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https://www.readbyqxmd.com/read/28447753/antitumor-activity-of-fucoidan-in-anaplastic-thyroid-cancer-via-apoptosis-and-anti-angiogenesis
#1
Hong-Yan Shen, Lan-Zhen Li, Ke-Cheng Xue, Dan-Dan Hu, Yu-Jun Gao
The present study demonstrated the effect of fucoidan, isolated from Fucus vesiculosus, on cell growth and apoptosis in anaplastic thyroid cancer cells. The cell viability was analyzed using a Cell Counting Kit‑8 cell proliferation kit. Diamidino-2-phenylindole and terminal deoxynucleotidyl transferase-mediated dUTP nick‑end labeling assays were used to examine the apoptotic effect of fucoidan, which revealed the presence of apoptotic bodies and DNA fragmentation. Fucoidan inhibited the growth of FTC133 and TPC1 ATC cells in a dose‑dependent manner...
March 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28445935/inhibition-of-mtorc2-component-rictor-impairs-tumor-growth-in-pancreatic-cancer-models
#2
Katharina M Schmidt, Claus Hellerbrand, Petra Ruemmele, Christoph W Michalski, Bo Kong, Alexander Kroemer, Christina Hackl, Hans J Schlitt, Edward K Geissler, Sven A Lang
Mammalian Target of Rapamycin complex 2 (mTORC2) and its regulatory component Rapamycin-insensitive companion of mTOR (RICTOR) are increasingly recognized as important players in human cancer development and progression. However, the role of RICTOR in human pancreatic ductal adenocarcinoma (PDAC) is unclear so far. Here, we sought to analyze the effects of RICTOR inhibition in human pancreatic cancer cell lines in vitro and in vivo. Furthermore, RICTOR expression was determined in human PDAC samples. Results demonstrate that depletion of RICTOR with siRNA (transient knock-down) or shRNA (stable knock-down) has an inhibitory effect on tumor growth in vitro...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#3
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#4
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#5
Guilhem Bousquet, Morad El Bouchtaoui, Tan Sophie, Christophe Leboeuf, Cédric de Bazelaire, Philippe Ratajczak, Sylvie Giacchetti, Anne de Roquancourt, Philippe Bertheau, Laurence Verneuil, Jean-Paul Feugeas, Marc Espié, Anne Janin
There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC)...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444899/tumour-vascular-leakage-defect-due-to-endothelium-targeted-fak-kinase-dead-mutation-is-abrogated-by-fak-y397e-expression
#6
Annika N Alexopoulou, Delphine M Lees, Natalia Bodrug, Tanguy Lechertier, Isabelle Fernandez, Gabriela D'Amico, Matthew Dukinfield, Silvia Batista, Bernardo Tavora, Bryan Serrels, Kairbaan Hodivala-Dilke
Focal adhesion kinase (FAK) inhibitors have been developed as potential anti-cancer agents and are in clinical trials. In vitro activation of FAK kinase domain triggers autophosphorylation of tyrosine 397 (Y397), Src activation and subsequent phosphorylation of other FAK tyrosine residues. However, how FAK-Y397 mutations affect FAK-kinase-dead phenotypes in tumour angiogenesis in vivo is unknown. We developed three Pdgfb-iCre(ert) -driven endothelial-cell (EC)-specific, tamoxifen-inducible homozygous mutant mouse lines: FAK wild-type (WT), FAK kinase-dead (KD), and double mutant (DM); KD with a putatively phosphomimetic Y397E mutation...
April 26, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28443291/a-review-of-the-development-of-tumor-vasculature-and-its-effects-on-the-tumor-microenvironment
#7
REVIEW
Jake C Forster, Wendy M Harriss-Phillips, Michael Jj Douglass, Eva Bezak
BACKGROUND: The imbalance of angiogenic regulators in tumors drives tumor angiogenesis and causes the vasculature to develop much differently in tumors than in normal tissue. There are several cancer therapy techniques currently being used and developed that target the tumor vasculature for the treatment of solid tumors. This article reviews the aspects of the tumor vasculature that are relevant to most cancer therapies but particularly to vascular targeting techniques. MATERIALS AND METHODS: We conducted a review of identified experiments in which tumors were transplanted into animals to study the development of the tumor vasculature with tumor growth...
2017: Hypoxia
https://www.readbyqxmd.com/read/28442959/evaluation-of-different-doses-of-dexmedetomidine-alone-versus-the-combination-of-dexmedetomidine-and-fentanyl-in-sedation-during-awake-fiberoptic-intubation-in-oral-cancer-surgery-patients-a-prospective-randomized-double-blind-clinical-trial
#8
Mohamed Elsayed Hassan, Essam Mahran
BACKGROUND: Awake fiberoptic intubation (AFOI) is one of the principal techniques in the management of difficult airway in oral cancer surgery. We hypothesized that the addition of a small dose of fentanyl could improve the sedative criteria of dexmedetomidine during AFOI technique, without the need to increase the dose of dexmedetomidine which may be associated with airway compromise. PATIENTS AND METHODS: One hundred and fifty American Society of Anesthesiologists physical status 1 and 2 patients planned for AFOI for oral cancer surgery patients were allocated into three groups (fifty patients each)...
