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Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Hypoxic stress has several effects on cells, such as metabolic changes and altered cell growth [77]. A major driver of cancer angiogenesis is hypoxia [65]. Reducing hypoxia is a possible target that can help control cancer [77]. In response to low oxygenation, cells upregulate the hypoxia-inducible factor (HIF), which is a transcription factor that has a role in coordinating an adaptive response within the pathophysiological and physiological range [78]. Under conditions of hypoxia, HIF is able to activate the transcription of several genes that have a role in maintaining oxygen homeostasis. HIF influences the expression of target genes involved in cell metabolism, invasiveness, angiogenesis, and erythropoiesis. Studies have shown that HIF has been correlated with poor outcomes in patients affected by cancer [79].
Alternative Tumor-Targeting Strategies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Studies have also shown that a heterodimeric transcription factor, Hypoxia Inducible Factor-1 (HIF-1), plays an important role in allowing tumor cells to adapt to a hypoxic environment. On detecting hypoxic conditions, HIF-1, which normally resides in the cytoplasm of cells, dimerizes and translocates to the nucleus where it binds to its cognate sequence in the promoter regions of key genes, and stimulates the expression of proteins that help the cell cope in its new harsher environment. Some of these expressed genes also lead to resistance to certain families of anticancer agents.
History of high altitude medicine and physiology
Published in Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson, Ward, Milledge and West's High Altitude Medicine and Physiology, 2021
Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson
As will become apparent in subsequent chapters in this book, one of the burgeoning areas of hypoxia research in recent years has been the role of the hypoxia-inducible factor (HIF). The pathway mediated by this gene transcription factor, which was discovered and worked out by William Kaelin Jr, Sir Peter Ratcliffe, and Gregg Semenza (Figure 1.13), is active in every cell and controls hundreds of downstream genes and physiologic processes in animals and humans. Further detailed information can be found in subsequent chapters of this book and several recent reviews (Ivan and Kaelin 2017; Schödel and Ratcliffe 2019; Semenza 2014). The work by these and other investigators has provided researchers and clinicians new routes for treatment of anemia, cancer, heart disease, and many other conditions and, in the years to come, is likely to fundamentally transform our understanding of most topics explored in this book. In recognition of the significance of this work, Kaelin, Ratcliffe, and Semenza were awarded the Nobel Prize in Physiology or Medicine in 2019.
Glucocorticoid receptors involved in ginsenoside compound K ameliorate adjuvant arthritis by inhibiting the glycolysis of fibroblast-like synoviocytes via the NF-κB/HIF-1α pathway
Published in Pharmaceutical Biology, 2023
Yating Wang, Xiurong Bao, Hao Xian, Fang Wei, Yining Song, Siyu Zhao, Yujie Zhang, Yumeng Wang, Ying Wang
The nuclear factor kappa-B (NF-κB) is crucial for the regulation of cell proliferation, apoptosis, immunity, and inflammatory processes (Hayden and Ghosh 2012; Taniguchi and Karin 2018). Notably, activated NF-κB leads to metabolic reprogramming of aerobic glycolysis, whereas hypoxia in the RA articular cavity is a key contributor in inducing NF-κB activation. The expression of hypoxia-inducible factor-1α (HIF-1α), a nuclear transcription factor that regulates oxygen balance in cells, increases under hypoxia. HIF-1α is reported to increase the expression of glucose transporter and glycolytic enzyme genes to enhance glycolysis and help cells adapt to energy deprivation during hypoxia (Mathupala et al. 2001; Luo et al. 2011; Masoud and Li 2015). Moreover, HIF-1α promoter is located at an NF-κB site, and NF-κB activation promotes HIF-1α expression under hypoxic conditions (Belaiba et al. 2007; Li et al. 2018).
Histological evaluation of peri-implant mucosal and gingival tissues in peri-implantitis, peri-implant mucositis and periodontitis patients: a cross-sectional clinical study
Published in Acta Odontologica Scandinavica, 2020
Ozkan Karatas, Hatice Balci Yuce, Mehmet Murat Taskan, Fikret Gevrek, Emre Lafci, Hayrunnisa Kasap
In hypoxic conditions, the response of the tissues against hypoxia is regulated by hypoxia-inducible factor (HIF)-1 α. In chronic inflammatory diseases such as periodontitis and diabetes, hypoxia, HIF-1α and its primary mediator, vascular endothelial growth factor (VEGF) are reported to be increased [5,10,11]. In normal oxygen levels, HIF-1α is rapidly degraded by prolyl hydroxylase (PH). PH is an oxygen-dependent enzyme that cannot function in oxygen depletion, and degradation of HIF is inhibited and HIF accumulates in the cytoplasm [10,12]. Increased hypoxia in chronic inflammation causes increased HIF-1α levels, and HIF-1α and hypoxia in periodontal tissues were reported to be associated with severe inflammation [5,13]. Vasconcelos et al. recently reported that healthy gingival tissues exhibited lower HIF-1α and VEGF levels while inflamed gingival tissues expressed increased levels [13]. Also, in another clinical study, the levels of HIF-1α, TNF-α and VEGF were found to be associated with the severity of periodontal inflammation [5]. Therefore, the existence of HIF-1α could be an indicator of inflammation in periodontal tissues [6,13,14].
Bifidobacterium-mediated high-intensity focused ultrasound for solid tumor therapy: comparison of two nanoparticle delivery methods
Published in International Journal of Hyperthermia, 2020
Chun Chen, Yaotai Wang, Yu Tang, Lu Wang, Fujie Jiang, Yong Luo, Xuan Gao, Pan Li, Jianzhong Zou
Eighteen tumor-bearing rabbits were randomly divided into two groups with nine rabbits in each group. All rabbits in one group were injected with 2 ml of B. longum (4 × 108 bacilli/mL), whereas those in the other group were injected with 2 ml of PBS. The rabbits in both the groups were sacrificed at 1, 3, and 7 days after injection, and the tumors were removed and sectioned. Immunohistochemical staining was performed to detect the expression of hypoxia-inducible factor (HIF)-1α. Positive HIF-1α expression was indicated as tan, brownish yellow, or light yellow colors in the sections. For each section, five fields of view were randomly selected for analysis (200× magnification). Image-Pro Plus 6.0 software (Rockville, MD) was used to measure the integral optical density value and area of positive cells in the tumor section, and to calculate the mean optical density value. A larger mean optical density value indicated a stronger intensity of the positive reaction.