Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2240-2245 ◽  
Author(s):  
Alvaro Aguayo ◽  
Hagop Kantarjian ◽  
Taghi Manshouri ◽  
Cristi Gidel ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Growth Factor ◽  
Blood Vessels ◽  
Myelodysplastic Syndromes ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Angiogenic Factors ◽  
Bone Marrow Biopsies ◽  
Tnf Α ◽  
Factor Α

Abstract Angiogenesis has been associated with the growth, dissemination, and metastasis of solid tumors. The aims of this study were to evaluate the vascularity and the levels of angiogenic factors in patients with acute and chronic leukemias and myelodysplastic syndromes (MDS). The numbers of blood vessels were measured in 145 bone marrow biopsies and the levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis growth factor-α (TNF-α), tumor growth factor-α (TGF-α), and hepatocyte growth factor (HGF) were determined in 417 plasma samples. Except for chronic lymphocytic leukemia (CLL), vascularity was significantly higher in all leukemias and MDS compared with control bone marrows. The highest number of blood vessels and largest vascular area were found in chronic myeloid leukemia (CML). VEGF, bFGF, and HGF plasma levels were significantly increased in acute myeloid leukemia (AML), CML, CLL, chronic myelomonocytic leukemia (CMML), and MDS. HGF, TNF-α, and bFGF but not VEGF were significantly increased in acute lymphoblastic leukemia (ALL). TNF-α levels were significantly increased in all diseases except for AML and MDS. No significant increase was found in TGF-α in any leukemia or MDS. The highest plasma levels of VEGF were in CML, and the highest plasma levels of bFGF were in CLL. The levels of HGF were highest in CMML. These data suggest that vascularity and angiogenic factors are increased in leukemias and MDS and may play a role in the leukemogenic process.

Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2240-2245 ◽  
Author(s):  
Alvaro Aguayo ◽  
Hagop Kantarjian ◽  
Taghi Manshouri ◽  
Cristi Gidel ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Growth Factor ◽  
Blood Vessels ◽  
Myelodysplastic Syndromes ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Angiogenic Factors ◽  
Bone Marrow Biopsies ◽  
Tnf Α ◽  
Factor Α

Angiogenesis has been associated with the growth, dissemination, and metastasis of solid tumors. The aims of this study were to evaluate the vascularity and the levels of angiogenic factors in patients with acute and chronic leukemias and myelodysplastic syndromes (MDS). The numbers of blood vessels were measured in 145 bone marrow biopsies and the levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis growth factor-α (TNF-α), tumor growth factor-α (TGF-α), and hepatocyte growth factor (HGF) were determined in 417 plasma samples. Except for chronic lymphocytic leukemia (CLL), vascularity was significantly higher in all leukemias and MDS compared with control bone marrows. The highest number of blood vessels and largest vascular area were found in chronic myeloid leukemia (CML). VEGF, bFGF, and HGF plasma levels were significantly increased in acute myeloid leukemia (AML), CML, CLL, chronic myelomonocytic leukemia (CMML), and MDS. HGF, TNF-α, and bFGF but not VEGF were significantly increased in acute lymphoblastic leukemia (ALL). TNF-α levels were significantly increased in all diseases except for AML and MDS. No significant increase was found in TGF-α in any leukemia or MDS. The highest plasma levels of VEGF were in CML, and the highest plasma levels of bFGF were in CLL. The levels of HGF were highest in CMML. These data suggest that vascularity and angiogenic factors are increased in leukemias and MDS and may play a role in the leukemogenic process.

scholarly journals The Effects of Rice Husk Liquid Smoke in Porphyromonas gingivalis-Induced Periodontitis

2021 ◽  
Author(s):  
Theresia Indah Budhy ◽  
Ira Arundina ◽  
Meircurius Dwi Condro Surboyo ◽  
Anisa Nur Halimah
Keyword(s):  
Growth Factor ◽  
Porphyromonas Gingivalis ◽  
Rice Husk ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Control Group ◽  
Proliferation Markers ◽  
Liquid Smoke ◽  
Tnf Α ◽  
Factor Α