April 2017: Saudi Journal of Anaesthesia
https://www.readbyqxmd.com/read/28442599/overcoming-cisplatin-resistance-in-osteosarcoma-through-the-mir-199a-modulated-inhibition-of-hif-1%C3%AE
#9
Ajimu Keremu, Abudureyimu Aini, Yusufuaji Maimaitirexiati, Zhilin Liang, Pazila Aila, Paizila Xierela, Aikebaier Tusun, Hanikezi Moming, Aihemaitijiang Yusufu
Dysregulation of microRNAs has been shown to contribute to multiple tumorigenic processes, as well as to correlate with tumor progression and prognosis. MiR-199a has been shown to be dysregulated in multiple tumor types. However, the association between miR-199a and the chemoresistance features of osteosarcoma is not well understood, and the target genes for miR-199a and the regulatory mechanisms are also unknown. In this study, we demonstrated that miR-199a is expressed at low levels in osteosarcoma cells and patient samples...
April 25, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28440459/hypoxia-induced-mir-210-promoter-demethylation-enhances-proliferation-autophagy-and-angiogenesis-of-schwannoma-cells
#10
Zhengguang Wang, Mingsi Deng, Zhendong Liu, Song Wu
Hypoxia, a dominant feature in cancer occurrence and evolution, exists throughout the progression of most malignant tumors. This study focused on the mechanism of hypoxia-induced miR-210 upregulation, and the miR-210 functions in schwannoma. We detected microvascular density, vascular endothelial growth factor (VEGF) and miR-210 expression levels using schwannoma tissue mciroarray. The results showed that miR-210 expression was significantly associated with VEGF. Moreover, the cytological tests showed that hypoxia induced miR-210 expression, while reduce ephrin-A3 expression...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#11
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436629/-hypoxia-inducible-factor-1%C3%AE-and-cd133-predicts-pathological-complete-response-and-survival-for-locally-advanced-rectal-cancer-patients-after-neoadjuvant-chemoradiotherapy
#12
Cheng Cai, Jianping Wang, Zhifeng Zhong, Zhihui Dai, Qinghua Wang, Wuzhen Dong, Hongqi Shi, Qingwei Liu, Jinlin DU
Objective: To investigate the expression of hypoxia-inducible factor 1α (HIF-1α) and CD133 in predicting pathologic remission and survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy. Methods: One hundred and fourteen patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from January 2010 to December 2015 in Jinhua Municipal Central Hospital were enrolled in the study. RT-PCR and immunohistochemistry methods were used to detect the mRNA and protein expression of HIF-1α and CD133 before and after chemoradiotherapy...
January 25, 2017: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28435457/tumor-hypoxia-regulates-forkhead-box-c1-to-promote-lung-cancer-progression
#13
Yu-Jung Lin, Woei-Cherng Shyu, Chi-Wei Chang, Chi-Chung Wang, Chung-Pu Wu, Hsu-Tung Lee, Liang-Jwu Chen, Chia-Hung Hsieh
Forkhead box C1 (FOXC1) is a member of the forkhead family of transcription factors that are characterized by a DNA-binding forkhead domain. Increasing evidence indicates that FOXC1 is involved in tumor progression. However, the role of tumor hypoxia in FOXC1 regulation and its impact on lung cancer progression are unclear. Here, we report that FOXC1 was upregulated in hypoxic areas of lung cancer tissues from rodents or humans. Hypoxic stresses significantly induced FOXC1 expression. Moreover, hypoxia activated FOXC1 transcription via direct binding of hypoxia-inducible factor-1α (HIF-1α) to the hypoxia-responsive element (HRE) in the FOXC1 promoter...
2017: Theranostics
https://www.readbyqxmd.com/read/28435451/ahnak2-is-a-novel-prognostic-marker-and-oncogenic-protein-for-clear-cell-renal-cell-carcinoma
#14
Minglei Wang, Xuefeng Li, Jin Zhang, Qiong Yang, Wenqi Chen, Weilin Jin, Yi-Ran Huang, Ru Yang, Wei-Qiang Gao
Integrative database analysis was performed to identify novel candidate oncogene AHNAK2 overexpressed in clear cell renal cell carcinoma (ccRCC). However, the function of AHNAK2 in cancer cells is currently unknown. In this study, we first confirmed the upregulation of AHNAK2 in ccRCC tissues compared with adjacent normal tissues in 15 pairs of samples. Then we analyzed AHNAK2 expression in a large cohort of ccRCC patient samples (n = 355), and found that up-regulation of AHNAK2 was positively correlated with tumor progression and poor survival (p = 0...
