Treatment of a Patient with Acute Promyelocytic Leukemia with Multiple Isolated Relapses in the Central Nervous System: A Case Report and Mini-Review of the Literature.

The efficacy of therapeutics for acute promyelocytic leukemia (APL) has exhibited an increase in recent years. Only a few patients experience relapse, including extramedullary relapse, and in patients with extramedullary relapse, the central nervous system (CNS) is the most common site. To date, there is no expert consensus or clinical guidelines available for CNS relapse, at least to the best of our knowledge. The optimal therapeutic strategy and management options for these patients remain unclear. The present study reports the treatment of a patient with APL with multiple isolated relapses in the CNS. In addition, through a mini-review of the literature, the present study provides a summary of various reports of this disease and discusses possible treatment options for these patients.

STVNa attenuates right ventricle hypertrophy and pulmonary artery remodeling in rats induced by transverse aortic constriction.

Right heart failure and pulmonary artery remodeling resulting from increased left heart pressure are prevalent in a clinical setting, and the specific pathological feature exhibits cancer-like cell proliferation in lung. STVNa has been previously demonstrated its anti-proliferation property. In this study, we want to verify the therapeutic effect of STVNa against right ventricle hypertrophy and pulmonary artery remodeling in rats induced by transverse aortic constriction (TAC). The results show that TAC surgery increased mean right ventricle pressure (mRVP) less in the STVNa group than that in the vehicle group (11.81 vs 22.71 mmHg/ml, p < 0.01). STVNa treatment reduced the right ventricle cardiomyocyte area (p < 0.05) and the proliferation of pathological smooth muscle cells proving by PCNA immunohistochemical staining. Gene expression of brain natriuretic peptide (BNP), smooth muscle actin (SMA) and CD31 assessed by real-time polymerase chain reaction were confirmed the above results. Also, STVNa treatment decreased the lung fibrosis content and alleviated the inflammation infiltration. The expression of ET-1 and the phosphorylation of signal-regulated kinase (ERK) were lower in STVNa group compared to vehicle group (p < 0.05). In summary, STVNa could relieve right ventricle hypertrophy and pulmonary artery remodeling formation in rats after 9 weeks of TAC surgery by reducing ET-1 expression and suppressing ERK phosphorylation signal and subsequently inhibiting cell proliferation.

Global mapping of rat plasma proteins with a native proteomic approach using nondenaturing micro 2DE and quantitative LC-MS/MS.

Plasma samples from adult male rats were separated by nondenaturing micro 2DE and a reference gel was selected, on which 136 CBB-stained spots were numbered and subjected to in-gel digestion and quantitative LC-MS/MS. The analysis provided the assignment of 1-25 (average eight) non-redundant proteins in each spot and totally 199 proteins were assigned in the 136 spots. About 40% of the proteins were detected in more than one spot and 15% in more than ten spots. We speculate this complexity arose from multiple causes, including protein heterogeneity, overlapping of protein locations and formation of protein complexes. Consequently, such results could not be appropriately presented as a conventional 2DE map, i.e. a list or a gel pattern with one or a few proteins annotated to each spot. Therefore, the LC-MS/MS quantity data was used to reconstruct the gel distribution of each protein and a library containing 199 native protein maps was established for rat plasma. Since proteins that formed a complex would migrate together during the nondenaturing 2DE and thus show similar gel distributions, correlation analysis was attempted for similarity comparison between the maps. The protein pairs showing high correlation coefficients included some well-known complexes, suggesting the promising application of native protein mapping for interaction analysis. With the importance of rat as the most commonly used laboratory animal in biomedical research, we expect this work would facilitate relevant studies by providing not only a reference library of rat plasma protein maps but a means for functional and interaction analysis.

Analysis of low-density lipoprotein-associated proteins using the method of digitized native protein mapping.

The method of digitized native protein mapping, combining nondenaturing micro 2DE, grid gel-cutting, and quantitative LC-MS/MS (in data-independent acquisition mode, or MS(E) ), was improved by using a new MS/MS mode, ion mobility separation enhanced-MS(E) (HDMS(E) ), and applied to analyze the area of human plasma low-density lipoprotein (LDL). An 18 mm × 4.8 mm rectangular area which included LDL on a nondenaturing micro 2D gel of human plasma was grid-cut into 72 square gel pieces and subjected to quantitative LC-MS/MS. Compared with MS(E) , HDMS(E) showed significantly higher performance, by assigning 50% more proteins and detecting each protein in more squares. A total of 253 proteins were assigned with LC-HDMS(E) and the quantity distribution of each was reconstructed as a native protein map. The maps showed that Apo B-100 was the most abundant protein in the grid-cut area, concentrated at pI ca. 5.4-6.1 and apparent mass ca. 1000 kDa, which corresponded to four gel pieces, squares 39-42. An Excel macro was prepared to search protein maps which showed protein quantity peaks localized within this concentrated region of Apo B-100. Twenty-two proteins out of the 252 matched this criterion, in which 19 proteins have been reported to be associated with LDL. This method only requires several microliters of a plasma sample and the principle of the protein separation is totally different from the commonly used ultracentrifugation. The results obtained by this method would provide new insights on the structure and function of LDL.

[Combined effect of anti-vascular endothelial growth factor antibody and recombinant human TRAIL on inducing apoptosis of leukemia K562 cells].

The objective of this study was to investigate the synergistic effect of soluble human recombinant tumor necrosis factor related apoptosis inducing ligand (TRAIL) protein combined with anti-vascular endothelial growth factor (anti-VEGF) antibody on inducing apoptosis of leukemia K562 cells. The inhibitory rates and apoptotic rates of K562 cells treated with TRAIL and anti-VEGF antibody alone and their combination for 48 hours were examined by CCK-8 assay and flow cytometry respectively. The results indicated that the apoptotic rates of K562 cells induced with 75, 100 and 150 ng/ml TRAIL after culture for 48 hours were (4.26±0.67)%, (8.91±0.55)% and (11.71±0.78)% respectively. The apoptotic rates of K562 cells induced with 2.5, 5 and 7.5 µg/ml anti-VEGF antibody after culture for 48 hours were (3.95±0.69)%, (7.98±0.74)% and (10.26±0.83)% respectively. The apoptotic rates of K562 cells treated with combination use of 2.5 µg/ml anti-VEGF antibody and 75 ng/ml TRAIL, 5 µg/ml anti-VEGF antibody and 100 ng/ml TRAIL, and 7.5 µg/ml anti-VEGF antibody and 150 ng/ml TRAIL for 48 hours were (22.16±0.93)%, (36.32±1.31)% and (49.19±0.71)% respectively. The combined use of above mentioned agents induced significantly higher apoptosis and cytotoxicity than that of TRAIL or anti-VEGF antibody alone (p<0.05). It is concluded that the combination use of TRAIL and anti-VEGF antibody can significantly increase the sensitivity of K562 cells to apoptosis.