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hypoxia tumor

Fahaid Al-Hashem, Suliman Al-Humayed, Shaimaa N Amin, Samaa S Kamar, Soheir S Mansy, Sarah Hassan, Lubna O Abdel-Salam, Mohamed Abd Ellatif, Mohammed Alfaifi, Mohamed A Haidara, Bahjat Al-Ani
The potential inhibitory effect of the antidiabetic and anti-inflammatory drug, metformin on thioacetamide (TAA)-induced hepatotoxicity associated with the inhibition of mammalian target of rapamycin (mTOR)-hypoxia-inducible factor-1α (HIF-1α) axis has not been investigated before. Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR-HIF-1α axis and profibrogenic and inflammatory biomarkers. Rats either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being killed after 10 weeks (model group) or were pretreated with metformin (200 mg/kg) daily for 2 weeks before TAA injections and continued receiving both agents until the end of the experiment, at Week 10 (protective group)...
October 18, 2018: Journal of Cellular Physiology
Xiao-Fei Ding, Jie Chen, Jun Zhou, Guang Chen, Ying-Liang Wu
Previous research has revealed that the von-Hippel-Lindau tumor suppressor protein (pVHL) may downregulate never-in-mitosis A-related kinase 8 (NEK8) via hypoxia-inducible factor-α (HIF-α). The HIF-independent functions of pVHL also serve an important role in its tumor-suppressor action. In the present study, the association between pVHL and NEK8 was demonstrated in the human gastric cancer cell line, SGC-7901, indicating a direct interaction of pVHL with NEK8. Subsequently, it was reported that MG-132, a specific proteasome inhibitor, may attenuate pVHL overexpression-induced reductions in NEK8 protein expression levels...
November 2018: Oncology Letters
Yuqing Zhang, Amanda Kirane, Huocong Huang, Noah B Sorrelle, Francis J Burrows, Michael T Dellinger, Rolf A Brekken
Resistance to standard therapy remains a major challenge in the treatment of pancreatic ductal adenocarcinoma (PDA). Although anti-VEGF therapy delays PDA progression, therapy-induced hypoxia results in a less differentiated mesenchymal-like tumor cell phenotype, which reinforces the need for effective companion therapies. COX-2 inhibition has been shown to promote tumor cell differentiation and improve standard therapy response in PDA. Here, we evaluate the efficacy of COX-2 inhibition and VEGF blockade in preclinical models of PDA...
October 17, 2018: Molecular Cancer Research: MCR
Susana Simões-Sousa, Samantha Littler, Sarah L Thompson, Paul Minshall, Helen Whalley, Bjorn Bakker, Klaudyna Belkot, Daniela Moralli, Daniel Bronder, Anthony Tighe, Diana C J Spierings, Nourdine Bah, Joshua Graham, Louisa Nelson, Catherine M Green, Floris Foijer, Paul A Townsend, Stephen S Taylor
Deviating from the normal karyotype dramatically changes gene dosage, in turn decreasing the robustness of biological networks. Consequently, aneuploidy is poorly tolerated by normal somatic cells and acts as a barrier to transformation. Paradoxically, however, karyotype heterogeneity drives tumor evolution and the emergence of therapeutic drug resistance. To better understand how cancer cells tolerate aneuploidy, we focused on the p38 stress response kinase. We show here that p38-deficient cells upregulate glycolysis and avoid post-mitotic apoptosis, leading to the emergence of aneuploid subclones...
October 16, 2018: Cell Reports
Wei Li, Ying-Yao Quan, Yong Li, Ligong Lu, Min Cui
Tumor vascular normalization alleviates hypoxia in the tumor microenvironment, reduces the degree of malignancy, and increases the efficacy of traditional therapy. However, the time window for vascular normalization is narrow; therefore, how to determine the initial and final points of the time window accurately is a key factor in combination therapy. At present, the gold standard for detecting the normalization of tumor blood vessels is histological staining, including tumor perfusion, microvessel density (MVD), vascular morphology, and permeability...
2018: Cancer Management and Research
Kaitlin Graham, Evan Unger
Hypoxia exists to some degree in most solid tumors due to inadequate oxygen delivery of the abnormal vasculature which cannot meet the demands of the rapidly proliferating cancer cells. The levels of oxygenation within the same tumor are highly variable from one area to another and can change over time. Tumor hypoxia is an important impediment to effective cancer therapy. In radiotherapy, the primary mechanism is the creation of reactive oxygen species; hypoxic tumors are therefore radiation resistant. A number of chemotherapeutic drugs have been shown to be less effective when exposed to a hypoxic environment which can lead to further disease progression...
