OBJECTIVETo investigate the variation in expression of ARHI, STAT3 and E2F1 and the correlation among them during carcinogenesis of ovarian serous carcinoma.

METHODSImmunohistochemical staining was used to detect the expression of ARHI, STAT3 and E2F1 in samples of 25 normal ovaries, 35 ovarian serous cystadenomas, 18 borderline serous cystadenomas and 56 ovarian serous carcinomas. The variation in expression of the three genes and relationship among them were analyzed.

RESULTSARHI expression was detected in 22 of 25 (88.0%) normal ovaries and 30 of 35 (85.7%) cystadenomas, but only in 10 of 18 (55.6%) borderline serous cystadenomas and 22 of 56 (39.3%) ovarian serous carcinomas, significantly lower than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). STAT3 expression was found in 14 of 18 (77.8%) borderline serous cystadenomas and 49 of 56 (87.5%) ovarian serous carcinomas, significantly higher than that in the normal ovaries and ovarian serous cystadenomas (P < 0.05). To compare with E2F1 expression in the normal ovaries, serous cystadenomas and borderline serous cystadenomas, E2F1 expression in 46 of 56 (82.1%) ovarian serous carcinomas was significantly higher (P < 0.05). It was found that the expression of ARHI was inversely correlated with that of STAT3 and E2F1.

CONCLUSIONOur findings indicate that ARHI expression is down-regulated, but STAT3 and E2F1 expressions are up-regulated, with an inverse correlation between ARHI and STAT3 in the carcinogenesis of ovarian serous carcinoma.

Adult ; Aged ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Cystadenoma, Serous ; metabolism ; pathology ; E2F1 Transcription Factor ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Ovarian Neoplasms ; metabolism ; pathology ; Ovary ; metabolism ; pathology ; STAT3 Transcription Factor ; metabolism ; rho GTP-Binding Proteins ; metabolism

OBJECTIVETo evaluate the expression of vascular endothelial growth factor C (VEGF-C) and peroxisome proliferators-activated receptors (PPARgamma) in extrahepatic cholangioadenocarcinoma (EHCAC) and to elucidate its correlation with clinicopathological factors and their significance in prognosis.

METHODSThe expressions of PPARgamma and VEGF-C were detected by immunohistochemistry in 69 cases of EHCAC, 12 cases of non-tumor bile duct epithelium, and their relationship to clinicopathological parameters and follow-up were analyzed.

RESULTSThe positive rate of PPARgamma expression in 69 cases of EHCAC was 59.4%, significantly higher than that in 12 cases of non-tumor bile duct epithelium (0%), (P < 0.01). The positive rate of VEGF-C in 69 cases of EHCAC was 84.1%, also significantly higher than 16.7% in 12 cases of benign bile duct epithelium (P < 0.05). PPARgamma expression was associated with clinical TNM stage and lymph node metastasis. VEGF-C expression was associated with lymph node metastasis. Cox analysis results showed that portal vein and/or hepatic artery invasion, lymph node metastasis and VEGF-C expression were independent prognostic factors of EHCAC (P < 0.05).

CONCLUSIONPPARgamma expression may play an important role during tumorigenesis of extrahepatic cholangioadenocarcinoma. The expressions of PPARgamma and VEGF-C are significantly correlated with the clinicopathological characteristics and biological behavior of EHCAC. Expression of VEGF-C is an independent prognosis factors in EHCAC. The detection of PPARgamma and VEGF-C is valuable for evaluation of prognosis of EHCAC.

Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms ; metabolism ; pathology ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; PPAR gamma ; metabolism ; Proportional Hazards Models ; Survival Rate ; Vascular Endothelial Growth Factor C ; metabolism

