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1

Adjuvant Intraoperative Photodynamic Therapy in Head and Neck Cancer  

PubMed Central

IMPORTANCE There is an immediate need to develop local intraoperative adjuvant treatment strategies to improve outcomes in patients with cancer who undergo head and neck surgery. OBJECTIVES To determine the safety of photodynamic therapy with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with surgery in patients with head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS Nonrandomized, single-arm, single-site, phase 1 study at a comprehensive cancer center among 16 adult patients (median age, 65 years) with biopsy-proved primary or recurrent resectable head and neck squamous cell carcinoma. INTERVENTIONS Intravenous injection of HPPH (4.0 mg/m2), followed by activation with 665-nm laser light in the surgical bed immediately after tumor resection. MAIN OUTCOMES AND MEASURES Adverse events and highest laser light dose. RESULTS Fifteen patients received the full course of treatment, and 1 patient received HPPH without intraoperative laser light because of an unrelated myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6 patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient, who received HPPH only). The most frequent adverse events related to photodynamic therapy were mild to moderate edema (9 patients) and pain (3 patients). One patient developed a grade 3 fistula after salvage laryngectomy, and another patient developed a grade 3 wound infection and mandibular fracture. Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter). The highest laser light dose was 75 J/cm2. CONCLUSIONS AND RELEVANCE The adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous cell carcinoma seems safe and deserves further study. PMID:23868427

Rigual, Nestor R.; Shafirstein, Gal; Frustino, Jennifer; Seshadri, Mukund; Cooper, Michele; Wilding, Gregory; Sullivan, Maureen A.; Henderson, Barbara

2015-01-01

2

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

3

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

PubMed Central

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

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

1997-01-01

4

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

5

Photodynamic therapy for mesothelioma.  

PubMed

Multiple trials of traditional cancer therapies for malignant pleural mesothelioma (including surgery, radiation therapy, and chemotherapy) have not convincingly demonstrated that any one treatment is superior to supportive care alone. Although there have been reports of long-term survivors who were treated with aggressive surgery combined with radiation and aggressive multi-agent chemotherapeutic regimens, these patient populations are highly selected and results cannot be generalized to a larger population. Despite attempts to use aggressive multimodality therapies, disease recurs in most patients. Local failure in particular is a large part of the natural history of mesothelioma, especially after surgery alone. Therefore, one of the major considerations in the development of new treatments is the inclusion of aggressive local therapies. Photodynamic therapy (PDT), a local treatment modality, is being evaluated as an adjuvant therapy to surgical resection. Clinical use of PDT requires the use of a photosensitizing agent and light of a wavelength specific to the absorption characteristics of the sensitizer in the presence of oxygen. The treatment effect of PDT is superficial, mostly because of the limited depth of light absorption in tissues. Therefore, it is theoretically an ideal treatment for tissue surfaces and body cavities after surgical debulking procedures. One theoretical advantage of PDT is that it can be used to treat the lung surface after a pleurectomy; therefore, patients may be treated with a pleurectomy rather than with an extrapleural pneumonectomy. Several studies have evaluated the efficacy of PDT in the treatment of mesothelioma. Clinical studies have not proven convincingly that the use of PDT is superior to the use of other adjuvant therapies or to surgery alone. The advent of newer photosensitizers and improved laser technology has led to a renewed interest in evaluating PDT. Additional studies are necessary to determine the role of PDT in the treatment of mesothelioma. PMID:12057100

Hahn, S M; Smith, R P; Friedberg, J

2001-10-01

6

Photodynamic Therapy: Other Uses  

Microsoft Academic Search

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

Amy Forman Taub

7

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

8

Photodynamic therapy laser system  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) treatment is a new treatment for tumour and Dermatology. With the successful development of the second-generation photosensitizer and the significant manifestations in clinics, PDT has shown a more extensive application potentials. To activate the photosensitizer, in this paper, we present a GaAs-based diode laser system with a wavelength of 635 nm. In this system, to prolong the working life-time of the diode lasers, we use specific feedback algorithm to control the current and the temperature of the diode laser with high precision. The clinic results show an excellent effect in the treatment of Condyloma combined with 5-ALA.

Shu, Xiaoqin; Lin, Qing; Wang, Feng; Shu, Chao; Wang, Jianhua

2009-08-01

9

Photodynamic Therapy (PDT): PDT Mechanisms  

PubMed Central

Photodynamic therapy (PDT) is a light based therapy used to ablate tumors. As practiced in oncology a photosensitizing agent is applied and then activated by a specific wavelength and energy of light. This light energy in the presence of oxygen will lead to the creation of the photodynamic reaction which is cyto and vasculo toxic. This paper will review the mechanisms of action of PDT and how they may be manipulated to improve clinical outcome in cancer patients. PMID:23422955

Allison, Ron R.

2013-01-01

10

Photosensitizers in photodynamic therapy.  

PubMed

Photodynamic therapy (PDT) is based on the use of light-sensitive molecules called photosensitizers. Photoactivation causes the formation of singlet oxygen, which produces peroxidative reactions that can cause cell damage and death. Porfimer sodium (Photofrin, manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, BC, Canada) is the photosensitizer that has been studied most extensively. Patients generally have to be hospitalized for 2 days prior to light treatment after administration of porfimer sodium; it takes approximately 48 hours after injection to reach optimal concentration in tumor tissue. The tumoricidal capacity of PDT with porfimer sodium is determined in part by the maximum depth of penetration of light having a wavelength of 630 nm. Porfimer sodium causes cutaneous photosensitivity that may last for up to 6 weeks. Benzoporphyrin derivative (BPD verteporfin; BPD-Quadra Logic Technologies, Inc, Vancouver, BC, Canada), another photosensitizer, accumulates more rapidly in tumor tissue, permitting optimal PDT 30 to 150 minutes following intravenous administration. It is rapidly cleared from the body, and skin photosensitivity does not extend beyond a few days. The primary mechanism of action of PDT is related to the selective accumulation of photosensitizers in cancer tissue. Photodynamic therapy also shows promise in the treatment of a number of nonneoplastic conditions, including psoriasis, macular degeneration of the retina, atherosclerotic plaque and restenosis, bone marrow purging for treatment of leukemias with autologous bone marrow transplantation, inactivation of viruses in blood or blood products, and several autoimmune conditions, including rheumatoid arthritis. Physiologic characteristics shared by this disparate group of diseases, and the mechanisms by which they may mediate photoactivation, are discussed. PMID:7992105

Levy, J G

1994-12-01

11

Photodynamic therapy for epilepsy  

NASA Astrophysics Data System (ADS)

Epilepsy is surgically curable if the seizure focus can be localized and does not include areas of eloquent cortex. Because epileptic cells are indistinct from surrounding brain, resection typically includes normal tissue. Using the rat kindling model of epilepsy, we evaluated Photodynamic Therapy (PDT) as a super-selective lesioning technique. We present a series of pilot studies to evaluate: 1) Protoporphyrin IX (PpIX) fluorescence, 2) the efficacy of PDT to raise seizure thresholds, 3) the safety of PDT using behavioral studies, and 4) histologic results. Bipolar electrodes were chronically implanted into the cortex and animals received successive low-level stimulation generating seizures of increasing severity. Following 5-aminolevulinic acid (ALA) administration, fully kindled rats received electrical stimulation to induce a generalized seizure. Animals were irradiated with laser light focused onto a temporal craniectomy. Our results show: 1) an increase in PpIX fluorescence in the seizure group, 2) PDT treated animals failed to demonstrate seizure activity following repeat stimulation, 3) no statistically significant difference between treated and control animals were observed on behavioral tests, 4) histology showed pyknotic hippocampal pyramidal cells in the CA3 region without areas of obvious necrosis. In conclusion, this is the first report of heightened PpIX-mediated fluorescence in epileptic brain. The selective accumulation of PpIX with laser PDT may provide a less invasive and more precise technique for obliteration of epileptic foci. PDT warrants additional research to determine if this technique may augment or replace existing procedures for the surgical management of epilepsy.

Zusman, Edie; Sidhu, Manpreet; Coon, Valerie; Scott, Nicholas; Bisland, Stuart; Tsukamoto, Tara

2006-02-01

12

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

PubMed Central

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

Yamada, Aécio M.; Suzuki, Luis C.; França, Cristiane M.; Cai, Silvana; Mayer, Márcia P.A.; Ribeiro, Adriana C.; Ribeiro, Martha S.

2011-01-01

13

Bacteriochlorophyll Sensitizers in Photodynamic Therapy  

Microsoft Academic Search

Recent progress in the bioproduction and chemical manipulation of bacteriochlorophyll (BChl) a has opened the way for utilization of highly potent sensitizers in photodynamic therapy. Although less stable than their\\u000a chlorin analogues in their native form, BChl derivatives provide a superior optical and biophysical profile for the generation\\u000a of reactive oxygen species (ROS). In fact this pigment family probably represents

Alexander S. Brandis; Yoram Salomon; Avigdor Scherz

14

Photodynamic therapy of recurrent cerebral glioma  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) was performed on 11 cases of recurrent cerebral glioma, including 3 cases of recurrent glioblastoma, 7 of recurrent anaplastic astrocytoma, and 1 recurrent ependymoma. Hematoporphyrin derivative (HPD) was administered intravenously at a dose of 4 - 7 mg/kg 5 - 24 hours before the operation. All patients underwent a craniotomy with a nearly radical excision of the tumor following which the tumor bed was irradiated with 630 nm laser light emitting either an argon pumped dye laser or frequency double YAG pumped dye laser for 30 to 80 minutes with a total dose of 50 J/cm2 (n equals 1), 100 J/cm2 (n equals 2), 200 J/cm2 (n equals 7), and 300 J/cm2 (n equals 1). The temperature was kept below 37 degree(s)C by irrigation. Two patients underwent postoperative radiotherapy. There was no evidence of increased cerebral edema, and no other toxicity by the therapy. All patients were discharged from the hospital within 15 days after surgery. We conclude that PDT using 4 - 7 mg/kg of HPD and 630 nm light with a dose of up to 300 J/cm2 can be used as an adjuvant therapy with no additional complications. Adjuvant PDT in the treatment of recurrent glioma is better than simple surgery.

