Cellular and plasma adriamycin concentrations in long-term infusion therapy of leukemia patients

Speth, P. A. J.; Linssen, P.C.M.; Boezeman, J.B.M.; Wessels, H.; Haanen, C.

doi:10.1007/bf00262581

Cited by 68 publications

(40 citation statements)

References 11 publications

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“…These findings suggest that use of LD doxorubicin may mediate death of hepatoma cells while avoiding damage to normal tissues including cardiotoxicity associated with HD doxorubicin. Supporting this idea, administration of LDs of doxorubicin for extensive periods of time rather than HDs for short periods of time may benefit patient survival [23]. In addition, our finding that Bcl-xL overexpression significantly blocked HD doxorubicin-induced apoptosis but not LD doxorubicin-induced cell death suggests that the apoptosis-inducing strategy using HD doxorubicin may not have a therapeutic effect on Bcl-xL-overexpressing hepatoma cells.…”

Section: Discussionmentioning

confidence: 74%

Bcl-xL blocks high dose doxorubicin-induced apoptosis but not low dose doxorubicin-induced cell death through mitotic catastrophe

Park

Kim

Eom

et al. 2007

Biochemical and Biophysical Research Communications

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Section: Discussionmentioning

confidence: 74%

Bcl-xL blocks high dose doxorubicin-induced apoptosis but not low dose doxorubicin-induced cell death through mitotic catastrophe

Park

Kim

Eom

et al. 2007

Biochemical and Biophysical Research Communications

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“…Induction of senescence or cell death through mitotic catastrophe by LD anticancer drugs may have several advantages for patients. As high plasma concentrations of doxorubicin tend to cause severe toxicity to normal tissues, including cardiotoxicity (Speth et al, 1987), administration of LDs of doxorubicin for extensive periods of time rather than HDs for short periods of time may benefit patient survival. Furthermore, since cell death through mitotic catastrophe is similar to necrosis in relation to the early loss of plasma membrane integrity, it is possible that induction of cell death though mitotic catastrophe may lead to inflammation and mobilization of the immune system against the tumor.…”

Section: Discussionmentioning

confidence: 99%

Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype

et al. 2005

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“…Accordingly, lymphoid and myeloid leukemic cells were exposed to typical treatment doses of 1 M dexamethasone and 1 M daunorubicin respectively. 5,6 Positive staining with either 0.9 M propidium iodide (PI) or 1 M Sytox Green (Invitrogen, Carlsbad, CA), markers for loss of cell membrane integrity, indicated cell death or late apoptosis. To identify early apoptosis, we used cresyl violet conjugated to Aspartate-Glutamate-ValineAspartate (Immunochemistry Technologies, Bloomington, MN), an indicator for caspase 3 and 7 activity.…”

mentioning

confidence: 99%

Chemotherapy exposure increases leukemia cell stiffness

Lam

Rosenbluth

Fletcher

2006

Blood

237

206

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Deformability of blood cells is known to influence vascular flow and contribute to vascular complications. Medications for hematologic diseases have the potential to modulate these complications if they alter blood cell deformability. Here we report the effect of chemotherapy on leukemia cell mechanical properties. Acute lymphoblastic and acute myeloid leukemia cells were incubated with standard induction chemotherapy, and individual cell stiffness was tracked with atomic force microscopy. When exposed to dexamethasone or daunorubicin, leukemia cell stiffness increased by nearly 2 orders of magnitude, which decreased their passage through microfluidic channels. This stiffness increase occurred before caspase activation and peaked after completion of cell death, and the rate of stiffness increase depended on chemotherapy type. Stiffening with cell death occurred for all cell types investigated and may be due to dynamic changes in the actin cytoskeleton. These observations suggest that chemotherapy itself may increase the risk of vascular complications in acute leukemia. IntroductionAlterations of biophysical properties of blood cells contribute to the pathophysiology of hematologic diseases. 1-3 While chemotherapy-induced cell death has been a mainstay of cancer treatment for decades and is well-studied biochemically, little is known about the mechanical effects chemotherapy may have on leukemia cells. Furthermore, since hyperleukocytosis accompanies some cases of acute leukemia, mechanical changes in leukemia cells due to chemotherapy could significantly alter the overall blood rheology.In this work, we quantified the effect of standard induction chemotherapy on the stiffness of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) cells using atomic force microscopy (AFM), a tool for imaging and characterization of materials at the nanometer scale. 4 The high force sensitivity of AFM and its ability to measure properties of individual cells over long times makes the technique particularly appropriate for measuring dynamic changes in cell stiffness. We find that when exposed to chemotherapy, leukemia cell stiffness increased by nearly 2 orders of magnitude at a rate dependent on the type of chemotherapy employed. Materials and methods Leukemia cell sources and reagentsLeukemia cells were isolated via centrifugation from the blood of patients with newly diagnosed acute leukemia noted to have peripheral blast cells. Leukemic cell lines were purchased commercially (ATCC, Manassas, VA). University of California, San Francisco (UCSF) and UC Berkeley institutional review boards approved all experimental procedures. Informed consent was obtained from each human subject, in accordance with the Declaration of Helsinki, before a blood sample was obtained. Dexamethasone and daunorubicin (Sigma-Aldrich, St Louis, MO) are mainstay induction chemotherapeutic agents for ALL and AML, respectively. Accordingly, lymphoid and myeloid leukemic cells were exposed to typical treatment doses of 1 M dexamethasone and 1 M...

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Cellular and plasma adriamycin concentrations in long-term infusion therapy of leukemia patients

Cited by 68 publications

References 11 publications

Bcl-xL blocks high dose doxorubicin-induced apoptosis but not low dose doxorubicin-induced cell death through mitotic catastrophe

Bcl-xL blocks high dose doxorubicin-induced apoptosis but not low dose doxorubicin-induced cell death through mitotic catastrophe

Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype

Chemotherapy exposure increases leukemia cell stiffness

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