Mitochondrial pro-apoptotic ARTS protein is lost in the majority of acute lymphoblastic leukemia patients

Acquired resistance towards apoptosis is the hallmark of most if not all types of cancer. We have previously identified and characterized ARTS, a broadly expressed protein localized to mitochondria. ARTS was initially shown to mediate TGF-beta induced apoptosis. Recently, we have found that high levels of ARTS induce apoptosis without additional pro-apoptotic stimuli. Further, ARTS promotes apoptosis in response to a wide variety of pro-apoptotic stimuli. Here, we report that the expression of ARTS is lost in all lymphoblasts of more than 70% of childhood acute lymphoblastic leukemia (ALL) patients. The loss of ARTS is specific, as the related non-apoptotic protein H5, bearing 83% identity to ARTS, is unaffected. During remission, ARTS expression is detected again in almost all patients. Two leukemic cell lines, ALL-1 and HL-60 lacking ARTS, were resistant to apoptotic induction by ara-C. Transfection of ARTS into these cells restored their ability to undergo apoptosis in response to this chemotherapeutic agent. We found that methylation process contributes to the loss of ARTS expression. We conclude that the loss of ARTS may provide a selective advantage for cells to escape apoptosis thereby contributing to their transformation to malignant lymphoblasts. We therefore propose that ARTS can function as a tumor suppressor protein in childhood ALL.     

Assessment of epidermal growth factor receptor with 99mTc-ethylenedicysteine-C225 monoclonal antibody

Epidermal growth factor receptor (EGFR) plays an important role in cell division and cancer progression, as well as angiogenesis and metastasis. Since many tumor cells exhibit the EGFR on their surface, functional imaging of EGFR provides not only a non-invasive, reproducible, quantifiable alternative to biopsies, but it also greatly complements pharmacokinetic studies by correlating clinical responses with biological effects. Moreover, molecular endpoints of anti-EGFR therapy could be assessed effectively. C225 is a chimeric monoclonal antibody that targets the human extracellular EGFR and inhibits the growth of EGFR-expressing tumor cells. Also, it has been demonstrated that C225, in combination with chemotherapeutic drugs or radiotherapy, is effective in eradicating well-established tumors in nude mice. We have developed 99mTc-labeled C225 using ethylenedicysteine (EC) as a chelator. This study aimed at measuring uptake of 99mTc-EC-C225 in EGFR+ tumor-bearing animal models and preliminary feasibility of imaging patients with head and neck carcinomas. In vitro Western blot analysis and cytotoxicity assays were used to examine the integrity of EC-C225. Tissue distribution studies of 99mTc-EC-C225 were evaluated in tumor-bearing rodents at 0.5-4 h. In vivo biodistribution of 99mTc-EC-C225 in tumor-bearing rodents showed increased tumor-to-tissue ratios as a function of time. In vitro and biodistribution studies demonstrated the possibility of using 99mTc-EC-C225 to assess EGFR expression. SPECT images confirmed that the tumors could be visualized with 99mTc-EC-C225 from 0.5 to 4 h in tumor bearing rodents. We conclude that 99mTc-EC-C225 may be useful to assess tumor EGFR expression. This may be useful in the future for selecting patients for treatment with C225.     

Intravenous lidocaine as adjuvant to sevoflurane anesthesia for endotracheal intubation in children

IMPLICATIONS: Supplementing a sevoflurane induction of anesthesia in children with IV lidocaine 2 mg/kg can suppress cough after tracheal intubation and thus improve intubating conditions. In addition, lidocaine minimizes blood pressure fluctuations after tracheal intubation.     

Comparison of blood loss with different high-flux and high-efficiency hemodialysis membranes

Iron deficiency is a common problem in patients on chronic HD. Earlier studies have shown significant blood loss per HD session. To identify whether the new more biocompatible high-flux or high-efficiency membranes are also responsible for significant blood loss during HD, we quantitated the amount of blood loss associated with 4 commonly used membranes (F-50, F-80, CA-210, and CT-190). The residual blood in each compartment of extracorporeal circuit was quantitated after total lysis of the red blood cells (RBC), hemoglobin assay, and calculation of the RBC volume using the patient's hemoglobin and hematocrit concentrations just prior to the study. The average residual RBC volume in different membranes was 0.2-0.3 ml. The residual RBC volume in the dialysis lines (arterial or venous) was 0.1-0.2 ml and did not correlate with the residual RBC volume in the dialysis membranes. The residual RBC volume in the whole extracorporeal circuit (HD membrane, arterial and venous lines) ranged from 0.5 to 0.6 ml. It was significantly higher with F-50 vs. CA-210. The residual RBC volume in the dialysis membrane was significantly higher in the F-80 vs. CA-210 and CT-190 dialyzers. There was also significant difference in the residual RBC volume in the arterial lines of F-50 vs. CT-190, and F-50 vs. F-80 dialyzers. CONCLUSION: Our results demonstrate for the first time that the total RBC loss per HD session is minimal in chronic HD patients.     

Comparison of transcatheter versus surgical closure of perimembranous ventricular septal defect in pediatric patients: A systematic review and meta-analysis

ObjectivePerimembranous ventricular septal defect (pmVSD) is a common congenital heart disease (CHD) usually treated with either catheter or surgical closure. Superiority of one procedure over the other in children is still a matter of debate. We performed this meta-analysis to compare the clinical outcomes and cost of transcatheter and surgical closure of pmVSD in children.Materials and methodsWe searched seven databases (MEDLINE, PubMed, EMBASE, Google Scholar, CENTRAL, CINHAL, and Cochrane library) and literature references for articles published in the past 10 years (between January 2008 and January 2018) comparing closure of pmVSD by both procedures in children. The outcomes of interest were success rate, residual shunt, need for blood transfusion, complications especially complete atrioventricular block, length of hospital stay, and cost.ResultsA total of 1750 articles were identified. However, only five studies fulfilled the inclusion criteria. As regards success rate, no significant difference was found between surgical and catheter closure. Residual shunt was significantly lower in catheter closure than surgical closure [risk ratio (RR) = 0.44; 95% confidence interval (CI), 0.23–0.83, p = 0.01). The need for blood transfusion and the length of hospital stay were significantly lower in the catheter closure compared to surgical closure (RR = 0.02; 95% CI, 0.01–0.08; p < 0.00001), (RR = ?4.81; 95% CI, ?7.76 to ?1.86; p = 0.001), respectively. However, overall complications, complete atrioventricular block, and the cost were comparable in both procedures.ConclusionTranscatheter closure of pmVSD in children was as effective as surgical closure with a lower residual shunt and need for blood transfusion, and shorter hospital stay.