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1

Calreticulin as Cancer Treatment Adjuvant: Combination with Photodynamic Therapy and Photodynamic Therapy-Generated Vaccines  

PubMed Central

Calreticulin is recognized as one of the pivotal damage-associated molecular pattern molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT). The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4?mg/mouse) was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT-vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT-vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor response elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities. PMID:25692097

Korbelik, Mladen; Banáth, Judit; Saw, Kyi Min; Zhang, Wei; ?iplys, Evaldas

2015-01-01

2

Mortality in experimental adjuvant intraoperative photodynamic therapy (AIOPDT) using ALA, Photofrin II, and mTHPC  

NASA Astrophysics Data System (ADS)

A clinical problem in the treatment of colorectal cancer is the high rate of local tumor recurrence. Adjuvant therapy methods are necessary to receive a better clinical outcome in minimizing local tumor relapse. Adjuvant intraoperative photodynamic therapy (AIOPDT) seems to be a promising alternative therapy in the treatment of malignant colorectal diseases. IN experimental settings the success of AIOPDT depends on the accumulation of the photosensitizer (PS) in tumor tissue and may be jeopardized by high mortality rates, due to inadequate energy doses. Our study evaluated mortality rates of nude mice after AIOPDT with ALA, Photofrin II and mTHPC using the following various light doses: ALA/Photofrin II: 100J, 50J, 25J; mTHPC: 30J, 15J, 5J generated by an Argon-Dye-laser system. There was a close correlation between laser energy applied for AIOPDT and postoperative mortality rate. Initial high mortality rates were lowered by stepwise reduction of the energy dose. Mortality rates reached a maximum 24 hours after AIOPDT in all groups.

Winkler, Steffi; Prosst, Ruediger L.; Stern, Josef; Rheinwald, Markus; Haase, Thomas; Herfarth, Christian; Gahlen, Johannes

2001-01-01

3

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

4

New Photodynamic Therapy Developments  

NASA Astrophysics Data System (ADS)

I am going go over photodynamic therapy first, just an overview for those of you not familiar with it, as it is quite different from most of the normal surgical laser applications. Then I will be talking about the various aspects of the technology, and what we feel the market potentials are in the various aspects of the photodynamic therapy.

Doiron, Dan

1988-09-01

5

Photodynamic Therapy  

MedlinePLUS

... can’t be treated with laser therapy alone Barrett’s esophagus with dysplasia, a pre-cancerous condition that may ... optic glass strand. To treat esophageal cancer or Barrett’s esophagus, the fiber-optic strand is passed down the ...

6

Photodynamic Therapy in Dermatology  

Microsoft Academic Search

hotodynamic therapy (PDT) uses exogenously administered or endogenously formed photosensitizers activated by light to induce cell death via formation of singlet oxygen and other free radicals. Photodynamic therapy is increasingly used for the treatment of skin cancers and other indications. The efficacy of PDT depends on the structure of the photosensitizer, the administration modality, the light source, and the treatment

Clemens Fritsch; Gunter Goerz; Thomas Ruzicka

1998-01-01

7

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

8

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

9

Photodynamic therapy for psoriasis.  

PubMed

Abstract Introduction: Photodynamic therapy for psoriasis showed promise in the early 1990s with reports of plaque clearance following topical aminolevulinic acid - photodynamic therapy (ALA-PDT). Methods: In December 2013, we conducted a systematic search of the PubMed Medline database using the keywords "psoriasis" and "photodynamic therapy". Results: Numerous clinical studies have failed to demonstrate a consistent, efficacious response to topical ALA-PDT. Furthermore, severe pain and burning sensations were repeatedly reported, many cases being intolerable for patients. Discussion: The variability in clinical response and the painful side effects have made topical ALA-PDT an unsuitable treatment option for chronic plaque psoriasis. Nonetheless, early clinical studies of other modalities such as topical hypericin and methylene blue, as well as systemic ALA and verteporfin, have shown that these photosensitizers are efficacious and much better tolerated than topical ALA. Conclusion: With the current landscape of phototherapy dominated by psoralen combined with ultraviolet A (PUVA) and narrow-band ultraviolet B (NB-UVB), an alternative light therapy utilizing the visible spectrum is certainly promising and a worthwhile endeavor to pursue. PMID:24881473

Choi, Young M; Adelzadeh, Lily; Wu, Jashin J

2014-06-17

10

Photodynamic therapy with fullerenes†  

PubMed Central

Fullerenes are a class of closed-cage nanomaterials made exclusively from carbon atoms. A great deal of attention has been focused on developing medical uses of these unique molecules especially when they are derivatized with functional groups to make them soluble and therefore able to interact with biological systems. Due to their extended ?-conjugation they absorb visible light, have a high triplet yield and can generate reactive oxygen species upon illumination, suggesting a possible role of fullerenes in photodynamic therapy. Depending on the functional groups introduced into the molecule, fullerenes can effectively photoinactivate either or both pathogenic microbial cells and malignant cancer cells. The mechanism appears to involve superoxide anion as well as singlet oxygen, and under the right conditions fullerenes may have advantages over clinically applied photosensitizers for mediating photodynamic therapy of certain diseases. PMID:17973044

Mroz, Pawel; Tegos, George P.; Gali, Hariprasad; Wharton, Tim; Sarna, Tadeusz; Hamblin, Michael R.

2010-01-01

11

Photodynamic therapy: oncologic horizons.  

PubMed

Photodynamic therapy (PDT) is a light-based intervention with a long and successful clinical track record for both oncology and non-malignancies. In cancer patients, a photosensitizing agent is intravenously, orally or topically applied and allowed time to preferentially accumulate in the tumor region. Light of the appropriate wavelength and intensity to activate the particular photosensitizer employed is then introduced to the tumor bed. The light energy will activate the photosensitizer, which in the presence of oxygen should allow for creation of the toxic photodynamic reaction generating reactive oxygen species. The photodynamic reaction creates a cascading series of events including initiation of apoptotic and necrotic pathways both in tumor and neovasculature, leading to permanent lesion destruction often with upregulation of the immune system. Cutaneous phototoxicity from unintentional sunlight exposure remains the most common morbidity from PDT. This paper will highlight current research and outcomes from the basic science and clinical applications of oncologic PDT and interpret how these findings may lead to enhanced and refined future PDT. PMID:24328413

Allison, Ron R

2014-01-01

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

Photodynamic Therapy for Cholangiocarcinoma  

PubMed Central

Cholangiocarcinoma is the primary malignancy arising from the biliary epithelium, and it presents as jaundice, cholestasis, and cholangitis. Over 50 percent of patients present with advanced-stage disease, and the prognosis is poor with the survival measured in months even after biliary decompression. Palliative management has become the standard of care for unresectable disease, and this involves an endoscopic approach. Photodynamic therapy (PDT) involves the administration of a photosensitizer followed by local irradiation with laser therapy. The use of PDT for palliation of bile-duct tumors has produced promising results. Several studies conducted in Europe and the United States have shown that PDT produces a marked improvement in the symptoms of cholestasis, survival, and quality of life. This chapter summarizes the principle of PDT, the technique employed, and the published experience regarding PDT for cholangiocarcinoma. PMID:21103297

Talreja, Jayant P.

2010-01-01

14

Intracranial Photodynamic Therapy  

NASA Astrophysics Data System (ADS)

This chapter presents the use of photodynamic therapy (PDT) for clinical applications in the brain, particularly treatment of patients with solid brain tumors such as malignant gliomas. The principles and background of PDT are first described, followed by a summary of brain tumors and presentation of a heuristic model that serves to illustrate how PDT may be utilized. Subsequent sections will summarize what has been achieved to date in intracranial applications of PDT, and then the particular technical challenges that brain tumors pose for effective delivery of PDT treatment and some of the photophysical, photochemical, and photobiological strategies that have been explored to overcome these. The final section looks ahead to potential future needs and developments, both fundamental and practical.

Wilson, Brian C.; Madsen, Steen J.

15

Photodynamic therapy in China  

NASA Astrophysics Data System (ADS)

After the pioneering work of photodynamic therapy of malignant tumors had been reported by Dr. Dougherty and his colleagues, applications of hematoporphyrin derivative for the diagnosis and treatment of human cancers has been reported by Professor Hayata et al. Chinese HpD was first made by Shi-Lin Xu, an engineer of Beijing Institute of Pharmaceutical Industry in 1980. The first patient to receive the PDT in China was a case of basal cell carcinoma of the lower eyelid, treated in 1981 by Dr. Ping Zhu a physician in Tong Ren Hospital in Beijing using a Chinese made laser. In 1982, research groups of PDT were established under the sponsorships of the State Science and Technology Commission of China, Beijing Commission for Science and Technology, etc. Physics, chemistry, preclinical and clinical research studies of PDT were then started widely.

Li, Junheng

1993-03-01

16

Photodynamic Therapy in Bone  

Microsoft Academic Search

Recent work within our group suggests that the application of photodynamic ther- apy (PDT) in bone holds considerable promise for a number of key conditions spe- cific to bone, including the treatment of primary and secondary cancers, infection, and skeletal deformity. In this chapter I will provide a synopsis of preclinical results obtained using PDT in bone that starts with

Stuart K. Bisland

17

Photodynamic Therapy, Optical Trapping and Photostimulated Emission Using  

E-print Network

by the photosensitizer, which generates singlet oxygen cell death #12;Photodynamic Therapy (PDT) Photosensitizer LightPhotodynamic Therapy, Optical Trapping and Photostimulated Emission Using Upconverting nanothermometry MRI Photodynamic Therapy #12;· Attractive features: - Stability with respect to photobleaching

Van Stryland, Eric

18

Endobronchial photodynamic therapy for hemoptysis  

NASA Astrophysics Data System (ADS)

Hemoptysis (sometimes life threatening) is a frequent symptom of patients with endobronchial tumors. We recorded the amount of hemoptysis of 140 patients before treatment of the tumors with Photodynamic Therapy (PDT) and at subsequent follow up examinations. Follow up was 100. A hemoptysis scale of: 0 equals none; 1 equals streaks; 2 equals drops and clots; 3 equals large clots life threatening; 4 equals massive (life threatening requiring transfusions) was recorded.

McCaughan, James S.; Williams, Thomas; Hawley, Philip; Miller, Cynthia

1994-07-01

19

Appraising Adjuvant Aromatase Inhibitor Therapy  

Microsoft Academic Search

Tamoxifen, once the gold standard adjuvant endocrine therapy for early breast cancer, is being challenged by third-generation aromatase inhibitors (AIs) that have demonstrated improved disease-free survival in a vari- ety of adjuvant settings for early breast cancer. Tamoxi- fen and AIs have different safety profiles, which should allow physicians to begin to individualize treatment based on a patient's comorbidities and

Edith A. Perez

20

Augmentation of tumor immunity with ENHANZYN adjuvant following verteporfin PDT: photodynamic vaccination (PDV)  

NASA Astrophysics Data System (ADS)

The immune system is implicated in the mechanism of tumor destruction following photodynamic therapy (PDT). Several investigators have shown that immune stimulation can augment PDT. In this study, a single intratumoral injection of ENHANZYNTM adjuvant was administered to tumor-bearing mice immediately following verteporfin PDT in a therapeutic modality referred to as Photodynamic Vaccination (PDV). After optimal PDT, little difference in the rate of tumor re-growth or time to tumor reappearance was seen upon addition of the adjuvant. This may be as expected as this treatment regimen results in effective long-term tumor cure in mice. The effect of adjuvant and sub-optimal PDT was less clear as both groups treated with either a high or low does of adjuvant showed tumor re-growth earlier than those animals treated with PDT alone. However, tumors of mice receiving sub-optimal PDT followed by high dose immune adjuvant did not show the rapid, uncontrolled growth seen in other groups and, in the majority of cases, tumor volume decreased steadily with time. This resulted in a superior period of survival despite the animals being tumor-bearing. Interestingly, the data obtained in this study clearly demonstrates the ability of PDT to protect against re- challenge with a second round of tumor implantation. This was seen in all groups and stresses the importance of the immune response in PDT tumor control. Addition of the high immune adjuvant does to sub-optimal PDT appeared to be the most effective treatment group in this respect, giving complete protection against tumor re-implantation.

Curry, P. M.; Stewart, A. J.; Hardwicke, L.; Smits, Claire; North, John R.

2001-07-01

21

Immunological effects of photodynamic therapy  

NASA Astrophysics Data System (ADS)

There are few reports in the literature regarding the effect that photodynamic therapy (PDT) might have on immune function. illumination of skin with light in the long UV range is well known to have immunosuppressive properties mediated by the amplification of a subpopulation of T suppressor cells1. However, PDT effected by light at between 600 and 700 nm and accompanied by an acute inflammatory response has not been studied in depth in terms of its influence on immune function. A few recent reports have documented suppression of immune function in the days immediately following PDTZ3. In one report, the cells responsible for this suppressive effect were characterized as a non-T cell population which were incapable of adoptively transferring the effect2. It is probable that the cells responsible for transient immunosupppression following PDT are activated macrophages, no doubt stimulated by the photodynamic effect and well known for their release ofprostaglandin E2 which is non-specifically immunosuppressive. On the other hand, there is anecdotal evidence from clinical studies attesting to what might be interpreted as immunological enhancement following PDT (infiltration of lymphocytes into inflammatory lesions), as well as reports of elevated levels of interleukin 2 (IL-2) in the urine of patients treated with PDT for bladder cancer'5. Some investigators have reported lymphokine involvement in photodynamically initiated lesions6. Recent work by Gomer and his associates have shown positive correlation with PDT and enhanced natural killer cell activity7 and have suggested that this could play a role in reduction of the metastatic potential of surviving tumor cells8.

Logan, Patricia M.; Newton, Jo-anne; Richter, Anna M.; Yip, Stephen; Levy, Julia G.

1990-07-01

22

Photodynamic therapy of acne vulgaris.  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) was tested for the treatment of acne vulgaris. Patients with acne were treated with ALA plus red light. Ten percent water solution of ALA was applied with 1,5-2 h occlusion and then 18-45 J/cm2 630 nm light was given. Bacterial endogenous porphyrins fluorescence also was used for acne therapy. Treatment control and diagnostics was realized by fluorescence spectra and fluorescence image. Light sources and diagnostic systems were used: semiconductor laser (?=630 nm, Pmax=1W), (LPhT-630-01-BIOSPEC); LED system for PDT and diagnostics with fluorescent imager (?=635 nm, P=2W, p=50 mW/cm2), (UFPh-630-01-BIOSPEC); high sensitivity CCD video camera with narrow-band wavelength filter (central wavelength 630 nm); laser electronic spectrum analyzer for fluorescent diagnostics and photodynamic therapy monitoring (LESA-01-BIOSPEC). Protoporphyrin IX (PP IX) and endogenous porphyrins concentrations were measured by fluorescence at wavelength, correspondingly, 700 nm and 650 nm. It was shown that topical ALA is converted into PP IX in hair follicles, sebaceous glands and acne scars. The amount of resulting PP IX is sufficient for effective PDT. There was good clinical response and considerable clearance of acne lesion. ALA-PDT also had good cosmetic effect in treatment acne scars. PDT with ALA and red light assist in opening corked pores, destroying Propionibacterium acnes and decreasing sebum secretion. PDT treatment associated with several adverse effects: oedema and/or erytema for 3-5 days after PDT, epidermal exfoliation from 5th to 10th day and slight pigmentation during 1 month after PDT. ALA-PDT is effective for acne and can be used despite several side effects.

Ershova, Ekaterina Y.; Karimova, Lubov N.; Kharnas, Sergey S.; Kuzmin, Sergey G.; Loschenov, Victor B.

2003-06-01

23

Photodynamic Cancer Therapy - Recent Advances  

SciTech Connect

The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular localization of PS is of vital importance when cell death mechanism is identified. Programmed cell death (PCD) viz. apoptosis, necrosis and autophagy have all been identified as inducible cell death mechanisms during PDT. While apoptosis is probably the preferred cell death mechanism, understanding the molecular differences and identifying the cross-talk between these mechanisms are crucial to the development of new PSs aimed at improving the killing efficiency and overall effectiveness of PDT as a cancer treatment modality. This paper reviews the process of PDT cancer therapy, the available PSs, their effectiveness for different cancers as well as the cell death mechanisms identified during PDT of different cancers associated with specific PSs.

Abrahamse, Heidi [Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein (South Africa)

2011-09-22

24

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

25

Photodynamic therapy for esophageal cancer  

PubMed Central

Photodynamic therapy (PDT) is a treatment that uses a photosensitizing drug that is administered to the patient, localized to a tumor, and then activated with a laser to induce a photochemical reaction to destroy the cell. PDT using porfimer sodium followed by excimer dye laser irradiation is approved as a curative treatment for superficial esophageal cancer in Japan. While endoscopic submucosal dissection (ESD) is currently more popular for esophageal cancer, there is evidence to support PDT as an alternative treatment and as a salvage treatment for local failure after chemoradiotherapy (CRT). A photosensitizing agent has also been developed that requires a shorter sun shade period after administration, and studies are currently underway to establish an esophageal cancer indication for this next-generation PDT in Japan. PMID:25333005

Hatogai, Ken; Morimoto, Hiroyuki; Yoda, Yusuke; Kaneko, Kazuhiro

2014-01-01

26

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

27

BODIPY dyes in photodynamic therapy.  

PubMed

BODIPY dyes tend 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 (3)O(2). 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; Burgess, Kevin

2013-01-01

28

Photodynamic therapy of gastrointestinal cancers  

NASA Astrophysics Data System (ADS)

A new photosensitizer (PS), meso-tetrahydroxyphenyl-chlorin(m-THPC), has been clinically evaluated for photodynamic therapy (PDT) of early squamous cell carcinomas located in the upper aerodigestive tract, the oesophagus and the tracheobronchial tree. The injected doses ranged between 0.1 - 0.3 mg/kg m-THPC and the wavelength of the excitation light was either at 514 nm or 652 nm. The evaluation of the m-THPC induced phototoxicity was carried out on healthy mucosae of the bronchi, the oral cavity and the skone cell population to the other. Appearance of aneuploid populations after PDT suggests that destruction of sensitive cell populations allows the growth of initially non FCM detectable aneuploid clones. MDA assay could thus be a good prognostic tool although larger series of patients are needed. 115

Foultier, Marie-Therese; Vonarx-Coinsmann, Veronique; Harel, Yann; Cordel, S.; Antona, B.; Patrice, Thierry

1994-03-01

29

Current Concepts in Gastrointestinal Photodynamic Therapy  

PubMed Central

Objective To review current concepts of photodynamic therapy (PDT) applied to the treatment of tumors of the gastrointestinal tract. Summary Background Data PDT initially involves the uptake or production of a photosensitive compound by tumor cells. Subsequent activation of the photoreactive compound by a specific wavelength of light results in cell death, either directly or as a result of vascular compromise and/or apoptosis. Methods The authors selectively review current concepts relating to photosensitization, photoactivation, time of PDT application, tissue selectivity, sites of photodynamic action, PDT effects on normal tissue, limitations of PDT, toxicity of photosensitizers, application of principles of PDT to tumor detection, and current applications of PDT to tumors of the gastrointestinal tract. Results PDT is clearly effective for small cancers, but it is not yet clear in which cases such treatment is more effective than other currently acceptable approaches. The major side effect of PDT is cutaneous photosensitization. The major limitation of PDT is depth of tumor kill. As data from current and future clinical trials become available, a clearer perspective of where PDT fits in the treatment of cancers will be gained. Many issues regarding pharmacokinetic data of photosensitizers, newer technology involved in light sources, optimal treatment regimens that take advantage of the pharmacophysiology of photoablation, and light dosimetry still require solution. One can foresee application of differing sensitizers and light sources depending on the specific clinical situation. As technologic advances occur, interstitial PDT may have significant application. Conclusions PDT has a potentially important role either as a primary or adjuvant mode of treatment of tumors of the gastrointestinal tract. PMID:10400031

Webber, John; Herman, Mark; Kessel, David; Fromm, David

1999-01-01

30

Current status of photodynamic therapy in oncology.  

PubMed

Photodynamic therapy (PDT) is a cancer treatment based on the accumulation in malignant tissue of a photosensitiser with low systemic toxicity. Subsequent illumination induces a type II photochemical reaction with singlet oxygen production that results in destruction of biomolecules and subcellular organelles. The first full clinical report of PDT dates from 1976. Haematoporphyrin derivative, a complex mixture of porphyrins, was initially used as a photosensitiser. An enriched fraction (porfimer sodium) is now the most commonly used clinical agent. After systemic administration porphyrins bind to albumin and lipoproteins. Accumulation occurs mainly in tumours and organs of the reticuloendothelial system. The light of an argon-dye laser can be tuned to the appropriate wavelength and delivered either superficially, interstitially or intraluminally. Light distribution can be assessed by using a radiation transport model and tissue optical properties, or direct measurement with light detectors. The effects of PDT depend in a complex way on: characteristics, tissue concentration and localisation of the photosensitiser; the target tissue optical properties and oxygenation; activation wavelength, power density and treatment regimen. Future research is directed towards: better photosensitisers (i.e. phthalocyanines, chlorins or protoporphyrin IX endogenously produced from 5-aminolevulinic acid); improved light generation and delivery; and combination with hyperthermia, chemotherapy, radiotherapy or surgery. Adjuvant intraoperative PDT is a promising approach to destroying residual tumour after surgery. PMID:7528127

van Hillegersberg, R; Kort, W J; Wilson, J H

1994-10-01

31

Light distributors for photodynamic therapy  

NASA Astrophysics Data System (ADS)

A brief overview is given of light distributors developed by our group in Lausanne for photodynamic therapy (PDT) of cancer. We focus on fiberoptic devices which have to a large extent been tested over the years in the clinic for PDT of the upper aerodigestive tract, the tracheobronchial tree, the esophagus, the uterus, and the skin. Both surface and interstitial light distributors are discussed. Several different physical principles for obtaining the desired light intensity distribution in tissue are demonstrated, including the use of specially shaped reflecting surfaces, light scattering and refraction by particles, the use of flexible highly reflecting balloons, controlled fiber core surface roughening, and microlenses. PDT can be improved using 'intelligent' light distributors, which permit the measurement of the light intensity reflected from the irradiated surface, as well as the dye fluorescence signals. Both are measured in situ and in real time during the treatment. The use of such devices, which can measure photobleaching kinetics, and enable one to adjust the light dose to the observed dye fluorescence signals, thus giving better PDT control, is discussed.

van den Bergh, Hubert; Mizeret, Jerome C.; Theumann, Jean-Francois; Woodtli, Alain; Bays, Roland; Robert, D.; Thielen, P.; Philippoz, J. M.; Braichotte, Daniel; Forrer, Martin; Savary, Jean-Francois; Monnier, Philippe; Wagnieres, Georges A.

1995-01-01

32

Photodynamic therapy of gastric cancer  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) with the use of laser endoscopic spectrum analyzer (LESA-5), the spectral-analyzing video-imaging system, Kr laser and various types of catheters for different tumor localizations, and Phthalocyanine aluminum photosensitizers in patients with gastric cancer was discussed. PDT was carried out in fifteen patients with gastric cancer. There were the following indications for PDT: early gastric cancer (3 patients), malignant stenosis of the cardia or pyloric portion of the stomach (4 patients), cancer of gastric stump with stenosis of gastrojejunal anastomosis (1 patient), preoperative treatment of patients with large but probably resectable gastric tumor size (7 patients). Usually we used 3 - 4 seances of laser treatment 10 - 30 minutes long. Concentration of photosensitizer in normal and malignant tissue was controlled by LESA-5. Treatment was monitored by spectral-analyzing video- imaging system in fluorescent light. The results show high efficiency of PDT especially in patients with early gastric cancer (necrosis of all tumor mass, i.e. complete regression of tumor). For all other patients we obtained partial regression of gastric cancer.

Kharnas, Sergey S.; Kuzin, N. M.; Zavodnov, Victor Y.; Sclyanskaya, Olga A.; Linkov, Kirill G.; Loschenov, Victor B.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Stratonnikov, Alexander A.; Steiner, Rudolf W.

1996-01-01

33

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.

34

Adjuvant therapy for endometrial cancer  

PubMed Central

Endometrial cancer is a common gynecologic malignancy typically diagnosed at early stage and cured with surgery alone. Adjuvant therapy is tailored according to the risk of recurrence, estimated based on the International Federation of Gynecology and Obstetrics (FIGO) stage and other histological factors. The objective of this manuscript is to review the evidence guiding adjuvant therapy for early stage and locally advanced uterine cancer. For patients with early stage disease, minimizing toxicity, while preserving outstanding cure rates remains the major goal. For patients with locally advanced endometrial cancer optimal combined regimens are being defined. Risk stratification based on molecular traits is under development and may aid refine the current risk prediction model and permit personalized approaches for women with endometrial cancer. PMID:24761218

DeLeon, Maria C.; Ammakkanavar, Natraj R.

2014-01-01

35

Antimicrobial Photodynamic Inactivation and Photodynamic Therapy for Infections  

PubMed Central

Photodynamic therapy (PDT) was initially discovered over 100 years ago by its ability to kill microorganisms, but its use to treat infections clinically has not been much developed. However, the present relentless increase in antibiotic resistance worldwide and the emergence of strains that are resistant to all known antibiotics has stimulated research into novel antimicrobial strategies such as PDT that are thought to be unlikely to lead to the development of resistance. In this chapter we will cover the use of PDT to kill pathogenic microbial cells in vitro and describe a mouse model of localized infection and its treatment by PDT without causing excessive damage to the host tissue. PMID:20552347

Huang, Liyi; Dai, Tianhong; Hamblin, Michael R.

2010-01-01

36

Photodynamic therapy photosensitizers derived from chlorophyll a  

NASA Astrophysics Data System (ADS)

A series of hydroxychlorins and another of (omega) -carboxyalkyloxy derivatives have been prepared from chlorophyll (alpha) , and their potential photosensitizing ability for the photodynamic therapy of cancer tested in vitro by the MTT assay. The results show that the monohydroxychlorin VI, because of its high photoactivity and its low dark toxicity, is the most promising compound of these series.

Bonnett, Raymond; Benzie, Robin; Grahn, Michael F.; Salgado, A.; Valles, Maria A.

1994-03-01

37

Heat-shock Proteins and Photodynamic Therapy  

NASA Astrophysics Data System (ADS)

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 mitochondria under non-stress conditions at higher levels than in normal cells. The objective of our work is to determine whether specific mitochondrial heat-shock proteins are responsible for the increased resistance of cancer cells to oxidative-based anti-cancer therapies. We will first determine which heat-shock proteins accumulate in the mitochondria of cancer cells (lung carcinomas). We will determine if the over-expression of specific heat-shock proteins in the mitochondria can protect cells from Photofrin®-mediated photodynamic therapy through protection of mitochondrial electron transport.

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

1998-11-01

38

Ocular Photodynamic Therapy – Standard Applications and New Indications (Part 1)  

Microsoft Academic Search

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)

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

2007-01-01

39

Photodynamic therapy for occluded biliary metal stents  

NASA Astrophysics Data System (ADS)

In this abstract we describe the use of photodynamic therapy (PDT) to recanalize occluded biliary metal stents. In patients with jaundice secondary to obstructed metal stents PDT was carried out 72 hours after the administration of m THPC. Red laser light at 652 nm was delivered endoscopically at an energy intensity of 50 J/cm. A week later endoscopic retrograde cholangiogram showed complete recanalization of the metal stent.

Roche, Joseph V. E.; Krasner, Neville; Sturgess, R.

1999-02-01

40

Combined surgery and photodynamic therapy of cancer  

NASA Astrophysics Data System (ADS)

According to the recent guidelines, the gold standard is resecting an extra 0.5-3 cm beyond the lesion margins that are visually detected and/or biopsy confirmed depending on type of malignancy and its localisation to avoid missing the residuals of the tumour. Often, such a large resection leads to dysfunctions of the organ or tissues, which underwent the surgery. In some cases, an extra tumour-free margin cannot be achieved because of tumour proximity to vital sites such as major vascular or nerve structures. Photodynamic Therapy (PDT) is an emerging clinical modality to locally destroy cancer lesions selectively. The limitation of photodynamic therapy is the curable depth of an order of one centimetre or less. A combination of cancer surgery following by PDT can bring a benefit to reduce the resection and minimise the impact on the organ or tissue functionality. Combination of cancer surgery and photodynamic therapy provides another opportunity-fluorescence image guidance of cancer removal. Most of the photosensitizers intensively fluoresce and hence facilitate a strong fluorescence contrast versus healthy adjacent tissues.

Douplik, Alexandre

41

Antitumor immune reaction elicited by photodynamic therapy  

NASA Astrophysics Data System (ADS)

This work examines why photodynamic therapy (PDT) is capable of eliciting a strong immune reaction against treated solid tumors. It is postulated that this phenomenon originates from the basic charter of the insult inflicted by the photodynamic treatment, which is dominated by singlet oxygen-mediated oxidative stress. The early event associated with this initial impact, which is of major relevance for the development of immune response, is the generation of photo-oxidative lesions responsible for the activation of cellular signal transduction pathways and consequent induction of stress proteins. Importantly, these lesions, as well as other types of PDT mediated oxidative injury, have a strong pro-inflammatory character. It is suggested that the antitumor immune response is primed and propagated by the PDT-induced inflammatory process. Of critical importance for the immune recognition of treated tumor is the generation of large amounts of cancer cell debris that occurs rapidly following PDT treatment.

Korbelik, Mladen

1999-06-01

42

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

43

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 is limited to one cancer cell line (HT29-A4), one photosensitiser (Chlorin e6), one photosensitiser dose (5µg

Paris-Sud XI, Université de

44

Interstitial photodynamic therapy for prostate cancer: a developing modality  

Microsoft Academic Search

Patients with early stage prostate cancer are generally treated with either a radical prostatectomy or radiotherapy. While both approaches have good survival outcomes, they are associated with significant side effects and non-trivial failure rates. Photodynamic therapy has been studied as a possible treatment for both recurrent and primary prostate cancer. Interstitial photodynamic therapy requires strict dosimetry, mandating an understanding of

Neil E. Martin; Stephen M. Hahn

2004-01-01

45

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

46

Photodynamic therapy for treatment subretinal neovascularization  

NASA Astrophysics Data System (ADS)

This work are devoted our experience with photodynamic therapy (PDT) with <> for patients with choroidal neovascularization (CNV). 18 patients with subfoveal CNV in age-related macular degeneration (AMD), 24 patients with subfoveal CNV in pathological myopia (PM) and 4 patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were observed. CNV was 100% classic in all study patients. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, biomicroscopy, fluorescein angiography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; were used to evaluate the results of photodynamic therapy with <> (0.02% solution of mixture sulfonated aluminium phtalocyanine 0.05 mg/kg, intravenously). A diode laser (<>, Inc, Moscow) was used operating in the range of 675 nm. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. At 3, 6, 9 month 26 (56.5%) patients had significant improvement in the mean visual acuity. At the end of the 12-month minimal fluorescein leakage from choroidal neovascularization was seen in 12 (26.1%) patients and the mean visual acuity was slightly worse than 0.2 which was not statistically significant as compared with the baseline visual acuity. Patients with fluorescein leakage from CNV underwent repeated PDT with <>. 3D-mode ultrasound shown the decreasing thickness of chorioretinal complex in CNV area. Photodynamic therapy with <> can safely reduce the risk of severe vision loss in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD, PM and toxoplasmic retinochoroiditis.

Avetisov, Sergey E.; Budzinskaja, Maria V.; Kiseleva, Tatyana N.; Balatskaya, Natalia V.; Gurova, Irina V.; Loschenov, Viktor B.; Shevchik, Sergey A.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

2007-07-01

47

Hormonal component of tumor photodynamic therapy response  

NASA Astrophysics Data System (ADS)

The involvement of adrenal glucocorticoid hormones in the response of the treatment of solid tumors by photodynamic therapy (PDT) comes from the induction of acute phase response by this modality. This adrenal gland activity is orchestrated through the engagement of the hypothalamic-pituitary-adrenal hormonal axis incited by stress signals emanating from the PDT-treated tumor. Glucocorticoid hormone activity engendered within the context of PDT-induced acute phase response performs multiple important functions; among other involvements they beget acute phase reactant production, systemic neutrophil mobilization, and control the production of inflammation-modulating and immunoregulatory proteins.

Korbelik, Mladen; Merchant, Soroush

2008-02-01

48

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

49

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

50

Topical photodynamic therapy in dermatology  

Microsoft Academic Search

Although photodyamiic therapy (PDT) was first used in the treatment of skin diseases, phase-III-clinical trials were primarily conducted for the treatment of bladder cancer, endobronchial and oesophageal carcinoma. In dermatology PDT has most extensively been used for the treatment of malignant cutaneous lesions. Up to now those patients have been treated systematically with first-generation photosensitizers. However, prolonged skin photosensitivity is

Rolf-Markus Szeimies; PierGiacomo Calzavara-Pinton; Sigrid Karrer; Bernhard Ortel; Michael Landthaler

1996-01-01

51

Graphene-based nanovehicles for photodynamic medical therapy  

PubMed Central

Graphene and its derivatives such as graphene oxide (GO) have been widely explored as promising drug delivery vehicles for improved cancer treatment. In this review, we focus on their applications in photodynamic therapy. The large specific surface area of GO facilitates efficient loading of the photosensitizers and biological molecules via various surface functional groups. By incorporation of targeting ligands or activatable agents responsive to specific biological stimulations, smart nanovehicles are established, enabling tumor-triggering release or tumor-selective accumulation of photosensitizer for effective therapy with minimum side effects. Graphene-based nanosystems have been shown to improve the stability, bioavailability, and photodynamic efficiency of organic photosensitizer molecules. They have also been shown to behave as electron sinks for enhanced visible-light photodynamic activities. Owing to its intrinsic near infrared absorption properties, GO can be designed to combine both photodynamic and photothermal hyperthermia for optimum therapeutic efficiency. Critical issues and future aspects of photodynamic therapy research are addressed in this review.

Li, Yan; Dong, Haiqing; Li, Yongyong; Shi, Donglu

2015-01-01

52

Role of multidrug resistance in photodynamic therapy  

NASA Astrophysics Data System (ADS)

Multidrug resistance in cancer chemotherapy is a well established phenomenon. One of the most common phenotypical changes in acquired or intrinsic multidrug resistance in human tumor cells is the overexpression of the mdrl gene product P-glycoprotein, which acts as an active efflux pump. Increased levels of P-glycoprotein are associated with resistance to a variety of anticancer drugs commonly used in tumor chemotherapy like anthracyclins, vinca- alcaloids, epipodophyllotoxins or actinomycin D. We investigated the efficacy or photodynamic therapy in the treatment of tumor cells expressing the multidrug resistance phenotype. Our data show that multidrug resistant cells are highly cross resistant to the phototoxic stain rhodamine 123 but exhibit only low degrees of cross resistance (2 - 3 -folds) to the photosensitizers Photosan-3, Clorin-2, methylene blue and meso-tetra (4- sulfonatophenyl) porphine (TPPS4). Resistance is associated with a decrease in intracellular accumulation of the photosensitizer. Verapamil, a membrane active compound known to enhance drug sensitivity in multidrug resistant cells by inhibition of P-glycoprotein, also increases phototoxicity in multidrug resistant cells. Our results imply that tumors expressing the multidrug resistance phenotype might fail to respond to photochemotherapy with rhodamine 123. On the other hand, multidrug resistance may not play an important role in photodynamic therapy with Photosan-3, Chlorin-2, methylene blue or TPPS4.

Diddens, Heyke C.

1992-06-01

53

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

54

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

55

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

56

Initiation of Autophagy by Photodynamic Therapy  

PubMed Central

Photodynamic therapy (PDT) involves the irradiation of photosensitized cells with light. Depending on localization of the photosensitizing agent, the process can induce photodamage to the endoplasmic reticulum (ER), mitochondria, plasma membrane, and/or lysosomes. When ER or mitochondria are targeted, antiapoptotic proteins of the Bcl-2 family are especially sensitive to photodamage. Both apoptosis and autophagy can occur after PDT, autophagy being associated with enhanced survival at low levels of photodamage to some cells. Autophagy can become a cell-death pathway if apoptosis is inhibited or when cells attempt to recycle damaged constituents beyond their capacity for recovery. While techniques associated with characterization of autophagy are generally applicable, PDT introduces additional factors related to unknown sites of photodamage that may alter autophagic pathways. This chapter discusses issues that may arise in assessing autophagy after cellular photodamage. PMID:19216899

Kessel, David; Oleinick, Nancy L.

2010-01-01

57

Somatostatin Analogues for Receptor Targeted Photodynamic Therapy  

PubMed Central

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

Kaš?áková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

2014-01-01

58

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

59

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

60

Photodynamic therapy of malignant mesothelioma of pleura  

NASA Astrophysics Data System (ADS)

Nine patients with malignant pleural mesothelioma underwent extensive surgery followed by intra-operative photodynamic therapy. Two mg/kg Photofrin was given 48 hours prior to surgery. The thoracic cavity and eventual remaining lung were exposed to 15 - 30 Joules/cm2 of 630 nm laser light. Tumor tissue was analyzed by microscopic photometrical techniques. Five patients with mixed or epithelioid tumors with fluorescence intensity > 100 gray level/pixel seemed to benefit from the given therapy. One patient was free of disease 18 months after treatment. Two patients were treated for metastasis after 12 months with no sign of intrathoracic recurrence. Both are still alive, one without further sign of disease 32 months after initial treatment. Two patients presented generalized disease after 9 and 13 months and intrathoracic recurrence several months later. Two patients with poorly differentiated tumors and 2 patients with moderate to highly differentiated tumors, but with fluorescence intensity < 100 gray level/pixel, presented recurrences after 4 months. PDT-efficiency seems to be predicted by the intensity and distribution of drug-induced fluorescence in tumor tissue. PDT may enhance the possibility to achieve complete local tumor control after excision. Multimodal therapeutic approach of local and systemic disease seems mandatory to further improve survival.

Warloe, Trond; Heyerdahl, Helen; Peng, Qian; Hoie, J.; Normann, E.; Solheim, O.; Moan, Johan; Giercksky, Karl-Erik

1995-03-01

61

System identification of the intracellular photoreaction process induced by photodynamic therapy  

E-print Network

-- Photodynamic therapy (PDT) is an alternative treatment for cancer that involves the administration. INTRODUCTION Photodynamic therapy (PDT) [1], [2], [12] is a treatment of displastic tissues such as cancersSystem identification of the intracellular photoreaction process induced by photodynamic therapy

Boyer, Edmond

62

Integrating spheres for improved skin photodynamic therapy.  

