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1

Adjuvant photodynamic therapy in surgical management of cerebral tumors  

NASA Astrophysics Data System (ADS)

We have performed high dose photoradiation therapy in patients with cerebral tumors. Twenty-seven patients had gliomas, two had metastatic cancer of the brain, one had malignant meningioma. Hematoporphyrin derivative was administered intravenously. All patients underwent a craniotomy with a radical or partial excision of the tumor. There was no evidence of increased cerebral edema and other toxicity from the therapy, and all patients were discharged from the hospital within 15 days after surgery. On the basis of animal experiments our institute started using photodynamic therapy (PDT) as an adjuvant measure to the operative therapy in 30 cases of cerebral tumors. Ten of these patients were excluded from this group because of the short postoperative following time. Here, the details of our experiences are presented as follows: 106 of C6 type glioma cell strain were implanted into the frontal lobe of a Chinese hamster. Fourteen days later intracranial gliomas developed, which were larger than 4 mm in diameter, HpD in a dosage of 4 mg/kg was injected into the tail vein of the animals. The fluorescence was seen 5 minutes later. The diagnostic laser used was He-Ca (Hc-type 15A, made at Shanghai Laser Institute) with a wavelength of 441.6 nm, power of 30 mw. The fluorescence reached its peak point 24 hours later, and the normal tissue can be identified by the lack of fluorescence. Then, the tumor tissue was further radiated with an Ar laser (made in Nanjing Electronic Factory, type 360), pumped dye-laser (made in Changchun Optic Machinery Institute, type 901) with a wavelength of 630 nm, and an energy density of more than 200 Joules/cm2, which might get the tumor cells destroyed selectively. The effect of photoradiation may reach as deep as 4 - 7 mm into the brain tissue without cerebral edema or necrosis.

Chen, Zong-Qian; Wu, Si-En; Zhu, Shu-Gan

1993-03-01

2

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.  

PubMed Central

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours. PMID:9010027

Korbelik, M.; Naraparaju, V. R.; Yamamoto, N.

1997-01-01

3

Adjuvant intraoperative photodynamic therapy diminishes the rate of local recurrence in a rat mammary tumour model.  

PubMed Central

The use of photodynamic therapy (PDT) as an adjunct to curative tumour resection was investigated in a tumour recurrence model, using rat mammary adenocarcinoma BN472. Tumours were inoculated subcutaneously in 60 animals and resected after 21 days of growth. Immediately after removal, the operation site was exposed to 320-450 nm light of 0.1 W cm-2 and 60 J cm-2 after photosensitisation with either Photofrin (5 mg kg-1 i.v. 48 h before illumination) or 5-aminolaevulinic acid (ALA) (2 mg ml-1 in drinking water for 9 days). Porphyrin concentrations were measured in tissue samples. After 28 days, animals treated with adjunctive PDT had a significantly longer tumour-free interval than controls (P < 0.01); median 25 days (Photofrin), 18 days (ALA), 14 days (controls). Moreover, in the PDT groups significantly fewer rats had lymph node metastasis. A prophyrin concentration ratio between tumour and mammary tissue of 2:1 was found after Photofrin and 4:1 after ALA. The results indicate that adjuvant intraoperative PDT may be a safe and effective method of destroying residual tumour, thereby preventing locoregional tumour recurrence. PMID:7710937

van Hillegersberg, R.; Hekking-Weijma, J. M.; Wilson, J. H.; Edixhoven-Bosdijk, A.; Kort, W. J.

1995-01-01

4

Photodynamic therapy.  

PubMed

Photodynamic therapy (PDT) relies on the interaction between a photosensitizer, the appropriate wavelength, and oxygen to cause cell death. First introduced about 100 years ago, PDT has continued to evolve in dermatology into a safe and effective treatment option for several dermatologic conditions. PDT is also used by pulmonologists, urologists, and ophthalmologists. This article focuses on the history of PDT, mechanism of action, photosensitizers and light sources used, therapeutic applications and expected dermatologic outcomes, as well as management of adverse events. PMID:24891062

Rkein, Ali M; Ozog, David M

2014-07-01

5

Indocyanine green (ICG) as a new adjuvant for the antimicrobial photo-dynamic therapy (aPDT) in dentistry  

NASA Astrophysics Data System (ADS)

Clinical surveys show a continuous increase of antimicrobial resistance related to the frequency of the administrated medication. The antimicrobial photodynamic therapy (aPDT) is an effective adjuvant to reduce the need of antibiotics in dentistry, especially in periodontics. The antimicrobial effect of lightactivated photosensitizers in periodontics is demonstrated in clinical studies and case reports. Indocyanine green (ICG) as a new adjuvant shows the high potential of antiphlogistic and antimicrobial effects in combination with laser-light activation. In trying to answer the question of just how far the influence of temperature is acting on bacteria, this study was carried out. The influences of ICG at different concentrations (0.01 up to 1 mg/ml) in combination with a culture medium (brain-heart-infusion) and a bacteria culture (Streptococcus salivarius) at different optical densities (OD600 0.5 and 0.1) were investigated under laser-light activation. Laser activation was carried out with diode laser at 810 nm and two different power settings (100 mW/300 mW). The pulse repetition rate was 2 kHz. Taking account of the fiber diameter, distance and spot size on the sample surface, the applicated intensities were 6.2 and 18.7 W/cm2. Total irradiation time was 20 s for all meaurements. Transmitted laser power and temperature increase in the culture medium as well as in the bacteria culture were determined. Additionally the influence of ICG regarding bacterial growth and bactericidal effect was investigated in the bacteria culture without laser irradiation. Without laser, no bactericidal effect of ICG was observed. Only a bacteriostatic effect could be proved. In dependence of the ICG concentration and the applied intensities a temperature increase of ?T up to 80°C was measured.

Meister, Joerg; Hopp, Michael; Schäfers, Johannes; Verbeek, Jonas; Kraus, Dominik; Frentzen, Matthias

2014-02-01

6

Photodynamic Therapy of Acne  

Microsoft Academic Search

\\u000a Topical therapies may be used for treating mild to moderate acne. In the recent years, antibiotics, especially tetracyclines,\\u000a have been used for the treatment of acne. For very severe cases, isotretinoin is still probably the therapy of choice. Photodynamic\\u000a therapy (PDT) may be an alternative to antibiotic treatment in selected cases. However, the exact treatment scheme is not\\u000a established yet.

Carin Sandberg; Ann-Marie Wennberg; Olle Larkö

7

Photodynamic Therapy: Other Uses  

Microsoft Academic Search

Mainstream uses for photodynamic therapy (PDT) in dermatology include nonmelanoma skin cancer and its precursors, acne vulgaris, photo- rejuvenation, and hidradenitis suppurativa. Each one of these entities and more is covered elsewhere in this issue. Many other dermatologic entities have been treated with PDT and published in the literature. These include psoriasis vulgaris, cuta- neous T-cell lymphoma (CTCL), disseminated actinic

Amy Forman Taub

8

Photodynamic therapy in dermatology  

Microsoft Academic Search

The combination of light and chemicals to treat skin diseases is widely practiced in dermatology. Within this broad use of light and drugs, in recent years the concept of photodynamic therapy (PDT) has emerged. PDT is a promising modality for the management of various tumors and nonmalignant diseases, based on the combination of a photosensitizer that is selectively localized in

Katrin Kalka; Hans Merk; Hasan Mukhtar

2000-01-01

9

Photodynamic therapy for cancer  

Microsoft Academic Search

The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed. At present, PDT is being tested in the clinic for use in oncology — to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin. How does PDT

Dennis E. J. G. J. Dolmans; Dai Fukumura; Rakesh K. Jain

2003-01-01

10

Nanofabricated upconversion nanoparticles for photodynamic therapy  

E-print Network

Nanofabricated upconversion nanoparticles for photodynamic therapy Baris Ungun,1 Robert K. Prud, "Upconverting nanoparticles as nanotransducers for photodynamic therapy in cancer cells," Nanomed. 3, 73, "Versatile photosensitizers for photodynamic therapy at infrared excitation," J. Am. Chem. Soc. 129, 4526

11

Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions  

NASA Astrophysics Data System (ADS)

In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

Yang, Deng-Fu; Hsu, Yih-Chih

2012-03-01

12

Nontumor photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) has become an approved treatment for different types of cancer in many countries over the last few years. As an example one might mention PDT of the early stages of bronchial or esophageal cancer which have been treated with only about 20% recurrence being observed over several years of follow-up. The low degree of invasion of PDT, as compared to most alternative treatments as well as minimal sided effects, and good repeatability, all speak for this treatment modality. Improved and cheap screening procedures, that are now being developed for the early stage disease, will lead to a more frequent application of PDT for these indications. Detailed studies of PDT showed that certain dyes, after systematic or topical application, could be taken up more in neoplastic tissue as compared to the surrounding normal tissue in the clinical context, thus leading to 'selective' or at least partially selective destruction of the tumor following light application. This selectivity of uptake of certain compounds in hyperproliferative tissue, as well as the observation that PDT can lead to blood vessel stasis, suggested that photodynamic therapy might be worth trying in non-tumor disease. Some of the diseases associated with hyperproliferation and/or neovascularization which are being considered for PDT are listed in table I.

van den Bergh, Hubert

1997-12-01

13

SYSTEM IDENTIFICATION OF PHOTOSENSITISER UPTAKE KINETICS IN PHOTODYNAMIC THERAPY  

E-print Network

SYSTEM IDENTIFICATION OF PHOTOSENSITISER UPTAKE KINETICS IN PHOTODYNAMIC THERAPY T. Bastogne L to the experimental modelling of photosensitiser uptake kinetics in photodynamic therapy. The experimental framework identification, pharmacokinetics, drug delivery, photodynamic therapy 1. INTRODUCTION Photodynamic therapy (PDT

Paris-Sud XI, Université de

14

Photodynamic Therapy in Pediatric Dentistry  

PubMed Central

Conservation of deciduous teeth with pulp alterations caused by caries and trauma is a major therapeutic challenge in pediatric dentistry as a result of the internal anatomy and life cycle characteristic. It is essential that the root canal procedures sanitizers have a performance in eliminating bacterial. In this context, antimicrobial photodynamic therapy (PAT) is promising and emerging as adjuvant therapy in an attempt to eliminate the microorganisms persistent to chemi-mechanical preparation. Since there is presence of oxygen in cells, photosensitizer activated by light can react with molecules in its vicinity by electrons' or hydrogen's transfer, leading to microorganism death. This paper reports the case of 4-year-old patient, female, with early childhood caries. The proposed endodontic treatment incuded chemomechanical treatment allied to PAT in the decontamination of root canals using methylene blue dye 50??g/mL during 3–5 minutes and 40?J/cm2 as energy density, taking into account the need for tissue penetration and effectiveness of PAT inside the dentinal tubules. PMID:25371829

da Silva Barbosa, Patricia; Duarte, Danilo Antonio; Leite, Mariana Ferreira; de Sant' Anna, Giselle Rodrigues

2014-01-01

15

Photodiagnosis and Photodynamic Therapy (2004) 1, 157--171 Photodynamic therapy for chest wall recurrence  

E-print Network

Photodiagnosis and Photodynamic Therapy (2004) 1, 157--171 REVIEW Photodynamic therapy for chest Available online 13 September 2004 KEYWORDS Photodynamic therapy; Chest wall recurrence; Breast cancer; LED success rates. Photodynamic therapy appears to be an underutilized salvage modality for this unfortunate

16

Photodynamic therapy of nonresectable cholangiocarcinoma  

Microsoft Academic Search

Background & Aims: Successful treatment in nonresectable Bismuth type III and IV cholangiocarcinoma is seldom achieved. The aim of this study was to evaluate the effect of photodynamic therapy on cholestasis, quality of life, and survival in these patients. Methods: Nine patients with advanced nonresectable cholangiocarcinomas Bismuth type III and IV, who showed no sufficient drainage (bilirubin decrease <50%) after

Jochen Liebetruth; Stefan Schreiber; Marco Hanft; Ullrich Wruck; Virginia Fusco; Joachim M. Müller; Heide Hörtnagl; Herbert Lochs

1998-01-01

17

Photodynamic Therapy, Optical Trapping and Photostimulated Emission Using  

E-print Network

Photodynamic Therapy, Optical Trapping and Photostimulated Emission Using Upconverting nanothermometry MRI Photodynamic Therapy #12;· Attractive features: - Stability with respect to photobleaching, 19, 2924-2929. 20 nm Ln3+-Doped Fluoride Nanoparticles #12;Photodynamic Therapy #12;Targeting

Van Stryland, Eric

18

Histomorphometric and Microbiological Assessment of Photodynamic Therapy as an Adjuvant Treatment for Periodontitis: A Short-Term Evaluation of Inflammatory Periodontal Conditions and Bacterial Reduction in a Rat Model  

PubMed Central

Abstract Objective: The aim of this study was to investigate the short-term effects of photodynamic therapy (PDT) in periodontal tissue when it is used as an adjuvant treatment for periodontitis. Background data: PDT has been used as an adjuvant in the combat of local infections, such as periodontitis, and combines a photosensitizer (PS) with a light source to induce reactive oxygen species (ROS) and kill microbial cells. Methods: Fifty healthy male rats were used in this study. Periodontitis was induced by placing a cotton ligature around the upper left second molar in a subgingival position. Posterior maxillas were removed and histologically prepared with hematoxylin & eosin (H&E) staining techniques. PDT was performed with a diode laser (?=660?nm) with an output power of 100?mW. Methylene blue aqueous solution (100??M) was used as the PS while control group used phosphate buffered saline (PBS). Collagen organization, inflammatory infiltrate, and bone loss were evaluated. Bacterial samples were collected before and immediately after treatment to determine bacterial reduction. Results: The experimental group that was treated with PDT presented better periodontal healing, as measured by collagen organization, inflammatory infiltrate, and bone loss. Significant bacterial reduction was achieved following treatment with or without PDT compared to control, with a higher microbial reduction observed in the PDT group. Conclusions: PDT used as an adjuvant treatment showed effective short-term control of periodontitis infection. PMID:21916615

Yamada, Aecio M.; Suzuki, Luis C.; Franca, Cristiane M.; Cai, Silvana; Mayer, Marcia P.A.; Ribeiro, Adriana C.; Ribeiro, Martha S.

2011-01-01

19

Treatment of rheumatoid arthritis using photodynamic therapy  

NASA Astrophysics Data System (ADS)

The only early therapy of rheumatoid arthritis in orthopedic surgery is a synovectomy, which is restricted to more or less big joints. A laser-synovectomy of small joints is ineffective yet. An alternative method may be photodynamic therapy. In our study we describe the photodynamic effect of Photosan 3 in a cell culture study.

Hendrich, Christian; Diddens, Heyke C.; Nosir, Hany R.; Siebert, Werner E.

1995-03-01

20

Treatment of rheumatoid arthritis using photodynamic therapy  

NASA Astrophysics Data System (ADS)

The only early therapy of rheumatoid arthritis in orthopedic surgery is a synovectomy, which is restricted to more or less big joints. A laser-synovectomy of small joints is ineffective yet. An alternative method may be photodynamic therapy. In our study we describe the photodynamic effect of Photosan 3 in a cell culture study.

Hendrich, Christian; Diddens, Heyke C.; Nosir, Hany R.; Siebert, Werner E.

1994-10-01

21

Photodynamic Diagnosis and Therapy of Cancer  

SciTech Connect

This paper gives brief information about photodynamic method used in diagnosis and therapy for cancer and other human body disorders. In particular it concentrates on detection and analysis of fluorescent dye, i.e. protoporphyrin IX (PpIX) and its two-photon excitation (TPE) process, which offers photodynamic method many fascinating possibilities.

Subiel, Anna [Institute of Experimental Physics, University of Gdansk, Wita Stwosza 57, 80-952 Gdansk (Poland)

2010-01-05

22

Photodynamic Therapy Treatment to Enhance Fracture Healing.  

National Technical Information Service (NTIS)

Long bone fractures resulting from high impact trauma can result in delayed healing. Photodynamic therapy (PDT) is a non-surgical, non-ionizing minimally invasive local treatment currently used to treat cancer and skin diseases. Surprisingly, recent findi...

A. J. Yee, B. C. Wilson, C. M. Whyne, D. Nam, M. K. Akens

2012-01-01

23

Photodynamic therapy toward selective endometrial ablation  

NASA Astrophysics Data System (ADS)

Potential applications of photodynamic therapy for endometrial disease are discussed. Experimental models that may lead to diagnosis and treatment of endometriosis as well as selective endometrial ablation are summarized.

Tadir, Yona; Tromberg, Bruce J.; Krasieva, Tatiana B.; Berns, Michael W.

1993-05-01

24

BODIPY Dyes In Photodynamic Therapy  

PubMed Central

BODIPY dyes tends to be highly fluorescent, but their emissions can be attenuated by adding substituents with appropriate oxidation potentials. Substituents like these have electrons to feed into photoexcited BODIPYs, quenching their fluorescence, thereby generating relatively long-lived triplet states. Singlet oxygen is formed when these triplet states interact with 3O2. In tissues, this causes cell damage in regions that are illuminated, and this is the basis of photodynamic therapy (PDT). The PDT agents that are currently approved for clinical use do not feature BODIPYs, but there are many reasons to believe that this situation will change. This review summarizes the attributes of BODIPY dyes for PDT, and in some related areas. PMID:23014776

Kamkaew, Anyanee; Lim, Siang Hui; Lee, Hong Boon; Kiew, Lik Voon; Chung, Lip Yong

2012-01-01

25

Treatment of experimental murine arthritis with transdermal photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) using benzoporphyrin derivative, monoacid ring A (BPD), and transdermal light was able to significantly treat symptoms of adjuvant-enhanced arthritis in MRL-lpr mice. Clinical and histological evaluation showed that PDT was able to modify the progression of adjuvant-enhanced arthritis up to 10 days after induction. When PDT was used on arthritic joints displaying swelling, it prevented further deterioration of clinical symptoms (76%, 16/21). However, it did not significantly effect the histopathologic parameters. As we have previously reported that mitogen activated MRL-lpr splenocytes were shown to be more susceptible to in vitro PDT we postulate that our findings reflect a selective destruction of adjuvant activated lymphocytes in the circulation and/or joints. The application of PDT to eliminate activated cells responsible for the inflammatory reaction at the arthritic site may have significant clinical implications for the treatment of rheumatoid arthritis.

Ratkay, Leslie G.; Chowdhary, R. K.; Neyndorff, Herma C.; Levy, Julia G.; Waterfield, J. D.

1994-10-01

26

Treatment of experimental murine arthritis with transdermal photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) using benzoporphyrin derivative, monoacid ring A (BPD), and transdermal light was able to significantly treat symptoms of adjuvant-enhanced arthritis in MRL-lpr mice. Clinical and histological evaluation showed that PDT was able to modify the progression of adjuvant-enhanced arthritis up to 10 days after induction. When PDT was used on arthritic joints displaying swelling, it prevented further deterioration of clinical symptoms (76%, 16/21). However, it did not significantly effect the histopathologic parameters. As we have previously reported that mitogen activated MRL-lpr splenocytes were shown to be more susceptible to in vitro PDT we postulate that our findings reflect a selective destruction of adjuvant activated lymphocytes in the circulation and/or joints. The application of PDT to eliminate activated cells responsible for the inflammatory reaction at the arthritic site may have significant clinical implications for the treatment of rheumatoid arthritis.

Ratkay, Leslie G.; Chowdhary, R. K.; Neyndorff, Herma C.; Levy, Julia G.; Waterfield, J. D.

1995-03-01

27

System identification of photosensitiser uptake kinetics in photodynamic therapy  

E-print Network

System identification of photosensitiser uptake kinetics in photodynamic therapy T. Bastogne1 , L delivery, pho- todynamic therapy. 1 Introduction Photodynamic therapy (PDT) (Moser (1998)) is an emerging apoptotic and necrotic death of tumour. In current clinical practice, photodynamic therapy is carried out

Paris-Sud XI, Université de

28

Photodynamic therapy for skin cancer  

NASA Astrophysics Data System (ADS)

Photodynamic therapy was used to treat 111 lesions in 27 cases with squamous and basal cell carcinoma. There were 82 squamous cell carcinomas and 29 basal cell carcinomas. Photofrin was administered intravenously at either 1.0 mg/kg or 0.75 mg/kg. An argon/dye laser was used to deliver 630 nm light to the lesion superficially at either 215 J/cm2 or 240 J/cm2. In some cases the laser light was delivered both superficially and interstitially. The laser light was delivered two to four days after the Photofrin injection. There were 105 complete responses and 5 partial responses. One patient was lost to follow-up. Among partial responses were basal cell carcinoma on the tip of the nose and morphea basal cell carcinoma of the left cheek. Another partial response occurred in a basal cell carcinoma patient where insufficient margins were treated due to the proximity to the eye. When 0.75 mg/kg drug dose was used, the selectivity of tumor necrosis was improved. Decreased period of skin photosensitivity was documented in some cases.

Panjehpour, Masoud; Julius, Clark E.; Hartman, Donald L.

1996-04-01

29

Adjuvant therapy in pancreatic cancer  

PubMed Central

Pancreatic cancer remains one of the leading causes of cancer related death worldwide with an overall five-year survival of less than 5%. Potentially curative surgery, which alone can improve 5-year survival to 10%, is an option for only 10%-20% of patients at presentation owing to local invasion of the tumour or metastatic disease. Adjuvant chemotherapy has been shown to improve 5-year survival to 20%-25% but conflicting evidence remains with regards to chemoradiation. In this article we review the current evidence available from published randomised trials and discuss ongoing phase III trials in relation to adjuvant therapy in pancreatic cancer. PMID:25356036

Jones, Owain Peris; Melling, James Daniel; Ghaneh, Paula

2014-01-01

30

Adjuvant and Neoadjuvant Therapy for Breast Cancer  

Cancer.gov

A fact sheet that explains different types of adjuvant therapy (treatment given after primary therapy to increase the chance of long-term survival) and neoadjuvant therapy (treatment given before primary therapy). Discusses side effects, risks, and benefits of adjuvant and neoadjuvant therapy for breast cancer.

31

Interstitial photodynamic laser therapy in interventional oncology  

Microsoft Academic Search

Photodynamic therapy (PDT) is a well-investigated locoregional cancer treatment in which a systemically administered photosensitizer is activated locally by illuminating the diseased tissue with light of a suitable wavelength. PDT offers various treatment strategies in oncology, especially palliative ones. This article focuses on the development and evaluation of interstitial PDT for the treatment of solid tumors, particularly liver tumors. The

Thomas J. Vogl; Katrin Eichler; Martin G. Mack; Stephan Zangos; Christopher Herzog; Axel Thalhammer; Kerstin Engelmann

2004-01-01

32

Nanoscopic micelle delivery improves the photophysical properties and efficacy of photodynamic therapy of protoporphyrin IX  

E-print Network

10 January 2011 Keywords: Polymeric micelles Photodynamic therapy Protoporphyrin IX Singlet oxygen the solubility and delivery efficiency of hydrophobic photosensitizers for photodynamic therapy (PDT reserved. 1. Introduction Recently, photodynamic therapy (PDT) has received considerable attention

Gao, Jinming

33

Benzoporphyrin derivative and light-emitting diode for use in photodynamic therapy: Applications of space light-emitting diode technology  

Microsoft Academic Search

Photodynamic therapy (PDT) is a cancer treatment modality that recently has been applied as adjuvant therapy for brain tumors. PDT consists of intravenously injecting a photosensitizer, which preferentially accumulates in tumor cells, into a patient and then activating the photosensitizer with a light source. This results in free radical generation followed by cell death. The development of more effective light

Harry T. Whelan; John M. Houle; Dawn M. Bajic; Meic H. Schmidt; Kenneth W. II Reichert; Glenn A. Meyer

1998-01-01

34

Retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization  

Microsoft Academic Search

PURPOSE: To report a case of retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization.METHODS: Case report. A 74-year-old woman with exudative age-related macular degeneration and classic subfoveal choroidal neovascularization RE underwent photodynamic therapy with verteporfin.RESULTS: Ophthalmoscopy and fluorescein angiography RE disclosed a retinal pigment epithelial tear in the area of photodynamic therapy.CONCLUSION: This case presents the first report

Faik Gelisken; Werner Inhoffen; Michael Partsch; Ulrike Schneider; Ingrid Kreissig

2001-01-01

35

Dosimetry for photodynamic therapy of malignant tumors  

NASA Astrophysics Data System (ADS)

The rationale of photodynamic therapy is based on the cytotoxic action of products generated by excited photosensitizers. Recent development has brought forward a series of promising photosensitizers ranging from hematoporphyrin derivative, various kinds of phthalocyanines and chlorins, to (delta) -aminolevulinic acid. The therapeutic efficacy is dependent on parameters such as tissue oxygenation, sensitizer distribution, drug clearance, optical irradiation, and exposure time. The general outline of a dosimetry model, which enables all these effects to be taken into account, is discussed.

Svaasand, Lars O.

1993-03-01

36

Heat-shock Proteins and Photodynamic Therapy  

Microsoft Academic Search

Many cancer treatments, such as photodynamic therapy, generate active oxygen species, often in the mitochondria. These oxygen species adversely react with cellular processes, thereby destroying cancer cells and tissue. Heat-shock proteins are up-regulated in response to heat stress or other environmental stresses and are known to protect cells from active oxygen species. In tumor cells, heat-shock proteins accumulate in the

Joanne Baylis; Craig A. Downs; Linda R. Jones; Scott A. Heckathorn

1998-01-01

37

Photodynamic therapy of cervical intraepithelial neoplasia  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

38

Multiphoton Biomedical Imaging and Photodynamic Therapy: Agents & Applications  

E-print Network

Multiphoton Biomedical Imaging and Photodynamic Therapy: Agents & Applications Kevin D. Belfield-reactive model Hydrophobic and hydrophilic dyes Two-Photon Photodynamic Therapy #12;"Two-photon laser scanning at the focus of the scanning pulsed-infrared laser beam, resulting in a much less harmful light dose during

Van Stryland, Eric

39

In vivo photodynamic therapy using upconversion nanoparticles as remote-  

E-print Network

Photodynamic therapy (PDT) involves a combination of light, light-sensitive drugs called photosensitizersIn vivo photodynamic therapy using upconversion nanoparticles as remote- controlled nanotransducers-damaging. However, upon irradiation with light of an appropriate wavelength, the photosensitizer becomes excited

Chaudhuri, Sanjay

40

Photodiagnosis and Photodynamic Therapy (2004) 1, 27--42 Photosensitizers in clinical PDT  

E-print Network

in photodynamic therapy are the vessels that allow for the transfer and translation of light energy into a type IIPhotodiagnosis and Photodynamic Therapy (2004) 1, 27--42 Photosensitizers in clinical PDT Ron R KEYWORDS Photosensitizers; Photodynamic therapy; Review Summary Photosensitizers in photodynamic therapy

41

Cell Death Pathways in Photodynamic Therapy of Cancer  

E-print Network

Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be ...

Mroz, Pawel

42

Acceleration Of Wound Healing Ny Photodynamic Therapy  

DOEpatents

Disclosed is a method for accelerating wound healing in a mammal. The method includes identifying an unhealed wound site or partially-healed wound site in a mammal; administering a photosensitizer to the mammal; waiting for a time period wherein the photosensitizer reaches an effective tissue concentration at the wound site; and photoactivating the photosensitizer at the wound site. The dose of photodynamic therapy is selected to stimulate the production of one or more growth factor by cells at the wound site, without causing tissue destruction.

Hasan, Tayyaba (Arlington, MA); Hamblin, Michael R. (Revere, MA); Trauner, Kenneth (Sacramento, CA)

2000-08-22

43

Photodynamic therapy and anti-tumour immunity  

PubMed Central

Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636

Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R.

2010-01-01

44

Adjuvant Biological Therapy for Pancreatic Cancer  

Cancer.gov

In this trial, patients with completely resected pancreatic cancer will receive adjuvant chemotherapy and radiation therapy plus additional treatment with either bevacizumab or cetuximab, monoclonal antibodies that target different proteins important for cancer growth and spread.

45

Photodynamic effect of functionalized single-walled carbon nanotubes: a potential sensitizer for photodynamic therapy  

NASA Astrophysics Data System (ADS)

Single-walled carbon nanotubes (SWNTs) possess unique physical and chemical properties, which make them very attractive for a wide range of applications. In particular, SWNTs and their composites have shown a great potential for photodynamic therapy (PDT). SWNTs have usually been used for photothermal therapy; herein, the photodynamic effect of two functionalized SWNTs are detected under visible light illumination in vitro and in vivo. The results indicated that the photodynamic effect is not entirely dependent on illumination time, but also on the modification method of the SWNTs. The ability of SWNTs complexes to combine with photodynamic therapy significantly improved the therapeutic efficacy of cancer treatment, and the combined treatment demonstrated a synergistic effect. These findings suggest that the SWNTs composite has great potential as sensitizer for PDT.

Wang, Lei; Shi, Jinjin; Liu, Ruiyuan; Liu, Yan; Zhang, Jing; Yu, Xiaoyuan; Gao, Jun; Zhang, Chaofeng; Zhang, Zhenzhong

2014-04-01

46

Stimulation of dendritic cells enhances immune response after photodynamic therapy  

E-print Network

Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis ...

Mroz, Pawel

47

Irradiation system for interstitial photodynamic therapy  

NASA Astrophysics Data System (ADS)

Interstitial Photodynamic Therapy (IPDT) is a promising form of treatment of deep-seated and bulky malignant tumors, based on the lethal cell response to the photochemical reactions when drug is light activated in presence of oxygen. In order to accomplish an effective internal illumination, laser sources are preferably used because of two important reasons: the monochromatic light can be confined to the narrow absorption band of the drug and the laser beam is easily focused into optical fibers. In this work the development of a diode-laser-light-source is presented. The system is tuned by temperature to get a better match in the 5-ALA absorption band. This system also comprises a trifurcated fiber system to accomplish interstitial illumination.

Pacheco, L.; Stolik, S.; De la Rosa, J.

2013-11-01

48

PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE  

PubMed Central

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. PMID:21617154

Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W.; Gollnick, Sandra O.; Hahn, Stephen M.; Hamblin, Michael R.; Juzeniene, Asta; Kessel, David; Korbelik, Mladen; Moan, Johan; Mroz, Pawel; Nowis, Dominika; Piette, Jacques; Wilson, Brian C.; Golab, Jakub

2011-01-01

49

Feasibility of chemiluminescence as photodynamic therapy dosimetor  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) utilizes light energy of a proper wavelength to activate a pre-administered photosensitizer in a target tissue to achieve a localized treatment effect. Current treatment protocol of photodynamic therapy (PDT) is defined by empirical values such as irradiation light fluence, fluence rate and the amount of administered photosensitizer. It is well known that Singlet oxygen is the most important cytotoxic agent responsible for PDT biological effects. An in situ monitoring of singlet oxygen production during PDT would provide a more accurate dosimeter for PDT. The presented study has investigated the feasibility of using Fhioresceinyl Cypridina Luciferin Analog (FCLA), a singlet oxygen specific chemiluminescence (CL) probe, as a dosimetric tool for PDT. Raji lymphoma cell suspensions were sensitized with Photofrin (R) of various concentrations and irradiated with 635 nm laser light at different fluence rates. FCLA-CL from singlet oxygen produced by the treatment was measured, in real time, with a photon multiplier tube (PMT) system, and linked to the cytotoxicity resulting from the treatment. We have observed that the CL intensity of FCLA is dependent on the PDT treatment parameters. After each PDT treatment and CL measurement, the irradiated cells were evaluated by MIT assay for their Viability. The results show that the cell viability is highly related to the accumulated CL. With 10 II quencher, we confirmed that the CL was mainly related to PDT produced 10 II The results suggest that the FCLA-CL system can be an effective means in measuring PDT 1O II production and may provide an alternative dosimetry technique for PDT.

Qin, Yanfang; Xing, Da; Zhong, Xueyun; Zhou, Jin; Luo, Shiming; Chen, Qun

2006-09-01

50

Colonic mucosectomy using laser photodynamic therapy  

SciTech Connect

Photodynamic therapy (PDT) involves photosensitizing tissue and then activating it with monochromatic light, causing necrosis. Precise control of the extent of injury should be possible by varying the energy density of the light applied to the target tissue. We tested the sensitivity of colonic tissue to PDT by injecting 10 mg/kg Photofrin II intraperitoneally in 10 rats. After 24 hr the left colon was opened and cleansed. A 1.0-cm2 area of mucosa was exposed to 630 nm (red) light produced by an argon-pumped dye laser. Pairs of rats were treated with energy densities of either 10, 20, 40, 60, or 80 J/cm2, controlled by varying exposure times. After 48 hr, we sacrificed the rats and fixed, sectioned, and stained the left colons. The depth of injury was measured with an ocular micrometer and expressed as a percentage of normal bowel wall thickness. A curve was fit to the data points by computerized nonlinear regression. The relationship between depth of injury (Y) and energy density (X) was found to fit the equation Y = 1 - aebx, where constants a = 1.15 and b = -0.0353, (R2 = 0.93, P less than 0.001). The relationship between injury and energy density is biphasic, rising rapidly from 0 to 40 J/cm2 and more slowly after this point, suggesting that colonic mucosa is more sensitive to PDT than muscularis, providing a margin of safety against perforation. Bowel perforation did not occur in this study but is predicted by extrapolation for energy densities of 100 J/cm2 or greater. These data indicate that photodynamic colonic mucosectomy is possible.

Fisher, D.G.; Rypins, E.B.; Watson, L.R.; Nelson, J.S.; Berns, M.W.

1989-06-01

51

[Adjuvant therapy of colon carcinoma].  

PubMed

In patients with stage III carcinoma of the colon, adjuvant chemotherapy is indicated after R0 resection. No age limitations exist. Combination chemotherapy with FOLFOX4 or (if oxaliplatin is contraindicated) monotherapy with a fluoropyrimidine, preferably capecitabine, can be regarded as the standard treatment. Because of its unfavorable toxicity profile, the 5-FU/folic acid bolus scheme (the Mayo scheme) should no longer be used, and combinations including irinotecan also do not play a part in colon carcinoma. The combination XELOX (oxaliplatin + capecitabine) is currently being studied in phase III trials. Data on the efficacy of the targeted drugs bevacizumab and cetuximab cannot be expected until at least 2010/2011. It is important that adjuvant treatment be started in a timely manner, within 8 weeks of surgery. As far as stage II disease is concerned, adjuvant chemotherapy analogous to that for stage III should be considered in high-risk patients (T4, emergency surgery, tumor perforation/tear, < 12 lymph nodes examined). The evidence for this recommendation is, however, based mainly on unplanned subgroup analyses of randomized trials. That low-risk stage II patients can also profit from adjuvant treatment was shown in the QUASAR trial(significant survival benefit of 3.6%), so this group of patients can be offered chemotherapy containing 5-FU. For treatments involving oxaliplatin in low-risk patients there is currently insufficient evidence. PMID:19033700

Trarbach, Tanja; Kubicka, Stefan; Hacker, Ulrich; Ridwelski, Karsten; Reinacher-Schick, Anke

2008-01-01

52

Photodynamic Therapy with Motexafin Lutetium for Rectal Cancer: A Preclinical Model in the Dog  

E-print Network

Photodynamic Therapy with Motexafin Lutetium for Rectal Cancer: A Preclinical Model in the Dog H despite multi-modality therapy. Photodynamic Therapy (PDT) is a cancer treatment which generates tumor of rectal resection after motexafin lutetium-mediated photodynamic therapy. Methods. Ten mixed breed dogs

Yodh, Arjun G.

53

Photodynamic Therapy for Infections: Clinical Applications  

PubMed Central

Background and Objective Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT. Study Design/Materials and Methods The published peer-reviewed literature was reviewed between 1960 and 2011. Results The basics of antimicrobial PDT are discussed. Clinical applications of antimicrobial PDT to localized viral infections caused by herpes and papilloma viruses, and nonviral dermatological infections such as acne and other yeast, fungal and bacterial skin infections are covered. PDT has been used to treat bacterial infections in brain abscesses and non-healing ulcers. PDT for dental infections including periodontitis and endodontics has been well studied. PDT has also been used for cutaneous Leishmaniasis. Clinical trials of PDT and blue light alone therapy for gastric Helicobacter pylori infection are also covered. Conclusion As yet clinical PDT for infections has been mainly in the field of dermatology using 5-aminolevulanic acid and in dentistry using phenothiazinium dyes. We expect more to see applications of PDT to more challenging infections using advanced antimicrobial photosensitizers targeted to microbial cells in the years to come. PMID:22057503

Kharkwal, Gitika B.; Sharma, Sulbha K.; Huang, Ying-Ying; Dai, Tianhong; Hamblin, Michael R.

2012-01-01

54

Melanoma resistance to photodynamic therapy: new insights  

PubMed Central

Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested for melanoma with some promising results, but melanoma is generally considered to also be resistant to PDT. Optical interference by the highly-pigmented melanin, the anti-oxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette (ABC) transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700–800-nm near infrared spectral region; interventions that can temporarily reduce the amount or the pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system to the treated tumor. PMID:23152406

Huang, Ying-Ying; Vecchio, Daniela; Avci, Pinar; Yin, Rui; Garcia-Diaz, Maria; Hamblin, Michael R.

2012-01-01

55

Photodynamic therapy: a promising alternative in oncology  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) is a treatment modality that is based on the administration of a photosensitizer and the following application of light in a wavelength range matching the absorption spectrum of the photosensitizer. Ideally the photosensitizer retains in the tumor tissue more than in normal tissue and thus allows targeted destruction of cancerous tissue. The use of PDT is slowly being accepted as a standard treatment for certain types of cancer. This includes mainly treatment strategies with only palliative intentions (obstructive esophageal cancer and advanced lung cancer) while for certain malignant conditions new applications exists that are already intended for cure (e.g. early stage of lung cancer). The main advantage of PDT is that the treatment can be repeated multiple times safely without major side effects. PDT can be safely combined with already established treatment options like surgery, chemotherapy or radiotherapy. A disadvantage of PDT is the only localized effect of the therapy, which usually cannot significantly alter the outcome of a systemic disease. In this paper we review the history of PDT as well as current clinical applications in oncology and future directions.

Nelius, Thomas; de Riese, Werner T. W.; Filleur, Stephanie

2004-07-01

56

Adjuvant Therapy in Pancreatic Cancer  

Microsoft Academic Search

Pancreatic cancer is one of the major causes of cancer death in Europe with a 5-year survival rate of less than 5%. Although surgery cannot guarantee a cure, the 5-year survival does improve to around 10% following resection and increases to 20–30% with adjuvant chemotherapy. The European Study Group for Pancreatic Cancer (ESPAC) 1 trial was the first adequately powered,

Amy Thomas; Khaled Dajani; John P. Neoptolemos; Paula Ghaneh

2010-01-01

57

A Review of Progress in Clinical Photodynamic Therapy  

PubMed Central

Photodynamic therapy (PDT) has received increased attention since the regulatory approvals have been granted to several photosensitizing drugs and light applicators world-wide. Much progress has been seen in basic sciences and clinical photodynamics in recent years. This review will focus on new developments of clinical investigation and discuss the usefulness of various forms of PDT techniques for curative or palliative treatment of malignant and non-malignant diseases. PMID:15896084

Huang, Zheng

2005-01-01

58

Systemic adjuvant therapy for breast cancer.  

PubMed

Systemic therapy for operable breast cancer can delay the time to recurrence. Recurrence of breast cancer can follow a variable clinical course but will lead to death in virtually all cases. This delay is reflected in an accompanying improvement in overall survival with treatment. Almost 35 years have passed since the introduction of adjuvant chemotherapy, whereas adjuvant tamoxifen trials were begun 17 years ago. In that time, only in a minority of patients has a clear consensus emerged on the appropriate use of adjuvant therapies. Overview analysis from large numbers of controlled clinical trials has produced a much larger data base for examining the effects of hormonal and cytotoxic therapy on the outcome of patients with early-stage breast cancer and provides greater statistical power to detect small differences in particular subgroups of patients, which may not have been apparent in individual studies. Patients with involved lymph nodes are now routinely treated with chemotherapy if they are premenopausal and with tamoxifen if they are postmenopausal, especially if their tumors contain estrogen receptor. More recent trials attempt to examine the use of these therapies outside of these prescribed groups as well as the introduction of new chemotherapeutic agents and dosage regimens, some of which are based on biologic principles of alternating, non-cross-resistant therapy and dose responsiveness. Treatment of node-negative breast cancer remains controversial. Small but real differences in odds of relapse have emerged with adjuvant treatment, although the nature of the risks and benefits remains to be defined. PMID:1457518

Tripathy, D; Henderson, I C

1992-12-01

59

FPGA-based Monte Carlo Computation of Light Absorption for Photodynamic Cancer Therapy  

E-print Network

FPGA-based Monte Carlo Computation of Light Absorption for Photodynamic Cancer Therapy Jason Luu1. INTRODUCTION Photodynamic therapy (PDT) is an emerging cancer treat- ment that uses light-sensitive drugs Cancer Institute University of Toronto, Toronto, Ontario, Canada Abstract--Photodynamic therapy (PDT

Rose, Jonathan

60

GPU-accelerated Monte Carlo simulation for photodynamic therapy treatment planning  

E-print Network

GPU-accelerated Monte Carlo simulation for photodynamic therapy treatment planning William Chun Yip processing units, Monte Carlo simulation, treatment planning, photodynamic therapy, MCML 1. INTRODUCTION Photodynamic therapy (PDT) is an emerging treatment modality in oncology and other fields.1 Improvements in PDT

Rose, Jonathan

61

Photodiagnosis and Photodynamic Therapy (2009) 6, 195--199 available at www.sciencedirect.com  

E-print Network

Photodiagnosis and Photodynamic Therapy (2009) 6, 195--199 available at www photodynamic therapy and pulsed dye laser for port wine stain birthmarks Joshua A. Tournasa,b , Jennifer Laia stain birthmarks; Pulsed dye laser; Photodynamic therapy; Vascular birthmarks Summary Background: Pulsed

Choi, Bernard

62

Detection and photodynamic therapy of inflamed atherosclerotic plaques in the carotid artery of rabbits  

E-print Network

Detection and photodynamic therapy of inflamed atherosclerotic plaques in the carotid artery Keywords: Atherosclerosis Vulnerable plaque Macrophage Fluorescence intensity Photodynamic therapy a b s t r a c t Photodynamic therapy (PDT) has been applied in the treatment of artery restenosis following

Cao, Wenwu

63

Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth of necrosis  

E-print Network

Correlation of in vivo photosensitizer fluorescence and photodynamic-therapy-induced depth the depth of necrosis response to photodynamic therapy (PDT) in a murine tumor model. Mice were implanted-Optical Instrumentation Engineers. [DOI: 10.1117/1.1560011] Keywords: spectroscopy; photodynamic therapy; light

Yodh, Arjun G.

64

Mathematical Modeling of Oxygen Transport, Cell Killing and Cell Decision Making in Photodynamic Therapy of Cancer  

E-print Network

Photodynamic Therapy (PDT) for simulation of the molecular interactions leading to cell death in time domain;#12;Mathematical Modeling of Oxygen Transport, Cell Killing and Cell Decision Making in Photodynamic Therapy Killing and Cell Decision making in Photodynamic Therapy of Cancer by Ioannis Gkigkitzis APPROVED BY

65

Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett's esophagus  

Microsoft Academic Search

Background: Endoscopic mucosal resection (EMR) and photodynamic therapy have been proposed as treatments for early stage cancers. EMR is limited by its focal nature whereas photodynamic therapy is dependent on precise staging. The combination of EMR and photodynamic therapy were studied in the treatment of superficial cancer in patients with Barrett's esophagus. Methods: Seventeen consecutive nonsurgical patients with superficial cancers

Navtej S. Buttar; Kenneth K. Wang; Lori S. Lutzke; Krishnawatie K. Krishnadath; Marlys A. Anderson

2001-01-01

66

Photodynamic therapy (PDT) as a biological modifier  

NASA Astrophysics Data System (ADS)

The capacity of photosensitizers and light to ablate cancerous tissues and unwanted neovasculature constitutes the classical application of photodynamic therapy (PDT). Cell death results from either necrotic or apoptotic processes. The use of photosensitizers and light at doses which do not cause death has been found to affect changes in certain cell populations which profoundly effect their expression of cell surface molecules and secretion of cytokines, thereby altering the functional attributes of the treated cells. Cells of the immune system and the skin may be sensitive to modulation by 'sub-lethal PDT.' Ongoing studies have been conducted to assess, at the molecular level, changes in both lymphocytes and epidermal cells (EC) caused by treatment with low levels of benzoporphyrin derivative monoacid ring A (BPD) (a photosensitizer currently in clinical trials for cancer, psoriasis, endometriosis and age-related macular degeneration) and light. Treatment of skin with BPD and light, at levels which significantly enhanced the length of murine skin allograft acceptance, have been found to down-regulate the expression of Langerhans cell (LC) surface antigen molecules [major histocompatibility complex (MHC) class II and intracellular adhesion molecule (ICAM)-1] and the formation of some cytokines (tumor necrosis factor-alpha (TNF- (alpha) ).

Obochi, Modestus; Tao, Jing-Song; Hunt, David W. C.; Levy, Julia G.

1996-04-01

67

Variables in photodynamic therapy for Barrett's esophagus  

NASA Astrophysics Data System (ADS)

Photodynamic therapy with porfimer sodium (PS) is a treatment option for high grade dysplasia associated with Barrett's esophagus. This study sought to investigate the optical properties of Barrett's dysplasia that may be useful in light dosimetry planning and to determine the effect of PS on tissue absorption and scattering. Fiber optic reflectance spectra were collected before and 48 hours after administration of 2 mg/kg PS. Mucosal biopsies were collected at the same locations. According to Monte Carlo analysis, the fiber optic probe sampled only the mucosal layer. A mathematical fit of the reflectance spectra was performed as a function of blood volume fraction, oxygen saturation and scattering. The average calculated blood volume was 100% higher in Barrett's tissue than normal esophageal tissue. The average scattering slope from 620 to 750 nm was 26% higher for Barrett's dysplasia than normal esophageal tissue, indicating an increase in the size of scattering particles. The difference in the scattering amplitude was not statistically significant, suggesting no significant increase in the number of scattering particles. PS tissue content was determined with extraction methods. Changes in the scattering slope due to PS sensitization were observed; however they were not proportional to the extracted PS concentration.

Jones, Linda R.; Preyer, Norris W.; Buchanan, Jane; Reynolds, Daryl M.; Wolfsen, Herbert C.; Wallace, Michael B.; Gill, Kanwar R. S.

2009-06-01

68

Photodynamic Therapy of Symptomatic Choroidal Nevi  

PubMed Central

Purpose: To evaluate the role of photodynamic therapy (PDT) for patients with symptomatic choroidal nevi involving the fovea or located near the fovea with subretinal fluid extending to the fovea. Materials and Methods: Retrospective review of five patients who underwent PDT for choroidal nevi at two separate centers in Ankara and Barcelona. Results: The mean initial logMAR visual acuity was 0.5 (range: 0 to 1.5). The mean largest tumor base diameter was 3.2 mm (range: 2.1–4.5 mm) and the mean tumor thickness was 1.1 mm (range: 0.7–1.6 mm). The mean number of PDT sessions was 1.6 (range:1–3). The mean final tumor thickness was 1.0 mm (range: 0–1.6 mm) at a mean follow-up of 19 months (range: 12–32 months). The mean final logMAR visual acuity was 0.4 (range: 0–1.5). Subfoveal fluid disappeared or decreased significantly in 4 of 5 eyes (80%) after PDT. Conclusions: PDT led to resolution of subretinal fluid with preservation of visual acuity in many symptomatic choroidal nevi in this study. Careful case selection is important as PDT of indeterminate pigmented tumors may delay the diagnosis and treatment of an early choroidal melanoma and thereby increase the risk for metastasis. PMID:22224021

Amselem, Luis; Gunduz, Kaan; Adan, Alfredo; Karsl?oglu, Melisa Zisan; Rey, Amanda; Sabater, Noelia; Valldeperas, Xavier

2011-01-01

69

Photodynamic therapy of advanced malignant tumors  

NASA Astrophysics Data System (ADS)

Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

1993-03-01

70

Photodynamic therapy: Biophysical mechanisms and molecular responses  

NASA Astrophysics Data System (ADS)

In photodynamic therapy (PDT), photochemical reactions induced by optical activation of sensitizer molecules cause destruction of the target tissue. In this thesis we present results of several related studies, which investigated the influence of photophysical properties and photobleaching mechanisms of sensitizers and oxygen-dependent tissue optical properties on PDT treatment efficacy. The bleaching mechanism of the sensitizer meso-tetra hydroxyphenyl chlorin (mTHPC) is examined indirectly using measurements of photochemical oxygen consumption during PDT irradiation of multicell tumor spheroids. Analysis of the results with a theoretical model of oxygen diffusion that incorporates the effects of sensitizer photobleaching shows that mTHPC is degraded via a singlet-oxygen (1O2)-mediated bleaching process. The analysis allows us to extract photophysical parameters of mTHPC which are used to account for its enhanced clinical photodynamic potency in comparison to that of Photofrin. Evaluation of the spatially-resolved fluorescence in confocal optical sections of intact spheroids during PDT irradiation allows for the direct experimental verification of mTHPC's 1O2-mediated bleaching mechanism. The technique is also used to investigate the complex bleaching kinetics of Photofrin. The results allow us to successfully reconcile apparently contradictory experimental observations and to confirm the predictions of a new theoretical model in which both 1O2 and excited triplet sensitizer molecules are allowed to contribute to photobleaching. Based on studies performed in tissue-simulating erythrocyte phantoms and in a murine tumor model in vivo, we present clinically relevant results which indicate that a shift toward increased hemoglobin-oxygen saturation due to improved tissue oxygenation reduces PDT treatment beam attenuation and may allow for more effective treatment of deeper lesions. Finally, we investigate the induction of the stress protein, heat shock protein 70 (HSP70), in response to mTHPC-PDT. The studies are performed using a murine tumor cell line transfected with a plasmid containing the gene for Green Fluorescent Protein (GFP) under the control of an hsp70 promoter. We obtain increased levels of GFP fluorescence at a cellular level and in vivo in response to sub-lethal doses of mTHPC-PDT. These results demonstrate the potential of using fluorescent reporter proteins as biomarkers of PDT-induced oxidative stress.

