Measurement of Plasma Levels of Vascular Endothelial Growth Factor in Prostate Cancer Patients: Relationship With Clinical Stage, Gleason Score, Prostate Volume, and Serum Prostate-Specific Antigen

Duque, Jose Luis F.; Loughlin, Kevin R.; Adam, Rosalyn M.; Kantoff, Philip W.; Mazzucchi, Eduardo; Freeman, Michael R.

doi:10.1590/s1807-59322006000500006

Cited by 35 publications

(26 citation statements)

References 15 publications

(15 reference statements)

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“…VEGF underexpression was associated with a higher risk of prostate cancer in our study. This is in contrast to earlier reports that reported a direct association between VEGF overexpression and risk of developing biochemical recurrence, lymph node metastases and distant metastases in patients with prostate cancer (8,20). This variability can be explained by the significant difference in the patient populations in the two studies.…”

Section: Discussioncontrasting

confidence: 98%

Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer

Parekh¹,

Ankerst²,

Baillargeon³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objective: We analyzed the association of 54 biomarkers from seven classes including adipokines, immune response metalloproteinases, adhesion molecules, and growth factors with prostate cancer risk adjusting for the Prostate Cancer Prevention Trial (PCPT) risk score. Methods: A total of 123 incident prostate cancer cases and 127 age-matched controls were selected from subjects in the San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. Prediagnostic serum concentrations were measured in the sample collected at baseline using LabMAP technology. The odds ratios (OR) of prostate cancer risk associated with serum concentrations of 54 markers were estimated using univariate conditional logistic regression before and after adjustment for the PCPT risk score. Two-way hierarchical unsupervised clustering techniques were used to evaluate whether the 54-marker panel distinguished cases from controls. Results: Vascular endothelial growth factor, resistin, interleukin 1Ra (IL-1Ra), granulocyte colony-stimulating factor, matrix metalloproteinase-3, plasminogen activator inhibitor, and kallikrein-8 were statistically significantly (P < 0.05) underexpressed in prostate cancer cases, and A-fetoprotein was statistically significantly overexpressed in prostate cancer cases, but all had area underneath the receiver-operating characteristic curve <60%; none were statistically significant adjusting for multiple comparisons (P < 0.0008) or after adjustment for the PCPT risk score. Statistical clustering of patients by the marker panel did not distinguish a separate group of cases from controls. Conclusions: This age-matched case-control study did not support findings of increased diagnostic potential from a 54-marker panel when compared with the conventional risk factors incorporated in the PCPT risk calculator. Future discovery of new biomarkers should always be tested and compared against conventional risk factors before applying them in clinical practice. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1966 -72)

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Section: Discussioncontrasting

confidence: 98%

Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer

Parekh¹,

Ankerst²,

Baillargeon³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…45). Recently, Duque and colleagues (46) showed that patients with PSA levels of >20 ng/mL (with disseminated disease) had significantly higher VEGF values than patients with PSA levels of <20 ng/mL. Interestingly, our study described a moderate but significant correlation between VEGF plasma levels and serum PSA concentrations, suggesting that, at least in our study, VEGF plasma levels may indicate the biochemical status of neoplastic disseminated disease.…”

Section: Discussionsupporting

confidence: 53%

Clinical and Pharmacodynamic Evaluation of Metronomic Cyclophosphamide, Celecoxib, and Dexamethasone in Advanced Hormone-refractory Prostate Cancer

