1768: Prognostic Significance of Plasma Placental Growth Factor Levels in Renal Cell Cancer: An Association with Clinical Characteristics and Vascular Endothelial Growth Factor Levels

Matsumoto, Kazuhisa; Suzuki, Kazuhiro; Koike, Hidekazu; Okamura, Keigo; Tsuchiya, Kiyotaka; Uchida, Tatsuo; Takezawa, Yutaka; Fukabori, Yoshitatsu; Kobayashi, Mikio; Yamanaka, Hidetoshi

doi:10.1016/s0022-5347(18)38960-2

Cited by 34 publications

(40 citation statements)

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“…Results linked high circulating PlGF to adverse prognosis in renal (Matsumoto et al 2003) and oral squamous cell carcinoma (Cheng et al 2012) but not in hepatocellular cancer (Nagaoka et al 2010), and high preoperative PlGF levels predicted reduced recurrence-free and overall survival in colorectal cancer patients undergoing curative surgery (Wei et al 2009, Rahbari et al 2011. The latter data fit with our observation that PlGF levels O50th percentile correlated with shorter TTP in the prospective intestinal NET cohort.…”

Section: Discussionsupporting

confidence: 81%

Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

Hilfenhaus¹,

Göhrig²,

Pape³

et al. 2013

Endocrine-Related Cancer

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Placental growth factor (PlGF), a VEGF-homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. Here, we addressed the expression, function, and prognostic value of PlGF in neuroendocrine tumors (NETs). PlGF was determined in NET patients' sera collected retrospectively (n=88) and prospectively (n=87) using Roche-Elecsys and correlated with clinicopathological data. Tumoral PlGF was evaluated by immunohistochemistry, effects of PlGF on proliferation and migration in vitro were assessed using different NET cell lines and effects on tumor growth in vivo in orthotopic xenografts. Circulating and tumoral PlGF was elevated in patients with pancreatic NETs (pNETs) compared with control sera and respective healthy tissue. De novo PlGF expression occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced NET proliferation and migration in vitro and, conversely, neutralizing antibodies to PlGF reduced tumor growth in vivo. Elevated circulating PlGF levels in NET patients correlated with advanced tumor grading and were associated with reduced tumor-related survival in pNETs. Subsequent determinations confirmed and extended our observation of elevated PlGF levels in a prospective cohort of grade 1 and grade 2 pNETs (n=30) and intestinal NETs (n=57). In low-grade pNETs, normal circulating PlGF levels were associated with better survival. In intestinal NETs, circulating PlGF above median emerged as an independent prognostic factor for shorter time-to-progression in multivariate analyses. These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as a prognostic parameter and therapeutic target.

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Section: Discussionsupporting

confidence: 81%

Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

Hilfenhaus¹,

Göhrig²,

Pape³

et al. 2013

Endocrine-Related Cancer

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“…In a larger retrospective cohort, these elevations in PlGF were seen after chemotherapy and bevacizumab but not after chemotherapy alone, suggesting that changes seen in PlGF are specific to those patients receiving bevacizumab. PlGF levels in plasma and tumors correlate with tumor stage, vascularity, recurrence, metastasis, and survival in various tumors [30,31] and has also been shown to increase cell sensitivity to VEGF-A [32]. Results from a randomized Phase III trial of ziv-aflibercept (a dualinhibitor of PlGF and VEGF-A) in patients that have progressed on prior chemotherapy demonstrate that continued blockade of VEGF family members is beneficial for patients with acquired resistance to bevacizumab, although further studies will be required to separate the relative contributions of PlGF and VEGF-A inhibition.…”

Section: Discussionmentioning

confidence: 99%

The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer.

Lieu¹,

Tran²,

Jiang³

et al. 2011

JCO

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“…A possible explanation includes that, tumor cells with advanced histological grade, because of a higher amount of nourishment consumption required to maintain rapid proliferation, need more proangiogenic factors such as VEGF and PIGF to stimulate endothelial cell migration and sprouting (25,26). Consequently, to regulate angiogenesis, the more negative factors were released in the bloodstream from the tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of serum and tumor tissue endostatin evaluation in operable non-small cell lung cancer

Zhang

et al. 2014

Biomedical Reports

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Abstract. Endostatin, as the most potential antiangiogenic factor, is a naturally occurring fragment of collagen XVIII in bloodstream capable of inhibiting tumor growth and metastasis. This study was conducted to explore the clinical value of endostatin in serum and tumor tissue in patients with operable non-small cell lung cancer (NSCLC). ELISA and immunohistochemistry were applied to detect the expression of endostatin in serum and tumor tissue in 105 patient-matched operable NSCLC patients. The serum level of endostatin was significantly higher in NSCLC patients than healthy individuals (P=0.0018). Cases with poorer differentiation showed a higher endostatin serum level (P=0.008). There was no significant correlation between tumor tissue expression and clinical parameters, such as TNM stage, differentiation degree, histological type and lymph node invasion status. A stronger expression of endostain in tumor tissue was associated with a higher serum level (r=0.223). The univariate and multivariate analyses with Cox proportional hazards model for overall survival showed that tumor stage and node status were independent prognostic factors, whereas neither endostatin levels in serum nor in tumor tissue showed potential in predicting the long-term survival of operable NSCLC patients. In conclusion, the results observed in the present study did not support the prediction of overall survival in operable NSCLC based on the expression levels of endostatin in serum and tumor tissue.

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1768: Prognostic Significance of Plasma Placental Growth Factor Levels in Renal Cell Cancer: An Association with Clinical Characteristics and Vascular Endothelial Growth Factor Levels

Cited by 34 publications

References 0 publications

Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer.

Clinical significance of serum and tumor tissue endostatin evaluation in operable non-small cell lung cancer

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