Mitra, Soumya

71

Laser effect in photodynamic therapy of tumors  

NASA Astrophysics Data System (ADS)

Photodynamic therapy is a method that provides a reasonable alternative to other treatment modalities for patients with certain cancers, and in some cases may be the preferred treatment. The therapy implies the intravenous administration of a light-sensitive substance, the photosensitizer. The used sensitizer must absorb at long wavelength. For these purposes, the carbon dioxide laser, He-Ne and the argon laser are particularly suitable. In this study we evaluate in vitro the cytotoxic activity of three synthesized metallo-phthalocyanines with absorption bands in the red part of the spectrum: zinc-di-sulphonated phthalocyanine (ZnS IIPc), zinc-tri-sulphonated phthalocyanine (ZnS 3Pc) and zinc-tetrasulphonated phthalocyanine (ZnS 4Pc). Some cellular models have been used in this paper, in order to optimize the conditions of this method, as we are presenting in this paper (LSR-SF(SR) - transplantable sarcoma in rat induced by Rous sarcoma virus strain Schmidt-Ruppin; LSCC-SF(Mc29) - transplantable chicken hepatoma induced by the myelocytomatosis virus Mc29, MCF-7 cell line (human breast adenocarcinoma) derived from a patient with metastatic breast cancer, 8-MG-BA - glioblastoma multiforme 8-MG-BA, K562 - lymphoblastic human cell line, LLC-WRC 256 - Walker epithelial carcinoma. Activation of these photosensitizers retained in the cancerous cells, by red light emitted from a He-Ne laser at ?= 632.8 nm laser system, or by a diode laser emitting at 672 nm, produces a photochemical reaction that results in the selective destruction of tumor cells.

Ion, Rodica-Mariana; Brezoi, Dragos-Viorel; Neagu, Monica; Manda, Gina; Constantin, Carolina

2007-03-01

72

Photodynamic tumor therapy: mitochondrial benzodiazepine receptors as a therapeutic target.  

PubMed Central

BACKGROUND: Photodynamic therapy employs photosensitive agents such as porphyrins to treat a variety of tumors accessible to light-emitting probes. This approach capitalizes on the selective retention of porphyrins by cancer cells. Cancer cells also have elevated levels of mitochondrial benzodiazepine receptors which bind porphyrins with high affinity. METHODS: Cultured cancer cell lines were exposed to porphyrin and porphyrin-like compounds and then irradiated with light. Cytotoxicity of this treatment was measured via clonogenic assays. Mitochondrial benzodiazepine receptor pharmacology was studied using [3H] PK11195 binding to cancer cell homogenates and isolated kidney mitochondrial membranes. RESULTS: We show that therapeutic potencies of porphyrins correlate closely with affinities for mitochondrial benzodiazepine receptors. Sensitivities of tumor cell lines to photodynamic therapy parallel their densities of these receptors. CONCLUSION: We propose that porphyrin photodynamic therapy is mediated by mitochondrial benzodiazepine receptors. PMID:9513188

Verma, A.; Facchina, S. L.; Hirsch, D. J.; Song, S. Y.; Dillahey, L. F.; Williams, J. R.; Snyder, S. H.

1998-01-01

73

Photodynamic Therapy: The Imminent Milieu For Treating Oral Lesions  

PubMed Central

Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC) and other oral lesions. Oral infections (such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis) are among the specific targets where PDT can be applied Photodynamic therapy (PDT) efficacy depends on the local dose deposited in the lesion as well as oxygen availability in the lesion. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry. PMID:23905154

Mohanty, Neeta; Jalaluddin, MD; Kotina, Sreekanth; Routray, Samapika; Ingale, Yashwant

2013-01-01

74

Mechanisms of Resistance to Photodynamic Therapy  

PubMed Central

Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes and activation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, cell detachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair of induced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption may also contribute to the appearance of resistant cells. The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellular localization. Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT and chemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy. The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complex and comprises different mechanisms. In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms most commonly found in chemo resistant cells. PMID:21568910

Casas, Adriana; Di Venosa, Gabriela; Hasan, Tayyaba; Batlle, Alcira

2013-01-01

75

A folic acid conjugated silica-titania porous hollow nanosphere for improved topical photodynamic therapy.  

PubMed

The folic acid conjugated hollow nanosphere is used to encapsulate protoporphyrin IX and is utilized for photodynamic therapy. This system represents a 3.33 times higher photodynamic efficiency than previous protoporphyrin IX-based systems. The result proposes a new opportunity for effective photodynamic therapy of folate receptor positive tumor cells. PMID:25348554

Jang, Yoonsun; Kim, Sojin; Oh, Wan-Kyu; Kim, Chanhoi; Lee, Inkyu; Jang, Jyongsik

2014-12-18

76

Optical delivery and monitoring of photodynamic therapy of prostate cancer  

NASA Astrophysics Data System (ADS)

Photodynamic therapy of recurrent prostate cancer is currently undergoing Phase II clinical trials with the vascular targeting drug TOOKAD. Proper PDT dosage requires sound estimates of the light fluence and drug concentration throughout the organ. The treatment requires multiple diffusing light delivery fibers placed in position according to a light dose treatment plan under ultrasound guidance. Fluence rate is monitored by multiple sensor fibers placed throughout the organ and in sensitive organs near the prostate. The combination of multiple light delivery and fluence sensor fibers is used to estimate the optical properties of the tissue and to provide a general fluence map throughout the organ. This fluence map is then used to estimate extent of photodynamic dose. Optical spectroscopy is used to monitor drug pharmacokinetics in the organ and blood hemodynamics within the organ. Further development of these delivery and monitoring techniques will permit full online monitoring of the treatment that will enable real-time patient-specific delivery of photodynamic therapy.

Weersink, Robert A.; Bogaards, Arjun; Gertner, Mark; Davidson, Sean; Zhang, Kai; Netchev, George; Giewercer, David J.; Trachtenberg, John; Wilson, Brian C.

2004-10-01

77

Photodynamic therapy by in situ nonlinear photon conversion  

NASA Astrophysics Data System (ADS)

In photodynamic therapy, light is absorbed by a therapy agent (photosensitizer) to generate reactive oxygen, which then locally kills diseased cells. Here, we report a new form of photodynamic therapy in which nonlinear optical interactions of near-infrared laser radiation with a biological medium in situ produce light that falls within the absorption band of the photosensitizer. The use of near-infrared radiation, followed by upconversion to visible or ultraviolet light, provides deep tissue penetration, thus overcoming a major hurdle in treatment. By modelling and experiment, we demonstrate activation of a known photosensitizer, chlorin e6, by in situ nonlinear optical upconversion of near-infrared laser radiation using second-harmonic generation in collagen and four-wave mixing, including coherent anti-Stokes Raman scattering, produced by cellular biomolecules. The introduction of coherent anti-Stokes Raman scattering/four-wave mixing to photodynamic therapy in vitro increases the efficiency by a factor of two compared to two-photon photodynamic therapy alone, while second-harmonic generation provides a fivefold increase.

Kachynski, A. V.; Pliss, A.; Kuzmin, A. N.; Ohulchanskyy, T. Y.; Baev, A.; Qu, J.; Prasad, P. N.

2014-06-01

78

How to access photodynamic therapy for bile duct carcinoma  

PubMed Central

Background Photodynamic therapy (PDT) is a promising treatment option for local control of remnant cancer after surgical resection or biliary stenosis by the unresectable tumor in patients with bile duct carcinomas (BDC). To achieve effective tumor necrosis, an appropriate approach to laser irradiation is necessary. Methods The efficacy of endoscopy-guided PDT using porfimer (n=12) or talaporfin sodium (n=13) was investigated by evaluating the transhepatic biliary routes and endoscopic retrograde biliary (ERB) routes in 25 patients with BDC. Results Diseases included perihilar intrahepatic cholangiocarcinoma (ICC) in four patients, extrahepatic BDCs in 19 and ampular carcinoma (AC) in two patients. Adjuvant PDT after surgical resection was performed in 18 patients, and PDT for tumor biliary stenosis was performed in seven. In patients undergoing surgical resections, the mean period between the operation and PDT was 87±42 days. In patients who underwent prior surgical resections, the transhepatic route was used in five (28%), the jejunal loop was used in 11 (61%), the T-tube route was used in one, and the endoscopic retrograde cholangiography (ERC) route via papilla Vater was used in one. In unresectable BDC, the ERC route was used in four patients (57%), and the transhepatic biliary route was used in three (43%). Endoscopic-guided PDT could not be performed in one patient because of a technical failure. Except for the complication of photosensitivity, endoscopy-related complications were not observed in any patients. Patients undergoing PDT with porfimer sodium had a significantly longer admission period compared to patients undergoing PDT with talaporfin sodium (36 vs. 5 days, respectively) (P<0.01). Conclusions PDT was safely and definitively performed using the endoscopy-guided approach via the transhepatic or ERC route. By considering the disadvantages of both routes, PDT must be adequately achieved for local control of BDC.

Isomoto, Hajime; Abo, Takafumi; Nonaka, Takashi; Morisaki, Tomohito; Arai, Junichi; Takagi, Katsunori; Ohnita, Ken; Shoji, Hiroyuki; Urabe, Shigetoshi; Senoo, Takemasa; Murakami, Goshi; Nagayasu, Takeshi

2014-01-01

79

Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study  

Microsoft Academic Search

Background & Aims:In nonrandomized trials, photodynamic therapy (PDT) had a promising effect on nonresectable cholangiocarcinoma (NCC). This prospective, open-label, randomized, multicenter study with a group sequential design compared PDT in addition to stenting (group A) with stenting alone (group B) in patients with NCC.

Marianne E. J Ortner; Karel Caca; Frieder Berr; Jochen Liebetruth; Ulrich Mansmann; Dominik Huster; Winfried Voderholzer; Guido Schachschal; Joachim Mössner; Herbert Lochs

2003-01-01

80

Long-term survival after photodynamic therapy for esophageal cancer  

Microsoft Academic Search

Background\\/Aims: Photodynamic therapy (PDT) has been adapted to the endoscopic treatment of digestive cancer, but its indications and efficacy remain uncertain. The aim of this study was to assess its feasibility in the curative treatment of small esophageal tumors. Methods: From 1983 to 1991, PDT was used to treat 123 patients with esophageal cancer who were recommended for nonsurgical treatment

Alain Sibille; René Lambert; Jean-Christophe Souquet; Ghislaine Sabben; Françoise Descos

1995-01-01

81

Photophysical and photobiological processes in the photodynamic therapy of tumours  

Microsoft Academic Search

Photodynamic therapy (PDT) is an innovative and attractive modality for the treatment of small and superficial tumours. PDT, as a multi-modality treatment procedure, requires both a selective photosensitizer and a powerful light source which matches the absorption spectrum of the photosensitizer. Quadra Logic's Photofrin®, a purified haematoporphyrin derivative, is so far the only sensitizer approved for phase III and IV

M. Ochsner

1997-01-01

82

Predictive analysis of photodynamic therapy applied to esophagus cancer  

Microsoft Academic Search

The use of optical techniques in medicine has revolutionized in many cases the medical praxis, providing new tools for practitioners or improving the existing ones in the fight against diseases. The application of this technology comprises mainly two branches, characterization and treatment of biological tissues. Photodynamic Therapy (PDT) provides a solution for malignant tissue destruction, by means of the inoculation

F. Fanjul-Vélez; M. del Campo-Gutiérrez; N. Ortega-Quijano; J. L. Arce-Diego

2008-01-01

83

Multifunctional gold nanoparticles for photodynamic therapy of cancer  

Microsoft Academic Search

As an important and growing branch of photomedicine, photodynamic therapy (PDT) is being increasingly employed in clinical applications particularly for the treatment of skin cancer. This dissertation focuses on the synthesis, characterization and deployment of gold nanoparticles for enhanced PDT of fibrosarcoma cancer cells. We have developed robust strategies and methods in fabrication of gold nanoparticles with positively- and negatively-tethered

Maung Kyaw Khaing Oo

2010-01-01

84

Model for monitoring the process of photodynamic therapy in patients  

Microsoft Academic Search

The photodynamic therapy (PDT) on tumors is quite effective and widely applied but usually carried out without an immediate evaluation of results. We measured the tumor fluorescence in mice with a fiber probe connected to a linear array spectral analyzer (PMA-11, Hamamatsu Photonics). The spectrum showed a transient change in fluorescence color from red to green during Photofrin?R-mediated PDT. In

Takato O. Yoshida; Eiji Kohno; Takashi Sakurai; Toru Hirano; Seiji Yamamoto; Susumu Terakawa

2005-01-01

85

Photodynamic Therapy for the Endodontic Treatment of a Traumatic Primary Tooth in a Diabetic Pediatric Patient  

PubMed Central

Conservation of deciduous teeth with pulp alterations caused by caries or trauma is a major therapeutic challenge in pediatric dentistry. It is essential that the sanitizers used in root canal procedures perform well in eliminating bacteria. Antimicrobial photodynamic therapy (PDT) is an emerging and promising adjuvant therapy for endodontic treatment in an attempt to eliminate microorganisms persistent after chemomechanical preparation. This paper reports the case of a five-year-old male with type I diabetes mellitus, presenting the need for pulp therapy in maxillary primary left central incisor due to injury. The proposed treatment included the use of PDT for decontamination of root canals with the application of 50 ?g/mL of methylene blue dye for 3-5 minutes and 40 J/cm2 as energy density, taking into account the need for tissue penetration and effec-tiveness of PDT inside the dentinal tubules. PMID:25024841

de Sant'Anna, Giselle

2014-01-01

86

Anti-tumor effects on the combination of photodynamic therapy with arsenic compound in TC-1 cells implanted C57BL/6 mice  

NASA Astrophysics Data System (ADS)

The effects of As4O6 were studied as adjuvant on photodynamic therapy. As4O6 is considered to have anticancer activity via several biological actions such as free radical producing and inhibition of VEGF expression. In vitro experiments, cell proliferation and morphology were determined by MTT assay. Also, quantitative PCR array was performed to study the synergetic mechanism. Additionally, this study was supported by the finding that combination of photodynamic therapy and As4O6 shows an inhibition effect of tumor growth in C57BL/6 mice with TC-1 cells xenographs in vivo. Radachlorin and As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P < 0.05). Antiproliferative effect of combination treatment was significantly higher than those of TC-1 cells treated with either photodynamic therapy or As4O6 (62.4 and 52.5% decrease, respectively, compared to photodynamic therapy or As4O6 alone, P < 0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% compared to vehicle-only treated TC-1 cells (P < 0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. Besides, the immunology response NEAT pathway (Ly- 12, CD178 and IL-2) also modulated after combination treatment of photodynamic therapy and As4O6. This combination effect apparently shows a same pattern in vivo model. These findings suggest the benefit of the combination treatment of photodynamic therapy and As4O6 for the inhibition of cervical cancer growth.

Lee, Kyu Wan; Wen, Lan Ying; Bae, Su Mi; Park, Choong Hak; Jeon, Woo Kyu; Lee, Doo Yun; Ahn, Woong Shick

2009-06-01

87

Effects of telomerase expression on photodynamic therapy of Barrett's esophagus  

NASA Astrophysics Data System (ADS)

Photodynamic therapy has been applied to Barrett's esophagus and has been shown in prospective randomized studies to eliminate dysplasia as well as decrease the occurrence of cancer. However, the therapy isnot always effective and there are issues with residual areas of Barrett's mucosa despite therapy. There has not been a good explanation for these residual areas and they seem to imply that there may exist a biological mechanisms by which these cells may be resistant to photodynamic therapy. It was our aim to determine if known abnormalities in Barrett's mucosa could be correlated with the lack of response of some of these tissues. We examined the tissue from mulitpel patients who had resonse to therapy as well as those who did not respond. We assessed the tissue for p53 mutations, inactivatino of p16, ploidy status, cell proliferation, telomerase activity, and degree of dysplasia. Interestingly, the only genetic marker than was found to be correlated with lack of reonse was p53 and telomerase activity. This suggests that cells that have lost mechanisms for cell death such as apoptosis or telomere shortengin may be more resistant to photodynamic therapy. In this study, we examined patients before and after PDT for telomerase activity.

Wang, Kenneth K.; Anderson, Marlys; Buttar, Navtej; WongKeeSong, Louis-Michel; Borkenhagen, Lynn; Lutzke, Lori

2003-06-01

88

Combined photodynamic therapy with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization  

Microsoft Academic Search

PurposeTo examine combined photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Richard F Spaide; John Sorenson; Leandro Maranan

2003-01-01

89

Immune Response Following Photodynamic Therapy For Bladder Cancer  

NASA Astrophysics Data System (ADS)

This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

Raymond K.

1989-06-01

90

Implicit and explicit dosimetry in photodynamic therapy: a New paradigm  

Microsoft Academic Search

Dosimetry for photodynamic therapy (PDT) is becoming increasingly complex as more factors are identified which may influence\\u000a the effectiveness of a given treatment. The simple prescription of a PDT treatment in terms of the administered photosensitizer\\u000a dose, the incident light and the drug-light time interval does not account for patient-to-patient variability in either the\\u000a photosensitizer uptake, tissue optical properties or

B. C. Wilson; M. S. Patterson; L. Lilge

1997-01-01

91

Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples  

Microsoft Academic Search

Background: Conventional photocoagulation of subfoveal choroidal neovascularization (CNV) is often accompanied by visual\\u000a loss due to thermal damage to adjacent retinal structures. Photodynamic therapy (PDT) allows vascular occlusion by selective\\u000a photochemical destruction of vascular endothelial cells only. In a pilot study we evaluated the use of PDT in CNV. Methods:\\u000a In a clinical phase I\\/II trial, patients with subfoveal CNV

Ursula Schmidt-Erfurth; Joan Miller; Michel Sickenberg; Arnd Bunse; Horst Laqua; Evangelos Gragoudas; Leonidas Zografos; Reginald Birngruber; Hubert van den Bergh; Andrew Strong; Ulrike Manjuris; Mario Fsadni; Bertrand Piguet; Neil M. Bressler

1998-01-01

92

Photodynamic therapy of tumours and other diseases using porphyrins  

Microsoft Academic Search

Photodynamic therapy (PDT) with porphyrins and red light (620–630 nm) is finding increasing clinical application for both\\u000a the eradication of relatively small tumours and the palliation of inoperable or obstructive tumours. PDT also shows some promise\\u000a for the sterilization of the tumour bed after surgical removal of neoplastic masses. Several porphyrins have been found to\\u000a be accumulated and retained by

John D. Spikes; Giulio Jori

1987-01-01

93

Optical coherence tomography findings following photodynamic therapy of choroidal neovascularization  

Microsoft Academic Search

PURPOSE: To develop an optical coherence tomography (OCT) classification system that monitors the response of eyes treated with photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD).DESIGN: Retrospective interventional case series.METHODS: Ninety eyes (88 patients) with AMD and predominantly classic subfoveal CNV treated with PDT using verteporfin were identified by a laser log and

Adam H Rogers; Adam Martidis; Paul B Greenberg; Carmen A Puliafito

2002-01-01

94

Breast Cancer With Chest Wall Progression: Treatment With Photodynamic Therapy  

Microsoft Academic Search

Background: Chest wall progression of breast carcinoma affects up to 5% of breast cancer patients and is a major source of their pain. Treatment options are limited or may not be offered to these patients. Low-dose Photofrin-induced photodynamic therapy (PDT) offers an excellent clinical response with minimal morbidity. We report our continued experience with PDT in this setting.Methods: Fourteen patients

Rosa E. Cuenca; Ron R. Allison; Claudio Sibata; Gordon H. Downie

2004-01-01

95

Identifiability and sensitivity analysis of a Photodynamic Therapy model Simona Dobrea  

E-print Network

by light at a specific wavelength. The photo-toxic phase of this therapy can be described by a dynamicIdentifiability and sensitivity analysis of a Photodynamic Therapy model Simona Dobrea *, Thierry, 54511, Vandoeuvre-lès-Nancy Cedex, France Abstract Photodynamic therapy (PDT) is an alternative

Boyer, Edmond

96

Collaborators and Funding Photodynamic therapy (PDT) has been proven to be effective treatment for non-melanoma skin  

E-print Network

Collaborators and Funding Photodynamic therapy (PDT) has been proven to be effective treatment. Contacts: Olena Kulyk, email: ok4@st-andrews.ac.uk Virtual prototyping of devices for Photodynamic therapy

Greenaway, Alan

97

Localized electric field of plasmonic nanoplatform enhanced photodynamic tumor therapy.  

PubMed

Near-infrared plasmonic nanoparticles demonstrate great potential in disease theranostic applications. Herein a nanoplatform, composed of mesoporous silica-coated gold nanorods (AuNRs), is tailor-designed to optimize the photodynamic therapy (PDT) for tumor based on the plasmonic effect. The surface plasmon resonance of AuNRs was fine-tuned to overlap with the exciton absorption of indocyanine green (ICG), a near-infrared photodynamic dye with poor photostability and low quantum yield. Such overlap greatly increases the singlet oxygen yield of incorporated ICG by maximizing the local field enhancement, and protecting the ICG molecules against photodegradation by virtue of the high absorption cross section of the AuNRs. The silica shell strongly increased ICG payload with the additional benefit of enhancing ICG photostability by facilitating the formation of ICG aggregates. As-fabricated AuNR@SiO2-ICG nanoplatform enables trimodal imaging, near-infrared fluorescence from ICG, and two-photon luminescence/photoacoustic tomography from the AuNRs. The integrated strategy significantly improved photodynamic destruction of breast tumor cells and inhibited the growth of orthotopic breast tumors in mice, with mild laser irradiation, through a synergistic effect of PDT and photothermal therapy. Our study highlights the effect of local field enhancement in PDT and demonstrates the importance of systematic design of nanoplatform to greatly enhancing the antitumor efficacy. PMID:25375193

Li, Yiye; Wen, Tao; Zhao, Ruifang; Liu, Xixi; Ji, Tianjiao; Wang, Hai; Shi, Xiaowei; Shi, Jian; Wei, Jingyan; Zhao, Yuliang; Wu, Xiaochun; Nie, Guangjun

2014-11-25

98

Hypericin-photodynamic therapy leads to interleukin-6 secretion by HepG2 cells and their apoptosis via  

E-print Network

OPEN Hypericin-photodynamic therapy leads to interleukin-6 secretion by HepG2 cells , EM Shankar1 , BJJ Abdullah2 , KL Goh3 and J Vadivelu*,1 Photodynamic therapy (PDT) has emerged effects on patients remains an urgent need in clinical practice. Photodynamic therapy (PDT) is a widely

Cai, Long

99

Optical dosimetry for interstitial photodynamic therapy  

SciTech Connect

An approach to photodynamic treatment of tumors is the interstitial implantation of fiber optic light sources. Dosimetry is critical in identifying regions of low light intensity in the tumor which may prevent tumor cure. We describe a numerical technique for calculating light distributions within tumors, from multiple fiber optic sources. The method was tested using four translucent plastic needles, which were placed in a 0.94 X 0.94 cm grid pattern within excised Dunning R3327-AT rat prostate tumors. A cylindrical diffusing fiber tip, illuminated by 630 nm dye laser light was placed within one needle and a miniature light detector was placed within another. The average penetration depth in the tumor region between the two needles was calculated from the optical power measured by the detector, using a modified diffusion theory. Repeating the procedure for each pair of needles revealed significant variations in penetration depth within individual tumors. Average values of penetration depth, absorption coefficient, scattering coefficient, and mean scattering cosine were 0.282 cm, 0.469 cm-1, 250 cm-1 and 0.964, respectively. Calculated light distributions from four cylindrical sources in tumors gave reasonable agreement with direct light measurements using fiber optic probes.

Arnfield, M.R.; Tulip, J.; Chetner, M.; McPhee, M.S. (Cross Cancer Institute, Edmonton, Alberta (Canada))

1989-07-01

100

Immune modulation using transdermal photodynamic therapy  

NASA Astrophysics Data System (ADS)

The photosensitizer benzoporphyrin derivative monoacid ring A (VerteporfinR or BPD) has maximum absorption characteristics (690 nm) and biodistribution characteristics which permit activation of the drug in capillaries of the skin without causing skin photosensitivity (transdermal PDT). This permits targeting of cells in the circulation for selective ablation. Since BPD has been shown to accumulate preferentially in activated lymphocytes and monocytes, studies have been undertaken to determine the effect of transdermal PDT on murine models for rheumatoid arthritis (the MRL/lpr adjuvant enhanced model) and multiple sclerosis (the experimental allergic encephalomyelitis (EAE) model in PL mice). Localized transdermal PDT with BPD was found to be completely successful in preventing the development of adjuvant enhanced arthritis in the MRL/lpr mouse as well as improving the underlying arthritic condition of these animals. In the EAE model, in which an adoptive transfer system was used, it was found that transdermal PDT of recipients was effective in preventing EAE if treatments were implemented up to 24 hours after cell transfer but was not effective if given later, indicating the requirement for circulating T cells for effective treatment.

Levy, Julia G.; Chowdhary, R. K.; Ratkay, Leslie G.; Waterfield, Douglas; Obochi, Modestus; Leong, Simon; Hunt, David W. C.; Chan, Agnes H.

1995-01-01

101

Hardware Acceleration of a Monte Carlo Simulation for Photodynamic Therapy Treatment Planning  

E-print Network

Hardware Acceleration of a Monte Carlo Simulation for Photodynamic Therapy Treatment Planning Yip Lo #12;ii #12;Abstract Hardware Acceleration of a Monte Carlo Simulation for Photodynamic Therapy, particularly for modelling light propagation in biological tissue. The iterative nature of MC simulations

Rose, Jonathan

102

Hardware acceleration of a Monte Carlo simulation for photodynamic therapy treatment planning  

E-print Network

Hardware acceleration of a Monte Carlo simulation for photodynamic therapy treatment planning for modeling light propa- gation in tissues. The high computation time for MC limits its use to solving only of the tissue. How- ever, applications such as photodynamic therapy treatment planning or image reconstruction

Rose, Jonathan

103

Mannose-targeted Mesoporous Silica Nanoparticles for Photodynamic Therapy. David Brevet1  

E-print Network

Mannose-targeted Mesoporous Silica Nanoparticles for Photodynamic Therapy. David Brevet1§ , Magali1-4 . In the course of our program dealing with one and two-photon light- activated MSN5,6 , we were interested in photodynamic therapy (PDT) 7 which is unprecedented with MSN. Several examples of silica

Paris-Sud XI, Université de

104

Contributions of experiment designs in photodynamic therapy: photosensitizer design, treatment analysis and optimization.  

E-print Network

Contributions of experiment designs in photodynamic therapy: photosensitizer design, treatment.bastogne@cran.uhp-nancy.fr Introduction One of the difficulties in the development of the photodynamic therapy (PDT) is inherent factors were examined: the nature of quantum dots, the excitation light wavelength, the incubation time

Boyer, Edmond

105

System identification of the intracellular photoreaction process induced by photodynamic therapy  

E-print Network

System identification of the intracellular photoreaction process induced by photodynamic therapy-- Photodynamic therapy (PDT) is an alternative treatment for cancer that involves the administration of a photosensitizing agent, which is activated by light at a specific wavelength. This illumination causes a sequence

Boyer, Edmond

106

Photodynamic therapy (PDT) utilizing PhotofrinR for treatment of early esophageal cancer  

NASA Astrophysics Data System (ADS)

Four lesions of early carcinoma of the esophagus found during endoscopic biopsies in three patients were treated with photodynamic therapy. Follow-up biopsies over 9 - 24 months remain negative for carcinoma. Endoscopic ultrasonography is essential for proper staging and treatment planning for these patients. Photodynamic therapy may provide an alternative to surgical resection for early esophageal carcinoma or severe dysplasia in Barrett's esophagus.

Overholt, Bergein F.; Panjehpour, Masoud; Teffeteller, Elmeria; Rose, S. Mark

1993-06-01

107

Synthesis of novel cationic amphiphilic phthalocyanine derivatives for next generation photosensitizer using photodynamic therapy of cancer  

Microsoft Academic Search

Phthalocyanine derivatives have attracted attention in the photodynamic therapy of cancer. The preparation of cationic amphiphilic zinc phthalocyanine derivatives is described. Novel amphiphilic non-peripheral substituted zinc phthalocyanine derivative is performed by quaternation. Amphiphilic zinc bis(1,4-didecylbenzo)-bis(3,4-pyrido)porphyrazine will be a useful photosensitizer for photodynamic therapy of cancer.

Keiichi Sakamoto; Taku Kato; Eiko Ohno-Okumura; Masaki Watanabe; Michael J. Cook

2005-01-01

108

Three-dimensional illumination procedure for photodynamic therapy of dermatology.  

PubMed

Light dosimetry is an important parameter that affects the efficacy of photodynamic therapy (PDT). However, the irregular morphologies of lesions complicate lesion segmentation and light irradiance adjustment. Therefore, this study developed an illumination demo system comprising a camera, a digital projector, and a computing unit to solve these problems. A three-dimensional model of a lesion was reconstructed using the developed system. Hierarchical segmentation was achieved with the superpixel algorithm. The expected light dosimetry on the targeted lesion was achieved with the proposed illumination procedure. Accurate control and optimization of light delivery can improve the efficacy of PDT. PMID:25202901

Hu, Xiao-ming; Zhang, Feng-juan; Dong, Fei; Zhou, Ya

2014-09-01

109

On molecular mechanism of the photodynamic therapy of tumors  

NASA Astrophysics Data System (ADS)

In this work we present the experimental results indicating that the photodestruction (inactivation) of glycolysis enzymes located in mitochondria and responsible for the energy providing of malignant tumors, could serve as a possible molecular mechanism of a photodynamic therapy of cancer. The formation of complexes between the glycolysis enzymes and sensitizer favors can lead to an effective photodestruction of the former [in the experiments lactate dehydrogenase (LDH), pyruvate kinase (PK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and water-soluble tetra(carboxiphenyl)porphyrine [T(CP)P] (the analogue of coprorphyrin) were used as photosensitizer.

Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Tretjakov, S. A.

1995-01-01

110

Photodynamic therapy of port wine stain: preliminary clinical studies  

NASA Astrophysics Data System (ADS)

The broad, long term objective of this work is the development of Photodynamic Therapy (PDT) for application in the clinical management of patients with port wine stain (PWS). PDT involves the use of an exogenous drug which is concentrated in a targeted tissue. When irradiated at wavelengths specifically absorbed by the drug, selective destruction of the targeted tissue, without the production of heat, occurs. The results of this preliminary study demonstrate in human PWS patients that a photosensitizer, such as PHOTOFRINR, activated by red light at the appropriate therapeutic wavelength, can cause destruction of subsurface blood vessels in the skin with a high degree of specificity, and further study appears warranted.

Nelson, J. Stuart

1993-07-01

111

Dramatic regression of presumed acquired retinal astrocytoma with photodynamic therapy.  

PubMed

Photodynamic therapy (PDT) has been used for treatment of various intraocular tumors including choroidal hemangioma, vasoproliferative tumor, amelanotic choroidal melanoma and choroidal neovascular membrane due to choroidal osteoma. This case report documents the effect of PDT for a presumed acquired retinal astrocytoma. A 42-year-old female with a juxtapapillary acquired astrocytoma was treated with a single session of PDT using standard parameters. The tumor showed dramatic regression over 6 months into a fibrotic scar. It remained regressed and stable with 20/20 vision after 51 months of follow-up. We believe that PDT can be used as a primary treatment for acquired retinal astrocytoma. PMID:25100919

Tuncer, Samuray; Cebeci, Zafer

2014-01-01

112

Dramatic Regression of Presumed Acquired Retinal Astrocytoma with Photodynamic Therapy  

PubMed Central

Photodynamic therapy (PDT) has been used for treatment of various intraocular tumors including choroidal hemangioma, vasoproliferative tumor, amelanotic choroidal melanoma and choroidal neovascular membrane due to choroidal osteoma. This case report documents the effect of PDT for a presumed acquired retinal astrocytoma. A 42-year-old female with a juxtapapillary acquired astrocytoma was treated with a single session of PDT using standard parameters. The tumor showed dramatic regression over 6 months into a fibrotic scar. It remained regressed and stable with 20/20 vision after 51 months of follow-up. We believe that PDT can be used as a primary treatment for acquired retinal astrocytoma. PMID:25100919

Tuncer, Samuray; Cebeci, Zafer

2014-01-01

113

Synthesis, bioanalysis and biodistribution of photosensitizer conjugates for photodynamic therapy  

PubMed Central

Photodynamic therapy (PDT) was discovered in 1900 by Raab, and has since emerged as a promising tool for treating diseases characterized by unwanted cells or hyperproliferating tissue (e.g., cancer or infectious disease). PDT consists of the light excitation of a photosensitizer (PS) in the presence of O2 to yield highly reactive oxygen species. In recent years, PDT has been improved by the synthesis of targeted bioconjugates between monoclonal antibodies and PS, and by investigating PS biodistribution and PD. Here, we provide a comprehensive review of major developments in PS-immunoconjugate-based PDT and the bioanalysis of these agents, with a specific emphasis on anticancer and antimicrobial PDT. PMID:23641699

Denis, Tyler GSt; Hamblin, Michael R

2013-01-01

114

Photodynamic therapy in combating the causative microorganisms from endodontic infections  

PubMed Central

Photodynamic therapy (PDT) is presented as a promising antimicrobial therapy that can eliminate microorganisms present in endodontic infections. This treatment is based on the use of a nontoxic photosensitizing agent followed by irradiation of a resonant light source being capable of generating highly reactive species that are harmful to microorganisms. The purpose of this paper is to review the dental literature about the main factors that encompass the use of PDT combined with endodontic treatment for decontamination of the root canal system. A literature search was performed using the following index databases: PubMed, ISI Web of Knowledge and MedLine, between 2000 and 2014, looking for studies regarding antimicrobial action of PDT and its application to endodontic therapy. It was observed that despite numerous promising results, it is still necessary to establish different parameters so that PDT can be used with maximum effectiveness in eliminating microorganisms that cause endodontic infections. PMID:25202228

de Oliveira, Bruna Paloma; Aguiar, Carlos Menezes; Camara, Andrea Cruz

2014-01-01

115

Efficient Photodynamic Therapy on Human Retinoblastoma Cell Lines  

PubMed Central

Photodynamic therapy (PDT) has shown to be a promising technique to treat various forms of malignant neoplasia. The photodynamic eradication of the tumor cells is achieved by applying a photosensitizer either locally or systemically and following local activation through irradiation of the tumor mass with light of a specific wavelength after a certain time of incubation. Due to preferential accumulation of the photosensitizer in tumor cells, this procedure allows a selective inactivation of the malignant tumor while sparing the surrounding tissue to the greatest extent. These features and requirements make the PDT an attractive therapeutic option for the treatment of retinoblastoma, especially when surgical enucleation is a curative option. This extreme solution is still in use in case of tumours that are resistant to conventional chemotherapy or handled too late due to poor access to medical care in less advanced country. In this study we initially conducted in-vitro investigations of the new cationic water-soluble photo sensitizer tetrahydroporphyrin-tetratosylat (THPTS) regarding its photodynamic effect on human Rb-1 and Y79 retinoblastoma cells. We were able to show, that neither the incubation with THPTS without following illumination, nor the sole illumination showed a considerable effect on the proliferation of the retinoblastoma cells, whereas the incubation with THPTS combined with following illumination led to a maximal cytotoxic effect on the tumor cells. Moreover the phototoxicity was lower in normal primary cells from retinal pigmented epithelium demonstrating a higher phototoxic effect of THPTS in cancer cells than in this normal retinal cell type. The results at hand form an encouraging foundation for further in-vivo studies on the therapeutic potential of this promising photosensitizer for the eyeball and vision preserving as well as potentially curative therapy of retinoblastoma. PMID:24498108

Walther, Jan; Schastak, Stanislas; Dukic-Stefanovic, Sladjana; Wiedemann, Peter; Neuhaus, Jochen; Claudepierre, Thomas

2014-01-01

116

Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma  

PubMed Central

Malignant melanoma is the most aggressive form of skin cancer and has been traditionally considered difficult to treat. The worldwide incidence of melanoma has been increasing faster than any other type of cancer. Early detection, surgery, and adjuvant therapy enable improved outcomes; nonetheless, the prognosis of metastatic melanoma remains poor. Several therapies have been investigated for the treatment of melanoma; however, current treatment options for patients with metastatic disease are limited and non-curative in the majority of cases. Photodynamic therapy (PDT) has been proposed as a promising minimally invasive therapeutic procedure that employs three essential elements to induce cell death: a photosensitizer, light of a specific wavelength, and molecular oxygen. However, classical PDT has shown some drawbacks that limit its clinical application. In view of this, the use of nanotechnology has been considered since it provides many tools that can be applied to PDT to circumvent these limitations and bring new perspectives for the application of this therapy for different types of diseases. On that ground, this review focuses on the potential use of developing nanotechnologies able to bring significant benefits for anticancer PDT, aiming to reach higher efficacy and safety for patients with malignant melanoma.

Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; de Azevedo, Ricardo Bentes

2014-01-01

117

Photodynamic therapy using Photofrin and Foscan and the treatment of malignancies of the head and neck  

NASA Astrophysics Data System (ADS)

One hundred thirty patients with neoplastic diseases of the larynx, oral cavity, pharynx and skin have been treated with photodynamic therapy (PDT) with follow-up to 79 months. Those patients with primary or recurrent leukoplakia, carcinoma-in- situ (CIS) and T1 carcinomas obtained a complete response after one PDT treatment and 87% remain free of disease. Sixteen patients with deeply invasive T2 and T3 carcinomas were treated with PDT. Of those sixteen, ten obtained a complete response, but six have recurred locally. Although a response can be achieved with PDT in the larger solid tumors, it is not a consistent complete response because of the depth of invasion of the tumor. This is due to the inability to adequately deliver laser light to the depths of the tumor bed. Fourteen patients with massive recurrences of squamous cell carcinomas were treated with intraoperative adjuvant PDT following tumor resection. Two patients developed a local recurrence within the field of treatment. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. T2 and T3 superficial carcinomas, with invasion less than 0.5 cm, are also curatively treated with PDT with significantly reduced morbidity compared to conventional modes of treatment. Also, intraoperative adjuvant PDT may increase cure rates of large infiltrating carcinomas of the head and neck.

Biel, Merrill A.

1998-05-01

118

Photodynamic therapy and the treatment of malignancies of the head and neck  

NASA Astrophysics Data System (ADS)

Seventy-nine patients with neoplastic diseases of the larynx, oral cavity, pharynx, and skin have been treated with photodynamic therapy (PDT) with follow-up to 65 months. Patients with carcinoma-in-situ (CIS) and T1 carcinomas obtained a complete response after one PDT treatment. All but two patients remain free of disease. Four patients with T2 and T3 superficial carcinomas were treated with PDT. One patient developed recurrence with 51- month follow-up. Eleven patients with deeply invasive T2, T3, and T4 carcinomas were treated with PDT. Of those eleven, eight obtained a complete response, but five have recurred locally. A response can be achieved with PDT, although not a consistent complete response because of the depth of invasion of the tumor. This is due to the inability to adequately deliver laser light to the depths of the tumor bed. Eight patients with massive neck recurrences of squamous cell carcinomas were treated with intraoperative adjuvant PDT following tumor resection. Only one patient developed recurrence with 30-month follow-up. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. T2 and T3 superficial carcinomas, with invasion less than 0.5 cm, are also curatively treated with PDT with significantly reduced morbidity compared to conventional modes of treatment. Also, intraoperative adjuvant PDT may increase cure rates of large infiltrating carcinomas of the head and neck.

Biel, Merrill A.; Boss, Ellen E.

1996-04-01

119

Hematoporphyrin derivative uptake and photodynamic therapy in pancreatic carcinoma  

SciTech Connect

Little information is currently available concerning the uptake of porphyrins by pancreatic tumors, or the effect of photodynamic therapy (PDT) on pancreatic cancer. In Syrian golden hamsters (n = 33), the organ distribution of /sup 125/I-labeled dihematoporphyrin ether (DHE) was studied in a pancreatic cancer model. In the same animal model the effect of PDT was studied using a gold vapor laser for energy delivery 3 hr after the injection of DHE (n = 7). DHE was 2.4 times more concentrated in the pancreatic tumor than in the nontumorous pancreas at 3 hr. Simultaneously there was a considerable accumulation of DHE in the surrounding gastrointestinal tract, causing perforation of the duodenum and jejunum with resultant death in four (57%) animals after PDT. Photodynamic therapy caused extensive tumor necrosis without any obvious effect on the nontumor-bearing pancreas. Damage to the surrounding tissue in the hamster indicates that precautions should be taken if PDT is to be used clinically in pancreatic cancer. Intratumoral injection of DHE may give higher drug concentrations with greater specificity for tumor treatment.

Schroder, T.; Chen, I.W.; Sperling, M.; Bell, R.H. Jr.; Brackett, K.; Joffe, S.N.

1988-05-01

120

Antivascular Treatment of Solid Melanoma Tumors with Bacteriochlorophyll–serine-based Photodynamic Therapy  

Microsoft Academic Search

We describe here a strategy for photodynamic eradica- tion of solid melanoma tumors that is based on photo- induced vascular destruction. The suggested protocol re- lies on synchronizing illumination with maximal circu- lating drug concentration in the tumor vasculature at- tained within the first minute after administrating the sensitizer. This differs from conventional photodynamic therapy (PDT) of tumors where illumination

Judith Zilberstein; Smadar Schreiber; Monique C. W. M. Bloemers; Peter Bendel; Michal Neeman; Edna Schechtman; Fortune Kohen; Avigdor Scherz; Yoram Salomon

2001-01-01

121

Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria  

Microsoft Academic Search

The increasing occurrence of multi-antibiotic resistant microbes has led to the search for alternative methods of killing pathogens and treating infections. Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill mammalian and microbial cells. Although the photodynamic inactivation of bacteria has been known for over a hundred years,

Tatiana N Demidova; Faten Gad; Touqir Zahra; Kevin P Francis; Michael R Hamblin

2005-01-01

122

Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group  

Microsoft Academic Search

Summary Topical photodynamic therapy (PDT) is effective in the treatment of certain non-melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic

C. A. Morton; S. B. Brown; S. Collins; S. Ibbotson; H. Jenkinson; H. Kurwa; K. Langmack; K. Mckenna; H. Moseley; A. D. Pearse; M. Stringer; D. K. Taylor; G. Wong; L. E. Rhodes

2002-01-01

123

Physical and mathematical modeling of antimicrobial photodynamic therapy  

NASA Astrophysics Data System (ADS)

Antimicrobial photodynamic therapy (aPDT) is a promising method to treat local bacterial infections. The therapy is painless and does not cause bacterial resistances. However, there are gaps in understanding the dynamics of the processes, especially in periodontal treatment. This work describes the advances in fundamental physical and mathematical modeling of aPDT used for interpretation of experimental evidence. The result is a two-dimensional model of aPDT in a dental pocket phantom model. In this model, the propagation of laser light and the kinetics of the chemical reactions are described as coupled processes. The laser light induces the chemical processes depending on its intensity. As a consequence of the chemical processes, the local optical properties and distribution of laser light change as well as the reaction rates. The mathematical description of these coupled processes will help to develop treatment protocols and is the first step toward an inline feedback system for aPDT users.

Bürgermeister, Lisa; López, Fernando Romero; Schulz, Wolfgang

2014-07-01

124

Photodynamic Therapy for Gynecological Diseases and Breast Cancer  

PubMed Central

Photodynamic therapy (PDT) is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy. PMID:23691448

Shishkova, Natashis; Kuznetsova, Olga; Berezov, Temirbolat

2012-01-01

125

Evaluation of photodynamic therapy in adhesion protein expression  

PubMed Central

Photodynamic therapy (PDT) is a treatment modality that has clinical applications in both non-neoplastic and neoplastic diseases. PDT involves a light-sensitive compound (photosensitizer), light and molecular oxygen. This procedure may lead to several different cellular responses, including cell death. Alterations in the attachment of cancer cells to the substratum and to each other are important consequences of photodynamic treatment. PDT may lead to changes in the expression of cellular adhesion structure and cytoskeleton integrity, which are key factors in decreasing tumor metastatic potential. HEp-2 cells were photosensitized with aluminum phthalocyanine tetrasulfonate and zinc phthalocyanine, and the proteins ?1-integrin and focal adhesion kinase (FAK) were assayed using fluorescence microscopy. The verification of expression changes in the genes for FAK and ?1 integrin were performed by reverse transcription-polymerase chain reaction (RT-PCR). The results revealed that HEp-2 cells do not express ?-integrin or FAK 12 h following PDT. It was concluded that the PDT reduces the adhesive ability of HEp-2 cells, inhibiting their metastatic potential. The present study aimed to analyze the changes in the expression and organization of cellular adhesion elements and the subsequent metastatic potential of HEp-2 cells following PDT treatment. PMID:25013490

PACHECO-SOARES, CRISTINA; MAFTOU-COSTA, MAIRA; DA CUNHA MENEZES COSTA, CAROLINA GENUNCIO; DE SIQUEIRA SILVA, ANDREZA CRISTINA; MORAES, KAREN C.M.

2014-01-01

126

Targeted photodynamic therapy for infected wounds in mice  

NASA Astrophysics Data System (ADS)

Although many workers have used photodynamic therapy to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We report on the use of a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) that can penetrate the Gram (-) outer membrane together with red laser light to kill Escherichia coli and Pseudomonas aeruginosa infecting excisional wounds in mice. We used genetically engineered luminescent bacteria that allowed the infection to be imaged in mouse wounds using a sensitive CCD camera. Wounds were infected with 5x106 bacteria, followed by application of the conjugate in solution and illumination. There was a light-dose dependent loss of luminescence as measured by image analysis in the wound treated with conjugate and light, not seen in control wounds. This strain of E coli is non-invasive and the infection in untreated wounds spontaneously resolved in a few days and all wounds healed equally well showing the photodynamic treatment did not damage the host tissue. P aeruginosa is highly invasive and mice with untreated or control wounds all died while 90% of PDT treated mice survived. PDT may have a role to play in the rapid treatment of infected wounds in view of the worldwide rise in antibiotic resistance.

Hamblin, Michael R.; O'Donnell, David A.; Zahra, Touqir; Contag, Christopher H.; McManus, Albert T.; Hasan, Tayyaba

2002-06-01

127

Computer model for photodynamic therapy of the prostate  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is an emerging minimally invasive treatment that can be employed in many human diseases including prostate cancer. This treatment of human prostate cancer depends on the localization of a drug (photosensitizer) into the prostate. The photosensitizer is activated by high- energy laser light and the active drug destroys cancerous tissue. The success of PDT depends on precise placement of light diffusers in the prostate. Since the prostate is irregular in shape, with different dimensions, a transurethral light delivery that is circular in distribution cannot be used in most cases of carcinoma of the prostate. Sources of light and their spatial distribution must be tailored to each individual patient. More uniform, therapeutic light distribution can be achieved by interstitial light irradiation. In this case, the light is delivered by diffusers placed within the substance of the prostate parallel to the urethra at a distance optimized to deliver adequate levels of light and to create the desired photodynamic effect. For this reason, we are developing a computer program that can calculate the distribution of energy depending on the number of light sources placed in the prostate, their position in the gland, the dimension of the prostate, and the attenuation coefficient. A patient's three-dimensional prostate model is built based on ultrasound images. Then the program is being designated to predict the best set of parameters and position of light diffusers in space, displays them in graphical form or in numerical form. The program is amenable for interfacing with robotic treatment systems.

Jankun, Jerzy; Zaim, Amjad; Jankun-Kelly, Monika; Keck, Rick W.; Selman, Steven H.

2000-05-01

128

Adjuvant therapy for gastric cancer: Current and future directions  

PubMed Central

The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies. PMID:25320509

Foo, Marcus; Leong, Trevor

2014-01-01

129

Systemic adjuvant therapy for node-negative breast cancer.  

PubMed Central

In response to recent advice from the US National Cancer Institute concerning the use of systemic adjuvant therapy for node-negative breast cancer we reviewed the literature and found that several studies have shown evidence of a disease-free, but not an overall, survival advantage for treated patients. The benefits have been modest and may not outweight the cost and toxic effects of such therapy. Routine use does not seem to be justified. Factors must be identified to differentiate between patients at low risk and those at high risk. It should then be determined if adjuvant therapy is truly beneficial in those who are at high risk. PMID:2670170

Ginsburg, A D; Perrault, D J; Pritchard, K I; Browman, G P; McCulloch, P B; Skillings, J

1989-01-01

130

Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy  

E-print Network

Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy Timothy K. Lua, there is a pressing need for new antibacterial therapies that can be readily designed and implemented. In this work, we engineered bacteriophage to overexpress proteins and attack gene networks that are not directly

Collins, James J.

