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https://www.readbyqxmd.com/read/28431398/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#1
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431267/mir-19-targeting-of-gsk3%C3%AE-mediates-sulforaphane-suppression-of-lung-cancer-stem-cells
#2
Jianyun Zhu, Shijia Wang, Yue Chen, Xiaoting Li, Ye Jiang, Xue Yang, Yuan Li, Xiaoqian Wang, Yu Meng, Mingming Zhu, Xiao Ma, Cong Huang, Rui Wu, Chunfeng Xie, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Hongyu Han
Cancer stem cells (CSCs) play a central role in the development of cancer. The canonical Wnt/β-catenin pathway is critical for maintaining stemness of CSCs. Phytochemicals from dietary compounds possess anti-CSCs properties and have been characterized as promising therapeutic agents for the prevention and treatment of many cancers. To date, the involvement and function of miR-19, a key oncogenic miRNA, in regulating Wnt/β-catenin pathway and lung CSCs has not been defined. Meanwhile, the effect of sulforaphane (SFN) on lung CSCs also remains to be elucidated...
April 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28431181/protective-effect-of-mesenchymal-stem-cells-against-the-development-of-intracranial-aneurysm-rupture-in-mice
#3
Atsushi Kuwabara, Jia Liu, Yoshinobu Kamio, Airan Liu, Michael T Lawton, Jae-Woo Lee, Tomoki Hashimoto
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stem or stromal cells found in multiple tissues. Intravenous MSC injections have been used to treat various diseases with an inflammatory component in animals and humans. Inflammation is emerging as a key component of pathophysiology of intracranial aneurysms. Modulation of inflammation by MSCs may affect sustained inflammatory processes that lead to aneurysmal rupture. OBJECTIVE: To assess the effect of MSCs on the development of aneurysm rupture using a mouse model...
April 19, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28431037/gestational-diabetes-alters-functions-in-offspring-s-umbilical-cord-cells-with-implications-for-cardiovascular-health
#4
Ajith Isaac Amrithraj, Anjaneyulu Kodali, Linh Nguyen, Adrian Kee Keong Teo, Cheng Wei Chang, Neerja Karnani, Kai Lyn Ng, Peter D Gluckman, Yap Seng Chong, Walter Stünkel
As non-communicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of GDM mothers compared to control subjects. We have assessed primary umbilical cord derived cells such as human umbilical vein endothelial cells (HUVECs) and Wharton's jelly derived mesenchymal stem cells (WJMSCs) from both, the offspring of GDM and non-GDM mothers. We have compared the primary isolates in cell based assays measuring proliferation, mitochondrial oxygen consumption, and the ability to support blood vessel growth...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28431019/identifying-cytomegalovirus-cmv-complications-using-the-quantiferon-cmv-assay-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
Michelle K Yong, Paul U Cameron, Monica Slavin, C Orla Morrissey, Krystal Bergin, Andrew Spencer, David Ritchie, Allen C Cheng, Assia Samri, Guislaine Carcelain, Brigitte Autran, Sharon R Lewin
Background: Cytomegalovirus (CMV) reactivation and disease remain a major cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. A simple test to identify recovery of CMV-specific T-cell immunity could assist clinicians in managing CMV-related complications. Methods: In an observational multi-centre prospective study of 94 allogeneic HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9 and 12 months post-transplant using the Quantiferon-CMV®, an ELISpot assay and in a subset, we also evaluated intracellular cytokine staining (ICS)...
