Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors

Moschetta, Marina Gobbe; Maschio, Larissa Bazela; Jardim‐Perassi, Bruna V.; Gelaleti, Gabriela Bottaro; Lopes, Jair; Leonel, Camila; Gonçalves, Naiane do Nascimento; Ferreira, Lívia Carvalho; Martins, Gustavo Rodrigues; Borin, Thaiz F.; Zuccari, Débora Aparecida Pires de Campos

doi:10.3892/or.2015.3856

Cited by 16 publications

(10 citation statements)

References 54 publications

(68 reference statements)

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“…Every neoplastic process includes the formation of new blood vessels on the base of already existing vessels. This is essential for delivering nutritional supplies for the tumor and maintaining tissues homeostasis [ 58 ]. With tumor growth, the angiogenic process is advanced.…”

Section: Biomarkers Of Angiogenesismentioning

confidence: 99%

“…In healthy tissues, VEGF is responsible for the formation of new vessels and regulates their functions and structure. VEGF stimulates cell migration and endothelial proliferation and increases microvascular permeability, which allows cells to escape from the blood vessels and form distant metastases; it also inhibits the regression of newly formed vessels stimulates endothelial cell invasion to form new vessels and, at the same time, inhibits apoptosis [ 58 , 60 – 63 ].…”

Section: Biomarkers Of Angiogenesismentioning

confidence: 99%

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Current biomarkers of canine mammary tumors

et al. 2018

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Mammary tumors are the second most common neoplasia in dogs. Due to the high similarity of canine mammary tumors (CMT) to human breast cancers (HBC), human biomarkers of HBC are also detectable in cases of CMT. The evaluation of biomarkers enables clinical diagnoses, treatment options and prognosis for bitches suffering from this disease. The aim of this article is to give a short summary of the biomarkers of CMT based on current literature. Very promising biomarkers are miRNAs, cancer stem cells, and circulating tumor cells, as well as mutations of the breast cancer 1 gene (BRCA1) and breast cancer 2 gene (BRCA2). Until now, the most studied and reliable biomarkers of CMT have remained antigen Ki-67 (Ki-67), endothelial growth factor receptor, human epidermal growth factor receptor 2 (HER-2), estrogen receptor, progesterone receptor and cyclooxygenase 1 (COX-2), which can be detected in both serum and tissue samples using different molecular methods. However, carcinoembryonic antigen and cancer antigen 15-3 (CA 15-3), while poorly studied, seem to be good biomarkers, especially for the early detection and prognosis of CMT. We will also mention the following: proliferative cell nuclear antigen, tumor protein p53 (p53), E-cadherin, vascular endothelial growth factor, microRNAs, cancer stem cells and circulating tumor cells, which can also be useful biomarkers. Although many studies have been conducted so far, the estimation of biomarkers in cases of CMT is still not a common practice, and more detailed research should be done.

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Section: Biomarkers Of Angiogenesismentioning

confidence: 99%

Section: Biomarkers Of Angiogenesismentioning

confidence: 99%

Current biomarkers of canine mammary tumors

et al. 2018

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“…Among the best studied ones are vascular endothelial growth factors (VEGFs) that regulate formation, function, and maintenance of vasculature (Simons et al, 2016). In most studies, VEGF expression in CMT has been closely correlated with metastasis to lymph nodes, clinical stage, tumor grade, and malignancy (Qiu et al, 2008;Vinothini et al, 2009;Clemente et al, 2010Clemente et al, , 2013Millanta et al, 2010;Klopfleisch et al, 2011;Queiroga et al, 2011a;Carvalho et al, 2015aCarvalho et al, , 2016bMoschetta et al, 2015;Mucha et al, 2016). However, a few reports have failed to see such an association (Millanta et al, 2006;Santos et al, 2010Santos et al, , 2014.…”

Section: Angiogenesismentioning

confidence: 99%

Know Thy Model: Charting Molecular Homology in Stromal Reprogramming Between Canine and Human Mammary Tumors

Markkanen

2019

Front. Cell Dev. Biol.

