Pregnancy and soluble VEGF receptor 1(sFlt-1)

Background and objective:Bevacizumab (BVZ) is a recombinant humanized antibody that inhibits the vascular endothelial growth factor A (VEGFA) and is used for the treatment of various types of cancer. BVZ is primarily given by the intravenous drip (I.V.), which often leads to low efficacy and various side effects. Therefore, the present study was to evaluate the effect of local delivery of BVZ against triple-negative breast cancer (TNBC) xenograft tumors.Methods:Mice 4T1 TNBC cells were engrafted in female BALB/c mice. After the tumors reached about 5 mm (diameter), animals were treated with BVZ through the local injection from four directions around the tumors. The tumor growth, survival and potential mechanisms of action were evaluated.Results:The growth and microvessel density of engrafted tumors were dramatically reduced with the tumor inhibition rate of 32.8 ± 3%. No obvious side effects were observed. The expression of VEGFA, VEGF receptor (VEGFR), matrix metalloproteinase (MMP)-2, MMP-9, Delta-like ligand 4 (DLL4) and Integrin-5 was significantly reduced in TNBC tumor tissues. In contrast, tissue inhibitor of matrix metalloproteinase (TIMP)-2 was significantly upregulated in xenograft tumors. Additionally, local delivery of BVZ led to the reduction of VEGFA and tumor necrosis factor (TNF)-alpha in the serum. Protein-protein interaction (PPI) analysis revealed that the proteins altered by the local delivery of BVZ were associated with angiogenesis and regulation of cell migration.Conclusion:This study provided evidence associated with local delivery of BVZ against TNBC tumors supporting the use of BVZ local injections to overcome some of the disadvantages associated with I.V. therapy with BVZ.

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Expression Profile of VEGF-C, VEGF-D, and VEGFR-3 in Different Grades of Endometrial Cancer

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190718164431 ◽

2019 ◽

Vol 20 (12) ◽

pp. 1004-1010

Author(s):

Marcin Oplawski ◽

Konrad Dziobek ◽

Nikola Zmarzły ◽

Beniamin Grabarek ◽

Tomasz Halski ◽

...

Keyword(s):

Endometrial Cancer ◽

Optical Density ◽

Metastatic Potential ◽

Vegf Receptor ◽

Vascular Endothelial ◽

Tumor Lymphangiogenesis ◽

Neoplastic Process ◽

The One ◽

Post Hoc ◽

Endothelial Growth Factor

Background: Vascular endothelial growth factor (VEGF)-C, -D, and VEGF receptor-3 are proteins characterized as crucial for tumor lymphangiogenesis. It is accompanied by angiogenesis during wound healing, but also in the neoplastic process. The research studies have shown that the lymphatic system plays a key role in the progression of carcinogenesis. Objective: The aim of this study was to evaluate changes in the expression of VEGF-C, VEGF-D and VEGFR-3 in different grades of endometrial cancer (G1-G3). Methods: The study included 45 patients diagnosed with endometrial cancer (G1=17; G2=15; G3=13) and 15 patients without neoplastic changes. The expression of VEGF-C, VEGF-D, and VEGFR-3 was assessed using microarray technique and immunohistochemistry. Statistical analysis was performed using the one-way ANOVA and Tukey's post-hoc test. Results: Statistically significant changes in the expression at the transcriptome level were found only in the case of VEGF-C (G1 vs. C, fold change - FC = -1.15; G2 vs. C, FC = -2.33; G3 vs. C, FC = - 1.68). However, VEGF-D and VEGFR-3 were expressed at the protein level. Analysis of VEGF-D expression showed that the optical density of the reaction product in G1 reached 101.7, while the values in G2 and G3 were 142.7 and 184.4, respectively. For VEGF-R3, the optical density of the reaction product reached the following levels: 72 in control, 118.77 in G1, 145.8 in G2, and 170.9 in G3. Conclusion: : An increase in VEGF-D and VEGFR-3 levels may indicate that VEGF-D-dependent processes are intensified along with the dedifferentiation of tumor cells. The lack of VEGF-C expression in endometrial cancer samples may suggest that this tumor is characterized by a different mechanism of metastasis than EMT. Our study emphasizes that when analyzing the metastatic potential of cancer, the expression of more than one factor should be taken into account.