Abstract Objectives The purpose of this study is to analyze the effects of rice husk liquid smoke in Porphyromonas gingivalis-induced periodontitis in the inflammatory and proliferation marker such as nuclear factor kappa β (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), fibroblast growth factor 2 (FGF2), collagen type 1 (COL-1) expression, and the number of macrophages, lymphocytes, and fibroblasts. Materials and Methods Rice husk liquid smoke is obtained by the pyrolysis process. Porphyromonas gingivalis-induced periodontitis in 20 μL phosphate-buffered saline containing 1 × 109 CFU was injected into the lower anterior gingival sulcus of Wistar rats. The periodontitis was then treated with 20 μL/20 g body weight of rice husk liquid smoke once a day for 2 and 7 days, respectively. After treatment, the bone and lower anterior gingival sulcus were analyzed with immunohistochemistry and hematoxylin–eosin staining. Results The treatment of periodontitis with rice husk liquid smoke showed a lower NF-kB, TNF-α, and IL-6 expression and a higher TGF-β, FGF2, and COL-1 expression than the control after treatment for 2 and 7 days (p < 0.05), respectively. The number of macrophages and fibroblasts was also higher when compared with the control group (p < 0.05), but the number of lymphocytes was lower than the control (p < 0.05). Conclusion Rice husk liquid smoke showed its effects on Porphyromonas gingivalis-induced periodontitis with a decrease in inflammatory markers and an increase in proliferation markers. The development of a rice husk liquid smoke periodontitis treatment is promising.

scholarly journals Tumor Necrosis Factor α Regulates Responses to Nerve Growth Factor, Promoting Neural Cell Survival but Suppressing Differentiation of Neuroblastoma Cells

2008 ◽  
Vol 19 (3) ◽  
pp. 855-864 ◽  
Author(s):  
Yoshinori Takei ◽  
Ronald Laskey
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Neuroblastoma Cells ◽  
Erk Activation ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Although nerve growth factor (NGF) promotes survival of neurons, tumor necrosis factor α (TNF-α) contributes to cell death triggered by NGF depletion, through TNF-α receptor (TNFR) 1. In contrast to this effect, TNF-α can promote neural cell survival via TNF-α receptor TNFR2. Although these findings demonstrate pivotal roles of TNF-α and NGF in cell fate decisions, cross-talk between these signaling pathways has not been clarified. We find that NGF can induce TNF-α synthesis through the nuclear factor-κB transcription factor. This provides a new basis for examining the cross-talk between NGF and TNF-α. Inhibition of TNFR2 shows opposite effects on two downstream kinases of NGF, extracellular signal-regulated kinase (Erk) and Akt. It increases Erk activation by NGF, and this increased activation induces differentiation of neuroblastoma cell lines. Reciprocally, inhibition of TNFR2 decreases Akt activation by NGF. Consistent with an essential role of Akt in survival signaling, inhibition of TNF-α signaling decreases NGF-dependent survival of neurons from rat dorsal root ganglia. Thus, NGF and NGF-induced TNF-α cooperate to activate Akt, promoting survival of normal neural cells. However, the NGF-induced TNF-α suppresses Erk activation by NGF, blocking NGF-induced differentiation of neuroblastoma cells. TNFR2 signaling could be a novel target to modulate cell responses to NGF.

Differential effect of selective block of α2-adrenoreceptors on plasma levels of tumour necrosis factor-α, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice

1995 ◽  
Vol 144 (3) ◽  
pp. 457-462 ◽  
Author(s):  
G Haskó ◽  
I J Elenkov ◽  
V Kvetan ◽  
E S Vizi
Keyword(s):  
Tumour Necrosis Factor ◽  
Interleukin 6 ◽  
Plasma Levels ◽  
Tumour Necrosis ◽  
Endotoxin Shock ◽  
Bacterial Lipopolysaccharide ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract The effect of selective block of α2-adrenoreceptors on plasma levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and corticosterone induced by bacterial lipopolysaccharide (LPS) was investigated in mice using ELISA and RIA. It was found that the LPS-induced TNF-α response was significantly blunted in mice pretreated with CH-38083, a novel and highly selective α2-adrenoreceptor antagonist (the α2/α1 ratio is >2000). In contrast, LPS-induced increases in both corticosterone and IL-6 plasma levels were further increased by CH-38083. Since it has recently been shown that the selective block of α2-adrenoreceptors located on noradrenergic axon terminals resulted in an increase in the release of noradrenaline (NA), both in the central and peripheral nervous systems, and, in our experiments, that propranolol prevented the effect of α2-adrenoreceptor blockade on TNF-α plasma levels induced by LPS, it seems likely that the excessive stimulation by NA of β-adrenoreceptors located on cytokine-secreting immune cells is responsible for this action. Since it is generally accepted that increased production of TNF-α is involved in the pathogenesis of inflammation and endotoxin shock on the one hand, and corticosterone and even IL-6 are known to possess anti-inflammatory properties on the other hand, it is suggested that the selective block of α2-adrenoreceptors might be beneficial in the treatment of inflammation and/or endotoxin shock. Journal of Endocrinology (1995) 144, 457–462

