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Preservation of male fertility in childhood acute leukemia : an experimental study addressing novel strategies and putative risks

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اقرأ أكثر حفظ في قائمتي
  • المؤلفون: Hou, Mi
  • نوع التسجيلة:
    Electronic Resource
  • الدخول الالكتروني :
    http://hdl.handle.net/10616/40027
    I. Hou M, Chrysis D, Nurmio M, Parvinen M, Eksborg S, Söder O, Jahnukainen K. (2005). Doxorubicin induces apoptosis in germ line stem cells in the immature rat testis and amifostine cannot protect against this cytotoxicity. Cancer Res. 65(21):9999-10005. ::pmid::16267025 ::isi::000232967000051
    II. Jahnukainen K, Hou M, Petersen C, Setchell B, Soder O. (2001). Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia. Cancer Res. 61(2):706-10. ::pmid::11212272 ::isi::000166819800051
    III. Hou M, Andersson M, Zheng CY, Sundblad A, Söder O, Jahnukainen K. (2007). Decontamination of leukemic cells and enrichment of germ cells from testicular samples from rats with Rosers leukemia by flow cytometric sorting. Reproduction. [Accepted] ::pmid::18042634 ::isi::000251688400006
    IV. Hou M, Andersson M, Zheng CY, Sundblad A, Söder O, Jahnukainen K. (2007). Immunomagnetic separation of normal rat testicular cells from Rosers T-cell leukemia cells is ineffective. International Journal of Andrology. ::pmid::17916184 ::doi::10.1111/j.1365-2605.2007.00819.x ::isi::000262226300006
    V. Hou M, Andersson M, Eksborg S, Söder O, Jahnukainen K. (2007). Xenotransplantation of testicular tissue into nude mice can be used for detecting leukemic cell contamination. Hum Reprod. 22(7): 1899-906. ::pmid::17452397 ::isi::000248051400016
  • معلومة اضافية
    • Publisher Information:
      Institutionen för kvinnors och barns hälsa / Department of Women's and Children's Health 2007-10-05
    • نبذة مختصرة :
      Although treatment of cancer in young boys with cytotoxic agents has long been known to cause infertility in the survivors, the mechanisms underlying drug-induced damage to the immature testis remain unclear. A number of clinical issues associated with transplantation of testicular germ cells or tissues also require clarification. The present investigation was designed to address some of these questions. First, we examined how a cytotoxic drug causes damage to immature testes. Following a single intraperitoneal injection of doxorubicin and, in some cases, additional administration of amifostine to 6-, 16- and 24 day-old rats, the frequency of apoptosis in microsegments of seminiferous tubules was evaluated. Gonocytes and migrating spermatogonia were identified as the targets for doxorubicin, which caused an 8-fold increase in the apoptosis of these cell types in the youngest rats. Activation of p53 and caspase-8 were the key initial events involved in germ cell apoptosis. Amifostine was incapable of protecting germ cells from doxorubicin-induced apoptosis (Paper I). In order to explore transplantation of testicular germ cells as a strategy for preservation of fertility, acute T-lymphoblastic leukemia (ALL) induced experimentally in rats was employed as a model for children with ALL. When testicular cells isolated from the testes of leukemic rats were transplanted into the seminifereous tubules of syngenic healthy rats, all of the recipients died from donor-derived leukemia, indicating a high risk of reseeding tumor cells into patients. The development of novel strategies for elimination of tumor cells and/or of animal models for detection of contaminated leukemic cells is thus required (Paper II). For this purpose, two purification procedures based on surface markers, the flow cytometric sorting (FACS) and immunomagnetic cell sorting (MACS), were evaluated. First CD4/MHC-Cl I and Ep-CAM, were identified as appropriate markers for leukemic and germ cells, respectivel
    • الموضوع:
      info:eu-repo/semantics/doctoralThesis
    • Note:
      English
    • Other Numbers:
      SEKIU oai:openarchive.ki.se:10616/40027
      978-91-7357-269-9
      20071026hou
      1134583903
    • Contributing Source:
      KAROLINSKA INSTITUTET UNIV
      From OAIster®, provided by the OCLC Cooperative.
    • الرقم المعرف:
      edsoai.on1134583903
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