Markers of angiogenesis (CD31, CD34, rCBV) and their prognostic value in low-grade gliomas

Majchrzak, Krzysztof; Kaspera, Wojciech; Szymaś, Janusz; Bobek-Billewicz, Barbara; Hebda, Anna; Majchrzak, H

doi:10.5114/ninp.2013.36757

Cited by 31 publications

(25 citation statements)

References 14 publications

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“…To verify activation of the pro-angiogenic pathway in the recipient myocardium, we measured expression of CD31 by IHC. CD31, a marker for angiogenesis 36, 37 , was significantly overexpressed in the hCM- and iCM-treated myocardium (Figure 6B-C, E-F, p<0.05 vs. hESC/iPSC groups), confirming the effect of pro-angiogenic cytokines from hCM and iCM supernatant.…”

Section: Resultsmentioning

confidence: 54%

Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium

Tachibana

Santoso

Mahmoudi

et al. 2017

Circulation Research

134

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Rationale Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction (LVEF). However, the mechanism underlying the functional benefit is unclear. Objective To evaluate whether the transplantation of cardiac lineage differentiated derivatives enhance myocardial viability and restore LVEF more effectively than undifferentiated pluripotent stem cells after a myocardial injury (MI). Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine MI model. Methods and Results Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intra-myocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14) and (5) PBS control (n=10). LVEF and myocardial viability, measured by cardiac-MRI and manganese-enhanced MRI (MEMRI), respectively, was significantly improved in hCM- and iCM-treated mice compared to pluripotent stem cell- or control-treated mice. Bioluminescence imaging (BLI) revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant up-regulation of the pro-migratory, pro-angiogenic, and anti-apoptotic targets in groups treated with cardiac lineage cells compared to pluripotent stem cell and control groups. Conclusions This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium more effectively than undifferentiated stem cells through their differential paracrine effects.

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Section: Resultsmentioning

confidence: 54%

Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium

Tachibana

Santoso

Mahmoudi

et al. 2017

Circulation Research

134

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“…Immunohistochemistry analysis shown an increase of CD34 + (microvascular density) in the patients. In the recent years, many studies have demonstrated that CD34 + blood vessels play a prominent part in tumour development and influence malignant severity . Tichet et al .…”

Section: Discussionmentioning

confidence: 99%

Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

Lima

Simoes

Castro

et al. 2019

J cachexia sarcopenia muscle

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Background Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro‐environment contributes to systemic inflammation and increased oxidative stress as well as to fibrosis. The aim of the present study was to characterise the inflammatory circulating factors and tumour micro‐environment profile, as potentially contributing to tumour fibrosis in cachectic cancer patients. Methods 74 patients (weight stable cancer n = 31; cachectic cancer n = 43) diagnosed with colorectal cancer were recruited, and tumour biopsies were collected during surgery. Multiplex assay was performed to study inflammatory cytokines and growth factors. Immunohistochemistry analysis was carried out to study extracellular matrix components. Results Higher protein expression of inflammatory cytokines and growth factors such as epidermal growth factor, granulocyte–macrophage colony‐stimulating factor, interferon‐α, and interleukin (IL)‐8 was observed in the tumour and serum of cachectic cancer patients in comparison with weight‐stable counterparts. Also, IL‐8 was positively correlated with weight loss in cachectic patients (P = 0.04; r = 0.627). Immunohistochemistry staining showed intense collagen deposition (P = 0.0006) and increased presence of α‐smooth muscle actin (P < 0.0001) in tumours of cachectic cancer patients, characterizing fibrosis. In addition, higher transforming growth factor (TGF)‐β1, TGF‐β2, and TGF‐β3 expression (P = 0.003, P = 0.05, and P = 0.047, respectively) was found in the tumour of cachectic patients, parallel to p38 mitogen‐activated protein kinase alteration. Hypoxia‐inducible factor‐1α mRNA content was significantly increased in the tumour of cachectic patients, when compared with weight‐stable group (P = 0.005). Conclusions Our results demonstrate TGF‐β pathway activation in the tumour in cachexia, through the (non‐canonical) mitogen‐activated protein kinase pathway. The results show that during cachexia, intratumoural inflammatory response contributes to the onset of fibrosis. Tumour remodelling, probably by TGF‐β‐induced transdifferentiation of fibroblasts to myofibroblasts, induces unbalanced inflammatory cytokine profile, angiogenesis, and elevation of extracellular matrix components (EMC). We speculate that these changes may affect tumour aggressiveness and present consequences in peripheral organs.

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“…5 In recent years, studies have demonstrated that CD34-positive vessels play pivotal roles in the development of gliomas and have an influence on the malignant severity. 10,11,13 There have been a few reports that have comprehensively described the significance of CD34 in glioma patients and the specific roles of CD34 in the grading and prognosis of gliomas remain unclear. Therefore, it is unclear whether CD34 can be used as a marker of WHO grades in gliomas.…”

Section: Discussionmentioning

confidence: 99%

“…This occurs by the increased supply of oxygen and other necessary metabolites, which leads to brain invasion and a worsened prognosis. 10–12 …”

Section: Introductionmentioning

confidence: 99%

CD34 Over-Expression is Associated With Gliomas’ Higher WHO Grade

Kong

Guan²,

Ma³

et al. 2016

Medicine

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CD34 is a transmembrane phosphoglycoprotein that was first identified on hematopoietic stem and progenitor cells. CD34 is known as an optimum marker for microvascular density studies and it is positively stained in pathological and physiologic vessels. The use of CD34 for the prognosis, diagnosis, and treatment of neoplasms has been increasingly discussed. The implications and utilities of CD34 in WHO grades of gliomas and its prognosis have been reported rarely. Also, the WHO grades and prognosis researches remains unclear and controversial. A meta-analysis is the best choice for drawing a convincing conclusion.Several databases were searched. We carefully assess the relevant articles and standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were estimated in terms of the relationship between CD34 expression levels with gliomas’ WHO grades, patients’ ages and gender. We used the Galbraith figure, the I2 test, and Cochran Q test to evaluate the heterogeneity of the included studies. A sensitivity analysis was conducted to assess the pooled results’ stability. A Contour-enhanced funnel plot evaluation was made to assess potential publication bias. Ethics review and approval was not necessary because the meta-analysis did not involve any direct human trials or animal experiments.There were 12 eligible studies, including 684 patients who were considered in the present meta-analysis. All of them were conducted in China. CD34 overexpression in glioma tissues was associated closely, according to the pooled SMD, with higher WHO grade (III + IV) (SMD -1.503, 95% CI -1.685 to -1.321; P = 0.000). There were no significant associations between CD34 and age (SMD -0.223, 95% CI -0.602 to 0.156; P = 0.248) and CD34 and gender (SMD -0.059, 95% CI -0.439, 0.321; P = 0.761). No publication bias was detected according to Contour-enhanced funnel plot.Our results suggested that CD34 overexpression is associated with higher WHO grades of gliomas. CD34 may serve as a potential diagnostic and prognostic marker, or it could be a useful therapy target.

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Markers of angiogenesis (CD31, CD34, rCBV) and their prognostic value in low-grade gliomas

Cited by 31 publications

References 14 publications

Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium

Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium

Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

CD34 Over-Expression is Associated With Gliomas’ Higher WHO Grade

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