Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors

Krishnamurthy, Satish; Powers, Stephen K.; Witmer, Peggy; Brown, Tony

doi:10.1002/1096-9101(2000)27:3<224::aid-lsm4>3.0.co;2-#

Cited by 63 publications

(26 citation statements)

References 30 publications

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“…226 reported a phase I/II trial involving 23 patients with glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). Other brain lesions treated with PDT included malignant ependymomas, 227-228 malignant meningiomas, 229 melanoma and lung cancer brain metastasis, 226,229 and recurrent pituitary adenomas. 230 The initial trails provided encouraging results and the authors concluded that PDT can be used as an adjuvant therapy in brain tumors patients.…”

Section: Clinical Pdtmentioning

confidence: 99%

Photodynamic therapy of cancer: An update

Agostinis

Berg

Cengel

et al. 2011

CA: A Cancer Journal for Clinicians

4,340

3,792

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Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.

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Section: Clinical Pdtmentioning

confidence: 99%

Photodynamic therapy of cancer: An update

Agostinis

Berg

Cengel

et al. 2011

CA: A Cancer Journal for Clinicians

4,340

3,792

View full text Add to dashboard Cite

show abstract

“…However, due to the limited penetration of light in tissues, tumor cells located at deeper sites beneath the resection cavity may not receive sufficient light illumination. Therefore, studying the response of photosensitized tumor cells receiving sub-lethal light doses may aid in determining the prognosis of glioblastoma patients undergoing PDT [13]–[18].…”

Section: Introductionmentioning

confidence: 99%

Photofrin Based Photodynamic Therapy and miR-99a Transfection Inhibited FGFR3 and PI3K/Akt Signaling Mechanisms to Control Growth of Human Glioblastoma In Vitro and In Vivo

2013

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Glioblastoma is the most common malignant brain tumor in humans. We explored the molecular mechanisms how the efficacy of photofrin based photodynamic therapy (PDT) was enhanced by miR-99a transfection in human glioblastoma cells. Our results showed almost similar uptake of photofrin after 24 h in different glioblastoma cells, but p53 wild-type cells were more sensitive to radiation and photofrin doses than p53 mutant cells. Photofrin based PDT induced apoptosis, inhibited cell invasion, prevented angiogenic network formation, and promoted DNA fragmentation and laddering in U87MG and U118MG cells harvoring p53 wild-type. Western blotting showed that photofrin based PDT was efficient to block the angiogenesis and cell survival pathways. Further, photofrin based PDT followed by miR-99a transfection dramatically increased miR-99a expression and also increased apoptosis in glioblastoma cell cultures and drastically reduced tumor growth in athymic nude mice, due to down regulation of fibroblast growth factor receptor 3 (FGFR3) and PI3K/Akt signaling mechanisms leading to inhibition of cell proliferation and induction of molecular mechanisms of apoptosis. Therefore, our results indicated that the anti-tumor effects of photofrin based PDT was strongly augmented by miR-99a overexpression and this novel combination therapeutic strategy could be used for controlling growth of human p53 wild-type glioblastomas both in vitro and in vivo.

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“…To date, most clinical PDT trials have employed short-term high fluence rate intraoperative or stereotactic light delivery techniques [23,24]. This is unlikely to eradicate tumor cells that have infiltrated into surrounding brain due to the inability to deliver toxic threshold light fluences in a reasonable time period.…”

Section: Introductionmentioning

confidence: 99%

The effects of ultra low fluence rate single and repetitive photodynamic therapy on glioma spheroids

et al. 2009

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Background and Objective Achieving local control of gliomas with photodynamic therapy (PDT) requires the delivery of adequate light fluences to depths of 1–2 cm in the resection margin where the majority of local recurrences originate. This is clinically impractical with current single-shot, intraoperative PDT treatments due to the length of time required to deliver adequate fluences. Multiple or extended treatment protocols would therefore seem to be required. The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated PDT using single or, repetitive light delivery protocols was investigated at both low and ultra low fluence rates. Study Design/Materials and Methods Human glioma spheroids (400 μm diameter) were subjected to sub-threshold light fluence (1.5, 3, or 6 J cm−2) ALA–PDT consisting of four light delivery schemes: single treatment given over either 1 or 24 hours, repetitive treatment given either as four 1 hour light treatments separated by a 4 day interval, or 24 hours light delivery, consisting of four 24 hours treatments separated by a 3 day interval. Treatment efficacy was evaluated using a growth assay. In some cases, confocal microscopy was used to image cell viability. Results The repetitive and single light treatment protocols were most effective when delivered at ultra low (μW cm−2) fluence rates. In all cases, growth inhibition was light dose-dependent. The repetitive ultra low fluence rate treatment (1.5 J cm−2; irradiance = 17 μW cm−2) light delivery protocol was the most effective resulting in total growth inhibition during the 2-week observation period. Conclusion Ultra low light fluence rate ALA–PDT results in significant spheroid growth inhibition. Repeated administration of ALA was required during repetitive and/or protracted single PDT treatment protocols. The existence of a lower fluence rate limit, below which the efficacy of threshold light fluences diminish was not found in these studies.

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Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors

Cited by 63 publications

References 30 publications

Photodynamic therapy of cancer: An update

Photodynamic therapy of cancer: An update

Photofrin Based Photodynamic Therapy and miR-99a Transfection Inhibited FGFR3 and PI3K/Akt Signaling Mechanisms to Control Growth of Human Glioblastoma In Vitro and In Vivo

The effects of ultra low fluence rate single and repetitive photodynamic therapy on glioma spheroids

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