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28430877/the-accessible-chromatin-landscape-during-conversion-of-human-embryonic-stem-cells-to-trophoblast-by-bmp4
#6
Yajun Liu, Dewu Ding, Hongde Liu, Xiao Sun
Human embryonic stem cells (hESC) exposed to the growth factor bone morphogenic protein 4 (BMP4) in the absence of FGF2 have been used as a model to study the development of placental development. However, little is known about the cis-regulatory mechanisms underlying this important process. In this study, we used the public available chromatin accessibility data of hESC H1 cells and BMP4-induced trophoblast (TB)cell lines to identify DNase I hypersensitive sites (DHSs) in the two cell lines, as well as the transcription factor binding sites within the DHSs...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28430648/radioimmunotherapy-for-cd133-colonic-cancer-stem-cells-inhibits-tumor-development-in-nude-mice
#7
Dinghu Weng, Xueyan Jin, Saimei Qin, Xiaoli Lan, Chong Chen, Xun Sun, Xianliang She, Changling Dong, Rui An
Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430641/the-regulation-of-%C3%AE-catenin-activity-and-function-in-cancer-therapeutic-opportunities
#8
REVIEW
Shuang Shang, Fang Hua, Zhuo-Wei Hu
Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430640/epithelial-mesenchymal-transition-in-prostate-cancer-an-overview
#9
REVIEW
Micaela Montanari, Sabrina Rossetti, Carla Cavaliere, Carmine D'Aniello, Maria Gabriella Malzone, Daniela Vanacore, Rossella Di Franco, Elvira La Mantia, Gelsomina Iovane, Raffaele Piscitelli, Raffaele Muscariello, Massimiliano Berretta, Sisto Perdonà, Paolo Muto, Gerardo Botti, Attilio Antonio Montano Bianchi, Bianca Maria Veneziani, Gaetano Facchini
Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer.Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430184/the-ubiquitin-ligase-lin41-trim71-targets-p53-to-antagonize-cell-death-and-differentiation-pathways-during-stem-cell-differentiation
#10
Duong Thi Thuy Nguyen, Daniel Richter, Geert Michel, Sibylle Mitschka, Waldemar Kolanus, Elisa Cuevas, F Gregory Wulczyn
Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming. Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28430167/induced-pluripotent-stem-cell-modeling-of-gaucher-s-disease-what-have-we-learned
#11
REVIEW
Dino Matias Santos, Gustavo Tiscornia
Gaucher's disease (GD) is the most frequently inherited lysosomal storage disease, presenting both visceral and neurologic symptoms. Mutations in acid β-glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, neither of these approaches is effective in treating the neurological aspect of the disease. The use of small pharmacological compounds that act as molecular chaperones is a promising approach that is still experimental...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28430163/long-non-coding-rnas-key-regulators-of-epithelial-mesenchymal-transition-tumour-drug-resistance-and-cancer-stem-cells
#12
REVIEW
Richard Heery, Stephen P Finn, Sinead Cuffe, Steven G Gray
Epithelial mesenchymal transition (EMT), the adoption by epithelial cells of a mesenchymal-like phenotype, is a process co-opted by carcinoma cells in order to initiate invasion and metastasis. In addition, it is becoming clear that is instrumental to both the development of drug resistance by tumour cells and in the generation and maintenance of cancer stem cells. EMT is thus a pivotal process during tumour progression and poses a major barrier to the successful treatment of cancer. Non-coding RNAs (ncRNA) often utilize epigenetic programs to regulate both gene expression and chromatin structure...
April 21, 2017: Cancers
https://www.readbyqxmd.com/read/28429768/reassembling-embryos-in-vitro-from-component-stem-cells
#13
Caroline Kubaczka, George Q Daley
Researchers at the University of Cambridge, UK have succeeded in reconstructing mouse embryos by combining pluripotent embryonic and multipotent trophoblast stem cells in a 3D scaffold; the study from the laboratory of Professor Zernicka-Goetz, recently published in Science, provides a break-through tool to probe early mammalian development outside the uterus. Achieving a similar feat with human cells might necessitate reconsideration of the 14-day rule as a limitation of such research.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28429280/synergistic-anti-cancer-effects-of-epigenetic-drugs-on-medulloblastoma-cells
#14
Juan Yuan, Núria Llamas Luceño, Bjoern Sander, Monika M Golas
PURPOSE: Medulloblastomas are aggressive brain malignancies. While considerable progress has been made in the treatment of medulloblastoma patients with respect to overall survival, these patients are still at risk of developing neurologic and cognitive deficits as a result of anti-cancer therapies. It is hypothesized that targeted molecular therapies represent a better treatment option for medulloblastoma patients. Therefore, the aim of the present study was to test a panel of epigenetic drugs for their effect on medulloblastoma cells under mild hypoxic conditions that reflect the physiological concentrations of oxygen in the brain...
