Angiogenic and growth factors in gastric cancer

Blank, Susanne; Deck, Catrin; Dreikhausen, Lena; Weichert, Wilko; Giese, N.; Falk, Christine S.; Schmidt, Thomas; Ott, Katja

doi:10.1016/j.jss.2014.11.028

Cited by 33 publications

(23 citation statements)

References 54 publications

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“…Prognostically, a tumour tissue level of FST below the median was associated with better survival. However, in primary resected and neoadjuvantly treated patients, FST levels in tissue had no impact (108). Therefore FST levels appear to have a further prognostic significance in gastric cancer.…”

Section: Value Of Follistatin In Diagnosis Prognosis and Of Solid Tumentioning

confidence: 89%

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Shi

Resaul

Owen

et al. 2016

CGP

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Abstract. Follistatin (FST) Follistatin (FST), which was first isolated from porcine and bovine follicular fluid (1, 2), was initially described as a protein involved in the regulation of the secretion of folliclestimulating hormone. This monomeric glycosylated polypeptide chain is encoded by a single gene located on the long arm chromosome 5q11.2 (3), which through alternative splicing may be transcribed into the mRNA precursors, FST317 and FST344. From these precursors, three major FST isoforms may be produced, namely FST288 (from pre-FST317), FST315 (from pre-FST344) and a third FST isoform, FST303, produced from the post-translational truncation of the FST315 C-terminus. These three main FST isoforms can also be glycosylated to yield six further FST isoforms that were previously identified in bovine (4) and porcine (5, 6) follicular fluid. At the core, all FST isoforms contain a 63 residue N-terminal domain and three follistatin domains, termed FSD1, FSD2 and FSD3. These domains comprise 73-77 amino acid residues and are characterised by an arrangement of 10 conserved cysteine residues (7). Both FST288 and FST315 are differentially expressed in human tissues (6-9). FST315 is the predominant isoform, whilst the FST288 isoform accounts for less than 5% of the encoded mRNA (10, 11). Some molecules such as activin, transforming growth factor-beta (TGFβ), forkhead domain transcription factor L2 (12, 13), gonadotropin-releasing hormone (14), zinc finger protein (GLI2) (15), dexamethasone (16), androgens (17), activators of winglessrelated integration site (WNT) signalling (18, 19) and 1,25-dihydroxyvitamin D (20) have been shown to regulate the transcription of the FST gene. In addition, down-regulation of FST gene expression by peroxisome proliferator-activated receptor gamma (PPARγ) or the transcription factor epiprofin (21, 22) has been shown.As an antagonist of TGFβ superfamily member activin, FST seems to primarily function in relation to the role that activin plays. Along with FST, activin acts as a pleiotropic growth factor system, which is involved in proliferation, differentiation, and apoptosis of a number of cell types (23-28). As such, the functions of the FST isoforms are therefore linked to their binding affinity for activin (6,10,11,(29)(30)(31)(32)(33)(34)(35)(36)(37). In fact, this critical binding and neutralisation of activin, either partial or complete, is based on the order of at least two of the FST cysteine domains and its Nterminal (38), conferring a difference in affinities for activin between the FST isoforms. The binding complex between activin and FST generally occurs in a 1:2 ratio, where the two FST molecules, connected C-terminus to N-425

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Section: Value Of Follistatin In Diagnosis Prognosis and Of Solid Tumentioning

confidence: 89%

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Shi

Resaul

Owen

et al. 2016

CGP

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“…It was demonstrated the importance of angiogenetic factors in serum and tumor tissue in gastric cancer for prognosis and treatment response [53]. Increased expression of VEGF-C may play a significant role in the carcinogenesis and progression of gastric adenocarcinoma [54].…”

