Update on immune-based therapy strategies targeting cancer stem cells.

Accumulating data reveals that tumors possess a specialized subset of cancer cells named cancer stem cells (CSCs), responsible for metastasis and recurrence of malignancies, with various properties such as self-renewal, heterogenicity, and capacity for drug resistance. Some signaling pathways or processes like Notch, epithelial to mesenchymal transition (EMT), Hedgehog (Hh), and Wnt, as well as CSCs' surface markers such as CD44, CD123, CD133, and epithelial cell adhesion molecule (EpCAM) have pivotal roles in acquiring CSCs properties. Therefore, targeting CSC-related signaling pathways and surface markers might effectively eradicate tumors and pave the way for cancer survival. Since current treatments such as chemotherapy and radiation therapy cannot eradicate all of the CSCs and tumor relapse may happen following temporary recovery, improving novel and more efficient therapeutic options to combine with current treatments is required. Immunotherapy strategies are the new therapeutic modalities with promising results in targeting CSCs. Here, we review the targeting of CSCs by immunotherapy strategies such as dendritic cell (DC) vaccines, chimeric antigen receptors (CAR)-engineered immune cells, natural killer-cell (NK-cell) therapy, monoclonal antibodies (mAbs), checkpoint inhibitors, and the use of oncolytic viruses (OVs) in pre-clinical and clinical studies. This review will mainly focus on blood malignancies but also describe solid cancers.

Intraoperative minimal acute normovolemic hemodilution in patients undergoing coronary artery bypass surgery.

BACKGROUND & OBJECTIVE: Efficacy of minimal acute normovolemic hemodilution (ANH) in avoiding homologous blood transfusion during cardiovascular surgery remains controversial. Postoperative bleeding and transfusion remain a source of morbidity and cost after open heart operations. Our objective was to evaluate the impact of minimal ANH on blood transfusion requirements during open cardiovascular surgery using cardiopulmonary bypass (CPB). METHODS: This study was a randomized controlled trial. One hundred one patients scheduled for elective coronary artery bypass graft (CABG) under cardiopulmonary bypass in October 2007 through March 2008 in Imam Khomeini hospital were randomly assigned to a control group (standard care, no = 47) or an ANH or study group (no = 54). We used minimal ANH (representing 10% of patients' blood volume). Mean 490 +/- 50 mL of fresh autologous blood was removed after induction of anesthesia and reinfused at the end of CPB. The blood transfusion guidelines were uniformly applied to all patients. RESULTS: Significant decrease in the number of red blood cell units transfused per patient per group (1.39 +/- 1.0 and 2.551.9 +/- units; p < 0.0001) in the ANH group versus the control group was observed. Conversely, chest tube output, postoperative hematocrits, and platelet count did not differ between two groups. Percentage of patients in whom allogeneic red blood cells were transfused was 44% in study group versus 76% in control group; (p < 0.01). No patient was transfused with platelet concentrates or fresh frozen plasma. CONCLUSIONS: Minimal ANH is safe and cost effective and its routine use in eligible patients is therefore justified. Intraoperative autologous blood donation in CABG surgery decreased perioperative allogeneic blood requirement. However, the removal and reinfusion of about one unit autologous blood had no effect on postoperative bleeding or platelet count.

Optimization of Human Peripheral Blood Mononuclear Cells (PBMCs) Cryopreservation.

Cryopreservation is the method of choice for long term storage of human PBMCs. This study was designed to compare the different combinations of variables affecting the cryopreservation of PBMCs samples. The viability of PBMCs separated from 2×5 ml peripheral blood samples obtained from 16 healthy adult volunteers, were measured using trypan blue dye exclusion method just before freezing with different concentrations of DMSO (10, 15, and 20%) and FBS (40 or 70%) at two different temperatures (either 4(o)C or 25(o)C). Then after 2 weeks the cells were thawed and the viability was measured again. Also the PBMCs response to PHA was measured after 48 h using MTT assay. The effects of the different variables were calculated and compared among the groups. A total of 192 PBMCs cryotubes made from blood samples of 16 volunteers were tested. The viability of the cells obtained by the two centrifugation procedure was the same (both more than 99%). The concentration of the FBS (40 vs 70%) did not show to have significant effects on either cells viability or response to PHA. On the other hand 20% DMSO concentration and freezing temperature at 25(o)C decreased both cells. Based on the obtained results, it is recommended to centrifuge the PBMCs under higher revolt speed at shorter time (700 g for 20 minutes) and decrease the FBS concentration to 40%. The DMSO concentration should be kept at 10-15% and the freezing medium be cooled down to 4(o)C.