PubMed

The prescribed radiant exposures for photodynamic therapy (PDT) of superficial skin cancers are chosen empirically to maximize the success of the treatment while minimizing adverse reactions for the majority of patients. They do not take into account the wide range of tissue optical properties for human skin, contributing to relatively low treatment success rates. Additionally, treatment times can be unnecessarily long for large treatment areas if the laser power is not sufficient. Both of these concerns can be addressed by the incorporation of an integrating sphere into the irradiation apparatus. The light fluence rate can be increased by as much as 100%, depending on the tissue optical properties. This improvement can be determined in advance of treatment by measuring the reflectance from the tissue through a side port on the integrating sphere, allowing for patient-specific treatment times. The sphere is also effective at improving beam flatness, and reducing the penumbra, creating a more uniform light field. The side port reflectance measurements are also related to the tissue transport albedo, enabling an approximation of the penetration depth, which is useful for real-time light dosimetry. PMID:21054127

Glennie, Diana L; Farrell, Thomas J; Hayward, Joseph E; Patterson, Michael S

2010-01-01

63

Light emitting fabric technologies for photodynamic therapy.  

PubMed

Photodynamic therapy (PDT) is considered to be a promising method for treating various types of cancer. A homogeneous and reproducible illumination during clinical PDT plays a determinant role in preventing under- or over-treatment. The development of flexible light sources would considerably improve the homogeneity of light delivery. The integration of optical fiber into flexible structures could offer an interesting alternative. This paper aims to describe different methods proposed to develop Side Emitting Optical Fibers (SEOF), and how these SEOF can be integrated in a flexible structure to improve light illumination of the skin during PDT. Four main techniques can be described: (i) light blanket integrating side-glowing optical fibers, (ii) light emitting panel composed of SEOF obtained by micro-perforations of the cladding, (iii) embroidery-based light emitting fabric, and (iv) woven-based light emitting fabric. Woven-based light emitting fabrics give the best performances: higher fluence rate, best homogeneity of light delivery, good flexibility. PMID:25481663

Mordon, Serge; Cochrane, Cédric; Tylcz, Jean Baptiste; Betrouni, Nacim; Mortier, Laurent; Koncar, Vladan

2015-03-01

64

Tissue temperature monitoring during interstitial photodynamic therapy  

NASA Astrophysics Data System (ADS)

During ?-aminolevulinic acid (ALA) based Interstitial Photodynamic Therapy (IPDT) a high light fluence rate is present close to the source fibers. This might induce an unintentional tissue temperature increase of importance for the treatment outcome. In a previous study, we have observed, that the absorption in the tissue increases during the treatment. A system to measure the local tissue temperature at the source fibers during IPDT on tissue phantoms is presented. The temperature was measured by acquiring the fluorescence from small Cr3+-doped crystals attached to the tip of the illumination fiber used in an IPDT-system. The fluorescence of the Alexandrite crystal used is temperature dependent. A ratio of the intensity of the fluorescence was formed between two different wavelength bands in the red region. The system was calibrated by immersing the fibers in an Intralipid solution placed in a temperature controlled oven. Measurements were then performed by placing the fibers interstitially in a pork chop as a tissue phantom. Measurements were also performed superficially on skin on a volunteer. A treatment was conducted for 10 minutes, and the fluorescence was measured each minute during the illumination. The fluorescence yielded the temperature at the fiber tip through the calibration curve. The measurements indicate a temperature increase of a few degrees during the simulated treatment.

Svensson, Jenny; Johansson, Ann; Svanberg, Katarina; Andersson-Engels, Stefan

2005-04-01

65

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

66

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

67

Melanoma: Adjuvant therapy and other treatment options  

Microsoft Academic Search

Opinion statement  Melanoma, diagnosed and treated at its earliest stages, can be successfully cured by surgery alone. However, when metastatic\\u000a beyond the regional nodes, it is almost uniformly deadly. Adjuvant therapy targeted toward the treatment of microscopic residual\\u000a disease after surgical resection is the subject of intense scientific investigation because this is the stage at which it\\u000a is possible to have

Alicia Terando; Michael S. Sabel; Vernon K. Sondak

2003-01-01

68

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

69

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. PMID:25332999

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

70

Fluorescence guided evaluation of photodynamic therapy as acne treatment  

Microsoft Academic Search

Photodynamic therapy (PDT) is an attractive alternative treatment for patients with acne because of its efficiency and few side effects. Propionibacterium acnes (P.acnes) are bacteria present in the skin, which produce endogenous porphyrins that act as photosensitisers. In addition, application of aminolaevulinic acid or its methyl ester (mALA) results in increased accumulation of porphyrins in the pilosebaceous units. This makes

Marica B. Ericson; Camilla Horfelt; Elaine Cheng; Frida Larsson; Olle Larko; Ann-Marie Wennberg

2005-01-01

71

Photochemical predictive analysis of photodynamic therapy in dermatology  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy is a recent treatment modality that allows malignant tissue destruction. The technique provides a localized effect and good cosmetic results. The application of Photodynamic Therapy is based on the inoculation of a photosensitizer and the posterior irradiation by an optical source. This radiation chemically activates the drug and provokes reactions that lead to tissue necrosis. Nowadays there are fixed clinical Photodynamic Therapy protocols that make use of a particular optical dose and photosensitizer amount. These parameters are independent of the patient and the lesion. In this work we present a Photodynamic Therapy model that tries to predict the effect of the treatment on the skin. First the results of a clinical study in the Dermatology Department of the Marqués de Valdecilla University Hospital are presented. The most common lesions and some unsuccessful cases are stated. The predictive model proposed is based on a 3D optical propagation of radiation by a Monte Carlo approach. Once the optical energy is obtained, a complex photochemical model is employed. This model takes into account the electronic transitions between molecular levels and particles concentrations. As the process of generation of photosensitizer is not homogeneous, the photosensitizer distribution is also taken into account. The optical power of the source, the exposition time and the optochemical characteristics of the tissue can be varied. This implies that these parameters could be adjusted to the particular pathology we are dealing with, so the unsuccessful cases could be better treated.

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

2010-02-01

72

Optical coherence tomography guided retreatment of photodynamic therapy  

Microsoft Academic Search

Aim: To evaluate the results of a retreatment modality of photodynamic therapy (PDT) based on optical coherence tomography (OCT) and fluorescein angiography (FA). To quantify the effect of PDT with the help of measurement of the retinal thickness.Methods: Eyes with predominantly classic subfoveal choroidal neovascularisation (CNV) due to age related macular degeneration were included. PDT was performed every three months,

I Krebs; S Binder; U Stolba; K Schmid; C Glittenberg; W Brannath; A Goll

2005-01-01

73

Mitochondria-based photodynamic anti-cancer therapy  

Microsoft Academic Search

As photodynamic therapy (PDT) becomes established as a treatment for cancer, there is increasing interest in identifying critical mechanisms of cell killing and understanding the bases for effective photosensitizers. The existence of multiple cellular targets makes it difficult to distinguish the critical events leading to cell death from PDT. However, with more sensitive techniques to detect photosensitizer localization, the isolation

Janet Morgan; Allan R Oseroff

2001-01-01

74

Multiphoton Biomedical Imaging and Photodynamic Therapy: Agents & Applications  

E-print Network

-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 visible excitation. #12;Two-Photon Imaging can Afford 3D Localization Prepare cell Visualize and irradiate

Van Stryland, Eric

75

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

76

New biotinylated phthalocyanines for the photodynamic therapy of cancer  

NASA Astrophysics Data System (ADS)

Suitable substituted phthalocyanines are promising and widely investigated photosensitizers (PS) for the photodynamic therapy of cancer (PDT). However, selective accumulation of the PSs in tumor tissues, avoiding contamination of healthy tissues, is still an unsolved central problem. We present first results on the synthesis of new biotinylated phthalocyanines as potentially selective photosensitizers when applied in a polyphasic tumor targeting (tumor cell plus first step: biotinylated/monoclonal antibody, second step: streptavidin, and third step: biotinylated PS). The binding and the photodynamic activity of biotinylated PS in this three step model is shown in tumor cell lines.

Hirth, Andreas; Bartik, Bernd; Bogdahn-Rai, Tatjana; Woehrle, Dieter; Kaul, Sepp

1997-12-01

77

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

78

Photodynamic Diagnosis and Therapy in Dermatology  

Microsoft Academic Search

The topical application of ?-aminolevulinic acid (ALA) induces porphyrin formation in the skin, preferentially in tumor tissues. Irradiation of the porphyrin-enriched tumor tissue with Wood’s light leads to emission of a brick-red fluorescence. This principle may be used as a diagnostic procedure which may be termed photodynamic diagnosis (PDD). In ALA-PDD, tumors and precancerous lesions of the skin reveal a

C. Fritsch; K. Lang; W. Neuse; T. Ruzicka; P. Lehmann

1998-01-01

79

Intravesical adjuvant therapy using mitomycin C.  

PubMed

Bladder cancer is mostly superficial at first diagnosis. High incidence of recurrence is the major problem after initial management with transurethral resection (TUR) of bladder tumor. Adjuvant chemotherapy has been advocated to reduce the incidence of recurrence. A study was carried out to observe the efficacy of intravesical adjuvant therapy with single immediate versus delayed multi-dose regimen of Mitomycin C (MMC) in preventing recurrence of superficial bladder cancer. One hundred Patients having intermediate risk superficial bladder cancer were randomized into two equal groups. All patients were followed carefully. Total duration of follow-up was minimum 12 months, maximum 36 months, mean 29 months. No recurrence was seen on 3(rd), 6(th) and 9(th) month of intravesical therapy. As much as 94% and 96% of recurrence free rate was observed in immediate single and delayed multi-dose group respectively on 12(th) month; 86% and 84% on 18(th) month; 74% and 72% on 24(th) month; 70% and 68% on 36(th) month of follow-up cystoscopy respectively. Efficacy of post transurethral resection of bladder tumour (TURBT) MMC single immediate dose was found similar to that of MMC delayed multi-dose regimen in preventing the recurrence of intermediate risk superficial bladder transitional cell carcinoma (TCC) in the study. The difference between the two groups insignificant (p>0.05). PMID:16467761

Islam, M A; Bhuiyan, Z H; Shameem, I A

2006-01-01

80

Vaccines and photodynamic therapies for oral microbial-related diseases.  

PubMed

The mouth is a favorable habitat for a great variety of bacteria. Microbial composition of dental plaque is the usual cause of various oral diseases in humans, including dental caries, periodontal disease and halitosis. In general, oral antibacterial agents such as antibiotics are commonly used to treat oral bacterial infection. Traditional periodontal surgery is painful and time-consuming. In addition, bacterial resistance and toxicity of antibiotics have become a global pandemic and unavoidable. Recently, vaccines for dental caries and periodontal disease have been developed and applied. Moreover, the use of photodynamic therapy has become an alternative to antibiotic drugs. The purpose of this article is to highlight the advantages of vaccine therapy and photodynamic therapy for oral microbial-related diseases compared to treatments with antimicrobial agents and traditional periodontal surgery. PMID:19149517

Liu, Pei-Feng; Zhu, Wen-Hong; Huang, Chun-Ming

2009-01-01

81

Vaccines and Photodynamic Therapies for Oral Microbial-Related Diseases  

PubMed Central

The mouth is a favorable habitat for a great variety of bacteria. Microbial composition of dental plaque is the usual cause of various oral diseases in humans, including dental caries, periodontal disease and halitosis. In general, oral antibacterial agents such as antibiotics are commonly used to treat oral bacterial infection. Traditional periodontal surgery is painful and time-consuming. In addition, bacterial resistance and toxicity of antibiotics have become a global pandemic and unavoidable. Recently, vaccines for dental caries and periodontal disease have been developed and applied. Moreover, the use of photodynamic therapy has become an alternative to antibiotic drugs. The purpose of this article is to highlight the advantages of vaccine therapy and photodynamic therapy for oral microbial-related diseases compared to treatments with antimicrobial agents and traditional periodontal surgery. PMID:19149517

Liu, Pei-Feng; Zhu, Wen-Hong; Huang, Chun-Ming

2009-01-01

82

Photodynamic therapy in treatment of oral lichen planus.  

PubMed

Oral lichen planus (OLP) is a relatively common chronic immunologic mucocutaneous disorder. Although there are many presenting treatments, some of them proved its failure. Recently, the use of photodynamic therapy (PDT) has been expanding due to its numerous advantages, as it is safe, convenient, and non-invasive and has toxic effect towards selective tissues. This article provides comprehensive review on OLP, its etiology, clinical features and recent non-pharmacological treatments. We also describe the topical PDT and its mechanisms. Our purpose was to evaluate the efficacy of PDT in treatment of OLP through collecting the data of the related clinical studies. We searched in PubMed website for the clinical studies that were reported from 2000 to 2014 using specific keywords: "photodynamic therapy" and "treatment of oral lichen planus". Inclusion criteria were English publications only were concerned. In the selected studies of photodynamic treatment, adult patients (more than 20 years) were conducted and the OLP lesions were clinically and histologically confirmed. Exclusion criteria were classical and pharmacological treatments of OLP were excluded and also the using of PDT on skin lesions of lichen planus. We established five clinical studies in this review where all of them reported improvement and effectiveness of PDT in treatment of OLP lesions. The main outcome of comparing the related clinical studies is that the photodynamic is considered as a safe, effective and promising treatment modality for OLP. PMID:25883701

Mostafa, Diana; Tarakji, Bassel

2015-06-01

83

Photodynamic Therapy in Treatment of Oral Lichen Planus  

PubMed Central

Oral lichen planus (OLP) is a relatively common chronic immunologic mucocutaneous disorder. Although there are many presenting treatments, some of them proved its failure. Recently, the use of photodynamic therapy (PDT) has been expanding due to its numerous advantages, as it is safe, convenient, and non-invasive and has toxic effect towards selective tissues. This article provides comprehensive review on OLP, its etiology, clinical features and recent non-pharmacological treatments. We also describe the topical PDT and its mechanisms. Our purpose was to evaluate the efficacy of PDT in treatment of OLP through collecting the data of the related clinical studies. We searched in PubMed website for the clinical studies that were reported from 2000 to 2014 using specific keywords: “photodynamic therapy” and “treatment of oral lichen planus”. Inclusion criteria were English publications only were concerned. In the selected studies of photodynamic treatment, adult patients (more than 20 years) were conducted and the OLP lesions were clinically and histologically confirmed. Exclusion criteria were classical and pharmacological treatments of OLP were excluded and also the using of PDT on skin lesions of lichen planus. We established five clinical studies in this review where all of them reported improvement and effectiveness of PDT in treatment of OLP lesions. The main outcome of comparing the related clinical studies is that the photodynamic is considered as a safe, effective and promising treatment modality for OLP.

Mostafa, Diana; Tarakji, Bassel

2015-01-01

84

Towards image-guided photodynamic therapy of Glioblastoma  

NASA Astrophysics Data System (ADS)

Glioblastoma (GBM) is an aggressive cancer with dismal survival rates and few new treatment options. Fluorescence guided resection of GBM followed by photodynamic therapy (PDT) has shown promise in several chemo- or radiotherapy non-responsive GBM treatments clinically. PDT is an emerging light and photosensitizer (PS) mediated cytotoxic method. However, as with other therapeutic modalities, the outcomes are variable largely due to the nonpersonalization of dose parameters. The variability can be attributed to the differences in heterogeneous photosensitizer accumulation in tumors. Building upon our previous findings on utilizing PS fluorescence for designing tumor-specific PDT dose, we explore the use of photoacoustic imaging, a technique that provides contrast based on the tissue optical absorption properties, to obtain 3D information on the tumoral photosensitizer accumulation. The findings of this study will form the basis for customized photodynamic therapy for glioblastoma and have the potential to serve as a platform for treatment of other cancers.

Mallidi, Srivalleesha; Huang, Huang-Chiao; Liu, Joyce; Mai, Zhiming; Hasan, Tayyaba

2013-03-01

85

Photodynamic therapy for implanted VX2 tumor in rabbit brains  

NASA Astrophysics Data System (ADS)

To evaluate the therapeutic effect and the safety of single photodynamic therapy (PDT) with hematoporphyrin derivative produced in China, 60 New Zealand adult rabbits with VX2 tumor implanted into the brain were divided randomly into non-PDT-group and PDT-group. 36 rabbits of the PDT-group were performed photodynamic therapy. The survival time, neurological deteriorations, intracranial pressure (ICP), histology, pathology, tumor volume and brain water content were measured. Other 12 rabbits were received hematoporphyrin derivative and light irradiation of the normal brain. The ICP, histology, pathology, and brain water content were measured. The result indicated that Simple PDT may elongate the average survival time of the rabbits with VX2 tumors significantly; kill tumor cells; cause transient brain edema and increase ICP, but it is safe to be used in treating brain tumor.

Li, Fei; Feng, Hua; Lin, Jiangkai; Zhu, Gang; Chen, Zhi; Li, Cong-yan

2005-07-01

86

Development of Low-Cost Photodynamic Therapy Device  

Microsoft Academic Search

Photodiagnosis and photodynamic therapy of non-melanoma skin cancers using delta-aminolevulinic acid\\/protoporphyrin IX (5-ALA\\/PpIX) give a combined application with broadest dissemination in the current clinical practice. The problems with using of lasers as light sources are the expenses associated with the operation of these types of installations. This is why we test the capability of cheaper sources - light-emitting diodes at

N. Momchilov; I. Bliznakova; E. Borisova; P. Troyanova

2007-01-01

87

A look at clinical applications and developments of photodynamic therapy  

Microsoft Academic Search

The battle against cancer is so important that all possible weapons must be considered. Photodynamic therapy (PDT) is a therapeutic\\u000a approach which has proved its capacity to give many excellent results, but it is having some difficulty in being imposed.\\u000a The simplicity of the mechanism of action of this technique has been compromised by the multidisciplinary approach required\\u000a for its

Arménio Serra; Marta Pineiro; Nelson Pereira; António Rocha Gonsalves; Mafalda Laranjo; Margarida Abrantes; Filomena Botelho

2008-01-01

88

Sealed hollow waveguide for catheter-based pulsed photodynamic therapy  

NASA Astrophysics Data System (ADS)

Sealed hollow waveguides have been used to transmit nanosecond red light pulses for photodynamic therapy. With a 1-mm inner diameter, 1-m long, COP (cyclic olefin polymer)-coated silver hollow waveguide, available transmitted pulse energy exceeded 15 mJ, the corresponding peak power and intensity at the output window being 3 MW and 380 MW/cm2 respectively. Because the diameter of the window was as small as 1.5 mm, the waveguide can be introduced to catheters.

Sato, Shunichi; Kawauchi, Satoko; Shi, Yi-Wei; Matsuura, Yuji; Miyagi, Mitsunobu

2004-06-01

89

Photodynamic therapy decreases cancer colonic cell adhesiveness and metastatic potential  

Microsoft Academic Search

Plasma membrane damage induced in various cell targets by hematoporphyrin (HPD) photodynamic therapy (PDT) could modify cancer\\u000a cell adhesiveness, an important parameter in cancer metastasis. We investigated the effect of HPD or HPD incubation followed\\u000a by argon laser light on the adhesiveness of progressive (PROb) or regressive (REGb) cancer cells of the same colonic origin\\u000a but with a different in

V. Vonarx; M.-T. Foultier; L. Xavier de Brito; L. Anasagasti; L. Morlet; T. Patrice

1995-01-01

90

On the combination of photodynamic therapy with ionizing radiation  

Microsoft Academic Search

Ehrlich ascites carcinoma growth and cell damage have been examined after photodynamic therapy (PDT), radiotherapy (RT) and combined treatment. Haematoporphyrin dimethyl ether (HPde) is used as a photosensitizer for PDT and tested as a radiosensitizer for RT. For PDT a non-coherent light source (370

Zivile Luksiene; Audrone Kalvelyte; Rosanna Supino

1999-01-01

91

Polymeric micelles to deliver photosensitizers for photodynamic therapy  

Microsoft Academic Search

Polymeric micelles are emerging as attractive drug delivery systems. Hydrophobic drugs including photosensitizers for photodynamic therapy can be covalently bound or physically entrapped in the core of the micelles and thus be systemically delivered to, for example, tumors using passive or active targeting strategies. Polymers used for photosensitizer encapsulation include pluronics, poly(ethylene glycol) (PEG)–lipid conjugates, and pH-sensitive poly(N-isopropylacrylamide) based micelles

Cornelus F van Nostrum

2004-01-01

92

Ocular Photodynamic Therapy – Standard Applications and New Indications (Part 2)  

Microsoft Academic Search

Photodynamic therapy (PDT) has become a well-established treatment for vascular forms of age-related macular degeneration (AMD). The implementation of evidence-based medicine principles into the treatment regimen of AMD seems to be immensly important, since AMD continues to be the most frequent cause of blindness among patients older than 65 years in industrialized countries. Numerous randomized prospective studies demonstrated high levels

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

2007-01-01

93

Photodynamic therapy of choroidal hemangioma: two case reports  

Microsoft Academic Search

Background: Photocoagulation, cryotherapy and radiotherapy have been used to treat angiomatous lesions. Depending on the location of\\u000a the angioma, these treatments can cause additional, significant functional damage. Photodynamic therapy (PDT) however, allows\\u000a a selective occlusion of vascular lesions without damaging adjacent retinal structures.?\\u000a Methods: Two patients with isolated choroidal hemangiomas involving the posterior pole were treated with PDT. Treatments were

Irene Barbazetto; Ursula Schmidt-Erfurth

2000-01-01

94

Photodynamic therapy in the treatment of basal cell carcinoma  

PubMed Central

Photodynamic therapy (PDT) is a medical procedure based on the activation of the molecules of various exogenous or endogenous chemical substances called photosensitizers by a light source emitting radiation of an adequate wavelength, usually situated in the visible spectrum; photosensitizers are chemical compounds bearing the capacity to selectively concentrate in the neoplastic cells. The energy captured by the molecules of these substances pervaded in the tumor cells is subsequently discharged in the surrounding tissue, triggering certain photodynamic reactions that result in the destruction of the tumor. The procedure is applicable in numerous medical fields. Skin basal cell carcinoma (BCC), the most frequent type of cancer of the human species, is a cutaneous tumor that responds very well to this innovative treatment method. By reviewing numerous recent studies in the field, this article aims to present the role and the indications of photodynamic therapy in the management of basal cell carcinoma, as well as the most important results achieved so far by this therapy in the field of dermato-oncology. PMID:23599819

Matei, C; Tampa, M; Poteca, T; Panea-Paunica, G; Georgescu, SR; Ion, RM; Popescu, SM; Giurcaneanu, C

2013-01-01

95

Fluorescence-guided resections and photodynamic therapy for malignant gliomas using 5-aminolevulinic acid  

NASA Astrophysics Data System (ADS)

Oral application of 20 mg/kg bw of 5-aminolevulinic acid results in a highly specific accumulation of fluorescent and phototoxic Protoporphyrin IX in malignant glioma tissue. Surgical removal with fluorescence guidance is studied in a phase III clinical trial, adjuvant Photodynamic Therapy (PDT) to the surgical cavity is in phase II and for interstitial PDT of recurrent gliomas, a phase I/II study has started. Fluorescence guided resections have been shown to be safe and effective in augmenting neurosurgical removal of malignant gliomas in 52 consecutive patients. Intra-operative fluorescence spectroscopy showed statistically significant higher sensitizer accumulation in vital brain tumor versus the infiltration zone and in the infiltration zone versus adjacent normal brain, which contained very little PPIX. This is promisingly exploited for PDT - both to the surgical cavity by surface irradiation and for stereotactically guided interstitial irradiation.

Stepp, Herbert G.; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Baumgartner, Reinhold; Stummer, Walter; Olzowy, Bernhard; Mehrkens, Jan H.; Tonn, Joerg C.; Reulen, Hans J.

2005-04-01

96

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

97

Adjuvant postoperative radiation therapy for colonic carcinoma.  

PubMed Central

One hundred thirty-three patients with Stage B2, B3, and C colonic carcinoma had resection for curative intent followed by adjuvant postoperative radiotherapy to the tumor bed. The 5-year actuarial local control and disease-free survival rates for these 133 patients were 82% and 61%, respectively. Stage for stage, the development of local regional failure was reduced for patients receiving postoperative radiotherapy compared with a historic control series. Local recurrence occurred in 8%, 21%, and 31% of patients with Stage B3, C2, and C3 tumors who had radiation therapy, respectively, whereas the local failure rates were 31%, 36%, and 53% in patients treated with surgery alone. There was a 13% and 12% improvement in the 5-year disease-free survival rate in the patients with Stage B3 and C3 lesions who had radiotherapy compared with the historic controls. For patients with Stage C disease, local control and disease-free survival rates decreased progressively with increasing nodal involvement; however, local control and disease-free survival rates were higher in the patients who had radiotherapy than in those who had surgery alone. Failure patterns in the patients who had radiotherapy did not show any notable changes compared with those for patients who had surgery alone. Postoperative radiation therapy for Stage B3, C2, and C3 colonic carcinoma is a promising treatment approach that deserves further investigation. PMID:3689006

Willett, C G; Tepper, J E; Skates, S J; Wood, W C; Orlow, E C; Duttenhaver, J R

1987-01-01

98

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

E-print Network

therapeutic factors: the phenotype of the cancer cell line, the food type, the nature of photosensitizerContributions 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

Boyer, Edmond

99

A Comprehensive Tutorial on In Vitro Characterization of New Photosensitizers for Photodynamic Antitumor Therapy and Photodynamic Inactivation of Microorganisms  

PubMed Central

In vitro research performed on eukaryotic or prokaryotic cell cultures usually represents the initial step for characterization of a novel photosensitizer (PS) intended for application in photodynamic therapy (PDT) of cancer or photodynamic inactivation (PDI) of microorganisms. Although many experimental steps of PS testing make use of the wide spectrum of methods readily employed in cell biology, special aspects of working with photoactive substances, such as the autofluorescence of the PS molecule or the requirement of light protection, need to be considered when performing in vitro experiments in PDT/PDI. This tutorial represents a comprehensive collection of operative instructions, by which, based on photochemical and photophysical properties of a PS, its uptake into cells, the intracellular localization and photodynamic action in both tumor cells and microorganisms novel photoactive molecules may be characterized for their suitability for PDT/PDI. Furthermore, it shall stimulate the efforts to expand the convincing benefits of photodynamic therapy and photodynamic inactivation within both established and new fields of applications and motivate scientists of all disciplines to get involved in photodynamic research. PMID:23762860

Maisch, Tim; Berneburg, Mark; Plaetzer, Kristjan

2013-01-01

100

Polyacrylamide nanoparticles as a delivery system in photodynamic therapy.  

PubMed

Nanoparticles can be targeted towards, and accumulate in, tumor tissue by the enhanced permeability and retention effect, if sequestration by the reticuloendothelial system (RES) is avoided. The application of nanoparticles in the field of drug delivery is thus an area of great interest, due to their potential for delivering high payloads of drugs site selectively. One area which may prove to be particularly attractive is photodynamic therapy, as the reactive oxygen species (ROS) which cause damage to the tumor tissue are not generated until the drug is activated with light, minimizing generalized toxicity and giving a high degree of spatial control over the clinical effect. In the present study, we have synthesized two types of nanoparticles loaded with photodynamic sensitizers: polylysine bound tetrasulfonato-aluminum phthalocyanine entrapped nanoparticles (PCNP) and polylysine bound tetrasulfonato-aluminum phthalocyanine entrapped nanoparticles coated with a second, porphyrin based, photosensitizer (PCNP-P) to enhance the capacity for ROS generation, and hence therapeutic potential. The mean sizes of these particles were 45 ± 10 nm and 95 ± 10 nm respectively. Uptake of the nanoparticles by human Caucasian colon adenocarcinoma cells (HT29) was determined by flow cytometry and confocal microscopy. Cell viability assays using PCNP-P and PCNP corresponding to the minimum uptake time (<5 min) and maximum uptake time (25 h) demonstrated that these cancer cells can be damaged by light activation of these photodynamic nanoparticles both in the external media and after internalization. The results suggest that, in order to induce photodynamic damage, the nanoparticles need only to be associated with the tumor cell closely enough to deliver singlet oxygen: their internalization within target cells may not be necessary. Clinically, this could be of great importance as it may help to combat the known ability of many cancer cells to actively expel conventional anticancer drugs. PMID:21410233

Kuruppuarachchi, Maheshika; Savoie, Huguette; Lowry, Ann; Alonso, Cristina; Boyle, Ross W

2011-06-01

101

Biomodulatory Approaches to Photodynamic Therapy for Solid Tumors  

PubMed Central

Photodynamic Therapy (PDT) uses a photosensitizing drug in combination with visible light to kill cancer cells. PDT has an advantage over surgery or ionizing radiation because PDT can eliminate tumors without causing fibrosis or scarring. Disadvantages include the dual need for drug and light, and a generally lower efficacy for PDT versus surgery. This minireview describes basic principles of PDT, photosensitizers available, and aspects of tumor biology that may provide further opportunities for treatment optimization. An emerging biomodulatory approach, using methotrexate or Vitamin D in combination with aminolevulinate-based PDT, is described. Finally, current clinical uses of PDT for solid malignancies are reviewed. PMID:22842096

Anand, Sanjay; Ortel, Bernhard J.; Pereira, Stephen P.; Hasan, Tayyaba; Maytin, Edward V.

2012-01-01

102

Characterizing low fluence thresholds for in vitro photodynamic therapy  

PubMed Central

The translation of photodynamic therapy (PDT) to the clinic has mostly been limited to superficial diseases where traditional light delivery is noninvasive. To overcome this limitation, a variety of mechanisms have been suggested to noninvasively deliver light to deep tissues. This work explores the minimum amount of light required by these methods to produce a meaningful PDT effect in the in vitro setting under representative low fluence and wavelength conditions. This threshold was found to be around 192 mJ/cm2 using the clinically approved photosensitizer aminolevulinic acid and 12 mJ/cm2 for the more efficient, second generation photosensitizer TPPS2a. PMID:25798302

Hartl, Brad A.; Hirschberg, Henry; Marcu, Laura; Cherry, Simon R.

2015-01-01

103

Photodynamic therapy of tumor-associated pathology of uterine cervix  

NASA Astrophysics Data System (ADS)

We have analyzed the results of photodynamic therapy using light-sensitizing agent "Photoheme" in 56 patients - 44 women with pre-cancerous lesions of cervix (group 1) and 12 women with early cervical cancer (group 2). The results were as follows: group 1 - c omplete regression - 3 7 ( 84%), p artial regression - 4 ( 9,%), s tabilization - 2 (4,6%), progression -1 (2,3%); group 2 - complete regression - 8 (66,7%), partial regression - 1 (8,3%), stabilization - 3 (25%). Anti-viral effect was registered in 38 (90,4%) cases after first procedure, in 4 cases - after second procedure.

Novikova, E. G.; Trushina, O. I.; Sokolov, V. V.; Filonenko, E. V.

2005-08-01

104

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

105

Optical dosimetry in photodynamic therapy of human uterus and brain  

NASA Astrophysics Data System (ADS)

Optical 'dose' is one of the fundamental parameters required in the design of an efficacious regimen of photodynamic therapy (PDT). The issues involved in delivering a sufficient optical dose to the human uterus and brain during PDT will be discussed. Specifically, measurements of optical properties and fluence rates in excised human uteri are presented. Measured fluence rates are compared to the predictions of a simple diffusion model and the clinical utility of the treatment is discussed. The delivery of light to brain tissue via a surgically implanted balloon applicator will also be considered. The time required to deliver and adequate dose is calculated based on known optical properties and diffusion theory.

Madsen, Steen J.; Svaasand, Lars O.; Hirschberg, Henry; Tadir, Yona; Tromberg, Bruce J.

1999-06-01

106

Prognostic factors related to photodynamic therapy for central serous chorioretinopathy  

Microsoft Academic Search

Background  To investigate the effects and prognostic factors related to photodynamic therapy (PDT) for central serous chorioretinopathy\\u000a (CSC).\\u000a \\u000a \\u000a \\u000a Methods  Retrospective medical record reviewing of consecutive CSC patients (chronic or persistent typical CSC) treated with conventional\\u000a PDT (full-dose verteporfin, laser (689 nm) delivery for 83 s, total light energy of 50 J\\/cm2) was performed. Besides overall anatomic and functional outcomes, the prognostic influences of various

Jun Woong Moon; Hyeong Gon Yu; Tae Wan Kim; Hyung Chan Kim; Hum Chung

2009-01-01

107

Photodynamic Therapy Using Endogenous Photosensitization for Gastrointestinal Tumors  

PubMed Central

Photodynamic therapy (PDT) is a novel approach in the treatment of carcinomas of the gastrointestinal tract. This review defines PDT, discusses means of photosensitization and considers the mechanisms by which PDT causes cell death of the target tissue while at the same time avoid damage to normal tissues. Additional considerations include the time of PDT application, activation of the photosensitizer, effectiveness and toxicity of PDT, potential need for additional modalities of treatment and concludes with application of PDT principals to the early detection of malignancy. Data regarding the long term effectiveness of PDT for digestive tract adenocarcinomas are lacking because this field is still in its infancy.

Webber, John; Kessel, David; Fromm, David

1997-01-01

108

Rose bengal acetate photodynamic therapy-induced autophagy.  

PubMed

Photodynamic therapy (PDT), an anticancer therapy requiring the exposure of cells or tissue to a photosensitizing drug followed by irradiation with visible light of the appropriate wavelength, induces cell death by the efficient induction of apoptotic as well as non-apoptotic mechanisms, such as necrosis and autophagy, or a combination of all three mechanisms. However, the exact role of autophagy in photodynamic therapy is still a matter of debate. To understand the role of autophagy in PDT, we investigated the induction of autophagy in HeLa cells photosensitized with Rose Bengal Acetate (RBAc). After incubation with Rose Bengal Acetate (10-5 M), HeLa cells were irradiated for 90 seconds (green LED DPL 305, emitting at 530 +15 nm to obtain 1.6 J/cm2 as the total light dose) and allowed to recover for 72 h. Induction of autophagy and apoptosis were observed with peaks at 8 h and 12 h after irradiation, respectively. Autophagy was detected by biochemical (Western Blotting for the LC3B protein) and morphological criteria (TEM, cytochemistry). In addition, the pan-caspase inhibitor, z-VAD, was unable to completely prevent cell death. The simultaneous onset of apoptosis and autophagy following Rose Bengal Acetate PDT is of remarkable interest in light of the findings that autophagy can result in the class II presentation of antigens and thus, explain why low dose PDT can yield anti-tumor immune responses. PMID:20935508

Dini, Luciana; Inguscio, Valentina; Tenuzzo, Bernardetta; Panzarini, Elisa

2010-11-15

109

Photodynamic therapy: Palliation and endoscopic technique in cholangiocarcinoma  

PubMed Central

Cholangiocarcinoma is the primary malignancy arising from the biliary epithelium. The disease is marked by jaundice, cholestasis, and cholangitis. Over 50 percent of patients present with advanced stage disease, precluding curative surgical resection as an option of treatment. Prognosis is poor, and survival has been limited even after biliary decompression. Palliative management has become the standard of care for unresectable disease and has evolved to include an endoscopic approach. Photodynamic therapy (PDT) consists of administration of a photosensitizer followed by local irradiation with laser therapy. Several studies conducted in Europe and the United States have shown a marked improvement in the symptoms of cholestasis, survival, and quality of life. This article summarizes the published experience regarding PDT for cholangiocarcinoma and the steps required to administer this therapy safely. PMID:21173912

Richter, James A; Kahaleh, Michel

2010-01-01

110

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. PMID:25317253

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

2014-01-01

111

Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer.  

PubMed Central

The prognosis for patients with the high-grade cerebral glioma glioblastoma multiforme is poor. The median survival for primary tumors is < 12 months, with most recurring at the site of the original tumor, indicating that a more aggressive local therapy is required to eradicate the unresectable "nests" of tumor cells invading into adjacent brain. Two adjuvant therapies with the potential to destroy these cells are porphyrin-sensitized photodynamic therapy (PDT) and boron-sensitized boron neutron capture therapy (BNCT). The ability of a boronated porphyrin, 2,4-(alpha, beta-dihydroxyethyl) deuteroporphyrin IX tetrakiscarborane carboxylate ester (BOPP), to act as a photosensitizing agent was investigated in vitro with the C6 rat glioma cell line and in vivo with C6 cells grown as an intracerebral tumor after implantation into Wistar rats. These studies determined the doses of BOPP and light required to achieve maximal cell kill in vitro and selective tumor kill in vivo. The data show that BOPP is more dose effective in vivo by a factor of 10 than the current clinically used photosensitizer hematoporphyrin derivative and suggest that BOPP may have potential as a dual PDT/BNCT sensitizer. Images Fig. 3 PMID:8618857

Hill, J S; Kahl, S B; Stylli, S S; Nakamura, Y; Koo, M S; Kaye, A H

1995-01-01

112

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

113

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

114

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

115

Adjuvant endocrine therapies for premenopausal women  

Microsoft Academic Search

Adjuvant endocrine treatment for premenopausal woman remains a controversial area in the therapeutical approach of early stages\\u000a of breast cancer. Metaanalysis show that ovarian ablation and suppression produce, in a global way, significant benefits in\\u000a terms of reduction of the risk of recurrence and death. Nevertheless, in the presence of adjuvant chemotherapy, the benefits\\u000a of ovarian suppression or ablation are

C. A. Rodríguez Sánchez

2007-01-01

116

Hilar Cholangiocarcinoma: Photodynamic Therapy and Stenting  

Microsoft Academic Search

Carcinomas of the biliary tree are rare tumors of the gastrointestinal tract with rising inci dence during the last years.\\u000a Endoscopic therapy plays a central role in the preopera-tive and palliative treatment of extrahepatic cholangiocarcinoma (CC).\\u000a In obstructive jaundice, biliary drainage may cause only few complications and relieves symptoms reliably. It can prevent\\u000a further complica tions and is indispensable in

Marcus Wiedmann; Joachim Mössner; Helmut Witzigmann

117

The use of photodynamic therapy to treat hidradenitis suppurativa a review and critical analysis.  

