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https://www.readbyqxmd.com/read/27910777/gastric-adenocarcinoma-biomarker-expression-profiles-and-their-prognostic-value
#1
Serkan Senol, Abdullah Aydin, Duygu Kosemetin, Dilek Ece, Ibrahim Akalin, Hasan Abuoglu, Esra Akdeniz Duran, Dincer Aydin, Burcak Erkol
Expression levels of several molecules implicated in carcinogenesis were examined by immunohistochemical staining, and the prognostic significance of their expression levels in gastric adenocarcinoma (GA) was evaluated. A total of 115 GA and 20 control gastric tissue samples were evaluated by immunohistochemistry using 33 antibodies targeting molecules known to play a part in the development of various tumors. Overexpression of carbonic anhydrase IX (CAIX) and loss of AT-rich interactive domain-containing protein 1A (ARID1A), aldehyde dehydrogenase 1 (ALDH1), and CD44 expression in GA patients were significantly correlated with lymph node (LN) metastasis, advanced tumor stage, and poor prognosis...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27910776/molecular-pathology-of-malignant-transformation-of-oral-submucous-fibrosis
#2
Amit Chattopadhyay, Jay Gopal Ray
Oral submucous fibrosis (OSF) is prevalent mostly in Southeast Asia, particularly in the Indian subcontinent. Chewing betel nuts and betel leaves, with or without tobacco, has been associated with OSF. Betel quid contents including guvacine, arecoline, guvacoline, arecaidine, and chavibetol are considered to play an important part in the occurrence of OSF. Transformation of OSF to squamous cell carcinoma (SCC) is variable, but up to 13% conversion of OSF to SCC has been reported. Various genetic and molecular mechanisms impact the malignant transformation of OSF, causing changes in the cell cycle, DNA, keratinocytes, and keratin; tumor-cell proliferation and survival; angiogenesis; fibrosis through epithelial-mesenchymal transitions (EMTs), and tissue hypoxia...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27909731/hypoxia-drives-the-transition-of-human-dermal-fibroblasts-to-a-myofibroblast-like-phenotype-via-the-tgf-%C3%AE-1-smad3-pathway
#3
Bin Zhao, Hao Guan, Jia-Qi Liu, Zhao Zheng, Qin Zhou, Jian Zhang, Lin-Lin Su, Da-Hai Hu
Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial‑mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring...
December 1, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27908927/corrigendum-reengineering-the-tumor-microenvironment-to-alleviate-hypoxia-and-overcome-cancer-heterogeneity
#4
John D Martin, Dai Fukumura, Dan G Duda, Yves Boucher, Rakesh K Jain
No abstract text is available yet for this article.
December 1, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27908264/hypoxia-and-inflammation-in-prostate-cancer-progression-cross-talk-with-androgen-and-estrogen-receptors-and-cancer-stem-cells
#5
Matteo A Russo, Linda Ravenna, Laura Pellegrini, Elisa Petrangeli, Luisa Salvatori, Thea Magrone, Massimo Fini, Marco Tafani
Tumors are complex tissues in which transformed cells communicate with the surrounding microenvironment and evolve traits promoting their own survival and malignancy. Hypoxia and inflammation are constant characteristics of prostate tumor microenvironment influencing both cancer stem cells and differentiated tumor cells. HIFs and NF-kB are the key regulators of the transcriptional response to hypoxic and inflammatory stresses, respectively, and a crosstalk between HIFs and NF-kB pathways has been widely documented...
