Objective To explore the related factors for the prognosis in elderly cancer patients with cerebral metastases,to study the adaptability of brain metastasis in recursive partitioning analysis (RPA)and the prognosis Assessment (GPA) Scale,in order to provide the basis for the prognosis assessment and treatment in the elderly patients with brain metastasis.Methods A retrospective analysis was studied in 102 elderly cancer patients with brain metastasis (aged 60 years and over) with complete follow-up data in our hospital from January 2005 to January 2012.Survival analysis was performed by using the Kaplan-Meier method.Univariate analysis of ethnicity,age,Karnofsky score,gender,smoking,primary tumor origin,the number of intracranial metastatic tumor,intracranial and extracranial metastasis,the efficacy of treatment for primary tumor,the treatment of brain metastases were analyzed by Log-rank test.Results The median survival time was 6 months.The 6-month and 12-month survival rates were 54.90％ and 16.67％ respectively.Univariate analysis showed that Karnofsky score,smoking,the number of intracranial metastatic tumor,time to diagnosis and treatment,the efficacy of treatment for primary tumor and other underlying diseases were the relative factors for prognosis of elderly cancer patients with brain metastases (x2 =20.828,5.737,7.395,5.379,11.556,6.844,all P＜0.05).Cox multivariate regression analysis showed that the Karnofsky score,the number of intracranial metastatic tumor,the efficacy of treatment for primary tumor and other underlying diseases were the independent prognostic factors (all P＜0.05).The median survival periods in RPA class Ⅰ,Ⅱ,Ⅲ were 11,7,4 month respectively (x2 =27.358,P＜0.001).The median survival periods in GPA class Ⅰ,Ⅱ,Ⅲ-Ⅳ were 5,8,13 months respectively (x2 =29.570,P＜0.001).Conclusions Karnofsky score,the number of intracranial metastatic tumor,the efficacy of treatment for primary tumor and other underlying diseases are the independent factors for the prognosis in elderly cancer patients with cerebral metastases.RPA and GPA classification have a good adaptability in elderly patients with brain metastases.

Brain Edema ; etiology ; Brain Stem ; pathology ; Encephalitis ; etiology ; Female ; Hand, Foot and Mouth Disease ; complications ; therapy ; Humans ; Infant, Newborn

Aged ; Bile Duct Neoplasms ; diagnostic imaging ; mortality ; pathology ; surgery ; Cholangiopancreatography, Magnetic Resonance ; Female ; Humans ; Male ; Middle Aged ; Mucins ; biosynthesis ; Radiography

OBJECTIVETo study the clinicopathological features of patients with urothelial carcinoma of the urinary bladder (UCB), and analyze the association of clinicopathological characteristics with tumor recurrence and progression.

METHODSAltogether 658 UCB cases in Fudan University Shanghai Cancer Center were collected from January 2006 to December 2010. The histopathologic materials and the clinical records were reviewed. Univariate and multivariate analyses were preformed to detect the association.

RESULTSThe mean age of the patients was 61.97 +/- 12.97 years (range, 20-90 years). Male to female ratio was about 5:1. A total of 517 cases (78.6%) were superficial at the time of diagnosis (stage Ta/T1). The mean follow-up period was 22.36 +/- 24.92 months. Twenty-five patients lacking follow-up information were excluded in calculating recurrence and progression rates, the recurrence rate was about 37.0% (234/633), and progression rate about 6.2% (39/633). Three variables (grade, tumor growth pattern, and pathological stage) were found to be significant risk factors for tumor progression in univariate and multivariate analyses (P < 0.05).

CONCLUSIONSMost of the newly diagnosed UCB cases may be superficial diseases. Grade, tumor growth pattern, and pathological stage are associated with tumor progression of UCB.