PubMed

Hidradenitis Suppurativa (HS) is an inflammatory disease that results in abscesses, keloids, and fistulas. Acne inversa is likely to result from aberrant cellular immunity and dysfunction of the hair follicle in which coagulase negative staphylococcus (CONS) and perhaps other bacteria appear e.g Corynebacterium sp.to play a role by creating biofilms and stimulating the immune system. One treatment that has been proposed for HS is photodynamic therapy. The cases series reported are small and not double blinded. As of October of 2104, 8 articles with 64 patients report success with photodynamic therapy using 5-aminolevulinic acid (PDT-ALA) or its methyl ester (PDT-MAL). One of these 8 reports noted superiority of the free methylene blue gel over niosomal methylene blue gel. Another report described success in a 27-patient trial using intralesional 5-aminolevulinic acid (ALA) in saline at a concentration of 1%. This was administered at a dose of 0.2 ml per cm3 and an HS fistula was irradiated by a continuous 630-nm laser diode through a 1-mm thick optical fiber to 1 Watt per cm3 for 3 minutes (180 Joules). However, 3 articles reported failure with PDT-ALA or pulse dye laser-mediated photodynamic therapy (PDL-PDT) and one article note 1 failure and 1 success. We suggest that it is the ability of PDT-ALA or PDT-MAL to break up the bio-film produced by CONS and other antibacterial effects that account for its success in treating HS in patients in whom bio-film plays a pivotal part of their pathogenesis. Other effects are also possible as well. Other mechanisms by which PDT may improve HS include cytotoxic effects, which cause selective cell necrosis, and immunomodulatory effects. The data suggests that if PDT is to be used, it should be with MAL or intralesional ALA. Note that there are a variety of causes of HS. These include hyperkeratosis of in the follicular infundibulum, aberrant cellular immunity, down regulations of defensins in stage III HS, and the infiltration of neutrophils, mast cells, plasma cells, and lymphocytes into the affected follicle, among others. However, it is likely that in individual cases one cause is primary and others secondary. In conclusion, PDT is not a first line treatment for HS but in some cases could be added as an adjuvant to therapies such as clindamycin and rifampin. PMID:25612117

Scheinfeld, Noah

2015-01-01

118

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

119

Measurement of intracellular oxygen concentration during photodynamic therapy in vitro.  

PubMed

A technique is introduced that monitors the depletion of intracellular ground state oxygen concentration ([(3)O(2)]) during photodynamic therapy of Mat-LyLu cell monolayers and cell suspensions. The photosensitizer Pd(II) meso-tetra(4-carboxyphenyl)porphine (PdT790) is used to manipulate and indicate intracellular [(3)O(2)] in both of the in vitro models. The Stern-Volmer relationship for PdT790 phosphorescence was characterized in suspensions by flowing nitrogen over the suspension while short pulses of 405 nm light were used to excite the sensitizer. The bleaching of sensitizer and the oxygen consumption rate were also measured during continuous exposure of the cell suspension to the 405 nm laser. Photodynamic therapy (PDT) was conducted in both cell suspensions and in cell monolayers under different treatment conditions while the phosphorescence signal was acquired. The intracellular [(3)O(2)] during PDT was calculated by using the measured Stern-Volmer relationship and correcting for sensitizer photobleaching. In addition, the amount of oxygen that was consumed during the treatments was calculated. It was found that even at large oxygen consumption rates, cells remain well oxygenated during PDT of cell suspensions. For monolayer treatments, it was found that intracellular [(3)O(2)] is rapidly depleted over the course of PDT. PMID:24521344

Weston, Mark A; Patterson, Michael S

2014-01-01

120

Upconversion Nanoparticles for Photodynamic Therapy and Other Cancer Therapeutics  

PubMed Central

Photodynamic therapy (PDT) is a non-invasive treatment modality for a variety of diseases including cancer. PDT based on upconversion nanoparticles (UCNPs) has received much attention in recent years. Under near-infrared (NIR) light excitation, UCNPs are able to emit high-energy visible light, which can activate surrounding photosensitizer (PS) molecules to produce singlet oxygen and kill cancer cells. Owing to the high tissue penetration ability of NIR light, NIR-excited UCNPs can be used to activate PS molecules in much deeper tissues compared to traditional PDT induced by visible or ultraviolet (UV) light. In addition to the application of UCNPs as an energy donor in PDT, via similar mechanisms, they could also be used for the NIR light-triggered drug release or activation of 'caged' imaging or therapeutic molecules. In this review, we will summarize the latest progresses regarding the applications of UCNPs for photodynamic therapy, NIR triggered drug and gene delivery, as well as several other UCNP-based cancer therapeutic approaches. The future prospects and challenges in this emerging field will be also discussed. PMID:23650479

Wang, Chao; Cheng, Liang; Liu, Zhuang

2013-01-01

121

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

122

Autologous bone marrow transplantation by photodynamic therapy  

NASA Astrophysics Data System (ADS)

Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.

Gulliya, Kirpal S.

1992-06-01

123

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

124

Photodynamic therapy in the treatment and diagnosis of cancers: a sixty-case report  

NASA Astrophysics Data System (ADS)

This 60-case report deals with the application of photodynamic therapy in the treatment and diagnosis of cancer. The application of photodynamic therapy in the treatment and diagnosis of cancer is a development from the late seventies. Since March 1989, we have diagnosed and treated 60 cancer patients with this therapy. Our results show that the positive rate in diagnosis is 100 percent, the effective rate in treatment is 75 percent.

Wang, Kang-jun; Shi, Weng-jun; Gong, Huai-nang; Zhan, Xi-de; Li, Zhi-jian

1993-03-01

125

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

126

Percutaneous transluminal photodynamic therapy of atheroma using mono-L-aspartyl chlorin e6  

NASA Astrophysics Data System (ADS)

Structural changes after photodynamic therapy of atherosclerotic lesions of the thoracic aorta were analyzed by scanning electron microscopy. Cholesterol fed atherosclerotic rabbits were injected intravenously with 5 mg/kg of NPe6. At 6 hours after NPe6 loading, a diode laser irradiated angioscopically on the surface of atheroma with the total energy of 200 mJ/cm2. Scanning electron microscopy showed degeneration of atherosclerotic plaques of the thoracic aorta examined at one week after photodynamic therapy. NPe6 could be a potent photosensitizer for photodynamic therapy of atheroma.

Hayashi, Junichi; Sato, Hideaki; Saito, Takashi; Kuroiwa, Yukari; Aizawa, Katsuo; Fujiwara, Tatsushi; Hosoda, Yasuhiro

1995-03-01

127

Adjuvant and Neoadjuvant Therapy for Breast Cancer  

MedlinePLUS

... can include chemotherapy, hormonal therapy, the targeted drug trastuzumab (Herceptin®), radiation therapy, or a combination of treatments. ... can include chemotherapy, hormonal therapy , the targeted drug trastuzumab (Herceptin®), radiation therapy , or a combination of treatments. ...

128

Photodynamic hyperthermal chemotherapy with indocyanine green: a novel cancer therapy for 16 cases of malignant soft tissue sarcoma  

PubMed Central

Sixteen cases of malignant soft tissue sarcoma (STS; 10 canines and six felines) were treated with a novel triple therapy that combined photodynamic therapy, hyperthermia using indocyanine green with a broadband light source, and local chemotherapy after surgical tumor resection. This triple therapy was called photodynamic hyperthermal chemotherapy (PHCT). In all cases, the surgical margin was insufficient. In one feline case, PHCT was performed without surgical resection. PHCT was performed over an interval of 1 to 2 weeks and was repeated three to 21 times. No severe side effects, including severe skin burns, necrosis, or skin suture rupture, were observed in any of the animals. No disease recurrence was observed in seven out of 10 (70.0%) dogs and three out of six (50.0%) cats over the follow-up periods ranging from 238 to 1901 days. These results suggest that PHCT decreases the risk of STS recurrence. PHCT should therefore be considered an adjuvant therapy for treating companion animals with STS in veterinary medicine. PMID:24136207

Onoyama, Masaki; Tsuka, Takeshi; Imagawa, Tomohiro; Osaki, Tomohiro; Minami, Saburo; Azuma, Kazuo; Kawashima, Kazuhiko; Ishi, Hiroshi; Takayama, Takahiro; Ogawa, Nobuhiko

2014-01-01

129

Photosensitizer nanocarriers modeling for photodynamic therapy applied to dermatological diseases  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy involves the therapeutic use of photosensitizers in combination with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell death. This technique has become widely used in medicine to treat tumors and other nonmalignant diseases. However, there are several factors related to illumination or the photosensitizer that limit an optimal treatment outcome. The use of nanoparticles (NP) for PDT has been proposed as a solution to current shortcomings. In this way, there are NPs that act as carriers for photosensitizers, NPs that absorb the light and transfer the energy to the photosensitizer and NPs that are themselves photodynamically active. In dermatology, the use of topical photosensitizers produces a time dependent inhomogeneous distribution within the tumor, where the stratum corneum is the main barrier to the diffusion of the photosensitizer to the deeper layers of skin. This produces an insufficient photosensitizer accumulation in tumor tissues and therefore, a low therapeutic efficiency in the case of deep lesions. This work focuses in the use of NPs as photosensitizer carriers to improve the actual topical drug distribution in malignant skin tissues. We present a mathematical model of PS distribution in tumor tissue using NPs that takes into account parameters related to nanoparticles binding. Once the concentration profile of NPs into tissue is obtained, we use a photochemical model which allows us to calculate the temporal evolution of reactive oxygen species according to PS distribution calculated previously from NPs profile.

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

2011-02-01

130

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

131

Immunomodulators as adjuvants for vaccines and antimicrobial therapy.  

PubMed

A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly. PMID:20946578

Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

2010-12-01

132

Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome  

Microsoft Academic Search

ObjectiveTo evaluate the safety and effect on visual acuity of photodynamic therapy with verteporfin (Visudyne, Novartis AG) in patients with subfoveal choroidal neovascularization (CNV) secondary to the ocular histoplasmosis syndrome (OHS).

David A Saperstein; Philip J Rosenfeld; Neil M Bressler; Robert H Rosa; Michel Sickenberg; Paul Sternberg; Thomas M Aaberg; Troy A Reaves

2002-01-01

133

Photodynamic therapy with verteporfin in ocular histoplasmosis: Uncontrolled, open-label 2-year study  

Microsoft Academic Search

ObjectiveTo evaluate the safety, effect on visual function, and fluorescein angiographic appearance of subfoveal choroidal neovascularization (CNV) through 2 years after photodynamic therapy with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) in patients with ocular histoplasmosis syndrome (OHS).

Philip J. Rosenfeld; David A. Saperstein; Neil M. Bressler; Troy A. Reaves; Michel Sickenberg; Robert H. Rosa; Paul Sternberg; Thomas M. Aaberg

2004-01-01

134

Anti-CTLA-4 antibody adjuvant therapy in melanoma.  

PubMed

Thus far the development of adjuvant therapies in melanoma has suffered greatly from the lack of effective drugs in stage IV melanoma. Chemotherapy, cytokines, vaccines, and combinations of drugs have been used with minimal success. This has led to adjuvant therapies that are not used uniformly or widely because of the rather marginal benefits, as no consistent and clinically significant impact on survival has been demonstrated. A new development for interferon-based adjuvant therapy seems to be the observation that better effects are observed in patients with lower tumor load and in patients with an ulcerated primary melanoma. A benefit for patients with more advanced lymphnodal involvement is quite unsure, clearly requiring new drugs to be explored. A new era in the treatment of melanoma treatment has arrived with the anti-cytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibodies. The randomized trial in advanced metastatic melanoma demonstrated a clear benefit with prolongation of survival. The anti-CTLA-4 monoclonal antibody ipilimumab has finally changed the landscape. It is therefore only logical that a worldwide adjuvant trial with ipilimumab versus placebo, the European Organization for Research and Treatment of Cancer (EORTC) 18071, is ongoing in patients with lymph node metastases, and that another adjuvant trial with ipilimumab compared to high-dose interferon (HDI) is planned in the United States. The EORTC 18071 trial will reach full accrual in 2011 and thus results are expected in 2013 or 2014. PMID:21074060

Eggermont, Alexander M M; Testori, Alessandro; Maio, Michele; Robert, Caroline

2010-10-01

135

Nanoparticles: their potential use in antibacterial photodynamic therapy.  

PubMed

Photodynamic therapy (PDT) has been proposed as a new technique to inactivate microorganisms as it does not lead to the selection of mutant resistant strains; a clear benefit compared to antibiotic treatment. PDT has also attracted the interest of nanotechnology as the effectiveness of the treatment can be greatly enhanced by the use of nanoparticles. In the last decade, different approaches to the combination of nanoparticles and PDT have been investigated in relation to the antimicrobial applications of the technique. One use of the nanoparticles is to improve the delivery of photosensitiser to the bacteria; others use the nanoparticles to improve the inactivation kinetics. A different approach utilises nanoparticles as a photosensitiser. In this review these diverse types of interactions will be described. PMID:21380441

Perni, Stefano; Prokopovich, P; Pratten, Jonathan; Parkin, Ivan P; Wilson, Michael

2011-05-01

136

Enhancing antibiofilm efficacy in antimicrobial photodynamic therapy: effect of microbubbles  

NASA Astrophysics Data System (ADS)

In this study, we tested the hypothesis that a microbubble containing photosensitizer when activated with light would enable comprehensive disinfection of bacterial biofilms in infected root dentin by antimicrobial photodynamic therapy (APDT). Experiments were conducted in two stages. In the stage-1, microbubble containing photosensitizing formulation was tested for its photochemical properties. In the stage-2, the efficacy of microbubble containing photosensitizing formulation was tested on in vitro infected root canal model, developed with monospecies biofilm models of Enterococcus faecalis on root dentin substrate. The findings from this study showed that the microbubble containing photosensitizing formulation was overall the most effective formulation for photooxidation, generation of singlet oxygen, and in disinfecting the biofilm bacteria in the infected root canal model. This modified photosensitizing formulation will have potential advantages in eliminating bacterial biofilms from infected root dentin.

Kishen, Anil; George, Saji

2013-02-01

137

Cationic porphycenes as potential photosensitizers for antimicrobial photodynamic therapy  

PubMed Central

Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines and phenothiazinium salts, with cationic charges at physiological pH values. However derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse 3rd degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log10 reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J·cm-2 of red light. PMID:20936792

Ragàs, Xavier; Sánchez-García, David; Ruiz-González, Rubén; Dai, Tianhong; Agut, Montserrat; Hamblin, Michael R.; Nonell, Santi

2010-01-01

138

Photodynamic therapy in patients with advanced breast cancer: preliminary results  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) using phtalocyanine Al, has been provided in 5 patients with advanced breast cancer (ABC). In 3 patients with ABC T4NO-2MO have been provided preoperative PDT, in 2 cases with T4N1Mx PDT have been done after previous combined treatment for subcutaneous metastases. Multiple lesions were treated in one patient. As a source of light we have used quantoscope (scanning electron beam semiconductive laser, and solid laser with doubled frequency. Combined surface and interstitial laser irradiation has been provided in cases of preoperative PDT. Preliminary results of our study show the pronounced efficacy of PDT for subcutaneous metastases of breast cancer and possibility of providing preoperative PDT for advanced breast cancer.

Vakoulovskaya, Elena G.; Khailenko, V. V.; Shental, Victor V.; Komov, D. V.; Meerovich, Gennadii A.; Bouidenok, Y. V.

1996-12-01

139

Blue laser system for photo-dynamic therapy  

NASA Astrophysics Data System (ADS)

A blue laser system for eye diseases (age related macular degeneration, sub-retinal neo-vascularisation in myopia and presumed ocular histoplasmosis syndrome - POHS) photo-dynamic therapy, based on riboflavin as photosensitive substance, has been developed. A CW diode laser at 445 nm wavelength was coupled through an opto-mechanical system to the viewing path of a bio-microscope. The laser beam power in the irradiated area is adjustable between 1 mW and 40 mW, in a spot of 3-5 mm diameter. The irradiation time can be programmed in the range of 1-19 minutes. Currently, the laser system is under clinic tests.

Dabu, R.; Carstocea, B.; Blanaru, C.; Pacala, O.; Stratan, A.; Ursu, D.; Stegaru, F.

2007-03-01

140

Photodynamic therapy of head and neck cancer with different sensitizers  

NASA Astrophysics Data System (ADS)

This paper deals with the results of clinical trials for sulfated aluminum phthalocyanine (PHS) (Photosens, Russia; Photogeme (PG) in Russia. The results of photodynamic therapy (PDT) of head and neck tumors (HNT), side effects and ways of their correction and prevention, as well as possibility to work out less toxic regimes of PDT with photosense, choice of laser and type of irradiation are discussed. PDT have been provided in 79 patients with different head and neck tumors. Efficacy of PDT depended on tumor size and its histological type. Undesirable changes in plasma content of antioxidants by means of high pressure liquid chromatography (HLPC) have been found in patients after PHS injection. Influence of short-term and long-term supplementation with beta-carotene and vitamin E on this parameters are discussed.

Vakoulovskaya, Elena G.; Shental, Victor V.; Abdoullin, N. A.; Kuvshinov, Yury P.; Tabolinovskaia, T. D.; Edinak, N. J.; Poddubny, Boris K.; Kondratjeva, T. T.; Meerovich, Gennadii A.; Stratonnikov, Alexander A.; Linkov, Kirill G.; Agafonov, Valery V.

1997-12-01

141

Endoscopic photodynamic therapy of tumors using gold vapor laser  

NASA Astrophysics Data System (ADS)

Compact sealed-off gold vapor laser (GVL) with 2 W average power and 628 nm wavelength was used for endoscopic photodynamic therapy in 20 patients with different tumors in respiratory system and upper gastrointestinal tract. Russian-made hematoporphyrin derivative (Hpd) `Photohem' was used as a photosensitizer. It was given intravenously at a dose of 2 - 2.5 mg/kg body weight 48 hours prior to tumor illumination with 628 nm light from GVL. Intermittent irradiation with GVL was done through flexible endoscope always under local anaesthesia at a power of 200 - 400 mW/sm2 and a dose of 150 - 400 J/sm2. 80% patients showed complete or partial response depending on stage of tumor. In cases of early gastric cancer all patients had complete remission with repeated negative biopsies. No major complication occurred.

Kuvshinov, Yury P.; Poddubny, Boris K.; Mironov, Andrei F.; Ponomarev, Igor V.; Shental, V. V.; Vaganov, Yu. E.; Kondratjeva, T. T.; Trofimova, E. V.

1996-01-01

142

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

143

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

144

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

145

Physicochemical properties of potential porphyrin photosensitizers for photodynamic therapy.  

PubMed

This research evaluated the suitability of synthetic photosensitizers for their use as potential photosensitizers in photodynamic therapy using steady state and time-resolved spectroscopic techniques. Four tetraphenylporphyrin derivatives were studied in ethanol and dimethyl sulfoxide. The spectroscopic properties namely electronic absorption and emission spectra, ability to generate singlet oxygen, lifetimes of the triplet state, as well as their fluorescence quantum yield were determined. Also time-correlated single photon counting method was used to precisely determine fluorescence lifetimes for all four compounds. Tested compounds exhibit high generation of singlet oxygen, low generation of fluorescence and they are chemical stable during irradiation. The studies show that the tested porphyrins satisfy the conditions of a potential drug in terms of physicochemical properties. PMID:25819312

Kempa, Marta; Kozub, Patrycja; Kimball, Joseph; Rojkiewicz, Marcin; Ku?, Piotr; Gryczy?ski, Zugmunt; Ratuszna, Alicja

2015-07-01

146

TransOral Robotic Photodynamic Therapy for the Oropharynx  

PubMed Central

Photodynamic therapy (PDT) has been used for head and neck carcinomas with little experience in the oropharynx due to technical challenges in achieving adequate exposure. We present the case of a patient with a second right tonsil carcinoma following previous treatment with transoral robotic surgery (TORS) and postoperative chemoradiation for a left tonsil carcinoma. Repeat TORS for the right tonsil carcinoma reviewed multiple positive surgical margins. The power output from the robotic camera was modified to facilitate safe intraoperative three dimensional visualization of the tumor bed. The robotic arms facilitated clear exposure of the tonsil and tongue base with stable administration of the fluence. Real-time measurements confirmed stable photobleaching with augmentation of the prescribed light fluence secondary to light scatter in the oropharynx. We report a potential new role using TORS for exposure and accurate PDT in the oropharynx. PMID:21333937

Quon, Harry; Finlay, Jarod; Cengel, Keith; Zhu, Timothy; O’Malley, Bert; Weinstein, Gregory

2015-01-01

147

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

148

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

149

Experimental use of photodynamic therapy in high grade gliomas: a review focused on 5-aminolevulinic acid.  

PubMed

Photodynamic therapy (PDT) consists of a laser light exposure of tumor cells photosensitized by general or local administration of a pharmacological agent. Nowadays, PDT is a clinically established modality for treatment of many cancers. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven its rational in fluoro-guided resection of malignant gliomas due to a selective tumor uptake and minimal skin sensitization. Moreover, the relatively specific accumulation of photosensitizing PPIX within the tumor cells has gained interest in the PDT of malignant gliomas. Several experimental and clinical studies have then established ALA-PDT as a valuable adjuvant therapy in the management of malignant gliomas. However, the procedure still requires optimizations in the fields of tissue oxygenation status, photosensitizer concentration or scheme of laser light illumination. In this extensive review, we focused on the methods and results of ALA-PDT for treating malignant gliomas in experimental conditions. The biological mechanisms, the effects on tumor and normal brain tissue, and finally the critical issues to optimize the efficacy of ALA-PDT were discussed. PMID:24905843

Tetard, Marie-Charlotte; Vermandel, Maximilien; Mordon, Serge; Lejeune, Jean-Paul; Reyns, Nicolas

2014-09-01

150

Photodynamic therapy repeated without reinjection of Photofrin (porfimer sodium)  

NASA Astrophysics Data System (ADS)

Background and objective: To compare the effectiveness in decreasing the amount of obstruction caused by endobronchial tumors when they are retreated with photodynamic therapy (PDT) several weeks after injection of PhotofrinR (porfimer sodium). Study design, materials and methods: The percentage of endobronchial obstruction from tumors before PDT and at the end of toilet bronchoscopy of 91 sites with PDT performed within 4 days after injection of porfimer sodium was compared to that obtained when PDT was repeated without re-injection of porfimer sodium in the time frames 2 - 4 weeks after injection to 11 sites and the period 4 - 8 weeks after injection to 17 sites. All patients were injected intravenously with 60 mg of PhotofrinR per square meter of body surface and all treatments were done with a power density of 500 mW/CF and a light dose of 400 J/CF delivered from cylinder diffusing fibers. Results: Paired Student's t tests and Wilcoxon signed ranks tests showed significant decreases in the percentage of endobronchial obstruction regardless of whether the PDT was first performed or repeated. Unpaired Student's t tests and Mann-Whitney U statistical comparisons showed a significant difference between the decrease of obstruction when treatment was performed within the first 4 days after injection (mean 41%) as compared to the repeated group 2 to 4 weeks after injection (mean 16%) and the group treated 4 to 8 weeks after injection (mean 19%). However there was no significant difference in the amount of decrease of obstruction between the 2 - 4 week group and the 4 - 8 week group. Conclusions: Photodynamic therapy to relieve endobronchial obstruction can be repeated without reinjection of PhotofrinR up to 8 weeks after injection with a significant decrease in the amount of obstruction. However, it will only be about 1/3 as effective as the initial treatment performed within the first four days of injection.

McCaughan, James S.

1998-05-01

151

The Disinfecting Efficacy of Root Canals with Laser Photodynamic Therapy  

PubMed Central

Introduction: Infecting microorganisms of the root canals are difficult to eliminate during endodontic treatment. In this study the effect of root canal disinfection with photodynamic therapy (PDT) at different time intervals in comparison to 2.5% sodium hypochlorite (NaOCl) irrigation and passive ultrasonic irrigation (PUI) in extracted teeth colonized with Enterococcus faecalis and Candida albicans was tested to assess which treatment reaches the best disinfection rate. Methods: One hundred and fifty-six extracted single-rooted teeth were collected, sterilized, and incubated with Enterococcus faecalis (ATCC 29212) and Candida albicans (ATCC 60193). The two groups were further divided into 6 groups depending on the treatment mode; HELBO®Endo Blue photosensitizer dye application followed by HELBO laser irradiation, with the output power 100 mW and emission of 660 nm, for a 1, 3 and 5 minutes, irrigation with 2.5% NaOCl, 10 second PUI with 2.5% NaOCl and control group. Flow cytometry and scanning electron microscopic (SEM) analysis were used to determine the effectiveness of the different disinfecting methods. Results: The different disinfecting methods had a significantly different effect on the percent of dead cells (p<0.001). A statistical significance of dead cells between organisms (p<0.001) was observed. Interaction between the disinfecting method and both of organisms had shown the statistical significance (p=0.045). Percent of dead cells in treatment groups were significantly higher compared to control group for both organisms (p<0.001). Conclusions: PUI still remains the most effective method for disinfection of infected root canals in endodontics compared to hand instrumentation for both microorganisms. SEM analysis only confirmed the results. Other results ex vivo suggested that prolonging the time from 1 to 5 minutes of PDT increased the number of killed microorganisms significantly, therefore longer times of photodynamic therapy were recommended. Irrigation with 2.5% NaOCl showed similar results to 5 min irradiation. PMID:25606335

Xhevdet, Aliu; Stubljar, David; Kriznar, Igor; Jukic, Tomislav; Skvarc, Miha; Veranic, Peter

2014-01-01

152

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

153

A meta-analysis of adjuvant therapy after potentially curative treatment for hepatocellular carcinoma  

PubMed Central

BACKGROUND: The high recurrence rate of hepatocellular carcinoma (HCC) after potentially curative treatment determines the long-term prognosis. OBJECTIVE: To evaluate the efficacy and safety of adjuvant therapies in patients with HCC who have undergone hepatic resection, transplantation or locoregional ablation therapy. METHODS: Several databases were searched to identify randomized controlled trials (RCTs) fulfilling the predefined selection criteria. Meta-analyses were performed to estimate the effects of adjuvant therapies of any modality on recurrence-free survival (RFS) and overall survival (OS). RESULTS: Eight adjuvant modalities were identified from 27 eligible RCTs conducted predominantly in Asian populations comparing adjuvant with no adjuvant therapy. Adjuvant chemotherapy, internal radiation and heparanase inhibitor PI-88 therapy failed to improve RFS or OS, while interferon (IFN) therapy yielded significant survival results. The findings of adjuvant vitamin analogue therapy required further examination. Adjuvant adoptive immunotherapy conferred significant benefit for RFS but not for OS. Although cancer vaccine therapy and radioimmunotherapy may improve survival after radical surgery, the results were from single, small-scale trials. Severe side effects were observed in the studies of adjuvant chemotherapy and of IFN therapy. CONCLUSIONS: Adjuvant IFN therapy can improve both RFS and OS; however, the benefits of using this agent should be weighed against its side effects. Combination of systemic and transhepatic arterial chemotherapy is not recommended for HCC after potentially curative treatment. Other adjuvant therapies produce limited success for survival. Additional RCTs with proper design are required to establish the role of adjuvant therapies for HCC. PMID:23781519

Wang, Jun; He, Xiao Dong; Yao, Nan; Liang, Wen Jia; Zhang, You Cheng

2013-01-01

154

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

155

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, we engineered bacteriophage to overexpress proteins and attack gene networks that are not directly bacteriophage en- hances killing by quinolones by several orders of magnitude in vitro and significantly

Collins, James J.

156

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

157

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

158

Anti-VEGF therapy for choroidal neovascularisation previously treated with photodynamic therapy  

Microsoft Academic Search

PurposeThis interventional, non-comparative case series assessed the outcome of intravitreal pan-anti-vascular endothelial growth factor (VEGF) agents in eyes with persistent or reactivated choroidal neovascularisation (CNV) following previous treatment with photodynamic therapy (PDT).MethodsBaseline assessments including best-corrected visual acuity, fluorescein angiography (FFA), and optical coherent tomography (OCT) were performed. Intravitreal ranibizumab and\\/ or bevacizumab were administered on a PRN basis, guided by

S Jyothi; H R Chowdhury; V Chong; S Sivaprasad

2010-01-01

159

Cost Effectiveness of Extended Adjuvant Letrozole in Postmenopausal Women after Adjuvant Tamoxifen Therapy: The UK Perspective  

Microsoft Academic Search

Background: MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg\\/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrolment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting. Methods:

Jonathan Karnon; Thomas Delea; Stephen R. D. Johnston; Robert Smith; Jane Brandman; Jennifer Sung; Paul E. Goss

2006-01-01

160

Adjuvant Therapy for Renal Cell Carcinoma: Past, Present, and Future  

PubMed Central

At the present time, the standard of care for patients who have received nephrectomy for localized renal cell carcinoma (RCC) is radiographic surveillance. With a number of novel targeted agents showing activity in the setting of metastatic RCC, there has been great interest in exploring the potential of the same agents in the adjuvant setting. Herein, we discuss the evolution of adjuvant trials in RCC, spanning from the immunotherapy era to the targeted therapy era. Pitfalls of current studies are addressed to provide a context for interpreting forthcoming results. Finally, we outline avenues to incorporate promising investigational agents, such as PD-1 (programmed death-1) inhibitors and MNNG transforming gene inhibitors, in future adjuvant trials. PMID:24969163

Pal, Sumanta K.

2014-01-01

161

Adjuvant therapy for renal cell carcinoma: past, present, and future.  

PubMed

At the present time, the standard of care for patients who have received nephrectomy for localized renal cell carcinoma (RCC) is radiographic surveillance. With a number of novel targeted agents showing activity in the setting of metastatic RCC, there has been great interest in exploring the potential of the same agents in the adjuvant setting. Herein, we discuss the evolution of adjuvant trials in RCC, spanning from the immunotherapy era to the targeted therapy era. Pitfalls of current studies are addressed to provide a context for interpreting forthcoming results. Finally, we outline avenues to incorporate promising investigational agents, such as PD-1 (programmed death-1) inhibitors and MNNG transforming gene inhibitors, in future adjuvant trials. PMID:24969163

Pal, Sumanta K; Haas, Naomi B

2014-08-01

162

Photodynamic therapy: An adjunct to conventional root canal disinfection strategies.  

PubMed

Although chemical-based root canal disinfectants are important to reduce microbial loads and remove infected smear layer from root dentin, they have only a limited ability to eliminate biofilm bacteria, especially from root complexities. This paper explores the novel photodynamic therapy (PDT) for antimicrobial disinfection of root canals. The combination of an effective photosensitizer, the appropriate wavelength of light and ambient oxygen is the key factor in PDT. PDT uses a specific wavelength of light to activate a non-toxic dye (photosensitizer), leading to the formation of reactive oxygen species. These reactive oxygen molecules can damage bacterial proteins, membrane lipids and nucleic acids, which promote bacterial cell death. In, addition PDT may enhance cross-linking of collagen fibrils in the dentin matrix and thereby improving dentin stability. The concept of PDT is plausible and could foster new therapy concepts for endodontics. The available knowledge should enable and encourage steps forward into more clinical-oriented research and development. This article discusses PDT as related to root canal disinfection, including its components, mechanism of action, reviews the current endodontic literature and also highlights the shortcomings and advancements in PDT techniques. PMID:25404404

Singh, Shipra; Nagpal, Rajni; Manuja, Naveen; Tyagi, Sashi Prabha

2014-11-17

163

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

164

Photodynamic Therapy for Bowen's Disease of the Vulva Area  

PubMed Central

Bowen's disease is a squamous cell carcinoma in situ and has the potential to progress to a squamous cell carcinoma. The authors treated two female patients (a 39-year-old and a 41-year-old) with Bowen's disease in the vulva area using topical photodynamic therapy (PDT), involving the use of 5-aminolaevulinic acid and a light-emitting diode device. The light was administered at an intensity of 80 mW/cm2 for a dose of 120 J/cm2 biweekly for 6 cycles. The 39-year-old patient showed excellent clinical improvement, but the other patient achieved only a partial response. Even though one patient underwent a total excision 1 year later due to recurrence, both patients were satisfied with the cosmetic outcomes of this therapy and the partial improvement over time. The common side effect of PDT was a stinging sensation. PDT provides a relatively effective and useful alternative treatment for Bowen's disease in the vulva area. PMID:24882981

Kang, Hong-Kyu; Yun, Jeong-Hwan; Son, Young-Min; Roh, Joo-Young

2014-01-01

165

Stimulation of anti-tumor immunity by photodynamic therapy  

PubMed Central

Photodynamic therapy (PDT) is a rapidly developing cancer treatment that utilizes the combination of nontoxic dyes and harmless visible light to destroy tumors by generating reactive oxygen species. PDT produces tumor-cell destruction in the context of acute inflammation that acts as a ‘danger signal’ to the innate immune system. Activation of the innate immune system increases the priming of tumor-specific T lymphocytes that have the ability to recognize and destroy distant tumor cells and, in addition, lead to the development of an immune memory that can combat recurrence of the cancer at a later point in time. PDT may be also successfully combined with immunomodulating strategies that are capable of overcoming or bypassing the escape mechanisms employed by the progressing tumor to evade immune attack. This article will cover the role of the immune response in PDT anti-tumor effectiveness. It will highlight the milestones in the development of PDT-mediated anti-tumor immunity and emphasize the combination strategies that may improve this therapy. PMID:21162652

Mroz, Pawel; Hashmi, Javad T; Huang, Ying-Ying; Lange, Norbert; Hamblin, Michael R

2011-01-01

166

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

167

Photodynamic therapy of non-melanoma skin cancers  

NASA Astrophysics Data System (ADS)

In this prospective study duly approved from Institutional Ethics Review Committee for research in medicine, PAEC General Hospital Islamabad, Pakistan, we investigate the efficacy, safety and tolerability along with cosmetic outcome of topical 5-aminolaevulinic acid photodynamic therapy for superficial nonmelanoma skin cancers (NMSCs) and their precursors. Patients with Histological diagnosis of NMSCs and their precursors were assessed for PDT, after photographic documentation of the lesions and written consent, underwent two (2) sessions of PDT in one month (4 weeks) according to standard protocol. A freshly prepared 20% 5-ALA in Unguentum base was applied under occlusive dressing for 4-6 h as Drug Light Interval (DLI) and irradiated with light of 630 nm wavelength from a diode laser at standard dose of 90 J/cm2. Approximately 11% patients reported pain during treatment which was managed in different simple ways. In our study we regularly followed up the patients for gross as well as histopathological response and recurrence free periods during median follow-up of 24 months. Regarding Basal cell carcinomas complete response was observed in 86.2% (25/29), partial response in 10.3% (3/29) and recurrence during first year in 3.5% (1/29) lesions. All the lesions which showed partial response or recurrence were nBCCs. Regarding Actinic Keratosis complete response was observed in 95.3% (20/21), partial response in 4.7% (1/21) while Bowen's disease showed 100% (2/2) results. 81.8% (9/11) Squamous Cell Carcinomas showed complete, 9% (1/11) partial response and 9% (1/11) presented with recurrence after 3 months. We observed excellent and good cosmetic results along with tumor clearance in our study. Treatment sessions were well tolerated with high level of patient's satisfaction and only minor side effects of pain during treatment sessions and inflammatory changes post photodynamic therapy were observed. We concluded that 5-ALA PDT is an effective and safe emerging treatment modality for management of superficial non-melanoma skin cancers and their precursors with better cosmetic outcome and minor side effects.

Ikram, M.; Khan, R. U.; Firdous, S.; Atif, M.; Nawaz, M.

2011-02-01

168

Predictive analysis of photodynamic therapy applied to esophagus cancer  

NASA Astrophysics Data System (ADS)

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 of a photosensitizer and irradiation by an optical source. The key factor of the procedure is the localization of the damage to avoid collateral harmful effects. The volume of tissue destroyed depends on the type of photosensitizer inoculated, both on its reactive characteristics and its distribution inside the tissue, and also on the specific properties of the optical source, that is, the optical power, wavelength and exposition time. In this work, a model for PDT based on the one-dimensional diffusion equation, extensible to 3D, to estimate the optical distribution in tissue, and on photosensitizer parameters to take into account the photobleaching effect is proposed. The application to esophagus cancer allows the selection of the right optical source parameters, like irradiance, wavelength or exposition time, in order to predict the area of tissue destruction.

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

2008-04-01

169

Core – shell upconversion nanoparticle – semiconductor heterostructures for photodynamic therapy  

PubMed Central

Core-shell nanoparticles (CSNPs) with diverse chemical compositions have been attracting greater attention in recent years. However, it has been a challenge to develop CSNPs with different crystal structures due to the lattice mismatch of the nanocrystals. Here we report a rational design of core-shell heterostructure consisting of NaYF4:Yb,Tm upconversion nanoparticle (UCN) as the core and ZnO semiconductor as the shell for potential application in photodynamic therapy (PDT). The core-shell architecture (confirmed by TEM and STEM) enables for improving the loading efficiency of photosensitizer (ZnO) as the semiconductor is directly coated on the UCN core. Importantly, UCN acts as a transducer to sensitize ZnO and trigger the generation of cytotoxic reactive oxygen species (ROS) to induce cancer cell death. We also present a firefly luciferase (FLuc) reporter gene based molecular biosensor (ARE-FLuc) to measure the antioxidant signaling response activated in cells during the release of ROS in response to the exposure of CSNPs under 980?nm NIR light. The breast cancer cells (MDA-MB-231 and 4T1) exposed to CSNPs showed significant release of ROS as measured by aminophenyl fluorescein (APF) and ARE-FLuc luciferase assays, and ~45% cancer cell death as measured by MTT assay, when illuminated with 980?nm NIR light. PMID:25652742

Dou, Qing Qing; Rengaramchandran, Adith; Selvan, Subramanian Tamil; Paulmurugan, Ramasamy; Zhang, Yong

2015-01-01

170

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

171

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

172

Failure to treat alopecia areata with photodynamic therapy.  

PubMed

We treated six patients with static alopecia areata (AA) with photodynamic therapy (PDT). All patients had received other treatment before starting PDT, but with no benefit. All previous treatments were stopped at least 3 months before beginning PDT, and no other treatment was given during the study period. PDT was used on only one of the affected areas, or if there was only one affected area, to only part of that area; untreated areas served as controls. For all patients methylaminolaevulinic acid was applied under occulsion 3 h after irradiation with red light at 630 nm (37 J/cm(2), 7.5 min). One session was carried out each month. Clinical and fluorescence photographs were taken with a digital camera connected to ultraviolet flashes, both before and after each treatment. None of the patients with AA of the scalp achieved complete hair regrowth, either in the treated or the untreated areas. Two of the patients showed growth of some thin hair over < 10 of the treated area. The remaining patients had no change. However, the patient with AA of the beard experienced complete regrowth after four sessions. To our knowledge, this is the first case of AA treated with PDT in this location. It may be that AA of beard hair responds better to PDT, but further studies are necessary. PMID:18355356

Fernández-Guarino, M; Harto, A; García-Morales, I; Pérez-García, B; Arrazola, J M; Jaén, P

2008-08-01

173

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

174

Angiolymphoid hyperplasia with eosinophilia: good response to photodynamic therapy.  

