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https://www.readbyqxmd.com/read/28819926/targeting-metabolic-pathways-for-head-and-neck-cancers-therapeutics
#1
Masashi Yamamoto, Hidenori Inohara, Takashi Nakagawa
Cancer cells have distinctive energy metabolism pathways that support their rapid cell division. The preference for anaerobic glycolysis under the normal oxygen condition is known as the Warburg effect and has been observed in head and neck cancers. These metabolic changes are controlled by cancer-related transcription factors, such as tumor suppressor gene and hypoxia inducible factor 1α. In addition, various metabolic enzymes also actively regulate cancer-specific metabolism including the switch between aerobic and anaerobic glycolysis...
August 17, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28819379/hypoxia-inducible-factor-1-alpha-correlates-with-tumor-associated-macrophages-infiltration-influences-survival-of-gastric-cancer-patients
#2
Wei-Jie Zhang, Cheng Chen, Zhi-Hua Zhou, Shan-Ting Gao, Teong Jin Tee, Liu-Qing Yang, Yuan-Yuan Xu, Tao-Hong Pang, Xin-Yun Xu, Qi Sun, Min Feng, Hao Wang, Chun-Lei Lu, Guo-Zhong Wu, Sheng Wu, Wen-Xian Guan, Gui-Fang Xu
Background: Hypoxia was a common feature for accelerating tumor metastasis by both inducting epithelial-mesenchymal transition (EMT) of tumor cells and polarization of tumor-associated macrophages (TAMs). The association and roles between hypoxia, EMT and TAMs in the biological behavior of gastric cancer (GC) for the time being recurrence is unclear. Material and methods: hypoixa by expression of hypoxia-inducible factor-1 alpha (HIF-1α), polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68 and CD163, and the expression of E-cadherin as EMT property had been evaluated in 236 patients consecutive with histologically confirmed GC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819378/hif-is-not-essential-for-suppression-of-experimental-tumor-growth-by-mtor-inhibition
#3
Karl X Knaup, Regina Guenther, Johanna Stoeckert, Juliana M Monti, Kai-Uwe Eckardt, Michael S Wiesener
The Hypoxia Inducible Transcription Factor (HIF) is the master regulator of cellular response to hypoxic adaptation. Solid tumors inevitably harbour hypoxic regions with subsequent stabilization and activation of HIF and HIF target genes due to poor vascularization and rapid growth. The mammalian target of rapamycin (mTOR) is a global regulator of cellular growth and proliferation, which can also regulate HIF expression independantly of hypoxia via specific activation of cellular translation and transcription...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819223/levobuipivacaine-induced-dissemination-of-a549-lung-cancer-cells
#4
Shun-Ming Chan, Bo-Feng Lin, Chih-Shung Wong, Wen-Ting Chuang, Yu-Ting Chou, Zhi-Fu Wu
While anaesthetics are frequently used on cancer patients during surgical procedures, their consequence on cancer progression remains to be elucidated. In this study, we sought to investigate the influence of local anesthetics on lung cancer cell dissemination in vitro and in vivo. A549 human non-small lung cancer cells were treated with various local anaesthetics including ropivacaine, lidocaine, levobupivacaine and bupivacaine. Cell barrier property was assessed using an electric cell-substrate impedance sensing (ECIS) system...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818483/intermittent-hypoxia-and-cancer-undesirable-bed-partners
#5
REVIEW
Isaac Almendros, David Gozal
The deleterious effects of intermittent hypoxia (IH) on cancer biology have been primarily evaluated in the context of the aberrant circulation observed in solid tumors which results in recurrent intra-tumoral episodic hypoxia. From those studies, IH has been linked to an accelerated tumor progression, metastasis and resistance to therapies. More recently, the role of IH in cancer has also been studied in the context of obstructive sleep apnea (OSA), since IH is a hallmark characteristic of this condition. Such recent studies are undoubtedly adding more information regarding the role of IH on tumor malignancy...
