OBJECTIVETo compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery.

METHODSThe clinical data of 54 cHCC-CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery.

RESULTSThe TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively.

CONCLUSIONThe 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment.

Bile Duct Neoplasms ; diagnosis ; surgery ; Carcinoma, Hepatocellular ; diagnosis ; surgery ; Cholangiocarcinoma ; diagnosis ; surgery ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; surgery ; Neoplasm Staging ; methods ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Survival Rate

BACKGROUNDDocetaxel (DOC) therapy is well tolerated and shows high response rates in patients with hormone refractory prostate cancer (HRPC). There are many reports on the effect of rapamycin (RPM) on the treatment of carcinogenesis. The goal of this study was to test whether RPM could enhance the susceptibility of both androgen-dependent and -independent prostate carcinoma cells to DOC.

METHODSProstate cancer (PC) cell lines (LNCap, PC3 and AILNCap) were cultured and treated with RPM and DOC alone or in combination. The effects of therapeutic agents on cells were determined by the WST-1 assay. Apoptosis induction was confirmed by flow cytometric analysis. The apopcyto caspase colorimetric assay kit was applied to measure the activities of caspases 3 and 9. The antitumor effects of RPM and DOC against PC cells were also assessed in nude mice using four randomized groups: control, RPM, DOC and combination drug therapy by measuring tumor size. All the animals tolerated both RPM and DOC without significant weight loss.

RESULTSRPM and DOC caused dosage-dependent growth suppression of PC cells. RPM could increase the susceptibility of PC cells to DOC significantly, and combined treatment with RPM and DOC caused synergistic growth suppression in all examined PC cell lines by isobolographic analysis. Both RPM and DOC significantly induced apoptosis in a dosage-dependent manner. RPM (10 nmol/L), DOC (1 nmol/L), and combined treatment induced apoptosis rate were 8%, 17% and 38%, respectively (the control was 2%). RPM could promote the apoptosis induced by DOC in PC cell lines. Both RPM and DOC significantly increased the caspase activity in a dosage-dependent manner. The relative activities of caspase 9 in control, RPM, DOC and RPM + DOC groups were 0.22 +/- 0.02, 0.36 +/- 0.06, 0.47 +/- 0.05 and 0.84 +/- 0.08, respectively. The relative activities of caspase 3 were 0.21 +/- 0.02, 0.24 +/- 0.05, 0.42 +/- 0.06 and 0.81 +/- 0.09, respectively. Either RPM or DOC alone significantly inhibited the growth of PC cells in nude mice compared to the control. The combination of RPM and DOC produced a significant reduction in tumor volume when compared to RPM or DOC alone. After 5-week treatment, the tumor sizes of LNCap in control, RPM, DOC and RPM + DOC groups were (570 +/- 56) mm(3), (412 +/- 41) mm(3), (425 +/- 46) mm(3) and (221 +/- 26) mm(3), respectively.

CONCLUSIONSRPM could significantly increase the susceptibility of both androgen-dependent and -independent PC cells to DOC; the synergy of RPM and DOC was demonstrated. RPM enhanced the DOC-induced upregulation of caspase activity, resulting in an increasing number of cells in sub-G1 phases. The synergy of the combined treatment might be observed in both androgen-dependent and -independent PC cell lines.

Animals ; Antineoplastic Agents ; therapeutic use ; Cell Line, Tumor ; Drug Synergism ; Flow Cytometry ; Humans ; Male ; Mice ; Mice, Nude ; Prostatic Neoplasms ; drug therapy ; Random Allocation ; Sirolimus ; therapeutic use ; Taxoids ; therapeutic use ; Xenograft Model Antitumor Assays

BACKGROUNDEarly onset severe preeclampsia is a specific type of severe preeclampsia, which causes high morbidity and mortality of both mothers and fetus. This study aimed to investigate the clinical definition, features, treatment, outcome and risk factors of early onset severe preeclampsia in Chinese women.

METHODSFour hundred and thirteen women with severe preeclampsia from June 2006 to June 2009 were divided into three groups according to the gestational age at the onset of preeclampsia as follows: group A (less than 32 weeks, 73 cases), group B (between 32 and 34 weeks, 71 cases), and group C (greater than 34 weeks, 269 cases). The demographic characteristics of the subjects, complications, delivery modes and outcome of pregnancy were analyzed retrospectively.

