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

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

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

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

OBJECTIVETo examine whether the enhanced expression of CD40L cDNA on murine ovarian cancer (OVHM) cells could induce the secretion of Th1 cytokines from dendritic cells (DC).

METHODSOVHM cells were transfected with the full-length mouse CD40L cDNA by lipofectamine 2000 and then G418 resistant cells as positive cells were selected. They were examined for their expression of CD40L with flow cytometry. Bone marrow cells were firstly depleted of erythrocytes, macrophages, T and B cells with PE-conjugated magnetic beads, and then cultured in 10% FCS RPMI 1640 medium supplemented with recombinant mouse GM-CSF and IL-4 for 10 days. PKH67-labeled tumor cells were cultured with DC, and then the stained cells were analyzed for the expression of MHC-I, MHC-II, CD80, CD86, CCR7 in DC with flow cytometry. The expression of p40, p19, p35, p28, EBI3 subunits, IL-18, IFN-gamma, Mig gene in cocultured DC-tumor cells were detected by RT-PCR.

RESULTSThe CD40L cDNA was successfully transfected into OVHM cells. Bone marrow-derived DCs, when cultured with CD40L/OVHM, formed clusters with the tumors and showed an upregulated expression of MHC- I, MHC-II, CD80, CD86, CCR7. Expression of the IL-12, IL-23, IL-27, IL-18, interferon-gamma (IFN-gamma) and Mig (monokine induced by IFN-gamma) genes was induced in the DCs that were cultured with CD40L/OVHM but not with OVHM cells.

CONCLUSIONThese data directly showed that the expression of CD40L on ovarian cancer cells facilitates the interaction between DCs and tumors, enhances the maturation of DCs, induces secretion of Th1 cytokines, especially for IL-12, IL-23 and IL-27, which maybe one of the possible antitumor mechanism for CD40L-transfected ovarian cancer cell line.

Animals ; CD40 Ligand ; genetics ; metabolism ; Cell Line, Tumor ; Cells, Cultured ; Coculture Techniques ; Cytokines ; secretion ; DNA, Complementary ; genetics ; Dendritic Cells ; cytology ; metabolism ; Female ; Interleukin-12 ; secretion ; Interleukin-23 ; secretion ; Interleukins ; secretion ; Mice ; Ovarian Neoplasms ; metabolism ; pathology ; Th1 Cells ; secretion ; Transfection

BACKGROUNDThe interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture of T lymphocytes and BV-2 microglia cells.

METHODSTotally, 72 male C57BL/6 mice were randomly assigned to three groups (n = 24 in each): Group A: intrathymic injection of 100 μl MBP (1 mg/ml); Group B: intrathymic injection of 100 μl phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens of T lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [IL]-1β, tumor necrosis factor-α [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis.

RESULTSThe levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The levels of CD154 in Group A showed a downward trend from the 3rd to 7th day, with an upward trend from the 7th to 14th day (10.00 ± 0.23%, 5.28 ± 0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The ratio of CD4+/CD8 + T in Group A showed a downward trend from the 3rd to 7th day, with the minimum at postoperative day 7, then an upward trend from the 7th to 14th day (P < 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4+/CD8 + T (CD45: 83.39 ± 2.56%, 82.74 ± 2.09%, 87.56 ± 2.11%; CD54: 3.80 ± 0.24%, 0.94 ± 0.40%, 3.41 ± 0.33% at postoperative days 3, 7, and 14, respectively, P < 0.05). The expressions of TNF-α, IL-1β, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P < 0.05). No significant difference was found between Groups B and C.

CONCLUSIONSIntrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Antigens, Surface ; analysis ; Brain Injuries, Traumatic ; drug therapy ; CD4-CD8 Ratio ; Coculture Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Microglia ; immunology ; Myelin Basic Protein ; administration & dosage ; pharmacology ; T-Lymphocytes ; immunology