scholarly journals CXCR3 from chemokine receptor family correlates with immune infiltration and predicts poor survival in osteosarcoma

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Yin Tang ◽  
Zhiqian Gu ◽  
Youwei Fu ◽  
Junjie Wang
Keyword(s):  
Chemokine Receptors ◽  
Plasma Cells ◽  
Vascular Endothelial ◽  
Free Survival ◽  
Immune Infiltration ◽  
Cxcr3 Expression ◽  
Kaplan Meier ◽  
Tnf Α ◽  
Cox Analysis ◽  
Endothelial Growth Factor

AbstractBackground: Chemokine receptors have a crucial role in regulating tumor mediating immunity and are also implicated in the prognosis of some cancers. Here, the association between CXC chemokine receptors (CXCR2–5) and prognosis in osteosarcoma was studied.Methods: Differences between CXCR2, CXCR3, CXCR4, and CXCR5 expression and overall survival (OS) and event-free survival (EFS) were compared using Kaplan–Meier analyses. The associations of CXCR3 expression with clinical features and the prognosis were also analyzed. The signaling pathways modulated by CXCR3 were investigated. The correlations between CXCR3 and immune infiltrates were investigated.Results: The expression of CXCR2, CXCR4, and CXCR5 was not associated with the prognosis, but CXCR3 low expression was correlated with worse OS and EFS of osteosarcoma, especially for female, patients aged less than 15.1 years, or patients without metastasis. Low CXCR3 expression was related to tumor site and histologic response (P<0.05), but not associated with other clinical characteristics. Multivariate Cox analysis revealed that CXCR3 remained independently associated with the prognosis, especially for OS (hazard ratio (HR) = 3.26, 95% CI = 1.15–9.24, P=0.026). The cell adhesion, apoptosis, metabolism, KRAS, P53, NOTCH, reactive oxygen species (ROS), PI3K/Akt/mTOR, vascular endothelial growth factor (VEGF), inflammation, and immune-related pathways such as IL-6/JAK/STAT3, TNF-α via NF-κB, Toll/NOD-like receptor, and complement were modulated by CXCR3. CXCR3 expression showed an especially positive correlation with immune infiltration of T cells CD8, macrophages M1, plasma cells, and NK cells activated.Conclusions: CXCR3 may be an independent risk factor for the prognosis and is most likely to benefit from immunotherapy in osteosarcoma.

A vascular endothelial growth factor A genetic variant is associated with improved ventricular function and transplant-free survival after surgery for non-syndromic CHD

2017 ◽  
Vol 28 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Constantine D. Mavroudis ◽  
Daniel Seung Kim ◽  
Nancy Burnham ◽  
Alexandra H. Morss ◽  
Jerry H. Kim ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Single Nucleotide Polymorphism ◽  
Growth Factor ◽  
Ventricular Function ◽  
Vascular Endothelial ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Free Survival ◽  
Endothelial Growth Factor

AbstractBackgroundWe have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.MethodsThis study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.ResultsGenetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).ConclusionsThese data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.

scholarly journals Trehalose 6,6′-Dimycolate (Cord Factor) of Mycobacterium tuberculosis Induces Corneal Angiogenesis in Rats

2000 ◽  
Vol 68 (10) ◽  
pp. 5991-5997 ◽  
Author(s):  
Norio Saita ◽  
Nagatoshi Fujiwara ◽  
Ikuya Yano ◽  
Kazuhiko Soejima ◽  
Kazuo Kobayashi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Neutralizing Antibodies ◽  
Early Stage ◽  
Vascular Endothelial ◽  
Cytokine Network ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Cord Factor ◽  
Factor Alpha ◽  
Endothelial Growth Factor