PubMed

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign vascular disease of unknown pathogenesis, that occurs as solitary or multiple nodules or papules. Lesions are located mainly on the head, forehead and neck, and may be persistent and difficult to eradicate. We report a case of ALHE treated with aminolaevulinic acid photodynamic therapy (ALA-PDT). Treatment consisted of two ALA-PDT sessions with a 2-week interval. Clinical evaluation, 8 weeks after treatment, showed marked improvement though not complete regression. The treatment was well tolerated. At follow-up 4 months after treatment, the lesions were stable. We believe that PDT could be an alternative therapeutic approach for ALHE or could be used as a neoadjuvant treatment to reduce lesion size especially where size or site of lesions limits the efficacy or acceptability of other treatments. The lack of cumulative effects allows repeated treatments with ALA-PDT, but long-term follow-up is advised for assessment of recurrence. PMID:19549233

Sotiriou, E; Apalla, Z; Patsatsi, A; Panagiotidou, D Devliotou; Ioannides, D

2009-12-01

175

New approaches to photodynamic therapy of tumors with Al phthalocyanine  

NASA Astrophysics Data System (ADS)

The aim of the study was to determine the efficacy of photodynamic therapy (PDT) of tumors of different localization and histology with new photosensitizer aluminum sulfonated phthalocyanine (Photosense, Russia). PDT have been provided in 106 patients with different tumors. The initial dose (2.0 - 2.5 mg/kg) of PHS was significantly reduced till 0.5 - 0.8 mg/kg during clinical trials because of phototoxicity. The results of PDT, side effects and ways of their correction and prevention, as well as possibility to work out less toxic regimes of PDT with photosense, choice of laser and type of irradiation are discussed. Efficacy of PDT depended on tumor size and it's histological type. Using low doses of PHS we've reduced the phototoxicity of sensitizer with the same direct effectiveness of treatment. Undesirable changes in plasma content of antioxidants by means of high pressure liquid chromatography have been found in patients after PHS injection. Influence of short-term and long-term supplementation with beta- carotene and vitamin E on this parameters are discussed.

Vakoulovskaya, Elena G.; Chental, V. V.; Kuvshinov, Yury P.; Poddubny, Boris K.

1999-12-01

176

Fluorescence guided evaluation of photodynamic therapy as acne treatment  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is an attractive alternative treatment for patients with acne because of its efficiency and few side effects. Propionibacterium acnes (P.acnes) are bacteria present in the skin, which produce endogenous porphyrins that act as photosensitisers. In addition, application of aminolaevulinic acid or its methyl ester (mALA) results in increased accumulation of porphyrins in the pilosebaceous units. This makes it possible to treat acne with PDT. This initial study investigates the possibility of fluorescence imaging as assessment tool in adjunct to PDT of patients with acne. Twenty-four patients with acne on the cheeks have been treated with PDT with and without mALA. Fluorescence images have been obtained before and after treatment. The clinical acne score was assessed as base line before PDT, and at every follow up visit. Additionally the amount of P.acnes was determined. The clinical evaluation showed a general improvement of acne, even though no difference between treatment with and without mALA was observed. By performing texture analysis and multivariate data analsysis on the fluorescence images, the extracted texture features were found to correlate with the corresponding clinical assessment (67%) and amount of P.acnes (72%). The analysis showed that features describing the highly fluorescent pores could be related to the clinical assessment. This result suggests that fluorescence imaging can be used as an objective assessment of acne, but further improvement of the technique is possible, for example by including colour images.

Ericson, Marica B.; Horfelt, Camilla; Cheng, Elaine; Larsson, Frida; Larko, Olle; Wennberg, Ann-Marie

2005-08-01

177

Light distribution in the endometrium during photodynamic therapy  

NASA Astrophysics Data System (ADS)

Hysterectomy is the most common major operation performed in the United States with dysfunctional uterine bleeding being a major indication. Endometrial destruction by photodynamic therapy (PDT) has been suggested as a possible alternative to invasive surgical procedures for abnormal uterine bleeding due to benign changes. Effective destruction of the endometrium during PDT requires a sufficient amount of light to be delivered to the entire endometrium in a reasonable time. To satisfy these criteria, we have developed a trifurcated optical applicator consisting of three cylindrical diffusing fibers. The applicator was inserted into freshly excised, intact human uteri and the optical distribution was measured with an isotropic fiber probe at various locations in the uterus. The results were in good agreement with the predictions of a mathematical model based on diffusion theory. The results indicate that irradiation of the endometrium by the trifurcated applicator can destroy tissue to a depth of 4 mm given an optical power of 100 mW per cm of diffusing tip (100 mW/cm) for an exposure time of less than 20 minutes.

Madsen, Sten; Svaasand, Lars O.; Fehr, Mathias K.; Tadir, Yona; Ngo, Phat; Tromberg, Bruce J.

1995-01-01

178

Core – shell upconversion nanoparticle – semiconductor heterostructures for photodynamic therapy  

NASA Astrophysics Data System (ADS)

Core-shell nanoparticles (CSNPs) with diverse chemical compositions have been attracting greater attention in recent years. However, it has been a challenge to develop CSNPs with different crystal structures due to the lattice mismatch of the nanocrystals. Here we report a rational design of core-shell heterostructure consisting of NaYF4:Yb,Tm upconversion nanoparticle (UCN) as the core and ZnO semiconductor as the shell for potential application in photodynamic therapy (PDT). The core-shell architecture (confirmed by TEM and STEM) enables for improving the loading efficiency of photosensitizer (ZnO) as the semiconductor is directly coated on the UCN core. Importantly, UCN acts as a transducer to sensitize ZnO and trigger the generation of cytotoxic reactive oxygen species (ROS) to induce cancer cell death. We also present a firefly luciferase (FLuc) reporter gene based molecular biosensor (ARE-FLuc) to measure the antioxidant signaling response activated in cells during the release of ROS in response to the exposure of CSNPs under 980 nm NIR light. The breast cancer cells (MDA-MB-231 and 4T1) exposed to CSNPs showed significant release of ROS as measured by aminophenyl fluorescein (APF) and ARE-FLuc luciferase assays, and ~45% cancer cell death as measured by MTT assay, when illuminated with 980 nm NIR light.

Dou, Qing Qing; Rengaramchandran, Adith; Selvan, Subramanian Tamil; Paulmurugan, Ramasamy; Zhang, Yong

2015-02-01

179

Photodynamic Therapy and the Development of Metal-Based Photosensitisers  

PubMed Central

Photodynamic therapy (PDT) is a treatment modality that has been used in the successful treatment of a number of diseases and disorders, including age-related macular degeneration (AMD), psoriasis, and certain cancers. PDT uses a combination of a selectively localised light-sensitive drug (known as a photosensitiser) and light of an appropriate wavelength. The light-activated form of the drug reacts with molecular oxygen to produce reactive oxygen species (ROS) and radicals; in a biological environment these toxic species can interact with cellular constituents causing biochemical disruption to the cell. If the homeostasis of the cell is altered significantly then the cell enters the process of cell death. The first photosensitiser to gain regulatory approval for clinical PDT was Photofrin. Unfortunately, Photofrin has a number of associated disadvantages, particularly pro-longed patient photosensitivity. To try and overcome these disadvantages second and third generation photosensitisers have been developed and investigated. This Review highlights the key photosensitisers investigated, with particular attention paid to the metallated and non-metallated cyclic tetrapyrrolic derivatives that have been studied in vitro and in vivo; those which have entered clinical trials; and those that are currently in use in the clinic for PDT. PMID:18815617

Josefsen, Leanne B.; Boyle, Ross W.

2008-01-01

180

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

181

On the combination of photodynamic therapy with ionizing radiation.  

PubMed

Ehrlich ascites carcinoma growth and cell damage have been examined after photodynamic therapy (PDT), radiotherapy (RT) and combined treatment. Haematoporphyrin dimethyl ether (HPde) is used as a photosensitizer for PDT and tested as a radiosensitizer for RT. For PDT a non-coherent light source (370 < lambda < 680 nm) equipped with filters is used. gamma-Irradiation consists of 60Co irradiation at a dose of 2 Gy. Both PDT and RT induce a significant delay and inhibition in tumour growth (33 and 38%, respectively). Nevertheless cell damage after these treatments is different: after PDT the cell membrane integrity is damaged and no serious chromosomal aberrations are observed; whereas after gamma-irradiation there is no cell membrane integrity damage, but more significant DNA injuries are observed. It seems evident that HPde is able to act as a photosensitizer as well as a radiosensitizer. Combining PDT and RT produces an additive effect, not dependent on the sequence in which the two treatments are given, when a 1 h time window is used. PMID:10643073

Luksiene, Z; Kalvelyte, A; Supino, R

1999-01-01

182

A robotic multi-channel platform for interstitial photodynamic therapy  

PubMed Central

A custom-made robotic multichannel platform for interstitial photodynamic therapy (PDT) and diffuse optical tomography (DOT) was developed and tested in a phantom experiment. The system, which was compatible with the operating room (OR) environment, had 16 channels for independent positioning of light sources and/or isotropic detectors in separate catheters. Each channel’s motor had an optical encoder for position feedback, with resolution of 1.5 mm, and a maximum speed of 5 cm/s. Automatic calibration of detector positions was implemented using an optical diode beam that defined the starting position of each motor, and by means of feedback algorithms controlling individual channels. As a result, the accuracy of zero position of 0.1 mm for all channels was achieved. We have also employed scanning procedures where detectors automatically covered the appropriate range around source positions. Thus, total scan time for a typical optical properties (OP) measurement throughout the phantom was about 1.5 minutes with point sources. The OP were determined based on the measured light fluence rates. These enhancements allow a tremendous improvement of treatment quality for a bulk tumor compared to the systems employed in previous clinical trials.

Sharikova, Anna V.; Finlay, Jarod C.; Dimofte, Andreea; Zhu, Timothy C.

2015-01-01

183

Reduction of Endotracheal Tube Biofilms Using Antimicrobial Photodynamic Therapy  

PubMed Central

Background Ventilator-associated pneumonia (VAP) is reported to occur in 12 to 25% of patients who require mechanical ventilation with a mortality rate of 24 to 71%. The endotracheal (ET) tube has long been recognized as a major factor in the development of VAP since biofilm harbored within the ET tube become dislodged during mechanical ventilation and have direct access to the lungs. The objective of this study was to demonstrate the safety and effectiveness of a non-invasive antimicrobial photodynamic therapy (aPDT) treatment method of eradicating antibiotic resistant biofilms from ET tubes in an in vitro model. Methods Antibiotic resistant polymicrobial biofilms of Pseudomonas aerugenosa and MRSA were grown in ET tubes and treated, under standard ventilator conditions, with a methylene blue (MB) photosensitizer and 664nm non-thermal activating light. Cultures of the lumen of the ET tube were obtained before and after light treatment to determine efficacy of biofilm reduction. Results The in vitro ET tube biofilm study demonstrated that aPDT reduced the ET tube polymicrobial biofilm by >99.9% (p<0.05%) after a single treatment. Conclusions MB aPDT can effectively treat polymicrobial antibiotic resistant biofilms in an ET tube. PMID:21987599

Biel, Merrill A.; Sievert, Chet; Usacheva, Marina; Teichert, Matthew; Wedell, Eric; Loebel, Nicolas; Rose, Andreas; Zimmermann, Ron

2011-01-01

184

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

185

Photodynamic therapy for bile duct invasion of hepatocellular carcinoma.  

PubMed

The prognosis of patients with obstructive jaundice caused by hepatocellular carcinoma (HCC) is dismal, because effective biliary drainage is difficult due to frequent malfunction of the drainage tube caused by hemobilia and/or tumor emboli. Photodynamic therapy (PDT) improves biliary patency and prolongs survival in hilar cholangiocarcinoma. The aim of this study was to assess the safety and efficacy of PDT in unresectable HCC with bile duct invasion. Between January 2009 and September 2010, eleven patients with bile duct invasion of unresectable HCC were enrolled at Samsung Medical Center. PDT was performed with 180 J cm(-1) light activation 48 hours after administration of the photosensitizer at a dose of 2 mg kg(-1) body weight. Biliary drainages were performed in all patients. The safety and efficacy of PDT were prospectively evaluated. Eleven patients had successful PDT and biliary drainage. Jaundice improved in seven out of ten patients who had jaundice before PDT. Hemobilia, which had developed in six cases, was controlled by PDT. There were no complications from the photosensitizer. There was no 30-day mortality, and the mean survival was 140.5 days. PDT controlled hemobilia associated with bile duct invasion of HCC and could be an effective treatment option in these patients. PMID:23175171

Bahng, Sunha; Yoo, Byung Chul; Paik, Seung Woon; Koh, Kwang Cheol; Lee, Kyu Teak; Lee, Jong Kyun; Lee, Joon Hyoek; Choi, Moon Seok; Lee, Kwang Hyuck

2013-03-01

186

Cationic porphyrin derivatives for application in photodynamic therapy of cancer  

NASA Astrophysics Data System (ADS)

Current studies in photodynamic therapy (PDT) against cancer are focused on the development of new photosensitizers (PSs), with higher phototoxic action. The aim of this study was to compare the therapeutic efficiency of tri-cationic meso-substituted porphyrin derivatives (Tri-Py+–Me–PF, Tri-Py+–Me–Ph, Tri-Py+–Me–CO2Me and Tri-Py+–Me–CO2H) with the well-known tetra-cationic T4PM. The phototoxic action of these derivatives was assessed in human colon adenocarcinoma cells by cell viability, intracellular localization and nuclear morphology analysis. In the experimental conditions used we determined that after light activation –PF, –Ph and –CO2Me cause a more significant decline of cell viability compared to –CO2H and T4PM. These results suggest that the nature of the peripheral substituent influences the extent of cell photodamage. Moreover, we have demonstrated that PS concentration, physicochemical properties and further light activation determine the PDT response. All porphyrins were clearly localized as a punctuated pattern in the cytoplasm of the cells, and the PDT scheme resulted in apoptotic cell death after 3 h post-PDT. The tri-cationic porphyrin derivatives Tri-Py+–Me–PF, Tri-Py+–Me–Ph and Tri-Py+–Me–CO2Me showed a promising ability, making them good photosensitizer candidates for oncological PDT.

Prack McCormick, Bárbara P.; Florencia Pansa, M.; Milla Sanabria, Laura N.; Carvalho, Carla M. B.; Faustino, M. Amparo F.; Neves, Maria Graça P. M. S.; Cavaleiro, José A. S.; Rumie Vittar, Natalia B.; Rivarola, Viviana A.

2014-04-01

187

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

188

Characterizing light propagation in bone for photodynamic therapy of osteosarcoma  

NASA Astrophysics Data System (ADS)

This work aims at characterizing how light propagates through bone in order to efficiently guide treatment of osteosarcoma with photodynamic therapy (PDT). Optical properties of various bone tissues need to be characterized in order to have a working model of light propagation in bone. Bone tissues of particular interest include cortical bone, red and yellow marrow, cancellous bone, and bone cancers themselves. With adequate knowledge of optical properties of osseous tissues, light dosimetry can determine how best to deliver adequate light to achieve phototoxic effects within bone. An optical fiber source-collector pair is used for diffuse reflectance spectroscopic measurements in order to determine the scattering and absorption properties of bone tissues. Native absorbers of interest at visible and near-IR wavelengths include water and oxygenated and deoxygenated hemoglobin. A cylindrically symmetric Monte Carlo model is then used, incorporating these results, in order to predict and guide the delivery of light within bone in order to achieve the desired phototoxic effect in PDT.

Rossi, Vincent M.; Gustafson, Scott B.; Jacques, Steven L.

2009-02-01

189

Synthesis of folate receptor-targeted photosensitizers for photodynamic therapy  

NASA Astrophysics Data System (ADS)

A series of amphiphilic benzylidene cycloalkanes ketone photosensitizers C1-C4 with or without folate receptor-targeted agent were designed and synthesized. Their photophysical properties and in vitro photodynamic therapy (PDT) effects were studied. The results showed that all compounds exhibited appropriate lipid-water partition coefficients and high reactive oxygen yields. The introduction of the folate receptor-targeted agent had no obvious influence on the basic photophysical & photochemical properties of C2 and C4 compared to those of their corresponding prototype compounds (C1 and C3). In vitro studies were carried out using MCF-7 cells (FR+), Hela cells (FR+) and A549 cells (FR-), which represented different levels of folate receptor (FR) expression. All of C1-C4 showed low dark toxicity and superior PDT effects compared with the clinical drug PSD-007 (a mixture of porphyrins). What's more, folate receptor-targeted photosensitizers (C2 and C4) achieved higher accumulation and more excellent PDT effects in MCF-7 cells (FR+) and Hela cells (FR+) than photosensitizers (C1 and C3) without folate receptor-targeted agent and PSD-007. The photocytotoxicity of these photosensitizers showed no obvious differences in A549 cells (FR-).

Fang, Yanyan; Wang, Xiaopu; Zou, Qianli; Zhao, Yuxia; Wu, Feipeng

2014-11-01

190

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

191

Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study  

Microsoft Academic Search

Background: Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK. Objective: We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using

R. M. Szeimies; S. Karrer; S. Radakovic-Fijan; A. Tanew; P. G. Calzavara-Pinton; C. Zane; A. Sidoroff; M. Hempel; J. Ulrich; T. Proebstle; H. Meffert; M. Mulder; D. Salomon; H. C. Dittmar; J. W. Bauer; K. Kernland; L. Braathen

2002-01-01

192

Antimicrobial photodynamic therapy: an effective alternative approach to control fungal infections  

PubMed Central

Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails, and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy (PDT) utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowledge of PDT as it specifically applies to fungal diseases. The data to date suggests that photodynamic treatment approaches hold great promise for combating certain fungal pathogens, particularly dermatophytes.

Baltazar, Ludmila M.; Ray, Anjana; Santos, Daniel A.; Cisalpino, Patrícia S.; Friedman, Adam J.; Nosanchuk, Joshua D.

2015-01-01

193

Photodynamic Therapy With Verteporfin in Subfoveal Choroidal Neovascularization Secondary to Central Serous Chorioretinopathy  

Microsoft Academic Search

Objective: To examine the efficacy and safety of pho- todynamic therapy with verteporfin in the treatment of subfoveal choroidal neovascularization secondary to cen- tral serous chorioretinopathy (CSC). Design: Prospective interventional, noncomparative case series. Methods: After the diagnosis of a subfoveal choroidal neovascularization secondary to CSC, 26 eyes of 24 pa- tients were treated with photodynamic therapy with verte- porfin. Patients

Erdem Ergun; Michael Tittl; Michael Stur

2004-01-01

194

Adjuvant Therapy of Breast Cancer – Bisphosphonates  

Microsoft Academic Search

The skeleton is a first site of recurrence in every third relapse in breast cancer. Approximately 705 (50–80%) of metastatic\\u000a breast cancer patients have bone metastases [1]. Bisphosphonates have been used successfully in the treatment of malignant\\u000a hypercalcaemia and skeletal metastases [2]. The use of bisphosphonates in addition to hormone therapy or chemotherapy reduces\\u000a the risk of developing skeletal events

Tiina Saarto

195

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

196

Radical Pleurectomy and Intraoperative Photodynamic Therapy for Malignant Pleural Mesothelioma  

PubMed Central

Background Radical pleurectomy (RP) for mesothelioma is often considered either technically infeasible or an operation limited to patients who would not tolerate a pneumonectomy. The purpose of this study was to review our experience using RP and intraoperative photodynamic therapy (PDT) for mesothelioma. Methods 38 patients (42–81 years) underwent RP-PDT. 35/38 (92%) patients also received systemic therapy. Standard statistical techniques were employed for analysis. Results 37/38 (97%) patients had Stage III/IV (AJCC) cancer and 7/38 (18%) patients had nonepithelial subtypes. Macroscopic complete resection was achieved in 37/38 (97%) patients. There was one postoperative mortality (stroke). At a median follow-up of 34.4 months, the median survival was 31.7 months for all 38 patients, 41.2 months for the 31/38 (82%) epithelial patients and 6.8 months for the 7/38 (18%) nonepithelial patients. The median progression free survivals were 9.6, 15.1 and 4.8 months, respectively. The median and progression free survivals for the 20/31 (64%) epithelial patients with N2 disease were 31.7 and 15.1 months, respectively. Conclusions It was possible to achieve a macroscopic complete resection utilizing lung-sparing surgery in 97% of these stage III/IV patients. The survival we observed with this approach was unusually long for the epithelial subtype patients but, interestingly, the progression free survival was not. The reason for this prolonged survival in spite of recurrence is not clear, but is potentially related to preservation of the lung and/or some PDT-induced effect. We conclude that the results of this lung-sparing approach are safe, encouraging and warrant further investigation. PMID:22541196

Friedberg, Joseph S.; Culligan, Melissa J.; Mick, Rosemarie; Stevenson, James; Hahn, Stephen M.; Sterman, Daniel; Punekar, Salman; Glatstein, Eli; Cengel, Keith

2015-01-01

197

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

198

Adjuvant Endocrine Therapy in Early Postmenopausal Breast Cancer  

PubMed Central

Summary Five years of adjuvant tamoxifen treatment has been the gold standard for women with early hormone-responsive breast cancer. Results from two large phase III, adjuvant studies have indicated that the third-generation aro-matase inhibitors (AIs) letrozole and anastrozole offer greater protection against recurrence than tamoxifen in upfront substitution strategies in the first 5 years. Similarly, changeover to an AI (exemestane or anastrozole) after 2-3 years of tamoxifen has been more efficient to prevent recurrence than 5 years of tamoxifen. Most early breast cancer recurrences occur 5 or more years after surgery. Letrozole has been shown to offer greater protection against recurrence than placebo in the 5 years after a standard course of tamoxifen. The optimal adjuvant use (duration and sequencing) of AIs requires further investigation. Safety implications of treatment with these AIs for 5 years or more are closely monitored. The anticipated effects of estrogen deprivation on bone health may be treatable with bisphosphonates. Effects on the cardiovascular system, and other estrogen-sensitive systems such as the central nervous system, are currently examined. The AIs letrozole, anastrozole, and ex-emestane have recently replaced tamoxifen as the recommended adjuvant endocrine therapy, on the basis of greater efficacy and better tolerability. PMID:20824026

Mundhenke, Christoph; Schem, Christian; Jonat, Walter

2008-01-01

199

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

200

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

201

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

PubMed Central

Abstract. 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. PMID:24365954

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

2013-01-01

202

Canine treatment with SnET2 for photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy is a treatment technique that utilizes the photoactived species of a drug to destroy tumor tissue. To be successful, the drug must localize in tumor tissue preferentially over normal tissue and must be activated by light of a specific wavelength. Currently the only drug to be approved for clinical use is Heinatoporphyrin Derivative (HpD) although a series of new drugs are being developed for use in the near future. One of the drugs belongs to a class called purpurins which display absorp-' tions between 630-711 nm. Along with several other investigators, we are currently exploring the characteristics of a specific purpurin (SnET2) in normal and tumorous canine tissue. The use of this compound has demonstrated increased tumor control rates in spontaneous dog tumors. Preliminary pharmacokinetic studies have been performed on 6 normal beagle dogs. SnET2 (2 mg/kg) was injected intravenously over 10 minutes and blood was collected at 5, 15, 30, 45 minutes and at 1, 2, 4, 8, 12 and 24 hours following administration for determination of drug concentration and calculation of pharinacokinetic parameters. Skin biopsies were collected at 1, 4, 8, 12 and 24 hours. Dogs were euthanized at 24 hours and tissues (liver, kidney muscle, esophagus, stomach, duodenum, jejunum, ileura, colon, adrenal gland, thyroid, heart, lung, urinary bladder, prostate, pancreas, eye, brain) were collected for drug raeasurement. Drug was shown to persist in liver and kidney for a prolonged period of time coiapared to other tissues. Knowledge of the pharmacokinetic properties of the drug will greatly add to the ability to treat patients with effective protocols.

Frazier, Donita L.; Milligan, Andrew J.; Vo-Dinh, Tuan; Morgan, Alan R.; Overholt, Bergein F.

1990-07-01

203

Nanophotonic ensembles for targeted multi-photon photodynamic therapy  

NASA Astrophysics Data System (ADS)

There has been a dramatic increase in the application of new technologies for the treatment of cancerous tumors over the past decade, but for the most part, the treatment of most tumors still involves some combination of invasive surgery, chemotherapy and radiation treatments. Photodynamic therapy (PDT), which involves the activation of an administered compound with laser light followed by a series of events leading to programmed cell death of the tumor, has been proposed as a noninvasive alternative treatment to replace the standard surgery/chemotherapy/radiation protocol. However, currently approved PDT agents operate in the Visible portion of the spectrum, and laser light in this region cannot penetrate the skin more than a few millimeters. Two-photon irradiation using more highly penetrating Near-infrared (NIR) light in the tissue transparency window (700-1000 nm) has been proposed for the treatment of subcutaneous tumors, but most porphyrins exhibit extremely small two-photon cross-sections. Classical PDT also suffers from the lengthy time necessary for accumulation at the tumor site, a relative lack of discrimination between healthy and diseased tissue, particularly at the tumor margins, and difficulty in clearing from the system in a reasonable amount of time. We have recently discovered a new design paradigm for porphyrins with greatly enhanced two-photon cross-sections, and are now proposing a nano-ensemble that would also incorporate small molecule targeting agents, and possibly one-photon NIR imaging agents along with these porphyrins in one therapeutic agent. Thus these ensembles would incorporate targeting/imaging/PDT functions in one therapeutic agent, and hold the promise of single-session outpatient treatment of a large variety of subcutaneous tumors.

Spangler, Charles W.; Meng, Fanqing; Gong, Aijun; Drobizhev, Mikhail A.; Karotki, Aliaksandr; Rebane, Aleksander, II

2004-06-01

204

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

205

Pentamethylpyrromethene boron difluoride complexes in human ovarian cancer photodynamic therapy  

NASA Astrophysics Data System (ADS)

Quasiaromatic heterocycles (QAM) such as substituted 1 , 3 , 5 , 7 , 8-pentamethylpyrromethene boron difluorides (PMP-BF2) and - (dimethoxyphosphinylmethyl, methyl) bimane have been evaluated for their abilities to produce cellular toxicities when used in photodynamic therapy (PDT) for ovarian cancer. The most active QAH tested to date has been the disodiuxn salt of PMP-2,6-disulfonate--BF2 (PMPDS-BF2). Human ovarian cancer cells from fifteen different patients have been grown in culture. Cells were obtained from biopsy material and grown in RPMI medium with 10% FBA plus penicillin and streptomycin. Cells were harvested and as single cell suspensions exposed to PMP-BF2 complexes or bimanes in concentrations of 0.004-0.4 ug/106 cells/ml of medium. Initially the cells were exposed to the chemicals for 30 minutes in a 5% CO2 incubator (37°C) with gentle shaking. The cells were washed with plain RPMI medium, then resuspended in the enriched RPMI medium and exposed to a sunlamp for 10-20 minutes. Cells were then allowed to grow in an soft agar culture media at 37°C (5% C02) for 14 days. When compared to controls (only light or only chemicals) there was 100% inhibition of all cellular growth for PMPDSBF2 at the 0.4 ug/mi concentrations. There was variations in concentrations of the chemical needed to produce 100% inhibition when the 15 different ovarian cancer cell specimens were compared at all concentrations. PMP-BF2 complexes are characterized by extremely high extinction coefficients, superior laser activity and little if any triplet-triplet absorption. The biamanes share these properties however are less active in ovarian cancer cell The lasing properties of PMP-BF2, and bimanes will be compared to their PDT effectiveness.

Morgan, Lee R.; Chaudhuri, Aulena; Gillen, Laura E.; Boyer, Joseph H.; Wolford, Lionel T.

1990-07-01

206

Galactodendritic Phthalocyanine Targets Carbohydrate-Binding Proteins Enhancing Photodynamic Therapy  

PubMed Central

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

207

Photodynamic therapy: a new antimicrobial approach to infectious disease?  

PubMed Central

Photodynamic therapy (PDT) employs a non-toxic dye, termed a photosensitizer (PS), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. PDT has the advantage of dual selectivity, in that the PS can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. It is known that Gram-(?) bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity in Gram-(+) species, and that PS bearing a cationic charge or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing Gram-(?) organisms. All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naïve strains, and that bacteria will not readily develop resistance to PDT. Treatment of localized infections with PDT requires selectivity of the PS for microbes over host cells, delivery of the PS into the infected area and the ability to effectively illuminate the lesion. Recently, there have been reports of PDT used to treat infections in selected animal models and some clinical trials: mainly for viral lesions, but also for acne, gastric infection by Helicobacter pylori and brain abcesses. Possible future clinical applications include infections in wounds and burns, rapidly spreading and intractable soft-tissue infections and abscesses, infections in body cavities such as the mouth, ear, nasal sinus, bladder and stomach, and surface infections of the cornea and skin. PMID:15122361

Hasan, Tayyaba

2011-01-01

208

Photodynamic Therapy for Acinetobacter baumannii Burn Infections in Mice?  

PubMed Central

Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 108 A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections. PMID:19564369

Dai, Tianhong; Tegos, George P.; Lu, Zongshun; Huang, Liyi; Zhiyentayev, Timur; Franklin, Michael J.; Baer, David G.; Hamblin, Michael R.

2009-01-01

209

Susceptibility of multispecies biofilm to photodynamic therapy using Photodithazine®.  

PubMed

This in vitro study evaluated the effect of photodynamic therapy (PDT) on the multispecies biofilm of Candida albicans, Candida glabrata, and Streptococcus mutans. Standardized fungal and bacterial suspensions were cultivated appropriately for each species and inoculated in 96-well microtiter plates for mix-biofilm formation. After 48 h of incubation, the biofilms were submitted to PDT (P?+?L+) using Photodithazine® (PDZ) at 100, 150, 175, 200, or 250 mg/mL for 20 min and 37.5 J/cm(2) of light-emitting diode (LED) (660 nm). Additional samples were treated only with PDZ (P?+?L-) or LED (P-L+), or neither (control, P-L-). Afterwards, the biofilms were evaluated by quantification of colonies (CFU/mL), metabolic activity (XTT reduction assay), total biomass (crystal violet staining), and confocal scanning laser microscopy (CSLM). Data were analyzed by one-way ANOVA and Tukey tests (p?

Quishida, Cristiane Campos Costa; Carmello, Juliana Cabrini; Mima, Ewerton Garcia de Oliveira; Bagnato, Vanderlei Salvador; Machado, Ana Lúcia; Pavarina, Ana Cláudia

2015-02-01

210

The design of a robotic multichannel platform for photodynamic therapy  

NASA Astrophysics Data System (ADS)

A compact robotic platform is designed for simultaneous multichannel motion control for light delivery and dosimetry during interstitial photodynamic therapy (PDT). Movements of light sources and isotropic detectors are controlled by individual motors along different catheters for interstitial PDT. The robotic multichannel platform adds feedback control of positioning for up to 16 channels compared to the existing dual-motor system, which did not have positioning encoders. A 16-channel servo motion controller and micro DC motors, each with high resolution optical encoder, are adopted to control the motions of up to 16 channels independently. Each channel has a resolution of 0.1mm and a speed of 5cm/s. The robotic platform can perform light delivery and dosimetry independently, allowing arbitrary positioning of light sources and detectors in each catheter. Up to 16 compact translational channels can be combined according to different operational scheme with real-time optimal motion planning. The characteristic of high speed and coordinating motion will make it possible to use short linear sources (e.g., 1- cm) to deliver uniform PDT treatment to a bulk tumor within reasonable time by source stepping optimization of multiple sources simultaneously. Advanced robotic control algorithm handles the various unexpected circumstance in clinical procedure, e.g., positiontorque/ current control will be applied to prevent excessive force in the case of resistance in the fiber or motorized mechanism. The robotic platform is fully compatible with operation room (OR) environment and improves the light delivery and dosimetry in PDT. It can be adopted for diffusing optical tomography (DOT), spectroscopic DOT and fluorescent spectroscopy.

Hu, Yida; Finlay, Jarod C.; Zhu, Timothy C.

2009-06-01

211

Target cell specific antibody-based photosensitizers for photodynamic therapy  

NASA Astrophysics Data System (ADS)

In photodynamic therapy (PDT), localized monochromatic light is used to activate targeted photosensitizers (PS) to induce cellular damage through the generation of cytotoxic species such as singlet oxygen. While first-generation PS passively targeted malignancies, a variety of targeting mechanisms have since been studied, including specifically activatable agents. Antibody internalization has previously been employed as a fluorescence activation system and could potentially enable similar activation of PS. TAMRA, Rhodamine-B and Rhodamine-6G were conjugated to trastuzumab (brand name Herceptin), a humanized monoclonal antibody with specificity for the human epidermal growth factor receptor 2 (HER2), to create quenched PS (Tra-TAM, Tra-RhoB, and Tra-Rho6G). Specific PDT with Tra-TAM and Tra-Rho6G, which formed covalently bound H-dimers, was demonstrated in HER2+ cells: Minimal cell death (<6%) was observed in all treatments of the HER2- cell line (BALB/3T3) and in treatments the HER2+ cell line (3T3/HER2) with light or trastuzumab only. There was significant light-induced cell death in HER2 expressing cells using Tra-TAM (3% dead without light, 20% at 50 J/cm2, 46% at 100 J/cm2) and Tra-Rho6G (5% dead without light, 22% at 50 J/cm2, 46% at 100 J/cm2). No efficacy was observed in treatment with Tra-RhoB, which was also non-specifically taken up by BALB/3T3 cells and which had weaker PS-antibody interactions (as demonstrated by visualization of protein and fluorescence on SDS-PAGE).

Rosenblum, Lauren T.; Mitsunaga, Makoto; Kakareka, John W.; Morgan, Nicole Y.; Pohida, Thomas J.; Choyke, Peter L.; Kobayashi, Hisataka

2011-03-01

212

Status of adjuvant endocrine therapy for breast cancer  

PubMed Central

Adjuvant endocrine therapy reduces the risk of recurrence and death from breast cancer in women with hormone receptor-positive early breast cancer. Tamoxifen has been the standard therapy for decades, and this is still the case for pre-menopausal women. Ovarian suppression is of similar efficacy but currently there is no strong evidence for adding this to tamoxifen and the additional morbidity can be considerable. Results from two important trials addressing this issue are imminent. In post-menopausal women, aromatase inhibitors (AIs) (letrozole, anastrozole, or exemestane) are superior to tamoxifen in preventing recurrence but only letrozole has been shown to improve survival. The main gain is against high-risk cancers, and tamoxifen gives very similar benefit for low-risk disease. Traditionally, treatment has been given for around 5 years, but many women remain at risk of relapse for 10 years or more. The AIs, and more recently tamoxifen, have been shown to reduce further the risk of late recurrence in women still in remission after 5 years of tamoxifen if given for a further 5 years. The comparative benefits of these two options and the selection of patients most likely to benefit from long-term adjuvant endocrine therapy are important topics for further research, as is the optimum duration of AI therapy started upfront. PMID:25032258

2014-01-01

213

Impact of Tamoxifen Adjuvant Therapy on Symptoms, Functioning, and Quality of Life  

Microsoft Academic Search

This article reviews the symptoms and everyday problems associated with tamoxifen adjuvant therapy and their im- pact on patients' quality of life. In addition, the purported toxic effects of tamoxifen therapy (e.g., premature meno- pause, weight gain, and depression) are discussed, and data are presented that refute claims of the toxicity of tamoxifen therapy. From randomized controlled trials of adjuvant

Patricia A. Ganz

214

Pheophorbide-a conjugates with cancer-targeting moieties for targeted photodynamic cancer therapy.  

PubMed

Pheophorbide-a, a non-selective photosensitizer, was conjugated with cancer-targeting moieties, such as folic acid, the CRGDLASLC peptide, the cRGDfK peptide and leuprorelin, for the purpose of targeted photodynamic cancer therapy. The cellular uptake of pheophorbide-a conjugates in cancer cells overexpressing the corresponding receptors of the targeting moieties was largely enhanced compared with that in the receptor-negative cells. In the study of in vitro photodynamic activity and selectivity of pheophorbide-a conjugates in the receptor-positive and receptor-negative cells, a pheophorbide-a conjugate, (14) with an ?v?6 ligand (CRGDLASLC) exhibited the highest selectivity in the positive FaDu cells. Targeted PDT with 14 induced cell death through apoptosis and morphological apoptosis-like characteristics. These results suggest that pheophorbide-a conjugate 14 could be utilized in selective photodynamic therapy for oral cancers primarily expressing the ?v?6 receptor. PMID:25753328

You, Hyun; Yoon, Hyo-Eun; Jeong, Pyeong-Hwa; Ko, Hyojin; Yoon, Jung-Hoon; Kim, Yong-Chul

2015-04-01

215

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

216

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.

217

Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma.  

PubMed

Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. PMID:25043500

Bae, Byoung-chan; Yang, Su-Geun; Jeong, Seok; Lee, Don Haeng; Na, Kun; Kim, Joon Mee; Costamagna, Guido; Kozarek, Richard A; Isayama, Hiroyuki; Deviere, Jacques; Seo, Dong Wan; Nageshwar Reddy, D

2014-10-01

218

Total Tumor Cell Elimination with Minimum Damage to Normal Tissues in Musculoskeletal Sarcomas following Photodynamic Therapy with Acridine Orange  

Microsoft Academic Search

Acridine orange (AO) has unique biological actions enabling tumor visualization (fluorovisualization) and a strong cytocidal effect (photodynamic therapy: AO-PDT) under illumination with blue light. Accordingly, in this study, we attempted to develop a new surgical technique for total tumor cell elimination using these photodynamic reactions with AO in a mouse osteosarcoma model. The results showed that local tumor recurrence was

Katsuyuki Kusuzaki; Katsuhiro Aomori; Takehiko Suginoshita; Ginjorou Minami; Hideyuki Takeshita; Hiroaki Murata; Shin Hashiguchi; Tsukasa Ashihara; Yasusuke Hirasawa

2000-01-01

219

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

220

Photodynamic Therapy With Motexafin Lutetium Induces Redox-Sensitive Apoptosis of Vascular Cells  

Microsoft Academic Search

Motexafin lutetium is a photosensitizer that accumulates in atherosclerotic plaque and, after activation by far-red light, produces cytotoxic singlet oxygen. The combination of photosensitizer and illumination, known as photodynamic therapy (PDT), has been shown to reduce atheroma formation in animal models and is under clinical investigation. However, the effects of PDT with motexafin lutetium on isolated vascular cells are unknown.

