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https://www.readbyqxmd.com/read/28202525/oncogenic-effects-of-high-mapk-activity-in-colorectal-cancer-mark-progenitor-cells-and-persist-irrespective-of-ras-mutations
#1
Cristina Blaj, Eva Marina Schmidt, Sebastian Lamprecht, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
About 40% of colorectal cancers have mutations in KRAS accompanied by downstream activation of MAPK signaling which promotes tumor invasion and progression. Here we report that MAPK signaling shows strong intratumoral heterogeneity and unexpectedly remains regulated in colorectal cancer irrespective of KRAS mutation status. Using primary colorectal cancer tissues, xenograft models and MAPK reporter constructs, we showed that tumor cells with high MAPK activity resided specifically at the leading tumor edge, ceased to proliferate, underwent epithelial-mesenchymal transition (EMT), and expressed markers related to colon cancer stem cells...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202042/hoxc8-regulates-self-renewal-differentiation-and-transformation-of-breast-cancer-stem-cells
#2
Mansi Shah, Ryan Cardenas, Belinda Wang, Jenny Persson, Nigel P Mongan, Anna Grabowska, Cinzia Allegrucci
BACKGROUND: Homeobox genes are master regulators of cell fate during embryonic development and their expression is altered in cancer. By regulating the balance between cell proliferation and differentiation, they maintain homeostasis of normal tissues. Here, we screened the expression of homeobox genes in mammary stem cells to establish their role in stem cells transformation in breast cancer. METHODS: Using a Homeobox Genes PCR array, we screened 83 homeobox genes in normal cancer breast stem/progenitor cells isolated by flow cytometry...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#3
Matthias Schröder, Simone Loos, Svenja Kerstin Naumann, Christopher Bachran, Marit Krötschel, Viktor Umansky, Laura Helming, Lee Kim Swee
Tumors are infiltrated by cells of the immune system that interact through complex regulatory networks. Although tumor-specific CD8(+) T cells can be found in peripheral blood and tumor samples from cancer patients, their function is inhibited by immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). Recent clinical successes have demonstrated that alleviating immunosuppression and T cell exhaustion translates into long-term clinical benefits...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196804/nipped-a-regulates-intestinal-stem-cell-proliferation-in-drosophila
#4
Helen Marie Tauc, Alpaslan Tasdogan, Patrick Meyer, Petra Pandur
Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In Drosophila, intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28192057/tongue-and-taste-organ-biology-and-function-homeostasis-maintained-by-hedgehog-signaling
#5
Charlotte M Mistretta, Archana Kumari
The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28186102/cancer-cell-secreted-igf2-instigates-fibroblasts-and-bone-marrow-derived-vascular-progenitor-cells-to-promote-cancer-progression
#6
Wen Wen Xu, Bin Li, Xin Yuan Guan, Sookja K Chung, Yang Wang, Yim Ling Yip, Simon Y K Law, Kin Tak Chan, Nikki P Y Lee, Kwok Wah Chan, Li Yan Xu, En Min Li, Sai Wah Tsao, Qing-Yu He, Annie L M Cheung
Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28181481/dpath-software-reveals-hierarchical-haemato-endothelial-lineages-of-etv2-progenitors-based-on-single-cell-transcriptome-analysis
#7
Wuming Gong, Tara L Rasmussen, Bhairab N Singh, Naoko Koyano-Nakagawa, Wei Pan, Daniel J Garry
Developmental, stem cell and cancer biologists are interested in the molecular definition of cellular differentiation. Although single-cell RNA sequencing represents a transformational advance for global gene analyses, novel obstacles have emerged, including the computational management of dropout events, the reconstruction of biological pathways and the isolation of target cell populations. We develop an algorithm named dpath that applies the concept of metagene entropy and allows the ranking of cells based on their differentiation potential...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28178280/knockdown-of-hspa9-induces-tp53-dependent-apoptosis-in-human-hematopoietic-progenitor-cells
#8
Tuoen Liu, Kilannin Krysiak, Cara Lunn Shirai, Sanghyun Kim, Jin Shao, Matthew Ndonwi, Matthew J Walter
Myelodysplastic syndromes (MDS) are the most common adult myeloid blood cancers in the US. Patients have increased apoptosis in their bone marrow cells leading to low peripheral blood counts. The full complement of gene mutations that contribute to increased apoptosis in MDS remains unknown. Up to 25% of MDS patients harbor and acquired interstitial deletion on the long arm of chromosome 5 [del(5q)], creating haploinsufficiency for a large set of genes including HSPA9. Knockdown of HSPA9 in primary human CD34+ hematopoietic progenitor cells significantly inhibits growth and increases apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28173797/tumour-associated-glial-host-cells-display-a-stem-like-phenotype-with-a-distinct-gene-expression-profile-and-promote-growth-of-gbm-xenografts
#9
Lina Leiss, Ercan Mutlu, Anne Øyan, Tao Yan, Oleg Tsinkalovsky, Linda Sleire, Kjell Petersen, Mohummad Aminur Rahman, Mireille Johannessen, Sidhartha S Mitra, Hege K Jacobsen, Krishna M Talasila, Hrvoje Miletic, Inge Jonassen, Xingang Li, Nicolaas H Brons, Karl-Henning Kalland, Jian Wang, Per Øyvind Enger
BACKGROUND: Little is known about the role of glial host cells in brain tumours. However, supporting stromal cells have been shown to foster tumour growth in other cancers. METHODS: We isolated stromal cells from patient-derived glioblastoma (GBM) xenografts established in GFP-NOD/scid mice. With simultaneous removal of CD11b(+) immune and CD31(+) endothelial cells by fluorescence activated cell sorting (FACS), we obtained a population of tumour-associated glial cells, TAGs, expressing markers of terminally differentiaed glial cell types or glial progenitors...
