Targeting pediatric leukemia propagating cells using anti-CD200 antibody therapy.

Treating refractory pediatric acute lymphoblastic leukemia (ALL) remains a challenge despite impressive remission rates (>90%) achieved in the last decade. The use of innovative immunotherapeutic approaches such as anti-CD19 chimeric antigen receptor T cells does not ensure durable remissions, because leukemia-propagating cells (LPCs) that lack expression of CD19 can cause relapse, which signifies the need to identify new markers of ALL. Here we investigated expression of CD58, CD97, and CD200, which were previously shown to be overexpressed in B-cell precursor ALL (BCP-ALL) in CD34(+)/CD19(+), CD34(+)/CD19(–), CD34(–)/CD19(+), and CD34(–)/CD19(–) LPCs, to assess their potential as therapeutic targets. Whole-genome microarray and flow cytometric analyses showed significant overexpression of these molecules compared with normal controls. CD58 and CD97 were mainly co-expressed with CD19 and were not a prerequisite for leukemia engraftment in immune deficient mice. In contrast, expression of CD200 was essential for engraftment and serial transplantation of cells in measurable residual disease (MRD) low-risk patients. Moreover, these CD200(+) LPCs could be targeted by using the monoclonal antibody TTI-CD200 in vitro and in vivo. Treating mice with established disease significantly reduced disease burden and extended survival. These findings demonstrate that CD200 could be an attractive target for treating low-risk ALL, with minimal off-tumor effects that beset current immunotherapeutic approaches

Functionalized triblock copolymer vectors for the treatment of acute lymphoblastic leukemia

The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia

Biodegradable, drug-loaded nanovectors via direct hydration as a new platform for cancer therapeutics

\u3cp\u3eThe stabilization and transport of low-solubility drugs, by encapsulation in nanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technologies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is necessary to reconsider the entire process from copolymer synthesis through self-assembly and functionalization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)-block-poly(trimethylene carbonate), synthesized via organocatalyzed ring-opening polymerization, undergo assembly into highly uniform, drug-loaded micelles without the use of harmful solvents or the need for purification. The direct hydration methodology, employing oligo(ethylene glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug-loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an exciting candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are generated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells).\u3c/p\u3

Impact of Squatting on Selected Cardiovascular Parameters Among College Students

Squatting is an active posture test used in assessing baroreflex sensitivity and the array of patients a physiotherapist handles, may benefit from this test to avoid the adverse effects of exercise. Therefore, this study aimed to evaluate the change in cardiovascular parameters that would occur during squatting among undergraduate students. 35 males (mean age = 22.94 ± 1.846) and 40 females (mean age = 22.28 ± 2.075) participated in this experimental study. Demographic data and baseline cardiovascular parameters (blood pressure and heart rate) were taken before exercise. The exercise protocol which was the squatting stress test was done for 2 minutes, after which post exercise blood pressure and heart rate were taken at an interval of one minute each. Paired and independent t-test was used to analyze the difference at 0.05 alpha level. It was found that there was a significant difference between pre and post-exercise blood pressure and heart rate in 1 and 2 minutes (p < 0.001) and also a significant difference in pre-exercise heart rate between lying and standing (p < 0.001). Also, there was no significant difference between 1 minute and 2 minutes post squatting exercise systolic blood pressure (p = 0.588), diastolic blood pressure (p = 0.381) and heart rate (p = 0.745). In conclusion, squatting trials among undergraduates revealed some statistically significant changes, especially between the cardiopulmonary parameters obtained in a standing position compared to lying, and those measured after one minute. Therefore, caution should be observed when administering exercises that require changes in posture

Impact of squatting on selected cardiovascular parameters among college students

Abstract Squatting is an active posture test used in assessing baroreflex sensitivity, and the array of patients a physiotherapist handles may benefit from this test to avoid the adverse effects of exercise. Therefore, this study is designed to evaluate the effect of squatting on heart rate and blood pressure among undergraduate students. 35 males (mean age = 22.94 ± 1.846) and 40 females (mean age = 22.28 ± 2.075) participated in this experimental study. Demographic data and baseline cardiovascular parameters (blood pressure and heart rate) were taken before exercise. The exercise protocol, the squatting stress test, was done for 2 min, after which post-exercise blood pressure and heart rate were taken at one minute each. A repeated measure ANOVA and independent t-test were used to analyse the difference at the 0.05 alpha level. It was found that there was a significant difference between pre-exercise in lying and squatting post-exercise blood pressure and heart rate in the first and second minutes (p < 0.01), pre-exercise in lying and standing post-exercise blood pressure and heart rate in the first and second minutes (p < 0.01), pre-exercise in standing and standing post-exercise blood pressure and heart rate in the first and second minutes (p < 0.01), and pre-exercise in standing and squatting post-exercise blood pressure and heart rate in the first and second minutes (p < 0.01). Also, there was a significant difference in pre-exercise heart rate between lying and standing (p < 0.05) and not between the first minute and second minute post-squatting or standing exercise systolic blood pressure (p = 0.588) or diastolic blood pressure (p = 0.22–1). In conclusion, squatting trials among undergraduates revealed some statistically significant changes, especially between the cardiopulmonary parameters obtained in a standing position compared to lying and those measured after one minute. Therefore, caution should be observed when administering exercises that require changes in posture