131

Postoperative adjuvant therapy for pancreatic cancer.  

PubMed

The majority of patients diagnosed with pancreatic cancer present at an advanced stage, and only a small percentage are considered technically resectable at diagnosis. The overall prognosis for the majority is dismal, with a median survival in untreated cases of only 24 weeks. Even in resected patients the overall 5-year survival rate is generally only 5% to 10%; however, some reports indicate higher 5-year survival rates in patients treated with surgery who are pathologically staged with no lymph node involvement. Even when macroscopically complete resection is achieved, local recurrence (LR) rates are unacceptably high (30% to 70%), which is usually attributed to the difficulty of obtaining microscopically free surgical margins. Microscopic clearance is difficult to achieve because these tumors frequently extend into the peripancreatic tissues (e.g., retropancreatic fat), abut or invade the adjacent large vessels (the portal vein and superior mesenteric artery), and have a propensity to invade the lymphovascular and perineural space. Other common sites of failure after attempted curative resection include metastasis to the liver and the peritoneal cavity. Patients who present with pancreatic cancer, and for whom curative surgery is deemed possible, are thus potential candidates for adjuvant therapy because of the high local failure rate following resection alone. The radiotherapy dose that can be achieved in the postoperative setting for pancreatic cancer is limited because of the proximity of critical structures (e.g., the kidney, liver, small intestines, stomach, and spinal cord). Newer techniques such as conformal radiotherapy and intensity-modulated radiotherapy have the advantage of being able (theoretically) to precisely localize the dose to the target volume while reducing the dose to critical structures. These techniques may potentially enable the tumorcidal dose to be increased; however, they are only now becoming widespread. Systemic radiation-sensitizing chemotherapy is also a promising approach to take advantage of additive or synergistic effects with radiation locally, and for the sterilization of systemic disease. This concept of concomitant chemotherapy with radiotherapy, or chemoradiotherapy, has proved effective in a number of sites, including the anal canal, rectum, lung, and pancreas. The recent trials reviewed here varied considerably in terms of the total dose and technique used, and the choice of radiation sensitizing treatment. PMID:14648783

Penberthy, David R; Rich, Tyvin A; Adams, Reid B

2003-01-01

132

A Review of Photodynamic Therapy for Herpes Simplex: Benefits and Potential Risks.  

National Technical Information Service (NTIS)

A recently developed photodynamic therapy for herpes simplex consists of exposing viral lesions to visible light following application of a photosensitizing dye. Animal and human clinical trials show reduction of oral and genital herpes virus infectivity....

L. E. Bockstahler, C. D. Lytle, K. B. Hellman

1974-01-01

133

Photodynamic Therapy of Skin using Porphyrin Precursors: Optical Monitoring, Vascular Effects and Personalized Medicine.  

E-print Network

??abstract__Abstract__ Photodynamic therapy (PDT) is based on a photochemical reaction that involves three basic components: (1) a photosensitizer, which is a light-sensitive molecule that mediates… (more)

T.A. Middelburg (Tom)

2014-01-01

134

Photodynamic therapy of cancer with the photosensitizer PHOTOGEM  

NASA Astrophysics Data System (ADS)

The first clinical trials of photodynamic therapy (PDT) in Russia were started in P. A. Hertzen Moscow Research Oncology Institute in October of 1992. Up to now, 61 patients with primary or recurrent malignant tumors of the larynx (3), trachea (1), bronchus (11), nose (1), mouth (3), esophagus (12), vagina and uterine cervix (3), bladder (2), skin (6), and cutaneous and subcutaneous metastases of breast cancer and melanomas (6) have been treated by PDT with the photosensitizer Photogem. At least partial tumor response was observed in all of the cases, but complete remission indicating no evident tumors has been reached in 51% of the cases. Among 29 patients with early and first stage cancer 14 patients had multifocal tumors. Complete remission of tumors in this group reached 86%.

Sokolov, Victor V.; Chissov, Valery I.; Filonenko, E. V.; Sukhin, Garry M.; Yakubovskaya, Raisa I.; Belous, T. A.; Zharkova, Natalia N.; Kozlov, Dmitrij N.; Smirnov, V. V.

1995-01-01

135

Photodynamic therapy with Photofrin II by bronchial artery infusion  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) utilizing Photofrin II is proving to be an effective modality in the treatment of early stage lung cancer. However, wider clinical application of Photofrin II as a photosensitizer for various cancers is hampered by the potentially serious and prolonged skin photosensitivity. To prevent these side effects and reduce the inpatient period, we recently tried to give reduced doses of Photofrin II by bronchial artery infusion (BAI). Six patients with endoscopically evaluated early stage carcinoma of the lung were given 0.7 mg/kg of Photofrin II by BAI 48 hours before PDT. Complete remission was obtained in all 6 cases, and there was no evidence of skin photosensitivity when exposed to outside light under careful surveillance at one week after PDT.

Okunaka, Tetsuya; Kato, Harubumi; Konaka, Chimori; Kinoshita, Komei; Yamada, Kimito

1993-03-01

136

Photodynamic therapy in dermatology: past, present, and future  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is a noninvasive therapeutic method first introduced in the field of dermatology. It is mainly used for the treatment of precancerous and superficial malignant skin tumors. Today PDT finds new applications not only for nononcologic dermatoses but also in the field of other medical specialties such as otorhinolaryngology, ophthalmology, neurology, gastroenterology, and urology. We are witnessing a broadening of the spectrum of skin diseases that are treated by PDT. Since its introduction, PDT protocol has evolved significantly in terms of increasing method efficacy and patient safety. In this era of evidence-based medicine, it is expected that much effort will be put into creating a worldwide accepted consensus on PDT. A review on the current knowledge of PDT is given, and the historical basis of the method's evolution since its introduction in the 1900s is presented. At the end, future challenges of PDT are focused on discussing gaps that exist for research in the field.

Darlenski, Razvigor; Fluhr, Joachim W.

2013-06-01

137

5-ALA-assisted photodynamic therapy in canine prostates  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) and interstitial thermotherapy are well known treatment modalities in urology. The approach of this study is to combine both to achieve a selective treatment procedure for benign prostatic hyperplasia (BPH) and prostate carcinoma. Measurements of thy in-vivo pharmacokinetics of 5-ALA induced porphyrins by means of fiber assisted ratiofluorometry showed a maximum fluorescence intensity at time intervals of 3 - 4 h post administration. Fluorescence microscopy at that time showed bright fluorescence in epithelial cells while in the stroma fluorescence could not be observed. Interstitial PDT using a 635-nm dye laser with an irradiation of 50 J/cm2 resulted in a nonthermic hemorrhagic lesion. The lesion size did not change significantly when an irradiation of 100 J/cm2 was used. The usefulness of PDT for treating BPH as well as prostate carcinoma has to be proven in further studies.

Sroka, Ronald; Muschter, Rolf; Knuechel, Ruth; Steinbach, Pia; Perlmutter, Aaron P.; Martin, Thomas; Baumgartner, Reinhold

1996-05-01

138

Monitoring oxygen concentration during photodynamic therapy using prompt photosensitizer fluorescence  

NASA Astrophysics Data System (ADS)

A novel technique is described that uses either time-resolved or steady state prompt photosensitizer fluorescence to measure local oxygen concentration. Solution experiments conducted with Al(III) phthalocyanine chloride tetrasulfonic acid confirmed that the steady state fluorescence signal is dependent on the oxygen concentration and fluence rate. A relationship between prompt sensitizer fluorescence and sensitizer triplet quenching efficiency is derived which does not require knowledge of the Stern-Volmer constant. Similar relationships are also derived for sensitizer delayed fluorescence and phosphorescence. An explicit photodynamic therapy (PDT) dose metric that incorporates light dosimetry, sensitizer dosimetry, and triplet quenching efficiency is introduced. All components of this metric can be determined by optical measurements.

Weston, Mark A.; Patterson, Michael S.

2013-10-01

139

Antifungal effect of TONS504-photodynamic therapy on Malassezia furfur.  

PubMed

Numerous reports indicate therapeutic efficacy of photodynamic therapy (PDT) against skin tumors, acne and for skin rejuvenation. However, few reports exist regarding its efficacy for fungal skin diseases. In order to determine the antifungal effect, PDT was applied on Malassezia furfur. M. furfur was cultured in the presence of a novel cationic photosensitizer, TONS504, and was irradiated with a 670-nm diode laser. TONS504-PDT showed a significant antifungal effect against M. furfur. The effect was irradiation dose- and TONS504 concentration-dependent and the maximal effect was observed at 100 J/cm(2) and 1 ?g/mL, respectively. In conclusion, TONS504-PDT showed antifungal effect against M. furfur in vitro, and may be a new therapeutic modality for M. furfur-related skin disorders. PMID:25226792

Takahashi, Hidetoshi; Nakajima, Susumu; Sakata, Isao; Iizuka, Hajime

2014-10-01

140

Photodynamic therapy induces an immune response against a bacterial pathogen  

PubMed Central

Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that both arms of the host immune system (innate and adaptive) are activated. When PDT is used for infectious disease, however, it has been assumed that the direct antimicrobial PDT effect dominates. Murine arthritis caused by methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT with intravenously injected Photofrin®. PDT with intra-articular Photofrin produced a biphasic dose response that killed bacteria without destroying host neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria while preserving neutrophils. We used bioluminescence imaging to noninvasively monitor murine bacterial arthritis and found that PDT with intra-articular methylene blue was not only effective, but when used before infection, could protect the mice against a subsequent bacterial challenge. The data emphasize the importance of considering the host immune response in PDT for infectious disease. PMID:22882222

Huang, Ying-Ying; Tanaka, Masamitsu; Vecchio, Daniela; Garcia-Diaz, Maria; Chang, Julie; Morimoto, Yuji; Hamblin, Michael R

2012-01-01

141

Daylight-mediated photodynamic therapy in Spain: advantages and disadvantages.  

PubMed

Photodynamic therapy (PDT) is an option for the treatment of actinic keratosis, Bowen disease, and certain types of basal cell carcinoma. It is also used to treat various other types of skin condition, including inflammatory and infectious disorders. The main disadvantages of PDT are the time it takes to administer (both for the patient and for health professionals) and the pain associated with treatment. Daylight-mediated PDT has recently been reported to be an alternative to the conventional approach. Several studies have shown it to be similar in efficacy to and better tolerated than classic PDT for the treatment of mild to moderate actinic keratosis. Nevertheless, most of these studies are from northern Europe, and no data have been reported from southern Europe. The present article reviews the main studies published to date, presents the treatment protocol, and summarizes our experience with a group of treated patients. PMID:24726043

Pérez-Pérez, L; García-Gavín, J; Gilaberte, Y

2014-09-01

142

Photodynamic therapy: Theoretical and experimental approaches to dosimetry  

NASA Astrophysics Data System (ADS)

Singlet oxygen (1O2) is the major cytotoxic species generated during photodynamic therapy (PDT), and 1O 2 reactions with biological targets define the photodynamic dose at the most fundamental level. We have developed a theoretical model for rigorously describing the spatial and temporal dynamics of oxygen (3O 2) consumption and transport and microscopic 1O 2 dose deposition during PDT in vivo. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin-3O 2 saturation within vessels, irreversible photosensitizer degradation due to photobleaching, therapy-induced blood flow decrease and the microscopic distributions of 3O2 and 1O 2 dose deposition under various irradiation conditions. mTHPC, a promising photosensitizer for PDT, is approved in Europe for the palliative treatment of head and neck cancer. Using the theoretical model and informed by intratumor sensitizer concentrations and distributions, we calculated photodynamic dose depositions for mTHPC-PDT. Our results demonstrate that the 1O 2 dose to the tumor volume does not track even qualitatively with long-term tumor responses. Thus, in this evaluation of mTHPC-PDT, any PDT dose metric that is proportional to singlet oxygen creation and/or deposition would fail to predict the tumor response. In situations like this one, other reporters of biological response to therapy would be necessary. In addition to the case study of mTHPC-PDT, we also use the mathematical model to simulate clinical photobleaching data, informed by a possible blood flow reduction during treatment. In a recently completed clinical trial at Roswell Park Cancer Institute, patients with superficial basal cell carcinoma received topical application of 5-aminolevulinic acid (ALA) and were irradiated with 633 nm light at 10-150 mW cm-2 . Protoporphyrin IX (PpIX) photobleaching in the lesion and the adjacent perilesion normal margin was monitored by fluorescence spectroscopy. We successfully simulate the in vivo photobleaching of PpIX in this patient population over a wide range of irradiances using the PDT model. For most cases, the rate of bleaching slows as treatment progresses, leaving a fraction of the PpIX unbleached despite sustained irradiation. To account for this feature, the model predicts that incorporation of ALA-PDT-induced blood flow reduction is necessary. In addition to using the theoretical method to understand the dose deposited by photodynamic therapy, experimentally, we propose a potential dose metric for Pc 4-PDT. Pc 4 is a promising second generation photosensitizer that is now in Phase I clinical trials for the treatment of cutaneous lesions. We have observed a significant irradiation-induced increase in Pc 4 fluorescence in tumor cell monolayers. The amount of the fluorescence increase observed in vitro strongly correlates to the cell death and mitochondrial swelling reported by the clonogenic cell survival assay and light scattering measurements, respectively. Based on those biological responses, we anticipate that irradiation-induced fluorescence enhancement in Pc 4-PDT may be a potential dose metric.

Wang, Ken Kang-Hsin

143

Intraoperative photodynamic therapy on spontaneous canine nasal tumors  

NASA Astrophysics Data System (ADS)

Promising results obtained by photodynamic therapy (PDT) with porphyrins on superficial spontaneous canine tumors suggested the experiment of this technique on intracavitary tumors, specifically at the endonasal site. The supposed neoplastic residual bed was irradiated directly during surgery at the end of the debulking. Five dogs referred to the surgical department of the veterinary school, University of Milan and affected by endonasal neoplasias were submitted to PDT after radiologic and cyto-histologic diagnosis and TNM stadiation. All the selected tumors were included in the clinical stage 1 (T1NOMO). Mean and median survival time (from the day of treatment) were 11.6 - 5.4 and 12 months, respectively. Different staging of the treated tumors limits the possibility of an objective comparison with other alternative therapeutic procedures.

Fonda, Diego; Mortellaro, Carlo M.; Romussi, Stefano; Taroni, Paola; Cubeddu, Rinaldo

1994-09-01

144

Current evidence and applications of photodynamic therapy in dermatology  

PubMed Central

In photodynamic therapy (PDT) a photosensitizer – a molecule that is activated by light – is administered and exposed to a light source. This leads both to destruction of cells targeted by the particular type of photosensitizer, and immunomodulation. Given the ease with which photosensitizers and light can be delivered to the skin, it should come as no surprise that PDT is an increasingly utilized therapeutic in dermatology. PDT is used commonly to treat precancerous cells, sun-damaged skin, and acne. It has reportedly also been used to treat other conditions including inflammatory disorders and cutaneous infections. This review discusses the principles behind how PDT is used in dermatology, as well as evidence for current applications of PDT. PMID:24899818

Wan, Marilyn T; Lin, Jennifer Y

2014-01-01

145

Blood Flow Dynamics after Photodynamic Therapy with Verteporfin in the RIF1 Tumor  

Microsoft Academic Search

Chen, B., Pogue, B. W., Goodwin, I. A., O'Hara, J. A., Wil- mot, C. M., Hutchins, J. E., Hoopes, P. J. and Hasan, T. Blood Flow Dynamics after Photodynamic Therapy with Verteporfin in the RIF-1 Tumor. Radiat. Res. 160, 452-459 (2003). In the present study, the effects of photodynamic therapy (PDT) with verteporfin on tumor blood flow and tumor re-

Bin Chen; Brian W. Pogue; Isak A. Goodwin; Julia A. O'Hara; Carmen M. Wilmot; John E. Hutchins; P. Jack Hoopesa; Tayyaba Hasanb

2003-01-01

146

Sclerotherapy — an adjuvant therapy to endometriosis  

Microsoft Academic Search

Objective: Recurrent endometriomas after medical or surgical treatmentis a difficult clinical problem for those patients who wish to perform ovulation induction. Therefore we tried to investigate the efficacy of sclerotherapy as an adjuvant management before ovulation induction to preserve more ovarian tissue for folliculogenesis in ART program. Methods: Thirty-two patients with persistent or recurrent endometrioma after surgical or medical treatment

C.-C. Chang; H.-F. Lee; H.-D. Tsai; H.-Y. Lo

1997-01-01

147

Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria  

PubMed Central

Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a new promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria, yeasts and fungi. The search for new approaches that can kill bacteria but do not induce the appearance of undesired drug-resistant strains suggests that PDT may have advantages over traditional antibiotic therapy. PDT is a non-thermal photochemical reaction that involves the simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS). Several PS have been studied for their ability to bind to bacteria and efficiently generate reactive oxygen species (ROS) upon photostimulation. ROS are formed through type I or II mechanisms and may inactivate several classes of microbial cells including Gram-negative bacteria such as Pseudomonas aeruginosa, which are typically characterized by an impermeable outer cell membrane that contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the sensitive inner membrane and cell wall. This review covers significant peer-reviewed articles together with US and World patents that were filed within the past few years and that relate to the eradication of Gram-negative bacteria via PDI or PDT. It is organized mainly according to the nature of the PS involved and includes natural or synthetic food dyes; cationic dyes such as methylene blue and toluidine blue; tetrapyrrole derivatives such as phthalocyanines, chlorins, porphyrins, chlorophyll and bacteriochlorophyll derivatives; functionalized fullerenes; nanoparticles combined with different PS; other formulations designed to target PS to bacteria; photoactive materials and surfaces; conjugates between PS and polycationic polymers or antibodies; and permeabilizing agents such as EDTA, PMNP and CaCl2. The present review also covers the different laboratory animal models normally used to treat Gram-negative bacterial infections with antimicrobial PDT. PMID:23550545

Sperandio, Felipe F; Huang, Ying-Ying; Hamblin, Michael R

2013-01-01

148

Bisphosphonates as adjuvant therapy for breast cancer  

Microsoft Academic Search

Breast cancer is the most common malignancy among women worldwide. Emerging results from clinical trials in patients with\\u000a breast cancer suggest that, in addition to preventing cancer treatment-induced bone loss, bisphosphonates may improve disease-free\\u000a survival (DFS). Although the first adjuvant studies using the early generation oral bisphosphonate clodronate suggested potential\\u000a reductions in distant recurrence versus placebo in patients with early

Michael Gnant; Peter Dubsky; Florian Fitzal; Thomas Bachleitner-Hofmann; Ruth Exner; Peter Blaha; Raimund Jakesz; Walter Schippinger; Richard Greil

2009-01-01

149

Photodynamic methods for fluorescence diagnosis and therapy of photosensitized tumors  

NASA Astrophysics Data System (ADS)

Several substances, e.g., hematoporphyrin derivatives (HpD), dihematoporphyrin ether/ester (DHE), phthalocyanines, porphycenes, and other drugs are known to be temporarily and selectively stored in tumors after systematic application. This transient marking opens up new perspectives for diagnostic and therapeutic procedures. The marker most commonly used today is DHE intravenously injected at doses of 0.2 up to 3.0 mg/kg bodyweight for diagnosis and therapy respectively. The corresponding clearance intervals after injection of DHE range from 3 - 48 h and 25 - 75 h. The highly sensitive two-wavelength laser excitation method with computerized fluorescence imaging offers great advantages for the detection of photosensitized tumors and adds support to conventional diagnostic techniques. Photoinduced production of singlet oxygen is said to be the initial process leading to tumor destruction. Homogeneous irradiation of the area to be treated and a reliable light dosimetry are prerequisites for an effective tumor therapy. Standard instruments for a routine application so far do not exist. Integral irradiation techniques and special laser fiber modifications, however, are under development, which guarantee a uniform distribution of light on the area to be treated. Positive results are such treatments--especially in urology, pneumology, and otorhinolaryngology--indicate the future potential of photodynamic therapy of tumors.

Unsoeld, Eberhard

1992-03-01

150

Advance in Photosensitizers and Light Delivery for Photodynamic Therapy  

PubMed Central

The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo. PMID:23423543

Yoon, Il; Li, Jia Zhu

2013-01-01

151

Magnetic resonance image-guided photodynamic therapy of xenograft pancreas tumors with verteporfin  

NASA Astrophysics Data System (ADS)

Pancreatic cancer generally has very poor prognosis, with less than 4% survival at 5 years after diagnosis. This dismal survival rate is in part due to the aggressive nature of the adenocarcinoma, leading to a late-stage at diagnosis and exhibits resistance to most therapies. Photodynamic therapy (PDT) is a model cellular and vascular therapy agent, which uses light activation of the delivered drug to photosensitize the local cellular millieu. We suggest that interstitial verteporfin (benzoporphyrin derivative monoacid ring A) PDT has the potential to be an adjuvant therapy to the commonly used Gemcitabine chemotherapy. In the current study, an orthotopic pancreatic cancer model (Panc-1) has undergone interstitial verteporfin PDT (40 J/cm with verteporfin and 40 J/cm without verteporfin). Prior to PDT, magnetic resonance (MR) imaging was used to determine the location and size of the tumor within the pancreas, allowing accurate placement of the diffusing fiber. The success of therapy was monitored in vivo by assessing the total tumor and vascular perfusion volumes 24 hours pre- and 48 hours post-PDT. Total tumor and vascular perfusion volumes were determined using T2 weighted (T2W) and Gd-DTPA difference T1 weighted (T1W) turbo spin echo (TSE) MR imaging sequences, respectively. The validity of the in vivo imaging for therapeutic response was confirmed by ex vivo fluorescence and histological staining of frozen tissue sections. The ex vivo DiOC7(3) fluorescence analysis correlates well with the information provided from the MR images, indicating that MR imaging will be a successful surrogate marker for interstitial PDT.

Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

2009-02-01

152

The benefits of photodynamic therapy on vertebral bone are maintained and enhanced by combination treatment with bisphosphonates and radiation therapy.  

PubMed

Photodynamic therapy (PDT) has been shown to ablate tumors within vertebral bone and yield short-term improvements in vertebral architecture and biomechanical strength, in particular when combined with bisphosphonate (BP) treatment. Longer-term outcomes of PDT combined with current treatments for skeletal metastases are essential to understand its therapeutic potential. The objective of this study is to evaluate the response of vertebrae to PDT after a longer (6-week) time period, alone and combined with previous BP or radiation treatment (RT). Sixty-three female rnu/rnu rats were randomized to six treatment groups: untreated control, BP-only, RT-only, PDT-only, combined BP + PDT and combined RT + PDT. L2 vertebrae were structurally analyzed through µCT-based analysis, axial compressive load-to-failure testing and histological analysis of morphology, osteoid formation and osteoclast activity. Combined BP + PDT treatment yielded the largest improvements in bone architecture with combined RT + PDT treatment yielding similar findings, but of a lesser magnitude. Mechanically, ultimate force and stress were correlated to stereological parameters that demonstrated a positive structural effect from combinatory treatment. Increased osteoid formation was observed in both combination therapies without any significant differences in osteoclast activity. Overall, multimodality treatment demonstrated a sustained positive effect on vertebral structural integrity, motivating PDT as a minimally-invasive adjuvant treatment for spinal metastases. PMID:23625821

Lo, Victor C K; Akens, Margarete K; Wise-Milestone, Lisa; Yee, Albert J M; Wilson, Brian C; Whyne, Cari M

2013-09-01

153

Photodynamic therapy in early esophageal squamous cell carcinoma  

NASA Astrophysics Data System (ADS)

From 1/1985 to 7/1993, 18 patients underwent endoscopic photodynamic therapy (PDT) for early stage esophageal squamous cell carcinoma -- as two patients had two synchronous esophageal cancers, 20 lesions were treated. Tumors were staged as Tis in 7 cases and T1 in 13. The average light energy delivered was 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. To obtain a more uniform distribution of laser light in 12 cases the irradiation was performed through the wall of a transparent tube previously placed over the endoscope and advanced into the stomach. The overall results show a complete response in 14/20 (70%) tumors. Three patients developed a local recurrence, 6, 12, and 14 months after therapy. After a follow-up of 5 to 75 months, there was no evidence of disease in 10/18 patients (56%). The actuarial survival rate was 95%, 79%, and 26% at 1, 3, and 5 years, respectively. Complications were skin reaction in one patient and esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage, in 2 patients. Endoscopic PDT proved to be safe and effective in the treatment of superficial carcinoma of the esophagus.

Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea; Massetti, Renato; Meroni, Emmanuele

1994-10-01

154

Photodynamic therapy in early esophageal squamous cell carcinoma  

NASA Astrophysics Data System (ADS)

From 1/1985 to 7/1993, 18 patients underwent endoscopic photodynamic therapy (PDT) for early stage esophageal squamous cell carcinoma -- as two patients had two synchronous esophageal cancers, 20 lesions were treated. Tumors were staged as Tis in 7 cases and T1 in 13. The average light energy delivered was 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. To obtain a more uniform distribution of laser light in 12 cases the irradiation was performed through the wall of a transparent tube previously placed over the endoscope and advanced into the stomach. The overall results show a complete response in 14/20 (70%) tumors. Three patients developed a local recurrence, 6, 12, and 14 months after therapy. After a follow-up of 5 to 75 months, there was no evidence of disease in 10/18 patients (56%). The actuarial survival rate was 95%, 79%, and 26% at 1, 3, and 5 years, respectively. Complications were skin reaction in one patient and esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage, in 2 patients. Endoscopic PDT proved to be safe and effective in the treatment of superficial carcinoma of the esophagus.

Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea; Massetti, Renato; Meroni, Emmanuele

1995-03-01

155

Photodynamic therapy for pancreatic and biliary tract carcinoma  

NASA Astrophysics Data System (ADS)

Patients with non-resectable pancreatic and biliary tract cancer (cholangiocarcinoma and gallbladder cancer) have a dismal outlook with conventional palliative therapies, with a median survival of 3-9 months and a 5 year survival of less than 3%. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then is associated with a 5-year survival of less than 30%. Although most applications of photodynamic therapy (PDT) in gastroenterology have been on lesions of the luminal gut, there is increasing experimental and clinical evidence for its efficacy in cancers of the pancreas and biliary tract. Our group has carried out the only clinical study of PDT in pancreatic carcinoma reported to date, and showed that PDT is feasible for local debulking of pancreatic cancer. PDT has also been used with palliative intent in patients with unresectable cholangiocarcinoma, with patients treated with stenting plus PDT reporting improvements in cholestasis, quality of life and survival compared with historical or randomized controls treated with stenting alone. Further controlled studies are needed to establish the influence of PDT and chemotherapy on the survival and quality of life of patients with pancreatic and biliary tract carcinoma.

Pereira, Stephen P.

2009-02-01

156

Effect of photodynamic therapy with verteporfin on tumor blood flow  

NASA Astrophysics Data System (ADS)

The success of photodynamic therapy with verteporfin is partially determined by the pharmacokinetic distribution of the sensitizer at the time of treatment. In this study tumor blood flow changes in the RIF-1 murine tumor model and tumor resopnse using the regrowth assay were measured, comparing two different intervals between drug and light administration. Blood flow measurements were taken with a laser Doppler system monitoring continuously over 1 hour and periodically up to 6 hours after treatment. Treatment after the longer interval caused significantly less flow decrease, to only 50% of the initial flow in 6 h. Hoechst staining of functional tumor vasculature confirmed the primary vascular damage and the decrease in tumor perfusion. The regrowth rate of tumors after the longer time interval, the regrowth rate was not signifincalty different from that of the control, indicating that only the 15-min interval group caused serious damage to the vascular bed of the tumor. These studies support the hypothesis that temporal pharmacokinetic changes in the photosensitizer distribution between the tumor parenchyma and blood vessels can significantly alter the mechanism of tumor targeting during therapy.

Chen, Bin; Pogue, Brian W.; Goodwin, Isak A.; O'Hara, Julia A.; Wilmot, Carmen M.; Hutchins, John E.; Hoopes, P. J.; Hasan, Tayyaba

2003-06-01

157

Breast cancer assessment tools and optimizing adjuvant therapy.  

PubMed

Recommendation of systemic adjuvant therapy and choice of optimal agents for early-stage breast cancer remains a challenge. Adjuvant therapy is indicated on the assumption of residual micrometastatic disease. Adjuvant assessment tools for prognosis and prediction of treatment benefit, including Adjuvant! Online, the St Gallen Consensus, Oncotype DX(®) and MammaPrint(®), aid clinical decision making. However, all of these tools have limitations that must be considered in their judicious application. Clinicopathological based tools are critically dependent on accurate, standardized measurement of parameters. Multigene tools are appealing for their objectivity and reproducibility, particularly regarding analysis of proliferation, but these approaches still overlook the biological heterogeneity within tumors evidenced by distinct cell subpopulations with different genomic patterns and function. The greatest treatment challenge remains for patients assessed as intermediate risk of relapse, a problem not overcome by multigene tools. Remarkable diversity in breast cancer dictates that adjuvant management must be biologically driven. Future identification of predictive biomarkers for specific chemotherapy sensitivity may allow targeted use of available agents, including anthracyclines, taxanes and DNA damaging agents. The presence of drug targets and targetable signaling pathways, rather than molecularly defined subgroups, may ultimately drive treatment decisions. PMID:20975745

Oakman, Catherine; Santarpia, Libero; Di Leo, Angelo

2010-12-01

158

Rethinking of photodynamic therapy on cerebral glioma: the difficult of necrotic tissue exclusion and its sequence  

NASA Astrophysics Data System (ADS)

The photodynamic therapy of cerebral gliomas is one kind of adjunctive therapy after operative tumor removal. But it is not widely accepted until now. We report two cases of failure treatment in our totally consecutive ten patients treated with this method and analyse the cause of the poor outcome. Unlike the uninary system and digest system, the difficult of necrotic tumor or brain tissue exclusion in the brain is marked and resulted in poor result. Our view is that the problem of massive necrotic tumor tissue exclusion which is the wish of therapist and the key of achieving good result might limit the further application of photodynamic therapy on cerebral gliomas.

Qiu, Yongming; Lu, Zhaofeng; Liu, Zhe; Luo, Qi-Zhong

2005-07-01

159

Photodynamic therapy and fluorescent diagnostics of breast cancer  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using Photosense have been provided in 26 patients with breast cancer (BC) and in 108 patients with skin metastases of BC. In 22 patients with T1-T2N0M0 primary tumor PDT was preoperative treatment, with radical mastectomy 7-10 days after PDT. 4 patients had residual tumor after radiotherapy. FD was fulfilled with spectranalyser. We used semiconductive laser for PDT-?=672+2nm, P=1,5 W, interstitial irradiation 2-24 hours after PS injection in light dose 150-200 J/cm3 in patients with primary tumor and multiple surface irradiations (1-4) with interval 24-48 hours and total light dose 400-600 J/cm2 for metastases. Partial regression of tumor with pathomorphosis of 2-4 degree has been found in 23 cases in first group. Treating metastases we had overall response rate of 86,9% with complete response (CR) in 51,5% and partial response in 35,4%. In a year after PDT in 52 patients with CR we had CR in 36,6%, local recurrences in 23,1%, progression (distant [lung or bone] metastasis) in 40,4% of cases. Our experience show pronounced efficacy of FD for detecting tumor borders and PDT for treating BC as preoperative modality and as palliation in cases of recurrencies.

Vakulovskaya, Elena G.; Letyagin, Victor P.; Umnova, Loubov V.; Vorozhcsov, Georgiu N.; Philinov, Victor

2004-06-01

160

Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin  

NASA Astrophysics Data System (ADS)

Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

161

Light dosimetry calculations for esophageal photodynamic therapy using porfimer sodium  

NASA Astrophysics Data System (ADS)

Background: Photodynamic therapy using porfimer sodium (Ps-PDT) is approved for use in patients with Barrett's highgrade dysplasia and esophageal carcinoma. Ps-PDT light dosimetry, however, is critically important to treatment outcomes since insufficient ablation results in residual dysplasia and carcinoma while excessive treatment results in stricture formation. Aim: The aim of this study was to model esophageal PDT with optical absorption and scattering coefficients derived from an ex-vivo porcine multilayer esophagus model. Methods: Optical coefficients were derived for the mucosal and muscle layers of normal pig esophagus. The mucosal layer (mucosa, muscularis mucosa and submucosa) was separated from the muscle layer. Diffuse reflectance and transmittance were measured with an integrating sphere spectrophotometer. Absorption and reduced scattering coefficients were determined with the inverse adding doubling method. (Table not available in abstract, see pdf of paper) Multilayer Monte Carlo simulation and single-layer mathematical dosimetry equations were employed to model esophageal PDT with the derived coefficients. Porfimer sodium addition was modeled with an increase in both absorption and scattering. Depth of injury, assumed to require a threshold light dose, was estimated for various light doses commonly used in clinical practice. Depth of injury was then compared to clinical outcomes reported in the literature for various light doses.

Jones, Linda R.; Preyer, Norris W., Jr.; Davis, Monica A.; Grimes, Carson; Edling, Kristie; Holdgate, Nicholas; Wallace, Michael B.; Wolfsen, Herbert C.

2006-02-01

162

Five years experience of photodynamic therapy with new chlorin photosensitizer  

NASA Astrophysics Data System (ADS)

Clinical results of photodynamic therapy (PDT) with a novel natural second generation chlorin-type photosensitizer "Radachlorin", mainly consisting of sodium chlorine e6, are presented. This sensitizer possesses a number of advantages over sensitizers of hematoporphyrin and phthalocyanine types. In particular, Radachlorin is excreted from organism much faster (in 1-2 days), as a result the problem of patient light hypersensitivity for a few months is non-actual for Radachlorin. As light source there was used a 662 nm diode laser specially designed for PDT with Radachlorin. The 5 year clinical results of PDT application to 89 patients with different malignant tumors are summarized and analysed. It is shown in particular that PDT with Radachlorin is a radical high efficient method for treatment of basal cell carcinoma of skin. At intravenous introduction in drug dose 0.5 mg/kg with light fluence 300-350 J/cm2 or in dose 1 mg/kg with fluence 200-250 J/cm2 the method gives full recovery in almost 100% cases with excellent cosmetic effect. The method was successfully combined with surgical operations, laser ablations, radio- and chemotherapy. Preoperative and intraoperative PDT favors improvement of results in complex treatment of malignant tumors. The method has a potential as palliative measure; in a number of incurable cases it allowed us to achieve recanalization of obturated hollow organs, eliminate the inflammatory complications, and as a result to improve life quality.

Privalov, Valery A.; Lappa, Alexander V.; Kochneva, Elena V.

2005-08-01

163

Measurement of photodynamic therapy drug concentrations in a tissue  

SciTech Connect

This is the final report of a one-year laboratory-directed research and development project at the Los Alamos National Laboratory (LANL). Photodynamic therapy (PDT) is an experimental treatment modality for cancer in which a photoactive molecule with an affinity for tumors in administered to the patient, then excited by light. Photoactivation creates singlet oxygen consequently killing the tissue. Knowledge of the concentration of the photoactive compound in the tissue is necessary for proper light dosimetry during PDT. Presently, the control of light application is problematic. If too much light is applied, damage to the surrounding tissue will occur. If insufficient light is applied, the targeted tissue volume will remain viable. The ideal implementation of PDT would use a feedback system for light delivery that incorporates the optical properties of the tissue and knowledge of the concentration of the photoactive compound. This project sought to develop a method for measuring photosensitizer concentrations in tissue phantoms that will lead to a noninvasive, endoscopically compatible, in vivo method of measuring PST drug concentrations.

Mourant, J.; Biglo, I.; Johnson, T.

1996-09-01

164

Photodynamic therapy for experimental intraocular melanoma using chloroaluminum sulfonated phthalocyanine  

SciTech Connect

Chloroaluminum sulfonated phthalocyanine (CASPc), a novel photosensitizing dye, was evaluated for treatment of experimental intraocular melanoma in 33 rabbit eyes. An argon ion pumped dye laser, operating at an emission of 675 nm, was used in a nonthermal mode to irradiate iris tumors in rabbits 24 hours after they received in intravenous dye injection (23 eyes). The effects of laser irradiation alone and dye alone were examined in ten control eyes. A threshold tumoricidal dose was established for photodynamic therapy with CASPc and laser irradiation. Vascular occlusion was produced in a well-circumscribed area corresponding to the boundaries of laser irradiation after CASPc injection. Tumors successfully treated with CASPc and laser irradiation were arrested in growth and exhibited no viable tumor cells on histologic examination. Control tumors continued rapid growth, unaffected by dye or laser. Our data indicate that CASPc demonstrates a strong photosensitizing effect on both tumor and normal tissue. These results suggest that CASPc is a potential photosensitizing compound that may be useful in the treatment of choroidal melanoma.

Panagopoulos, J.A.; Svitra, P.P.; Puliafito, C.A.; Gragoudas, E.S.

1989-06-01

165

Photodynamic Therapy with the Phthalocyanine Photosensitizer Pc 4  

PubMed Central

Photodynamic therapy (PDT) is emerging as a promising non-invasive treatment for cancers. PDT involves either local or systemic administration of a photosensitizing drug, which preferentially localizes within the tumor, followed by illumination of the involved organ with light, usually from a laser source. Here, we provide a selective overview of our experience with PDT at Case Western Reserve University, specifically with the silicon phthalocyanine photosensitizer Pc 4. We first review our in-vitro studies evaluating the mechanism of cell killing by Pc 4-PDT. Then we briefly describe our clinical experience in a Phase I trial of Pc 4-PDT and our preliminary translational studies evaluating the mechanisms behind tumor responses. Preclinical work identified (a) cardiolipin and the anti-apoptotic proteins Bcl-2 and Bcl-xL as targets of Pc 4-PDT, (b) the intrinsic pathway of apoptosis, with the key participation of caspase-3, as a central response of many human cancer cells to Pc 4-PDT, (c) signaling pathways that could modify apoptosis, and (d) a formulation by which Pc 4 could be applied topically to human skin and penetrate at least through the basal layer of the epidermis. Clinical-translational studies enabled us to develop an immunohistochemical assay for caspase-3 activation, using biopsies from patients treated with topical Pc 4 in a Phase I PDT trial for cutaneous T-cell lymphoma. Results suggest that this assay may be used as an early biomarker of clinical response. PMID:17397888

Miller, Janine D.; Baron, Elma D.; Scull, Heather; Hsia, Andrew; Berlin, Jeffrey C.; McCormick, Thomas; Colussi, Valdir; Kenney, Malcolm E.; Cooper, Kevin D.; Oleinick, Nancy L.

2007-01-01

166

Linear feasibility algorithms for treatment planning in interstitial photodynamic therapy  

NASA Astrophysics Data System (ADS)

Interstitial Photodynamic therapy (IPDT) has been under intense investigation in recent years, with multiple clinical trials underway. This effort has demanded the development of optimization strategies that determine the best locations and output powers for light sources (cylindrical or point diffusers) to achieve an optimal light delivery. Furthermore, we have recently introduced cylindrical diffusers with customizable emission profiles, placing additional requirements on the optimization algorithms, particularly in terms of the stability of the inverse problem. Here, we present a general class of linear feasibility algorithms and their properties. Moreover, we compare two particular instances of these algorithms, which are been used in the context of IPDT: the Cimmino algorithm and a weighted gradient descent (WGD) algorithm. The algorithms were compared in terms of their convergence properties, the cost function they minimize in the infeasible case, their ability to regularize the inverse problem, and the resulting optimal light dose distributions. Our results show that the WGD algorithm overall performs slightly better than the Cimmino algorithm and that it converges to a minimizer of a clinically relevant cost function in the infeasible case. Interestingly however, treatment plans resulting from either algorithms were very similar in terms of the resulting fluence maps and dose volume histograms, once the diffuser powers adjusted to achieve equal prostate coverage.

Rendon, A.; Beck, J. C.; Lilge, Lothar

2008-02-01

167

Photodynamic therapy with fullerenes in vivo: reality or a dream?  

PubMed

Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine. PMID:22122587

Sharma, Sulbha K; Chiang, Long Y; Hamblin, Michael R

2011-12-01

168

Photodynamic therapy for melanoma: efficacy and immunologic effects  

NASA Astrophysics Data System (ADS)

Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

2014-02-01

169

Photodynamic therapy for locally advanced pancreatic cancer: early clinical results  

NASA Astrophysics Data System (ADS)

Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

2010-02-01

170

Photodynamic Therapy Induces Apoptosis in Intimal Hyperplastic Arteries  

PubMed Central

Photodynamic therapy (PDT) generates free radicals through the absorption of light by photosensitizers. PDT shows promise in the treatment of intimal hyperplasia, which contributes to restenosis, by completely eradicating cells in the vessel wall. This study investigates the mechanisms of PDT-induced cell death. PDT, using the photosensitizer chloroaluminum-sulfonated phthalocyanine (1 mg/kg) and laser light (? = 675 nm) 100 J/cm2 was administered to rat carotid arteries after balloon injury-induced intimal hyperplasia. Apoptosis was determined by cell morphology with light microscopy and transmission electron microscopy, DNA cleavage by terminal dUTP nick-end labeling staining, and nucleosomal fragmentation (ladder pattern) by DNA agarose gel electrophoresis. Four hours after PDT, apoptosis was observed in vascular cells, as evidenced by terminal dUTP nick-end labeling staining and transmission electron microscopy. Within 24 hours no cells were present in the neointima and media. Immunofluorescence using an ?-smooth muscle cell actin antibody confirmed the disappearance of all neointimal and medial cells within 24 hours. No inflammatory cell infiltrate was observed during this time frame. Apoptosis was sharply confined to the PDT treatment field. These data demonstrate that vascular PDT induces apoptosis as a mechanism of rapid, complete, and precise cell eradication in the artery wall. These findings and the lack of inflammatory reaction provide the basis for understanding and developing PDT for a successful clinical application in the treatment of hyperplastic conditions such as restenosis. PMID:10980126

LaMuraglia, Glenn M.; Schiereck, Jan; Heckenkamp, Joerg; Nigri, Giuseppe; Waterman, Peter; Leszczynski, Dariusz; Kossodo, Sylvie

2000-01-01

171

Model for monitoring the process of photodynamic therapy in patients  

NASA Astrophysics Data System (ADS)

The photodynamic therapy (PDT) on tumors is quite effective and widely applied but usually carried out without an immediate evaluation of results. We measured the tumor fluorescence in mice with a fiber probe connected to a linear array spectral analyzer (PMA-11, Hamamatsu Photonics). The spectrum showed a transient change in fluorescence color from red to green during Photofrin?R-mediated PDT. In order to examine the source of green fluorescence, the mitochondria were accessed under a Nipkow disk-scanning confocal microscope in the HeLa cell in culture after labeling them with a red fluorescent protein (DsRed1-mito) and staining the cell with Photofrin?R (Axcan Scandipharm). Changes in fluorescence color from red to green were observed in the area of mitochondria upon their swelling during irradiation. This finding in vitro provided clear evidence that the change in fluorescence color from red to green observed in vivo was due to the mitochondrial destruction associated with the cell-death by PDT. This technique of spectral monitoring in tumor may be useful for detection of the cell-death signal during PDT in patients.

Yoshida, Takato O.; Kohno, Eiji; Sakurai, Takashi; Hirano, Toru; Yamamoto, Seiji; Terakawa, Susumu

2005-07-01

172

Photodynamic therapy with fullerenes in vivo: reality or a dream?  

PubMed Central

Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine. PMID:22122587

Sharma, Sulbha K; Chiang, Long Y; Hamblin, Michael R

2012-01-01

173

Photodynamic therapy on the ultrastructure of glioma cell  

NASA Astrophysics Data System (ADS)

OBJECTIVE ?the main purpose of this experiment was to study the change of C6 glioma cells' ultrastructure treated by photodynamic therapy(PDT), observe the change of morphology METHOD ?Make the model of rat glioma by transplanted C6 glioma cells into caudate nucleus?treated the glioma rat by PDT after two weeks. Observed the difference of subcellular structure before and after PDT by electron microscope. RESULT ? Apoptosis and necrosis can be seen after treated by PDT in the C6 glioma, basal membrance damaged ?number of cellular organ of endothelial cell of blood capillary declined?tight junction of endothelial cell lengthen and the gap enlarge. The PDT has slightly effect on the nomorl rat"s subcellular structue. CONCLUSION: PDT can induce the apoptosis and necrosis of C6 glioma cell. The damage of the ultramicrostructure of mitochondria and endoplasmic reticulum was the foundmentol of the change. PDT initiate the damage of BBB of the C6 glioma cell and weeken the function?and makes it a useful way of treating the glioma combained with chemotherapy.

Hu, Shaoshan; Zhang, Ruyou; Zheng, Yongri

2005-07-01

174

Using fluorescence to augment the efficacy of photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) is a relatively novel oncological treatment modality, in which a patient is administered a photosensitive drug, called a photosensitizer. After allowing sufficient time for biodistribution, the cancerous area is irradiated with light of the appropriate wavelength, activating the photosensitizer to produce highly reactive singlet oxygen, which produces a highly localized cell kill. The efficacy of PDT is determined by a) the intensity of the light b) the local concentration of the photosensitizer, and c) the availability of oxygen. However, with the clinical application of PDT, the patient is simply administered a body mass dependent quantity of photosensitizer, and then the target area is administered a prescribed amount of radiant energy (joules per cubic centimetre). For treatment of superficial malignancies, PDT has many successes; however, interstitial PDT (PDT of solid, internal malignancies) has inconsistent outcomes mostly due to the inability to predict, calculate or measure the variables that affect PDT: the radiation dose, oxygen concentration, and the photosensitizer concentration. We have developed sophisticated methods to determine the behaviour of light in homogeneous biological tissues. Tissue oxygen levels can be replenished by fractionating the light dose - allowing areas of your target tissue to go through a "dark" cycle during PDT. However, to date, there has not been an accurate method of determining tissue photosensitizer concentrations in-vivo. We are researching the efficacy of a novel hypocrellin derivative, SL-052. Like other photosensitizers available, SL-052 shows strong therapeutic photodynamic activity when irradiated by 635 nm light. Like most photosensitizers, SL-052 exhibits fluorescent activity, but SL-052 also shows strong fluorescent emission at 725nm when excited by 635 nm. The intensity of the fluorescent emission can been correlated with the local concentration of the photosenstizer. However, many clinically available photosensitizers require that fluorescence is excited using a wavelength of light much shorter than the therapeutic wavelength. This characteristic allows us to monitor the availability of the photosensitizer during PDT and to correlate the outcome of PDT to the observed fluorescence. In this paper, we monitor the temporal distribution of SL-052 in the Dunning R3327-AT cell line grown on the flank of a Fisher Copenhangen rats.

Dickey, Dwayne J.; Liu, Weiyang; Naicker, Selvaraj; Woo, Thomas; Moore, Ronald B.; Tulip, John

2006-09-01

175

Barrett's esophagus: photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa, and treatment of superficial esophageal cancer  

Microsoft Academic Search

Fifteen patients with Barrett's esophagus and dysplasia were treated with photodynamic therapy. Four patients also had early, superficial esophageal cancers and 5 had esophageal polyps. Light was delivered via a standard diffuser or a centering esophageal balloon. Eight patients maintained on omeprazole and followed for 6 - 54 months are the subject of this report. Photodynamic therapy ablated dysplastic or

Bergein F. Overholt; Masoud Panjehpour

1995-01-01

176

Simultaneous but Not Prior Inhibition of VEGF165 Enhances the Efficacy of Photodynamic Therapy in Multiple Models of Ocular Neovascularization  

Microsoft Academic Search

PURPOSE. To investigate the effect of the combined treatment of photodynamic therapy and specific VEGF165 inhibition with pegaptanib sodium (Macugen; Eyetech Pharmaceuticals, Lex- ington, MA) on ocular neovascularization. METHODS. Photodynamic therapy's (PDT's) effects on the integ- rity of pegaptanib sodium were analyzed by HPLC, a VEGF165- binding assay, and a VEGF165-induced tissue factor gene ex- pression assay. The effects of

Meihua Ju; Carolina Mailhos; John Bradley; Tracy Dowie; Mary Ganley; Gary Cook; Perry Calias; Norbert Lange; Anthony P. Adamis; David T. Shima; Gregory S. Robinson

2008-01-01

177

Photodynamic therapy: a promising new modality for the treatment of cancer  

Microsoft Academic Search

The first reports on photodynamic therapy (PDT) date back to the 1970s. Since then, several thousands of patients, both with early stage and advanced stage solid tumours, have been treated with PDT and many claims have been made regarding its efficacy. Nevertheless, the therapy has not yet found general acceptance by oncologists. Therefore it seems legitimate to ask whether PDT

J. J. Schuitmaker; P. Baas; H. L. L. M. van Leengoed; F. W. van der Meulen; W. M. Star; N. van Zandwijk

1996-01-01

178

Evaluating outcomes of palliative photodynamic therapy: instrument development and preliminary results  

Microsoft Academic Search

Background: Subjective measures are considered the gold standard in palliative care evaluation, but no studies have evaluated palliative photodynamic therapy (PDT) subjectively. If PDT is to be accepted as a palliative therapy for later-stage obstructing esophageal and lung cancer, evidence of its effectiveness and acceptability to patients must be made known. Study Design\\/Materials and Methods: This ongoing study's major aim

Teresa T. Goodell; Paulo R. Bargo; Steven L. Jacques

2002-01-01

179

Photodynamic therapy of cancer: five-year clinical experience  

NASA Astrophysics Data System (ADS)

The results of application of photodynamic therapy (PDT) for treatment of malignant tumors of skin, breasts, tongue, oral mucose, lower lip, larynx, stomach, bladder, rectum and other localizations were assessed. In 1992 - 1997 more than 1200 tumoral foci in 288 patients have been treated with PDT. Most of the patients have been taken for PDT for tumoral recurrences or intradermal metastases after surgery, gamma- therapy or combined treatment. A certain number of patients had not been treated before due to severe accompanying diseases or old age. Russian photosensitizers Photoheme in dosage 1.0 - 5.0 mg/kg body weight, and Photosense in dosage 0.5 - 1.5 mg/kg body weight were used. Laser irradiation was performed using Coherent 'Innova-200' and Russian laser devices: copper vapor-pumped dye laser (wavelength 630 nm, output power -- 5 W), gold-vapor lasers (wavelength 628 nm, output power -- 2 W), solid-state laser (wavelength 670 nm, output power -- 2 W). In several cases non-laser light emitting devices have been employed. Up to date we possess the follow-up data in term from 2 months to 5 years. Therapeutic effect took place in 94.4% of the cases, including complete tumor resorption in 56.2% and partial resorption in 38.2% of the cases. The results of PDT application for treating malignant tumors allow one to estimate PDT as an adequate technique and in some tumor localizations PDT might become a method of choice. This new promising technique of cancer treatment is successfully applied in Russia. New photosensitizers and sources of light for PDT and fluorescent diagnostics are being developed.

