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Tumor hypoxia

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https://www.readbyqxmd.com/read/28633062/blue-light-induced-reactive-oxygen-species-from-flavin-mononucleotide-and-flavin-adenine-dinucleotide-on-lethality-of-hela-cells
#1
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
#2
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
#3
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
#4
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
#5
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/28630232/long-noncoding-rna-h19-promotes-neuroinflammation-in-ischemic-stroke-by-driving-histone-deacetylase-1-dependent-m1-microglial-polarization
#6
Jue Wang, Haiping Zhao, Zhibin Fan, Guangwen Li, Qingfeng Ma, Zhen Tao, Rongliang Wang, Juan Feng, Yumin Luo
BACKGROUND AND PURPOSE: Long noncoding RNA H19 is repressed after birth, but can be induced by hypoxia. We aim to investigate the impact on and underlying mechanism of H19 induction after ischemic stroke. METHODS: Circulating H19 levels in stroke patients and mice subjected to middle cerebral artery occlusion were assessed using real-time polymerase chain reaction. H19 siRNA and histone deacetylase 1 (HDAC1) plasmid were used to knock down H19 and overexpress HDAC1, respectively...
June 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28627761/biological-effects-of-hydrogen-peroxide-administered-intratumorally-with-or-without-irradiation-in-murine-tumors
#7
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
#8
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
#9
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/28624797/lymph-node-metastasis-and-the-physicochemical-micro-environment-of-pancreatic-ductal-adenocarcinoma-xenografts
#10
Lise Mari K Andersen, Catherine S Wegner, Trude G Simonsen, Ruixia Huang, Jon-Vidar Gaustad, Anette Hauge, Kanthi Galappathi, Einar K Rofstad
Pancreatic ductal adenocarcinoma (PDAC) patients develop lymph node metastases early and have a particularly poor prognosis. The poor prognosis has been shown to be associated with the physicochemical microenvironment of the tumor tissue, which is characterized by desmoplasia, abnormal microvasculature, extensive hypoxia, and highly elevated interstitial fluid pressure (IFP). In this study, we searched for associations between lymph node metastasis and features of the physicochemical microenvironment in an attempt to identify mechanisms leading to metastatic dissemination and growth...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624320/prognostic-value-of-the-vhl-hif-1%C3%AE-and-vegf-signaling-pathway-and-associated-mapk-erk1-2-and-erk5-pathways-in-clear-cell-renal-cell-carcinoma-a-long-term-study
#11
Antonio S Salinas-Sánchez, Leticia Serrano-Oviedo, Syongh Y Nam-Cha, Olga Roche-Losada, Ricardo Sánchez-Prieto, José M Giménez-Bachs
BACKGROUND: The prognostic value of molecular markers in renal cell carcinoma has been investigated in several studies. Although their value is still not confirmed, various proteins are important. We describe the effect on long-term survival of the status of the von Hippel-Lindau (VHL) hypoxia-inducible factor 1-α (HIF1-α) signaling pathway as well as associated mitogen-activated protein kinase (extracellular signal-regulated kinase [ERK]1/2 and ERK5). PATIENTS AND METHODS: A prospective, longitudinal cohort study was conducted with 50 patients diagnosed with clear-cell renal cell carcinoma to analyze VHL mutations and hypermethylation as well as VHL, HIF1-α, vascular endothelial growth factor (VEGF), ERK1/2, and ERK5 protein expression...
May 25, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28623514/the-potential-roles-of-bacteria-to-improve-radiation-treatment-outcome
#12
REVIEW
E Kouhsari, A Ghadimi-Daresajini, H Abdollahi, N Amirmozafari, S R Mahdavi, S Abbasian, S H Mousavi, H F Yaseri, M Moghaderi
Many combined therapies have been proposed to enhance radiotherapy outcome, but they have several limitations. As a new feasible strategy, combination of radiotherapy with bacteria showed a significant positive impact on the tumor treatment and metastasis inhibition. Although probiotic bacteria and radiotherapy alone can be effective in the treatment of different cancers, the combination of these two therapies seems to enhance therapeutic outcome and is cost-effective. Bacterial cells can act as therapeutic/gene/drug delivery vehicles as well as theranostic agents...
June 16, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28622163/novel-roles-for-mucin-1-in-the-kidney
#13
Mohammad M Al-Bataineh, Rebecca P Hughey
PURPOSE OF REVIEW: Recent studies in the kidney have revealed that the well characterized tumor antigen mucin 1 (MUC1/Muc1) also has numerous functions in the normal and injured kidney. RECENT FINDINGS: Mucin 1 is a transmembrane mucin with a robust glycan-dependent apical targeting signal and efficient recycling from endosomes. It was recently reported that the TRPV5 calcium channel is stabilized on the cell surface by galectin-dependent cross-linking to mucin 1, providing a novel mechanism for regulation of ion channels and normal electrolyte balance...
June 15, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28621524/harnessing-the-power-of-nanotechnology-for-enhanced-radiation-therapy
#14
Shreya Goel, Dalong Ni, Weibo Cai
Radiotherapy has emerged as one of the first lines of treatment in oncology. The past few decades have seen dramatic changes in the delivery of radiation therapy, with dose fractionation and treatment planning being the major focuses of research. Although effective, such empirical approaches are hardly optimal, and instances of patient mortality and tumor relapse are not rare. In this Perspective, we review the emerging technologies for optimization of radiosensitization, hypoxia modulation, and combinatorial therapeutic regimes for improved treatment outcomes in preclinical tumor models, with a focus on nanotechnology-mediated approaches...