February 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28170182/primary-salivary-human-stem-progenitor-cells-undergo-microenvironment-driven-acinar-like-differentiation-in-hyaluronate-hydrogel-culture
#10
Padma Pradeepa Srinivasan, Vaishali N Patel, Shuang Liu, Daniel A Harrington, Matthew P Hoffman, Xinqiao Jia, Robert L Witt, Mary C Farach-Carson, Swati Pradhan-Bhatt
Radiotherapy for head and neck cancer often has undesirable effects on salivary glands that lead to xerostomia or severe dry mouth, which can increase oral infections. Our goal is to engineer functional, three-dimensional (3D) salivary gland neotissue for autologous implantation to provide permanent relief. An immediate need exists to obtain autologous adult progenitor cells as the use of embryonic and induced pluripotent stem cells potentially pose serious risks such as teratogenicity and immunogenic rejection...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28167342/cellular-transformation-of-human-mammary-epithelial-cells-by-satb2
#11
Wei Yu, Yiming Ma, Augusto C Ochoa, Sharmila Shankar, Rakesh K Srivastava
Breast tumors are heterogeneous and carry a small population of progenitor cells that can produce various subtypes of breast cancer. SATB2 (special AT-rich binding protein-2) is a newly identified transcription factor and epigenetic regulator. It is highly expressed in embryonic stem cells, but not in adult tissues, and regulates pluripotency-maintaining factors. However, the molecular mechanisms by which SATB2 induces transformation of human mammary epithelial cells (HMECs) leading to malignant phenotype are unknown...
February 1, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28163951/a-review-on-the-relationship-between-aspirin-and-bone-health
#12
REVIEW
Kok-Yong Chin
Aspirin is a cyclooxygenase inhibitor commonly used in primary prevention of cardiovascular diseases and cancers. Its users are elderly population susceptible to osteoporosis. It also inhibits the synthesis of prostaglandin E2 essential in bone remodeling. This prompts the question whether it can influence bone health among users. This review aimed to summarize the current literature on the use of aspirin on bone health. A literature search on experimental and clinical evidence on the effects of aspirin on bone health was performed using major scientific databases...
2017: Journal of Osteoporosis
https://www.readbyqxmd.com/read/28163927/rna-binding-protein-samd4-regulates-skeleton-development-through-translational-inhibition-of-mig6-expression
#13
Ningning Niu, Jian-Feng Xiang, Qin Yang, Lijun Wang, Zhanying Wei, Ling-Ling Chen, Li Yang, Weiguo Zou
Protein translation regulation has essential roles in inflammatory responses, cancer initiation and the pathogenesis of several neurodegenerative disorders. However, the role of the regulation of protein translation in mammalian skeleton development has been rarely elaborated. Here we report that the lack of the RNA-binding protein sterile alpha motif domain containing protein 4 (SAMD4) resulted in multiple developmental defects in mice, including delayed bone development and decreased osteogenesis. Samd4-deficient mesenchymal progenitors exhibit impaired osteoblast differentiation and function...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28163189/future-of-circulating-tumor-cells-in-the-melanoma-clinical-and-research-laboratory-settings
#14
Luisa M De Souza, Bailey M Robertson, Gavin P Robertson
Circulating tumor cells (CTC) have become a field of interest for oncologists based on the premise that they constitute the underpinning for metastatic dissemination. The lethal nature of cancer is no longer attributed to solid tumor formation, but rather to the process of metastasis; shifting the focus of current studies towards the isolation and identification of metastatic progenitors, such as CTCs. CTCs originate from primary tumor masses that undergo morphologic and genetic alterations, which involve the release of mesenchymal-like cancer cells into the bloodstream, capable of invading nearby tissues for secondary tumor development...