scholarly journals Angiopoietin-2 is released during anaphylactic hypotension in anesthetized and unanesthetized rats

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242026
Author(s):  
Tao Zhang ◽  
Toshishige Shibamoto ◽  
Mamoru Tanida ◽  
Makoto Taniguchi ◽  
Yuhichi Kuda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Acute Lung Injury ◽  
Growth Factor ◽  
Vascular Permeability ◽  
Plasma Levels ◽  
Blue Dye ◽  
Arterial Blood ◽  
Tnf Α ◽  
Angiopoietin 2

Angiopoietin (Angpt)-2, a permeability-increasing growth factor, is involved in vascular leakage of sepsis and acute lung injury, and could be released from endothelium in response to anaphylaxis-related secretagogues such as histamine and leukotrienes, or cytokines. However, roles of Angpt-2 in the hyperpermeability during systemic anaphylaxis are not known. Thus, we determined plasma levels of Angpt-2 and cytokines and vascular permeability during anaphylactic hypotension in unanesthetized rats. Anaphylaxis was induced by an intravenous injection of ovalbumin antigen. Mean arterial blood pressure (MBP) was measured, and hematocrit (Hct) and plasma levels of Angpt-2 and cytokines were assessed for 24 h after antigen injection. Separately, vascular permeability was measured in various organs using the Evans blue dye method, and Angpt-2 mRNA expression in liver was measured. After antigen injection, MBP decreased to the nadir at 6 min, and returned to baseline at 45 min, and Hct peaked at 20 min and thereafter progressively declined, suggesting that vascular leak and hypotension occurred within 20 min. Plasma Angpt-2 levels began to increase significantly at 1 h after antigen, reaching the peak 2.7-fold baseline at 6 h with a return to baseline at 24 h. Detected cytokines of IL-1α, IL-1β, IL-6, IL-10, and TNF-α peaked 1 or 2 h after antigen. Angpt-2 mRNA increased at 2 h and showed an increasing tendency at 6 h. Vascular permeability in bronchus, trachea, intestines, mesentery and skeletal muscle was increased at 10 min but not at 6 h after antigen. In addition, we confirmed using anesthetized rat anaphylaxis models that plasma Angpt-2 levels increased at 1 h after antigen. In conclusion, plasma Angpt-2 is elevated presumably due to increased cytokines and enhanced gene transcription during anaphylaxis in anesthetized and unanesthetized rats.

Regulation of Murine Protein C Gene Expression In Vivo: Effects of Tumor Necrosis Factor-α, Interleukin-1, and Transforming Growth Factor-β

1999 ◽  
Vol 82 (10) ◽  
pp. 1297-1301 ◽  
Author(s):  
Takayoshi Shimokawa ◽  
Tetsuhito Kojima ◽  
David Loskutoff ◽  
Hidehiko Saito ◽  
Koji Yamamoto
Keyword(s):  
Growth Factor ◽  
Protein C ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Transforming Growth Factor Β ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

SummaryProtein C is a precursor of the anticoagulant serine protease, activated protein C, which inhibits coagulation factors Va and VIIIa. Although the liver appears to be the primary site of protein C synthesis, we previously demonstrated that the kidney and male reproductive organs also expressed abundant protein C mRNA in the mouse. In the present study, we further investigated the effects of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and transforming growth factor-β (TGF-β) on the expression of protein C mRNA in the principal producing organs, i.e., the liver, kidney, and testis. Both quantitative reverse transcription-PCR assay and in situ hybridization analysis revealed that TNF-α decreased protein C mRNA expression in the liver, kidney, and testis. IL-1 also down-regulated protein C mRNA expression in the liver and testis, but not in the kidney. In contrast, TGF-β unchanged the expression level of protein C mRNA in these three organs. These observations suggest that TNF-α and IL-1 may contribute to an increase in the procoagulant potential by down-regulation of protein C synthesis in the tissues during inflammatory processes.

