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Hypoxia and metastasis

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https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-receptor-expression-to-promote-metastasis
#1
Julia A Ju, Ines Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
: Metastasis is the leading cause of breast cancer (BCa)mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM binding receptors in this process was explored. Using a bioinformatics approach the expression of all integrin receptor subunits, in two independent BCa patient data sets, were analyzed to determine if integrin status correlates with a validated hypoxiainducible gene signature...
February 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#2
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28209257/synthesis-and-evaluation-of-n-benzofuran-5-yl-aromaticsulfonamide-derivatives-as-novel-hif-1-inhibitors-that-possess-anti-angiogenic-potential
#3
Jinlian Wei, Yingrui Yang, Yali Li, Xiaofei Mo, Xiaoke Guo, Xiaojin Zhang, Xiaoli Xu, Zhengyu Jiang, Qidong You
Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis, and poor patient prognosis has been recognized as an important cancer drug target. A novel series of N-(benzofuran-5-yl)aromaticsulfonamide derivatives were synthesized and evaluated as HIF-1 inhibitor. Among these compounds, 7q exhibited specific inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. It inhibited the HIF-1 transcriptional activity (IC50=12.5±0.7μM) and secretion of VEGF (IC50=18...
June 11, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28198519/correlation-of-hypoxia-inducible-transcription-factor-in-breast-cancer-and-suvmax-of-f-18-fdg-pet-ct
#4
Young-Ju Jeong, Jae-Won Jung, Yoon-Young Cho, Sung-Hwan Park, Hoon-Kyu Oh, Sungmin Kang
BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed...
2017: Nuclear Medicine Review. Central & Eastern Europe
https://www.readbyqxmd.com/read/28198007/modulating-tumor-hypoxia-by-nanomedicine-for-effective-cancer-therapy
#5
REVIEW
Rana Jahanban-Esfahlan, Miguel de la Guardia, Delshad Ahmadi, Bahman Yousefi
Hypoxia, a characteristic feature of tumors, is indispensable to tumor angiogenesis, metastasis, and multi drug resistance. Hypoxic avascular regions, deeply embedded inside the tumors significantly hinder delivery of therapeutic agents. The low oxygen tension results in resistance to the current applied anti-cancer therapeutics including radiotherapy, chemotherapy and photodynamic therapy, the efficacy of which is firmly tied to the level of tumor oxygen supply. However, emerging data indicate that nanocarriers/nanodrugs can offer substantial benefits to improve the efficacy of current therapeutics, through modulation of tumor hypoxia...
February 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28187917/oxygen-and-placental-development-parallels-and-differences-with-tumour-biology
#6
Graham J Burton, Eric Jauniaux, Andrew J Murray
Human placentation involves the invasion of the conceptus into the wall of the uterus, and establishment of a blood supply from the maternal spiral arteries. The placenta has therefore been likened to a malignant tumour, albeit a highly regulated one. Oxygen plays an important role in controlling both placental development and tumour behaviour. In the placenta, early development takes place in a physiological low oxygen environment, which undergoes a transition with onset of the full maternal arterial circulation towards the end of the first trimester...
February 1, 2017: Placenta
https://www.readbyqxmd.com/read/28182306/effect-of-a-hypoxic-microenvironment-after-radiofrequency-ablation-on-residual-hepatocellular-cell-migration-and-invasion
#7
Yuyang Tong, Haiyun Yang, Xiaolin Xu, Jingliang Ruan, Ming Liang, Jiayi Wu, Baoming Luo
Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored...
February 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28179306/hif1%C3%AE-in-tumorigenesis-of-adenoid-cystic-carcinoma
#8
Yun-Sung Lim, Wonjae Cha, Min-Woo Park, Woo-Jin Jeong, Soon-Hyun Ahn
BACKGROUND: Tumor hypoxia induces hypoxia-inducible factor-1α (HIF1α), which can influence tumorigenesis and metastasis. We evaluated the expression of HIF1α and the effect of HIF1α inhibitors in adenoid cystic carcinoma (ACC). MATERIALS AND METHODS: HIF1α expression was demonstrated in ACC cell lines (ACC2 and ACCM). The effect of HIF1α inhibitors was evaluated. A systemic metastasis model was developed. The number of metastatic pulmonary nodules were analyzed...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28173803/hypoxia-inducible-microrna-224-promotes-the-cell-growth-migration-and-invasion-by-directly-targeting-rassf8-in-gastric-cancer
#9
Chuan He, Libo Wang, Jiantao Zhang, Hong Xu
BACKGROUND: Hypoxia plays an important role in the development of various cancers. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and modulate the tumorigenesis, including gastric cancer. However, the roles and molecular mechanism of miR-224 in gastric cancer under hypoxia remain poorly understood. METHOD: Real-time PCR and Northern blot assay were used to examine the effects of hypoxia and HIF-1α on miR-224 expression. Luciferase and ChIP assays were performed to determine whether miR-224 was a transcriptional target of HIF-1α...