ABSTRACT Neovascularization or angiogenesis is required for the progression of chronic inflammation. The mechanism of inflammatory neovascularization in tuberculosis remains unknown. Trehalose 6,6′-dimycolate (TDM) purified from Mycobacterium tuberculosis was injected into rat corneas. TDM challenge provoked a local granulomatous response in association with neovascularization. Neovascularization was seen within a few days after the challenge, with the extent of neovascularization being dose dependent, although granulomatous lesions developed 14 days after the challenge. Cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), IL-1β, and vascular endothelial growth factor (VEGF), were found in lesions at the early stage (within a few days after the challenge) and were detectable until day 21. Neovascularization was inhibited substantially by neutralizing antibodies to VEGF and IL-8 but not IL-1β. Treatment with anti-TNF-α antibodies resulted in partial inhibition. TDM possesses pleiotropic activities, and the cytokine network plays an important role in the process of neovascularization.

scholarly journals Endothelial Rap1B mediates T-cell exclusion to promote tumor growth -a novel mechanism underlying vascular immunosuppression

2021 ◽  
Author(s):  
Guru Prasad Sharma ◽  
Ramoji Kosuru ◽  
Sribalaji Lakshmikanthan ◽  
Shikan Zheng ◽  
Yao Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Cancer Immunotherapy ◽  
Small Gtpase ◽  
Vascular Endothelial ◽  
Promote Tumor Growth ◽  
Tnf Α ◽  
Inflammatory Stimuli ◽  
Endothelial Growth Factor

Overcoming vascular immunosuppression: lack of endothelial cell (EC) responsiveness to inflammatory stimuli in the proangiogenic environment of tumors, is essential for successful cancer immunotherapy. The mechanisms through which Vascular Endothelial Growth Factor (VEGF) modulates tumor EC response to exclude T cells are not well understood. The goal was to determine the role of EC Rap1B, a small GTPase that positively regulates VEGFangiogenesis during development, in tumor growth in vivo. Using mouse models of Rap1B deficiency, Rap1B+/- and EC-specific Rap1B KO (Rap1BiΔEC) we demonstrate that EC Rap1B restricts tumor growth and angiogenesis. More importantly, EC-specific Rap1B deletion leads to an altered tumor microenvironment with increased recruitment of leukocytes and increased activity of tumor CD8+ T cells. We find that tumor growth, albeit not angiogenesis, is restored in Rap1BiΔEC mice by depleting CD8+ T cells. Mechanistically, global transcriptome analysis indicated upregulation of the tumor cytokine, TNF-α, -induced signaling and NFκB transcriptional activity in Rap1B-deficient ECs. Functionally, EC Rap1B deletion led to upregulation of NFκB activity and enhanced Cell Adhesion Molecules (CAMs) expression in TNF-α stimulated ECs. Importantly, CAM expression was upregulated also in tumor ECs from Rap1BiΔEC mice, vs. controls. Significantly, deletion of Rap1B abrogated VEGF immunosuppressive downregulation of CAM expression, demonstrating that Rap1B is essential for VEGF-suppressive signaling. Thus, our studies identify a novel endothelial-endogenous mechanism underlying VEGF-dependent desensitization of EC to pro-inflammatory stimuli. Significantly, they identify EC Rap1 as a potential novel vascular target in cancer immunotherapy.

scholarly journals Prognostic Value of Vascular Endothelial Growth Factor A in the Prediction of the Tumor Aggressiveness in Clear Cell Renal Cell Carcinoma

2017 ◽  
Vol 5 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Fahredin Veselaj ◽  
Suzana Manxhuka-Kerliu ◽  
Arber Neziri ◽  
Labinot Shahini ◽  
Shefki Xharra ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Renal Cell ◽  
Prognostic Value ◽  
Clear Cell ◽  
Vascular Endothelial ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Endothelial Growth Factor

