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https://www.readbyqxmd.com/read/28228260/chemotherapy-induced-ca-2-release-stimulates-breast-cancer-stem-cell-enrichment
#1
Haiquan Lu, Ivan Chen, Larissa A Shimoda, Youngrok Park, Chuanzhao Zhang, Linh Tran, Huimin Zhang, Gregg L Semenza
Breast cancer stem cells (BCSCs) play a critical role in tumor recurrence and metastasis. Exposure of breast cancer cells to chemotherapy leads to an enrichment of BCSCs. Here, we find that chemotherapy induces the expression of glutathione S-transferase omega 1 (GSTO1), which is dependent on hypoxia-inducible factor 1 (HIF-1) and HIF-2. Knockdown of GSTO1 expression abrogates carboplatin-induced BCSC enrichment, decreases tumor initiation and metastatic capacity, and delays tumor recurrence after chemotherapy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28223135/cell-physiology-regulation-by-hypoxia-inducible-factor-1-targeting-oxygen-related-nanomachineries-of-hypoxic-cells
#2
REVIEW
Morteza Eskandani, Somayeh Vandghanooni, Jaleh Barar, Hossein Nazemiyeh, Yadollah Omidi
Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions...
February 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28216300/boronic-acid-tethered-amphiphilic-hyaluronic-acid-derivative-based-nanoassemblies-for-tumor-targeting-and-penetration
#3
Jae Young Jeong, Eun-Hye Hong, Song Yi Lee, Jae-Young Lee, Jae-Hyoung Song, Seung-Hak Ko, Jae-Seong Shim, Sunghwa Choe, Dae-Duk Kim, Hyun-Jeong Ko, Hyun-Jong Cho
(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and > 90% drug encapsulation efficiency were fabricated...
February 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-receptor-expression-to-promote-metastasis
#4
Julia A Ju, Ines Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
: Metastasis is the leading cause of breast cancer (BCa)mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM binding receptors in this process was explored. Using a bioinformatics approach the expression of all integrin receptor subunits, in two independent BCa patient data sets, were analyzed to determine if integrin status correlates with a validated hypoxiainducible gene signature...
February 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209257/synthesis-and-evaluation-of-n-benzofuran-5-yl-aromaticsulfonamide-derivatives-as-novel-hif-1-inhibitors-that-possess-anti-angiogenic-potential
#5
Jinlian Wei, Yingrui Yang, Yali Li, Xiaofei Mo, Xiaoke Guo, Xiaojin Zhang, Xiaoli Xu, Zhengyu Jiang, Qidong You
Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis, and poor patient prognosis has been recognized as an important cancer drug target. A novel series of N-(benzofuran-5-yl)aromaticsulfonamide derivatives were synthesized and evaluated as HIF-1 inhibitor. Among these compounds, 7q exhibited specific inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. It inhibited the HIF-1 transcriptional activity (IC50=12.5±0.7μM) and secretion of VEGF (IC50=18...
June 11, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28208156/oncogenic-role-of-pdk4-in-human-colon-cancer-cells
#6
D Leclerc, D N T Pham, N Lévesque, M Truongcao, W D Foulkes, C Sapienza, R Rozen
BACKGROUND: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model. Decreased methylation of four consecutive PDK4 CpGs was observed in normal mucosa of patients. Although other members of the PDK family have been investigated for transformation potential, PDK4 has not been extensively studied...
February 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#7
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202394/platelet-rich-plasma-prp-induces-chondroprotection-via-increasing-autophagy-anti-inflammatory-markers-and-decreasing-apoptosis-in-human-osteoarthritic-cartilage
#8
Mayssam Moussa, Daniel Lajeunesse, George Hilal, Oula El Atat, Gaby Haykal, Rim Serhal, Antonio Chalhoub, Charbel Khalil, Nada Alaaeddine
OBJECTIVES: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration...
