Chronic lymphocytic leukemia (CLL) is a kind of malignant B-cell chronic lymphoproliferative disorder with highly heterogeneous clinical courses. Due to the recent advances in immunology, cellular genetics and molecular biology, several prognostic markers based on genetic, phenotypic, and molecular biology characteristics of CLL cells have emerged in the past decade. This article reviews the reports from the 57th American Society of Hematology (ASH) annual meeting on the progress of the prognosis of CLL.

Objective To investigate the effect and underlying mechanism of Caudatin combined with Gefitinib on Gefitinib resistance induced by HGF in PC-9.Methods Model of EGFR-TKIs resistance in PC-9 cells was induced by exogenous HGF and co-cultured with MRC-5.Caudatin was tested as a drug resistant modulator to reverse the resistance of Gefitinib in PC-9 cells induced by HGF by MTT assay.Western blot was performed to observe the mechanism of Caudatin combined with Gefitinib reversing the resistance of PC-9 induced by HGF.Results The resistance of gefitinib to PC-9 was induced by exogenous HGF and co-cultured with MRC-5 which could reduce relative inhibitory rate ( P<0.05 ) .Neither caudatin ( 0-32 μM ) or Gefitinib (1μM) alone could significantly inhibit proliferation of PC-9 in the presence of HGF, which could be inhibited in a dose-dependent manner by Caudatin combined with Gefitinib ( P<0.05 ); Caudatin combined with Gefitinib down-regulated the phosphorylation levels of Met and PI3K/Akt simultaneously (P<0.05).Conclusion Caudatin could reverse the drug resistance of Gefitinib in PC-9 induced by HGF, the mechanism of which may be related to the inhibition of Met/PI3K/AKT pathway.

Objective To discuss the method for operative treatment of acetabular fractures and assess corresponding results.MethodTotally 34 cases of acetabular fractures treated operatively from February 2000 to December 2005 were reviewed. There were 22 males and 12 females, with an average age of 39 years (16 to 61).On the basis of X-ray and computed tomography,all fractures were classified according to the Letournel-Judet classification,13 cases were simple fractures and 21 complicated ones. Kocher-Langenbeck approach(23 cases),illioinguinal approach(6 cases) and anterior combined posterior approach(5 cases) were adopted for different fractures with reconstruction plates and screws.The mean operation time was 150 min.The average blood loss was 600 mL.ResultAll cases were followed up for average 31 months(12 to 64 months).According to the criteria of Matta radiographicgrade,there were 18 cases with anatomic reduction, 9 with satisfactory reduction,3 with unsatisfactory reduction and 4 with joint contour reduction.Based on the modified Merle D' Aubigne and Postel clinical grading system for joint functions,11 cases(32.4%)showed excellent results,15(44.1%)good,4(11.8%)fair and 4(11.8%)poor. The excellent and good rate for anatomic and satisfactory reduction groups were 85.2%,while unsatisfactory reduction and joint contour reduction were 42.9%(P

Objective To explore differentiation in vitro of rat adipose-derived stem cells into photoreceptor cells and RPE cells.Methods The ADSCs were cultured by adhering to the flask surface and purified by continual passaging.Surface antigens including CD45、CD90、CD49d、CD106 were indentified by flow cytometry.ADSCs were induced to differentiate by EGF,activin A,taurine,retinoic acid(RA) and extracted liquid of retina respectively.Meanwhile,ADSCs were induced by EGF+taurine,EGF+RA,taurine + RA,EGF+taurine+RA respectively.Immunofluorescence was used for detecting the expression of rhodopsin,CK and S-100,and flow cytometry was used for quantification.Results For primary culture,the phenotypes of ADSCs were: CD45,CD90,CD49d and CD106,with a positive percentage of 1.6%,71.3%,7.8% and 3.5%,respectively.From passage 1 to 5,these phenotypes were: CD45(0.8%～9.3%),CD90(84.7%～94.8%),CD49d(16.8%～31.0%)and CD106(8.3%～22.2%).There was a higher CD49d percentage than CD106 in all the passages.The induction efficacy of ADSCs was 17.5%～46.0% for rhodopsin,19.7%～79.3% for CK and 27.3%～50.7% for S-100.Conclusion It is suggested that ADSC has potential to differentiate into photoceptors and RPE cells as evidenced by thepresence of the specific markers of photoceptors(rhodopsin) and RPE markers(CK and S-100).

OBJECTIVE: To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism. METHODS: MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting. RESULTS: HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells. CONCLUSIONS HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Breast Neoplasms ; drug therapy ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; ErbB Receptors ; metabolism ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Signal Transduction ; drug effects

OBJECTIVE: To investigate the inhibitory effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI) HS-10296 on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells and explore the possible molecular mechanism. METHODS: MDA-MB-231 cells were treated with HS-10296 for 24, 48, or 72 h, and CCK-8 assay was used to assess the changes in the cell viability. The inhibitory effect of HS-10296 on cell proliferation was determined by clonogenic assay. JC-1 and flow cytometry were employed for analyzing the cell apoptosis, and the ultrastructure of the cells was observed under electron microscope. After pretreatment with autophagy inhibitor chloroquine (CQ), MDA-MB-231 cells were divided into control group, CQ treatment group, HS-10296 (4 and 6 μmol/L) treatment groups and combined treatment groups, and the sensitivity of the treated cells to HS-10296 was determined using CCK-8 assay. The effects of HS-10296 on EGFR pathway and apoptosis- and autophagy-related proteins in MDA-MB-231 cells were investigated using Western blotting. RESULTS: HS-10296 significantly inhibited the proliferation of MDA-MB-231 cells with IC values at 24, 48 and 72 h of 8.393, 2.777 and 2.016 μmol/L, respectively. JC-1 and flow cytometry showed that HS-10296 induced obvious apoptosis of MDA-MB-231 cells, which showed an apoptosis rate of (21.63 ± 2.97)% following treatment with 8 μmol/L HS-10296. Autophagy vesicles were observed in the cells treated with HS-10296 under electron microscope. In MDA-MB-231 cells pretreated with CQ, inhibition of autophagy significantly enhanced HS-10296-induced cell death. Western blotting showed that the apoptosis-related protein caspase-3 was activated after HS-10296 treatment to cut its substrate PARP. The expression of autophagy-related protein light chain 3B (LC3B) was significantly enhanced after HS-10296 treatment ( < 0.01), which also resulted in inhibited phosphorylation of EGFR and AKT proteins in the cells. CONCLUSIONS HS-10296 can inhibit the proliferation and induce autophagy and apoptosis of MDA-MB-231 cells by inhibiting the EGFR/PI3K/AKT signaling pathway.
Apoptosis ; Autophagy ; Breast Neoplasms ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors ; Humans ; Phosphatidylinositol 3-Kinases ; Protein Kinase Inhibitors