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Statins: A Conceivable Remedial Role for the Regulation of Cancer Progression

Current Cancer Therapy Reviews ◽

10.2174/1573394714666180611113834 ◽

2019 ◽

Vol 15 (2) ◽

pp. 131-145

Author(s):

Gajanan V. Sherbet

Keyword(s):

Cell Proliferation ◽

Growth Factor ◽

Tumour Growth ◽

Cell Function ◽

Mevalonate Pathway ◽

Biological Effects ◽

Vegf Receptor ◽

Mesenchymal Transition ◽

Cancer Management ◽

Metabolic Role

The mevalonate pathway (also known as the cholesterol biosynthesis pathway) plays a crucial metabolic role in normal cell function as well as in the pathological environment. It leads to the synthesis of sterol and non-sterol isoprenoid biomolecules which subserve a variety of cellular functions. It is known to be deregulated in many disease processes. Statins and bisphosphonates are prominent inhibitors of the mevalonate pathway. They inhibit cell proliferation and activate apoptotic signalling and suppress tumour growth. Statins subdue metastatic spread of tumours by virtue of their ability to suppress invasion and angiogenesis. The induction of autophagy is another feature of statin effects that could contribute to the suppression of metastasis. Herein highlighted are the major signalling systems that statins engage to generate these biological effects. Statins can constrain tumour growth by influencing the expression and function of growth factor and receptor systems. They may suppress epithelial mesenchymal transition with resultant inhibition of cell survival signalling, together with the inhibition of cancer stem cell generation, and their maintenance and expansion. They can suppress ER (oestrogen receptor)-α in breast cancer cells. Statins have been implicated in the activation of the serine/threonine protein kinase AMPK (5' adenosine monophosphate-activated protein) leading to the suppression of cell proliferation. Both statins and bisphosphonates can suppress angiogenic signalling by HIF (hypoxia- inducible factor)-1/eNOS (endothelial nitric oxide synthase) and VEGF (vascular endothelial growth factor)/VEGFR (VEGF receptor). Statins have been linked with improvements in disease prognosis. Also attributed to them is the ability of cancer prevention and reduction of risk of some forms of cancer. The wide spectrum of cancer associated events which these mevalonate inhibitors appear to influence would suggest a conceivable role for them in cancer management. However, much deliberation is warranted in the design and planning of clinical trials, their scope and definition of endpoints, modes risk assessment and the accrual of benefits.

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Extracellular vesicles from human airway basal cells respond to cigarette smoke extract and affect vascular endothelial cells

Scientific Reports ◽

10.1038/s41598-021-85534-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ashish Saxena ◽

Matthew S. Walters ◽

Jae-Hung Shieh ◽

Ling-Bo Shen ◽

Kazunori Gomi ◽

...

Keyword(s):

Endothelial Cells ◽

Cigarette Smoke ◽

Extracellular Vesicles ◽

Basal Cell ◽

Mapk Signaling ◽

Cigarette Smoke Extract ◽

Vegf Receptor ◽

Vascular Endothelial ◽

Basal Cells ◽

Human Airway

AbstractThe human airway epithelium lining the bronchial tree contains basal cells that proliferate, differentiate, and communicate with other components of their microenvironment. One method that cells use for intercellular communication involves the secretion of exosomes and other extracellular vesicles (EVs). We isolated exosome-enriched EVs that were produced from an immortalized human airway basal cell line (BCi-NS1.1) and found that their secretion is increased by exposure to cigarette smoke extract, suggesting that this stress stimulates release of EVs which could affect signaling to other cells. We have previously shown that primary human airway basal cells secrete vascular endothelial growth factor A (VEGFA) which can activate MAPK signaling cascades in endothelial cells via VEGF receptor–2 (VEGFR2). Here, we show that exposure of endothelial cells to exosome-enriched airway basal cell EVs promotes the survival of these cells and that this effect also involves VEGFR2 activation and is, at least in part, mediated by VEGFA present in the EVs. These observations demonstrate that EVs are involved in the intercellular signaling between airway basal cells and the endothelium which we previously reported. The downstream signaling pathways involved may be distinct and specific to the EVs, however, as increased phosphorylation of Akt, STAT3, p44/42 MAPK, and p38 MAPK was not seen following exposure of endothelial cells to airway basal cell EVs.

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VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs

EJNMMI Research ◽

10.1186/s13550-020-00626-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Lynne L. Johnson ◽

Jordan Johnson ◽

Ziad Ali ◽

Yared Tekabe ◽

Rebecca Ober ◽

...

Keyword(s):

Limb Ischemia ◽

Vegf Receptor ◽

Targeted Imaging ◽

Angiogenic Response

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Two molecules related to the VEGF receptor are expressed in early endothelial cells during avian embryonic development

Mechanisms of Development ◽

10.1016/0925-4773(93)90096-g ◽

1993 ◽

Vol 42 (1-2) ◽

pp. 33-48 ◽

Cited By ~ 122

Author(s):

Anne Eichmann ◽

Christophe Marcelle ◽

Christiane Bréant ◽

Nicole M. Le Douarin

Keyword(s):

Endothelial Cells ◽

Embryonic Development ◽

Vegf Receptor

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