70 bpm during scan),the proportion of segments that could not be assessed because of motion artifact were 0.1%(1/759),1.1%(7/649),2.5% (10/407),42.6%(103/242),and 75.5%(108/143),respectively.With conventional selective coronary angiography as the golden standard,the sensitivity,specificity,positive and negative prediction values to detect≥50% stenotic lesions in the assessable segments were 79.2%,96.0%,83.8%,and 94.6%,respectively.There was a significant correlation between the number of segments per patient not assessable because of motion artifact and heart rate during the scan(r=0.655,P=0.000).Conclusion MSCT is capable of achieving high accuracy for detection of coronary artery stenosis,and is a reliable technique to diagnose coronary artery disease.

This study was purposed to investigate the expression of Btk and NFκB in acute myeloid leukemia (AML) cells and its significance. Bone marrow mononuclear cell specimens were taken from 14 AML patients who were in new diagnosis and complete remission respectively, the expressions of Btk and NFκB at mRNA and protein levels were detected by RT-PCR and Western blot, respectively. The results showed that Btk and NFκB expressed in all the samples at RNA and protein levels. At protein level, Btk and NFκB expressions were higher in the cells from newly diagnosed AML patients than that in the cells from patients in complete remission stage (P < 0.05). It is concluded that Btk and NFκB may play an important role in the development and progression of AML, they may be used as potential therapeutic targets of AML and used in predicting the prognosis.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; Male ; Middle Aged ; NF-kappa B ; genetics ; Prognosis ; Protein-Tyrosine Kinases ; genetics ; RNA, Messenger ; genetics ; Young Adult

OBJECTIVETo investigate the effects of the epidermal growth factor on the mRNA expression of endothelin-1 and its receptors (ET(A)R, ET(B)R) in hormone refractory prostate cancer (HRPC) PC-3 cell lines.

METHODSPC-3 cells were cultured in vitro. After the treatment with EGF, the mRNA expressions of endothelin-1, ET(A)R and ET(B)R were detected by RT-PCR in PC-3 cell lines. The levels of the mRNA expression of endothelin-1 and its receptors were examined at different time points by RT-PCR.

RESULTSThe expressions of endothelin-1 and ET(A)R mRNA but not the mRNA expression of ET(B)R was observed in PC-3 cell lines. After 24 hours of treatment with EGF, the expressions of endothelin-1 and ET(A)R in PC-3 cell lines were both up-regulated and there was significant difference (P < 0.05) between the experimental and control groups. Different expression levels of endothelin-1 and ET(A)R mRNA were noted at different time points of EGF intervention, up-regulated with the increase of treatment time, and with significant difference (P < 0.05).

CONCLUSIONEGF can up-regulate the mRNA expressions of endothelin-1 and ET(A)R in PC-3 cell lines and play a great role in prostate cancer progression, which may offer a substructure of molecular biology for the treatment of HRPC.

Cell Line, Tumor ; Endothelin-1 ; genetics ; Epidermal Growth Factor ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Male ; Prostatic Neoplasms ; genetics ; pathology ; RNA, Messenger ; genetics ; metabolism ; Receptor, Endothelin A ; genetics ; Receptor, Endothelin B ; genetics ; Receptors, Endothelin ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUNDIn humans telomerase is expressed in most cancers and immortal cell lines, and activation of telomerase may play important roles in tumorigenesis and immortalization. This study was to investigate the roles of telomerase activity (TA) and human telomerase RNA (hTR) in sebaceous carcinoma of the eyelid.

METHODSThe telomerase repeated amplification protocol (TRAP) was used to demonstrate telomerase activity in 12 cases of sebaceous carcinoma of the eyelid. In situ hybridization (ISH) was used to demonstrate the expression of hTR in 55 cases of paraffin-embedded sebaceous carcinoma of the eyelid, and the results were compared with the proliferative index determined by Mib-1 immuno-labeling, histological patterns and recurrence of the tumor.

