Treatment outcome of anti-angiogenesis through VEGF-pathway in the management of gastric cancer: a systematic review of phase II and III clinical trials

Mawalla, Brian; Yuan, Xianglin; Luo, Xiaoxiao; Chalya, Phillip L.

doi:10.1186/s13104-018-3137-8

Cited by 41 publications

(19 citation statements)

References 38 publications

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“…Gastric cancer, a typical inflammation-related solid cancer, is significantly correlated with chronic uncontrollable inflammatory stimulation and tumor angiogenesis, which are induced by the tumor microenvironment, in the occurrence and development of tumors [9 -11]. VEGF can stimulate endothelial cell growth, migration, and survival of preexisting vasculature via a network of signaling processes triggered by activation of the VEGF-VEGFR signaling axis, which is the most important regulator of angiogenesis and specifically acts on vascular endothelial cells [11]. IL-6 is a chemokine that causes chronic active gastritis, mainly by inducing dense infiltration of neutrophils and macrophages in the gastric mucosa and inducing a proliferative response.…”

Section: Introductionmentioning

confidence: 99%

Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance

Wang

Yin

et al. 2020

Med Sci Monit

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Departmental sources Background: With the growing global burden of gastric carcinoma (GC) and the urgent need for biomolecular targeted therapies, this study aimed to elucidate the relationship between EphA1 and the tumor microenvironment (focusing primarily on the key inflammatory cytokines IL-6 and tumor angiogenic cytokine VEGF) to identify a new potential therapeutic target. Material/Methods: IHC and qRT-PCR were performed to quantify the protein and gene expression levels of EphA1, IL-6, and VEGF in normal mucosal tissues, carcinoma tissues, and paracarcinomatous tissues from 57 GC patients. Spearman's rank correlation test was performed to determine the relationship between EphA1, IL-6, and VEGF expression levels. The relationships of EphA1 with clinicopathologic parameter and survival in GC patients were also evaluated. Results: The protein and gene expression levels of EphA1 were all attenuated gradually from carcinoma tissues to paracarcinomatous tissues and then to normal mucosal tissues in GC patients. Additionally, significant correlations between the overexpression of EphA1 with aggressive clinicopathological features and shorter survival time of GC patients were verified. In particular, we found a significant positive correlation between the expression of EphA1 and tumor microenvironment hallmark proteins IL-6 and VEGF in carcinoma tissues and paracarcinomatous tissues. Conclusions: EphA1 can promote the occurrence and development of GC by its selective high expression in cancer tissues and its relationship with malignant clinical features and prognosis of GC patients. The underlying potential mechanism appears to involve enhancement of the tumor microenvironment, which via drives the expression of tumor microenvironment hallmark proteins IL-6 and VEGF.

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Section: Introductionmentioning

confidence: 99%

Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance

Wang

Yin

et al. 2020

Med Sci Monit

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“…In the past two decades, although great progress has been made in the diagnosis and therapy of GC, the overall survival rate remains unsatisfactory, especially in advanced disease 1, 2. Anti-angiogenesis treatment offers new hope for the treatment of GC, especially in chemotherapy-resistant patients 3. It was long believed that angiogenesis via the sprouting of endothelial vessels from existing ones was the exclusive form of tumor vascularization, and anti‑angiogenesis therapy was considered as a promising method to treat tumors 3, 4.…”

Section: Introductionmentioning

confidence: 99%

“…Anti-angiogenesis treatment offers new hope for the treatment of GC, especially in chemotherapy-resistant patients 3. It was long believed that angiogenesis via the sprouting of endothelial vessels from existing ones was the exclusive form of tumor vascularization, and anti‑angiogenesis therapy was considered as a promising method to treat tumors 3, 4. However, with the wide application of angiogenesis inhibitors in clinical practice, it was established that the effect of antiangiogenic drugs was limited 5.…”

Section: Introductionmentioning

confidence: 99%

Galectin-1 Promotes Vasculogenic Mimicry in Gastric Cancer by Upregulating EMT Signaling