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

1993-03-01

15

Treatment of rheumatoid arthritis using photodynamic therapy  

NASA Astrophysics Data System (ADS)

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

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

1994-10-01

16

Treatment of rheumatoid arthritis using photodynamic therapy  

NASA Astrophysics Data System (ADS)

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

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

1995-03-01

17

Photodynamic Therapy and Antitumor Immunity  

PubMed Central

Preclinical studies have shown that local photodynamic therapy (PDT) enhances systemic antitumor immunity. In addition, it has long been known that the long-term efficacy of PDT depends on the presence of an intact adaptive immune system. Years of research in the laboratory have attempted to shed light on the mechanisms of the PDT-enhanced antitumor immune response, suggesting that increased expression of proinflammatory cytokines may play a key role. This overview on the immunologic potential of PDT briefly explores these proposed mechanisms and addresses preliminary results with PDT vaccines in combination with surgery as perhaps a new clinical strategy for cancer treatment outside the laboratory. PMID:23055214

Gollnick, Sandra O.

2013-01-01

18

Photodynamic therapy: a targeted therapy in periodontics.  

PubMed

The oral cavity is colonized by a large number and highly diversified communities of micro-organisms. Bacterial biofilm present on tooth or root surface is a major cause of gingivitis and periodontitis. Chemical antimicrobial agents are widely used in prophylactic and therapeutic regimens for dental plaque related diseases, which are among the most common human infections. As these agents are difficult to maintain at therapeutic concentrations in the oral cavity and can be rendered ineffective by resistance development in target organisms, there is a need for an alternative antimicrobial approach. A novel approach, photodynamic therapy (PDT), could be a solution to these problems. Lethal photosensitization of many bacteria, both Gram positive and Gram negative was found in many studies. The advantage of this new approach includes rapid bacterial elimination, minimal chance of resistance development and safety of adjacent host tissue and normal microflora. Thus, the available knowledge of photodynamic therapy should encourage a more clinically oriented application of this technique. PMID:19737261

Raghavendra, M; Koregol, A; Bhola, S

2009-09-01

19

Adjuvant Therapy for Kidney Cancer  

Cancer.gov

In this trial, patients who have kidney cancer that can be surgically removed and who are at high risk for recurrence will be given sunitinib (Sutent®), sorafenib (Nexavar®), or a placebo as postoperative (adjuvant) therapy.

20

Photodynamic Diagnosis and Therapy of Cancer  

SciTech Connect

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

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

2010-01-05

21

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

22

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

23

Treatment of experimental murine arthritis with transdermal photodynamic therapy  

NASA Astrophysics Data System (ADS)

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

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

1994-10-01

24

Treatment of experimental murine arthritis with transdermal photodynamic therapy  

NASA Astrophysics Data System (ADS)

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

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

1995-03-01

25

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

26

Adjuvant therapy in pancreatic cancer  

PubMed Central

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

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

2014-01-01

27

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.

28

Nanoparticles in photodynamic therapy: an emerging paradigm.  

PubMed

Photodynamic therapy (PDT) has emerged as one of the important therapeutic options in management of cancer and other diseases [M. Triesscheijn, P. Baas, J.H. Schellens, F.A. Stewart, Photodynamic therapy in oncology, Oncologist 11 (2006) 1034-1044]. Most photosensitizers are highly hydrophobic and require delivery systems. Previous classification of delivery systems was based on presence or absence of a targeting molecule on the surface [Y.N. Konan, R. Gurny, E. Allemann, State of the art in the delivery of photosensitizers for photodynamic therapy, J. Photochem. Photobiol., B 66 (2002) 89-106]. Recent reports have described carrier nanoparticles with additional active complementary and supplementary roles in PDT. We introduce a functional classification for nanoparticles in PDT to divide them into passive carriers and active participants in photosensitizer excitation. Active nanoparticles are distinguished from non-biodegradable carriers with extraneous functions, and sub-classified mechanistically into photosensitizer nanoparticles, [A.C. Samia, X. Chen, C. Burda, Semiconductor quantum dots for photodynamic therapy, J. Am. Chem. Soc. 125 (2003) 15736-15737, R. Bakalova, H. Ohba, Z. Zhelev, M. Ishikawa, Y. Baba, Quantum dots as photosensitizers? Nat. Biotechnol. 22 (2004) 1360-1361] self-illuminating nanoparticles [W. Chen, J. Zhang, Using nanoparticles to enable simultaneous radiation and photodynamic therapies for cancer treatment, J. Nanosci. Nanotechnology 6 (2006) 1159-1166] and upconverting nanoparticles [P. Zhang, W. Steelant, M. Kumar, M. Scholfield, Versatile photosensitizers for photodynamic therapy at infrared excitation, J. Am. Chem. Soc. 129 (2007) 4526-4527]. Although several challenges remain before they can be adopted for clinical use, these active or second-generation PDT nanoparticles probably offer the best hope for extending the reach of PDT to regions deep in the body. PMID:18930086

Chatterjee, Dev Kumar; Fong, Li Shan; Zhang, Yong

2008-12-14

29

Porphyrins for photodynamic therapy of cancer  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) of cancer is based on the dye- sensitized photooxidation of different biological targets in the tumoral tissue yielding to a photochemically induced cell's death. The effectiveness of this treatment method depends on the photophysical and photochemical properties of the used photosensitizer-drug during the irradiation with visible light (laser beam) and/or the ionizing radiation. The purpose of this paper is to summarize the photodynamic therapy applications: substitution effects, ionization and aggregation processes effects, photodegradation reaction implications, the correlation with some medical applications on human brain cells.

Ion, Rodica-Mariana; Pascu, Mihail-Lucian

2001-06-01

30

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

31

[Photodynamic therapy in dermatology: basic principles].  

PubMed

Photodynamic therapy involves the administration of a photosensitizing drug and its subsequent activation by light at wavelengths matching the absorption spectrum of the photosensitizer. Currently, topical photodynamic therapy has received approval for the treatment of cutaneous oncologic conditions such as actinic keratoses, Bowen's disease and superficial basal cell carcinoma in many countries in the world. Multicenter randomized controlled studies have demonstrated high efficacy and superior cosmetic outcome over standard therapies. For many non-oncologic dermatological diseases such as acne vulgaris, viral warts and localized scleroderma, case reports and small series have confirmed the potential of photodynamic therapy. After the development of topical photosensitizers 5-aminolevulinic acid (ALA) or its methyl ester (MAL), photodynamic therapy has gained worldwide popularity in dermatology, as these drugs do not induce prolonged phototoxicity as the systemic photosensitizing hematoporphyrin derivatives do. The production of reactive oxygen intermediates such as singlet oxygen depends on the concentration and localization of the photosensitizer in the diseased tissue as well as the applied light dose. Either incoherent lamps or LED arrays are suitable for the cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving inflammatory condition. PMID:20098846

Torezan, Luís; Niwa, Ane Beatriz Mautari; Neto, Cyro Festa

2009-01-01

32

Interstitial photodynamic laser therapy in interventional oncology  

Microsoft Academic Search

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

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

2004-01-01

33

Light delivery schemes for uterine photodynamic therapy  

Microsoft Academic Search

The use of photodynamic therapy in the removal of the endometrial layer of the uterus provides the possibility of a rapid and effective treatment of menorrhagia avoiding the difficulties and complications of conventional methods. A treatment is proposed in which topical application of 5-aminolaevulinic acid to the inner surface of the uterus is followed by illumination at 630 nm. The

Mark R. Stringer; Emma J. Hudson; Colin P. Dunkley; Jeanetta C. Boyce; Michael J. Gannon; Michael A. Smith

1994-01-01

34

Endodontic photodynamic therapy ex vivo  

PubMed Central

Objective To evaluate the anti-microbial effects of photodynamic therapy (PDT) on infected human teeth ex vivo. Materials and Methods Fifty-two freshly extracted teeth with pulpal necrosis and associated periradicular radiolucencies were obtained from 34 subjects. Twenty-six teeth with 49 canals received chemomechanical debridement (CMD) with 6% NaOCl and twenty-six teeth with 52 canals received CMD plus PDT. For PDT, root canal systems were incubated with methylene blue (MB) at concentration of 50 µg/ml for 5 minutes followed by exposure to red light at 665 nm with an energy fluence of 30 J/cm2. The contents of root canals were sampled by flushing the canals at baseline and following CMD alone or CMD+PDT and were serially diluted and cultured on blood agar. Survival fractions were calculated by counting colony-forming units (CFU). Partial characterization of root canal species at baseline and following CMD alone or CMD+PDT was performed using DNA probes to a panel of 39 endodontic species in the checkerboard assay. Results The Mantel-Haenszel chi-square test for treatment effects demonstrated the better performance of CMD+PDT over CMD (P=0.026). CMD+PDT significantly reduced the frequency of positive canals relative to CMD alone (P=0.0003). Following CMD+PDT, 45 of 52 canals (86.5%) had no CFU as compared to 24 of 49 canals (49%) treated with CMD (canal flush samples). The CFU reductions were similar when teeth or canals were treated as independent entities. Post-treatment detection levels for all species were markedly lower for canals treated by CMD+PDT than were for those treated by CMD alone. Bacterial species within dentinal tubules were detected in 17/22 (77.3%) and 15/29 (51.7%) of canals in the CMD and CMD+PDT group, respectively (P= 0.034). Conclusion Data indicate that PDT significantly reduces residual bacteria within the root canal system, and that PDT, if further enhanced by technical improvements, holds substantial promise as an adjunct to CMD. PMID:21238805

Ng, Raymond; Singh, Fiza; Papamanou, Despoina A.; Song, Xiaoqing; Patel, Chitrang; Holewa, Colleen; Patel, Niraj; Klepac-Ceraj, Vanja; Fontana, Carla R.; Kent, Ralph; Pagonis, Tom C.; Stashenko, Philip P.; Soukos, Nikolaos S.

2010-01-01

35

Interstitial Photodynamic Therapy of Brain Tumors  

Microsoft Academic Search

Malignant gliomas are associated with poor prognosis. Photodynamic therapy (PDT), relying on light-activated toxicity of a photosensitizer, has been investigated as a means for improving patient survival. This review presents a summary of clinical results obtained with PDT using different photosensitizers for treating brain malignancies. Particular emphasis is on the use of 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX). PpIX

Ann Johansson; Friedrich-Wilhelm Kreth; Walter Stummer; Herbert Stepp

2010-01-01

36

Photodynamic therapy in dermatology: a review  

Microsoft Academic Search

Photodynamic therapy (PDT) is used for the prevention and treatment of non-melanoma skin cancer. Until recently, clinically\\u000a approved indications have been restricted to actinic keratoses, nodular and superficial basal cell carcinoma, and, since 2006,\\u000a Bowen disease. However, the range of indications has been expanding continuously. PDT is also used for the treatment of non-malignant\\u000a conditions such as acne vulgaris and

Sonal Choudhary; Keyvan Nouri; Mohamed L. Elsaie

2009-01-01

37

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

38

Subluminescence photodynamic therapy of recalcitrant foot warts.  

