Genotoxic and Cytotoxic Effects of Testosterone Undecanoate on Bone Marrow and Germ Cells in Mice = التأثيرات السمية الخلوية و الوراثية لعقار Testosterone Undecanoateفي خلايا نقي العظم و الخلايا الجنسية للفئران

2016 ◽  
Vol 9 (3) ◽  
pp. 155-161
Author(s):  
Farha A. Ali Shafi
Keyword(s):  
Bone Marrow ◽  
Germ Cells ◽  
Cytotoxic Effects ◽  
Testosterone Undecanoate

scholarly journals Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yiyi Yao ◽  
Fenglin Li ◽  
Jiansong Huang ◽  
Jie Jin ◽  
Huafeng Wang
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chemotherapy Resistance ◽  
Bone Marrow Microenvironment ◽  
Cytotoxic Effects ◽  
High Relapse Rate ◽  
Underlying Mechanisms ◽  
Acute Myeloid

AbstractDespite the advances in intensive chemotherapy regimens and targeted therapies, overall survival (OS) of acute myeloid leukemia (AML) remains unfavorable due to inevitable chemotherapy resistance and high relapse rate, which mainly caused by the persistence existence of leukemia stem cells (LSCs). Bone marrow microenvironment (BMM), the home of hematopoiesis, has been considered to play a crucial role in both hematopoiesis and leukemogenesis. When interrupted by the AML cells, a malignant BMM formed and thus provided a refuge for LSCs and protecting them from the cytotoxic effects of chemotherapy. In this review, we summarized the alterations in the bidirectional interplay between hematopoietic cells and BMM in the normal/AML hematopoietic environment, and pointed out the key role of these alterations in pathogenesis and chemotherapy resistance of AML. Finally, we focused on the current potential BMM-targeted strategies together with future prospects and challenges. Accordingly, while further research is necessary to elucidate the underlying mechanisms behind LSC–BMM interaction, targeting the interaction is perceived as a potential therapeutic strategy to eradicate LSCs and ultimately improve the outcome of AML.

scholarly journals The cytokinetic and cytotoxic effects of ICRF-159 and ICRF-187 in vitro and ICRF-187 in human bone marrow in vivo

1983 ◽  
Vol 1 (4) ◽  
Author(s):  
RichardH. Wheeler ◽  
DanielJ. Clauw ◽  
RonaldB. Natale ◽  
RaymondW. Ruddon
Keyword(s):  
Bone Marrow ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cytotoxic Effects

scholarly journals Oocyte Generation in Adult Mammalian Ovaries by Putative Germ Cells in Bone Marrow and Peripheral Blood

Cell ◽  
2005 ◽  
Vol 122 (2) ◽  
pp. 303-315 ◽  
Author(s):  
Joshua Johnson ◽  
Jessamyn Bagley ◽  
Malgorzata Skaznik-Wikiel ◽  
Ho-Joon Lee ◽  
Gregor B. Adams ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Germ Cells ◽  
Peripheral Blood

217 PROTEIN-INDUCED TRANSDIFFERENTIATION INTO MALE GERM CELL-LIKE LINEAGE FROM CHICKEN FETAL BONE MARROW STEM CELLS

2012 ◽  
Vol 24 (1) ◽  
pp. 220
Author(s):  
J. M. Yoo ◽  
J. J. Park ◽  
K. Gobianand ◽  
J. Y. Ji ◽  
J. S. Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Retinoic Acid ◽  
Germ Cell ◽  
Germ Cells ◽  
Cultured Cells ◽  
Male Germ Cell ◽  
Male Germ Cells ◽  
Germ Cell Differentiation ◽  
Transgenic Chickens

Bone marrow (BM)-derived stem cells are capable of transdifferentiation into multilineage cells like muscle, bone, cartilage, fat and nerve cells. In this study, we investigated the capability of mesenchymal stem cells (MSC) derived from BM into germ cell differentiation in the chicken. Chicken MSCs were isolated from BM of day 20 fertilized fetal chicken with Ficoll-Paque Plus. Isolated cells were cultured in advance-DMEM (ADMEM) supplemented with 10% fetal bovine serum and antibiotics. Once confluent, cells were subcultured until five passages. The cultured cells showed fibroblast-like morphology. The cells had positive expressions of Oct4, Sox2 and Nanog. Two induction methods were conducted to examine the ability of transdifferentation into male germ cells. In group 1, MSC were cultured in ADMEM containing retinoic acid and chicken testicular extracts proteins for 10 to 15 days. In group 2, MSC were permeabilized by streptolysin O and treated with chicken testicular protein extracts. In both treatment groups, MSC were cultured in ADMEM containing retinoic acid for 10 to 15 days. We found that chicken MSC had a positive expression of pluripotent proteins such as Oct4, Sox2, Nanog and a small population of chicken MSC seem to transdifferentiate into male germ cell-like cells. These cells expressed early germ cell markers and male germ-cell-specific markers (Dazl, C-kit, Stra8 and DDX4) as analysed by reverse transcription-PCR and immunohistochemistry. These results demonstrated that chicken MSC may differentiate into male germ cells and the same might be used as a potential source of cells for production of transgenic chickens. This study was carried out with the support of Agenda Program (Project No. PJ0064692011), RDA and Republic of Korea.

