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https://www.readbyqxmd.com/read/28107201/homeodomain-interacting-protein-kinase-2-hipk2-a-promising-target-for-anti-cancer-therapies
#1
Yuanyuan Feng, Lihong Zhou, Xiaoting Sun, Qi Li
The HIPK2 (serine/threonine homeodomain-interacting protein kinase 2) is a "caretaker" gene, its inactivation increases tumorigenicity while its activation inhibits tumor growth. This report reviews the anti-tumorigenic mechanisms of HIPK2, which include promotion of apoptosis, inhibition of angiogenesis in hypoxia, prevention of tumor invasion/metastasis and attenuation of multidrug resistance in cancer. Additionally, we summarize conditions or factors that may increase HIPK2 activity.
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107190/radiosynthesis-and-validation-of-%C3%A2-18f-3-fluoro-2-hydroxypropionate-18f-flac-as-a-pet-tracer-of-lactate-to-monitor-mct1-dependent-lactate-uptake-in-tumors
#2
Vincent F Van Hée, Daniel Labar, Gwenaël Dehon, Debora Grasso, Vincent Grégoire, Giulio G Muccioli, Raphaël Frédérick, Pierre Sonveaux
Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106780/integrins-and-cell-metabolism-an-intimate-relationship-impacting-cancer
#3
REVIEW
Rehman Ata, Costin N Antonescu
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106284/oxidative-stress-promotes-doxorubicin-induced-pgp-and-bcrp-expression-in-colon-cancer-cells-under-hypoxic-conditions
#4
Martha L Pinzón-Daza, Yenith Cuellar-Saenz, Francisco Nualart, Alejandro Ondo-Mendez, Lilia Del Riesgo, Fabio Castillo-Rivera, Ruth Garzón
P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) are ATP binding cassette (ABC) transporters that are overexpressed in different drug-resistant cancer cell lines. In this study, we investigated whether doxorubicin promotes Pgp and/or BCRP expression to induce drug resistance in colon cancer cells under hypoxic conditions. We analyzed HIF-1α activity via ELISA, Pgp and BCRP expression by qRT-PCR and the relationship between doxorubicin uptake and ABC transporter expression via confocal microscopy in HT-29WT and HT-29 doxorubicin-resistant colon cancer cells (HT-29DxR)...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#5
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105369/potassium-channels-of-t-lymphocytes-take-center-stage-in-the-fight-against-cancer
#6
EDITORIAL
Laura Conforti
A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K(+) homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K(+) channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K(+) channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105231/pigment-epithelium-derived-factor-has-a-role-in-the-progression-of-papillary-thyroid-carcinoma-by-affecting-the-hif1%C3%AE-vegf-signaling-pathway
#7
Yichen Lv, Yu Sun, Tiefeng Shi, Chenlei Shi, Huadong Qin, Zhaozhu Li
The progression mechanism of papillary thyroid carcinoma (PTC) remains largely unknown. Accumulating evidence has suggested that various targets of pigment epithelium-derived factor (PEDF) are able to inhibit cancer progression. The aim of the present study was to examine PEDF expression in PTC patients and to investigate its relationship with aggressive clinicopathological features, as well as to explore whether PEDF affects the progression of PTC via the hypoxia-inducible factor 1α (HIF1α)-vascular endothelial growth factor (VEGF) pathway...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105174/improved-sensitization-effect-of-sunitinib-in-cancer-cells-of-the-esophagus-under-hypoxic-microenviroment
#8
Yu-Qiong Ding, Qin Qin, Yan Yang, Xin-Chen Sun, Xi Yang, Hong-Cheng Zhu, Xiao-Chen Chen, Hao Zhang, Yue-Hua Yang, Lei Gao, Ju-Dong Luo, Xi-Fa Zhou
Radiotherapy is widely used in esophageal squamous cell carcinoma (ESCC) treatment. Promoting the radiation sensitivity of cancer cells is required. Recent studies have shown that sunitinib can inhibit the growth of several cancer lines. However, few studies on the radiosensitive effect of sunitinib on ESCC cells under hypoxic conditions have been conducted. In the present study, the radiosensitive effects of sunitinib on human ESCC cells were assessed, and the underlying mechanisms were explored. ESCC cells were exposed to hypoxia and treated with sunitinib at different concentrations prior to irradiation...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105173/interleukin-6-promotes-tumor-progression-in-colitis-associated-colorectal-cancer-through-hif-1%C3%AE-regulation
