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https://www.readbyqxmd.com/read/28644546/-18-f-fluoromisonidazole-uptake-in-advanced-stage-non-small-cell-lung-cancer-a-voxel-by-voxel-pet-kinetics-study
#1
Daniel R McGowan, Ruth E Macpherson, Sara L Hackett, Dan Liu, Fergus V Gleeson, W Gillies McKenna, Geoff S Higgins, John D Fenwick
PURPOSE: To determine the relative abilities of compartment models to describe time-courses of 18F-fluoromisonidazole (FMISO) uptake in tumor voxels of patients with non-small cell lung cancer (NSCLC) imaged using dynamic positron emission tomography. Also to use fits of the best-performing model to investigate changes in fitted rate-constants with distance from the tumor edge. METHODS: Reversible and irreversible two- and three-tissue compartment models were fitted to 24,662 individual voxel time activity curves (TACs) obtained from tumors in 9 patients, each imaged twice...
June 23, 2017: Medical Physics
https://www.readbyqxmd.com/read/28644090/transdermal-administration-of-melatonin-coupled-to-cryopass-laser-treatment-as-noninvasive-therapy-for-prostate-cancer
#2
Laura Terraneo, Paola Bianciardi, Eleonora Virgili, Elena Finati, Michele Samaja, Rita Paroni
Melatonin, a pineal gland hormone, exerts oncostatic activity in several types of human cancer, including prostate, the most common neoplasia and the third most frequent cause of male cancer death in the developed world. The growth of androgen-sensitive LNCaP prostate cancer cells in mice is inhibited by 3 mg/kg/week melatonin (0.09 mg/mouse/week) delivered by i.p. injections, which is equivalent to a dose of 210 mg/week in humans. The aim of this study is to test an alternative noninvasive delivery route based on transdermal administration of melatonin onto the tumor area followed by cryopass-laser treatment...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28643452/emerging-nanotechnology-and-advanced-materials-for-cancer-radiation-therapy
#3
REVIEW
Guosheng Song, Liang Cheng, Yu Chao, Kai Yang, Zhuang Liu
Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia-associated radiation resistance is a well-known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation-induced DNA damages...
June 23, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28642487/hypoxia-is-a-key-driver-of-alternative-splicing-in-human-breast-cancer-cells
#4
Jian Han, Jia Li, Jolene Caifeng Ho, Grace Sushin Chia, Hiroyuki Kato, Sudhakar Jha, Henry Yang, Lorenz Poellinger, Kian Leong Lee
Adaptation to hypoxia, a hallmark feature of many tumors, is an important driver of cancer cell survival, proliferation and the development of resistance to chemotherapy. Hypoxia-induced stabilization of hypoxia-inducible factors (HIFs) leads to transcriptional activation of a network of hypoxia target genes involved in angiogenesis, cell growth, glycolysis, DNA damage repair and apoptosis. Although the transcriptional targets of hypoxia have been characterized, the alternative splicing of transcripts that occurs during hypoxia and the roles they play in oncogenesis are much less understood...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28639619/long-noncoding-rna-lnchifcar-mir31hg-is-a-hif-1%C3%AE-co-activator-driving-oral-cancer-progression
#5
Jing-Wen Shih, Wei-Fan Chiang, Alexander T H Wu, Ming-Heng Wu, Ling-Yu Wang, Yen-Ling Yu, Yu-Wen Hung, Wen-Chang Wang, Cheng-Ying Chu, Chiu-Lien Hung, Chun A Changou, Yun Yen, Hsing-Jien Kung
Long noncoding RNAs (lncRNAs) have been implicated in hypoxia/HIF-1-associated cancer progression through largely unknown mechanisms. Here we identify MIR31HG as a hypoxia-inducible lncRNA and therefore we name it LncHIFCAR (long noncoding HIF-1α co-activating RNA); we describe its oncogenic role as a HIF-1α co-activator that regulates the HIF-1 transcriptional network, crucial for cancer development. Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor...