Section: Gastric Cancermentioning

confidence: 99%

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

Costache

Ioana

Iordache

et al. 2015

Romanian Journal of Internal Medicine

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Angiogenesis is a crucial event for tumor growth and it is regulated predominantly by several different growth factors. Vascular endothelial growth factor protein family (VEGF) and its receptors are probably the most important tissue factors responsible for angioblast differentiation and tube formation. VEGF protein family currently comprises several members: VEGF (or VEGF-A), VEGF-B, VEGF-C and VEGF-D, VEGF-F, placental growth factor (PlGF), and their receptors VEGFR-1, VEGFR-2 and VEGFR-3. VEGF is a key angiogenic growth factor and its level of expression is a critical marker for detection of the angiogenic diseases. The potent role of VEGF in tumor angiogenesis has been widely described in the past decade, being expressed in most types of nondigestive and digestive cancers. VEGF family members play an important role in the development of pancreatic cancer (especially VEGF-A, VEGF-C, VEGF-D, VEGFR-1 and VEGFR-2). VEGF-A is the most specific and prominent angiogenic factor among all family members and VEGFR-2 is the most important receptor in evaluating the angiogenesis in pancreatic cancer. Thus, VEGF overexpression may be considered as a diagnostic marker and as a poor prognostic factor of the disease.

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“…Serum VEGF levels are significantly higher in GC patients with remaining tumor and decrease with radical resection. High preoperative serum VEGF-A correlate with poor survival, tumor invasion and distant metastases [11]. In contrast, in GC patients treated with the VEGF-A antibody bevacizumab high plasma VEGF-A predicted improved OS [12, 13].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, the prognostic significance of VEGF-A concentrations could be demonstrated for non-Asian population only [12, 14]. Additionally, a correlation of VEGF expression in GC tumor tissue with histopathological response was shown [11, 13, 15, 16]. …”

Section: Introductionmentioning

confidence: 99%

Sunitinib added to FOLFIRI versus FOLFIRI in patients with chemorefractory advanced adenocarcinoma of the stomach or lower esophagus: a randomized, placebo-controlled phase II AIO trial with serum biomarker program

et al. 2016

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BackgroundAs a multi-targeted anti-angiogenic receptor tyrosine kinase (RTK) inhibitor sunitinib (SUN) has been established for renal cancer and gastrointestinal stromal tumors. In advanced refractory esophagogastric cancer patients, monotherapy with SUN was associated with good tolerability but limited tumor response.MethodsThis double-blind, placebo-controlled, multicenter, phase II clinical trial was conducted to evaluate the efficacy, safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI (NCT01020630). Patients were randomized to receive 6-week cycles including FOLFIRI plus sodium folinate (Na-FOLFIRI) once every two weeks and SUN or placebo (PL) continuously for four weeks followed by a 2-week rest period. The primary study endpoint was progression-free survival (PFS). Preplanned serum analyses of VEGF-A, VEGF-D, VEGFR2 and SDF-1α were performed retrospectively.ResultsOverall, 91 patients were randomized, 45 in each group (one patient withdrew). The main grade ≥3 AEs were neutropenia and leucopenia, observed in 56 %/20 % and 27 %/16 % for FOLFIRI + SUN/FOLFIRI + PL, respectively. Median PFS was similar, 3.5 vs. 3.3 months (hazard ratio (HR) 1.11, 95 % CI 0.70–1.74, P = 0.66) for FOLFIRI + SUN vs. FOLFIRI + PL, respectively. For FOLFIRI + SUN, a trend towards longer median overall survival (OS) compared with placebo was observed (10.4 vs. 8.9 months, HR 0.82, 95 % CI 0.50–1.34, one-sided P = 0.21). In subgroup serum analyses, significant changes in VEGF-A (P = 0.017), VEGFR2 (P = 0.012) and VEGF-D (P < 0.001) serum levels were observed.ConclusionsAlthough sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer, a trend towards better OS was observed. Further biomarker-driven studies with other anti-angiogenic RTK inhibitors are warranted.Trial registrationThis study was registered prospectively in the NCT Clinical Trials Registry (ClinicalTrials.gov) under NCT01020630 on November 23, 2009 after approval by the leading ethics committee of the Medical Association of Rhineland-Palatinate, Mainz, in coordination with the participating ethics committees (see Additional file 2) on September 16, 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2736-9) contains supplementary material, which is available to authorized users.

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Angiogenic and growth factors in gastric cancer

Cited by 33 publications

References 54 publications

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

Clinical and Therapeutic Implications of Follistatin in Solid Tumours

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

Sunitinib added to FOLFIRI versus FOLFIRI in patients with chemorefractory advanced adenocarcinoma of the stomach or lower esophagus: a randomized, placebo-controlled phase II AIO trial with serum biomarker program

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