2018: International Journal of Nanomedicine
Masoud Najafi, Bagher Farhood, Keywan Mortezaee
Alteration in the density and composition of extracellular matrix (ECM) occurs in tumors. The alterations toward both stiffness and degradation are contributed to tumor growth and progression. Cancer-associated fibroblasts (CAFs) are the main contributors to ECM stiffness and degradation. The cells interact with almost all cells within the tumor microenvironment (TME) that could enable them to modulate ECM components for tumorigenic purposes. Cross-talks between CAFs with cancer cells and macrophage type 2 (M2) cells are pivotal for ECM stiffness and degradation...
October 15, 2018: Journal of Cellular Biochemistry
Paul R Walker
The stroma of solid tumors can exclude or limit immune infiltration, or lead to the recruitment of tumor-promoting rather than tumor-attacking immune cells. This finding was reported by Jayaprakash et al. in this issue of the JCI, and it was particularly prominent in the hypoxic zones of tumors in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer models. A current clinical goal of immune checkpoint blockade (ICB) is to extend its utility to more patients by converting immunologically "cold" tumors that do not provoke a strong immunological response to "hot" tumors that are invaded by swarms of T cells...
October 15, 2018: Journal of Clinical Investigation
Jingya Zeng, Ying Pan, Baohong Cui, Taiyu Zhai, Song Gao, Qianyu Zhao, Yihua Sun
Acute myocardial infarction (AMI) is a disease associated with inflammation. T lymphocytes are involved by secreting cytokines and inflammatory factors. In our previous study, it was found that the T lymphocytes exhibited certain functional changes, the onset of which was induced by modulating calcium‑sensing receptor (CaSR) in AMI. In the present study, western blotting was used to verified the expression of T lymphocyte CaSR and pathway proteins, including phosphorylated extracellular signal‑regulated kinase (P‑ERK)1/2 and phosphorylated c‑Jun N‑terminal kinase (P‑JNK), and used cytometric bead array to detect the secretion of interleukin (IL)‑4, IL‑6, IL‑10 and tumor necrosis factor (TNF)‑α in AMI onset, the results demonstrated that they were all increased...
October 10, 2018: International Journal of Molecular Medicine
Jesús Valencia-Cervantes, Sara Huerta-Yepez, Guillermo Aquino-Jarquín, Sara Rodríguez-Enríquez, Daniel Martínez-Fong, José-Antonio Arias-Montaño, Víctor Manuel Dávila-Borja
Medulloblastomas are among the most frequently diagnosed pediatric solid tumors, and drug resistance remains as the principal cause of treatment failure. Hypoxia and the subsequent activation of hypoxia‑inducible factor 1α (HIF‑1α) are considered key factors in modulating drug antitumor effectiveness, but the underlying mechanisms in medulloblastomas have not yet been clearly understood. The aim of the present study was to determine whether hypoxia induces resistance to cyclophosphamide (CPA) and ifosfamide (IFA) in DAOY medulloblastoma cells, whether the mechanism is dependent on HIF‑1α, and whether involves the modulation of the expression of cytochromes P450 (CYP)2B6, 3A4 and 3A5 and the control of cell proliferation...
October 12, 2018: Oncology Reports
Cheng Zheng, Jia-Feng Lin, Zhong-Hao Lin, Wei-Qian Lin, Saroj Thapa, Yuan-Zheng Lin, Hao Lian, Zhi-Rui Liu, Jia-Hui Chen, Xiao-Wei Li
With the chronic ischemia persisting after acute myocardial infarction, the accompanying low-degree inflammation and subsequent fibrosis result in progression of cardiac remodeling and heart failure. Recently, Sodium Houttuyfonate (SH), a pure compound extracted from Houttuynia cordata , has been confirmed exerting anti-inflammatory and anti-fibrotic effects under diseased situations. Here, we aimed to investigate whether SH could reverse the cardiac remodeling post-myocardial infarction by alleviating cardiac inflammation and fibrosis...
2018: Frontiers in Pharmacology
Jia Li, Wenting Shang, Yong Li, Sirui Fu, Jie Tian, Ligong Lu
Hypoxia within solid tumors is often responsible for the failure of radiotherapy. The development of hypoxia-targeting nanomaterials - aimed at enhancing the effect of radiotherapy by electrical or heat effects and at modulating hypoxia in the tumor microenvironment - is a promising strategy to address this issue. We provide an overview of recently developed advanced materials that potentiate radiotherapy. First, we summarize novel materials for oxygen delivery or production to modify the tumor microenvironment, thus improving the effects of ionizing radiation...
2018: International Journal of Nanomedicine
Hans-Jonas Meyer, Gordian Hamerla, Anne Kathrin Höhn, Alexey Surov
RATIONALE AND OBJECTIVES: Histogram analysis is an imaging analysis in which a whole tumor can be assessed, and every voxel of a radiological image is issued into a histogram. Thereby, statistically information about tumor can be obtained. The purpose of the study was to analyze possible relationships between histogram parameters derived from conventional MRI sequences and several histopathological features in cervical squamous cell carcinomas. METHODS: A total of 18 female patients (age range 32-79 years) with squamous cell cervical carcinoma were retrospectively enrolled into the study...
