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Tumor hypoxia

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https://www.readbyqxmd.com/read/28735175/cancer-cell-membrane-coated-biomimetic-platform-for-tumor-targeted-photodynamic-therapy-and-hypoxia-amplified-bioreductive-therapy
#1
Shi-Ying Li, Hong Cheng, Wen-Xiu Qiu, Lu Zhang, Shuang-Shuang Wan, Jing-Yue Zeng, Xian-Zheng Zhang
Modulating tumor microenvironment to amplify the therapeutic efficiency would be a novel strategy for effective cancer treatment. In this work, based on the TPZ-loaded porphyrinic metal organic framework PCN-224 (PCN stands for porous coordination network), a cancer cell membrane-coated nanoplatform (TPZ@PCN@Mem) was fabricated for tumor targeted PDT and the successively resulting hypoxia-amplified bioreductive therapy. After administration, TPZ@PCN@Mem exhibited the selective accumulation and long-term retention at tumor tissue due to the immune escape and homologous targeting endowed by the cancer membrane coating...
July 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28734730/multifaceted-c-x-c-chemokine-receptor-4-inhibition-interferes-with-anti-vascular-endothelial-growth-factor-therapy-induced-glioma-dissemination
#2
Jean-Pierre Gagner, Yasmeen Sarfraz, Valerio Ortenzi, Fawaz M Alotaibi, Luis A Chiriboga, Awab T Tayyib, Garry J Douglas, Eric Chevalier, Barbara Romagnoli, Gérald Tuffin, Michel Schmitt, Guillaume Lemercier, Klaus Dembowsky, David Zagzag
Resistance to antiangiogenic therapy glioblastoma (GBM) patients may involve hypoxia-induced expression of stromal cell-derived factor (SDF)-1α receptor C-X-C chemokine receptor 4 (CXCR4) on invading tumor, macrophage/microglial cells (MGCs), and glioma stem cells (GSCs). We determined whether antagonizing CXCR4 with peptide epitope mimetic POL5551 disrupts anti-vascular endothelial growth factor therapy-induced glioma growth and dissemination. Mice bearing orthotopic CT-2A or GL261 gliomas received POL5551 and/or anti-vascular endothelial growth factor antibody B20-4...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28734696/-18-f-fluoromisonidazole-positron-emission-tomography-fmiso-pet-may-reflect-hypoxia-and-cell-proliferation-activity-in-oral-squamous-cell-carcinoma
#3
Jun Sato, Yoshimasa Kitagawa, Shiro Watanabe, Takuya Asaka, Noritaka Ohga, Kenji Hirata, Shozo Okamoto, Tohru Shiga, Masanobu Shindoh, Yuji Kuge, Nagara Tamaki
OBJECTIVE: Hypoxia is a common feature and prognostic factor in cancer. (18)F-fluoromisonidazole (FMISO) positron emission tomography (PET) can detect tumor hypoxia noninvasively. The aim of this study was to assess the correlations between FMISO-PET and (18) F-fluorodexyglucose (FDG)-PET parameters with cell proliferation and hypoxia in patients with oral squamous cell carcinoma (OSCC). STUDY DESIGN: Twenty-three preoperative patients with OSCC were included. The tumor/muscle ratio (TMR) of FMISO-PET, the maximum standardized uptake values (SUVmax) of FDG-PET, metabolic tumor volume, and total lesion glycolysis were measured...
June 8, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28734156/a-novel-hypoxia-response-element-regulates-oxygen-related-repression-of-tissue-factor-pathway-inhibitor-in-the-breast-cancer-cell-line-mcf-7
#4
Xue Yan Cui, Grethe Skretting, Mari Tinholt, Benedicte Stavik, Anders Erik Astrup Dahm, Kristine Kleivi Sahlberg, Sandip Kanse, Nina Iversen, Per Morten Sandset
BACKGROUND: Hypoxia is one of the most pervasive physiological stresses in solid tumors. We have previously demonstrated that tissue factor (TF) pathway inhibitor (TFPI) expression was transcriptionally repressed by the activation of hypoxia inducible factor (HIF)-1α under hypoxic conditions. However, the role of HIF-2α, also known as endothelial PAS domain-containing protein 1 (EPAS1), on TFPI expression remains unclear. AIM: To explore the role of HIF-2α/EPAS1 in the regulation of TFPI expression under hypoxia in breast cancer cells...
