Objective To explore the reversing mechanism of multidrug resistance of ciclosporin(CsA) on K562/A02 cell line,attenuating DNA damage repair through H2AX suppression.Methods K563 and K562/A02 respectively co-cultured with adriamycin(ADM) of different concentrations and CsA.MTT assay was employed to determine the inhibitory concentration of 50 percent(IC50),the resistance times and the reversal times.The K562/A02 cells treated with CsA,and reverse transcriptase(RT)-PCR technique was used to examine the mdr1 and H2AX mRNA level.Flow cytometry was used to measure P-glycoprotein(P-gp) and H2AX expression.Neutral comet assay was used to detect the level of DNA double strands break(DSBs) of the K562/A02 treated with ?H2AX antibody.Results 2?10-3g/L CsA could increase the sensitivity of K562/A02 to ADM,and the reversal times was 5.28.Mdr1 mRNA level and H2AX mRNA level were decreased when treated with CsA(P

Calcium Channel Blockers ; pharmacology ; Cell Survival ; drug effects ; Drug Antagonism ; Humans ; Kidney ; cytology ; drug effects ; Lead ; toxicity

Objective To analyze the karyotypes of 11 cases of Turner syndrome with marker chromosome,and study the phenotypic effects resulting from the abnormal karyotype.Methods Eleven Turner syndrome patients had a mosaic karyotype and carried a marker chromosome,and 6 marker chromosomes were ring chromosomes.Their karyotypes were showed as mos.45,X/46,X,+mar or mos. 45,X/46,X,+r.Fluorescence in situ hybridization(FISH)technique with X/Y centromere probes was performed to determine the origin of the marker chromosome.Reverse chromosome painting technique was used to identify the breakpoints of two largest markers.Phenotype effects with different chromosome breakpoints were compared.Results All the 11 marker chromosomes were ring X chromosomes.The breakpoints of the r(X)were involved in Xp22,Xq22,Xq24 and Xq26,etc.Conclusions The marker chromosomes in Turner syndrome mainly originate from X chromosome and form ring chromosome X.Each r (X)in our patients was mosaic,indicating it was originated from mitosis error during early embryo development.To analyze the origin of the marker chromosome and the breakpoint of r(X)will provide guidance for the therapy and prognosis of the Turner syndrome patient.

OBJECTIVETo investigate the prognostic predictors of nasal NK/T cell lymphoma.

METHODSThe clinicopathologic feature data of 61 patients with nasal NK/T cell lymphoma proven by pathological examination from Jan. 1997 to Jan. 2005 were collected. Expression of survivin, CD44, nm23, p53, Ki-67, MDR-1 and CD95 was detected by immunohistochemical staining in 30 patients with available histologic specimens. The correlation between these factors and prognosis were analyzed.

RESULTSIn univariate analysis, performance status, LDH level, clinical stage, initial treatment response, CD56, Ki-67 and CD95 were found to be the prognostic factors associated with time to progression (TTP) in nasal NK/T cell lymphoma, while the performance status, B symptoms, LDH level, initial treatment response, Ki-67 and CD95 were demonstrated as prognostic factors related to overall survival. In multivariate analysis, clinical stage, initial treatment response and performance status were independent prognostic factors for TTP, while the latter two factors were independent prognostic factors of overall survival.

CONCLUSIONClinical stage and initial treatment response, and performance status are found to be independent prognostic factors for TTP, whereas the latter two factors are demonstrated as independent prognostic factors of the overall survival. Overexpression of Ki-67 may be an unfavorable prognostic factor, but overexpression of CD95 may be a favorable one.

Adolescent ; Adult ; Aged ; Analysis of Variance ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; analysis ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Hyaluronan Receptors ; analysis ; Immunohistochemistry ; statistics & numerical data ; Inhibitor of Apoptosis Proteins ; Ki-67 Antigen ; analysis ; Killer Cells, Natural ; drug effects ; metabolism ; pathology ; Lymphoma, T-Cell ; drug therapy ; metabolism ; pathology ; Male ; Microtubule-Associated Proteins ; analysis ; Middle Aged ; Neoplasm Proteins ; analysis ; Neoplasm Staging ; Nose Neoplasms ; drug therapy ; metabolism ; pathology ; Prednisone ; therapeutic use ; Prognosis ; Proportional Hazards Models ; Vincristine ; therapeutic use ; fas Receptor ; analysis

OBJECTIVETo elucidate the clinicopathologic features, immunophenotype and differential diagnosis of intracystic papillary carcinoma (IPC).

