Expression of hypoxia-inducible factors and vascular endothelial growth factor during pregnancy in the feline uterus

Ağaoğlu, Özgecan Korkmaz; Ağaoğlu, Ali Reha; Güzeloğlu, Aydın; Kurar, Ercan; Kayış, Seyit Ali; Özmen, Özlem; Schäfer-Somi, Sabine; Aslan, Selim

doi:10.1016/j.theriogenology.2015.02.009

Cited by 18 publications

(19 citation statements)

References 63 publications

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“…However; the prognostic threshold for VEGF is 72.1%, which is not a conventional method to evaluate the result of VEGF expression [16]. Therefore, a more conventional scoring principle to evaluate VEGF expression, one used in recent studies in FMGCs and human breast cancers, was chosen in this study [19,40].…”

Section: Discussionmentioning

confidence: 99%

“…IHC analysis was performed by using anti-HIF-1α (Clone: H1alpha67; diluted 1:200; Abcam, Cambridge, UK) and VEGF antibody (Clone: A-20; diluted 1:100; Santa Cruz Biotechnology, Inc., CA), which had good cross-reactivity with feline tissues [3,40]. Tissue sections were deparaffinized in xylene, rehydrated in a graded series of ethanol solutions (100, 100, 95, and 80%), and then microwaved at 95 °C for 45 min for HIF-1α and 30 min for VEGF in commercial trilogy (Cell Marque, California, USA) for antigen retrieval, and then allowed to cool for 20 min.…”

Section: Ihc Stainings Of Hif-1α and Vegfmentioning

confidence: 99%

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Expression of HIF-1α and VEGF in feline mammary gland carcinomas: association with pathological characteristics and clinical outcomes

Chen

Lin

et al. 2020

BMC Vet Res

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Background The microenvironment within solid malignant tumors, including feline mammary gland carcinomas (FMGCs), is commonly hypoxic, possibly due to the lack of functional blood vessels in rapidly proliferating neoplastic tissue. Malignant cells can undergo genetic and adaptive changes that prevent them from dying due to oxygen deprivation through expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Therefore, HIF-1α and VEGF are ideal biomarkers for cancer therapy and prognostic evaluation. The aims of this study were to evaluate the expression of HIF-1α and VEGF in feline mammary carcinomas and analyze their correlations with clinical and pathological factors, such as clinical stage, histologic grading, regional metastasis, and overall survival rate. Results Paraffin-embedded tissue samples collected from 72 cats with FMGCs were retrospectively studied. Histologic pattern and histologic grading (Elston and Ellis grading system) of these FMGCs were determined. Our data indicated that grade II tubulopapillary carcinomas (43/72, 59.7%) prevailed in this study, and most FMCGs showed apparent necrosis, squamous metaplasia, and intratumoral stromal response. According to the results of immunohistochemical (IHC) stainings performed in tissue microarrays (TMAs), HIF-1α and VEGF overexpressions were respectively noted in 69.4% (50/72) and 77.8% (56/72) of FMGC cases. Chi-square test showed no correlation of HIF-1α overexpression with clinical and pathological factors. VEGF overexpression was significantly correlated with histologic pattern (p = 0.021), stromal response (p = 0.048), squamous metaplasia (p = 0.001), and lymphovascular invasion (p = 0.007). However, neither HIF-1α nor VEGF overexpression was correlated with histologic grading and metastasis. Of 38 cats with 1-year follow-up, IHC stainings of HIF-1α and VEGF were performed on whole tissue sections. The results showed that overexpression of HIF-1α was significantly correlated with the overall survival rate (p < 0.05) (log-rank test), whereas there was no significant correlation between VEGF overexpression and overall survival rate. Conclusions This study suggests that the overexpression of HIF-1α may indicate poor prognosis/overall survival rate in cats with FMGCs. Developing compounds that inhibit HIF-1α may be a potential approach to FMGC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Ihc Stainings Of Hif-1α and Vegfmentioning

confidence: 99%

Expression of HIF-1α and VEGF in feline mammary gland carcinomas: association with pathological characteristics and clinical outcomes

Chen

Lin

et al. 2020

BMC Vet Res

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“…Although studies of angiogenesis in animal cancer are relatively limited compared to human cancer research, HIFs and VEGF have been shown to have critical roles during placentation in cats (198). In the context of cancer, Brown et al (199) showed that HIF-1a upregulation is responsible for increased VEGF in feline OSCC cell lines (199).…”

Section: Comparative Oncology: Inflammation and Hypoxia In Domestic Animal Cancer Comparative Biology Of Tumour Hypoxiamentioning

confidence: 99%

Intersecting Mechanisms of Hypoxia and Prostaglandin E2-Mediated Inflammation in the Comparative Biology of Oral Squamous Cell Carcinoma

Nasry

Martin

2021

Front. Oncol.

