It has been suggested that HCN1 is primarily expressed in hippocampus, however little is known about its effects on spatial learning and memory. In the present study, we investigated the effects of non-specific HCN1 blocker CsCl on spatial learning and memory by using Morris water maze and in situ hybridization in mice. The results showed CsCl 160 mg/kg ip for 4 days, and the mean escape latency was 34 s longer than that of normal control (P<0.01). In hippocampal tissues, staining for the HCN1 mRNA was stronger in the DG and CA1 region of the hippocampus (P <0.05, P<0.05, when CsCl-administration group was compared with normal group). Our results suggested that CsCl could significantly affect the spatial learning and memory in mice, and HCN channel is involved in the process of learning and memory.

Objective: To evaluate the effect of clusterin with and without leader sequence on overexpression preventing apoptosis in human prostate LNCaP cells. Methods:The plasmid pIRES2 EGFP was used to generate the clusterin expression constructs with full length or without the leader sequence (designated as pIRES2 EGFP/cluac, pIRES2 EGFP/clubc, respectively). Western blot analysis was employed to compare clusterin expression levels in the lysis and supernatant fluid of clusterin transfected LNCaP cells in vitro . The distribution of different functional domains of clusterin in cells was detected with Immunocytochemical staining. The clusterin's protective role of Na 2SeO 3 induced apoptosis in LNCaP cells was examined by flow cytometry (FCM) and fluorescence microscope. Results: Clusterin expression was detected in the lysis and supernatant fluid of pIRES2 EGFP/cluac transfected LNCaP cells, while clusterin was found only in lysis liquid of pIRES2 EGFP/clubc transfected LNCaP cells, but not found in their supernatant fluid. The distribution of cluserin in the plasm of pIRES2 EGFP/cluac transfected cells was aggregative, and on the other hand, clusterin distributed dispersedly in pIRES2 EGFP/clubc transfected cells. Its anti apoptotic property in LNCaP cells was proved by FCM and fluorescence microscope.Conclusion: It is apparent that clusterin plays an important role in preventing apoptosis in prostate cancer, and the presence of the leader sequence is necessary for clusterin's anti apoptotic function.

OBJECTIVETo clarify the various diagnostic connotations of pseudomyxoma peritonei (PMP) and to study their prognostic implications.

METHODSClinicopathologic features and follow-up data of 40 patients with PMP diagnosed in The General Hospital of PLA were retrospectively reviewed. The cases were histologically classified into 3 subcategories: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and PMCA with intermediate or discordant features (PMCA-I/D). The survival rate was calculated using Kaplan-Meier method and the difference was statistically analyzed.

RESULTSTwelve of the 40 patients died on follow up. The duration of survival ranged from 2 to 348 months (medium = 37.5 months). In general, the 3-year, 5-year and 10-year survival rates were 79.0%, 69.4% and 53.0%, respectively. The mean age of the patients at the time of diagnosis was 50.3 years (age range = 22 to 76 years). The male-to-female ratio was 1:1. The age and sex of patients, frequency of operation and presence of ovarian involvement did not correlate with duration of survival. On the other hand, the presence of appendiceal tumor, parenchymal invasion of abdominal viscera, cellularity, architecture, nuclear atypia and mitotic activity of the peritoneal lesion significantly correlated with survival. There was also significant difference in survival between DPAM, PMCA-I/D and PMCA subcategories (P = 0.018). The difference in survival rate between PMCA-I/D and PMCA subgroups however was not statistically significant (P = 0.096). The outcome of DPAM was significantly better when compared with the combined group of PMCA-I/D and PMCA (P = 0.006).

CONCLUSIONSIn general, the 10-year survival rate of PMP was low, despite the relatively benign-looking or low-grade pathologic appearance. Peritoneal lesions with higher cellularity, conspicuous nuclear atypia and higher mitotic activity are associated with a lower survival rate. The prognosis was even worse in the presence of appendiceal carcinoma or parenchymal invasion of abdominal viscera. It is thus advisable to subclassify PMP into DPAM, PMCA and PMCA-I/D, due to the difference in prognostic implication.