Stranadko, Eugeny P.; Skobelkin, Oleg K.; Vorozhtsov, Georgy N.; Mironov, Andrei F.; Beshleul, Stanislav E.; Markitchev, Nikolai A.; Riabov, Michail V.

1997-12-01

180

Stimulation of dendritic cells enhances immune response after photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

2009-02-01

181

Photodynamic therapy for localized infections - state of the art  

PubMed Central

Photodynamic therapy (PDT) was discovered over one hundred years ago by observing the killing of microorganisms when harmless dyes and visible light were combined in vitro. Since then it has primarily been developed as a treatment for cancer, ophthalmologic disorders and in dermatology. However in recent years interest in the antimicrobial effects of PDT has revived and it has been proposed as a therapy for a large variety of localized infections. This revival of interest has largely been driven by the inexorable increase in drug resistance amongst many classes of pathogen. Advantages of PDT include equal killing effectiveness regardless of antibiotic resistance, and a lack of induction of PDT resistance. Disadvantages include the cessation of the antimicrobial effect when the light is turned off, and less than perfect selectivity for microbial cells over host tissue. This review will cover the use of PDT to kill or inactivate pathogens in ex vivo tissues and in biological materials such as blood. PDT has been successfully used to kill pathogens and even to save life in several animal models of localized infections such as surface wounds, burns, oral sites, abscesses and the middle ear. A large number of clinical studies of PDT for viral papillomatosis lesions and for acne refer to its anti-microbial effect, but it is unclear how important this microbial killing is to the overall therapeutic outcome. PDT for periodontitis is a rapidly growing clinical application and other dental applications are under investigation. PDT is being clinically studied for other dermatological infections such as leishmaniasis and mycobacteria. Antimicrobial PDT will become more important in the future as antibiotic resistance is only expected to continue to increase. PMID:19932449

Dai, Tianhong; Huang, Ying-Ying; Hamblin, Michael R

2009-01-01

182

Toluidine blue O-conjugated gold nanoparticles for photodynamic therapy of cultured colon cancer  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is an emerging technique for the treatment of cancerous and non-cancerous conditions. Gold nanoparticles (GNPs) possess unique physical and chemical properties which allow them to act as multifunctional agents in nanomedicine. GNP- photosensitizer conjugates have attracted increasing attention in drug delivery for photodynamic cancer therapy. In the present investigation, we prepared covalent conjugates of the photosensitizer Toluidine Blue O (TBO) and thiol protected GNPs. The suitability of TBO- GNPs conjugates for in vitro PDT was assayed using the SW480 Human colon adenocarcinoma cell line. Our results suggest that gold nanoparticle conjugates are an excellent vehicle for delivery of photosensitizer agents in the photodynamic therapy of cultured tumour cells.

Al-Majmaie, Rasoul; Alattar, Nebras; Zerulla, Dominic; Al-Rubeai, Mohamed

2012-06-01

183

DNA minigene vaccination for adjuvant neuroblastoma therapy.  

PubMed

The disruption of self-tolerance against neuroblastoma is the ultimate goal of an effective DNA-vaccine. We demonstrate the induction of protective immunity against syngeneic murine NXS2 neuroblastoma in A/J mice following vaccination with tyrosine hydroxylase (TH)-derived antigens. Oral gene delivery was accomplished using an attenuated strain of Salmonella typhimurium as a carrier harboring vectors encoding for mouse tyrosine hydroxylase (mTH) antigens. Vaccination was effective in protecting animals from a lethal challenge with wild-type NXS2 tumor cells. These findings were extended by comparing efficacy of mTH minigene vaccines with a minigene vaccine comprising three novel epitopes isolated fom NXS2 neuroblastoma cells. For this purpose, MHC class I was immunoprecipitated from NXS2 cell lysates, and peptides were eluted and examined in tandem-mass spectrometry analysis. This led to the identification of three novel natural MHC class I peptide ligands: TEALPVKLI, from ribonucleotide reductase M2; NEYIMSLI, from Ser/Thr protein phosphatase 2A; and FEMVSTLI, of unknown origin. Two minigenes were constructed, one encoding for the three novel epitopes and the second for three known mTH-derived epitopes with high predicted binding affinity to MHC class I, by cloning them into the mammalian expression vector pCMV-3FUB. Immunized mice showed a reduction in primary tumor growth and the absence of spontaneous liver metastasis in the majority of animals. Importantly, there was no significant difference between the two minigenes, suggesting that, compared with tumor peptide isolation, mTH epitope prediction is similarly effective for designing efficient DNA-minigene vaccines. In summary, these findings establish proof of the concept that disruption of self-tolerance against neuroblastoma-associated epitopes may be an effective adjuvant therapeutic strategy. PMID:15650237

Lode, Holger N; Huebener, Nicole; Zeng, Yan; Fest, Stefan; Weixler, S; Gaedicke, Gerhard

2004-12-01

184

[Laparoscopic surgery and adjuvant therapy for colon cancer].  

PubMed

At present, about 10% of all oncological procedures in the colon are carried out laparoscopically. Acceptance is increasing. After successful R0 resection, the rule for stage III patients is: adjuvant therapy is indicated regardless of age. Regimens containing oxaliplatin should be used. If there are contraindications for oxaliplatin, then fluoropyrimidine monotherapy is indicated, with oral fluoropyrimidines (capecitabine) being given precedence over infusional schemes. The use of 5-FU bolus regimens is regarded as obsolete. For stage II, the following applies: If an adjuvant chemotherapy is planned in these patients on the basis of the QUASAR data, then fluoropyrimidine monotherapy (e. g. capecitabine) can be given. Since patients whose tumours show a high frequency of microsatellite instability (MSI) do not benefit from a fluoropyrimidine monotherapy, the MSI status should be determined before choosing therapy. PMID:19546595

Kubicka, Stefan; Geissler, Michael; Bruch, Hans-Peter; Trarbach, Tanja

2009-01-01

185

Contrast enhanced-magnetic resonance imaging as a surrogate to map verteporfin delivery in photodynamic therapy  

NASA Astrophysics Data System (ADS)

The use of in vivo contrast-enhanced magnetic resonance (MR) imaging as a surrogate for photosensitizer (verteporfin) dosimetry in photodynamic therapy of pancreas cancer is demonstrated by correlating MR contrast uptake to ex vivo fluorescence images on excised tissue. An orthotopic pancreatic xenograft mouse model was used for the study. A strong correlation (r=0.57) was found for bulk intensity measurements of T1-weighted gadolinium enhancement and verteporfin fluorescence in the tumor region of interest. The use of contrast-enhanced MR imaging shows promise as a method for treatment planning and photosensitizer dosimetry in human photodynamic therapy (PDT) of pancreas cancer.

Samkoe, Kimberley S.; Bryant, Amber; Gunn, Jason R.; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

2013-12-01

186

Quantum dot-folic acid conjugates as potential photosensitizers in photodynamic therapy of cancer.  

PubMed

This study examined the in vitro potential of bioconjugated quantum dots (QDs) as photosensitizers for photodynamic therapy (PDT). According to our previous approaches using photosensitizers, folic acid appears to be an optimal targeting ligand for selective delivery of attached therapeutic agents to cancer tissues. We synthesized hydrophilic near infrared emitting CdTe(S)-type QDs conjugated with folic acid using different spacers. Photodynamic efficiency of QDs conjugated or not with folic acid was evaluated on KB cells, acting as a positive control due to their overexpression of FR-?, and HT-29 cells lacking FR-?, as negative control. A design of experiments was suggested as a rational solution to evaluate the impacts of each experimental factor (QD type and concentration, light fluence and excitation wavelength, time of contact before irradiation and cell phenotype). We demonstrated that, for concentrations lower than 10 nM, QDs displayed practically no cytotoxic effect without light exposure for both cell lines. Whereas QDs at 2.1 nM displayed a weak photodynamic activity, a concentration of 8 nM significantly enhanced the photodynamic efficiency characterized by a light dose-dependent response. A statistically significant difference in photodynamic efficiency between KB and HT-29 cells was evidenced in the case of folic acid-conjugated QDs. Optimal conditions led to an enhanced photocytotoxicity response, allowing us to validate the ability of QDs to generate a photodynamic effect and of folic acid-conjugated QDs for targeted PDT. PMID:21479314

Morosini, Vincent; Bastogne, Thierry; Frochot, Céline; Schneider, Raphaël; François, Aurélie; Guillemin, François; Barberi-Heyob, Muriel

2011-05-01

187

Low dose mTHPC photodynamic therapy for cholangiocarcinoma  

NASA Astrophysics Data System (ADS)

Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

2013-06-01

188

Galactodendritic phthalocyanine targets carbohydrate-binding proteins enhancing photodynamic therapy.  

PubMed

Photosensitizers (PSs) are of crucial importance in the effectiveness of photodynamic therapy (PDT) for cancer. Due to their high reactive oxygen species production and strong absorption in the wavelength range between 650 and 850 nm, where tissue light penetration is rather high, phthalocyanines (Pcs) have been studied as PSs of excellence. In this work, we report the evaluation of a phthalocyanine surrounded by a carbohydrate shell of sixteen galactose units distributed in a dendritic manner (PcGal16) as a new and efficient third generation PSs for PDT against two bladder cancer cell lines, HT-1376 and UM-UC-3. Here, we define the role of galacto-dendritic units in promoting the uptake of a Pc through interaction with GLUT1 and galectin-1. The photoactivation of PcGal16 induces cell death by generating oxidative stress. Although PDT with PcGal16 induces an increase on the activity of antioxidant enzymes immediately after PDT, bladder cancer cells are unable to recover from the PDT-induced damage effects for at least 72 h after treatment. PcGal16 co-localization with galectin-1 and GLUT1 and/or generation of oxidative stress after PcGal16 photoactivation induces changes in the levels of these proteins. Knockdown of galectin-1 and GLUT1, via small interfering RNA (siRNA), in bladder cancer cells decreases intracellular uptake and phototoxicity of PcGal16. The results reported herein show PcGal16 as a promising therapeutic agent for the treatment of bladder cancer, which is the fifth most common type of cancer with the highest rate of recurrence of any cancer. PMID:24763311

Pereira, Patrícia M R; Silva, Sandrina; Cavaleiro, José A S; Ribeiro, Carlos A F; Tomé, João P C; Fernandes, Rosa

2014-01-01

189

Photodynamic antimicrobial therapy of curcumin in biofilms and carious dentine.  

PubMed

Photodynamic therapy (PDT) is a technique that involves the activation of photosensitizers by light in the presence of oxygen, resulting in the production of reactive radicals that are capable of inducing cell death. The present study evaluated the susceptibility of Streptococcus mutans and Lactobacillus acidophilus to PDT grown as multi-species in the biofilm phase versus in dentine carious lesions. A brain-heart infusion culture medium supplemented with 1% glucose, 2% sucrose, and 1% young primary culture of L. acidophilus 10(8) CFU/mL and S. mutans 10(8) CFU/mL was used to develop multi-species biofilms and to induce caries on human dentine slabs. Five different concentrations of curcumin (0.75, 1.5, 3.0, 4.0, and 5.0 g/L) were used associated with 5.7 J/cm(2) light emission diode. Four different groups were analyzed L-D- (control group), L-D+ (drug group), L+D- (light group), and L+D+ (PDT group). ANOVA/Tukey's tests were conducted to compare groups. A significant reduction (p <0.05) in cell viability was observed in the biofilm phase following photosensitization with all curcumin concentrations tested. To achieve significant bacterial reduction (p <0.05) in carious dentine, it was necessary to utilize 5.0 g/L of curcumin in association with blue light. No significant reduction was found for L-D+, supporting the absence of the drug's dark toxicity. S. mutans and L. acidophilus were susceptible to curcumin in the presence of blue light. However, due to light penetration and drug diffusion difficulties, these microorganisms within dentine carious lesions were less affected than they were in the biofilm phase. PMID:23793414

Araújo, N C; Fontana, C R; Bagnato, V S; Gerbi, M E M

2014-03-01

190

Interstitial photodynamic therapy for the prostate: a canine feasibility study  

NASA Astrophysics Data System (ADS)

Prior to a possible clinical application of photodynamic therapy (PDT) for prostatic diseases such as benign prostatic hyperplasia and prostate cancer, optical properties of the prostate gland need to be studied. The specific objectives of this study were (1) to determine the light penetration depth, (2) to document the photosensitizer levels in the prostate, and (3) to document the lesion size after PDT. Sixteen dogs were injected with Photofrin II (1, 3 and 5 mg/kg) 24 hrs prior to laser application. After laparotomy and exposure of prostate, monochromatic light (630 nm, via an argon pumped dye laser) was applied through an isotropic fiber at 100 mw for a total dose of 400 joules. Continuous light fluence and temperature were documented. Prostates were harvested at 1 week and examined histologically for the lesion size. Four sham dogs were treated without Photofrin II. At Photofrin doses of 1, 3 and 5 mg/kg the mean prostatic Photofrin levels were 1.78 plus or minus 0.33, 1.47 plus or minus 0.08 and 1.95 plus or minus 0.44 (mu) gm/ml. The mean light penetration depths were 2.08, 1.37 and 1.64 mm respectively. Photofrin dose escalation (1, 3 and 5 mg/kg) increased the lesion size to radius of 4.1 plus or minus 0.9 mm, 4.4 plus or minus 0.8 mm and 6.3 plus or minus 0.9 mm. There were no lesions seen in sham dogs. These results demonstrate that light penetration in prostate is consistent and therapeutic levels of photosensitizer are achieved in prostatic tissue. Moreover, increasing size of the lesions were documented with dose escalation.

Shetty, Sugandh D.; Sirls, Larry T.; Chen, Qun; Hetzel, Fred W.; Cerny, Joseph C.

1996-05-01

191

Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets  

NASA Astrophysics Data System (ADS)

Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment.Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03753g

Liu, Teng; Wang, Chao; Cui, Wei; Gong, Hua; Liang, Chao; Shi, Xiaoze; Li, Zhiwei; Sun, Baoquan; Liu, Zhuang

2014-09-01

192

Optical Dosimetry and Treatment Planning for Photodynamic Therapy  

NASA Astrophysics Data System (ADS)

Accurate dosimetry and treatment planning for photodynamic therapy (PDT) require knowledge of tissue optical properties and models of light propagation. We present techniques, based on reflectance and fluorescence spectroscopy, to examine these problems using analytical approximations and Monte Carlo (MC) simulations. We begin with studies that monitored PDT in mouse models using reflectance and fluorescence spectroscopy. In the first, spectroscopy informed the optimization of treatment parameters for methylene blue PDT, with dependencies on injection vehicle, drug-light interval, and fluence found. In the second, fluorescence photobleaching during Pc 4 PDT was examined for correlation to tumor response. Irradiance-dependent photobleaching was demonstrated, but was not predictive of tumor response. Next we outline the graphics processing unit enhanced MC model that was used to simulate light propagation in tissue. We demonstrate a number of source models that were used in subsequent experiments. We then focus on the recovery of optical properties from diffuse reflectance measurements by examining two studies. In the first study, diffuse reflectance measurements were made at the surface of human kidneys to extract optical properties, which were then used in MC simulations of interstitial PDT. We found that the optical properties measured make PDT feasible in human kidneys. We then examined the interstitial recovery of optical properties using a custom optical probe. This recovery was based on a MC model of the probe used, with a mean error of 6.5% in the determination of absorption. We examined fluorescence detection by cylindrical diffusing fibers using a MC model. This model predicted heterogeneous fluorescence detection, which was verified experimentally. Recovery of intrinsic fluorescence from point, interstitial measurements was demonstrated. This technique did not require a prori knowledge of the tissue optical properties, and was used to determine these values. Mean error of fluorophore concentration recovery was 12%, while mean error for background absorption was 23%. Finally, we demonstrate a treatment planning modality for interstitial PDT based on clinical imaging, optical spectroscopy, and MC simulations. This allows for individualized therapy based on the patient's anatomy and optical properties. We demonstrate optimization of diffuser placement, and show results for determination of deposited dose.

Baran, Timothy M.

193

In vivo resistance to photofrin-mediated photodynamic therapy in radiation-induced fibrosarcoma cells resistant to in vitro Photofrin-mediated photodynamic therapy  

Microsoft Academic Search

The effects of Photofrin-mediated photodynamic therapy (PDT) on the in vitro cell survival and in vivo tumor growth of murine radiation-induced fibrosarcoma (RIF) cell tumors have been examined following in vivo PDT treatment of tumors. The response to in vivo PDT is examined in tumors derived from RIF-1 mouse fibrosarcoma cells and in tumors derived from RIF-8A cells, which show

Kathryn Adams; Andrew J. Rainbow; Brian C. Wilson; Gurmit Singh

1999-01-01

194

Apoptosis of vascular smooth muscle cells induced by photodynamic therapy with protoporphyrin IX  

E-print Network

Apoptosis of vascular smooth muscle cells induced by photodynamic therapy with protoporphyrin IXIX) on the viability of vascular smooth muscle cells (SMCs) and to define the cell-death pathway. FluorescenceIX concentration. The loss of mito- chondrial membrane potential coincided with the apoptotic ratio. Our results

Cao, Wenwu

195

Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: Potential for enhanced topical photodynamic therapy  

Microsoft Academic Search

Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA). In this study, silicon microneedle arrays were used, for the first time, to enhance skin penetration of ALA in vitro and in vivo. Puncturing excised murine skin with 6×7 arrays of microneedles 270 ?m in height, with a

Ryan F. Donnelly; Desmond I. J. Morrow; Paul A. McCarron; A. David Woolfson; Anthony Morrissey; Petras Juzenas; Asta Juzeniene; Vladimir Iani; Helen O. McCarthy; Johan Moan

2008-01-01

196

Photodynamic Therapy of Vulvar Intraepithelial Neoplasia III Using Topically Applied 5-Aminolevulinic Acid  

Microsoft Academic Search

Objectives. The aim of this study was twofold: first, to determine the feasibility of photodynamic therapy (PDT) of vulvar intraepithelial neoplasia III (VIN III) using topically applied 5-aminolevulinic acid (ALA) for photosensitization, and second, to compare PDT results with those of laser evaporation and local excision.Methods. Fifteen patients with VIN III had 10 g of 10% ALA gel applied to

Mathias K. Fehr; René Hornung; Viola A. Schwarz; René Simeon; Urs Haller; Pius Wyss

2001-01-01

197

Topical ALA-Photodynamic Therapy for the Treatment of Acne Vulgaris  

Microsoft Academic Search

Topical aminolevulinic acid is converted into a potent photosensitizer, protoporphyrin, in human hair follicles and sebaceous glands. Photodynamic therapy with topical aminolevulinic acid was tested for the treatment of acne vulgaris, in an open-label prospective human study. Each of 22 subjects with acne on the back was treated in four sites with aminolevulinic acid plus red light, aminolevulinic acid alone,

Wichai Hongcharu; Charles R. Taylor; Yuchiao Chang; David Aghassi; Kittisak Suthamjariya; R. Rox Anderson

2000-01-01

198

State of the art in the delivery of photosensitizers for photodynamic therapy  

Microsoft Academic Search

In photodynamic therapy, one of the problems limiting the use of many photosensitizers (PS) is the difficulty in preparing pharmaceutical formulations that enable their parenteral administration. Due to their low water solubility, the hydrophobic PS cannot be simply injected intravenously. Different strategies, including polymer–PS conjugation or encapsulation of the drug in colloidal carriers such as oil-dispersions, liposomes and polymeric particles,

Yvette Niamien Konan; Robert Gurny; Eric Allémann

2002-01-01

199

Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)  

Microsoft Academic Search

Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg-1 of

V H Fingar; P K Kik; P S Haydon; P B Cerrito; M Tseng; E Abang; T J Wieman

1999-01-01

200

Buried Barrett's Epithelium Following Photodynamic Therapy Shows Reduced Crypt Proliferation and Absence of DNA Content Abnormalities  

Microsoft Academic Search

OBJECTIVES:Photodynamic therapy (PDT) is increasingly used for the treatment of patients with Barrett's esophagus (BE) with dysplasia or early carcinoma. Post-PDT, some patients show residual BE either exposed to the luminal surface (nonburied) or buried underneath reepithelialized squamous mucosa (buried BE). Buried BE may be a serious clinical problem since it can go unnoticed during surveillance endoscopies. The neoplastic potential

Jason L Hornick; Mari Mino-Kenudson; Gregory Y Lauwers; Weitian Liu; Raj Goyal; Robert D Odze

2008-01-01

201

Chapter 6 Light sources for photodynamic therapy and fluorescence diagnosis in dermatology  

Microsoft Academic Search

Photoactivation of sensitizers is a basic requirement in photodynamic therapy (PDT) and fluorescence diagnosis (FD). After absorption of light by a sensitizer the energy of the light is stored in the singlet or triplet state of the sensitizer molecule. In the singlet state the energy is converted to heat or is emitted as light used for fluorescence diagnosis, whereas the

Wolfgang Bäumler

2001-01-01

202

Photodynamic therapy on bacterial reduction in dental caries: in vivo study  

Microsoft Academic Search

The reduction of pathogenic microorganisms in supragingival plaque is one of the principal factors in caries prevention and control. A large number of microorganisms have been reported to be inactivated in vitro by photodynamic therapy (PDT). The purpose of this study was to develop a rat model to investigate the effects of PDT on bacterial reduction in induced dental caries.

Alessandra Baptista; Renato Araujo Prates; Ilka Tiemy Kato; Marcello Magri Amaral; Anderson Zanardi de Freitas; Martha Simões Ribeiro

2010-01-01

203

Development of a device for photodynamic therapy of oral cavity mucous  

NASA Astrophysics Data System (ADS)

The device, offered for reviewing, was designed and developed for photodynamic therapy of oral cavity mucous diseases and for laboratory experiments on the red light influence on the bacterial colonies in presence of a dye. The device has rather simple construction, it is cheap but convenience in use.

Ovchinnikov, Ilya S.; Tuchin, Valery V.; Ulyanov, Sergey S.

1999-03-01

204

Laser speckle imaging of dynamic changes in flow during photodynamic therapy  

Microsoft Academic Search

We present a study investigating the use of laser speckle imaging (LSI) for monitoring blood flow during photodynamic therapy (PDT) utilizing the therapeutic illumination radiation. The coherent nature of a laser source, often used in PDT, offers the possibility of obtaining information on the blood flow without interrupting treatment. We have found that in the rat skin-fold observation chamber, it

B. Kruijt; H. S. de Bruijn; A. van der Ploeg-van den Heuvel; H. J. C. M. Sterenborg; D. J. Robinson

2006-01-01

205

Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens  

Microsoft Academic Search

Background and Objectives: Previous in vitro studies demonstrated the potential utility of benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy (PDT) for vascular destruction. Moreover, the effects of PDT were enhanced when this intervention was followed immediately by pulsed dye laser (PDL) irradiation (PDT\\/ PDL). We further evaluate vascular effects of PDT alone, PDL alone and PDT\\/PDL in an in

Tia K. Smith; Bernard Choi; J. Stuart Nelson; Kathryn Osann; Kristen M. Kelly

2006-01-01

206

Evaluation of cytotoxic effect of photodynamic therapy in combination with electroporation in vitro  

Microsoft Academic Search

Under the influence of electric pulses cells undergo membrane electroporation (EP), which results in increased permeability of the membrane to exogenous compounds. EP is applied in oncology as a method to enhance delivery of anticancer drugs.For that reason it was essential to combine photodynamic tumor therapy (PDT)—the cancer treatment method based on the use of photosensitizers that localize selectively in

J. Labanauskiene; J. Gehl; J. Didziapetriene

2007-01-01

207

Comparison between scaling-root-planing (SRP) and SRP/photodynamic therapy: six-month study  

PubMed Central

Introduction The purpose of this long-term clinical study was to examine the additional efficacy of photodynamic therapy (PDT) to scaling and root planing (SRP) in patients with chronic periodontal disease. Methods A total of 22 patients (mean age: 59.3 ± 11.7 years) with chronic periodontal disease and four teeth with probing depth ? 5 mm were enrolled in the study. Inclusion criteria were: no systemic disease, no smoking, no pregnancy and no long-term medication. Beside the anamnesis, the following clinical parameters were assessed at baseline (one week before therapy), and one, three and six months after the therapy: bleeding on probing (BOP), plaque index (PI) probing depth (PD), and clinical attachment loss. All measurements were done by the same examiner with a fixed periodontal probe (PCP 12, Hu-Friedy) at six measurements/tooth. In each patient, two teeth were treated with SRP alone and two teeth with SRP and PDT (Periowave, Ondine Biopharma, Vancouver, Canada). The nonparametric Wilcoxon test for paired samples was used for comparison of the effect of the two treatments (p ? 0.05). Results After both types of treatment, the number of teeth positive for BOP declined. At baseline, the CAL measured 7.2 ± 1.2 mm (SRP) or 8.1 ± 1.3 mm (SRP/PDT); one, three and six months after both types of treatment an improvement was observed. At baseline, the probing depth was 5.9 ± 0.8 mm (SRP) or 6.4 ± 0.8 mm (SRP/PDT); after six months, an improvement of 2.4 ± 0.6 mm (SRP) or 2.9 ± 0.8 mm (SRP/PDT) was found. The greater reduction of the PD, achieved by a combination of SRP/PDT, was statistically significant after six months (p = 0.007). Conclusion This clinical study demonstrates that SRP in combination with PDT seems to be effective and is therefore suitable as an adjuvant therapy to the mechanical conditioning of the periodontal pockets in patients with chronic periodontal diseases. PMID:22480188

2012-01-01

208

Multifunctional gold nanoparticles for photodynamic therapy of cancer  

NASA Astrophysics Data System (ADS)

As an important and growing branch of photomedicine, photodynamic therapy (PDT) is being increasingly employed in clinical applications particularly for the treatment of skin cancer. This dissertation focuses on the synthesis, characterization and deployment of gold nanoparticles for enhanced PDT of fibrosarcoma cancer cells. We have developed robust strategies and methods in fabrication of gold nanoparticles with positively- and negatively-tethered surface charges by photo-reduction of gold chloride salt using branched polyethyleneimine and sodium citrate respectively. An optimal concentration window of gold salt has been established to yield the most stable and monodispersed gold nanoparticles. 5-aminolevulinic acid (5-ALA), a photosensitizing precursor, has been successfully conjugated on to positively charged gold nanoparticles through electrostatic interactions. The 5-ALA/gold nanoparticle conjugates are biocompatible and have shown to be preferably taken up by cancer cells. Subsequent light irradiation results in the generation of reactive oxygen species (ROS) in cancer cells, leading to their destruction without adverse effects on normal fibroblasts. We have demonstrated for the first time that gold nanoparticles can enhance PDT efficacy by 50% compared to the treatment with 5-ALA alone. Collected evidence has strongly suggested that this enhancement stems from the elevated formation of ROS via the strongly localized electric field of gold nanoparticles. Through single cell imaging using surface-enhanced Raman scattering enabled by the very same gold nanoparticles, we have shown that multifunctionality of gold nanoparticles can be harvested concurrently for biomedical applications in general and for PDT in specific. In other words, gold nanoparticles can be used not only for targeted drug delivery and field-enhanced ROS formation, but also for monitoring cell destructions during PDT. Finally, our COMSOL Multiphysics simulation of the size-dependent electric field intensity, the measured increase in ROS formation and SERS sensitivity with the particle size all converge to a common origin of the surface plasmon resonance of gold nanoparticles and serve to indicate its beneficial role in field-enhanced processes. By integrating nanotechnology with PDT and with the promising outcome, this research has made a significant contribution in advancing the frontier of photomedicine.

Khaing Oo, Maung Kyaw

209

A rationale for treating leg length discrepancy using photodynamic therapy  

NASA Astrophysics Data System (ADS)

This study investigates the use of photodynamic therapy (PDT) in regulating bone development with a view to its potential role in treating Juvenile leg length discrepancy (LLD). Transgenic mice expressing the luciferase firefly gene upon activation of a promoter sequence specific to the vascular endothelial growth factor (VEGF) gene were subject to benzoporphyrin derivative monoacid (BPD-MA)-mediated PDT in the right, tibial epiphyseal growth plate at the age of 3 weeks. BPD-MA was administered intracardially (2mg/kg) followed 10 mins later by a laser light (690 +/- 5 nm) at a range of doses (5-27J, 50 mW output) delivered either as a single or repeat regimen (x2-3). Contra-lateral legs served as no-light controls. Further controls included animals that received light treatment in the absence of photosensitizer or no treatment. Mice were imaged for VEGF related bioluminescence (photons/sec/steradian) at t= 0, 24, 48, 72 h and 1-4 weeks post PDT. FaxitronTM x-ray images provided accurate assessment of bone morphometry. Upon sacrifice, the tibia and femur of the treated and untreated limbs were harvested, imaged and measured again and prepared for histology. A number of animals were sacrificed at 24 h post PDT to allow immunohistochemical staining for CD31, VEGF and hypoxia-inducible factor (HIF-1 alpha) within the bone. PDT-treated (10 J, x2) mice displayed enhanced bioluminescence at the treatment site (and ear nick) for up to 4 weeks post treatment while control mice were bioluminescent at the ear-nick site only. Repeat regimens provided greater shortening of the limb than the corresponding single treatment. PDT-treated limbs were shorter by 3-4 mm on average as compared to the contra lateral and light only controls (10 J, x2). Immunohistochemistry confirmed the enhanced expression VEGF and CD31 at 4 weeks post-treatment although no increase in HIF-1? was evident at either 24 h or 4 weeks post PDT treatment. Results confirm the utility of PDT to provide localized effects on bone development that may be applicable to other related skeletal deformities.

Bisland, Stuart K.; Johnson, Crystal; Diab, Mohammed; Wilson, Brian C.; Burch, Shane

2005-09-01

210

Treatment parameters affecting the response of normal brain to photodynamic therapy  

NASA Astrophysics Data System (ADS)

Different aspects of photodynamic therapy in normal rat brain tissue have been studied, in an effort to understand and improve the dosimetry of this new modality in treatment of brain tumors. dosimetry parameters, including light energy dose, fluence rate and beam size, and drug dosage were studied. PDT induced lesion depth in brain was measured as a biological endpoint. Effective attenuation depth and absolute light fluence rate distribution under superficial irradiation were measured using invasive optical probes. Photosensitizer uptake was quantified using HPLC analysis. The results indicate that normal brain have a high intrinsic sensitivity to PDT treatment, based on the estimated photodynamic threshold.

Chen, Qun; Chopp, Michael; Dereski, Mary O.; Wilson, Brian C.; Patterson, Michael S.; Kessel, David; Heads, Larry; Hetzel, Fred W.

1993-06-01

211

Study Of Laser Hyperthermia, Photodynamic Therapy And The Combined Therapy For Human Pancreatic Cancer Cell Line  

NASA Astrophysics Data System (ADS)

I have conducted laser hyperthermia, photodynamic therapy (PDT) and the combined therapy of laser hyperthermia and PDT for solid tumor of human pancreatic carcinoma transplanted to nude mice. Following experimental therapies have begun 5-6 weeks after transplantation. 1) Laser hyperthermia: The Frosted Probe was punctured under controlling temperature near the margin of a tumor at 42-43C with 3W for 10 minutes. This therapy caused 70-80% necrosis of the total area of pancreatic tumors after 7 days of the treatment. 2) PDT: Argon dye laser was irradiated into a tumor with 300-400mW in 72 hours after hematoporphyrine derivative (HpD) in a dose of 3mg/kg was intravenously injected. Histological changes detected 7 days after the therapy were coagulated necrosis and fibrosis in the tissues ranging from 30-50% of the area. 3) The combined therapy of laser hyperthermia and PDT: A new quartz fiber, which was originally designed to deliver both Nd:YAG laser and argon dye laser simultaneously, was used. Conditions of laser hyperthermia and PDT were same as above. Necrosis amounted 100% of the total area in tumors of 3 out of 6 mice histopathologically 7 days after the therapy. As for the remaining 3 mice, almost all tissues changed into necrosis. Effects of thermal and laser energy to the tumor tissues were also studied by in vitro experiments under the same conditions. The most remarkable decrease in viability was recognized in the combined therapy of laser hyperthermia and PDT among three types of therapies in vitro. The combined therapy of laser hyperthermia and PDT has proven to be highly effective by in vivo and in vitro study using human pancreatic cancer cell line. It will thus be possible to adopt the therapy, with the use of the new quartz fiber, as one of the useful endoscopic laser therapies.

Tajiri, Hisao

1988-06-01

212

Research Article Chemiluminescent Nanomicelles for Imaging Hydrogen Peroxide and Self-Therapy in Photodynamic Therapy  

E-print Network

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hydrogen peroxide is a signal molecule of the tumor, and its overproduction makes a higher concentration in tumor tissue compared to normal tissue. Based on the fact that peroxalates can make chemiluminescence with a high efficiency in the presence of hydrogen peroxide, we developed nanomicelles composed of peroxalate ester oligomers and fluorescent dyes, called peroxalate nanomicelles (POMs), which could image hydrogen peroxide with high sensitivity and stability. The potential application of the POMs in photodynamic therapy (PDT) for cancer was also investigated. It was found that the PDT-drug-loaded POMs were sensitive to hydrogen peroxide, and the PDT drug could be stimulated by the chemiluminescence from the reaction between POMs and hydrogen peroxide, which carried on a self-therapy of the tumor without the additional laser light resource. 1.

Rui Chen; Luzhong Zhang; Jian Gao; Wei Wu; Yong Hu; Xiqun Jiang

213

Genomic subtypes in choosing adjuvant therapy for breast cancer.  

PubMed

The use of gene expression profiling has impacted our understanding of breast cancer biology and increasingly has played a role in guiding clinical decisions. We have used hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status for years to guide selection of therapy. More recently, gene expression analysis has facilitated the identification of at least five intrinsic subtypes of breast cancer. Potential therapeutic targets have also been identified using genomic profiling. Several tests, such as the 21-gene recurrence score assay (Oncotype DX) and the 70-gene prognosis signature (MammaPrint), have been well validated as prognostic tools for early-stage breast cancer, and have aided in adjuvant therapy decisions for early-stage, HR-positive breast cancer patients. Genomic profiling has the potential to provide additional insight into drug discovery and clinical trial design by identifying appropriate targeted therapies for subtypes of breast cancer. PMID:23687790

Zelnak, Amelia B; O'Regan, Ruth M

2013-03-01

214

Racial and Ethnic Differences in Adjuvant Hormonal Therapy Use  

PubMed Central

Abstract Background In the United States, 5-year breast cancer survival is highest among Asian American women, followed by non-Hispanic white, Hispanic, and African American women. Breast cancer treatment disparities may play a role. We examined racial/ethnic differences in adjuvant hormonal therapy use among women aged 18–64 years, diagnosed with hormone receptor-positive breast cancer, using data collected by the Northern California Breast Cancer Family Registry (NC-BCFR), and explored changes in use over time. Methods Odds ratios (OR) comparing self-reported ever-use by race/ethnicity (African American, Hispanic, non-Hispanic white vs. Asian American) were estimated using multivariable adjusted logistic regression. Analyses were stratified by recruitment phase (phase I, diagnosed January 1995–September 1998, phase II, diagnosed October 1998–April 2003) and genetic susceptibility, as cases with increased genetic susceptibility were oversampled. Results Among 1385 women (731 phase I, 654 phase II), no significant racial/ethnic differences in use were observed among phase I or phase II cases. However, among phase I cases with no susceptibility indicators, African American and non-Hispanic white women were less likely than Asian American women to use hormonal therapy (OR 0.20, 95% confidence interval [CI]0.06–0.60; OR 0.40, CI 0.17–0.94, respectively). No racial/ethnic differences in use were observed among women with 1+ susceptibility indicators from either recruitment phase. Conclusions Racial/ethnic differences in adjuvant hormonal therapy use were limited to earlier diagnosis years (phase I) and were attenuated over time. Findings should be confirmed in other populations but indicate that in this population, treatment disparities between African American and Asian American women narrowed over time as adjuvant hormonal treatments became more commonly prescribed. PMID:22731764

Li, Christopher; John, Esther M.; Terry, Mary Beth; Daly, Mary; Buys, Saundra S.; Habel, Laurel; Thompson, Beti; Yanez, N. David; Coronado, Gloria D.

2012-01-01

215

Photochemical properties and activity of water-soluble polymer/c(60) nanohybrids for photodynamic therapy.  

PubMed

Water-soluble star-like poly(vinyl alcohol)/C(60) and poly{[poly(ethylene glycol) acrylate]-co-(vinyl acetate)}/C(60) nanohybrids are prepared by grafting macroradicals onto C(60) and are assessed as photosensitizers for photodynamic therapy. The photophysical and biological properties of both nanohybrids highlight key characteristics influencing their overall efficiency. The macromolecular structure (linear/graft) and nature (presence/absence of hydroxyl groups) of the polymeric arms respectively impact the photodynamic activity and the stealthiness of the nanohybrids. The advantages of both nanohybrids are encountered in a third one, poly[(N-vinylpyrrolidone)-co-(vinyl acetate)]/C(60) , which has linear grafts without hydroxyl groups, and shows a better photodynamic activity. PMID:23197401

Hurtgen, Marie; Debuigne, Antoine; Hoebeke, Maryse; Passirani, Catherine; Lautram, Nolwenn; Mouithys-Mickalad, Ange; Guelluy, Pierre-Henri; Jérôme, Christine; Detrembleur, Christophe

2013-01-01

216

Use of Erythropoietin as adjuvant therapy in nerve reconstruction  

Microsoft Academic Search

Background and aims  Adjuvant therapies may improve the outcome after nerve reconstruction. We analyzed the influence of recombinant human Erythropoietin\\u000a (rHuEpo), which has proven angiogenic and neuroprotective effects, on the quality of peripheral nerve regeneration.\\u000a \\u000a \\u000a \\u000a Methods  Thirty two female Lewis rats underwent nerve reconstruction by means of tubulization (groups I and II) or autologous sciatic\\u000a nerve grafting (groups III and IV). Groups

J. A. Lohmeyer; E. Essmann; S. J. Richerson; C. Hagel; J. T. Egana; A. Condurache; P. Ganske; K. Schulz; P. Mailänder; H. G. Machens

2008-01-01

217

Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets.  

PubMed

Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment. PMID:25126952

Liu, Teng; Wang, Chao; Cui, Wei; Gong, Hua; Liang, Chao; Shi, Xiaoze; Li, Zhiwei; Sun, Baoquan; Liu, Zhuang

2014-10-01

218

Using antimicrobial adjuvant therapy in cancer treatment: a review  

PubMed Central

Recent clinical and pre-clinical data demonstrate that adjuvant antimicrobial therapy is beneficial in cancer treatment. There could be several reasons for this effect, which include treating cancer associated bacteria and viruses, prophylaxis of post-chemotherapy infections due to immunosuppression, and antiproliferative effect of certain antimicrobials. Targeting cancer associated viruses and bacteria with antimicrobial agents is currently used for gastric, cervical, hematopoietic, liver and brain cancer. However this treatment is effective only in combination with conventional therapies. Antimicrobials can also have a direct antiproliferative and cytotoxic effect, and can cause apoptosis. Moreover, some antimicrobials are known to be helpful in overcoming side effects of drugs commonly used in cancer treatment. Chemotherapy related bacteremia and neutropenia can be overcome by the appropriately timed use of antimicrobials. This review summarizes the data on the effects of antivirals and antibiotics on cancer treatment and describes their mechanisms. PMID:23164412

2012-01-01

219

5-aminolevulinic acid in photodynamic diagnosis and therapy of urological malignancies  

NASA Astrophysics Data System (ADS)

Completeness and certainty of tumor detection are very important issues in clinical oncology. Recent technological developments in ultrasound, radiologic and magnetic resonance imaging diagnostics are very promising, but could not improve the detection rate of early stage malignancies. One of the most promising new approaches is the use of 5-aminolevulinic acid, a potent photosensitizer, in photodynamic diagnosis and therapy. 5-aminolevulinic acid is meanwhile a well-established tool in the photodynamic diagnosis of bladder cancer. It has been shown to improve the sensitivity of detection of superficial tumors and carcinoma in situ, which enables to reduce the risk of tumor recurrence related to undetected lesions or incomplete transurethral resection of the primary lesions. The use of 5-aminolevulinic acid is steadily expanding in diagnostics of urological malignancies. First clinical results are now reported in detection of urethral and ureteral lesions as well as in urine fluorescence cytology. Furthermore, due to the selective accumulation in transitional cell carcinoma of the bladder, 5-aminolevulinic acid may be an ideal candidate for photodynamic therapy in superficial bladder cancer. Summarizing the data of multiple clinical trials, 5-aminolevulinic acid is a promising agent in photodynamic diagnostics and treatment of superficial bladder cancer.

Nelius, Thomas; de Riese, Werner T. W.

2003-06-01

220

PEGylated fullerene/iron oxide nanocomposites for photodynamic therapy, targeted drug delivery and MR imaging.  

PubMed

Recently, fullerene and fullerene derivatives owning to their highly enriched physical and chemical properties have been widely explored for applications in many different fields including biomedicine. In this study, iron oxide nanoparticles (IONPs) were decorated onto the surface of fullerene (C60), and then PEGylation was performed to improve the solubility and biocompatibility of C60-IONP, obtaining a multi-functional C60-IONP-PEG nanocomposite with strong superparamagnetism and powerful photodynamic therapy capacity. Hematoporphyrin monomethyl ether (HMME), a new photodynamic anti-cancer drug, was conjugated to C60-IONP-PEG, forming a C60-IONP-PEG/HMME drug delivery system, which demonstrated an excellent magnetic targeting ability in cancer therapy. Compared with free HMME, remarkably enhanced photodynamic cancer cell killing effect using C60-IONP-PEG/HMME was realized not only in a cultured B16-F10 cells in vitro but also in an in vivo murine tumor model due to 23-fold higher HMME uptake of tumor and strong photodynamic activity of C60-IONP-PEG. Moreover, C60-IONP-PEG could be further used as a T2-contrast agent for in vivo magnetic resonance imaging. Our work showed C60-IONP-PEG/HMME had a great potential for cancer theranostic applications. PMID:24034498

Shi, Jinjin; Yu, Xiaoyuan; Wang, Lei; Liu, Yan; Gao, Jun; Zhang, Jing; Ma, Rou; Liu, Ruiyuan; Zhang, Zhenzhong

2013-12-01

221

Predictive model for photodynamic therapy with gold nanoparticles as vehicle for the photosensitizer delivery  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

222

Cell cycle phase influences tumour cell sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro  

Microsoft Academic Search

Photodynamic therapy (PDT) is a form of cancer treatment based on the destruction of cells by the interaction of light, oxygen and a photosensitizer. Aminolaevulinic acid (ALA) is the prodrug of the photosensitizer protoporphyrin IX (PpIX). ALA-induced PDT depends on the rate of cellular synthesis of PpIX, which may vary with cell cycle phase. This study has investigated the relationship

L Wyld; O Smith; J Lawry; MWR Reed; NJ Brown

1998-01-01

223

Endoscopic photodynamic therapy with hematoporphyrin derivative for primary treatment of gastrointestinal neoplasms in inoperable patients  

Microsoft Academic Search

Endoscopic photodynamic therapy with hematoporphyrin derivative was used in the primary treatment of 54 patients with inoperable gastrointestinal neoplasms. Patients were divided into three groups including 24 with esophageal squamous cell carcinoma, 14 with adenocarcinoma of the stomach or lower third of the esophagus, and 16 with rectosigmoid adenocarcinoma. After infusion of 2.5–5.0 mg hematoporphyrin derivative\\/kg of body weight, lesions

T. Patrice; M. T. Foultier; S. Yactayo; F. Adam; J. P. Galmiche; M. C. Douet; L. Le Bodic

1990-01-01

224

Heat shock protein 70 is acute phase reactant: response elicited by tumor treatment with photodynamic therapy  

Microsoft Academic Search

Oxidative stress in photodynamic therapy (PDT)-treated tumor cells is known to instigate a strong upregulation of the expression\\u000a of heat shock proteins. However, the treatment of mouse Lewis lung carcinoma (LLC) cells with Photofrin™ PDT resulted in the\\u000a upregulation of heat shock protein 70 (Hsp70) gene not only in these cells but also in co-incubated untreated Hepa 1-6 cells.\\u000a To

Soroush Merchant; Mladen Korbelik

2011-01-01

225

Treatment of ovarian cancer with photodynamic therapy and immunoconjugates in a murine ovarian cancer model  

Microsoft Academic Search

In photodynamic therapy (PDT), photosensitisers accumulate somewhat preferentially in malignant tissues; photoactivation with appropriate wavelength of light release toxic molecular species which lead to tumour tissue death. In order to target ovarian cancer with increased specificity, a chlorin-based photosensitiser (chlorin e6 monoethylendiamine monoamide) was conjugated to OC125, a monoclonal antibody recognising an antigen expressed in 80% of non-mucinous ovarian cancers.

BA Goff; J Blake; MP Bamberg; T Hasan

1996-01-01

226

Curative effect of photodynamic therapy for 42 cases of moderate or late stage in esophagus cancer  

NASA Astrophysics Data System (ADS)

34 patients with advanced esophagus cancer and 8 cases of cancer of gastric cardia were treated by photodynamic therapy. The therapeutic effectiveness of the treatment was evaluated according the criteria used in China. CR 63.2 percent SR 11.3 percent, MR 2 percent. The total effective rate was 76.5 percent. There was no significant side effect in this group except mild skin photosensitization and pigmentation and exacerbation of pain in a few cases.

Bai, Xiao-Min; Shen, Guang-Rong; Chen, Weng-Ge; Guo, Tao

1998-11-01

227

Robot-assisted light dose evaluation for endoscopically guided photodynamic therapy: A preliminary study  

Microsoft Academic Search

Conventional endoscope-guided photodynamic therapy (PDT) suffers mostly from motion artifacts, therefore expert hand-eye coordination was always needed during manual operations. In this paper we introduced a visual servo scheme to handle the tracking problem between the focused area and the targeted lesions. The scheme is consisted of real-time feature matching, relative motion cancellation and real-time light dose surveillance. Experiments were

Dongwen Zhang; Lei Wang; Jia Gu; Zhen Zheng

2009-01-01

228

Photodynamic Therapy of B16F10 Murine Melanoma with Lutetium Texaphyrin  

Microsoft Academic Search

Photodynamic therapy (PDT) of pigmented melanoma has generally been unsuccessful because of insufficient light penetration in such tissues. In this study, the responsiveness of the heavily pigmented B16F10 murine melanoma to lutetium texaphyrin (PCI-0123), a water-soluble sensitizer with strong absorbance in the near infrared (700–760 nm), was examined. These studies were carried out in both normal and ApoE deficient C57BL\\/6

Kathryn W. Woodburn; Qing Fan; David Kessel; Yu Luo; Stuart W. Young

1998-01-01

229

In Vitro Photodynamic Therapy of Human Lung Cancer: Investigation of Dose-Rate Effects  

Microsoft Academic Search

The influence of light dose-rate delivery was studied in human lung adenocarcinoma A549 cells treated with hematoporphyrin derivative (Photofrin II)-hased photodynamic therapy. Clonogenic cell survival curves were generated for cells treated for 2 h with 25 Mg\\/mlof Photofrin II followed by exposure to light delivered at 0.3, 0.15, 0.075, or 0.0375 milliwatts\\/cm2. Cellular sensitizer levels, as determined by fluorescence measurements,

Wilbert Matthews; John Cook; James B. Mitchell; Roger R. Perry; Steven Evans; Harvey I. Pass

230

Development of pH sensitive 2-(diisopropylamino)ethyl methacrylate based nanoparticles for photodynamic therapy.  

