Cytostatic sensitivity and MDR in bladder carcinoma cells: implications for tumor therapy

Schuldes, H.; Jh, Dolderer; Schoch, Claudia; Bickeböller, Ralf; Bg, Woodcock

doi:10.5414/cpp38204

Cited by 7 publications

(4 citation statements)

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“…Ultrasound could alter the membrane lipid arrangement, increasing membrane fluidity that could facilitate drug transport to overcome drug resistance [122]. Similarly, as a means of chemical methods, R-verapamil and linolenic acid have been shown to reverse drug resistance in human bladder carcinoma cell lines by modifying the membrane fluidity [123, 124]. Due to lipophilic nature, R-verapamil can accumulates in the hydrophobic region, the steric effects of isopropyl sides chain seem to reduces the van der Waals forces between lipid molecules, resulting in more fluid membranes.…”

Section: Strategies To Improve Np-based Drug Delivery To Overcome mentioning

confidence: 99%

Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles

Peetla

Vijayaraghavalu

Labhasetwar

2013

Advanced Drug Delivery Reviews

235

214

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In this review, we focus on the biophysics of cell membrane lipids, particularly when cancers develop acquired drug resistance, and how biophysical changes in resistant cell membrane influence drug transport and nanoparticle-mediated drug delivery. Recent advances in membrane lipid research show the varied roles of lipids in regulating membrane P-glycoprotein function, membrane trafficking, apoptotic pathways, drug transport, and endocytic functions, particularly endocytosis, the primary mechanism of cellular uptake of nanoparticle-based drug delivery systems. Since acquired drug resistance alters lipid biosynthesis, understanding the role of lipids in cell membrane biophysics and its effect on drug transport is critical for developing effective therapeutic and drug delivery approaches to overcoming drug resistance. Here we discuss novel strategies for (a) modulating the biophysical properties of membrane lipids of resistant cells to facilitate drug transport and regain endocytic function and (b) developing effective nanoparticles based on their biophysical interactions with membrane lipids to enhance drug delivery and overcome drug resistance.

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Section: Strategies To Improve Np-based Drug Delivery To Overcome mentioning

confidence: 99%

Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles

Peetla

Vijayaraghavalu

Labhasetwar

2013

Advanced Drug Delivery Reviews

235

214

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“…The difficulties of simulating the physiological ECM and of maintaining viability for normal cells in culture have been noted [47]. These considerations suggest the hypothesis that fluidization of the plasma membrane caused by UFAs [21,48,49] is a key event triggering ultimate tumor cell death, as has been proposed [50,51]. …”

Section: Discussionmentioning

confidence: 99%

“…Finally, additional possibilities for clinical benefits are raised by findings that multidrug resistant (MDR) malignant cell lines were as sensitive [7,14,87] or more sensitive [88] to UFA agents than their non-MDR counterparts and that drug resistance could be reversed by UFA application [51,89,90]. This suggests the possibility that should the proposed 3-day combination regimen fail to achieve response, it could still potentially reverse drug resistance in MDR tumor cells or selectively target them and allow response to be achieved in subsequent chemotherapy treatments.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of unsaturated fatty acids in fresh human tumor explants: concentration thresholds and implications for clinical efficacy

Scheim¹

2009

Lipids Health Dis

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BackgroundUnsaturated fatty acids (UFAs) exhibit in vitro cytotoxicity against many malignant cell lines and yield decreased cancer incidence and reduced tumor growth in animal models. But clinical and animal studies to date have achieved response using only localized delivery methods such as intratumoral infusion. To explore possibilities for enhanced clinical efficacy, fresh surgical explants of tumors from 22 patients with five malignancies were exposed to γ-linolenic acid (GLA) and α-linolenic acid (ALA) and analyzed with an in vitro chemosensitivity testing system, the Fluorescent Cytoprint Assay (FCA). A total of 282 micro-organ cultures derived from these malignant tumors were exposed to GLA and ALA at different concentrations.ResultsGLA and ALA exhibited greater than 90% cytotoxicity at a sharp concentration threshold between 500 μM and 1 mM against all but two malignant micro-organ cultures tested in 5-10% serum. In tests using 30-40% serum, GLA and ALA killed tumor at concentrations of 2 mM and above.ConclusionsThe concentration threshold of 500 μM to 2 mM exhibited for antitumor activity by GLA and ALA is much higher than that observed in most previously reported cell culture studies but consistent with physiological concentrations found to kill tumor clinically and in animals. A mechanism of antitumor activity by unsaturated fatty acids through selective destabilization of the malignant plasma membrane is considered. An oral regimen is proposed for phase I clinical testing that could push the area under the curve for serum concentration of unbound unsaturated fatty acids over time to much higher levels than previously achieved for systemic administration and into the range that could yield antitumor response.

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“…The increased expression of glycoprotein GP-170, an energy-dependent transmembrane pump, expelling several chemotherapeutic agents from the cells, can be a factor involved in drug resistance (Schuldes et al 2000). GP-170 is encoded by one of the genes responsible for Multiple Drug Resistance (MDR-1).…”

Section: Introductionmentioning

confidence: 99%

Correlation between GP-170 expression, prognosis, and chemoresistance of superficial bladder carcinoma

Serretta

Pavone

Allegro

et al. 2003

Journal of Cancer Research and Clinical Oncology

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GP-170 seems to be an independent prognostic factor for recurrence in superficial bladder tumors. A negative GP-170 pattern and high levels of GP-170 are associated with an increasing risk of recurrence but have no impact upon progression. In our experience, GP-170 is neither induced nor modified by intravesical chemotherapy, although it might represent a factor of chemoresistance when strongly expressed.

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Cytostatic sensitivity and MDR in bladder carcinoma cells: implications for tumor therapy

Cited by 7 publications

References 0 publications

Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles

Biophysics of cell membrane lipids in cancer drug resistance: Implications for drug transport and drug delivery with nanoparticles

Cytotoxicity of unsaturated fatty acids in fresh human tumor explants: concentration thresholds and implications for clinical efficacy

Correlation between GP-170 expression, prognosis, and chemoresistance of superficial bladder carcinoma

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