Oxaliplatin-related neurotoxicity: How and why?

Pasetto, Lara Maria; D’Andrea, Mario; Rossi, Elena; Monfardini, S.

doi:10.1016/j.critrevonc.2006.01.001

Cited by 229 publications

(186 citation statements)

References 42 publications

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“…Oxaliplatin, in combination with 5-fluorouracil, has been considered the standard first-line treatment for metastatic colorectal cancer (21). Oxaliplatin is generally well tolerated but can be associated with significant side effects (22) especially after cumulative dosing. This study establishes, for the first time, the comparable or greater growthinhibitory and apoptotic effects of liposomal curcumin with oxaliplatin, with virtually no side effects for the former, at least in animals.…”

Section: Discussionmentioning

confidence: 99%

Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer

Lan

Ahmed

Mehta

et al. 2007

Molecular Cancer Therapeutics

303

153

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The role of curcumin (diferuloylmethane), a proapoptotic compound, for the treatment of cancer has been an area of growing interest. Curcumin in its free form is poorly absorbed in the gastrointestinal tract and therefore may be limited in its clinical efficacy. Liposome encapsulation of this compound would allow systemic administration. The current study evaluated the preclinical antitumor activity of liposomal curcumin in colorectal cancer. We also compared the efficacy of liposomal curcumin with oxaliplatin, a standard chemotherapy for this malignancy. In vitro treatment with liposomal curcumin induced a dose-dependent growth inhibition [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt] and apoptosis [poly(ADP-ribose) polymerase] in the two human colorectal cancer cell lines tested (LoVo and Colo205 cells). There was also synergism between liposomal curcumin and oxaliplatin at a ratio of 4:1 in LoVo cells in vitro. In vivo, significant tumor growth inhibition was observed in Colo205 and LoVo xenografts, and the growth inhibition by liposomal curcumin was greater than that for oxaliplatin (P < 0.05) in Colo205 cells. Tumors from animals treated with liposomal curcumin showed an antiangiogenic effect, including attenuation of CD31 (an endothelial marker), vascular endothelial growth factor, and interleukin-8 expression by immunohistochemistry. This study establishes the comparable or greater growth-inhibitory and apoptotic effects of liposomal curcumin with oxaliplatin both in vitro and in vivo in colorectal cancer. We are currently developing liposomal curcumin for introduction into the clinical setting.

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Section: Discussionmentioning

confidence: 99%

Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer

Lan

Ahmed

Mehta

et al. 2007

Molecular Cancer Therapeutics

303

153

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“…PERIPHERAL NEUROPATHY is the most common dose-limiting factor of oxaliplatin chemotherapy (for reviews, see Argyriou et al 2008;Krishnan et al 2005;Pasetto et al 2006). Acute neurotoxicity, predominantly sensory in nature, is seen in nearly all patients and is characterized by cold intolerance, dysthesias, and, less commonly, laryngeal spasms (Wilson et al 2002).…”