February 7, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28169279/corrigendum-daxx-inhibits-hypoxia-induced-lung-cancer-cell-metastasis-by-suppressing-the-hif-1%C3%AE-hdac1-slug-axis
#10
Ching-Wen Lin, Lu-Kai Wang, Shu-Ping Wang, Yih-Leong Chang, Yi-Ying Wu, Hsuan-Yu Chen, Tzu-Hung Hsiao, Wei-Yun Lai, Hsuan-Hsuan Lu, Ya-Hsuan Chang, Shuenn-Chen Yang, Ming-Wei Lin, Chi-Yuan Chen, Tse-Ming Hong, Pan-Chyr Yang
No abstract text is available yet for this article.
February 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28169245/evaluation-of-hypoxia-inducible-factor-1-alpha-gene-expression-in-colorectal-cancer-stages-of-iranian-patients
#11
Reyhaneh Nassiri Mansour, Seyed Ehsan Enderami, Abdolreza Ardeshirylajimi, Koorosh Fooladsaz, Mojtaba Fathi, Shahla Moahammad Ganji
AIM OF STUDY: Colorectal cancer (CRC) is the fourth most prevalent cancer globally. Several factors have roles in cancer establishment. One of the most important factors is hypoxia that induces hypoxia inducible factor-1 (HIF-1). The HIF-1 alpha overexpressed in hypoxia conditions and plays a pivotal role in carcinogenesis features. In this study, we aimed to examine the efficiency of HIF-1 alpha gene expression at mRNA and protein's level for CRC diagnosing and staging. MATERIALS AND METHODS: In this study, the cases included into 75 cancer specimens in different stages (Group 2 = Stage 1, Group 3 = Stage 2, and Group 4 = Stage 3, 4) and ten normal specimens as control (Group 1)...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28168807/hypoxia-induced-hif1%C3%AE-targets-in-melanocytes-reveal-a-molecular-profile-associated-with-poor-melanoma-prognosis
#12
Stacie K Loftus, Laura L Baxter, Julia C Cronin, Temesgen D Fufa, William J Pavan
Hypoxia and HIF1α signaling direct tissue-specific gene responses regulating tumor progression, invasion and metastasis. By integrating HIF1α knockdown and hypoxia-induced gene expression changes, this study identifies a melanocyte-specific, HIF1α-dependent / hypoxia-responsive gene expression signature. Integration of these gene expression changes with HIF1α ChIP-Seq analysis identifies 81 HIF1α direct target genes in melanocytes. The expression levels for ten of the HIF1α direct targets - GAPDH, PKM, PPAT, DARS, DTWD1, SEH1L, ZNF292, RLF, AGTRAP, and GPC6 - are significantly correlated with reduced time of Disease Free Status (DFS) in melanoma by logistic regression (P-value =0...
February 6, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28166483/the-importance-of-regulatory-ubiquitination-in-cancer-and-metastasis
#13
L H Gallo, J Ko, D J Donoghue
Ubiquitination serves as a degradation mechanism of proteins, but is involved in additional cellular processes such as activation of NFκB inflammatory response and DNA damage repair. We highlight the E2 ubiquitin conjugating enzymes, E3 ubiquitin ligases and Deubiquitinases that support the metastasis of a plethora of cancers. E3 ubiquitin ligases also modulate pluripotent cancer stem cells attributed to chemotherapy resistance. We further describe mutations in E3 ubiquitin ligases that support tumor proliferation and adaptation to hypoxia...
February 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28165392/sphingosine-kinase-1-involves-the-inhibitory-action-of-hif-1%C3%AE-by-chlorogenic-acid-in-hypoxic-du145-cells
#14
Myoung-Sun Lee, Seon-Ok Lee, Kyu-Ri Kim, Hyo-Jeong Lee
Hypoxia enhances cancer development in a solid tumor. Hypoxia-inducible factor-1 α (HIF-1α) is a transcription factor that is dominantly expressed under hypoxia in solid tumor cells and is a key factor that regulates tumor. HIF-1α regulates several target genes involved in many aspects of cancer progression, including angiogenesis, metastasis, anti-apoptosis and cell proliferation as well as imparts resistance to cancer treatment. In this study, we assessed Crataegus Pinnatifida Bunge var. typical Schneider ethanol extract (CPE) for its anti-cancer effects in hypoxia-induced DU145 human prostate cancer cell line...