#9
Jun Han, Qiulei Xi, Qingyang Meng, Jingzheng Liu, Yongxian Zhang, Yusong Han, Qiulin Zhuang, Yi Jiang, Qiurong Ding, Guohao Wu
Interleukin-6 (IL-6) is a well-known etiological factor of colitis-associated colorectal cancer (CAC) and has a significant role in CAC progression. In addition, hypoxia-inducible factor 1α (HIF-1α) serves a primary role in the progression of CAC. However, the association between IL-6 and HIF-1α during the progression of CAC remains unclear. To investigate this association, the present study induced CAC in a mouse model using azoxymethane and dextran sulfate sodium. In addition, an anti-IL-6 receptor antibody was used to inhibit IL-6...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105105/silencing-of-hypoxia-inducible-factor-1%C3%AE-promotes-thyroid-cancer-cell-apoptosis-and-inhibits-invasion-by-downregulating-wwp2-wwp9-vegf-and-vegfr2
#10
Zhong-Yang Ding, Yun-Juan Huang, Jian-Dong Tang, Gan Li, Pan-Qiang Jiang, Hao-Tian Wu
Adaptation to hypoxia is an important process physiologically and pathologically. Hypoxia-inducible factor-1α (HIF-1α) participates in the cancer biology of numerous endocrine tumors, including their proliferation and differentiation. In the present study, the hypothesis that HIF-1α promotes tumorigenesis in thyroid cancer via upregulating angiogenesis-associated markers is investigated. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to examine the expression of HIF-1α in thyroid cancer cell lines, and to detect the expression of WW domain containing E3 ubiquitin protein ligase (WWP)2, WWP9, vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in MZ-CRC-1 and TT thyroid cancer cells...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28104392/scutellarein-antagonizes-the-tumorigenesis-by-modulating-cytokine-vegf-mediated-neoangiogenesis-and-dff-40-actuated-nucleosomal-degradation
#11
Prabhu Thirusangu, V Vigneshwaran, B R Vijay Avin, H Rakesh, H M Vikas, B T Prabhakar
Neoplastic cells often reside in distinctive tumor hypoxia armed with a series of adaptive responses including oxidative stress, defective apoptotic machinery and neoangiogenesis, through that further confer cell survival improvement. Plants still acts as reservoir of natural chemicals to provide newer active pharmacophores. Scutellarein is flavones which has wide range of pharmacophoral effects. In our current research, scutellarein employed for targeting oxidative stress mediated tumor angiogenesis and apoptotic nuclear fragmentation...
January 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28101358/novel-predictive-biomarkers-for-cervical-cancer-prognosis
#12
Pablo Moreno-Acosta, Schyrly Carrillo, Oscar Gamboa, Alfredo Romero-Rojas, Jinneth Acosta, Monica Molano, Joseph Balart-Serra, Martha Cotes, Chloé Rancoule, Nicolas Magné
High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28099149/clinically-relevant-hif-1%C3%AE-dependent-metabolic-reprogramming-in-oropharyngeal-squamous-cell-carcinomas-includes-coordinated-activation-of-caix-and-the-mir-210-iscu-signaling-axis-but-not-mct1-and-mct4-upregulation
#13
Inés Sáenz-de-Santa-María, Cristóbal Bernardo-Castiñeira, Pablo Secades, Sandra Bernaldo-de-Quirós, Juan Pablo Rodrigo, Aurora Astudillo, María-Dolores Chiara
Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28097375/hypoxia-induced-fibroblast-growth-factor-11-stimulates-osteoclast-mediated-resorption-of-bone
#14
Helen J Knowles
Over-activation of osteoclasts is directly responsible for pathological bone loss in conditions such as rheumatoid arthritis and cancer metastasis to bone. Hypoxia is a common feature of these conditions, associated with poor prognosis, which also stimulates osteoclast-mediated bone resorption via induction of the hypoxia-inducible transcription factor HIF-1α. Here, we investigate the effects of fibroblast growth factor 11 (FGF11) on osteoclast function. FGF11 is an intracellular FGF that was induced both by hypoxia (2% O2, p < 0...
