Photodynamic therapy of transitional cell carcinoma multicellular tumor spheroids with hypericin

Kamuhabwa, Appolinary; Huygens, Ann; Witte, Peter de

doi:10.3892/ijo.23.5.1445

Cited by 11 publications

(15 citation statements)

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“…Our previous in vitro (10) and in vivo (11) studies demonstrate that, although TCC tumor cells accumulate hypericin sufficiently, malignant cells are not completely destroyed after light irradiation. The 595-nm laser light used for photoactivation of hypericin penetrates readily across the 500-μm spheroid.…”

Section: Discussionmentioning

confidence: 99%

Enhancing the photodynamic effect of hypericin in human bladder transitional cell carcinoma spheroids by the use of the oxygen carrier, perfluorodecalin

Kamuhabwa¹,

Huygens²,

Roskams³

et al. 2006

Int J Oncol

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Abstract. In the present study, we evaluated the possibility of enhancing the photodynamic effect of hypericin in transitional cell carcinoma (TCC) spheroids by the use of the oxygen carrier, perfluorodecalin. Following incubation with hypericin, RT-112 TCC spheroids were irradiated in the presence or absence of perfluorodecalin, at light doses of 7 J/cm 2 or 28 J/ cm 2 , delivered at a fluence rate of 15 mW/cm 2 . The photodynamic therapy (PDT) efficacy was evaluated and apoptotic cells were visualized. The results show that, in the absence of perfluorodecalin, spheroidal TCC cells are inadequately sensitive to hypericin PDT. As was shown by fluorescence microscopy, this lack of activity was not due to insufficient photoactive concentrations of hypericin reaching the inner parts of the spheroids. Conversely, enhanced oxygenation of spheroids by perfluorodecalin led to a dramatic enhancement of hypericin PDT efficacy. The detection of nuclear shrinkage or fragmentation with DAPI staining and the assessment of cell morphology by light microscopy indicated that apoptosis was the most prominent response of spheroids to hypericin PDT in the presence of perfluorodecalin. In conclusion, the results of this study suggest that perfluorocarbons, such as perfluorodecalin, are useful in enhancing the oxygenation of tumor tissue, resulting in highly efficient hypericin PDT. Since hypericin becomes concentrated specifically in human bladder urothelial carcinoma lesions and the bladder is very well suited to instillation with a perfluorocarbon, combining the techniques looks very promising for an efficient and selective whole bladder wall photodynamic antitumoral treatment in a urological clinical setting.

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Section: Discussionmentioning

confidence: 99%

Enhancing the photodynamic effect of hypericin in human bladder transitional cell carcinoma spheroids by the use of the oxygen carrier, perfluorodecalin

Kamuhabwa¹,

Huygens²,

Roskams³

et al. 2006

Int J Oncol

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“…Accordingly, MCTS have served as a model for a variety of experimental therapy studies using radiotherapy, chemotherapy, radioimmunotherapy, cell-and antibody-based immunotherapy, hyperthermia, gene therapy, and photodynamic treatment. [55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71] MCTS have also been used extensively in basic studies of the microenvironmental regulation of proliferation, viability, energy metabolism, nutrient metabolism, invasion, cell-cell interactions, and extracellular matrix composition. Based on their long-term experience, experts in the field agree with Mueller-Klieser's final conclusion in a 2000 review article: "Keeping in mind the fundamental differences between monolayers and spheroids with regard to cellular sensitivity to various treatment modalities, tumor spheroids should be mandatory models in applied cancer research, for example in major programs for drug screening and development.…”