PubMed

Nongenital cutaneous warts are a widespread disease and although various treatment options exist, cure rates are limited and often frustrating. As an additional option, photodynamic therapy (PDT) has been introduced to treat viral warts with response rates ranging from 42.6% to 100%.(1-8) Several protocols have been proposed regarding pretreatment of lesions, application of photosensitizer and repetition of cycles. This article is protected by copyright. All rights reserved. PMID:25132106

Vogel, S; Ruzicka, T; Berking, C

2014-08-16

39

Photodynamic Therapy for Juxtapapillary Retinal Capillary Hemangioma  

PubMed Central

Various treatment modalities have been described for retinal capillary hemangioma. Our purpose is to present a case of juxtapapillary retinal capillary hemangioma treated with photodynamic therapy. A 69-year-old woman with no previous ocular history presented with blurred vision and photopsias in the right eye three months ago. At presentation, her best corrected visual acuity was 6/9 in the right eye and 6/6 in the left eye. The anterior segment was totally normal and IOP was normal in both eyes as well. Dilated fundoscopy revealed a yellowish, well-circumscribed, elevated area with blood vessels, on the inferior margin of the right optic disc, as optic disc edema. Fluorescein angiography and angiogram with indocyanine green confirmed the diagnosis of juxtapapillary retinal capillary hemangioma. The patient was treated with photodynamic therapy with verteporfin and three months later her visual acuity was 6/7.5 in the right eye, while the lesion was slightly smaller. These findings remained stable at the one-year follow-up. In conclusion, photodynamic therapy offers promising anatomical and functional results for juxtapapillary retinal capillary hemangioma, providing visual acuity improvement or even stabilization and restriction of enlargement of the lesion. PMID:24716060

Mitropoulos, Panagiotis G.; Chatziralli, Irini P.; Peponis, Vasileios G.; Tsiotra, Vasileia A.; Parikakis, Efstratios A.

2014-01-01

40

Exploiting apoptosis in photodynamic therapy: is it possible?  

NASA Astrophysics Data System (ADS)

Glioblastoma Multiforme is the most common form of malignant brain tumors and accounts for approximately 25% of all primary brain tumors. Only 5% of these patients survive longer than 2 years. The standard form of treatment is radiation therapy and surgery if the site is accessible. Different forms of adjuvant chemotherapy have been largely proven unsuccessful. Another form of adjuvant therapy, Photodynamic Therapy (PDT), has undergone preliminary trials showing some promising results but at the cost of increased side effects like rise in intracranial blood pressure and neurological deficiency. Apoptotic cell kill used as a biological treatment endpoint can possibly ameliorate these side effects. This study evaluates the significance of apoptotic cell death in the 9L rat gliosarcoma using the aminolevulinic acid (ALA) induced endogenous photosensitizer Protophorphyrin IX (PpIX). A strong influence of drug incubation time with cell kill was observed. The percentage of apoptotic cell death was less than 10% for 2 and 4 hours incubation times and irradiation times ensuring up to 70 and 80% cell kill respectively. Accumulation of PpIX in the mitochondria and cytoplasm was quantified by confocal fluorescence microscopy showing a linear relationship of PpIX fluorescence with concentration. The possibility of an in vitro threshold in the PDT dose is discussed, above which cell repair mechanisms may become exhausted. In conclusion for the range of parameters investigated, apoptotic cell kill may be hard to exploit therapeutically in this tumor model.

Rendon, Cesar A.; Lilge, Lothar D.

2003-06-01

41

Photodynamic therapy-generated cancer vaccines.  

PubMed

Eradication of cancer by an intervention producing a potent immune response capable of rejecting both primary and metastatic deposits remains the most pragmatic approach in cancer therapy. Cancer vaccine generated by photodynamic therapy (PDT) is therefore of considerable interest, particularly as it is becoming increasingly clear that it holds unique prospects for optimally presenting tumor antigens and because of emerging indications that its efficacy can be further potentiated by continued development. The present report dissects the preparation of PDT vaccine in a mouse model of squamous cell carcinoma. PMID:20552346

Korbelik, Mladen

2010-01-01

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

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

44

Adjuvant Biological Therapy for Pancreatic Cancer  

Cancer.gov

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

45

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

46

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

47

Flexible textile light diffuser for photodynamic therapy  

NASA Astrophysics Data System (ADS)

In this article a new medical application is introduced using textile production techniques to deliver a defined radiation dose. The advantage for photodynamic therapy (PDT) is that a flat luminous textile structure can homogeneously illuminate unequal body surfaces. The optical properties of this two-dimensional luminous pad are characterized with a set of bench-scale tests. In vitro investigations on petri dishes with cultivated cells and first clinical tests on animal patients are promising. In addition first measurement results are presented together with an outlook to future developments.

Selm, Barbel; Camenzind, Martin

2005-03-01

48

Photosensitizer and light diffusion through dentin in photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy has been considered a potential antimicrobial modality against oral infections, including dental caries. A model to estimate the penetration of both photosensitizers and light through human dentin, a factor of interest in photodynamic therapy, is proposed. The photoacoustic spectroscopy technique was used to evaluate in vitro dentin permeability of three different photosensitizers. Using the dentin optical absorption and scattering coefficients, it was possible to propose a semi-quantitative model predicting both photosensitizer and light doses within dentin. The graphic illustrations obtained provided guidelines that may be useful in photodynamic therapy protocols used as antimicrobial tools in caries lesions.

Nogueira, Ana C.; Graciano, Ariane X.; Nagata, Juliana Y.; Fujimaki, Mitsue; Terada, Raquel S. S.; Bento, Antonio C.; Astrath, Nelson G. C.; Baesso, Mauro L.

2013-05-01

49

Photodynamic Therapy and Its Role in Combined Modality Anticancer Treatment.  

PubMed

Photodynamic therapy (PDT) is a relatively new modality for anticancer treatment and although the interest has increased greatly in the recent years, it is still far from clinical routine. As PDT consists of administering a nontoxic photosensitizing chemical and subsequently illuminating the tumor with visible light, the treatment is not subject to dose-limiting toxicity, which is the case for established anticancer treatments like radiation therapy or chemotherapy. This makes PDT an attractive adjuvant therapy in a combined modality treatment regimen, as PDT provides an antitumor immune response through its ability to elicit the release of damage-associated molecular patterns and tumor antigens, thus providing an increased antitumor efficacy, potentially without increasing the risk of treatment-related toxicity. There is great interest in the elicited immune response after PDT and the potential of combining PDT with other forms of treatment to provide potent antitumor vaccines. This review summarizes recent studies investigating PDT as part of combined modality treatment, hopefully providing an accessible overview of the current knowledge that may act as a basis for new ideas or systematic evaluations of already promising results. PMID:25377424

Brodin, N Patrik; Guha, Chandan; Tomé, Wolfgang A

2014-11-01

50

Death pathways associated with photodynamic therapy  

PubMed Central

When the mitochondria and/or the endoplasmic reticulum were targeted by photodynamic therapy, photodamage to the anti-apoptotic protein Bcl-2 was observed. This led to an apoptotic outcome if that death pathway was available. Lysosomal photodamage ultimately resulted in activation of the pro-apoptotic protein Bid, also leading to apoptosis. Photodamage to the plasma membrane was associated with migration of sensitizers to the cytosol and procaspase photodamage, with apoptosis impaired. Where apoptosis was unavailable because of lack of necessary components of the program, an autophagic outcome has been observed. It is also clear that autophagy can occur along with apoptosis as a PDT response, and may play a role in immunologic responses to photodamaged tumor cells. PMID:19890442

Kessel, David

2009-01-01

51

Photodynamic therapy in dermatology: a review.  

PubMed

Photodynamic therapy (PDT) is used for the prevention and treatment of non-melanoma skin cancer. Until recently, clinically approved indications have been restricted to actinic keratoses, nodular and superficial basal cell carcinoma, and, since 2006, Bowen disease. However, the range of indications has been expanding continuously. PDT is also used for the treatment of non-malignant conditions such as acne vulgaris and leishmaniasis, as well as for treating premature skin aging due to sun exposure. The production of reactive oxygen intermediates like singlet oxygen depends on the light dose applied as well as the concentration and localization of the photosensitizer in the diseased tissue. Either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving inflammatory skin conditions are induced. Treating superficial non-melanoma skin cancer, PDT has been shown to be highly efficient, despite the low level of invasiveness. The excellent cosmetic results after treatment are beneficial, too. PMID:19653060

Choudhary, Sonal; Nouri, Keyvan; Elsaie, Mohamed L

2009-11-01

52

Photodynamic therapy: current status and future directions.  

PubMed

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality used for the management of a variety of cancers and benign diseases. The destruction of unwanted cells and tissues in PDT is achieved by the use of visible or near-infrared radiation to activate a light-absorbing compound (a photosensitizer, PS), which, in the presence of molecular oxygen, leads to the production of singlet oxygen and other reactive oxygen species. These cytotoxic species damage and kill target cells. The development of new PSs with properties optimized for PDT applications is crucial for the improvement of the therapeutic outcome. This review outlines the principles of PDT and discusses the relationship between the structure and physicochemical properties of a PS, its cellular uptake and subcellular localization, and its effect on PDT outcome and efficacy. © 2014 S. Karger AG, Basel. PMID:24820409

Benov, Ludmil

2015-01-01

53

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

54

Dosimetry for photodynamic therapy of endometrial tissue  

NASA Astrophysics Data System (ADS)

Hysterectomy is the most common major operation performed in the United States with dysfunctional uterine bleeding as one of the major indications. The clinical needs for simple and safe endometrial destruction are essential. Photodynamic therapy (PDT) may offer a simple and cost effective solution for the treatment of dysfunctional uterine bleeding. The dosimetry is discussed for the case of topical application of photosensitizer. This technique might be the method of preference because undesired side effects such as skin photosensitization that is typical for systemically injected photosensitizers, can be avoided. Effective PDT requires a sufficient amount of light delivered to the targeted tissue in a reasonable period of time. A trifurcated optical applicator consisting of three cylindrical diffusing fibers has been constructed, and this applicator can deliver a typical required optical dose of about 50-100 J/cm2 to the full depth of the endometrium for an exposure time of 10-20 minutes.

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

1995-05-01

55

Guidelines for topical photodynamic therapy: update.  