August 14, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28812986/epigenome-aberrations-emerging-driving-factors-of-the-clear-cell-renal-cell-carcinoma
#6
REVIEW
Ali Mehdi, Yasser Riazalhosseini
Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28811968/il-32%C3%AE-induced-inflammation-constitutes-a-link-between-obesity-and-colon-cancer
#7
Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez, Victor A Ortega, José Luis Hernández-Lizoain, Jorge Baixauli, Sara Becerril, Fernando Rotellar, Víctor Valentí, Rafael Moncada, Camilo Silva, Javier Salvador, Gema Frühbeck
Growing evidence indicates that adipose tissue inflammation is an important mechanism whereby obesity promotes cancer risk and progression. Since IL-32 is an important inflammatory and remodeling factor in obesity and is also related to colon cancer (CC) development, the aim of this study was to explore whether IL-32 could function as an inflammatory factor in human obesity-associated CC promoting a microenvironment favorable for tumor growth. Samples obtained from 84 subjects [27 lean (LN) and 57 obese (OB)] were used in the study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810656/hypoxia-inducible-factor-1%C3%AE-participates-in-hypoxia-induced-epithelial-mesenchymal-transition-via-response-gene-to-complement-32
#8
Liang Zhu, Qiu Zhao
The aim of the present study was to explore the function of response gene to complement 32 (RGC-32) in hypoxia-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer. Three kinds of hypoxia-inducible factor 1α (HIF-1α) small interfering (si)RNA were synthesized and the different effects on the expression of HIF-1α were detected by western blotting. In human pancreatic cancer BxPC-3 cells, HIF-1α levels were diminished using siRNA transfection or HIF-1α inhibitor pretreatment, and the expression levels of RGC-32 and EMT-associated proteins were analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810235/obesity-as-a-conditioning-factor-for-high-altitude-diseases
#9
Rocío San Martin, Julio Brito, Patricia Siques, Fabiola León-Velarde
Obesity, a worldwide epidemic, has become a major health burden because it is usually accompanied by an increased risk for insulin resistance, diabetes, hypertension, cardiovascular diseases, and even some kinds of cancer. It also results in associated increases in healthcare expenditures and labor and economic consequences. There are also other fields of medicine and biology where obesity or being overweight play a major role, such as high-altitude illnesses (acute mountain sickness, hypoxic pulmonary hypertension, and chronic mountain sickness), where an increasing relationship among these two morbid statuses has been demonstrated...
August 16, 2017: Obesity Facts
https://www.readbyqxmd.com/read/28808589/anti-angiogenic-agents-for-the-treatment-of-solid-tumors-potential-pathways-therapy-and-current-strategies-a-review
#10
REVIEW
Ahmed M Al-Abd, Abdulmohsin J Alamoudi, Ashraf B Abdel-Naim, Thikryat A Neamatallah, Osama M Ashour
Recent strategies for the treatment of cancer, other than just tumor cell killing have been under intensive development, such as anti-angiogenic therapeutic approach. Angiogenesis inhibition is an important strategy for the treatment of solid tumors, which basically depends on cutting off the blood supply to tumor micro-regions, resulting in pan-hypoxia and pan-necrosis within solid tumor tissues. The differential activation of angiogenesis between normal and tumor tissues makes this process an attractive strategic target for anti-tumor drug discovery...
November 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28808304/hypoxia-induced-tet1-facilitates-trophoblast-cell-migration-and-invasion-through-hif1%C3%AE-signaling-pathway
#11
Jingping Zhu, Kai Wang, Ting Li, Jiayu Chen, Dandan Xie, Xinwen Chang, Julei Yao, Jinting Wu, Qian Zhou, Yuanhui Jia, Tao Duan
Low oxygen is a typical extrinsic factor for the regulation of trophoblast biological function, including cell migration, invasion and proliferation. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1), an enzyme converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), is transcriptionally activated by hypoxia in cancer cells. Therefore, we focus on the role of TET1 on trophoblast function in a physiologically hypoxic environment (3% oxygen), which is related to early placentation. Here, we found that TET1 was highly expressed in first trimester villi compared with normal term placentas...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28806945/tumor-microenvironment-conditions-alter-akt-and-na-h-exchanger-nhe1-expression-in-endothelial-cells-more-than-hypoxia-alone-implications-for-endothelial-cell-function-in-cancer
#12
A K Pedersen, J Mendes Lopes de Melo, N Mørup, K Tritsaris, S F Pedersen
BACKGROUND: Chronic angiogenesis is a hallmark of most tumors and takes place in a hostile tumor microenvironment (TME) characterized by hypoxia, low nutrient and glucose levels, elevated lactate and low pH. Despite this, most studies addressing angiogenic signaling use hypoxia as a proxy for tumor conditions. Here, we compared the effects of hypoxia and TME conditions on regulation of the Na(+)/H(+) exchanger NHE1, Ser/Thr kinases Akt1-3, and downstream effectors in endothelial cells...
August 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28805936/characterizing-hypoxia-in-human-glioma-a-simultaneous-multimodal-mri-and-pet-study
#13
Christine Preibisch, Kuangyu Shi, Anne Kluge, Mathias Lukas, Benedikt Wiestler, Jens Göttler, Jens Gempt, Florian Ringel, Mohamed Al Jaberi, Jürgen Schlegel, Bernhard Meyer, Claus Zimmer, Thomas Pyka, Stefan Förster
Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high-grade glioma, where we directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[(18) F]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([(18) F]-FMISO)...