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The importance of inflammation in the pathogenesis of cancer was first proposed by Rudolph Virchow over 150 years ago, and our understanding of its significance has grown over decades of biomedical research. The arachidonic acid pathway of inflammation, including cyclooxygenase (COX) enzymes, PGE2 synthase enzymes, prostaglandin E2 (PGE2) and PGE2 receptors has been extensively studied and has been associated with different diseases and different types of cancers, including oral squamous cell carcinoma (OSCC). In addition to inflammation in the tumour microenvironment, low oxygen levels (hypoxia) within tumours have also been shown to contribute to tumour progression. Understandably, most of our OSCC knowledge comes from study of this aggressive cancer in human patients and in experimental rodent models. However, domestic animals develop OSCC spontaneously and this is an important, and difficult to treat, form of cancer in veterinary medicine. The primary goal of this review article is to explore the available evidence regarding interaction between hypoxia and the arachidonic acid pathway of inflammation during malignant behaviour of OSCC. Overlapping mechanisms in hypoxia and inflammation can contribute to tumour growth, angiogenesis, and, importantly, resistance to therapy. The benefits and controversies of anti-inflammatory and anti-angiogenic therapies for human and animal OSCC patients will be discussed, including conventional pharmaceutical agents as well as natural products.

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“…Pregnancy is one of the most complex reproductive activities of mammals and is tightly regulated by the external environment, various endocrine factors, and the expression of a large number of genes [3, 4]. The ovary plays a vital role during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of differentially expressed genes between the ovaries from pregnant and nonpregnant goats using RNA-Seq

Quan

Zheng

Ling

et al. 2019

J of Biol Res-Thessaloniki

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Background A multitude of genes tightly regulate ovarian follicular development and hormone secretion. These complex and coordinated biological processes are altered during pregnancy. In order to further understand the regulatory role of these genes during pregnancy, it is important to screen the differentially expressed genes (DEGs) in the ovaries of pregnant and nonpregnant mammals. To detect the genes associated with the development of pregnancy in goats, DEGs from the ovaries from pregnant and nonpregnant Anhui white goats (pAWGs and nAWGs, respectively) were analyzed using RNA sequencing technology (RNA-Seq). Results In this study, 13,676,394 and 13,549,560 clean reads were generated from pAWGs and nAWGs, respectively, and 1724 DEGs were identified between the two libraries. Compared with nAWGs, 1033 genes were upregulated and 691 genes were downregulated in pAWGs, including PGR , PRLR , STAR and CYP19A1 , which play important roles in goat reproduction. Gene Ontology analysis showed that the DEGs were enriched for 49 functional GO terms. Kyoto Encyclopedia of Genes and Genomes analysis revealed that 397 DEGs were significantly enriched in 13 pathways, including “cell cycle”, “cytokine–cytokine receptor interaction” and “steroid biosynthesis”, suggesting that the genes may be associated with cell cycle regulation, follicular development and hormone secretion to regulate the reproduction process. Additionally, quantitative real-time PCR was used to verify the reliability of the RNA-Seq data. Conclusions The data obtained in this work enrich the genetic resources of goat and provide a further understanding of the complex molecular regulatory mechanisms occurring during the development of pregnancy and reproduction in goats. The DEGs screened in this study may play an important role in follicular development and hormone secretion and they would provide scientific basis for related research in the future. Electronic supplementary material The online version of this article (10.1186/s40709-019-0095-9) contains supplementary material, which is available to authorized users.

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Expression of hypoxia-inducible factors and vascular endothelial growth factor during pregnancy in the feline uterus

Cited by 18 publications

References 63 publications

Expression of HIF-1α and VEGF in feline mammary gland carcinomas: association with pathological characteristics and clinical outcomes

Expression of HIF-1α and VEGF in feline mammary gland carcinomas: association with pathological characteristics and clinical outcomes

Intersecting Mechanisms of Hypoxia and Prostaglandin E2-Mediated Inflammation in the Comparative Biology of Oral Squamous Cell Carcinoma

Comparative analysis of differentially expressed genes between the ovaries from pregnant and nonpregnant goats using RNA-Seq

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