PubMed

Multicentre randomized controlled studies now demonstrate high efficacy of topical photodynamic therapy (PDT) for actinic keratoses, Bowen's disease (BD) and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC, while confirming the superiority of cosmetic outcome over standard therapies. Long-term follow-up studies are also now available, indicating that PDT has recurrence rates equivalent to other standard therapies in BD and superficial BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast, current evidence does not support the use of topical PDT for squamous cell carcinoma. PDT can reduce the number of new lesions developing in patients at high risk of skin cancer and may have a role as a preventive therapy. Case reports and small series attest to the potential of PDT in a wide range of inflammatory/infective dermatoses, although recent studies indicate insufficient evidence to support its use in psoriasis. There is an accumulating evidence base for the use of PDT in acne, while detailed study of an optimized protocol is still required. In addition to high-quality treatment site cosmesis, several studies observe improvements in aspects of photoageing. Management of treatment-related pain/discomfort is a challenge in a minority of patients, and the modality is otherwise well tolerated. Long-term studies provide reassurance over the safety of repeated use of PDT. PMID:18945319

Morton, C A; McKenna, K E; Rhodes, L E

2008-12-01

56

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

57

[Adjuvant therapy of colon carcinoma].  

PubMed

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

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

2008-01-01

58

Adjuvant Therapy in Pancreatic Cancer  

Microsoft Academic Search

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

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

2010-01-01

59

Purpurins: Improved Photosensitizers For Photodynamic Therapy  

NASA Astrophysics Data System (ADS)

Two new groups of photosensitizers, purpurins and metallopurpurins were tested for photodynamic activity when combined with visible light (>590nm), in the treatment of transplantable urothelial tumors (FANFT induced) in Fischer 344 rats. In preliminary studies, animals were injected with 10 mg/kg body weight (b.w.) of the free base purpurins (NT1, NT2, NT2H2, GG1, ET2, ET2H2 and JP1) and treated with 360J/cm2 of red light. Tumors were excised, fixed in formalin and stained for light microscopic examination. Purpurin based photodynamic therapy (PDT) was found to cause extensive hemorrhagic tumor necrosis. Control tumors shielded from the light showed no histological changes. These experiments were repeated using the same experimental design for the metallopurpurins (ZnET2, SnET2, ZnNT2H2, SnNT2H2, AgNT2H2 and ZnNT1). These compounds were also found to cause extensive hemorrhagic necrosis. These studies were followed by a dose response analysis in which groups of animals were treated with decreasing doses of drug while the light dose was kept constant. Response was determined by tumor dry weight, 12 days after completion of PDT. For the free base purpurins, drug doses as low as 1.0 mg/kg b.w. caused significant tumor regression while seleted metallopurpurins caused tumor regression at doses as low as 0.5 mg/kg b.w. In a series of related experiments the effect of purpurins on tumor blood flow was investigated since it has previously been shown that tumor blood flow is disrupted during porphyrin and phthalocyanine phototherapy. By using the radioactive microsphere technique, it was shown that both the free base purpurins and metallopurpurins caused a rapid decrease in tumor blood flow.

Morgan, Alan R.; Kreimer-Birnbaum, Martha; Garbo, Greta M.; Keck, Rick W.; Selman, Steven H.

1988-02-01

60

Photodynamic therapy and its role in periodontitis treatment.  

PubMed

Photodynamic therapy is a novel therapeutic approach for eradicating pathogenic bacteria in periodontal disease. Inactivation of microorganisms using photodynamic therapy has been defined as either antimicrobial photodynamic therapy (aPDT), photodynamic antimicrobial chemotherapy (PACT) or photodynamic disinfection. The use of aPDT requires a non-toxic photosensitizer, harmless visible light and oxygen. The photosensitizer binds to targeted bacteria and then can be activated by light of the appropriate wavelength in the presence of oxygen. Photoinactivation of bacteria is tightly restricted to the localization of the photosensitizer, ensuring the protection of distant cells from side-effects. Because of the fact that conventional treatment such as scaling and root planing (SRP) does not completely eliminate periodontal pathogens, especially in deep periodontal pockets, aPDT may be considered to be an alternative therapeutic strategy. This article describes the mechanism of aPDT and novel approaches such as nanoparticles. The aim of the study was to review the literature concerning the assessment of the effectiveness of aPDT in periodontitis treatment. Although studies have not indicated the superiority of aPDT compared to conventional periodontitis treatment, antimicrobial photodynamic treatment has been reported to be effective as an adjunct to conventional therapy to destroy bacteria in sites where there is limited access for mechanical instrumentation. PMID:24379246

Mielczarek-Badora, Ewa; Szulc, Ma?gorzata

2013-01-01

61

Photodynamic therapy in head and neck cancer.  

PubMed

Photodynamic therapy (PDT) is a special type of treatment involving the use of a photosensitizer or a photosensitizing agent along with a special type of light, which, combined together, induces production of a form of oxygen that is used to kill surrounding cells in different areas of the human body. Specification of the head and neck region requires different approaches due to the surrounding of vital structures. PDT can also be used to treat cells invaded with infections such as fungi, bacteria and viruses. The light beam placed in tumor sites activates locally applied drugs and kills the cancer cells. Many studies are taking place in order to invent better photosensitizers, working on a larger scale and to treat deeply placed and larger tumors. It seems that PDT could be used as an alternative surgical treatment in some tumor types; however, all clinicians should be aware that the surgical approach is still the treatment of choice. PDT is a very accurate and effective therapy, especially in early stages of head and neck squamous cell carcinomas (HNSCC), and can greatly affect surgical outcomes in cancerous patients. We present a detailed review about photosensitizers, their use, and therapeutic advantages and disadvantages. PMID:24491903

Nelke, Kamil H; Pawlak, Wojciech; Leszczyszyn, Jaros?aw; Gerber, Hanna

2014-01-01

62

Photodynamic therapy in head and neck cancer.  

PubMed

Photodynamic therapy (PDT) is a special type of treatment involving the use of a photosensitizer or a photosensitizing agent along with a special type of light, which, combined together, induces production of a form of oxygen that is used to kill surrounding cells indifferent areas of the human body. Specification of the head and neck region requires different approaches due to the surrounding of vital structures. PDT can also be used to treat cells invaded with infections such as fungi, bacteria and viruses. The light beam placed in tumor sites activates locally applied drugs and kills the cancer cells. Many studies are taking place in order to invent better photosensitizers, working on a larger scale and to treat deeply placed and larger tumors. It seems that PDT could be used as an alternative surgical treatment in some tumor types; however, all clinicians should be aware that the surgical approach is still the treatment of choice. PDT is a very accurate and effective therapy, especially in early stages of head and neck squamous cell carcinomas (HNSCC), and can greatly affect surgical outcomes in cancerous patients. We present a detailed review about photosensitizers,their use, and therapeutic advantages and disadvantages. PMID:24988638

Nelke, Kamil H; Pawlak, Wojciech; Leszczyszyn, Jaros?aw; Gerber, Hanna

2014-01-01

63

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

64

Mitochondria-targeting for improved photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is an emerging cancer therapeutic modality, with great potential to selectively treat surface cancers, thus minimizing systemic side effects. In this dissertation, two approaches to deliver photosensitizers to mitochondria were investigated: 1) Reducing photosensitizer sizes to improve endocytosis and lysosomal localization. Upon irradiation the photosensitizers would then produce singlet oxygen which could rupture the lysosomal membrane releasing the lysosomally trapped photosensitizers to the cytosol, from where they could relocalize to mitochondria by passive diffusion (photochemical internalization). 2) Using delocalized lipophilic cationic dyes (DLCs) to exploit membrane potential differences between the cytoplasm and mitochondria in delivering photosensitizers to mitochondria. To investigate the effects of steric hindrance on mitochondrial localization and photodynamic response, a series of eight thiaporphyrins were studied. Two new thiaporphyrin analogues 6 and 8 with reduced steric hindrance at the 10- and 15- meso positions were studied in comparison to 5,20-diphenyl-10,15-bis[4 (carboxymethyleneoxy)-phenyl]-21,23-dithiaporphyrin 1, previously validated as a potential second generation photosensitizer. Although 6 showed an extraordinarily high uptake (7.6 times higher than 1), it was less potent than 1 (IC 50 = 0.18 muM versus 0.13 muM) even though they both showed similar sub-cellular localization patterns. This low potency was attributed to its high aggregation tendency in aqueous media (4 times higher than 1), which might have affected its ability to generate singlet oxygen in vitro . 8 on the other hand showed an even lower potency than 6 (2.28 vs 0.18 muM). However this was attributed to its low cellular uptake (20 times less than 6) and inefficient generation of singlet oxygen. Overall, although the structural modifications did improve the cellular uptake of 6, 6 was still less potent than the lead photosensitizers 1. Thus, other strategies to target mitochondria for improved photodynamic activity were investigated. In a continuing project, we evaluated the ability of delocalized lipophilic cationic dyes to deliver photosensitizers to mitochondria by exploiting the membrane potential difference between the cytoplasm and mitochondria. Two conjugates: a porphyrin--rhodamine B conjugate (TPP--Rh) and a porphyrin-acridine orange conjugate (TPP--AO), each possessing a single delocalized lipophilic cation, were designed and synthesized. The conjugates were synthesized by conjugating a monohydroxy porphyrin (TPP-OH) to rhodamine B (Rh B) and acridine orange base (AO), respectively, via saturated hydrocarbon linkers. To evaluate the efficiency of the conjugates as photosensitizers, their photophysical properties and in vitro photodynamic activities were studied in comparison to those of TPP-OH, the parent porphyrin photosensitizer. Although fluorescence energy transfer (FRET) was observed in the conjugates, they were capable of generating singlet oxygen at rates comparable to TPP-OH. In a final project, we evaluated the photophysical potential of TPP-Rh to act as a two-photon photosensitizer for PDT. Two-photon PDT is a rational approach used to improve light penetration through the skin. Rhodamine B is an effective two-photon chromophore and could significantly improve the two-photon absorption of the porphyrin photosensitizer in the TPP-Rh dyad system following energy transfer. Thus the porphyrin--rhodamine B dyad (TPP--Rh), previously demonstrated to preferentially accumulate in the mitochondria, was photophysically evaluated as a potential two-photon photosensitizer. To evaluate the efficiency of TPP-Rh as a two-photon photosensitizer, its two-photon photophysical properties were compared with those of its individual components (Rh B and TPP-OH). This included: the two-photon cross sections (sigma 2), RET kinetics and dynamics and rates of singlet oxygen generation. A FRET efficiency of ~99 % was observed from the Rh moiety (donor) to the TPP moiety (acceptor) of the system. This sig

Ngen, Ethel J.

65

A Review of Progress in Clinical Photodynamic Therapy  

PubMed Central

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

Huang, Zheng

2005-01-01

66

The use of photodynamic therapy in dermatology.  

