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2012年7月17日星期二

Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment epithelial cells.

Cell cycle regulation by bevacizumab in ARPE-19 human retinal pigment epithelial cells.

Mol Med Report. 2012 Jul 11;

Authors: Kuo CN, Chen CY, Lai CH, Lai LJ, Wu PC, Hung CH, Chen CH

Abstract
Bevacizumab, a recombinant humanized monoclonal antibody, binds vascular endothelial growth factor (VEGF) and inhibits its interaction with receptors found on endothelial cells. Bevacizumab has been increasingly used as an off-label treatment for exudative age-related macular degeneration (AMD). Whether or not bevacizumab is capable of arresting the growth of human retinal pigment epithelial cells remains to be clarified. In this study, flow cytometry was used to evaluate whether bevacizumab markedly induced the G1/S phase arrest. The G1/S phase cycle-related protein analysis demonstrated that the expression of cyclin-dependent kinase (CDK)2, 4 and 6 and of cyclin D and E, as well as the phosphorylation of retinoblastoma tumor suppressor protein (ppRB) production were found to be markedly reduced by bevacizumab. By contrast, the protein levels of p53, p16, p21 and p27 were increased in bevacizumab-treated ARPE-19 cells (a human retinal pigment epithelial cell line). These events of G1/S arrest induced by bevacizumab in ARPE-19 cells suggest that a preventive effect of bevacizumab exists in AMD.

PMID: 22798045 [PubMed - as supplied by publisher]

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New mirsinane-type diterpenes from Euphorbia microsciadia Boiss. with inhibitory effect on VEGF-induced angiogenesis.

New mirsinane-type diterpenes from Euphorbia microsciadia Boiss. with inhibitory effect on VEGF-induced angiogenesis.

J Nat Med. 2012 Jul 15;

Authors: Ghanadian SM, Ayatollahi AM, Afsharypuor S, Javanmard SH, Dana N

Abstract
Euphorbia microsciadia (Euphorbiaceae) is a perennial plant growing in Iran. Two new cyclomyrsinol esters, 3-O-propionyl-5, 10, 14-O-triacetyl-8-O-(2'-methyl-butanoyl)-cyclomyrsinol (1) and 3, 5, 10, 14, 15-O-pentaacetyl-8-O-isobutanoyl-cyclomyrsinol (2) were isolated from the methanolic extract of its dried aerial parts. The structures were elucidated based on (13)C- and (1)H-NMR as well as 2D-NMR, IR and different MS spectra. Anti-angiogenic activity was also evaluated on vascular endothelium growth factor (VEGF)-induced angiogenesis in cultured human umbilical vein endothelial cells in vitro by assessing capillary-like tube network formation.

PMID: 22798201 [PubMed - as supplied by publisher]

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2012年7月16日星期一

Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis.

Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis.

Ann Oncol. 2012 Apr;23(4):1030-6

Authors: Fasol U, Frost A, B�chert M, Arends J, Fiedler U, Scharr D, Scheuenpflug J, Mross K

Abstract
BACKGROUND: EndoTAG-1 (ET), a novel formulation of cationic liposomes carrying embedded paclitaxel (Taxol), shows antitumoral activity, targeting tumor endothelial cells in solid tumors. Patients with advanced metastatic cancer were evaluated investigating effects on pharmacokinetics and tumor vasculature using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and contrast-enhanced ultrasound (CEUS).
PATIENTS AND METHODS: The pharmacokinetic (PK) profile of ET (22 mg/m(2) i.v.) was evaluated after single and repeated doses. DCE-MRI and CEUS explored hepatic metastases before, during and after the 4-week treatment cycle. Angiogenic biomarkers were assessed. Tumor response was evaluated by modified RECIST.
RESULTS: The PK profile demonstrated slight accumulation of paclitaxel after repeated doses. DCE-MRI parameters K(trans) and/or iAUC(60) showed a trend to decrease. Changes of blood flow-dependent parameters of DCE-MRI and CEUS were well correlated. Angiogenic biomarkers revealed no clear trend. ET was generally well tolerated; common toxic effects were fatigue and hypersensitivity reactions. Nine (9 of 18) patients had stable disease after the first treatment cycle. Four patients without disease progression continued treatment.
CONCLUSIONS: This study including multiple pretreated patients with different metastatic cancer revealed individually distinctive hemodynamic alterations by DCE-MRI. The PK profiles of ET were similar as observed previously.

PMID: 21693769 [PubMed - indexed for MEDLINE]

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Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis.

Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis.