Zhiping Chen; Kathryn W. Woodburn; Can Shi; Daniel C. Adelman; Campbell Rogers; Daniel I. Simon

2010-01-01

221

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

222

Photorejuvenation--topical photodynamic therapy as therapeutic opportunity for skin rejuvenation.  

PubMed

The intrinsic aging process of the skin in unavoidable and depends on the passage of time per se. Among harmful environmental factors that contribute to extrinsic aging, long-term effects of repeated exposure to ultraviolet radiation are the most significant and are referred to as photoaging. Photoaging is directly correlated to the quantity of UV rays received during the course of a lifetime. Topical photodynamic therapy is well-established procedure for the treatment of actinic keratoses, Bowen disease and basal cell carcinomas. Clinical experience has demonstrated that extensive treatment of actinic keratoses on sun-damaged skin also produces as a positive side effects significant improvement of the signs of skin aging. An improvement of lentigines, skin roughness, fine lines, increases in skin smoothness and improvement of actinic elastosis, skin colour and reduction of hyperpigmentation were seen. The reversible side effects of photodynamic therapy include pain, erythema, oedema, scaling and crusting, and sometimes in darker skin types post-inflammatory hyperpigmentation. Photodynamic therapy is promising approach for treatment ofphotoinduced skin aging and takes place between ablative and non-ablative methods for skin rejuvenation. Effective improvement of photoaged skin, the possibility of repeated treatments and imitated side effects makes photodynamic therapy a promising procedure for skin rejuvenation. PMID:25842769

Sjerobabski Masnec, Ines; Situm, Mirna

2014-12-01

223

Photodynamic therapy of early stage cancer of lung, esophagus, and stomach with two different photosensitizers  

NASA Astrophysics Data System (ADS)

The paper presents the results of photodynamic therapy (PDT) of early-stage cancer of lung (17 patients), esophagus (8 patients) and stomach (10 patients). Fifteen patients had second primary tumors. New drugs photoheme and photosens were used as photosensitizers. Complete remission was obtained in 87%. The patients are followed up without relapses to 2.5 years.

Chissov, Valery I.; Sokolov, Victor V.; Trakhtenberg, A. K.; Mamontov, A. S.; Vaschakmadze, L. A.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Belous, T. A.; Gladunov, V. K.; Aristarkhova, E. I.; Zharkova, Natalia N.; Menenkov, V. D.

1996-01-01

224

Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI  

Microsoft Academic Search

Antivascular photodynamic therapy (PDT) of tumors with palladium-bacteriopheophorbide (TOOKAD) relies on in situ photosensitization of the circulating drug by local generation of cytotoxic reactive oxygen species, which leads to rapid vascular occlusion, stasis, necrosis and tumor eradication. Intravascular production of reactive oxygen species is associated with photoconsumption of O2 and consequent evolution of paramagnetic deoxyhemoglobin. In this study we evaluate

Shimon Gross; Assaf Gilead; Avigdor Scherz; Michal Neeman; Yoram Salomon

2003-01-01

225

Response Surface Methodology: An Extensive Potential to Optimize in vivo Photodynamic Therapy Conditions  

Microsoft Academic Search

Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as

Loraine Tirand; Thierry Bastogne; Denise M. Sc. Bechet; Michel Linder; Noémie Thomas; Céline Frochot; François Guillemin; Muriel Barberi-Heyob

2009-01-01

226

Photodynamic therapy for treatment of AIDS-related mucocutaneous Kaposi's sarcoma (Invited Paper)  

NASA Astrophysics Data System (ADS)

Since 1975, Phase I/II studies have demonstrated the successfulness of hematoporphyrin derivative photodynamic therapy (PDT) in the treatment of various malignancies of the skin, eye, bladder, lung, and head and neck. Moreover, in 1981 two cases of traditional Western cutaneous Kaposi's sarcoma (TKS) have been treated with photodynamic therapy with both early and late complete response. To date, attempts to cure and palliation of the more aggressive AIDS-related oral Kaposi's sarcoma with conventional radiation, chemotherapy or immunotherapy, or surgical excision have been limited and often associated with debilitating mucositis and further immunosuppression. Certain aspects of photodynamic therapy may be efficacious for treatment of mucocutaneous Kaposi's sarcoma: (1) the selective retention of hematoporphyrin derivative by neoplastic lesions (endothelial cell tumors); (2) a tumor- specific cytotoxic agent (i.e., free oxygen radical); (3) absence of systemic toxicity from immunosuppression; (4) the potential for retreatment without increasing side effects; and (5) porphyrin-mediated photoinactivation of enveloped viruses. Herein presented are seven cases of AIDS-related KS (EKS) with diffuse, superficial, and nodular mucocutaneous lesions treated with dihematoporphyrin derivative and photodynamic therapy with subsequent dramatic early partial and complete responses.

Schweitzer, Vanessa G.

1992-06-01

227

Photodynamic therapy suppresses tumor growth in an in vivo model of human hemangioma.  

PubMed

The authors investigated the efficacy of photodynamic therapy against infantile hemangioma using a hemangioma animal model. Eighty-three hemangioma specimens from five children were implanted into nude mice. The gross and volume changes of the implants were evaluated for up to 13 weeks. The histological change of the implant was evaluated at 5 weeks after transplantation. Photodynamic therapy was performed between 6 and 10 weeks after transplantation. The photosensitizer uptake of the implant was evaluated at 24 h after photosensitizer administration. The implant response was evaluated at 0, 12, and 24 h after light delivery. The change in ATF3 levels, a transcription factor induced under severe hypoxic conditions, was investigated immediately after treatment. The implant volume increased slowly during the first 4 weeks and then involuted. At 5 weeks after transplantation, plump endothelial cells formed tightly packed sinusoidal channels, and the endothelial cells were positive for CD31 and GLUT1 expression. At 24 h after photosensitizer administration, confocal analysis showed that the photosensitizer was present within CD31-positive cells. The implant volume was significantly decreased in the treated implants compared with the untreated implants (p < 0.0001). At 24 h after light delivery, most cells had collapsed. ATF3 expression increased gradually and then reached a maximum level at 4 h after treatment. Photodynamic therapy was effective in the treatment of infantile hemangioma. Apoptosis, a major mechanism of hemangioma destruction in the early phase, might be caused by ischemic injury as well as direct effects of photodynamic therapy. PMID:23784382

Choi, Jaehoon; Kim, Woo Jung; Park, Sang Woo; Xu, Lianji; Kim, Sang-Hyon; Min, Hye Sook; Kwon, Geun-Yong; Cho, Chung-Hyun; Kim, Sukwha; Choi, Tae Hyun

2014-01-01

228

Antibacterial Effect of Photodynamic Therapy on Prepared Tooth Structure Contaminated with Streptococcus mutans  

Microsoft Academic Search

Several studies during the last few years have demonstrated the antibacterial potential of photodynamic therapy (PDT). The overall objective of ongoing studies in our laboratory is to assess the efficiency of antibacterial PDT on various oral pathogenic bacteria, as well as to determine the side-effects of PDT upon tooth structure. The aim of the present study was to evaluate the

Lei Sui; Pingting Wang; Rui Li; Changyi Li

2009-01-01

229

Photodynamic therapy for Barrett’s esophagus with high-grade dysplasia  

Microsoft Academic Search

This article describes advances in photodynamic therapy for patients with Barrett’s esophagus and high-grade dysplasia—an\\u000a important, minimally invasive treatment option proven to safely and durably ablate Barrett’s dysplasia and prevent carcinoma\\u000a while preserving the gastroesophageal junction.

Herbert C. Wolfsen

2005-01-01

230

Phototherapy, Photodynamic therapy and Photophoresis in the Treatment of Connective-Tissue Diseases: A Review.  

PubMed

Connective-tissue disorders, which include lupus erythematosus, morphea/scleroderma, and dermatomyositis, are characterized by cutaneous manifestations that are sometimes resistant to conventional therapy. Light treatments, which include phototherapy, photodynamic therapy, and photopheresis, are routinely utilized in the treatment of dermatologic conditions and may provide unique mechanisms of action in the treatment of these connective-tissue disorders. The objective of this study is to conduct a review of the literature that describes the use of phototherapy, photodynamic therapy and photopheresis in the treatment of lupus erythematosus, morphea/scleroderma, and dermatomyositis. A MEDLINE search was conducted to find articles that discussed treatment of connective-tissue diseases with light therapies and greater than 30 publications that discussed light therapy for these diseases were identified. These ranged in design from case reports to randomized, prospective trials. Study outcomes and details were summarized and presented within each connective-tissue disease by light therapy modality, which include phototherapy, photodynamic therapy and photopheresis. Although there is a known association between photosensitivity and connective-tissue diseases, light therapies, when used appropriately, may be legitimate therapeutic options for recalcitrant cutaneous manifestations in lupus erythematosus, morphea/scleroderma, and dermatomyositis. This article is protected by copyright. All rights reserved. PMID:25400115

Gordon Spratt, E A; Gorcey, L V; Soter, N A; Brauer, J A

2014-11-15

231

Near-IR-triggered photothermal/photodynamic dual-modality therapy system via chitosan hybrid nanospheres.  

PubMed

Gold nanorods (AuNR)- and indocyanine green (ICG)-encapsulated chitosan hybrid nanospheres (CS-AuNR-ICG NSs) were successfully prepared and used for photothermal and photodynamic combined therapy with a single irradiation. These nanospheres were characterized by transmission electron microscopy, dynamic light scattering and UV-Vis absorption spectra. The in vivo anticancer effects of the hybrid nanospheres were examined by photodynamic therapy (PDT), photothermal therapy (PTT), and PTT/PDT combined therapy. It was found that the hybrid nanospheres had spherical size of 180 nm and a broad adsorption from 650 nm to 900 nm. The spherical chitosan matrix could effectively load ICG and protect it from the rapid hydrolysis. In vivo near-infrared fluorescence imaging and biodistribution demonstrated that ICG and AuNR could be selectively delivered to the tumor site with high accumulation. With the irradiation by 808 nm laser, chitosan hybrid nanospheres were capable to simultaneously produce sufficient hyperthermia and reactive oxygen species to kill cancer cells at irradiation sites, resulting in the complete tumor disappearance in the most of tumor-bearing mice. Compared with photothermal therapy or photodynamic therapy alone, the combined therapy had a significantly synergistic effect and improved the therapeutic efficacy. PMID:23896004

Chen, Rui; Wang, Xin; Yao, Xikuan; Zheng, Xianchuang; Wang, Jing; Jiang, Xiqun

2013-11-01

232

[Adjuvant therapies for sepsis and shock: which are more effective?].  

PubMed

Adjuvant therapy for severe sepsis and shock can be divided into 4 groups. The first group comprises those compounds with proven efficacy in human studies (activated protein C and recombinant bacterial permeability-increasing protein). The second group includes compounds with potential efficacy (heparin), while the third group represents those with no demonstrated efficacy in randomised clinical trials (tumour necrosis factor and interleukin-1 antibodies and receptor antagonists). The fourth group includes those drugs which have been found to be potentially effective in animal studies, but which have not yet been evaluated in humans (i.e., tyrosine kinase inhibitors, selective inducible nitric oxide synthase inhibitors, polyadenosine-diphosphate-ribose-polymerase and caspase III (apoptosis) inhibitors). Formal clinical comparisons between the various treatment options are necessary to assist the clinician in selecting the appropriate form of therapy. PMID:11572169

Groeneveld, A B; Beishuizen, A; Appelmelk, B J; Girbes, A R

2001-09-01

233

Own Experience in Treatment of Patients with Penile Cancer Using Photodynamic Therapy  

PubMed Central

Penile cancer is a rare pathology. For penile cancer surgical treatment, radiotherapy, chemotherapy, and combined modality treatment are available. Because of great importance of this organ for mental condition of patient, the development of organ-preserving methods allowing to minimize impact on patient's quality of life without compromising of oncological results is desirable. In the Center of Laser and Photodynamic diagnosis and treatment of tumors in P.A. Herzen Moscow Cancer Research Institute the methods of photodynamic therapy in patients with penile cancer have been developed. From 2011 to 2013 the treatment was conducted in 11 patients with precancer and cancer of penile. The average age was 56.6. According to morphological diagnosis photodynamic therapy (PDT) was performed using two methods. One method included topical application of agent for PDT and the second intravenous administration of photosensitizer. For topical application alasens was used and for intravenous injection we applied radachlorine. All patients had no complications. Complete regression was achieved in 9 patients, and partial regression in 2. Thus, the results showed that photodynamic therapy for penile cancer stage Tis-1N0M0 permits performing organ-preserving treatment with satisfactory oncological results and no impairment of patient's quality of life.

Filonenko, Elena; Kaprin, Andrey; Alekseev, Boris; Urlova, Antonina

2015-01-01

234

Apoptosis triggered by pyropheophorbide-? methyl ester-mediated photodynamic therapy in a giant cell tumor in bone  

NASA Astrophysics Data System (ADS)

A giant cell tumor in bone is the common primary bone tumor with aggressive features, occurring mainly in young adults. Photodynamic therapy is a new therapeutic technique for tumors. In this study, we investigated the effects of Pyropheophorbide-? methyl ester (MPPa)-mediated photodynamic therapy on the proliferation of giant cell tumor cells and its mechanism of action. Cell proliferation was evaluated using an MTT assay. Cellular apoptosis was detected by Hoechst nuclear staining, and flow cytometric assay. Mitochondrial membrane potential changes and cytochrome c, caspase-9, caspase-3, and Bcl-2 expression was assessed. Finally, we found that MPPa-mediated photodynamic therapy could effectively suppress the proliferation of human giant cell tumor cells and induce apoptosis. The mitochondrial pathway was involved in the MPPa-photodynamic therapy-induced apoptosis.

Li, K.-T.; Zhang, J.; Duan, Q.-Q.; Bi, Y.; Bai, D.-Q.; Ou, Y.-S.

2014-06-01

235

Application of benzo[a]phenoxazinium chlorides in Antimicrobial Photodynamic Therapy of Candida albicans biofilms.  

PubMed

The use of Antimicrobial Photodynamic Therapy (APDT) as a new approach to treat localized Candida infections is an emerging and promising field nowadays. The aim of this study was to verify the efficacy of photodynamic therapy using two new benzo[a]phenoxazinium photosensitizers against Candida albicans biofilms: N-(5-(3-hydroxypropylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSc) and N-(5-(11-hydroxyundecylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSd). The photodynamic activity of dyes against C. albicans biofilms was evaluated by incubating biofilms with dyes in the range of 100-300 ?M for 3 or 18 h followed by illumination at 12 or 36 J cm(-2), using a xenon arc lamp (600 ± 2 nm). A total photoinactivation of C. albicans biofilm cells was achieved using 300 ?M of FSc with 18 h of incubation, followed by illumination at 36 J cm(-2). Contrarily, FSd had insignificant effect on biofilms inactivation by APDT. The higher uptake of FSc than FSd dye by biofilms during the dark incubation may explain the greater photodynamic effectiveness achieved with FSc. The results obtained stresses out the FSc-mediated APDT potential use to treat C. albicans infections. PMID:25463655

Lopes, Marisa; Alves, Carlos Tiago; Rama Raju, B; Gonçalves, M Sameiro T; Coutinho, Paulo J G; Henriques, Mariana; Belo, Isabel

2014-12-01

236

Breast cancer as photodynamic therapy target: Enhanced therapeutic efficiency by overview of tumor complexity  

PubMed Central

Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operative approaches have been investigated for the ablation of a broad range of superficial or bulky solid tumors such as breast cancer, the majority of approved photodynamic therapy protocols are for the treatment of superficial lesions of skin and luminal organs. This review article will discuss recent progress in research focused mainly on assessing the efficacies of various photosensitizers used in photodynamic therapy, as well as the combinatory strategies of various therapeutic modalities for improving treatments of parenchymal and/or stromal tissues of breast cancer solid tumors. Cytotoxic agents are used in cancer treatments for their effect on rapidly proliferating cancer cells. However, such therapeutics often lack specificity, which can lead to toxicity and undesirable side effects. Many approaches are designed to target tumors. Selective therapies can be established by focusing on distinctive intracellular (receptors, apoptotic pathways, multidrug resistance system, nitric oxide-mediated stress) and environmental (glucose, pH) differences between tumor and healthy tissue. A rational design of effective combination regimens for breast cancer treatment involves a better understanding of the mechanisms and molecular interactions of cytotoxic agents that underlie drug resistance and sensitivity. PMID:25493228

Lamberti, María Julia; Vittar, Natalia Belén Rumie; Rivarola, Viviana Alicia

2014-01-01

237

Breast cancer as photodynamic therapy target: Enhanced therapeutic efficiency by overview of tumor complexity.  

PubMed

Photodynamic therapy is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with specific light activation of a photosensitizer agent. Whereas interstitial and intra-operative approaches have been investigated for the ablation of a broad range of superficial or bulky solid tumors such as breast cancer, the majority of approved photodynamic therapy protocols are for the treatment of superficial lesions of skin and luminal organs. This review article will discuss recent progress in research focused mainly on assessing the efficacies of various photosensitizers used in photodynamic therapy, as well as the combinatory strategies of various therapeutic modalities for improving treatments of parenchymal and/or stromal tissues of breast cancer solid tumors. Cytotoxic agents are used in cancer treatments for their effect on rapidly proliferating cancer cells. However, such therapeutics often lack specificity, which can lead to toxicity and undesirable side effects. Many approaches are designed to target tumors. Selective therapies can be established by focusing on distinctive intracellular (receptors, apoptotic pathways, multidrug resistance system, nitric oxide-mediated stress) and environmental (glucose, pH) differences between tumor and healthy tissue. A rational design of effective combination regimens for breast cancer treatment involves a better understanding of the mechanisms and molecular interactions of cytotoxic agents that underlie drug resistance and sensitivity. PMID:25493228

Lamberti, María Julia; Vittar, Natalia Belén Rumie; Rivarola, Viviana Alicia

2014-12-10

238

Photodynamic therapy (ALA-PDT) in the treatment of pathological states of the cornea  

NASA Astrophysics Data System (ADS)

Each year an increasing amount of research is published on the use of photodynamic therapy in medicine. The most recent research has focused mostly on the use of photosensitizer called vertoporphyrin (Visudyne) is the treatment of subretinal neovascularization in age-related macular degeneration (AMD) or myopia, following a substantial amount of ophthalmology research mostly experimental on the application of the method in diagnosis and treatment of some eye tumors. In the Department of Ophthalmology of Polish Medical University in Warsaw, PDT was used as supplementary method in a selected group of patients with chronic virus ulcer of the cornea and keratopathies. During the treatment 5-aminolevulinic acid (5-ALA) was applied in ointment form as a photosensitizer activated with light wave of 633 nm. It appears, on the basis of the results obtained, that photodynamic therapy (ALA-PDT) may become in the future a valuable supplement to the methods being used at the present treating pathological states of the cornea.

Switka-Wieclawska, Iwona; Kecik, Tadeusz; Kwasny, Miroslaw; Graczyk, Alfreda

2003-10-01

239

Photodynamic therapy and endoscopic metal stent placement for esophageal papillomatosis associated with squamous cell carcinoma.  

PubMed

Esophageal squamous papillomatosis is a rare condition associated with human papilloma virus infection and has been complicated by the development of squamous cell carcinoma. Photodynamic therapy using porfimer sodium has been used for the treatment of esophageal cancer but has not been utilized in the treatment of esophageal squamous papillomatosis. We report here the first case of papillomatosis and obstructing squamous cell carcinoma of the esophagus palliated with porfimer sodium photodynamic therapy indicating successful photosensitizer uptake in papilloma-laden tissue. Extensive debulking of papilloma and tumor allowed esophageal recanalization and placement of a self-expanding metal stent for long-term dysphagia palliation. This unique case highlights the combined use of endoscopic techniques for optimal treatment results. PMID:15230738

Wolfsen, H C; Hemminger, L L; Geiger, X J; Krishna, M; Woodward, T A

2004-01-01

240

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

241

Studying Light Propagation in Bone for Treatment of Bone Cancers with Photodynamic Therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy makes use of light, photosensitizing agents, and oxygen as a selective means of treating cancer. The work presented is aimed at applying photodynamic therapy towards treatment of osteosarcoma in small animal clinics. To best facilitate clinical treatments, we must first understand how light propagates and how best to deliver adequate light to achieve phototoxic effects within bone. This work aims at characterizing how light propagates through bone and then applying that knowledge towards predicting light distributions in bone. Reflectance spectroscopy using an optical fiber source-collector pair is used to determine the scattering properties of bone tissues, and the absorption due to water and oxygenated and deoxygenated hemoglobin---native absorbers at visible and near-IR wavelengths. Resulting optical characterizations are then applied to a cylindrically symmetric Monte Carlo model in order to predict and guide the delivery of light within bone in order to achieve the desired phototoxic effect.

Rossi, Vincent; Gustafson, Scott; Jacques, Steven

2008-05-01

242

Modification by vasoactive drugs of tumour destruction by photodynamic therapy with haematoporphyrin derivative.  

PubMed Central

Since the vascular endothelium is a primary site of damage after photodynamic therapy (PDT), it seemed likely that drugs which affect the vasculature may modify the outcome of PDT. Noradrenaline, propranolol, hydralazine and phenoxybenzamine inhibited photodynamic damage to tumours if these drugs were administered concurrently with HPD, 2 h before irradiation. This inhibition was associated with reduced uptake of HPD into tumours. There was no inhibition if irradiation was delayed until 24 h after administration of vasoactive drug, presumably because HPD uptake continued after the drugs had ceased to affect the vasculature. Verapamil enhanced photodynamic destruction of tumours when administered concurrently with HPD and the enhancement was associated with increased uptake of HPD into tumours. Verapamil neither increased uptake of HPD nor enhanced photodynamic destruction of cells in vitro. When verapamil was administered after irradiation, regrowth of tumours was inhibited. A similar effect was previously demonstrated with glucocorticoids. Other calcium channel blocking agents diltiazem and nifedipine had no effect on uptake of HPD or inhibition of regrowth of tumours after PDT. Inhibition of capillary or stromal ingrowth into tumours seems a plausible explanation of this effect of verapamil. This commonly used drug may be useful to enhance the efficacy of PDT. PMID:2525402

Cowled, P. A.; Forbes, I. J.

1989-01-01

243

Adjuvant trials of aromatase inhibitors: determining the future landscape of adjuvant endocrine therapy  

Microsoft Academic Search

This review will discuss the role of aromatase inhibitors (AIs) in the adjuvant setting, and will summarize major strategies behind individual adjuvant trials using aromatase inhibitors. Studies with the third generation AIs including anastrozole, letrozole and exemestane, have shown better outcome and improved therapeutic ratio over second line hormonal approaches (i.e. progestins or aminoglutethimide) and, more recently, over tamoxifen also.

Joseph Ragaz

2001-01-01

244

Cost-effectiveness of Extended Adjuvant Letrozole Therapy After 5 Years of Adjuvant Tamoxifen Therapy in Postmenopausal Women With Early-stage Breast Cancer  

Microsoft Academic Search

model. Methods: Using a Markov model, we estimated the incremen- tal cost per quality-adjusted life-year (QALY) gained with extended adjuvant letrozole vs no extended adjuvant therapy. Probabilities of breast cancer recurrence or new contralateral tumor adverse effects and death were estimated using data from the MA.17 study and other secondary sources. Costs (in 2004 US dollars) and quality-of- life effects

Thomas E. Delea; Jonathan Karnon; Robert E. Smith

2006-01-01

245

Harnessing cellular differentiation to improve ALA-based photodynamic therapy in an artificial skin model  

Microsoft Academic Search

During ALA-based photodynamic therapy (PDT), a pro-drug (aminolevulinic acid; ALA) is taken up by tumor cells and metabolically converted to a photosensitizing intermediate (protoporphyrin IX; PpIX). ALA-based PDT, while an emerging treatment modality, remains suboptimal for most cancers (e.g. squamous cell carcinoma of the skin). Many treatment failures may be largely due to insufficient conversion of ALA to PpIX within

Edward Maytin; Sanjay Anand; Nobuyuki Sato; Judith Mack; Bernhard Ortel

2005-01-01

246

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

247

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

248

Optimizing light dosimetry in photodynamic therapy of the bronchi by fluorescence spectroscopy  

Microsoft Academic Search

Under identical conditions (drug and light dose, timing), the results of photodynamic therapy (PDT) of carcinomas of the bronchi with tetra(meta-hydroxyphenyl)chlorin (mTHPC) show large variations between patients. Before patients underwent PDT treatment, the mTHPC level was measured in the lesion, the normal surrounding tissue and the oral cavity, with an apparatus based on fluorescence spectroscopy. The fluctuations in degree of

D. Braichotte; J.-F. Savary; T. Glanzmann; P. Monnier; G. Wagnières; H. Bergh

1996-01-01

249

Histological findings of a surgically excised myopic choroidal neovascular membrane after photodynamic therapy  

Microsoft Academic Search

Background The authors describe a myopic choroidal neovascular membrane excised 4 months after photodynamic therapy (PDT). Methods A 68-year-old woman with classic choroidal neovascularization (CNV) due to pathologic myopia underwent PDT with verteporfin in the left eye. Four months after treatment a full-thickness macular hole was diagnosed in the same eye and the patient underwent vitrectomy with submacular membranectomy. The

A. Scupola; L. Ventura; A. C. Tiberti; D. D’Andrea; E. Balestrazzi

2004-01-01

250

Enhancement of the efficiency of photodynamic therapy of tumours by t-butyl-4-hydroxyanisole  

Microsoft Academic Search

The effects of photodynamic therapy (PDT) alone and in combination with 3(2)-t-butyl-4-hydroxyanisole (BHA) on Ehrlich ascites carcinoma (EAC) cells have been investigated. BHA, a widely used food antioxidant, administered to the cells prior to light exposure is found to cause concentration-dependent alterations of the haematoporphyrin derivative (HpD)-based PDT. BHA (0.15 mM) causes a small (about 10%) inhibition in the rate

Igor Shevchuk; Vladimir Chekulayev; Lyudmila Chekulayeva

1998-01-01

251

Photosensitizer-Conjugated Silica-Coated Gold Nanoclusters for Fluorescence Imaging-Guided Photodynamic Therapy  

PubMed Central

Multifunctional theranostics have recently been intensively explored to optimize the efficacy and safety of therapeutic regimens. In this work, a photo-theranostic agent based on chlorin e6 (Ce6) photosensitizer-conjugated silica-coated gold nanoclusters (AuNCs@SiO2-Ce6) is strategically designed and prepared for fluorescence imaging-guided photodynamic therapy (PDT). The AuNCs@SiO2-Ce6 shows the following features: i) high Ce6 photosensitizer loading; ii) no non-specific release of Ce6 during its circulation; iii) significantly enhanced cellular uptake efficiency of Ce6, offering a remarkably improved photodynamic therapeutic efficacy compared to free Ce6; iv) subcellular characterization of the nanoformula via both the fluorescence of Ce6 and plasmon luminescence of AuNCs; v) fluorescence imaging-guided photodynamic therapy (PDT). This photo-theranostics owns good stability, high water dispersibility and solubility, non-cytotoxicity, and good biocompatibility, thus facilitating its biomedical applications, particularly for multi-modal optical, CT and photoacoustic (PA) imaging guided PDT or sonodynamic therapy. PMID:23523428

Huang, Peng; Lin, Jing; Wang, Shouju; Zhou, Zhijun; Li, Zhiming; Wang, Zhe; Zhang, Chunlei; Yue, Xuyi; Niu, Gang; Yang, Min; Cui, Daxiang; Chen, Xiaoyuan

2013-01-01

252

Effective near-infrared photodynamic therapy assisted by upconversion nanoparticles conjugated with photosensitizers  

PubMed Central

A drug model photosensitizer–conjugated upconversion nanoparticles nanocomplex was explored for application in near-infrared photodynamic therapy. As near-infrared penetrates deeper into the tissue, the model is useful for the application of photodynamic therapy in deeper tissue. The nanocomplex that was synthesized had low polydispersity, and the upconversion nanoparticle was covalently conjugated with the photosensitizer. The robust bond could prevent the undesired premature release of photosensitizer and also enhance the singlet-oxygen generation. Singlet-oxygen generation rate from this nanocomplex was evaluated in solution. The photodynamic therapy effect was assessed with MCF-7 cells in two different methods, 3-(4,5-dimethylth-iazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead assay. The assay results showed that promising efficacy (>90%) can be achieved with a low concentration (50 ?g mL?1) of this nanocomplex and mild dosage (7 mW cm?2) of near-infrared laser treatment. PMID:25609954

Dou, Qing Qing; Teng, Choon Peng; Ye, Enyi; Loh, Xian Jun

2015-01-01

253

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

254

Adjuvant endocrine therapy for postmenopausal breast cancer in the era of aromatase inhibitors: an update  

Microsoft Academic Search

There is overwhelming evidence that optimal adjuvant endocrine therapy for hormone sensitive breast cancer in postmenopausal women should include a third generation aromatase inhibitor (AI). On current evidence, adjuvant anstrozole or letrozole should be used upfront in such patients especially in those with high risk disease (node positive and\\/or tumours > 2 cm). The sequential approach of tamoxifen for 2–3

Ramia Mokbel; Isabella Karat; Kefah Mokbel

2006-01-01

255

Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome  

NASA Astrophysics Data System (ADS)

Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

2006-02-01

256

Tetrakis(p-Carboranylthio-Tetrafluorophenyl)Chlorin (TPFC): Application for Photodynamic Therapy and Boron Neutron Capture Therapy.  

PubMed

Carboranyl-containing chlorins have emerged as promising dual sensitizers for use in both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT), by virtue of their known tumor affinity, low cytotoxicity in dark conditions, and their strong absorptions in the red region of the optical spectrum. Tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC) is a new synthetic carboranyl-containing chlorin of high boron content (24% by weight). To evaluate TPFC's applicability as sensitizer for both PDT and BNCT, we performed an in vitro and in vivo study using F98 rat glioma cells and F98 rat glioma-bearing brain tumor models. For the in vivo BNCT study, we used boronophenylalanine (BPA), which is currently used in clinical BNCT studies, via intravenous administration (i.v.) and/or used TPFC via convection-enhanced delivery (CED), a method for local drug infusion directly into the brain. In the in vitro PDT study, the cell surviving fraction following laser irradiation (9 J/cm(2) ) was 0.035 whereas in the in vitro BNCT study, the cell surviving fraction following neutron irradiation (thermal neutron = 1.73 × 10(12) n/cm(2) ) was 0.04. In the in vivo BNCT study, the median survival time following concomitant administration of BPA (i.v.) and TPFC (CED) was 42 days (95% confidence interval; 37-43 days). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:962-970, 2015. PMID:25546823

Hiramatsu, Ryo; Kawabata, Shinji; Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Ono, Koji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko; Hao, Erhong; Vicente, M Graça H

2015-03-01

257

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

258

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.

259

New approaches to local destruction of tumors: interstitial laser hyperthermia and photodynamic therapy  

NASA Astrophysics Data System (ADS)

Lasers are well established as the treatment of choice in certain types of cancer, particularly the use of carbon dioxide laser for eradication of early tumors of the cervix and for lesions of the upper airways. More recently, the high-power Nd:YAG laser has proven itself of value for endoscopic palliation of advanced obstructing tumors of the gastrointestinal tract and major airways in patients who are unsuitable for surgery. However, current techniques are only scratching the surface of the potential applications of lasers in medical and surgical practice, and this article outlines two ways in which laser therapy for cancer may develop--low power interstitial hyperthermia and photodynamic therapy.

Bown, Stephen G.

1991-11-01

260

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

PubMed

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

261

Where does photodynamic therapy fit in the esophageal cancer treatment jigsaw puzzle?  

PubMed

Traditional treatment options for esophageal cancer have centered on the triad of surgery, chemotherapy, and radiotherapy. Although surgery remains the gold standard for operable disease, photodynamic therapy (PDT) is emerging as a valid minimally invasive option for select patients with inoperable disease. Years of experience with PDT for esophageal cancer seem to suggest that it may be particularly useful for treatment of early unresectable lesions, palliation of locally advanced disease, and salvage therapy for stent blockage or local tumor recurrence. Further investigation into the ideal role for PDT, perhaps through a comparative study with other nonsurgical options, may help clarify where it fits in the treatment armamentarium for esophageal cancer. PMID:23055217

Moghissi, Keyvan

2012-10-01

262

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

263

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

264

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

265

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

266

Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing  

NASA Astrophysics Data System (ADS)

Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02495h

Wang, Xin; Liu, Kai; Yang, Guangbao; Cheng, Liang; He, Lu; Liu, Yumeng; Li, Yonggang; Guo, Liang; Liu, Zhuang

2014-07-01

267

Photodynamic therapy of malignant brain tumours: a complementary approach to conventional therapies.  

PubMed

The poor outcome of primary malignant brain tumours is predominantly due to local invasion and local recurrence and their prognosis is highly dependent on the degree of resection. They have no border and, at best, a marginal zone that remains invisible to the surgeon. Photodynamic therapy (PDT) appears to be an interesting modality to fill the need for a targeted treatment that may reduce recurrence and extend survival with minimal side effects. In this review, we summarize the different technologies of brain tumour PDT employed such as interstitial PDT, and PDT-associated surgical resection, describing new light delivery devices. The role of dosimetry - one of the key factors behind successful brain tumour PDT - is discussed. This can be achieved by integrating results from in vivo studies. In this context, the development of new therapeutic photosensitizer delivery systems is also an area of significant research interest. Multifunctionality can be engineered into a single nanoplatform to provide tumour-specific detection, treatment, and follow-up. Such multitasking systems appear to be complementary to conventional technologies. PMID:22858248

Bechet, Denise; Mordon, Serge R; Guillemin, François; Barberi-Heyob, Muriel A

2014-03-01

268

Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy  

NASA Astrophysics Data System (ADS)

Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

Petryk, Alicia Ailie

269

Polymeric micelles encapsulating photosensitizer: structure/photodynamic therapy efficiency relation.  

PubMed

Various polymeric micelles were formed from amphiphilic block copolymers, namely, poly(ethyleneoxide-b-?-caprolactone), poly(ethyleneoxide-b-d,l-lactide), and poly(ethyleneoxide-b-styrene). The micelles were characterized by static and dynamic light scattering, electron microscopy, and asymmetrical flow field-flow fractionation. They all displayed a similar size close to 20 nm. The influence of the chemical structure of the block copolymers on the stability upon dilution of the polymeric micelles was investigated to assess their relevance as carriers for nanomedicine. In the same manner, the stability upon aging was assessed by FRET experiments under various experimental conditions (alone or in the presence of blood proteins). In all cases, a good stability over 48 h for all systems was encountered, with PDLLA copolymer-based systems being the first to release their load slowly. The cytotoxicity and photocytotoxicity of the carriers were examined with or without their load. Lastly, the photodynamic activity was assessed in the presence of pheophorbide a as photosensitizer on 2D and 3D tumor cell culture models, which revealed activity differences between the 2D and 3D systems. PMID:24552313

Gibot, Laure; Lemelle, Arnaud; Till, Ugo; Moukarzel, Béatrice; Mingotaud, Anne-Françoise; Pimienta, Véronique; Saint-Aguet, Pascale; Rols, Marie-Pierre; Gaucher, Mireille; Violleau, Frédéric; Chassenieux, Christophe; Vicendo, Patricia

2014-04-14

270

Psychosocial implications of clinical trials on patients with age-related macular degeneration and pathologic myopia as seen in the photodynamic therapy trials  

Microsoft Academic Search

Photodynamic therapy is a combination of the systemically injected photosensitizing drug, verteporfin, and the subsequent exposure of the affected retina to a low-beam diode laser. Eligible participants in the photodynamic therapy clinical trial were those with “wet” cases of age-related macular degeneration with subfoveal, predominantly classic lesions. The expected outcome of the treatment is to preserve vision, not to restore

Tracey Porter; Pat Nesbitt

2001-01-01

271

Sustained Activation of the Extracellular Signal-regulated Kinase Pathway Protects Cells from Photofrin-mediated Photodynamic Therapy1  

Microsoft Academic Search

Photodynamic therapy (PDT) is a cancer therapy in which a photosen- sitizer selectively accumulates in tumor cells and is subsequently activated by light of a specific wavelength. The activation of the photosensitizer leads to cytotoxic photoproducts that result in tumor regression. PDT can lead to several cellular responses including cell cycle arrest, necrosis, and apoptosis, as well as trigger many

Zhimin Tong; Gurmit Singh; Andrew J. Rainbow

272

Enhanced photodynamic efficacy and efficient delivery of Rose Bengal using nanostructured poly(amidoamine) dendrimers: potential application in photodynamic therapy of cancer  

Microsoft Academic Search

Photodynamic therapy (PDT) is a promising treatment methodology whereby diseased cells and tissues are destroyed by reactive\\u000a oxygen species (ROS) by using a combination of light and photosensitizers (PS). The medical application of Rose Bengal (RB),\\u000a photosensitizer with very good ROS generation capability, is limited due to its intrinsic toxicity and insufficient lipophilicity.\\u000a In this report, we evaluate the potential

Krishnamoorthy Karthikeyan; Anish Babu; Sang-Jae Kim; Ramachandran Murugesan; Kadarkaraithangam Jeyasubramanian

273

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

274

Combination of photodynamic and ultrasonic therapy for treatment of infected wounds in animal model  

NASA Astrophysics Data System (ADS)

One of the important problems of modern medicine is treatment of infected wounds. There are many diversified expedients of treatment, but none of them obey the modern physician completely. The aim of this study is to develop and test a new combined method of photodynamic ultrasonic therapy (PDUST) for treatment of infected wounds with focus on experimental trials. PDUST is based on a combination of two methods: photodynamic (PD) therapy (PDT) with photosensitizer and low frequency ultrasonic (US) therapy with antibiotic as tools for treatment of wounds and effectively killing bacteria. The main parameters are: US frequency - 26.5 kHz; US tip elongation - 40+/-20 ?m wavelength of light emitting diodes (LED) array - 660+/-10 nm; light intensity on biotissue surface - 1-2 mW/cm2; photosensitizer - an aluminum disulfonated phtalocyanine dissolved in a physiological solution in concentration 10 mg/l. The experiments were carried out with 70 male chinchilla rabbits divided into 7 groups, thus the dynamics of wounds healing were studied in different modes of PDUST. The PD and US methods supplement each other and in conjunction provide additive and especially synergetic effects. The experimental data demonstrated advantages of new technology in comparison with conventional methods in cases of treatment of extended suppurative inflammatory and profound wounds. The more detailed study of PDUST method's mechanism, which is based on low intensity of LED light, PD therapy and US influence is required.

