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https://www.readbyqxmd.com/read/29156730/generation-of-patient-specific-human-neural-stem-cells-from-niemann-pick-disease-type-c-patient-derived-fibroblasts
#1
Eun-Ah Sung, Kyung-Rok Yu, Ji-Hee Shin, Yoojin Seo, Hyung-Sik Kim, Myung Guen Koog, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Tae-Hoon Shin, Jin Young Lee, Seunghee Lee, Tae-Wook Kang, Soon Won Choi, Kyung-Sun Kang
Niemann-Pick disease type C (NPC) is a neurodegenerative and lysosomal lipid storage disorder, characterized by the abnormal accumulation of unesterified cholesterol and glycolipids, which is caused by mutations in the NPC1 genes. Here, we report the generation of human induced neural stem cells from NPC patient-derived fibroblasts (NPC-iNSCs) using only two reprogramming factors SOX2 and HMGA2 without going through the pluripotent state. NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156720/novel-strategies-of-raman-imaging-for-brain-tumor-research
#2
Imiela Anna, Polis Bartosz, Polis Lech, Abramczyk Halina
Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156535/hdacis-class-i-cancer-stem-cell-and-phytochemicals-cancer-therapy-and-prevention-implications
#3
REVIEW
Sahar Bayat, Mahmoud Shekari Khaniani, Jalal Choupani, Mohammad Reza Alivand, Sima Mansoori Derakhshan
Epigenetics is independent of the sequence events that physically affect the condensing of chromatin and genes expression. The unique epigenetic memories of various cells trigger exclusive gene expression profiling. According to different studies, the aberrant epigenetic signatures and impaired gene expression profiles are master occurrences in cancer cells in which oncogene and tumor suppressor genes are affected. Owing to the facts that epigenetic modifications are performed earlier than expression and are reversible, the epigenetic reprogramming of cancer cells could be applied potentially for their prevention, control, and therapy...
November 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156376/comparative-transcriptomic-analysis-of-endothelial-progenitor-cells-derived-from-umbilical-cord-blood-and-adult-peripheral-blood-implications-for-the-generation-of-induced-pluripotent-stem-cells
#4
Xiugong Gao, Jeffrey J Yourick, Robert L Sprando
Induced pluripotent stem cells (iPSCs) offer the potential to generate tissues with ethnic diversity enabling toxicity testing on selected populations. Recently, it has been reported that endothelial progenitor cells (EPCs) derived from umbilical cord blood (CB) or adult peripheral blood (PB) afford a practical and efficient cellular substrate for iPSC generation. However, differences between EPCs from different blood sources have rarely been studied. In the current study, we derived EPCs from blood mononuclear cells (MNCs) and reprogrammed EPCs into iPSCs...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29155818/snail1-mediated-downregulation-of-foxa-proteins-facilitates-the-inactivation-of-transcriptional-enhancer-elements-at-key-epithelial-genes-in-colorectal-cancer-cells
#5
Sabine Jägle, Hauke Busch, Vivien Freihen, Sven Beyes, Monika Schrempp, Melanie Boerries, Andreas Hecht
Phenotypic conversion of tumor cells through epithelial-mesenchymal transition (EMT) requires massive gene expression changes. How these are brought about is not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anticorrelated in transcriptomes of colorectal tumors and cell lines...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155716/evaluation-of-injury-induced-senescence-and-in-vivo-reprogramming-in-the-skeletal-muscle
#6
Coralie Cazin, Aurelie Chiche, Han Li
Cellular senescence is a stress response that is characterized by a stable cellular growth arrest, which is important for many physiological and pathological processes, such as cancer and ageing. Recently, senescence has also been implicated in tissue repair and regeneration. Therefore, it has become increasingly critical to identify senescent cells in vivo. Senescence-associated β-galactosidase (SA-β-Gal) assay is the most widely used assay to detect senescent cells both in culture and in vivo. This assay is based on the increased lysosomal contents in the senescent cells, which allows the histochemical detection of lysosomal β-galactosidase activity at suboptimum pH (6 or 5...
October 26, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29154162/epigenetic-reprogramming-in-metabolic-disorders-nutritional-factors-and-beyond
#7
REVIEW
Zhiyong Cheng, Louise Zheng, Fabio A Almeida
Environmental factors (e.g., malnutrition and physical inactivity) contribute largely to metabolic disorders including obesity, type 2 diabetes, cardiometabolic disease and nonalcoholic fatty liver diseases. The abnormalities in metabolic activity and pathways have been increasingly associated with altered DNA methylation, histone modification and noncoding RNAs, whereas lifestyle interventions targeting diet and physical activity can reverse the epigenetic and metabolic changes. Here we review recent evidence primarily from human studies that links DNA methylation reprogramming to metabolic derangements or improvements, with a focus on cross-tissue (e...
