scholarly journals Hypoxia-Inducible Factor in Thyroid Carcinoma

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Natalie Burrows ◽  
Muhammad Babur ◽  
Julia Resch ◽  
Kaye J. Williams ◽  
Georg Brabant
Keyword(s):  
Thyroid Carcinoma ◽  
Potential Role ◽  
Hypoxia Inducible Factor ◽  
Current Data ◽  
Low Oxygen ◽  
Expression Of Genes ◽  
Mitogen Activated Protein ◽  
Growth Factor Signalling ◽  
Pi3k Signalling

Intratumoural hypoxia (low oxygen tension) is associated with aggressive disease and poor prognosis. Hypoxia-inducible factor-1 is a transcription factor activated by hypoxia that regulates the expression of genes that promote tumour cell survival, progression, metastasis, and resistance to chemo/radiotherapy. In addition to hypoxia, HIF-1 can be activated by growth factor-signalling pathways such as the mitogen-activated protein kinases- (MAPK-) and phosphatidylinositol-3-OH kinases- (PI3K-) signalling cascades. Mutations in these pathways are common in thyroid carcinoma and lead to enhanced HIF-1 expression and activity. Here, we summarise current data that highlights the potential role of both hypoxia and MAPK/PI3K-induced HIF-1 signalling in thyroid carcinoma progression, metastatic characteristics, and the potential role of HIF-1 in thyroid carcinoma response to radiotherapy. Direct or indirect targeting of HIF-1 using an MAPK or PI3K inhibitor in combination with radiotherapy may be a new potential therapeutic target to improve the therapeutic response of thyroid carcinoma to radiotherapy and reduce metastatic burden.

scholarly journals Myeloid HIF1α Is Involved in the Extent of Orthodontically Induced Tooth Movement

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 796
Author(s):  
Christian Kirschneck ◽  
Nadine Straßmair ◽  
Fabian Cieplik ◽  
Eva Paddenberg ◽  
Jonathan Jantsch ◽  
...  
Keyword(s):  
Bone Density ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Hypoxia Inducible Factor ◽  
Myeloid Cells ◽  
Orthodontic Tooth Movement ◽  
Periodontal Ligament Fibroblasts ◽  
Expression Of Genes ◽  
Periodontal Bone Loss

During orthodontic tooth movement, transcription factor hypoxia-inducible factor 1α (HIF1α) is stabilised in the periodontal ligament. While HIF1α in periodontal ligament fibroblasts can be stabilised by mechanical compression, in macrophages pressure application alone is not sufficient to stabilise HIF1α. The present study was conducted to investigate the role of myeloid HIF1α during orthodontic tooth movement. Orthodontic tooth movement was performed in wildtype and Hif1αΔmyel mice lacking HIF1α expression in myeloid cells. Subsequently, µCT images were obtained to determine periodontal bone loss, extent of orthodontic tooth movement and bone density. RNA was isolated from the periodontal ligament of the control side and the orthodontically treated side, and the expression of genes involved in bone remodelling was investigated. The extent of tooth movement was increased in Hif1αΔmyel mice. This may be due to the lower bone density of the Hif1αΔmyel mice. Deletion of myeloid Hif1α was associated with increased expression of Ctsk and Acp5, while both Rankl and its decoy receptor Opg were increased. HIF1α from myeloid cells thus appears to play a regulatory role in orthodontic tooth movement.