Adult ; Aged ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; pathology ; Prognosis ; Urinary Bladder Neoplasms ; pathology

This study was aimed to investigate the expressions of tumor necrosis factor-alpha (TNF-alpha), Interleukin-6 (IL-6) in serum and the incidence of multiple organ dysfunction syndrome (MODS) in pigs with hemorrhagic shock after the blood transfusion simultaneously combined with different doses of free hemoglobin (FHb) so as to provide guidance of banked blood with high concentration of FHb during war injury through understanding effect of FHb on the animals. The different doses of FHb were given intravenously during the recovery of pig from shock, the vital signs and functional changes of vital organs were monitored and the incidence of MODS was determined, as well as the serum specimens were collected and the TNF-alpha, IL-6 levels in serum were detected by ELISA. The results showed that there were statistical differences of serum levels of TNF-alpha and IL-6 in pigs after FHb 10 mg/kg infusion, as compared to shock control group. There was significantly difference of the serum levels of TNF-alpha, IL-6 after FHb 15 mg/kg infusion, compared to the control group. The incidence of MODS increased significantly. It is concluded that the blood infusion containing high dose (more than 10 mg/kg) of FHb influences significantly on the cytokines in pigs with hemorrhagic shock, and increases damage of cytokines to vital organs and the incidence of MODS. The tolerance dose of the pigs to free hemoglobin is about 10 mg/kg or so. The infusion of blood with less than 10 mg/kg is relatively safe for pig in hemorrhagic shock.
Animals ; Disease Models, Animal ; Hemoglobins ; analysis ; Interleukin-6 ; blood ; Multiple Organ Failure ; etiology ; Serum ; metabolism ; Shock, Hemorrhagic ; blood ; Swine ; Tumor Necrosis Factor-alpha ; blood

AIM To investigate the effects of diosgenin on autophagy of human osteosarcoma cells.METHODS Human osteosarcoma MG63 and U2OS cells with or without exposure to diosgenin had their proliferation detected by MTT assay,their ultrastructure observed by transmission electron microscopy,their expression of autophagy protein Beclin1 observed by immunofluorescence staining,and their expressions of autophagy molecular markers LC3,Beclin1 and PI3K/Akt/mTOR signaling pathway related proteins detected by Western blot.The MG63 and U2OS cells cotreated with diosgenin and PI3K pathway inhibitor LY294002 had the expression of Beclin1 mRNA detected by RT-qPCR.The MG63 and U2OS cells cotreated with autophagy inhibitor 3-methyladenine(3-MA)had their inhibition rate of proliferation detected by MTT assay,their expression of cleaved-caspase3 protein detected by Western blot,and their expression of caspase3 mRNA detected by RT-qPCR.RESULTS Upon osteosarcoma MG63 and U2OS cells,diosgenin inhibited their proliferation,promoted the generation of autophagosomes,increased the protein expression of LC3 Ⅱ and Beclin1(P<0.05,P<0.01),reduced the protein expression of LC3 I(P<0.01),and inhibited the protein phosphorylation level of PI3K/Akt/mTOR pathway(P<0.05,P<0.01),whose effects were offset by the intervention with autophagy inhibitors in terms of the reduced proliferation inhibition and down-regulated expressions of caspase3 mRNA and cleaved-caspase3 protein(P<0.01).CONCLUSION Diosgenin can inhibit the proliferation of osteosarcoma cells and induce their autophagy leading to their death and autophagy apoptosis,which may be related to the activation of PI3K/Akt/mTOR signaling pathway and up-regulation of the expression of LC3 Ⅱ and Beclin1 proteins.

OBJECTIVETo explore the prognosis factors of hilar cholangiocarcinoma, and investigate the relation between operative procedure and prognosis of it.

