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https://www.readbyqxmd.com/read/28722778/breast-cancer-stem-cells-are-involved-in-trastuzumab-resistance-through-the-her2-modulation-in-3d-culture
#1
Cristina Elisa Rodríguez, Damian Emilio Berardi, Marianela Abrigo, Laura Beatriz Torado, Elisa Dora Bal de Kier Joffé, Gabriel León Fiszman
Breast cancer human cells culture as spheroids develop autophagy and apoptosis, which promotes Trastuzumab resistance in HER2 overexpressing cells. Our aim was to study the association of the hostile environment developed in 3D with the breast cancer stem cells population and the HER2 modulation. Human mammary adenocarcinoma cell lines were cultured as spheroids using the hanging drop method. We generated hypoxia conditions by using a hypoxic chamber and CoCl2 treatment. Breast cancer stem cells were measured with mammosphere assays, the analysis of CD44 + CD24(low) population by flow cytometry and the pluripotent gene expression by RT-qPCR...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28722140/erythrocyte-membrane-enveloped-perfluorocarbon-as-nanoscale-artificial-red-blood-cells-to-relieve-tumor-hypoxia-and-enhance-cancer-radiotherapy
#2
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
#3
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/28721060/clinical-use-of-lenvatinib-in-combination-with-everolimus-for-the-treatment-of-advanced-renal-cell-carcinoma
#4
REVIEW
Alessandro Leonetti, Francesco Leonardi, Melissa Bersanelli, Sebastiano Buti
INTRODUCTION: Renal cell carcinoma (RCC) represents 2%-3% of all cancers in adults, and its pathogenesis is mainly related to altered cellular response to hypoxia. Lenvatinib, a novel multitarget tyrosine kinase inhibitor (TKI), represents a therapeutic option, in combination with mammalian target of rapamycin (mTOR) inhibitor everolimus, for the treatment of metastatic RCC (mRCC). AIM: The objective of this article is to review the evidence about the treatment of mRCC with combination of lenvatinib plus everolimus...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28720067/hpv16-e6-e7-upregulates-hif-2%C3%AE-and-vegf-by-inhibiting-lkb1-in-lung-cancer-cells
#5
Jian-Shuang Shao, Jian Sun, Shiyu Wang, Katherine Chung, Jin Tong Du, Jason Wang, Xue-Shan Qiu, En-Hua Wang, Guang-Ping Wu
Long-term persistent infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. However, molecular mechanisms of HPV16 E6/E7 induction of lung cancer are not fully understood. Using bi-directional genetic manipulation and four well-established lung cancer cell lines, we showed HPV16 E6/E7 downregulated expression of liver kinase B1 at both protein and messenger RNA levels; liver kinase B1 downregulated hypoxia-inducible factor 2α at protein level but not at messenger RNA level, and hypoxia-inducible factor 2α upregulated vascular endothelial growth factor at both protein and messenger RNA levels...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28718406/targeting-hypoxia-inducible-factors-for-antiangiogenic-cancer-therapy
#6
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/28715484/multiple-renal-cancer-susceptibility-polymorphisms-modulate-the-hif-pathway
#7
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/28714513/in-vivo-evaluation-of-tumour-acidosis-for-assessing-the-early-metabolic-response-and-onset-of-resistance-to-dichloroacetate-by-using-magnetic-resonance-ph-imaging
#8
Annasofia Anemone, Lorena Consolino, Laura Conti, Francesca Reineri, Federica Cavallo, Silvio Aime, Dario Livio Longo
Dichloroacetate (DCA) can reverse the glycolytic phenotype that is responsible of increased lactate production and extracellular pH acidification in cancer cells. Magnetic resonance imaging-chemical exchange saturation transfer (MRI-CEST) pH mapping is a novel non-invasive imaging approach that can measure in vivo extracellular tumour pH. We examined whether MRI-CEST pH mapping can monitor in vivo changes in tumour acidosis for assessing treatment response to DCA. Cell viability and extracellular pH were assessed in TS/A breast cancer cells treated with 1-10 mM DCA for 24 h in normoxia or hypoxia (1% O2) conditions...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28713976/melittin-exerts-an-antitumor-effect-on-non%C3%A2-small-cell-lung-cancer-cells
#9
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
#10
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/28713155/hypoxia-induces-universal-but-differential-drug-resistance-and-impairs-anticancer-mechanisms-of-5-fluorouracil-in-hepatoma-cells
#11
Jing-Qiu Li, Xian Wu, Lu Gan, Xiang-Liang Yang, Ze-Hong Miao
Hepatocellular carcinoma (HCC) is one of the most refractory cancers. The mechanisms by which hypoxia further aggravates therapeutic responses of advanced HCC to anticancer drugs remain to be clarified. Here, we report that hypoxia (1% O2) caused 2.55-489.7-fold resistance to 6 anticancer drugs (sorafenib, 5-fluorouracil [5-FU], gemcitabine, cisplatin, adriamycin and 6-thioguanine) in 3 HCC cell lines (BEL-7402, HepG2 and SMMC-7721). Among the 6 drugs, sorafenib, the sole one approved for HCC therapy, inhibited proliferation with little influence from hypoxia and displayed the smallest variation among the 3 HCC cell lines tested...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28712399/-expressions-of-stem-cell-factor-and-hypoxia-inducible-factor-1-alpha-in-pancreatic-cancer-cells-and-related-mechanism
#12
Min Zhang, Yunjian Wang, Qiong Li, Qingjun Li, Nanmu Yang, Guohua You, Li Wang