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is the most predominant renal tumour with unpredictable tumour behaviour. The aim of the study is to investigate the prognostic value of vascular endothelial growth factor A (VEGF-A) expression in CCRCC and to correlate it with other histological parameters as well as with patient's survival.MATERIAL AND METHODS: Tumour blocks were taken from 40 patients with histopathology diagnosis of CCRCC and tissue block from 20 normal kidneys as a control group were examined using the immuno-histochemical staining for VEGF-A.RESULTS: The VEGF A expression in CCRCC was significantly higher than in the normal kidney tissues (U’ = 720, P < 0.0001). VEGF A expression values in CCRCC were positively correlated with Disease Free Survival (r = 0.335, P = 0.034) and the tumor necrosis degree (r = 0.181, P = 0.262). VEGF-A expression values in CCRCC did not correlate with CD 31 expression (r = -0.09, P = 0.549), and Progression Free Survival (r = -0.07, P = 0.838). VEGF A expression values in CCRCC were negatively correlated with the tumor nuclear grade (r = -0.161, P = 0.318); the pathological tumor stage (r = -0.371, P = 0.018); the tumor size (r = -0.361, P = 0.022); the degree of tumor hemorrhage (r = -0.235, P = 0.143); and Cancer Specific Survival   (r = -0.207, P = 0.713).CONCLUSIONS: VEGF-A expression can be used to stratify advanced and metastatic CCRCC patients into low-benefit and high-benefit groups. Based on this study outcome it would be useful to perform IHC staining for VEGF-A expression in all patients with advanced and metastatic CCRCC.

Evaluation of the Effects of Peritoneal Lavage with Rosmarinus officinalis Extract against the Prevention of Postsurgical-Induced Peritoneal Adhesion

Planta Medica ◽  
2020 ◽  
Vol 86 (06) ◽  
pp. 405-414 ◽  
Author(s):  
Yasamin Roohbakhsh ◽  
Vafa Baradaran Rahimi ◽  
Samaneh Silakhori ◽  
Hamed Rajabi ◽  
Pouria Rahmanian-Devin ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Vehicle Group ◽  
Vascular Endothelial ◽  
Abdominal Adhesions ◽  
Peritoneal Adhesion ◽  
Tnf Α ◽  
Endothelial Growth Factor

AbstractPostoperative adhesions are regarded as the major complication following abdominal surgery. Rosmarinus officinalis has shown antioxidative and anti-inflammatory effects. Therefore, we aimed to assess the influence of 70% v/v hydro-ethanolic extract of the aerial parts of R. officinalis against postoperative abdominal adhesions in a rat model. Forty-eight male Wistar rats (190 ± 20 g) were divided into six groups of eight: group 1 = normal group, without any surgical procedures, group 2 = control group, group 3 = vehicle group, and groups 3, 4, and 5 = experimental groups receiving 2 mL of 4, 2, or 1% w/v R. officinalis treatment. Adhesion levels were macroscopically examined. Additionally, the levels of inflammatory cytokines (interleukin-6, interleukin-1β, and TNF-α), growth factors (transforming growth factor-β1, and vascular endothelial growth factor), oxidative (NO, nitric oxide and MDA, malondialdehyde), and antioxidative (GSH, glutathione) factors were evaluated. Our results revealed that the adhesion score, interleukin-6, interleukin-1β, TNF-α, transforming growth factor-β1, vascular endothelial growth factor, NO, and MDA levels were significantly increased in the vehicle group, while the GSH level was diminished. R. officinalis treatment notably ameliorated the adhesion score following postoperative abdominal adhesions compared with the vehicle group. Our results also revealed that R. officinalis markedly reduced inflammatory cytokines, oxidative factors, fibrosis, and angiogenesis biomarkers, whereas it increased the antioxidative factor. Therefore, R. officinalis may be a potential candidate for the management of postoperative peritoneal adhesion.

scholarly journals Cocoa polyphenols suppress TNF-α-induced vascular endothelial growth factor expression by inhibiting phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase kinase-1 (MEK1) activities in mouse epidermal cells

2010 ◽  
Vol 104 (7) ◽  
pp. 957-964 ◽  
Author(s):  
Jong-Eun Kim ◽  
Joe Eun Son ◽  
Sung Keun Jung ◽  
Nam Joo Kang ◽  
Chang Yong Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Ribosomal Protein S6 ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor ◽  
Protein Kinase Kinase