January 18, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28091613/adrenomedullin-promotes-angiogenesis-in-epithelial-ovarian-cancer-through-upregulating-hypoxia-inducible-factor-1%C3%AE-and-vascular-endothelial-growth-factor
#15
Yi Zhang, Yang Xu, Jian Ma, Xiaoyan Pang, Mei Dong
Adrenomedullin (ADM) is a multi-functional peptide related to many kinds of tumors. This study was aimed to investigate the role of ADM on angiogenesis in epithelial ovarian cancer (EOC) and its possible mechanism. The expressions of ADM, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α) and CD34 were examined by immunohistochemistry staining. The relationship among ADM, HIF-1α, VEGF and micro-vessel density (MVD) was assessed in 56 EOC tissues. CAOV3 cells were stably transfected with pcDNA-ADM (plasmid overexpressing ADM gene) or pRNA-shADM (small interfering RNA for ADM gene)...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089910/glioblastoma-cancer-stem-cells-evade-innate-immune-suppression-of-self-renewal-through-reduced-tlr4-expression
#16
Alvaro G Alvarado, Praveena S Thiagarajan, Erin E Mulkearns-Hubert, Daniel J Silver, James S Hale, Tyler J Alban, Soumya M Turaga, Awad Jarrar, Ofer Reizes, Michelle S Longworth, Michael A Vogelbaum, Justin D Lathia
Tumors contain hostile inflammatory signals generated by aberrant proliferation, necrosis, and hypoxia. These signals are sensed and acted upon acutely by the Toll-like receptors (TLRs) to halt proliferation and activate an immune response. Despite the presence of TLR ligands within the microenvironment, tumors progress, and the mechanisms that permit this growth remain largely unknown. We report that self-renewing cancer stem cells (CSCs) in glioblastoma have low TLR4 expression that allows them to survive by disregarding inflammatory signals...
December 27, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28089831/monomethyltransferase-setd8-regulates-breast-cancer-metabolism-via-stabilizing-hypoxia-inducible-factor-1%C3%AE
#17
Run Huang, Yang Yu, Xiangyun Zong, Xiaolin Li, Lisi Ma, Qi Zheng
SETD8 is a methyltransferase that specifically catalyzes the monomethylation of lysine 20 on histone H4. Previous studies have demonstrated that SETD8 is associated with proper cell cycle progression, DNA damage response, and transcriptional regulation. A recent study revealed that SETD8 played an important role in epithelial-mesenchymal transition (EMT) in association with TWIST and enhanced metastatic potential of breast cancer cells. However, the contribution of SETD8 to metabolism reprogramming, one hallmark of cancer, has never been reported...
January 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28089830/tumor-suppressor-spop-ubiquitinates-and-degrades-egln2-to-compromise-growth-of-prostate-cancer-cells
#18
Linli Zhang, Shan Peng, Xiangpeng Dai, Wenjian Gan, Xin Nie, Wenyi Wei, Guoqing Hu, Jianping Guo
EglN prolyl hydroxylases, a family of oxygen-sensing enzymes, hydroxylate distinct proteins to modulate diverse physiopathological signals. Aberrant regulations of EglNs result in multiple human diseases, including cancer. Different from EglN1 which function largely depends on the role of hypoxia-induce factor alpha (HIFα) in tumors, the functional significance and the upstream regulatory mechanisms of EglN2, especially in prostate cancer setting, remain largely unclear. Here, we demonstrated that dysregulation of EglN2 facilitated prostate cancer growth both in cells and in vivo...
January 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28089517/hypoxia-induces-a-hif-1-dependent-transition-from-collective-to-amoeboid-dissemination-in-epithelial-cancer-cells
#19
Steffi Lehmann, Veronika Te Boekhorst, Julia Odenthal, Roberta Bianchi, Sjoerd van Helvert, Kristian Ikenberg, Olga Ilina, Szymon Stoma, Jael Xandry, Liying Jiang, Reidar Grenman, Markus Rudin, Peter Friedl
Cancer metastases arise from a multi-step process that requires metastasizing tumor cells to adapt to signaling input from varying tissue environments [1]. As an early metastatic event, cancer cell dissemination occurs through different migration programs, including multicellular, collective, and single-cell mesenchymal or amoeboid migration [2-4]. Migration modes can interconvert based on changes in cell adhesion, cytoskeletal mechanotransduction [5], and/or proteolysis [6], most likely under the control of transcriptional programs such as the epithelial-to-mesenchymal transition (EMT) [7, 8]...
January 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28088787/hint2-downregulation-promotes-colorectal-carcinoma-migration-and-metastasis
#20
Weihua Li, Shaoxin Cai, Le Wang, Changshun Yang, Biaohuan Zhou, Huan Wang
Histidine triad nucleotide-binding 2 (HINT2), a member of the histidine triad proteins family, sensitizes cells to apoptosis in hepatocellular carcinoma. Here, we showed that HINT2 expression is lower in primary colorectal cancer (CRC) and metastasis tissues than in normal colorectal tissues, and that HINT2 abundance is inversely correlated with CRC tumor stage. Treating CRC cells with 5-aza-2'-deoxycytidine, a demethylating agent, upregulated HINT2, suggesting HINT2 downregulation is caused by methylation of the gene promoter...
January 10, 2017: Oncotarget
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