July 14, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28733543/the-role-of-adrenomedullin-in-the-pathogenesis-of-gastric-cancer
#5
Fuhao Qiao, Jian Fang, Jinfeng Xu, Wenqiu Zhao, Ying Ni, Bufugdi Andreas Akuo, Wei Zhang, Yun Liu, Fangfang Ding, Guanlin Li, Baoguo Liu, Hua Wang, Shihe Shao
Adrenomedullin has been shown to be overexpressed in many tumors, including gastric cancer tumors; however, its mechanism of action remains unclear. In this study, we examined the role of adrenomedullin in the pathogenesis of gastric cancer. Using clinical specimens and immunohistochemistry, we found that the expression levels of adrenomedullin and its receptors are inordinately elevated as compared to the adjacent non-tumor gastric tissues. We used siRNA gene silencing, in BGC-823 gastric cancer cell lines, to target adrenomedullin genes, and found that increased adrenomedullin expression results in the proliferation of tumor cells, tumor invasion, and metastasis...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730961/novel-fluorinated-porphyrins-sensitize-tumor-cells-to-photodamage-in-normoxia-and-hypoxia-synthesis-and-biocompatible-formulations
#6
Elizaveta V Belyaeva, Alina A Markova, Dmitry N Kaluzhnyb, Andrei L Sigan, Lev L Gervitz, Aida N Ataeva, Nikolai D Chkanikov, Alexander A Shtil
: Background. Hypoxia renders tumor cells refractory to treatment. One way to overcome this problem is the design of drug delivery systems that contain the antitumor agent within an oxygen supply medium. OBJECTIVE: to evaluate whether the perfluorocarbon liquids (capable of retaining up to 50% v/v amounts of O2 gas) can be tools for delivery of photosensitizers to hypoxic tumors. METHOD: We synthesized a series of compounds in which fluoroaliphatic or fluoroaromatic moieties were conjugated to the porphyrin ring in meso-positions...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28729699/pten-foxo3-akt-pathway-regulates-cell-death-and-mediates-morphogenetic-differentiation-of-colorectal-cancer-cells-under-simulated-microgravity
#7
Raj Pranap Arun, Divya Sivanesan, Prasanna Vidyasekar, Rama Shanker Verma
Gravity is a major physical factor determining the stress and strain around cells. Both in space experiments and ground simulation, change in gravity impacts the viability and function of various types of cells as well as in vivo conditions. Cancer cells have been shown to die under microgravity. This can be exploited for better understanding of the biology and identification of novel avenues for therapeutic intervention. Here, we described the effect of microgravity simulated using Rotational Cell Culture System-High Aspect Ratio Vessel (RCCS-HARV) on the viability and morphological changes of colorectal cancer cells...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726915/oleuropein-represses-the-radiation-resistance-of-ovarian-cancer-by-inhibiting-hypoxia-and-microrna-299-targetted-heparanase-expression
#8
Yubai Xing, Dawei Cui, Shun Wang, Pingping Wang, Xiaojing Xing, Hui Li
Radiotherapy in ovarian cancer frequently invokes resistance; this severely compromises its therapeutic effect and results in poor clinical prognosis. How to overcome the acquired resistance and re-sensitize tumors to radiation is the central question in this clinical setting. Cancer cell survival was evaluated using a clonogenic assay. The microRNA expression profile was analyzed using a microarray. Transcript expression was determined using real time PCR. The expression of protein was determined by immunoblotting...
July 20, 2017: Food & Function
https://www.readbyqxmd.com/read/28726849/o2-controllable-hydrogels-for-studying-cellular-responses-to-hypoxic-gradients-in-three-dimensions-in-vitro-and-in-vivo
#9
Daniel M Lewis, Michael R Blatchley, Kyung Min Park, Sharon Gerecht
Oxygen (O2) acts as a potent upstream regulator of cell function. In both physiological and pathophysiological microenvironments, the O2 concentration is not uniformly distributed but instead follows a gradient that depends on distance from oxygen-carrying blood vessels. Such gradients have a particularly important role in development, tissue regeneration, and tumor growth. In this protocol, we describe how to use our previously reported gelatin-based O2-controllable hydrogels that can provide hypoxic microenvironments in vitro...
August 2017: Nature Protocols
https://www.readbyqxmd.com/read/28726782/pkc%C3%AE-phosphorylates-traf2-to-protect-against-intestinal-ischemia-reperfusion-induced-injury
#10
Wei Zhou, Jihong Yao, Guangzhi Wang, Zhao Chen, Zhenlu Li, Dongcheng Feng, Yang Li, Wasim Qasim, Wenzhi Tan, Shili Ning, Xiaofeng Tian
Intestinal ischemia-reperfusion (I/R) is a common clinical problem that occurs during various clinical pathological processes. Excessive apoptosis has an indispensable role in intestinal I/R injury. Tumor necrosis factor receptor-associated factor 2 (TRAF2) and PKCζ have an essential role in apoptosis. Here, we aimed to investigate the effects of PKCζ and TRAF2 and to explore the correlation between PKCζ and TRAF2 in intestinal I/R injury. Mice were subjected to intestinal I/R injury in vivo. In vitro experiments were conducted by treating Caco-2 cells with hypoxia/reoxygenation (H/R) stimulation to simulate intestinal I/R...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28722140/erythrocyte-membrane-enveloped-perfluorocarbon-as-nanoscale-artificial-red-blood-cells-to-relieve-tumor-hypoxia-and-enhance-cancer-radiotherapy
#11
Min Gao, Chao Liang, Xuejiao Song, Qian Chen, Qiutong Jin, Chao Wang, Zhuang Liu
Hypoxia, a common feature within many types of solid tumors, is known to be closely associated with limited efficacy for cancer therapies, including radiotherapy (RT) in which oxygen is essential to promote radiation-induced cell damage. Here, an artificial nanoscale red-blood-cell system is designed by encapsulating perfluorocarbon (PFC), a commonly used artificial blood substitute, within biocompatible poly(d,l-lactide-co-glycolide) (PLGA), obtaining PFC@PLGA nanoparticles, which are further coated with a red-blood-cell membrane (RBCM)...