METHODSThe clinical and pathological characteristics of 14 cases of breast IPC were studied. Immunohistochemical study of SMA, MSA, ER, PR, p63, AE1/AE3, 34betaE12 and CK5/6 was performed using Envision method.

RESULTSThe age of IPC patients ranged from 42 to 79, with a mean age of 65.4 years. A palpable mass was the most common symptom. There were two morphological features: (1) Slender papillae lined by tall columnar epithelial cells which were present directly on the fibrovascular cores without an intervening myoepithelial cell layer (9 cases). (2) The proliferation may assume a cribriform architecture with rigid, punched-out regular spaces or a solid glandular pattern, studded with fibrovascular cores (5 cases). Low nuclear grade is typically seen. Among the 14 cases of IPC, 11 were of pure type. Ductal carcinoma in situ (DCIS) in adjacent ducts was found in one case, and invasive carcinoma was found in two cases. Immunohistochemical results showed that the tumor cells were homogenously strongly positive for ER and PR, but were negative or focally and weakly positive for CK5/6 and 34betaE12. Myoepithelial cell staining was negative within the tumor; and was diminished or scattered at the periphery of the tumor.

CONCLUSIONSIPC is a rare entity that usually arises in older women. It is specific enough in its clinical presentation and morphologic appearance to warrant distinction from other breast lesions.

Adult ; Aged ; Biomarkers, Tumor ; analysis ; Breast ; Breast Neoplasms ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; secondary ; Carcinoma, Papillary ; pathology ; Female ; Humans ; Middle Aged

OBJECTIVETo characterize a supernumerary marker chromosome (SMC) by comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH) and traditional cytogenetic techniques, and to explore the clinical application of these techniques in delineating de novo marker chromosomes.

METHODSA mental retardation patient received chromosome test by ordinary G banding. CGH and FISH techniques were used to analyze the origin of the de novo SMC, and N banding technique and C banding techniques were used to analyze the SMC structure. The phenotypic effects of the SMC were analyzed after the karyotype was determined.

RESULTSBy G banding technique, the patient was showed to have a mosaic karyotype with SMC: mos.47, XX, +mar [31]/48, XX, +2mar[29]. CGH analysis showed a gain of 15q11 --> q14, and the result was confirmed by FISH with chromosome 15 painting probe. The further FISH analysis showed the SMC had two signals with UBE3A probe for detecting Prader-willi syndrome/Angelman syndrome (PWS/AS). N banding and C banding analysis showed the SMC had a double satellite and double centromere, respectively. Combined with the above results, the karyotype of the patient was: mos.47, XX, +der (15) (pter --> q14::q14 --> pter) [31]/48, XX, +2der (15) (pter --> q14::q14 --> pter) [29]. ish der(15)(WCP15+, UBE3A++, PML-).

CONCLUSIONCGH is a valuable method to detect imbalanced chromosomal rearrangement. Combined with FISH and the traditional cytogenetic technique, it provides a valuable technique platform for characterizing the structure of the de novo SMC, and a basis for exploring the relation between karyotype and phenotype, prognosis and recurrent risk.

Chromosome Aberrations ; Chromosome Banding ; Comparative Genomic Hybridization ; Cytogenetic Analysis ; methods ; Cytogenetics ; methods ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Intellectual Disability ; diagnosis ; genetics ; Karyotyping

OBJECTIVETo determine the karyotype of a patient with Prader-Willi-like syndrome features.

METHODSChromosomal high resolution banding was carried out to analyze the karyotype of the patient, and methylation-specific PCR was used to analyze the imprinting region of chromosome 15. Subtelomeric region was screened by multiplex ligation-dependent probe amplification (MLPA), and fluorescent in situ hybridization (FISH) and real-time quantitative PCR were further performed to identify the deleted region.

RESULTSNo abnormality was discovered by high resolution karyotype analysis and methylation-specific PCR studies. MLPA analysis showed that the patient had a deletion of 1p subtelomeric area, which was confirmed by FISH analysis. The deleted region was shown within a 4.2 Mb in the distal 1p by 3 BAC FISH probes of 1p36 combined with real-time PCR technique. Family pedigree investigation showed the chromosome abnormality was de novo. Therefore, partial monosomy 1p36 was likely responsible for the mental retardation of the patient.

CONCLUSIONMolecular cytogenetic techniques should be performed to those patients with Prader-Willi-like syndrome features, to determine their karyotypes.