Analysis of the mechanism(s) of metaphase I arrest in strain LT mouse oocytes: participation of MOS

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5107-5113
Author(s):  
Y. Hirao ◽  
J.J. Eppig
Keyword(s):  
Potential Role ◽  
Inbred Strains ◽  
Mitogen Activated Protein Kinase ◽  
Null Mutation ◽  
Mitogen Activated Protein ◽  
Cytostatic Factor ◽  
Almost All ◽  
Dependent Mechanism ◽  
Metaphase I

Oocytes of almost all vertebrates become arrested at metaphase II to await fertilization. Arrest is achieved with the participation of a protein complex known as cytostatic factor (CSF) that stabilizes histone H1 kinase activity. MOS and mitogen-activated protein kinase (MAPK) are important components of CSF. Strain LT/Sv mice, and strains related to LT/Sv, produce a high percentage of atypical oocytes that are arrested at metaphase I when normal oocytes have progressed to metaphase II. The potential role of MOS in metaphase I arrest was investigated using strain LT/Sv and LT-related recombinant inbred strains, LTXBO and CX8-4. MOS and MAPK are produced and functional in maturing LT oocytes. Two experimental paradigms were used to reduce or delete MOS in LT oocytes and assess effects on metaphase I arrest. First, sense and antisense Mos oligonucleotides were microinjected into metaphase I-arrested oocytes. Antisense, but not sense, Mos oligonucleotides promoted the activation of metaphase I-arrested oocytes. Second, mice carrying a Mos null mutation were crossed with LT mice, the null mutation was backcrossed three times to LT mice, and Mos(+/−) N3 mice were intercrossed to produce Mos(−/−), Mos(+/−) and Mos(+/+) N3F1 mice. Oocytes of all three Mos genotypes of N3F1 mice sustained meiotic arrest for 17 hours indicating that metaphase I arrest is not initiated by a MOS-dependent mechanism. However, unlike Mos(+/+) and Mos(+/−) CX8-4 N3F1 oocytes, metaphase I arrest of Mos(−/−) CX8-4 N3F1 oocytes was not sustained after 17 hours and became reversed gradually. These results, like the antisense Mos oligonucleotide microinjection experiments, suggest that MOS participates in sustaining metaphase I arrest in LT oocytes.

scholarly journals Low oxygen enhances trophoblast column growth by potentiating the extravillous lineage and promoting LOX activity

2019 ◽  
Author(s):  
Jenna Treissman ◽  
Victor Yuan ◽  
Jennet Baltayeva ◽  
Hoa T. Le ◽  
Barbara Castellana ◽  
...  
Keyword(s):  
Lysyl Oxidase ◽  
Atmospheric Oxygen ◽  
Extravillous Trophoblast ◽  
Low Oxygen ◽  
Placental Development ◽  
Trophoblast Differentiation ◽  
Expression Of Genes ◽  
Summary Statement ◽  
Insight Into

ABSTRACTEarly placental development and the establishment of the invasive trophoblast lineage take place within a low oxygen environment. However, conflicting and inconsistent findings have obscured the role of oxygen in regulating invasive trophoblast differentiation. In this study, the effect of hypoxic, normoxic, and atmospheric oxygen on invasive extravillous pathway progression was examined using a human placental explant model. Here, we show that exposure to low oxygen enhances extravillous column outgrowth and promotes the expression of genes that align with extravillous trophoblast (EVT) lineage commitment. By contrast, super-physiological atmospheric levels of oxygen promote trophoblast proliferation while simultaneously stalling EVT progression. Low oxygen-induced EVT differentiation coincided with elevated transcriptomic levels of lysyl oxidase (LOX) in trophoblast anchoring columns, where functional experiments established a role for LOX activity in promoting EVT column outgrowth. The findings of this work support a role for low oxygen in potentiating the differentiation of trophoblasts along the extravillous pathway. Additionally, these findings generate insight into new molecular processes controlled by oxygen during early placental development.Summary StatementLow oxygen promotes extravillous trophoblast differentiation

scholarly journals THERAPEUTIC TARGETING OF HYPOXIA-INDUCIBLE FACTOR SIGNALING PATHWAYS- A PROMISING APPROACH IN CANCER TREATMENT

2020 ◽  
Vol 8 (9) ◽  
pp. 1332-1337
Author(s):  
Anjum Mohammad Shaik ◽  
◽  
Valli Harisomayajula ◽  
Saranya M.L ◽  
Phani Greeshma Veeramachaneni ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Immune Cells ◽  
Cell Cycle Regulation ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factors ◽  
Low Oxygen ◽  
Therapeutic Targeting ◽  
Expression Of Genes ◽  
Transcription Regulators ◽  
Cycle Regulation

