ABSTRACT
Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.
ABSTRACT
Object: The object of this study was to compare the outcome of primary PCI of ostial versus non ostial occlusion of LAD artery
Materials and Methods: This observational study was conducted at National Institute of Cardivascular Diseases Karachi, Pakistan from January 1[st], 2008 to December 31[st], 2008. A total of 70 patients presented to the catheterization laboratory for primary PCI of LAD artery in whom baseline coronary angiogram showed acute occlusion of left anterior descending artery were enrolled for the study. All patients received Aspirin, Clopidogrel and Platelet Glycoprotein IIB IIIA inhibitor. Patients were followed at one month, 3 months and 6 months
Results: Out of 70 cases 50 had nonostial and 20 had ostial occlusion. Baseline characteristics were similar between both groups. Stenting was done in 95% of all patients and was similar in patients with ostial or nonostial narrowing. Procedural success was the same for ostial and nonostial Primary PCI [100% vs. 96%]. Six months event free survival was also similar in both groups [75% vs. 76%]. Total event rate and mortality was also same in both groups [25% vs. 24% and 10% vs. 10%]
Conclusion: Primary PCI of ostial LAD occlusion with suitable anatomy is as safe and similar as non ostial LAD occlusion and optimal results can be achieved in this high risk group of patients in a developing country at a tertiary care public sector hospital. To validate our results further studies with larger cohort are needed