METHODSA retrospective cohort study was investigated in 198 patients with hilar cholangiocarcinoma, who were treated in our hospital from December 1997 to December 2002. There were 117 males and 81 females. The age ranged from 27 to 81 years old with a mean of 56. Jaundice (94.5%), pruritus (56.6%) and abdominal pain (33.8%) were the main present symptoms. According to Bismuth-Corlette classification, there were 14 type I cases, 19 type II cases, 12 type IIIa cases, 15 type IIIb cases, 112 type IV cases and 26 unclassifiable cases. One hundred and forty four cases received open operative treatment, and the others only were treated with endoscopic approach (including ERBD or EMBE 21 cases, ENBD 31 cases) or percutaneous transhepatic cholangiodrainage (2 cases). Tumor resection was performed on 120 cases with a resection rate of 83.3%, included radical resection 59 cases (41.0%). Twenty-four cases underwent paunched biliary exploration and drainage.

RESULTSThe Cox's regression model analysis showed that occupation, preoperative maximum total serum bilirubin level, operative procedure and postoperative adjuvant radiation affected postoperative survival significantly, but gender, age, choledocholithiasis, hepatitis, preoperative serum CA19-9 level, Bismuth-Corlette type, histopathologic grading and postoperative chemotherapy were not significant prognostic factors. The postoperative survival of biliary drainage group, palliative resection group and radical resection group, which statistically differed pairwise. Between ERBD or EMBE group and palliative resection group, there was no statistical difference. So was between ERBD or EMBE group and biliary drainage group, or between ENBD group and biliary drainage group. The survival differed statistically between ERBD or EMBE group and ENBD group.

CONCLUSIONSOperative procedure was the most important prognosic factor of hilar cholangiocarcinoma, radical resection still was the primary measure to cure and long term survival. For irresectable hilar cholangiocarcinoma, the effect of ERBD or EMBE could not be considered to be worse than that of open operative treatment.

Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms ; surgery ; Bile Ducts, Intrahepatic ; surgery ; Biliary Tract Surgical Procedures ; methods ; Cholangiocarcinoma ; surgery ; Drainage ; methods ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

Glucosamine, a naturally occurring amino monosaccharide, has been reported to play a role in the regulation of apoptosis more than half century. However the effect of glucosamine on tumor cells and the involved molecular mechanisms have not been thoroughly investigated. Glucosamine enters the hexosamine biosynthetic pathway (HBP) downstream of the rate-limiting step catalyzed by the GFAT (glutamine:fluctose-6-phosphate amidotransferase), providing UDP-GlcNAc substrates for O-linked beta-N-acetylglucosamine (O-GlcNAc) protein modification. Considering that O-GlcNAc modification of proteasome subunits inhibits its activity, we examined whether glucosamine induces growth inhibition via affecting proteasomal activity. In the present study, we found glucosamine inhibited proteasomal activity and the proliferation of ALVA41 prostate cancer cells. The inhibition of proteasomal activity results in the accumulation of ubiquitinated proteins, followed by induction of apoptosis. In addition, we demonstrated that glucosamine downregulated proteasome activator PA28gamma and overexpression of PA28gamma rescued the proteasomal activity and growth inhibition mediated by glucosamine. We further demonstrated that inhibition of O-GlcNAc abrogated PA28gamma suppression induced by glucosamine. These findings suggest that glucosamine may inhibit growth of ALVA41 cancer cells through downregulation of PA28gamma and inhibition of proteasomal activity via O-GlcNAc modification.
Acetylglucosamine/chemistry/metabolism ; Alloxan/pharmacology ; Apoptosis/*drug effects ; Autoantigens/genetics/*metabolism ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Gene Expression Regulation, Neoplastic ; Glucosamine/*pharmacology ; Humans ; Male ; Phosphorylation ; Prostatic Neoplasms/*enzymology ; Proteasome Endopeptidase Complex/*antagonists & inhibitors/genetics/metabolism ; RNA, Small Interfering/genetics ; Ubiquitinated Proteins/metabolism

BACKGROUNDRunt-related transcription factor 1 (Runx1) plays a crucial role in hematogenesis and its dysfunction may contribute to leukemogenesis. However, it is not clear whether or not abnormal expression of Runx1 will induce leukemia and how the change of Runx1 expression level could affect BCR-ABL-induced leukemogenesis. In the present study, we aimed to analyze if abnormal expression of Runx1 in BaF3 cells alone would induce leukemogenesis. And we also wanted to know if abnormal expression of Runx1 in leukemic cells would affect leukemogenesis. Furthermore, we investigated whether overexpression or knock-down of Runx1 in BaF3 cells would induce leukemogenesis.