February 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28161224/cox-2-inhibitor-prevents-tumor-induced-down-regulation-of-classical-dc-lineage-specific-transcription-factor-zbtb46-resulting-in-immunocompetent-dc-and-decreased-tumor-burden
#15
Vipul K Pandey, Prayag J Amin, Bhavani S Shankar
The interaction between the immune and tumor cells in the microenvironment is an important factor deciding the progression of cancer. Though many of the soluble mediators in the microenvironment that mediate immunosuppression are known, the mechanism by which the tumor affects the distal progenitors is not known. We report that the tumor derived prostanoids down regulated classical dendritic cells DC (cDC) lineage specific transcription factor Zbtb46 in the progenitor cells which affects its differentiation...
February 1, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28159836/c-myc-downregulation-is-required-for-preacinar-to-acinar-maturation-and-pancreatic-homeostasis
#16
Victor J Sánchez-Arévalo Lobo, Luis César Fernández, Enrique Carrillo-de-Santa-Pau, Laia Richart, Isidoro Cobo, Jaroslaw Cendrowski, Ulisses Moreno, Natalia Del Pozo, Diego Megías, Bernardette Bréant, Christopher V Wright, Mark Magnuson, Francisco X Real
BACKGROUND AND AIMS: c-Myc is highly expressed in pancreatic multipotent progenitor cells (MPC) and in pancreatic cancer. The transition from MPC to unipotent acinar progenitors is associated with c-Myc downregulation; a role for c-Myc in this process, and its possible relationship to a role in cancer, has not been established. DESIGN: Using coimmunoprecipitation assays, we demonstrate that c-Myc and Ptf1a interact. Using reverse transcriptase qPCR, western blot and immunofluorescence, we show the erosion of the acinar programme...
February 3, 2017: Gut
https://www.readbyqxmd.com/read/28155657/a-machine-learning-approach-for-the-identification-of-key-markers-involved-in-brain-development-from-single-cell-transcriptomic-data
#17
Yongli Hu, Takeshi Hase, Hui Peng Li, Shyam Prabhakar, Hiroaki Kitano, See Kiong Ng, Samik Ghosh, Lawrence Jin Kiat Wee
BACKGROUND: The ability to sequence the transcriptomes of single cells using single-cell RNA-seq sequencing technologies presents a shift in the scientific paradigm where scientists, now, are able to concurrently investigate the complex biology of a heterogeneous population of cells, one at a time. However, till date, there has not been a suitable computational methodology for the analysis of such intricate deluge of data, in particular techniques which will aid the identification of the unique transcriptomic profiles difference between the different cellular subtypes...
December 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28154085/loss-of-foxm1-promotes-erythropoiesis-through-increased-proliferation-of-erythroid-progenitors
#18
Minyoung Youn, Nan Wang, Corinne LaVasseur, Elena Bibikova, Sharon Kam, Bertil Glader, Kathleen M Sakamoto, Anupama Narla
FOXM1 belongs to the fork head/winged-helix family of transcription factors and regulates a network of proliferation-associated genes. Its abnormal upregulation has been shown to be a key driver of cancer progression and an initiating factor in oncogenesis. FOXM1 is also highly expressed in stem/progenitor cells and inhibits their differentiation, suggesting that FOXM1 plays a role in the maintenance of multipotency. However, the exact molecular mechanisms by which FOXM1 regulates human stem/progenitor cells are still uncharacterized...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28153092/gm-csf-and-il-4-fusion-cytokine-induces-b-cell-dependent-hematopoietic-regeneration
#19
Jiusheng Deng, Yanqiu Li, Andrea Pennati, Shala Yuan, Jian Hui Wu, Edmund K Waller, Jacques Galipeau
Hematopoietic stem cells (HSCs) have the capacity to self-renew and differentiate into hematopoietic cells and have been utilized to replace diseased bone marrow for patients with cancers and blood disorders. Although remarkable progress has been made in developing new tools to manipulate HSCs for clinic use, there is still no effective method to expand HSCs in vivo for quick repopulation of hematopoietic cells following sublethal irradiation. We have recently described a novel synthetic cytokine that is derived from the fusion of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4; named as GIFT4), and we have now discovered that GIFT4 fusokine promotes long-term hematopoietic regeneration in a B cell-dependent manner...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28152020/highly-tumorigenic-hepatocellular-carcinoma-cell-line-with-cancer-stem-cell-like-properties
#20
Benoit Lacoste, Valérie-Ann Raymond, Shamir Cassim, Pascal Lapierre, Marc Bilodeau
There are limited numbers of models to study hepatocellular carcinoma (HCC) in vivo in immunocompetent hosts. In an effort to develop a cell line with improved tumorigenicity, we derived a new cell line from Hepa1-6 cells through an in vivo passage in C57BL/6 mice. The resulting Dt81Hepa1-6 cell line showed enhanced tumorigenicity compared to Hepa1-6 with more frequent (28±12 vs. 0±0 lesions at 21 days) and more rapid tumor development (21 (100%) vs. 70 days (10%)) in C57BL/6 mice. The minimal Dt81Hepa1-6 cell number required to obtain visible tumors was 100,000 cells...
2017: PloS One
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