Fontana

Galli

Fioravanti

et al. 2009

Clinical Cancer Research

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Purpose: The aims of the present study were to evaluate the clinical activity and the pharmacodynamic profile of the novel schedule of a single i.v. standard dose of cyclophosphamide (CTX) immediately followed by an oral metronomic CTX regimen with celecoxib (CXB) and dexamethasone (DEX) in advanced hormone-refractory prostate cancer patients. Experimental Design: Twenty-eight patients (68% docetaxel-resistant) received 500 mg/m 2 CTX i.v. bolus on day 1 and, from day 2, 50 mg/day CTX p.o. plus 200 mg/twice a day CXB p.o. and 1 mg/day DEX p.o. until disease progression. Plasma vascular endothelial growth factor (VEGF) and thrombospondin-1 were detected by ELISA, and real-time reverse transcription-PCR of VEGF and thrombospondin-1 gene expression on peripheral blood mononuclear cell and of VE-cadherin (VE-C) in blood samples was done. Results: A confirmed prostate-specific antigen decrease of ≥50% from baseline was observed in 9 of 28 patients (32%). Median progression-free survival and overall survival were 3 months (95% confidence interval, 2.2-4.2 months) and 21 months (95% confidence interval, 12.4-29.4 months), respectively. Toxicity was mild and no grade 3 to 4 toxicities occurred. A significant relationship was found between plasma VEGF and prostate-specific antigen values (r = 0.4223; P < 0.001). VEGF levels significantly increased in nonresponders, whereas the responder patients maintained significantly lower levels of VE-C gene expression after the beginning of the treatment if compared with nonresponder ones. Conclusion: Metronomic CTX plus CXB and DEX showed favorable toxicity and activity profile in patients. VE-C gene expression and VEGF levels represent potentially useful pharmacodynamic markers for the clinical response.Metronomic oral cyclophosphamide (CTX) alone-the chronic administration of CTX at low doses with no prolonged drugfree breaks-and in association with antiangiogenic drugs is a promising clinical approach to metastatic breast and ovarian cancers (1, 2). The antitumor and antiangiogenic activity of metronomic CTX has been shown in various experimental models of human prostate cancer (3). Phase II clinical studies have obtained interesting results using metronomic oral CTX alone (50 mg/m 2 /day; ref. 4) or in combination with dexamethasone (DEX; 50 mg/day CTX plus 1 mg/day DEX; ref. 5) in hormone-refractory prostate cancer (HRPC) patients. Metronomic CTX was safe and well-tolerated, showing a prostatespecific antigen (PSA) of ≥50% decline in 69% of patients with a response duration of 8 months (5). The administration of metronomic CTX with drugs targeting angiogenesis has shown a high preclinical activity (6, 7). Celecoxib (CXB), a cyclooxygenase-2 inhibitor, has shown both antiangiogenic properties (8) and antitumor activity in a transgenic mouse model of prostate adenocarcinoma (9) with a marked decrease in vascular endothelial growth factor (VEGF) expression (10). Moreover, CXB

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“…Low VEGF-A levels have been found in many androgen-independent cell lines (39-41) as well as castration-resistant human prostate cancer tissue (42). In contrast, plasma levels of VEGF-A is increased with metastatic disease (42)(43)(44), similar to what we found, but not further elevated after castration-resistant metastatic disease (45). Several other proangiogenic factors than VEGF-A can be stimulated by HIF-1a, among them basic fibroblast growth factor, platelet-derived growth factor-h, plasminogen activator inhibitor-1, angiopoietins 1 and 2, and matrix metalloproteinase-2 and -9 as well as VEGF receptors (Flt-1 and Flk-1) and Tie-2 receptor (25,41,(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Proliferation of Immature Tumor Vessels Is a Novel Marker of Clinical Progression in Prostate Cancer

Gravdal¹,

Halvorsen²,

Haukaas

et al. 2009

Cancer Research

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Nestin (neuroepithelial stem cell protein) is expressed in immature endothelial cells, and we here introduce coexpression of Nestin and Ki-67 as a novel angiogenesis marker on tissue sections. Including vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1A (HIF-1A) expression, we studied relation to disease progression in prostate cancer. Different patient series were included. Sections from 104 radical prostatectomies with long follow-up, 33 castration-resistant prostate cancers, 28 nonskeletal metastases, 13 skeletal metastases, and 41 benign prostatic hyperplasias were immunostained for Nestin/Ki-67, VEGF-A, and HIF-1A. Vascular proliferation by Nestin/Ki-67-positive vessels was counted within ''hotspot'' areas. Median vascular proliferation counts were 4-to 5-fold higher in castration-resistant prostate cancers and metastases versus localized cancers and prostatic hyperplasias (P < 0.0005). Among localized cancers, high vascular proliferation was significantly related to adverse clinicopathologic features and was a strong and independent predictor of biochemical failure (P < 0.005), clinical recurrence (P = 0.005), and skeletal metastasis (P = 0.025) in multivariate analysis. Castration-resistant cancers were characterized by reduced VEGF-A and increased HIF-1A expression, and vascular proliferation was associated with reduced patient survival in this group. Thus, vascular proliferation was of independent prognostic importance among prostate cancers. When compared with localized cancers, vascular proliferation was significantly increased in castration-resistant cases and metastatic lesions. The castration-resistant tumors exhibited weak VEGF-A but strong HIF-1A expression. These novel data might have an effect on clinical evaluation and treatment of prostate cancer patients. [Cancer Res 2009;69(11):4708-15]

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Measurement of Plasma Levels of Vascular Endothelial Growth Factor in Prostate Cancer Patients: Relationship With Clinical Stage, Gleason Score, Prostate Volume, and Serum Prostate-Specific Antigen

Cited by 35 publications

References 15 publications

Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer

Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer

Clinical and Pharmacodynamic Evaluation of Metronomic Cyclophosphamide, Celecoxib, and Dexamethasone in Advanced Hormone-refractory Prostate Cancer

Proliferation of Immature Tumor Vessels Is a Novel Marker of Clinical Progression in Prostate Cancer

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