mentioning

confidence: 99%

Oxaliplatin neurotoxicity of sensory transduction in rat proprioceptors

Bullinger

Nardelli

Wang

et al. 2011

Journal of Neurophysiology

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Bullinger KL, Nardelli P, Wang Q, Rich MM, Cope TC. Oxaliplatin neurotoxicity of sensory transduction in rat proprioceptors. J Neurophysiol 106: 704 -709, 2011. First published May 18, 2011 doi:10.1152/jn.00083.2011.-Neurotoxic effects of oxaliplatin chemotherapy, including proprioceptive impairments, are debilitating and dose limiting. Here, we sought to determine whether oxaliplatin interrupts normal proprioceptive feedback by impairing sensory transduction of muscle length and force by neurons that are not damaged by dying-back neuropathy. Oxaliplatin was administered over 4 wk to rats in doses that produced systemic changes, e.g., decreased platelets and stunted weight gain, but no significant abnormality in the terminal ends of primary muscle spindle sensory neurons. The absence of neuropathy enabled the determination of whether oxaliplatin caused functional deficits in sensory encoding without the confounding issue of axon death. Rats were anesthetized, and action potentials encoding muscle stretch and contraction were recorded intra-axonally from dorsal roots. In striking contrast with normal proprioceptors, those from oxaliplatin-treated rats typically failed to sustain firing during static muscle stretch. The ability of spindle afferents to sustain and centrally conduct trains of action potentials in response to rapidly repeated transient stimuli, i.e., vibration, demonstrated functional competence of the parent axons. These data provide the first evidence that oxaliplatin causes persistent and selective deficits in sensory transduction that are not due to axon degeneration. Our findings raise the possibility that even those axons that do not degenerate after oxaliplatin treatment may have functional deficits that worsen outcome. chemotherapy; neuropathy; muscle spindle; electrophysiology; afferent PERIPHERAL NEUROPATHY is the most common dose-limiting factor of oxaliplatin chemotherapy (for reviews, see Argyriou et al. 2008;Krishnan et al. 2005;Pasetto et al. 2006). Acute neurotoxicity, predominantly sensory in nature, is seen in nearly all patients and is characterized by cold intolerance, dysthesias, and, less commonly, laryngeal spasms (Wilson et al. 2002). With continued treatment, a cumulative sensory neuropathy can develop similar to that seen in patients treated with other platinum compounds. The onset of the neuropathy is gradual, and the severity worsens with an increase in cumulative dose. Chronic neuropathy is thought to primarily affect large-diameter sensory fibers (for evidence and earlier citations, see Jamieson et al. 2005), which include muscle afferents that provide the central nervous system with proprioceptive information. Consistent with this notion, patients often lose deep tendon reflexes, mediated by muscle spindle afferents, and develop proprioceptive loss seen as problems with coordinating movement, e.g., loss of dexterity and sensory ataxia.Sensory contributions to behavior and experience depend on conduction and central transmission of signals that are encoded by specialize...

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“…Cells were seeded at 1x10 4 plates were visualised and quantitated using the Odyssey infrared imaging system.…”

Section: In-cell Westernsmentioning

confidence: 99%

“…Peripheral neuropathies present as the major dose-limiting factor within oxaliplatinbased regimes [3,4], so it is of great importance to design treatment strategies that allow similar therapeutic indices, whilst decreasing the likelihood of toxic events. To this end, we have chosen to assess the effects of combining oxaliplatin with the dietderived chemopreventive agent indole-3-carbinol (I3C).…”

Section: Introductionmentioning

confidence: 99%

Indole-3-carbinol enhances anti-proliferative, but not anti-invasive effects of oxaliplatin in colorectal cancer cell lines

Howells

Neal²,

Brown³

et al. 2008

Biochemical Pharmacology

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Abstract.The primary aim of this study was to determine whether combination of the chemopreventive agent indole-3-carbinol with oxaliplatin would decrease proliferative index and invasive potential of human colorectal tumour cells.Combination of the agents resulted in a 170-fold decrease in proliferative capacity in SW480 and SW620 cell lines, which was approximately 6-fold greater than for oxaliplatin alone. Decreased proliferation was attributed to enhanced S-phase cell cycle arrest for SW480, and increased apoptosis for SW620 cells.The combined agents resulted in significantly increased E-cadherin levels in SW480 cells, and β-catenin levels in both cell lines (assessed by in-cell westerns). In SW480 cells confocal microscopy revealed an increase in membrane-associated β-catenin levels, with oxaliplatin treatments enhancing nuclear export and cytoplasmic localisation. In SW620 cells, all treatments increased membrane localisation of Ecadherin.Whilst both oxaliplatin and I3C decreased invasive capacity of SW480 cells, this was not further enhanced by the combined treatment.

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Oxaliplatin-related neurotoxicity: How and why?

Cited by 229 publications

References 42 publications

Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer

Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer

Oxaliplatin neurotoxicity of sensory transduction in rat proprioceptors

Indole-3-carbinol enhances anti-proliferative, but not anti-invasive effects of oxaliplatin in colorectal cancer cell lines

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