Cocoa polyphenols have antioxidant and anti-inflammatory effects. TNF-α is a pro-inflammatory cytokine that has a vital role in the pathogenesis of inflammatory diseases such as cancer and psoriasis. Vascular endothelial growth factor (VEGF) expression is associated with tumorigenesis, CVD, rheumatoid arthritis and psoriasis. We tested whether cocoa polyphenol extract (CPE) inhibited TNF-α-induced VEGF expression in promotion-sensitive JB6 mouse epidermal cells. CPE significantly inhibited TNF-α-induced up-regulation of VEGF via reducing TNF-α-induced activation of the nuclear transcription factors activator protein-1 (AP-1) and NF-κB, which are key regulators of VEGF expression. CPE also inhibited TNF-α-induced phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase. CPE blocked activation of their downstream kinases, p70 kDa ribosomal protein S6 kinase and p90 kDa ribosomal protein S6 kinase. CPE suppressed phosphoinositide 3-kinase (PI3K) activity via binding PI3K directly. CPE did not affect TNF-α-induced phosphorylation of mitogen-activated protein kinase kinase-1 (MEK1) but suppressed TNF-α-induced MEK1 activity. Collectively, these results indicate that CPE reduced TNF-α-induced up-regulation of VEGF by directly inhibiting PI3K and MEK1 activities, which may contribute to its chemopreventive potential.

Comparison of fludarabine (F), cyclophosphamide (C), and rituximab (R) versus FCR plus bevacizumab (B) in relapse chronic lymphocytic leukemia (CLL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6598-6598
Author(s):  
Hun Ju Lee ◽  
William G. Wierda ◽  
Alessandra Ferrajoli ◽  
Jan Andreas Burger ◽  
Long Trinh ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Lymphocytic Leukemia ◽  
Vascular Endothelial ◽  
Free Survival ◽  
Solid Malignancies ◽  
Report Data ◽  
Baseline Characteristics ◽  
Endothelial Growth Factor

6598 Background: There is significant data to show that vascular endothelial growth factor (VEGF) is important in the development and progression of CLL. Bevacizumab (B) is an anti-VEGF monoclonal antibody associated with improvement in progression free survival (PFS) when combined with chemotherapy in pts with solid malignancies. FCR is the most active chemoimmunotherapy in treatment of CLL. We report data on a phase II trial combining FCR-B and comparing the results to those seen in a trial with FCR for pts with relapsed CLL (Badoux et al. Blood, March 2011). Methods: FCR consisted of F: 25 mg/m2 and C: 250 mg/m2 on D2-4; R: 375 mg/m2 on D1 (for the first course) and 500 mg/m2 for courses 2-6, every 4 weeks for 6 courses. FCR-B consisted as above for FCR and (B) 10 mg/kg was given on D3 of each cycle. Indications for treatment and response assessment were according to 1996 NCI-WG guidelines for both groups. Results: Baseline characteristics, complete remission (CR), overall response rate (ORR), PFS and OS of relapsed CLL pts are shown (Table). Conclusions: In relapsed pts with CLL, FCR-B showed a trend toward improved PFS compared to FCR. [Table: see text]

Circulating VEGF levels as a biomarker to clinical benefit to PTC299, the first inhibitor of VEGF synthesis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13588-e13588
Author(s):  
Claude Paul George ◽  
Jason John Luke ◽  
J. Winkelman ◽  
Yen Thi Kim Hong Cao ◽  
LaShaina Shakes ◽  
...  
Keyword(s):  
Stable Disease ◽  
Vascular Endothelial ◽  
Incurable Cancer ◽  
Angiogenic Therapy ◽  
Kaplan Meier ◽  
Prolonged Duration ◽  
Phase 1B ◽  
Grade 3 ◽  
Stratified Analysis ◽  
Endothelial Growth Factor