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwise. The incidence rate of HCC is high and is easy to metastasis and recurrence, which seriously affects human health. Traditional chemical drugs have some challenges such as toxicity, side effects, and multidrug resistance, thus it is urgent to find new drugs and effective targets. Here we synthesized a novel chemical, protonic bis-phenanthroline (H-BP), and the antitumor effect was investigated in the study. The results showed that H-BP could selectively inhibit the proliferation of tumor cells and cause HCC apoptosis. And also, in HCC tumor-bearing mice, H-BP could effectively prevent the growth of tumor mass, even completely eliminate the tumor at medium dose (5 mg·kg^-1) and high dose (10 mg·kg^-1), and meanwhile H-BP has no significant effect on the body weight of mice. The experimental protocol was approved by the Animal Ethics Committee of Southwest University, and the experimental operation was strictly carried out in accordance with the ethical principles of animal use and care. Mechanism studies showed that H-BP induced HCC apoptosis was related to down-regulation the expression of pleomorphic adenoma gene like-2 (PLAGL2), a oncogene transcription factor, resulting in the down-regulation of PLAGL2 downstream proteins hypoxia inducible factor and β-catenin. This study not only introduces the dimerization method to form novel compounds that will provide a new approach for drug design, but also suggests that PLAGL2 may be an effective target in tumor therapy.

BACKGROUNDGastric stromal tumors arising from the muscularis propria are located in deeper layers. Endoscopic resection may be contraindicated due to the possibility of perforation. These tumors are therefore usually removed by surgical or laparoscopic procedures. This study evaluated the curative effects, safety and feasibility of endoscopic full-thickness resection (EFR) of gastric stromal tumors originating from the muscularis propria.

METHODSThis study enrolled 92 patients with gastric stromal tumors >2.5 cm originating from the muscularis propria. Fifty patients underwent EFR, and 42 underwent laparoscopic intragastric surgery. Operation time, complete resection rate, length of hospital stay, incidence of complications, and recurrence rates were compared in these two groups.

RESULTSEFR resulted in complete resection of all 50 gastric stromal tumors, with a mean procedure time of 85 ± 20 min, a mean hospitalization time of 7.0 ± 1.5 days and no complications. Laparoscopic intragastric surgery also resulted in a 100% complete resection rate, with a mean operation time of 88 ± 12 min and a mean hospitalization period of 7.5 ± 1.6 days. The two groups did not differ significantly in operation time, complete resection rates, hospital stay or incidence of complications (P > 0.05). No patient in either group experienced tumor recurrence.

CONCLUSIONSEFR technique is effective and safe for the resection of gastric stromal tumors arising from the muscularis propria.

Adult ; Female ; Gastric Mucosa ; pathology ; surgery ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms ; pathology ; surgery ; Treatment Outcome

Two female patients with rectal tumor undergoing proctectomy via vagina, namely natural orifice transluminal endoscopic surgery (NOTES), are reported. The operations were performed on June 8 and August 10, 2010, respectively. No Trocar was used in the abdomen except for the transumbilical incision. There were no visible scars in the abdomen. Tubulovillous adenoma and moderately differentiated adenocarcinoma were diagnosed respectively through postoperative pathological examination. Both patients resumed normal work and life at the most recent follow up. Sexual life was satisfactory.
Adult ; Female ; Humans ; Natural Orifice Endoscopic Surgery ; methods ; Rectal Neoplasms ; surgery ; Vagina ; surgery

OBJECTIVETo explore the enhancing effect of compound Kusheg injection in chemotherapy for patients with stage III and IV non-small cell lung cancer (NSCLC).

METHODSA total of 286 patients with advanced NSCLC were enrolled in this study. The patients were treated with either compound Kusheng injection in combination with NP (NVB + CBP) chemotherapy (vinorelbine and carboplatin, n = 144), or with NP (NVB + CBP) chemotherapy alone (n = 142). The chemotherapy was performed for 4 cycles of 3 weeks, and the therapeutic efficacy was evaluated every 2 weeks. The following indicators were observed: levels of Hb, WBC, PLT and T cell subpopulations in blood, serum IgG level, short-term efficacy, adverse effects and quality of life.

RESULTSThe gastrointestinal reactions and the myelosuppression in the combination chemotherapy group were alleviated as compared with the chemotherapy alone group, showing a significant difference (P < 0.05). CD(8)(+) cells were markedly declined in the combination chemotherapy group, and the CD(4)(+)/CD(8)(+) ratio showed an elevation trend in the chemotherapy alone group. The KPS scores and serum IgM and IgG levels were higher in the combination chemotherapy group than those in the chemotherapy alone group (P < 0.01 and P < 0.05). The serum lgA levels were not significantly different in the two groups.