June 16, 2017: ACS Nano
https://www.readbyqxmd.com/read/28620133/the-pvhl172-isoform-is-not-a-tumor-suppressor-and-up-regulates-a-subset-of-pro-tumorigenic-genes-including-tgfb1-and-mmp13
#15
P Hascoet, F Chesnel, F Jouan, C Le Goff, A Couturier, E Darrigrand, F Mahé, N Rioux-Leclercq, X Le Goff, Y Arlot-Bonnemains
The von Hippel-Lindau (VHL) tumor suppressor gene is often deleted or mutated in ccRCC (clear cell renal cell carcinoma) producing a non-functional protein. The gene encodes two mRNA, and three protein isoforms (pVHL213, pVHL160 and pVHL172). The pVHL protein is part of an E3 ligase complex involved in the ubiquitination and proteasomal degradation of different proteins, particularly hypoxia inducible factors (HIF) that drive the transcription of genes involved in the regulation of cell proliferation, angiogenesis or extracellular matrix remodelling...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620021/correction-for-wolff-et-al-cell-type-dependent-regulation-of-mtorc1-by-redd1-and-the-tumor-suppressors-tsc1-tsc2-and-lkb1-in-response-to-hypoxia
#16
Nicholas C Wolff, Silvia Vega-Rubin-de-Celis, Xian-Jin Xie, Diego H Castrillon, Wareef Kabbani, James Brugarolas
No abstract text is available yet for this article.
July 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28619756/alpha-particle-enhanced-blood-brain-tumor-barrier-permeabilization-in-glioblastomas-using-integrin-alpha-v-beta-3-targeted-liposomes
#17
Anirudh Sattiraju, Xiaobing Xiong, Darpan N Pandya, Thaddeus J Wadas, Ang Xuan, Yao Sun, Youngkyoo Jung, Kiran Kumar Solingapuram Sai, Jay F Dorsey, King C Li, Akiva Mintz
<span style="font-size: 11.0pt; line-height: 200%; color: windowtext;">Glioblastoma (GBM) is the most common primary malignant astrocytoma characterized by extensive invasion, angiogenesis, hypoxia and micrometastasis. Despite the relatively leaky nature of GBM blood vessels, effective delivery of anti-tumor therapeutics has been a major challenge due to the complications caused by the blood brain barrier (BBB) and the highly torturous nature of newly formed tumor vasculature (blood tumor barrier-BTB)...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28619735/the-evolving-role-of-succinate-in-tumor-metabolism-an-18-f-fdg-based-study
#18
Philippe Garrigue, Aurore Bodin-Hullin, Laure Balasse, Samantha Fernandez, Wassim Essamet, Françoise Dignat-George, Karel Pacak, Benjamin Guillet, David Taieb
Objective: In recent years, inherited and acquired mutations in the TCA cycle enzymes have been reported in diverse cancers. Pheochromocytomas and paragangliomas (PPGLs) often exhibit dysregulation of glucose metabolism which is also driven by mutations in genes encoding the TCA cycle enzymes or by activation of hypoxia signaling. PPGLs associated with succinate dehydrogenase (SDH) deficiency are characterized by high (18)F-fluorodeoxyglucose ([(18)F]-FDG) avidity. This association is currently only partially explained...
June 15, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28619042/metabolic-targeting-of-hif-dependent-glycolysis-reduces-lactate-increases-oxygen-consumption-and-enhances-response-to-high-dose-single-fraction-radiotherapy-in-hypoxic-solid-tumors
#19
Eric Leung, Rob A Cairns, Naz Chaudary, Ravi N Vellanki, Tuula Kalliomaki, Eduardo H Moriyama, Hilda Mujcic, Brian C Wilson, Bradly G Wouters, Richard Hill, Michael Milosevic
BACKGROUND: A high rate of glycolysis leading to elevated lactate content has been linked to poor clinical outcomes in patients with head and neck and cervical cancer treated with radiotherapy. Although the biological explanation for this relationship between lactate and treatment response remains unclear, there is a continued interest in evaluating strategies of targeting metabolism to enhance the effectiveness of radiotherapy. The goal of this study was to investigate the effect of metabolic-targeting through HIF-1α inhibition and the associated changes in glycolysis, oxygen consumption and response on the efficacy of high-dose single-fraction radiotherapy (HD-SFRT)...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28617871/hypoxia-inducible-factor-1%C3%AE-plays-roles-in-epstein-barr-virus-s-natural-life-cycle-and-tumorigenesis-by-inducing-lytic-infection-through-direct-binding-to-the-immediate-early-bzlf1-gene-promoter
#20
Richard J Kraus, Xianming Yu, Blue-Leaf A Cordes, Saraniya Sathiamoorthi, Tawin Iempridee, Dhananjay M Nawandar, Shidong Ma, James C Romero-Masters, Kyle G McChesney, Zhen Lin, Kathleen R Makielski, Denis L Lee, Paul F Lambert, Eric C Johannsen, Shannon C Kenney, Janet E Mertz
When confronted with poor oxygenation, cells adapt by activating survival signaling pathways, including the oxygen-sensitive transcriptional regulators called hypoxia-inducible factor alphas (HIF-αs). We report here that HIF-1α also regulates the life cycle of Epstein-Barr virus (EBV). Incubation of EBV-positive gastric carcinoma AGS-Akata and SNU-719 and Burkitt lymphoma Sal and KemIII cell lines with a prolyl hydroxylase inhibitor, L-mimosine or deferoxamine, or the NEDDylation inhibitor MLN4924 promoted rapid and sustained accumulation of both HIF-1α and lytic EBV antigens...
June 15, 2017: PLoS Pathogens
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