Proteomics Based Identification of Proteins with Deregulated Expression in B Cell Lymphomas

Follicular lymphoma and diffuse large B cell lymphomas comprise the main entities of adult B cell malignancies. Although multiple disease driving gene aberrations have been identified by gene expression and genomic studies, only a few studies focused at the protein level. We applied 2 dimensional gel electrophoresis to compare seven GC B cell non Hodgkin lymphoma (NHL) cell lines with a lymphoblastoid cell line (LCL). An average of 130 spots were at least two folds different in intensity between NHL cell lines and the LCL. We selected approximately 38 protein spots per NHL cell line and linked them to 145 unique spots based on the location in the gel. 34 spots that were found altered in at least three NHL cell lines when compared to LCL, were submitted for LC-MS/MS. This resulted in 28 unique proteins, a substantial proportion of these proteins were involved in cell motility and cell metabolism. Loss of expression of B2M, and gain of expression of PRDX1 and PPIA was confirmed in the cell lines and primary lymphoma tissue. Moreover, inhibition of PPIA with cyclosporine A blocked cell growth of the cell lines, the effect size was associated with the PPIA expression levels. In conclusion, we identified multiple differentially expressed proteins by 2-D proteomics, and showed that some of these proteins might play a role in the pathogenesis of NHL

Effects of Shugan Hewei Granule on Depressive Behavior and Protein Expression Related to Visceral Sensitivity in a Rat Model of Nonerosive Reflux Disease

Objective. To explore the effect of Shugan Hewei Granule (SGHWG) and to provide the experimental basis for its clinical application. Methods. 40 healthy male Wistar rats were divided into 5 groups, with 8 rats in each group, including control group, model group, normal saline (NS) group, SGHWG group, and Rabeprazole group. The control group was not treated. The model group was treated with fructose intake and mental stress to be the model of NERD. The other groups were treated as the model group and then gavaged with the corresponding drugs. The pH value of lower third of esophagus, immobile time in tail suspension test, CRF protein expression in both hypothalamus and anterior cingulate cortex (ACC), and SP protein in esophageal mucosa in lower third of esophagus detected by immunofluorescence and NMDAR1 protein expression in spinal cord detected by immunohistochemistry of each group were compared. Results. The pH values of both the SGHWG group and the Rabeprazole group were higher than that of the model group (P<0.01), but the Rabeprazole group increased more obviously. The immobile time of the SGHWG group was shorter than that of the model group (P<0.01) and the Rabeprazole group (P<0.05). The expression of the CRF in the hypothalamus and ACC, NMDAR1 in the spinal cord, and SP in the esophageal mucosa in lower third of esophagus of the SGHWG group decreased significantly, compared with the model group (P<0.01), and was obviously lower than that in the Rabeprazole group (P<0.05). Conclusions. This study provided an evidence that SGHW formula was inferior to Rabeprazole in acid inhibition, but it might reduce the expression of CRF protein of hypothalamus and ACC, lower the levels of NMDAR1 in spinal dorsal horn and SP in esophageal mucosa in lower third of esophagus, and regulate depressive behavior simultaneously, related to the improvement of visceral hypersensitivity in rat model of NERD

DKI_201310999

Breast tumor DKI part

Characterization of breast tumors using diffusion kurtosis imaging (DKI).

The aim of this study was to investigate and evaluate the role of magnetic resonance (MR) diffusion kurtosis imaging (DKI) in characterizing breast lesions.One hundred and twenty-four lesions in 103 patients (mean age: 57 ± 14 years) were evaluated by MR DKI performed with 7 b-values of 0, 250, 500, 750, 1,000, 1,500, 2,000 s/mm2 and dynamic contrast-enhanced (DCE) MR imaging. Breast lesions were histologically characterized and DKI related parameters--mean diffusivity (MD) and mean kurtosis (MK)--were measured. The MD and MK in normal fibroglandular breast tissue, benign and malignant lesions were compared by One-way analysis of variance (ANOVA) with Tukey's multiple comparison test. Receiver operating characteristic (ROC) analysis was performed to assess the sensitivity and specificity of MD and MK in the diagnosis of breast lesions.The benign lesions (n = 42) and malignant lesions (n = 82) had mean diameters of 11.4 ± 3.4 mm and 35.8 ± 20.1 mm, respectively. The MK for malignant lesions (0.88 ± 0.17) was significantly higher than that for benign lesions (0.47 ± 0.14) (P < 0.001), and, in contrast, MD for benign lesions (1.97 ± 0.35 (10(-3) mm2/s)) was higher than that for malignant lesions (1.20 ± 0.31 (10(-3) mm2/s)) (P < 0.001). At a cutoff MD/MK 1.58 (10(-3) mm2/s)/0.69, sensitivity and specificity of MD/MK for the diagnosis of malignant were 79.3%/84.2% and 92.9%/92.9%, respectively. The area under the curve (AUC) is 0.86/0.92 for MD/MK.DKI could provide valuable information on the diffusion properties related to tumor microenvironment and increase diagnostic confidence of breast tumors

