Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review

Stage, Tore Bjerregaard; Bergmann, Troels K.; Kroetz, Deanna L.

doi:10.1007/s40262-017-0563-z

Cited by 144 publications

(118 citation statements)

References 98 publications

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“…Both capsaicin and -meATP evoked calcium transients in subpopulations of iPSC-SNs(Figures 2b and 2c), demonstrating functional activity of nociceptive sensory neurons. A large number of mature sensory neurons also showed high calcium flux in response to glutamate(Figures 2b and 2c), indicating an excitatory glutamatergic neuronal phenotype.Paclitaxel cytotoxicityInvestigation of the molecular mechanisms underlying paclitaxel-induced neurotoxicity in the iPSC-SNs requires conditions where neuron morphology and function are disrupted without overt cytotoxicity at clinically relevant concentrations (≤10 M)28 . Treatment with up to 10 M paclitaxel for 24 hr had no significant effect on cell viability(Figure 3a).…”

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confidence: 99%

Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel

Xiong

Chua

Stage

et al. 2020

Preprint

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Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event associated with treatment with paclitaxel and other chemotherapeutic agents. The prevention and treatment of CIPN are limited by a lack of understanding of the molecular mechanisms underlying this toxicity. In the current study, a human induced pluripotent stem cell-derived sensory neuron (iPSC-SN) model was developed for the study of chemotherapy-induced neurotoxicity. The iPSC-SNs express proteins characteristic of nociceptor, mechanoreceptor and proprioceptor sensory neurons and show Ca 2+ influx in response to capsaicin, ,-meATP and glutamate. iPSC-SNs are relatively resistant to the cytotoxic effects of paclitaxel, with IC 50 values of 38.1 M (95% CI: 22.9 -70.9 M) for 48 hr exposure and 9.3 M (95% CI: 5.7 -16.5 M) for 72 hr treatment. Paclitaxel causes dose-and time-dependent changes in neurite network complexity detected by III-tubulin staining and high content imaging. The IC 50 for paclitaxel reduction of neurite area was 1.4 M (95% CI: 0.3 -16.9 M) for 48 hr exposure and 0.6 M (95% CI: 0.09 -9.9 M) for 72 hr exposure. Decreased mitochondrial membrane potential, slower movement of mitochondria down the neurites and changes in glutamate-induced neuronal excitability were also observed with paclitaxel exposure. The iPSC-SNs were also sensitive to docetaxel, vincristine and bortezomib.Collectively, these data support the use of iPSC-SNs for detailed mechanistic investigations of genes and pathways implicated in chemotherapy-induced neurotoxicity and the identification of novel therapeutic approaches for its prevention and treatment.

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confidence: 99%

Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel

Xiong

Chua

Stage

et al. 2020

Preprint

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“…It is known to act on microtubules, i.e., the structures responsible for the formation of the mitotic spindle during cell division and cytoplasmic movement in the cell; more specifically, the drug promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. It thus blocks metaphase-anaphase transitions, inhibits mitosis, and induces apoptosis in a wide range of cancer cells [70].…”

Section: Paclitaxelmentioning

confidence: 99%

“…The drug is used in the treatment of a range of conditions including lung, ovarian, breast, stomach, esophageal, cervical, and prostate cancer, as well as lymphoma and leukemia [70]. As this drug is widely used in cancer therapy in humans, there is great interest in increasing its productivity from natural sources.…”

Section: Paclitaxelmentioning

confidence: 99%

Transgenesis as a Tool for the Efficient Production of Selected Secondary Metabolites from Plant in Vitro Cultures

Kowalczyk

Wieczfińska

Skała

et al. 2020

Plants

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The plant kingdom abounds in countless species with potential medical uses. Many of them contain valuable secondary metabolites belonging to different classes and demonstrating anticancer, anti-inflammatory, antioxidant, antimicrobial or antidiabetic properties. Many of these metabolites, e.g., paclitaxel, vinblastine, betulinic acid, chlorogenic acid or ferrulic acid, have potential applications in medicine. Additionally, these compounds have many therapeutic and health-promoting properties. The growing demand for these plant secondary metabolites forces the use of new green biotechnology tools to create new, more productive in vitro transgenic plant cultures. These procedures have yielded many promising results, and transgenic cultures have been found to be safe, efficient and cost-effective sources of valuable secondary metabolites for medicine and industry. This review focuses on the use of various in vitro plant culture systems for the production of secondary metabolites.