October 23, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29153923/macrophages-sensing-oxidized-damps-reprogram-their-metabolism-to-support-redox-homeostasis-and-inflammation-through-a-tlr2-syk-ceramide-dependent-mechanism
#8
Vlad Serbulea, Clint M Upchurch, Katelyn W Ahern, Gael Bories, Paxton Voigt, Dory E DeWeese, Akshaya K Meher, Thurl E Harris, Norbert Leitinger
OBJECTIVE: Macrophages control tissue homeostasis and inflammation by sensing and responding to environmental cues. However, the metabolic adaptation of macrophages to oxidative tissue damage and its translation into inflammatory mechanisms remains enigmatic. METHODS: Here we identify the critical regulatory pathways that are induced by endogenous oxidation-derived DAMPs (oxidized phospholipids, OxPL) in vitro, leading to formation of a unique redox-regulatory metabolic phenotype (Mox), which is strikingly different from conventional classical or alternative macrophage activation...
November 7, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29153483/crosstalks-between-translation-and-metabolism-in-cancer
#9
REVIEW
Stefano Biffo, Nicola Manfrini, Sara Ricciardi
Albeit cancer patients' heterogeneity, all tumor cells have alterations of both metabolism and translation. The simplest explanation for this common feature is that several oncogenes coordinate a translational and metabolic reprogramming that is necessary for tumor cells to thrive. Overall, at least three oncogenic pathways, namely c-Myc, RAS and PI3K-mTOR, are known to affect both translation and metabolism by stimulating glycolysis and protein synthesis. The crosstalk between metabolite production and the translational machinery is, instead, less understood...
November 15, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29152916/serum-and-urine-metabolomics-study-reveals-a-distinct-diagnostic-model-for-cancer-cachexia
#10
Quan-Jun Yang, Jiang-Rong Zhao, Juan Hao, Bin Li, Yan Huo, Yong-Long Han, Li-Li Wan, Jie Li, Jinlu Huang, Jin Lu, Gen-Jin Yang, Cheng Guo
BACKGROUND: Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance-based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model...
November 19, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29152128/modulation-of-cabozantinib-efficacy-by-the-prostate-tumor-microenvironment
#11
Manisha Tripathi, Srinivas Nandana, Sandrine Billet, Karen A Cavassani, Rajeev Mishra, Leland W K Chung, Edwin M Posadas, Neil A Bhowmick
The tumor microenvironment (TME) is increasingly recognized as the arbiter of metastatic progression and drug resistance in advanced prostate cancer (PCa). Cabozantinib is a potent tyrosine kinase inhibitor (TKI) with reported biological activity in the PCa epithelia, but failed to provide an overall survival benefit in phase 3 clinical trials. However, the promising biologic efficacy of the drug in early trials warranted a better understanding of the mechanism of action, with the goal of improving patient selection for TKI-based therapy such as cabozantinib...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152108/microrna-31-suppresses-the-self-renewal-capability-of-%C3%AE-2%C3%AE-1-liver-tumor-initiating-cells-by-targeting-isl1
#12
Yuan Zhang, Wei Zhao, Haibo Han, Sheng Li, Dongji Chen, Zhiqian Zhang
Accumulating evidence demonstrates that miRNAs, a class of small non-coding RNAs, are involved in the regulation of tumor-initiating cells (TICs) which are considered to be the origin of cancer development according to the cancer stem cell hypothesis. We have previously identified that miR-31 may play suppressive roles in α2δ1(+) hepatocellular carcinoma (HCC) TICs. Here, we confirm that the expression of miR-31 is significantly downregulated in α2δ1(+) HCC TICs. Overexpression of miR-31 in α2δ1(+) HCC TICs results in significant suppression of the self-renewal and tumorigenicity abilities of these cells...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152106/disrupting-glucose-6-phosphate-isomerase-fully-suppresses-the-warburg-effect-and-activates-oxphos-with-minimal-impact-on-tumor-growth-except-in-hypoxia
#13
Monique Cunha de Padua, Giulia Delodi, Milica Vučetić, Jérôme Durivault, Valérie Vial, Pascale Bayer, Guilhermina Rodrigues Noleto, Nathalie M Mazure, Maša Ždralević, Jacques Pouysségur
As Otto Warburg first observed, cancer cells largely favor fermentative glycolysis for growth even under aerobic conditions. This energy paradox also extends to rapidly growing normal cells indicating that glycolysis is optimal for fast growth and biomass production. Here we further explored this concept by genetic ablation of fermentative glycolysis in two fast growing cancer cell lines: human colon adenocarcinoma LS174T and B16 mouse melanoma. We disrupted the upstream glycolytic enzyme, glucose-6-phosphate isomerase (GPI), to allow cells to re-route glucose-6-phosphate flux into the pentose-phosphate branch...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151989/human-induced-pluripotent-stem-cells-and-the-modelling-of-alzheimer-s-disease-the-human-brain-outside-the-dish
#14
REVIEW
Godwin Tong, Pablo Izquierdo, Rana Arham Raashid
Background: Neurodegenerative diseases like Alzheimer's Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments. Summary: With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth...
