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https://www.readbyqxmd.com/read/28210556/are-breast-cancer-stem-cells-the-key-to-resolving-clinical-issues-in-breast-cancer-therapy
#1
REVIEW
Hidetaka Shima, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo
Despite the dramatic advances in breast cancer treatment over the past two decades, it is still the most common malignancies in women. One of the reasons patients succumb to breast cancer is treatment resistance leading to metastasis and recurrence. Recently, cancer stem cells (CSCs) have been suggested as a cause of metastasis and recurrence in several cancers because of their unique characteristics, including self-renewal, pluripotency, and high proliferative ability. Increasing evidence has implicated breast cancer stem cells (BCSCs) as essential for tumor development, progression, recurrence, and treatment resistance...
February 2017: Gland Surgery
https://www.readbyqxmd.com/read/28192990/dual-stimuli-activatable-oxidative-stress-amplifying-agent-as-a-hybrid-anticancer-prodrug
#2
Eunji Han, Byeongsu Kwon, Donghyuck Yoo, Changsun Kang, Gilson Khang, Dongwon Lee
Compared to normal cells, cancer cells have a higher level of reactive oxygen species (ROS) due to aberrant metabolism and disruption of redox homeostasis which drive their proliferation and promote progression and metastasis of cancers. The altered redox balance and biological difference between normal cells and cancer cells provide a basis for the development of anticancer agents which are able to generate pharmacological ROS insults to kill cancer cells preferentially. In this study, we report a new hybrid anticancer drug, termed OSamp, which undergoes esterase- and acid-catalyzed hydrolysis to deplete antioxidant glutathione (GSH) and generate ROS, simultaneously...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28181495/expression-of-%C3%AE-globin-by-cancer-cells-promotes-cell-survival-during-blood-borne-dissemination
#3
Yu Zheng, David T Miyamoto, Ben S Wittner, James P Sullivan, Nicola Aceto, Nicole Vincent Jordan, Min Yu, Nezihi Murat Karabacak, Valentine Comaills, Robert Morris, Rushil Desai, Niyati Desai, Erin Emmons, John D Milner, Richard J Lee, Chin-Lee Wu, Lecia V Sequist, Wilhelm Haas, David T Ting, Mehmet Toner, Sridhar Ramaswamy, Shyamala Maheswaran, Daniel A Haber
Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28177238/design-synthesis-and-biological-evaluation-of-mitochondria-targeted-flavone-naphthalimide-polyamine-conjugates-with-antimetastatic-activity
#4
Fujun Dai, Qian Li, Yuxia Wang, Chaochao Ge, Chenyang Feng, Songqiang Xie, Haoying He, Xiaojuan Xu, Chaojie Wang
Approximately 90% of cancer-associated deaths result from disseminated tumors, indicating the ineffectiveness of current therapies and the imperative need of antimetastatic drugs. A novel pharmacophore with flavonoid and naphthalimide moieties was constructed by using a fragment-based drug design and a series of eight flavone-naphthalimide-polyamine conjugates were synthesized. In vitro evaluation revealed that compound 6c with a homospermidine motif displayed better cell selectivity between cancerous and normal liver cells than amonafide did...
February 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28150492/mesoporous-silica-nanoparticles-as-an-anti-tumoral-angiogenesis-strategy
#5
Magdiel Inggrid Setyawati, David Tai Leong
Tumors depend heavily on angiogenesis for nutrient derivation and subsequently metastasis. Targeting tumor induced angiogenesis per se can address both tumor growth and progression simultaneously. Here, we show that we could elegantly restrict the endothelial cells angiogenic behavior through digital size control of mesoporous silica nanoparticle (MSN). This anti-angiogenesis effect was derived from the particle size dependent uptake and production of intracellular reactive oxygen species (ROS) that directly interfered with p53 tumor suppressor pathway...