You¹,

Liu²,

Wu³

et al. 2019

J. Cancer

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Background: Galectin-1 (Gal-1) expression was positively associated with vasculogenic mimicry (VM) in primary gastric cancer (GC) tissue, and that both Gal-1 expression and VM in GC tissue are indicators of poor prognosis. However, whether Gal-1 promotes VM, and by what mechanismsremains unknown.Methods: To investigate the underlying mechanisms,wound healing assay, proliferation assay, invasion assay, and three-dimensional culture were used to evaluate the invasion, metastasis and promoted VM formation effects of the Gal-1. We monitored the expression level of sociated proteins in GC tissues, cell lines in vitro and nude mice tumorigenicity in vivo by immunohistochemistry and western blot.Results: Gal-1 overexpression significantly promoted the proliferation, invasion, migration, and VM formation of MGC-803 cells. Gal-1 was associated with E-cadherin and vimentin in vitro and in clinical samples. The epithelial-to-mesenchymal transition (EMT) induced in MGC-803 cells by TGF-β1 was accompanied by Gal-1 activation and promotion of VM formation, while knockdown of Gal-1 reduced the response to TGF-β1, suggesting that Gal-1 promotes VM formation by activating EMT signaling. Overexpression of Gal-1 accelerated subcutaneous xenograft growth and facilitated pulmonary metastasis in athymic mice, enhanced the expression of EMT markers, and promoted VM formation in vivo.Conclusion: Our results indicated that Gal-1 promotes VM in GC by upregulating EMT signaling; thus, Gal-1 and this pathway are potential novel targets to treat VM in GC.

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“…Its inconspicuous early symptoms and the lack of effective means for early screening lead to the fact that many patients have developed advanced GC once diagnosed [14]. Worse still, the mainstream treatment today remains surgery combined with chemoradiotherapy, whose efficacy is limited to some extent, resulting in poor prognosis of many patients [15,16]. Along with the in-depth development of molecular biology, more and more attention has been paid to the role of molecular markers in the diagnosis and treatment of GC, in that finding a stable and highly sensitive molecular marker is of great clinical significance for patients with GC.…”

Section: Discussionmentioning

confidence: 99%

lncRNA NEAT1 Inhibits Proliferation, Invasion and Epithelial-mesenchymal Transition of Gastric Cancer Cells by Regulating MiR-129-5p/PBX3 Axis

Ji¹,

Zhang²

2020

Preprint

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Purpose: lncRNA NEAT1 has been reported as a tumor-promoting gene in a variety of tumors, but few studies have explored its role and mechanism in gastric cancer. In the face of increasing incidence of gastric cancer, how to improve the diagnostic accuracy and therapeutic effect of gastric cancer is a major clinical problem. Therefore, we studied the effect and mechanism of lncRNA NEAT1 on the proliferation, invasion and epithelial-mesenchymal transition of gastric cancer cells. To inquiry into the effect of lncRNA NEAT1 on the proliferation, invasion and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating miR-129-5p/PBX3 axis. Methods: Totally 63 GC diagnosed and treated in our hospital were selected as the study subjects, whose paired GC tissues and pericarcinomatous tissues were collected as the study specimens after obtaining their consent. QRT-PCR was employed to detect the NEAT1 expression in tissues and cells to analyze the relationship between NEAT1 and clinicopathological data of GC patients. In addition, stable and transient overexpression and inhibition vectors were established and transfected into GC cells HCG-27 and MKN-45. CCK-8, traswell, and flow cytometry were employed to evaluate the proliferation, invasion, and apoptosis of transfected cells. The correlation of miR-129-5p between PBX3 and NEAT1 was assessed using dual luciferase reporter assay, while that between NEAT1 and miR-129-5p was assessed by RNA-binding protein immunoprecipitation (RIP) . Western blot was applied for the detection of apoptosis and EMT related proteins.Results: NEAT1 was overexpressed in GC patients and had a high diagnostic value. The expression of NEAT1 was related to the pathological stage, differentiation degree, tumor size and lymph node metastasis of patients with GC. Down-regulated NEAT1 brought decreased cell proliferation, invasion and EMT, and increased apoptosis. According to dual luciferase reporter assay, NEAT1 could target miR-129-5p, while in turn miR-129-5p could target PBX3. Functional analysis exhibited that miR-129-5p overexpression inhibited PBX3 in GC cells, affecting cell proliferation, invasion, EMT and apoptosis, and rescue experiments demonstrated that these effects were eliminated by up-regulating NEAT1 expression.Conclusion: Inhibition of NEAT1 could mediate miR-129-5p/PBX3 axis to promote apoptosis of GC cells, and reduce cell proliferation, invasion and EMT.

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Treatment outcome of anti-angiogenesis through VEGF-pathway in the management of gastric cancer: a systematic review of phase II and III clinical trials

Cited by 41 publications

References 38 publications

Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance

Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance

Galectin-1 Promotes Vasculogenic Mimicry in Gastric Cancer by Upregulating EMT Signaling

lncRNA NEAT1 Inhibits Proliferation, Invasion and Epithelial-mesenchymal Transition of Gastric Cancer Cells by Regulating MiR-129-5p/PBX3 Axis

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