Parameters affecting the ex vivo cytotoxic drug sensitivity of human hematopoietic cells

Abstract

The drug sensitivity of normal cells provides a baseline for determining the therapeutic index, and therefore the effectiveness, of cytotoxic drugs, yet little is known about the factors that affect normal cell chemosensitivity. Some parameters are known to have a profound effect on tumor cell sensitivity. The purpose of this study was to determine how cytotoxic drug sensitivity of hematopoietic cells isolated from cancer patients was affected by various parameters. These included previous chemotherapy (yes or no), sex, age, tumor type (leukemias or solid tumors), sample source (blood, bone marrow, serous effusions, or tumor biopsies) and predominant cell lineage (lymphoid, myeloid, macrophage, or mixed). Mononuclear cells isolated from blood, bone marrow, serous effusions, and tumor biopsies were incubated for four days with a median of 16 drugs. The differential staining cytotoxicity assay, an ex vivo apoptotic drug sensitivity test in which cell survival is determined morphologically, was used to assess normal hematopoietic and tumor cell response to cytotoxic drugs. One hundred forty-six specimens yielded hematopoietic cell chemosensitivity results with 3-36 drugs. Compared with tumor cells, there was far less interpatient variation in chemosensitivity of hematopoietic cells. Mean hematopoietic cell drug sensitivity showed little variation due to previous chemotherapy, sex, age, tumor type, and sample source or cell lineage. We therefore concluded that cytotoxic drug sensitivity of hematopoietic cells from a variety of sources could be used for assessment of therapeutic index. Drug therapeutic index results are a valuable tool in identifying novel cytotoxic agents and individually tailored chemotherapy regimens.

Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

“…With regards to cancer treatment, most current anticancer regimes do not effectively differentiate between cancerous and normal cells. This indiscriminate action frequently leads to systemic toxicity and debilitating adverse effects in normal body tissues including bone marrow suppression, neurotoxicity, and cardiomyopathy [5,6]. Nanotechnology and nanomedicine can offer a more targeted approach which promises significant improvements in the treatment of cancer [5].…”

Plasma‐activated medium as an innovative anticancer strategy: Insight into its cellular and molecular impact on in vitro leukemia cells

“…Cell lines differ from primary cells taken directly from the living tissue, in terms of growth kinetics and pharmacological determinants (e.g., sex, age, presence of mutations, etc.). [ 78 ] We obtained preliminary results on blasts from patients with acute myeloid leukemia (see Supporting Information Materials, Table S1 and Figure S1), where PAM induced a milder cytotoxic effect, compared with T‐leukemia Jurkat cells. A different cytotoxic effect of CAP on primary cells, compared with cell lines, was observed, for example, for prostate cancer.…”

Antileukemic Activity of Sulforaphane in Primary Blasts from Patients Affected by Myelo- and Lympho-Proliferative Disorders and in Hypoxic Conditions

“…Ex vivo samples represent a quite good surrogate for determining the cellular response of the patient to the treatment and predicting the clinical outcome [32]–[34]. This can not be realized by using cell lines, which markedly differ from blasts directly taken from leukemic patients in terms of growth kinetics and pharmacological determinants [35].…”