Inhibition of Intimal Thickening After Balloon Angioplasty in Porcine Coronary Arteries by Targeting Regulators of the Cell Cycle

Gallo, Richard; Padurean, Adrian; Jayaraman, Thottala; Marx, Steven O.; Roqué, Mercè; Adelman, Steven J.; Chesebro, James H.; Fallon, John T.; Fuster, Valentı́n; Marks, Andrew R.; Badimón, Juan J.

doi:10.1161/01.cir.99.16.2164

Cited by 442 publications

(273 citation statements)

References 40 publications

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“…Sirolimus exposure results in G1 cell cycle arrest of T and B cells (22,25). The anti-proliferative effect of sirolimus has also been observed in smooth muscle cells, resulting in potent inhibition of neointimal proliferation after balloon-induced vascular injury in animal models (26,27). Interestingly, a recent report strongly suggests that sirolimus may exert a similar anti-proliferative effect in renal tubular cells (28).…”

Section: Discussionmentioning

confidence: 99%

Sirolimus Prolongs Recovery from Delayed Graft Function After Cadaveric Renal Transplantation

McTaggart

Gottlieb

Brooks

et al. 2003

American Journal of Transplantation

163

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Sirolimus, lacking known nephrotoxicity, appeared to be an ideal immunosuppressive agent in the setting of delayed graft function (DGF) after renal transplantation. Coincident with our use of sirolimus however, we noticed prolongation of DGF. To investigate possible causes of prolonged DGF, extensive donor, recipient, transplant, and post-transplant data were collected on 132 consecutive cases of DGF at the University of California, San Francisco between 1/1/97 and 6/30/01. Cox proportional hazards analysis of time to graft function was used in univariate and multivariate models to identify factors that prolong DGF. Sirolimus had a large and highly significant effect on time to graft function (hazard ratio 0.48, p = 0.0007). The hazard ratio indicates that a recipient on sirolimus is half as likely to resolve DGF or twice as likely to remain on dialysis as a recipient without sirolimus. Two other factors had less potent but still significant association with DGF duration: recipient sensitization (hazard ratio 0.66, p = 0.037), and Novartis score (hazard ratio 0.93 per 1.0 increase; p = 0.034). Sirolimus retained its profound negative association with time to graft function in all multivariate models. Because sirolimus appears to prolong DGF, it may not be the optimal immunosuppressive choice in the DGF setting.

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Section: Discussionmentioning

confidence: 99%

Sirolimus Prolongs Recovery from Delayed Graft Function After Cadaveric Renal Transplantation

McTaggart

Gottlieb

Brooks

et al. 2003

American Journal of Transplantation

163

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“…Mice (4-6 weeks) were divided into two groups for systemic administration of rapamycin-loaded micelles and rapamycin-loaded nanosuspensions. Rapamycin-loaded nanosuspensions were prepared according to the reported method 21 and the mean particle size of these formulations was around 230 nm. Rapamycin-loaded micelles or rapamycin nanosuspensions were injected into the tail vein of the mice at a single dose of 7.5 mg/kg body weight.…”

Section: In Vivo Pharmacokinetics and Biodistribution Studiesmentioning

confidence: 99%

Poly(ethylene glycol)-Block-Poly(2-methyl-2-benzoxycarbonyl-propylene Carbonate) Micelles for Rapamycin Delivery: In Vitro Characterization and Biodistribution

Mahato

2011

Journal of Pharmaceutical Sciences

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Our objective was to synthesize an amphiphilic diblock copolymer for micellar delivery of rapamycin. Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) (PEG-b-PBC) with different hydrophobic core lengths were synthesized from methoxy poly(ethylene glycol) and 2-methyl-2-benzoxycarbonyl-propylene carbonate through ring-opening polymerization using 1,8-diazabicycloundec-7-ene as a catalyst. The critical micelle concentration of PEG-b-PBC was around 10 −8 M and depends on the hydrophobic core length. Rapamycin was effectively incorporated into micelles and drug loading increased with increasing hydrophobic core length, with maximal drug loading of 10% (w/w, drug/polymer), drug loading efficiency of about 85%, and mean particle size of around 70 nm. The drug release profile was also dependent on the hydrophobic core length and the drug release from PEG 114 -b-PBC 30 micelles was the slowest. We also determined the toxicity of rapamycin micelles on insulinoma (INS-1E) $-cells and human islets. Encapsulation of rapamycin into PEG-b-PBC micelles reduced its toxicity. Biodistribution of rapamycin-loaded PEG-b-PBC micelles was determined after systemic administration into mice. Rapamycin-loaded PEG-b-PBC micelles showed little difference in pharmacokinetics and biodistribution characteristics in mice compared with rapamycin carrying nanosuspension. In conclusion, rapamycin formulated with PEG-b-PBC micelles showed significantly reduced toxicity on INS-1E $-cells and human islets, but had similar biodistribution profiles as those of nanosuspensions.

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“…Preliminary data suggest that HPV may promote atherosclerosis and may be a risk factor for CVEs after RT. Specifically, inhibition of macrophage p53 and Rb (retinoblastoma protein) are linked to the oncogenicity of HPV and to inflammation and accelerated atherosclerosis 9, 10, 11, 12. Furthermore, data suggest that vaginal HPV status may be associated with an increased risk of cardiovascular events in women 13.…”

Section: Introductionmentioning

confidence: 99%

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer

Seidelmann

Janjua

Emami

et al. 2017

JAHA

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BackgroundRadiation therapy (RT) is a standard treatment for head and neck cancer; however, it is associated with inflammation, accelerated atherosclerosis, and cerebrovascular events (CVEs; stroke or transient ischemic attack). Human papillomavirus (HPV) is found in nearly half of head and neck cancers and is associated with inflammation and atherosclerosis. Whether HPV confers an increased risk of CVEs after RT is unknown.Methods and ResultsUsing an institutional database, we identified all consecutive patients treated with RT from 2002 to 2012 for head and neck cancer who were tested for HPV. The outcome of interest was the composite of ischemic stroke and transient ischemic attack, and the association between HPV and CVEs was assessed using Cox proportional hazard models, competing risk analysis, and inverse probability weighting. Overall, 326 participants who underwent RT for head and neck cancer were tested for HPV (age 59±12 years, 75% were male, 9% had diabetes mellitus, 45% had hypertension, and 61% were smokers), of which 191 (59%) were tumor HPV positive. Traditional risk factors for CVEs were similar between HPV‐positive and ‐negative patients. Over a median follow‐up of 3.4 years, there were 18 ischemic strokes and 5 transient ischemic attacks (event rate of 1.8% per year). The annual event rate was higher in the HPV‐positive patients compared with the HPV‐negative patients (2.6% versus 0.9%, P=0.002). In a multivariable model, HPV‐positive status was associated with a >4 times increased risk of CVEs (hazard ratio: 4.4; 95% confidence interval, 1.5–13.2; P=0.008).ConclusionsIn this study, HPV‐positive status is associated with an increased risk of stroke or transient ischemic attack following RT for head and neck cancer.

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Inhibition of Intimal Thickening After Balloon Angioplasty in Porcine Coronary Arteries by Targeting Regulators of the Cell Cycle

Cited by 442 publications

References 40 publications

Sirolimus Prolongs Recovery from Delayed Graft Function After Cadaveric Renal Transplantation

Sirolimus Prolongs Recovery from Delayed Graft Function After Cadaveric Renal Transplantation

Poly(ethylene glycol)-Block-Poly(2-methyl-2-benzoxycarbonyl-propylene Carbonate) Micelles for Rapamycin Delivery: In Vitro Characterization and Biodistribution

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer

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