RESULTSDifferent telomerase activity was shown in the 12 cases of sebaceous carcinoma of the eyelid. The positive expression of hTR was 85.5% (47/55) in tumor cells, but not in the adjacent tissues. The positive expression of hTR was correlated with the proliferative activity (as assessed by Mib-1 immunolabelling, r = 0.942, P < 0.001) and the differentiation of sebaceous carcinoma of the eyelid (chi(2) = 17.621, P < 0.001), but not significantly related to tumor recurrence. The level of hTR expression increased with the decrease of differentiation of sebaceous carcinoma of the eyelid.

CONCLUSIONSThe results suggest that the up-regulation of telomerase expression plays some roles in tarsal gland carcinogenesis, and the expression of hTR is a useful marker for malignant degree of sebaceous carcinoma of the eyelid.

Biomarkers, Tumor ; analysis ; Eyelid Neoplasms ; enzymology ; pathology ; Humans ; In Situ Hybridization ; Neoplasm Recurrence, Local ; enzymology ; RNA ; analysis ; Sebaceous Gland Neoplasms ; enzymology ; pathology ; Telomerase ; analysis

OBJECTIVETo explore the risk factors for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the measures of prophylaxis and treatment.

METHODSWe summarized the clinical data of 82 patients with hematologic malignancies who were treated in our hospital from August 2003 to December 2008. Factors including age, sex, ABO blood group disparity of donor and recipient as well as the type of donor, status of disease, HLA-match, conditioning regimen, whether or not having developed acute GVHD and chronic GVHD, infusion number of CD34(+) cells, relationship between CMV infection and relapse post-transplantation were considered and analyzed.

RESULTSSingle factor analysis indicated that there were five independent risk factors related with the disease relapse (P < 0.05), including status of disease, time of diagnosis to transplantation, acute graft versus host disease (aGVHD), conditioning regimen, and chronic graft versus host disease (cGVHD). Simultaneously, the type of donor was a substantial factor (P < 0.01), determined by multi-factor Cox regression analysis. Cox regression analysis determined that disease status (OR = 2.58, 95%CI 1.26 - 5.01, P = 0.01), time from diagnosis to treatment (OR = 1.98, 95%CI 1.11 - 3.63, P = 0.025) and cGVHD (OR = 3.74, 95%CI 1.96 - 7.97, P < 0.001) were major factors for relapse of the patients who had undergone transplantation.

CONCLUSIONSRelapse remains the primary cause of failure after allo-HSCT. Status of disease, time from diagnosis to treatment and not cGVHD are the major risk factors. Effective prevention and treatment of relapse after engraftment can improve the efficacy of HSCT.

Adolescent ; Adult ; Child ; Female ; Follow-Up Studies ; Graft vs Host Disease ; etiology ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Infection ; etiology ; Male ; Middle Aged ; Recurrence ; Risk Factors ; Time Factors ; Transplantation Conditioning ; Transplantation, Homologous ; Young Adult

The aim of this study was to analyze the risk factors for overall survival at 5 years in 96 patients undergoing allogeneic hematopoietic stem cell transplantation by retrospective analysis. 11 clinical parameters including age, sex, disease status, HLA locus, donor type, donor-recipient blood type, conditioning regimen, aGVHD, HC, VOD and IP were selected for univariate analysis by using a Cox regression. Factors have statistic significance at the 0.1 level on univariate analysis were evaluated by multivariate analysis by a Coxs regression. The cumulative incidence of aGVHD and survival rate of patients were calculated by the method of Kaplan and Meier. The results showed that 95 patients achieved sustained donor engraftment except 1 patients. The median time of leukocyte engraftment (ANC > or = 0.5 x 10(9)/L) was 13 days. The aGVHD of I - IV grade was observed in 42 out of 96 patients (43.75%), in which 11 patients were with aGVHD of I grade (11.46%), 19 patients were with aGVHD of II grade (19.79%), 12 patients were with aGVHD of III - IV grade (12.50%). Out of 96 patients 10 relapsed and 38 dead, the overall survival at 5 years was 60.42%. The Cox regression analysis showed that aGVHD and disease status before transplant were main factors affecting long-term survival of patients, relative risks of which were 2.996 and 2.619 respectively. It is concluded that the main factors affecting long-term survival of patients are aGVHD and disease status. The key to improve the outcome of allo-HSCT is to reduce the incidence and severity of aGVHD, meanwhile to select the CR1 for allo-HSCT to treat the patients in advanced refractory and relapsed situation should be considered as important risk factors.
Adolescent ; Adult ; Child ; Disease-Free Survival ; Female ; Graft vs Host Disease ; etiology ; mortality ; Hematopoietic Stem Cell Transplantation ; mortality ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Survival Rate ; Transplantation, Homologous ; Young Adult

