Adenoviridae ; genetics ; Animals ; Apoptosis ; drug effects ; Carcinoma, Squamous Cell ; genetics ; metabolism ; therapy ; Cell Cycle ; drug effects ; Clinical Trials as Topic ; Genes, p53 ; Genetic Therapy ; Genetic Vectors ; Humans ; Mouth Neoplasms ; genetics ; metabolism ; therapy ; Mutation ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Viral Vaccines ; pharmacology ; therapeutic use

Objective To investigate the clinical results of occlusal splint in the treatment of sagittal fracture of mandibular condyle (SFMC) in children.Methods Thirty-nine patients (48 condyles) aged 3-8 years with sagittal fracture of mandibular condyle were included in this study.All the patients were treated by occlusal splint.Slight open occlusion was maintained by occlusal splint for 3-6 months.Clinical and radiological examination was performed six mouths and every year after treatment.Results Good mandibular function was observed in 39 patients.Maximal mouth opening over 35 mm was achieved at 6 months.But 11 of the 39 patients presented with deviation on mouth opening at 6 months.The radiology showed an complete remodeling in 32 condyles (28 patients) and partial remodeling in 16 condyles (11 patients).Poor remodelling was not observed in any patients.Conclusions Good clinical results can be obtained by using occlusal splint in the treatment of pediatric sagittal fracture of mandibular condyle.

BACKGROUNDStatins are one of the most common agents prescribed for ischemic stroke patients, but their side effects on the liver are worrisome to both physicians and patients. This study aimed to analyze the features and related factors of the hepatic side effects of statins in patients with ischemic stroke.

METHODSFour hundred and eighty-one patients with ischemic stroke who had been treated with statins at our department from July 1, 2008 to June 30, 2009 were investigated retrospectively. Liver function, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), within 6 months after they began to use statins and related factors were analyzed.

RESULTSThe incidence of mild ALT and AST elevation, less than three times the upper limit of normal, and the incidence of moderate elevation, ALT and AST levels 3-10 times the upper limit of normal, in ischemic stroke patients who had been treated with statins were 2.3% and 2.1%, respectively. These incidences were higher than in patients with common hyperlipidemia or coronary heart disease. The relatively high incidence was associated with older age (≥ 65 years) and chronic liver diseases, and was not related to the type of stroke, gender, and reduction of low-density lipoprotein. The levels of ALT and AST normalized after withdrawal of statins or lowering the dosage. None of the patients developed hepatic failure.

CONCLUSIONSAsymptomatic elevation of ALT and AST after administration of statins is more likely to occur in ischemic stroke patients than in others, and the elevation is related to age and chronic liver diseases. However, statins are still safe for ischemic stroke patients.

Age Distribution ; Aged ; Alanine Transaminase ; metabolism ; Aspartate Aminotransferases ; metabolism ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; adverse effects ; therapeutic use ; Liver ; drug effects ; metabolism ; Male ; Middle Aged ; Retrospective Studies ; Stroke ; drug therapy

BACKGROUNDBariatric surgery offers successful resolution of type 2 diabetes mellitus (T2DM). However, recurrence of T2DM has been observed in a number of patients with initial resolution after bariatric surgery. This study aimed to induce reversal of the improvement of diabetes in T2DM rats after duodenal-jejunal bypass (DJB), and identify the effects of weight changes and gut hormones that might be involved.

METHODSDJB surgery was performed in two T2DM rat models (n=20 for each group): non-obese Goto-Kakizaki (GK) rats, and moderately-obese T2DM rats induced by a combination of a high-fat diet (HFD) and low-dose streptozotocin (HS rats). The controls were sham-operated and non-treated rats. All rats were then randomly divided into HFD- and low-fat diet (LFD)-fed groups. Glucose tolerance, insulin tolerance, glucose-stimulated insulin, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion, food intake and body weight were measured and compared with controls.

RESULTSDJB surgery resulted in a significant improvement in glucose tolerance in both GK and HS rats fed with either HFD or LFD. In contrast to LFD-fed rats, improved glucose tolerance was impaired in GK and HS rats fed with an HFD, accompanied by re-impairment of insulin tolerance and failure in enhancement of insulin secretion. There was no significant difference in food intake and body weight between DJB-operated and control rats, and between HFD- and LFD-fed rats. Glucose-stimulated GLP-1 and PYY levels were significantly increased after DJB surgery; however, they were not significantly different between HFD- and LFD-fed rats.

CONCLUSIONAn HFD reverses the improvement in glucose tolerance induced by DJB surgery in T2DM rats, primarily ascribing to the re-impairment of insulin sensitivity, but does not change body weight, GLP-1 and PYY levels.

Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus, Type 2 ; blood ; chemically induced ; pathology ; surgery ; Diet, High-Fat ; adverse effects ; Gastric Bypass ; Glucose Tolerance Test ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the response rate and adverse reactions of exemestane (a new aromatase inactivator) in the treatment of postmenopausal women with advanced breast cancer.

