Engraftment of Post 5-Fluorouracil Murine Marrow into Minimally Myeloablated (100 cGy) Murine Hosts

Abstract

Minimal myeloablative approaches are now being widely applied in the treatment of different hematological malignancies. One hundred cGy whole-body irradiation is a stem-cell-toxic, relatively non-myelotoxic treatment that allows for relatively high levels of donor chimerism. 5-Fluorouracil (5-FU) treatment leads to a relative concentration of high proliferative potential-colony-forming cell (HPP-CFC) and is an approach that has been used to induce in vivo progenitor/stem cell cycling to facilitate retroviral integration in gene therapy approaches. We have now evaluated the capacity of marrow harvested 1, 2, 6, or 12 days after 5-FU treatment (150 mg/kg) to engraft in 100 cGy-treated female BALB/c mice. Engraftment was assessed at 3, 10, and 24 weeks. A rapid induction of an engraftment defect occurred 1 day post 5-FU and persisted through day 6 with a recovery by day 12. To evaluate cell cycle status of normal and 5-FU-treated marrow cells, male donors received hydroxyurea (900 mg/kg i.v.) or phosphate-buffered saline (PBS), 2 h prior to marrow harvest and transplantation into submyeloablated female recipients. Engraftment levels were similar for hydroxyurea-treated mice and controls. Thus, these studies show transiently defective engraftment of 5-FU-treated marrow into submyeloablated hosts, which may be related to the cell cycle status of the stem cells.

Granulocyte Colony-Stimulating Factor Prior to Nonmyeloablative Irradiation Decreases Murine Host Hematopoietic Stem Cell Function and Increases Engraftment of Donor Marrow Cells

“…Fluorescence in situ hybridization assays were adapted from D'Hondt et al [25] with modifications. Female recipient mice were bled by the tail vein.…”

Pharmacologically Inactive Bisphosphonates as an Alternative Strategy for Targeting Osteoclasts: In Vivo Assessment of 5-Fluorodeoxyuridine-Alendronate in a Preclinical Model of Breast Cancer Bone Metastases

“…Fluoropyrimidines and particularly 5-FdU are known to accumulate in the bone marrow and induce marrow depression. (36)(37)(38) The decrease of the serum markers after weekly 5-FdU administration may therefore not be reflective of the bone metabolic status but a consequent of transient bone marrow toxicity. However, there is no suggestion that 5-FdU-ale induced similar toxicity since changes in serum markers correlated with bone metabolic parameters.…”

Profile of Students Analytical Thinking Skills in Learning Style for Completing Substance Pressure Problems

“…The questions made are adjusted to the indicators contained in the skill to think analytically. The indicator of analytical thinking used as a reference is an indicator of analytical thinking (Dierks et al, 2016;Lopez & Tancinco, 2016). The indicators of analytical thinking are (1) identifying a problem, (2) finding and knowing relationship patterns carefully, (3) identifying and evaluating various errors, (4) concluding the main idea, which in each indicator also contains the skill of scientific processing.…”

“…However, if this is not done, it will result in the science teaching and learning process not being optimal, which will lead to higher-order thinking skills, especially the students' analytical thinking, which will not develop properly. Increasing the teaching and learning process effectiveness is necessary to conduct in-depth research on student learning (Lopez & Tancinco, 2016). Learning style is the preferred way for someone to think, process, and understand information.…”