Elevation of Plasma Von Willebrand Factor and Tumor Necrosis Factor-α in Obese Subjects and Their Reduction by Low Molecular Weight Heparin.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4053-4053
Author(s):  
Shaker A. Mousa
Keyword(s):  
Tumor Necrosis Factor ◽  
Plasma Levels ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Normal Weight ◽  
Tnf Α ◽  
Obese Subjects ◽  
Factor Α ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background: Increased plasma-soluble von Willebrand factor (vWF) level, a marker of vascular endothelial cell dysfunction, is a predictor of atherosclerotic cardiovascular disease in the general population. We compared associations between vWF level and markers of inflammation as well as the effects of low molecular weight heparin (LMWH) in obese as compared to healthy human subjects. Methods: Plasma samples were obtained from healthy volunteers (n = 32) and obese subjects (n = 12) before and after administration of a single subcutaneous (SC) dose of tinzaparin, given at a deep vein thrombosis (DVT) prophylaxis dose of 75 IU/kg once a day. These samples were analyzed for vWF and tumor necrosis factor-α (TNF-α) by ELISA. Also examined was the effect of different LMWH on the release of vWF from human umbilical vein endothelial cells (HUVEC) in response to various stimuli, such as oxidized low density lipoprotein (LDL) or endotoxin. Results: Obese subjects showed higher plasma levels of TNF-α compared with normal-weight subjects. Regression analysis showed plasma vWF levels to be directly associated with the presence of higher plasma levels of TNF-α in these obese subjects. Tinzaparin, given at a prophylaxis dose for DVT (75 IU/kg, SC, QD), significantly reduced elevated plasma levels of endothelial dysfunction marker vWF associated with higher inflammatory TNF-α levels (P &lt;0.01). HUVEC, when treated with oxidized LDL or endotoxin, demonstrated a significant elevation of vWF release into the medium in a time-dependent manner. Tinzaparin and enoxaparin significantly reduced this increased vWF release from HUVEC in the media. Conclusion: Plasma values of vWF and TNF-α are higher in obese than in normal-weight individuals. Treatment with tinzaparin lowers plasma levels of TNF-α in both obese and normal-weight subjects. The levels of vWF were higher in obese subjects than in normal-weight ones because of the higher levels of circulating TNF-α. Tinzaparin reduced vWF levels in these obese subjects. Table 1. Effect of Tinzaparin (75 IU/kg, SC, QD) on Plasma vWF in Obese and Normal-Weight Subjects Table 2. Effect of Tinzaparin (75 IU/kg, SC) on Plasma TNF-α in Obese and Normal-Weight Subjects Subjects Mean Plasma vWF (IU/mL) ± SD Pre-Tinzaparin Mean Plasma vWF (IU/mL) ± SD Post-Tinzaparin (2 h) * P &lt;0.05 obese versus normal-weight subjects before treatment with tinzaparin; †P &lt;0.01 post- versus pre-tinzaparin; vWF = von Willebrand factor. Normal body weight (n = 32) 0.44 ± 0.15 0.36 ± 0.12 Obese (n = 12) 0.68 ± 0.20* 0.29 ± 0.11† Subjects Mean Plasma TNF- α (pg/mL) ± SD Pre-Tinzaparin Mean Plasma TNF- α (pg/mL) ± SD Post-Tinzaparin * P &lt;0.05 obese compared with normal-weight subjects before treatment with tinzaparin; †P &lt;0.01 post- compared with pre-tinzaparin; TNF-α = tumor necrosis factor-α. Normal body weight (n = 32) 1.68 ± 0.55 1.37 ± 0.33 Obese (n = 32) 2.82 ± 0.38* 1.45 ± 0.25†

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