February 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28165223/tumor-penetrating-nanoparticles-for-enhanced-anticancer-activity-of-combined-photodynamic-and-hypoxia-activated-therapy
#15
Yazhe Wang, Ying Xie, Jing Li, Zheng-Hong Peng, Yuri Sheinin, Jianping Zhou, David Oupický
Poor tumor penetration is a major challenge for the use of nanoparticles in anticancer therapy. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in inadequate exposure to antitumor therapeutics and contributes to development of chemoresistance and increased metastasis. In the present study, we developed iRGD-modified nanoparticles for simultaneous tumor delivery of a photosensitizer indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine (TPZ). The iRGD-modified nanoparticles loaded with ICG and TPZ showed significantly improved penetration in both 3D tumor spheroids in vitro and orthotopic breast tumors in vivo...
February 6, 2017: ACS Nano
https://www.readbyqxmd.com/read/28153790/hif-2-dependent-expression-of-stem-cell-factor-promotes-metastasis-in-hepatocellular-carcinoma
#16
Xiuchao Wang, Jie Dong, Li Jia, Tiansuo Zhao, Mingxiao Lang, Zengxun Li, Chungen Lan, Xin Li, Jihui Hao, Hongwei Wang, Tai Qin, Chongbiao Huang, Shengyu Yang, Ming Yu, He Ren
Stem cell factor (SCF) is a multifunctional cytokine responsible for tumorigenesis and progression. In this study, we report that increased expression of SCF in hepatocellular carcinoma (HCC) patients is highly associated with metastasis and poor prognosis. SCF inhibition with RNAi inhibited HCC cell migration, invasion in vitro, and reduced intrahepatic metastases burden and significantly prolonged survival in a HCC xeograft mouse model. SCF depletion in HCC xeograft decreased the expression of vimentin and increase the expression of E-cadherin, implicating a role for SCF in epithelial-mesenchymal transition...
January 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28141797/a-combination-of-low-dose-bevacizumab-and-imatinib-enhances-vascular-normalisation-without-inducing-extracellular-matrix-deposition
#17
L M Schiffmann, M Brunold, M Liwschitz, V Goede, S Loges, M Wroblewski, A Quaas, H Alakus, D Stippel, C J Bruns, M Hallek, H Kashkar, U T Hacker, O Coutelle
BACKGROUND: Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy...
January 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28137473/targeting-ph-regulating-proteins-for-cancer-therapy-progress-and-limitations
#18
REVIEW
Scott K Parks, Jacques Pouysségur
Tumour acidity induced by metabolic alterations and incomplete vascularisation sets cancer cells apart from normal cellular physiology. This distinguishing tumour characteristic has been an area of intense study, as cellular pH (pHi) disturbances disrupt protein function and therefore multiple cellular processes. Tumour cells effectively utilise pHi regulating machinery present in normal cells with enhancements provided by additional oncogenic or hypoxia induced protein modifications. This overall improvement of pH regulation enables maintenance of an alkaline pHi in the continued presence of external acidification (pHe)...
January 27, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28134767/hdac-inhibitors-and-reck-modulate-endoplasmic-reticulum-stress-in-tumor-cells
#19
REVIEW
Yun Chen, Ya-Hui Tsai, Sheng-Hong Tseng
In the tumor microenvironment hypoxia and nutrient deprived states can induce endoplasmic reticulum (ER) stress. If ER stress is not relieved, the tumor cells may become apoptotic. Therefore, targeting ER homeostasis is a potential strategy for cancer treatment. Various chemotherapeutic agents including histone deacetylase (HDAC) inhibitors can induce ER stress to cause cell death in cancers. Some HDAC inhibitors can prevent HDAC from binding to the specificity protein 1-binding site of the promoter of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and up-regulate RECK expression...
January 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28127049/hhip-regulates-tumor-stroma-mediated-upregulation-of-tumor-angiogenesis
#20
Vijayendra Agrawal, Dong Young Kim, Young-Guen Kwon
Tumor growth is governed by the coordinated action of various types of cells that are present in the tumor environment. Fibroblasts, which constitute a major fraction of the stroma, participate actively in various signaling events and regulate tumor development and metastasis. The Hedgehog (Hh) pathway plays an important role in promoting tumor malignancy via fibroblasts; however, the role of hedgehog interacting protein (hhip; inhibitor of Hh pathway) in tumor growth is poorly understood. Here we implanted B16F10 tumors in hhip+/- mice to study the tumor growth characteristics and the vascular phenotype...
January 27, 2017: Experimental & Molecular Medicine
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