Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma

Quyn, Aaron; Ziyaie, Dorin; Polignano, Francesco M.; Tait, Iain S.

doi:10.1111/j.1477-2574.2009.00102.x

Cited by 66 publications

(28 citation statements)

References 53 publications

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“…In contrast, the cure rates for nasopharyngeal carcinoma [5] and superficial recurrent urothelial carcinoma HCl [6, 7] are suboptimal with respect to PDT and warrant improvement. Moreover, non-resectable perihilar cholangiocarcinomas respond better to PDT than to any other last-line treatment such as chemotherapy [8], but all available treatments (including PDT) are currently palliative and not curative. The recalcitrant nature of these tumor types to PDT is believed to stem from the use of photosensitizers with suboptimal spectral properties and poor pharmacokinetics as well as the activation of cell survival pathways by tumor cells following PDT [2, 9].…”

Section: Introductionmentioning

confidence: 99%

Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy

Weijer

Clavier

Zaal

et al. 2016

Cell. Mol. Life Sci.

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Photodynamic therapy (PDT) is an established palliative treatment for perihilar cholangiocarcinoma that is clinically promising. However, tumors tend to regrow after PDT, which may result from the PDT-induced activation of survival pathways in sublethally afflicted tumor cells. In this study, tumor-comprising cells (i.e., vascular endothelial cells, macrophages, perihilar cholangiocarcinoma cells, and EGFR-overexpressing epidermoid cancer cells) were treated with the photosensitizer zinc phthalocyanine that was encapsulated in cationic liposomes (ZPCLs). The post-PDT survival pathways and metabolism were studied following sublethal (LC50) and supralethal (LC90) PDT. Sublethal PDT induced survival signaling in perihilar cholangiocarcinoma (SK-ChA-1) cells via mainly HIF-1-, NF-кB-, AP-1-, and heat shock factor (HSF)-mediated pathways. In contrast, supralethal PDT damage was associated with a dampened survival response. PDT-subjected SK-ChA-1 cells downregulated proteins associated with EGFR signaling, particularly at LC90. PDT also affected various components of glycolysis and the tricarboxylic acid cycle as well as metabolites involved in redox signaling. In conclusion, sublethal PDT activates multiple pathways in tumor-associated cell types that transcriptionally regulate cell survival, proliferation, energy metabolism, detoxification, inflammation/angiogenesis, and metastasis. Accordingly, tumor cells sublethally afflicted by PDT are a major therapeutic culprit. Our multi-omic analysis further unveiled multiple druggable targets for pharmacological co-intervention.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-016-2401-0) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy

Weijer

Clavier

Zaal

et al. 2016

Cell. Mol. Life Sci.

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“…Numerous studies, including two randomized clinical trials, have found that PDT is superior to biliary stenting alone in the treatment of unresectable cholangiocarcinoma, improving both survival as well as quality of life 2,3,8-13. Additionally, it was recently shown that survival in patients who underwent PDT was similar to those in whom curative surgery was attempted but who had positive resection margins, despite the fact that the PDT group had more advanced clinical T stages 14…”

Section: Discussionmentioning

confidence: 99%

Photodynamic Therapy in Unresectable Cholangiocarcinoma: Not for the Uncommitted

et al. 2013

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Background/AimsPhotodynamic therapy (PDT) in unresectable cholangiocarcinoma has been associated with improved survival. We report a single tertiary care center experience over the past 6 years.MethodsFifty-five patients with unresectable cholangiocarcinoma received PDT between 2004 and 2010. Plastic stents were placed after PDT to prevent cholangitis.ResultsTwenty-seven patients (49%) showed Bismuth type IV, 22 (41%) showed Bismuth type III, and six (10%) showed Bismuth type I and II. Twenty patients (37%) received chemotherapy and radiation therapy, five (9%) received chemotherapy only; and one (2%) received radiation therapy only. Mean number of PDT sessions was 1.9±1.5 sessions (range, 1 to 9). Mean survival duration was 293±266 days (median, 190; range, 25 to 1,332). PDT related complications included three (5%) facial burn, three (5%) photosensitivity, and two (3%) rash. Kaplan-Meier analysis comparing the survival means of patients who received PDT and chemotherapy/radiation therapy (median survival 257 days; 95% confidence interval [CI], 166 to 528) versus who received PDT only (median survival 183 days; 95% CI, 129 to 224) showed no significant difference (log-rank p=0.20).ConclusionsPDT has a measurable impact on survival in unresectable cholangiocarcinoma but requires aggressive stenting posttherapy.

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“…При активации препарата образуются свободные радика-лы кислорода, приводящие к повреждению окружающих клеток опухоли. В ряде исследований было показано, что медиана выживаемости при ФДТ как неоадъювантного метода терапии составила от 330 до 493 дней после поста-новки диагноза и однолетняя выживаемость -от 45 до 83% [20,24].…”

Section: хирургия 4 2015unclassified

View of the problem of Rlatskin tumor

Czhao¹,

Шевченко²,

Zharikov³

2015

Khir. Z. im. N.I. Pirogova

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Ключевые слова: опухоль Клатскина, факторы риска, классификация, диагностика, лечение, прогноз. Klatskin tumorarises from the common hepatic duct and its bifurcation the bile ducts and is the most common primary malignancy of the biliary tree. The location of the tumor and its close relationship with vascular structures at the hepatic hilum have resulted in a low resectability and high rate morbidity and mortality. Improvementof instrumental diagnostics and operative techniquesallowsto performextendedresectionand complexinterventions onthe liver, bile ductsand vascularstructuresat the hepatic hilum. The role ofchemoradiotherapyandphotodynamic therapyis not fullyunderstood. Thus, questions of treatmentandprognosis of the diseaseare remain relevantandrequire further study.

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Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma

Abstract: This prospective clinical cohort study has demonstrated that radical surgery and palliative Photofrin-PDT are associated with an increased survival in patients with hilar cholangiocarcinoma.

Cited by 66 publications

References 53 publications

Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy

Multi-OMIC profiling of survival and metabolic signaling networks in cells subjected to photodynamic therapy

Photodynamic Therapy in Unresectable Cholangiocarcinoma: Not for the Uncommitted

View of the problem of Rlatskin tumor

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