June 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28638459/towards-prognostic-profiling-of-non-small-cell-lung-cancer-new-perspectives-on-the-relevance-of-polo-like-kinase-1-expression-the-tp53-mutation-status-and-hypoxia
#6
Jolien Van den Bossche, Christophe Deben, Ken Op de Beeck, Vanessa Deschoolmeester, Christophe Hermans, Ines De Pauw, Julie Jacobs, Paul Van Schil, Jan Baptist Vermorken, Patrick Pauwels, Marc Peeters, Filip Lardon, An Wouters
Background: Currently, prognosis of non-small cell lung cancer (NSCLC) patients is based on clinicopathological factors, including TNM stage. However, there are considerable differences in patient outcome within a similar staging group, even when patients received identical treatments. In order to improve prognostic predictions and to guide treatment options, additional parameters influencing outcome are required. Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division and the DNA damage response, is considered as a new potential biomarker in this research area...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28638274/hypoxia-regulated-microrna-210-overexpression-is-associated-with-tumor-development-and-progression-in-upper-tract-urothelial-carcinoma
#7
Hung-Lung Ke, Wei-Ming Li, Hui-Hui Lin, Wei-Chi Hsu, Ya-Ling Hsu, Lin-Li Chang, Chun-Nung Huang, Ching-Chia Li, Hsin-Ping Chang, Hsin-Chih Yeh, Chien-Feng Li, Wen-Jeng Wu
BACKGROUND: Hypoxia has been shown to facilitate tumor progression. Hypoxia-regulated microRNA-210 (miR-210) may play an important role in carcinogenesis and tumor progression. In this study, we evaluated the clinical significance of miR-210 expression in upper tract urothelial carcinoma (UTUC). METHODS: Eighty-three UTUC patients participated in this study. All of them provided cancer tissue samples and 50 of them provided non-cancerous urothelium samples. Clinicopathologic data were collected by reviewing medical records...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28637793/endothelial-cell-metabolism-in-health-and-disease-impact-of-hypoxia
#8
REVIEW
Brian W Wong, Elke Marsch, Lucas Treps, Myriam Baes, Peter Carmeliet
In contrast to the general belief, endothelial cell (EC) metabolism has recently been identified as a driver rather than a bystander effect of angiogenesis in health and disease. Indeed, different EC subtypes present with distinct metabolic properties, which determine their function in angiogenesis upon growth factor stimulation. One of the main stimulators of angiogenesis is hypoxia, frequently observed in disease settings such as cancer and atherosclerosis. It has long been established that hypoxic signalling and metabolism changes are highly interlinked...
June 21, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28637353/hallmarks-of-pulmonary-hypertension-mesenchymal-and-inflammatory-cell-metabolic-reprogramming
#9
Angelo D'Alessandro, Karim El Kasmi, Lydie Plecita-Hlavata, Petr Jezek, Min Li, Hui Zhang, Sachin A Gupte, Kurt Randall Stenmark
The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e. macrophages) promotes a persistent inflammatory state, pathological angiogenesis and fibrosis that is driven by metabolic reprogramming of mesenchymal and immune cells. Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28633062/blue-light-induced-reactive-oxygen-species-from-flavin-mononucleotide-and-flavin-adenine-dinucleotide-on-lethality-of-hela-cells
#10
Ming-Yeh Yang, Chih-Jui Chang, Liang-Yü Chen
Photodynamic therapy (PDT) is a safe and non-invasive treatment for cancers and microbial infections. Various photosensitizers and light sources have been developed for clinical cancer therapies. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the cofactor of enzymes and are used as photosensitizers in this study. Targeting hypoxia and light-triggering reactive oxygen species (ROS) are experimental strategies for poisoning tumor cells in vitro. HeLa cells are committed to apoptosis when treated with FMN or FAD and exposed to visible blue light (the maximum emitted wavelength of blue light is 462nm)...