Menyaev, Yulian A.; Zharov, Vladimir P.

2006-02-01

275

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

276

Conscious sedation with inhaled 50% nitrous oxide/oxygen premix in photodynamic therapy sessions for vulvar lichen sclerosus treatment*  

PubMed Central

Photodynamic therapy has been described as an effective therapeutic option in selected cases of anogenital lichen sclerosus that are refractory to first-line treatments. However, procedure-related pain is a limiting factor in patient adherence to treatment. The authors report the case of a 75-year-old woman with highly symptomatic vulvar lichen sclerosus, successfully treated with photodynamic therapy. An inhaled 50% nitrous oxide/oxygen premix was administered during sessions, producing a pain-relieving, anxiolytic, and sedative effect without loss of consciousness. This ready-to-use gas mixture may be a well-tolerated and accepted alternative to classical anesthetics in Photodynamic therapy, facilitating patients' adherence to illumination of pain-prone areas. PMID:25672311

Cabete, Joana; Campos, Sara; Lestre, Sara

2015-01-01

277

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

278

How I Perform ALA-Photodynamic Therapy in My Practice  

Microsoft Academic Search

\\u000a ALA-PDT is a safe and efficacious therapy for the treatment and rejuvenation of sun-damaged skin, AKs and actinic porokeratoses,\\u000a and acne. Clearance rates are typically very high with only several treatments. ALA-PDT does not require prolonged application\\u000a and contact time compared with chemotherapeutic agents, resulting in reduced adverse events. Further, compared with other\\u000a topical or systemic therapies, ALA-PDT is cost

Dore J. Gilbert

279

Postoperative adjuvant therapy for resectable thoracic esophageal squamous cell carcinoma: a retrospective analysis of 426 cases.  

PubMed

The aim of this study was to evaluate the value of postoperative adjuvant therapy for resectable thoracic esophageal squamous cell carcinoma (ESCC) in China. We retrospectively analyzed 426 eligible patients seen between October 2007 and November 2011. Specifically, we assessed clinicopathological characteristics and the disease-free and overall survival rates. Of the 426 patients, 272 cases underwent surgery alone, and 154 cases received postoperative adjuvant therapy (67 cases with radiotherapy, 57 cases with chemotherapy, and 30 cases with simultaneous chemoradiotherapy). The median follow-up time was 48.0 months (23.0-72.0 months), and the median survival time was 48.4 months (1.0-72.0 months). We found a significant difference between the surgery-alone and adjuvant therapy groups in the status of lymph node (LN) metastasis (N stage; P < 0.01), but there were no differences between the two groups with regard to other clinicopathological characteristics, including age, sex, lesion location, T stage, differentiation grades, surgery approach, or average number of LN dissections. The 5-year disease-free survival (DFS) rates of the surgery-alone and adjuvant therapy groups were 48.9 and 37.1 %, respectively (P < 0.001); no significant difference was found in 5-year overall survival (OS) rate between the two groups (P > 0.05). A stratification analysis based on N stage suggested that the 5-year DFS and OS rates were similar in N0-N3 subgroups (P > 0.05), except that patients with surgery alone had a higher 5-year DFS than those with postoperative adjuvant therapy in N0 subgroup (P = 0.013). Our data suggest that patients with resectable thoracic ESCC may not benefit from postoperative adjuvant therapy. Further prospective studies are required to elucidate the utility of postoperative adjuvant therapy and to standardize individualized treatments for resectable ESCC. PMID:25479943

Chen, Hailu; Wu, Zhiyong; Chen, Jiexin; Lin, Xiaorong; Zheng, Chunpeng; Fan, Yanghang; Zhang, Zechun; Yao, Xiaodong; Wu, Jianyi; Xu, Liyan; Li, Enmin

2015-01-01

280

Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections  

PubMed Central

Aims Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. Materials & methods We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 × 107 cells) and Pseudomonas aeruginosa (5 × 106 cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm2 of broadband white light (400–700 nm). Results In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). Conclusion These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue. PMID:21143031

Lu, Zongshun; Dai, Tianhong; Huang, Liyi; Kurup, Divya B; Tegos, George P; Jahnke, Ashlee; Wharton, Tim; Hamblin, Michael R

2011-01-01

281

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

282

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

283

Oleic Acid as Optimizer of the Skin Delivery of 5-Aminolevulinic Acid in Photodynamic Therapy  

Microsoft Academic Search

\\u000a Purpose  In photodynamic therapy (PDT), topically applied aminolevulinic acid (5-ALA) is converted to protoporphyrin IX (PpIX), which\\u000a upon light excitation induces tumor destruction. To optimize 5-ALA-PDT via improving the highly hydrophilic 5-ALA limited\\u000a penetration into the skin, we propose the use of the known skin penetration enhancer, oleic acid (OA).\\u000a \\u000a \\u000a \\u000a Methods  In vitro skin penetration and retention of 5-ALA (1% w\\/w) were measured

Maria Bernadete Riemma Pierre; Eduardo Ricci Jr; Antonio Cláudio Tedesco; Maria Vitória Lopes Badra Bentley

2006-01-01

284

Photodynamic Therapy in Bowen Disease of the First Web Space of the Hand  

PubMed Central

Bowen disease (BD), or intraepithelial squamous cell carcinoma (SCC), may progress to an invasive SCC. Although surgery is preferred because of the low recurrence rate, it can result in hypertrophic scarringor contracture, particularly in lesions on the hands. We report a case of BD in the first web space of the hand, which was treated with ablative fractional laser-assisted photodynamic therapy (AFXL-assisted PDT). After multiple AFXL-assisted PDT sessions, the lesion showed no clinical or pathological abnormalities. Thus, we believe that PDT can be an alternative treatment for BD occurring in the web space of the hand. PMID:25673936

Jung, Soo-Eun; Kim, Sue Kyung

2015-01-01

285

The pilot experience of immunotherapy-combined photodynamic therapy for advanced gastric cancer in elderly patients  

Microsoft Academic Search

Background. Therapeutic efficacy of endoscopic photodynamic therapy (PDT) for advanced gastric cancer is limited. Recent animal studies\\u000a have clarified the very important role of host immune cells in PDT. We expected a potential cooperative effect of PDT and\\u000a immunotherapy, and developed immunotherapy-combined PDT (I-PDT) for advanced gastric cancer.\\u000a \\u000a \\u000a Methods and Materials. We applied I-PDT for two elderly patients with complicated

Hideo Yanai; Yasuyuki Kuroiwa; Norio Shimizu; Yoshitaka Matsubara; Takeshi Okamoto; Atsuyoshi Hirano; Youhei Nakamura; Kiwamu Okita; Teruaki Sekine

2002-01-01

286

Toluidine blue-mediated photodynamic therapy of oral wound infections in rats  

Microsoft Academic Search

The purpose of this study was to examine the effect of toluidine blue (TB)-mediated photodynamic therapy (PDT) on oral wound\\u000a infections in rats. The study called for a combination treatment of a 1mg\\/ml solution of TB with a red light at three intensity\\u000a settings of 12 J\\/cm2, 24 J\\/cm2 and 48 J\\/cm2. In the group that was given the highest light dose of

J. Lin; L. J. Bi; Z. G. Zhang; Y. M. Fu; T. T. Dong

2010-01-01

287

808 nm driven Nd3+-sensitized upconversion nanostructures for photodynamic therapy and simultaneous fluorescence imaging  

NASA Astrophysics Data System (ADS)

The in vivo biological applications of upconversion nanoparticles (UCNPs) prefer excitation at 700-850 nm, instead of 980 nm, due to the absorption of water. Recent approaches in constructing robust Nd3+ doped UCNPs with 808 nm excitation properties rely on a thick Nd3+ sensitized shell. However, for the very important and popular Förster resonance energy transfer (FRET)-based applications, such as photodynamic therapy (PDT) or switchable biosensors, this type of structure has restrictions resulting in a poor energy transfer. In this work, we have designed a NaYF4:Yb/Ho@NaYF4:Nd@NaYF4 core-shell-shell nanostructure. We have proven that this optimal structure balances the robustness of the upconversion emission and the FRET efficiency for FRET-based bioapplications. A proof of the concept was demonstrated for photodynamic therapy and simultaneous fluorescence imaging of HeLa cells triggered by 808 nm light, where low heating and a high PDT efficacy were achieved.The in vivo biological applications of upconversion nanoparticles (UCNPs) prefer excitation at 700-850 nm, instead of 980 nm, due to the absorption of water. Recent approaches in constructing robust Nd3+ doped UCNPs with 808 nm excitation properties rely on a thick Nd3+ sensitized shell. However, for the very important and popular Förster resonance energy transfer (FRET)-based applications, such as photodynamic therapy (PDT) or switchable biosensors, this type of structure has restrictions resulting in a poor energy transfer. In this work, we have designed a NaYF4:Yb/Ho@NaYF4:Nd@NaYF4 core-shell-shell nanostructure. We have proven that this optimal structure balances the robustness of the upconversion emission and the FRET efficiency for FRET-based bioapplications. A proof of the concept was demonstrated for photodynamic therapy and simultaneous fluorescence imaging of HeLa cells triggered by 808 nm light, where low heating and a high PDT efficacy were achieved. Electronic supplementary information (ESI) available: TEM images, XRD patterns and NIR emission spectra of UCNPs. See DOI: 10.1039/c4nr04953e

Wang, Dan; Xue, Bin; Kong, Xianggui; Tu, Langping; Liu, Xiaomin; Zhang, Youlin; Chang, Yulei; Luo, Yongshi; Zhao, Huiying; Zhang, Hong

2014-11-01

288

Aromatase Inhibitors as Adjuvant Therapy for Postmenopausal Patients With Early Stage Breast Cancer  

Microsoft Academic Search

ABSTRACT Endocrine therapy of hormone,receptor-positive breast tumors,is widely used as palliative therapy for metastatic breast cancer,and,as adjuvant,therapy for early stage breast cancer. Tamoxifen has been the definitive standard,of hormonal,therapies for the last 30 years because,of its documented,efficacy and,reasonable,safety profile. Based on encouraging results from trials utilizing the selective, third generation aromatase inhibitors (AIs) in metastatic breast cancer, a number of

Ragini Kudchadkar; Ruth M. O'regan

289

New distributors for homogeneous and monitorable light delivery in photodynamic therapy  

NASA Astrophysics Data System (ADS)

Novel light distributors for interstitial and esophageal photodynamic therapy are presented. A cylindrical light diffuser has been developed mainly for medical applications like interstitial photodynamic therapy, treatment of the bronchi and arterisclerosis. It can be made with a diameter as small as 1 mm or even less. For interstitial therapy, it can be introduced via a hypodermic needle. The main property of this light diffuser is the homogeneity of the light intensity emitted along its whole length which can be 100 mm or more, as well as its excellent radial homogeneity (360 degree(s)) and flexibility. Furthermore, its optical properties are hardly dependent on wavelength used for treatment (500 - 700 nm). Light distributors for esophageal treatment with homogeneity better than +/- 10% have been built and successfully used clinically. A measuring optical fiber allows the control of the dosimetry during the irradiation. Some other properties like the photosensitizer uptake in the tissue or the photobleaching can also be measured in situ and in real time during the treatment.

Mizeret, Jerome C.; Thielen, P.; Theumann, Jean-Francois; Bays, Roland; Wagnieres, Georges A.; Savary, Jean-Francois; Monnier, Philippe; van den Bergh, Hubert

1995-01-01

290

Potential of microneedles in enhancing delivery of photosensitising agents for photodynamic therapy.  

PubMed

Photodynamic therapy can be used in the treatment of pre-malignant and malignant diseases. It offers advantages over other therapies currently used in the treatment of skin lesions including avoidance of damage to surrounding tissue and minimal or no scarring. Unfortunately, systemic delivery of photosensitising agents can result in adverse effects, such as prolonged cutaneous photosensitivity; while topical administration lacks efficacy in the clearance of deeper skin lesions and those with a thick overlying keratotic layer. Therefore, enhancement of conventional photosensitiser delivery is desired. However, the physicochemical properties of photosensitising agents, such as extreme hydrophilicity or lipophilicity and large molecular weights make this challenging. This paper reviews the potential of microneedles as a viable method to overcome these delivery-limiting physicochemical characteristics and discusses the current benefits and limitations of solid, dissolving and hydrogel-forming microneedles. Clinical studies in which microneedles have successfully improved photodynamic therapy are also discussed, along with benefits which microneedles offer, such as precise photosensitiser localisation, painless application and reduction in waiting times between photosensitiser administration and irradiation highlighted. PMID:25291556

Kearney, Mary-Carmel; Brown, Sarah; McCrudden, Maelíosa T C; Brady, Aaron J; Donnelly, Ryan F

2014-12-01

291

Lobular carcinoma of the breast metastatic to the uterus in a patient under adjuvant anastrozole therapy.  

PubMed

This is the first report of breast carcinoma metastatic to the endometrium in a patient on adjuvant anastrozole therapy. We report a case of metastatic lobular carcinoma of the breast in a 63-year-old patient on adjuvant anastrozole therapy for 8 months. She was asymptomatic and metastatic endometrium was diagnosed after transvaginal ultrasound revealed suspicious findings along with elevated Ca 15-3 levels. As further work up showed no other metastatic sites her uterus was taken out along with her ovaries and pelvic lymph nodes. Uterine metastases should be kept in mind in asymptomatic patients on anastrozole therapy. PMID:16311034

Erkanli, Serkan; Kayaselcuk, Fazilet; Kuscu, Esra; Bolat, Filiz; Sakalli, Hakan; Haberal, Ali

2006-08-01

292

Comparative effects of adjuvant cimetidine and omeprazole during pancreatic enzyme replacement therapy  

Microsoft Academic Search

In a double-blind, randomized crossover study, the hypotheses were tested that more powerful inhibition of gastric acid secretion by adjuvant omeprazole further improves the efficacy of pancreatic enzyme replacement therapy compared to adjuvant cimetidine and that excluding the influence of pH-related factors, by virtually complete inhibition of gastric acid secretion with 60 mg omeprazole daily, does not lead to total

M. J. Bruno; E. A. J. Rauws; F. J. Hoek; G. N. J. Tytgat

1994-01-01

293

In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent  

PubMed Central

In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision medicine” in line with stem cell and gene therapies as tools in cancer therapy. PMID:25453097

Zhang, Tao; Lan, Rongfeng; Chan, Chi-Fai; Law, Ga-Lai; Wong, Wai-Kwok; Wong, Ka-Leung

2014-01-01

294

Combination of chemotherapy and photodynamic therapy using graphene oxide as drug delivery system.  

PubMed

Previous research indicated that graphene oxide (GO) can be used to deliver photosensitive anticancer drug, Hypocrellin A (HA), in photodynamic therapy (PDT). However, the anticancer activity of HA was obviously decreased after been loaded on GO. To solve this problem, a chemotherapy drug, 7-ethyl-10-hydroxycamptothecin (SN-38), was co-loaded on the HA loaded GO (HA/SN-38/GO) as a multimodal carrier for the synergistic combination of PDT and chemotherapy for cancer. In vitro results showed that the combination therapy exhibited a synergistic antiproliferative effect compared with PDT and chemotherapy alone. Therefore, HA/SN-38/GO delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer. PMID:24792568

Zhou, Lin; Zhou, Lin; Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong; Jiang, Huijun; Li, Fuyou; Shen, Jian

2014-06-01

295

Combining magnetic hyperthermia and photodynamic therapy for tumor ablation with photoresponsive magnetic liposomes.  

PubMed

The ongoing nanotech revolution has the potential to transform diagnostic and therapeutic methods. Stimuli-triggered nanotherapies based on remotely activated agents have become attractive alternatives to conventional chemotherapy. Herein, we designed an optimized smart nanoplatform based on dually loaded hybrid liposomes to achieve enhanced tumor therapy. The aqueous core was highly loaded with iron oxide nanoparticles, while the lipid bilayer was supplied with a photosensitizer payload. The double cargo translated into double functionality: generation of singlet oxygen under laser excitation and heat production under alternating magnetic field stimulation, coupling photodynamic therapy (PDT) to magnetic hyperthermia (MHT). These liposomes address both therapeutic agents within tumor cells, and the combined PDT/MHT therapy resulted in complete cancer cell death in vitro while total solid-tumor ablation was achieved in an in vivo rodent model. PMID:25695371

Di Corato, Riccardo; Béalle, Gaëlle; Kolosnjaj-Tabi, Jelena; Espinosa, Ana; Clément, Olivier; Silva, Amanda K A; Ménager, Christine; Wilhelm, Claire

2015-03-24

296

Radiation therapy quality control in a clinical trial of adjuvant postoperative treatment for rectal cancer  

Microsoft Academic Search

Purpose: Deviations from protocol can detract from the reliability of results obtained in prospective clinical trials. In an effort to decrease the number of deviations in a prospective trial of adjuvant treatment for rectal cancer, we undertook pretreatment review of the irradiated fields.Methods and Materials: Before initiation of radiation therapy, patients' radiation therapy fields were simulated by their radiation oncologists

James A. Martenson; Rodolfo Urias; Stephen R. Smalley; Lawrence R. Coia; Joel E. Tepper; Marvin Rotman; Tyvin A. Rich; Michael J. O'Connell

1995-01-01

297

Adjuvant physical therapy versus occupational therapy in patients with reflex sympathetic dystrophy\\/complex regional pain syndrome type I  

Microsoft Academic Search

Oerlemans HM, Oostendorp RAB, de Boo T, van der Laan L, Severens JL, Goris RJA. Adjuvant physical therapy versus occupational therapy in patients with reflex sympathetic dystrophy\\/complex regional pain syndrome type I. Arch Phys Med Rehabil 2000;81:49-56. Objective: To investigate the effectiveness and cost of physical therapy (PT) or occupational therapy (OT) in patients with reflex sympathetic dystrophy (RSD). Design:

H. Margreet Oerlemans; Rob A. B. Oostendorp; Theo de Boo; Lyckle van der Laan; Johan L. Severens; R. Jan A. Goris

2000-01-01

298

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

NASA Astrophysics Data System (ADS)

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 malignant mucosa in patients with superficial cancer. Healing and partial replacement of Barrett's mucosa with normal squamous epithelium occurred in all patients and complete replacement with squamous epithelium was found in two. Side effects included photosensitivity and mild-moderate chest pain and dysphagia for 5 - 7 days. In three patients with extensive circumferential mucosal ablation in the proximal esophagus, healing was associated with esophageal strictures which were treated successfully by esophageal dilation. Strictures were not found in the distal esophagus. Photodynamic therapy combined with long-term acid inhibition provides effective endoscopic therapy of Barrett's mucosal dysplasia and superficial (Tis-T1) esophageal cancer. The windowed centering balloon improves delivery of photodynamic therapy to diffusely abnormal esophageal mucosa.

Overholt, Bergein F.; Panjehpour, Masoud

1995-03-01

299

Quantitative approach to skin field cancerization using a nanoencapsulated photodynamic therapy agent: a pilot study  

PubMed Central

Background This paper introduces a new nanoformulation of 5-aminolevulinic acid (nano-ALA) as well as a novel quantitative approach towards evaluating field cancerization for actinic keratosis and/or skin photodamage. In this pilot study, we evaluated field cancerization using nano-ALA and methyl aminolevulinate (MAL), the latter being commercialized as Metvix®. Methods and results Photodynamic therapy was used for the treatment of patients with selected skin lesions, whereas the fluorescence of the corresponding photosensitizer was used to evaluate the time evolution of field cancerization in a quantitative way. Field cancerization was quantified using newly developed color image segmentation software. Using photodynamic therapy as the precancer skin treatment and the approach introduced herein for evaluation of fluorescent area, we found that the half-life of field cancerization reduction was 43.3 days and 34.3 days for nano-ALA and MAL, respectively. We also found that nano-ALA targeted about 45% more skin lesion areas than MAL. Further, we found the mean reduction in area of skin field cancerization was about 10% greater for nano-ALA than for MAL. Conclusion Although preliminary, our findings indicate that the efficacy of nano-ALA in treating skin field cancerization is higher than that of MAL. PMID:23450821

Passos, Simone K; de Souza, Paulo EN; Soares, Priscila KP; Eid, Danglades RM; Primo, Fernando L; Tedesco, Antonio Cláudio; Lacava, Zulmira GM; Morais, Paulo C

2013-01-01

300

Applications of natural compounds in the photodynamic therapy of skin cancer.  

PubMed

Despite significant advances in early diagnosis and treatment, skin cancer is one of the leading causes of death. Photodynamic therapy (PDT) is a new therapeutic modality that is emerging as an important resource against malignant tumors. This strategy is based on the action of photosensitizers, i.e. of molecules which may accumulate preferentially inside tumor cells where they exert a cytotoxic effect after excitation by light at appropriate wavelengths. Some forms of skin cancers and also some non-tumor pathologies are now treated with PDT. Several compounds with photosensitizing activity have been identified, and some of these molecules are commercially available. Many photoactive principles are natural compounds. Numerous reviews in the last decade have focused on photodynamic therapy, its effects and applications, but less attention has been paid to plant extracts or molecules of natural origin studied for their phototoxic activity to date.This review critically examines the potential role of various plant extracts and naturally occurring compounds in the treatment of skin cancer. Both in vitro and in vivo effects of these agents, together with their known related cellular and molecular mechanisms, are presented and discussed. PMID:23531223

Marrelli, M; Menichini, G; Provenzano, E; Conforti, F

2014-01-01

301

Cell-Penetrating Peptide Enhanced Intracellular Raman Imaging and Photodynamic Therapy  

PubMed Central

We present the application of a theranostic system combining Raman imaging and photodynamic therapy (PDT) effect. The theranostic nanoplatform was created by loading the photosensitizer, Protoporphyrin IX, onto a Raman-labeled gold nanostar. A cell-penetrating peptide, TAT, enhanced intracellular accumulation of the nanoparticles in order to improve their delivery and efficacy. The plasmonic gold nanostar platform was designed to increase the Raman signal via the surface-enhanced resonance Raman scattering (SERRS) effect. Theranostic SERS imaging and photodynamic therapy using this construct were demonstrated on BT-549 breast cancer cells. The TAT peptide allowed for effective Raman imaging and photosensitization with the nanoparticle construct after a 1-hour incubation period. In the absence of the TAT peptide, nanoparticle accumulation in the cells was not sufficient to be observed by Raman imaging, or to produce any photosensitization effect after this short incubation period. There was no cytotoxic effect observed after nanoparticle incubation, prior to light-activation of the photosensitizer. This report shows the first application of combined SERS imaging and photosensitization from a theranostic nanoparticle construct. PMID:23659475

Fales, Andrew M.; Yuan, Hsiangkuo; Vo-Dinh, Tuan

2013-01-01

302

Photodynamic therapy of experimental sarcoma M-1 with boronated chlorine as a photosensitizer.  

PubMed

Using rat model of experimental sarcoma M-1 we studied the efficacy of photodynamic therapy with boronated chlorine as a photosensitizer in doses of 1.25, 2.5, 5.0, and 10.0 mg/ kg body weight. Laser irradiation was performed at energy densities of 150, 300 J/cm(2) and power density of 0.25 and 0.42 W/cm(2). Treatment efficacy was evaluated by the percentage of animals with complete tumor regression, percentage of tumor recurrence and, in cases of its growth, by tumor growth coefficient. The efficacy of photodynamic therapy depended on the dose of boronated chlorine and parameters of the laser irradiation. Optimal conditions were the dose of 2.5 mg/kg at laser energy density of 300 J/cm(2) and power density of 0.42 W/cm(2) and a dose of 5.0 mg/kg at 150 J/cm(2) and 0.25 W/cm(2). PMID:24909720

Kaplan, M A; Ol'shevskaya, V A; Osipchuk, Yu S; Nikitina, R G; Kalinin, V N

2014-05-01

303

Meso-tetraphenylporphyrin in liposomes as a suitable photosenzitizer for photodynamic therapy of tumors.  

PubMed

The suitability of a liposomal form of hydrophobic nonsulfonated meso-tetraphenyl porphyrin (TPP) for the photodynamic therapy of tumors was investigated. TPP was solubilized in small unilamellar lipid vesicles prepared by extrusion on a LIPOSOFAST apparatus. These samples were studied by laser-excited time resolved luminescence and triplet-triplet absorption spectroscopy. In this lipid environment TPP was still an efficient singlet oxygen producer, as indicated by the characteristic singlet oxygen phosphorescence at 1270 nm in D2O, when excited with a 28 ns laser pulse at 412 nm. Moreover, unlike with sulfonated TPP (TPPS4), liposomal TPP showed the reduced decay rates of TPP triplet-states with the increasing time of pre-illumination by a Xenon lamp. This was shown in an indirect way, based upon the appearance of a second component of the luminescence decay at 1270 nm in D2O; and by direct TPP triplet state monitoring, detecting triplet-triplet absorption at 440 nm in H2O. The deactivation of higher triplet states was delayed upon pre-illumination. This reflects an irreversible interaction of singlet oxygen with membrane lipids, thus demonstrating the potential of the liposomal form of TPP to efficiently disintegrate tumor cell membranes and to be a suitable preparation for the photodynamic therapy. PMID:10517287

Lovcinský, M; Borecký, J; Kubát, P; Jezek, P

1999-06-01

304

Low-dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for cancer: lack of vascular normalization  

PubMed Central

Photodynamic therapy (PDT) is an effective clinical treatment for a number of different cancers. PDT can induce hypoxia and inflammation, pro-angiogenic side effects, which may counteract its angio-occlusive mechanism. The combination of PDT with anti-angiogenic drugs offers a possibility for improved anti-tumour outcome. We used two tumour models to test the effects of the clinically approved angiostatic tyrosine kinase inhibitors sunitinib, sorafenib and axitinib in combination with PDT, and compared these results with the effects of bevacizumab, the anti-VEGF antibody, for the improvement of PDT. Best results were obtained from the combination of PDT and low-dose axitinib or sorafenib. Molecular analysis by PCR revealed that PDT in combination with axitinib suppressed VEGFR-2 expression in tumour vasculature. Treatment with bevacizumab, although effective as monotherapy, did not improve PDT outcome. In order to test for tumour vessel normalization effects, axitinib was also applied prior to PDT. The absence of improved PDT outcome in these experiments, as well as the lack of increased oxygenation in axitinib-treated tumours, suggests that vascular normalization did not occur. The current data imply that there is a future for certain anti-angiogenic agents to further improve the efficacy of photodynamic anti-cancer therapy. PMID:24450440

Weiss, Andrea; van Beijnum, Judy R; Bonvin, Debora; Jichlinski, Patrice; Dyson, Paul J; Griffioen, Arjan W; Nowak-Sliwinska, Patrycja

2014-01-01

305

808 nm driven Nd3+-sensitized upconversion nanostructures for photodynamic therapy and simultaneous fluorescence imaging.  

PubMed

The in vivo biological applications of upconversion nanoparticles (UCNPs) prefer excitation at 700-850 nm, instead of 980 nm, due to the absorption of water. Recent approaches in constructing robust Nd(3+) doped UCNPs with 808 nm excitation properties rely on a thick Nd(3+) sensitized shell. However, for the very important and popular Förster resonance energy transfer (FRET)-based applications, such as photodynamic therapy (PDT) or switchable biosensors, this type of structure has restrictions resulting in a poor energy transfer. In this work, we have designed a NaYF4:Yb/Ho@NaYF4:Nd@NaYF4 core-shell-shell nanostructure. We have proven that this optimal structure balances the robustness of the upconversion emission and the FRET efficiency for FRET-based bioapplications. A proof of the concept was demonstrated for photodynamic therapy and simultaneous fluorescence imaging of HeLa cells triggered by 808 nm light, where low heating and a high PDT efficacy were achieved. PMID:25406514

Wang, Dan; Xue, Bin; Kong, Xianggui; Tu, Langping; Liu, Xiaomin; Zhang, Youlin; Chang, Yulei; Luo, Yongshi; Zhao, Huiying; Zhang, Hong

2015-01-01

306

Gold nanomaterials conjugated with indocyanine green for dual-modality photodynamic and photothermal therapy.  

PubMed

Light-exposure-mediated higher temperatures that markedly accelerate the degradation of indocyanine green (ICG) in aqueous solutions by thermal decomposition have been a serious medical problem. In this work, we present the example of using gold nanorods (Au NRs) and gold nanoparticles (Au NPs) simultaneously serving as photodynamic and photothermal agents to destroy malignant cells. Au NRs and Au NPs were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and photothermal therapy (PTT). We also demonstrated that Au NRs and Au NPs conjugated with ICG displayed high chemical stability and acted as a promising diagnostic probe. Moreover, the photochemical destruction ability would have a gradually increase depending on different sizes of Au NPs. Due to its stability even via higher temperatures mediated by laser irradiation, the combination of PTT and PDT proved to be efficiently killing cancer cells as compared to PTT or PDT treatment alone and enhanced the effectiveness of photodestruction and was demonstrated to enhance its photostability. As a result, the preparation of Au-based nanomaterials conjugated with ICG as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials. PMID:22289264

Kuo, Wen-Shuo; Chang, Yi-Ting; Cho, Keng-Chi; Chiu, Kuo-Chih; Lien, Chi-Hsiang; Yeh, Chen-Sheng; Chen, Shean-Jen

2012-04-01

307

Enhancing Targeted Tumor Treatment by Near IR Light-Activatable Photodynamic–Photothermal Synergistic Therapy  

PubMed Central

For several decades, cancer has been one of the most life-threatening diseases. For enhancing anticancer efficiency with minimum side effects, combination therapy is envisioned. The current manuscript reports for the first time the development of a methylene blue (MB) bound nanoplatform, which is capable of delivering targeted diagnostic and combined synergistic photothermal and photodynamic treatment of cancer. Experimental data found that, once the nanoparticle binds with the target cell surface, it can detect LNCaP human prostate cancer cell selectively using fluorescence imaging. Our result shows that the therapeutic actions can be controlled with external NIR light. No cytotoxicity was observed in the absence of NIR light. Targeted photodynamic and photothermal treatment using 785 nm NIR light indicates that the multimodal treatment enhances the possibility of destroying LNCaP prostate cancer cells in vitro dramatically. We discuss the operating principle for the targeted imaging and possible mechanisms for combined therapeutic actions. Our experimental data show that NIR light activated combined therapy for cancer may become a highly effective treatment procedure in clinical settings. PMID:24568338

2015-01-01

308

Determination of the optical properties of vascular tissues: potential applications in vascular-targeting photodynamic therapy  

NASA Astrophysics Data System (ADS)

It has been proven that photodynamic therapy (PDT) is effective in treating various malignant and non-malignant diseases. In the treatment of certain non-malignant vascular diseases, such as wet age-related macular degeneration (AMD) and port wine stains (PWS), unlike in the treatment of malignant solid tumors, light irradiation usually starts immediately after the intravenous (IV) injection of photosensitizers while the photosensitizers is mainly circulating inside blood vessels. Under such vascular-targeting action mode, photoreactions between photosensitizers and light can selectively destruct the vascular tissues. Light distribution is complex so that it is important to understand the optical properties of targeted vessels and surrounding tissues. To better determine the optical properties of vascular tissues, we developed a tissue-simulating phantom and adopted frequency-domain measurement of phase difference. Absorption and reduced scattering coefficients in blood vessels were estimated and light distribution was simulated by the Monte Carlo method. These determinations are essential for the implication of better light dosimetry models in clinical photodynamic therapy and vascular-targeting PDT, in particular.

Tian, Yongbin; Chen, Ping; Lin, Lie; Huang, Zheng; Tang, Guoqing; Xu, Heping

2007-11-01

309

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

310

Comparison of light emitting diodes and semiconductor laser inducing photodynamic therapy of cancer cells in vitro  

NASA Astrophysics Data System (ADS)

The goal of anticancer therapy is achievement of balance between destruction of tumour cells and tissues and conservation of physiological functions of noncancer cells. Photodynamic therapy (PDT) is one of novel alternative treatment modality of malignant neoplasms. This method is based on cytotoxic action of excited sensitizers in the oxygen-rich environment. Sensitizers bound to cells and are excited by light source identical to absorption maximum of sensitizer. Photodynamic reactions lead to production of reactive oxygen species (ROS), which cause necrosis or apoptosis of cancer cells. The objective of our work was to analyse of phototoxicity in the sense of DNA damage in cancer cells after PDT by single cell gell electrophoresis (SCGE, comet assay) using ZnTPPS4 (zinc(II)-5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrine and disulfonated chloraluminium phthalocyanine ClAlPcS II as sensitizers. Violet light emitting diodes (LEDs; 1.5 mJ.cm -2.s -1; 418 nm) and semiconductor laser (50mW; 675 nm) were used as sources of radiation. Level of DNA fragmentation was detected after application of different light doses.

Macecek, Jaroslav; Kolarova, Hana; Bajgar, Robert; Strnad, Miroslav

2007-03-01

311

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

PubMed

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

2012-09-01

312

Nanostructures of an amphiphilic zinc phthalocyanine polymer conjugate for photodynamic therapy of psoriasis.  

PubMed

Psoriasis is a chronic inflammatory skin disease affecting 2-5% of the population worldwide and it severely affects patient quality of life. In this study, an amphiphilic zinc phthalocyanine polymer conjugate (ZPB) was synthesized, in which zinc phthalocyanine (ZnPc) was conjugated with the poly(ethylene glycol) (PEG) chain of Brij 58. ZPB showed two maximum UV-vis absorption wavelengths, 348nm and 678nm. A monomolecular micelle of ZPB formed in water with a mean size of 25nm and zeta potential of -15mV. The nanostructures aggregated into cloudy precipitates, which were easily dispersed. The nanostructure showed the shell-core structure with the ZnPc segments as the core and the PEG chains as the shell. The anti-psoriasis effect of the ZPB nanostructure was explored using a guinea pig psoriasis model. After comparing the anti-psoriasis effects of saline, light alone, ZPB alone, and the combination of light and ZPB, the combination of light and ZPB showed the best photodynamic therapy of psoriasis based on the light excitation of the photosensitizer ZPB and the psoriasis was nearly cured according to the histopathological investigation. The ZPB nanostructure is a promising anti-psoriasis nanomedicine based on photodynamic therapy. PMID:25766924

Jin, Yiguang; Zhang, Xiaohan; Zhang, Baolei; Kang, Hongxiang; Du, Lina; Li, Miao

2015-04-01

313

Antimicrobial photodynamic therapy with two photosensitizers on two oral streptococci: an in vitro study  

NASA Astrophysics Data System (ADS)

Periodontal diseases are caused by infection of tissues supporting the teeth due to complex aggregate of bacteria known as biofilm and firstly colonized by streptococci. The aim of this in vitro study was to evaluate the effect of Radachlorin® and Toluidine Blue O (TBO)-mediated photodynamic therapy (PDT) on the viability of two oral streptococci. Bacterial suspensions of Streptococcus mutans and Streptococcus sanguis were subjected to either TBO or Radachlorin®, Then exposed to two different diode laser light at energy densities of 3, 6 J/cm2 at 633 nm and 6, 12 J/cm2 at 662 nm, respectively. The control groups were subjected to laser light alone, photosensitizer alone or received neither photosensitizer nor light exposure. The suspensions were then spread over specific agar mediums and viable microorganisms were counted after overnight incubation aerobically at 37°C, 5% CO2 and then reported as colony forming unit. The results indicated that photosensitization by the energy density of 6 J/cm2 with Radachlorin® and both 3 and 6 J/cm2 with TBO caused significant reduction in bacterial colony formation ( p < 0.05). Radachlorin® and TBO-mediated photodynamic therapy seem to show excellent potential in significantly killing of two oral streptococci in vitro.

Vahabi, S.; Fekrazad, R.; Ayremlou, S.; Taheri, S.; Lizarelli, R. F. Z.; Kalhori, K. A. M.

2011-12-01

314

Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells  

NASA Astrophysics Data System (ADS)

Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved.

Wang, Haiping; Wang, Pan; Zhang, Kun; Wang, Xiaobing; Liu, Quanhong

2015-03-01

315

Postsurgical adjuvant tumor therapy by combining anti-angiopoietin-2 and metronomic chemotherapy limits metastatic growth.  

PubMed

Antiangiogenic tumor therapy has failed in the adjuvant setting. Here we show that inhibition of the Tie2 ligand angiopoietin-2 (Ang2) effectively blocks metastatic growth in preclinical mouse models of postsurgical adjuvant therapy. Ang2 antibody treatment combines well with low-dose metronomic chemotherapy (LDMC) in settings in which maximum-dose chemotherapy does not prove effective. Mechanistically, Ang2 blockade could be linked to quenching the inflammatory and angiogenic response of endothelial cells (ECs) in the metastatic niche. Reduced EC adhesion molecule and chemokine expression inhibits the recruitment of tumor-promoting CCR2(+)Tie2(-) metastasis-associated macrophages. Moreover, LDMC contributes to therapeutic efficacy by inhibiting the recruitment of protumorigenic bone marrow-derived myeloid cells. Collectively, these data provide a rationale for mechanism-guided adjuvant tumor therapies. PMID:25490450

Srivastava, Kshitij; Hu, Junhao; Korn, Claudia; Savant, Soniya; Teichert, Martin; Kapel, Stephanie S; Jugold, Manfred; Besemfelder, Eva; Thomas, Markus; Pasparakis, Manolis; Augustin, Hellmut G

2014-12-01

316

Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy  

Microsoft Academic Search

The role of Bax in the release of cytochrome c from mitochondria and the induction of apoptosis has been demonstrated in many systems. Using immunocytochemical staining, we observed that photodynamic therapy (PDT) with the photosensitiser Pc 4 induced Bax translocation from the cytosol to mitochondria, and the release of cytochrome c from mitochondria as early signalling for the intrinsic pathway

S-M Chiu; L-Y Xue; J Usuda; K Azizuddin; N L Oleinick

2003-01-01

317

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

318

Safety profiles of tamoxifen and the aromatase inhibitors in adjuvant therapy of hormone-responsive early breast cancer  

Microsoft Academic Search

Adjuvant endocrine therapy plays an important role in the management of hormone-receptor-positive early breast cancer, and has increased life expectancy for millions of women. Many patients receive adjuvant treatment for at least 5 years following tumor resection, hence good long-term safety is important for endocrine agents to gain widespread acceptance. Tamoxifen has been used as adjuvant therapy for early breast

E. A. Perez

2007-01-01

319

Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma  

SciTech Connect

Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of IHC.