PubMed

Photodynamic therapy is an effective treatment for tumors that involves the administration of light-activated photosensitizers. However, most photosensitizers are insoluble and non-specific. To target the acid environment of tumor sites, we synthesized three poly(ethylene glycol) methacrylate-co-2-(diisopropylamino)ethyl methacrylate (PEGMA-co-DPA) copolymers capable of self-assembly to form pH sensitive nanoparticles in an aqueous environment, as a means of encapsulating the water-insoluble photosensitizer, meso-tetra(hydroxyphenyl)chlorin (m-THPC). The critical aggregation pH of the PEGMA-co-DPA polymers was 5.8-6.6 and the critical aggregation concentration was 0.0045-0.0089 wt% at pH 7.4. Using solvent evaporation, m-THPC loaded nanoparticles were prepared with a high drug encapsulation efficiency (approximately 89%). Dynamic light scattering and transmission electron microscopy revealed the spherical shape and 132 nm diameter of the nanoparticles. The in vitro release rate of m-THPC at pH 5.0 was faster than at pH 7.0 (58% versus 10% m-THPC released within 48 h, respectively). The in vitro photodynamic therapy efficiency was tested with the HT-29 cell line. m-THPC loaded PEGMA-co-DPA nanoparticles exhibited obvious phototoxicity in HT-29 colon cancer cells after light irradiation. The results indicate that these pH sensitive nanoparticles are potential carriers for tumor targeting and photodynamic therapy. PMID:20332561

Peng, Cheng-Liang; Yang, Li-Yuan; Luo, Tsai-Yueh; Lai, Ping-Shan; Yang, Shu-Jyuan; Lin, Wuu-Jyh; Shieh, Ming-Jium

2010-04-16

231

Current treatment of early breast cancer: adjuvant and neoadjuvant therapy  

PubMed Central

Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC) revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM) is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +), hormone receptor positive (estrogen or progesterone +), both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer. PMID:25400908

Miller, Elizabeth; Lee, Hee Jin; Lulla, Amriti; Hernandez, Liz; Gokare, Prashanth; Lim, Bora

2014-01-01

232

Vaginal Speculum For Photodynamic Therapy And Method Of Using The Same  

DOEpatents

An improved vaginal speculum for photodynamic therapy of intraepithelial tissue and in particular vaginal, cervical and vulvar neoplasia utilizes a precisely and accurately positionable optic fiber through which a predetermined dose of light in the range of 620 to 700 nanometers is delivered over a controlled area which has been previously treated with photodynamic therapeutic substances. In particular, the neoplastic area has been treated with hematoporphyrin derivatives and other photosensitizers which are selectively taken into the cancerous tissue. Exposure to the appropriate wavelength laser light photoactivates the absorbed hematoporphyrins causing the release of singlet oxygen which internally oxidizes and ultimately causes cell death. The fiber optic tip from which the laser light is transmitted is precisely positioned within the body cavity at a predetermined distance from the intraepithelial neoplasia in order to obtain the appropriate spot size and location to minimize damage to healthy tissue and maximize damage to the selectively impregnated cancerous tissue.

Tadir, Yona (Irvine, CA); Berns, Michael W. (Trabuco Canyon, CA); Monk, Brad J. (Long Beach, CA); Profeta, Glen (Rancho Santa Margarita, CA); Tromberg, Bruce J. (Irvine, CA)

1995-10-17

233

Direct imaging of singlet oxygen luminescence generated in blood vessels during photodynamic therapy  

NASA Astrophysics Data System (ADS)

Singlet oxygen (1O2) is commonly recognized to be a major phototoxic component for inducing the biological damage during photodynamic therapy (PDT). In this study, a novel configuration of a thermoelectrically-cooled near-infrared sensitive InGaAs camera was developed for imaging of photodynamically-generated 1O2 luminescence. The validation of 1O2 luminescence images for solution samples was performed with the model photosensitizer Rose Bengal (RB). Images of 1O2 luminescence generated in blood vessels in vivo in a well-controlled dorsal skinfold window chamber model were also recorded during PDT. This study demonstrated the capacity of the newly-developed imaging system for imaging of 1O2 luminescence, and the first reported images of 1O2 luminescence in blood vessels in vivo. This system has potential for elucidating the mechanisms of vascular targeted PDT.

Lin, Lisheng; Lin, Huiyun; Chen, Defu; Chen, Longchao; Wang, Min; Xie, Shusen; Gu, Ying; Wilson, Brian C.; Li, Buhong

2014-05-01

234

Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy  

PubMed Central

Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and ?-? stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT. PMID:21562631

Huang, Peng; Xu, Cheng; Lin, Jing; Wang, Can; Wang, Xiansong; Zhang, Chunlei; Zhou, Xuejiao; Guo, Shouwu; Cui, Daxiang

2011-01-01

235

Photophysical and photochemical properties of ?-(8-quinolinoxy) zinc phthalocyanine for photodynamic therapy  

NASA Astrophysics Data System (ADS)

The photophysical and photochemical properties of a newly developed photosensitizer ?-(8-quinolinoxy) zinc phthalocyanine (?-(8-QLO)PcZn) were investigated for application in photodynamic therapy (PDT). The maximal Q band for ?-(8-QLO)PcZn in dimethylformamide around 675 nm with the molar extinction coefficient of about 1.89×105 mol-1cm-1. The fluorescence quantum and singlet oxygen (1O2) yields were determined to be 0.18+/-0.02 and 0.62+/-0.03, respectively. ?-(8-QLO) PcZn has a diffuse cytoplasmic distribution in nasopharyngeal carcinoma C666-1 cells, and the efficient photodynamic cytotoxicity was observed. Our findings of this study suggest that ?-(8-QLO)PcZn is a promising second-generation photosensitizer for PDT.

Lv, Yuehui; Yu, Songlin; Lin, Huiyun; Li, Buhong; Xue, Jinping; Xie, Shusen

2009-02-01

236

Endonyx toenail onychomycosis caused by Trichophyton rubrum: treatment with photodynamic therapy based on methylene blue dye*  

PubMed Central

This study shows the effectiveness of photodynamic therapy based on methylene blue dye for the treatment of endonyx toenail onychomycosis. Four patients with endonyx onychomycosis caused by Trichophyton rubrum were treated with 2% methylene blue aqueous solution irradiated with light emission diode at 630 nm and an energy density of 36 J/cm2 for 6 months at 2-week intervals. The preliminary study showed the effectiveness of this therapy in the treatment of endonyx onychomycosis, and also indicated that the disease can be caused by T. rubrum. PMID:24474123

Souza, Linton Wallis Figueiredo; Souza, Simone Vilas Trancoso; Botelho, Ana Cristina de Carvalho

2013-01-01

237

Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors  

NASA Astrophysics Data System (ADS)

A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

1994-10-01

238

Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors  

NASA Astrophysics Data System (ADS)

A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

1995-03-01

239

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis  

SciTech Connect

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.

Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Garg, Madhur K. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Aparo, Santiago; Kaubisch, Andreas [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Tome, Wolfgang [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kennedy, Timothy J. [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Guha, Chandan [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)] [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2013-06-01

240

The role of aromatase inhibitors as adjuvant therapy for early breast cancer in postmenopausal women.  

PubMed

For endocrine therapy of hormone-sensitive advanced breast cancer in postmenopausal women, the third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane, are effective both as alternatives to tamoxifen in first-line treatment and following first-line tamoxifen failure. These three agents are currently being evaluated as adjuvant therapy of early breast cancer, again relative to the standard, tamoxifen. Three treatment strategies are under investigation: replacement of tamoxifen as adjuvant therapy for 5 years (early adjuvant therapy); sequencing of tamoxifen before or after an aromatase inhibitor during the first 5 years (early sequential adjuvant therapy); or following 5 years of tamoxifen (extended adjuvant therapy). Results of the first early adjuvant trial (Arimidex, Tamoxifen Alone or in Combination [ATAC]) demonstrated that anastrozole was significantly more effective than tamoxifen in reducing the risk of disease recurrence. Two trials sequencing 2-3 years of an aromatase inhibitor after 2-3 years of tamoxifen have also reported results. A large trial (International Collaborative Cancer Group [ICCG] trial 96) found switching to exemestane to be significantly superior to continuing on tamoxifen in disease-free survival, and in a small study (Italian Tamoxifen Arimidex [ITA] trial), similarly sequencing anastrozole after tamoxifen significantly reduced the hazard of recurrence compared with remaining on tamoxifen. Extended adjuvant therapy with 5 years of letrozole versus placebo following 5 years of tamoxifen was evaluated in the MA.17 trial. Compared with placebo, letrozole resulted in a significant improvement in disease-free survival that was irrespective of whether patients had lymph node-positive or -negative tumours. Results of these four trials emphasise the important role of aromatase inhibitors in the adjuvant setting, yet the optimal approach still needs to be defined. A number of trials further evaluating the three adjuvant treatment strategies are ongoing. PMID:16098456

Mouridsen, Henning T; Robert, Nicholas J

2005-08-01

241

Baylor study finds obesity linked to worse survival outcomes in breast cancer adjuvant therapy:  

Cancer.gov

Obesity may contribute to worse survival outcomes in early stage breast cancer patients who have received adjuvant therapy to treat their disease, said researchers from the Lester and Sue Smith Breast Center at Baylor College of Medicine.

242

Efficacy of photodynamic therapy against larvae of Aedes aegypti: confocal microscopy and fluorescence-lifetime imaging  

NASA Astrophysics Data System (ADS)

Recently a few demonstration on the use of Photodynamic Reaction as possibility to eliminate larvae that transmit diseases for men has been successfully demonstrated. This promising tool cannot be vastly used due to many problems, including the lake of investigation concerning the mechanisms of larvae killing as well as security concerning the use of photosensitizers in open environment. In this study, we investigate some of the mechanisms in which porphyrin (Photogem) is incorporated on the Aedes aegypti larvae previously to illumination and killing. Larvae at second instar were exposed to the photosensitizer and after 30 minutes imaged by a confocal fluorescence microscope. It was observed the presence of photosensitizer in the gut and at the digestive tract of the larva. Fluorescence-Lifetime Imaging showed greater photosensitizer concentration in the intestinal wall of the samples, which produces a strong decrease of the Photogem fluorescence lifetime. For Photodynamic Therapy exposition to different light doses and concentrations of porphyrin were employed. Three different light sources (LED, Fluorescent lamp, Sun light) also were tested. Sun light and fluorescent lamp shows close to 100% of mortality after 24 hrs. of illumination. These results indicate the potential use of photodynamic effect against the LARVAE of Aedes aegypti.

de Souza, L. M.; Pratavieira, S.; Inada, N. M.; Kurachi, C.; Corbi, J.; Guimarães, F. E. G.; Bagnato, V. S.

2014-03-01

243

Zinc phthalocyanine-loaded PLGA biodegradable nanoparticles for photodynamic therapy in tumor-bearing mice.  

PubMed

Nanoparticles formulated from the biodegradable copolymer poly(lactic-coglycolic acid) (PLGA) were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting of zinc(II) phthalocyanine (ZnPc) for photodynamic therapy. Three ZnPc nanoparticle formulations were prepared using a solvent emulsion evaporation method and the influence of sonication time on nanoparticle shape, encapsulation and size distribution, in vitro release, and in vivo photodynamic efficiency in tumor-bearing mice were studied. Sonication time did not affect the process yield or encapsulation efficiency, but did affect significantly the particle size. Sonication for 20 min reduced the mean particle size to 374.3 nm and the in vitro release studies demonstrated a controlled release profile of ZnPc. Tumor-bearing mice injected with ZnPc nanoparticles exhibited significantly smaller mean tumor volume, increased tumor growth delay and longer survival compared with the control group and the group injected with free ZnPc during the time course of the experiment. Histopathological examination of tumor from animals treated with PLGA ZnPc showed regression of tumor cells, in contrast to those obtained from animals treated with free ZnPc. The results indicate that ZnPc encapsulated in PLGA nanoparticles is a successful delivery system for improving photodynamic activity in the target tissue. PMID:19957005

Fadel, Maha; Kassab, Kawser; Fadeel, Doa Abdel

2010-03-01

244

Concepts and Principles of Photodynamic Therapy as an Alternative Antifungal Discovery Platform  

PubMed Central

Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants. PMID:22514547

Dai, Tianhong; Fuchs, Beth B.; Coleman, Jeffrey J.; Prates, Renato A.; Astrakas, Christos; St. Denis, Tyler G.; Ribeiro, Martha S.; Mylonakis, Eleftherios; Hamblin, Michael R.; Tegos, George P.

2012-01-01

245

Extending the benefits of adjuvant therapy in early HR+ breast cancer  

Microsoft Academic Search

The benefits of adjuvant tamoxifen are well documented, but therapy is limited to 5 years because of reports of an unfavorable\\u000a risk: benefit profile in later years. However, the risk of relapse continues beyond the end of therapy. Before the MA.17 trial,\\u000a no agent given after the standard 5 years of adjuvant tamoxifen had been shown to provide additional benefit,

Paul E. Goss

2008-01-01

246

Effectiveness of 5-aminolevulinic acid photodynamic therapy in the treatment of hidradenitis suppurativa: a report of 5 cases.  

PubMed

Hidradenitis suppurativa has been described as a chronic, recurrent, and disabling inflammatory disease involving the entire hair follicle. Several treatments, including photodynamic therapy, have been used, but the results have been inconsistent and recurrence is high. In this prospective study, we evaluated disease severity, quality of life, and treatment tolerance in 5 patients with moderate to severe hidradenitis suppurativa treated with photodynamic therapy using 5-aminolevulinic acid and a 635-nm light source. Treatment effectiveness was evaluated using the Sartorius severity score, the Dermatology Life Quality Index, and a visual analog scale for pain and disease activity. Significant improvements were observed with all 3 instruments and the effects remained visible at 8 weeks. Our results suggest that photodynamic therapy with 5-aminolevulinic acid and a light wavelength of 635 nm could reduce disease severity and improve quality of life in patients with difficult-to-treat hidradenitis suppurativa. PMID:24472519

Andino Navarrete, R; Hasson Nisis, A; Parra Cares, J

2014-01-01

247

Active immunotherapy of Walker-256 carcinosarcoma by tumor-infiltrating lymphocytes associated with photodynamic therapy  

NASA Astrophysics Data System (ADS)

Experiments were performed on five batches of Wistar inbred rats with Walker-256 carcinosarcoma receiving as sole treatment photodynamic therapy (PDT), tumor-infiltrating lymphocytes (TIL), or associated therapy (PDT + TIL - A; PDT + TIL - B). The control batch (HBSS) consisted of animals with untreated Walker-256 tumors. The results were as follows: the sole treatment (PDT, TIL) gave survival rates between 41.4 and 52.9%, the cure rates ranging from 13.8 to 38.2%. The `combined' therapy in multiple doses increased significantly (92.8%) the survival rate of tumor bearing rats as well as the highest incidence of complete tumor regression (82.1%). Cell-mediated immunity test values in batches III and IV exposed to multiple doses of PDT + TIL showed higher values as compared to the values noticed in batches I - II and the control batch V, performed at 10 and 21 days post-treatment. Summing up, this work demonstrates that `combined' photodynamic therapy with immunotherapy with TIL stimulates cell-mediated antitumoral activity, increases survival rates, and reduces incidence of Walker-256 carcinosarcoma in the rat model.

Dima, Vasile F.; Vasiliu, Virgil V.; Laky, Dezideriu; Ionescu, Paul; Dima, Stefan V.

1995-01-01

248

An irradiation system for photodynamic therapy with a fiber-optic sensor for measuring tissue oxygen  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy is a well known treatment based on the interaction of light of specific wavelength with a photosensitizing drug. In the presence of oxygen molecules, the illumination of the photosensitizer can activate the production of reactive oxygen species, which leads to the death of target cells within the treated tissue. In order to obtain the best therapy response, the tissue oxygen concentration should be measured to adjust the therapy parameters before and during the treatment. In this work, an irradiation system for 5-Aminolevulinic Acid Photodynamic Therapy is presented. It allows the application of visible light radiation of 630 nm using as a light source a high-brightness light emitting diode with an optical-power automatic control considering a light depth-distribution model. A module to measure the tissue oxygen saturation has been implemented into the system. It is based on two light emitting diodes of 660 nm and 940 nm as light sources, a photodiode as a detector and a new handheld fiber optic reflectance pulse oximetry sensor for estimating the blood oxygen saturation within the tissue. The pulse oximetry sensor was modeled through multilayered Monte Carlo simulations to study the behavior of the sensor with changes in skin thickness and melanin content.

Quintanar, L.; Fabila, D.; Stolik, S.; de la Rosa, J. M.

2013-11-01

249

Enhanced photodynamic therapy and effective elimination of cancer stem cells using surfactant-polymer nanoparticles.  

PubMed

Photodynamic therapy is a potentially curative treatment for various types of cancer. It involves energy transfer from an excited photosensitizer to surrounding oxygen molecules to produce cytotoxic singlet oxygen species, a process termed as type II reaction. The efficiency of photodynamic therapy is greatly reduced because of the reduced levels of oxygen, often found in tumor microenvironments that also house cancer stem cells, a subpopulation of tumor cells that are characterized by enhanced tumorigenicity and resistance to conventional therapies. We show here that encapsulation of a photosensitizer, methylene blue, in alginate-Aerosol OT nanoparticles leads to an increased production of reactive oxygen species (ROS) under both normoxic and hypoxic conditions. ROS generation was found to depend on the interaction of the cationic photosensitizer with the anionic alginate polymer. Dye-polymer interaction was characterized by formation of methylene blue dimers, potentially enabling electron transfer and a type I photochemical reaction that is less sensitive to environmental oxygen concentration. We also find that nanoparticle encapsulated methylene blue has the capacity to eliminate cancer stem cells under hypoxic conditions, an important goal of current cancer therapy. PMID:25061685

Usacheva, Marina; Swaminathan, Suresh Kumar; Kirtane, Ameya R; Panyam, Jayanth

2014-09-01

250

KillerRed and miniSOG as genetically encoded photosensitizers for photodynamic therapy of cancer  

NASA Astrophysics Data System (ADS)

Despite of the success of photodynamic therapy (PDT) in cancer treatment, the problems of low selective accumulation of a photosensitizer in a tumor and skin phototoxicity have not resolved yet. The idea of encoding of a photosensitizer in genome of cancer cells is attractive, particularly because it can provide highly selective light induced cell killing. This work is aimed at the development of new approach to PDT of cancer, namely to using genetically encoded photosensitizers. A phototoxicity of red fluorescent GFP-like protein KillerRed and FMN-binding protein miniSOG was investigated on HeLa tumor xenografts in nude mice. The tumors were generated by subcutaneous injection of HeLa cells stably expressing the phototoxic proteins. The tumors were irradiated with 594 nm or 473 nm laser at 150 mW/cm2 for 20 or 30 min, repeatedly. Fluorescence intensity of the tumors was measured in vivo before and after each treatment procedure. Detailed pathomorphological analysis was performed 24 h after the therapy. On the epi-fluorescence images in vivo photobleaching of both proteins was observed indicating photodynamic reaction. Substantial pathomorphological abnormalities were found in the treated KillerRed-expressing tumor tissue, such as vacuolization of cytoplasm, cellular and nuclear membrane destruction, activation of apoptosis. In contrast, miniSOG-expressing tumors displayed no reaction to PDT, presumably due to the lack of FMN cofactor needed for fluorescence recovery of the flavoprotein. The results are of interest for photodynamic therapy as a proof of possibility to induce photodamages in cancer cells in vivo using genetically encoded photosensitizers.

Shirmanova, Marina V.; Serebrovskaya, Ekaterina O.; Snopova, Ludmila B.; Kuznetsova, Maria M.; Ryumina, Alina P.; Turchin, Ilya V.; Sergeeva, Ekaterina A.; Ignatova, Nadezhda I.; Klementieva, Natalia V.; Lukyanov, Konstantin A.; Lukyanov, Sergey A.; Zagaynova, Elena V.

2013-06-01

251

Alteration of photosensitizer content and parameters of free radical reactions in a patient's blood under photodynamic therapy of malignant tumors  

NASA Astrophysics Data System (ADS)

The purpose of this study was to determine the changes in concentrations of the two Russian photosensitizers in blood plasma of patients under Photodynamic therapy. In this work were used two sensitizers of domestic production: Photohem (hematoporphyrin derivative) and Photosense (sulfonated aluminium phtalocyanine). It was found that one month after injection the concentrations of the photosensitizers in blood plasma remained high enough. Was shown alteration of level of apo-(beta) -lipoproteins oxidation and antioxidant activity of blood plasma under the influence of Photodynamic therapy.

Lubchenko, G. N.; Chichuk, Tatyana V.; Stranadko, Eugeny P.

1999-12-01

252

Multifunctional hybrid nanoparticles for two-photon fluorescence imaging and photodynamic therapy  

NASA Astrophysics Data System (ADS)

We review our work on several strategies to elaborate multifunctional nanoparticules for two-photon imaging or/and photodynamic therapy. Our first strategy is based on the incorporation of two-photon hydrophobic fluorophors in bio-compatible pluronic micelles using the mini-emulsion technique. Our second strategy is based on fluorescent organic nanocrystal grown in silicate spheres. These core-shell hybrid nanoparticles are obtained by a spray-drying process from sol-gel solutions. Our third strategy consists in the encapsulation of hydrophilic molecules in the water core of gold nanospheres. They are obtained by a stabilized emulsion in biphasic liquid-liquid medium without surfactant.

Baldeck, Patrice L.; Maurin, Mathieu; Philipot, Cecile; Zaiba, Soraya; Gallavardin, Thibault; Maury, Olivier; Andraud, Chantal; Dubois, Fabien; Ibanez, Alain; Lerouge, Frédéric; Parola, Stéphane; Stephan, Olivier; van Der Sanden, Baudwin

2011-02-01

253

Progress of photodynamic therapy applications in the treatment of musculoskeletal sarcoma (Review)  

PubMed Central

Photodynamic therapy (PDT) has clinical approval for use as a minimally invasive therapeutic procedure that is able to exert selective cytotoxic activity toward pathological cells, particularly malignant cells. Following a number of recent technological improvements, PDT has been widely applied to the diagnosis and treatment of malignancies, including lung, esophageal, gastrointestinal, bladder, prostate, head and neck, oral and skin cancer. Studies have shown that osteosarcoma is a malignant tumor afflicting young adults worldwide, and recently, the incidence of bone and soft-tissue malignant tumors has been shown to be increasing, so the use of PDT has become an area of focus for the diagnosis and treatment of musculoskeletal sarcoma.

ZHANG, XIANGHONG; LIU, TANG; LI, ZHIHONG; ZHANG, XIANGSHENG

2014-01-01

254

Near Infrared Light-Triggered Drug Generation and Release from Gold Nanoparticle Carriers for Photodynamic Therapy  

PubMed Central

A photoprecursor Pc 227 is covalently bound onto gold nanoparticles (Au NPs) to produce the known photodynamic therapy (PDT) drug Pc 4 upon 660 nm photoirradiation. The photochemical formation of the photoproduct Pc 4 is identified by spectroscopy, chromatography, and mass spectrometry and its PDT efficacy is equal to Pc 4 when administered non-covalently by Au NPs, with the added benefit of improved covalent delivery and targeted NIR-triggered release from the covalent Pc 227-Au NP conjugate, while during transport the attached Pc 227 is quenched by the Au NP and PDT inactivated. PMID:24515950

Cheng, Yu; Doane, Tennyson L.; Chuang, Chi-Hung; Ziady, Assem; Burda, Clemens

2014-01-01

255

Sm3+-doped germanate glass channel waveguide as light source for minimally invasive photodynamic therapy surgery.  

PubMed

In Sm(3+)-doped K(+)-Na(+) ion-exchanged aluminum germanate (NMAG) glass channel waveguide, a clear and compact red amplified spontaneous emission (ASE) trace is observed under the excitation of a 488nm Ar(+) laser. 78% photons of ASE fluorescence in visible region are demonstrated to be located in 600-730nm wavelength range. High-directivity and high-brightness ASE fluorescence of Sm(3+)-doped NMAG glass channel waveguide, which matches the excitation band of most photosensitizers (PS) currently used in photodynamic therapy (PDT) or clinical trials, has promising potential application as an excitation light source for PDT treatment. PMID:22274434

Chen, B J; Shen, L F; Pun, E Y B; Lin, H

2012-01-16

256

Use of Photodynamic Therapy for Treatment of Actinic Keratoses in Organ Transplant Recipients  

PubMed Central

Solid organ transplant recipients are predisposed to actinic keratoses (AK) and nonmelanoma skin cancers, owing to the lifelong immunosuppression required. Today, increasing numbers of organ transplants are being performed and organ transplant recipients (OTRs) are surviving much longer. Photodynamic therapy (PDT) is proving a highly effective treatment modality for AK amongst this susceptible group of patients. Following an overview of the pathogenesis of AK amongst OTRs, the authors review current safety and efficacy data and how this relates to the role of PDT for the treatment of AK in OTRs. PMID:23509711

Wlodek, Christina; Ali, Faisal R.; Lear, John T.

2013-01-01

257

Enhanced antitumoral efficacy by intratumoral perfusion of activated macrophages associated with photodynamic therapy  

NASA Astrophysics Data System (ADS)

Experiments were performed on five batches of Wistar inbred rats with Walker-256 carcinosarcoma receiving photodynamic therapy (PDT), rMuIFN-gamma activated macrophages (AM(Phi) ) or associated therapy (PDT-AM(Phi) -A; PDT-AM(Phi) -B); the control batch (HBSS) consisted of animals with untreated Walker-256 tumors. The results were as follows: the sole treatment (PDT, AM(Phi) ) gave survival rates between 57.2 and 57.7% and cure rates ranging from 23.1 to 34.3%. The 'combined' therapy in multiple doses increased significantly (87.9%) the survival rate of tumor bearing rats as well as the rate of complete tumor regression (72.7%). Cell-mediated immunity test values in batches III and IV exposed to multiple doses of PDT-AM(Phi) showed higher values as compared to the values noticed in batches I - II and the control batch V, performed at 12 and 21 days post-treatment. Summing up, these results demonstrate that 'combined' photodynamic treatment and biotherapy with interferon activated macrophages stimulate cell-mediated antitumoral activity, increase survival rates and reduce incidence of Walker-256 carcinosarcoma in rat model.

Dima, Vasile F.; Vasiliu, Virgil V.; Laky, Dezideriu; Ionescu, Paul; Dima, Stefan V.

1996-01-01

258

The p53-mediated cytotoxicity of photodynamic therapy of cancer: Recent advances  

SciTech Connect

Photodynamic therapy (PDT) is a promising modality for the treatment of both pre-malignant and malignant lesions. The mechanism of action converges mainly on the generation of reactive oxygen species which damage cancer cells directly as well as indirectly acting on tumor vasculature. The exact mechanism of PDT action is not fully understood, which is a formidable barrier to its successful clinical application. Elucidation of the mechanisms of cancer cell elimination by PDT might help in establishing highly specific, non-genotoxic anti-cancer treatment of tomorrow. One of the candidate PDT targets is the well-known tumor suppressor p53 protein recognized as the guardian of the genome. Together with its family members, p73 and p63 proteins, p53 is involved in apoptosis induction upon stress stimuli. The wild-type and mutant p53-targeting chemotherapeutics are currently extensively investigated as a promising strategy for highly specific anti-cancer therapy. In photodynamic therapy porphyrinogenic sensitizers are the most widely used compounds due to their potent biophysical and biochemical properties. Recent data suggest that the p53 tumor suppressor protein might play a significant role in porphyrin-PDT-mediated cell death by direct interaction with the drug which leads to its accumulation and induction of p53-dependent cell death both in the dark and upon irradiation. In this review we describe the available evidence on the role of p53 in PDT.

Zawacka-Pankau, Joanna [Department of Biotechnology, Division of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk (Poland); Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Nobelsvaeg 16, 171 77 Stockholm (Sweden)], E-mail: jzawacka@biotech.ug.gda.pl; Krachulec, Justyna [Department of Biotechnology, Division of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk (Poland)], E-mail: justynak3@wp.pl; Grulkowski, Ireneusz [University of Gdansk, Institute of Experimental Physics, Wita Stwosza 57, 80-952 Gdansk (Poland)], E-mail: dokig@ug.gda.pl; Bielawski, Krzysztof P. [Department of Biotechnology, Division of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Kladki 24, 80-822 Gdansk (Poland)], E-mail: bielawsk@biotech.ug.gda.pl; Selivanova, Galina [Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Nobelsvaeg 16, 171 77 Stockholm (Sweden)], E-mail: galina.selivanova@ki.se

2008-11-01

259

Oncologic photodynamic diagnosis and therapy: confocal Raman/fluorescence imaging of metal phthalocyanines in human breast cancer tissue in vitro.  

PubMed

Raman microspectroscopy and confocal Raman imaging combined with confocal fluorescence were used to study the distribution and aggregation of aluminum tetrasulfonated phthalocyanine (AlPcS4) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and aggregation of aluminum phthalocyanine, which is a potential photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. We have observed that the distribution of aluminum tetrasulfonated phthalocyanine confined in cancerous tissue is markedly different from that in noncancerous tissue. We have concluded that Raman imaging can be treated as a new and powerful technique useful in cancer photodynamic therapy, increasing our understanding of the mechanisms and efficiency of photosensitizers by better monitoring localization in cancer cells as well as the clinical assessment of the therapeutic effects of PDT and PIT. PMID:25203552

Abramczyk, Halina; Brozek-Pluska, Beata; Surmacki, Jakub; Musial, Jacek; Kordek, Radzislaw

2014-11-01

260

NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles.  

PubMed

The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects. PMID:25130329

Yuan, Youyong; Min, Yuanzeng; Hu, Qinglian; Xing, Bengang; Liu, Bin

2014-10-01

261

NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles  

NASA Astrophysics Data System (ADS)

The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho-nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects.

Yuan, Youyong; Min, Yuanzeng; Hu, Qinglian; Xing, Bengang; Liu, Bin

2014-09-01

262

Zinc(II) phthalocyanine loaded PLGA nanoparticles for photodynamic therapy use.  

PubMed

Sophisticated delivery systems, such as nanoparticles, represent a growing area in biomedical research. Nanoparticles (Np) were prepared using a solvent emulsion evaporation method (SEEM) to load zinc(II) phthalocyanine (ZnPc). Np were obtained using poly (D,L latic-co-glycolic acid) (PLGA). ZnPc is a second generation of photoactive agents used in photodynamic therapy. ZnPc loaded PLGA nanoparticles were prepared by SEEM, characterized and available in cellular culture. The process yield and encapsulation efficiency were 80 and 70%, respectively. The nanoparticles have a mean diameter of 285 nm, a narrow size distribution with polydispersive index of 0.12, smooth surface and spherical shape. ZnPc loaded nanoparticles maintains its photophysical behavior after encapsulation. Photosensitizer release from nanoparticles was sustained with a moderate and burst effect of 15% for 3 days. The photocytotoxicity of ZnPc loaded PLGA Np was evaluated on P388-D1 cells what were incubated with ZnPc loaded Np (5 microM) by 6h and exposed to red light (675 nm) for 120 s, and light dose of 30 J/cm(2). After 24h of incubation, the cellular viability was determined, obtaining 61% of cellular death. All the physical-chemical, photophysical and photobiological measurements performed allow us conclude that ZnPc loaded PLGA nanoparticles is a promising drug delivery system for photodynamic therapy. PMID:16442755

Ricci-Júnior, Eduardo; Marchetti, Juliana Maldonado

2006-03-01

263

Biodistribution of indium 111-labeled dihematoporphyrin ether in papillomas and body tissues. Relevance to photodynamic therapy  

SciTech Connect

Hematoporphyrin derivative and its newly purified form, dihematoporphyrin ether, have been shown to localize selectively in malignant tissues and virally induced papillomas. Its use as a probe to distinguish tumors from normal tissues has been largely based on its fluorescence when activated by UV light. These findings are largely subjective, and a direct correlation to its use as a photosensitizing agent to selectively kill transformed cells when activated by an appropriate wavelength of light could not be made. The efficacy of dihematoporphyrin ether photodynamic therapy to selectively kill papillomavirus-transformed cells is based on the increased localization of dihematoporphyrin ether within these tissues as compared with normal tissues. Using cottontail rabbit papillomavirus, cutaneous papillomas were induced on the backs of Dutch belted rabbits. Dihematoporphyrin ether was labeled with indium 111 and intravenously injected into the rabbits. The animals were scanned twice daily for indium 111 activity on a large-field-of-view gamma camera. At 50 hours after injection, the rabbits were killed and papillomas, skin, and major organs collected for biodistribution studies. The results of this study and their relationship to dihematoporphyrin ether photodynamic therapy for the treatment of virally induced papilloma disease is discussed.

Shikowitz, M.J.; Galli, R.; Bandyopadhyay, D.; Hoory, S.

1989-07-01

264

Spectral domain optical coherence tomography guided photodynamic therapy for choroidal hemangioma: a case report  

PubMed Central

Introduction Circumscribed choroidal hemangiomas are vascular tumors associated with secondary changes in the overlying retinal pigment epithelium and neuro-sensory retina. Spectral-domain optical coherence tomography, a recent advancement in fundus imaging techniques provides high resolution images of the retina. We describe spectral domain Optical coherence tomography findings in a case of circumscribed choroidal hemangioma which was successfully treated with photodynamic therapy. Case presentation A 41-year-old white male presented with decreased vision in his right eye. Fundus evaluation showed findings consistent with circumscribed choroidal hemangioma. Spectral-domain optical coherence tomography revealed a large serous retinal detachment overlying the tumor with an intact photoreceptor layer. The patient underwent photodynamic therapy and a repeat tomography scan confirmed the resolution of serous detachment with return of normal foveal contour. Conclusion Spectral domain optical coherence tomography is an emerging modality in imaging of the retina and reveals ultrastructural changes occurring in various retina pathologies. In this case report we illustrate the use of spectral domain optical coherence tomography for the first time to document retinal changes overlying a choroidal hemangioma and its role as a non-invasive tool in planning the treatment and prognosticating the final visual outcome following treatment for circumscribed subfoveal choroidal hemangiomas. PMID:20184695

2009-01-01

265

Enhanced tumor control following sequential treatments of photodynamic therapy (PDT) and localized microwave hyperthermia in vivo.  

PubMed

Photodynamic therapy (PDT), or photoradiation therapy (PRT), utilizing hematoporphyrin derivative (HPD) as photosensitizer and an argon-dye laser system as the light source, was used alone and in combination with localized microwave hyperthermia (2450 MHz) to treat axillary tumors of the SMT-F mammary carcinoma in mice. Thirty-minute heat treatments were applied either immediately before or immediately after a standard PDT treatment of 630 nm light at 75 mW/cm2 for 30 min (135 J/cm2) given 24 hr post-7.5 mg/kg HPD, intraperitoneally (i.p.). Tumor control as judged by lack of tumor regrowth 35 days or longer after the combined treatments was compared to that following each treatment when given alone. Little or no enhancement of tumor control was seen when sublethal temperatures of 37.5, 38.5, and 39.5 degrees C were applied for 30 min immediately following the PDT treatment. However, increasing levels of enhancement were seen when heat treatments of 40.5 and 41.5 degrees C or 44.5 degrees C, given for 30 min, were applied immediately before or after the photodynamic treatment. PMID:6235420

Waldow, S M; Henderson, B W; Dougherty, T J

1984-01-01

266

HPMA copolymer delivery of chemotherapy and photodynamic therapy in ovarian cancer.  

PubMed

Our studies document a unique and unexpected advantage of the combination of HPMA copolymer bound doxorubicin with mesochlorin e6/photodynamic therapy in the treatment of ovarian cancer. Each drug's activity is individually enhanced when compared with free (low molecular weight) drugs, furthermore, in combination these HPMA copolymer bound agents act synergistically to create an unexpected biological effect. Figure 8 depicts the known activities of each agent which may play synergistic roles. HPMA copolymer-doxorubicin has been widely evaluated in preclinical and clinical studies. It demonstrates marked advantages over free doxorubicin: control of biodistribution and accumulation via molecular weight restrictions, biodegradability, minimal immunogenicity, subcellular localization, anticancer activity, enhanced permeability and retention, increased apoptosis, lipid peroxidation, DNA damage, and reduced nonspecific toxicity. Recent clinical trials in the UK provide "proof of principle" of the "enhanced permeability and retention effect" for solid tumors and the unique advantages of this novel drug delivery system for the treatment of ovarian cancer. With regards to photodynamic therapy using the photosensitizer mesochlorin e6, the preclinical evaluations thus far document: control of biodistribution and accumulation via molecular weight restrictions, biodegradability, subcellular localization, anticancer activity, enhanced permeability and retention, and reduced nonspecific toxicity. Ongoing microarray studies document unique cellular pathways and new pharmaceutical properties which are initiated by the HPMA copolymer delivery delivery of these agents, and predict an exciting future for this novel drug delivery system. PMID:12675211

Peterson, C Matthew; Shiah, Jane-Guo; Sun, Yongen; Kopecková, Pavla; Minko, Tamara; Straight, Richard C; Kopecek, Jindrich

2003-01-01

267

Photodynamic Therapy for Cancer and for Infections: What Is the Difference?  

PubMed Central

Photodynamic therapy (PDT) was discovered over one hundred years ago when it was observed that certain dyes could kill microorganisms when exposed to light in the presence of oxygen. Since those early days, PDT has mainly been developed as a cancer therapy and as a way to destroy proliferating blood vessels. However, recently it has become apparent that PDT may also be used as an effective antimicrobial modality and a potential treatment for localized infections. This review discusses the similarities and differences between the application of PDT for the treatment of microbial infections and for cancer lesions. Type I and type II photodynamic processes are described, and the structure-function relationships of optimal anticancer and antimicrobial photosensitizers are outlined. The different targeting strategies, intracellular photosensitizer localization, and pharmacokinetic properties of photosensitizers required for these two different PDT applications are compared and contrasted. Finally, the ability of PDT to stimulate an adaptive or innate immune response against pathogens and tumors is also covered. PMID:23248387

Sharma, Sulbha K.; Mroz, Pawel; Dai, Tianhong; Huang, Ying-Ying; St. Denis, Tyler G.; Hamblin, Michael R.

2012-01-01

268

Mean platelet volume increase after tamoxifen, but not after anastrazole in adjuvant therapy of breast cancer  

Microsoft Academic Search

Aim To investigate differences of platelet indices in breast cancer patients after tamoxifen (tmx) and anastrazole adjuvant treatment.\\u000a Methods In this retrospective study, 46 postmenopausal women (20 with tmx and 26 with anastrazole) with breast cancer who received\\u000a adjuvant hormone therapy were enrolled. The biochemical and complete blood count (CBC) parameters were documented before hormone\\u000a treatment start and after 1

Bülent Karagöz; O?uz Bilgi; Ahmet Alacac?o?lu; Alpaslan Özgün; Özkan Sayan; Alev Akyol Erikçi; Emin Gökhan Kandemir

2010-01-01

269

On-line dosimetry for photodynamic therapy: part I--incident irradiance versus space irradiance for human skin  

Microsoft Academic Search

One of the key components of photodynamic therapy dosimetry studies is the actual light dose delivered to the tissue at a targeted, therapeutic depth. The light dose delivered to the tissue is dependent upon the incident irradiance at the initial point of light application as well as the tissue optical properties. Since the parameters defining the light and therapeutic dose

Christine J. Radasky; David H. Crean; Daniel R. Doiron

1996-01-01

270

A laser-spectroscopy system for fluorescent diagnostics and photodynamic therapy of diseases of eye retina and choroid  

SciTech Connect

A laser-spectroscopy system for the fluorescent diagnostics and photodynamic therapy of pathologic eye-fundus changes combined with the use of the Photosens compound is developed. The system is tested on experimental animals (mice and rabbits). (laser biology and medicine)

Meerovich, G A; Shevchik, S A; Loshchenov, M V [Natural Science Center, A.M. Prokhorov General Physics Institute, Russian Academy of Sciences, Moscow (Russian Federation); Budzinskaya, M V; Ermakova, N A [Helmholtz Moscow Research Institute of Eye Diseases, Moscow (Russian Federation); Kharnas, S S [I.M. Sechenov Moscow Academy of Medicine, Moscow (Russian Federation)

2002-11-30

271

Photodetection and photodynamic therapy of ‘early’ squamous cell carcinomas of the pharynx, oesophagus and tracheo-bronchial tree  

Microsoft Academic Search

The efficacy of photodynamic therapy (PDT) alone was evaluated on 41 ‘early’ squamous cell carcinomas of the pharynx (10), oesophagus (15) and tracheo-bronchial tree (16). All lesions but two were synchronous second primaries in ENT-patients suffering from a more extensive cancer, governing the overall oncological prognosis.

Ph. Monnier; M. Savary; Ch. Fontolliet; G. Wagnieres; A. Chatelain; P. Cornaz; Ch. Depeursinge; H. Van Den Bergh

1990-01-01

272

Adjuvant therapy for resected high-risk colon cancer: Current standards and controversies  

PubMed Central

This evidence-based review will discuss the current standard of adjuvant chemotherapy for resected high-risk colon cancer and address existing controversies including strategies for risk-stratification, the status of targeted therapy, treatment of the elderly and the optimal duration of therapy. PMID:25336789

Gill, Sharlene

2014-01-01

273

Photodynamic therapy: a promising new modality for the treatment of cancer.  

PubMed

The first reports on photodynamic therapy (PDT) date back to the 1970s. Since then, several thousands of patients, both with early stage and advanced stage solid tumours, have been treated with PDT and many claims have been made regarding its efficacy. Nevertheless, the therapy has not yet found general acceptance by oncologists. Therefore it seems legitimate to ask whether PDT can still be described as "a promising new therapy in the treatment of cancer". Clinically, PDT has been mainly used for bladder cancer, lung cancer and in malignant diseases of the skin and upper aerodigestive tract. The sensitizer used in the photodynamic treatment of most patients is Photofrin, (Photofrin, the commercial name of dihematoporphyrin ether/ester, containing > 80% of the active porphyrin dimers/oligomers (A.M.R. Fisher, A.L. Murphee and C.J. Gomer, Clinical and preclinical photodynamictherapy, Review Series Article, Lasers Surg. Med., 17 (1995) 2-31). It is a complex mixture of porphyrins derived from hematoporphyrin. Although this sensitizer is effective, it is not the most suitable photosensitizer for PDT. Prolonged skin photosensitivity and the relatively low absorbance at 630 nm, a wavelength where tissue penetration of light is not optimal, have been frequently cited as negative aspects hindering general acceptance. A multitude of new sensitizers is currently under evaluation. Most of these "second generation photosensitizers" are chemically pure, absorb light at around 650 nm or greater and induce no or less general skin photosensitivity. Another novel approach is the photosensitization of neoplasms by the induction of endogenous photosensitizers through the application of 5-aminolevulinic acid (ALA). This article addresses the use of PDT in the disciplines mentioned above and attempts to indicate developments of PDT which could be necessary for this therapy to gain a wider acceptance in the various fields. PMID:8765658

Schuitmaker, J J; Baas, P; van Leengoed, H L; van der Meulen, F W; Star, W M; van Zandwijk, N

1996-06-01

274

Regulation of miRNA Expression by Low-Level Laser Therapy (LLLT) and Photodynamic Therapy (PDT)  

PubMed Central

Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression. PMID:23807510

Kushibiki, Toshihiro; Hirasawa, Takeshi; Okawa, Shinpei; Ishihara, Miya

2013-01-01

275

Two combined photosensitizers: a goal for more effective photodynamic therapy of cancer.  

PubMed

Photodynamic therapy (PDT) is a clinically approved therapeutic modality for the treatment of diseases characterized by uncontrolled cell proliferation, mainly cancer. It involves the selective uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species upon irradiation with light, leading to tumor regression. Here a synergistic cell photoinactivation is reported based on the simultaneous administration of two PSs, zinc(II)-phthalocyanine (ZnPc) and the cationic porphyrin meso-tetrakis(4-N-methylpyridyl)porphine (TMPyP) in three cell lines (HeLa, HaCaT and MCF-7), using very low doses of PDT. We detected changes from predominant apoptosis (without cell detachment) to predominant necrosis, depending on the light dose used (2.4 and 3.6?J/cm(2), respectively). Analysis of changes in cytoskeleton components (microtubules and F-actin), FAK protein, as well as time-lapse video microscopy evidenced that HeLa cells were induced to undergo apoptosis, without losing adhesion to the substrate. Moreover, 24?h after intravenous injection into tumor-bearing mice, ZnPc and TMPyP were preferentially accumulated in the tumor area. PDT with combined treatment produced significant retardation of tumor growth. We believe that this combined and highly efficient strategy (two PSs) may provide synergistic curative rates regarding conventional photodynamic treatments (with one PS alone). PMID:24625981

Acedo, P; Stockert, J C; Cañete, M; Villanueva, A

2014-01-01

276

Fiber optic probes for tissue illumination in photodynamic diagnosis and therapy  

NASA Astrophysics Data System (ADS)

Photodynamic diagnosis (PDD) and therapy (PDT) require light application devices which enable homogeneous illumination of tissue in hollow organs. Three techniques based on modification of the aperture of single fibers are presented mainly for use in urology and pneumology in combination with rigid and flexible endoscopes. All illumination systems allow for nearly entire illumination of the endoscope's viewing field. A microlens system is used for fluorescence diagnostic purposes in the lung. The system, consisting of two plano convex lenses in a condenser configuration, is attached directly to the fiber. The beam profile is optimized by ray tracing calculations. For fluorescence excitation of the tumormarker Photofrin II in the urinary bladder a 500 micrometers plastic fiber is used. The tip of the fiber is polished to a double cone with angles of 12 degree(s) and 7 degree(s). With this modification the aperture is increased by a factor of two. Photodynamic treatment of confined superficial tumors in the lung was successfully performed with a fused silica fiber coupled to the endoscope in a special adaptive device. In this procedure laserlight at 630 nm is guided through the optics channel of rigid endoscopes. A homogeneous circular illumination pattern is obtained following exactly the deflection angle of the endoscope.

Baumgartner, Reinhold; Beyer, Wolfgang; Friedsam, G.; Jocham, Dieter; Noack, Axel; Sroka, Ronald; Stepp, Herbert G.; Unsoeld, Eberhard

1992-08-01

277

Induction of immune cell infiltration into murine SCCVII tumour by photofrin-based photodynamic therapy.  

PubMed Central

Cellular populations in the squamous cell carcinoma SCCVII, growing in C3H/HeN mice given Photofrin, were examined at various time intervals during the photodynamic light treatment and up to 8 h later. Cell populations present within excised tumours were identified by monoclonal antibodies directed against cell type-specific membrane markers using a combination of the indirect immunoperoxidase and Wright staining or by flow cytometry. Photofrin-based photodynamic therapy (PDT) induced dramatic changes in the level of different cellular populations contained in the treated tumour. The most pronounced was a rapid increase in the content of neutrophils, which increased 200-fold within 5 min after the initiation of light treatment. This was followed immediately by an increase in the levels of mast cells, while another type of myeloid cells, most likely monocytes, invaded the tumour between 0 and 2 h after PDT. The examination of cytolysis of in vitro cultured SCCVII tumour cells mediated by macrophages harvested from the SCCVII tumour revealed a pronounced increase in the tumoricidal activity of tumour-associated macrophages isolated at 2 h post PDT. It seems, therefore, that the PDT-induced acute inflammatory infiltration of myeloid cells into the treated tumour is associated with functional activation of immune cells. PMID:7880738

Krosl, G.; Korbelik, M.; Dougherty, G. J.

1995-01-01

278

Topical delivery of a preformed photosensitizer for photodynamic therapy of cutaneous lesions  

NASA Astrophysics Data System (ADS)

Photosensitizers for photodynamic therapy (PDT) are most commonly delivered to patients or experimental animals via intravenous injection. After initial distribution throughout the body, there can be some preferential accumulation within tumors or other abnormal tissue in comparison to the surrounding normal tissue. In contrast, the photosensitizer precursor, 5-aminolevulinic acid (ALA) or one of its esters, is routinely administered topically, and more specifically, to target skin lesions. Following metabolic conversion to protoporphyrin IX, the target area is photoilluminated, limiting peripheral damage and targeting the effective agent to the desired region. However, not all skin lesions are responsive to ALA-PDT. Topical administration of fully formed photosensitizers is less common but is receiving increased attention, and some notable advances with selected approved and experimental photosensitizers have been published. Our team has examined topical administration of the phthalocyanine photosensitizer Pc 4 to mammalian (human, mouse, pig) skin. Pc 4 in a desired formulation and concentration was applied to the skin surface at a rate of 5-10 ?L/cm2 and kept under occlusion. After various times, skin biopsies were examined by confocal microscopy, and fluorescence within regions of interest was quantified. Early after application, images show the majority of the Pc 4 fluorescence within the stratum corneum and upper epidermis. As a function of time and concentration, penetration of Pc 4 across the stratum corneum and into the epidermis and dermis was observed. The data indicate that Pc 4 can be delivered to skin for photodynamic activation and treatment of skin pathologies.

Oleinick, Nancy L.; Kenney, Malcolm E.; Lam, Minh; McCormick, Thomas; Cooper, Kevin D.; Baron, Elma D.