March 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28201982/transcriptome-profile-of-rat-genes-in-injured-spinal-cord-at-different-stages-by-rna-sequencing
#9
Ling-Ling Shi, Nan Zhang, Xiu-Mei Xie, Yue-Juan Chen, Rui Wang, Lin Shen, Jian-Sheng Zhou, Jian-Guo Hu, He-Zuo Lü
BACKGROUND: Spinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology. RESULTS: RNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n = 3 in every group)...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28193910/hif1-2%C3%AE-mediates-hypoxia-induced-ldha-expression-in-human-pancreatic-cancer-cells
#10
Xin-Gang Cui, Zhi-Tao Han, Shao-Hui He, Xing-da Wu, Tian-Rui Chen, Cheng-Hao Shao, Dan-Lei Chen, Ning Su, Yuan-Ming Chen, Ting Wang, Jing Wang, Dian-Wen Song, Wang-Jun Yan, Xing-Hai Yang, Tie-Long Liu, Hai-Feng Wei, Jianru Xiao
Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages...
10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185835/requirement-of-hsp105-in-cocl2-induced-hif-1%C3%AE-accumulation-and-transcriptional-activation
#11
Hiroki Mikami, Youhei Saito, Namiko Okamoto, Ayana Kakihana, Takahisa Kuga, Yuji Nakayama
The mammalian stress protein Hsp105α protects cells from stress conditions. Several studies have indicated that Hsp105α is overexpressed in many types of solid tumors, which contain hypoxic microenvironments. However, the role of Hsp105α in hypoxic tumors remains largely unknown. We herein demonstrated the involvement of Hsp105α in HIF-1 functions induced by the hypoxia-mimetic agent CoCl2. While Hsp105α is mainly localized in the cytoplasm under normal conditions, a treatment with CoCl2 induces the nuclear localization of Hsp105α, which correlated with HIF-1α expression levels...
February 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28181420/hypoxia-inducible-factor-1-a-urinary-biomarker-of-kidney-disease
#12
S Movafagh, D Raj, M Sanaei-Ardekani, D Bhatia, K Vo, M Mahmoudieh, R Rahman, E H Kim, A F Harralson
Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF-1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF-1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF-1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF-1a mRNA is of kidney origin, we examined colocalization of HIF-1a mRNA with two kidney specific markers in urine cells...
February 9, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28179109/mechanisms-of-defense-against-products-of-cysteine-catabolism-in-the-nematode-caenorhabditis-elegans
#13
Leonid Livshits, Arijit Kumar Chatterjee, Netanel Karbian, Rachel Abergel, Zohar Abergel, Einav Gross
Cysteine catabolism presents cells with a double-edged sword. On the one hand, cysteine degradation provides cells with essential molecules such as taurine and sulfide. The formation of sulfide in cells is thought to regulate important and diverse physiological processes including blood circulation, synaptic activity and inflammation. On the other hand, the catabolism of cysteine by gut microbiota can release high levels of sulfide that may underlie the development or relapse of ulcerative colitis, an inflammatory bowel disease affecting millions of people worldwide...
March 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28169245/evaluation-of-hypoxia-inducible-factor-1-alpha-gene-expression-in-colorectal-cancer-stages-of-iranian-patients
#14
Reyhaneh Nassiri Mansour, Seyed Ehsan Enderami, Abdolreza Ardeshirylajimi, Koorosh Fooladsaz, Mojtaba Fathi, Shahla Moahammad Ganji
AIM OF STUDY: Colorectal cancer (CRC) is the fourth most prevalent cancer globally. Several factors have roles in cancer establishment. One of the most important factors is hypoxia that induces hypoxia inducible factor-1 (HIF-1). The HIF-1 alpha overexpressed in hypoxia conditions and plays a pivotal role in carcinogenesis features. In this study, we aimed to examine the efficiency of HIF-1 alpha gene expression at mRNA and protein's level for CRC diagnosing and staging. MATERIALS AND METHODS: In this study, the cases included into 75 cancer specimens in different stages (Group 2 = Stage 1, Group 3 = Stage 2, and Group 4 = Stage 3, 4) and ten normal specimens as control (Group 1)...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28165799/the-balance-between-proliferation-and-transcription-of-angiogenic-factors-of-mesenchymal-stem-cells-in-hypoxia
#15
Arina T Buizer, Sjoerd K Bulstra, Albert G Veldhuizen, Roel Kuijer
Bridging large bone defects with mesenchymal stromal cells-seeded scaffolds remains a big challenge in orthopedic surgery, due to the lack of vascularization. Within such a cell-scaffold construct cells are exposed to ischemic conditions. When human mesenchymal stem cells (hMSCs) encounter hypoxic conditions, they show higher cell proliferation than at ambient oxygen levels. However, when hMSCs are exposed to prolonged ischemia, cell proliferation ceases completely. Exposure of hMSCs to hypoxic conditions is known to result in the transcription of angiogenic factors (AGF), which can promote the development of a new blood vessels...