METHODSOne hundred and seventy-three patients with advanced breast cancer entered this study with two patients excluded because of postmenopausal time being less than one year. Therefore, 173 patients could be evaluated for adverse events and 171 patients could be evaluated for efficacy. Exemestane, 25 mg orally daily for 4 weeks as one cycle was given.

RESULTSIn the 171 patients evaluated for efficacy, 4 (2.3%) experienced a complete response (CR) and 40 (23.4%) a partial response (PR), with the overall response rate of 25.7%. Ninety patients (52.6%) had stable disease (SD), with 25 having SD for at least 24 weeks. The clinical benefit (CR + PR + SD > or = 24 weeks) was shown in 69 (40.4%) patients. Progressive disease (PD) was shown in 37 (21.6%) patients. The untreated patients had a higher objective response rate (33.8%) than the retreated ones (18.1%) with significant difference (P = 0.019 7). The response rates for soft-tissue, bone involvement and visceral metastasis were 32.8%, 23.9%, and 12.4% (P = 0.002). There was no significant difference in different ages, time of menopause, disease-free interval or receptor status (P > 0.05). Drug-related adverse events were gastric discomfort (17.9%), malaise (17.9%), nausea (13.9%), hot flushes (11.0%) and dysphoria (5.8%). Other side reactions and abnormal laboratory parameters were observed occasionally which were irrelevant.

CONCLUSIONExemestane can be used to treat postmenopausal women with advanced breast cancer giving only mild adverse reactions which are well tolerated.

Adult ; Aged ; Androstadienes ; adverse effects ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Aromatase Inhibitors ; Breast Neoplasms ; drug therapy ; Enzyme Inhibitors ; therapeutic use ; Female ; Humans ; Middle Aged ; Postmenopause

OBJECTIVETo assay the expression of cytidine deaminase (CDA), ribonucleotide reductase subunit 1 (RRM1), phosphatase and tensin homologue deleted from chromosome 10 (PTEN), excision repair cross-complementation group 1 (ERCC1), deoxycytidine kinase (dCK) and RRM1(-)37A/C polymorphism, which have been shown relevant to gemcitabine resistance in two human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem, so as to make clear how do they vary during the course of acquiring resistance to gemcitabine.

METHODSThe human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem were established in our Department by repeated clinical serum peak concentration and gradually increasing doses. Real-time fluorescent quantitative PCR was used to examine the expression of CDA, RRM1, PTEN, ERCC1, dCK and RRM1(-)37A/C polymorphism in those cell lines at different time points during their induction process.

RESULTSThe resistance indexes of A549/Gem and NCI-H460/Gem cells reached 163.228 and 181.684, and then remained stable at 115.297 and 129.783, respectively. The expression of CDA, RRM1, PTEN and ERCC1 varied along with the changing gemcitabine resistance indexes, but expression of dCK did not change apparently. The wild type promoter was able to amplify the genomic DNA in different induction stages of A549/Gem and NCI-H460/Gem cells, but allelotype did not, indicating that the gene type of A549/Gem, NCI-H460/Gem and their parental cells remaining still wild type.

CONCLUSIONCompared with their parental cells, the expressions of CDA, RRM1, PTEN and ERCC1 in human gemcitabine-resistant non-small cell lung cancer cell lines A549/Gem and NCI-H460/Gem rise, the expression of dCK changes inapparently, therefore, their gene type are remaining wild type.

Antimetabolites, Antineoplastic ; pharmacology ; Carcinoma, Large Cell ; genetics ; metabolism ; pathology ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cytidine Deaminase ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Deoxycytidine Kinase ; genetics ; metabolism ; Drug Resistance, Neoplasm ; Endonucleases ; genetics ; metabolism ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; PTEN Phosphohydrolase ; genetics ; metabolism ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; RNA, Messenger ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo study the promoter hypermethylation of several tumor suppressor genes in gastric carcinoma (GC) tissue and adjacent normal gastric foveolar epithelium (GFE).

METHODSMethylation specific PCR (MSP) was used to examine the promoter methylation of tumor suppressor genes E-cadherin, hMLH1, APC and MGMT in paraffin-embedded gastric cancer tissue and adjacent normal foveolar epithelium in 106 cases.

RESULTSThe positive rate of genes promoter methylation was 44.3% (47/106 cases) and 72.6% (77/106 cases) at one or more genes tested in the normal GFE and GC tissue, respectively. There was a significant difference in the positive rates of gene promoter methylation between normal GFE and GC tissue (P = 0.0001). There was a significant association with Laurén classification, degree of differentiation and pTNM staging in GC (P < 0.05), but no significant association with Ming's classification (P > 0.05).