PubMed

In dermatology, topical photodynamic therapy (PDT) is a well established treatment modality which has mainly shown to be effective for dermato-oncologic conditions like actinic keratosis, Bowen's disease, in-situ squamous cell carcinoma and superficial basal cell carcinoma. However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare as well as for aesthetic indications like photo aged skin or sebaceous gland hyperplasia. Recent work has been focused on the development and evaluation of topical photosensitizers like the hem precursor 5-aminolevulinic acid or its methyl ester inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes incoherent lamps or LED arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness < 2-3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment. PMID:20930696

Babilas, P; Szeimies, R M

2010-10-01

67

Photodynamic therapy in dermatology--an update.  

PubMed

Topical photodynamic therapy (PDT) is a well-established treatment modality which has mainly shown to be effective for dermatooncologic conditions like actinic keratoses (AK), Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma (BCC). However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare. Recent work has been focused on the development and evaluation of topical photosensitizers like the heme precursor 5-aminolevulinic acid (5-ALA) or its methyl ester (methyl aminolevulinate) inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes, incoherent lamps or light-emitting diode arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness <2-3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment. PMID:15888131

Babilas, Philipp; Karrer, Sigrid; Sidoroff, Alexis; Landthaler, Michael; Szeimies, Rolf-Markus

2005-06-01

68

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

69

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

70

Photodynamic therapy of breast cancer with photosense  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) using photosensitizer Photosense (PS) in dose 0.5 mg per kg of body weight have been provided in 24 patients with breast cancer. In 22 patients with T1-T2N0M0 primary tumor was treated as the preoperative treatment, radical mastectomy has been fulfilled 7-10 days after PDT with subsequent histological examination. 2 patients had recurrencies of breast cancer with lymph node metastases after radiotherapy. Fluorescent diagnostics of tumor, accumulation of PS in tumor, adjacent tissue, skin before and during PDT was fulfilled with spectranalyzer LESA-01. We used semiconductive laser for PDT - ? = 672+2nm, P=1,5 W, interstitial irradiation 2-24 hours after PS injection has been done in light dose 150-200 J/cm3, 1-3 irradiations with interval 24-48 hours and total light dose 400-600 J/cm3 depending mostly of size and fluorescent data. Partial regression of tumor with pathomorphosis of 2-4 degrees has been found in 19 cases. Our experience shows pronounced efficacy of PDT for treating breast cancer as preoperative modality and as palliation in cases of recurrencies.

Vakoulovskaya, Elena G.; Shental, Victor V.; Oumnova, Loubov V.; Vorozhcsov, Georgiu N.

2003-06-01

71

Light delivery schemes for uterine photodynamic therapy  

NASA Astrophysics Data System (ADS)

The use of photodynamic therapy in the removal of the endometrial layer of the uterus provides the possibility of a rapid and effective treatment of menorrhagia avoiding the difficulties and complications of conventional methods. A treatment is proposed in which topical application of 5-aminolaevulinic acid to the inner surface of the uterus is followed by illumination at 630 nm. The surface layer would in this way be rendered necrotic to slough off over subsequent days. The removal of the entire endometrium must be achieved in order to prevent the return of the original condition, which demands that a therapeutic dose of both light and photosensitizer must be achieved throughout the depth of the tissue. This work presents a method of light delivery suitable for intra-uterine PDT along with in vitro optical phantom and ex vivo tissue measurements that aid in the characterization of the light field prior to treatment. These measurements allow the prediction of a treatment time suitable for the delivery of an effective light dose.

Stringer, Mark R.; Hudson, Emma J.; Dunkley, Colin P.; Boyce, Jeanetta C.; Gannon, Michael J.; Smith, Michael A.

1994-03-01

72

Pecularities of clinical photodynamic therapy of cancer  

NASA Astrophysics Data System (ADS)

The analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of the skin, mammary glands, tongue, oral mucous, lower lip, larynx, lungs, urinary bladder rectum and other locations has been made. During 1992 - 1995 478 tumoral foci in 125 patients have been treated with PDT. All patients were previously treated with conventional techniques without effect or they were not treated due to contraindications either because of severe accompanying diseases or because of old age. A part of the patients had PDT because of recurrences or intradermal metastases in 1 - 2 years after surgical, radial or combined treatment. Two home-made preparations were used as photosensitizers: Photohem (hematoporphyrine derivative) and Photosense (aluminum sulfonated phthalocyanine). Light sources were: the argon pumped dye laser (`Innova-200', `Coherent') and home-made laser devices: copper-vapor laser-pumped dye laser (`Yakhroma-2', Frjazino), gas-discharge unit `Ksenon' (wavelength 630 nm), gold-vapor laser (wavelength 627.8 nm) for Photohem; while for Photosense sessions we used solid-state laser on ittrium aluminate `Poljus-1' (wavelength 670 nm). Up to now we have follow-up control data within 2 months and 3 years. Positive effect of PDT was seen in 92% of patients including complete regression of tumors in 66.4% and partial in 25.6%. Currently, this new perspective technique of treating malignant neoplasms is successfully being used in Russia; new photosensitizers and light sources for PDT and fluorescent tumor diagnostics are being developed as well.

Stranadko, Eugeny P.; Skobelkin, Oleg K.; Litvin, Grigory D.; Astrakhankina, Tamara A.

1996-01-01

73

[Photodynamic visudyne therapy for subretinal neovascularization].  

PubMed

A total of 199 sessions of photodynamic therapy (PDT) with visudine were performed in 119 patients (227 eyes) at the Laser Center, T. I. Yeroshevsky Samara eye diseases hospital. Analysis of the changes occurring in visual function in the presence of the subretinal neovascular membrane developing in age-related macular dystrophy and high complicated myopia showed an increase in visual functions in the first 3-6 months after PDT, which is, in the authors' opinion, associated with the diminution of macular edema and the resolution of hemorrhage. In the subsequent months, visual acuity tended to slightly lower. The late follow-up periods (after 1.5 years) saw visual function stabilization. Visudine PDT for subretinal neovascularization is an effective, safe, technically simple, well-tolerable procedure that makes it possible not only to stabilize, but, in many cases, to improve visual functions. A follow-up of patients for as long as 18 months demonstrated that stable visual functions were retained with a slight tendency for their reduction during continued PDT sessions. PMID:18225519

Zolotarev, A V; Malyshev, A S; Fadeeva, A V; Morozova, Iu V; Podsevakina, T A

2007-01-01

74

Laser effect in photodynamic therapy of tumors  

NASA Astrophysics Data System (ADS)

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

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

2007-03-01

75

Multiple laser irradiation of ORL organ tumors in photodynamic therapy  

NASA Astrophysics Data System (ADS)

The results of ORL organ tumor photodynamic therapy with the use of Phtalocyanine Al and multiple sequences of laser irradiation are presented. The possibility of decreasing the concentration of the preparation in accordance with laser irradiation tactics was investigated. The process of tissue necrotization for big and difficult tumors for laser irradiation access has been investigated. The estimation of photosensitizer distribution character for local injection has been carried out. The principal possibility of using local injection of photosensitizer for photodynamic therapy has been shown.

Shental, V. V.; Edynak, N. E.; Abdoulin, N. A.; Kuvshinov, Yury P.; Poddubny, Boris K.; Tabolinovskaia, T. D.; Loschenov, Victor B.; Poleshkin, P. V.; Lukyanets, Eugeny A.

1995-01-01

76

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

77

Photodynamic therapy by in situ nonlinear photon conversion  

NASA Astrophysics Data System (ADS)

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

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

2014-06-01

78

How to access photodynamic therapy for bile duct carcinoma  

PubMed Central

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

79

Photodynamic therapy for the endodontic treatment of a traumatic primary tooth in a diabetic pediatric patient.  

PubMed

Conservation of deciduous teeth with pulp alterations caused by caries or trauma is a major therapeutic challenge in pediatric dentistry. It is essential that the sanitizers used in root canal procedures perform well in eliminating bacteria. Antimicrobial photodynamic therapy (PDT) is an emerging and promising adjuvant therapy for endodontic treatment in an attempt to eliminate microorganisms persistent after chemomechanical preparation. This paper reports the case of a five-year-old male with type I diabetes mellitus, presenting the need for pulp therapy in maxillary primary left central incisor due to injury. The proposed treatment included the use of PDT for decontamination of root canals with the application of 50 ?g/mL of methylene blue dye for 3-5 minutes and 40 J/cm(2) as energy density, taking into account the need for tissue penetration and effec-tiveness of PDT inside the dentinal tubules. PMID:25024841

de Sant'Anna, Giselle

2014-01-01

80

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

PubMed Central

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

de Sant’Anna, Giselle

2014-01-01

81

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

82

Dynamics of phthalocyanine Al accumulation in stomach cancer photodynamic therapy  

NASA Astrophysics Data System (ADS)

Methods of stomach cancer photodynamic therapy with the use of Kr laser and photosensitizer-phthalocyanine (Al-Pc) are discussed. The level of preparation accumulation in the tumor and surrounding tissues has been investigated with the use of laser spectroanalyzer LESA-4 (`Biospec'). Dynamics of (Al-Pc) accumulation investigated depend on different types of tumors and different parameters of laser irradiation.

Kharnas, Sergey S.; Loschenov, Victor B.; Stratonnikov, Alexander A.; Kramarenko, T. A.; Artemjeva, O. V.; Bakonin, V. P.; Kuzin, M. I.; Zavodnov, Victor Y.; Steiner, Rudolf W.

1995-01-01

83

Sequential whole bladder photodynamic therapy treatments: A preclinical study  

Microsoft Academic Search

We postulated that sequential whole bladder photodynamic therapy (WBPDT) treatments with a low WBPDT dose would result in improved safety profile and good local tumor control. However, the drawback with such a proposal is the potential cumulative effect of sequential WBPDT treatments on bladder function. We designed this preclinical study to determine the safety of sequential WBPDT treatments. Six female

Uniyime O. Nseyo; Henry Kim; Joe DeBord; Karen Tate; Jean DeHaven

1997-01-01

84

Photodynamic Therapy for Barrett's Esophagus and Esophageal Carcinoma  

PubMed Central

This paper reviews the use of photodynamic therapy (PDT) in patients with Barrett's esophagus and esophageal carcinoma. We describe the history of PDT, mechanics, photosensitizers for PDT in patients with esophageal disease. Finally, we discuss its utility and limitations in this setting. PMID:23423151

Qumseya, Bashar J.; David, Waseem

2013-01-01

85

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

86

Photodynamic therapy of Porphyromonas gingivalis via liposome-encapsulated sensitizers.  

