Mechanisms Behind the Resistance of Spheroids to Photodynamic Treatment: A Flow Cytometry Study

West, Catharine M L; Moore, James

doi:10.1111/j.1751-1097.1992.tb04257.x

Cited by 20 publications

(11 citation statements)

References 19 publications

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“…23 However, the heterogeneity of PS uptake has been demonstrated in various in vitro and in vivo models. 24,25 The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of MDR, and are related to altered PS uptake and e®lux rates or altered intracellular tra±cking within cancer cells. 26 …”

Section: Interaction Of Mdr and Psmentioning

confidence: 99%

Photodynamic therapy of cancer — Challenges of multidrug resistance

Huang

Hsu

et al. 2015

J. Innov. Opt. Health Sci.

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can lead to the generation of cytotoxic reactive oxygen species (ROS) and consequently destroy cancer. Similar to many other anticancer therapies, PDT is also subject to intrinsic cancer resistance mediated by multidrug resistance (MDR) mechanisms. This paper will review the recent progress in understanding the interaction between MDR transporters and PS uptake. The strategies that can be used in a clinical setting to overcome or bypass MDR will also be discussed.

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Section: Interaction Of Mdr and Psmentioning

confidence: 99%

Photodynamic therapy of cancer — Challenges of multidrug resistance

Huang

Hsu

et al. 2015

J. Innov. Opt. Health Sci.

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“…7,17 Tumor size heterogeneity can play a critical role in the establishment of differential gradients within the tumor microenvironment, such as hypoxia, pH, nutrients, growth factors, cytokines, waste products, and metabolic stress, and consequently their responses to drug treatment. 18 Thus, there is an unmet need for methods to generate sufficient tumor aggregates of controlled sizes so that they can be utilized for preclinical cancer drug efficacy screening. Emerging microfabrication and micromolding techniques 19 offer an opportunity to control the size of 3D tissue constructs more efficiently.…”

mentioning

confidence: 99%

Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation

Singh

Mukundan

et al. 2015

ASSAY and Drug Development Technologies

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Despite significant investments in cancer research and drug discovery/development, the rate of new cancer drug approval is £5% and most cases of metastatic cancer remain incurable. Ninety-five percent of new cancer drugs fail in clinical development because of a lack of therapeutic efficacy and/or unacceptable toxicity. One of the major factors responsible for the low success rate of anticancer drug development is the failure of preclinical models to adequately recapitulate the complexity and heterogeneity of human cancer. For throughput and capacity reasons, high-throughput screening growth inhibition assays almost exclusively use two-dimensional (2D) monolayers of tumor cell lines cultured on tissue culture-treated plastic/glass surfaces in serum-containing medium. However, these 2D tumor cell line cultures fail to recapitulate the three-dimensional (3D) context of cells in solid tumors even though the tumor microenvironment has been shown to have a profound effect on anticancer drug responses. Tumor spheroids remain the best characterized and most widely used 3D models; however, spheroid sizes tend to be nonuniform, making them unsuitable for high-throughput drug testing. To circumvent this challenge, we have developed defined size microwell arrays using nonadhesive hydrogels that are applicable to a wide variety of cancer cell lines to fabricate sizecontrolled 3D microtumors. We demonstrate that the hydrogel microwell array platform can be applied successfully to generate hundreds of uniform microtumors within 3-6 days from many cervical and breast, as well as head and neck squamous cell carcinoma (HNSCC) cells. Moreover, controlling size of the microwells in the hydrogel array allows precise control over the size of the microtumors. Finally, we demonstrate the application of this platform technology to probe activation as well as inhibition of epidermal growth factor receptor (EGFR) signaling in 3D HNSCC microtumors in response to EGF and cetuximab treatments, respectively. We believe that the ability to generate large numbers of HNSCC microtumors of uniform size and 3D morphology using hydrogel arrays will provide more physiological in vitro 3D tumor models to investigate how tumor size influences signaling pathway activation and cancer drug efficacy.

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“…40 Some studies suggest that cells which are resistant to PDT have reduced LDL uptake. 38 Another explanation may be that the Photosan-3 TM penetrates the spheroids poorly, leading the inner core of the spheroids relatively free for HpD. However, other spheroid studies have demonstrated the presence of HpD in the spheroid centre after 24 h of drug exposure.…”

Section: Discussionmentioning

confidence: 99%

“…These cells have been shown to be more resistant to PDT than cycling cells. 38 Quiescent cells may undergo many changes with loss of surface microvilli, decrease in uidity and inhibition of phagocytosis leading to a reduction in the permeability and transport of molecules. 39 There is evidence that the low-density lipoprotein (LDL) pathway is important for photosensitizer uptake into cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of photodynamic therapy on glioma spheroids

Terzis

Dietze²,

Bjerkvig³

et al. 1997

British Journal of Neurosurgery

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The present study describes the sensitivity of glioma cells to a haematoporphyrin derivative (Photosan-3) under laser activation (argon-pumped dye laser). The effects of photodynamic therapy (PDT) on cell growth, directional migration and cell invasion were investigated on two human glioma cell lines (GaMg and U-251 Mg). The directional cell migration and spheroid growth was determined for both cell lines exposed to increasing laser energy output (15-35J/cm2) with concentrations of 5 and 7 micrograms/ml of Photosan-3. Both cell lines showed a dose-dependent migratory response to increasing laser irradiation, that was more prominent in the 7 micrograms/ml treatment group. This effect occurred during the first 4 days after drug exposure. Also, spheroids from both cell lines showed a drug and laser output energy dose-dependent inhibition of growth which became apparent after a lag period of 6 days. The lag period was characterized by a decreased growth rate as compared with the control group. During this period the outer cell layers of the spheroids fell apart. The remaining spheroid tissue was not able to migrate and to regrow when exposed to the highest laser energy outputs (30-35J/cm2, 5 and 7 micrograms/ml Photosan-3). These spheroids showed, however, the ability for invasion when confronted with normal brain cell aggregated in vivo. Light microscopic observations of co-cultures between tumour tissue and brain cell aggregates revealed a normal tumour morphology. This indicates that the remaining tumour cells were not dead and could be stimulated to invade the normal tissue when exposed to a normal brain microenvironment.

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Mechanisms Behind the Resistance of Spheroids to Photodynamic Treatment: A Flow Cytometry Study

Cited by 20 publications

References 19 publications

Photodynamic therapy of cancer — Challenges of multidrug resistance

Photodynamic therapy of cancer — Challenges of multidrug resistance

Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation

Effects of photodynamic therapy on glioma spheroids

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