Serum levels of angiogenic cytokines decrease after radiotherapy in non-Hodgkin lymphomas

Ria, Roberto; Cirulli, Teresa; Giannini, Teresa; Bambace, Santa; Serio, Gabriella; Portaluri, Maurizio; Ribatti, Doménico; Vacca, Angelo; Dammacco, Franco

doi:10.1007/s10238-008-0170-2

Cited by 19 publications

(17 citation statements)

References 23 publications

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“…The involvement of PDGF and its receptors have been described in several human hematopoietic malignancies (Ho et al, 2005;Renné et al, 2005;Karabatsou et al, 2005;Karabatsou et al, 2006;Ria et al, 2008;Piccaluga et al, 2014). The existence of an autocrine and/or paracrine loop contributing to the uncontrollable growth of malignant cells has been also correlated to the clinical outcome in PTCL (Piccaluga et al, 2005, Piccaluga et al, 2014.…”

Section: Discussionmentioning

confidence: 99%

Platelet-derived Growth Factors and Receptors in Canine Lymphoma

Aricò

Guadagnin

Ferraresso

et al. 2014

Journal of Comparative Pathology

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Platelet-derived growth factors (PDGFs) belong to a family of polypeptide growth factors that signal through cell surface tyrosine kinase receptors to stimulate growth, proliferation and differentiation. Platelet-derived growth factor receptors (PDGFRs) are also considered important targets for specific kinase inhibitors in the treatment of several human tumours. The aim of this study was to investigate the role of PDGF-A, PDGF-B, PDGFR-α and PDGFR-β in canine lymphoma by determining gene and protein expression in lymph nodes of dogs with diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), T-lymphoblastic lymphoma (T-LBL) and in healthy control dogs. One lymph node was also studied at the end of therapy in a subset of dogs in remission for DLBCL. In controls, PDGF-A, PDGFR-α and PDGFR-β mRNA levels were significantly higher than in DLBCLs, PTCLs and T-LBLs. However, PDGFR-α and PDGFR-β were minimally expressed by lymphocytes and plasma cells in normal lymph nodes as determined by immunohistochemistry, while neoplastic B and T cells showed the highest score (P <0.05). This discordant result may be compatible with the constitutive expression of these molecules by endothelial cells and fibroblasts in normal lymph nodes, thereby influencing gene expression results. Furthermore, these cells were not included in the immunohistochemical analysis. Similarly, dogs with DLBCL that were in remission at the end of therapy showed significantly higher gene expression of PDGFs and receptors than at the time of diagnosis and with an opposite trend to the protein assay. PDGF-B protein and mRNA were overexpressed in PTCLs and T-LBLs when compared with DLBCLs and controls (P <0.05). Additionally, there was a correlation between protein expression of PDGF-B and both PDGFRs in PTCLs and T-LBLs, suggesting an autocrine or paracrine loop in the aetiology of aggressive canine T-cell lymphomas. These data provide a rationale for the use of PDGFR antagonists in the therapy of aggressive T-cell lymphomas, but not in DLBCLs.

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Section: Discussionmentioning

confidence: 99%

Platelet-derived Growth Factors and Receptors in Canine Lymphoma

Aricò

Guadagnin

Ferraresso

et al. 2014

Journal of Comparative Pathology

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“…Forty-six patients with esophageal cancer treated with concurrent chemoradiation to 60–64 Gy showed significant decreases in serum VEGF levels, with the changes correlating with overall survival at two-year follow up [ 44 ]. Twenty non-Hodgkin’s lymphoma patients treated to median 26 Gy also showed serum VEGF levels decline post-RT, as did 37 patients with pharyngeal and laryngeal SCC treated to a total dose of 40 Gy [ 24 , 45 ]. Prior animal studies have examined the importance of VEGF in tumor associated angiogenesis and tumor growth, and the expression of this cytokine by head and neck squamous cell carcinoma lines driven by MEK-MAPK and IKK-NF-Kb pathways [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of definitive chemoradiation on circulating immunologic angiogenic cytokines in head and neck cancer patients

