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https://www.readbyqxmd.com/read/29660518/hoxb4-knockdown-enhances-the-cytotoxic-effect-of-paclitaxel-and-cisplatin-by-downregulating-abc-transporters-in-ovarian-cancer-cells
#1
Ying Li, Jingli Sun, Shaofeng Gao, Heping Hu, Pengmu Xie
Therapeutic effects of anti-cancer drugs for ovarian cancer were limited due to the rapid development of chemotherapy resistance. The aim of this study was to test whether knockdown of Homeobox B4 (HOXB4) enhanced the cytotoxic effect of paclitaxel and cisplatin in ovarian cancer cells. HOXB4 expressions at mRNA and protein levels were upregulated in Taxol-resistant A2780 (A2780/Taxol) and DDP-resistant SKOV-3 (SKOV-3/DDP) cells. HOXB4 knockdown enhanced the cytotoxic effects of Taxol and DDP in A2780/Taxol and SKOV-3/DDP cells, respectively...
April 13, 2018: Gene
https://www.readbyqxmd.com/read/29617431/membrane-permeabilizing-amphiphilic-peptide-delivers-recombinant-transcription-factor-and-crispr-cas9-cpf1-ribonucleoproteins-in-hard-to-modify-cells
#2
Thomas Del'Guidice, Jean-Pascal Lepetit-Stoffaes, Louis-Jean Bordeleau, Joannie Roberge, Vanessa Théberge, Coraline Lauvaux, Xavier Barbeau, Jessica Trottier, Vibhuti Dave, Denis-Claude Roy, Bruno Gaillet, Alain Garnier, David Guay
Delivery of recombinant proteins to therapeutic cells is limited by a lack of efficient methods. This hinders the use of transcription factors or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) ribonucleoproteins to develop cell therapies. Here, we report a soluble peptide designed for the direct delivery of proteins to mammalian cells including human stem cells, hard-to-modify primary natural killer (NK) cells, and cancer cell models. This peptide is composed of a 6x histidine-rich domain fused to the endosomolytic peptide CM18 and the cell penetrating peptide PTD4...
2018: PloS One
https://www.readbyqxmd.com/read/29574166/stem-cells-from-apical-papilla-promote-differentiation-of-human-pluripotent-stem-cells-towards-retinal-cells
#3
Fereshteh Karamali, Mohammad-Hossein Nasr Esfahani, Sara Taleahmad, Leila Satarian, Hossein Baharvand
Recently, we have found that human stem cells from apical papilla (SCAP) show a stromal cell-derived inducing activity (SDIA). To examine SDIA competence for retinal cells differentiation, we co-cultured SCAP with human pluripotent stem cells (hPSCs). In comparison with Matrigel-cultured hPSCs, SCAP significantly induces hPSCs to differentiate into rostral neural cells as demonstrated by upregulation of OTX2 and PAX6 and down-regulation of EN1, HOXB4 and HOXC8. Furthermore, the differentiated cells on SCAP significantly expressed eye-field markers, RAX, PAX6, LHX2 and SIX3 and showed five folds pigmented colonies...
March 2, 2018: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29456178/hoxb4-promotes-hemogenic-endothelium-formation-without-perturbing-endothelial-cell-development
#4
Nadine Teichweyde, Lara Kasperidus, Sebastian Carotta, Valerie Kouskoff, Georges Lacaud, Peter A Horn, Stefan Heinrichs, Hannes Klump
Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells, in vitro, holds great promise for regenerative therapies. Primarily, this has been achieved in mouse cells by overexpression of the homeotic selector protein HOXB4. The exact cellular stage at which HOXB4 promotes hematopoietic development, in vitro, is not yet known. However, its identification is a prerequisite to unambiguously identify the molecular circuits controlling hematopoiesis, since the activity of HOX proteins is highly cell and context dependent...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29321952/fasciculation-and-elongation-zeta-1-protein-fez1-interacts-with-the-retinoic-acid-receptor-and-participates-in-transcriptional-regulation-of-the-hoxb4-gene
#5
Mariana Bertini Teixeira, Ana Carolina M Figueira, Ariane S Furlan, Bruno Aquino, Marcos R Alborghetti, Adriana F Paes Leme, Li-Na Wei, Jörg Kobarg
Fasciculation and elongation zeta-1 (FEZ1) protein is involved in axon outgrowth and is highly expressed in the brain. It has multiple interaction partners, with functions varying from the regulation of neuronal development and intracellular transport mechanisms to transcription regulation. One of its interactors is retinoic acid receptor (RAR), which is activated by retinoic acid and controls many target genes and physiological process. Based on previous evidence suggesting a possible nuclear role for FEZ1, we wanted to deepen our understanding of this function by addressing the FEZ1-RAR interaction...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29190932/multigene-methylation-analysis-of-enriched-circulating-tumor-cells-associates-with-poor-progression-free-survival-in-metastatic-breast-cancer-patients