Adenocarcinoma, Mucinous ; pathology ; surgery ; Adenoma ; pathology ; surgery ; Adult ; Aged ; Appendectomy ; Appendiceal Neoplasms ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Peritoneal Neoplasms ; classification ; pathology ; surgery ; Pseudomyxoma Peritonei ; classification ; pathology ; surgery ; Retrospective Studies ; Survival Rate ; Young Adult

There have been very few studies on the effect of Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction in inhibiting apoptosis in myocardial ischemial injury caused by coronary heart disease. In this experiment, Gualou Xiebai Banxia decoction combined with-Xuefu Zhuyu decoction were used to intervene the miniature swine phlegm and blood stasis type coronary heart disease model, in order to observe the effect of the combined prescription on the myocardial apoptosis and the expressions of Bcl-2, Bax, Caspase-3, Caspase-9 in the model. Totally 15 Chinese experimental miniature swine were adopted and randomly divided into the control group, the model group and the phlegm and stasis-treating group. The model group and the stasis-treating group were fed with high fat diets for two weeks, intervened with the coronary artery injury and then given drugs and high fat diets for eight weeks. The control group was fed with ordinary diets for 10 weeks, without the coronary artery injury. After the experiment, myocardia at the juncture of infracted areas were collected and made into formalin-fixed paraffin sections. The TDT-mediate dUTP nick end labeling (TUNEL) assay was used to detect the myocardial apoptosis. The immunohistochemistry (IHC) technique was applied to detect Bcl-2, Bax, Caspase-3, Caspase-9 levels in myocardial tissues. According to the findings, the apoptosis indexes (AI) for the control group, the model group and the phlegm and stasis-treating group were 0.92%, 27.68%, 17.28%, respectively. The AI of the phlegm and stasis-treating group was significantly lower than that of the model group (P < 0.01). Compared with the model group, the phlegm and stasis-treating group showed significantly higher Bcl-2 protein expression (P < 0.01) and lower Bax, Caspase-3 and Caspase-9 protein expressions (P < 0.01). In conclusion, Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction have a significant protective effect against the myocardial apoptosis in miniature swine phlegm and blood stasis type coronary heart disease model.
Animals ; Apoptosis ; drug effects ; Caspases ; metabolism ; Coronary Disease ; drug therapy ; Disease Models, Animal ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Male ; Medicine, Chinese Traditional ; Myocardium ; pathology ; Phytotherapy ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Swine ; Swine, Miniature ; bcl-2-Associated X Protein ; analysis

Arteriovenous Malformations ; diagnosis ; etiology ; genetics ; Child ; Humans ; Immunoglobulin E ; blood ; Job Syndrome ; complications ; diagnosis ; genetics ; Lung ; diagnostic imaging ; pathology ; Male ; Mutation ; Radiography ; STAT3 Transcription Factor ; genetics

Adult ; Burns, Inhalation ; diagnostic imaging ; Explosions ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Radiography

OBJECTIVETo study the clinicopathologic features and histologic differential diagnosis of small cell neuroendocrine carcinoma (SmCC) of kidney.

METHODSThe clinicopathologic features of 12 cases of SmCC of kidney encountered during the period from 1999 to 2010 were retrospectively reviewed.

RESULTSSix cases of primary and 6 cases of metastatic SmCC involving kidney were identified. Amongst the primary renal SmCC, 2 were located in renal parenchyma and 4 in renal pelvis. Chest X-ray showed negative findings. Five of them underwent radical nephrectomy. On gross examination, the tumor was located centrally around the renal pelvis in 4 cases and peripherally in renal parenchyma in 1 case. On the other hand, 4 of the 6 cases of metastatic SmCC were discovered during therapy for pulmonary SmCC. Two of these patients presented with abdominal pain and gross hematuria, with lung and renal tumor masses identified simultaneously. The diagnosis of all the 6 cases of metastatic SmCC was confirmed by fine needle aspiration biopsy. Microscopically, pure SmCC was demonstrated in the 2 cases of primary renal parenchymal SmCC and 6 cases of metastatic SmCC. The 4 primary renal pelvic SmCC coexisted with urothelial carcinoma component. On immunohistochemical study, all cases were positive for cytokeratin, synaptophysin and CD56. All metastatic cases and 4 primary cases were also positive for TTF-1. Of six patients with primary SmCC two died 4 and 9 months after operation, and two were alive with a follow-up of 25 and 138 months, respectively. Five of six cases with metastatic SmCC died 3 - 8 months after diagnosis. The other 3 cases were failed to follow-up.

CONCLUSIONSBoth primary and metastatic SmCC can be found in the kidney. Although rare, primary SmCC is located either in renal parenchyma or in pelvis. The diagnosis of SmCC relies on morphologic examination and immunohistochemical study. TTF-1 immunostaining cannot reliably distinguish primary from metastatic SmCC in kidney. Correlation with clinicoradiologic findings and demonstration of coexisting urothelial carcinoma component (if any) is helpful in delineation of the tumor origin.

