VEGF is a target molecule for peritoneal metastasis and malignant ascites in gastric cancer: prognostic significance of VEGF in ascites and efficacy of anti-VEGF monoclonal antibody

Fushida, Sachio; Oyama, Katsunobu; Koyama, Jun; Yagi, Yasushi; Okamoto, Kazuko; Tajima, Hidehiro; Ninomiya, Itasu; Fujimura, Takashi; Ohta, Tetsuo

doi:10.2147/ott.s51916

Cited by 36 publications

(33 citation statements)

References 37 publications

(35 reference statements)

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“…Although VEGF level reportedly was high in malignant pleural effusion, the level of serum VEGF level was not associated with high level of pleural VEGF, that was consistent with the relationship between VEGF level of brain tumor cysts and serum. While, the serum VEGF levels and ascites VEGF levels were highly correlated in malignant ascites patients, which may be the result of much higher liquid volume in ascites than pleural effusion and brain tumor cysts.…”

Section: Discussionmentioning

confidence: 93%

Effect of bevacizumab against cystic components of brain tumors

et al. 2019

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BackgroundBevacizumab improves symptoms via reducing the peritumoral edema and/or normalizing blood brain barrier, and occasionally via reducing the tumor size. However, the effect against active cystic components has not been documented yet.Materials and MethodsBetween 2008 and 2018, 139 patients with primary or metastatic brain tumors were treated with bevacizumab (BEV) in our institution. The images and symptoms before and after administration of BEV were examined, and changes in size of cysts were evaluated as follows: CR (complete disappearance), PR (reduction by ≥50%), MR (reduction by ≥25%), SD (size change <25%), PD (increase by ≥25%). The effect of BEV on tumor itself was determined according to Response Assessment in Neuro‐Oncology criteria.ResultsOf the 139 patients, 21 (15.1%) had cystic components. The best responses of cysts to BEV treatment were as follows: CR 6, PR 7, MR 4, SD 4. The group of patients with progressively increasing cysts prior to BEV treatment had significant cyst size reduction compared to stable cyst size groups, at initial imaging after BEV (mean 62.6% vs 22.5%, P = .0055) and at best response timing (mean 76.3% vs 32.8%, P = .0050). Patients with cysts showed significant improvement in symptoms after the treatment with BEV compared to patients without cysts (P = .0033). However, response rate was not different between patients with or without cysts. Overall survival after starting BEV was not different between glioblastoma patients with or without cysts.ConclusionBevacizumab is effective against progressively increasing cysts. Although cysts reduction effect and tumor response and/or overall survival are independent, BEV may be effective in patients who are symptomatic due to cyst enlargement.

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Section: Discussionmentioning

confidence: 93%

Effect of bevacizumab against cystic components of brain tumors

et al. 2019

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“…), in patients with ascites secondary to a variety of solid tumours, predominantly ovarian cancer. However, the sample sizes were rather small, ranging from 1e9 patients [7,12]. For the largest series, published in abstract form, ElShami et al reported resolution or at least distinctly delayed reaccumulation of ascites in all of the nine patients enrolled, after only one i.p.…”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study – AIO SUP-0108

Jordan

Luetkens

Gog

et al. 2016

European Journal of Cancer

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Purpose: Malignant ascites is debilitating for patients with advanced cancer. As shown previously, tumour cell production of vascular endothelial growth factor might be a major cause of the formation of malignant ascites. Intraperitoneal bevacizumab could therefore be an option for symptom control in refractory ascites. Patients and methods: Patients with advanced gastrointestinal cancer and malignant ascites who had undergone paracentesis at least twice within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal bevacizumab (400 mg absolute) or placebo after paracentesis. During the 8-week treatment period, a minimum interval of 14 d was kept between the applications of the study drug. Primary end-point was paracentesis-free survival (ParFS). Results: Fifty-three patients (median age 63 years) were randomised. Forty-nine patients received at least one study drug application and qualified for the main analysis. The

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“…VEGF expression is correlated with the progress and prognosis of gastric cancer. 40 The activities of VEGF secretion by tumor cells and B7H1 expression level in tolerogenic APCs are associated with the STAT3 signaling pathway. We showed that wogonin directly inhibited the phosphorylation of STAT3, and the expression of B7H1, MICA, and CRT was regulated by the STAT3 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Wogonin Inhibits Tumor-derived Regulatory Molecules by Suppressing STAT3 Signaling to Promote Tumor Immunity

Xiao

Yin³

et al. 2015

Journal of Immunotherapy

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Wogonin exerts effective antitumor activities through direct cytotoxicity against cancer cells and indirect immune modulation. However, the molecular mechanisms of these activities remain poorly understood and need further study. We found that wogonin could efficiently downregulate the expression of B7H1, retinoic acid early induced transcript-1ε (RAE-1ε), and vascular endothelial growth factor in gastric cancer cells. Wogonin also promoted the secretion of calreticulin and high-mobility group protein 1 by tumor cells. Apoptotic bodies from dying tumor cells treated with wogonin were susceptible for uptake by neighboring dendritic cells (DCs). With the xenograft tumor model, wogonin inhibited tumor growth and promoted the recruitment of DC, T, and NK cells into tumor tissues. Infiltrated frequencies of DC, T, and NK cells in tumors were inversely correlated with expression levels of vascular endothelial growth factor, B7H1, and RAE-1ε of tumor tissues. Wogonin directly inhibited the activation of STAT3 on tyrosine 705 in tumor cells. The dephosphorylation of STAT3 contributed to the decreased expression of B7H1 and MHC class I chain-related protein A, and the enhancement of calreticulin on the cell membrane. Our study confirmed the immune-enhancing function of wogonin, and indicated that wogonin could be used in collaboration with DC vaccine or activated lymphocytes for tumor therapy.

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VEGF is a target molecule for peritoneal metastasis and malignant ascites in gastric cancer: prognostic significance of VEGF in ascites and efficacy of anti-VEGF monoclonal antibody

Cited by 36 publications

References 37 publications

Effect of bevacizumab against cystic components of brain tumors

Effect of bevacizumab against cystic components of brain tumors

Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study – AIO SUP-0108

Wogonin Inhibits Tumor-derived Regulatory Molecules by Suppressing STAT3 Signaling to Promote Tumor Immunity

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