scholarly journals Xenotransplantation of testicular tissue into nude mice can be used for detecting leukemic cell contamination

2007 ◽  
Vol 22 (7) ◽  
pp. 1899-1906 ◽  
Author(s):  
M. Hou ◽  
M. Andersson ◽  
S. Eksborg ◽  
O. Soder ◽  
K. Jahnukainen
2017 ◽  
Vol 91 ◽  
pp. 154-162 ◽  
Author(s):  
Hiroyuki Kaneko ◽  
Kazuhiro Kikuchi ◽  
Nguyen Thi Men ◽  
Michiko Nakai ◽  
Junko Noguchi ◽  
...  
Keyword(s):  

2006 ◽  
Vol 18 (2) ◽  
pp. 247 ◽  
Author(s):  
K. Kikuchi ◽  
M. Nakai ◽  
N. Kashiwazaki ◽  
M. Ozawa ◽  
N. Maedomari ◽  
...  

The utilization of spermatogonia from testicular tissue after xenografting into immuno-deficient mice should lead to new insights for the conservation of male gametes. However, successful embryo production using sperm cells from xenografted testicular tissues has been limited to rhesus monkeys (Honaramooz et al. 2004 Biol. Reprod. 70, 1500-1503). In the present study, the objective was to establish this new technology for pig conservation in combination with intracytoplasmic sperm injection. Testes were obtained from male piglets 6 to 15 days old, in which most of the germ cells were gonocytes; these were minced into pieces of approximately 1.5 � 1.5 � 1.5 mm. Approximately 20 fragments were transplanted under the back skin of castrated nude mice 5 to 8 weeks old. The testicular grafts were recovered between 125 and 192 days after xenografting, minced in Dulbecco's phosphate-buffered saline, and centrifuged several times, to serve as a sperm suspension. In vitro maturation of the recipient oocytes (Kikuchi et al. 2002 Biol. Reprod. 66, 1033-1041) and injection with an intact spermatozoon, followed by electrical stimulation at 1 h post-injection (Nakai et al. 2003 Biol. Reprod. 68, 1003-1008), were carried out. The putative zygotes were cultured in vitro for 6 days (Kikuchi et al. 2002), and were then fixed, stained, and assessed for embryonic development and quality. From a total of 27 mice that were xenografted with testicular tissues, spermatids and spermatozoa were obtained in 19 of the mice (70.4%). Most of the spermatozoa were matured morphologically, showing faint motility after release into the collection medium. From a total of 253 oocytes (four replications) that were injected with sperm, 63 (24.9 � 7.1%) oocytes developed to the blastocyst stage. The average total cell number was 41.9 � 3.9. These values are comparable to those in in vitro fertilization by frozen-thawed spermatozoa, resulting in developmental ability to piglets after embryo transfer (25.3% and 48.7 cells; Kikuchi et al. 2002). These results suggest the possibility of embryo production using porcine spermatozoa that are differentiated from gonocytes within the xenografts.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4413-4413
Author(s):  
Dong Wu ◽  
Maofang Lin

Abstract Background: Berbamine is a kind of bis-benzylisoquinoline extracted from Chinese herb. In our past research, it had been proven that berbamine could obviously inhibit the proliferation and induce apoptosis in different kinds of leukemic cell lines including K562, Jurkat, NB4 in a time-and dosage-dependent manner in vitro. The down-regulation expressions of survivin gene, bcr/abl gene and bcr/abl -related P210 may play an important role in the apoptotic effect of Berbamine in leukemic cells. However, the effects in vivo and its mechanism remain to be identified. In this study, the effects of berbamine in nude mice bearing human leukemic cell xenografts were tested. Methods: The nude mice (BALB/C-nu/nu) were pre-treated with X ray 400cGy/2min, then 2×107 K562 cells and Jurkat cells were subcutaneously injected into the mice respectively. Rapid growth of solid tumors was observed in nude mice. One week later, the tumor-bearing mice were randomly divided into three treatment groups: untreated controls; berbamine-treated group (a dose of 1.0mg/day × 20 day, subcutaneously injected); Ara-C-treated group(a dose of 0.8mg/day, × 7 day, subcutaneously injected). Four weeks later, all the experimental mice were euthanized. Results: Mice that received berbamine had significantly slower tumor growth rate than did untreated mice. In K562-bearing mice, the tumor weight of berbamine-treated group was lower than that of the control group(1.46g±0.43g vs 2.90g±0.94g, P<0.01 )and the inhibition rate was 49.66%. In Jurkat-bearing mice, the tumor weight of berbamine-treated group was also lower than that of untreated group(0.96g±0.64g vs 2.28g±0.33g, P<0.01), although it was comparable to that of Ara-C-treated group(0.54g±0.38g, P=0.311). The inhibition rates were 57.89% and 76.32% respectively. Moreover, in Jurkat-bearing mice berbamine inhibited the tumor cells invasion into bone marrow. In K562-bearing mice, berbamine down-regulated the expression level of bcr/abl gene of tumor cells ((berbamine-treated group 1.07±0.05 vs untreated group 1.58±0.24, P<0.05). In addition, no harmful side effects were attributed to berbamine. Conclusion: In vivo, berbamine could aslo take a better antileukemia effect and the dose of berbamine used was safe with almost no side effects in nude mice. Berbamine extracted from Chinese herb might be a promising candidate of new drugs for clinical anticancer treatment, especially for bcr-abl+ diseases.


