The crucial role of blood VEGF kinetics in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy

Chen, Yen‐Hao; Lu, Hung-I; Lo, Chien-Ming; Wang, Yu Ming; Chou, Shang-Yu; Hsiao, Chang‐Chun; Huang, Chao‐Cheng; Shih, Li-Hsueh; Chen, Suwei; Li, Shau-Hsuan

doi:10.1186/s12885-018-4731-9

Cited by 9 publications

(16 citation statements)

References 30 publications

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“… 46 The depletion of VEGF was employed for superior clinical outcomes of ESCC during concurrent chemoradiotherapy. 47 VEGF along with its family factors is documented as the central components of abnormal angiogenesis with extensive functionality in a wide variety of tumors and diseases. 22 Mechanically, solid tumors by producing VEGF supply the oxygen and essential nutrients for angiogenesis by producing VEGF, thus making the inhibition of VEGF signaling capable of impairing tumor angiogenesis, to consequently suppress tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

<p>Exosome-Encapsulated MicroRNA-21 from Esophageal Squamous Cell Carcinoma Cells Enhances Angiogenesis of Human Umbilical Venous Endothelial Cells by Targeting SPRY1</p>

Zhuang¹,

Wang²,

Yang³

et al. 2020

CMAR

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Objective Esophageal squamous cell carcinoma (ESCC) persists among the most prevalent cancers worldwide. Angiogenesis represents a crucial element necessitated for tumor growth and metastasis in ESCC. In this study, we aimed to study the effect of microRNA (miR)-21 on angiogenesis in ESCC and its underlying mechanism. Materials and Methods Initially, the expression patterns of miR-21, SPRY1, and VEGF were determined in ESCC tissues and cells. The relationship between miR-21 and SPRY1 was identified using dual-luciferase reporter assay. Exosomes were subsequently isolated from the ESCC cells, followed by co-culture with the human umbilical venous endothelial cells (HUVECs). HUVEC proliferation and angiogenesis were determined by means of CCK-8, colony formation, and microtubule formation in vitro. Chicken chorioallantoic membrane (CAM) model and mouse xenograft model of ESCC cells were established to substantiate the function of miR-21 corresponding to the angiogenesis and tumor growth of ESCC, followed by microvascular density (MVD) evaluation. Results Expression patterns of miR-21 and VEGF were elevated, while the SPRY1 expression pattern was repressed in ESCC tissues and cells. The downregulation of miR-21 and exosome-derived miR-21 impeded the proliferation and angiogenesis in HUVECs. Our data revealed that miR-21 could negatively target SPRY1, and positively target VEGF. The downregulation of miR-21 could evidently encumber the angiogenesis and tumor growth of ESCC in vivo, as evidenced by the decrease in number of branches of the microvessels and MVD. Conclusion Collectively, ESCC cell-derived exosome containing miR-21 promotes the proliferation and angiogenesis of HUVECs via SPRY1 downregulation and VEGF upregulation.

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Section: Discussionmentioning

confidence: 99%

<p>Exosome-Encapsulated MicroRNA-21 from Esophageal Squamous Cell Carcinoma Cells Enhances Angiogenesis of Human Umbilical Venous Endothelial Cells by Targeting SPRY1</p>

Zhuang¹,

Wang²,

Yang³

et al. 2020

CMAR

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“…There is a clinical benefit for patients who experience a significant tumor remission after CCRT, while there is a problem for patients who are not sensitive to CCRT. VEGF kinetics is a prognostic factor for locally advanced ESCC patients receiving CCRT [ 50 ]. Y.H.…”

Section: Discussionmentioning

confidence: 99%

STAT3β Enhances Sensitivity to Concurrent Chemoradiotherapy by Inducing Cellular Necroptosis in Esophageal Squamous Cell Carcinoma

