Selective enrichment of hypericin in malignant glioma: Pioneering in vivo results

Noell, Susan; Mayer, Daniel; Strauß, Wolfgang S. L.; Tatagiba, Marcos; Ritz, Rainer

doi:10.3892/ijo.2011.968

Cited by 19 publications

(11 citation statements)

References 44 publications

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“…The accumulation of hypericin in the brain was studied ex vivo under a fluorescence microscope. The tumor-to-normal ratio (TNR) was 19.8, after correction for auto-fluorescence [70]. No adverse effects were observed.…”

Section: Resultsmentioning

confidence: 99%

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

et al. 2016

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BackgroundFluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma.MethodsWe searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.ResultsThe search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.Conclusions5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.

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Section: Resultsmentioning

confidence: 99%

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

et al. 2016

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“…They have been identified in the infiltrative peritumoral parenchyma of GBM, where the BBB remains intact (or less altered), resulting in lower accessibility of these regions to free TMZ [34,35]. The restricted bioavailability of free TMZ to CSCs in these areas of tumor infiltration as well as the intrinsic drug-resistance of CSCs may combine to limit the efficacy of current treatment regimens that utilize free TMZ.…”

Section: Discussionmentioning

confidence: 99%

Encapsulation of temozolomide in a tumor-targeting nanocomplex enhances anti-cancer efficacy and reduces toxicity in a mouse model of glioblastoma

et al. 2015

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Although temozolomide (TMZ) is the current first-line chemotherapy for glioblastoma multiforme (GBM), most patients either do not respond or ultimately fail TMZ treatment. Both intrinsic tumor resistance and limited access of TMZ to brain tumors as a result of the blood-brain barrier (BBB) contribute to poor response and ultimately to poor prognosis for GBM patients. We have developed a "dual-targeting" nanomedicine that both actively crosses the BBB and actively targets cancer cells once in the brain parenchyma. This nanomedicine (termed scL-TMZ) is sized ~40 nm and comprised of a cationic liposome (DOTAP:DOPE) encapsulating TMZ. The surface of liposome is decorated with anti-transferrin receptor single-chain antibody fragments to facilitate the crossing of the BBB by the scL-TMZ in addition to targeting GBM in the brain. This novel formulation was found to be markedly more effective than standard TMZ in both TMZ-resistant and TMZ-sensitive GBM. Encapsulation of TMZ also markedly enhanced its efficacy in killing a variety of non-GBM tumor cells. The scL-TMZ nanocomplex was shown to target cancer stem cells, which have been linked to both drug resistance and recurrence in GBM. Most significantly, systemically administered scL-TMZ significantly prolonged survival in mice bearing intracranial GBM tumors. The improved efficacy of scL-TMZ compared to standard TMZ was accompanied by reduced toxicity, so we conclude that the scL-TMZ nanomedicine holds great promise as a more effective therapy for GBM and other tumor types.

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“…There are several possible explanations for this inconsistency. First, in some studies, the “tumor-specific” evidence of porphyrin was represented by combined enhancements in both the tumor and necrotic areas, without associated pathological data; therefore, it could not be separated and evaluated whether the porphyrin retention was located in the viable or necrotic tumor parts 36, 39-42. Additionally, while the metalloporphyrins were found to have an affinity for neoplastic tissues, substantial extra-tumoral concentrations were also noted.…”

Section: Necrosis-avid Contrast Agents (Nacas)mentioning

confidence: 99%

Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

Jiang¹,

Jichen²,

Ni³

et al. 2013

Theranostics

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Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [123I]iodohypericin, [124I]iodohypericin, and [131I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin.

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Selective enrichment of hypericin in malignant glioma: Pioneering in vivo results

Cited by 19 publications

References 44 publications

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

Encapsulation of temozolomide in a tumor-targeting nanocomplex enhances anti-cancer efficacy and reduces toxicity in a mouse model of glioblastoma

Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

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