PubMed

Photodynamic therapy exploits the light-activation of a photosensitizer to cause cytotoxicity. Liposomes can be used to deliver hydrophobic photosensitizers to bacteria. Positively charged dioleoyltrimethylammoniumpropane:palmitoyloleoylphosphatidylcholine (1:1) liposomes bound quantitatively to the periodontal pathogen, Porphyromonas gingivalis. Following illumination, free and liposomal zinc phthalocyanine reduced the colony-forming unit (CFU) to 65 percent and 23 percent of controls, respectively. Thus, localization of the photosensitizer at the surface of bacteria via liposome binding enhanced the photodynamic cytotoxicity of zinc phthalocyanine. PMID:24341134

Ko, Alex; Yee, Michael; Skupin-Mrugalska, Paulina; Düzgünes, Nejat

2013-11-01

87

Erythroplasia of Queyrat treated with topical methyl aminolevulinate photodynamic therapy.  

PubMed

An 82-year-old man presented with invasive squamous cell carcinoma of the glans penis arising in erythroplasia of Queyrat. He underwent Mohs' micrographic surgery for the invasive carcinoma. Seven weeks later, the residual erythroplasia of Queyrat was treated using photodynamic therapy. Methyl aminolevulinate cream was applied to the glans of the penis under occlusion for 3 hours and then, after local anaesthesia, irradiated with a 630-nm red-light-emitting diode lamp at a dose of 37 J/cm(2) for 8 min. The patient experienced some mild swelling, redness and pain, which subsided over the following 5 days. Eighteen weeks after photodynamic therapy, there had been no recurrence of the lesion, when the patient died from an unrelated cause. PMID:16008656

Lee, Michael R; Ryman, William

2005-08-01

88

Enhancement of photodynamic tumor therapy effectiveness by electroporation in vitro.  

PubMed

The aim of our study was to determine if electroporation could improve the efficacy of photodynamic tumor therapy. A disadvantage of photodynamic therapy is a slow and in some cases insufficient accumulation of photosensitizer in tumor tissue, which could restrict the achievement of an efficient dose. Under the action of electric pulses, cells undergo membrane electroporation, which results in an increased permeability to various exogenous molecules. In this study, murine hepatoma MH22A cells were exposed to light in vitro in the presence of a photosensitizer, either chlorin e6 or aluminum phthalocyanine tetrasulfonate, following electroporation. Accumulation of the photosensitizers was registered by fluorescence microscopy. Cell viability was determined by the MTT assay. Our results demonstrate that electroporation improves an access of chlorin e6 and aluminum phthalocyanine tetrasulfonate to MH22A cells. Electroporation in combination with photosensitization significantly reduces viability of the treated cells even at low doses of photosensitizers. PMID:19535883

Labanauskiene, J?rate; Satkauskas, Saulius; Kirveliene, Vida; Venslauskas, Mindaugas; Atkocius, Vydmantas; Didziapetriene, Janina

2009-01-01

89

Simultaneous two-photon excitation of photodynamic therapy agents  

SciTech Connect

The spectroscopic and photochemical properties of several photosensitive compounds are compared using conventional single-photon excitation (SPE) and simultaneous two-photon excitation (TPE). TPE is achieved using a mode-locked titanium:sapphire laser, the near infrared output of which allows direct promotion of non-resonant TPE. Excitation spectra and excited state properties of both type 1 and type 2 photodynamic therapy (PDT) agents are examined.

Wachter, E.A.; Fisher, W.G. [Oak Ridge National Lab., TN (United States)]|[Photogen, Inc., Knoxville, TN (United States); Partridge, W.P. [Oak Ridge National Lab., TN (United States); Dees, H.C. [Photogen, Inc., Knoxville, TN (United States); Petersen, M.G. [Univ. of Tennessee, Knoxville, TN (United States). College of Veterinary Medicine

1998-01-01

90

Topical methyl aminolevulinate photodynamic therapy for the treatment of folliculitis.  

PubMed

Photodynamic therapy (PDT) has been found to be effective for the treatment of acne vulgaris. We now wish to present a case series of seven patients who were successfully treated for chronic folliculitis with PDT after photosensitization with topical methyl aminolevulinate. The folliculitis had occurred in areas of acne-prone skin of the patients, mainly after long-term administration of antibiotics. PMID:17598868

Horn, Michael; Wolf, Peter

2007-08-01

91

Potentiation of photodynamic therapy of cancer by complement: the effect of ?-inulin  

PubMed Central

Host response elicited by photodynamic therapy (PDT) of cancerous lesions is a critical contributor to the clinical outcome, and complement system has emerged as its important element. Amplification of complement action was shown to improve tumour PDT response. In search of a clinically relevant complement activator for use as a PDT adjuvant, this study focused on ?-inulin and examined its effects on PDT response of mouse tumours. Intralesional ?-inulin (0.1?mg?mouse?1) delivered immediately after PDT rivaled zymosan (potent classical complement activator) in delaying the recurrence of B16BL6 melanomas. This effect of ?-inulin was further enhanced by IFN-? pretreatment. Tumour C3 protein levels, already elevated after individual PDT or ?-inulin treatments, increased much higher after their combination. With fibrosarcomas MCA205 and FsaR, adjuvant ?-inulin proved highly effective in reducing recurrence rates following PDT using four different photosensitisers (BPD, ce6, Photofrin, and mTHPC). At 3 days after PDT plus ?-inulin treatment, over 50% of cells found at the tumour site were CTLs engaged in killing specific targets via perforin–granzyme pathway. This study demonstrates that ?-inulin is highly effective PDT adjuvant and suggests that by amplifying the activation of complement system, this agent potentiates the development of CTL-mediated immunity against PDT-treated tumours. PMID:17146472

Korbelik, M; Cooper, P D

2006-01-01

92

Apoptosis occurs in lymphoma cells but not in hepatoma cells following ionizing radiation and photodynamic therapy  

Microsoft Academic Search

The aim of this study was to determine the relative role of apoptosis in photodynamically-induced cytotoxicity or radiation-induced cytotoxicity for hepatoma and lymphoma cells. Human hepatoma cells and mouse lymphoma cells were treated with either photodynamic therapy (PDT) or ionizing radiation. Dosimetry studies of immediate cell death following photodynamic therapy in the hepatoma cell line demonstrated second-order kinetics, similar to

Mark A. Laukka; Kenneth K. Wang; James A. Bonner

1994-01-01

93

Fluorescent Molecular Imaging and Dosimetry Tools in Photodynamic Therapy  

PubMed Central

Measurement of fluorescence and phosphorescence in vivo is readily used to quantify the concentration of specific species that are relevant to photodynamic therapy. However, the tools to make the data quantitatively accurate vary considerably between different applications. Sampling of the signal can be done with point samples, such as specialized fiber probes or from bulk regions with either imaging or sampling, and then in broad region image-guided manner. Each of these methods is described below, the application to imaging photosensitizer uptake is discussed, and developing methods to image molecular responses to therapy are outlined. PMID:20552350

Pogue, Brian W.; Samkoe, Kimberley S.; Gibbs-Strauss, Summer L.; Davis, Scott C.

2013-01-01

94

Diblock copolymers to deliver hydrophobic photosensitizers for photodynamic therapy  

NASA Astrophysics Data System (ADS)

Polymeric micelles, self-assemblies of block copolymers, are emerging as attractive drug delivery systems for hydrophobic photodynamic sensitizers. Recent advances in the formulation of photosensitizers for photodynamic therapy (PDT) with diblock copolymers are presented. This paper reviews the main characteristics of existing drug-loading micelles with diblock copolymers, including loading efficiency, particle size and morphology, stability, cellular uptake, subcellular distribution and therapeutic efficiency. The results indicate that diblock polymeric micelles are potentially useful for the delivery and release of hydrophobic photosensitizers in PDT. While significant progress has been achieved, many challenges remain in elucidating the detailed internalization mechanisms of the micelles and resulting mechanisms for enhanced photocytotoxicity. Some critical issues for diblock copolymers to deliver hydrophobic photosensitizers for PDT are highlighted.

Li, Buhong

2007-11-01

95

Immune modulation using transdermal photodynamic therapy  

NASA Astrophysics Data System (ADS)

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

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

1995-01-01

96

Photodynamic therapy--mechanism and employment.  

PubMed

Photodynamic terapy (PDT) is a new treatment for a wide variety of malignancies and premalignant dysplasias, as well as some non-cancer indications. Therapeutic response to PTD is achieved through the activation of non-toxic photosensitiser located within neoplastic tissue, using visible light tuned to the appropriate absorption band of the photosensitiser molecule. This produces cytotoxic free radical such as singlet oxigen, which result in local photo-oxidation, cell damage and destruction of the tumour cells. Systemic administration of photosensitisers has been used with endoscopic light exposure to treat a variety of internal malignances. A topical drug delivery is used in the skin deseases treatment. The selective distribution of photosensitiser in the target tissue is the fundamental to the process of PDT. This tissue specific photosensitation and normal tissue sparing results in good healing and often very good cosmetic results. Peterson PTD can be used for the treatment of cutaneous lesions (e.g., SCC, BCC, Bowen's disease, mycosis fungoides, erythroplasia of Queyrat, Gorlin's Syndrome, actinic keratoses), lower genital tract neoplasia (VIN and CIN), gastrointestinal tumours, etc., as well as nononcological indications (e.g., acne, condyloma acuminatum, lichen planus, psoriasis, vitiligo, vulval lichen sclerosus, warts and verrucae). PMID:16146137

Szpringer, Ewa; Lutnicki, Krzysztof; Marciniak, Andrzej

2004-01-01

97

Photosensitizer delivery for photodynamic therapy of choroidal neovascularization.  

PubMed

The present review examines the importance of improving photosensitizer delivery for choroidal neovascularization (CNV) in light of the clinical impact of photodynamic therapy (PDT) for CNV. An overview of the classes of available photosensitizers is provided and the properties governing photosensitizer uptake and circulation in serum are discussed. Current delivery systems, for example liposomal formulations as well as the use of the promising strategy of antibody targeted delivery as a strategy to improve PDT selectivity and efficiency for CNV treatment are described. A summary of the work using Verteporfin, tin ethyl purpurin and Lu-Tex--photosensitizers currently in clinical trials for CNV--is given. PMID:11672876

Renno, R Z; Miller, J W

2001-10-31

98

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

99

Dramatic regression of presumed acquired retinal astrocytoma with photodynamic therapy.  