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“…Moreover, there was no precipitate during the investigated reaction time. 1 H NMR spectrum in DMSO-d 6 after 4 h showed decrease (ca. 25%) in intensities of the proton resonances near platinum(II) coordination sphere (C3'H 2 and C4'H 2 ), indicating possible coordination of solvent molecules.…”

Section: Scheme 1 Synthesis Of Batrispt Complex and Numeration Of H mentioning

confidence: 99%

“…Metal-based drugs (e.g., cisplatin, oxaliplatin), natural products and their derivatives (e.g., paclitaxel, doxorubicin), or even their combination (e.g., 5-fluorouracil, oxaliplatin, irinotecan) are frequently used as chemotherapeutic drugs for cancer treatment [1][2][3][4]. However, along with killing the cancer cells, such drugs cause severe side effects [5].…”

Section: Introductionmentioning

confidence: 99%

(18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity

et al. 2017

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Synthesis of platinum(II) conjugate with acetylated betulinic acid tris(hydroxymethyl) aminomethane ester (BATRIS) is presented (BATRISPt). HR-ESI-MS and multinuclear NMR spectroscopy, as well as elemental analysis were used for characterization of BATRISPt. Cytotoxicity (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), crystal violet (CV), and sulforhodamine B (SRB) assays) of BA, BATRIS, BATRISPt, and cisplatin were assessed on seven different tumor cell lines: melanoma B16, colon HCT116 and DLD-1, adenocarcinoma HeLa, breast MCF-7, and anaplastic thyroid tumor 8505C and SW1736; as well as normal MRC-5 fibroblasts. Furthermore, the effect of the mentioned compounds on the apoptosis (Annexin V/PI assay) and autophagy induction (acridine orange (AO) assay) as well as caspase 3, 8, and 9 activation were investigated on the selected B16 melanoma cell line. BATRISPt showed lower activity than BA, BATRIS, or cisplatin. All tested compounds triggered apoptosis in B16 cells. Induction of autophagy was observed in B16 cells exposed only to BATRIS. On the other hand, new conjugate activates caspases 8 and 9 in B16 cells with higher impact than BATRIS or cisplatin alone.Inorganics 2017, 5, 56 2 of 13 instance, how such compounds can be delivered, metabolized, and how and to which magnitude they may enter the tumor cells. On the other side, two components covalently linked to each other-double drug [13], presumably-may possess different behavior than single components alone.Even lower in activity than paclitaxel or doxorubicin [14,15], a cell-type-specific antitumor active compound betulinic acid (BA) has drawn more attention in the last few years and is still explored by many groups [16][17][18][19][20][21][22][23][24]. BA is a naturally occurring pentacyclic triterpenoid which is isolated from the bark of several species of plants (e.g., white birch). Betulinic acid and its derivatives present compounds with numerous biological activities-for instance, antioxidant, antiviral, antimicrobial, anti-inflammatory, antidiabetic, immunomodulatory, etc. [25,26]. However, investigations on betulinic acid in the last few years have been pointed toward the field of antitumor properties [27][28][29][30][31].We recently reported the synthesis and characterization of the new series of betulinic acid-cisplatin conjugates, which are both apoptosis inducing agents [32]. However, their cytotoxicity was found to be lower than parental drugs cisplatin and betulinic acid. Herein we report on the synthesis, characterization, and in vitro activity of acetylated betulinic acid derivative tris(hydroxymethyl)aminomethane (TRIS) ester conjugated with PtCl 3 -fragment.

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Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review

Cited by 144 publications

References 98 publications

Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel

Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel

Transgenesis as a Tool for the Efficient Production of Selected Secondary Metabolites from Plant in Vitro Cultures

(18-Crown-6)potassium(I) Trichlorido[28-acetyl-3-(tris-(hydroxylmethyl)amino-ethane)betulinic ester-κN]platinum(II): Synthesis and In Vitro Antitumor Activity

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