February 2, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28138033/targeted-treatment-of-metastatic-breast-cancer-by-plk1-sirna-delivered-by-an-antioxidant-nanoparticle-platform
#6
Jingga Morry, Worapol Ngamcherdtrakul, Shenda Gu, Moataz Reda, David J Castro, Thanapon Sangvanich, Joe W Gray, Wassana Yantasee
Metastatic breast cancer is developed in about 20-30% of newly diagnosed early stage breast cancer patients despite treatments. Herein, we report a novel nanoparticle platform with intrinsic anti-metastatic properties for the targeted delivery of Polo-like kinase 1 siRNA (siPLK1). We first evaluated it in a triple negative breast cancer (TNBC) model, which shows high metastatic potential. PLK1 was identified as the top therapeutic target for TNBC cells and tumor initiating cells in a kinome-wide screen. The platform consists of a 50-nm mesoporous silica nanoparticle (MSNP) core coated layer-by-layer with bioreducible cross-linked PEI and PEG polymers, conjugated with an antibody for selective uptake into cancer cells...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28137309/induction-of-metastasis-cancer-stem-cell-phenotype-and-oncogenic-metabolism-in-cancer-cells-by-ionizing-radiation
#7
REVIEW
Su Yeon Lee, Eui Kyong Jeong, Min Kyung Ju, Hyun Min Jeon, Min Young Kim, Cho Hee Kim, Hye Gyeong Park, Song Iy Han, Ho Sung Kang
Radiation therapy is one of the major tools of cancer treatment, and is widely used for a variety of malignant tumours. Radiotherapy causes DNA damage directly by ionization or indirectly via the generation of reactive oxygen species (ROS), thereby destroying cancer cells. However, ionizing radiation (IR) paradoxically promotes metastasis and invasion of cancer cells by inducing the epithelial-mesenchymal transition (EMT). Metastasis is a major obstacle to successful cancer therapy, and is closely linked to the rates of morbidity and mortality of many cancers...
January 30, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28123307/basal-oxidative-stress-ratio-of-head-and-neck-squamous-cell-carcinomas-correlates-with-nodal-metastatic-spread-in-patients-under-therapy
#8
D Dequanter, R Dok, S Nuyts
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that is strongly associated with oxidative damage and oxidative stress. Tobacco and alcohol - sources of massive quantities of reactive oxygen species (ROS) - have been clearly identified as etiologic factors that contribute to these malignancies. Considering the role of glutathione (GSH) in ROS detoxification, we hypothesized that potential biological markers can be found in addition to the parameters of oxidative stress...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28109867/interactions-between-interleukin-6-and-myeloid-derived-suppressor-cells-drive-the-chemoresistant-phenotype-of-hepatocellular-cancer
#9
Min Xu, Zhongwei Zhao, Jingjing Song, Xilin Lan, Siming Lu, Minjiang Chen, Zufei Wang, Weiqian Chen, Xiaoxi Fan, Fazong Wu, Li Chen, Jianfei Tu, Jiansong Ji
Emerging evidence implicates an important role for myeloid-derived suppressor cells (MDSCs) in tumor growth, angiogenesis and metastasis. However, limited knowledge is known about the function of MDSCs in response to chemotherapies. In this study, we find that drug-resistant hepatocellular cancer (HCC) cells-derived conditioned medium significantly enhances the expansion and immunosuppressive function of MDSCs compared to their parental sensitive cells, which is demonstrated by increased level of arginase, nitric oxide (NO), and reactive oxygen species (ROS)...
