Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia.

List, Alan F.; Spier, Catherine M.; Greer, John P.; Wolff, Steven N.; Hutter, John J.; Dorr, Robert T.; Salmon, Sydney E.; Futscher, Bernard W.; Baier, Monika; Dalton, William S.

doi:10.1200/jco.1993.11.9.1652

Cited by 273 publications

(126 citation statements)

References 26 publications

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“…94 To improve treatment efficacy, combination of MDR1 inhibitors with specific drugs have been tested, showing notably encouraging results in term of overall survival in patients with AML. 22,95–97 Most of these studies used first or second generation inhibitors. The use of much more specific third or upcoming fourth generation inhibitors could allow to improve these results and decrease toxicities associated with combination treatments.…”

Section: Introductionmentioning

confidence: 99%

MDR1 in immunity: friend or foe?

et al. 2018

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MDR1 is an ATP-dependent transmembrane transporter primarily studied for its role in the detoxification of tissues and for its implication in resistance of tumor cells to chemotherapy treatment. Several studies also report on its expression on immune cells where it plays a protective role from xenobiotics and toxins. This review provides an overview of what is known on MDR1 expression in immune cells in human, and its implications in different pathologies and their treatment options.

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Section: Introductionmentioning

confidence: 99%

MDR1 in immunity: friend or foe?

et al. 2018

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“…Recent studies in experimental animals (Nozue et al, 1993) and in humans (List et al, 1993) showed an association between hypomagnesaemia and the use of cyclosporin, possibly due to intracellular migration. Furthermore, hypomagnesaemia was reported to be associated with chemotherapy with cisplatin (Fossa et al, 1995), as well as a combination of cisplatin and 5-¯uorouracil (Evans et al, 1995), owing to increased losses of minerals with urine.…”

Section: Micronutrient De®cienciesmentioning

confidence: 99%

Nutritional considerations in children undergoing bone marrow transplantation

Papadopoulou

1998

Eur J Clin Nutr

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Bone marrow transplantation is often associated with multiple organ failure which is usually reversible. Oral mucositis and dysphagia, vomiting, diarrhoea, protein losing enteropathy, transient exocrine pancreatic impairment, hypoalbuminaemia, biochemical trace element and mineral de®ciencies are all common following transplantation and have profound nutritional consequences. Malnutrition affects negatively the clinical outcome. Nutritional support is provided to malnourished patients and those who suffer deterioration in nutritional status despite the provision of dietetic counselling. Only a few randomised studies comparing enteral with parenteral nutrition after transplant exist. Both enteral tube feeding (in the absence of mucositis) and parenteral nutrition are effective in maintaining nutritional status. However, enteral nutrition is associated with a better nutritional response and fewer complications than parenteral. With existing enteral and parenteral nutrition regimens close monitoring of trace element and mineral status is required.

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“…Phase I studies showed that both CsA and PSC 833 increased the area under the curves of etoposide, daunorubicin and doxorubicin. [50][51][52][53][54] However, a disadvantage of this increase in plasma levels is that drug doses should be reduced to limit the toxic sideeffects. Side-effects have been reported at the clinically achievable concentrations of PSC 833, CsA and Vp used in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…55 The toxicity of CsA was milder, mainly resulting in myelosuppression and hypomagnesemia. 52,56,57 The lowest toxicities were reported for PSC 833 and included ataxia and intestinal neuropathy.…”

Section: Discussionmentioning

confidence: 99%

The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in vitro cytotoxicity and intracellular content of daunorubicin in childhood acute lymphoblastic leukemia

et al. 1998

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Resistance to anthracyclines is related to a poor prognosis in childhood acute lymphoblastic leukemia (ALL). Resistance to this class of drugs may (partly) be reversed by modulating agents, as has been demonstrated in a variety of cell lines. However, it is unknown which modulators may be of clinical benefit in childhood ALL. Therefore, we studied the modulating effect of PSC 833, cyclosporin A (CsA), verapamil (Vp) and genistein on daunorubicin (DNR) cytotoxicity, accumulation and retention in childhood ALL cells. DNR cytotoxicity was determined using the MTT assay; DNR accumulation, DNR retention and the expression of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and major vault protein/lung resistance protein (LRP) were determined by flow cytometry. In the majority of samples PSC 833 (19/26), CsA (22/26) and Vp (15/18) sensitized the cells to DNR whereas genistein made 25 out of 26 samples more resistant to DNR. The sensitizing effect on the cytotoxicity of DNR was median 1.2-fold using 2 M PSC 833 (P = 0.025), 1.5-fold using 4 M CsA (P = 0.003) and 1.6-fold using 6 M Vp (P = 0.012) whereas the adverse effect of 25 M genistein was median 1.8-fold (P Ͻ 0.0001). No relationship was found between the sensitizing effect of PSC 833, CsA or Vp and the degree of DNR resistance. In contrast, the adverse effect of genistein was largest in DNR sensitive samples (P = 0.003). The effect of each modulator on the cytotoxicity of DNR did not differ between initial and relapse ALL samples although the latter were median 1.4-fold more resistant to DNR (P = 0.005). Modulation of DNR cytotoxicity was not correlated with changes in the accumulated and retained intracellular DNR content or with the expression of Pgp, MRP and LRP. Besides genistein, PSC 833, CsA and Vp incidentally made ALL cells more resistant to DNR. CsA stimulated the leukemic cell survival in seven out of 26 samples, a phenomenon that was not related to the degree of DNR resistance. In conclusion, PSC 833, CsA and Vp but not genistein may be used to sensitize cells to DNR in childhood ALL. The data also indicate that not all patients may have a therapeutic benefit from these modulators. Therefore, an in vitro culture assay may be necessary to screen for patients who may benefit by a modulator in their therapy.

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Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia.

Cited by 273 publications

References 26 publications

MDR1 in immunity: friend or foe?

MDR1 in immunity: friend or foe?

Nutritional considerations in children undergoing bone marrow transplantation

The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in vitro cytotoxicity and intracellular content of daunorubicin in childhood acute lymphoblastic leukemia

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