Data from: Characterization of breast tumors using diffusion kurtosis imaging (DKI)

Aim: The aim of this study was to investigate and evaluate the role of magnetic resonance (MR) diffusion kurtosis imaging (DKI) in characterizing breast lesions. Materials and Methods: One hundred and twenty-four lesions in 103 patients (mean age: 57±14 years) were evaluated by MR DKI performed with 7 b-values of 0, 250, 500, 750, 1,000, 1,500, 2,000 s/mm2 and dynamic contrast-enhanced (DCE) MR imaging. Breast lesions were histologically characterized and DKI related parameters—mean diffusivity (MD) and mean kurtosis (MK)—were measured. The MD and MK in normal fibroglandular breast tissue, benign and malignant lesions were compared by One-way analysis of variance (ANOVA) with Tukey's multiple comparison test. Receiver operating characteristic (ROC) analysis was performed to assess the sensitivity and specificity of MD and MK in the diagnosis of breast lesions. Results: The benign lesions (n = 42) and malignant lesions (n = 82) had mean diameters of 11.4±3.4 mm and 35.8±20.1 mm, respectively. The MK for malignant lesions (0.88±0.17) was significantly higher than that for benign lesions (0.47±0.14) (P<0.001), and, in contrast, MD for benign lesions (1.97±0.35 (10−3 mm2/s)) was higher than that for malignant lesions (1.20±0.31 (10−3 mm2/s)) (P<0.001). At a cutoff MD/MK 1.58 (10−3 mm2/s)/0.69, sensitivity and specificity of MD/MK for the diagnosis of malignant were 79.3%/84.2% and 92.9%/92.9%, respectively. The area under the curve (AUC) is 0.86/0.92 for MD/MK. Conclusions: DKI could provide valuable information on the diffusion properties related to tumor microenvironment and increase diagnostic confidence of breast tumors

Resveratrol induces autophagy-dependent apoptosis in HL-60 cells

Abstract Background All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. Methods Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry. Pharmaceutical or genetic inhibition of autophagy involved were carried by 3- methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Differences between two values were tested by Student’s unpaired t test. Results We show that resveratrol-induced apoptosis occurs through both the intrinsic and extrinsic apoptotic pathways. Mitochondrial membrane potential and apoptosis-related markers, such as an increased Bax/Bcl-2 ratio, and cleaved forms of caspase-8 and caspase-3, arise following resveratrol addition. Moreover, we find that resveratrol increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, and further demonstrate that resveratrol-induced autophagy depends on the LKB1-AMPK-mTOR pathway. We next reveal that some apoptosis-related markers induced by resveratrol are further attenuated by the inhibition of autophagy with 3-methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Conclusions These results suggest that resveratrol induced apoptotic cell death of HL-60 cells depends on the autophagy activated through both the LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways

Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in esophageal squamous cell carcinoma

The anti-cancer activity of resveratrol in human esophageal squamous cell carcinoma (ESCC) was investigated focusing on the role of autophagy and its effects on apoptotic cell death. We demonstrated that resveratrol inhibits ESCC cell growth in a dose-dependent manner by inducing cell cycle arrest at the sub-G1 phase and resulting in subsequent apoptosis. Mechanistically, resveratrol-induced autophagy in the ESCC cells is AMPK/mTOR pathway independent. Since both pharmacological and genetic inhibition of autophagy enhanced the resveratrol-induced cytotoxicity to the ESCC cells, this provided a novel strategy in potentiating the anti-cancer effects of resveratrol and other chemotherapeutic reagents in ESCC cancer treatment. © 2013 Elsevier Ireland Ltd