Oxygen and nutrients are delivered to the cells with the help of the vascular networking system, which makes availability of oxygen as primary regulator for many processes. Low oxygen availability condition activates the Hypoxia Inducible Factors (HIF), which are transcription regulators helping in the expression of genes related to cell cycle regulation and angiogenesis. HIF is hence regarded as the master regulator of angiogenesis. The oxygen deprival is due to the increased consumption of oxygen in the tumor microenvironment and in turn leads to hypoxia. A thorough understanding of how hypoxia influences angiogenesis mediated by several pathways has become essential for identifying novel strategies targeting HIF thereby blocking angiogenesis. In this review we would discuss about the HIF signaling pathways and altered functions of immune cells due to hypoxia by considering that reducing or targeting hypoxia may in turn prevent the suppression of anti-tumor immune response.

scholarly journals Exosomes and the role of exosomal miRNA in the diagnosis of lung cancer

2021 ◽  
Vol 136 (3) ◽  
pp. 51-63
Author(s):  
R.I. Bersimbaev ◽  
◽  
O.V. Bulgakova ◽  
A.A. Aripova ◽  
A.Zh. Kausbekova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Types ◽  
Current Data ◽  
Expression Of Genes ◽  
Diagnostic Potential ◽  
Oncological Diseases ◽  
Diagnosis Of Lung Cancer ◽  
The Moment ◽  
Almost All

Exosomes are extracellular vesicles secreted by almost all cell types that can function as a cell-to-cell carrier of information, providing pleiotropic functions in intercellular communication. Exosomes can transport various biomolecules, including proteins and nucleic acids, into recipient cells. The review analyzed the current data on the role of exosomes and the possibility of using exosomal microRNAs as a biomarker in the diagnosis of lung cancer. MicroRNAs can act as oncogenes or tumor suppressors, so they can regulate the expression of genes that play an important role in oncogenesis. At the moment, microRNAs of exosomes are one of the main candidates for the role of molecular markers in liquid biopsy for the diagnosis of oncological diseases. The review analyzes the diagnostic potential of the use of exosomes in carcinogenesis in general, with an emphasis on the use of exosomal microRNAs as biomarkers of lung cancer.

scholarly journals Mouse models of aneuploidy to understand chromosome disorders

2021 ◽  
Author(s):  
Justin Tosh ◽  
Victor Tybulewicz ◽  
Elizabeth M. C. Fisher
Keyword(s):  
Mouse Models ◽  
Potential Role ◽  
Gene Dosage ◽  
Extra Chromosome ◽  
Expression Of Genes ◽  
Ideal System ◽  
Autosomal Aneuploidy ◽  
Great Insight ◽  
Aneuploid Chromosome

AbstractAn organism or cell carrying a number of chromosomes that is not a multiple of the haploid count is in a state of aneuploidy. This condition results in significant changes in the level of expression of genes that are gained or lost from the aneuploid chromosome(s) and most cases in humans are not compatible with life. However, a few aneuploidies can lead to live births, typically associated with deleterious phenotypes. We do not understand why phenotypes arise from aneuploid syndromes in humans. Animal models have the potential to provide great insight, but less than a handful of mouse models of aneuploidy have been made, and no ideal system exists in which to study the effects of aneuploidy per se versus those of raised gene dosage. Here, we give an overview of human aneuploid syndromes, the effects on physiology of having an altered number of chromosomes and we present the currently available mouse models of aneuploidy, focusing on models of trisomy 21 (which causes Down syndrome) because this is the most common, and therefore, the most studied autosomal aneuploidy. Finally, we discuss the potential role of carrying an extra chromosome on aneuploid phenotypes, independent of changes in gene dosage, and methods by which this could be investigated further.

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