Child ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; genetics ; Female ; Humans ; Karyotyping ; Prader-Willi Syndrome ; genetics

OBJECTIVETo investigate the efficacy of CARTO-guided stepwise ablation approaches for treatment of patients with nonparoxysmal atrial fibrillation(AF).

METHODSStepwise ablation approaches were performed in 40 patients with nonparoxysmal atrial fibrillation. Pulmonary vein atrium isolation (PVAI), linear ablation in atria, complex fractionated atrial electrograms (CFAEs) ablation and cardioversion were applied sequentially till sinus rhythm (SR) restoration. All patients were followed up 6 to 18 months.

RESULTSSR was restored in 11 patients after PVAI, in 11 patients after linear ablation and in 6 patients after CFEAs ablation. SR was restored in the remaining 13 patients post cardioversion. During follow-up, 3 atrial fibrillation, 3 atrial tachycardia and 5 atrial flutter were evidenced. Seven out of the 11 patients with reoccurred arrhythmia were treated only by PVAI.

CONCLUSIONSCARTO-guided stepwise ablation approaches are safe and effective in the treatment of patients with nonparoxysmal atrial fibrillation. PVAI approach was associated with lower successful rate and high recurrence rate.

Aged ; Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome

OBJECTIVETo observe the protective effects on acute myocardial infarction of QDYX in dog.

METHODThe corconary ciculation and cardial oxygen metabolism, the degree and range of myocardial ischemia, myocardial infarct size, and the changes of the enzymes in serum were determined by using the acute myocardial infarction model of ligation of LAD in the anaesthetized open-chest dogs.

RESULTThe coronary resistance and cardial oxygen consumption were decreased and the myocardial blood flow was increased in dogs treated with QDYX of 1.0,2.0 mg.kg-1. The degree and range of myocardial ischemia, myocardial infarct size and the activity of serum CK, LDH were decreased in acute myocardial infarcion dogs treated with QDYX of 1.0,2.0 mg.kg-1.

CONCLUSIONQDYX can decrease cardial oxygen consumption in dogs, thus having protective effect on myocardial ischemia.

Administration, Oral ; Animals ; Astragalus membranaceus ; chemistry ; Cardiotonic Agents ; administration & dosage ; pharmacology ; Coronary Circulation ; drug effects ; Dogs ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Male ; Myocardial Infarction ; pathology ; physiopathology ; Ophiopogon ; chemistry ; Plants, Medicinal ; chemistry ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo investigate clinicopathologic features and clinical value of the chromosomal translocation involving anaplastic lymphoma kinase (ALK) in anaplastic large cell lymphoma (ALCL) by fluorescence in situ hybridization (FISH).

METHODSA total of 55 cases, including 45 cases of ALCL and 10 reactive lymphoid hyperplasia, were collected during 1999 to 2006 in the Department of Pathology, Fudan University Shanghai Cancer Center, and Xinhua Hospital Affiliated to Shanghai Jiaotong University. All cases were studied by FISH using dual color break apart probes of ALK for detection of chromosomal translocation, compared with the previous results of immunohistochemistry (IHC) and reverse-transcriptase polymerase chain reaction (RT-PCR) for the detection of ALK aberrations.

RESULTSThe result of FISH showed that the clear red and green fluorescence signals were detected in 38 cases of ALCL, in which conspicuous split signals were observed in tumor cells in 24 cases (63.2%), suggesting the rearrangement of the ALK locus, with multiple copies of ALK gene in one case. In addition, the rearrangement of the ALK locus was not identified in 14 of 38 cases (36.8%); and the FISH results were unable to be evaluated in 7 cases, because no fluorescent signals involving ALK gene were found or signals were too weak to be analyzed. The concordance for the detection ALK aberrations in ALCL between FISH and RT-PCR, FISH and IHC were both statistically significant (P < 0.01). Chromosomal translocation involving ALK gene was not found in all 10 cases of reactive lymphoid hyperplasia.

CONCLUSIONSALCL is an entity of lymphoma characterized by special clinical presentation, morphology, and ALK aberrations. FISH is helpful for detection of the chromosomal translocations involving ALK in ALCL, however, the detection efficiency by FISH may be affected by storage time of the paraffin-embedded tissue; and therefore combined detection with IHC and RT-PCR could complement each other and help for differential diagnosis of ALK(+)ALCL from ALK(-)ALCL.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymphoma, Large-Cell, Anaplastic ; genetics ; pathology ; Male ; Middle Aged ; Paraffin Embedding ; Receptor Protein-Tyrosine Kinases ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; Young Adult