e13588 Background: Solid tumor growth is dependent on angiogenesis, a process mediated primarily by vascular endothelial growth factor (VEGF). Currently approved anti-angiogenic agents sequester VEGF or block activation of VEGF receptors. Despite extensive investigations, no reliable biomarkers have been identified for these agents. PTC299 is an investigational oral small molecule that differs from existing therapies by inhibiting VEGF synthesis at the translational level while conserving physiologic VEGF expression. Methods: A phase 1b clinical trial is evaluating PTC299 monotherapy (36 pts) or in combination with docetaxel (10 pts) from 0.3 mg/kg to 600 mg bid in patients with advanced incurable cancer. Serum VEGF was assessed at baseline and during therapy. The maximum on‑treatment reduction in VEGF at any post-baseline visit was used for a stratified analysis. Decreases in VEGF, defined as <10% (low) and ≥10% (high), identified the strata. Duration of therapy was used as a surrogate for stable disease in a Kaplan‑Meier analysis. Results: The study enrolled 46 patients (20 males; 26 females; median age: 62 years). Patients with lower VEGF reductions while on therapy (<10%, n=12) had a median duration of stable disease of 5.3 weeks while patients with greater maximal VEGF reductions (≥10%, n=31) had significantly longer stable disease (median 12.0 weeks, log-rank p<0.001). VEGF decreases were greater in patients with higher baseline values. No Grade 3 or 4 hypertension, bleeding, or proteinuria occurred. One patient had an acute liver injury. Conclusions: Reductions in circulating VEGF are associated with prolonged duration of anti-angiogenic therapy and stable disease. Results are consistent with preclinical experiments and support the hypothesis that PTC299 does not affect physiologic VEGF but inhibits pathologic VEGF. In this study, oral administration of PTC299 as monotherapy or in combination with docetaxel therapy has been generally well tolerated at all doses tested.

A randomized double-blind trial of carboplatin plus paclitaxel (CP) with daily oral cediranib (CED), an inhibitor of vascular endothelial growth factor receptors, or placebo (PLA) in patients (pts) with previously untreated advanced non-small cell lung cancer (NSCLC):  NCIC Clinical Trials Group study BR29.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7511-7511 ◽  
Author(s):  
Scott Andrew Laurie ◽  
Benjamin J. Solomon ◽  
Lesley Seymour ◽  
Peter Michael Ellis ◽  
Glenwood D. Goss ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Vascular Endothelial ◽  
Double Blind ◽  
Free Survival ◽  
Endothelial Growth Factor ◽  
To Receive ◽  
Unacceptable Toxicity

7511 Background: In NCIC CTG study BR24, CED 30 mg/d + CP increased objective response rate (RR) and progression-free survival (PFS), but there were concerns regarding toxicity in some pts. BR29 tested a lower dose of CED 20 mg/d limiting accrual to pts without significant weight loss/hypoalbuminemia. Methods: Consenting, eligible adult pts with advanced incurable NSCLC of any histology were randomized to receive CED 20 mg/d or PLA with up to 6 cycles of C (AUC = 6) P (200 mg/m2); non-progressing pts continued CED/PLA after CP until progression, unacceptable toxicity or pt request. The primary endpoint was overall survival (OS). An interim analysis (IA) for PFS was planned after 170 events in the first 260 pts; the study would continue if the hazard ratio (HR) for PFS was < 0.7. Accrual continued until the required number of events was reached then held pending IA. Results: The trial was halted when the IA (n=260) revealed a HR for PFS of 0.89 (95% CI 0.66-1.20). A final analysis including all 306 randomized pts (median age 62, male 55%, PS 0 26%, PS 1 74%, adenocarcinoma 64%, squamous 13%, other histology 23%. RR was significantly higher with CED (52% vs 34 %, p = 0.001). For CED/PLA, respectively, median OS and PFS were 12.2/12.1 [HR: 0.95 (0.69-1.30, p=0.74)] and 5.5/5.5 months [HR: 0.91 (0.71-1.18, p=0.5)]. Grade >3 hypertension (15% vs 3%, p=0.0002), anorexia (7% vs 1%, p=0.02) and diarrhea (16% vs 1%, p<0.0001) were all significantly increased with CED; there were 2 deaths possibly-related to CED [1 each hemorrhage, leukoencephalopathy (prior radiation)]. Conclusions: Adding a lower dose of CED to CP increased RR and toxicity, but not PFS or OS.

Sign in / Sign up

Export Citation Format

Share Document