Naturally occurring resistance of bone marrow mononuclear and metastatic cancer cells to anticancer agents
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Numerous cancer patients fail standard chemotherapy or develop resistance to chemotherapy during the course of treatment. The purpose of this study is to elucidate the overall response of cells obtained from cancer patients and from normal individuals to chemotherapeutic agents. We analysed the chemosensitivity of cancer cells derived from bone marrow and from pleural effusions or ascites fluids from patients with different cancers. Chemosensitivity to doxorubicin, cisplatin and paclitaxel was determined using the MTT assay. We also determined the response of bone marrow mononuclear (BMMN) cells. There was a wide range of responses to chemotherapy drugs in samples from different individuals. This was observed in cells derived from bone marrow and from ascites or pleural fluids. Large variations were also observed among morphologically normal BMMN cells and metastatic cancer cells from chemo-naïve patients. Cancer cells can easily be collected from ascites or pleural fluids and reliably assayed for chemosensitivity. We describe here that inherent chemoresistance may be a reason for the lack of response to chemotherapy in some patients. We discuss the potential of using the determination of natural resistance to dictate the drugs to be employed for treatment.
KeywordsChemotherapy Resistance Cytotoxicity Ascites Bone marrow
This research was funded by grants provided by the Canadian Institutes for Health Research (to JPHT and WCMD). We are grateful for the contributions of Drs. Huan, Chan, Vergidis, Falkson, Anthes and Dhaliwal in obtaining the samples and for technical assistance of Dr. Shi in isolating the bone marrow mononuclear cells.
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