Photodynamic Therapy Using Verteporfin Photosensitization in the Pancreas and Surrounding Tissues in the Syrian Golden Hamster

Ayaru, Lakshmana; Wittmann, J.; MacRobert, AJ; Novelli, Marco; Bown, Stephen G.; Pereira, Stephen P.

doi:10.1159/000101874

Cited by 47 publications

(32 citation statements)

References 27 publications

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“…Photodynamic therapy (PDT) produces localized tissue necrosis with light (most conveniently from a laser), after administration of a photosensitizing agent in the presence of oxygen [10][11][12] , based on the use of photosensitizing compounds that localize quite selectively in neoplastic/hyperplastic tissues and become cytotoxic when exposed to light [12][13][14] . In view of the antitumor effect of single treatment, PDT is local.…”

Section: Introductionmentioning

confidence: 99%

Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

Xie¹,

Jia²,

Liu³

et al. 2009

WJG

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AIM:To investigate the anti-tumor effects of combined cytotoxic drug (gemcitabine) and photodynamic therapy (PDT) on human pancreatic cancer xenograft in nude mice. METHODS:Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group (without treatment), photosensitizer treatment group (2 mg/kg photosan, without illumination), chemotherapy group (50 mg/kg gemcitabine i.p.), PDT group (2 mg/kg photosan + laser irradiation) and combined treatment group (photosan + chemotherapy), with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition (TGI). RESULTS:No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy (0.24 ± 0.15-0.49 ± 0.08 vs 0.43 ± 0.18-1.25 ± 0.09, P < 0.05). PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group (0.12 ± 0.07-0.28 ± 0.12 vs 0.39 ± 0.15-1.20 ± 0.11, P < 0.05), small dose chemotherapy group (0.12 ± 0.07-0.28 ± 0.12 vs 0.32 ± 0.14-1.16 ± 0.08, P < 0.05) and control group (0.12 ± 0.07-0.28 ± 0.12 vs 0.43 ± 0.18-1.25 ± 0.09, P < 0.05). TGI was higher in the combined treatment group (82.42%) than in the PDT group (58.18%). CONCLUSION:PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.

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Section: Introductionmentioning

confidence: 99%

Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

Xie¹,

Jia²,

Liu³

et al. 2009

WJG

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“…The biliary system is a key example but other lesions that are of interest to gastroenterologist include pancreatic cancers and other non-luminal lesions [19, 20]. The treatment of these lesions is still in the exploratory phase but with the use of EUS guidance and the development of smaller and more flexible fibers, most locations in the mediastinum and abdominal cavity are now treatable.…”

Section: Current Clinical Applicationsmentioning

confidence: 99%

Role of photodynamic therapy for the upper gut

Wang

2010

Techniques in Gastrointestinal Endoscopy

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It may be questioned if PDT is still relevant for practicing gastroenterologists since other types of therapy have currently gained momentum. Important aspects of PDT that continue its development are it’s intrinsic applicability to the luminal GI tract where there are often areas of mechanical narrowing, unusual topography, and difficult accessibility where a modality that does not require contact or optical visualization has advantages. Although not used as often in the upper gastrointestinal tract for it’s original approved indications such as esophageal cancer or Barrett’s esophagus, its value in biliary lesions appears to be well substantiated. In this paper, we will review its current application in the upper gastrointestinal tract.

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“…The major advantages of VP over previous photosensitizers are: 1) deeper penetration of light into the treatment area [3]; and 2) rapid tissue clearance resulting in a shorter period of skin sensitivity. Verteporfin has been used in animal studies including, in normal pancreas with PDT of the pancreas and surrounding tissue of Syrian golden hamster [4]and EUS guided PDT for ablation of normal pancreatic tissue in porcine tissue [5].…”

Section: Introductionmentioning

confidence: 99%

Histologic differences between orthotopic xenograft pancreas models affect Verteporfin uptake measured by fluorescence microscopy and spectroscopy

et al. 2012

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Photodynamic therapy (PDT) that uses the second generation photosensitizer, verteporfin (VP), is a developing therapy for pancreatic cancer. The optimal timing of light delivery related to VP uptake and distribution in pancreatic tumors will be important information to obtain to improve treatment for this intractable disease. In this work we examined uptake and distribution of VP in two orthotopic pancreatic tumors with different histological structure. ASPC-1 (fast-growing) and Panc-1 (slower growing) tumors were implanted in SCID mice and studied when tumors were approximately 100mm 3 . In a pilot study, these tumors had been shown to differ in uptake of VP using lightinduced fluorescence spectroscopy (LIFS) in vivo and fluorescence imaging ex vivo and that work is extended here. In vivo fluorescence mean readings of tumor and liver increased rapidly up to 15 minutes after photosensitizer injection for both tumor types, and then continued to increase up to 60 minutes post injection to a higher level in ASPC-1 than in Panc-1. There was variability among animals with the same tumor type, in both liver and tumor uptake and no selectivity of tumor over liver. In this work we further examined VP uptake at multiple time points in relation to microvascular density and perfusion, using DiOC 7 (to mark blood vessels) and VP fluorescence in the same tissue slices. Analysis of DiOC 7 fluorescence indicates that AsPC-1 and Panc-1 have different vascular densities but AsPC-1 vasculature is more perfusive. Analysis of colocalized DiOC 7 and VP fluorescence showed ASPC-1 with higher accumulation of VP 3 hrs after injection and more VP at a distance from blood vessels compared to Panc-1. This work shows the need for techniques to analyze photosensitizer distribution in order to optimize photodynamic therapy as an effective treatment for pancreatic tumors.

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Photodynamic Therapy Using Verteporfin Photosensitization in the Pancreas and Surrounding Tissues in the Syrian Golden Hamster

Cited by 47 publications

References 27 publications

Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

Role of photodynamic therapy for the upper gut

Histologic differences between orthotopic xenograft pancreas models affect Verteporfin uptake measured by fluorescence microscopy and spectroscopy

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