ABSTRACT
OBJECTIVE@#To trace a rare case of chronic myeloid leukemia (CML) with a four-way Philadelphia chromosome variant by cytogenetic analysis in order to provide a basis for the selection of treatment.@*METHODS@#Bone marrow morphology, chromosomal karyotyping, fluorescence in situ hybridization (FISH) and real-time quantitative PCR (RQ-PCR) were used for the diagnosis and staging of the disease. Point mutations in the tyrosine kinase domain of ABL1 gene were detected by Sanger sequencing.@*RESULTS@#The patient was initially diagnosed as CML in chronic phase (CML-CP) with a chromosomal karyotype of 46,XX,t(5;9;22;6)(q13;q34;q11;q25), while FISH revealed presence of a variant Philadelphia chromosome translocation. Clonal evolution has occurred after 38 months of tyrosine kinase inhibitor (TKI) treatment, when cytogenetic analysis revealed coexisting t(5;9;22;6)(q13;q34;q11;q25) and t(5;9;22;6;17)(q13;q34;q11;q25;q11). After 57 months of TKIs treatment, only the t(5;9;22;6;17) clone was detected. Three months later, hyperdiploidy with additional abnormalities were detected in addition to t(5;9;22;6;17). Three mutations, including p.Tyr253Phe, p.Thr315Ile and p.Gly250Glu, were identified in the tyrosine kinase domain of the ABL1 gene during the course of disease. The patient did not attain cytogenetic and molecular response to TKIs.@*CONCLUSION@#The four-way variant translocation may be genetically unstable. Clonal evolution and genetic mutations are likely to occur during TKIs treatment, resulting in poor response to drug therapy. This observation, however, needs to be confirmed by large-scale studies.
Subject(s)
Female , Humans , Enzyme Inhibitors/therapeutic use , Evolution, Molecular , In Situ Hybridization, Fluorescence , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Mutation/genetics , Philadelphia Chromosome , Translocation, GeneticABSTRACT
Objective To investigate operation time on biliary duct stone with acute gallstone pancreatitis.Methods The clinical data of 44 patients with acute gallstone pancreatitis who were admitted to Department of General Surgery,Taicang First People's Hospital for surgical management from January 2011 to December 2013 were retrospectively analyzed.Patients were divided into early surgery group and delayed surgery group according to the timing.Early surgery group was defined as the patients whose symptoms of pancreatitis were basically disappeared after conservative treatment and surgery was performed within two weeks,while delayed surgery group was defined as the patients who underwent surgery after two weeks.Results Of the 44 acute gallstone pancreatitis cases,18 patients were males,and 26 were females,with median age of 54 years old (range 26-83 years old).Forty-two cases were mild acute pancreatitis and the other two cases were severe acute pancreatitis.Preoperative imaging indicated both cholecystolithiasis and choledocholithiasis in 5 patients,cholecystolithiasis alone in 39 patients.The 5 patients underwent cholecystectomy and choledocholithotomy with T-tube drainage.Among these 5 cases,one patient with concomitant acute suppurative cholangitis had an emergency surgery,two patients with Ranson score ≤3 had early surgery,and two patients with Ranson score ≥4 had delayed surgery,and all the patients were cured and discharged.Thirty-nine cases with cholecystolithiasis alone were treated with laparoscopic cholecystectomy.Among the 39 patients,25 patients underwent early laparoscopic cholecystectomy,and the other 14 patients underwent delayed surgery,and all the patients were cured and discharged.When compared with delayed group,the average age and Ranson score of early group were lower [(46 ± 12) yrs vs (64 ± 11) yrs and (1.0 ± 0.5) vs (1.5 ± 0.8)],and the median hospital length of stay and the cost were significantly less in the early group than those in the delayed group [(14.0 ± 2.8) d vs (18.1 ± 3.3) d and (17 899 ± 3461) Yuan vs (23 710 ± 3230) Yuan],and the difference between the two groups was statistically significant (P＜0.05).Nevertheless,there was no difference between the operation time and recovery time.There was no conversion to open surgery or post-operative complication in the two groups.Conclusions For severe acute pancreatitis,the delayed operation is recommended when the symptom of pancreatitis is completely improved after conservative management,while for mild acute pancreatitis,early surgery does not increase operation difficulty and complication,and it can decrease the length of hospital stays and costs.
ABSTRACT
Objective To investigate the role of miR-200b on gemcitabine induced epithelialmesenchymal transition (EMT) in pancreatic cancer cell line MiaPaCa-2.Methods Different concentrations of gemcitabine were used to induce MiaPaCa-2,and the concentration of 50％ cell proliferation inhibited (IC50) was applied to obtain drug-resistant MiaPaCa-2 cells.MiR-200b or nonsense small molecular fragments (negative control,NC) was transfected into MiaPaCa-2 cells by liposomes,then gemcitabine of IC50 was used to induce cells to obtain drug-resistant MiaPaCa-2 cells transfected with miR-200b or NC.The morphological characteristics of MiaPaCa-2 cells were observed by inverted microscope.Invasion of cells were detected by transwell chamber.The expression of miR-200b was measured by using real-time PCR.The expressions of Ecadherin,Vimentin,Zebl,Zeb2 proteins were determined by Western blot.Results After gemcitabine treatment,the cells' size gradually diminished,intercellular junctions decreased,pseudopodium increased,which presented the characteristics of mesenchymal morphology.The invaded cell number increased from (26 ± 3) to (85 ± 6),and the expression of Vimentin Zebl,Zeb2 was increased to (1.87 ± 0.17),(2.57 ±0.21),(5.24 ± 0.83) folds of the parent cells.The expression of miR-200b was decreased to (0.36 ± 0.01)folds of the parent cells,and the expression of E-cadherin was decreased to 0.47 ± 0.05 folds of the parent cells,while the invaded cell number of drug-resistant MiaPaCa-2 transfected with miR-200b was decreased to (42 ± 4),and the expression of Zebl,Zeb2 was decreased to (0.36 ± 0.07),(0.08 ± 0.01) folds of drugresistant MiaPaCa-2 transfected with NC.Conclusions The occurrence of EMT is observed in pancreatic cancer cell line MiaPaCa-2 during gemcitabine induction,and miR-200b down-regulation may be a possible mechanism.