2012-02-01

279

Photodynamic therapy of endometriosis with HpD (Photosan III) in a new in vitro model  

NASA Astrophysics Data System (ADS)

As a new treatment model for endometriosis, photodynamic therapy was applied to endometriotic and endometrial cultures. It could be demonstrated that both endometrial components (epithelium and stroma) were present in the cultures, proved by immunocytology and electron microscopy. No major differences were seen between endometriotic and endometrial cells. The cultures were treated by HpD-sensitized PDT. Incubation time was 24 h and concentrations of 5 and 10 (mu) g/ml were used. Irradiation was performed by an argon-pumped dye laser at 630 nm with a power density of 80 mW/cm2. Evaluation both morphologically and by trypan blue exclusion test, was effected 24 h after irradiation. Toxicity in endometriotic and endometrial cultures was practically identical. Stroma cells were more sensitive to photodynamic treatment than epithelial cells. Complete stromal cell destruction was reached at 15 J/cm2, whereas epithelial cells showed 100 lethality at 40 J/cm2 (10(mu) g/ml HpD). These and subsequent results demonstrate that the sensitivity of stromal cells was about seven times higher than that of epithelial cells.

Viereck, Volker; Werter, Wiebke; Rueck, Angelika C.; Steiner, Rudolf W.; Keckstein, J.

1994-07-01

280

Pheophorbide a mediated photodynamic therapy against human epidermoid carcinoma cells (A431)  

NASA Astrophysics Data System (ADS)

The objective of this study was to characterize the death mechanism of human epidermoid carcinoma cells (A431) triggered by photodynamic therapy (PDT) with pheophorbide a. First of all, significant inhibition on the survival of A431 cells (< 20 %) was observed when an irradiation dose of 5.1 J/cm2 combined with 125 ng/ml of pheophorbide a was applied. Survival rate of human keratinocyte cells was over 70 % under the same PDT parameters, suggesting that pheophorbide a killed cancer cells selectively. Mitochondria were the main target sites where pheophorbide a accumulated. Formation of reactive oxygen species (ROS) was detected after PDT. Addition of antioxidant N-Acetyl cysteine prevented ROS production and increased cell survival thereafter. The decrease in cellular ATP level was also observed at 6 hrs after PDT. Typical apoptotic cellular morphology and a collapse of mitochondrial membrane potential occurred after PDT. The loss of mitochondrial membrane potential led to the release of cytochrome c from the mitochondria to the cytosol, followed by activation of caspase-9 and caspase-3. The activation of caspase-3 resulted in poly(ADP-ribose) polymerase (PARP) cleavage in A431 cells, followed by DNA fragmentation. In conclusion, the results demonstrated that pheophorbide a possessed photodynamic action against A431 cells, mainly through apoptosis mediated by mitochondrial intrinsic pathway triggered by ROS.

Chen, Yi-Chun; Li, Wen-Tyng

2011-02-01

281

The neovessel occlusion efficacy of 15-hydroxypurpurin-7-lactone dimethyl ester induced with photodynamic therapy.  

PubMed

In this study, the photodynamic therapy (PDT) induced efficacy of a semi-synthesized analogue 15(1)-hydroxypurpurin-7-lactone dimethyl ester or G2, in terms of chick chorioallantoic membrane blood vessel occlusion was evaluated in reference to verteporfin. Early formulation studies showed that G2 prepared in a system of cremophor EL 2.5% and ethanol 2.5% in saline was biocompatible up to 20 microL volume of injection. Following injection, G2 accumulation peaked within the first minute and its extravasation from intra- to extra-vascular occurred somewhat slower as compared with verteporfin. In the PDT study, closure of capillaries and small neovessels was observed with 4 microg per embryo of G2 and a light dose of 20 J cm(-2) at a fluence rate of 40 mW cm(-2) filtered at 400-440 nm-a result that may be considered optimum for the treatment of age-related macular degeneration (AMD). Also, partial occlusion of the large vessels was observed using the same dose of G2 and light-an effect which is desirable for cancer treatment. From this study, we conclude that G2 has the potential to be developed as a therapeutic agent for photodynamic treatment for AMD and cancer. PMID:20074086

Lim, Siang Hui; Nowak-Sliwinska, Patrycja; Kamarulzaman, Fadzly Adzhar; van den Bergh, Hubert; Wagnières, Georges; Lee, Hong Boon

2010-01-01

282

Anti-tumor immune response after photodynamic therapy  

NASA Astrophysics Data System (ADS)

Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp3+) and potentiate immune response after PDT in the case of tumors that express self-antigens. These data suggest that PDT alone will stimulate a strong immune response when tumors express a robust antigen, and in cases where tumors express a self-antigen, T-reg depletion can unmask the immune response after PDT.

Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

2009-06-01

283

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma  

SciTech Connect

Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients {>=}75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age {>=}75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were {>=}75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

Horowitz, David P.; Hsu, Charles C.; Wang Jingya [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States)

2011-08-01

284

Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and therapy.  

PubMed

Tumor-targeted imaging and therapy have been the challenging issue in the clinical field. Herein, we report tumor-targeting hyaluronic acid nanoparticles (HANPs) as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6) for simultaneous photodynamic imaging and therapy. First, self-assembled HANPs were synthesized by chemical conjugation of aminated 5?-cholanic acid, polyethylene glycol (PEG), and black hole quencher3 (BHQ3) to the HA polymers. Second, Ce6 was readily loaded into the HANPs by a simple dialysis method resulting in Ce6-loaded hyaluronic acid nanoparticles (Ce6-HANPs), wherein in the loading efficiency of Ce6 was higher than 80%. The resulting Ce6-HANPs showed stable nano-structure in aqueous condition and rapid uptake into tumor cells. In particular Ce6-HANPs were rapidly degraded by hyaluronidases abundant in cytosol of tumor cells, which may enable intracellular release of Ce6 at the tumor tissue. After an intravenous injection into the tumor-bearing mice, Ce6-HANPs could efficiently reach the tumor tissue via the passive targeting mechanism and specifically enter tumor cells through the receptor-mediated endocytosis based on the interactions between HA of nanoparticles and CD44, the HA receptor on the surface of tumor cells. Upon laser irradiation, Ce6 which was released from the nanoparticles could generate fluorescence and singlet oxygen inside tumor cells, resulting in effective suppression of tumor growth. Overall, it was demonstrated that Ce6-HANPs could be successfully applied to in vivo photodynamic tumor imaging and therapy simultaneously. PMID:22364699

Yoon, Hong Yeol; Koo, Heebeom; Choi, Ki Young; Lee, So Jin; Kim, Kwangmeyung; Kwon, Ick Chan; Leary, James F; Park, Kinam; Yuk, Soon Hong; Park, Jae Hyung; Choi, Kuiwon

2012-05-01

285

Maintenance Therapy With Capecitabine in Patients With Resected Pancreatic Adenocarcinoma After Adjuvant Therapy: A Retrospective Cohort Study  

PubMed Central

ABSTRACT BACKGROUND: The 5-year survival of pancreatic adenocarcinoma with surgery and adjuvant chemotherapy is below 25%. The original Gastrointestinal Tumor Study Group (GITSG) adjuvant study demonstrated a survival benefit attributed to weekly intravenous boluses of 5-fluorouracil (5-FU) for 2 years in addition to chemoradiation compared to surgery alone. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that remain in G0 arrest and kill them as they infrequently enter the G1/S phase. We retrospectively evaluated outcomes in patients who were treated with adjuvant chemotherapy and maintenance capecitabine compared with those who received only adjuvant chemotherapy. METHODS: Patients who had undergone surgical resection with curative intent and received adjuvant chemotherapy were analyzed. Those who subsequently received maintenance capecitabine therapy were compared to those who received adjuvant chemotherapy only. The primary end points were disease recurrence and all-cause mortality. RESULTS: The median overall survival (OS) of patients receiving maintenance capecitabine was greater than 48.4 months (the exact estimate was not available, since the survival probability curve does not cross 0.5). It was 22.0 months (95% confidence interval [CI], 16.6–29.2) in patients who received adjuvant chemotherapy only (P < .001 by log-rank test). The median recurrence-free survival (RFS) was also longer in the maintenance capecitabine group: 54.3 (95% CI, 22.2–Inf) compared to 14.1 (95% CI, 11.6–16.7) months (P < .001, by log-rank test). CONCLUSIONS: In this retrospective study, patients with resected pancreatic adenocarcinoma who received adjuvant chemotherapy had improved OS and RFS with additional maintenance therapy with capecitabine. These findings should be confirmed with a randomized, controlled trial.

Wang, Hongkun; Yang, Xuezhong; Wu, Christina S.; Pishvaian, Michael J.; He, Aiwu R.; Marshall, John L.; Hwang, Jimmy J.

2014-01-01

286

Increasing oxygenation and radiation sensitivity following photodynamic therapy with verteporfin in the RIF-1 tumor  

NASA Astrophysics Data System (ADS)

The combination of verteporfin-based photodynamic therapy (PDT) wiht radiaiton therapy from an orthovoltage device has been examiend in the radiation induced fibrosarcoma tumor model. PDT with verteporfin using a 3 hour delay between injection and the time of optical irradiation has been shown to cause a significant rise in overlal tumor oxygenation. It was huypothesized that this mechanism arises from the reduced oxygen consumption from cells where the PDT has targeted the mitochondria and shut down cellular respiration. Tumor blood flow was measured and found to be still be patent immediately following therapy. This increasing oxygenation was thought to provide an opportunity to increase the radiation sensitivity of the tumor immediately following PDT. When this type of treatment was combined with radiation therapy, a delay in the tumor regrowth time demonstrated that the combined effect was greater than additive. Further study of this phenomenon will provide a more complete mechanistic understanding of the effect and possibly provide a viable pre-treatment for radiation therapy of tumore that increases the therapeutic ratio. This effect could be used to either increase the radiaton dose without increasing the side effects or decrease the dose needed for the same effect on the tumor.

Pogue, Brian W.; O'Hara, Julia A.; Demidenko, Eugene; Wilmot, Carmen M.; Chen, Bin; Swartz, Harold M.; Hasan, Tayyaba

2003-06-01

287

Advances in adjuvant systemic therapy for non-small-cell lung cancer.  

PubMed

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies. PMID:25302167

Leong, David; Rai, Rajat; Nguyen, Brandon; Lee, Andrew; Yip, Desmond

2014-10-10

288

Advances in adjuvant systemic therapy for non-small-cell lung cancer  

PubMed Central

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

Leong, David; Rai, Rajat; Nguyen, Brandon; Lee, Andrew; Yip, Desmond

2014-01-01

289

The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment.  

PubMed

Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

2013-01-01

290

The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment  

PubMed Central

Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

2013-01-01

291

Dynamic model of thermal reaction of biological tissues to laser-induced fluorescence and photodynamic therapy.  

PubMed

The aim of this work was to evaluate the temperature fields and the dynamics of heat conduction into the skin tissue under several laser irradiation conditions with both a pulsed ultraviolet (UV) laser (?=337??nm) and a continuous-wave (cw) visible laser beam (?=632.8??nm) using Monte Carlo modeling. Finite-element methodology was used for heat transfer simulation. The analysis of the results showed that heat is not localized on the surface, but is collected inside the tissue in lower skin layers. The simulation was made with the pulsed UV laser beam (used as excitation source in laser-induced fluorescence) and the cw visible laser (used in photodynamic therapy treatments), in order to study the possible thermal effects. PMID:23839531

Seteikin, Alexey Yu; Krasnikov, Ilya V; Drakaki, Eleni; Makropoulou, Mersini

2013-07-01

292

Controlling silica coating thickness on TiO2 nanoparticles for effective photodynamic therapy.  

PubMed

Photosensitive nanoparticles are useful in developing phototherapeutic agents for targeted cancer therapy. In this paper, core-shell structured titanium dioxide-silica (TiO2-SiO2) nanoparticles, with varying shell thickness, were synthesized. The influence of the silica shell thickness on the photoreactivity, cytotoxicity and photo-killing ability of the TiO2 nanoparticles was investigated. Silica coating reduced the photocatalytic reactivity but improved the cytocompatibility of the TiO2 nanoparticles. This effect was amplified with increasing silica shell thickness. When the silica thickness was about 5.5 nm, the coated TiO2 not only retained a high level photodynamic reactivity, comparable to the non-coated TiO2 nanoparticles, but also demonstrated an improved cell compatibility and effective photo-killing ability upon the mouse fibroblast cells (L929). PMID:23502045

Feng, Xiaohui; Zhang, Shaokun; Lou, Xia

2013-07-01

293

Application of backward diffuse reflection spectroscopy for monitoring the state of tissues in photodynamic therapy  

SciTech Connect

The application of backward diffuse reflection (BDR) spectroscopy for in vivo monitoring the degree of haemoglobin oxygenation and concentration of photosensitisers in tissues subjected to photodynamic therapy is demonstrated. A simple experimental technique is proposed for measuring diffuse reflection spectra. The measurements are made under steady-state conditions using a fibreoptic probe with one transmitting and one receiving fibre separated by a fixed distance. Although this approach does not ensure the separation of contributions of scattering and absorption to the spectra being measured, it can be used for estimating the degree of haemoglobin oxygenation and concentration of photosensitisers in the tissues. Simple expressions for estimating the concentration of photosensitisers from the BDR spectra are presented and the accuracy of this approach is analysed. The results of application of BDR spectroscopy for monitoring various photosensitisers are considered. (special issue devoted to multiple radiation scattering in random media)

Stratonnikov, Aleksandr A; Meerovich, G A; Ryabova, A V; Savel'eva, T A; Loshchenov, V B [Natural Science Center, A.M. Prokhorov General Physics Institute, Russian Academy of Sciences, Moscow (Russian Federation)

2006-12-31

294

Photodynamic therapy by topical meso-tetraphenylporphinesulfonate tetrasodium salt administration in superficial basal cell carcinomas  

SciTech Connect

The efficacy of an originally developed photodynamic approach, using topical administration of tetraphenylporphinesulfonate as the photosensitizer, was evaluated in a series of 292 basal cell carcinoma lesions (less than 2-mm thick) in 50 treated patients. The lack of indication for conventional therapies was the main selection criterion. The photosensitizing agent (2% solution) was topically applied at 0.1 ml/cm2, followed by light irradiation with a dye laser emitting at 645 nm (120 or 150 J/cm2). After initial treatment, all lesions responded, with 273 (93.5%) complete responses. Recurrences were observed in 29 (10.6%). A second application of photoradiation was performed in 15 persistent lesions and 11 relapsed lesions, producing 19/26 complete responses. Our results suggest that this technique can be considered a promising alternative treatment modality in selected cases of superficial basal cell carcinomas.

Santoro, O.; Bandieramonte, G.; Melloni, E.; Marchesini, R.; Zunino, F.; Lepera, P.; De Palo, G. (Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan (Italy))

1990-08-01

295

Serum levels of hematoporphyrin derivatives in the photodynamic therapy of malignant tumors  

NASA Astrophysics Data System (ADS)

In photodynamic therapy (PDT), red light is administered 24 - 72 hours post intravenous (i.v.) injection of hematoporphyrin derivatives (HpD). In an earlier animal model study, more effective therapeutic response was obtained when red light irradiation was carried out 15 mins after the injection of HpD. The effectiveness of this immediate PDT protocol has been correlated to the high serum level of HpD immediately after administration and the destruction of the microcirculation system as the dominant tumor destruction mechanism. This study examines the pharmacokinetics and the serum levels of HpD in rats and also in human patients. Such data can assist in defining the optimum time delay for light irradiation in the PDT of cancer.

Chan, H. K.; Low, K. S.; Haji Baba, A. S.; Arimbalam, S.; Yip, C. H.; Chang, K. W.; Baskaran, G.; Lo, Y. L.; Jayalakshmi, P.; Looi, L. M.; Tan, N. H.

1994-10-01

296

Serum levels of hematoporphyrin derivatives in the photodynamic therapy of malignant tumors  

NASA Astrophysics Data System (ADS)

In photodynamic therapy (PDT), red light is administered 24 - 72 hours post intravenous (i.v.) injection of hematoporphyrin derivatives (HpD). In an earlier animal model study, more effective therapeutic response was obtained when red light irradiation was carried out 15 mins after the injection of HpD. The effectiveness of this immediate PDT protocol has been correlated to the high serum level of HpD immediately after administration and the destruction of the microcirculation system as the dominant tumor destruction mechanism. This study examines the pharmacokinetics and the serum levels of HpD in rats and also in human patients. Such data can assist in defining the optimum time delay for light irradiation in the PDT of cancer.

Chan, H. K.; Low, K. S.; Haji Baba, A. S.; Arimbalam, S.; Yip, C. H.; Chang, K. W.; Baskaran, G.; Lo, Y. L.; Jayalakshmi, P.; Looi, L. M.; Tan, N. H.

1995-03-01

297

Primary stage of photodestruction of malignant cells under photodynamic therapy of tumors  

NASA Astrophysics Data System (ADS)

In this work we present the experimental results indicating that under photodynamic therapy the primary stage of the photodestruction of malignant cells is based on the irreversible photodestruction of glycolysis enzymes located, first of all, in mitochondria playing a key role in the energy supply for the tumor cells. It was shown that the formation of complexes between glycolysis enzymes and a sensitizer promotes an effective destruction of the formers. The formation of strong complexes was demonstrated for a number of glycolysis enzymes (glyceraldehyde-2-phosphate dehydrogenase, pyruvate kinase, lactate dehydrogenase) with the use of water-soluble pigments chlorin e6 and tetra(carboxyphenyl)porphyrin (T(CP)P) as sensitizers. The direct correlation was shown between the effectiveness of the photodestruction of enzyme molecules and the enzyme-sensitizer binding constant.

Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Tretjakova, Antonina I.

1996-01-01

298

Dye laser photodynamic therapy for Bowen's disease in a patient with epidermodysplasia verruciformis.  

PubMed

Epidermodysplasia verruciformis (EV) is a rare heritable skin disease that results in unusual susceptibility to infection with specific types of human papillomavirus (HPV). Here we report a 53-year-old man with EV who developed Bowen's disease on his lower eyelid and the chest. Mutation analysis of EVER1 gene revealed homozygous splice acceptor site mutation (IVS8-2, A > T). In this patient, HPV3, HPV14, and HPV38 had been identified from the skin lesions. The Bowen's skin lesion on the left lower eye-lid was treated by photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) and pulsed dye laser (PDL). After two rounds of the PDT treatment, the skin lesion disappeared and a skin biopsy confirmed the efficacy of the treatment. This method was simple, less invasive than other treatments, and achieved a satisfactory cosmetic result. PMID:23610850

Sunohara, Mari; Ozawa, Toshiyuki; Morimoto, Kuniyuki; Harada, Teruichi; Ishii, Masamitsu; Fukai, Kazuyoshi

2012-12-01

299

New diffuser/applicator for use in the treatment of esophageal cancer by photodynamic therapy  

NASA Astrophysics Data System (ADS)

We have designed and constructed a simple, cheap and effective diffuser/applicator for intraluminal photodynamic therapy in oesophageal cancer. A cylindrical diffusing optical fiber can be easily located in the center of the oesophageal lumen with the use of a modified naso- gastric Ryles tube. This allows more uniform illumination of the luminal circumference. Measurements are presented of the light field generated by this delivery system in an optical phantom. These demonstrate that the presence of the Ryles tube imposes only a small modification on the output of the bare diffuser. The light doses received adjacent to the diffusing section are identical, within the accuracy of measurement, both with and without the tube. This ensures adequate illumination of a circumferential oesophageal tumor using a contained fiber, without adjustment of the established treatment parameters.

Hudson, Emma J.; Stringer, Mark R.; Dixon, Kate; Moghissi, Keyvan

1995-03-01

300

Photodynamic therapy induced leukocyte adherence in normal subcutaneous, but not in tumor microvessels  

NASA Astrophysics Data System (ADS)

Leukocyte mediated tissue damage is proposed to contribute to the tumoricidal effect of photodynamic therapy (PDT). To elucidate this hypothesis leukocyte-endothelium interaction and red blood cell velocity in the microvasculature of an amelanotic melanoma and normal tissue in a skin fold chamber preparation were investigated before and after PDT (5 mg/kg PhotofrinR; 630 nm; 10 or 100 J/cm2). One hour after PDT (10 and 100 J/cm2) the number of adhering leukocytes increased in subcutaneous but not in tumor microvessels. At this time red blood cell velocity remained unaltered in microvessels of subcutaneous tissue but decreased (10 J/cm2) and even ceased (100 J/cm2) in tumor microvessels. These results indicate that tumor destruction induced by PDT is not mediated by leukocyte-endothelium interaction.

Dellian, Marc; Abels, Christoph; Kuhnle, Gerhard E.; Goetz, Alwin E.

1995-03-01

301

Photodynamic therapy induced leukocyte adherence in normal subcutaneous, but not in tumor microvessels  

NASA Astrophysics Data System (ADS)

Leukocyte mediated tissue damage is proposed to contribute to the tumoricidal effect of photodynamic therapy (PDT). To elucidate this hypothesis leukocyte-endothelium interaction and red blood cell velocity in the microvasculature of an amelanotic melanoma and normal tissue in a skin fold chamber preparation were investigated before and after PDT (5 mg/kg PhotofrinR; 630 nm; 10 or 100 J/cm2). One hour after PDT (10 and 100 J/cm2) the number of adhering leukocytes increased in subcutaneous but not in tumor microvessels. At this time red blood cell velocity remained unaltered in microvessels of subcutaneous tissue but decreased (10 J/cm2) and even ceased (100 J/cm2) in tumor microvessels. These results indicate that tumor destruction induced by PDT is not mediated by leukocyte-endothelium interaction.

Dellian, Marc; Abels, Christoph; Kuhnle, Gerhard E.; Goetz, Alwin E.

1994-10-01

302

Corneal heat scar caused by photodynamic therapy performed through an implanted corneal inlay.  

PubMed

A 60-year-old man had a combination of laser in situ keratomileusis and Kamra corneal inlay implantation to correct presbyopia. Although the outcome was favorable postoperatively, central serous chorioretinopathy was observed in the left eye along with a decrease in the uncorrected (UDVA) and corrected (CDVA) distance visual acuities and the corrected near visual acuity (CNVA). Photodynamic therapy (PDT) was later performed in a university hospital. After PDT, the patient experienced a decline in the visual acuity and came to our clinic a month after the PDT. Degeneration and a scar were observed at the location of the inlay due to the heat and burning. Flattening of the corneal topography was also observed where the corneal scar was located, along with a significant decrease in CDVA in the left eye. Prior to any surgery in which the corneal inlay is an impediment, surgeons should take advantage of the reversibility of the Kamra inlay by explanting the inlay. PMID:24160386

Mita, Mariko; Kanamori, Tomomi; Tomita, Minoru

2013-11-01

303

Treatment of actinic cheilitis by photodynamic therapy with 5-aminolevulinic acid and blue light activation.  

PubMed

Actinic cheilitis (AC), a common disorder of the lower lip, should be treated early to prevent progression to invasive squamous cell carcinoma. This study evaluated the safety and efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) activated by blue light for the treatment of AC. Fifteen patients with clinically evident or biopsy-proven AC received two treatments with ALA PDT with blue light activation. Treatments were spaced three to five weeks apart. Most patients achieved 65% to 75% clearance three to five weeks after the first treatment and all achieved more than 75% clearance one month after the second treatment. Three patients achieved complete clearance. Pain and burning during irradiation were absent or mild. All patients said they would repeat the procedure. ALA PDT with 417 nm blue light is a promising option for the treatment of AC of the lower lip. PMID:22052302

Zaiac, Martin; Clement, Annabelle

2011-11-01

304

Antimicrobial Photodynamic Therapy and Dental Plaque: A Systematic Review of the Literature  

PubMed Central

Background. The aim of this study was to perform a systematic review of the literature on the efficacy of antimicrobial photodynamic therapy (PDTa) on cariogenic dental biofilm. Types of Studies Reviewed. Studies in vivo, in vitro, and in situ were included. Articles that did not address PDTa, those that did not involve cariogenic biofilm, those that used microorganisms in the plankton phase, and reviews were excluded. Data extraction and quality assessments were performed independently by two raters using a scale. Results. Two hundred forty articles were retrieved; only seventeen of them met the eligibility criteria and were analyzed in the present review. Considerable variability was found regarding the methodologies and application protocols for antimicrobial PDTa. Two articles reported unfavorable results. Practical Implications. The present systematic review does not allow drawing any concrete conclusions regarding the efficacy of antimicrobial PDTa, although this method seems to be a promising option. PMID:25379545

Santin, G. C.; Oliveira, D. S. B.; Galo, R.; Borsatto, M. C.; Corona, S. A. M.

2014-01-01

305

Treatment of rat Walker-256 carcinosarcoma with photodynamic therapy and endotoxin irradiated with high-energy electrons  

NASA Astrophysics Data System (ADS)

Experiments were performed on five batches of Wistar inbred rats with Walker-256 carcinosarcoma receiving sole treatment photodynamic therapy (PDT), irradiated endotoxin (R-LPS), native-endotoxin (N-LPS), or associated therapy (PDT + R-LPS) and the control batch (saline) consisted of animals with untreated Walker-256 tumors. The results were as follows: the sole treatment (PDT, R-LPS, N-LPS) gave survival rates between 56.3 and 60.7% and cure rates ranging from 32.1 to 37.5%. The `combined' therapy in multiple doses increased significantly (88.6%) the survival rate of tumor bearing rats as well as the highest incidence of complete tumor regression (71.4%). This work demonstrates that `combined' photodynamic and immunotherapy with irradiated endotoxin stimulates cell-mediated antitumoral activity and induces changes in the tumoral incidence in Walker-256 carcinosarcoma in the rat model.

Dima, Vasile F.; Vasiliu, Virgil V.; Laky, Dezideriu; Ionescu, Mircea D.; Dima, Stefan V.

1994-03-01

306

Endoscopic photodynamic therapy with hematoporphyrin derivative in the treatment of malignant tumors: report of 120 cases  

NASA Astrophysics Data System (ADS)

One-hundred-twenty cases of malignant tumors treated by endoscopic photodynamic therapy with hematoporphyrin derivative from August 1982 - July 1990 are reported. Of the 120 cases, including 97 males and 23 females ages varying from 39 to 77 years old, 40 cases were primary tumors and 80 cases were local residual or recurrent after surgery or radiotherapy or chemotherapy. All cases were confirmed in pathological biopsy, including 58 squamous cell carcinoma, 28 various adenocarcinoma, and 34 transitional cell carcinoma. Twenty-four, 48 and/or 72 hours after intravenous injection of HpD 2.0 - 3.0 mg/kg, or DHE 1.5 - 2.0 mg/kg, or Y-HpD 5.0 mg/kg, the tumor was irradiated with 630 nm wavelength of argon dye laser via a quartz light fiber inserted through the forceps channel of the endoscope. Of the 120 cases treated, CR was obtained in 38 cases, PR in 25 cases, MR in 52 cases, and NR in 5 cases. Total response rate was 95.8%; significant response rate 52.5%; and tumor eradicated rate 31.7%. The 38 cases included: 14 cases of early esophageal carcinoma, 3 cases of early cardiac carcinoma, 1 case of early lung cancer, 1 case of early gastric carcinoma, 15 cases of superficial bladder carcinoma, 3 cases of local residual recurrent micro lung cancer, and 1 case of cardiac carcinoma. The longest cancer-free survival was over eight years. Endoscopic photodynamic therapy is, therefore, curative effective in the treatment of early and superficial carcinoma, and palliative effective in the treatment of advanced carcinoma. Standardized and controlled trials are required to assess its place in combined treatment of malignant tumors.

Tian, Mao-en; Liu, Fa-wen; Qian, Jia-ping; Ji, Qing; Feng, Yun-qiu

1993-03-01

307

Photodynamic therapy for subfoveal choroidal neovascularisation in Vogt-Koyanagi-Harada disease  

PubMed Central

Aim To assess the effects of photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) secondary to Vogt?Koyanagi?Harada disease (VKH). Methods Six eyes of six patients with VKH who developed subfoveal CNV underwent standard PDT. Repeated treatments were performed at 3?month intervals for persistent leakage. Charts and angiographic data were analysed retrospectively. Results Age of patients ranged between 17?years and 27?years. Five CNV lesions were recent and classic (greatest lesion diameter was 1100–3100??m). One CNV was chronic and partially scarred. Mean visual acuity (VA) at presentation was 20/200. Five patients had more than 1?year of follow up. In five eyes there was active inflammation and CNV. Of these eyes, the first three required one PDT each. The final CNV scar was smaller/stable with improvement of VA in two eyes. The third developed a larger CNV scar with loss of two lines of VA. Submacular fibrosis developed in all three. In the fourth eye, mild CNV leakage persisted after one PDT but hazy media precluded a second PDT. At 18?months the CNV scar and VA were stable. The fifth case, with mild inflammation, required three PDT. The CNV leakage became minimal, the lesion became smaller, and VA improved significantly. The sixth eye with CNV had no inflammation and needed two PDT sessions to halt the CNV leakage. The final lesion was smaller and vision was stable. There were no PDT related complications in our series. Conclusion Photodynamic therapy with verteporfin appears to be a safe and viable treatment option for subfoveal CNV secondary to VKH. It offers a chance for stabilisation or even improvement of vision. Further study is warranted. PMID:16687455

Nowilaty, S R; Bouhaimed, M; Group, the Photodynamic Therapy Study

2006-01-01

308

Photodynamic therapy of human squamous cell carcinoma in vitro and in xenografts in nude mice.  

PubMed

Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systematically administered photosensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photosensitizer was 1.6 or 1.5, respectively. Administration of Pf-II (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm2, 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo. PMID:8361317

Megerian, C A; Zaidi, S I; Sprecher, R C; Setrakian, S; Stepnick, D W; Oleinick, N L; Mukhtar, H

1993-09-01

309

Dependence of photodynamic threshold dose on treatment parameters in normal rat liver in vivo  

NASA Astrophysics Data System (ADS)

The validity and utility of the measurement of the photodynamic threshold dose as an in vivo tool for quantitatively assessing the effectiveness of performing photodynamic therapy (PDT) using differing photosensitizers, irradiation protocols and adjuvant treatments was examined. The depth of the boundary between necrotic tissue and normal tissue following surface irradiation of normal rat liver was used to calculate the photodynamic threshold, a quantity independent of photosensitizer concentration, light fluence and wavelength. PDT was performed using Photofrin II to investigate the changes in photodynamic threshold using four different treatment conditions. Using a range of values for photosensitizer concentration and total light fluence, the photodynamic threshold was found to be independent of these parameters and estimated as (3.4 +/- 0.3) X 1018 photons cm-3. Using periodic light irradiation schedules to determine if diffusion of 3O2 affects the threshold measurement, the photodynamic thresholds were found not to be significantly different from those using normal irradiation which suggests that this model is not sensitive to this parameter. PDT was performed in conjunction with hyperthermia and significant reductions in the photodynamic threshold were obtained if hyperthermia followed PDT but not if hyperthermia preceded PDT. Finally, the effects of the radio-protecting agents WR-77913 and WR-2721 were examined and significant increases in the photodynamic threshold were obtained for PDT performed following injection of sufficient quantity of either radio-protecting drug.

Farrell, Thomas J.; Wilson, Brian C.; Patterson, Michael S.; Chow, Rowena

1991-06-01

310

Ocular photodynamic therapy--standard applications and new indications (part 1). Review of the literature and personal experience.  

PubMed

Ocular photodynamic therapy (PDT) was introduced as a novel treatment for neovascular forms of age-related macular degeneration and choroidal neovascularization (CNV) secondary to pathologic myopia in the mid/end 1990s. The current treatment recommendations are based on the results of two large, prospective, multicenter, randomized clinical trials (Treatment of Age-Related Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic Therapy Studies) and thousands of patients have been treated worldwide over the last years. Meanwhile, PDT has been performed in several other ocular pathologies with some remarkable results, however, with most reports being case reports and small case series without statistical significance. These extended applications include CNV secondary to choroiditis and retinochoroiditis, angioid streaks, central serous chorioretinopathy, retinal angiomatous proliferation, parafoveal telangiectasia or CNV associated with macular dystrophy and idiopathic CNV, as well as diseases without CNV, such as choroidal hemangioma, retinal hamartoma, choroidal melanoma, chronic central serous chorioretinopathy, angiomatous lesions secondary to systemic diseases, rubeosis iridis or neovascular glaucoma. To date, with the introduction of anti-VEGF therapy, the role of PDT will certainly change. However, it is reasonable to believe that it will maintain an important role in combination therapy due to its unique properties of selective vascular targeting. Therefore, it is essential for the ophthalmologist to be familiar with the extended applications and their modifications of treatment parameters. This review will summarize the standard and experimental applications of PDT based on our own results and the literature. PMID:17579286

Mennel, Stefan; Barbazetto, Irene; Meyer, Carsten H; Peter, Silvia; Stur, Michael

2007-01-01

311

Photodynamic Therapy  

MedlinePLUS

... sunlight, but you don’t have stay in dark rooms. Some indoor light is important because it ... sure windows and skylights are fully covered. Bring dark sunglasses, gloves, a wide brimmed hat, long pants, ...

312

Vascular Targeted Photodynamic Therapy With Palladium-Bacteriopheophorbide Photosensitizer for Recurrent Prostate Cancer Following Definitive Radiation Therapy: Assessment of Safety and Treatment Response  

Microsoft Academic Search

Purpose: Tookad® is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external

J. Trachtenberg; A. Bogaards; R. A. Weersink; M. A. Haider; A. Evans; S. A. McCluskey; A. Scherz; M. R. Gertner; C. Yue; S. Appu; A. Aprikian; J. Savard; B. C. Wilson; M. Elhilali

2007-01-01

313

A comprehensive mathematical model of microscopic dose deposition in photodynamic therapy  

SciTech Connect

We have developed a comprehensive theoretical model for rigorously describing the spatial and temporal dynamics of oxygen ({sup 3}O{sub 2}) consumption and transport and microscopic photodynamic dose deposition during photodynamic therapy (PDT) in vivo. Previously published models have been improved by considering perfused vessels as a time-dependent {sup 3}O{sub 2} source and linking the {sup 3}O{sub 2} concentration in the vessel to that within the tissue through the Hill equation. The time-dependent photochemical {sup 3}O{sub 2} consumption rate incorporates sensitizer photobleaching effects and an experimentally determined initially nonuniform photosensitizer distribution. The axial transport of {sup 3}O{sub 2} is provided for in the capillaries and in the surrounding tissue. A self-sensitized singlet oxygen ({sup 1}O{sub 2})-mediated bleaching mechanism and the measured, initially nonuniform distribution of meso-tetrahydroxyphenyl chlorin at 3 h after intravascular administration were used to demonstrate the capabilities of the model. Time-evolved distributions of {sup 3}O{sub 2} concentration were obtained by numerically solving two-dimensional diffusion-with-reaction equations both in the capillary and the adjacent tissue. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin-{sup 3}O{sub 2} saturation (SO{sub 2}) within the vessels, irreversible sensitizer degradation due to photobleaching, and the microscopic distributions of {sup 3}O{sub 2}, sensitizer concentration, and {sup 1}O{sub 2} dose deposition under various irradiation conditions. The simulations reveal severe axial gradients in {sup 3}O{sub 2} and in photodynamic dose deposition in response to a wide range of clinically relevant treatment parameters. Thus, unlike former Krogh cylinder-based models, which assume a constant {sup 3}O{sub 2} concentration at the vessel, this new model identifies conditions in which {sup 3}O{sub 2} depletion and minimal deposition of reacting {sup 1}O{sub 2} exist near the end of axial segments of vessels and shows that treatment-limiting {sup 3}O{sub 2} depletion is induced at fluence rates as low as 10 mW cm{sup -2}. These calculations also demonstrate that intercapillary heterogeneity of photosensitizer contributes significantly to the distribution of photodynamic dose. This more rigorous mathematical model enables comparison with experimentally observable, volume-averaged quantities such as SO{sub 2} and the loss of sensitizer fluorescence through bleaching that have not been included in previous analyses. Further, it establishes some of the intrinsic limitations of such measurements. Specifically, our simulations demonstrate that tissue measurements of SO{sub 2} and of photobleaching are necessarily insensitive to microscopic heterogeneity of photodynamic dose deposition and are sensitive to intercapillary spacing. Because prior knowledge of intercapillary distances in tumors is generally unavailable, these measurements must be interpreted with caution. We anticipate that this model will make useful dosimetry predictions that should inform optimal treatment conditions and improve current clinical protocols.

Kang-Hsin Wang, Ken; Mitra, Soumya; Foster, Thomas H. [Department of Physics and Astronomy, University of Rochester, Rochester, New York 14642 (United States); Department of Imaging Sciences, University of Rochester, Rochester, New York 14642 (United States); Department of Imaging Sciences, Department of Physics and Astronomy, and Institute of Optics, University of Rochester, 601 Elmwood Avenue, Box 648, Rochester, New York 14642 (United States)

2007-01-15

314

Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation: where do we stand?  

PubMed

Liver transplantation (LT) for hepatocellular carcinoma (HCC) within Milan criteria is a widely accepted optimal therapy. Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent dropout during the waiting period and as a down-staging method for the patient with intermediate HCC to qualify for liver transplantation. Transarterial chemoembolization and radiofrequency ablation are the most commonly used method for locoregional therapy. The data associated with newer modalities including drug-eluting beads, radioembolization with Y90, stereotactic radiation therapy and sorafenib will be discussed as a tool for converting advanced HCC to LT candidates. The concept "ablate and wait" has gained the popularity where mandated observation period after neo-adjuvant therapy allows for tumor biology to become apparent, thus has been recommended after down-staging. The role of neo-adjuvant therapy with conjunction of "ablate and wait" in living donor liver transplantation for intermediate stage HCC is also discussed in the paper. PMID:24833861

Fujiki, Masato; Aucejo, Federico; Choi, Minsig; Kim, Richard

2014-05-14

315

Chronic active hepatitis and liver cirrhosis in association with combined tamoxifen\\/tegafur adjuvant therapy  

Microsoft Academic Search

Summary Two female breast cancer patients who received combined tamoxifen and tegafur as postsurgical adjuvant therapy developed severe hepatotoxicity after being treated for three and eight months, respectively. Shortly after the cessation of the treatment, routine liver tests showed gradual recovery, but liver biopsies revealed chronic active hepatitis in one patient and liver cirrhosis in the other. Four and five

Shigeo Maruyama; Chisato Hirayama; Juro Abe; Jun Tanaka; Katsuaki Matsui

1995-01-01

316

Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy  

SciTech Connect

Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

Showalter, Timothy N., E-mail: timothy.showalter@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Ohri, Nitin; Teti, Kristopher G. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Foley, Kathleen A. [Strategic Consulting, Thomson Reuters Healthcare, Cambridge, MA (United States); Keith, Scott W. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Trabulsi, Edouard J.; Lallas, Costas D. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Hoffman-Censits, Jean [Department of Medical Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Pizzi, Laura T. [School of Pharmacy, Thomas Jefferson University, Philadelphia, PA (United States); Gomella, Leonard G. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

2012-02-01

317

Taxanes in adjuvant and neoadjuvant therapies for breast cancer.  

PubMed

Paclitaxel (Taxol) is a diterpene originally obtained from the bark of the Pacific Yew Tree, Taxus Brevifolia. Its mechanism of action is unique. It stabilizes microtubule polymerization, thus blocking cells in the G2/M phase of the cell cycle. In breast cancer, initial studies using paclitaxel demonstrated high activity. The first study was reported in 1991 by Holmes et al who gave paclitaxel as a 24-hour infusion at 250 mg/m2 to 25 patients with metastatic breast cancer following only one prior chemotherapy regimen--they achieved a 56% response rate. Since then, numerous studies have confirmed the effectiveness of paclitaxel in patients with metastatic disease. A second taxane, docetaxel (Taxotere), has also demonstrated excellent activity. Clinical research is now focused on integrating the taxanes into combination drug regimens and into neoadjuvant and adjuvant schedules for patients with early stage breast cancer, as well as looking at the biologic determinants of response and resistance to taxanes. This article will review developments in the use of taxanes in the adjuvant and neoadjuvant settings and it will review the information on possible molecular markers that may be useful in predicting tumor responsiveness to taxanes. PMID:9516599

O'Leary, J; Volm, M; Wasserheit, C; Muggia, F

1998-01-01

318

Immune response after photodynamic therapy increases anti-cancer and anti-bacterial effects  

PubMed Central

Photodynamic therapy (PDT) is a clinically approved procedure for treatment of cancer and infections. PDT involves systemic or topical administration of a photosensitizer (PS), followed by irradiation of the diseased area with light of a wavelength corresponding to an absorbance band of the PS. In the presence of oxygen, a photochemical reaction is initiated, leading to the generation of reactive oxygen species and cell death. Besides causing direct cytotoxic effects on illuminated tumor cells, PDT is known to cause damage to the tumor vasculature and induce the release of pro-inflammatory molecules. Pre-clinical and clinical studies have demonstrated that PDT is capable of affecting both the innate and adaptive arms of the immune system. Immune stimulatory properties of PDT may increase its beneficial effects giving the therapy wider potential to become more extensively used in clinical practice. Be sides stimulating tumor-specific cytotoxic T-cells capable to destroy distant untreated tumor cells, PDT leads to development of anti-tumor memory immunity that can potentially prevent the recurrence of cancer. The immunological effects of PDT make the therapy more effective also when used for treatment of bacterial infections, due to an augmented infiltration of neutrophils into the infected regions that seems to potentiate the outcome of the treatment.

Reginato, Eleonora; Wolf, Peter; Hamblin, Michael R

2014-01-01

319

Hematoporphyrin-mediated photodynamic therapy for treatment of head and neck cancer: clinical update 1996  

NASA Astrophysics Data System (ADS)

From 1983 to 1996 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 55 of 56 patients treated with hematoporphyrin-derivative or PHOTOFRIN-mediated photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial 'condemned mucosa' or 'field cancerization' of the oral cavity and larynx (7 cases); (2) Stage III/IV head and neck cancer (25 cases); (3) mucocutaneous AIDS-associated Kaposi's sarcoma of the upper aerodigestive tract and non AIDS-related Kaposi's sarcoma of the lower extremity (15 cases); (4) recurrent laryngotracheal papillomatosis (3 cases); (5) severe dysplasia/adenocarcinoma or squamous cell carcinoma in situ in Barrett's esophagus (4 cases); (6) partial or completely obstructing terminal esophageal cancer (9 cases). At the time of this report, HPD-PDT produced complete responses in 24 patients (follow up 6 months to 9 years) with 'field cancerization' (CIS, T1N0M0) of the oral cavity and larynx (6 cases), adenocarcinoma in situ in Barrett's esophagus (3 cases), mucocutaneous Kaposi's sarcoma (12 cases), obstructing esophageal carcinoma (1 case), and stage IV squamous cell carcinoma of the nasopharynx (1 case), and radiation therapy or solar-induced basal cell/squamous cell carcinomas (2 cases). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck cancer are reviewed in this article.

Schweitzer, Vanessa G.

1996-04-01

320

Theranostic nanocells for simultaneous imaging and photodynamic therapy of pancreatic cancer  

NASA Astrophysics Data System (ADS)

Nanotechnology has the potential to deliver multiple imaging and therapeutic agents to the "right place at the right time". This could dramatically improve treatment responses in cancer which have been so far, dismal as well as allow us to monitor this response online. Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5% and there is a desperate need for effective treatments. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Here, we investigate the effect of neutralizing intracellular VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies against cancer. Our studies demonstrate significant enhancement in treatment outcomes when nanocell-based PDT is combined with Avastin in orthotopic PanCa mouse models. We propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

Spring, Bryan; Mai, Zhiming; Rai, Prakash; Chang, Sung; Hasan, Tayyaba

2010-02-01

321

Cost-effectiveness analysis of adjuvant physical or occupational therapy for patients with reflex sympathetic dystrophy  

Microsoft Academic Search

Objective: To study from a societal viewpoint the cost-effectiveness of adjuvant treatment for patients with reflex sympathetic dystrophy (RSD) of one upper extremity.Design: A two-center randomized clinical trial comparing pairwise physical therapy (PT), occupational therapy (OT), and control treatment (CT).Patients: One hundred thirty-five patients with RSD for less than 1 year participated.Interventions: PT and OT were given according to protocols.

Johan L. Severens; H. Margreet Oerlemans; Antonius J. P. G. Weegels; Martin A. van't Hof; Rob A. B. Oostendorp; R. Jan A. Goris

1999-01-01

322

Treatment of ovarian cancer with photodynamic therapy and immunoconjugates in a murine ovarian cancer model.  

PubMed Central

In photodynamic therapy (PDT), photosensitisers accumulate somewhat preferentially in malignant tissues; photoactivation with appropriate wavelength of light release toxic molecular species which lead to tumour tissue death. In order to target ovarian cancer with increased specificity, a chlorin-based photosensitiser (chlorin e6 monoethylendiamine monoamide) was conjugated to OC125, a monoclonal antibody recognising an antigen expressed in 80% of non-mucinous ovarian cancers. In previous work, this immunoconjugate (IC) was shown to be selectively phototoxic to cancer cells from ovarian cancer patients ex vivo and to localise preferentially in ovarian cancer tissue in vivo. In this study we report results from in vivo phototoxicology and photodynamic treatment studies using this IC in a murine model for ovarian cancer. A comparison of single vs multiple treatments was also made. For in vivo experimentation, Balb C nude mice were injected with 30 x 10(6) NIH:OVCAR 3 cancer cells to create an ascitic tumour model. Animals were then given intraperitoneal injections of the immunoconjugate (0.5 mg kg-1). Twenty-four hours later the intraperitoneal surfaces were exposed to 656 nm light from an argon-ion pumped-dye laser (50 mW, 656 nm), using a cylindrical diffusing tip fibre. The overall treatment was given either once or multiply. No animals died from treatment complications. Twenty-four hours following one and three PDT treatments, the percentage of viable tumour cells in the ascites of the treated animals analysed ex vivo was 34% and 5% of control for one and three treatments respectively. With respect to survival, all control mice (n = 18) died between 30 and 50 days. However, for those treated three times (n = 10), 40% were still alive after 50 days, and for those treated four times (n = 12) 58% were alive after 50 days. Evaluation with log-rank test revealed a significant survival with intraperitoneal PDT compared with controls (P = 0.0006). These preliminary results suggest that PDT with an OC125 immunoconjugate may be an effective therapy for the management of advanced ovarian cancer. Clinical application of this therapy needs to be further optimised and may require multiple treatments, similar to fractionated radiation therapy and cyclic chemotherapy, in order to control malignant disease with acceptable toxicity to normal tissue. PMID:8883404

Goff, B. A.; Blake, J.; Bamberg, M. P.; Hasan, T.

1996-01-01

323

Preliminary study of verteporfin photodynamic therapy in a canine prostate model  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) mediated with verteporfin was investigated as an alternative modality for the treatment of prostate cancer. Materials and Methods: Vertoporfin-mediated photodynamic effects on the prostate and its adjacent structures (underlying colon and bladder) were evaluated in a healthy canine model. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (689 nm) and 1-cm cylindrical diffuser fibers at various light doses and drug-light intervals (DLI) to activate the IV administrated photosensitizer (0.5 or 2 mg/kg). The sensitivity of the adjacent tissues to Vertoporfin-PDT was determined by superficially irradiating the serosal surface of the bladder and colon with a microlens fiber. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathological examination. Results: Histopathological examinations confirmed that verteporfin PDT could destroy a clinically significant volume of prostatic tissue in the animal model. At the drug dose of 0.5 mg/kg, the light irradiation of 100 J/cm could induce a lesion diameter of 2 cm at DLI of 15 min and 1.2 cm at DLI of 3 hrs, respectively. This implies a strong influence of DLI on the lesion volume. The shorter DLI might produce stronger vascular effect and therefore more severe tissue damage. The colon was more sensitive to verteporfin PDT than the bladder. At the possible light dose level caused by light scattering during intra-prostate irradiation, the damage to the bladder and colon were superficial and minimal. Conclusions: The preliminary results clearly demonstrate that verteporfin PDT could be an effective means to destroy prostate gland and its usefulness for the treatment of prostate cancer is worth further investigation.

Huang, Zheng; Hetzel, Fred; Dole, Ken; Luck, David; Beckers, Jill; Maul, Don

2009-06-01

324

Three-dimensional cell culturing by magnetic levitation for evaluating efficacy/toxicity of photodynamic therapy  

NASA Astrophysics Data System (ADS)

We used three dimensional cell cultures (3D) based on the magnetic levitation method (MLM) to evaluate cytotoxicity of photodynamic therapy (PDT). First, we decorated Hep G2 and MDA-MB-321 cells with NanoShuttle by introducing it in the media and incubated overnight. Next day, we transferred the cells to a 6-well plate and placed a magnetic driver on the top of the plate to start levitation. We monitored the formation of the 3D cell culture by optical microscopy and after four days, we added the photosensitizer Photogem (PG) in the culture media in concentrations of 50, 25, 12.5, 6.25?g/ml. We incubated them for 24 hours, after that we washed the cultures with PBS and added fresh media. Samples were then illuminated for 600s using a 630nm LED-based device, generating light intensities of 30 mW/cm2 in a total light fluence of 18 J/cm2. Following the illumination, we added fresh media, and 30 hours later, the 3D structures were broken using a pipettor and the cells seeded in 96 well plates, 105 cells per well, with a magnetic drive placed on the bottom of the plate to create cell culture dots. After 24 hours, we used a MTT assay to evaluate PDT cytotoxicity. The PDT effect, evaluated by the half maximal effective concentration (EC50), in MDA-MB-231 cells (EC50 =3.14 ?g/ml) is more aggressive compared to the effect of PDT in Hep G2 cells (EC50 = 7.48 ?g/ml). It suggests that the cell culture structure and its interaction facilitated the PG uptake and consequently elevated the Photodynamic effect for MDA-MB-231.