PubMed

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

Tuncer, Samuray; Cebeci, Zafer

2014-01-01

100

Fractional Resurfacing Aiding Photodynamic Therapy of a Recalcitrant Plantar Verruca  

PubMed Central

Fractional resurfacing has become a very popular laser modality in recent years, and photodynamic therapy (PDT) has become a mainstay of many practices treating a wide array of clinical entities. In this case report, we describe a recalcitrant verrucous lesion on the foot that is unresponsive to cryotherapy, pulsed dye laser, and pulsed dye laser with PDT. The lesion did, however, respond very well to the use of a fractional laser to enhance the penetration of the PDT photosensitizer and then responded to pulsed dye laser with PDT. Fractional resurfacing prior to PDT may be a novel dermatologic treatment approach, making PDT an even better treatment option in the future. PMID:21103307

Pope, Amy

2008-01-01

101

Monitoring the efficiency of photodynamic therapy in tissue  

NASA Astrophysics Data System (ADS)

Transcutaneous oxygen electrodes are used to non-invasively measure tissue oxygen tension during photodynamic therapy (PDT). Measurements are performed on VX-2 skin carcinomas in rabbit ears. The degree of tumor oxygen tension reduction is proportional to the applied light dose. In the absence of irradiation, oxygen tension returns to pre-irradiation levels until a "damage threshold" has been reached. For 50mW/cm2 irradiations of Photofrmn II (at 630 nm) and tetraphenylporphine tetrasulfonate (at 657 tim), the cumulative dose required to irreversibly deplete tumor iranscutaneous oxygen was approximately 300 kJ/M2 and 600 kJ/M2, respectively.

Orenstein, Arie; Kimel, Sol; Tromberg, Bruce J.; Nelson, J. Stuart; Berns, Michael W.

1990-06-01

102

Spectroscopic evaluation of photodynamic therapy of the intraperitoneal cavity  

NASA Astrophysics Data System (ADS)

We present the results of spectroscopic measurements of diffuse reflectance and fluorescence before and after photodynamic therapy of healthy canine peritoneal cavity. Animals were treated intra-operatively after iv injection of the benzoporphyrin derivative (BPD). The small bowel was treated using a uniform light field projected by a microlens-tipped fiber. The cavity was then filled with scattering medium and the remaining organs were treated using a moving diffuser. Diffuse reflectance and fluorescence measurements were made using a multi-fiber optical probe positioned on the surface of various tissues within the cavity before and after illumination. The measured data were analyzed to quantify hemoglobin concentration and oxygenation and sensitizer concentration.

Finlay, Jarod C.; Sandell, Julia L.; Zhu, Timothy C.; Lewis, Robert; Cengel, Keith A.; Hahn, Stephen M.

2010-02-01

103

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

104

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

105

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

106

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

107

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

108

Efficient photodynamic therapy on human retinoblastoma cell lines.  

PubMed

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

109

Photodynamic therapy potentiates the paracrine endothelial stimulation by colorectal cancer  

NASA Astrophysics Data System (ADS)

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death worldwide. Recurrence is a major problem and is often the ultimate cause of death. In this context, the tumor microenvironment influences tumor progression and is considered as a new essential feature that clearly impacts on treatment outcome, and must therefore be taken into consideration. Photodynamic therapy (PDT), oxygen, light and drug-dependent, is a novel treatment modality when CRC patients are inoperable. Tumor vasculature and parenchyma cells are both potential targets of PDT damage modulating tumor–stroma interactions. In biological activity assessment in photodynamic research, three-dimensional (3D) cultures are essential to integrate biomechanical, biochemical, and biophysical properties that better predict the outcome of oxygen- and drug-dependent medical therapies. Therefore, the objective of this study was to investigate the antitumor effect of methyl 5-aminolevulinic acid-PDT using a light emitting diode for the treatment of CRC cells in a scenario that mimics targeted tissue complexity, providing a potential bridge for the gap between 2D cultures and animal models. Since photodynamic intervention of the tumor microenvironment can effectively modulate the tumor–stroma interaction, it was proposed to characterize the endothelial response to CRC paracrine communication, if one of these two populations is photosensitized. In conclusion, we demonstrated that the dialogue between endothelial and tumor populations when subjected to lethal PDT conditions induces an increase in angiogenic phenotype, and we think that it should be carefully considered for the development of PDT therapeutic protocols.

Lamberti, María Julia; Florencia Pansa, María; Emanuel Vera, Renzo; Belén Rumie Vittar, Natalia; Rivarola, Viviana Alicia

2014-11-01

110

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

111

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

112

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

113

Treatment of spontaneously occurring veterinary tumors with photodynamic therapy  

NASA Astrophysics Data System (ADS)

Chloroaluminum phthalocyanine tetrasulfonate was administered intravenously (1.0 mg/kg) to client owned cats and a dog with spontaneously occurring squamous cell carcinoma of head and neck. Light was delivered 48 hours post injection of the photosensitizer. An argon- pumped dye-laser was used to illuminate the lesions with 675 nm light delivered through a microlens fiber and/or a cylindrical diffuser. The light dose was 100 J/cm2 superficially or 300 J/cm interstitially. Eleven photodynamic therapy treatments in seven cats and one dog were performed. Two cats received a second treatment in approximately sixty days after the initial treatment. The superficial dose of light was increased to 200 J/cm2 for the second treatment. While the longest follow-up is twelve months, the responses are encouraging. The dog had a complete response. Among the cats, three showed complete response, three showed partial response and one showed no response. One cat expired two days post treatment. It is early to evaluate the response in two cats that received second treatments. Photodynamic therapy with chloroaluminum phthalocyanine tetrasulfonate was effective in treating squamous cell carcinoma in pet animals.

Panjehpour, Masoud; Legendre, Alfred; Sneed, Rick E.; Overholt, Bergein F.

1992-06-01

114

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

Microsoft Academic Search

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

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

2002-01-01

115

Photodynamic Therapy for Gynecological Diseases and Breast Cancer  

PubMed Central

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

Shishkova, Natashis; Kuznetsova, Olga; Berezov, Temirbolat

2012-01-01

116

Erythroplasia of Queyrat treated by topical aminolaevulinic acid photodynamic therapy.  

PubMed

Erythroplasia of Queyrat (EQ) is an intraepithelial carcinoma in situ affecting the mucosal surfaces of the penis, with a significant risk of invasion and metastasis. Treatment is often difficult and is associated with significant recurrence rates. Topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) combines a photosensitizer precursor and visible light to produce a photodynamic effect. It has been used successfully to treat benign, premalignant and malignant skin diseases. We present four patients with EQ who have been treated by topical ALA PDT. Of two patients with limited disease one has achieved a long-term complete response (36 months) and the other developed a recurrence at 18 months after a complete response. Two further patients with more extensive disease achieved a significant improvement, allowing easier treatment by laser vaporization. Although topical ALA PDT offers the advantages of tumour specificity, preservation of function and a good cosmetic result, more extensive EQ appears less responsive to this new therapeutic modality using current treatment parameters. PMID:10233277

Stables, G I; Stringer, M R; Robinson, D J; Ash, D V

1999-03-01

117

Simultaneous two-photon excitation of photodynamic therapy agents  

NASA Astrophysics Data System (ADS)

The spectroscopic and photochemical properties of several photosensitive compounds are compared using conventional single-photon excitation (SPE) and simultaneous two-photon excitation (TPE). TPE is achieved using a mode-locked titanium:sapphire laser, the near infrared output of which allows direct promotion of non-resonant TPE. Excitation spectra and excited state properties of both type I and type II photodynamic therapy (PDT) agents are examined. In general, while SPE and TPE selection rules may be somewhat different, the excited state photochemical properties are equivalent for both modes of excitation. In vitro promotion of a two-photon photodynamic effect is demonstrated using bacterial and human breast cancer models. These results suggest that use of TPE may be beneficial for PDT, since the technique allows replacement of visible or ultraviolet excitation with non- damaging near infrared light. Further, a comparison of possible excitation sources for TPE indicates that the titanium:sapphire laser is exceptionally well suited for non- linear excitation of PDT agents in biological systems due to its extremely short pulse width and high repetition rate; these features combine to effect efficient PDT activation with minimal potential for non-specific biological damage.

Wachter, Eric A.; Partridge, W. P., Jr.; Fisher, Walter G.; Dees, Craig; Petersen, Mark G.

1998-07-01

118

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

119

Evaluation of photodynamic therapy in adhesion protein expression  

PubMed Central

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

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

2014-01-01

120

Evaluation of photodynamic therapy in adhesion protein expression.  

PubMed

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

Pacheco-Soares, Cristina; Maftou-Costa, Maira; DA Cunha Menezes Costa, Carolina Genúncio; DE Siqueira Silva, Andreza Cristina; Moraes, Karen C M

2014-08-01

121

ALA-Butyrate prodrugs for Photo-Dynamic Therapy  

NASA Astrophysics Data System (ADS)

The use of 5-aminolevulinic acid (ALA) administration has led to many applications of photodynamic therapy (PDT) in cancer. However, the hydrophilic nature of ALA limits its ability to penetrate the cells and tissues, and therefore the need for ALA derivatives became an urgent research target. In this study we investigated the activity of novel multifunctional acyloxyalkyl ester prodrugs of ALA that upon metabolic hydrolysis release active components such as, formaldehyde, and the histone deacetylase inhibitory moiety, butyric acid. Evaluation of these prodrugs under photo-irradiation conditions showed that butyryloxyethyl 5-amino-4-oxopentanoate (ALA-BAC) generated the most efficient photodynamic destruction compared to ALA. ALA-BAC stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells which resulted in generation of intracellular ROS, reduction of mitochondrial activity, leading to apoptotic and necrotic death of the cells. The apoptotic cell death induced by ALA / ALA-BAC followed by PDT equally activate intrinsic and extrinsic apoptotic signals and both pathways may occur simultaneously. The main advantage of ALA-BAC over ALA stems from its ability to induce photo-damage at a significantly lower dose than ALA.

Berkovitch, G.; Nudelman, A.; Ehenberg, B.; Rephaeli, A.; Malik, Z.