November 30, 2016: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/27902970/activity-of-the-novel-polo-like-kinase-4-inhibitor-cfi-400945-in-pancreatic-cancer-patient-derived-xenografts
#6
I Lohse, J M Mason, P J Cao, Melania Pintilie, M R Bray, D W Hedley
BACKGROUND: Polo-like kinase 4 (PKL4) plays a key role in centriole replication. Hence PLK4 inhibition disrupts mitosis, and offers a novel approach to treating chromosomally unstable cancers, including pancreatic cancer. CFI-400945 is a first in class small molecule PLK4 inhibitor, currently undergoing early phase clinical trials. RESULTS: Treatment with CFI-400945 significantly reduced tumor growth and increased survival in four out of the six models tested. Consistent with PLK4 inhibition, we observed reduced expression of the proliferation marker Ki-67 associated with an increase in nuclear diameter during treatment with CFI-400945...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902963/homology-modeling-and-molecular-dynamics-simulation-of-the-hif2%C3%AE-degradation-related-hif2%C3%AE-vhl-complex
#7
Xiaotian Dong, Xiaoru Su, Jiong Yu, Jingqi Liu, Xiaowei Shi, Qiaoling Pan, Jinfeng Yang, Jiajia Chen, Lanjuan Li, Hongcui Cao
BACKGROUND: Hypoxia-inducible factor 2 alpha (HIF2α), prolyl hydroxylase domain protein 2 (PHD2), and the von Hippel Lindau tumor suppressor protein (pVHL) are three principal proteins in the oxygen-sensing pathway. Under normoxic conditions, a conserved proline in HIF2α is hydroxylated by PHD2 in an oxygen-dependent manner, and then pVHL binds and promotes the degradation of HIF2α. However, the crystal structure of the HIF2α-pVHL complex has not yet been established, and this has limited research on the interaction between HIF and pVHL...
November 21, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27902314/newcastle-disease-virus-degrades-hif-1%C3%AE-through-proteasomal-pathways-independent-of-vhl-and-p53
#8
Noraini Abd-Aziz, Eric Stanbridge, Norazizah Shafee
Newcastle disease virus (NDV) is a candidate agent for oncolytic virotherapy. Despite its potential, the exact mechanism of its oncolysis is still not known. Recently, we reported that NDV exhibited an increased oncolytic activity in hypoxic cancer cells. These types of cells negatively affect therapeutic outcome by overexpressing pro-survival genes under the control of the hypoxia-inducible factor (HIF). HIF-1 is a heterodimeric transcriptional factor consisting of a regulated alpha (HIF-1α) and a constitutive beta subunit (HIF-1β)...
October 6, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901496/cancer-initiating-cells-are-enriched-in-the-ca9-positive-fraction-of-primary-cervix-cancer-xenografts
#9
Delphine Tamara Marie-Egyptienne, Naz Chaudary, Tuula Kalliomäki, David William Hedley, Richard Peter Hill
Numerous studies have suggested that Cancer Initiating Cells (CIC) can be identified/enriched in cell populations obtained from solid tumors based on the expression of cell surface marker proteins. We used early passage primary cervix cancer xenografts to sort cells based on the expression of the intrinsic hypoxia marker Carbonic Anhydrase 9 (CA9) and tested their cancer initiation potential by limiting dilution assay. We demonstrated that CICs are significantly enriched in the CA9+ fraction in 5/6 models studied...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901482/hyperglycemia-triggers-hipk2-protein-degradation
#10
Silvia Baldari, Alessia Garufi, Marisa Granato, Laura Cuomo, Giuseppa Pistritto, Mara Cirone, Gabriella D'Orazi
Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900001/expression-of-glucose-transporter-1-is-correlated-with-hypoxia-inducible-factor-1%C3%AE-and-malignant-potential-in-pancreatic-neuroendocrine-tumors
#11
Minoru Fujino, Shinichi Aishima, Koji Shindo, Yasunori Oda, Katsuya Morimatsu, Kosuke Tsutsumi, Takao Otsuka, Masao Tanaka, Yoshinao Oda
The present study aimed to investigate the prognostic usefulness of the expression of glucose transporter type 1 (GLUT-1) and GLUT-2, hypoxia-inducible factor 1α (HIF-1α) and insulin-like growth factor II messenger RNA-binding protein 3 (IMP3) in pancreatic neuroendocrine tumors (pNETs). Immunohistochemical staining for GLUT-1, GLUT-2, HIF-1α and IMP3 was performed in 70 pNET specimens. The expression of GLUT-1 and HIF-1α was significantly higher in the World Health Organization grade 2 (G2), neuroendocrine carcinoma cases and mixed-type pNETs compared with the G1 cases...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898465/the-intragraft-microenvironment-as-a-central-determinant-of-chronic-rejection-or-local-immunoregulation-tolerance
#12