Sabino, Luis G.; Menezes, Priscila F. C.; Bagnato, Vanderlei S.; Souza, Glauco; Killian, Thomas C.; Kurachi, Cristina

2014-03-01

325

Sensitizer localization and immune response in photodynamic therapy of B16 cells  

NASA Astrophysics Data System (ADS)

This paper proposes to extend the exploration of mouse melanoma B16 cells death by photodynamic therapy (PDT), under irradiation with different light sources and in the presence of 5,10,15,20-tetrap-sulphonato-phenyl-porphyrin (TSPP). The viability studies showed that B16 mouse melanoma is sensitive to photodynamic damage induced by TSPP 1 mM for either one, two, three or four hours. The control had TSPP added immediately prior to timelapse imaging (no incubation). They were then irradiated with red light He-Ne laser (? = 632.8 nm, energy 180 J/cm2 for 20 min). Also, it has been used a laser diode GaInAs 25 mW/cm2, ? = 650 nm. The cells demonstrated clear morphological changes associated with apoptosis by mitochondrial pathway. There were changes in texture, as expected. Changes appeared to occur more quickly at lamp irradiation than at HeNe and GaInAs diode laser. Addition of TSPP just prior to exposure and observation, with no incubation, did not result in changes in cell morphology or cell death. Also, the proteins changes have been observed, because those with high molecular weights have been scissored under irradiation and this could be reason of the proteins concentrating in the area of low molecular weights, and the dissapearing of the proteic band of 75 kDa in the electrophoregramm. The immunized animals with B16-TSPP had the highest survival rate (40 days) by comparison with the control (death at 20 days) or with immunized animals with supernatants B16 (death at 25 days).

Pop, S.-F.; Ion, R.-M.; Neagu, M.; Constantin, C.

2011-03-01

326

Photodynamic therapy for inactivating endodontic bacterial biofilms and effect of tissue inhibitors on antibacterial efficacy  

NASA Astrophysics Data System (ADS)

Complex nature of bacterial cell membrane and structure of biofilm has challenged the efficacy of antimicrobial photodynamic therapy (APDT) to achieve effective disinfection of infected root canals. In addition, tissue-inhibitors present inside the root canals are known to affect APDT activity. This study was aimed to assess the effect of APDT on bacterial biofilms and evaluate the effect of tissue-inhibitors on the APDT. Rose-bengal (RB) and methylene-blue (MB) were tested on Enterococcus faecalis (gram-positive) and Pseudomonas aeruginosa (gram-negative) biofilms. In vitro 7- day old biofilms were sensitized with RB and MB, and photodynamically activated with 20-60 J/cm2. Photosensitizers were pre-treated with different tissue-inhibitors (dentin, dentin-matrix, pulp tissue, bacterial lipopolysaccharides (LPS), and bovine serum albumin (BSA)) and tested for antibacterial effect of APDT. Microbiological culture based analysis was used to analyze the cell viability, while Laser Scanning Confocal Microscopy (LSCM) was used to examine the structure of biofilm. Photoactivation resulted in significant reduction of bacterial biofilms with RB and MB. The structure of biofilm under LSCM was found to be disrupted with reduced biofilm thickness. Complete biofilm elimination could not be achieved with both tested photosensitizers. APDT effect using MB and RB was inhibited in a decreasing order by dentin-matrix, BSA, pulp, dentin and LPS (P< 0.05). Both strains of bacterial biofilms resisted complete elimination after APDT and the tissue inhibitors existing within the root canal reduced the antibacterial activity at varying degrees. Further research is required to enhance the antibacterial efficacy of APDT in an endodontic environment.

Shrestha, Annie; Kishen, Anil

327

Amplifying the red-emission of upconverting nanoparticles for biocompatible clinically used prodrug-induced photodynamic therapy.  

PubMed

A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal ?-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP-PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major step forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors. It also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics. PMID:25291544

Punjabi, Amol; Wu, Xiang; Tokatli-Apollon, Amira; El-Rifai, Mahmoud; Lee, Hyungseok; Zhang, Yuanwei; Wang, Chao; Liu, Zhuang; Chan, Emory M; Duan, Chunying; Han, Gang

2014-10-28

328

Initial evaluation of whole bladder wall photodynamic therapy after intravesical ALA sensitization for carcinoma in situ of the bladder  

NASA Astrophysics Data System (ADS)

Carcinoma in situ (CIS) of the bladder is a treacherous entity, that will develop into invasive cancer. Early treatment is mandatory in order to prevent progression. When conservative measures, such as Bacillus Calmette Querin (BCG) instillations have failed, radical cystectomy and urinary diversion is recommended. Whole bladder wall photodynamic therapy (PDT) with Photofrin II has been shown to be effective in eradicating carcinoma in situ, but often resulted in bladder shrinking. We wanted to evaluate the effects of PDT after aminolevulinic acid (ALA) sensitization. Six patients with refractory carcinoma in situ of the bladder were treated with whole bladder wall photodynamic therapy, after intravesical sensitization with aminolevulinic acid. The total light dose (scattered plus non scattered) was 75 J/cm2. No skin sensitization occurred, nor loss of bladder capacity. One patient did not respond and was successfully treated with BCG. Another patient developed distant metastases. Carcinoma in situ was completely absent after 3 months in four patients (66%).

D'Hallewin, Marie-Ange; Star, Willem M.; Baert, Luc

1997-12-01

329

The efficacy of second-line hormone therapy for recurrence during adjuvant hormone therapy for breast cancer  

PubMed Central

Objectives: The recurrence of breast cancer during adjuvant hormone therapy is often targeted by second-line hormone therapy. However, there has been a lack of prior success with such treatments. We retrospectively investigated the efficacy of subsequent hormone therapy. Methods: Patients who underwent breast cancer surgery between 2006 and 2012 at our institution were investigated. Results: A total of 20 patients developed recurrence during adjuvant hormone therapy. There were four patients with luminal A, seven with luminal B and six with luminal HER2 tumors, respectively. Twelve patients received subsequent hormone therapy, and eight patients received chemotherapy. Subsequent hormone therapy produced one partial response (PR), two long stable disease (SD), one SD and five progressive disease (PD). A clinical benefit (CB) was obtained by 33%. Subsequent chemotherapy produced one complete response (CR), two PRs, one long SD and two PD, resulting in a CB in 66%. Among those who received any hormone therapy, the best responses were two PR, three long SD and one SD. A CB was obtained by 38%, while seven patients did not have any CB from hormone therapy. Meanwhile, the best responses to chemotherapy were two CRs, four PRs, three SD and two PD, thus resulting in a CB in 72%. All luminal A cases obtained a long SD or SD with hormone therapy. However, the CB of hormone therapy for non-luminal A cases was only 30%. Conclusions: The efficacy of hormone therapy for recurrence during adjuvant hormone therapy is poor, and when selecting therapy for such patients, the breast cancer subtype should be taken into account. PMID:24587829

Nagao, Yasuko

2014-01-01

330

Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial  

Microsoft Academic Search

Background: Photodynamic therapy (PDT) is a different type of laser treatment from Nd:YAG thermal ablation for palliation of dysphagia from esophageal cancer.Methods: In this prospective, multicenter study, patients with advanced esophageal cancer were randomized to receive PDT with porfimer sodium and argon-pumped dye laser or Nd:YAG laser therapy.Results: Two hundred thirty-six patients were randomized and 218 treated (PDT 110, Nd:YAG

Charles J. Lightdale; Stephen K. Heier; Norman E. Marcon; James S. McCaughan; Hans Gerdes; Bergein F. Overholt; Michael V. Sivak; Gregory V. Stiegmann; Hector R. Nava

1995-01-01

331

Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma  

Microsoft Academic Search

Background: Patients with malignant pleural mesothelioma (MPM) usually die of progressive local disease. This report describes the results\\u000a of a Phase III trial comparing maximum debulking surgery and postoperative cisplatin, interferon ?-2b, and tamoxifen (CIT)\\u000a immunochemotherapy with and without intraoperative photodynamic therapy (PDT) to determine (1) whether such a multimodal approach\\u000a can be performed with minimum morbidity and mortality in

Harvey I. Pass; Barbara K. Temeck; Karen Kranda; Gunther Thomas; Angelo Russo; Paul Smith; Walt Friauf; Seth M. Steinberg

1997-01-01

332

Organically Modified Silica Nanoparticles with Intraparticle Heavy-Atom Effect on the Encapsulated Photosensitizer for Enhanced Efficacy of Photodynamic Therapy  

PubMed Central

We report a novel nanoassembly formulation for photodynamic therapy, which is composed of covalently iodine-concentrated organically modified silica (ORMOSIL) nanoparticles (diameter <30 nm) and a hydrophobic photosensitizer embedded therein. Comparative studies with iodinated and non-iodinated nanoparticles have demonstrated that the intraparticle external heavy-atom effect on the encapsulated photosensitizer molecules significantly enhances the efficiency of 1O2 generation, and thereby, the in vitro PDT efficacy. PMID:23795227

Kim, Sehoon; Ohulchanskyy, Tymish Y.; Bharali, Dhruba; Chen, Yihui; Pandey, Ravindra K.; Prasad, Paras N.

2013-01-01

333

In Vitro Efficacy and Mechanistic Role of Indocyanine Green as a Photodynamic Therapy Agent for Human Melanoma  

SciTech Connect

Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway.

Mamoon, A.; Gamal-Eldeen, A; Ruppel, M; Smith, R; Tsang, T; Miller, L

2009-01-01

334

Development of a brain tumor model for investigating the effects of photodynamic and anti-angiogenic therapies  

NASA Astrophysics Data System (ADS)

An in vivo shell-less chick chorioallantoic membrane (CAM) brain tumor model has been developed to investigate the effects of photodynamic therapy (PDT) and anti-antiogenic treatments. Multicellular human glioma spheroids were placed on the CAM at day 7 of embryonic development. Angiogenesis was observed four days post implantation. Significant damage to the CAM vasculature was observed immediately following 5-aminolevulinic acid (ALA) mediated PDT.

De Magalhaes, Nzola; Sun, Chung-Ho; Madsen, Steen J.; Hirschberg, Henry; Tromberg, Bruce J.

2005-04-01

335

Stability enhanced polyelectrolyte-coated gold nanorod-photosensitizer complexes for high/low power density photodynamic therapy.  

PubMed

Photodynamic therapy (PDT) is a promising treatment modality for cancer and other malignant diseases, however safety and efficacy improvements are required before it reaches its full potential and wider clinical use. Herein, we investigated a highly efficient and safe photodynamic therapy procedure by developing a high/low power density photodynamic therapy mode (high/low PDT mode) using methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4 photosensitizer complexes. mPEG-SH conjugated to the surface of simple polyelectrolyte-coated GNRs was verified using Fourier transform infrared spectroscopy; this improved stability, reduced cytotoxicity, and increased the encapsulation and loading efficiency of the nanoparticle dispersions. The GNR-photosensitizer complexes were exposed to the high/low PDT mode (high light dose = 80 mW/cm(2) for 0.5 min; low light dose = 25 mW/cm(2) for 1.5 min), and a high PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic plasmonic photothermal properties of the complexes, the high/low PDT mode demonstrated improved efficacy over using single wavelength continuous laser irradiation. Additionally, no significant loss in viability was observed in cells exposed to free AlPcS4 photosensitizer under the same irradiation conditions. Consequently, free AlPcS4 released from GNRs prior to cellular entry did not contribute to cytotoxicity of normal cells or impose limitations on the use of the high power density laser. This high/low PDT mode may effectively lead to a safer and more efficient photodynamic therapy for superficial tumors. PMID:24855961

Shi, Zhenzhi; Ren, Wenzhi; Gong, An; Zhao, Xinmei; Zou, Yuehong; Brown, Eric Michael Bratsolias; Chen, Xiaoyuan; Wu, Aiguo

2014-08-01

336

Pharmacology of photosensitizer in rats with metastatic breast cancer: time point determination for photodynamic therapy (PDT) treatment of vertebral metastases  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) as a non-radiative treatment has been applied successfully in various cancers. PDT may be a useful adjunct in the treatment of vertebral metastases. PDT efficacy requires the administration of a photosensitiser drug followed by subsequent drug activation by wavelength specific light. The study purpose was to establish the pharmacokinetic profiles for 2 photosensitisers, BPD-MA and 5-ALA induced PpIX, to determine the optimal drug-light interval for vertebral PDT.

Akens, Margarete K.; Yee, Albert J. M.; Lilge, Lothar; Burch, Shane; Whyne, Cari; Wilson, Brian C.; Bisland, Stuart K.

2005-09-01

337

The application of antimicrobial photodynamic therapy on S. aureus and E. coli using porphyrin photosensitizers bound to cyclodextrin.  

PubMed

Photodynamic therapy is usually used against malignant and non-malignant tumors. Nowadays, due to resistance of bacterial strains, we are looking for a new antimicrobial strategy to destroy bacteria with minimal invasive consequences. The worldwide increase in antibiotic resistance among different classes of gram-positive and gram-negative bacteria has led to the search for alternative anti-microbial therapies such as antimicrobial PDT (aPDT). Development antimicrobial technology combines a nontoxic compound, called photosensitizer, visible light of the appropriate wavelength, and the generation of reactive oxygen species. In this work, the photosensitizers TMPyP and ZnTPPS4 are investigated for photodynamic and antimicrobial photodynamic therapy. We tested these two porphyrins on two cell lines and two bacterial strains to compare effectiveness. In addition, we applied photosensitizers bound in the complex created with hp-?-cyclodextrin. The light-emitting diodes were used at the doses 0, 1, 5, 10 J/cm(2) for cells and 0, 150 J/cm(2) for bacteria. Tested concentrations for cells and microbes were from 0.5 to 50 ?M and from 0.78 to 100 ?M, respectively. From this work it can be concluded that TMPyP is a promising compound both in aPDT and in PDT, particularly in contrast to ZnTPPS4, which was efficient only in PDT. Furthermore, the eradication of gram-positive bacteria is possible only with higher concentrations of ZnTPPS4. PMID:23899404

Hanakova, Adela; Bogdanova, Katerina; Tomankova, Katerina; Pizova, Klara; Malohlava, Jakub; Binder, Svatopluk; Bajgar, Robert; Langova, Katerina; Kolar, Milan; Mosinger, Jiri; Kolarova, Hana

2014-01-01

338

Preliminary safety evaluation of photodynamic therapy for blood purification: an animal study.  

PubMed

Photodynamic therapy (PDT) has been shown to inactivate blood-borne pathogenic microorganisms in vitro. The method may be used to purify blood in the body, kill pathogenic microorganisms, and treat difficult diseases. Our aim was to investigate the safety of photodynamic blood purification (PBP) therapy using an in vivo blood circulation experiment in an animal model. Twenty-four New Zealand rabbits were used as experimental subjects; 12 received PDT and 12 served as negative controls. Extracorporeal blood bypass was established using the femoral artery and vein. A sterile disposable irradiation chamber was connected in the bypass pathway. Hematoporphyrin monomethyl ether was injected intravenously as a photosensitizer with an initial bolus of 3.7?mg, followed by a continuous infusion at 24?mg/h during PDT administration. Five minutes after initial injection, a laser beam was vertically focused on the irradiation chamber side wall, with a 9.5?cm(2) spot area, 1?h exposure time, and 20?mW/cm(2) power density. Six animals received a single PDT application, and six received PDT every other day for three applications. The 12 control group animals underwent extracorporeal blood circulation but did not receive the photosensitizer or light treatment. Blood samples were taken 20?min, 1 day, 4 days, and 7 days after PDT treatment for analysis of cell counts, coagulation, liver and renal function, and other biochemical changes. On the 7th day, animals were sacrificed, and parenchymal organs were evaluated for morphological changes. There were no significant differences in white blood cells, red blood cells, or destroyingplatelets after PDT compared with the control group. There was a little significant difference in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, ?-glutamyl transpeptidase, uric acid, blood urea nitrogen, and creatinine in the PDT group compared with the control group, except at individual time points. We found no significant damage in the heart, liver, spleen, lungs, kidneys, or other organs after PDT. This short-duration, fixed-strength PBP method did not cause changes in blood parameters or in the structure or function of major organs in an animal model. These findings suggest that PBP is safe in vivo and has potential as a new therapy for inactivating blood-borne microorganisms. PMID:24443947

Yin, Huijuan; Zhang, Guorong; Chen, Hongli; Wang, Weichao; Kong, Deling; Li, Yingxin

2014-06-01

339

Cardiovascular toxicity associated with adjuvant trastuzumab therapy: prevalence, patient characteristics, and risk factors  

PubMed Central

Before the advent of the human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody trastuzumab, HER2-positive breast cancers were difficult to treat and had a poor prognosis. Adjuvant trastuzumab is now an important part of the treatment regimen for many women with HER2-positive breast cancer and has undoubtedly resulted in a significant improvement in prognosis, but it is associated with a risk for cardiotoxicity. In this review, we describe the prevalence, patient characteristics, and risk factors for cardiotoxicity associated with use of adjuvant trastuzumab. Understanding risk factors for trastuzumab-induced cardiotoxicity and appropriate patient monitoring during trastuzumab treatment allows for safe and effective use of this important adjuvant therapy. PMID:25083270

Engel, Jessica M.; Stankowski, Rachel V.

2014-01-01

340

Cardiovascular toxicity associated with adjuvant trastuzumab therapy: prevalence, patient characteristics, and risk factors.  

PubMed

Before the advent of the human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody trastuzumab, HER2-positive breast cancers were difficult to treat and had a poor prognosis. Adjuvant trastuzumab is now an important part of the treatment regimen for many women with HER2-positive breast cancer and has undoubtedly resulted in a significant improvement in prognosis, but it is associated with a risk for cardiotoxicity. In this review, we describe the prevalence, patient characteristics, and risk factors for cardiotoxicity associated with use of adjuvant trastuzumab. Understanding risk factors for trastuzumab-induced cardiotoxicity and appropriate patient monitoring during trastuzumab treatment allows for safe and effective use of this important adjuvant therapy. PMID:25083270

Onitilo, Adedayo A; Engel, Jessica M; Stankowski, Rachel V

2014-08-01

341

Combined Concurrent Photodynamic and Gold Nanoshell Loaded Macrophage-Mediated Photothermal Therapies: An In Vitro Study on Squamous Cell Head and Neck Carcinoma  

PubMed Central

Background and Objective Treatment modalities, such as hyperthermia and photodynamic therapy (PDT) have been used in the treatment of a variety of head and neck squamous cell carcinoma (HNSCC), either alone or as an adjuvant therapy. Macrophages loaded with gold nanoshells, which convert near-infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on HNSCC cells. Study Design/Materials and Methods Gold nanoshell loaded rat macrophages either alone or combined with human FaDu squamous cells in hybrid monolayers were subjected to PTT, PDT, or a simultaneous combination of the two light treatments. Therapies were given concurrently employing two laser light sources of ? = 670 nm (PDT) and ? = 810 nm (PTT), respectively. Results Significant uptake of gold nanospheres (AuNS) by rat alveolar macrophages was observed thus providing the rationale for their use as delivery vectors. Viability of the AuNS-loaded Ma was reduced to 35 and 12% of control values at an irradiance of 14 or 28 W/cm2 administered over a 5 minute period respectively. No significant cytotoxicity was observed for empty Ma for similar PTT exposure. AlPcS2a mediated PDT at a fluence level of 0.25 J/cm2 and PTT at 14 W/cm2 irradiance had little effect on cell viability for the FaDu/Ma (ratio 2:1) hybrid monolayers. In contrast, combined treatment reduced the cell viability to less than 40% at these same laser power settings. Conclusions The results of this study provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately. PMID:24648368

Trinidad, Anthony J.; Hong, Seok Jin; Peng, Qian; Madsen, Steen J.; Hirschberg, Henry

2014-01-01

342

Pluronic-encapsulated natural chlorophyll nanocomposites for in vivo cancer imaging and photothermal/photodynamic therapies.  

PubMed

A great challenge in developing nanotechnologies for cancer diagnosis and therapy has been the combined functionalities required for complicated clinical procedures. Among all requirements, toxicity has been the major hurdle that has prevented most of the nano-carriers from clinical use. Here, we extracted chlorophyll (Chl) from vegetable and encapsulated it into polymer (pluronic F68, Plu) micelles for cancer imaging and therapy. The results showed that the Chl-containing nanocomposites were capable of mouse tumor targeting, and the nanocomposite fluorescence within the tumor sites remained at high intensity more than two days after tail-vein injection. It is interesting that oral administration with the nanocomposites was also successful for tumor target imaging. Furthermore, the dietary Chl was found to be able to efficiently convert near-infrared laser irradiation to heat. The growths of melanoma cells and mouse tumors were effectively inhibited after being treated with the nanocomposites and irradiation. The suppression of the tumors was achieved by laser-triggered photothermal and photodynamic synergistic effects of Chl. As a natural substance from vegetable, Chl is non-toxic, making it an ideal nano-carrier for cancer diagnosis and treatment. Based on the results of this research, the Plu-Chl nanocomposites have shown promise for future clinical applications. PMID:25002262

Chu, Maoquan; Li, Haikuo; Wu, Qiang; Wo, Fangjie; Shi, Donglu

2014-09-01

343

Effect of photodynamic therapy supplemented with quercetin in HEp-2 cells.  

PubMed

Photodynamic therapy (PDT) is a technique that can be used as a complementary therapy in cancer treatment combined with other therapeutic modalities. Quercetin (QCT) is known to be effective in the treatment of cancer, by reducing the cell viability of different cancer cell lines. This study aimed to evaluate the influence of different concentrations of QCT in PDT on the viability, mitochondrial membrane potential and induction of apoptosis/necrosis in the human larynx carcinoma cells (HEp-2). The HEp-2 cells were treated with aluminum phthalocyanine tetrasulfonate (AlPcS4) and QCT and subsequently irradiated with a diode laser light (685 nm, 35 mW, 4.5 J/cm(2)). The results demonstrated that treatment of HEp-2 cells with high concentrations of QCT (at least 50 ?M) reduced cell viability. This response was enhanced in cells subjected to PDT supplemented with high concentrations of QCT. In addition, was observed decrease in the mitochondrial membrane potential and characteristics of late apoptosis and/or initial necrosis process. QCT at concentrations from 50 ?M improves PDT-induced cytotoxicity by significantly reducing cell viability by apoptosis and/or necrosis, and mitochondrial membrane potential of Hep-2 cells. PMID:24470266

de Paula Rodrigues, Rafael; Tini, Italo Rigotti Pereira; Soares, Cristina Pacheco; da Silva, Newton Soares

2014-06-01

344

Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models  

SciTech Connect

Purpose: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Methods and Materials: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. Results: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. Conclusions: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

Samkoe, Kimberley S., E-mail: samkoe@dartmouth.ed [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States); Chen, Alina [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States); Rizvi, Imran [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States); Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA (United States); O'Hara, Julia A. [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States); Hoopes, P. Jack [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States); Department of Surgery, Dartmouth Medical School, Hanover, NH (United States); Pereira, Stephen P. [Institute of Hepatology, University College London Medical School, London (United Kingdom); Hasan, Tayyaba [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA (United States); Pogue, Brian W. [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States); Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA (United States); Department of Surgery, Dartmouth Medical School, Hanover, NH (United States)

2010-01-15

345

Evaluation of the Photodynamic Therapy effect using a tumor model in Chorioallantoic Membrane with Melanoma cells  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) is a type of cancer treatment that is based on the interaction of light (with specific wavelength), a photosensitizing agent and molecular oxygen. The photosensitizer (PS) is activated by light and reacts with oxygen resulting in the production of singlet oxygen that is highly reactive and responsible for the cell death. The Chick Chorioallantoic Membrane (CAM) model is a transparent membrane that allows visualization and evaluation of blood vessels and structural changes, where a tumor model was developed. Two induction tumor models were investigated: tumor biopsy or cell culture. It was used a murine melanoma cell B16F10 in culture and a biopsy from a xenograft tumor in hairless mouse. Two PS were tested: Photodithazine® and Photogem®, a chlorine and porphyrin compounds, respectively. Using intravenous administration, the light-drug interval was of 30 minutes, 1 and 3 hours. Illumination was performed at 630 nm and 660 nm, and the vascular and tumor response was monitored and analyzed. The PS distribution was checked with confocal microscopy. This model can be useful to study several parameters of PDT and the effect of this therapy in the cancer treatment since it allows direct visualization of its effects.

Buzzá, Hilde H.; Pires, Layla; Bagnato, Vanderlei S.; Kurachi, Cristina

2014-03-01

346

Photodynamic therapy--1994: treatment of benign and malignant upper aerodigestive tract disease  

NASA Astrophysics Data System (ADS)

From 1983 to 1994 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 46 of 47 patients treated with hematoporphyrin-derivative photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial `condemned mucosa' or `field cancerization' of the oral cavity; (2) stage III/IV head and neck cancer; (3) mucocutaneous AIDS-related Kaposi's sarcoma of the upper aerodigestive tract; (4) recurrent laryngotracheal papillomatosis; (5) severe dysplasia/adenocarcinoma in situ in Barrett's esophagus; (6) partial or completely obstructing terminal esophageal cancer. HPD-PDT produced complete responses in 19 patients (follow up 6 months to 8 years) with `field cancerization' (CIS, T1) of the oral cavity and larynx (6), adenocarcinoma in situ in Barrett's esophagus (2), mucocutaneous Kaposi's sarcoma (9), obstructing esophageal carcinoma (1), and stage IV squamous cell carcinoma of the nasopharynx (1). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck disease are reviewed.

Schweitzer, Vanessa G.

1994-10-01

347

Photodynamic therapy--1994: treatment of benign and malignant upper aerodigestive tract disease  

NASA Astrophysics Data System (ADS)

From 1983 to 1994 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 46 of 47 patients treated with hematoporphyrin-derivative photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial `condemned mucosa' or `field cancerization' of the oral cavity; (2) stage III/IV head and neck cancer; (3) mucocutaneous AIDS-related Kaposi's sarcoma of the upper aerodigestive tract; (4) recurrent laryngotracheal papillomatosis; (5) severe dysplasia/adenocarcinoma in situ in Barrett's esophagus; (6) partial or completely obstructing terminal esophageal cancer. HPD-PDT produced complete responses in 19 patients (follow up 6 months to 8 years) with `field cancerization' (CIS, T1) of the oral cavity and larynx (6), adenocarcinoma in situ in Barrett's esophagus (2), mucocutaneous Kaposi's sarcoma (9), obstructing esophageal carcinoma (1), and stage IV squamous cell carcinoma of the nasopharynx (1). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck disease are reviewed.

Schweitzer, Vanessa G.

1995-03-01

348

The dynamics of reactive oxygen species in photodynamic therapy with tetra sulfophenyl-porphyrin.  

PubMed

Photodynamic therapy (PDT) is a promising therapy especially in skin cancer, using the systemic administration of a photosensitizer (PS), followed by the local irradiation of the tumor with visible light. The antitumor effects of PDT are determined especially by the generation of cytotoxic reactive oxygen species (ROS). The 5,10,15,20-tetra-sulfo-phenyl-porphyrin (TSPP) is a synthetic photosensitizer, which proved its efficiency in in vitro studies. Our study evaluates the effects of PDT with TSPP upon the tumor levels of ROS and upon the metalloproteinases 2 (MMP2) activities on Wistar male rats bearing 256 Walker carcinosarcoma in correlation with the accumulation of PS in the tumor and with the intratumor histological alterations. The evaluations were performed dynamically, at 3 hours, 6 hours, 24 hours and 14 days after the PDT with TSPP. Our results emphasize that 24 hours after the PDT with TSPP, the ROS generation increases, as revealed by protein carbonyls and malondialdehyde levels and the antioxidant capacity (hydrogen donors, thiol groups) decreases in the tumor tissue. These parameters were correlated with the appearance of the histological disorders. The MMP-2 activity increases exponentially in the 24 hours-14 days post PDT interval. PDT with TSPP offers, in vivo , consistent results regarding ROS generation, MMP2 activation and cytotoxic capacity. PMID:20233689

Clichici, Simona; Filip, A; Daicoviciu, D; Ion, R M; Mocan, T; Tatomir, C; Rogojan, L; Olteanu, D; Muresan, A

2010-03-01

349

Photodynamic therapy for port wine stains assisted by a novel robotic system  

NASA Astrophysics Data System (ADS)

Port wine stains (PWS) is a vascular malformation consisting of dilated capillaries in the superficial dermis. Photodynamic therapy (PDT) is an effective approach in the treatment of PWS. However, the procedure of treatment is a low efficient and hard work, as the doctor need to hold laser fiber to irradiate for 20 min to 50 min per lesion. So an assisted novel robotic system was developed to instead part of doctor's work. The robotic system consisted of 7 degrees of freedom, in which there were 5 passive joints and 2 active joints. Binocular surveillance system was used as guidance for the robot. Clinical trial compared 20 patients (38 lesions) treated by the robotic system with another 20 patients (38 lesions) treated by a doctor. The patients in both groups were injected intravenously with photosensitizer (PSD-007, 4-5mg/kg) and irradiated with 532 nm laser (100mW/cm2, 120-300J/cm2) immediately. Both groups had same good therapeutic results. The robotic system is helpful in the PWS-PDT and hopefully would become a part of PWS therapy machine in the future.

Huang, Naiyan; Zhu, Jianguo; Wang, Ying; Bian, Guibin; Duan, Xingguang; Liu, Weifeng; Tang, Xiaoying; Wang, Xingtao; Cui, Shihu; Zhang, Chunyu; Gu, Ying

2010-11-01

350

Water-soluble benzylidene cyclopentanone photosensitizers for two-photon excited photodynamic therapy  

NASA Astrophysics Data System (ADS)

A series of benzylidene cyclopentanone photosensitizers modified by polyethylene glycol, carboxylate anionic or pyridyl cationic groups with gradient lipid-water partition coefficients were reported. Detailed characterization and systematic studies of these photosensitizers, including their linear and nonlinear photophysical properties, in vitro photodynamic therapy (PDT) and two-photon excited PDT (2PE-PDT) activities were conducted and compared with a clinical drug PSD-007 (a mixture of porphyrins). Three of them exhibited appropriate lipid-water partition coefficients, high reactive oxygen yields, large two-photon absorption cross-section and low dark toxicity under therapy dosage, could be absorbed efficiently by liver hepatocellular HepG2 cells and presented strong PDT and 2PE-PDT activity by in vitro cell experiments. Furthermore, in vivo tumor experiments were carried out on BALB/c mouse models using B3 as the photosensitizer. The results showed that the tumor growth could be effectively suppressed by B3 under 2PE-PDT. This work demonstrated the feasibility of using a simple molecular structure to construct high efficient photosensitizers for 2PE-PDT.

Fang, Yanyan; Zhao, Hongyou; Zou, Qianli; Zhao, Yuxia; Gu, Ying; Wu, Feipeng

2013-12-01

351

Selenorhodamine photosensitizers for photodynamic therapy of p-glycoprotein-expressing cancer cells.  

PubMed

We examined a series of selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenorhodamine core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their colocalization with mitochondrial specific agents in Colo-26 cells. Thioamide derivatives 16b and 18b were more effective photosensitizers than amide derivatives 15b and 17b. Selenorhodamine thioamides 16b and 18b were useful in a combination therapy to treat Colo-26 cells in vitro: a synergistic therapeutic effect was observed when Colo-26 cells were exposed to PDT and treatment with the cancer drug doxorubicin. PMID:25250825

Hill, Jacqueline E; Linder, Michelle K; Davies, Kellie S; Sawada, Geri A; Morgan, Janet; Ohulchanskyy, Tymish Y; Detty, Michael R

2014-10-23

352

Photodynamic therapy in two murine tumor models with sulfonated aluminum phthalocyanine  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) with sulfonated aluminum phthalocyanine (AlSPC), i.e., AlSPC-PDT, in two murine tumor models is reported here. The encouraging therapy results were observed in S180 fibrosarcoma transplanted in white mice of the Kunming line and in human hepatocellular carcinoma transplanted in balb/c nu/nu nude mice. The experimental tumors in the mice were chosen of those 0.5 - 0.8 cm in diameter and 0.4 - 0.7 cm in thickness. Photofrin II (PII) and Photosensitizing drug-007 (PSD-007), two kinds of porphyrin derivative dyes, were chosen as the contrast photosensitizers of AlSPC. A dose of 10 mg/kg AlSPC or PII or PSD-007 was given (iv). The dose of light (600 - 750 nm) was 180 J/cm2. `Cure (short-term)' was defined as regression of neoplastic tissue to a non-palpable tumor within 14 days after PDT. `Cure (long-term)' was defined as absence of local tumor tissue and tumor metastasis on gross and microscopic examinations within 107 days after PDT. The curative results suggest that AlSPC may be a more effective sensitizer than both PII and PSD-007.

Yu, Hong-Yu; Dong, Rong-Chun; Chen, Ji-Yao; Cai, Huai-Xin

1993-03-01

353

Susceptibility of Candida albicans to photodynamic therapy using methylene blue and toluidine blue as photosensitizing dyes.  

PubMed

The increased resistance of Candida albicans to antibiotic therapy indicates the need for alternative treatments for oral candidiasis. Photodynamic therapy (PDT) has been researched as an alternative tool to inactivate pathogenic microorganisms. It uses a combination of a photosensitizer and a visible light source. This study evaluated the susceptibility of C. albicans to PDT and compared the efficacy of 100 microg/mL methylene blue (MB) and toluidine blue (TB) as photosensitizers. The light source was Indium-Gallium-Aluminum Phosphide (InGaAIP) laser at 53 J/cm2. Suspensions of 108 cells/mL of C. albicans were subject to PDT for 5 minutes in 96-well plates, then decimal dilutions were plated on Sabouraud Dextrose agar After 48h incubation at 37 degreesC, the number of CFU/mL were obtained and submitted to statistical analysis using Kolmogorov-Smirnov, ANOVA (p<0.0001) and Tukey tests. The results showed that MB or laser irradiation alone did not have statistically significant antifungal activity compared to the positive control group (p> 0. 05). Conversely, the number of viable C. albicans cells was reduced significantly after PDT using MB or mainly TB associated to diode laser irradiation. The data proved the efficacy of PDT against C. albicans cells, regardless of the photosensitizer used. PMID:22165318

Pupo, Yasmine M; Gomes, Giovana M; Santos, Elizabete B; Chaves, Luzia; Michel, Milton D; Kozlowski, Vitoldo A; Gomes, Osnara M M; Gomes, Joãdo Carlos

2011-01-01

354

Analysis of the Bacterial Heat Shock Response to Photodynamic Therapy-Mediated Oxidative Stress  

PubMed Central

Antimicrobial photodynamic therapy (PDT) has recently emerged as an effective modality for the selective destruction of bacteria and other pathogenic microorganisms. We investigated whether PDT induced protective responses such as heat shock proteins in bacteria. Using the photosensitizer Toluidine Blue O (TBO) at sub-lethal PDT conditions, a 7-fold increase in bacterial heat shock protein GroEL and a 3-fold increase in heat shock protein DnaK were observed in Escherichia coli post PDT. Pretreatment with 50o C heat for 30 minutes reduced PDT killing in both E. coli and in Enterococcus faecalis, with the most pronounced inhibition occurring at 50-?M TBO with 5-J/cm2 635 nm light, where E. coli killing was reduced by 2- log10 and E. faecalis killing was reduced by 4-log10. Finally, inhibition of the highly conserved chaperone DnaK using a small molecule benzylidene lactam heat shock protein inhibitor potentiated (but not significantly) the effect of PDT at a TBO concentration of 2.5 ?M in E. faecalis; however, this effect was not observed in E. coli presumably because inhibitor could not gain access due to Gram-negative permeability barrier. Induction of heat shock proteins may be a mechanism whereby bacteria could become resistant to PDT and warrants the need for further study in the application of dual PDT-heat shock protein-inhibition therapies. PMID:21261628

St. Denis, Tyler G.; Huang, Liyi; Dai, Tianhong; Hamblin, Michael R.

2011-01-01

355

Photodynamic therapy stimulates anti-tumor immunity in a murine mastocytoma model  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species that eventually cause vascular shutdown and tumor cell apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, recognition of tumor-specific antigens, and induction of heat-shock proteins, while the three commonest cancer therapies (surgery, chemotherapy and radiotherapy) all tend to suppress the immune system. Like many other immunotherapies, the extent of the immune response after PDT tends to depend on the antigenicity of the particular tumor, or in other words, whether the tumor contains proteins with the correct characteristics to provide peptides that can bind to MHC class I molecules and provide a target for cytolytic T lymphocytes. We have described certain mouse tumors containing defined or naturally occurring tumor associated antigens that respond particularly well to PDT, and potent immune responses capable of destroying distant untreated tumors can be induced. In this report we address the induction of immunity after PDT of the DBA2 mastocytoma known as P815. This tumor was the first mouse tumor to be shown to possess a tumor-rejection antigen capable of being recognized by cytotoxic T-cells.

Mroz, Pawel; Hamblin, Michael R.

2008-02-01

356

Effective photodynamic therapy against microbial populations in human deep tissue abscess aspirates  

PubMed Central

Background and Objective The primary therapy for deep tissue abscesses is drainage accompanied by systemic antimicrobial treatment. However, the long antibiotic course required increases the probability of acquired resistance, and the high incidence of polymicrobial infections in abscesses complicates treatment choices. Photodynamic therapy (PDT) is effective against multiple classes of organisms, including those displaying drug resistance, and may serve as a useful adjunct to the standard of care by reduction of abscess microbial burden following drainage. Study Design/Materials and Methods Aspirates were obtained from 32 patients who underwent image-guided percutaneous drainage of the abscess cavity. The majority of the specimens (24/32) were abdominal, with the remainder from liver and lung. Conventional microbiological techniques and nucleotide sequence analysis of rRNA gene fragments were used to characterize microbial populations from abscess aspirates. We evaluated the sensitivity of microorganisms to methylene blue-sensitized PDT in vitro both within the context of an abscess aspirate and as individual isolates. Results Most isolates were bacterial, with the fungus Candida tropicalis also isolated from two specimens. We examined the sensitivity of these microorganisms to methylene blue-PDT. Complete elimination of culturable microorganisms was achieved in three different aspirates, and significant killing (p < 0.0001) was observed in all individual microbial isolates tested compared to controls. Conclusions These results and the technical feasibility of advancing optical fibers through catheters at the time of drainage motivate further work on including PDT as a therapeutic option during abscess treatment. PMID:23996629

Haidaris, Constantine G.; Foster, Thomas H.; Waldman, David L.; Mathes, Edward J.; McNamara, JoAnne; Curran, Timothy

2014-01-01

357

Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy  

PubMed Central

Background: Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target. Methods: Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour cells and corresponding primary human mammary epithelial cells (HMEC). Results: Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180?mM) or lonidamine (300??M) with 10?J?cm?2 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24?h, and by 10-fold in 9-day clonogenic assays). However, glycolysis inhibition only slightly increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of 9% death after 24?h). The potentiation of PDT cytotoxicity only occurred if the glycolysis inhibitors were added after ALA incubation, as they inhibited intracellular accumulation of photosensitiser if coincubated with ALA. Conclusion: As 2DG and lonidamine are already used as cancer chemotherapeutic agents, our results are directly translatable to combination therapies with existing topical PDT. PMID:23860536

Golding, J P; Wardhaugh, T; Patrick, L; Turner, M; Phillips, J B; Bruce, J I; Kimani, S G

2013-01-01

358

Combination approaches to potentiate immune response after photodynamic therapy for cancer†  

PubMed Central

Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not advanced to a mainstream cancer treatment. Although it has been shown to be an efficient way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT great potential to become more widely used. Although the stimulation of tumor-specific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. This review will cover these combination approaches using immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen-associated molecular patterns, cytokines growth factors, and approaches that target regulatory T-cells. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised. PMID:21479313

St Denis, Tyler G.; Aziz, Kanza; Waheed, Anam A.; Huang, Ying-Ying; Sharma, Sulbha K.; Mroz, Pawel; Hamblin, Michael R.

2012-01-01

359

Lasers in Surgery and Medicine 40:644650 (2008) Vascular Effects of Photodynamic and Pulsed Dye Laser  

E-print Network

vascu- lar destruction with benzoporphyrin derivative (BPD) monoacid ring A photodynamic therapy (PDT. Key words: benzoporphyrin derivative; laser speckle imaging; photodynamic therapy; port wine stains of current PDL therapy, alternative treatment modalities should be evaluated. In photodynamic therapy (PDT

Choi, Bernard

360

Designing Multi-Branched Gold Nanoechinus for NIR Light Activated Dual Modal Photodynamic and Photothermal Therapy in the Second Biological Window.  

PubMed

Gold nanoechinus can sensitize the formation of singlet oxygen in the first and the second near-infra red (NIR) biological windows and exert in vivo dual modal photodynamic and photothermal therapeutic effects (PDT and PTT) to destruct the tumors completely. This is the first literature example of the destruction of tumors in NIR window II induced by dual modal nanomaterial-mediated photodynamic and photothermal therapy (NmPDT & NmPTT). PMID:25042520

Vijayaraghavan, Priya; Liu, Cheng-Hong; Vankayala, Raviraj; Chiang, Chi-Shiun; Hwang, Kuo Chu

2014-10-01

361

Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.

Renschler, Markus F.; Yuen, Alan R.; Panella, Timothy J.; Wieman, Thomas J.; Dougherty, Shona; Esserman, Laura; Panjehpour, Masoud; Taber, Scott W.; Fingar, Victor H.; Lowe, Elizabeth; Engel, Julie S.; Lum, Bert; Woodburn, Kathryn W.; Cheong, Wai-Fung; Miller, Richard A.

1998-05-01

362

Monitoring photodynamic therapy of head and neck malignancies with optical spectroscopies  

PubMed Central

In recent years there has been significant developments in photosensitizers (PSs), light sources and light delivery systems that have allowed decreasing the treatment time and skin phototoxicity resulting in more frequent use of photodynamic therapy (PDT) in the clinical settings. Compared to standard treatment approaches such as chemo-radiation and surgery, PDT has much reduced morbidity for head and neck malignancies and is becoming an alternative treatment option. It can be used as an adjunct therapy to other treatment modalities without any additive cumulative side effects. Surface illumination can be an option for pre-malignant and early-stage malignancies while interstitial treatment is for debulking of thick tumors in the head and neck region. PDT can achieve equivalent or greater efficacy in treating head and neck malignancies, suggesting that it may be considered as a first line therapy in the future. Despite progressive development, clinical PDT needs improvement in several topics for wider acceptance including standardization of protocols that involve the same administrated light and PS doses and establishing quantitative tools for PDT dosimetry planning and response monitoring. Quantitative measures such as optical parameters, PS concentration, tissue oxygenation and blood flow are essential for accurate PDT dosimetry as well as PDT response monitoring and assessing therapy outcome. Unlike conventional imaging modalities like magnetic resonance imaging, novel optical imaging techniques can quantify PDT-related parameters without any contrast agent administration and enable real-time assessment during PDT for providing fast feedback to clinicians. Ongoing developments in optical imaging offer the promise of optimization of PDT protocols with improved outcomes. PMID:24303476

Sunar, Ulas

2013-01-01

363

Heat shock protein 70 is acute phase reactant: response elicited by tumor treatment with photodynamic therapy  

PubMed Central

Oxidative stress in photodynamic therapy (PDT)-treated tumor cells is known to instigate a strong upregulation of the expression of heat shock proteins. However, the treatment of mouse Lewis lung carcinoma (LLC) cells with Photofrin™ PDT resulted in the upregulation of heat shock protein 70 (Hsp70) gene not only in these cells but also in co-incubated untreated Hepa 1-6 cells. To investigate whether this phenomenon extends in vivo, LLC tumors growing in C57BL/6 mice were treated with Photofrin™ PDT. The tumors and the livers from the mice were collected at 4, 8, or 24 h after therapy for quantitative reverse transcriptase polymerase chain reaction-based analysis of Hsp70 gene expression. Increased Hsp70 gene expression was detected in both the tumor and liver tissues and was most pronounced at 4 h after PDT. This effect was inhibited by treatment of host mice with glucocorticoid synthesis inhibitor metyrapone. Hsp70 protein levels in the livers of mice bearing PDT-treated tumors gradually decreased after therapy while serum levels increased at 4 h after therapy and then continually decreased. The exposure of in vitro PDT-treated LLC cells to Hsp70 and subsequent flow cytometry analysis revealed binding of this protein to cells that was dependent on PDT dose and more pronounced with dying than viable cells. Thus, following the induction of tumor injury by PDT, Hsp70 can be produced in the liver and spleen as acute phase reactant and released into circulation, from where it can be rapidly sequestered to damaged tumor tissue to facilitate the disposal of dying cells. PMID:20865355

Merchant, Soroush

2010-01-01

364

Cardiorespiratory fitness in breast cancer patients undergoing adjuvant therapy.  

PubMed

Abstract Purpose. The aim of this work was to investigate cardiorespiratory fitness in breast cancer patients at different time points of anti-cancer treatment. Patients and methods. Non-metastatic breast cancer patients (n = 222, mean age 55 years) were categorized into four subgroups according to their treatment status. Cardiopulmonary exercise testing (CPET) was used to measure patients' cardiorespiratory fitness, including oxygen delivery and metabolic muscle function. Testing was performed by bicycle ergometry, and maximal oxygen uptake (VO2peak) was measured. Heart rate during exercise at 50 watts (HR50) was assessed as a cardiocirculatory parameter and ventilatory threshold (VT) was used as an indicator of the O2 supply to muscle. Analysis of covariance was used to estimate the impact of different cancer treatments on cardiorespiratory fitness with adjustment for clinical factors. Results. Submaximal measures were successfully assessed in 220 (99%) and 200 (90%) patients for HR50 and VT, while criteria for maximal exercise testing were met by 176 patients (79%), respectively. The mean VO2peak was 20.6 ± 6.7 ml/kg/min, mean VT 10.7 ± 2.9 ml/min/kg and mean HR50 112 ± 16 beats/min. Chemotherapy was significantly associated with decreased VO2peak, with significantly lower adjusted mean VO2peak among patients post adjuvant chemotherapy compared to patients with no chemotherapy or those who just started chemotherapy regime (all p < 0.01). Patients post adjuvant chemotherapy reached only 63% of the VO2peak level expected for their age- and BMI-category (mean VO2peak 15.5 ± 4.8 ml/kg/min). Similarly, HR50 was significantly associated with treatment. However, VT was not associated with treatment. Conclusion. Breast cancer patients have marked and significantly impaired cardiopulmonary function during and after chemotherapy. Hereby, chemotherapy appears to impair cardiorespiratory fitness by influencing the oxygen delivery system rather than impacting metabolic muscle function. Our findings underline the need of exercise training in breast cancer patients to counteract the loss of cardiorespiratory fitness during the anti-cancer treatment. PMID:24837860

Klassen, Oliver; Schmidt, Martina E; Scharhag-Rosenberger, Friederike; Sorkin, Mia; Ulrich, Cornelia M; Schneeweiss, Andreas; Potthoff, Karin; Steindorf, Karen; Wiskemann, Joachim

2014-10-01

365

Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials  

Microsoft Academic Search

About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma. All patients underwent surgical resection plus comprehensive staging and,

Robert C. Young; Leslie A. Walton; Susan S. Ellenberg; Howard D. Homesley; George D. Wilbanks; David G. Decker; Alexander Miller; Robert Park; Francis Major

1990-01-01

366

Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy  

SciTech Connect

Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm{sup 2}) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 J/cm{sup 2}) delivered 3 h after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at 1 h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments. Histologic studies confirmed that this combined treatment led to damage to both tumor vasculature and tumor cells. Importantly, the combined PDT treatment did not increase normal tissue damage and tissue recovered well at 60 days after treatment. Conclusions: Our results suggest that targeting both tumor vascular and cellular compartments by combining a long-interval PDT with a short-interval PDT can be an effective and safe way to enhance PDT damage to tumor tissue.