RESULTSThe systolic blood pressure at admission and the incidence of severe complications were significantly lower in group C than those in groups A and B, prolonged gestational weeks and days of hospitalization were significantly shorter in group C than those in groups A and B. Liver and kidney dysfunction, pleural and peritoneal effusion, placental abruption and postpartum hemorrhage were more likely to occur in group A compared with the other two groups. Twenty-four-hour urine protein levels at admission, intrauterine fetal death and days of hospitalization were risk factors that affected complications of severe preeclampsia. Gestational week at admission and delivery week were also risk factors that affected perinatal outcome.

CONCLUSIONSEarly onset severe preeclampsia should be defined as occurring before 34 weeks, and it is featured by more maternal complications and a worse perinatal prognosis compared with that defined as occurring after 34 weeks. Independent risk factors should be used to tailor the optimized individual treatment plan, to balance both maternal and neonatal safety.

Adult ; Cardiovascular Diseases ; epidemiology ; etiology ; Female ; Fetal Death ; Gestational Age ; Humans ; Pre-Eclampsia ; epidemiology ; mortality ; Pregnancy ; Pregnancy Complications ; epidemiology ; mortality ; Risk Factors

OBJECTIVETo investigate the main risk factors for postoperative severe complications, and establish Logistic regression model to predict severe complications in gastric cancer following gastrectomy.

METHODSThe data of 1728 gastric cancer patients underwent gastrectomy between June 2001 and June 2007 were analyzed retrospectively. Logistic regression analysis was used to investigate the risk factors for postoperative severe complications in those patients.

RESULTSPostoperative severe complications were associated with extent of lymph node dissection (D(2)(+)-D(3)), chronic obstructive pulmonary disease (COPD), invasion to the adjacent organ, combined organ resection, extent of lymph node dissection (D(2)), diabetes mellitus (DM), TNM staging IV, heart diseases, malnutrition, surgeon's operative volume, operative time, blood loss and age. The Logistic regression model was P = 1/[1+e((14.806-2.523X1-1.792X2-1.558X3-1.551X4-1.270X5-1.150X6-1.101X7-0.981X8-0.817X9-0.657X10-0.578X11-0.542X12-0.309X13))]. A testing sample showed that the accuracy, sensitivity and specificity of the Logistic model were 72.5%, 70.0% and 75.0%, respectively.

CONCLUSIONSThe extent of nodal dissection (D(2)(+)-D(3)), COPD, invasion to the adjacent organ, combined organ resection, extent of nodal dissection (D(2)), diabetes mellitus, TNM staging IV, heart diseases, malnutrition, surgeon's operative volume, operative time, blood loss and age are the independent risk factors associated with severe complications in gastric cancer post gastrectomy. The Logistic regression model based on these factors is reliable in predicting the severe complications.

Adult ; Aged ; Aged, 80 and over ; Female ; Gastrectomy ; adverse effects ; Humans ; Logistic Models ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; surgery

OBJECTIVETo determine the accuracy and clinical value of combining 64 multi-slice spiral computer tomography (MSCT) and serum amyloid A protein (SAA) in the preoperative staging of rectal cancer.

METHODSProspectively enrolled patients with rectal cancer from October 2007 to October 2008. The patients were randomly assigned into two groups: MSCT and SAA combined group: both MSCT and SAA combinative assessment were performed for preoperative evaluation; MSCT group: only MSCT was performed preoperatively for tumor staging. The accuracy of the preoperative T, N, M, and TNM staging and the concordance rate of predictive operative strategy were compared between the two groups.

RESULTSTotal of 225 cases with rectal cancer were enrolled in this study. There were 110 cases in MSCT and SAA combined group and 115 cases in MSCT group. The baseline characteristics was comparable between the two groups. For MSCT and SAA combined group, the accuracies of preoperative staging of T, N, M and TNM was 87.3%, 85.2%, 100% and 86.4%, respectively; and for MSCT group, the corresponding rates was 85.2%, 67.0%, 100% and 66.1%, respectively. Statistical differences was found in the accuracy of preoperative N and TNM staging between the two groups (P = 0.009 and 0.001, respectively). In addition, there was statistical difference in the accuracy of prediction to operative procedures between the two groups (94.7% vs. 81.7%, P = 0.003).

CONCLUSIONCombinative assessment of MSCT and SAA could improve the accuracy of preoperative staging, and thus provide higher predictive coincidence rate of operative procedures.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Preoperative Care ; Prospective Studies ; Rectal Neoplasms ; diagnosis ; surgery ; Serum Amyloid A Protein ; analysis ; Tomography, Spiral Computed ; methods

OBJECTIVETo investigate the effects of Echinococcus multilocularis on host liver cell proliferation in vivo using a BALB/c mouse alveolar hydatid infection model.