Shinohara, Eric T. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)], E-mail: Shinohara@xrt.upenn.edu; Mitra, Nandita; Guo Mengye [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Metz, James M. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

2008-12-01

320

A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation  

PubMed Central

Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen (1O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce 1O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of 1O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility. PMID:25105845

Ge, Jiechao; Lan, Minhuan; Zhou, Bingjiang; Liu, Weimin; Guo, Liang; Wang, Hui; Jia, Qingyan; Niu, Guangle; Huang, Xing; Zhou, Hangyue; Meng, Xiangmin; Wang, Pengfei; Lee, Chun-Sing; Zhang, Wenjun; Han, Xiaodong

2014-01-01

321

9-Nitroanthracene derivative as a precursor of anthraquinone for photodynamic therapy.  

PubMed

Anthraquinones are typical photosensitizers used in photodynamic therapy (PDT). However, systemic toxicity is a major problem for anthraquinones due to their ability not only to bind DNA but also to cause oxidative stress even without photoirradiation. To avoid such disadvantages in cancer therapy, we designed and synthesized a novel 9-nitroanthracene derivative (1) as a precursor of anthraquinone. Under photoirradiation, 1 is converted into anthraquinone via generation of nitric oxide as confirmed by ESR. Strong DNA cleavage specifically at guanine under photoirradiation was also observed, characteristic of DNA-cleaving reactions by photoirradiated anthraquinones. We propose development of 1 as an alternative approach toward PDT that reduces the systemic toxicity of anthraquinone. PMID:17400461

Fukuhara, Kiyoshi; Oikawa, Shinji; Hakoda, Nana; Sakai, Yasunori; Hiraku, Yusuke; Shoda, Takuji; Saito, Shinichi; Miyata, Naoki; Kawanishi, Shosuke; Okuda, Haruhiro

2007-06-01

322

Regression of drusen after combined treatment using photodynamic therapy with verteporfin and ranibizumab.  

PubMed

Drusen are the clinical hallmark of age-related macular degeneration. The regression of these deposits in patients treated with argon, krypton, or diode laser photocoagulation has been reported previously. However, previous protocols with conventional laser for drusen may result in retinal pigment epithelium (RPE) damage and unwanted scotomas. The authors report a case of complete regression of soft drusen in a 65-year-old man with central visual loss and metamorphopsia due to a drusenoid RPE detachment and soft drusen who underwent reduced-fluence photodynamic therapy (PDT) and three monthly intravitreal injections of ranibizumab. Reduced-fluence PDT combined with anti-VEGF therapy may reduce drusen without inducing RPE cell damage. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:275-278.]. PMID:25707058

Novais, Eduardo Amorim; Badaró, Emmerson; Regatieri, Caio Vinicius Saito; Duker, Jay; de Oliveira Bonomo, Pedro Paulo

2015-02-01

323

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

324

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. PMID:25302167

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

2014-01-01

325

Effects of chlorin e6-mediated photodynamic therapy on human colon cancer SW480 cells  

PubMed Central

Objective: This study is to investigate the antitumor effects and possible mechanisms of chlorin e6-mediated photodynamic therapy (Ce6-PDT) on human colon cancer SW480 cells. Methods: SW480 cells were treated with Ce6, followed by photodynamic irradiation. Subcellular localization of Ce6 in SW480 cells was observed with confocal laser scanning microscopy (LSCM). Reactive oxygen species (ROS) levels were monitored with fluorescence microscopy. Cell proliferation and apoptosis were detected by the MTT assay and flow cytometry, respectively. Scratch test and colony formation assay were employed to analyze the cell migration ability and colony formation ability. Results: LSCM showed that, in SW480 cells, Ce6 was evenly distributed within the ER and lysosomes, with nearly no distribution in the mitochondria and nuclei. When SW480 cells were subjected to Ce6-PDT, the ROS levels would be elevated, in a dose-dependent manner. Moreover, Ce6-PDT treatment could inhibit the cell proliferation and enhance the apoptotic process, in SW480 cells. However, Ce6 treatment alone without photodynamic irradiation could not induce any significant differences in the cell proliferation and apoptosis. In addition, the migration ability and colony formation ability of SW480 cells were decreased by Ce6-PDT treatment at appropriate dosages. Conclusion: Ce6-PDT treatment could enhance ROS production and apoptosis, inhibit cell proliferation, decrease migration ability and colony formation ability, in SW480 cells, in a dose-dependent manner. These findings might provide experimental evidence for the application of Ce6-PDT in clinical treatment of colorectal cancer. PMID:25663983

Li, Yuhua; Yu, Yalu; Kang, Ling; Lu, Ying

2014-01-01

326

Cardiac effects of adjuvant therapy for early breastcancer  

Microsoft Academic Search

Adjuvant chemotherapy is an established standard of care for most patients diagnosed with early breast cancer, and its popularity is gaining worldwide. The systemic armamentarium presently includes anthracyclines and taxanes, alkylating agents, fluoropyrimidines, and antimetabolites; in the future, it may include platinum compounds and the recombinant humanized anti-HER2 monoclonal antibody, trastuzumab, as well. Anti-estrogens continue to play an important role

Maria Theodoulou; Andrew D Seidman

2003-01-01

327

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

328

Laser surgery and medicine including photodynamic therapy in China today  

NASA Astrophysics Data System (ADS)

The development of laser medicine in China is correlated with the development of laser science in China. After the first Chinese laser, ruby laser came into being in 1961, Chinese medical scientists began to do the studies about laser medicine in the middle 1960s. For example, ruby laser was adopted for the retina coagulation experiment in 1965. Since 1970s, through the free choice of utilizing Co2, He-Ne, Nd:YAG argon, ruby lasers, laser surgery and medicine has been widely applied to the treatment for diseases of the eyes, ENT, dermatology, surgery, gynecology, tumors and diseases suitable to physical therapy or acupuncture with satisfactory effects. In June 1977, a nation-wide laser medicine symposium was held at Wuhan, Hubei Province with 200 participants including medical doctors and laser technologies from 23 provinces and municipal towns. Till the end of seventies, utilization of lasers has been extended to Nd glass laser, N laser and tunable dye lasers. The scope covered most of the clinical sections. After Dr. Thomas J. Dougherty developed the PDT for cancers in Roswell Park Memorial Institute in Buffalo in late 1970s and Professor Yoshihiro Hayata successfully applied the PDT in clinical treatment for lung cancer in 1980, Chinese pharmacists successfully produced the Chinese HpD and the first case of PDT, a lower eyelid basal cell carcinoma patient was treated with the Chinese laser equipment in 1981 in Beijing. Its success brought attention establishing a research group supported by the government in 1982. The members of the group consisted the experts on preclinical and clinical research, pharmaceutical chemistry, laser physicists and technologists. A systemic research on PDT was then carried out and obvious result was achieved. The step taken for PDT also accelerated the researchers on other kinds of laser medicine and surgery because the medical doctors had begun to master the knowledge about laser science. The prosperous situation of rapid development of laser science, bio-medical lasers, laser medicine and surgery as well as PDT was prolonged in the whole nineteen eighties.

Li, Junheng

2000-10-01

329

Effect of photodynamic therapy using benzoporphyrin derivative on the cutaneous immune response  

NASA Astrophysics Data System (ADS)

In this study, the effect of transdermal photodynamic therapy (PDT) using benzoporphyrin derivative monoacid ring A (BPD) on the development of the immunologically mediated contact hypersensitivity (CHS) response against the hapten dinitrofluorobenzene (DNFB) and on the duration of skin allograft acceptance has been evaluated. In the CHS model it was found that the treatment of hairless strain mice with whole-body transdermal PDT using BPD (1 mg/kg) and LED light (15 J/cm2) resulted in a profound suppression of the CHS reaction if treatment was applied either 48 or 24 hours prior or up to 72 hours after sensitization of abdominal skin with DNFB. Less inhibition of the CHS response was observed if PDT was given one day before the ear challenge with DNFB which was applied 5 days following the initial DNFB sensitization. However, DNFB-exposed, PDT-treated mice retained the capacity to respond maximally to the unrelated contact sensitizer oxazolone. These results are consistent with other models of experimentally induced immune tolerance. allogeneic skin graft studies demonstrated that pretreatment of skin with BPD and light, at levels that did not cause significant tissue damage, significantly enhanced the length of engraftment. Using a separate protocol, photodynamic treatment of recipient mice at various times after transplant had no significant effect on allograft acceptance. Irradiation of skin in the presence of BPD may significantly inhibit the initiation of certain immunological responses within these tissues.

Simkin, Guillermo O.; Obochi, Modestus; Hunt, David W. C.; Chan, Agnes H.; Levy, Julia G.

1995-05-01

330

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

331

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

332

Delivery of lipophilic porphyrin by liposome vehicles: preparation and photodynamic therapy activity against cancer cell lines.  

PubMed

Porphyrin photosensitizers are mostly used components in photodynamic therapy (PDT). The poor solubility of porphyrins in aqueous medium is the problem to be solved for the in vivo applications. The delivery of photosensitizers to the tumor cells using liposome vehicles can help to overcome this problem. In this work, we have first functionalized the protoporphyrin IX with lipophilic oleylamine arms and encapsulated it into 1,2 dioleyl-sn-glycero-phosphatidylcholine (DOPC) liposomes. The appropriate sizes of liposomes are about 140 nm and have the characteristic Soret and Q band absorptions at 405 nm (Soret), 507 nm, 541 nm, 577 nm and 631 nm (Q bands), respectively. In the photodynamic activity studies, the liposomal porphyrins were irradiated with light (375 nm, 10 mW) in the presence of cancer cell lines, HeLa and AGS. We have found that both liposomal porphyrins and oleylamine conjugated porphyrins are much more effective than PpIX. This result can be attributed to the drug delivery characteristic of the liposomes which plays effective role in endocytosis. We also found that, in AGS cells, liposomal PpIX-Ole induced apoptosis more than HeLa cells under light conditions. PMID:25107838

Temizel, Emine; Sagir, Tugba; Ayan, Esra; Isik, Sevim; Ozturk, Ramazan

2014-12-01

333

Hetergeneous tumour response to photodynamic therapy assessed by in vivo localised 31P NMR spectroscopy.  

PubMed Central

Photodynamic therapy (PDT) is efficacious in the treatment of small malignant lesions when all cells in the tumour receive sufficient drug, oxygen and light to induce a photodynamic effect capable of complete cytotoxicity. In large tumours, only partial effectiveness is observed presumably because of insufficient light penetration into the tissue. The heterogeneity of the metabolic response in mammary tumours following PDT has been followed in vivo using localised phosphorus NMR spectroscopy. Alterations in nucleoside triphosphates (NTP), inorganic phosphate (Pi) and pH within localised regions of the tumour were monitored over 24-48 h following PDT irradiation of the tumour. Reduction of NTP and increases in Pi were observed at 4-6 h after PDT irradiation in all regions of treated tumours. The uppermost regions of the tumours (those nearest the skin surface and exposed to the greatest light fluence) displayed the greatest and most prolonged reduction of NTP and concomitant increase in Pi resulting in necrosis. The metabolite concentrations in tumour regions located towards the base of the tumour returned a near pre-treatment levels by 24-48 h after irradiation. The ability to follow heterogeneous metabolic responses in situ provides one means to assess the degree of metabolic inhibition which subsequently leads to tumour necrosis. Images Figure 4 PMID:1829953

Ceckler, T. L.; Gibson, S. L.; Kennedy, S. D.; Hill, R.; Bryant, R. G.

1991-01-01

334

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

PubMed Central

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/cm2, 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

335

Polyion complex micelles entrapping cationic dendrimer porphyrin: effective photosensitizer for photodynamic therapy of cancer.  

PubMed

Photosensitizers play a crucial role in the photodynamic therapy (PDT) of cancer. In this study, a third-generation aryl ether dendrimer porphyrin with 32 primary amine groups on the periphery, [NH2CH2CH2NHCO]32DPZn, and pH-sensitive, polyion complex micelles (PIC) composed of the porphyrin dendrimer and PEG-b-poly(aspartic acid), were evaluated as new photosensitizers (PSs) for PDT in the Lewis Lung Carcinoma (LLC) cell line. The preliminary photophysical characteristics of [NH2CH2CH2NHCO]32DPZn and the corresponding micelles were investigated. Electrostatic assembly resulted in a red-shift of the Soret peak of the porphyrin core and the enhanced fluorescence. Compared to the dendrimer porphyrin [NH2CH2CH2NHCO]32DPZn, relatively low cellular uptake of dendrimer porphyrin [NH2CH2CH2NHCO]32DPZn incorporated in the PIC micelle was observed, yet the latter exhibited enhanced photodynamic efficacy on the LLC cell line. Importantly, the use of PIC micelles as a delivery system reduced the dark toxicity of the cationic dendrimer porphyrin, probably due to the biocompatible PEG shell of the micelles. PMID:14636720

Zhang, Guo-Dong; Harada, Atsushi; Nishiyama, Nobuhiro; Jiang, Dong-Lin; Koyama, Hiroyuki; Aida, Takuzo; Kataoka, Kazunori

2003-12-01

336

Near-infrared Au nanorods in photodynamic therapy, hyperthermia agents, and near-infrared optical imaging  

NASA Astrophysics Data System (ADS)

The development of multifunctional nanomaterials is currently a topic of interest in the field of nanotechnology. Integrated systems that incorporate therapeutics, molecular targeting, and diagnostic imaging capabilities are considered to be the next generation of multifunctional nanomedicine. In this work, we present the first example of using Au nanorods simultaneously serving not only as photodynamic and photothermal agents to destroy A549 malignant cells but also as optical contrast agents simultaneously to monitor cellular image. Au nanorods were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and hyperthermia. With the combination of PDT and hyperthermia proved to be efficiently killing cancer cells as compared to PDT or hyperthermia treatment alone and enhanced the effectiveness of photodestruction. Moreover, Au nanorods conjugated with ICG displayed high chemical stability and simultaneously acted as a promising cellular image probe. As a result, the preparation of Au nanorods conjugated with photosensitizers as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.

Kuo, Wen-Shuo; Chang, Chich-Neng; Chang, Yi-Ting; Yang, Meng-Heng; Chien, Yi-Hsin; Chen, Shean-Jen; Yeh, Chen-Sheng

2011-03-01

337

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

338

5-aminolaevulinic acid for fluorescence diagnosis and photodynamic therapy of bronchial cancer: a case report  

NASA Astrophysics Data System (ADS)

Five-aminolaevulinic acid (ALA) was applied orally and by aerosol inhalation to one patient in order to check the feasibility of photodynamic therapy (PDT) and photodynamic fluorescence diagnosis (PDD) of lung cancer. For PDD, ALA was given by inhalation using a conventional jet nebulizer. Protoporphyrin IX (PP IX)-fluorescence in the bronchial mucosa and the tumor was assessed visually and by spectroscopy using an optical multichannel analyzer. At a second session ALA was given orally and PDD as well as PDT were performed. The therapeutic effect on the tumor was controlled by bronchoscopy 5 and 12 weeks after PDT. Inhalative and oral application of ALA were both well tolerated. No adverse effects were observed. PP IX- fluorescence could be easily detected 3 h after ALA administered by inhalation or 5 h after ALA orally. Fluorescence ratio between tumor and normal tissues was better after the oral administration of ALA. Five and twelve weeks after PDT, marked reduction of tumor volume and recanalization of the left upper lobe were found.

Gamarra, Fernando; Baumgartner, Reinhold; Stepp, Herbert G.; Rick, Kai; Leberig, A.; Huber, Rudolf M.

1995-03-01

339

18 years long-term results of facial port-wine stain (PWS) after photodynamic therapy (PDT) - A case report.  

PubMed

Port-wine stain (PWS) is still a challenging condition for clinician to treat, because in the majority of cases, the stains are not lifted fully by treatment with laser therapy. Photodynamic therapy (PDT) was considered recently as a promising alternative treatment for PWS. We report here long-term follow-up measures 18 years on PWS lesion treated with PDT and the histological data of residual PWS. PMID:25461965

Yu, Wenxin; Ma, Gang; Qiu, Yajing; Chen, Hui; Jin, Yunbo; Yang, Xi; Hu, Xiaojie; Chang, Lei; Wang, Tianyou; Zhou, Henghua; Li, Wei; Lin, Xiaoxi

2015-03-01

340

Is photodynamic therapy a selective treatment? Analysis of local complications after endoscopic photodynamic therapy of early stage tumors of gastrointestinal, tracheobronchial, and urinary tracts  

NASA Astrophysics Data System (ADS)

Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea

1995-03-01

341

Photosensitizer-incorporated G-quadruplex DNA-functionalized magnetofluorescent nanoparticles for targeted magnetic resonance/fluorescence multimodal imaging and subsequent photodynamic therapy of cancer.  

PubMed

A smart heteronanostructure has been constructed for targeted photodynamic therapy and magnetic fluorescent imaging of cancer cells using photosensitizer-incorporated G-quadruplex DNA functionalized magnetic nanoparticles. PMID:22622597

Yin, Meili; Li, Zhenhua; Liu, Zhen; Ren, Jinsong; Yang, Xinjian; Qu, Xiaogang

2012-07-01

342

Effectiveness of adjuvant occupational therapy in employees with depression: design of a randomized controlled trial  

Microsoft Academic Search

BACKGROUND: Major depressive disorder is among the medical conditions with the highest negative impact on work outcome. However, little is known regarding evidence-based interventions targeting the improvement of work outcomes in depressed employees. In this paper, the design of a randomized controlled trial is presented in order to evaluate the effectiveness of adjuvant occupational therapy in employees with depression. This

Hiske L Hees; Maarten WJ Koeter; Gabe de Vries; Wendy Ooteman; Aart H Schene

2010-01-01

343

Positive effect of tamoxifen as part of adjuvant chemo-endocrine therapy for breast cancer  

Microsoft Academic Search

A prospective randomised multicentre clinical study was undertaken for 2 years and 3 months from November 1982, with the aim of examining the significance of using a combination of ftorafur (FT) and tamoxifen (TAM) for post-operative adjuvant therapy of breast cancer. Patients had either stage II or stage IIIa disease, were age 75 or below and had undergone radical mastectomy.

J Uchino; N Samejima; T Tanabe; H Hayasaka; M Mito; Y Hata; K Asaishi

1994-01-01

344

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

345

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

346

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

347

Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater  

SciTech Connect

Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

Krishnan, Sunil [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)], E-mail: skrishnan@mdanderson.org; Rana, Vishal [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Evans, Douglas B. [Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Varadhachary, Gauri [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Das, Prajnan; Bhatia, Sumita; Delclos, Marc E.; Janjan, Nora A. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Crane, Christopher H. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Pisters, Peter W. [Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

2008-03-01

348

A Case of Advanced Malignant Pleural Mesothelioma Treatment with Chemotherapy and Photodynamic Therapy  

PubMed Central

Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant, and generally fatal disease. A 68-year-old male who was diagnosed with MPM at another hospital came to our hospital with dyspnea. We advised him to take combination chemotherapy but he refused to take the treatment. That was because he had already received chemotherapy with supportive care at another hospital but his condition worsened. Thus, we recommended photodynamic therapy (PDT) to deal with the dyspnea and MPM. After PDT, the dyspnea improved and the patient then decided to take the combination chemotherapy. Our patient received chemotherapy using pemetrexed/cisplatin. Afterwards, he received a single PDT treatment and then later took chemotherapy using gemcitabine/cisplatin. The patient showed a survival time of 27 months, which is longer than median survival time in advanced MPM patients. Further research and clinical trials are needed to demonstrate any synergistic effect between the combination chemotherapy and PDT. PMID:25653696

Ryu, Jae-Wook

2015-01-01

349

Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status  

NASA Astrophysics Data System (ADS)

Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

1995-03-01

350

Photodynamic therapy of spread-skin malignancies with scanning electron beam-pumped semiconductor laser  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) using quantoscope (scanning electron-beam pumped semiconductor laser, (lambda) equals 670 +/- 2 nm, P equals 10 W) and Phthalocyanine Al as photosensitizer (PS) have been provided in nine patients (27 tumor sites) with spread skin malignancies (basal cell, squamous cell cancer, melanoma, metastases of breast cancer) and cancer of lip T1 - T2 N0 M0. During PDT power density has been from 200 to 450 mW/cm2, light doses ranging from 150 to 700 J/cm2. We have fulfilled diagnostic of tumor after injection of PS and have controlled treatment using Spectral-Fluorescent Video Complex. In five patients (23 sites) we had complete clinical response and in four patients (4 sites) partial response after PDT. Results of our study show that using of scanning electron- beam pumped semiconductor laser is perspective in treating of spread skin malignancies.

Vakoulovskaya, Elena G.; Meerovich, Gennadii A.; Shental, Victor V.; Ulasyuk, V. N.

1996-01-01

351

Photodynamic therapy of spread skin malignancies with scanning electron-beam-pumped semiconductor laser  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) using quantoscope (scanning electron-beam pumped semiconductor laser, (lambda) equals 670 plus or minus 2 nm, P equals 10 W) and Phtalocyanine Al as photosensitizer (PS) have been provided in nine patients (27 tumor sites) with spread skin malignancies (basal cell, squamous cell cancer, melanoma, metastases of breast cancer) and cancer of the lip T2 N0 M0. During PDT power density has been from 200 to 450 mW/cm2, light doses ranging from 150 to 700 J/cm2. We have fulfilled diagnostic of tumor after injection of PS and have controlled treatment using spectral- fluorescent video complex. In five patients (23 sites) we had complete clinical response and in four patients (4 sites) partial response after PDT. Results of our study show that use of scanning electron-beam-pumped semiconductor laser is promising in the treatment of spread skin malignancies.

Vakoulovskaya, Elena G.; Meerovich, Gennadii A.; Shental, Victor V.; Ulasyuk, V. N.; Lukyanets, Eugeny A.

1996-01-01

352

Current Status of Photodynamic Therapy in Digestive Tract Carcinoma in Japan  

PubMed Central

Photodynamic therapy (PDT) is an effective local treatment modality as a cancer-specific laser ablation in malignancy of some organs including digestive tracts or bile duct. In Japan, PDT has been applied at the early period after the first clinical induction in 1980’s. Although the useful efficacy was clarified, PDT has not been fully applied because of the phototoxicity of the porfimer sodium. The next generated talaporfin-sodium was used for PDT, in which phototoxicity was reduced and, however, the clinical efficacy for digestive tract malignancy has not yet been clarified. By proceeding the experimental and clinical trials, it is necessary to clarify the evidence of efficacy as a local powerful treatment with the conventional surgery, brachiotherapy and chemotherapy in the future step. PMID:25690028

Nanashima, Atsushi; Nagayasu, Takeshi

2015-01-01

353

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

354

The simulation of light distribution in photodynamic therapy for port wine stains  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy is regarded as the best treatment for port wine stains, which has the main adverse effect of various degrees of pain (mild to moderate) during the illumination. Though the cooling and cold water have been used to reduce such pain, there is still no scientific evidence for these relief. In this paper, a realistic skin model is built to simulate the distribution of light under treatment, which helps control the light dose and temperature, and improve the clinical results. Comparing with the general parallel skin model, a curving stratum basale layer is used in this paper, and various blood vessel configurations such as single and multiple vessels with horizontally and vertically oriented, curve vessels, various vessel diameter and various radius of curvature of stratum basale layer are simulated. The results shows a more realistic modeling for the thermal damage and help to relief the pain in the treatment.

Zhang, Shi-Yu; Hu, Xiao-Ming; Zhou, Ya

2014-11-01

355

Optical Doppler tomography for monitoring vascularization during photodynamic therapy of skin cancer lesions  

NASA Astrophysics Data System (ADS)

We investigate vascular changes during Photodynamic therapy (PDT) of skin tumors using optical Doppler tomography (ODT). The effect of vascular shut down on tumor destruction is currently not known, and to optimize treatment it is relevant to investigate this issue further. Optical Doppler tomography is capable of measuring blood flow in biological tissue down to 1-2 mm with sub-mm/s velocity sensitivity and micrometer spatial resolution making it suitable for blood flow measurements in the skin. We demonstrate the ability of detecting blood flow in the human skin using non-interstitial ODT to preserve the non-invasiveness. In general a very limited blood flow activity was observed in normal skin and around skin tumors making monitoring of changes difficult. We suggest solutions to a number of practical issues such as sampling errors and natural fluctuations in flow activity for future work.

Thomsen, J.; Bendsøe, N.; Svanberg, K.; Andersson-Engels, S.; Jørgensen, T. M.; Thrane, L.; Larsen, H. E.; Pedersen, F.; Andersen, P. E.

2008-04-01

356

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

357

Cutaneous Sporotrichosis Treated with Photodynamic Therapy: An in Vitro and in Vivo Study  

PubMed Central

Abstract Background: Sporotrichosis is a fungal infection caused by Sporothrix schenckii complex, usually restricted to the skin, subcutaneous cellular tissue, and adjacent lymphatic vessels. Antimicrobial photodynamic therapy (aPDT) could be a good alternative to manage localized, superficial infections. Case report: A 65-year-old African woman was diagnosed with a fixed cutaneous sporotrichosis on her left arm, treated with itraconazol and oral terbinafine with partial improvement. Topical 16% methyl aminolevulinate (MAL, Metvix®)-PDT was used without success. Methods: An in vitro photoinactivation test with the isolated microorganism revealed phenothiazinium salts to be more effective than MAL. Conclusions: PDT with intralesional 1% methylene blue (MB) in combination with intermittent low doses of itraconazole obtained complete microbiological and clinical response. PMID:24328608

Aspiroz, Carmen; Alejandre, M. Carmen; Andres-Ciriano, Elena; Fortuño, Blanca; Charlez, Luis; Revillo, Maria Jose; Hamblin, Michael R.; Rezusta, Antonio

2014-01-01

358

Vessel constriction correlated with local singlet oxygen generation during vascular targeted photodynamic therapy  

NASA Astrophysics Data System (ADS)

In this study, the vessel constriction was measured as a biological indicator of acute vascular response after vascular targeted photodynamic therapy (V-PDT). During V-PDT treatment, the near-infrared (NIR) singlet oxygen (1O2) luminescence at 1270 nm generated in blood vessels in a dorsal skinfold window chamber model in vivo was directly monitored using a custom built high-sensitive NIR imaging system. In order to compare the acute vascular response, various irradiances with the same light dose were utilized for treatments. The obtained results show that the complete arteriole constriction occurred frequently, while some of the larger veins were constricted partially. For the vessels that have significant constriction after V-PDT, our preliminary data suggest that the vasoconstriction in the selected ROIs are roughly correlated with the local cumulative 1O2 luminescence intensities. This study implies that the 1O2 luminescence dosimetry maybe also effective for evaluating V-PDT efficiency.

Lin, Lisheng; Li, Yirong; Zhang, Jinde; Tan, Zou; Chen, Defu; Xie, Shusen; Gu, Ying; Li, Buhong

2014-11-01

359

A case of advanced malignant pleural mesothelioma treatment with chemotherapy and photodynamic therapy.  

PubMed

Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant, and generally fatal disease. A 68-year-old male who was diagnosed with MPM at another hospital came to our hospital with dyspnea. We advised him to take combination chemotherapy but he refused to take the treatment. That was because he had already received chemotherapy with supportive care at another hospital but his condition worsened. Thus, we recommended photodynamic therapy (PDT) to deal with the dyspnea and MPM. After PDT, the dyspnea improved and the patient then decided to take the combination chemotherapy. Our patient received chemotherapy using pemetrexed/cisplatin. Afterwards, he received a single PDT treatment and then later took chemotherapy using gemcitabine/cisplatin. The patient showed a survival time of 27 months, which is longer than median survival time in advanced MPM patients. Further research and clinical trials are needed to demonstrate any synergistic effect between the combination chemotherapy and PDT. PMID:25653696

Ryu, Jae-Wook; Kim, Youn Seup

2015-01-01

360

Nanocarriers with ultrahigh chromophore loading for fluorescence bio-imaging and photodynamic therapy.  

PubMed

We describe the design of original nanocarriers that allows for ultrahigh chromophore loading while maintaining the photo-activity of each individual molecule. They consist in shells of charged biocompatible polymers grafted on gold nanospheres. The self-organization of extended polymer chains results from repulsive charges and steric interactions that are optimized by tuning the surface curvature of nanoparticles. This type of nano-scaffolds can be used as light-activated theranostic agents for fluorescence imaging and photodynamic therapy. We demonstrate that, labeled with a fluorescent photosensitizer, it can localize therapeutic molecules before triggering the cell death of B16-F10 melanoma with an efficiency that is similar to the efficiency of the polymer conjugate alone, and with the advantage of extremely high local loading of photosensitizers (object concentration in the picomolar range). PMID:23915950

Navarro, Julien R G; Lerouge, Frédéric; Cepraga, Cristina; Micouin, Guillaume; Favier, Arnaud; Chateau, Denis; Charreyre, Marie-Thérèse; Lanoë, Pierre-Henri; Monnereau, Cyrille; Chaput, Frédéric; Marotte, Sophie; Leverrier, Yann; Marvel, Jacqueline; Kamada, Kenji; Andraud, Chantal; Baldeck, Patrice L; Parola, Stephane

2013-11-01

361

Photodynamic therapy as a new treatment modality for inflammatory and infectious conditions.  

PubMed

Photodynamic therapy (PDT) is currently used as a minimally invasive therapeutic modality for cancer. Whereas antitumor treatment regimens require lethal doses of photosensitizer and light, sublethal doses may have immunomodulatory effects, antibacterial action and/or regenerative properties. A growing body of evidence now indicates that non-lethal PDT doses can alleviate inflammation or treat established soft-tissue infections in various murine models of arthritis, experimental encephalomyelitis, inflammatory bowel disease and chronic skin ulcers. Furthermore, PDT is already used in clinical application and clinical trial for the treatment of psoriasis, chronic wounds and periodontitis in humans. Sublethal PDT should be regarded as a new viable option for the treatment of inflammatory conditions. PMID:25837708

Reinhard, Aurélie; Sandborn, William J; Melhem, Hassan; Bolotine, Lina; Chamaillard, Mathias; Peyrin-Biroulet, Laurent

2015-05-01

362

Fluorescence tissue distribution of methylene blue used for photodynamic therapy of Helicobacter Pylori  

NASA Astrophysics Data System (ADS)

Helicobacter pylori is associated with a wide range of pathologies in the upper gastrointestinal tract. Current treatments employing antibiotics are disappointing, and an endoscopic PDT might offer a better alternative. Methylene blue is a widely known histological dye and has been in use for photodynamic therapy experimentally for some years. A prospective application of MB is photosensitization of Helicobacter pylori, but little is known about its effect with light on normal mucosa of the stomach. We studied the fluorescence microscopy of the stomachs of 3 ferrets which had been sensitized by oral route with three different concentrations of MB 1 hour prior to sacrifice. MB at all doses was seen to concentrate on the surface of the mucosa and shows little deeper penetration. As Helicobacter lie on the superficial mucosa, this study suggests that oral dosing with MB should sensitize these bacteria. These findings are an important preliminary to an in vivo trial of PDT for the treatment of H pylori.

Millson, Charles E.; Buonaccorsi, Giovanni A.; MacRobert, Alexander J.; Mlkvy, Peter; Bown, Stephen G.

1995-03-01

363

An alternative model for photodynamic therapy of cancers: Hot-band absorption  

NASA Astrophysics Data System (ADS)

The sulfonated aluminum phthalocyanine (AlPcS), a photosensitizer for photodynamic cancer therapy (PDT), has an absorption tail in the near-infrared region (700-900 nm) which is so-called hot band absorption (HBA). With the HBA of 800 nm, the up-conversion excitation of AlPcS was achieved followed by the anti-Stocks emission (688 nm band) and singlet oxygen production. The HBA PDT of AlPcS seriously damaged the KB and HeLa cancer cells, with a typical light dose dependent mode. Particularly, the in vitro experiments with the AlPcS shielding solutions further showed that the HBA PDT can overcome a self-shielding effect benefiting the PDT applications.

Wang, Jing; Chen, Jiyao

2013-12-01

364

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

365

Interleukin-6 trans signalling enhances photodynamic therapy by modulating cell cycling  

PubMed Central

Photodynamic therapy (PDT) of solid tumours causes tissue damage that elicits local and systemic inflammation with major involvement of interleukin-6 (IL-6). We have previously reported that PDT-treated cells lose responsiveness to IL-6 cytokines. Therefore, it is unclear whether PDT surviving tumour cells are subject to regulation by IL-6 and whether this regulation could contribute to tumour control by PDT. We demonstrate in epithelial tumour cells that while the action of IL-6 cytokines through their membrane receptors is attenuated, regulation by IL-6 via trans-signalling is established. Soluble interleukin-6 receptor-? (IL-6R?) (sIL-6R?) and IL-6 were released by leucocytes in the presence of conditioned medium from PDT-treated tumour cells. Cells that had lost their membrane receptor IL-6R? due to PDT responded to treatment with the IL-6R–IL-6 complex (Hyper-IL-6) with activation of signal transducers and activator of transcription (STAT3) and ERK. Photodynamic therapy-treated cells, which were maintained during post-PDT recovery in presence of IL-6 or Hyper-IL-6, showed an enhanced suppression of proliferation. Cytokine-dependent inhibition of proliferation correlated with a decrease in cyclin E, CDK2 and Cdc25A, and enhancement of p27kip1 and hypophosphorylated Rb. The IL-6 trans-signalling-mediated attenuation of cell proliferation was also effective in vivo detectable by an improved Colon26 tumour cure by PDT combined with Hyper-IL-6 treatment. Prevention of IL-6 trans-signalling using soluble gp130 reduced curability. The data suggest that the post-PDT tumour milieu contains the necessary components to establish effective IL-6 trans-signalling, thus providing a means for more effective tumour control. PMID:17987036

Wei, L-H; Baumann, H; Tracy, E; Wang, Y; Hutson, A; Rose-John, S; Henderson, B W

2007-01-01

366

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

367

Changes in esophageal motility after porfimer sodium photodynamic therapy for Barrett's dysplasia and mucosal carcinoma.  

PubMed

Esophageal dysmotility is common in patients with Barrett's esophagus. Previously we have reported deterioration of esophageal motility after photodynamic therapy (PDT) in a heterogeneous group of patients with esophageal carcinoma. This prospective study in consecutive patients describes changes in motility noted after endoscopic ablation. Forty-seven patients referred to our institution for endoscopic ablation for Barrett's high grade dysplasia or mucosal carcinoma between August 2001 and May 2003 were prospectively evaluated with esophageal manometry before and after porfimer sodium PDT. Six patients did not complete the study. Manometry results were classified as normal, diffuse esophageal spasm, ineffective esophageal motility, or aperistalsis. Abnormal esophageal motility was found in 14 of 47 (30%) patients at study entry ([diffuse esophageal spasm] DES-3, [ineffective esophageal motility] IEM-7, Aperistalsis-4). After PDT, 11 of 41 patients with paired studies experienced a change in manometric diagnosis. Three patients had an improvement in motility, seven a worsening and one changed diagnosis, but did not particularly worsen or improve. No patient developed new aperistalsis. Therefore, abnormal motility was present in 19 of 41 (46%) patients after PDT (DES-2, IEM-14, Aperistalsis-3). There was a statistically significant (P = 0.016) relationship with longer segment Barrett's esophagus and deterioration of function. Baseline abnormalities in motility can occur in patients with Barrett's high-grade dysplasia or mucosal carcinoma. Changes in esophageal function also may occur following photodynamic therapy, but usually are not clinically significant. Worsening in function was more likely to occur in patients with longer segment Barrett's esophagus. PMID:16984528

Shah, A K; Wolfsen, H C; Hemminger, L L; Shah, A A; DeVault, K R

2006-01-01

368

Single particle and ensemble spectroscopy of conjugated polymer nanoparticles and their development for photodynamic therapy  

NASA Astrophysics Data System (ADS)

Energy transport in conjugated polymers is the combination of energy transfer and exciton diffusion. There is considerable ongoing research in this field, converging to develop better organic photovoltaics, polymer light emitting diodes (PLEDs) and organic solar cells, to name a few. One way these phenomena can be explored is by doing solution dependent studies on conjugated polymer nanoparticles. With experiments on CP dots in an aqueous solution and the addition of a water miscible organic solvent in varying concentrations, dynamics occurring in the folding process can be better understood, and also exciton and fluorescence quenching properties can be extracted as a function of nanoparticle collapse. Steady state and time resolved fluorescence measurements were taken for two types of CP dots in bulk solution under varying solvent environments, including quantum yield, photobleaching and reversible photobleaching. The time-domain technique of time-correlated single photon counting (TCSPC) was used to determine excited state lifetimes and fluorescent decay traces. Simulating the TCSPC data provides insight on the relative number of quenchers that are observed by the polymer in each environment. In addition, single molecule fluorescence spectroscopy measurements were done on CP dots under varying solvent vapor atmospheres. Using the phenomenon of energy transfer, we have proven that doping the singlet oxygen photosensitizer tetraphenylporphyrin (TPP) into our conjugated polymer nanoparticles acts as an efficient and powerful photosensitizer for photodynamic therapy. The nanoparticles exhibit highly efficient collection of excitation light due to the large excitation cross-section of the polymer. A quantum efficiency of 0.5 was determined. Extraordinarily large cross-sections for two-photon absorption were found which is promising for near infrared multiphoton photodynamic therapy, and gel electrophoresis of DNA after irradiation in the presence of CP dots indicated extensive purine base and backbone DNA damage.

Grimland, Jennifer L.

