We previously identified NR4A1 and NR4A3 as functionally redundant suppressors of AML development. However, their role in hematopoietic stem cell (HSC) homeostasis remains to be disclosed. Using a conditional Nr4a1/Nr4a3 knockout mouse (CDKO), we show that codepletion of NR4A1/3 promotes acute changes in HSC homeostasis including loss of HSC quiescence, accumulation of oxidative stress and DNA damage while maintaining stem cell regenerative and differentiation capacity...
January 17, 2018: Blood
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