Antisense strategies for the treatment of hematological malignancies and solid tumors

Kronenwett, Ralf; Haas, Rainer

doi:10.1007/s002770050404

Cited by 21 publications

(13 citation statements)

References 116 publications

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“…This kind of packaging leads to the formation of micromolecular complexes with a positive charge on the surface, permitting binding to the negatively charged membrane. Following attachment to the cell, the complexes are presumably taken up via endocytosis (2,4,10,11). In the present study, we discerned that liposome formation with lipofectin of AS-ODNs increased the intracellular delivery of AS-ODN, achieving levels of approximately double.…”

Section: Discussionsupporting

confidence: 49%

Myeloablative Treatment Supported by Autologous Stem Cell Infusion with Neuroblastoma

et al. 2003

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Bcr-abl antisense oligodeoxynucleotides (AS-ODNs) have provided evidence of an antileukemia effect when tested in vitro against Philadelphia-positive cells. In order to investigate the efficacy of AS-ODNs as purging agents in chronic myeloid leukemia (CML) patients, K562 cells, a human CML cell line, were treated in vitro with various types of AS-ODNs and interferon-alpha. Cells were treated in vitro for 0 and 36 hr with 40 microgram/mL of AS-ODNs, respectively, and incubated at 37 degrees C for 36 hr. Cytotoxic effects were measured by counting the number of viable cells as well as by MTT test. Clonogenic activities were evaluated by methylcellulose culture for 2 weeks. The effects of purging agents on the rearrangement of bcrabl gene were evaluated by RT-PCR. AS-ODNs inhibited the proliferation of K562 cells with time in cell count assay and MTT test. AS-ODNs were superior to INF-alpha in inhibiting clonogenic activity (recovery rate; 26.3% vs 64.0%). After incubation with bcr-abl AS-ODNs primers and mRNA isolated from K562 cells, positive bands were abolished, especially of b3a2 type and phosphorothioate type. Our results suggest that AS-ODNs mediated purging may be one of the efficient methods and that autograft may be an alternative treatment for allograft in high-risk group patients of CML if they do not have a stem cell donor.

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Section: Discussionsupporting

confidence: 49%

Myeloablative Treatment Supported by Autologous Stem Cell Infusion with Neuroblastoma

et al. 2003

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“…Decreasing levels through emerging antisense technology may prove to be highly successful. 75 Caspases are key effectors of cellular death and have been implicated as predictors of survival in AML and ALL. 32,76 In particular, caspase-3 has been shown to be involved in the apoptosis seen in leukemia in response to many chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Diversity of the apoptotic response to chemotherapy in childhood leukemia

et al. 2002

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Apoptosis is the primary mechanism through which most chemotherapeutic agents induce tumor cell death. The purpose of this study was to determine the extent to which blasts from children with leukemia undergo a uniform apoptotic death pathway in vivo. The expression of pro-and anti-apoptotic proteins p53, p21, MDM-2, BCL-2, BCL-X L , BCL-X S , and BAX, and caspase-3 activity was determined in circulating blasts collected from the peripheral blood of children with leukemia prior to, and at serial time points following chemotherapy. Culturing blasts ex vivo for 12 h assessed spontaneous apoptosis and the increment induced by chemotherapy. Baseline apoptosis varied between 3% and 29%. Twenty-four hours following chemotherapy the increase in the percentage of cells undergoing apoptosis ranged from Ͻ1% to 38%. Eleven of 20 patients who received initial treatment with a p53-dependent drug showed an increase in p53 expression. In these patients, the levels of p53 target genes were also increased. A uniform pattern of BCL-2 family protein expression was not observed and only a minority of samples showed a change that would favor apoptosis. We conclude that that the initial apoptotic response to chemotherapy in children with leukemia is variable involving both p53-dependent and p53-independent pathways.

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“…Thus, structural modifications have to be introduced into ODN structure to increase in vivo stability, while preserving specific hybridization properties and minimizing non-specific ODN interaction with other macromolecules such as proteins. 2,11 Liposomes are non-toxic lipid vesicles containing aqueous compartments separated by lipid bilayers. 12 They can be used as carrier for ODN's while reducing toxic side effects and maintaining their efficiencies.…”

Section: Introductionmentioning

confidence: 99%

Liposomal Delivery of Antisense Oligonucleotides for Efficient Downregulation of Bcl-2 and Induction of Apoptosis

Buck

Shen

Schirrmeister

et al. 2002

Cancer Biotherapy and Radiopharmaceuticals

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Antisense strategies for the treatment of hematological malignancies and solid tumors

Cited by 21 publications

References 116 publications

Myeloablative Treatment Supported by Autologous Stem Cell Infusion with Neuroblastoma

Myeloablative Treatment Supported by Autologous Stem Cell Infusion with Neuroblastoma

Diversity of the apoptotic response to chemotherapy in childhood leukemia

Liposomal Delivery of Antisense Oligonucleotides for Efficient Downregulation of Bcl-2 and Induction of Apoptosis

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