METHODSSixty-five 8-10-week-old female BALB/c mice were randomly divided into an experimental group (n = 40) and a control group (n = 25) and administered an abdominal injection into the left liver lobe of E. multilocularis protoscolices in saline solution or saline solution alone, respectively. At post-injection day 2, 8, 30, 60, and 90, liver samples were collected for analysis of lesions and lesion-adjacent tissue by hematoxylin-eosin staining and differential expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin A, and cyclin B1 by immunohistochemical staining. The significance of intergroup differences was assessed by Student's t-test.

RESULTSThe control group showed normal liver histology at all time points. The experimental group developed E. multilocularis lesions that showed increased severity of pathological features, such as inflammatory cell invasion, steatosis and fibrous connective tissue hyperplasia, over time. At post-injection days 2 and 8, enlarged, binuclear and apocyte hepatocytes were observed close to the lesions. At post-injection days 30, 60, and 90, the number of hepatocytes expressing PCNA progressively increased in the experimental group, and the numbers were significantly higher than in the control group (7.01 +/- 1.89 vs. 1.03 +/- 0.52, 8.41 +/- 2.80 vs. 0.93 +/- 0.31, and 13.4 +/- 4.43 vs. 1.07 +/- 0.94; all P < 0.05). The same progressively increasing trend was seen in the number of hepatocytes expressing CyclinD1, but was only significantly different from controls at post-injection days 30 and 60 (6.73 +/- 2.52 vs. 0.48 +/- 0.43 and 8.22 +/- 3.09 vs. 0.55 +/- 0.34; both P < 0.05). In contrast, the number of hepatocytes expressing cyclin A was significantly increased at post-injection day 30 and then showed a decreasing trend at days 60 and 90, although the numbers of expressing cells remained significantly higher than control levels at all time points (7.75 +/- 3.05 vs. 0.69 +/- 0.36, 3.42 +/- 1.80 vs. 1.14 +/- 0.42, and 3.03 +/- 1.50 vs. 0.69 +/- 0.31; all P < 0.05). The number of hepatocytes expressing CyclinB1 in the experimental group was less robust than the other cyclins (with a general temporal trend of increase followed by decrease), but the differential expression was not significantly different from the control levels at any time point.

CONCLUSIONE. multilocularis infection may promote the expression of host factors related to proliferation and anti-apoptosis in liver. This pathogen-mediated modulation of host cell-survival mechanisms may provide a rationale explanation for the clinical observations of hepatomegaly and the unexpected survival of alveolar echinococcosis patients following major hepatic resection.

Animals ; Apoptosis ; Cell Cycle ; Cell Proliferation ; Echinococcosis ; pathology ; Echinococcus multilocularis ; Female ; Hepatocytes ; cytology ; pathology ; Liver ; pathology ; Mice ; Mice, Inbred BALB C

OBJECTIVETo investigate the effect of peroxisome proliferator-activated receptor (PPAR)α agonist bezafibrate and oxidized low density lipoprotein (ox-LDL) on fibroblast growth factor 21 (FGF21) expression and apoptosis in cardiac endothelial cells.

METHODSThe mRNA level of FGF21 was determined by real time-PCR and the protein concentration of FGF21 in culture media was detected by enzyme-linked immunosorbent assay in cultured cardiac microvascular endothelial cells (CMECs) incubated with 10, 50, 100 µg/ml ox-LDL, 50, 100 or 200 µmol/L bezafibrate alone or in combination with 100 µg/ml ox-LDL. CMECs apoptosis in various treatment groups was also determined.

RESULTSFGF21 mRNA and protein expressions were significantly upregulated in proportion to increased ox-LDL, and 200 µmol/L bezafibrate alone also significantly upregulated FGF21 expression and CMECs apoptosis was significantly reduced in 200 µmol/L bezafibrate + 100 µg/ml ox-LDL group compared to 100 µg/ml ox-LDL group (P < 0.05).

CONCLUSIONSOur data suggest that bezafibrate and ox-LDL induced upregulation of FGF21 might mediate the protective effect against apoptosis. Endogenous FGF21 could thus play important roles in improving the endothelial function at the early stage of atherosclerosis and slowing the development of coronary heart disease.

Animals ; Apoptosis ; Atherosclerosis ; metabolism ; pathology ; Bezafibrate ; pharmacology ; Cells, Cultured ; Endothelium, Vascular ; cytology ; metabolism ; Fibroblast Growth Factors ; metabolism ; Lipoproteins, LDL ; pharmacology ; PPAR alpha ; agonists ; Rats ; Rats, Wistar

BACKGROUNDFibroblast growth factor 21 (FGF21) is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.