Adult ; Aged ; CD56 Antigen ; metabolism ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; secondary ; surgery ; Carcinoma, Renal Cell ; metabolism ; pathology ; Carcinoma, Small Cell ; metabolism ; pathology ; secondary ; surgery ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Keratins ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; secondary ; surgery ; Lung Neoplasms ; pathology ; secondary ; Lymphoma ; metabolism ; pathology ; Male ; Middle Aged ; Nephrectomy ; Nuclear Proteins ; metabolism ; Retrospective Studies ; Sarcoma, Ewing ; metabolism ; pathology ; Synaptophysin ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism ; Treatment Outcome ; Wilms Tumor ; metabolism ; pathology

Objective To investigate the levels of serum vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in patients with non-small cell lung cancer(NSCLC) and relationships with c1inicopatho1ogica1 characteristics and their clinical significance. Methods The concentrations of serum VEGF and bFGF were detected by enzyme-linked immunosorbent assay(ELISA) in 40 patients with NSCLC before and after chemotherapy. Results The level of serum VEGF in patients with Ⅳ stage NSCLC was significantly higher than that of Ⅲ stage(P

OBJECTIVETo study the clinical and pathologic characteristics of small cell neuroendocrine carcinoma of urinary tract.

METHODSAll cases of urinary tract carcinoma encountered in the General Hospital of People Liberation Army during the period from 1999 to 2010 were retrospectively reviewed. The clinicopathologic data of small cell neuroendocrine carcinomas were further analyzed, with literature review.

RESULTSA total of 16 cases of small cell neuroendocrine carcinoma were identified, including 10 from urinary bladder, 2 from ureter, 3 from renal pelvis, and 1 multifocal tumor involving renal pelvis and ureter. There were altogether 8 males and 8 females. The median age of the patients was 63 years (range = 24 to 79 years). Gross hematuria (11 cases) represented the main presenting symptom. Four patients had flank pain and 4 had urinary irritation symptoms. Seven patients underwent radical cystectomy. Six other patients underwent radical nephroureterectomy, 1 partial cystectomy, 1 TURBT and the remaining case biopsy only. The size of the tumor ranged from 0.8 to 8.0 cm (median = 4.5 cm). Histologically, 15 cases represented mixed small cell neuroendocrine carcinoma (with 13 mixed with transitional cell carcinoma and 2 with adenocarcinoma). Immunohistochemical study showed positive staining for neuroendocrine markers. On presentation, 1 patient was in stage pT1, 7 in stage pT2, 6 in stage pT3, 2 in stage pT4. Six patients died of the disease after operation. The overall survival was 25 months and the 5-year survival rate was 32.4%.

CONCLUSIONSSmall cell neuroendocrine carcinoma of urinary bladder is a highly malignant disease and associated with poor prognosis. The diagnosis relies on detailed histologic examination. Early diagnosis, when coupled with cystectomy or nephroureterectomy and adjuvant chemotherapy, represents the mainstay of management.

Adult ; Aged ; CD56 Antigen ; metabolism ; Carcinoma, Neuroendocrine ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Small Cell ; drug therapy ; metabolism ; pathology ; surgery ; Chemotherapy, Adjuvant ; Cystectomy ; Female ; Follow-Up Studies ; Humans ; Keratins ; metabolism ; Kidney Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Staging ; Nephrectomy ; Phosphopyruvate Hydratase ; metabolism ; Retrospective Studies ; Survival Rate ; Synaptophysin ; metabolism ; Ureteral Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Urinary Bladder Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Urologic Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Young Adult

OBJECTIVETo investigate the efficiency of blockage of constitutively activated STAT3 signaling by small interfering RNA (siRNA), and to explore the inhibitory effects on the proliferation of human esophageal squamous carcinoma cells (EC9706 and Eca109).

METHODSEC9706 and Eca109 were transfected with chemical synthesized STAT3 siRNA (100 nmol/L). RT-PCR and Western blot were used to detect STAT3 mRNA and protein expression, including phosphorylated-STAT3 (p-STAT3) before and after the transfection respectively. The changes of DNA-binding activity and cell proliferation were evaluated by electrophoretic mobility gel shift assay and MTT, respectively. Stages of cell cycle were determined by flow cytometry.

RESULTSExpression levels of STAT3 mRNA and STAT3, p-STAT3 proteins were progressively inhibited by STAT3 siRNA at various time points after transfection. STAT3-DNA-binding activity was suppressed after transfection evidenced by electrophoretic mobility gel shift assay. The cell cycle was arrested at G(0)/G(1) phase along with a significant inhibition of cell proliferation after STAT3 siRNA treatment.

CONCLUSIONSTAT3 siRNA specifically and efficiently blocks the constitutively activated STAT3 signaling pathway in human esophageal squamous carcinoma cells, resulting in cell cycle arrest and proliferation inhibition.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Phosphorylation ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; STAT3 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; Transfection