Proteomic Profiling of Small Extracellular Vesicles Isolated from the Plasma of Vietnamese Patients with Non-Small Cell Lung Cancer Reveals Some Potential Biomarkers

Background: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins.  Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC–MS/MS) was used for analyzing. Results: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. Conclusion: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future.     

Failure of gated SPECT and echocardiography to detect large apical aneurysm secondary to hyperdynamic left ventricular wall at the aneurysm neck

We present a patient with a history of coronary artery disease and exertional angina after an acute anterior myocardial infarction. Angiography and ventriculography revealed multivessel coronary artery disease and a large apical aneurysm. Echocardiography and gated SPECT studies were performed for further evaluation of ischemia and assessment of left ventricular function. Gated SPECT and echocardiography failed to detect a large apical aneurysm due to a hyperdynamic left ventricular wall at the neck of the aneurysm. This case demonstrates the importance of using multiple imaging modalities in the evaluation of ventricular function in the setting of coronary artery disease.     

Glutathione trapping to measure microsomal oxidation of furan to cis-2-butene-1,4-dial.

Furan is a liver carcinogen and toxicant. Furan is oxidized to the reactive dialdehyde, cis-2-butene-1,4-dial, by microsomal enzymes. This reactive metabolite readily reacts with glutathione nonenzymatically to form conjugates. A high-performance liquid chromatography-electrochemical method for the detection of cis-2-butene-1,4-dial-glutathione (GSH) conjugates in microsomal preparations was developed to measure the extent of furan metabolism to cis-2-butene-1,4-dial in vitro. Previously unobserved mono-GSH reaction products of cis-2-butene-1,4-dial were detected in addition to the already characterized bis-GSH conjugates. Chemical characterization of these compounds indicated that the alpha-amino group of glutathione had reacted with cis-2-butene-1,4-dial to form a thiol-substituted pyrrole adduct. The analytical method was used to estimate the extent of furan oxidation in rat liver microsomes from untreated or acetone-pretreated F344 rats as well as in human P450 2E1 Supersomes. Our results confirm that cytochrome P450 2E1 can catalyze the oxidation of furan to cis-2-butene-1,4-dial. However, the data are also consistent with the involvement of other P450 enzymes in the oxidation of furan in untreated animals. This assay will be a valuable tool to explore tissue and species differences in rates of furan oxidation.     

Apolipoprotein B polymorphism and altered apolipoprotein B concentrations in Congolese blacks

The immunoreactivity of apolipoprotein B (apo B) in plasma obtained from 238 unrelated black African male subjects from the People's Republic of Congo was analysed by non-competitive Enzyme Linked-Immunosorbent Assay (ELISA) with monoclonal BIP 45 anti-LDL antibody. The polymorphism detected by BIP 45 monoclonal antibody is identical to the Ag(c,g) polymorphism. Antibody BIP 45 distinguishes three apo B allotypes (immunophenotypes) encoded by the two allelic genes apo B Ag(c) and apo B Ag(g). Because of co-dominant transmission, genotypes may be inferred from allotypes, and it has been shown that BIP 45 binds strongly to the Ag(c) factor and only weakly to the allelic Ag(g) factor. Analysis of the Congolese plasma samples indicated that 67.65% of them bound BIP 45 with low affinity (Ag(c-,g+) genotype), 28.15% with intermediate affinity (Ag(c+,g+) genotype) and 4.20% with high affinity (Ag(c+,g-) genotype). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.817 and 0.183 for the type Ag(g)/Ag(c) alleles, respectively. After adjustment for age and body-mass index, it was found that the Ag(c) allele decreases the apo B level by 9.62 mg/dl and that the Ag(g) allele increases apo B by 0.43 mg/dl. Therefore, as much as 4.30% of the genetic variance for apo B level could be accounted for by the Ag(c,g) gene locus.     

Successful pregnancy following allogeneic bone marrow transplantation after conditioning by thoraco-abdominal irradiation

A 26-year-old woman delivered a normal child 5 years after bone marrow transplantation for severe aplastic anemia. The conditioning regimen comprised high dose cyclophosphamide and thoraco-abdominal irradiation (6 Gy). This and two previous cases demonstrate that normal pregnancy can follow total body or thoracoabdominal irradiation.     

Electroimmuno- and immunonephelometric assays of apolipoprotein A-I by using a mixture of monoclonal antibodies

The use of mixtures of well-defined monoclonal antibodies may represent a step forward in the standardization of immunochemical assays. We developed and optimized working conditions for using such a mixture to determine apolipoprotein A-I in human sera by two independent techniques (electroimmuno- and immunonephelometric-assays). Six monoclonal antibodies, each addressed to distinct epitopes located at the surface of apolipoprotein A-I, were used in combination to permit a reproducible measurement of the protein, without prior delipidation of samples. Parallel standard curves for a high-density lipoprotein subfraction (HDL3, the primary standard) and a reference serum (the secondary standard) were obtained. Within- and between-run coefficients of variation were acceptable for both methods. Apolipoprotein A-I concentrations, as measured in 60 subjects selected to present a large range of apolipoprotein content by electroimmunoassay (y1) and immunonephelometric assay (y2) with monoclonal antibodies, compared well with those measured by the same techniques but with polyclonal antibodies (x): r1 = 0.96, r2 = 0.99; y1 = 1.19x - 0.11 g/L, y2 = 0.98x. Comparison of results obtained by electroimmunoassay and immunonephelometric assay performed with monoclonal antibodies was also good: r = 0.96; y2 = 1.08y1 + 0.13 g/L.     

Could proteinuria evaluation be helpful in predicting renal progression in apolipoprotein E-deficient (E-/-) mice with chronic renal failure?

Sir, We read with interest the recent article by Buzello et al. [1]on renal changes in apo E^-/- mice after subtotal nephrectomy.They compared renal lesion development in male wild-type C57BL/6mice with that of genetically modified male apo E^-/- mice aftereither sham operation, unilateral nephrectomy or subtotal nephrectomy(SNX) by removal of 75% of the cortex in one kidney and removalof the contralateral kidney. They found     

Estimation of the bronchodilatory effect of deep inhalation after a free run in children.

The bronchomotor effects of a deep inhalation (DI) may provide relevant information about the mechanisms of exercise-induced airway obstruction in children and may be assessed by respiratory conductance (Grs) measured using the forced oscillation technique. The aims of the present study were to assess the effect of DI on Grs after exercise in relationship to the lung function response to exercise. Grs at 12 Hz using a head generator and spirometric data were measured in 62 children suspected of asthma before and 5 min after a 6-min free run. After exercise, Grs was significantly increased by DI in 38 subjects, who also showed larger Grs and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) responses to exercise than the 24 nonresponders. Stepwise regression indicated significant correlation between the response of Grs to DI and both Grs and FEV1/FVC responses to exercise. The data are consistent with exercise-induced bronchoconstriction being reversed by deep inhalation.