July 19, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28721903/clinical-advances-of-hypoxia-activated-prodrugs-in-combination-with-radiation-therapy
#12
REVIEW
Ishna N Mistry, Matthew Thomas, Ewen D D Calder, Stuart J Conway, Ester M Hammond
With the increasing incidence of cancer worldwide, the need for specific, effective therapies is ever more urgent. One example of targeted cancer therapeutics is hypoxia-activated prodrugs (HAPs), also known as bioreductive prodrugs. These prodrugs are inactive in cells with normal oxygen levels but in hypoxic cells (with low oxygen levels) undergo chemical reduction to the active compound. Hypoxia is a common feature of solid tumors and is associated with a more aggressive phenotype and resistance to all modes of therapy...
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28718406/targeting-hypoxia-inducible-factors-for-antiangiogenic-cancer-therapy
#13
REVIEW
Sergio Rey, Luana Schito, Bradly G Wouters, Scott Eliasof, Robert S Kerbel
Hypoxia (low O2) is a pathobiological hallmark of solid cancers, resulting from the imbalance between cellular O2 consumption and availability. Hypoxic cancer cells (CCs) stimulate blood vessel sprouting (angiogenesis), aimed at restoring O2 delivery to the expanding tumor masses through the activation of a transcriptional program mediated by hypoxia-inducible factors (HIFs). Here, we review recent data suggesting that the efficacy of antiangiogenic (AA) therapies is limited in some circumstances by HIF-dependent compensatory responses to increased intratumoral hypoxia...
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28715686/a-new-aggregation-induced-emission-fluorescent-probe-for-rapid-detection-of-nitroreductase-and-its-application-in-living-cells
#14
Gaoping Xu, Yonghe Tang, Yanyan Ma, An Xu, Weiying Lin
The biological activity of nitroreductase (NTR) is closely related to biological hypoxia status in organisms. The development of effective methods for monitoring the activity of NTR is of great significance for medical diagnosis and tumor research. Toward this goal, we have developed a new aggregation-induced emission (AIE) fluorescence NTR probe TPE-HY used the tetraphenylethene as the fluorophore, and used the nitro group as the NTR recognition site. The probe TPE-HY has many excellent properties, including rapid response, AIE characteristics, high sensitivity and selectivity, and low cytotoxicity...
July 3, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28715484/multiple-renal-cancer-susceptibility-polymorphisms-modulate-the-hif-pathway
#15
Steffen Grampp, Virginia Schmid, Rafik Salama, Victoria Lauer, Franziska Kranz, James L Platt, James Smythies, Hani Choudhry, Margarete Goppelt-Struebe, Peter J Ratcliffe, David R Mole, Johannes Schödel
Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28713976/melittin-exerts-an-antitumor-effect-on-non%C3%A2-small-cell-lung-cancer-cells
#16
Su-Fang Zhang, Zhe Chen
Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713928/upregulation-of-wnt-signaling-under-hypoxia-promotes-lung-cancer-progression
#17
Chun-Fu Hong, Wei-You Chen, Cheng-Wen Wu
The hypoxic tumor microenvironment induces epithelial-mesenchymal transition (EMT) in tumor cells and increases tumor cell malignancy. Previous studies indicated that malfunction of Wnt signaling is observed in some lung cancer patients. Athough crosstalk between hypoxia and Wnt signaling in tumor cells has recently been revealed, the detailed underlying mechanisms have not been well defined. In the present study, we demonstrated that hypoxia in lung adenocarcinoma cells can enhance Wnt signaling activity by stabilizing β-catenin and altering its localization into the nucleus...
July 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28710377/antiangiogenic-activity-of-phthalides-enriched-angelica-sinensis-extract-by-suppressing-wsb-1-pvhl-hif-1%C3%AE-vegf-signaling-in-bladder-cancer
#18
Meng-Chuan Chen, Wen-Lin Hsu, Wen-Liang Chang, Tz-Chong Chou
The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708593/microrna-33a-5p-increases-radiosensitivity-by-inhibiting-glycolysis-in-melanoma
#19
Ke Cao, Jingjing Li, Jia Chen, Li Qian, Aijun Wang, Xiang Chen, Wei Xiong, Jintian Tang, Shijie Tang, Yong Chen, Yao Chen, Yan Cheng, Jianda Zhou
Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (HIF-1α), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707601/potential-role-of-natural-compounds-as-anti-angiogenic-agents-in-cancer
#20
Muthu K Shanmugam, Sudha Warrier, Alan Prem Kumar, Gautam Sethi, Frank Arfuso
BACKGROUND: Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the body. Any disruption in this process can lead to the development of various chronic diseases, including cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth to malignant phenotypes and promoting metastasis...
July 12, 2017: Current Vascular Pharmacology
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