#6
Theresa Benezeder, Verena Tiran, Alexandra A N Treitler, Christoph Suppan, Christopher Rossmann, Herbert Stoeger, Richard J Cote, Ram H Datar, Marija Balic, Nadia Dandachi
Blood-based biomarkers such as circulating tumor cells (CTCs) provide dynamic real-time assessment of molecular tumor characteristics beyond the primary tumor. The aim of this study was to evaluate the feasibility of a size-based microfilter to assess multigene methylation analysis of enriched CTCs in a prospective proof-of principle study. We examined the quantitative methylation status of nine genes ( AKR1B1, BMP6, CST6, HOXB4, HIST1H3C, ITIH5, NEUROD1, RASSF1, SOX17 ) in enriched CTCs from metastatic breast cancer patients...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163771/inhibition-of-hox-pbx-dimer-formation-leads-to-necroptosis-in-acute-myeloid-leukemia-cells
#7
Raed A Alharbi, Hardev S Pandha, Guy R Simpson, Ruth Pettengell, Krzysztof Poterlowicz, Alexander Thompson, Kevin Harrington, Mohamed El-Tanani, Richard Morgan
The HOX genes encode a family of transcription factors that have key roles in both development and malignancy. Disrupting the interaction between HOX proteins and their binding partner, PBX, has been shown to cause apoptotic cell death in a range of solid tumors. However, despite HOX proteins playing a particularly significant role in acute myeloid leukemia (AML), the relationship between HOX gene expression and patient survival has not been evaluated (with the exception of HOXA9 ), and the mechanism by which HOX/PBX inhibition induces cell death in this malignancy is not well understood...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081736/human-ipsc-derived-cerebellar-neurons-from-a-patient-with-ataxia-telangiectasia-reveal-disrupted-gene-regulatory-networks
#8
Sam P Nayler, Joseph E Powell, Darya P Vanichkina, Othmar Korn, Christine A Wells, Refik Kanjhan, Jian Sun, Ryan J Taft, Martin F Lavin, Ernst J Wolvetang
Ataxia-telangiectasia (A-T) is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and GBX2, and later more mature cerebellar markers including PTF1α, MATH1, HOXB4, ZIC3, PAX6, and TUJ1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29067121/effect-of-testosterone-and-hypoxia-on-the-expansion-of-umbilical-cord-blood-cd34-cells-in-vitro
#9
Liping Zhou, Xiaowei Zhang, Panpan Zhou, Xue Li, Xuejing Xu, Qing Shi, Dong Li, Xiuli Ju
Successfully expanding hematopoietic stem cells (HSCs) is advantageous for clinical HSC transplantation. The present study investigated the influence of testosterone on the proliferation, antigen phenotype and expression of hematopoiesis-related genes in umbilical cord blood-derived cluster of differentiation (CD)34+ cells under normoxic or hypoxia conditions. Cord blood (CB) CD34+ cells were separated using magnetic activated cell sorting. A cytokine cocktail and feeder cells were used to stimulate the expansion of CD34+ cells under normoxic (20% O2 ) and hypoxic (1% O2 ) conditions for 7 days and testosterone was added accordingly...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29039487/functional-analysis-of-hoxa10-and-hoxb4-in-human-medulloblastoma-cell-lines
#10
Ricardo Bonfim-Silva, Fernanda Ursoli Ferreira Melo, Carolina Hassibe Thomé, Kuruvilla Joseph Abraham, Fábio Augusto Labre De Souza, Fernando Silva Ramalho, Hélio Rubens Machado, Ricardo Santos De Oliveira, Angelo A Cardoso, Dimas Tadeu Covas, Aparecida Maria Fontes
Medulloblastoma (MB) is a malignant childhood brain tumor which at molecular level is classified into at least four major subtypes: WNT, SHH, group C and group D differing in response to treatment. Previous studies have associated changes in expression levels and activation of certain HOX genes with MB development. In the present study, we investigate the role of HOX genes in two attributes acquired by tumor cells: migration and proliferation potential, as well as, in vivo tumorigenic potential. We analyzed UW402, UW473, DAOY and ONS-76 human pediatric MB cell lines and cerebellum primary cultures...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28994199/inhibition-of-mek-erk-signalling-pathway-promotes-erythroid-differentiation-and-reduces-hscs-engraftment-in-ex-vivo-expanded-haematopoietic-stem-cells
#11
Morteza Zarrabi, Elaheh Afzal, Mohammad Hossein Asghari, Monireh Mohammad, Hamidreza Aboulkheyr Es, Marzieh Ebrahimi
The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34+ cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34+ and CD34+  CD38- cells, while there is no change in the expression of stemness-related genes (HOXB4, BMI1)...
March 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28986286/differential-responses-of-lineages-committed-hematopoietic-progenitors-and-altered-expression-of-self-renewal-and-differentiation-related-genes-in-1-4-benzoquinone-1-4-bq-exposure
#12
Paik Wah Chow, Nor Fadilah Rajab, Kien Hui Chua, Kok Meng Chan, Zariyantey Abd Hamid
Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self-renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5μM for 24h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay...
October 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28969513/hoxb4-immunoreactivity-in-endometrial-tissues-from-women-with-or-without-endometriosis
#13
Ghadeer M AlKusayer, Julia R Pon, Bo Peng, Christian Klausen, Sarka Lisonkova, Mary Kinloch, Paul Yong, Eman M S Muhammad, Peter C K Leung, Mohamed A Bedaiwy
Endometriosis is a common disease characterized by the presence of ectopic endometrial tissue. Although the pathogenesis of endometriosis remains unclear, several factors have been implicated, including the dysregulation of homeobox ( HOX) genes. Our objective was to investigate the localization and immunoreactivity of HOXB4 in endometrial tissues from women with or without endometriosis. We studied samples of eutopic endometrium (EE), endometriomas (Eoma), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE) from 34 women with endometriosis, as well as eutopic endometrium from 38 women without endometriosis (EC)...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28911908/enhancement-of-mouse-hematopoietic-stem-progenitor-cell-function-via-transient-gene-delivery-using-integration-deficient-lentiviral-vectors
#14
Maria E Alonso-Ferrero, Niek P van Til, Kerol Bartolovic, Márcia F Mata, Gerard Wagemaker, Dale Moulding, David A Williams, Christine Kinnon, Simon N Waddington, Michael D Milsom, Steven J Howe
Integration-deficient lentiviruses (IdLVs) deliver genes effectively to tissues but are lost rapidly from dividing cells. This property can be harnessed to express transgenes transiently to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of hematopoietic stem and progenitor cells (HSPCs) during transplantation by delivering HOXB4 and Angptl3 using IdLVs to enhance the engraftment of HSPCs. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells...
January 2018: Experimental Hematology
https://www.readbyqxmd.com/read/28852427/seven-cpg-based-prognostic-signature-coupled-with-gene-expression-predicts-survival-of-oral-squamous-cell-carcinoma
#15
Sipeng Shen, Guanrong Wang, Qianwen Shi, Ruyang Zhang, Yang Zhao, Yongyue Wei, Feng Chen, David C Christiani
BACKGROUND: DNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma. METHODS: A multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28726548/wnt-yes-associated-protein-interactions-during-neural-tissue-patterning-of-human-induced-pluripotent-stem-cells
#16
Julie Bejoy, Liqing Song, Yi Zhou, Yan Li
Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests...
August 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28626363/hoxb4-increases-runx1-expression-to-promote-the-de-novo-formation-of-multipotent-hematopoietic-cells
#17
Nadine Teichweyde, Peter A Horn, Hannes Klump
BACKGROUND: The de novo generation of patient-specific hematopoietic stem and progenitor cells from induced pluripotent stem cells (iPSCs) has become a promising approach for cell replacement therapies in the future. However, efficient differentiation protocols for producing fully functional human hematopoietic stem cells are still missing. In the mouse model, ectopic expression of the human homeotic selector protein HOXB4 has been shown to enforce the development of hematopoietic stem cells (HSCs) in differentiating pluripotent stem cell cultures...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#18
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#19
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/28009288/engineered-murine-hscs-reconstitute-multi-lineage-hematopoiesis-and-adaptive-immunity
#20
Yi-Fen Lu, Patrick Cahan, Samantha Ross, Julie Sahalie, Patricia M Sousa, Brandon K Hadland, Wenqing Cai, Erik Serrao, Alan N Engelman, Irwin D Bernstein, George Q Daley
Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs) could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients...
December 20, 2016: Cell Reports
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