No abstract

The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 µM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML.

Adipocytokines was stated to exert biological effect on tumor cells. Two adipokines, leptin and adiponectin in particular, have come to be recognized for their influence on tumor biology including leukemia. The prognostic effect of leptin and adiponectin concentrations in acute leukemia patients remains to be identified. This study was conducted on 80 acute leukemia patients: 35 acute myeloid leukemia (AML), 45 acute lymphoid leukemia (ALL), and 20 controls of matched age and sex. Leptin and adiponectin were assayed by enzyme-linked immunosorbent assay at diagnosis. Serum leptin levels were significantly higher in ALL patients, and significantly lower in AML patients when compared with normal controls (P = 0.01, P = 0.04 respectively). On the other hand, serum adiponectin levels were significantly lower in AML and ALL patients as compared with normal controls (P = 0.00 for both). No significant differences exist regarding body mass index between acute leukemia patients and normal controls (P > 0.05). Correlation studies revealed that there were significant negative correlations between serum adiponectin levels and bone marrow (BM) blast cells and serum lactic dehydrogenase (sLDH) in acute leukemia groups (r 0.542, P < 0.01, r 0.699, P < 0.001, respectively). Regarding serum leptin levels there were positive significant correlations with BM blast cells (r 0.74, P < 0.01), total WBC counts (r = 0.59, P < 0.05), sLDH (r 0.738, P < 0.01) in ALL group; and significant negative correlations with BM blast cells (r 0.542, P < 0.01) and sLDH in the AML group. Adipocytokines may represent a new non-invasive biomarker in acute leukemia patients. Estimation of adiponectin and leptin serum levels at acute leukemia diagnosis could also be considered as a prognostic marker, which will be used in acute leukemia stratification.

No abstract

The incidence of lymphoid malignancies has been increasing rapidly. Despite growing evidence for a relationship between serum 25-hydroxivitamin D [25(OH)D] concentrations and solid tumor risk, far less is known about the relationship between 25(OH)D and the risk of hematologic malignancy. This study aimed to assess the prognostic relevance of serum 25(OH)D concentrations in patients with B chronic lymphocytic leukemia (B-CLL) and non Hodgkin's lymphoma (NHL). The study was carried out on 195 newly diagnosed patients (75 B-CLL and 120 NHL) as well as 30 normal healthy controls. For all patients and normal controls serum 25(OH)D concentrations were assayed by enzyme-linked immunosorbent assay. Serum 25(OH)D levels were significantly lower in B-CLL and NHL patients as compared with normal controls (P = 0.00 for both). Also, there are significant associations between serum 25(OH)D levels and positive CD 38, positive ZAP 70 as well as Binet stages (χ(2) = 16.071, 16.644, 21.134 respectively; P = 0.00 for all) in the B-CLL patient group. Moreover, there are significant associations between serum 25(OH)D status and international prognostic index (IPI), performance status (χ(2) = 6.994, 9.212, P = 0.02, 0.01 respectively), but not with clinical stages (χ(2) = 3.115, P = 0.539) in NHL. Multivariate analysis revealed that 25(OH)D insufficiency is an independent poor prognostic factor in both B-CLL and NHL patient groups. In conclusion, 25(OH)D insufficiency is an independent poor prognostic factor in patients with B-CLL and NHL. 25(OH)D might be a therapeutic target in lymphoid malignancies.