Johannes Wedel, Hironao Nakayama, Nora M Kochupurakkal, Josephine Koch, Michael Klagsbrun, Diane R Bielenberg, David M Briscoe
PURPOSE OF REVIEW: Chronic rejection is associated with persistent mononuclear cell recruitment, endothelial activation and proliferation, local tissue hypoxia and related biology that enhance effector immune responses. In contrast, the tumor microenvironment elicits signals/factors that inhibit effector T cell responses and rather promote immunoregulation locally within the tissue itself. The identification of immunoregulatory check points and/or secreted factors that are deficient within allografts is of great importance in the understanding and prevention of chronic rejection...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27895979/optical-redox-ratio-identifies-metastatic-potential-dependent-changes-in-breast-cancer-cell-metabolism
#13
Kinan Alhallak, Lisa G Rebello, Timothy J Muldoon, Kyle P Quinn, Narasimhan Rajaram
The development of prognostic indicators of breast cancer metastatic risk could reduce the number of patients receiving chemotherapy for tumors with low metastatic potential. Recent evidence points to a critical role for cell metabolism in driving breast cancer metastasis. Endogenous fluorescence intensity of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) can provide a label-free method for assessing cell metabolism. We report the optical redox ratio of FAD/(FAD + NADH) of four isogenic triple-negative breast cancer cell lines with varying metastatic potential...
November 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27895745/evaluation-of-the-association-between-hif-1%C3%AE-and-her-2-expression-hormone-receptor-status-ki-67-expression-histology-and-tumor-fdg-uptake-in-breast-cancer
#14
Sevi M Sureyya Cerci, Kemal Kursat Bozkurt, Hasan Erol Eroglu, Celal Cerci, Evrim Erdemoglu, Pinar Talip Bulbul, Meltem Cetin, Recep Cetin, Ibrahim Metin Ciris, Mahmut Bulbul
The present study aimed to examine hypoxia-inducible factor (HIF)-1α expression and its association with glucose uptake in invasive breast cancer. In addition, connections between glucose uptake and several other prognostic parameters of breast cancer were studied. Between August 2013 and April 2015, 92 patients with biopsy-diagnosed breast cancer were subjected to (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. The primary tumor and nodal maximum standardized uptake values (SUVmax) were recorded, and HIF-1α expression and clinical parameters, including tumor mass, estrogen receptor (ER) and progesterone receptor (PgR) levels, human epidermal growth factor receptor-2 (HER-2), Ki-67 index, grade and histology, were analyzed...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27893711/the-induction-of-mig6-under-hypoxic-conditions-is-critical-for-dormancy-in-primary-cultured-lung-cancer-cells-with-activating-egfr-mutations
#15
H Endo, J Okami, H Okuyama, Y Nishizawa, F Imamura, M Inoue
The biologic activity of individual cancer cells is highly heterogeneous. Hypoxia, one of the prominent features of a tumor microenvironment, is thought to be causal in generating this cellular heterogeneity. In this study, we revealed that primary lung cancer cells harboring activating epidermal growth factor receptor (EGFR) mutations generally entered a dormant state when hypoxic. We found that heterodimer formation of the ERBB family receptor tyrosine kinases (RTKs), and their subsequent downstream signaling, was diminished under hypoxic conditions, although phosphorylation of the EGFR was retained...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27890795/inhibition-of-histone-lysine-acetyltransferase-activity-kills-cocl2-treated-and-hypoxia-exposed-gastric-cancer-cells-and-reduces-their-invasiveness
#16
Suvasmita Rath, Lopamudra Das, Shrikant Babanrao Kokate, Nilabh Ghosh, Pragyesh Dixit, Niranjan Rout, Shivaram P Singh, Subhasis Chattopadhyay, Hassan Ashktorab, Duane T Smoot, Mahadeva M Swamy, Tapas K Kundu, Sheila E Crowe, Asima Bhattacharyya
Hypoxia enhances immortality and metastatic properties of solid tumors. Deregulation of histone acetylation has been associated with several metastatic cancers but its effect on hypoxic responses of cancer cells is not known. This study aimed at understanding the effectiveness of the hydrazinocurcumin, CTK7A, an inhibitor of p300 lysine/histone acetyltransferase (KAT/HAT) activity, in inducing apoptosis of gastric cancer cells (GCCs) exposed to cobalt chloride (CoCl2), a hypoxia-mimetic chemical, or 1% O2. Here, we show that CTK7A-induced hydrogen peroxide (H2O2) generation in CoCl2-exposed and invasive gastric cancer cells (GCCs) leads to p38 MAPK-mediated Noxa expression and thereafter, mitochondrial apoptotic events...
