The present report describes work examining the manner in which nonmalignant bone marrow stromal cells prevent acute lymphoblastic leukemia (ALL) cell death. The initial focus was on the role of stromal cell-derived C-X-C motif chemokine 12 (CXCL12). Interference with CXCL12 production by stroma or blockade of its interactions with ALL by plerixafor did increase ALL cell death and in sensitive ALLs there was synergistic effect with conventional chemotherapy drugs. However, in contrast to most reports, there was considerable heterogeneity regarding the effect between 7 unique primary ALLs, with several exhibiting no sensitivity to CXCL12 blockade. The diversity in effect was not explained by differences in the expression of ALL cell surface receptors for CXCL12. The modest and variable effects of interference with CXCL12 on ALL led to the assessment of gene expression profiles of stromal cells and ALL cells. Gene set enrichment analysis identified pathways associated with metabolism and redox reactions as potentially important in the stromal cell: leukemia cell interaction. Exploratory imaging studies demonstrated bidirectional transfer of intracellular calcien-labelled molecules and also bidirectional transfer of mitochondria between stromal cells and ALL cells, providing potential means of metabolic interdependence of stromal cells and ALL cells.
Pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma are prescribed a daily oral chemotherapy medication named 6-mercaptopurine. Adherence to this medication is vital for survival and decreased risk for disease relapse. Adaptive problem-solving strategies are important for adhering to this complex regimen. This manuscript examined ethnic and racial differences in social problem-solving domains (Social Problem-Solving Inventory) among patients aged 7-19 years old who were diagnosed with cancer; and, their caregivers (N = 139). This was a 15-month longitudinal study. We also examined differences in medication adherence based on behavioral adherence measures. Our study found significant differences between minority and non-minority reporters across multiple social problem-solving domains (p < 0.05). However, there were no significant differences observed for medication adherence. Our findings underscore the importance of implementing culturally sensitive interventions in clinical care that could ultimately positively impact health behaviors, interactions with healthcare providers, and long-term health outcomes.
group n [ 4) and (4) CMVp-Cont inoculation with Veh group n [ 4).RESULTS: The number of NVCs (0.30 AE 0.12/min) in the CMVp-G2M-IVM group was significantly decreased, compared to other three groups (0.86 AE 0.12, 1.25 AE 0.14 and 1.27 AE 0.26 in Groups 2-4, respectively) (Figure 1).CONCLUSIONS: Gene therapy with replication-deficient HSV vectors encoding IVM-sensitive, mutant glycine receptors with exogenous ligand application could be a novel chemogenetic "druggable" treatment that can avoid systemic adverse events for neurogenic bladder dysfunction in SCI.
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