METHODSPlasmids containing full-length Runx1 cDNA were transduced into BaF3 cells and BaF3-P185wt cells (BCR-ABL transformed BaF3 cells) by electroporation. Plasmids containing a short hairpin RNA of Runx1 were transduced into BaF3 cells and BaF3-P185wt cells by electroporation. Runx1 expression level was quantified by Western blotting and quantitative real-time PCR. The effects of overexpression or knock-down of Runx1 on proliferation, apoptosis and migration of cells were detected in vitro. Then, using MSCV-P185wt-EGFP as a control, we transplanted MSCV-P185wt-Runx1 cells or MSCV-P185wt-shRNA cells into Balb/c mice through tail vein and observed tumorgenesis of the different phenotypes.

RESULTSIn vitro analysis revealed that overexpression of Runx1 in P185wt cells could inhibit cell proliferation and slow down cell migration; while knock-down of Runx1 could promote cell proliferation and speed up cell migration. In vivo analysis indicated that mice transplanted with MSCV-P185wt-Runx1 survived longer than controls. In contrast, mice transplanted with MSCV-P185wt-shRNA survived shorter than the control group. Gross pathological analysis revealed that the MSCV-P185wt-Runx1 group had less severe splenomegaly and hepatomegaly compared to the control group, and the MSCV-P185wt-shRNA group had more severe splenomegaly and hepatomegaly. No splenomegaly or hepatomegaly was detected in mice transplanted with MSCV-BaF3-Runx1 cells or MSCV-BaF3-shRNA cells. Both the mice of MSCV-BaF3-Runx1 group and MSCV-BaF3-shRNA group were healthy with no sign of leukemia for up to three months.

CONCLUSIONSOverexpression or knock-down of Runx1 gene in BaF3 cells alone could not induce leukemogenesis. However, in BaF3-P185wt cells, alteration of Runx1 expression could affect BCR-ABL-induced proliferation and migration in vitro and leukemogenesis in vivo.

Animals ; Apoptosis ; drug effects ; Blotting, Western ; Cell Line ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; physiology ; Fusion Proteins, bcr-abl ; pharmacology ; Leukemia ; genetics ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; Polymerase Chain Reaction

OBJECTIVETo study prognostic factors after surgical procedure for distal bile duct cancer.

METHODSA retrospective clinical analysis was made in 173 cases of distal bile duct cancer, admitted to our hospital from February 1996 to December 2002. Fourteen clinicopathologic factors that could possibly influence survival were selected. A multivariate analysis of these individuals was performed using the Cox Proportional Hazards Model.

RESULTSThere were 99 males and 74 females. The age ranged from 27 to 74 years old with a mean of 55.5. Radical resection was performed on 152 cases with radical resection rate of 87.9%. 29 cases died of liver metastasis with a rate of 46.8% in total death cases. The statistical analysis showed that surgical procedure, lymph node metastasis and pathological differentiation grade affected postoperative survival significantly, but transfusion, invasion of pancreas, postoperative radiotherapy and chemotherapy, ERCP, diameter of tumour, serum level of CA-19-9, preoperative total serum bilirubin level (TBIL), ratio of albumin to globulin (A/G), sex and age are not significant factors influencing postoperative survival.

CONCLUSIONSRadical resection is only curative treatment modality. Aggressive treatment and prevention on postoperative liver metastasis is a important strategy to improve the survival for distal bile duct cancer.

Adult ; Aged ; Bile Duct Neoplasms ; mortality ; pathology ; surgery ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate