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Yubo Xiao, Min Feng, Haiying Ran, Xiao Han, Xuegang Li
Increasing evidence has indicated that the abnormal expressions of certain genes serve important roles in tumorigenesis, progression and metastasis. The aim of the present study was to explore the key differentially expressed genes (DEGs) between non‑small cell lung cancer (NSCLC) and matched normal lung tissues by analyzing 4 different mRNA microarray datasets downloaded from the Gene Expression Omnibus (GEO) database. In improving the reliability of the bioinformatics analysis, the DEGs in each dataset that met the cut‑off criteria (adjust P‑value <0...
March 9, 2018: Molecular Medicine Reports
Yi-Chao Lee, Ying-Chao Chang, Chia-Ching Wu, Chao-Ching Huang
Therapy targeting the neurovascular unit may provide effective neuroprotection against neonatal hypoxia-ischemia (HI). We hypothesized that the peripheral injection of hypoxia-preconditioned human umbilical vein endothelial cells (HUVECs) following HI protects against neurovascular damage and provides long-term neuroprotection in a postpartum (P) day-7 rat pup model. Compared with normoxic HUVECs, hypoxic HUVECs showed enhanced migration and angiogenesis in vitro and had augmented migration effects into the brain when administered intraperitoneally in vivo after HI...
February 19, 2018: Molecular Neurobiology
Jie Li, Hiroki Shima, Hironari Nishizawa, Masatoshi Ikeda, Andrey Brydun, Mitsuyo Matsumoto, Hiroki Kato, Yuriko Saiki, Liang Liu, Miki Watanabe-Matsui, Kenji Iemura, Kozo Tanaka, Takuma Shiraki, Kazuhiko Igarashi
The transcription repressor BACH1 performs mutually independent dual roles in transcription regulation as well as chromosome alignment during mitosis by supporting polar ejection force of mitotic spindle. We now found that the mitotic spindles became oblique relative to the adhesion surface following endogenous BACH1 depletion in HeLa cells. This spindle orientation rearrangement was rescued by re-expression of BACH1 depending on its interactions with HMMR and CRM1, both of which are required for the positioning of mitotic spindle, but independently of its DNA binding activity...
February 19, 2018: Biochemical Journal
Helen Chen, Marisa Connell, Lin Mei, Gregor S D Reid, Christopher A Maxwell
Mitotic spindle assembly and organization require forces generated by motor proteins. The activity of these motors is regulated by non-motor adaptor proteins. However, there are limited studies reporting the functional importance of adaptors on the balance of motor forces and the promotion of faithful and timely cell division. Here, we show that genomic deletion or siRNA silencing of the non-motor adaptor Hmmr/HMMR disturbs spindle microtubule organization and bipolar chromosome-kinetochore attachments with a consequent elevated occurrence of aneuploidy...
January 31, 2018: Molecular Biology of the Cell
Susana Eibes, Núria Gallisà-Suñé, Miquel Rosas-Salvans, Paula Martínez-Delgado, Isabelle Vernos, Joan Roig
Centrosomes [1, 2] play a central role during spindle assembly in most animal cells [3]. In early mitosis, they organize two symmetrical microtubule arrays that upon separation define the two poles of the forming spindle. Centrosome separation is tightly regulated [4, 5], occurring through partially redundant mechanisms that rely on the action of microtubule-based dynein and kinesin motors and the actomyosin system [6]. While centrosomes can separate in prophase or in prometaphase after nuclear envelope breakdown (NEBD), prophase centrosome separation optimizes spindle assembly and minimizes the occurrence of abnormal chromosome attachments that could end in aneuploidy [7, 8]...
December 13, 2017: Current Biology: CB
Aaron M Horning, Yao Wang, Che-Kuang Lin, Anna D Louie, Rohit R Jadhav, Chia-Nung Hung, Chiou-Miin Wang, Chun-Lin Lin, Nameer B Kirma, Michael A Liss, Addanki P Kumar, LuZhe Sun, Zhijie Liu, Wei-Ting Chao, Qianben Wang, Victor X Jin, Chun-Liang Chen, Tim H-M Huang
Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen-deprivation therapy. In this study, we investigated this phenomenon by stratifying cell subpopulations based on transcriptome profiling of 144 single LNCaP prostate cancer cells treated or untreated with androgen after cell cycle synchronization. Model-based clustering of 397 differentially expressed genes identified eight potential subpopulations of LNCaP cells, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation...
December 12, 2017: Cancer Research
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
Junyang Li, Yali Zhou, Handong Wang, Yongyue Gao, Liwen Li, Sung Hee Hwang, Xiangjun Ji, Bruce D Hammock
Aims: Cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) dual inhibitor, PTUPB, has been demonstrated to inhibit angiogenesis, primary tumor growth and metastasis. The aim of this study is to investigate the effects of PTUPB on glioblastoma cells and xenograft model. Results: We show here that PTUPB inhibits glioblastoma cell proliferation and G1 phase cell cycle arrest in vitro, and suppresses the tumor growth and angiogenesis in vivo. The expression and activation of epidermal growth factor receptor (EGFR) and its downstream kinases, ERK1/2 and AKT, are reduced by PTUPB, indicating that the EGF/EGFR signaling pathway is a potential target...
October 20, 2017: Oncotarget
Marisa Connell, Helen Chen, Jihong Jiang, Chia-Wei Kuan, Abbas Fotovati, Tony Lh Chu, Zhengcheng He, Tess C Lengyell, Huaibiao Li, Torsten Kroll, Amanda M Li, Daniel Goldowitz, Lucien Frappart, Aspasia Ploubidou, Millan S Patel, Linda M Pilarski, Elizabeth M Simpson, Philipp F Lange, Douglas W Allan, Christopher A Maxwell
Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis. Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centrosomes in a PLK1-dependent pathway that locates active Ran and modulates the cortical localization of NuMA-dynein complexes to correct mispositioned spindles. This pathway was discovered through the creation and analysis of Hmmr-knockout mice, which suffer neonatal lethality with defective neural development and pleiotropic phenotypes in multiple tissues...
October 10, 2017: ELife
Tony L H Chu, Marisa Connell, Lixin Zhou, Zhengcheng He, Jennifer R Won, Seyed M Rahavi, Helen Chen, Pooja Mohan, Oksana Nemirovsky, Abbas Fotovati, Miguel Angel Pujana, Gregor Sd Reid, Torsten O Nielsen, Nelly Pante, Christopher A Maxwell
Cell cycle progression and the acquisition of a migratory phenotype are hallmarks of human carcinoma cells that are perceived as independent processes but may be interconnected by molecular pathways that control microtubule nucleation at centrosomes. Here, cell cycle progression dramatically impacts the engraftment kinetics of 4T1-luciferase2 breast cancer cells in immunocompetent BALB/c or immunocompromised NOD-SCID gamma (NSG) mice. Multi-parameter imaging of wound closure assays was used to track cell cycle progression, cell migration, and associated phenotypes in epithelial cells or carcinoma cells expressing a fluorescence ubiquitin cell cycle indicator...
October 9, 2017: Molecular Cancer Research: MCR
Marcy C Purnell
Mechanisms that regulate cancer cell metastasis are often intricately linked to mechanisms that control cell migration in wound repair. Hyaluronan Mediated Motility Receptor (HMMR) encodes a receptor for hyaluronan-mediated motility (RHAMM), a non-integral cell surface hyaluronan receptor and intracellular protein that promotes mitotic spindle formation and cell motility. RHAMM has been found to have increased expression in both cancers and wounds, and when cancers show increased RHAMM expression poor outcomes have occurred...
April 2017: Discovery Medicine
Jaime L Stafford, Gregory Dyson, Nancy K Levin, Sophia Chaudhry, Rita Rosati, Hasini Kalpage, Courtney Wernette, Nancie Petrucelli, Michael S Simon, Michael A Tainsky
While up to 25% of ovarian cancer (OVCA) cases are thought to be due to inherited factors, the majority of genetic risk remains unexplained. To address this gap, we sought to identify previously undescribed OVCA risk variants through the whole exome sequencing (WES) and candidate gene analysis of 48 women with ovarian cancer and selected for high risk of genetic inheritance, yet negative for any known pathogenic variants in either BRCA1 or BRCA2. In silico SNP analysis was employed to identify suspect variants followed by validation using Sanger DNA sequencing...
2017: PloS One
Zhengcheng He, Nagarajan Kannan, Oksana Nemirovsky, Helen Chen, Marisa Connell, Brian Taylor, Jihong Jiang, Linda M Pilarski, Markus C Fleisch, Dieter Niederacher, Miguel Angel Pujana, Connie J Eaves, Christopher A Maxwell
BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features...
May 16, 2017: Oncotarget
S B Bahrami, C Tolg, T Peart, C Symonette, M Veiseh, J U Umoh, D W Holdsworth, J B McCarthy, L G Luyt, M J Bissell, A Yazdani, E A Turley
Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation. Here, we show that CD44 expression is required for subcutaneous adipogenesis, whereas RHAMM expression suppresses this process. We designed RHAMM function blocking peptides to promote subcutaneous adipogenesis as a clinical and tissue engineering tool. Adipogenic RHAMM peptides were identified by screening for their ability to promote adipogenesis in culture assays using rat bone marrow mesenchymal stem cells, mouse pre-adipocyte cell lines and primary human subcutaneous pre-adipocytes...
March 1, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
Laura E Stevens, William K C Cheung, Sally J Adua, Anna Arnal-Estapé, Minghui Zhao, Zongzhi Liu, Kelly Brewer, Roy S Herbst, Don X Nguyen
Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. In this study, we show how differential expression of a network of extracellular matrix (ECM) molecules and their interacting proteins contributes to risk of relapse in distinct LUAD subtypes. Overexpression of the hyaluronan receptor HMMR in primary LUAD was associated with an inflammatory molecular signature and poor prognosis. Attenuating HMMR in LUAD cells diminished their ability to initiate lung tumors and distant metastases...
April 15, 2017: Cancer Research
Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J Tienari
Somatic mutations have a central role in cancer but their role in other diseases such as autoimmune disorders is poorly understood. Earlier work has provided indirect evidence of rare somatic mutations in autoreactive T-lymphocytes in multiple sclerosis (MS) patients but such mutations have not been identified thus far. We analysed somatic mutations in blood in 16 patients with relapsing MS and 4 with other neurological autoimmune disease. To facilitate the detection of somatic mutations CD4+, CD8+, CD19+ and CD4-/CD8-/CD19- cell subpopulations were separated...
February 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Wei Liu, Jun Ma, Yong Cheng, Hongbo Zhang, Wengguang Luo, Hongyan Zhang
Recently, accumulating evidence has suggested that long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis and cancer progression. Hyaluronan-mediated motility receptor (HMMR) is an essential cancer-related gene in basal-like breast cancer (BLBC). In our study, HMMR antisense RNA 1 (HMMR-AS1) was analyzed in BLBC patients through polymerase chain reaction analysis. Here, we found that the expression of HMMR was positively correlated with HMMR-AS1 (RP11-80G.1). When HMMR-AS1 (RP11-80G.1) was knocked down, the expression of HMMR markedly reduced...
2016: Breast Cancer: Targets and Therapy
Yannick Willemen, Johan M J Van den Bergh, Sarah M Bonte, Sébastien Anguille, Carlo Heirman, Barbara M H Stein, Herman Goossens, Tessa Kerre, Kris Thielemans, Marc Peeters, Viggo F I Van Tendeloo, Evelien L J Smits, Zwi N Berneman
We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation...
November 8, 2016: Oncotarget
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
BACKGROUND: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. RESULTS: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
August 11, 2016: Oncotarget
N P Akent'eva, S S Shushanov, A I Kotel'nikov
RHAMM-selective peptides in a concentration of 10 μg/ml (2×10(-7) M) inhibited the growth of MDA-MB-231 breast cancer cells over 48 h. Treatment of cancer cells with RHAMM-selective peptides induced apoptosis and necrosis and increased caspase-3 activity (by 30%).
September 2015: Bulletin of Experimental Biology and Medicine
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