February 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28106298/inhibition-of-inositol-1-4-5-trisphosphate-receptor-induce-breast-cancer-cell-death-through-deregulated-autophagy-and-cellular-bioenergetics
#10
Aru Singh, Megha Chagtoo, Swasti Tiwari, Nelson George, Bandana Chakravarti, Sajid Khan, Sripada Lakshmi, Madan M Godbole
Inositol 1,4,5-trisphosphate receptors (IP3 Rs) regulate autophagy in normal cells and are associated with metastasis in cancer cells. In breast cancer, however, the regulation and role of IP3 Rs is not clear. To study this we used MCF-7 breast cancer cell line and mouse model of breast cancer. Inhibiting IP3 R sub types resulted in compromised bioenergetics both in terms of glucose and mitochondrial metabolism. The siRNA mediated silencing of IP3 R or its blocking by its inhibitors Xestospongin C and 2-Amino-ethoxy diphenyl borate increased cell death and LC3II expression in MCF-7 cells as well as attenuated cellular bioenergetics...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28098862/rhein-suppresses-matrix-metalloproteinase-production-by-regulating-the-rac1-ros-mapk-ap-1-pathway-in-human-ovarian-carcinoma-cells
#11
Guomei Zhou, Fenghui Peng, Yanping Zhong, Yanhua Chen, Min Tang, Danrong Li
Matrix metalloproteinases (MMPs) are a family of calcium-dependent zinc-containing endopeptidases, which play an integral role in migration and invasion of ovarian cancer. Rac1 proteins might mostly influence cell migration and invasion by generating endogenous reactive oxygen species. Therefore, inhibiting MMPs and regulating the Rac1/ROS/MAPK/AP-1 pathway may be a new therapeutic strategy for ovarian cancer. In this study, we found that rhein could suppress the invasion and migration of SKOV3-PM4 cells with characteristics of directional highly lymphatic metastasis...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28088622/reactive-oxygen-species-and-cancer-paradox-to-promote-or-to-suppress
#12
REVIEW
Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy...
January 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28088520/palmitic-acid-increases-invasiveness-of-pancreatic-cancer-cells-aspc-1-through-tlr4-ros-nf-%C3%AE%C2%BAb-mmp-9-signaling-pathway
#13
Makena J Binker-Cosen, Daniel Richards, Brenda Oliver, Herbert Y Gaisano, Marcelo G Binker, Laura I Cosen-Binker
Pancreatic cancer (PC) is an aggressive malady with proclivity for early metastasis. Overexpression of toll-like receptor 4 (TLR4) in pancreatic ductal adenocarcinoma, the most common type of pancreatic malignancy, correlates to tumor size, lymph node involvement, venous invasion and pathological stage. Lipopolysaccharides (LPS) are natural TLR4 ligands that have been shown to increase the invasive ability of PC cells. However, rapid inactivation of circulating LPS and low systemic absorption of inhaled LPS from the bronchoalveolar compartment make other agonists such as saturated fatty acids more suitable to be considered for TLR4-related cell invasiveness...
January 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28086938/alpha-enolase-eno1-controls-alpha-v-beta-3-integrin-expression-and-regulates-pancreatic-cancer-adhesion-invasion-and-metastasis
#14
Moitza Principe, Simone Borgoni, Mariafrancesca Cascione, Michelle Samuel Chattaragada, Sammy Ferri-Borgogno, Michela Capello, Sara Bulfamante, Jennifer Chapelle, Francesca Di Modugno, Paola Defilippi, Paola Nisticò, Paola Cappello, Chiara Riganti, Stefano Leporatti, Francesco Novelli
BACKGROUND: We have previously shown that in pancreatic ductal adenocarcinoma (PDA) cells, the glycolytic enzyme alpha-enolase (ENO1) also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28081539/regulation-of-anoikis-resistance-by-nadph-oxidase-4-and-epidermal-growth-factor-receptor
#15
Hyeryeong Kim, Jee Young Sung, Eun-Kyung Park, Seongho Kho, Kyung Hee Koo, Seog-Yun Park, Sung-Ho Goh, Yoon Kyung Jeon, Sekyung Oh, Byung-Kiu Park, Yong-Keun Jung, Yong-Nyun Kim
BACKGROUND: Normal cells are sensitive to anoikis, which is a cell detachment-induced apoptosis. However, cancer cells acquire anoikis resistance that is essential for successful metastasis. This study aimed to demonstrate the function and potential mechanism of NADPH oxidase 4 (NOX4) and EGFR activation in regulating anoikis resistance in lung cancer. METHODS: Cells were cultured either in the attached or suspended condition. Cell viability was measured by cell counting and live and dead cell staining...