2017: Theranostics
https://www.readbyqxmd.com/read/28435293/expression-and-significance-of-grhl2-in-esophageal-cancer
#15
Chengcheng Shao, Chushu Ji, Xiaoqiu Wang, Bing Hu
Esophageal cancer (EC) is one of the most common causes of cancer-related mortality in the world. Although much effort has been made to improve the 5-year survival rate of patients with EC, it still remains low due to diagnosis at an advanced stage, aggressive local invasion, early metastasis, and resistance to chemotherapy. Although grainyhead-like 2 (GRHL2) has attracted interest since it has been recently identified as a novel suppressor of the epithelial-mesenchymal transition, clinical values of GRHL2 and its relationship with the metastasis-related factors, such as hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), remain unclear...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28435028/antagonistic-effects-of-p53-and-hif1a-on-microrna-34a-regulation-of-ppp1r11-and-stat3-and-hypoxia-induced-epithelial-to-mesenchymal-transition-in-colorectal-cancer-cells
#16
Huihui Li, Matjaz Rokavec, Longchang Jiang, David Horst, Heiko Hermeking
BACKGROUND & AIMS: In colorectal tumors, hypoxia causes resistance to therapy and promotes metastasis. Loss of the tumor suppressor p53 (encoded by TP53) provides cancer cells with a selective advantage under conditions of hypoxia, but little is known about the mediators of this effect. METHODS: Isogenic CRC cell lines with different TP53 genotypes were placed under conditions of hypoxia. We examined the effects on levels and activity of microRNA-34 a (MIR34A) in CRC cells...
April 20, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28434798/prognostic-value-of-dynamic-hypoxia-pet-in-head-and-neck-cancer-results-from-a-planned-interim-analysis-of-a-randomized-phase-ii-hypoxia-image-guided-dose-escalation-trial
#17
Stefan Welz, David Mönnich, Christina Pfannenberg, Konstantin Nikolaou, Mathias Reimold, Christian La Fougère, Gerald Reischl, Paul-Stefan Mauz, Frank Paulsen, Markus Alber, Claus Belka, Daniel Zips, Daniela Thorwarth
BACKGROUND AND PURPOSE: To prospectively assess the prognostic value of tumour hypoxia determined by dynamic [(18)F]Fluoromisonidazole (dynFMISO) PET/CT, and to evaluate both feasibility and toxicity in patients with locally advanced squamous cell carcinomas of the head and neck (LASCCHN) treated with dynFMISO image-guided dose escalation (DE) using dose-painting by contours. PATIENTS AND METHODS: We present a planned interim analysis of a randomized phase II trial...
April 20, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28433659/carbonic-anhydrase-xii-functions-in-health-and-disease
#18
REVIEW
Abdul Waheed, William S Sly
Human CAXII was initially identified as a cancer marker in different cancers and tumors. Expression of CAXII is regulated by hypoxia and estrogen receptors. CAXII expression has been also detected in several tissues, whereas in cancer and tumor tissues its expression is several fold higher. In brain tumors, an alternatively spliced form of CAXII is expressed. Higher expression of CAXII in breast cancer is indicative of lower grade disease. CAXII plays a key role in several physiological functions. Mutation in the CAXII gene causes cystic fibrosis-like syndrome and salt wasting disease...
April 19, 2017: Gene
https://www.readbyqxmd.com/read/28430808/quantification-of-hypoxia-related-gene-expression-as-a-potential-approach-for-clinical-outcome-prediction-in-breast-cancer
#19
Abderrahim El Guerrab, Anne Cayre, Fabrice Kwiatkowski, Maud Privat, Jean-Marc Rossignol, Fabrice Rossignol, Frédérique Penault-Llorca, Yves-Jean Bignon
Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by "hypoxia inducible factors" that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28429085/the-role-of-rna-alternative-splicing-in-regulating-cancer-metabolism
#20
REVIEW
Itamar Kozlovski, Zahava Siegfried, Adi Amar-Schwartz, Rotem Karni
Tumor cells alter their metabolism by a wide array of mechanisms to promote growth and proliferation. Dysregulated expression and/or somatic mutations of key components of the glycolytic pathway/TCA cycle as well as other metabolic pathways allow tumor cells to improve their ability to survive harsh conditions such as hypoxia and the presence of reactive oxygen species, as well as the ability to obtain nutrients to increase lipids, protein, and nucleic acids biogenesis. Approximately 95% of the human protein encoding genes undergo alternative splicing (AS), a regulated process of gene expression that greatly diversifies the proteome by creating multiple proteins from a single gene...
April 20, 2017: Human Genetics
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