June 13, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28632992/targeting-the-rhogtpase-rock-pathway-for-the-treatment-of-vhl-hif-pathway-driven-cancers
#11
Jordan M Thompson, Jaime Landman, Olga V Razorenova
The loss of the von Hippel-Lindau (VHL) tumor-suppressor is a major driver of Clear Cell Renal Cell Carcinoma (CC-RCC) resulting in the stabilization and overactivation of hypoxia inducible factors (HIFs). ROCK 1 is a well-known protein serine/threonine kinase which is recognized as having a role in cancer including alterations in cell motility, metastasis and angiogenesis. As a function of the later effect, we recently investigated and identified a synthetic lethal interaction between VHL loss and ROCK1 inhibition in CC-RCC that is dependent on HIF overactivation...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28632134/targeting-hypoxic-cancer-stem-cells-cscs-with-doxycycline-implications-for-optimizing-anti-angiogenic-therapy
#12
Ernestina Marianna De Francesco, Marcello Maggiolini, Herbert B Tanowitz, Federica Sotgia, Michael P Lisanti
Here, we report new mechanistic insight into how chronic hypoxia increases 'stemness' in cancer cells. Using chemical inhibitors, we provide direct experimental evidence that ROS production and mitochondrial biogenesis are both required for the hypoxia-induced propagation of CSCs. More specifically, we show that hypoxic CSCs can be effectively targeted with i) simple mitochondrial anti-oxidants (Mito-TEMPO) and/or ii) inhibitors of mitochondrial biogenesis (Doxycycline). In this context, we discuss the idea that mitochondrial biogenesis itself may be a primary driver of "stemness" in hypoxic cancer cells, with metabolic links to fatty acid oxidation (FAO)...
June 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28631600/inhibition-of-carbonic-anhydrase-ix-by-ureidosulfonamide-inhibitor-u104-reduces-prostate-cancer-cell-growth-but-does-not-modulate-daunorubicin-or-cisplatin-cytotoxicity
#13
Anne Riemann, Antje Güttler, Verena Haupt, Henri Wichmann, Sarah Reime, Matthias Bache, Dirk Vordermark, Oliver Thews
Carbonic anhydrase IX has emerged as a promising target for cancer therapy. It is highly up-regulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells in concern of potential therapeutic implications...
June 19, 2017: Oncology Research
https://www.readbyqxmd.com/read/28630300/g9a-drives-hypoxia-mediated-gene-repression-for-breast-cancer-cell-survival-and-tumorigenesis
#14
Francesco Casciello, Fares Al-Ejeh, Greg Kelly, Donal J Brennan, Shin Foong Ngiow, Arabella Young, Thomas Stoll, Karolina Windloch, Michelle M Hill, Mark J Smyth, Frank Gannon, Jason S Lee
G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse factor in tumor growth and metastasis, the role of G9a in regulating gene expression in hypoxia has not been described extensively. Here, we show that G9a protein stability is increased in hypoxia via reduced proline hydroxylation and, hence, inefficient degradation by the proteasome...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28627761/biological-effects-of-hydrogen-peroxide-administered-intratumorally-with-or-without-irradiation-in-murine-tumors
#15
Taiki Takaoka, Yuta Shibamoto, Masayuki Matsuo, Chikao Sugie, Taro Murai, Yasutaka Ogawa, Akifumi Miyakawa, Yoshihiko Manabe, Takuhito Kondo, Koichiro Nakajima, Dai Okazaki, Takahiro Tsuchiya
Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H2 O2 ) is increasingly being used clinically for radioresistant tumors. Especially, this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. The purpose of this study was to investigate the biological effects and appropriate combination methods of irradiation and H2 O2 in vivo. SCCVII tumor cells transplanted into the legs of C3H/HeN mice were used...