CONCLUSIONThe compound Kusheng injection plus NP chemotherapy regimen shows better therapeutic effect, reduces adverse effects of chemotherapy and improves the quality of life in patients with stage III and IV NSCLC.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; CD4-CD8 Ratio ; Carboplatin ; administration & dosage ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Phytotherapy ; Quality of Life ; Vinblastine ; administration & dosage ; analogs & derivatives

OBJECTIVETo explore the role of sorafenib in reversing multidrug resistance (MDR) in hepatoma BEL-7402/FU cells and its possible mechanisms.

METHODSMTT colorimetric assay was used to obtain the dose-response curve of sorafenib in BEL-7402/FU cells, and flow cytometry performed to assess the effect of sorafenib on Rho123 concentration in the cells. The optimal dose of sorafenib for cell treatment was determined according to the results of MTT assay and flow cytometry. MTT assay was employed to evaluate the effect of sorfenib on the cytotoxicity of the antitumor drugs, flow cytometry performed to determine the expression of cell membrane transport protein (P-gp), and RT-PCR used to detect mdr1 gene expression in the cells treated with sorafenib at the optimal dose.

RESULTSSorafenib at the concentration of 4 micromol/L, efficiently reversed the MDR of the cells with minimal side effects. At the concentration of 4 micromol/L, sorafenib partially reversed the drug resistance of BEL-7402/FU cells to ADM, 5-FU, GEM and DDP, with reversal indexes of 2.98, 7.16, 1.99 and 10.08, respectively. Treatment of the cells with 4 micromol/L, sorafenib also partially down-regulated P-gp expression in BEL-7402/FU cells, and caused a reduction of mdr1 gene expression by 27.3% in comparison with the control cells.

CONCLUSIONSorafenib can reverse MDR in human hepatoma cells probably in association with down-regulation of mdr1 gene expression and increased accumulation of the chemotherapeutic agents in the cells.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Benzenesulfonates ; pharmacology ; Cell Line, Tumor ; Down-Regulation ; drug effects ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Liver Neoplasms ; genetics ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; pharmacology

OBJECTIVEIt was noticed that coxsackievirus A16 (CA16) and enterovirus 71 (EV71) were two major etiological agents of hand, foot and mouth disease (HFMD) in children. Recently there were several large outbreaks of HFMD in the Asia-Pacific region, and there was a propensity to cause severe complications or death in children under 5 years of age. The severe forms were associated with EV71 infection. Although epidemics of HFMD have been reported in the mainland of China, few reports about EV71 as the pathogen of HFMD epidemics are available. The present study was conducted to investigate the causal agent of an HFMD epidemic in children in Shanghai from April to June of 2002.

METHODSTotally 102 specimens (including vesicle fluid, stool and throat swabs) were collected from 72 patients with HFMD. The specimens were inoculated into Vero and/or RD cells. At first all the isolates were respectively neutralized by the RIVM pools of enterovirus antiserum, the type-specific antisera to EV71 or to CA16. Secondly all untyped isolates were tested by RT-PCR assay with two specific primer pairs for VP1 genes of EV71 and CA16 respectively. The EV71 and CA16 were identified depending on the size of PCR products. Sequence analyses of VP1 genes of 9 virus strains were performed by the laboratory of China CDC.

RESULTSViruses were isolated from 91 specimens from 67 patients. Serotyping by neutralization failed for all the isolates. But the RT-PCR results indicated that the viruses isolated from 78 specimens from 58 patients were identified as positive for CA16 and the isolates from 13 specimens from 9 patients were identified as positive for EV71, the ratio between CA16 and EV71 was 6.4:1. The results of sequence analyses were consistent with those of PCR assay. Two EV71 strains isolated in this study belonged to a new lineage (C4) within genogroup C. One patient with EV71-associated HFMD had a complication of encephalitis with convulsion, shock, coma and dyspnea.

CONCLUSIONCA16 and EV71 were the primary causes of HFMD during the epidemic. It was the first report of EV71-associated severe encephalitis occurred in patients with HFMD in Shanghai.