2020 ◽  
Vol 91 (1) ◽  
Author(s):  
Hiroyuki Kaneko ◽  
Kazuhiro Kikuchi ◽  
Nguyen Thi Men ◽  
Thanh Quang Dang‐Nguyen ◽  
Motoharu Oyadomari ◽  
...  

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2442-2442
Author(s):  
Masako Yokoo ◽  
Yasushi Kubota ◽  
Sakiko Mochinaga ◽  
Aya Maeda ◽  
Tatsuo Ichinohe ◽  
...  

Abstract Abstract 2442 Cyclodextrins (CyDs) are cyclic oligosaccharides that can remove cholesterol from cell membranes and thereby affect receptor function, and are widely used in the pharmaceutical field because of those abilities to improve solubility, dissolution rate and bioavailability of the drugs. A number of studies have demonstrated that methyl-β- cyclodextrin (MβCD) can damage tumor cells and induce cell death. Very recently, Yan et al reported, on the basis of in vitro experiments, that MβCD induces apoptosis of chronic myeloid leukemia (CML) cells and have synergistic anti-leukemic effect combined with imatinib. 2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is clinically used as a pharmaceutical excipient, which has been successfully applied to poorly water-soluble drugs. Recently HP-β-CyD has been approved for the treatment of Niemann-Pick type C disease, a rare lysosomal lipid storage disorder. In the present study, we examined the antiproliferative effect of HP-β-CyD on the in vitro growth of leukemic cell lines and in vivo model using mice transplanted with leukemic cell line. First in vitro proliferation was assessed using the modified MTT assay. The human Ph+ leukemic cell line BV173 and BaF3 cells expressing p190 wild type BCR-ABL (hereafter BaF3/BCR-ABL) were used for evaluation. The growth of BV173 and BaF3/BCR-ABL cells were similarly inhibited by HP-β-CyD in a time- and dose-dependent manner with IC50 value of 4.68 ± 0.98 and 6.01 ± 1.04 mM, respectively. In contrast, IC50 value for hepatocytes was 18.65 ± 4.84 mM, suggesting some therapeutic window between normal cells and CML cells. We next determined if the inhibition of leukemic cell growth by HP-β-CyD was associated with the induction of apoptosis. BaF3/BCR-ABL and BV173 cells were exposed to HP-β-CyD for 12, 24, 48 hours at concentrations of 5, 10, 15 and 25mM. Assessment of apoptosis by 7-AAD/Annexin V double staining revealed that HP-β-CyD induced apoptosis in both cell lines in a time- and dose-dependent manner. The toxicity of HP-β-CyD on normal hematopoietic progenitors was also examined. The susceptibility of normal hematopoieic progenitors was investigated by colony-forming units (CFU-C) assay. When normal progenitors were treated with 5, 15 or 25 mM HP-β-CyD, the percentage of colonies was 92.7 ± 8.6 %, 83.8 ± 23.5 % and 52.4 ± 9.7 % of control, respectively. These results also indicate that HP-β-CyD may not induce bone marrow suppression up to 15mM. Because in vitro assay showed significant effects against leukemia cell growth, we also investigated the in vivo efficacy of HP-β-CyD. Six-week-old nude mice were injected with 1×106 BaF3/BCR-ABL cells, and were intraperioneally treated with 200 μl of either vehicle, 50mM HP-β-CyD or 150mM HP-β-CyD twice a day (BID) for 20 days from 3days after transplantation. The vehicle-treated mice died of a condition resembling acute leukemia by 29 days after transplantation; HP-β-CyD- treated mice survived more than 40 days, significantly improved the survival (50mM: P=0.003, 150mM: P=0.001, respectively) compared with control mice (Figure 1). These results clearly demonstrate that HP-β-CyD itself has a certain level of anti-leukemic potential. Though further investigations are required to elucidate the mechanisms underlying the antiproliferative function of HP-β-CyD, we should take notice of additional effect when the evaluation of drug efficacy is performed for anti-cancer agents complexed with HP-β-CyD. Figure 1. Administration of HP-β-CyD prolonged the survival in mice model of BCR-ABL-induced leukemia. Nude mice were injected with 1×106 BaF3 cells expressing p190 BCR-ABL. These mice were treated with vehicle or HP-β-CyD (50 or 150mM) for 20days from 3 days after transplantation. Figure 1. Administration of HP-β-CyD prolonged the survival in mice model of BCR-ABL-induced leukemia. Nude mice were injected with 1×106 BaF3 cells expressing p190 BCR-ABL. These mice were treated with vehicle or HP-β-CyD (50 or 150mM) for 20days from 3 days after transplantation. Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Author(s):  
Kazuhiro Kikuchi ◽  
Junko Noguchi ◽  
Hiroyuki Kaneko
Keyword(s):  

Author(s):  
Gene K. Potter ◽  
Anwar N. Mohamed ◽  
Nicholas C. Dracopoli ◽  
Susan L. B. Groshen ◽  
Rong Nian Shen ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e70989 ◽  
Author(s):  
Hiroyuki Kaneko ◽  
Kazuhiro Kikuchi ◽  
Michiko Nakai ◽  
Tamas Somfai ◽  
Junko Noguchi ◽  
...  

2014 ◽  
Vol 82 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Hiroyuki Kaneko ◽  
Kazuhiro Kikuchi ◽  
Fuminori Tanihara ◽  
Junko Noguchi ◽  
Michiko Nakai ◽  
...  

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