BACKGROUND AND OBJECTIVEAllogeneic hematopoietic cell transplantation (allo-HSCT) is a potent procedure for the treatment of hematologic diseases, yet it is associated with high risks of treatment-related complications. Except for transplant-related organ toxicities, renal insufficiencies which emerge earlier significantly limit patients' long survival. To analyze risk factors for acute kidney injury (AKI), we conducted a retrospective cohort study of 96 patients undergoing HSCT.

METHODSDuring the first 100 days after allo-HSCT, all patients were evaluated for renal function by measuring serum creatinine clearance and glomerular filtration rate (GFR) with a classification below: Grade 0 (<25%, decline in creatinine clearance), Grade 1 (≥25% decline in creatinine clearance but <2-fold increase in serum creatinine), Grade 2 (≥2-fold rise in serum creatinine but no need for dialysis), and Grade 3 (≥2-fold rise in serum creatinine and need for dialysis). Cox regression model was used to calculate the hazard ratios (HRs) of demographic data, clinical variables, and risk factors for AKI.

RESULTSTwenty-eight (29.2%) patients occurred Grades 1-3 renal dysfunction (Grade 1, 14 patients; Grade 2, 12 patients; Grade 3, 2 patients), and ratios of early kidney injury increased in high-risk malignancy group (HR = 2.945, 95% confidence interval (CI)=1.293-6.421), patients treated with myeloablative conditioning regimen (HR=2.463, 95% CI=1.757-4.320), and patients with acute GVHD (HR=3.553, 95% CI=1.809-6.978), sepsis (HR=3.215, 95% CI=1.189-6.333 ), or hepatic veno-occlusive disease (VOD) (HR=3.487, 95% CI=1.392-6.524). Whereas, HLA histocompatibility showed no striking increased risk for acute renal injury (HR=1.684, 95% CI=0.648-4.378). The survival rate was lower in patients with severe nephrotoxicity (21.4%) than in patients without nephrotoxicity (70.6%) (P=0.001).

CONCLUSIONSNephrotoxicity is the primary risk factor for AKI, severely impacting on survival. Sorts of risk factors mentioned will be useful for evaluation for kidney function of patients undergoing allo-HSCT.

Acute Kidney Injury ; etiology ; Adolescent ; Adult ; Child ; Cohort Studies ; Creatinine ; blood ; Female ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Kidney Function Tests ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; surgery ; Leukemia, Myeloid, Acute ; surgery ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; surgery ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Risk Factors ; Survival Rate ; Transplantation Conditioning ; Transplantation, Homologous ; Young Adult

OBJECTIVETo explore the potential risk factors of intrahepatic cholangiocarcinoma (ICC) in China.

METHODA case-control study including 317 patients with pathologically confirmed ICC and 634 healthy individuals was conducted. The cases and controls were matched in age, sex and inhabitancy. Data were statistically analyzed by Chi-square test and conditional logistic regression.

RESULTSUnivariate analysis showed significant difference in HBsAg seropositivity, liver cirrhosis, hepatolithiasis, choledocholithiasis and schistosomiasis between ICC patients and healthy controls (P < 0.05). Multivariate analysis confirmed that HBsAg seropositivity, liver cirrhosis, hepatolithiasis and hepatic schistosomiasis were associated with ICC, and their adjusted odds ratio (95% confidence interval) were 10.265 (6.676-15.783), 13.101 (5.265-32.604), 18.242 (3.580-92.958), 18.435 (1.930-176.082), 15.102 (4.607-49.499) and 11.820 (3.522-39.668), respectively. The incidence of hepatic cyst, cholecystolithiasis, hepatic hemangioma, fatty liver, diabetes mellitus, smoking and drinking were not significantly different between ICC patients and controls.

