The immunopharmacology of paclitaxel (Taxol®), docetaxel (Taxotere®), and related agents

Fitzpatrick, F. A.; Wheeler, Richard

doi:10.1016/j.intimp.2003.08.007

Cited by 103 publications

(87 citation statements)

References 91 publications

(97 reference statements)

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“…These findings speak for a role of paclitaxel in boosting this response to F8-IL2. Indeed, there is an emerging body of data confirming that paclitaxel, like other related taxanes, displays immunomodulatory properties that endorse its therapeutic application beyond tumor chemotherapy (27,39). We are aware of the possible limits of studies done in immunodeficient nude mice, in which most of the immunomodulating effects were underestimated and restricted to innate immunity (nude mice cannot generate mature T lymphocytes; ref.…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

et al. 2012

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The selective delivery of bioactive agents to tumors reduces toxicity and enhances the efficacy of anticancer therapies. In this study, we show that the antibody F8, which recognizes perivascular and stromal EDA-fibronectin (EDA-Fn), when conjugated to interleukin-2 (F8-IL2) can effectively inhibit the growth of EDA-Fn-expressing melanomas in combination with paclitaxel. We obtained curative effects with paclitaxel administered before the immunocytokine. Coadministration of paclitaxel increased the uptake of F8 in xenografted melanomas, enhancing tumor perfusion and permeability. Paclitaxel also boosted the recruitment of F8-IL2-induced natural killer (NK) cells to the tumor, suggesting a host response as part of the observed therapeutic benefit. In support of this likelihood, NK cell depletion impaired the antitumor effect of paclitaxel plus F8-IL2. Importantly, this combination reduced both the tumor burden and the number of pulmonary metastatic nodules. The combination did not cause cumulative toxicity. Together, our findings offer a preclinical proof that by acting on the tumor stroma paclitaxel potentiates the antitumor activity elicited by a targeted delivery of IL2, thereby supporting the use of immunochemotherapy in the treatment of metastatic melanoma. Cancer Res; 72(7); 1814-24. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

et al. 2012

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“…A549 cells were shown to have a concentration-dependant growth inhibition to gliotoxin [22] which could be attributed to reactive oxygen species generated through redox cycling [23][24][25]. In rat macrophages and human colonic epithelial cells, gliotoxin inhibited NF-κB activation and significantly inhibited cytokine secretion when stimulated with lipopolysaccharide [26].…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of Bacterial-Derived Toxins to Immortal Lung Epithelial and Macrophage Cells

Peterson

Collier

Katterman

et al. 2009

Appl Biochem Biotechnol

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Health risks associated with inhalation and deposition of biological materials have been a topic of great concern due to highly publicized cases of inhalation anthrax, of new regulations on the release of particulate matter, and to increased concerns on the hazards of indoor air pollution. Here, we present an evaluation of the sensitivity of two immortal cell lines (A549, human lung carcinoma epithelia) and NR8383 (rat alveolar macrophages) to a variety of bacterial-derived inhalation hazards and simulants including etoposide, gliotoxin, streptolysin O, and warfarin. The cell response is evaluated through quantification of changes in mitochondrial succinate dehydrogenase activity, release of lactate dehydrogenase, initiation of apoptosis, and through changes in morphology as determined by visible light microscopy and scanning electron microscopy. These cells display dose-response relations to each toxin, except for triton which has a step change response. The first observable responses of the epithelial cells to these compounds are changes in metabolism for one toxin (warfarin) and alterations in membrane permeability for another (gliotoxin). The other four toxins display a similar time course in response as gauged by changes in metabolism and loss of membrane integrity. Macrophages are more sensitive to most toxins; however, they display a lower level of stability. This information can be used in the design of cell-based sensors responding to these and similar hazards.

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“…These include expanding cellular stress, potentially by altering the lipid or chemotherapeutic formulations or by adding radiation ( 5,46 ), and the use of antimitotic cancer drugs such as paclitaxel ( 53,54 ), which could lead to a more substantial increase of apoptotic up-regulation and greater tumor necrosis. These fi ndings also encourage exploration of combined treatment for other methods of tumor ablation.…”

Section: Experimental Studies: Increasing Stress and Apoptosis At Ablmentioning

confidence: 99%

Liposomal Doxorubicin Increases Radiofrequency Ablation–induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways

Solazzo

Ahmed²,

Schor-Bardach³

et al. 2010

Radiology

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Purpose:To determine if oxidative and nitrative stress and/or apoptosis contribute to increased coagulation when combining radiofrequency (RF) ablation with liposomal doxorubicin. Materials and Methods:Animal care committee approval was obtained. R3230 mammary adenocarcinomas in Fischer rats were treated with either RF ablation ( n = 43), 1 mg of intravenously injected liposomal doxorubicin ( n = 26), or combined therapy ( n = 30) and were compared with control subjects ( n = 11). A subset of animals receiving combination therapy ( n = 24) were treated in the presence or absence of N -acetylcysteine (NAC) administered 24 hours and 1 hour before RF ablation. Tumors were analyzed 2 minutes to 72 hours after treatment to determine the temporal range of response by using immunohistochemical staining of the apoptosis marker cleaved caspase-3, phosphorylated g H2AX , and Results:By 4 hours after RF ablation alone, a 0.48-mm 6 0.13 (standard deviation ) peripheral band with 57.0% 6 7.3 cleaved caspase-3 positive cells was noted at the ablation margin, whereas a 0.73-mm 6 0.18 band with 77.7% 6 6.3 positivity was seen for combination therapy ( P , .03 for both comparisons). Combination therapy caused increased and earlier staining for 4-HNE-modifi ed proteins, 8-OHdG, NT, and g H2AX with colocalization to cleaved caspase-3 staining. A rim of increased HSP70 was identifi ed peripheral to the area of cleaved caspase-3. Parameters of oxidative and nitrative stress were signifi cantly inhibited by NAC 1 hour following RF ablation, resulting in decreased cleaved caspase-3 positivity (0.28-mm 6 0.09 band of 25.9% 6 7.4 positivity vs 0.59-mm 6 0.11 band of 62.9% 6 6.0 positivity, P , .001 for both comparisons). Conclusion:Combining RF ablation with liposomal doxorubicin increases cell injury and apoptosis in the zone of increased coagulation by using a mechanism that involves oxidative and nitrative stress that leads to accelerated apoptosis.q RSNA, 2010

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The immunopharmacology of paclitaxel (Taxol®), docetaxel (Taxotere®), and related agents

Cited by 103 publications

References 91 publications

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

Cytotoxicity of Bacterial-Derived Toxins to Immortal Lung Epithelial and Macrophage Cells

Liposomal Doxorubicin Increases Radiofrequency Ablation–induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways

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