August 14, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28804704/hypoxia-in-cervical-cancer-from-biology-to-imaging
#14
REVIEW
Heidi Lyng, Eirik Malinen
PURPOSE: Hypoxia imaging may improve identification of cervical cancer patients at risk of treatment failure and be utilized in treatment planning and monitoring, but its clinical potential is far from fully realized. Here, we briefly describe the biology of hypoxia in cervix tumors of relevance for imaging, and evaluate positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques that have shown promise for assessing hypoxia in a clinical setting. We further discuss emerging imaging approaches, and how imaging can play a role in future treatment strategies to target hypoxia...
2017: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28801910/application-of-synthetic-tumor-specific-promoters-responsive-to-the-tumor-microenvironment
#15
Eduardo G Cafferata, Maria Veronica Lopez, Felipe J Nuñez, Maria A R Maenza, Osvaldo L Podhajcer
Activity of endogenous promoters can be altered by including additional responsive elements (REs). These elements can be responsive to features of the tumor environment or alternatively to signaling pathways specifically activated in cancer cells. These REs incorporated into tumor-specific promoters can improve cancer targeting, the replicative capacity, and lytic activity of conditionally replicative adenovirus. Here we outline an approach to incorporate hypoxia and inflammation REs into a specific fragment of the SPARC promoter and the steps to clone a nucleosome positioning sequence (NPS ) identified in the osteocalcin promoter that contains a Wnt RE upstream of a heterologous synthetic promoter...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28801636/inhibition-of-hypoxic-response-decreases-stemness-and-reduces-tumorigenic-signaling-due-to-impaired-assembly-of-hif1-transcription-complex-in-pancreatic-cancer
#16
Olivia McGinn, Vineet K Gupta, Patricia Dauer, Nivedita Arora, Nikita Sharma, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number of hypoxia mediated signaling pathways including cell proliferation, metabolism and cell survival. Previous studies from our laboratory have shown that Minnelide, a water-soluble pro-drug of triptolide (anti-cancer compound), decreases viability of cancer cells in vitro as well as in vivo. However, its mechanism of action remain elusive. In the current study we evaluated the effect of Minnelide, on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28799237/anticancer-efficacy-of-the-hypoxia-activated-prodrug-evofosfamide-is-enhanced-in-combination-with-proapoptotic-receptor-agonists-against-osteosarcoma
#17
Vasilios Liapis, Aneta Zysk, Mark DeNichilo, Irene Zinonos, Shelley Hay, Vasilios Panagopoulos, Alexandra Shoubridge, Christopher Difelice, Vladimir Ponomarev, Wendy Ingman, Gerald J Atkins, David M Findlay, Andrew C W Zannettino, Andreas Evdokiou
Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death...
August 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28798809/hypoxia-inducible-tumour-specific-promoters-as-a-dual-targeting-transcriptional-regulation-system-for-cancer-gene-therapy
#18
REVIEW
Bita Javan, Majid Shahbazi
Transcriptional targeting is the best approach for specific gene therapy. Hypoxia is a common feature of the tumour microenvironment. Therefore, targeting gene expression in hypoxic cells by placing transgene under the control of a hypoxia-responsive promoter can be a good strategy for cancer-specific gene therapy. The hypoxia-inducible gene expression system has been investigated more in suicide gene therapy and it can also be of great help in knocking down cancer gene therapy with siRNAs. However, this system needs to be optimised to have maximum efficacy with minimum side effects in normal tissues...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28798482/retinoblastoma-protein-rb-links-hypoxia-to-altered-mechanical-properties-in-cancer-cells-as-measured-by-an-optical-tweezer
#19
S Khakshour, M P Labrecque, H Esmaeilsabzali, F J S Lee, M E Cox, E J Park, T V Beischlag
Hypoxia modulates actin organization via multiple pathways. Analyzing the effect of hypoxia on the biophysical properties of cancer cells is beneficial for studying modulatory signalling pathways by quantifying cytoskeleton rearrangements. We have characterized the biophysical properties of human LNCaP prostate cancer cells that occur in response to loss of the retinoblastoma protein (Rb) under hypoxic stress using an oscillating optical tweezer. Hypoxia and Rb-loss increased cell stiffness in a fashion that was dependent on activation of the extracellular signal-regulated kinase (ERK) and the protein kinase B (AKT)- mammalian target of rapamycin (MTOR) pathways...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798230/association-of-bmi-with-propofol-dosing-and-adverse-events-in-children-with-cancer-undergoing-procedural-sedation
#20
Colin M Rogerson, Kamal Abulebda, Michael J Hobson
OBJECTIVES: Obesity increases the risk of complications during pediatric procedural sedation. The risk of being underweight has not been evaluated in this arena. We therefore investigated the association of BMI with sedation dosing and adverse events in children across a range of BMIs. METHODS: A total of 1976 patients ages 2 to 21 years old with oncologic diagnoses underwent lumbar punctures and/or bone marrow aspirations. All children received a standard adjunctive dose of ketamine before sedation with propofol...
August 10, 2017: Hospital Pediatrics
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