{"id":641,"date":"2017-05-19T03:11:12","date_gmt":"2017-05-19T08:11:12","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=641"},"modified":"2017-05-19T03:11:12","modified_gmt":"2017-05-19T08:11:12","slug":"cytotoxic-effects-of-treosulfan-and-busulfan-against-leukemic-cells-of-pediatric-patients","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/cytotoxic-effects-of-treosulfan-and-busulfan-against-leukemic-cells-of-pediatric-patients\/","title":{"rendered":"Cytotoxic effects of treosulfan and busulfan against leukemic cells of pediatric patients"},"content":{"rendered":"

Treosulfan<\/a> is an alkylating agent that is structurally related\u00a0to busulfan. It is used in the treatment of ovarian carcinoma\u00a0and currently considered in clinical trials as a conditioning\u00a0agent prior to autologous and allogeneic stem cell transplantation (SCT). While high-dose busulfan is\u00a0associated with severe dose-limiting adverse effects such\u00a0as interstitial pneumonia, hemorrhagic cystitis, convulsion,\u00a0mucositis and an increased risk for venoocclusive disease, high-dose treosulfan has been found to\u00a0be less toxic on non-hematological tissues. In\u00a0addition, treosulfan combines favorably myeloablative and\u00a0immunosuppressive efficacy and might be a preferential\u00a0agent in combination with the immunosuppressive drugs\u00a0fludarabine or cyclophosphamide for conditioning protocols. Therefore, it seems an ideal candidate to replace\u00a0busulfan in myeloablative therapy for allogeneic SCT. First\u00a0successful results in adult hematological malignancies have\u00a0been reported by Casper et al.. Although childhood and\u00a0adult leukemias are biologically different, treosulfan\u00a0might be of interest for the treatment of childhood leukemia as well, because of both its very low nonhematological toxicity and its broad spectrum of antineoplastic activity against various cancers. To date, the prognosis of children with relapsed or\u00a0therapy refractory leukemia remains still dissatisfactory\u00a0despite multimodal chemotherapy and SCT. This is\u00a0necessitating optimization of high-dose chemotherapy\u00a0(HDC) protocols similar to the approach of Den Boer et al. for patient stratification based on drug resistance profiles in children with leukemia. Accordingly, the\u00a0development of new HDC protocols requires several stages\u00a0of pre-clinical and clinical investigations including in vivo\u00a0and in vitro studies.<\/p>\n

There is little data available describing in vitro and in\u00a0vivo efficacy of treosulfan compared to busulfan in leukemic cells, and literature lacks such in vitro data in\u00a0leukemic cells of pediatric patients. Lanvers-Kaminsky\u00a0et al. show a high sensitivity of adult leukemic cell\u00a0lines towards treosulfan, which has been superior, compared to busulfan incubation. Most importantly, xenograft\u00a0mouse models described by Fichtner et al. Yielded\u00a0promising in vivo results for three childhood leukemias\u00a0when comparing treosulfan with busulfan.<\/p>\n

We, therefore, sought to evaluate the cytotoxic effect\u00a0and dose response of treosulfan and busulfan on both\u00a0freshly isolated leukemic pediatric cell samples and normal\u00a0hematological cells like stem cells, T cells and natural\u00a0killer (NK) cells. The nucleoside-analogue fludarabine was\u00a0added in some experiments to evaluate possible interactions, because fludarabine is commonly combined with\u00a0busulfan. Additionally, the rapid cell apoptosis was\u00a0accessed by increased cleavage of pro-caspase 3 in the high\u00a0active parts of this proteinase to detect the apoptotic action\u00a0in leukemic cells.<\/p>\n

Reference:<\/p>\n

Munkelt, Doreen, et al. “Cytotoxic effects of treosulfan and busulfan against leukemic cells of pediatric patients.”\u00a0Cancer chemotherapy and pharmacology\u00a062.5 (2008): 821-830.<\/p>\n","protected":false},"excerpt":{"rendered":"

Treosulfan is an alkylating agent that is structurally related\u00a0to busulfan. It is used in the treatment of ovarian carcinoma\u00a0and currently considered in clinical trials as a conditioning\u00a0agent prior to autologous […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[181],"tags":[428],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/641"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=641"}],"version-history":[{"count":1,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/641\/revisions"}],"predecessor-version":[{"id":642,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/641\/revisions\/642"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=641"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=641"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=641"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}