BackgroundElevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer.MethodsEligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed.ResultsEight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3–9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0–10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF.ConclusionsBEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease.Trial registrationClinicalTrials.gov identifying number NCT01281696.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1290-1) contains supplementary material, which is available to authorized users.
Single
cell analysis strives to probe molecular heterogeneity in
morphologically similar cell populations through quantitative or qualitative
measurements of genetic, proteomic, or metabolic products. Here, we
applied mass analysis of single neurons to investigate cell–cell
signaling peptides. The multiplicity of endogenous cell–cell
signaling peptides is a common source of chemical diversity among
cell populations. Certain peptides can undergo post-translational
isomerization of select residues, which has important physiological
consequences. The limited number of single cell analysis techniques
that are sensitive to peptide stereochemistry make it challenging
to study isomerization at the individual cell level. We performed
capillary electrophoresis (CE) with mass spectrometry (MS) detection
to characterize the peptide content of single cells. Using complementary
trapped ion mobility spectrometry (TIMS) separations, we measured
the stereochemical configurations of three neuropeptide gene products
derived from the pleurin precursor in individual neurons (N = 3) isolated from the central nervous system of Aplysia californica. An analysis of the resultant mobility
profiles indicated >98% of the detectable pleurin-derived peptides
exist as the nonisomerized, all-l forms in individual neuron
cell bodies. However, we observed 44% of the Plrn2 peptide from the
pleurin precursor was present as the isomerized, d-residue-containing
form in the nerve tissue. These findings demonstrate an unusual distribution
of isomerized peptides in A. californica and establish
CE–TIMS MS as a powerful analytical tool for investigating
peptide stereochemistry at the single cell level.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.