Section: Multicellular Tumor Spheroidsmentioning

confidence: 99%

The Use of 3-D Cultures for High-Throughput Screening: The Multicellular Spheroid Model

et al. 2004

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Over the past few years, establishment and adaptation of cell-based assays for drug development and testing has become an important topic in high-throughput screening (HTS). Most new assays are designed to rapidly detect specific cellular effects reflecting action at various targets. However, although more complex than cell-free biochemical test systems, HTS assays using monolayer or suspension cultures still reflect a highly artificial cellular environment and may thus have limited predictive value for the clinical efficacy of a compound. Today's strategies for drug discovery and development, be they hypothesis free or mechanism based, require facile, HTS-amenable test systems that mimic the human tissue environment with increasing accuracy in order to optimize preclinical and preanimal selection of the most active molecules from a large pool of potential effectors, for example, against solid tumors. Indeed, it is recognized that 3-dimensional cell culture systems better reflect the in vivo behavior of most cell types. However, these 3-D test systems have not yet been incorporated into mainstream drug development operations. This article addresses the relevance and potential of 3-D in vitro systems for drug development, with a focus on screening for novel antitumor drugs. Examples of 3-D cell models used in cancer research are given, and the advantages and limitations of these systems of intermediate complexity are discussed in comparison with both 2-D culture and in vivo models. The most commonly used 3-D cell culture systems, multicellular spheroids, are emphasized due to their advantages and potential for rapid development as HTS systems. Thus, multicellular tumor spheroids are an ideal basis for the next step in creating HTS assays, which are predictive of in vivo antitumor efficacy. (Journal of Biomolecular Screening 2004:273-285)

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“…Over one third of our articles (15 articles) utilized RT-112 as a model of moderately differentiated (grade 2) transitional cell carcinoma. Eight studies used this cell line for tumor diagnosis using hypericin and related analogs (15,16,19,(28)(29)(30)(31)(32); five studies utilized this cell line for cancer therapeutics, including chemotherapeutics and reoviral therapy (24)(25)(26)(27)33); and two studies used RT-112 for tumor characterization studies, including pH imbalance and tissue remodeling (12,34). Other grade 2 carcinoma cell lines included the urothelial carcinoma cell line 5637 (5 articles).…”

Section: Human Urothelial Cellsmentioning

confidence: 99%

“…Cell survival in spheroids was a function of dose and intensity of light exposure, but generally was significantly higher than in monolayer culture. Fluorescent imaging showed that the spheroids had a negative hypericin gradient from the rim to the core (28). Hypoxic spheroid-core conditions were hypothesized to cause low hypericin sensitivity; this was investigated in two follow-up studies.…”

Section: Applicationsmentioning

confidence: 99%

Bladder Organoids and Spheroids: Potential Tools for Normal and Diseased Tissue Modelling

et al. 2019

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Bladder-related diseases are among the most common and costly to the healthcare system, and therefore require new approaches to treatment. Organoids and spheroids are 3D cultures that mimic organ features ex vivo and offer novel approaches for diagnostic and therapeutic assessment. The aim of this article was to provide a systematic review of the literature related to bladder organoids and spheroids, applied to disease diagnosis, characterization, and treatment. PubMed and Web of Science were utilized in March 2018 to compile 191 articles satisfying search criteria related to bladder organoids or spheroids and 58 articles were included in the final review. Finally, cell types and techniques utilized for spheroid and organoid manufacture were characterized. The applications of bladder carcinoma spheroids and organoids followed three themes: cancer characterization, diagnosis, and treatment. Tumor characterization studies included a focus on extracellular matrix, microenvironment, genetics, and growth of tumor cells. Diagnostic studies explored the use of endogenous fluorophores and white light for photodiagnosis. Treatment studies investigated cancer chemotherapy, immunotherapy, oncolytic viruses, and gene therapy. Ten studies explored hypericin as a tool for diagnostics and photodynamic therapy. Additionally, two studies applied organoids to urinary tract infections.

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Photodynamic therapy of transitional cell carcinoma multicellular tumor spheroids with hypericin

Cited by 11 publications

References 0 publications

Enhancing the photodynamic effect of hypericin in human bladder transitional cell carcinoma spheroids by the use of the oxygen carrier, perfluorodecalin

Enhancing the photodynamic effect of hypericin in human bladder transitional cell carcinoma spheroids by the use of the oxygen carrier, perfluorodecalin

The Use of 3-D Cultures for High-Throughput Screening: The Multicellular Spheroid Model

Bladder Organoids and Spheroids: Potential Tools for Normal and Diseased Tissue Modelling

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