November 23, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27889560/microrna-let-7g-inhibited-hypoxia-induced-proliferation-of-pasmcs-via-g0-g1-cell-cycle-arrest-by-targeting-c-myc
#17
Wei-Fang Zhang, You-Wen Xiong, Tian-Tian Zhu, Ai-Zhen Xiong, Hui-Hui Bao, Xiao-Shu Cheng
AIMS: Pulmonary hypertension (PH) is a proliferative disorder characterized by enhanced proliferation and suppressed apoptosis of intrapulmonary vascular smooth muscle cells. Recently, network-based bioinformatics have identified let-7 family, a tumor suppressive microRNA, regulate multiple interacting targets relevant to PH. However, the role of let-7 in vascular homeostasis in PH remains unknown. Thus, we wanted to investigate the role of let-7 in hypoxia-induced PASMCs proliferation and the underlying mechanism in hypoxic pulmonary hypertension (HPH)...
November 23, 2016: Life Sciences
https://www.readbyqxmd.com/read/27889433/the-protective-effect-of-curcumin-in-olfactory-ensheathing-cells-exposed-to-hypoxia
#18
Roberta Bonfanti, Teresa Musumeci, Cristina Russo, Rosalia Pellitteri
Curcumin, a phytochemical component derived from the rhizomes of Curcuma longa, has shown a great variety of pharmacological activities, such as anti-inflammatory, anti-tumor, anti-depression and anti-oxidant activity. Therefore, in the last years it has been used as a therapeutic agent since it confers protection in different neurodegenerative diseases, cerebral ischemia and excitotoxicity. Olfactory Ensheathing Cells (OECs) are glial cells of the olfactory system. They are able to secrete several neurotrophic growth factors, promote axonal growth and support the remyelination of damaged axons...
November 23, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27886571/apigenin-inhibited-hypoxia-induced-stem-cell-marker-expression-in-a-head-and-neck-squamous-cell-carcinoma-cell-line
#19
Yuwaporn Ketkaew, Thanaphum Osathanon, Prasit Pavasant, Sireerat Sooampon
OBJECTIVE: Cancer stem cells contribute to tumor recurrence, and a hypoxic environment is critical for maintaining cancer stem cells. Apigenin is a natural product with anticancer activity. However, the effect of apigenin on cancer stem cells remains unclear. Our aim was to investigate the effect of apigenin on cancer stem cell marker expression in head and neck squamous cell carcinoma cells under hypoxia. DESIGN: We used three head and neck squamous cell carcinoma cell lines; HN-8, HN-30, and HSC-3...
November 15, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/27886551/reconsidering-azobenzene-as-a-component-of-small-molecule-hypoxia-mediated-cancer-drugs-a-theranostic-case-study
#20
Peter Verwilst, Jiyou Han, Jiyeong Lee, Sora Mun, Hee-Gyoo Kang, Jong Seung Kim
An azobenzene scaffold serves as both a fluorescence quencher and nitrogen mustard deactivator in a mitochondrial targeting unit bearing theranostic drug delivery system (DDS). The DDS exhibited a tissue selectivity for tumors with aggressive phenotypes, and the efficient in vitro and in vivo azoreduction under hypoxia conditions resulted in bright fluorescence at the tumor site as well as the in situ activation of the prodrug. In vivo therapeutic experiments demonstrated a significant reduction in tumor growth versus number of controls and ex vivo tissue analysis confirmed tissue normalization with strongly reduced angiogenic markers and suppressed cell proliferation...
November 16, 2016: Biomaterials
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