April 20, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28429049/dysregulation-of-haematopoietic-stem-cell-regulatory-programs-in-acute-myeloid-leukaemia
#15
REVIEW
Silvia Basilico, Berthold Göttgens
Haematopoietic stem cells (HSC) are situated at the apex of the haematopoietic differentiation hierarchy, ensuring the life-long supply of mature haematopoietic cells and forming a reservoir to replenish the haematopoietic system in case of emergency such as acute blood loss. To maintain a balanced production of all mature lineages and at the same time secure a stem cell reservoir, intricate regulatory programs have evolved to control multi-lineage differentiation and self-renewal in haematopoietic stem and progenitor cells (HSPCs)...
April 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28428936/multistate-models-on-pleural-effusion-after-allogeneic-hematopoietic-stem-cell-transplantation
#16
Joohyoung Lee, Dipenkumar Modi, Hyejeong Jang, Joseph P Uberti, Seongho Kim
A multistate model is more complicated than competing risk models and composed of finite number of states and transitions between states. Unlike competing risk models, this model has the ability to assess the effect of occurrence order of time-to-event data. Pleural effusion (PE) is a severe complication that often occurs after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients develop pleural effusion during the first 100 days after allogeneic HSCT and graft-versus-host disease (GVHD) occurs either before or after the development of PE, implying that the occurrence order of PE and GVHD (i...
2017: Open Access Medical Statistics
https://www.readbyqxmd.com/read/28428898/severe-acute-hepatitis-b-in-hbv-vaccinated-partner-of-a-patient-with-multiple-myeloma-treated-with-cyclophosphamide-bortezomib-and-dexamethasone-and-autologous-stem-cell-transplant
#17
Majed M Almaghrabi, Kyle J Fortinsky, David Wong
Hepatitis B reactivation can occur with various forms of immunosuppression. Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) chemotherapy is commonly used for the treatment of multiple myeloma and has not been noted in guidelines to be causative in HBV reactivation. Indeed, current guidelines do not recommend providing antiviral prophylaxis to patients with prior HBV infection. We present a case of HBV reactivation as a result of CYBOR-D and autologous stem cell transplant which is complicated by the patient's partner who developed acute hepatitis B...
2017: Case Reports in Hepatology
https://www.readbyqxmd.com/read/28428276/micellar-delivery-of-mir-34a-modulator-rubone-and-paclitaxel-in-resistant-prostate-cancer
#18
Di Wen, Yang Peng, Feng Lin, Rakesh K Singh, Ram I Mahato
Treatment of prostate cancer with paclitaxel (PTX) often fails due to development of chemoresistance caused by downregulation of the tumor suppressor gene miR-34a. In this study, we demonstrate that co-delivery of PTX and 2'-hydroxy-2,4,4',5,6'-pentamethoxychalcone (termed rubone) drives upregulation of miR-34a and chemosensitizes PTX-resistant prostate cancer cells, killing both cancer stem-like cells (CSCs) and bulk tumor cells. Rubone upregulated miR-34a and reversed its downstream target genes in DU145-TXR and PC3-TXR cells...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428263/different-requirements-of-functional-telomeres-in-neural-stem-cells-and-terminally-differentiated-neurons
#19
Anastasia Lobanova, Robert She, Simon Pieraut, Charlie Clapp, Anton Maximov, Eros Lazzerini Denchi
Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons...
April 20, 2017: Genes & Development
https://www.readbyqxmd.com/read/28427858/mice-with-conditional-neurod1-knockout-display-reduced-aberrant-hippocampal-neurogenesis-but-no-change-in-epileptic-seizures
#20
Rebecca Brulet, Jingfei Zhu, Mahafuza Aktar, Jenny Hsieh, Kyung-Ok Cho
Adult neurogenesis is significantly increased in the hippocampus of rodent models of temporal lobe epilepsy (TLE). These adult-generated neurons have recently been shown to play a contributing role in the development of spontaneous recurrent seizures (SRS). In order to eventually target pro-epileptic adult neurogenesis in the clinical setting, it will be important to identify molecular players involved in the control of aberrant neurogenesis after seizures. Here, we focused on NeuroD1 (ND1), a member of the bHLH family of transcription factors previously shown to play an essential role in the differentiation and maturation of adult-generated neurons in the hippocampus...
April 18, 2017: Experimental Neurology
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