CONCLUSIONTumor suppressor genes promoter methylation is frequently present in GC and adjacent normal gastric foveolar epithelium, especially in Laurén diffuse type GC, poorly differentiated GC, mucus-secreting (signet ring) cell GC and pTNM stage III and IV GC. Our findings indicate that the gene promoter methylation is a common and early event in GC carcinogensis.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Adenomatous Polyposis Coli Protein ; genetics ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Cadherins ; genetics ; metabolism ; DNA Methylation ; DNA Modification Methylases ; genetics ; metabolism ; DNA Repair Enzymes ; genetics ; metabolism ; Epithelium ; metabolism ; pathology ; Female ; Gastric Mucosa ; metabolism ; pathology ; Genes, APC ; Genes, Tumor Suppressor ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; Neoplasm Staging ; Nuclear Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; genetics ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Tumor Suppressor Proteins ; genetics ; metabolism ; Young Adult

OBJECTIVETo construct a RNA interference expression vector targeting human telomerase reverse transcriptase gene (hTERT) gene and investigate its effects on telomerase activity and proliferation in breast cancer cells in vitro.

METHODSThe shRNA sequences targeting hTERT gene were designed and recombined into pSuper-retro-puro vector. The breast cancer cell lines MCF-7 and MDA-MB231 were transfected with the recombined vector, and the telomerase activity of the cells was tested by telomerase repeat sequence amplification-enzyme linked immunosorbent assay (TRAP-ELISA). The proliferation of the transfected cells was assessed using MTT and soft-agar clone formation assays.

RESULTSThe recombinant plasmids pSuper-retro-puro-TERT RNAi#1 and #2 were successfully constructed as confirmed by enzymatic digestion and DNA sequencing. The telomerase activity in the transfected breast cancer cells were down-regulated significantly as compared with that in negative control cells (Plt;0.005). The transfection resulted in significant inhibition of the proliferation of both MCF-7 and MDA-MB231 cells as detected by MTT assay (Plt;0.05) and soft agar clone formation assay (Plt;0.001).

CONCLUSIONTransfection with the recombinant plasmid containing the shRNA targeting hTERT gene can down-regulate telomerase activity and inhibit proliferation of breast cancer cells in vitro, suggesting the potential of gene therapy targeting telomerase in the treatment of breast cancer.

Breast Neoplasms ; enzymology ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Genetic Therapy ; Genetic Vectors ; genetics ; Humans ; RNA Interference ; RNA, Messenger ; biosynthesis ; genetics ; RNA, Small Interfering ; genetics ; metabolism ; Telomerase ; biosynthesis ; genetics ; metabolism ; Transfection

BACKGROUNDWWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present.

METHODSReverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma.

RESULTSCompared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA (WWOX rate ratio = 2.95, 95% CI 1.24 - 7.08; FHIT rate ratio = 4.58, 95% CI 1.82 - 11.81) and Western blotting detectable protein (WWOX rate ratio = 4.12, 95% CI 1.63 - 10.73; FHIT rate ratio = 3.76, 95% CI 1.44 - 10.06). For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance (P > 0.05 for each analysis). Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance (P > 0.05 for each analysis).

CONCLUSIONExpression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.

Acid Anhydride Hydrolases ; analysis ; genetics ; Breast ; pathology ; Breast Neoplasms ; genetics ; Chromosome Fragile Sites ; Female ; Genes, Tumor Suppressor ; Humans ; Hyperplasia ; Neoplasm Proteins ; analysis ; genetics ; Oxidoreductases ; analysis ; genetics ; Tumor Suppressor Proteins ; analysis ; genetics ; WW Domain-Containing Oxidoreductase

BACKGROUNDEstrogen receptor (ER)-negative breast cancer cells are more aggressive than ER-positive cells. Elevated levels of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C) expression have been detected in cultured human breast cancer cells and are associated with negative hormone receptor status. In this study, we created ERalpha stable transfectants in MDA-MB-231 cells to explore the effect of ERalpha on cell growth and COX-2 and VEGF-C expression.

METHODSThe green fluorescent protein (GFP)-ERalpha plasmids were stably transfected into ER-negative MDA-MB-231 cells. The proliferation and migration of untransfected MDA-MB-231 cells, ERalpha-transfected MDA-MB-231 cells and ER-positive MCF-7 cells were determined. The expression of COX-2, and the levels of VEGF-C mRNA and the VEGF-C secretion concentration were assayed in these cell lines.

RESULTSThe proliferation and migration capacities of ERalpha-tranfected MDA-MB-231 cells were significantly decreased (P < 0.05). The expression of COX-2 was significantly lower in ERalpha-tranfected MDA-MB-231 cells than in untranfected MDA-MB-231 cells. The mRNA and protein levels of VEGF-C were lower in ERalpha-tranfected MDA-MB-231 cells than in untransfected MDA-MB-231 cells (P < 0.05).

CONCLUSIONSERalpha stable transfection inhibits proliferation and migration capacities of MDA-MB-231 cells and decreases expression of COX-2 and VEGF-C. The decreases of proliferation and migration capacities may be related to suppression of COX-2 and VEGF-C expression.

Blotting, Western ; Breast Neoplasms ; genetics ; metabolism ; Cell Cycle ; genetics ; physiology ; Cell Line, Tumor ; Cell Movement ; genetics ; physiology ; Cell Proliferation ; Cyclooxygenase 2 ; genetics ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Flow Cytometry ; Humans ; Polymerase Chain Reaction ; Transfection ; Vascular Endothelial Growth Factor C ; genetics ; metabolism