Integrin beta 7 (ß7), a subunit of the integrin receptor, is expressed on the surface of immune cells and mediates cell–cell adhesions and interactions, e.g., antitumor or autoimmune reactions. Here, we analyzed, whether the stimulation of immune cells by dendritic cells (of leukemic derivation in AML patients or of monocyte derivation in healthy donors) leads to increased/leukemia-specific ß7 expression in immune cells after T-cell-enriched mixed lymphocyte culture—finally leading to improved antileukemic cytotoxicity. Healthy, as well as AML and MDS patients’ whole blood (WB) was treated with Kit-M (granulocyte–macrophage colony-stimulating factor (GM-CSF) + prostaglandin E1 (PGE1)) or Kit-I (GM-CSF + Picibanil) in order to generate DCs (DCleu or monocyte-derived DC), which were then used as stimulator cells in MLC. To quantify antigen/leukemia-specific/antileukemic functionality, a degranulation assay (DEG), an intracellular cytokine assay (INTCYT) and a cytotoxicity fluorolysis assay (CTX) were used. (Leukemia-specific) cell subtypes were quantified via flow cytometry. The Kit treatment of WB (compared to the control) resulted in the generation of DC/DCleu, which induced increased activation of innate and adaptive cells after MLC. Kit-pretreated WB (vs. the control) led to significantly increased frequencies of ß7-expressing T-cells, degranulating and intracellular cytokine-producing ß7-expressing immune cells and, in patients’ samples, increased blast lysis. Positive correlations were found between the Kit-M-mediated improvement of blast lysis (vs. the control) and frequencies of ß7-expressing T-cells. Our findings indicate that DC-based immune therapies might be able to specifically activate the immune system against blasts going along with increased frequencies of (leukemia-specific) ß7-expressing immune cells. Furthermore, ß7 might qualify as a predictor for the efficiency and the success of AML and/or MDS therapies.
Background:Background: There are virtually no treatment options for therapy-refractory or relapsed AML/MDS and high rates of relapse in successfully treated patients. The combination of the (clinically approved) immune-modulatory compounds GM-CSF+ Prostaglandine (PGE)1, the combination referred to as KIT-M converts myeloid blasts into dendritic cells of leukemic origin (DC leu ). After stimulation with DC leu , antileukemic (T)cells are activated.
Aims:Aims: Kit-M treatment may be an attractive tool for immunotherapy in myeloid leukemia.
Methods:Methods: Generation of DC from leukemic whole blood (WB) samples. Mixed lymphocyte culture (MLC) followed by functional antileukemic assays.
INTRODUCTION AND OBJECTIVES: During the last years there has been an effort in miniaturizing the endoscopic devices. The video presents an alternative for the management of distal ureteral stone, using a ureteral access of 4.85Fr and 27cm of length, previously described as micro-ureteroscopy. METHODS: This procedure was performed through a 3-part allseeing needle, consisting of micro-optics 0.9mm in diameter with a 120degree angle of view, an irrigation channel and an integrated light. RESULTS: Seven year-old boy, with history of preterm birth (29 weeks) was referred to our consultation complaining of left back pain and an elevation of serum creatinine. The renal ultrasound revealed a left ureterohydronephrosis, caused by a 10mm stone located 13mm from the ureterovesical junction. The patient underwent a micro-ureteroscopy with laser lithotripsy. The stone was fragmented with an average energy of 0.5J with 12Hz of frequency. The total energy spent was 12514J. At the end of the procedure, a double J stent was placed. The procedure lasted 45 minutes and was uneventful. The patient was discharged 24h after the procedure without complaints and remained stone free. CONCLUSIONS: Micro-ureteroscopy is a safe and effective technique in distal ureteral lithiasis treatment in children. The small dimensions of the equipment increase the safety of the procedure making this a good option for the treatment of ureteral stones in children.
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