Sridharan¹,

Margalit²,

Lynch³

et al. 2016

j. immunotherapy cancer

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BackgroundPreclinical studies suggest a synergistic effect between radiation, immunotherapy and anti-angiogenic therapy, although the mechanisms are unclear. Angiogenic cytokines are known to affect the immune system, and their levels may be associated with response to immunotherapy. Here, we assess changes in circulating VEGF, as well as angiogenic cytokines angiopoietin-1 and -2 (Ang1, Ang2), and placental growth factor (PLGF) that occur during definitive chemo-radiotherapy in HNSCC patients.MethodsWe prospectively collected blood samples from patients receiving definitive radiation with or without chemotherapy. Serum Ang1, Ang2, VEGF, and PLGF were measured via cytokine assays.ResultsThe majority of patients had advanced stage, node positive HPV-associated oropharyngeal cancer, and received radiation to a median dose of 70 Gy with concurrent cisplatin. Over the course of treatment, serum VEGF and Ang1 levels decreased in 20/24 (84 %, p < 0.0001) and 21/24 (88 %, p < 0.0001) patients, respectively, and Ang2 and PLGF levels increased in 20/24 (83 %, p < 0.0001) patients.ConclusionsWe find significant changes in angiogenic cytokines in the majority of HNSCC patients over the course of chemoradiation. Decreases in VEGF caused by radiation may represent one mechanism of potential synergy with immunotherapy. Increases in Ang2 and PLGF are interesting given their link to tumor associated angiogenesis and poor prognosis. Additional studies are needed to explore synergies between anti-angiogenic treatments, immunotherapy, and chemoradiation in HNSCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-016-0138-9) contains supplementary material, which is available to authorized users.

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“…Serum levels of angiogenic cytokines decrease after radiotherapy in patients with hematologic malignancy and become undetectable in patients with complete remission [29]. However, by exposing normal tissue to radiation, we determined that the positively influencing factors of the angiogenesis pathway increased, while the negatively influencing factor decreased.…”

Section: Resultsmentioning

confidence: 91%

An Experimental Study of Radiation Effect on Normal Tissue: Analysis of HIF-1α, VEGF, eIF2, TIA-1, and TSP-1 Expression

Aktaş

Kurtman

Özbilgin

et al. 2013

tjh

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Abstract:Objective: This study investigated whether or not the stress and hypoxia, which are the effects of radiation on normal vascular endothelium, leading to the release of HIF-1α, VEGF, eIF2, TIA-1, and TSP-1 were related and the possibility of them stimulating angiogenesis.Materials and Methods: Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1), and the second, third, and fourth groups were euthanized after 24 h (Group 2), 48 h (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Immunohistochemistry and light microscopy were used to investigate whether there would be an increase or not in the angiogenesis pathway by using the HIF-1α, VEGF, eIF2, TIA-1, and TSP-1 antibodies.Results: The HIF-1α antibody showed strong staining in Group 3, while the staining intensity was less in other groups. VEGF showed weak staining in Groups 1 and 4, while moderate staining in Group 2 and strong staining in Group 3 was observed. eIF2 showed strong staining in Groups 1 and 4. Groups 2 and 3 were stained weakly. In the present study, staining with TSP-1 was very strong in the samples belonging to Group 1, while other groups showed very weak staining.Conclusion: When normal tissue was exposed to radiation, the positively effective factors (HIF-1, VEGF, eIF2, and TIA-1) on the angiogenesis pathway were increased while the negative factor (TSP-1) was decreased. Radiation may initiate physiological angiogenesis in the normal tissue and accelerate healing in the damaged normal tissue.

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Serum levels of angiogenic cytokines decrease after radiotherapy in non-Hodgkin lymphomas

Abstract: Soluble FGF-2, VEGF and PDGF-beta levels decline after radiotherapy in NHLs, and may have predictive significance for response to treatment and recurrence.

Cited by 19 publications

References 23 publications

Platelet-derived Growth Factors and Receptors in Canine Lymphoma

Platelet-derived Growth Factors and Receptors in Canine Lymphoma

Effects of definitive chemoradiation on circulating immunologic angiogenic cytokines in head and neck cancer patients

An Experimental Study of Radiation Effect on Normal Tissue: Analysis of HIF-1α, VEGF, eIF2, TIA-1, and TSP-1 Expression

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