Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma

Weber, Friedrich; Asher, Anthony L.; Bucholz, Richard D.; Berger, Mitchel S.; Prados, Michael D.; Chang, Susan M.; Bruce, Jeffrey N.; Hall, Walter A.; Rainov, Nikolai G.; Westphal, Manfred; Warnick, Ronald E.; Rand, Robert W.; Floeth, Frank; Rommel, Frank Risto; Pan, Henry; Hingorani, Vijay N.; Puri, Raj K.

doi:10.1007/bf02700027

Cited by 153 publications

(83 citation statements)

References 16 publications

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“…Eotaxin could regulate eosinophil trafficking into the airways along with other chemotactic factors, such as IL-4 which is a pleiotropic cytokine that elicits a wide spectrum of physiological and pathogenic events including cell proliferation, differentiation, apoptosis and inflammation [26][27][28]. The enhanced level of IL-4 in the asthma subgroup was attenuated with the addition of γT, with almost the same function as dexamethasone.…”

Section: Discussionmentioning

confidence: 99%

Comparable Function of γ-Tocopherols in Asthma Remission by Affecting Eotaxin and IL-4

Xue

Zhang

et al. 2016

Adv Clin Exp Med

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Background. Bronchial asthma is one of the world's most common chronic disorders dangerous to human health. It has been hypothesized that the increased number of asthma sufferers may be due to changing antioxidant intake or vitamin deficiency. However, the influence of vitamins on asthma has rarely been considered. Objectives. The aim of this study was to explore the effects of γ-tocopherols, a specific form of vitamin E, on asthma remission together with the possible mechanism behind the process. Material and Methods. Eosinophil counting was applied to detect the total number of cells, eosinophils and lymphocytes. Meanwhile, HE staining was used for morphological detection. In addition, the eotaxin and IL-4 levels in the serum and bronchoalveolar lavage fluid were measured using ELISA technology. Results. The cell counting results showed that γ-tocopherols possesses the capability to reduce the number of eosinophils. Moreover, the exudation of inflammatory cells together with the hyperplasia of goblet cells was also found to experience significant inhibition when treated with γ-tocopherols. Furthermore, the high levels of eotaxin and IL-4 in the asthma group were evidently reduced under the treatment of γ-tocopherols which was comparable with hexadecadrol. Conclusions. γ-tocopherols can remit asthma by regulating the level of eotaxin and IL-4. Moreover, γ-tocopherols may be regarded as a potential candidate for asthma treatment after much deeper explorations (Adv Clin Exp Med 2016, 25, 4, 643-648).

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Section: Discussionmentioning

confidence: 99%

Comparable Function of γ-Tocopherols in Asthma Remission by Affecting Eotaxin and IL-4

Xue

Zhang

et al. 2016

Adv Clin Exp Med

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“…The optimal choice among the treatments may depend on the overall time of the infusion protocol. For example, clinical trials of CED of therapeutic proteins often involve infusion protocols that last several days [53]; in some cases multiple infusions are separated by more than a week [13]. For these longer protocols, enzymatic degradation of the ECM may be a preferable strategy to enhance particle distribution, because the regeneration of hyaluronan takes up to 12 days [49].…”

Section: Discussionmentioning

confidence: 99%

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

et al. 2007

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This study investigates methods of manipulating the brain extracellular matrix (ECM) to enhance the penetration of nanoparticle drug carriers in convection-enhanced delivery (CED). A probe was fabricated with two independent microfluidic channels to infuse, either simultaneously or sequentially, nanoparticles and ECM-modifying agents. Infusions were performed in the striatum of the normal rat brain. Monodisperse polystyrene particles with a diameter of 54 nm were used as a model nanoparticle system. Because the size of these particles is comparable to the effective pore size of the ECM, their transport may be significantly hindered compared with the transport of low molecular weight molecules. To enhance the transport of the infused nanoparticles, we attempted to increase the effective pore size of the ECM by two methods: dilating the extracellular space and degrading selected constituents of the ECM. Two methods of dilating the extracellular space were investigated: co-infusion of nanoparticles and a hyperosmolar solution of mannitol, and pre-infusion of an isotonic buffer solution followed by infusion of nanoparticles. These treatments resulted in an increase in the nanoparticle distribution volume of 50% and 123%, respectively. To degrade hyaluronan, a primary structural component of the brain ECM, a pre-infusion of hyaluronidase (20,000 U/mL) was followed after 30 min by infusion of nanoparticles. This treatment resulted in an increase in the nanoparticle distribution of 64%. Our results suggest that both dilation and enzymatic digestion can be incorporated into CED protocols to enhance nanoparticle penetration.

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“…The safety and toxicity of IL-4(38-37)-PE-38KDEL was also examined in a multicenter, doseescalation phase I/II trial with intratumoral administration in 31 patients with recurrent malignant glioma, and it was suggested that compared to historical control there was an increase in overall median survival. 53 Further development of this agent is planned.…”

Section: Il-4mentioning

confidence: 99%

Novel Drug Delivery Strategies in Neuro-Oncology

2009

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Summary: Treatment of malignant gliomas represents one of the most formidable challenges in oncology. Despite treatment with surgery, radiation therapy, and chemotherapy, the prognosis remains poor, particularly for glioblastoma, which has a median survival of 12 to 15 months. An important impediment to finding effective treatments for malignant gliomas is the presence of the blood brain barrier, which serves to prevent delivery of potentially active therapeutic compounds. Multiple efforts are focused on developing strategies to effectively deliver active drugs to brain tumor cells. Blood brain barrier disruption and convectionenhanced delivery have emerged as leading investigational delivery techniques for the treatment of malignant brain tumors. Clinical trials using these methods have been completed, with mixed results, and several more are being initiated. In this review, we describe the clinically available methods used to circumvent the blood brain barrier and summarize the results to date of ongoing and completed clinical trials. Key Words: Convection-enhanced delivery, blood brain barrier disruption, brain neoplasm, drug delivery system.

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Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma

Abstract: NBI-3001 appears to have an acceptable safety and toxicity profile when administered intratumorally in patients with recurrent malignant glioma.

Cited by 153 publications

References 16 publications

Comparable Function of γ-Tocopherols in Asthma Remission by Affecting Eotaxin and IL-4

Comparable Function of γ-Tocopherols in Asthma Remission by Affecting Eotaxin and IL-4

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

Novel Drug Delivery Strategies in Neuro-Oncology

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