Expression of HDAC4 in human lung adenocarcinoma and its relationship with chemotherapy resistance / 医学研究生学报

Objective There have been few research on the relationship between expression of HDAC4 and chemotherapy resistance in human lung adenocarcinoma.The present study aims to investigate the expression and clinical significance of HDAC4 in human lung adenocarcinoma tissues.Methods We selected 72 tissues in lung adenocarcinoma patients with docetaxel-resistant from January 2006 to December 2007 in Department of Oncology and Thoracic Surgery, Nanjing General Hospital of Nanjing Military Region, then evaluated the recent efficacy according to the RECIST criteria and divided the tissues into sensitive(n=32, included complete remission and partial remission) and insensitive(n=40, included stability and progress) groups.The expression of HDAC4 in tissues≥the HDAC4 optimal relative expression cut-off value(78.7) was high level HDAC4 group(n=35), otherwise it was low level HDAC4 group(n=37).QRT-PCR analysis was performed to detect the HDAC4 expression levels in sensitive group and insensitive group.Analyzed the progression free survival in high level HDAC4 group and low level HDAC4 group.Results The expression of HDAC4 was significantly higher in the insensitive group compared with the sensitive group [(1.42±0.30) vs (0.60±0.15), P<0.01].The median progression free survival was significantly shortened in the high level HDAC4 group compared with the low level HDAC4 group (10.2 months vs 5.8 months, P<0.05).ConclusionThe expression of HDAC4 increased in docetaxel-resistant lung adenocarcinoma patients, and it is expected to be a predictive indicator of the resistance of docetaxel.

Aurora-A/NF-κB is involved in the radioresistance of human lung adenocarcinoma SPC-A1/DTX cells / 医学研究生学报

Objective Human lung adenocarcinoma SPC-A1/DTX cells have a higher radioresistance than SPC -A1cells. This study was to investigate the role of Aurora-An/uclear factor κB ( NF-κB) in the radioresistance of human lung adenocarcinoma SPC-A1/DTX cells and its possible molecular mechanisms . Metho ds We collected human lung adenocarcinoma SPC-A1 and SPC A1/DTX cells and divided them into four groups:sh-Aurora-A ( Aurora-A plasmid interference ) , sh-NC, NF-κB inhibition ( SPC-A1/DTX +NF-κB inhibitor ) , and DMSO control .We measured the in vitro radio-sensitivity of the cells by MTT assay , determined their proliferation ability by cloning assay , and detected the mRNA and protein expressions of the target genes by real -time quantitative RT-PCR and Western blot , respectively . Results The 50% effective doses ( ED50 ) of the SPC-A1 and SPC-A1/DTX cells on radiotherapy were (6.5 ±0.3) and (12.8 ±0.6) Gy, respectively, with statisti-cally significant difference between the two groups ( P <0.01 ) .In the radiation doses of 0, 2, 4, and 6 Gy, the numbers of the cloned SPC-A1 cells were 345 ±20 , 252 ±22 , 170 ±15 , and 81 ±10 , sig-nificantly lower than those of the cloned SPC -A1/DTX cells (402 ±21, 370 ±18, 301 ±16, and 252 ±15) (P<0.05).The protein and mRNA expressions of Aurora-A were remarkably higher in the SPC-A1/DTX than in the SPC-A1 cells (1.00 ±0.08 and 1.00 ±0. 06 vs 0.49 ±0.03 and 0.22 ±0.02, P<0.05).MTT assay showed a higher ED50 in the sh-NC than in the sh-Aurora-A cells ([11. 8 ±0.5] vs [7.1 ±0.3] Gy, P<0.01) as well as in the control than in the NF-κB inhibition group ([11.7 ±0.5] vs [6.1 ±0.3] Gy, P<0.01).Inhibition of Aurora-A increased the expression of IκBa by 2.18 ±0.32 times (P<0.01) and that of NF-κB by 0.24 ±0.03 times (P<0.01).The expressions of IκBa (1.00 ±0.05) and NF-κB (1.00 ±0.04) were significantly lower in the parent strains of SPC-A1 than 0.65 ±0.04 and 2.18 ±0.15 in the drug-resistant strains of SPC-A1/DTX (P<0.01). Conclusi on Auro-ra-A/NF-κB is involved in the radioresistance of human lung adenocarcinoma SPC-A1/DTX cells.