In vivo mutagenicity evaluation of domperidone in Drosophila germ cells and rat bone marrow cells

Toxicology ◽  
1985 ◽  
Vol 36 (2-3) ◽  
pp. 147-150 ◽  
Author(s):  
P VANPARYS ◽  
J GILOTDELHALLE ◽  
J MOUTSCHEN ◽  
M MOUTSCHENDAHMEN ◽  
R MARSBOOM
Keyword(s):  
Bone Marrow ◽  
Germ Cells ◽  
Bone Marrow Cells ◽  
In Vivo Mutagenicity ◽  
Rat Bone ◽  
Marrow Cells

Genotoxicity of crotonaldehyde in the bone marrow and germ cells of laboratory mice

2007 ◽  
Vol 632 (1-2) ◽  
pp. 69-77 ◽  
Author(s):  
Anand M. Jha ◽  
Akhilesh C. Singh ◽  
Uma Sinha ◽  
Mithilesh Kumar
Keyword(s):  
Bone Marrow ◽  
Germ Cells ◽  
Laboratory Mice

An Acidic Milieu Created In Myeloma-Osteoclast Interaction Enhances Tumor Growth, but Triggers Anti-Myeloma Activity of Reveromycin A, a Novel Anti-Resorptive Agent

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 454-454
Author(s):  
Keiichiro Watanabe ◽  
Masahiro Abe ◽  
Qu Cui ◽  
Makoto Kawatani ◽  
Masahiro Hiasa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Cell Growth ◽  
Bone Marrow Cells ◽  
Lactate Production ◽  
Bone Destruction ◽  
Cytotoxic Effects ◽  
Acidic Microenvironment ◽  
Pit Formation ◽  
Rabbit Bone

Abstract Abstract 454 Multiple myeloma (MM) develops and expands in the bone marrow, and causes devastating bone destruction by enhancing osteoclastic bone resorption in their close vicinity. In MM bone lesions, thus induced osteoclasts (OCs) in turn enhance MM cell growth and survival, thereby forming a vicious cycle between the progression of bone destruction and MM tumor expansion. Such cellular interactions create an acidic milieu not only through acids produced by OCs but also through a large amount of lactate by proliferating tumor cells (Warburg effect). Reveromycin A (RM-A), a small microbial metabolite, preferentially induces cellular apoptosis in an acidic milieu, and draws considerable attention as a novel anti-resorptive agent. In the present study, we explored whether an acidic condition induced by MM-OC interaction affects MM expansion and whether RM-A targets not only OCs but also such an acidic microenvironment to regress tumor expansion in MM. INA6 and RPMI8226 MM cells potently enhanced osteoclastogenesis and osteoclastic pit formation when cocultured with rabbit bone marrow cells on bone slices. Notably, large multinucleated OCs were almost completely disappeared and pit formation on bone slices was abolished upon the treatment with RM-A at concentrations as low as 100nM. The cocultures with rabbit bone marrow cells stimulated INA6 MM cell growth; RM-A at 1microM was however able to substantially decrease the MM cell viability in the cocultures after 12 hours, although RM-A at this concentration did not affect MM cell growth when MM cells were cultured alone at pH7.4. The suppression of INA6 MM cell viability by RM-A was obviously more potent than that under bisphosphonate treatment in which mature OCs and pits on bone slices similarly decreased in number, suggesting that the anti-MM effects of RM-A is not merely due to depletion of mature OCs. Blockade of acid release by the proton pump inhibitor concanamycin A abolished such RM-A effects. Because an acidic microenvironment increases cell permeability of RM-A to cause apoptosis, it is plausible that a highly acidic milieu created by OC-MM interaction allows RM-A to act on nearby MM cells as well as OCs. In order to clarify a role of tumor acidity in RM-A-triggered cell death, we examined the effects of RM-A on MM cell growth upon acidification with lactic acid. When lactic acid was added to media to adjust their pH to be 7.0 and 6.75, the growth of INA6 and RPMI8226 MM cells was enhanced up to 150 and 120%, respectively, after 24 hours compared to that at pH7.4. However, RM-A at 1microM induced cell death in these MM cells at pH7.0 (60-70% reduction of alive MM cells compared to those at pH7.4) and at pH6.75 (>90%), suggesting cytocidal effects of RM-A on lactate-producing MM cells densely proliferated in an acidic milieu. Because metoformin, anti-diabetic agent, up-regulates lactate production through stimulation of glycolysis, we next examined the effects of RM-A on MM cells in combination with metoformin. Metoformin dose-dependently enhanced lactate production by MM cells to decrease pH in their culture media over time; RM-A at 1microM showed potent cytotoxic effects on MM cells upon 24-hour preceded treatment with metoformin at 5 mM even when MM cells were started to be cultured at pH7.4, suggesting induction of anti-MM activity of RM-A with metoformin. Finally, in vivo RM-A effects were studied using INA6 MM cell-bearing SCID-rab mice. We injected RM-A sc at 4mg/kg twice daily for 18 days to the mice after confirming MM cell growth at 4 weeks after the MM cell inoculation. The RM-A treatment substantially decreased osteolytic lesions in X-ray and microCT images and MM tumor area in bone sections along with a reduction of INA6 cell-derived human soluble IL-6 receptor levels in mouse sera as a marker of MM tumor burden. These results collectively suggest that acidic microenvironment produced by MM-OC interaction enhances MM tumor progression but can trigger cytotoxic effects of RM-A on MM cells besides acid-producing OCs. RM-A may become a candidate for a novel therapeutic agent against MM with extensive bone resorption. Disclosures: No relevant conflicts of interest to declare.

BMP4 can generate primordial germ cells from bone-marrow-derived pluripotent stem cells

2012 ◽  
Vol 36 (12) ◽  
pp. 1185-1193 ◽  
Author(s):  
Reza Shirazi ◽  
Amir Hassan Zarnani ◽  
Masoud Soleimani ◽  
Mir Abbas Abdolvahabi ◽  
Karim Nayernia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Primordial Germ Cells
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