METHODSThe present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein (ox-LDL), and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells (CMECs) were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMECs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.

RESULTSThe secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 µmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis (P < 0.05).

CONCLUSIONSFGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.

Animals ; Apoptosis ; Bezafibrate ; pharmacology ; Cells, Cultured ; Coronary Artery Disease ; prevention & control ; Endothelial Cells ; physiology ; Fibroblast Growth Factors ; analysis ; antagonists & inhibitors ; genetics ; physiology ; Lipoproteins, LDL ; toxicity ; Male ; PPAR alpha ; physiology ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar

BACKGROUNDCystic echinococcosis due to Echinococcus granulosus (E. granulosus) is one of the most important chronic helminthic diseases, especially in sheep/cattle-raising regions. The larval stage of the parasite forms a cyst that grows in the liver, lung, or other organs of the host. To ensure a long life in the host tissues, the parasite establishes complex inter-cellular communication systems between its host to allow its differentiation toward each larval stage. Recent studies have reported that this communication is associated with the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade in helminth parasites, and in particular that these protein kinases might serve as effective targets for a novel chemotherapy for cystic echinococcosis. The aim of the present study investigated the biological function of a novel ERK ortholog from E. granulosus, EgERK.

METHODSDNA encoding EgERK was isolated from protoscolices of E. granulosus and analyzed using the LA Taq polymerase chain reaction (PCR) approach and bioinformatics. Reverse transcription PCR (RT-PCR) was used to determine the transcription level of the gene at two different larval tissues. Western blotting was used to detect levels of EgERK protein. The expression profile of EgERK in protoscolices was examined by immunofluorescence.

RESULTSWe cloned the entire Egerk genomic locus from E. granulosus. In addition, two alternatively spliced transcripts of Egerk, Egerk-A, and Egerk-B were identified. Egerk-A was found to constitutively expressed at the transcriptional and protein levels in two different larval tissues (cyst membranes and protoscolices). Egerk-A was expressed in the tegumental structures, hooklets, and suckers and in the tissue surrounding the rostellum of E. granulosus protoscolices.

CONCLUSIONSWe have cloned the genomic DNA of a novel ERK ortholog from E. granulosus, EgERK (GenBank ID HQ585923), and found that it is constitutively expressed in cyst membrane and protoscolex. These findings will be useful in further study of the biological functions of the gene in the growth and development of Echinococcus and will contribute to research on novel anti-echinococcosis drug targets.

Animals ; Blotting, Western ; Computational Biology ; DNA, Helminth ; genetics ; Echinococcus granulosus ; enzymology ; genetics ; Genome, Helminth ; genetics ; Helminth Proteins ; genetics ; metabolism ; Polymerase Chain Reaction

OBJECTIVETo evaluate the clinical efficacy of transrectal 125 I seeds implantation brachytherapy (BT) combined with intermittent hormonal therapy (IHT) in the treatment of locally advanced prostate cancer.

METHODSWe treated 27 patients with locally advanced prostate cancer by transrectal 125I seeds implantation BT combined with IHT, and dynamically observed the changes in the PSA level, prostate volume, maximum urinary flow rate (Qmax) and International Prostate Symptoms Score (IPSS).

RESULTSAll the implantation procedures were completed smoothly, lasting 20 to 35 minutes, with 40 to 58 seeds implanted. At 6 months after implantation, the PSA level was < 0.2 microg/L in all the patients (< 0.1 microg/L in 19 cases), the prostate volume was significantly reduced (P < 0.05), and Qmax and IPSS remarkably improved (P < 0.05). At 3 years after implantation, 19 cases were in the first cycle and the other 8 in the third cycle of IHT, of which 2 progressed to androgen-independent prostate cancer, and another 2 developed early bone metastasis. The rates of 3-year biochemically and clinically progression-free survival were 70.3% and 85.2%, respectively, and the rate of therapeutic effectiveness was 92.6%. No severe complications occurred in any of the cases.

CONCLUSIONTransrectal 125I seeds implantation BT combined with IHT is a safe and minimally invasive procedure for locally advanced prostate cancer, which can effectively retard its clinical progression with no such complications as severe urethral, rectal or erectile dysfunction.

Aged ; Brachytherapy ; Combined Modality Therapy ; Hormones ; therapeutic use ; Humans ; Iodine Radioisotopes ; administration & dosage ; therapeutic use ; Male ; Prostatic Neoplasms ; radiotherapy ; therapy ; Treatment Outcome