Disease mechanisms and emergence therapies: protein kinases and their inhibitors in cardiovascular diseases / 中国病理生理杂志

Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality in the world. So far, there has been substantial progress toward understanding the pathophysiology and treatment of CVDs. There are multiple cell signaling cascades, some of which are beneficial or compensatory and others deleterious. The balance between these pathways determines the outcome as a diseased or non-diseased state. Protein phosphorylation, which is mediated by enzymes, called protein kinases, is a major mechanism for transducing external stimuli into intracellular signals. Electively targeting of signaling pathways using protein kinase inhibitors would have a potential advantage over receptor blockers. By now, there are types of protein kinase inhibitiors available for treating several diseases. The success of kinase inhibitors in cancer treatment has strongly supported application in the treatment of CVDs. Here, we will review several kinds of protein kinases as potential targets for CVDs and some difficulty in identifying a protein kinase as a putative therapeutic target for CVDs.

Incidence of essential tremor associated with depression and related factors / 中华神经科杂志

Objective To study the incidence of depression in essential tremor (ET) and associated factors. Methods Depression in 62 ET patients and 60 healthy subjects as control was evaluated by means of Hamilton Depression Scale ( HAMD ) , as well as Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and Pittsburgh Sleep Quality Index (PSQI). Results Fifty-three point two percent(33/62) of ET patients and 11.7% (7/60) of healthy subjects were found to have at least mildly depression (HAMD score of 8 or higher), 35. 5% (22/62) of ET patients and 8. 3% (5/60) of healthy subjects fell into the mildly-to-mederately depression (HAMD score between 8 and 20 ), 17.7% (11/62) of ET patients and 3.3% (2/60) of healthy subjects were classified into moderately-to-severely depressed range (HAMD score between 21 and 35). There were statistical differences in ET group and healthy subjects group (X2= 23.898, 13.043, 6.649, all P <0.01). Additionally, there were statistical differences in anxiety/ somatization (t=-6.747, P<0.01), cognitive impairment (t=-2.017, P=0.05), block(t= -4.145, P<0.01), sleep disorders (t=-4.500, P<0.01) and despair (t=-3.591, P<0.01) between depression group and non-depression group. There were marked differences in PSQI total score ( t =-3.196, P=0.003 ), subjective sleep ( F1, t=-3.037, P=0.004), quality sleep latency (F2, t= -4.674, P<0.01) and sleep disturbances (F5, t=-2.594, P=0.013 ) between depression disorder group and non-depression disorder group. Meanwhile, the score of TRS, PSQI and sex were closely correlated with HAMD (β=0.589, P=0.000 ;β=0.469,P=0.000 ;β=0.256, P=0.027 ). Conclusions The incidence of depression is high in ET. Manifestation of depression are anxiety, reduced interest in work, sleep disorders, retardneas, inferiority complex, etc. The degree of symptoms relates to the severity of ET, sleep quality and gender.

Disease mechanisms and emergence therapies:protein kinases and their inhibitors in cardiovascular diseases / 中国病理生理杂志

Cardiovascular diseases(CVDs) are a major cause of morbidity and mortality in the world.So far,there has been substantial progress toward understanding the pathophysiology and treatment of CVDs.There are multiple cell signaling cascades,some of which are beneficial or compensatory and others deleterious.The balance between these pathways determines the outcome as a diseased or non-diseased state.Protein phosphorylation,which is mediated by enzymes,called protein kinases,is a major mechanism for transducing external stimuli into intracellular signals.Electively targeting of signaling pathways using protein kinase inhibitors would have a potential advantage over receptor blockers.By now,there are types of protein kinase inhibitiors available for treating several diseases.The success of kinase inhibitors in cancer treatment has strongly supported application in the treatment of CVDs.Here,we will review several kinds of protein kinases as potential targets for CVDs and some difficulty in identifying a protein kinase as a putative therapeutic target for CVDs.