Continuous pemetrexed treatment for brain metastasis in non-small cell lung cancer-A report of two cases.
Nobuaki Ochi, Hiromichi Yamane, Tomoko Yamagishi, Nagio Takigawa
Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.
Lung cancer (Amsterdam, Netherlands) (Impact Factor: 3.14). 12/2012; DOI:10.1016/j.lungcan.2012.12.010
Source: PubMed
ABSTRACT Brain metastasis is a major complication in patients with advanced non-small cell lung cancer (NSCLC), which is the malignancy that metastasizes most frequently to the central nervous system (CNS). Although the CNS is protected from cytotoxic agents by the blood-brain barrier under normal conditions, the blood-brain barrier is thought to become less functional in the presence of brain metastasis. Here, we describe two NSCLC patients who relapsed with brain metastases. Following brain stereotactic irradiation, salvage chemotherapy using pemetrexed was given. Continuous pemetrexed treatment resulted in no recurrence, including brain metastasis, over 2 years without whole-brain irradiation. Our experience suggests that pemetrexed suppresses brain metastasis after stereotactic irradiation.
罗氏的Brain Shuttle技术 http://www.roche.com/research_an ... s/brain_shuttle.htm
Brain Shuttle is a technology that we have developed at Roche to increase penetration of large molecules such as antibodies into the brain. Access of large molecules to the brain is restricted by the blood brain barrier (BBB), a gatekeeper between the blood and the brain tissue that carefully filters which molecules can enter the brain. By using the Roche antibody engineering platform, we have created antibodies that are able to cross the blood brain barrier by binding to one of the protein receptors located on its surface. The so-called “brain shuttle” technology could potentially transport all types of therapeutic molecules into the brain, regardless of their intrinsic ability to cross the blood brain barrier.
Associations between Single Nucleotide Polymorphisms in the PI3K/PTEN/AKT/mTOR Pathway and Increased Risk of Brain Metastasis in Patients with Non-Small-Cell Lung Cancer http://clincancerres.aacrjournal ... stract.html?papetoc
Purpose:Non-small cell lung cancer (NSCLC) metastasizes fairly often to the brain, but identifying which patients will develop brain metastases (BM) is problematic. The phosphatidylinositol-3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is important in the control of cell growth, tumorigenesis, and cell invasion. We hypothesized that genotype variants in this pathway could predict BM in patients with NSCLC. Experimental Design:We genotyped 16 single nucleotide polymorphisms (SNPs) in 5 core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) by using DNA from blood samples of 317 patients with NSCLC and evaluated potential associations with the subsequent development of BM, the cumulative incidence of which was estimated with Kaplan-Meier analysis. Multivariate Cox regression analysis was used to analyze correlations between genotype variants and the occurrence of BM. Results:In analysis of individual SNPs, the GT/GG genotype of AKT1: rs2498804, CT/TT genotype of AKT1: rs2494732 and AG/AA genotype of PIK3CA: rs2699887 were associated with higher risk of BM at 24 months' follow-up (respective hazard ratios [HRs] 1.860, 95% confidence interval [CI] 1.199-2.885, P=0.006; HR 1.902, 95% CI 1.259-2.875, P = 0.002; and HR 1.933, 95% CI 1.168-3.200, P=0.010). We further found that these SNPs had a cumulative effect on BM risk, with that risk being highest for patients carrying both of these unfavorable genotypes (P=0.003). Conclusions:Confirmation of our findings, the first to indicate that genetic variations in PI3K-AKT-mTOR can predict BM, in prospective studies would facilitate stratification of patients for BM prevention trials.
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