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Spontaneous canine simple mammary tumors (CMTs) are often viewed as models of human breast cancer. Cancer-associated stroma (CAS) is central for initiation and progression of human cancer, and is likely to play a key role in canine tumors as well. Until recently, however, canine CAS in general, and in CMT in particular, lacked detailed characterization and it remained unclear how canine and human CAS compare. This void in knowledge regarding canine CAS and the resulting lack of unbiased crossspecies analysis of molecular homologies and differences undermined the validity of the canine model for human disease. To assess stromal reprogramming in canine breast tumors, we have recently established a protocol to specifically isolate and analyze CAS and matched normal stroma from archival, formalin-fixed paraffin embedded (FFPE) clinical tumor samples using laser-capture microdissection followed by next-generation RNA-sequencing. Using this approach, we have analyzed stromal reprogramming in both malignant canine mammary carcinomas (mCAs) as well as benign canine mammary adenomas in a series of studies. Our results demonstrate strong stromal reprogramming in CMTs and identify high-grade molecular homology between human and canine CAS. Here, I aim to give a short background on the value of comparative oncology in general, and spontaneous CMT in particular. This will be followed by a concise review of the current knowledge of stromal reprogramming in both malignant canine mCA and benign adenoma. Finally, I will conclude with insights on highly conserved aspects of stromal reprogramming between CMT and human breast cancer that accentuate the relevance of CAS in CMT as a model for the human disease.

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“…To exploit the cellular response of cancer cells to low O 2 levels, the expression levels of hypoxia-induced genes, mRNAs, and proteins have also been employed as biomarkers of hypoxia (77)(78)(79)(80). In dogs with mammary tumors, high VEGFA gene expression has been associated with poor outcome, with one study suggesting that it could be used as a prognostic marker to identify dogs at risk of disease progression (81). However, markers including HIF-1, CA9, VEGF and GLUT1, analyzed either at the mRNA or protein level, or through the use of nitroimidazole, have frequently brought about contradictory results.…”

Section: Tumor Functional Assessmentmentioning

confidence: 99%

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology

et al. 2020

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Treating individual patients on the basis of specific factors, such as biomarkers, molecular signatures, phenotypes, environment, and lifestyle is what differentiates the precision medicine initiative from standard treatment regimens. Although precision medicine can be applied to almost any branch of medicine, it is perhaps most easily applied to the field of oncology. Cancer is a heterogeneous disease, meaning that even though patients may be histologically diagnosed with the same cancer type, their tumors may have different molecular characteristics, genetic mutations or tumor microenvironments that can influence prognosis or treatment response. In this review, we describe what methods are currently available to clinicians that allow them to monitor key tumor microenvironmental parameters in a way that could be used to achieve precision medicine for cancer patients. We further describe exciting novel research involving the use of implantable medical devices for precision medicine, including those developed for mapping tumor microenvironment parameters (e.g., O 2 , pH, and cancer biomarkers), delivering local drug treatments, assessing treatment responses, and monitoring for recurrence and metastasis. Although these research studies have predominantly focused on and were tailored to humans, the results and concepts are equally applicable to veterinary patients. While veterinary clinical studies that have adopted a precision medicine approach are still in their infancy, there have been some exciting success stories. These have included the development of a receptor tyrosine kinase inhibitor for canine mast cell tumors and the production of a PCR assay to monitor the chemotherapeutic response of canine high-grade B-cell lymphomas. Although precision medicine is an exciting area of research, it currently has failed to gain significant translation into human and veterinary healthcare practices. In order to begin to address this issue, there is increasing awareness that cross-disciplinary approaches involving human and veterinary clinicians, engineers and chemists may be needed to help advance precision medicine toward its full integration into human and veterinary clinical practices.

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Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors

Cited by 16 publications

References 54 publications

Current biomarkers of canine mammary tumors

Current biomarkers of canine mammary tumors

Know Thy Model: Charting Molecular Homology in Stromal Reprogramming Between Canine and Human Mammary Tumors

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology

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