CONCLUSIONSThe HBV infection, liver cirrhosis, hepatolithiasis and hepatic schistosomiasis may be the risk factors for ICC in China.

Adult ; Aged ; Bile Duct Neoplasms ; epidemiology ; etiology ; Bile Ducts, Intrahepatic ; Case-Control Studies ; Cholangiocarcinoma ; epidemiology ; etiology ; Cholelithiasis ; complications ; epidemiology ; Female ; Hepatitis B ; complications ; epidemiology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Humans ; Liver Cirrhosis ; complications ; epidemiology ; Liver Diseases ; complications ; epidemiology ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Risk Factors

OBJECTIVETo investigate the inhibitory effect of HSP90 inhibitory 17-AAG on proliferation of multiple myeloma cells and its main mechanism.

METHODSThe multiple myeloma cells U266 were treated with 17-AAG of different concentrations (200, 400, 600 and 800 nmol/L) for 24, 48, and 72 hours respectively, then the proliferation rate, expression levels of β-catenin and C-MYC protein, as well as cell cycle of U266 cells were treated with 17-AAG and were detected by MTT method, Western blot and flow cytometry, respectively.

RESULTSThe 17-AAG showed inhibitory effect on the proliferation of U266 cells in dose- and time-depetent manners (r = -0.518, P < 0.05 and r = -0.473, P < 0.05), while the culture medium without 17-AAG displayed no inhibitory effect on proliferation of U266 cells (P > 0.05). The result of culturing U266 cells for 72 hours by 17-AAG of different concentrations showed that the more high of 17-AAG concentration, the more low level of β-catenin and C-MYC proteins (P < 0.05); At same time of culture, the more high of 17-AAG concentration, the more high of cell ratio in G1 phase (P < 0.05), at same concentration of 17-AAG, the more long time of culture, the more high of cell ratio in G1 phase (P < 0.05).

CONCLUSIONThe HSP90 inhibitory 17-AAG can inhibit the proliferation of multiple myeloma cells, the down-regulation of Wnt/β-catenin signaling pathway and inhibition of HSP90 expression may be the main mechnisms of 17-AAG effect.

Apoptosis ; Benzoquinones ; pharmacology ; Cell Cycle ; Cell Division ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Down-Regulation ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; Humans ; Lactams, Macrocyclic ; pharmacology ; Multiple Myeloma ; metabolism ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

UNLABELLEDObjective：To explore the influence of co-inhibiting mTORC2 and HSP90 on the proliferation and apoptosis of multiple myeloma(MM) cell line U266.

METHODSDuring culture, the human MM cell line U266 were treated with 20 nmol/L of rapamycin, 600 nmol/L 17-AAG, 20 nmol/L of rapamycin + 600 nmol/L 17-AGG and phosphate-buffered saline (PBS), then the growth inhibition rate, morphologic changes, apoptosis rate and the expression of caspase 3 and ATK protein in U266 cells were compared and analyzed.

RESULTSThe rapamycin and 17-AAG both could inhibit the growth of U266 cells, while the inhibitory effect of rapamycin in combination with 17-AAG on growth of U266 cells was significantly higher them that of rapamycin and 17-AAG alone and control (PBS); the apoptosis rate of U266 cells treated with rapamycin, 17-AAG and their combination was higher than that of control PBS groups, and the efficacy of 2 drug conbination was higher than that of control PBS group, and the efficacy of 2 drug combination was superior to single drug. The expression levels of caspase 3 and ATK in U266 cells treated with rapamycin, 17-AAG and their combination were higher and lower than those in control group respectively, and the efficacy of 2 drug combination was superior to signle drug. There were significant difference between them (P<0.05).

CONCLUSIONThe co-inhibition of mTORC2 and HSP90 can suppress the proliferation and induce the apoptosis of MM cells.

Apoptosis ; Benzoquinones ; Caspase 3 ; Cell Line, Tumor ; Cell Proliferation ; HSP90 Heat-Shock Proteins ; Humans ; Lactams, Macrocyclic ; Mechanistic Target of Rapamycin Complex 2 ; Multiple Myeloma ; Multiprotein Complexes ; Sirolimus ; TOR Serine-Threonine Kinases