Objective To study the correlation between the expressions of stem cell factor (SCF) and hypoxia inducible factor 1 alpha (HIF-1α) in pancreatic cancer, and investigate the mechanism by which SCF regulates the expression of HIF-1α. Methods Immunohistochemistry was used to detect the expressions of SCF and HIF-1α in pancreatic cancer specimens and to analyze the correlation between SCF and HIF-1α expressions. Pancreatic cancer PANC-1 cells were treated with different doses of SCF (0, 1, 10, 100 ng/mL) alone or combined with c-KIT inhibitor Gleevec (5 μmol/L)...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28712397/-stem-cell-factor-enhances-invasive-ability-of-bxpc-3-cells-via-hypoxia-inducible-factor-1%C3%AE-hif-1%C3%AE
#13
Min Zhang, Kang Guo, Qiong Li, Yunjian Wang, Ling Zhang, Tao He, Baishun Wan, Xiaoqian Wang
Objective To investigate the effect of stem cell factor (SCF)/c-KIT system on the invasion of BxPC-3 pancreatic cancer cells and the role of hypoxia-inducible factor 1 alpha (HIF-1α) in this effect. Methods BxPC-3 cells were cultured in normoxia and hypoxia. The cells cultured in normoxia were treated with SCF. Real-time quantitative PCR and Western blotting were used to investigate the expressions of HIF-1α mRNA and protein, respectively. Small interference RNA of HIF-1α (siHIF-1α) was designed and synthesized, and then transfected into BxPC-3 cells...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
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
#14
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/28707601/potential-role-of-natural-compounds-as-anti-angiogenic-agents-in-cancer
#15
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
https://www.readbyqxmd.com/read/28707199/radiation-induced-inflammatory-cascade-and-its-reverberating-crosstalks-as-potential-cause-of-post-radiotherapy-second-malignancies
#16
REVIEW
Sonia Gandhi, Sudhir Chandna
The disease-free survival following radiotherapy is often limited by the development of second/secondary cancers. This significant impediment to effective cancer treatment implicated even in the modern-day radiotherapy needs to be countered effectively. Critical analysis reveals that besides achieving effective tumor control, radiotherapy elicits certain cellular and systemic inflammatory events in tumor infiltrate, which remain relatively stable and tend to facilitate "in-field" or "out of field" oncogenesis in due course of time...
July 13, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28705895/asymmetric-distribution-of-hypoxia-inducible-factor-%C3%AE-regulates-dorsoventral-axis-in-the-early-sea-urchin-embryo
#17
Wei-Lun Chang, Yi-Cheng Chang, Kuan-Ting Lin, Han-Ru Li, Chih-Yu Pai, Jen-Hao Chen, Yi-Hsien Su
Hypoxia signaling is an ancient pathway by which animals can respond to low oxygen. Malfunction of this pathway disturbs the hypoxic acclimation and results in various diseases, including cancers. The role of the hypoxia pathway in early embryogenesis remains unclear. Here, we show that in the sea urchin Strongylocentrotus purpuratus blastula, hypoxia-inducible factor α (HIFα), the downstream transcription factor of this pathway, is localized and transcriptionally active on the future dorsal side. This asymmetric distribution is attributable to its oxygen-sensing ability...
July 13, 2017: Development
https://www.readbyqxmd.com/read/28705806/roles-of-autophagy-and-metabolism-in-pancreatic-cancer-cell-adaptation-to-environmental-challenges
#18
Sandrina Maertin, Jason M Elperin, Ethan Lotshaw, Matthias Sendler, Steven D Speakman, Kazuki Takakura, Benjamin M Reicher, Olga A Mareninova, Paul J Grippo, Julia Mayerle, Markus M Lerch, Anna S Gukovskaya
Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly vascularized desmoplastic stromal reaction, and therefore pancreatic cancer (PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we investigate the roles of autophagy and metabolism in PaCa cell adaptation to environmental stresses, amino acid (AA) depletion and hypoxia. It is known that in healthy cells, basal autophagy is at a low level, but it is greatly activated by environmental stresses. By contrast, we find that in PaCa cells basal autophagic activity is relatively high, but AA depletion and hypoxia activate autophagy only weakly or not at all, due to their failure to inhibit mTOR...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28705470/hypoxia-and-hypoxia-response-associated-molecular-markers-in-esophageal-cancer-a-systematic-review
#19
REVIEW
Jurgen Peerlings, Lien Van De Voorde, Cristina Mitea, Ruben Larue, Ala Yaromina, Sebastian Sandeleanu, Linda Spiegelberg, Ludwig Dubois, Philippe Lambin, Felix M Mottaghy
PURPOSE: In this systematic review, the existing evidence of available hypoxia-associated molecular response biomarkers in esophageal cancer (EC) patients is summarized and set into the context of the role of hypoxia in the prediction of esophageal cancer, treatment response and treatment outcome. METHODS: A systematic literature search was performed in Web of Science, MEDLINE, and PubMed databases using the keywords: hypoxia, esophagus, cancer, treatment outcome and treatment response...
July 10, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28705232/hypoxia-inducible-factor-2%C3%AE-promotes-tumor-progression-and-has-crosstalk-with-wnt-%C3%AE-catenin-signaling-in-pancreatic-cancer
#20
Qi Zhang, Yu Lou, Jingying Zhang, Qihan Fu, Tao Wei, Xu Sun, Qi Chen, Jiaqi Yang, Xueli Bai, Tingbo Liang
BACKGROUND: Pancreatic cancer is a devastating disease that is characterized by persistent hypoxia. The roles of hypoxia-inducible factor-2α (hif-2α) are different to those of hif-1α, although both are critical for tumor cells to adapt to the hypoxic microenvironment. However, unlike the well-studied hif-1α, the role of hif-2α in tumors, including pancreatic cancer, is poorly understood. METHODS: Herein, we used a mutated hif-2α (A530T) to figure out the problem that wild-type hif-2α is quickly degraded which limits the study of its function...
July 14, 2017: Molecular Cancer
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