Animals ; Cercopithecus aethiops ; Child ; Child, Preschool ; China ; epidemiology ; Coxsackievirus Infections ; diagnosis ; epidemiology ; Disease Outbreaks ; Enterovirus ; isolation & purification ; Enterovirus A, Human ; isolation & purification ; Female ; Genes, Viral ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male ; RNA, Viral ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Vero Cells

OBJECTIVETo evaluate the H. pylori and Epstein-Barr virus infection in cardiac and distal gastric adenocarcinoma tissues in residents in Cixian county, a high risk area of esophageal cancer in Hebei province, and to explore the putative role of H. pylori and Epstein-Barr virus infection in the carcinogenesis of adenocarcinoma at different subsites of stomach.

METHODSH. pylori and Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) immunopositivities were determined by Elivision(TM) plus immunohistochemical staining in 190 gastric adenocarcinoma tissues including 144 cases of cardiac adenocarcinoma and 46 cases of distal gastric adenocarcinoma. The relationship between H. pylori and Epstein-Barr virus infection and the subsite, Laurén type as well as other clinicopathological features of gastric adenocarcinoma were analyzed.

RESULTSNo significant difference was found between the H. pylori detection rates in cardiac and distal gastric adenocarcinomas(56.9% vs. 65.2%, P > 0.05). The detection rate of H. pylori in intestinal type was significantly higher than that in the diffuse type distal gastric adenocarcinomas (71.8% vs. 28.6%, P < 0.05). No positive expression of EBV-LMP1 was found in the gastric adenocarcinomas in this study.

CONCLUSIONSNo significant differences in H. pylori and EBV-LMP1 infections were found between cardiac and distal gastric adenocarcinomas in Cixian county. H. pylori infection is related with the intestinal type of distal gastric adenocarcinoma.

Adenocarcinoma ; microbiology ; pathology ; virology ; Aged ; Cardia ; China ; Epstein-Barr Virus Infections ; pathology ; Female ; Helicobacter Infections ; pathology ; Helicobacter pylori ; isolation & purification ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; microbiology ; pathology ; virology ; Viral Matrix Proteins ; metabolism

OBJECTIVEDendritic cells play an important role in the pathogenesis of atherosclerosis. To explore the effects of hyperglycemia on the maturation and immune function of human monocyte derived dendritic cells (MDCs).

METHODSImmature MDCs were cultured in RPMI1640 medium with either 5.5 mmol/L D-glucose (NG), 25 mmol/L D-glucose (HG) or 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol (HM) in the absence or presence of 30 mmol/L N-acetylcysteine [NAC, a reactive oxygen species inhibitor (ROS)] for 48 hours. FACS was used to investigate the MDCs immunophenotypic expression. Immune function was evaluated by allogeneic mixed T lymphocyte reaction and measurement of cytokine levels from culture supernatants. Intracellular ROS production in MDCs was also measured by 2', 7'-dichlorodihydrofluorescein (DCF, 10 micromol/L) fluorescence using confocal laser-scanning microscopy techniques.

RESULTSCompared with NG and HM treated MDCs, the expression of maturation markers such as CD1a, HLA-DR, CD83, CD86 were significantly upregulated, allogeneic T cells proliferation as well as the cytokines secretions (IL-2, IL-12, IL-10 and IFN-gamma) significantly increased in HG treated MDCs. Intracellular ROS production in MDCs was also significantly increased and all these stimulatory effects of HG could be partially attenuated by NAC.

CONCLUSIONHigh glucose promote the maturation of MDCs and augment their capacity to stimulate T-cell proliferation and cytokine secretions at least in part through enhancing intracellular ROS generation. These stimulating effects of high glucose on MDCs maturation may be one of the mechanisms of accelerated atherosclerosis found in patients with diabetes.

Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Culture Media ; Cytokines ; biosynthesis ; Dendritic Cells ; drug effects ; immunology ; metabolism ; Glucose ; adverse effects ; pharmacology ; Humans ; Immunophenotyping ; Monocytes ; cytology ; Reactive Oxygen Species ; metabolism ; T-Lymphocytes ; cytology