Mechanism of multidrug resistance

Bradley, Grace; Juranka, Peter F.; Ling, Victor

doi:10.1016/0304-419x(88)90006-6

Cited by 328 publications

(272 citation statements)

References 86 publications

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“…An extensive study demonstrating this decreased growth inhibition by chemotherapeutic agents (drug resistance) in the presence of p53 mutations was recently reported (15). P-glycoprotein is a transmembrane protein that functions as an energy-dependent drug efflux pump for selective resistance to anthracyclines (daunorubicin and doxorubicin), vinca alkaloids, podophyllotoxins (etoposide), antimicrotubule agents (paclitaxel and colchicine), and actinomycin D (1,13,16,17). This multidrug resistance may be reversed or overcome by such agents as calciumchannel blockers, analogs of anthracyclines and vinca alkaloids, steroids and hormonal analogs, cyclosporine analogs, and miscellaneous hydrophobic cationic compounds (3, 18 -20).…”

Section: Discussionmentioning

confidence: 99%

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Effects of Multidrug Resistance Gene Expression in Acute Erythroleukemia

et al. 2000

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Acute erythroleukemia is a relatively rare disorder of a multilineal nature. Patients with this type of leukemia traditionally have been treated with a standard myeloid protocol, with a wide variation in prognosis between M6a, which has a similar prognosis to acute myelogenous leukemias, and M6b, with an extremely poor outcome despite aggressive therapy.Forty-eight archival cases of acute erythroleukemia, subtypes M6a (the traditional FAB-M6), M6b (pure erythroleukemia), and M6c (>30% myeloblasts and >30% pronormoblasts by FAB exclusion criteria), were evaluated for multidrug resistance gene (MDR-1) status. Findings were correlated with clinical course and karyotypes.Immunohistochemical stain for the protein product of MDR-1, P-glycoprotein, was variably positive in 11 of 23 patients with M6a, as well as in all of the patients with M6b (strongly positive) and M6c (weakly positive). P-glycoprotein expression positively correlated with unfavorable cytogenetic aberrations, poor response to chemotherapeutic agents, and short survival. Most significant was that P-glycoprotein expression demonstrated a negative additive effect on response to treatment and prognosis with unfavorable cytogenetic anomalies. P-glycoprotein expression and multiple cytogenetic anomalies most probably contribute to the resistance to chemotherapy and poor survival characteristic of the patients with M6b (mean survival

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Section: Discussionmentioning

confidence: 99%

“…The hallmark of the multidrug resistance phenotype is cross-resistance to multiple compounds that are unrelated in structure, cellular target, and mode of action (1). Overexpression of the protein product of the multidrug resistance gene (MDR-1), P-glycoprotein, is a major, as well as the best understood, mechanism of multidrug resistance.…”

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confidence: 99%

Effects of Multidrug Resistance Gene Expression in Acute Erythroleukemia

et al. 2000

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“…Many studies have speculated on the mechanisms involved in the acquisition of resistance to chemotherapeutic agents by tumour cells (Schimke, 1984;Bradly et al, 1988;Gottesman, 1988;Kramer et al, 1988). These studies reveal at least two types of drug resistance; one is quite specific for a selected agent, such as an increase in the amount of dihydrofolate reductase in methotrexate-selected cells, and the other is less specific to selecting agents, such as an increase in the level of P-glycoprotein (Schimke, 1984;Gottesman, 1988).…”

Section: Disussionmentioning

confidence: 99%

“…The resistance to chemotherapeutic agents caused by genetic changes in tumour cells is one of the factors involved in tumour progression (Goldie and Coldman, 1979). Studies to elucidate the mechanisms underlying the acquisition of resistance to drugs have revealed that many genes, such as MDRI and GST-7r, are involved in this process (Kramer et al, 1988;Bradly et al, 1988;Gottesman 1988. Genetic changes in tumour cells can also result in the escape of tumour cells from surveillance by host immune system (Johnson et al, 1989;Tanaka and Tevethia, 1988;Doherty et al, 1984).…”

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confidence: 99%

Cancer cell progression and chemoimmunotherapy-dual effects in the induction of resistance to therapy

Hamuro

Kikuchi²,

Takatsuki³

et al. 1996

Br J Cancer

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Summary To determine whether resistance to chemoimmunotherapy is acquired during therapy, we investigated the effects of chemotherapeutic agents and anti-tumour polysaccharide, lentinan, on the progression of Rous sarcoma virus-induced S908.D2 fibrosarcomas. The chemoimmunotherapy was effective against the parental S908.D2-bearing mice. Nearly all the mice that were treated with cyclophosphamide (CY) and lentinan achieved complete tumour regression. Only a few of the mice that achieved complete regression of the primary tumours showed a recurrence of the tumour in regional lymph nodes. S908.D2-vp.1 was established from metastatic tumours that developed in the regional lymph nodes of parental S908.D2-bearing mice during therapy. S908.D2-vp.2-or vp.3 cells were sequentially derived in a similar way from S908.D2-vp. 1-or-vp.2-bearing mice respectively, im which complete tumour regression at each primary site was achieved during therapy. These lines acquired resistance to CY and lentinan and also to 5-fluorouracil (5-FU)/5'-deoxy-5-fluorouracil and lentanin. No significant difference in either the sensitivity to 5-FU or 4-deoxycyclophosphamide in vitro or in the susceptibility to immune effector cells was observed between the parental and progressed lines (S908.D2-vp.1--vp.3). There was an increase in the level of prostaglandin E2 (PGE2) in the progressed lines during repeated therapy (parental, 1171 pg ml-1; vp.1, 2199 pg ml-'; vp.2, 5500 pg m 1-1; vp3, 16187 pg ml-'). There was no significant increase in the production of transforming growth factor ,B (TGF-,B). The amount of interleukin-2 (IL-2) produced by spleen cells isolated from the S908.D2-vp.2-bearing mice was decreased compared with the amount produced by the parental S908.D2-bearing mice. Furthermore, combination therapy with lentinan and IL-2 achieved complete tumour regression in all the mice transplanted with S908.D2 progressed tumour lines, although IL-2 alone did not show any anti-tumour effects in either the S908.D2 parental or progressed lines. The findings suggest that the reduced production of IL-2 induced an increase in the production of the PGE2 by progressed tumour lines is involved in the acquisition of resistance.

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“…Multidrug esistance (MDR) appears to be a major obstacle to chemoherapeutic success. Selection of numerous cell lines in vitro to ~tudy the MDR phenomenon by a single anticancer drug, such ts an anthracycline, a Vinca alkaloid, or a taxane often results n a coordinate resistance to other structurally and functionally mrelated drugs [1][2][3][4][5][6][7]. In many instances, MDR-cells overex~ress P-glycoprotein, a 150,000-180,000 Da integral membrane ~rotein, by the mdrl gene which is believed to confer resistance :Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

Lack of elevated drug efflux in adriamycin‐resistant immunoblastic B lymphoma cells with mdr1 overexpression

Chao¹

1995

FEBS Letters

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Mechanism of multidrug resistance

Cited by 328 publications

References 86 publications

Effects of Multidrug Resistance Gene Expression in Acute Erythroleukemia

Effects of Multidrug Resistance Gene Expression in Acute Erythroleukemia

Cancer cell progression and chemoimmunotherapy-dual effects in the induction of resistance to therapy

Lack of elevated drug efflux in adriamycin‐resistant immunoblastic B lymphoma cells with mdr1 overexpression

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