October 11, 2018: Academic Radiology
Keywan Mortezaee, Nasser Hashemi Goradel, Peyman Amini, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Masoud Najafi, Bagher Farhood
BACKGROUND: Radiotherapy is a treatment modality for cancer. For better therapeutic efficiency, it could be used in combination with surgery, chemotherapy or immunotherapy. In addition to its beneficial therapeutic effects, exposure to radiation leads to several toxic effects on normal tissues. Also, it may induce some changes in genomic expression of tumor cells, thereby increasing the resistance of tumor cells. These changes lead to the appearance of some acute reactions in irradiated organs, increased risk of carcinogenesis, and reduction in the therapeutic effect of radiotherapy...
October 10, 2018: Current Molecular Pharmacology
Zhe Zhang, Na Niu, Xi Gao, Fuqin Han, Zhijun Chen, Shujun Li, Jian Li
Hypoxia is the main characteristic of tumor microenvironment, and the one of the key factors that cause the drug resistance of cancer cells for chemotherapy. Anticancer drug such as DOX cannot react with sufficient oxygen to produce reactive oxygen species (ROS) in hypoxic environment, which affects the therapeutic efficiency of the drug. In this work, we constructed a multi-functional nano-carrier (named as FeSiAuO) containing Fe3 O4 , mesoporous SiO2 and Au2 O3 with magnetic, large surface ratio and light induced oxygen production properties...
October 5, 2018: Colloids and Surfaces. B, Biointerfaces
Amirhossein Jahangiri, Maryam Dadmanesh, Khodayar Ghorban
Signal transducer and activator of transcription 3 (STAT3) interacts with many gene promoters and transcription factors such as hypoxia-induced factor 1α (HIF-1α). Recent evidences proposed that STAT3 and HIF-1α together are responsible for angiogenesis and immune response suppression. The main aim of this study was to inhibit STAT3 and HIF-1α and assess their effects on the expression of immunosuppressive cytokines. S31-201 and PX-478 were used to inhibit STAT3 and HIF-1α, respectively. In both hypoxic and normoxic conditions, intracellular levels of HIF-1α were evaluated by western blotting and flow cytometry...
October 12, 2018: In Vitro Cellular & Developmental Biology. Animal
Kaiyao Shi, Huan Sun, Hongli Zhang, Di Xie, Bo Yu
Myocardial infarction (MI) is an unsolved health problem which seriously affects human health around the world. miR-34a-5p acting as a tumor-suppressor is associated with left ventricular remodeling. We aimed to explore the functional roles of miR-34a-5p in cardiomyocytes. Hypoxia-induced cell injury in H9c2, HL-1 and human cardiac myocytes was analyzed according to the decrease of cell viability and increase of apoptosis. Expression of miR-34a-5p was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) when the concentration of O2 was decreased...
October 12, 2018: Biological Chemistry
Wei Sun, Yuqing Chen, Yuerong Wang, Pei Luo, Min Zhang, Hongyang Zhang, Ping Hu
This paper reports a single-layered microfluidic device for studying the interaction of cancer cells and fibroblasts in an oxygen gradient. This gradient can be established from 1.9% to 18.8% using a spatially confined oxygen scavenging chemical reaction. Due to the spatial design of the chip, only cancer cells can sustain low oxygen conditions when co-cultured with fibroblasts in the adjacent channels, simulating the cell-cell interactions of the hypoxic cancer cells and the surrounding fibroblasts in tumor microenvironment in vivo...
October 12, 2018: Analyst
Malina Xiao, Muhammad Zaeem Noman, Ludovic Menard, Andy Chevigne, Martyna Szpakowska, Manon Bosseler, Markus Ollert, Guy Berchem, Bassam Janji
Autophagy is a quality control process executed at the basal level in almost all cell types. However, in cancer cells, autophagy is activated by several stimuli, including hypoxia. Depending on tumor type, stage, and genetic context, autophagy is a double-edged sword. Autophagy promotes regression in newly established tumors; however, it supports tumor progression in well-established tumors by maintaining cancer cell survival under stress conditions. These data, in addition to the emerging role of autophagy in impairing antitumor immunity, have attracted significant interest in developing autophagy inhibitors as a new approach to cancer treatment...
2018: Critical Reviews in Oncogenesis
Yuhao Wang, Benjamin Bonavida
The complexities of molecular signaling in cancer cells have been hypothesized to mediate cross-network alterations of oncogenic processes such as uncontrolled cell growth, proliferation, acquisition of epithelial-to-mesenchymal transition (EMT) markers, and resistance to cytotoxic therapies. The two biochemically exclusive processes/proteins examined in the present review are the metastasis suppressor Raf-1 kinase inhibitory protein (RKIP) and the cell-intrinsic system of macroautophagy (hereafter referred to as autophagy)...
2018: Critical Reviews in Oncogenesis
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