369

The impact of antimicrobial photodynamic therapy on Streptococcus mutans in an artificial biofilm model  

NASA Astrophysics Data System (ADS)

The aim of the study was to assess the impact of laser induced antimicrobial photodynamic therapy on the viability of Streptococcus mutans cells employing an aritificial biofilm model. Employing sterile chambered coverglasses, a salivary pellicle layer formation was induced in 19 chambers. Streptococcus mutans cells were inoculated in a sterile culture medium. Using a live/dead bacterial viability kit, bacteria with intact cell membranes stain fluorescent green. Test chambers containing each the pellicle layer and 0.5 ml of the bacterial culture were analyzed using a confocal laser scan microscope within a layer of 10 ?m at intervals of 1 ?m from the pellicle layer. A photosensitizer was added to the test chambers and irradiated with a diode laser (wavelength: 660 nm, output power: 100 mW, Helbo) for 2 min each. Comparing the baseline fluorescence (median: 13.8 [U], min: 3.7, max: 26.2) with the values after adding the photosensitizer (median: 3.7, min: 1.1, max: 9), a dilution caused decrease of fluorescence could be observed (p<0.05). After irradiation of the samples with a diode laser, an additional 48 percent decrease of fluorescence became evident (median: 2.2, min: 0.4, max: 3.4) (p<0.05). Comparing the samples with added photosensitizer but without laser irradiation at different times, no decrease of fluorescence could be measured (p>0.05). The present study indicates that antimicrobial photodynamic therapy can reduce living bacteria within a layer of 10 ?m in an artificial biofilm model. Further studies have to evaluate the maximum biofilm thickness that still allows a toxic effect on microorganisms.

Schneider, Martin; Kirfel, Gregor; Krause, Felix; Berthold, Michael; Brede, Olivier; Frentzen, Matthias; Braun, Andreas

2010-02-01

370

Re-endothelialization following balloon injury and photodynamic therapy of the rabbit aorta  

NASA Astrophysics Data System (ADS)

De-endothelialization is the main stimulus of intimal hyperplasia following vascular injury. In this study we investigated the time course of re-endothelialization in balloon injured and photodynamic therapy (PDT) treated aortas of New Zealand white rabbits. Twenty rabbits underwent balloon denudation of the abdominal aorta and were then sacrificed in groups of 4 animals 0, 1, 2, 4 and 8 weeks later. Twenty more rabbits underwent similar balloon denudation and were treated immediately afterwards with photodynamic therapy using the photosensitizer metatetrahydroxy phenyl-chlorin and endovascular illumination with 652 nm light. PDT treated rabbits were also sacrificed in groups of 4 animals at the same time intervals. A further 4 rabbits were sacrificed without any treatment to act as normal controls. The vasculature was perfusion fixed at 100 mmHg with 10% formal saline. The abdominal aortas were retrieved and five sections were cut from each aorta at 1 cm intervals, embedded in wax, sectioned and stained for endothelial cells using the Avidin Biotin complex/horseradish peroxidase technique for use with the monoclonal primary antibody CD31 from the clone JC70. Endothelial covering was measured using a light microscope and Magiscan image analysis system. Normal arteries showed a near full (92.1% plus or minus 3.0, mean plus or minus SEM) endothelial covering. Endothelium was removed completely after both balloon injury and PDT. In balloon injury alone there was progressive endothelial regrowth with (54.1 plus or minus 7.2) covering at 8 weeks. In contrast, endothelial regrowth was retarded in the aortas treated with balloon injury and PDT, with only (7.1 plus or minus 2.9) of covering at 8 weeks. The slow pace of re-endothelialisation is consistent with greater production of intimal hyperplasia in PDT treated vessels.

Koenig, Thomas C.; Sobeh, Mohammed S.; Ham, Robert J.; Cross, Frank W.; Greenwald, Stephen E.

1997-05-01

371

Aromatase inhibitor adjuvant chemotherapy of breast cancer results in cancer therapy induced bone loss.  

PubMed

Aromatase Inhibitors are anti-estrogen agents that have proven efficacy for adjuvant therapy of estrogen receptor positive breast cancer primarily in post menopausal women with estrogen receptor positive breast cancer but increase the risk of cancer therapy induced bone loss (CTIBL). Recent studies have shown the potential benefit of bisphosphonate therapy to play a dual role in the management of breast cancer. These studies provide evidence that bisphosphonate therapy in conjunction with aromatase inhibitors (AI), not only decreases the risk of osteoporosis but, in addition, may improve survival from breast cancer. PMID:23408144

Rinaldi, Renee Z

2013-03-01

372

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

373

Radiofrequency hyperthermia as adjuvant therapy following surgical resection of an experimental malignant neoplasm.  

PubMed

Local recurrence after radical surgery is a major problem with many primary solid cancers. The use of radiofrequency hyperthermia (RFHT) as adjuvant therapy to surgery was explored in the Fischer bladder carcinoma (FBCa)/F344 rat tumor system. After subcutaneous innoculation of 34 rats with 10(6) FBCa cells in suspension, RFHT was administered to 17 animals on days 1, 5, 8, and 12. The development of palpable tumors was delayed but not prevented, and tumor growth was retarded in RFHT-treated animals. In another experiment 40 rats were innoculated by subcutaneous trocar injection with a 1 mm3 piece of FBCa. After tumor excision on day 17, adjuvant therapy (untreated control, mitomycin C, RFHT, or RFHT plus mitomycin C) was started on day 20 (10 rats/treatment). The 20 RFHT-treated rats had only 1 incisional recurrence as compared to 9 recurrences in sham-heated rats (P less than 0.005). The authors conclude that RFHT has considerable value as adjuvant therapy to surgery in these tumors. Additional studies of RFHT as adjuvant treatment after surgical excision of tumors are planned. PMID:3995484

Dalfen, R; Calhoun, K; Gilas, T; Mathews, T; Falk, M; Moffat, F L; Makowka, L; Rotstein, L E; Langer, J C; Venturi, D

1985-06-01

374

Use of Adjuvant Endocrine Therapy in Postmenopausal Hormone Receptor-Positive Breast Cancer at German Breast Cancer Centers and University Hospitals - Results of an Enquiry (Adjuvant Endocrine Therapy Enquiry)  

Microsoft Academic Search

SummaryBackground: Many studies about the adjuvant endocrine therapy of postmenopausal patients with hormone receptor-positive breast cancer have shown significant superiority of aromatase inhibitors (AIs) compared to tamoxifen only. Within these studies, different AIs (anastrozole, letrozole, exemestane) and treatment strategies (upfront, switch, extended adjuvant) were applied. Material and Methods: The intention of our enquiry was to evaluate the implementation of the

Thomas Kolben; Susanne Engelmann; Susanne Maurer; Martin Kolben

2012-01-01

375

Assessment of Photodynamic Therapy (PDT) in Disinfection of Deeper Dentinal Tubules in a Root Canal System: An In Vitro Study  

PubMed Central

Context: The success of endodontic treatment therapy depends on how well we eliminate pathogenic microflora from the root canal system as micro organism as the major cause of root canal infection. Conventional root canal treatment can fail if microorganisms cannot be removed sufficiently by thorough cleaning, shaping of root canal. Newer modalities such as photodynamic therapy are being tried now a days for disinfection of root canals. Aim & Objectives: The basic aim of this study was assessment of the antimicrobial efficacy of Photodynamic Therapy in deeper dentinal tubules for effective disinfection of root canals using microbiological and scanning electron microscopic examination in vitro. Materials and Methods: The study was conducted at Teerthanker Mahaveer Dental College & Research Centre. The teeth required for study was collected from Department of Oral and Maxillofacial Surgery. Only freshly extracted 20 intact, non carious single rooted teeth which were indicated for orthodontic treatment were taken for this study. Statistical analysis was done using Student’s Unpaired t-test were at (p<0.001) was found to be highly significant. Microbiological examination of samples were done and colony forming units were counted to assess the disinfection potential of photodynamic therapy. Scanning electron microscopic examination of samples was done to check penetration of bacteria’s into deeper dentinal tubules. Results: On examination, there was a marked reduction in microbial growth after use of photodynamic therapy. On scanning electron microscopic examination, it was observed that there were less number of bacteria’s in deeper dentinal tubules in case of PDT group as compared to control group. Conclusion: The results of the present study indicate that PDT can be effectively used during antimicrobial procedures along with conventional disinfection procedure for sterilization of root canals. PMID:25584321

Bhaskar, Dara John; Agali, Chandan R; Punia, Himanshu; Gupta, Vipul; Singh, Vikas; Kadtane, Safalya; Chandra, Sneha

2014-01-01

376

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

377

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. PMID:25364655

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

2014-01-01

378

Immunotherapy regimens for combination with photodynamic therapy aimed at eradication of solid cancers  

NASA Astrophysics Data System (ADS)

Due to inflammatory/immune responses elicited by photodynamic therapy (PDT), this modality is particularly suitable in combination with various forms of immunotherapy for an improved therapeutic gain. A wide variety of approaches that may be applicable in this context include those focusing on amplifying the activity of particular immune cell types (neutrophils, macrophages, dendritic cells, natural killer cells, helper or cytotoxic T lymphocytes). Another type of approach is to focus on a specific phase of immune response development, which comprises the activation of non-specific inflammatory immune effectors, immune recognition, immune memory, immune rejection, or blocking of immune suppression. These different strategies call for a variety of immunotherapeutic protocols to be employed in combination with PDT. These include treatments such as: (1) non-specific immunoactivators (e.g. bacterial vaccines), (2) specific immune agents (cytokines, or other activating factors), (3) adoptive immunotherapy treatments (transfer of dendritic cells, tumor-sensitized T lymphocytes or natural killer cells), or (4) their combinations. Techniques of gene therapy employed in some of these protocols offer novel opportunities for securing a potent and persistent immune activity. Using PDT and immunotherapy represents an attractive combination for cancer therapy that is capable of eradicating both localized and disseminated malignant lesions.

Korbelik, Mladen

2000-06-01

379

WSTO9 (TOOKAD) mediated photodynamic therapy as an alternative modality in the treatment of prostate cancer  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) utilizes optical energy to activate a pre-administered photosensitizer drug to achieve a localized tumor control. In the presented study, PDT mediated with a second-generation photosensitizer, WST09 (TOOKAD, Steba Biotech, The Netherlands), is investigated as an alternative therapy in the treatment of prostate cancer. In vivo canine prostate is used as the animal model. PDT was performed by irradiating the surgically exposed prostates both superficially and interstitially with a diode laser (763 nm) to activate the intra-operatively i.v. infused photosensitizer. During light irradiation, tissue optical properties, and temperature were monitored. During the one-week to 3-month period post PDT treatment, the dogs recovered well with little or no complications. The prostates were harvested and subjected to histopathological evaluations. Maximum lesion size of over 3 cm in dimension could be achieved with a single treatment, suggesting the therapy is extremely effective in destroying prostatic tissue. Although we found there was loss of epithelial lining in prostatic urethra, there was no evidence it had caused urinary tract side effects as reported in those studies utilizing transurethral irradiation. In conclusion, we found second generation photosensitizer WST09 mediated PDT may provide an excellent alternative to treat prostate cancer.

Chen, Qun; Huang, Zheng; Luck, David L.; Beckers, Jill; Brun, Pierre-Herve; Wilson, Brian C.; Scherz, Avigdor; Salomon, Yoram; Hetzel, Fred W.

2002-06-01

380

Angiostatic treatment prior to chemo- or photodynamic therapy improves anti-tumor efficacy  

PubMed Central

Tumor vasculature is known to be poorly organized leading to increased leakage of molecules to the extravascular space. This process can potentially increase interstitial fluid pressure impairing intra-tumoral blood flow and oxygen supply, and can affect drug uptake. Anti-angiogenic therapies are believed to reduce vascular permeability, potentially reducing interstitial fluid pressure and improving the extravasation of small molecule-based chemotherapeutics. Here we show that pretreatment of human ovarian carcinoma tumors with sub-optimal doses of the VEGFR targeting tyrosine kinase inhibitor axitinib, but not the EGFR targeting kinase inhibitor erlotinib, induces a transient period of increased tumor oxygenation. Doxorubicin administered within this window was found to enter the extravascular tumor space more rapidly compared to doxorubicin when applied alone or outside this time window. Treatment with the chemotherapeutics, doxorubicin and RAPTA-C, as well as applying photodynamic therapy during this period of elevated oxygenation led to enhanced tumor growth inhibition. Improvement of therapy was not observed when applied outside the window of increased oxygenation. Taken together, these findings further confirm the hypothesis of angiostasis-induced vascular normalization and also help to understand the interactions between anti-angiogenesis and other anti-cancer strategies. PMID:25758612

Weiss, Andrea; Bonvin, Débora; Berndsen, Robert H.; Scherrer, Edoardo; Wong, Tse J.; Dyson, Paul J.; Griffioen, Arjan W.; Nowak-Sliwinska, Patrycja

2015-01-01

381

Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer  

PubMed Central

Semiconductor quantum dots and nanoparticles composed of metals, lipids or polymers have emerged with promising applications for early detection and therapy of cancer. Quantum dots with unique optical properties are commonly composed of cadmium contained semiconductors. Cadmium is potentially hazardous, and toxicity of such quantum dots to living cells, and humans, is not yet systematically investigated. Therefore, search for less toxic materials with similar targeting and optical properties is of further interest. Whereas, the investigation of luminescence nanoparticles as light sources for cancer therapy is very interesting. Despite advances in neurosurgery and radiotherapy the prognosis for patients with malignant gliomas has changed little for the last decades. Cancer treatment requires high accuracy in delivering ionizing radiation to reduce toxicity to surrounding tissues. Recently some research has been focused in developing photosensitizing quantum dots for production of radicals upon absorption of visible light. In spite of the fact that visible light is safe, this approach is suitable to treat only superficial tumours. Ionizing radiation (X-rays and gamma rays) penetrate much deeper thus offering a big advantage in treating patients with tumours in internal organs. Such concept of using quantum dots and nanoparticles to yield electrons and radicals in photodynamic and radiation therapies as well their combination is reviewed in this article. PMID:18840487

Juzenas, Petras; Chen, Wei; Sun, Ya-Ping; Coelho, Manuel Alvaro Neto; Generalov, Roman; Generalova, Natalia; Christensen, Ingeborg Lie

2009-01-01

382

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

383

Adjuvant Therapy in Lymph Node–Positive Vulvar Cancer: The AGO-CaRE-1 Study  

PubMed Central

Background: Women with node-positive vulvar cancer have a high risk for disease recurrence. Indication criteria for adjuvant radiotherapy are controversial. This study was designed to further understand the role of adjuvant therapy in node-positive disease. Methods: Patients with primary squamous-cell vulvar cancer treated at 29 gynecologic cancer centers in Germany from 1998 through 2008 were included in this retrospective exploratory multicenter cohort study. Of 1618 documented patients, 1249 had surgical groin staging and known lymph node status and were further analyzed. All statistical tests were two-sided. Results: Four hundred forty-seven of 1249 patients (35.8%) had lymph node metastases (N+). The majority of N+ patients had one (172 [38.5%]) or two (102 [22.8%]) positive nodes. The three-year progression-free survival (PFS) rate of N+ patients was 35.2%, and the overall survival (OS) rate 56.2% compared with 75.2% and 90.2% in node-negative patients (N-). Two hundred forty-four (54.6%) N+ patients had adjuvant therapy, of which 183 (40.9%) had radiotherapy directed at the groins (+/-other fields). Three-year PFS and OS rates in these patients were better compared with N+ patients without adjuvant treatment (PFS: 39.6% vs 25.9%, hazard ratio [HR] = 0.67, 95% confidence interval [CI[= 0.51 to 0.88, P = .004; OS: 57.7% vs 51.4%, HR = 0.79, 95% CI = 0.56 to 1.11, P = .17). This effect was statistically significant in multivariable analysis adjusted for age, Eastern Cooperative Oncology Group, Union internationale contre le cancer stage, grade, invasion depth, and number of positive nodes (PFS: HR = 0.58, 95% CI = 0.43 to 0.78, P < .001; OS: HR = 0.63, 95% CI = 0.43 to 0.91, P = .01). Conclusion: This large multicenter study in vulvar cancer observed that adjuvant radiotherapy was associated with improved prognosis in node-positive patients and will hopefully help to overcome concerns regarding adjuvant treatment. However, outcome after adjuvant radiotherapy remains poor compared with node-negative patients. Adjuvant chemoradiation could be a possible strategy to improve therapy because it is superior to radiotherapy alone in other squamous cell carcinomas. PMID:25618900

Jueckstock, Julia; Hilpert, Felix; Neuser, Petra; Harter, Philipp; de Gregorio, Nikolaus; Hasenburg, Annette; Sehouli, Jalid; Habermann, Annika; Hillemanns, Peter; Fuerst, Sophie; Strauss, Hans-Georg; Baumann, Klaus; Thiel, Falk; Mustea, Alexander; Meier, Werner; du Bois, Andreas; Griebel, Lis-Femke; Woelber, Linn

2015-01-01

384

In vivo measurement of fluorescence emission in the human prostate during photodynamic therapy  

NASA Astrophysics Data System (ADS)

Among the challenges to the clinical implementation of photodynamic therapy (PDT) is the delivery of a uniform photodynamic dose to induce uniform damage to the target tissue. As the photodynamic dose depends on both the local sensitizer concentration and the local fluence rate of treatment light, knowledge of both of these factors is essential to the delivery of uniform dose. In this paper, we investigate the distribution and kinetics of the photosensitizer motexafin lutetium (MLu, Lutrin) as revealed by its fluorescence emission. Our current prostate treatment protocol involves interstitial illumination of the organ via cylindrical diffusing fibers (CDF"s) inserted into the prostate though clear catheters. For planning and treatment purposes, the prostate is divided into 4 quadrants. We use one catheter in each quadrant to place an optical fiber-based fluorescence probe into the prostate. This fiber is terminated in a beveled tip, allowing it to deliver and collect light perpendicular to the fiber axis. Excitation light is provided by a 465 nm light emitting diode (LED) source coupled to a dichroic beamsplitter, which passes the collected fluorescence emission to a CCD spectrograph. Spectra are obtained before and after PDT treatment in each quadrant of the prostate and are analyzed via a linear fitting algorithm to separate the MLu fluorescence from the background fluorescence originating in the plastic catheter. A computer-controlled step motor allows the excitation/detection fiber to be moved along the catheter, building up a linear profile of the fluorescence emission spectrum of the tissue as a function of position. We have analyzed spectral fluorescence profiles obtained in 4 patients before and after MLu-mediated PDT. We find significant variation both within individual prostates and among patients. Within a single quadrant, we have observed the fluorescence signal to change by as much as a factor of 3 over a distance of 2 cm. Comparisons of pre- and post-PDT spectra allow a quantification treatment-induced photobleaching. Like the drug distribution, the extent of photobleaching varies widely among patients. In two cases, we observed bleaching of approximately 50% of the drug, while others exhibited negligible photobleaching.

Finlay, Jarod C.; Zhu, Timothy C.; Dimofte, Andreea; Stripp, Diana; Malkowicz, S. B.; Whittington, Richard; Miles, Jeremy; Glatstein, Eli; Hahn, Stephen M.

2005-04-01

385

Efficacy of Chlorin e6-Mediated Sono-Photodynamic Therapy on 4T1 Cells  

PubMed Central

Abstract Purpose: The present study aims to investigate the antitumor effect and possible mechanisms of chlorin e6 (Ce6)-mediated sono-photodynamic therapy (Ce6-SPDT) on murine 4T1 mammary cancer cells in vitro. Materials: Cellular uptake and intracellular distribution of Ce6 in 4T1 cells were detected by flow cytometry and confocal microscope. Cells after loading with 1??g/mL Ce6 were exposed to ultrasound at 1.0?MHz for up to 1 minute with an intensity of 0.36?W/cm2 and laser light with total radiation dose of 1.2?J/cm2. Cell viability and clonogenicity were determined by MTT assay and colony formation assay. Apoptosis was analyzed by DAPI staining, Western blots were used to detect the activity of Caspase-3. DNA damage, mitochondrial membrane potential (MMP), and intracellular reactive oxygen species (ROS) of 4T1 cells were also evaluated by flow cytometry. FD500 was employed to detect changes of membrane permeability after ultrasound. Results: Ce6 rapidly entered 4T1 cells within 4 hours after it has been added and displayed a mitochondria-localization pattern. Compared with sonodynamic therapy (SDT) and photodynamic therapy (PDT) alone, the combined SPDT treatment further enhanced cell viability loss, DNA damage, and clonogenicity inhibition. DAPI staining and western blots analysis reflected that cells with apoptotic morphological characteristics and the activity of Caspase-3 were apparently increased in the combined group. Besides, SPDT caused obvious MMP loss and intracellular ROS generation at early 1 hour post treatment. Interestingly, the SPDT induced cell viability loss and cell apoptosis was greatly inhibited by pre-treatment with ROS scavenger N-acetylcysteine and Caspase inhibitor z-VAD-fmk. FD500 detection showed that ultrasound enhanced cell membrane permeability, implying much higher uptake of Ce6 might be involved in PDT therapy by pre-ultrasound treatment. Conclusions: The findings demonstrated that Ce6-mediated SPDT enhanced the antitumor efficacy on 4T1 cells compared with SDT and PDT alone, a Caspase-dependent apoptosis and loss of MMP, generation of ROS may be involved. PMID:24206161

Li, Qing; Wang, Xiaobing; Wang, Pan; Zhang, Kun; Wang, Haiping; Feng, Xiaolan

2014-01-01

386

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

387

Photodynamic therapy effect of zinc monoamino phthalocyanine-folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells.  

PubMed

This work reports on the photodynamic therapy effect of zinc monoamino phthalocyanine linked to folic acid represented as ZnMAPc-FA, which was further immobilized onto single walled carbon nanotube represented as ZnMAPc-FA-SWCNT on melanoma A375 cell line, the effect of SWCNT-FA (without ZnMAPc) was also examined. All the compounds were non-toxic to the melanoma A375 cell line in the absence of light. Upon irradiation of the melanoma A375 cell line with a 676 nm diode laser at a power density of 98 mW/cm(2) at 5 J/cm(2) about 60% and 63% cell death was observed in the presence of ZnMAPc-FA and ZnMAPc-FA-SWCNT respectively. SWCNT-FA had no significant photodynamic therapy or photothermal effect to the cell, only 23% of cell death was observed after irradiation. PMID:25305603

Ogbodu, Racheal O; Ndhundhuma, Ivy; Karsten, Aletta; Nyokong, Tebello

2015-02-25

388

Photodynamic therapy effect of zinc monoamino phthalocyanine-folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells  

NASA Astrophysics Data System (ADS)

This work reports on the photodynamic therapy effect of zinc monoamino phthalocyanine linked to folic acid represented as ZnMAPc-FA, which was further immobilized onto single walled carbon nanotube represented as ZnMAPc-FA-SWCNT on melanoma A375 cell line, the effect of SWCNT-FA (without ZnMAPc) was also examined. All the compounds were non-toxic to the melanoma A375 cell line in the absence of light. Upon irradiation of the melanoma A375 cell line with a 676 nm diode laser at a power density of 98 mW/cm2 at 5 J/cm2 about 60% and 63% cell death was observed in the presence of ZnMAPc-FA and ZnMAPc-FA-SWCNT respectively. SWCNT-FA had no significant photodynamic therapy or photothermal effect to the cell, only 23% of cell death was observed after irradiation.

Ogbodu, Racheal O.; Ndhundhuma, Ivy; Karsten, Aletta; Nyokong, Tebello

2015-02-01

389

Interlesion differences in the local photodynamic therapy response of oral cavity lesions assessed by diffuse optical spectroscopies.  

PubMed

Photodynamic therapy (PDT) efficacy depends on the local dose deposited in the lesion as well as oxygen availability in the lesion. We report significant interlesion differences between two patients with oral lesions treated with the same drug dose and similar light dose of 2-1[hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH)-mediated photodynamic therapy (PDT). Pre-PDT and PDT-induced changes in hemodynamic parameters and HPPH photosensitizer content, quantified by diffuse optical methods, demonstrated substantial differences between the two lesions. The differences in PDT action determined by the oxidative cross-linking of signal transducer and activator of transcription 3 (STAT3), a molecular measure of accumulated local PDT photoreaction, also showed >100-fold difference between the lesions, greatly exceeding what would be expected from the slight difference in light dose. Our results suggest diffuse optical spectroscopies can provide in vivo metrics that are indicative of local PDT dose in oral lesions. PMID:23024908

Rohrbach, Daniel J; Rigual, Nestor; Tracy, Erin; Kowalczewski, Andrew; Keymel, Kenneth L; Cooper, Michele T; Mo, Weirong; Baumann, Heinz; Henderson, Barbara W; Sunar, Ulas

2012-09-01

390

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

391

Efficacy of gallium phthalocyanine as a photosensitizing agent in photodynamic therapy for the treatment of cancer  

NASA Astrophysics Data System (ADS)

Photodynamic therapy is a revolutionary treatment aimed at treating cancers without surgery or chemotherapy. It is based on the discovery that certain chemicals known as photosensitizing agents (e.g. porphyrins, phthalocyanines, etc.) can kill cancerous cells when exposed to low level laser light at a specific wavelength. The present study investigates the cellular uptake and photodynamic effect of gallium (III) phthalocyanine chloride (GaPcCl) on Caco-2 cancer cells. Caco-2 cells were treated with different concentrations of GaPcCl for 2 h before treatment with a diode laser (? = 661 nm, laser power = 90 mW) delivering a light dose of 2.5 J/cm2, 4.5 J/cm2 or 8.5 J/cm2. After 24 h, the cell viability of post-irradiated cells was measured using the MTT assay. Cellular uptake studies were performed by photosensitizing cells with GaPcCl for 30 min, 2 h, 10 h, 12 h, 18 h and 24 h before lysing the treated cells into solution to measure the GaPcCl fluorescence emission at an excitation wavelength of 600 nm. Results showed an increase in fluorescence intensity of emission peaks at longer incubation times, indicating a greater cellular uptake of GaPcCl by Caco-2 cells at 24 h in comparison to 30 min. GaPcCl at a concentration of 100 ?g/ml activated with a laser light dose of 8.5 J/cm2 reduced the cell viability of Caco-2 cells to 27%. This concludes that GaPcCl activated with low level laser light can be used as a photosensitizing agent for the in vitro PDT treatment of colon cancer.

Maduray, Kaminee; Odhav, Bharti

2012-12-01

392

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

393

Sensitization of cerebral tissue in nude mice with photodynamic therapy induces ADAM17\\/TACE and promotes glioma cell invasion  

Microsoft Academic Search

In the present study, we tested the hypothesis that a mild cerebral tissue injury promotes subsequent glioma invasion via activation of the ADAM17-EGFR-PI3K-Akt pathway. Mild injury was induced by photodynamic therapy (PDT), which employs tissue-penetrating laser light exposure following systemic administration of a tumor-localizing photosensitizer. Athymic nude mice were treated with sublethal PDT (80J\\/cm2 with 2mg\\/kg Photofrin). Hypoxic stress and

Xuguang Zheng; Feng Jiang; Mark Katakowski; Xuepeng Zhang; Hao Jiang; Zheng Gang Zhang; Michael Chopp

2008-01-01

394

Light parameters influence cell viability in antifungal photodynamic therapy in a fluence and rate fluence-dependent manner  

Microsoft Academic Search

The aim of this study was to investigate the influence of light parameters on yeast cells. It has been proposed for many years\\u000a that photodynamic therapy (PDT) can inactivate microbial cells. A number of photosensitizer and light sources were reported\\u000a in different light parameters and in a range of dye concentrations. However, much more knowledge concerning the importance\\u000a of fluence,

Renato A. Prates; Eriques G. da Silva; Aécio M. Yamada; Luis C. Suzuki; Claudete R. Paula; Martha S. Ribeiro

2009-01-01

395

Clinical results of photodynamic therapy for superficial skin malignancies or actinic keratosis using topical 5-aminolaevulinic acid  

Microsoft Academic Search

Photodynamic therapy (PDT) with topical application of 5-aminolaevulinic acid (ALA, 20% w\\/w) was used to treat superficial basal cell carcinoma (BCC, 16 patients), Morbus Bowen (one patient), basal cell naevus syndrome (BCNS, three patients), actinic keratosis (AK, two patients), chronic inflammation (CI, one patient), and metastasized BCC (one patient). The interval between ALA application and illumination was 3–6 h. The

P. J. N. Meijnders; W. M. Star; R. S. Bruijn; A. D. Treurniet-Donker; M. J. M. Mierlo; S. J. M. Wijthoff; B. Naafs; H. Beerman; P. C. Levendag

1996-01-01

396

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

397

Interstitial photodynamic therapy in subcutaneously implanted urologic tumors in rats after intravenous administration of 5-aminolevulinic acid  

Microsoft Academic Search

Photodynamic therapy (PDT) may be an attractive option for treatment of early stage prostate cancer. Aminolevulinic acid (ALA) acts as a pro-drug leading to a selective accumulation of a photosensitizer, protoporphyrin IX (PpIX), in epithelial cells. We investigated the efficacy of ALA-mediated PDT for rat R3327-H prostate cancer, compared with the AY-27 bladder tumor. Rats bearing either AY-27 or R3327-H

Zhengwen Xiao; Yahya Tamimi; Kevin Brown; John Tulip; Ronald Moore

2002-01-01

398

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

399

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

400

Studies on Preparation of Photosensitizer Loaded Magnetic Silica Nanoparticles and Their Anti-Tumor Effects for Targeting Photodynamic Therapy  

NASA Astrophysics Data System (ADS)

As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT) is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs) were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl)-13,17-bis-(3-hydroxypropyl) porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe3O4) and PHPP were incorporated into silica nanoparticles by microemulsion and sol-gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20-30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.

Chen, Zhi-Long; Sun, Yun; Huang, Peng; Yang, Xiao-Xia; Zhou, Xing-Ping

2009-05-01

401

Photodynamic therapy for Barrett's esophagus using a 20-mm diameter light-delivery balloon  

NASA Astrophysics Data System (ADS)

Background and Objective: Patients with high grade dysplasia (HGD) in Barrett's esophagus are at a high risk for developing esophageal adenocarcinoma. Esophagectomy is the standard treatment for such patients. The objective of this study was to evaluate the safety and efficacy of photodynamic therapy (PDT) using an improved light delivery balloon for ablation of Barrett's esophagus with high grade dysplasia and/or early cancer. Materials and Methods: 20 patients with HGD or early cancer (19 with HGD, 1 with T1 cancer) received 2 mg/kg of porfimer sodium, intravenously. Two to three days after the injection, laser light was delivered using a cylindrical diffuser inserted inside a 20-mm diameter reflective esophageal PDT balloon. Initially, the balloon was inflated to a pressure of 80 mm Hg. The balloon pressure was gradually reduced to 30 mm Hg. A KTP/dye laser at 630 nm was used as the light source. Light dose of 115 J/cm was delivered at an intensity of 270 mw/cm. Nodules were pre- treated with an extra 50 J/cm using a short diffuser inserted through the scope. Patients were maintained on PPI therapy to keep the gastric pH higher than 4. Eighteen patients required one treatment, while two patients were treated twice. Follow-up consisted of endoscopy with four quadrant biopsies at every 2 cm of the treated area. Thermal ablation was used to treat small residual islands on the follow-ups. The follow-up endoscopies ranged from 6 to 17 months. Results: On follow-up endoscopy, 12 patients had complete replacement of their Barrett's mucosa with neosquamous mucosa. Five patients had residual non-dysplastic Barrett's mucosa, one had indefinite dysplasia, two had low grad dysplasia. There were no residual HGD or cancers. The average length of Barrett's was reduced from 5.4 cm to 1.2 cm. High balloon pressure resulted in wide variation in PDT response among patients. Lower balloon pressures resulted in more consistent destruction of Barrett's mucosa among patients. Five patients developed strictures which responded well to dilations. One patient developed atrial fibrillation which responded to medications. Conclusions: Photodynamic therapy using a 20 mm diameter balloon was effective for ablation of high grade dysplasia and early cancer in Barrett's esophagus. Low balloon inflation pressure was a critical parameter in producing consistent tissue destruction.

Panjehpour, Masoud; Overholt, Bergein F.; Phan, Mary N.; Haydek, John M.; Robinson, Amy R.

2002-06-01

402

Studies of vascular acting photosensitizer Tookad for the photodynamic therapy of prostate cancer  

NASA Astrophysics Data System (ADS)

In this pre-clinical study, photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (palladium-bacteriopheophorbide) is investigated as an alternative treatment modality for the ablation of prostate cancer. Canine prostate was used as the animal model. PDT was performed by interstitially irradiating the surgically exposed prostates with a diode laser (763 nm) to activate the IV infused photosensitizer. The effects of drug dose, drug-light interval, and light fluence rate on PDT efficacy were evaluated. The prostates and adjacent tissues were harvested at one-week post PDT and subjected to histopathological examination. The dogs recovered well with little or no urethral complications. Urinalysis showed trace blood. Histological examination showed minimal damage to the prostatic urethra. These indicated that the urethra was well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis with a clear demarcation. Maximum lesion volume of ~3 cm3 could be achieved with a single 1-cm diffuser fiber at a dose level of 1 mg/kg and 200 J/cm, suggesting the therapy is very effective in ablating prostatic tissue. PDT induced lesion could reach the capsule layers but adjacent tissues were well preserved. The novel photosensitizer is a vascular drug and cleared rapidly from the circulation. Light irradiation can be performed during drug infusion thereby eliminating waiting time. The novel vascular acting photosensitizer Tookad-mediated PDT could provide an effective alternative to treat prostate cancer.

Huang, Zheng; Chen, Qun; Blanc, Dominique; Hetzel, Fred W.

2005-01-01

403

Doppler optical coherence tomography to monitor the effect of photodynamic therapy on tissue morphology and perfusion.  

PubMed

We investigated the feasibility of using optical coherence tomography (OCT) for noninvasive real-time visualization of the vascular effects of photodynamic therapy (PDT) in normal and tumor tissue in mice. Perfusion control measurements were initially performed after administrating vaso-active drugs or clamping of the subcutaneous tumors. Subsequent measurements were made on tumor-bearing mice before and after PDT using the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC). Tumors were illuminated using either a short drug light interval (D-L, 3 h), when mTHPC is primarily located in the tumor vasculature or a long D-L interval (48 h), when the drug is distributed throughout the whole tumor. OCT enabled visualization of the different layers of tumor, and overlying skin with a maximal penetration of < or =0.5-1 mm. PDT with a short D-L interval resulted in a significant decrease of perfusion in the tumor periphery, to 20% of pre-treatment values at 160 min, whereas perfusion in the skin initially increased by 10% (at 25 min) and subsequently decreased to 60% of pre-treatment values (at 200 min). PDT with a long D-L interval did not induce significant changes in perfusion. The concept of using noninvasive OCT measurements for monitoring early, treatment-related changes in morphology and perfusion may have applications in evaluating effects of anti-angiogenic or antivascular (cancer) therapy. PMID:16965168

Aalders, Maurice C G; Triesscheijn, Martijn; Ruevekamp, Marjan; de Bruin, Martijn; Baas, Paul; Faber, Dirk J; Stewart, Fiona A

2006-01-01

404

Photodynamic therapy for recurrent and residual malignant tumors of the oropharyngeal area  

NASA Astrophysics Data System (ADS)

The frequency of tumor recurrences, according to the modern literature, remains high even in early stages of cancer (15% to 35%), the efficacy of conventional therapy for recurrent tumors is insufficient. In the State Research Center for Laser Medicine in 1992-97 photodynamic therapy with russian photosensitizers Photoheme ((lambda) equals 630 nm) and Photosense ((lambda) equals 670 nm) has been applied to 42 patients with recurrent and/or residual tumors (size corresponding to T1 - T4 symbols) of oropharyngeal area. We used laser irradiation for 3 - 30 minutes, power density used was from 0.05 to 1.0 W/cm2, energy density - 300 J/cm2. Therapeutic effect in term from 3 to 45 months was achieved in 39 (92.9%) patients. Complete resorption of tumors took place in 23 (54.8%) cases, partial resorption - in 16 (38.1%); in 3 cases (7.1%) the results of PDT were assessed as no response (tumor size decrease by less than 50%). Absolute resistance to PDT has not been noticed. The data obtained shows that PDT is a promising treatment modality for managing recurrent and residual tumors of oropharyngeal area.

Stranadko, Eugeny P.; Garbusov, Max I.; Markitchev, Nikolai A.; Riabov, Michail V.

1999-12-01

405

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

406

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

407

Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy  

PubMed Central

Photodynamic therapy (PDT) is a treatment modality that uses a specific photosensitizing agent, molecular oxygen, and light of a particular wavelength to kill cells targeted by the therapy. Topically administered aminolevulinic acid (ALA) is widely used to effectively treat cancerous and precancerous skin lesions, resulting in targeted tissue damage and little to no scarring. The targeting aspect of the treatment arises from the fact that ALA is preferentially converted into protoporphyrin IX (PpIX) in neoplastic cells. To monitor the amount of PpIX in tissues, techniques have been developed to measure PpIX-specific fluorescence, which provides information useful for monitoring the abundance and location of the photosensitizer before and during the illumination phase of PDT. This review summarizes the current state of these fluorescence detection techniques. Non-invasive devices are available for point measurements, or for wide-field optical imaging, to enable monitoring of PpIX in superficial tissues. To gain access to information at greater tissue depths, multi-modal techniques are being developed which combine fluorescent measurements with ultrasound or optical coherence tomography, or with microscopic techniques such as confocal or multiphoton approaches. The tools available at present, and newer devices under development, offer the promise of better enabling clinicians to inform and guide PDT treatment planning, thereby optimizing therapeutic outcomes for patients. PMID:25599015

Rollakanti, Kishore R.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

2014-01-01

408

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

409

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

410

Recent advances in the prevention and treatment of skin cancer using photodynamic therapy  

PubMed Central

Photodynamic therapy (PDT) is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to produce reactive oxygen species that specifically destroy target cells. Recently, PDT has been widely used in treating non-melanoma skin malignancies, the most common cancer in the USA, with superior cosmetic outcomes compared with conventional therapies. The topical ‘photosensitizers’ commonly used are 5-aminolevulinic acid (ALA) and its esterified derivative methyl 5-aminolevulinate, which are precursors of the endogenous photosensitizer protoporphyrin IX. After treatment with ALA or methyl 5-aminolevulinate, protoporphyrin IX preferentially accumulates in the lesion area of various skin diseases, which allows not only PDT treatment but also fluorescence diagnosis with ALA-induced porphyrins. Susceptible lesions include various forms of non-melanoma skin cancer such as actinic keratosis, basal cell carcinoma and squamous cell carcinoma. The most recent and promising developments in PDT include the discovery of new photosensitizers, the exploitation of new drug delivery systems and the combination of other modalities, which will all contribute to increasing PDT therapeutic efficacy and improving outcome. This article summarizes the main principles of PDT and its current clinical use in the management of non-melanoma skin cancers, as well as recent developments and possible future research directions. PMID:21080805

Zhao, Baozhong; He, Yu-Ying

2011-01-01

411

The Effect of Iron Ion on the Specificity of Photodynamic Therapy with 5-Aminolevulinic Acid  

PubMed Central

Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study w