Ann Oncol. 2012 Apr;23(4):1030-6

Authors: Fasol U, Frost A, B�chert M, Arends J, Fiedler U, Scharr D, Scheuenpflug J, Mross K

PMID: 21693769 [PubMed - indexed for MEDLINE]

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Phase I dose-escalation study of aflibercept in combination with docetaxel and cisplatin in patients with advanced solid tumours.

Phase I dose-escalation study of aflibercept in combination with docetaxel and cisplatin in patients with advanced solid tumours.

Br J Cancer. 2012 Jul 12;

Authors: Freyer G, Isambert N, You B, Zanetta S, Falandry C, Favier L, Trillet-Lenoir V, Assadourian S, Soussan-Lazard K, Ziti-Ljajic S, Fumoleau P

Abstract
Background:This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours.Methods:Patients received intravenous aflibercept 4, 5, or 6?mg?kg(-1) with docetaxel and cisplatin (75?mg?m(-2) each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination.Results:During the dose-escalation phase (n=16), there were two DLTs of febrile neutropenia (at 4 and 5?mg?kg(-1)). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6?mg?kg(-1) and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting >3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs.Conclusion:Aflibercept 6?mg?kg(-1) with docetaxel and cisplatin 75?mg?m(-2) every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs.British Journal of Cancer advance online publication, 12 July 2012; doi:10.1038/bjc.2012.304 www.bjcancer.com.

PMID: 22790797 [PubMed - as supplied by publisher]

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2012年7月15日星期日

Glaucoma Filtration Surgery Following Sustained Elevation of Intraocular Pressure Secondary to Intravitreal Anti-VEGF Injections.

Glaucoma Filtration Surgery Following Sustained Elevation of Intraocular Pressure Secondary to Intravitreal Anti-VEGF Injections.

Ophthalmic Surg Lasers Imaging. 2012 Jul 1;43(4):328-34

Authors: Skalicky SE, Ho I, Agar A, Bank A

Abstract
BACKGROUND AND OBJECTIVE: To document cases of sustained elevation of intraocular pressure (IOP) while receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents and subsequent management.
PATIENTS AND METHODS: A retrospective series of all cases managed by the authors and colleagues was performed.
RESULTS: Six patients developed sustained elevated IOP; five received ranibizumab and one bevacizumab. Four received unilateral and two received bilateral injections. Two had preexisting primary open-angle glaucoma and one had pseudoexfoliative glaucoma, all with stable IOP prior to anti-VEGF treatment. Angles were open in all cases. Peak IOP averaged 43 mm Hg (range: 34 to 60 mm Hg). The mean number of injections preceding the IOP increase was 10 (range: 1 to 20). Four patients required trabeculectomy, one selective laser trabeculoplasty, and one multiple topical medications.
CONCLUSION: A sustained increase in IOP requiring glaucoma filtering surgery is a rare but important treatment complication for patients receiving intravitreal anti-VEGF therapy, especially those with preexisting glaucoma or glaucoma risk factors.

PMID: 22788585 [PubMed - in process]

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The expression of vascular endothelial growth factor in mast cells promotes the neovascularisation of human pterygia.

The expression of vascular endothelial growth factor in mast cells promotes the neovascularisation of human pterygia.

Br J Ophthalmol. 2012 Jul 11;

Authors: Liang K, Jiang Z, Zhao B, Shen J, Huang D, Tao L

Abstract
AIMS: To analyse the relationship between mast cells and vascularisation in pterygia and to determine whether mast cells play an important role in the vascularisation of pterygia through the secretion of vascular endothelial growth factor (VEGF). METHODS: Fifty-two pterygia and forty-four normal conjunctiva samples were obtained. Formalin-fixed, paraffin wax-embedded tissues were analysed by immunohistochemistry with CD31 and VEGF antibodies. Dual-immunofluorescence was used to see the location of mast cells and microvessels. To prove that mast cells have the function of secreting VEGF, we used dual-immunofluorescence, toluidine blue stain and immunohistochemisty study. RESULTS: Mast cells are located near the microvessels. The numbers of mast cells in pterygia (10.8�2.7) were significantly higher compared with those in conjunctiva (4.7�2.4, p<0.01). The numbers of microvessels in pterygia (20.7�5.4) were also significantly higher than those in conjunctiva (9.3�2.9, p<0.01). There was an association between mast cell count and microvessel density in pterygia (r=0.77, p<0.001). The cells were positive for toluidine blue staining and could express VEGF through a serial section stain. Dual-immunofluorescence showed that VEGF and mast cell tryptase (MCT) were expressed in the same cell. CONCLUSION: The results suggest that mast cells have a function in the vascularisation of pterygia through the secretion of VEGF.

PMID: 22790437 [PubMed - as supplied by publisher]

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