2017: Open Neurology Journal
https://www.readbyqxmd.com/read/29151965/combined-inhibitions-of-glycolysis-and-akt-autophagy-can-overcome-resistance-to-egfr-targeted-therapy-of-lung-cancer
#15
Mingtong Ye, Sufan Wang, Ting Wan, Rui Jiang, Yun Qiu, Lei Pei, Nengzhi Pang, Yuanling Huang, Yufeng Huang, Zhenfeng Zhang, Lili Yang
Efficacy of EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, to treat human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR is not persistent due to drug resistance. Reprogramming in energy (especially glucose) metabolism plays an important role in development and progression of acquired resistance in cancer cells. We hypothesize that glucose metabolism in EGFR-TKI sensitive HCC827 cells and erlotinib-resistant sub-line of HCC827 (which we name it as erlotinib-resistant 6, ER6 cells in this study) is different and targeting glucose metabolism might be a treatment strategy for erlotinib-resistant NSCLCs...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151932/restoration-of-klf4-inhibits-invasion-and-metastases-of-lung-adenocarcinoma-through-suppressing-mmp2
#16
Shaoli Li, Lixia Huang, Jincui Gu, Jian Wu, Weijun Ou, Jinglun Feng, Baomo Liu, Xiaoxian Xu, Yanbin Zhou
BACKGROUND: KLF4 is a zin-finger transcription factor that plays roles in differentiation, development, and proliferation. Recent studies show that KLF4 is involved in tumorigenesis and somatic cells reprogramming. Metastasis is the primary cause of death in patients with lung cancer, and its biological mechanisms are poorly understood. GOALS: In this study, we aim to explore the expression pattern and biological function of KLF4 in lung adenocarcinoma. METHODS: We determined KLF4 in lung adenocarcinoma tissue and cell lines, using immunohistochemistry and western blotting...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151926/the-glycolytic-switch-in-tumors-how-many-players-are-involved
#17
REVIEW
Li Yu, Xun Chen, Xueqi Sun, Liantang Wang, Shangwu Chen
Reprogramming of cellular metabolism is a hallmark of cancers. Cancer cells more readily use glycolysis, an inefficient metabolic pathway for energy metabolism, even when sufficient oxygen is available. This reliance on aerobic glycolysis is called the Warburg effect, and promotes tumorigenesis and malignancy progression. The mechanisms of the glycolytic shift in tumors are not fully understood. Growing evidence demonstrates that many signal molecules, including oncogenes and tumor suppressors, are involved in the process, but how oncogenic signals attenuate mitochondrial function and promote the switch to glycolysis remains unclear...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151641/foliar-treatment-of-bacillus-methylotrophicus-ke2-reprograms-endogenous-functional-chemicals-in-sesame-to-improve-plant-health
#18
Ramalingam Radhakrishnan, In-Jung Lee
The present study was aimed to investigate the health of vegetative and reproductive parts of sesame plants during Bacillus methylotrophicus KE2 interaction by their pigments, sugars, organic acid, amino acids, hormones and antioxidant production analysis. In a green-house study, B. methylotrophicus KE2 was sprayed to sesame plants at late flowering stage. The bacterial treatment enhanced photosynthetic pigments of plants including pods than their controls. The shoots of plants had higher amount of sucrose, glucose, galactose, xylitol and malic acid, and while the pods of plants showed the more accumulation of sucrose, glucose, inulin and xylitol in bacterium treated plants...
December 2017: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/29151585/defining-the-molecular-basis-of-oncogenic-cooperation-between-tal1-expression-and-pten-deletion-in-t-all-using-a-novel-pro-t-cell-model-system
#19
S Bornschein, S Demeyer, R Stirparo, O Gielen, C Vicente, E Geerdens, B Ghesquière, S Aerts, J Cools, C E de Bock
T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple mutations combined with the ectopic expression of transcription factors in developing T cells. However, the molecular basis underlying cooperation between transcription factor expression and additional oncogenic mutations in driving T-ALL has been difficult to assess due to limited robust T cell model systems. Here we utilize a new ex vivo pro-T cell model to study oncogenic cooperation. Using a systems biological approach we first dissect the pro-T cell signaling network driven by interleukin-7 (Il7), stem cell factor (Scf) and Notch1 and identify key downstream Akt, Stat, E2f and Myc genetic signaling networks...
November 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29150092/generation-of-integration-free-induced-pluripotent-stem-cell-lines-derived-from-two-patients-with-x-linked-alport-syndrome-xlas
#20
Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, Angel Raya
Skin biopsies were obtained from two male patients with X-linked Alport syndrome (XLAS) with hemizygous COL4A5 mutations in exon 41 or exon 46. Dermal fibroblasts were extracted and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53 shRNA. The generated induced Pluripotent Stem Cell (iPSC) lines AS-FiPS2-Ep6F-28 and AS-FiPS3-Ep6F-9 were free of genomically integrated reprogramming genes, had the specific mutations, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro...
September 9, 2017: Stem Cell Research
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