January 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28068066/gold-nanospheres-stabilized-indocyanine-green-as-a-synchronous-photodynamic-photothermal-therapy-platform-that-inhibits-tumor-growth-and-metastasis
#16
Wei Li, Hanbo Zhang, Xiaomeng Guo, Zuhua Wang, Fenfen Kong, Lihua Luo, Qingpo Li, Chunqi Zhu, Jie Yang, Yan Lou, Yongzhong Du, Jian You
Both photothermal therapy (PTT) and photodynamic therapy (PDT) are phototherapeutic approaches, which have been widely investigated for cancer therapy mediated by an external light source. Here, a nanosystem presenting the synchronous PTT and PDT effect realized through one-step near-infrared (NIR) light irradiation is reported. This system was fabricated by conjugating indocyanine green (ICG) on hollow gold nanospheres (HAuNS) using branched-polyethylenimine (PEI, MW = 10 kDa) as optimal linker, which provided a high ICG payload as well as a covering layer with suitable thickness on HAuNS to maintain ICG fluorescence and reactive oxygen species (ROS) productivity...
February 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28049506/novel-derivative-of-aminobenzenesulfonamide-3c-induces-apoptosis-in-colorectal-cancer-cells-through-ros-generation-and-inhibits-cell-migration
#17
Khayal Al-Khayal, Ahmed Alafeefy, Mansoor-Ali Vaali-Mohammed, Amer Mahmood, Ahmed Zubaidi, Omar Al-Obeed, Zahid Khan, Maha Abdulla, Rehan Ahmad
BACKGROUND: Colorectal cancer (CRC) is the 3(rd) most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. METHODS: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument...
January 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28034671/stat5a-mediated-nox5-l-expression-promotes-the-proliferation-and-metastasis-of-breast-cancer-cells
#18
So Hee Dho, Ji Young Kim, Kwang-Pyo Lee, Eun-Soo Kwon, Jae Cheong Lim, Chang-Jin Kim, Dongjun Jeong, Ki-Sun Kwon
NADPH oxidase (NOX) generates reactive oxygen species (ROS) and has been suggested to mediate cell proliferation in some cancers. Here, we show that an increase in the expression of NOX5 long form (NOX5-L) is critical for tumor progression in breast tumor tissues. Immunostaining of clinical samples indicated that NOX5 was overexpressed in 41.1% of breast ductal carcinoma samples. NOX5-L depletion consistently suppressed cell proliferation, invasion, and migration in vitro. Antibody-mediated neutralization of NOX5-L attenuated tumor progression in a mouse xenograft model...
December 26, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/28012439/oxidative-stress-in-cancer-and-fibrosis-opportunity-for-therapeutic-intervention-with-antioxidant-compounds-enzymes-and-nanoparticles
#19
REVIEW
Jingga Morry, Worapol Ngamcherdtrakul, Wassana Yantasee
Oxidative stress, mainly contributed by reactive oxygen species (ROS), has been implicated in pathogenesis of several diseases. We review two primary examples; fibrosis and cancer. In fibrosis, ROS promote activation and proliferation of fibroblasts and myofibroblasts, activating TGF-β pathway in an autocrine manner. In cancer, ROS account for its genomic instability, resistance to apoptosis, proliferation, and angiogenesis. Importantly, ROS trigger cancer cell invasion through invadopodia formation as well as extravasation into a distant metastasis site...
December 16, 2016: Redox Biology
https://www.readbyqxmd.com/read/28007895/hypoxia-inducible-factors-coupling-glucose-metabolism-and-redox-regulation-with-induction-of%C3%A2-the-breast-cancer-stem-cell-phenotype
#20
REVIEW
Gregg L Semenza
Reduced oxygen availability (hypoxia) leads to increased production of reactive oxygen species (ROS) by the electron transport chain. Here, I review recent work delineating mechanisms by which hypoxia-inducible factor 1 (HIF-1) mediates adaptive metabolic responses to hypoxia, including increased flux through the glycolytic pathway and decreased flux through the tricarboxylic acid cycle, in order to decrease mitochondrial ROS production. HIF-1 also mediates increased flux through the serine synthesis pathway and mitochondrial one-carbon (folate cycle) metabolism to increase mitochondrial antioxidant production (NADPH and glutathione)...
February 1, 2017: EMBO Journal
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