Zheng

Yang

Luo

et al. 2021

Cancers

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Concurrent chemoradiotherapy (CCRT), especially platinum plus radiotherapy, is considered to be one of the most promising treatment modalities for patients with advanced esophageal cancer. STAT3β regulates specific target genes and inhibits the process of tumorigenesis and development. It is also a good prognostic marker and a potential marker for response to adjuvant chemoradiotherapy (ACRT). We aimed to investigate the relationship between STAT3β and CCRT. We examined the expression of STAT3α and STAT3β in pretreatment tumor biopsies of 105 ESCC patients who received CCRT by immunohistochemistry. The data showed that ESCC patients who demonstrate both high STAT3α expression and high STAT3β expression in the cytoplasm have a significantly better survival rate, and STAT3β expression is an independent protective factor (HR = 0.424, p = 0.003). Meanwhile, ESCC patients with high STAT3β expression demonstrated a complete response to CCRT in 65 patients who received platinum plus radiation therapy (p = 0.014). In ESCC cells, high STAT3β expression significantly inhibits the ability of colony formation and cell proliferation, suggesting that STAT3β enhances sensitivity to CCRT (platinum plus radiation therapy). Mechanistically, through RNA-seq analysis, we found that the TNF signaling pathway and necrotic cell death pathway were significantly upregulated in highly expressed STAT3β cells after CCRT treatment. Overall, our study highlights that STAT3β could potentially be used to predict the response to platinum plus radiation therapy, which may provide an important insight into the treatment of ESCC.

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“…Patients with recurrence within 1 year after treatment tended to have lower levels of growth factors. In previous studies, VEGF and EGF have been shown to correlate with worse prognosis in both head and neck cancer and esophageal cancer (26–28). A similar connection was not seen in our material.…”

Section: Discussionmentioning

confidence: 91%

Systemic Inflammatory Reaction in Patients With Head and Neck Cancer—An Explorative Study

et al. 2019

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Aim: To assess the longitudinal pattern of pro-inflammatory cytokines and growth factors in serum up to 1 year following treatment for head and neck cancer.Materials and Methods: Patients with newly diagnosed, curable head and neck cancer were included (n = 30). The most common subsite was oropharynx (n = 13) followed by oral cavity (n = 9). Blood was drawn from all patients at regular intervals (before treatment, 7 weeks after the start of the treatment, and at 3 months and 1 year after termination of treatment) and analyzed for cytokines (Il-1β, Il-2, Il-4, Il-5, Il-6, Il-8, Il-10, GM-CSF, TNF-α, and IFN-γ) and growth factors (G-CSF, FGF-2, EGF, and VEGF).Results: The time point of the peak level of pro-inflammatory cytokines was 7 weeks after start of treatment which corresponded for the majority of patients with termination of radiotherapy or chemoradiotherapy. Patients undergoing chemoradiotherapy exhibited a significant increase of IL-1β, IL-6, and IL-10 at 7 weeks as compared to pre-treatment levels. At 1 year after termination of treatment four patients experienced recurrence of disease while 26 patients were considered disease-free. The patients with recurrence had significantly higher levels of IL-1β, IL-6, IL-8, and IL-10 at 7 weeks after the start of treatment than patients without recurrence. Correlated with T stadium patients with T3-T4 had higher levels of IL-1β and IL-8 than patients with T1-T2 7 weeks after the start of treatment.Conclusions: The observed immune response in this explorative study demonstrates that chemoradiotherapy may induce not only a local treatment effect on the immune system but also effects far outside the irradiated field. The result of the study indicates that analysis of a pro-inflammatory panel of cytokines in serum at 7 weeks after the start of treatment could be of prognostic value in patients with head and neck cancer. Further study of a larger cohort could help identify patients at larger risk for recurrent disease with measurements of pro-inflammatory cytokines under and after treatment.

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The crucial role of blood VEGF kinetics in patients with locally advanced esophageal squamous cell carcinoma receiving curative concurrent chemoradiotherapy

Cited by 9 publications

References 30 publications

<p>Exosome-Encapsulated MicroRNA-21 from Esophageal Squamous Cell Carcinoma Cells Enhances Angiogenesis of Human Umbilical Venous Endothelial Cells by Targeting SPRY1</p>

<p>Exosome-Encapsulated MicroRNA-21 from Esophageal Squamous Cell Carcinoma Cells Enhances Angiogenesis of Human Umbilical Venous Endothelial Cells by Targeting SPRY1</p>

STAT3β Enhances Sensitivity to Concurrent Chemoradiotherapy by Inducing Cellular Necroptosis in Esophageal Squamous Cell Carcinoma

Systemic Inflammatory Reaction in Patients With Head and Neck Cancer—An Explorative Study

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