February 6, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28163173/increased-oxidative-stress-and-hypoxia-inducible-factor-1-expression-during-arteriovenous-fistula-maturation
#16
Nirvana Sadaghianloo, Kota Yamamoto, Hualong Bai, Masayuki Tsuneki, Clinton D Protack, Michael R Hall, Serge Declemy, Réda Hassen-Khodja, Joseph Madri, Alan Dardik
BACKGROUND: The poor clinical results that are frequently reported for arteriovenous fistulae (AVF) for hemodialysis are typically due to failure of AVF maturation. We hypothesized that early AVF maturation is associated with generation of reactive oxygen species and activation of the HIF-1 pathway, potentially promoting neointimal hyperplasia. We tested this hypothesis using a previously reported mouse AVF model that recapitulates human AVF maturation. METHODS: Aortocaval fistulae were created in C57Bl/6 mice, and compared to sham-operated mice...
February 2, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28161619/combination-of-metformin-with-chemotherapeutic-drugs-via-different-molecular-mechanisms
#17
REVIEW
Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits...
January 23, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28137601/genome-wide-mrna-analysis-reveals-a-tubd1-isoform-profile-as-a-potential-biomarker-for-diabetic-retinopathy-development
#18
Vanessa Villegas-Ruiz, Ferdinand Hendlmeier, Beatriz Buentello-Volante, José L Rodríguez-Loaiza, Antonio Miranda-Duarte, Juan C Zenteno
Diabetic retinopathy (DR) affects approximately one third of all diabetic subjects and is the leading cause of blindness in young to middle-aged adults in the developed world. While early diagnosis is crucial for preventing DR-associated visual loss, the identification of accessible biomarkers that could lead to presymptomatic recognition of the disease is of great clinical importance. The aim of this work was to investigate the possible involvement of alternative splicing events in DR development by performing a genome-wide transcriptional profiling comparing blood-derived RNA from DR subjects and from diabetic-non DR controls...
January 27, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28137309/induction-of-metastasis-cancer-stem-cell-phenotype-and-oncogenic-metabolism-in-cancer-cells-by-ionizing-radiation
#19
REVIEW
Su Yeon Lee, Eui Kyong Jeong, Min Kyung Ju, Hyun Min Jeon, Min Young Kim, Cho Hee Kim, Hye Gyeong Park, Song Iy Han, Ho Sung Kang
Radiation therapy is one of the major tools of cancer treatment, and is widely used for a variety of malignant tumours. Radiotherapy causes DNA damage directly by ionization or indirectly via the generation of reactive oxygen species (ROS), thereby destroying cancer cells. However, ionizing radiation (IR) paradoxically promotes metastasis and invasion of cancer cells by inducing the epithelial-mesenchymal transition (EMT). Metastasis is a major obstacle to successful cancer therapy, and is closely linked to the rates of morbidity and mortality of many cancers...
January 30, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28133530/endurance-training-induces-fiber-type-specific-revascularization-in-hindlimb-skeletal-muscles-of-rats-with-chronic-heart-failure
#20
Kamal Ranjbar, Malihe Ardakanizade, Farzad Nazem
OBJECTIVES: Previous studies showed that skeletal muscle microcirculation was reduced in chronic heart failure. The aim of this study was to investigate the effects of endurance training on capillary and arteriolar density of fast and slow twitch muscles in rats with chronic heart failure. MATERIALS AND METHODS: Four weeks after surgeries (left anterior descending (LAD) artery occlusion), chronic heart failure rats were divided into 3 groups: Sham (Sham, n=10); Sedentary (Sed, n=10); Exercise training (Ex, n=10)...
January 2017: Iranian Journal of Basic Medical Sciences
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