Chen Bin [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States); Pogue, Brian W. [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States) and Wellman Laboratories of Photomedicine, Massachusetts General Hospital (United States) and Department of Dermatology, Harvard Medical School, Boston, MA (United States)]. E-mail: pogue@dartmouth.edu; Hoopes, P. Jack [Thayer School of Engineering, Dartmouth College, Hanover, NH (United States); Department of Surgery, Dartmouth Medical School, Hanover, NH (United States); Hasan, Tayyaba [Wellman Laboratories of Photomedicine, Massachusetts General Hospital, and Department of Dermatology, Harvard Medical School, Boston, MA (United States)

2005-03-15

367

Versatile RBC-derived vesicles as nanoparticle vector of photosensitizers for photodynamic therapy  

NASA Astrophysics Data System (ADS)

Various nanocarriers for photosensitizers have been developed to solve the problems of limiting the clinical utility of photodynamic therapy (PDT); however, to date, no carriers capable of supplying oxygen have been reported. We reported the development of a novel system composed of red blood cell (RBC)-derived vesicles (RDVs) generated by osmotic stress and demonstrated the capacity of RDVs for encapsulating and delivering external cargo into targeted cells due to the cellular uptake of RDVs. In this study, protoporphyrin IX (PpIX)-encapsulated RDVs (PpIX@RDVs) were prepared by the hypotonic incorporation of PpIX into RDVs in an aqueous environment, characterized, and utilized for PDT of cancer. PpIX@RDVs were rapidly uptaken by tumor cells via endocytosis in vitro, and the highly phototoxic effect of PpIX@RDVs was demonstrated upon irradiation. Superoxide anion (O2&z.rad;) and singlet oxygen (1O2) were involved in PpIX@RDV-induced cell apoptosis and necrosis. Finally, we demonstrated that RDVs with an oxygen supply capacity have potential as versatile delivery vehicles for efficient PDT.Various nanocarriers for photosensitizers have been developed to solve the problems of limiting the clinical utility of photodynamic therapy (PDT); however, to date, no carriers capable of supplying oxygen have been reported. We reported the development of a novel system composed of red blood cell (RBC)-derived vesicles (RDVs) generated by osmotic stress and demonstrated the capacity of RDVs for encapsulating and delivering external cargo into targeted cells due to the cellular uptake of RDVs. In this study, protoporphyrin IX (PpIX)-encapsulated RDVs (PpIX@RDVs) were prepared by the hypotonic incorporation of PpIX into RDVs in an aqueous environment, characterized, and utilized for PDT of cancer. PpIX@RDVs were rapidly uptaken by tumor cells via endocytosis in vitro, and the highly phototoxic effect of PpIX@RDVs was demonstrated upon irradiation. Superoxide anion (O2&z.rad;) and singlet oxygen (1O2) were involved in PpIX@RDV-induced cell apoptosis and necrosis. Finally, we demonstrated that RDVs with an oxygen supply capacity have potential as versatile delivery vehicles for efficient PDT. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32506c

Wang, Leng-Yin; Shi, Xuan-Yu; Yang, Chung-Shi; Huang, Dong-Ming

2012-12-01

368

Hyperbaric oxygen therapy augments the photodynamic action of methylene blue against bacteria in vitro  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) entails the combination of photosensitizer and light to generate cytotoxic molecules that derive from molecular oxygen (O II). The presence of sufficient O II within the target tissues is critical to the efficiency of PDT. This study investigates the use of hyperbaric oxygen therapy in combination with PDT (HOTPDT) to augment the photodynamic action of methylene blue (MB) or 5-aminolevulinic acid (ALA) against gram positive and gram negative bacterial strains in vitro. Staphylococcus aureus or Pseudomonas aeruginosa were grown in trypticase soy broth as planktonic cultures (~10 8/mL) or as established biofilms in 48 well plates (3 days old) at 32°C. Dark toxicity and PDT response in the presence or absence of HOT (2 atmospheres, 100% O II for 30, 60 or 120 min) was established for both MB (0-0.1 mM) and ALA (0- 1 mM) for a range of incubation times. The number of surviving colonies (CFU/mL) was plotted for each treatment groups. Light treatments (5, 10, 20 or 30 J/cm2) were conducted using an array of halogen bulbs with a red filter providing 90% transmittance over 600-800 nm at 21 mW/cm2. HOT increased the dark toxicity of MB (30 min, 0.1 mM) from < 0.2 log cell kill to 0.5 log cell kill. Dark toxicity of ALA (4 hr, 1 mM) was negligible and did not increase with HOT. For non-dark toxic concentrations of MB or ALA, (0.05 mM and 1 mM respectively) HOT-PDT enhanced the antimicrobial effect of MB against Staphylococcus aureus in culture by >1 and >2 logs of cell kill (CFU/mL) at 5 and 10 J/cm2 light dose respectively as compared to PDT alone. HOT-PDT also increased the anti-microbial effects of MB against Staphylococcus aureus biofilms compared to PDT, albeit less so (> 2 logs) following 10 J/cm2 light dose. Anti-microbial effects of PDT using ALA were not significant for either strain with or without HOT. These data suggest that HOTPDT may be useful for improving the PDT treatment of bacterial infections.

Bisland, S. K.; Dadani, F. N.; Chien, C.; Wilson, B. C.

2007-02-01

369

Coronary Heart Disease Mortality and Adjuvant Tamoxifen Therapy  

Microsoft Academic Search

Background and Purpose: Data from randomized clinical tri- als in Scotland and Sweden testing the efficacy of tamoxifen therapy in patients with breast cancer have suggested that the drug may also reduce the risk of coronary heart disease. In view of these findings, we examined mortality from coro- nary heart disease among patients with early stage breast cancer who were

Joseph P. Costantino; Lewis H. Kuller; Diane G. Ives; Bernard Fisher; James Dignam

370

Self-Assembled Nanoparticles Based on PEGylated Conjugated Polyelectrolyte and Drug Molecules for Image-Guided Drug Delivery and Photodynamic Therapy.  

PubMed

A drug delivery system based on poly(ethylene glycol) (PEG) grafted conjugated polyelectrolyte (CPE) has been developed to serve as a polymeric photosensitizer and drug carrier for combined photodynamic and chemotherapy. The amphiphilic brush copolymer can self-assemble into micellar nanopaticles (NPs) in aqueous media with hydrophobic conjugated polyelectrolyte backbone as the core and hydrophilic PEG as the shell. The NPs have an average diameter of about 100 nm, with the absorption and emission maxima at 502 and 598 nm, respectively, making them suitable for bioimaging applications. Moreover, the CPE itself can serve as a photosensitizer, which makes the NPs not only a carrier for drug but also a photosensitizing unit for photodynamic therapy, resulting in the combination of chemo- and photodynamic therapy for cancer. The half-maximal inhibitory concentration (IC50) value for the combination therapy to U87-MG cells is 12.7 ?g mL(-1), which is much lower than that for the solely photodynamic therapy (25.5 ?g mL(-1)) or chemotherapy (132.8 ?g mL(-1)). To improve the tumor specificity of the system, cyclic arginine-glycine-aspartic acid (cRGD) tripeptide as the receptor to integrin ?v?3 overexpressed cancer cells was further incorporated to the surface of the NPs. The delivery system based on PEGylated CPE is easy to fabricate, which integrates the merits of targeted cancer cell image, chemotherapeutic drug delivery, and photodynamic therapy, making it promising for cancer treatment. PMID:25075548

Yuan, Youyong; Liu, Bin

2014-09-10

371

Photodynamic therapy and fluorescence diagnostics of breast cancer metastases with photosense and alasense  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using photosensitizers Photosense (Aluminium Phtalocyanine, (NIOPIC, Russia)(PS) and Alasense have been provided in 101 patients with breast cancer as a multicenter study. All patients had recurrences of breast cancer (skin metastases) after combined treatment, chemotherapy and radiotherapy. FD of tumor with detecting of subclinical sites, accumulation of PS in tumor, adjacent tissue, skin before and during PDT was fulfilled. Multiple surface irradiations were carried on with interval 24-72 hours (semiconductive laser - (lambda) =672+2nm) in light does 100J/cm2 and total light does 300-900 J/cm2. 2 months after PDT we had overall response rate of 86,87% with complete response (CR) in 51,48% and partial response in 35,39%. During year after PDT in 52 patients with CR we had CR in 36,6% local recurrences in 23,1%, progression (distant (lung or bone) metastasis) in 40,4% of cases. Our experience show pronounced efficacy of PDT for skin metastases of breast cancer.

Vakoulovskaya, Elena G.; Shental, Victor V.; Letyagin, Victor P.; Brjezovsky, Vitaly J.; Oumnova, L. V.; Vorozhtsov, Georgy N.; Philinov, V.; Stranadko, Eugeny P.

2002-06-01

372

Adjunctive arterial injury and photodynamic therapy with aluminium disulphonated phthalocyanine inhibits intimal hyperplasia  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) of proliferative vascular smooth muscle cells (SMC) reduces intimal hyperplasia (FCIH). We assess the effects of adjunctive balloon injury and immediate PDT on contractile SMC, using aluminum disulphonated phthalocyanine (AlS2Pc) sensitization, on intimal hyperplasia. Groups of 5 Wistar rats underwent tail vein injection with 2.5 mg/kg of aluminum disulphonated phthalocyanine (AlS2Pc). Standard carotid artery balloon injury was performed with a 2FG Fogarty embolectomy catheter and the artery irradiated with 50 J/cm2. Control groups were also studied. Rats were killed at 2 and 4 weeks after treatment and perfusion fixed H&E stained cross-sections assessed by computerized morphometric measurements. Three sections per rat were analyzed. PDT treated arteries were free of FCIH formation in all cases. Laser alone (and to a lesser extent sensitizer alone) produced some reduction in the levels of FCIH compared to untreated but balloon injured vessels. The ratio of the area of intimal hyperplasia in treated vessels to the area of intimal hyperplasia in untreated (balloon only) rats were sensitizer only 98%, laser only 68% and PDT 0% at 4 weeks. PDT given at the time of angioplasty may be affective in the management of restenosis.

Nyamekye, Isaac; McEwan, Jean R.; MacRobert, Alexander J.; Bishop, Christopher C. R.; Bown, Stephen G.

1994-12-01

373

Photodynamic therapy induces epidermal thickening in hairless mice skin: an optical coherence tomography assessment  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) promotes skin improvement according to many practitioners, however the immediately in vivo assessment of its response remains clinically inaccessible. As a non-invasive modality, optical coherence tomography (OCT) has been shown a feasible optical diagnostic technique that provides images in real time, avoiding tissue biopsies. For this reason, our investigation focused on evaluates the PDT effect on a rodent model by means of OCT. Therefore, a normal hairless mouse skin has undergone a single-session PDT, which was performed with topical 5- aminolevulinic acid (ALA) cream using a red (630 nm) light emitting diode (LED) which reached the light dose of 75 J/cm2. As the optical imaging tool, an OCT (930 nm) with axial resolution of 6.0 microns in air was used, generating images with contact to the mouse skin before, immediately after, 24 hours, and 2 weeks after the correspondent procedure. Our result demonstrates that, within 24 hours after ALA-PDT, the mouse skin from the PDT group has shown epidermal thickness (ET), which has substantially increased after 2 weeks from the treatment day. Moreover, the skin surface has become evener after ALA-PDT. Concluding, this investigation demonstrates that the OCT is a feasible and reliable technique that allows real-time cross-sectional imaging of skin, which can quantify an outcome and predict whether the PDT reaches its goal.

Jorge, Ana Elisa S.; Campos, Carolina P.; Freitas, Anderson Z.; Bagnato, Vanderlei S.

2014-03-01

374

Pulsed light imaging for wide-field dosimetry of photodynamic therapy in the skin  

NASA Astrophysics Data System (ADS)

Photodynamic therapy using aminoluvelinic acid (ALA) is an FDA-approved treatment for actinic keratoses, pre-cancerous skin lesions which pose a significant risk for immunocompromised individuals, such as organ transplant recipients. While PDT is generally effective, response rates vary, largely due to variations in the accumulation of the photosensitizer protoporphyrin IX (PpIX) after ALA application. The ability to quantify PpIX production before treatment could facilitate the use of additional interventions to improve outcomes. While many groups have demonstrated the ability to image PpIX in the clinic, these systems generally require darkening the room lights during imaging, which is unpopular with clinicians. We have developed a novel wide-field imaging system based on pulsed excitation and gated acquisition to image photosensitizer activity in the skin. The tissue is illuminated using four pulsed LED's to excite PpIX, and the remitted light acquired with a synchronized ICCD. This approach facilitates real-time background subtraction of ambient light, precluding the need to darken the exam room. Delivering light in short bursts also allows the use of elevated excitation intensity while remaining under the maximum permissible exposure limits, making the modality more sensitive to photosensitizer fluorescence than standard approaches. Images of tissue phantoms indicate system sensitivity down to 250nM PpIX and images of animals demonstrate detection of PpIX fluorescence in vivo under normal room light conditions.

Davis, Scott C.; Sexton, Kristian; Chapman, Michael Shane; Maytin, Edward; Hasan, Tayyaba; Pogue, Brian W.

2014-03-01

375

Ultra low fluence rate photodynamic therapy: simulation of light emitted by the Cerenkov effect  

NASA Astrophysics Data System (ADS)

PDT has been shown to be most effective at low fluence rates. Many radionuclides used for both diagnostic and therapeutic purposes produce measurable amounts of visible radiation when they decay via the Cerenkov effect which occurs when a charged particle travels faster in a dielectric medium than the speed of light in that medium. Cerenkov radiation from radiopharmaceuticals could serve as a source of extended duration, low level "internal" light, to mediate PDT, with the ultimate goals of overcoming some its current limitations. Using laser light, we are exploring the effects of fluence rates that could be generated by Cerenkov radiation on PDT efficacy. ALA or TPPS2a mediated PDT of rat gliomas monolayers or multicell spheroids ( F98, C6) was performed with 410 nm laser light exposure over an extended period of 24-96hrs. Photosensitizers were delivered either as a bolus or continuously with light exposure. At fluence rate of 20?W/cm2 effective PDT was obtained as measured by decrease in cell viability or inhibition of spheroid growth. PDT is effective at ultra low fluence rates if given over long time periods. No lower threshold has been ascertained. Since the half-life of 90Y, a radionuclide with a high Cherenkov yield is 64 hrs it is a good candidate to supply sufficient light activation for PDT. The combination of radionuclide and photodynamic therapies could improve the effectiveness of cancer treatment by exploiting synergies between these two modalities.

Gonzales, Jonathan; Wang, Fred; Zamora, Genesis; Trinidad, Anthony; Marcu, Laura; Cherry, Simon; Hirschberg, Henry

2014-03-01

376

CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy  

NASA Astrophysics Data System (ADS)

The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R2 = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.

Jermyn, Michael; Davis, Scott C.; Dehghani, Hamid; Huggett, Matthew T.; Hasan, Tayyaba; Pereira, Stephen P.; Bown, Stephen G.; Pogue, Brian W.

2014-04-01

377

Signaling from lysosomes enhances mitochondria-mediated photodynamic therapy in cancer cells  

NASA Astrophysics Data System (ADS)

In photodynamic therapy (PDT), visible light activates a photosensitizing drug added to a tissue, resulting in singlet oxygen formation and cell death. Assessed by confocal microscopy, the photosensitizer phthalocyanine 4 (Pc 4) localizes primarily to mitochondrial membranes in cancer cells, resulting in mitochondria-mediated cell death. A Pc 4 derivative, Pc 181, accumulates into lysosomes. In comparison to Pc 4, Pc 181 was a more effective photosensitizer promoting killing cancer cells after PDT. The mode of cell death after Pc 181-PDT is predominantly apoptosis, and pancaspase and caspase-3 inhibitors prevent onset of the cell death. To assess further how lysosomes contribute to PDT, we monitored cell killing of A431cells after PDT in the presence and absence of bafilomycin, an inhibitor of the acidic vacuolar proton pump that collapses the pH gradient of the lysosomal/endosomal compartment. Bafilomycin by itself did not induce toxicity but greatly enhanced Pc 4-PDT-induced cell killing. In comparison to Pc 4, less enhancement of cell killing by bafilomycin occurred after Pc 181-PDT at photosensitizer doses producing equivalent cell killing in the absence of bafilomycin. These results indicate that lysosomal disruption can augment PDT with Pc 4, which targets predominantly mitochondria, but less so after PDT with Pc 181, since Pc 181 already targets lysosomes.

Quiogue, Geraldine; Saggu, Shalini; Hung, Hsin-I.; Kenney, Malcolm E.; Oleinick, Nancy L.; Lemasters, John J.; Nieminen, Anna-Liisa

2009-06-01

378

Preliminary study of transurethral photodynamic therapy mediated with Tookad in a canine prostate model  

NASA Astrophysics Data System (ADS)

Background: photodynamic therapy (PDT) mediated with vascular acting photosensitizer Tookad (pd-bacteriopheophorbide) was investigated as an alternative modality for treating prostate cancer. Our previous studies show that Tookad PDT can induce marked prostatic tissue lesion but minimal urethral lesion. In this study a transurethral procedure was used to evaluate the response of the prostatic urethra to direct urethral irradiation. Materials and Methods: Tookad solution (2.5 mg/ml) was administered (1 mg/kg) through IV catheter by an infusion pump over 10 min. A diffuser fiber (1 cm active length) was inserted into the prostatic urethra. The light irradiation (50 or 100 J/cm) started at 4 min after the onset of drug infusion. Urinalysis was performed for 24 - 48 h post PDT. One week after PDT, prostates (n = 4) were removed at necropsy and subjected to histopathological examination. Results: The cross section of prostates showed severe hemorrhagic and necrotic lesions on the right lobe. The diameter of the lesion, measured from urethra to capsule, was >13 mm for 50 J/cm treatment and >18 mm for 100 J/cm, respectively. Although underlying periurethral lesion was visible, the urethral surface was intact and prostatic urethra was open. Conclusions: The joint point of the diffuser tip and the guide fiber might be bent while passing through the sharp turn at the Ischial Arch, which could affect the light distribution and cause the asymmetric lesion. Nonetheless, the transurethral direct irradiation can induce marked prostatic tissue lesion but minimal urethral lesion.

Huang, Zheng; Hetzel, Fred W.; Chen, Qun; Dole, Kenneth C.

2008-02-01

379

Photodynamic therapy of nonmelanoma skin malignancies with topical delta-amino levulinic acid: diagnostic measurements  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) using topical application of the Protoporphyrin IX (PpIX) precursor (delta) -amino levulinic acid (ALA) in various malignant skin tumors is a new promising treatment modality. We have treated an extensive number of non-melanoma malignancies of the skin over the past three years with very satisfying initial results. For superficial, shallow lesions one treatment session is sufficient. In thicker lesions, such as nodular basal cell carcinomas, complete treatment response is achieved after two or three treatment sessions. In conjunction with the treatment procedure the tissue fluorescence and the superficial blood flow have been investigated during and after the treatment procedures. The PpIX build-up has been detected in vivo and the degree of tumor selectivity has been evaluated using laser-induced fluorescence. Also changes in the bloodflow in tumors compared to normal skin before, during, and after the treatment procedure has been followed using a laser- Doppler perfusion imaging system. Results from the measurements in basal cell carcinomas (BCCs), Mb. Bowen lesions (squamous cell carcinoma in situ) and cutaneous T-cell lymphoma lesions are presented.

Wang-Nordman, Ingrid; Svanberg, Katarina; Andersson-Engels, Stefan; Berg, Roger; Svanberg, Sune

1994-10-01

380

Photodynamic therapy of nonmelanoma skin malignancies with topical delta-amino levulinic acid: diagnostic measurements  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) using topical application of the Protoporphyrin IX (PpIX) precursor (delta) -amino levulinic acid (ALA) in various malignant skin tumors is a new promising treatment modality. We have treated an extensive number of non-melanoma malignancies of the skin over the past three years with very satisfying initial results. For superficial, shallow lesions one treatment session is sufficient. In thicker lesions, such as nodular basal cell carcinomas, complete treatment response is achieved after two or three treatment sessions. In conjunction with the treatment procedure the tissue fluorescence and the superficial blood flow have been investigated during and after the treatment procedures. The PpIX build-up has been detected in vivo and the degree of tumor selectivity has been evaluated using laser-induced fluorescence. Also changes in the bloodflow in tumors compared to normal skin before, during, and after the treatment procedure has been followed using a laser- Doppler perfusion imaging system. Results from the measurements in basal cell carcinomas (BCCs), Mb. Bowen lesions (squamous cell carcinoma in situ) and cutaneous T-cell lymphoma lesions are presented.

Wang-Nordman, Ingrid; Svanberg, Katarina; Andersson-Engels, Stefan; Berg, Roger; Svanberg, Sune

1995-03-01

381

Results and survival after photodynamic therapy in early-stage esophageal carcinoma  

NASA Astrophysics Data System (ADS)

From January 1985 to December 1994, 23 early stage carcinomas of the esophagus were treated by photodynamic therapy in 21 patients. The stage of the tumors was assessed by esophagoscopy with multiple biopsies, CT scan and, from June 1991, also by endoscopic ultrasonography: 7 lesions were classified as carcinoma in situ (Tis) and 16 as invasive (T1). The photosensitizers used for PDT were hematoporphyrin derivative 3 mg/kg in 4 patients and dihematoporphyrin ether 2 mg/kg in 17. Light irradiation was performed using an Argon-dye laser system at a wavelength of 630 nm with an average energy of 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. A complete response was achieved in 17/23 (74%) tumors, 15/21 (71%) patients. In the follow-up period from 6 to 78 months (median 36 months) 3 recurrences occurred 6, 12, and 14 months after PDT, respectively. Seven patients died due to concomitant diseases, not related to tumor progression. The actuarial survival rate was 95%, 75% and 37% at 1, 3, and 5 years, respectively. Complications included 1 case of sunburn and 2 cases of esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage.

Spinelli, Pasquale; Mancini, Andrea; Dal Fante, Marco; Meroni, Emmanuele; Jasinskas, Algirdas

1996-01-01

382

Effects of photodynamic therapy for superficial esophageal squamous cell carcinoma in vivo and in vitro  

PubMed Central

Photodynamic therapy (PDT) is an ablative treatment leading to intracellular photoexcitation and injury. A total of 15 patients with superficial esophageal squamous cell carcinoma (ESCC) without metastasis underwent PDT and 48–72 h after intravenous Photofrin, the patients were treated with a 630-nm excimer dye laser. A total of 13 patients had local tumor recurrence after definitive chemoradiotherapy (CRT) consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP). Of 6 patients, 5 had submucosal ESCC and were treated with S-1. Complete reponse was achieved by 11 patients with initial PDT, but 2 had recurrences. The recurrent/residual tumors were successfully treated with repeated PDT. Two patients with intramucosal ESCC succumbed due to metastatic disease, but 11 patients were disease-free. The 5 patients treated with S-1 remained alive despite submucosal ESCC. PDT was applied to human ESCC cells in vitro in the presence or absence of 5-FU or CDDP. The combination of PDT with 5-FU or CDDP resulted in enhanced cytotoxic effects, thereby reducing the effective dosage of each drug. PDT is a promising treatment option for selected ESCC cases, particularly for local recurrence following CRT. Our experience suggests that PDT is more effective when combined with chemotherapy. PMID:22966398

KAWAZOE, KAORU; ISOMOTO, HAJIME; YAMAGUCHI, NAOYUKI; INOUE, NAOKI; UEHARA, RYOHEI; MATSUSHIMA, KAYOKO; ICHIKAWA, TATSUKI; TAKESHIMA, FUMINAO; NONAKA, TAKASHI; NANASHIMA, ATSUSHI; NAGAYASU, TAKESHI; UEHARA, MASATAKA; ASAHINA, IZUMI; NAKAO, KAZUHIKO

2010-01-01

383

Mechanisms for optimising photodynamic therapy: second-generation photosensitisers in combination with mitomycin C.  

PubMed Central

Mechanisms for improving photodynamic therapy (PDT) were investigated in the murine RIF1 tumour using meso-tetrahydroxyphenylchlorin (m-THPC) or bacteriochlorin a (BCA) as photosensitisers and comparing these results with Photofrin-mediated PDT. The 86Rb extraction technique was used to measure changes in perfusion at various times after interstitial PDT. Non-curative combinations of light doses with m-THPC and BCA PDT markedly decreased vascular perfusion. This decrease was more pronounced for both new photosensitisers than for Photofrin. Comparison of tumour perfusion after PDT with tumour response revealed an inverse correlation for all three photosensitisers, but the relationship was less clear for m-THPC and BCA. In vivo/in vitro experiments were performed after Photofrin or m-THPC PDT in order to assess direct tumour kill (immediate plating) vs indirect vascular effects (delayed plating). For both photosensitisers, there was little direct cell killing but clonogenic survival decreased as the interval between treatment and excision increased. When m-THPC PDT was combined with mitomycin C (MMC), light doses could be decreased by a factor of 2 for equal tumour effects. Lower light and m-THPC doses could be used compared with Photofrin PDT in combination with MMC. BCA PDT with MMC did not result in a greater tumour response compared with BCA PDT alone. Reduction in both light and photosensitiser does for effective PDT regimes in combination with MMC offers substantial clinical advantages, since both treatment time and skin photosensitisation will be reduced. PMID:7640216

van Geel, I. P.; Oppelaar, H.; Oussoren, Y. G.; Schuitmaker, J. J.; Stewart, F. A.

1995-01-01

384

Targeting cytochrome C oxidase in mitochondria with Pt(II)-porphyrins for Photodynamic Therapy  

E-print Network

Mitochondria are the power house of living cells, where the synthesis of the chemical "energy currency" adenosine triphosphate (ATP) occurs. Oxidative phosphorylation by a series of membrane protein complexes I to IV, that is, the electron transport chain, is the source of the electrochemical potential difference or proton motive force (PMF) of protons across the inner mitochondrial membrane. The PMF is required for ATP production by complex V of the electron transport chain, i.e. by FoF1-ATP synthase. Destroying cytochrome C oxidase (COX; complex IV) in Photodynamic Therapy (PDT) is achieved by the cationic photosensitizer Pt(II)-TMPyP. Electron microscopy revealed the disruption of the mitochondrial christae as a primary step of PDT. Time resolved phosphorescence measurements identified COX as the binding site for Pt(II)-TMPyP in living HeLa cells. As this photosensitizer competed with cytochrome C in binding to COX, destruction of COX might not only disturb ATP synthesis but could expedite the release of c...

Boersch, Michael

2010-01-01

385

Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond  

PubMed Central

Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction of molecular oxygen. Four major ROS are recognized comprising: superoxide (O2•?), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen (1O2), but they display very different kinetics and levels of activity. The effects of O2•? and H2O2 are less acute than those of •OH and 1O2, since the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and non-enzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or 1O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics, and non-pharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma and medicinal honey. A brief final section covers, reactive nitrogen species, and related therapeutics, such as acidified nitrite and nitric oxide releasing nanoparticles. PMID:23802986

Vatansever, Fatma; de Melo, Wanessa C.M.A.; Avci, Pinar; Vecchio, Daniela; Sadasivam, Magesh; Gupta, Asheesh; Chandran, Rakkiyappan; Karimi, Mahdi; Parizotto, Nivaldo A; Yin, Rui; Tegos, George P; Hamblin, Michael R

2013-01-01

386

Photodynamic Therapy with Ablative Carbon Dioxide Fractional Laser in Treatment of Actinic Keratosis  

PubMed Central

Background Recently, photodynamic therapy (PDT) has been shown to be an effective first-line treatment for actinic keratosis (AK). However, a major limitation of PDT is the long incubation time required to allow penetration of the photosensitizer. Objective The aim of this study was to assess if pretreatment with an ablative carbon dioxide (CO2) fractional laser can reduce the incubation time of the photosensitizer. Methods Initially, 29 patients with a total of 34 AK lesions were treated with an ablative CO2 fractional laser at Ajou University Hospital between January and December 2010. Immediately after the laser treatment, topical 20% 5-aminolevulinic acid or methyl-aminolevulinate was applied to the AK lesions and incubated for 70 to 90 minutes. Then, the treated areas were illuminated with a red light source. Improvement was clinically or histologically assessed eight weeks after the treatment. Results In spite of the short incubation time, 24 lesions (70.6%) showed a complete response (CR) within three sessions of PDT (10 lesions a clinical CR and 14 lesions a clinical/histological CR). There were no significant side effects associated with the combination of ablative CO2 fractional laser and PDT. Conclusion Ablative CO2 fractional laser may be considered an additional treatment option for reducing the incubation time of the photosensitizer in PDT. PMID:24371387

Jang, Yong Hyun; Lee, Dong Jun; Shin, Jaeyoung; Kang, Hee Young; Lee, Eun-So

2013-01-01

387

Photodynamic Therapy with Ablative Carbon Dioxide Fractional Laser for Treating Bowen Disease  

PubMed Central

Background Topical photodynamic therapy (PDT) has been increasingly used to treat malignant skin tumors including the Bowen disease. However, patients could be displeased with the long incubation time required for conventional PDT. Objective We evaluated the efficacy and safety of PDT with a short incubation time of ablative CO2 fractional laser pretreatment for treating Bowen disease. Methods Ten patients were included. Just before applying the topical photosensitizer, all lesions were treated with ablative CO2 fractional laser, following the application of methyl aminolevulinate and irradiation with red light (Aktilite CL 128). Histological confirmation, rebiopsy, and clinical assessments were performed. Adverse events were also recorded. Results Five of the ten (50%) lesions showed a complete response (CR) within three PDT sessions. After four treatment sessions, all lesions except one penile shaft lesion (90%) achieved clinical and histological CR or clinical CR only. The average number of treatments to CR was 3.70±1.70. The treatments showed favorable cosmetic outcomes and no serious adverse events. Conclusion The results suggest that pretreatment with an ablative fractional CO2 laser before PDT has similar treatment efficacy and requires a shorter photosensitizer incubation time compared with the conventional PDT method. PMID:24003277

Kim, Sue Kyung; Park, Ji-Youn; Song, Hyo Sang; Kim, You-Sun

2013-01-01

388

Photodynamic therapy (PDT) to treat a chronic skin wound in a dog  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) is an emerging and promising therapeutic modality for treatment of a wide variety of malignant and nononcologic tumors, as well as in the treatment of infected skin ulcers. This study evaluated the effectiveness of the PDT to treat a chronic skin wound that had been already subjected to several clinical and surgical type treatments in a dog. The animal with an infected chronic skin wound with 8 cm diameter in the left leg received an injection of an aqueous solution of 1% methylene blue (MB) with 2% lidocaine into the lesion. After MB injection the wound was irradiated using a LED (LED-VET MMOptics(r)) with a wavelength between 600 and 700 nm, 2 cm diameter circular light beam, of 150 mW of power, light dose of 50 J/cm2. After 3 and 6 weeks PDT was repeated and the wound was re-evaluated. Complete healing was achieved 10 weeks after the first procedure.

Hage, Raduan; Plapler, Hélio; Bitar, Renata A.

2008-02-01

389

ROS-Responsive Activatable Photosensitizing Agent for Imaging and Photodynamic Therapy of Activated Macrophages  

PubMed Central

The optical properties of macrophage-targeted theranostic nanoparticles (MacTNP) prepared from a Chlorin e6 (Ce6)-hyaluronic acid (HA) conjugate can be activated by reactive oxygen species (ROS) in macrophage cells. MacTNP are nonfluorescent and nonphototoxic in their native state. However, when treated with ROS, especially peroxynitrite, they become highly fluorescent and phototoxic. In vitro cell studies show that MacTNP emit near-infrared (NIR) fluorescence inside activated macrophages. The NIR fluorescence is quenched in the extracellular environment. MacTNP are nontoxic in macrophages up to a Ce6 concentration of 10 ?M in the absence of light. However, MacTNP become phototoxic upon illumination in a light dose-dependent manner. In particular, significantly higher phototoxic effect is observed in the activated macrophage cells compared to human dermal fibroblasts and non-activated macrophages. The ROS-responsive MacTNP, with their high target-to-background ratio, may have a significant potential in selective NIR fluorescence imaging and in subsequent photodynamic therapy of atherosclerosis with minimum side effects. PMID:24396511

Kim, Hyunjin; Kim, Youngmi; Kim, In-Hoo; Kim, Kyungtae; Choi, Yongdoo

2014-01-01

390

Photodynamic Therapy: Occupational Hazards and Preventative Recommendations for Clinical Administration by Healthcare Providers  

PubMed Central

Abstract Objective: Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these treatment devices and photosensitizing agents administered to patients. Materials and methods: Here we outline and identify pertinent health and safety considerations to be taken by healthcare staff during PDT procedures. Results: Physical hazards (for example, non-ionizing radiation generated by the light-emitting device, with potential for skin and eye exposure) and chemical hazards (including the photosensitizing agents administered to patients that have the potential for exposure via skin, subcutaneous, ingestion, or inhalation routes) must be considered for safe use of PDT by the healthcare professional. Conclusions: Engineering, administrative, and personal protective equipment controls are recommendations for the safe use and handling of PDT agents and light-emitting technologies. PMID:23859750

Lacey, Steven E.; Vesper, Benjamin J.; Paradise, William A.; Radosevich, James A.; Colvard, Michael D.

2013-01-01

391

Apoptosis induced by 2-aryl benzothiazoles-mediated photodynamic therapy in melanomas via mitochondrial dysfunction.  

PubMed

A mild and efficient synthetic development of 2-arylbenzothiazoles 5 mediated by ceric ammonium nitrate (CAN) via intramolecular cyclization of N-phenyl-thiobenzamides 4 was achieved. Further compounds 5 were reduced to corresponding amines 6, and their photodynamic therapy (PDT) effect was evaluated on malignant human melanoma A375 cells. Amine 6l plus ultraviolet A (UVA) induced caspase-3 activity, poly(ADP-ribose)polymerase cleavage, M30 positive CytoDeath staining, and subsequent apoptotic cell death. Our data disclosed that treatment of A375 cells with 6l plus UVA resulted in a decrease in mitochondrial membrane potential (??mt), oxidative phosphorylation system (OXPHOS) subunits, and adenosine triphosphate (ATP) but an increase in mitochondrial DNA 4977-bp deletion via reactive oxygen species (ROS) generation. Transmission electron microscopy (TEM) observations also showed major ultrastructural alterations of mitochondria. Additionally, 6l plus UVA was also shown to reduce murine melanoma size in a mouse model. The present study supports the hypothesis that 6l-PDT may serve as a potential ancillary modality for the treatment of melanoma. PMID:24892656

Chen, Yin-Kai; Senadi, Gopal Chandru; Lee, Chih-Hung; Tsai, Yi-Min; Chen, Yan-Ren; Hu, Wan-Ping; Chou, Yu-Wei; Kuo, Kung-Kai; Wang, Jeh-Jeng

2014-07-21

392

Role of Photodynamic Therapy in the Palliation of Obstructing Esophageal Cancer  

PubMed Central

Background/Aims The aim of this non-randomized study was to determine the role of photodynamic therapy (PDT) in a multimodal approach for the palliation of advanced esophageal carcinoma. Methods Twenty consecutive patients with obstructing esophageal cancer were enrolled in this study. Each subject had dysphagia, and nine could not swallow fluid. External beam radiotherapy or a self-expandable metal stent was used following PDT for dysphagia due to recurrence of the malignancy. Results At 4 weeks post-PDT, a significant improvement in the dysphagia score was observed in 90% of patients, from 2.75 ± 0.91 to 1.05 ± 0.83 (p < 0.05). Patients with recurrent dysphagia underwent stent insertion at an average of 63 days (range, 37 to 90). The rate of major complications was 10%. Two esophageal strictures occurred, which were treated by placement of a modified expandable stent across the stricture. The median survival in these cases was 7.0 ± 0.6 months. One patient that was treated with PDT and radiotherapy is alive and showed a complete tumor response. Conclusions PDT as a multimodality treatment is safe and effective for relieving malignant esophageal obstruction with minimal complications. PMID:23019392

Yoon, Hyeon Young; Choi, Hye Jin; Shim, Chan Sup

2012-01-01

393

Nanoscopic micelle delivery improves the photophysical properties and efficacy of photodynamic therapy of protoporphyrin IX.  

PubMed

Nanodelivery systems have shown considerable promise in increasing the solubility and delivery efficiency of hydrophobic photosensitizers for photodynamic therapy (PDT) applications. In this study, we report the preparation and characterization of polymeric micelles that incorporate protoporphyrin IX (PpIX), a potent photosensitizer, using non-covalent encapsulation and covalent conjugation methods. Depending on the incorporation method and PpIX loading percentage, PpIX existed as a monomer, dimer or aggregate in the micelle core. The PpIX state directly affected the fluorescence intensity and (1)O(2) generation efficiency of the resulting micelles in aqueous solution. Micelles with lower PpIX loading density (e.g. 0.2%) showed brighter fluorescence and higher (1)O(2) yield than those with higher PpIX loading density (e.g. 4%) in solution. However, PDT efficacy in H2009 lung cancer cells showed an opposite trend. In particular, 4% PpIX-conjugated micelles demonstrated the largest PDT therapeutic window, as indicated by the highest phototoxicity and relatively low dark toxicity. Results from this study contribute to the fundamental understanding of nanoscopic structure-property relationships of micelle-delivered PpIX and establish a viable micelle formulation (i.e. 4% PpIX-conjugated micelles) for in vivo evaluation of antitumor efficacy. PMID:21232562

Ding, Huiying; Sumer, Baran D; Kessinger, Chase W; Dong, Ying; Huang, Gang; Boothman, David A; Gao, Jinming

2011-05-10

394

Polyethylene glycol-functionalized bis(arylidene)cycloalkanone photosensitizers for two-photon excited photodynamic therapy  

NASA Astrophysics Data System (ADS)

We report the properties of two series of polyethylene glycol-functionalized bis(arylidene)cycloalkanone photosensitizers designed for two-photon excited photodynamic therapy (PDT) with the aim to reveal the effect of the size of central ring on the two-photon excited PDT efficiency. These photosensitizers are the derivatives of bis(arylidene) cyclopentanone (B2, B3) and bis(arylidene) cyclobutanone (Q1-Q4). The bis(arylidene) cyclopentanone type photosensitizers were found to have larger two-photon absorption cross sections than the bis(arylidene) cyclopentanone ones with the same substituents. The singlet oxygen yields of the bis(arylidene) cyclobutanone derivatives are higher than the data of bis(arylidene) cyclopentanone derivatives. All the studied photosensitizers showed no obvious toxicity under dark situation. One- and two-photon excited PDT activities were successfully demonstrated by in vitro cell experiments. Owing to the capability of destructing the cancerous cells under two-photon irradiation, bis(arylidene)cycloalkanone based photosensitizers with proper substituents can be good candidates for two-photon excited PDT applications in the future.

Zou, Qianli; Zhao, Hongyou; Zhao, Yuxia; Wang, Ying; Gu, Ying; Wu, Feipeng

2012-12-01

395

Choosing optimal wavelength for photodynamic therapy of port wine stains by mathematic simulation  

NASA Astrophysics Data System (ADS)

Many laser wavelengths have been used in photodynamic therapy (PDT) for port wine stains (PWS). However, how these wavelengths result in different PDT outcomes has not been clearly illuminated. This study is designed to analyze which wavelengths would be the most advantageous for use in PDT for PWS. The singlet oxygen yield in PDT-treated PWS skin under different wavelengths at the same photosensitizer dosage was simulated and the following three situations were simulated and compared: 1. PDT efficiency of 488, 532, 510, 578, and 630 nm laser irradiation at clinical dosage (100 mW/cm2, 40 min); 2. PDT efficiency of different wavelength for PWS with hyperpigmentation after previous PDT; 3. PDT efficiency of different wavelengths for PWS, in which only deeply located ectatic vessels remained. The results showed that singlet oxygen yield is the highest at 510 nm, it is similar at 532 nm and 488 nm, and very low at 578 nm and 630 nm. This result is identical to the state in clinic. According to this theoretical study, the optimal wavelength for PDT in the treatment of PWS should near the absorption peaks of photosensitizer and where absorption from native chromophores (haemoglobin and melanin) is diminished.

Wang, Ying; Gu, Ying; Zuo, Zhaohui; Huang, Naiyan

2011-09-01

396

New optional photodynamic therapy laser wavelength for infantile port wine stains: 457 nm  

NASA Astrophysics Data System (ADS)

To expand the optional laser wavelengths of photodynamic therapy (PDT) for port wine stain (PWS), the feasibility of applying a 457 nm laser to the PDT for infantile PWS was analyzed by mathematical simulation and was validated by clinical experiment. Singlet oxygen yield of 457 nm PDT or 532 nm PDT in an infantile PWS model and an adult PWS model was theoretically simulated. Fifteen PWS patients (14 infants and 1 adult) with 40 spots were treated with 457 nm (20 spots) and 532 nm (20 spots), respectively, in two PDT courses. Simulation results showed that under the same power density and irradiation time, singlet oxygen yield of 457 nm PDT and 532 nm PDT are similar in infantile PWS vessels. Yet, in adult PWS vessels, singlet oxygen yield of 457 nm PDT is lower than 532 nm PDT. Clinical outcomes showed that no statistic difference existed between 457 nm PDT and 532 nm PDT for infantile PWS. The result of this study suggested that 457 nm wavelength laser has the potential to be applied in PDT for infantile PWS.

Wang, Ying; Zuo, Zhaohui; Gu, Ying; Huang, Naiyan; Chen, Rong; Li, Buhong; Qiu, Haixia; Zeng, Jing; Zhu, Jianguo; Liang, Jie

2012-06-01

397

Photodynamic therapy affects the expression of IL-6 and IL-10 in vivo  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response which potentiates anti-tumor immunity, but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood, but are likely to involve meditation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10. IL-6 mRNA and protein are rapidly and strongly enhanced in the PDT treated EMT6 tumor. Previous studies have shown that intratumoral injection of IL- 6 or transduction of the IL-6 gene into tumor cells can enhance tumor immunogenicity and inhibit tumor growth in experimental murine tumor systems. Thus, PDT may enhance local anti-tumor immunity by up-regulating IL-6. PDT also results in an increase in IL-10 mRNA and protein in the skin. The same PDT regime which enhances IL-10 production in the skin has been shown to strongly inhibit the CHS response. The kinetics of IL-10 expression coincide with the known kinetics of PDT induced CHS suppression and we propose that the enhanced IL-10 expression plays a role in the observed suppression of cell mediated responses seen following PDT.

Gollnick, Sandra O.; Musser, David A.; Henderson, Barbara W.

1998-05-01

398

Immunogenic cell death: can it be exploited in PhotoDynamic Therapy for cancer?  

PubMed

Immunogenic Cell Death (ICD) could represent the keystone in cancer management since tumor cell death induction is crucial as well as the control of cancer cells revival after neoplastic treatment. In this context, the immune system plays a fundamental role. The concept of Damage-Associated Molecular Patterns (DAMPs) has been proposed to explain the immunogenic potential of stressed or dying/dead cells. ICD relies on DAMPs released by or exposed on dying cells. Once released, DAMPs are sensed by immune cells, in particular Dendritic Cells (DCs), acting as activators of Antigen-Presenting Cells (APCs), that in turn stimulate both innate and adaptive immunity. On the other hand, by exposing DAMPs, dying cancer cells change their surface composition, recently indicated as vital for the stimulation of the host immune system and the control of residual ill cells. It is well established that PhotoDynamic Therapy (PDT) for cancer treatment ignites the immune system to elicit a specific antitumor immunity, probably linked to its ability in inducing exposure/release of certain DAMPs, as recently suggested. In the present paper, we discuss the DAMPs associated with PDT and their role in the crossroad between cancer cell death and immunogenicity in PDT. PMID:23509727

Panzarini, Elisa; Inguscio, Valentina; Dini, Luciana

2013-01-01

399

Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)  

PubMed Central

Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg?1 of BPD intravenously 5 min to 180 min before light treatment of 150 J cm?2 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction. © 1999 Cancer Research Campaign PMID:10206280

Fingar, V H; Kik, P K; Haydon, P S; Cerrito, P B; Tseng, M; Abang, E; Wieman, T J

1999-01-01

400

In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma  

SciTech Connect

Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. In the cell death pathway, {sup 1}O{sub 2} generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-{Kappa}B P65, and the enhancement of DNA fragmentation, and histone acetylation. ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.

Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.; Ruppel, M. E.; Smith, R. J.; Tsang, T.; Miller, L. M.

2009-05-02

401

Design of a protocol for combined laser hyperthermia-photodynamic therapy in the esophagus  

SciTech Connect

Photodynamic laser therapy (PDT) for esophageal cancer has recently been studied in animal and clinical trials. In several animal experiments a synergetic effect was found by simultaneously applying PDT and hyperthermia (HT). In this paper an optical fiber system is described which can be used in the esophagus for combined PDT with a 1 W dye laser and HT with a 15--40 W Nd-YAG laser. Phantoms were developed to simulate the geometry of the esophagus using cow muscle. The spatial-temporal temperature field during HT was measured. The results were compared with calculations using a coupled Monte Carlo laser transport/finite difference heat transport model using the LATIS computer program. Measurements and calculations yield a realistic description of the temperature distribution during HT under various experimental conditions. The LATIS program allows the prediction of the effects of blood perfusion for in-vivo situations. The results show that the perfusion has considerable influence on the temperature field, which must be considered for in-vivo applications.

London, R A; Eichler, J; Liebetrudt, J; Ziegenhagen, L

2000-02-01

402

(-)-epigallocatechin-3-gallate ameliorates photodynamic therapy responses in an in vitro T lymphocyte model.  

PubMed

(-)-Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic constituent in green tea, is known as a powerful antioxidant but concomitantly possesses a prooxidant property. We investigated the effect of EGCG on phloxine B (PhB)-induced photocytotoxicity in human T lymphocytic leukemia Jurkat cells. EGCG significantly potentiated PhB-induced photocytotoxic effects, including the inhibition of cell proliferation, DNA fragmentation, and caspase-3 activity induction in Jurkat cells. Catalase attenuated the enhanced cytotoxicity by EGCG, suggesting the involvement of extracellularly produced hydrogen peroxide. Indeed, EGCG significantly enhanced extracellular hydrogen peroxide formation induced by photo-irradiated PhB. The EGCG also enhanced intracellular reactive oxygen species accumulation, c-Jun N-terminal kinase (JNK) phosphorylation, and interferon-? (IFN-?) gene expression, all of which are involved in PhB-induced apoptosis. Taken together, our data suggest that EGCG is capable of potentiating photodynamic therapy responses, presumably through the intracellular oxidative stress-sensitive JNK/IFN-? pathway by exogenous hydrogen peroxide formation. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24700514

Qi, Hang; Abe, Naomi; Zhu, Beiwei; Murata, Yoshiyuki; Nakamura, Yoshimasa

2014-10-01

403

Choroidal thickness changes with photodynamic therapy for a diffuse choroidal hemangioma in Sturge–Weber syndrome.  

PubMed

The aim of this study was to evaluate the choroidal thickness (CT) changes associated with visual function following photodynamic therapy (PDT) for a diffuse choroidal hemangioma in Sturge–Weber syndrome. We report a case of Sturge–Weber syndrome and symptomatic serous retinal detachment (SRD) with diffuse choroidal hemangioma treated with PDT. Visual acuity (VA), macular sensitivity measured by means of MP1 microperimeter (Nidek Technologies, Padova, Italy), retinal and CT, measured by means of enhanced depth optical coherence tomography (EDI–OCT, Spectralis, Heidelberg Engineering, Heidelberg, Germany) were analyzed at baseline, 3 and 12 months follow-up.After the PDT VA and macular sensitivity improved.The OCT examination showed the resolution of SRD. The choroid was measured after PDT using EDI–OCT. At baseline, the subfoveal CT showed a progressive thickness reduction from 251 to 83 lm during follow-up. To our knowledge, this is the first report of CT changes after PDT for a diffuse choroidal hemangioma in Sturge–Weber syndrome in a longterm follow-up. The CT measurement represents a potential parameter to better follow choroidal hemangiomas and their response to treatment. However,the long-term choroidal changes should be carefully taken into account. PMID:24658736

Cacciamani, Andrea; Scarinci, Fabio; Parravano, Mariacristina; Giorno, Paola; Varano, Monica

2014-10-01

404

Response of U-87MG in nude rats in photodynamic therapy  

NASA Astrophysics Data System (ADS)

The response of a human glioma cell line (U-87MG) and normal rat brain to photodynamic therapy (PDT) was investigated in athymic nude rats. U-87MG was implanted in the right hemisphere, and allowed to grow for 17 days. The animals were injected IV with PhotofrinR (12.5 mg/kg) 48 h prior to PDT of both normal and tumored brain (35 to 280 J/cm2, 100 mW/cm2). The results were compared with that obtained under identical conditions with 9L gliosarcoma implanted in Fisher 344 rats. No tumor or normal tissue response was evident in the Nude rats at 35 J/cm2. Tumor and normal tissue response was evident at incident optical energy dose levels of 140 and 280 J/cm2. The response of the U-87MG tumor is consistent with that observed with the 9L gliosarcoma, however, the response in the nude rat normal brain was less than that observed in the Fisher 344 animals. These data indicate: (1) a possible contribution of the cellular immune system to the PDT reaction, (2) the human glioma xenograft model may contribute important insights into tumor and normal brain PDT responses.

Dereski, Mary O.; Chopp, Michael; Madigan, Lara; Roosen, Norbert

1995-03-01

405

Response of U-87MG in nude rats in photodynamic therapy  

NASA Astrophysics Data System (ADS)

The response of a human glioma cell line (U-87MG) and normal rat brain to photodynamic therapy (PDT) was investigated in athymic nude rats. U-87MG was implanted in the right hemisphere, and allowed to grow for 17 days. The animals were injected IV with PhotofrinR (12.5 mg/kg) 48 h prior to PDT of both normal and tumored brain (35 to 280 J/cm2, 100 mW/cm2). The results were compared with that obtained under identical conditions with 9L gliosarcoma implanted in Fisher 344 rats. No tumor or normal tissue response was evident in the Nude rats at 35 J/cm2. Tumor and normal tissue response was evident at incident optical energy dose levels of 140 and 280 J/cm2. The response of the U-87MG tumor is consistent with that observed with the 9L gliosarcoma, however, the response in the nude rat normal brain was less than that observed in the Fisher 344 animals. These data indicate: (1) a possible contribution of the cellular immune system to the PDT reaction, (2) the human glioma xenograft model may contribute important insights into tumor and normal brain PDT responses.

Dereski, Mary O.; Chopp, Michael; Madigan, Lara; Roosen, Norbert

1994-10-01

406