June 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28627695/targeted-cdx2-expression-inhibits-aggressive-phenotypes-of-colon-cancer-cells-in-vitro-and-in-vivo
#16
Jianbao Zheng, Sai He, Jie Qi, Xiaolong Wang, Junhui Yu, Yunhua Wu, Qi Gao, Kai Wang, Xuejun Sun
Loss of caudal type homeobox 2 (CDX2) is associated with the development of human colorectal cancer, while human telomerase reverse transcriptase (hTERT) frequently occurs in variety of human cancers. We investigated the effects of restoration of CDX2 expression using a hypoxia-inducible hTERT promoter-driven vector (pLVX-5HRE-hTERTp-CDX2-3FLAG) on colon cancer cell viability, cell cycle distribution, apoptosis, colony formation, invasion ability and xenograft tumor growth in nude mice. CDX2 overexpression significantly inhibited viability, colony formation, and the invasion and migration ability of LoVo cells, and induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions...
June 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28627686/hypoxia-and-acidosis-driven-aberrations-of-secreted-micrornas-in-endometrial-cancer-in-vitro
#17
Julia Eismann, Marc Hirschfeld, Thalia Erbes, Gerta Rücker, Markus Jäger, Andrea Ritter, Daniela Weiss, Gerald Gitsch, Sebastian Mayer
Due to their post-transcriptional regulatory impact on gene expression, microRNAs (miRNA, miRs) influence decisively cellular processes of differentiation, proliferation and apoptosis. In oncogenic pathways various miRNAs exert either oncogenic or tumor suppressor activities in a stage-specific manner. Dysregulation of miRNA expression pattern has been associated with several human cancers including endometrial cancer (EC). In the present study, expression profile alterations of EC associated secreted miRNAs were determined under the microenvironmental stress situations hypoxia and acidosis occurring in tumor progression and metastasis...
June 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627618/hypoxia-inducible-factor-1%C3%AE-regulates-autophagy-via-the-p27-e2f1-signaling-pathway
#18
Pan Wang, Meijing Long, Shijie Zhang, Zhenyun Cheng, Xin Zhao, Fucheng He, Hongchun Liu, Liang Ming
Autophagy is a highly conserved process by which the cell contents are delivered to lysosomes for degradation, or are used to provide macromolecules for energy generation under conditions of nutritional starvation. It has previously been demonstrated that cancer cells in hypoxic regions, with an oxygen concentration below the normal physiological level, express hypoxia inducible factor (HIF)‑1α, in order to adapt and survive. HIF‑1α is important in the regulation of oxygen homeostasis and the transcription of hundreds of genes in response to conditions of hypoxia, hence maintaining energy and redox homeostasis...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627586/hsp70-acetylation-prevents-caspase-dependent-independent-apoptosis-and-autophagic-cell-death-in-cancer-cells
#19
Yoo Hoi Park, Ji Hae Seo, Ji-Hyeon Park, Hye Shin Lee, Kyu-Won Kim
Cancer cells are continuously challenged by adverse environmental factors including hypoxia, metabolite restriction, and immune reactions, and must adopt diverse strategies to survive. Heat shock protein (Hsp) 70 plays a central role in protection against stress-induced cell death by maintaining protein homeostasis and interfering with the process of programmed cell death. Recent findings have suggested that Hsp70 acetylation is a key regulatory modification required for its chaperone activity, but its relevance in the process of programmed cell death and the underlying mechanisms involved are not well understood...
June 12, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28624448/identification-of-functional-hypoxia-inducible-factor-response-elements-in-the-human-lysyl-oxidase-gene-promoter
#20
Victoria Wang, David A Davis, Robert Yarchoan
Human lysyl oxidase (LOX) is a hypoxia-responsive gene whose product catalyzes collagen crosslinking and is thought to be important in cancer metastasis and osteoarthritis. We previously demonstrated that LOX was upregulated by hypoxia inducible factor 2 (HIF-2) more strongly than hypoxia inducible 1 (HIF-1). We further investigated the response of the LOX gene and LOX promoter to HIFs. LOX mRNA, measured by real time reverse transcriptase-PCR, was strongly up-regulated (almost 40-fold), by transfection of HEK-293T cells with a plasmid encoding the HIF-2α subunit of HIF-2, but only three-fold by a plasmid encoding HIF-1α...
June 14, 2017: Biochemical and Biophysical Research Communications
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