2010-05-01

122

Controversies in the Adjuvant Therapy of Endometrial Cancer  

PubMed Central

Endometrial cancer is the most common malignancy of the female genital tract. Surgical treatment includes hysterectomy, bilateral salpingo-oophorectomy, and an appropriate staging procedure. Relapse of endometrial cancer may occur in patients with high risk factors, such as old age, grade 3 cancer, deep myometrial invasion, and papillary serous and clear cell types. In recent years, several randomized trials reported the results of adjuvant therapy for patients with high risk factors. Nonetheless, some controversies still exist. This paper presents and discusses the results of important randomized trials of adjuvant therapy for endometrial cancer with risk factors. PMID:21977327

Hsiao, Sheng-Mou; Wei, Lin-Hung

2011-01-01

123

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

124

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

125

Advanced optical techniques for monitoring dosimetric parameters in photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is based on the generation of highly reactive singlet oxygen through interactions of photosensitizer, light and molecular oxygen. PDT has become a clinically approved, minimally invasive therapeutic modality for a wide variety of malignant and nonmalignant diseases. The main dosimetric parameters for predicting the PDT efficacy include the delivered light dose, the quantification and photobleaching of the administrated photosensitizer, the tissue oxygen concentration, the amount of singlet oxygen generation and the resulting biological responses. This review article presents the emerging optical techniques that in use or under development for monitoring dosimetric parameters during PDT treatment. Moreover, the main challenges in developing real-time and noninvasive optical techniques for monitoring dosimetric parameters in PDT will be described.

Li, Buhong; Qiu, Zhihai; Huang, Zheng

2012-12-01

126

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

127

Photodynamic therapy in dermatology: state-of-the-art.  

PubMed

Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo-aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non-oncologic indications. PMID:20584250

Babilas, Philipp; Schreml, Stephan; Landthaler, Michael; Szeimies, Rolf-Markus

2010-06-01

128

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

129

Mitochondria-involved apoptosis induced by MPPa mediated photodynamic therapy  

NASA Astrophysics Data System (ADS)

Numerous new photosensitizers are now in various stages of trials demonstrating the broad applicability of Photodynamic therapy (PDT). However, only a handful of photosensitizers have received regulatory approval. Lack of effective photosensitizers has become a major limit for extensive application of PDT. Our previous study showed MPPa to be a good photosensitizer candidature, MPPa-PDT can lead PC-3M cell line to death mainly via apoptotic way both in vitro and in vivo, and part of the mechanism was investigated. Mitochondria may play a key role in the process, in order to further elucidate the mechanism, we investigated the level of ROS, GSH, NO, Ca2+, mitochondrial membrane potential, as well as cytochrome C. All in all, ROS production, depletion of GSH, and the activation of ROS downstream, such as mitochondria depolarization, cytochrome C release, were detected in our study. The results provide a mechanism by which oxidative stress provokes apoptosis of PC-3M cells.

Tian, Y. Y.; Xu, D. D.; Tian, X.; Cui, F. A.; Yuan, H. Q.; Leung, W. N.

2008-10-01

130

Antifungal effect of TONS504-photodynamic therapy on Malassezia furfur.  

PubMed

Numerous reports indicate therapeutic efficacy of photodynamic therapy (PDT) against skin tumors, acne and for skin rejuvenation. However, few reports exist regarding its efficacy for fungal skin diseases. In order to determine the antifungal effect, PDT was applied on Malassezia furfur. M. furfur was cultured in the presence of a novel cationic photosensitizer, TONS504, and was irradiated with a 670-nm diode laser. TONS504-PDT showed a significant antifungal effect against M. furfur. The effect was irradiation dose- and TONS504 concentration-dependent and the maximal effect was observed at 100 J/cm2 and 1 ?g/mL, respectively. In conclusion, TONS504-PDT showed antifungal effect against M. furfur in vitro, and may be a new therapeutic modality for M. furfur-related skin disorders. PMID:25226792

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

2014-10-01

131

Photodynamic therapy: Theoretical and experimental approaches to dosimetry  

NASA Astrophysics Data System (ADS)

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

Wang, Ken Kang-Hsin

132

Antimicrobial Photodynamic Therapy for Methicillin-Resistant Staphylococcus aureus Infection  

PubMed Central

Nowadays methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug resistant bacteria both in hospitals and in the community. In the last two decades, there has been growing concern about the increasing resistance to MRSA of the most potent antibiotic glycopeptides. MRSA infection poses a serious problem for physicians and their patients. Photosensitizer-mediated antimicrobial photodynamic therapy (PDT) appears to be a promising and innovative approach for treating multidrug resistant infection. In spite of encouraging reports of the use of antimicrobial PDT to inactivate MRSA in large in vitro studies, there are only few in vivo studies. Therefore, applying PDT in the clinic for MRSA infection is still a long way off. PMID:23555074

Fu, Xiu-jun; Fang, Yong; Yao, Min

2013-01-01

133

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

134

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

135

Self-assembled liposomal nanoparticles in photodynamic therapy  

PubMed Central

Photodynamic therapy (PDT) employs the combination of non-toxic photosensitizers (PS) together with harmless visible light of the appropriate wavelength to produce reactive oxygen species that kill unwanted cells. Because many PS are hydrophobic molecules prone to aggregation, numerous drug delivery vehicles have been tested to solubilize these molecules, render them biocompatible and enhance the ease of administration after intravenous injection. The recent rise in nanotechnology has markedly expanded the range of these nanoparticulate delivery vehicles beyond the well-established liposomes and micelles. Self-assembled nanoparticles are formed by judicious choice of monomer building blocks that spontaneously form a well-oriented 3-dimensional structure that incorporates the PS when subjected to the appropriate conditions. This self-assembly process is governed by a subtle interplay of forces on the molecular level. This review will cover the state of the art in the preparation and use of self-assembled liposomal nanoparticles within the context of PDT. PMID:24348377

Sadasivam, Magesh; Avci, Pinar; Gupta, Gaurav K.; Lakshmanan, Shanmugamurthy; Chandran, Rakkiyappan; Huang, Ying-Ying; Kumar, Raj; Hamblin, Michael R.

2013-01-01

136

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

137

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

138

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

139

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

140

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

141

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.

142

Advance in photosensitizers and light delivery for photodynamic therapy.  

PubMed

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; Shim, Young Key

2013-01-01

143

Photodynamic therapy for cutaneous and subcutaneous malignant neoplasms.  

PubMed

Twenty-seven patients with cutaneous and subcutaneous malignant neoplasms were treated with photodynamic therapy. Therapy was administered to 248 areas during a total of 72 separate treatment sessions after patients received a total of 45 injections of sensitizer. Seven patients had basal cell carcinoma, three had squamous cell carcinoma, three had malignant melanoma, one had liposarcoma, and 12 had breast cancers. One patient had Bowen's disease. Treatment was given either by surface radiation or interstitially. One month after treatment, 48 (67%) of the treatment sessions resulted in a complete response (no clinical evidence of tumor), and 19 (26%) resulted in a partial response (greater than 50% reduction in the number or size of tumors). Fifteen patients were examinable 12 months after treatment, and in this group, 31 treatment sessions were evaluated as a complete response one month after therapy, 15 (48%) of which retained this status at one year after treatment. By comparing the ability of different light-delivery instrumentation, it was concluded that the Yellow Springs radiometer (Yellow Springs Instruments, model 65A, Yellow Springs, Ohio) provided the most reliable spot power density readings. Straight-tipped fibers are nonhomogeneous and can result in overtreatment of the central area with necrosis and pain and in undertreatment of the periphery. PMID:2916942

McCaughan, J S; Guy, J T; Hicks, W; Laufman, L; Nims, T A; Walker, J

1989-02-01

144

Metformin associated with photodynamic therapy--a novel oncological direction.  

PubMed

The aim of our study was to assess the effect of the combined treatment of Metformin (Metf) and 5, 10, 15, 20-tetra-sulfophenyl-porphyrin (TSPP)-mediated photodynamic therapy (PDT) on an in vivo tumour model. Wistar male rats were divided in 6 groups: group 1, treated with TSPP; groups 2 and 4 treated with TSPP and Metf, respectively, and irradiated 24h thereafter; group 3 was treated with Metf and the last two groups received the combined treatment, Metf administered prior (group 5) or after (group 6) irradiation. 72 h from the start of the treatment, tumour tissue was sampled for the investigation of oxidative and nitrosative stress. The apoptotic rate, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions and matrix metalloproteinases activities were also quantified. Malondialdehyde and glutathione levels were significantly elevated in the groups treated with combined therapy (p<0.05). Metf associated with TSPP-PDT reduced iNOS and COX-2 expressions and enhanced nitrotyrosine levels in both therapeutic regimens. Peroxynitrate formation and its cytotoxic effect on tumour cells were related to an elevated index of apoptosis and necrosis. Moreover, MMP-2 activity reached a minimum in the groups which received combined therapy. Our results confirmed that the association of Metf with PDT might prove a new and promising oncological approach. PMID:24911275

Nenu, Iuliana; Popescu, Tiberiu; Aldea, Mihaela D; Craciun, Lucian; Olteanu, Diana; Tatomir, Corina; Bolfa, Pompei; Ion, Rodica M; Muresan, Adriana; Filip, Adriana G

2014-09-01

145

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

146

Designing photosensitizers for photodynamic therapy: strategies, challenges and promising developments.  

PubMed

Photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) are techniques that combine the effects of visible light irradiation with subsequent biochemical events that arise from the presence of a photosensitizing drug (possessing no dark toxicity) to cause destruction of selected cells. Despite its still widespread clinical use, Photofrin(®) has several drawbacks that limit its general clinical use. Consequently, there has been extensive research into the design of improved alternative photosensitizers aimed at overcoming these drawbacks. While there are many review articles on the subject of PDT and PACT, these have focused on the photosensitizers that have been used clinically, with little emphasis placed on how the chemical aspects of the molecule can affect their efficacy as PDT agents. Indeed, many of the PDT/PACT agents used clinically may not even be the most appropriate within a given class. As such, this review aims to provide a better understanding of the factors that have been investigated, while aiming at improving the efficacy of a molecule intended to be used as a photosensitizer. Recent publications, spanning the last 5 years, concerning the design, synthesis and clinical usage of photosensitizers for application in PDT and PACT are reviewed, including 5-aminolevulinic acid, porphyrins, chlorins, bacteriochlorins, texaphyrins, phthalocyanines and porphycenes. It has been shown that there are many important considerations when designing a potential PDT/PACT agent, including the influence of added groups on the lipophilicity of the molecule, the positioning and nature of these added groups within the molecule, the presence of a central metal ion and the number of charges that the molecule possesses. The extensive ongoing research within the field has led to the identification of a number of potential lead molecules for application in PDT/PACT. The development of the second-generation photosensitizers, possessing shorter periods of photosensitization, longer activation wavelengths and greater selectivity for diseased tissue provides hope for attaining the ideal photosensitizer that may help PDT and PACT move from laboratory investigation to clinical practice. PMID:21426032

Garland, Martin J; Cassidy, Corona M; Woolfson, David; Donnelly, Ryan F

2009-07-01

147

Early-stage thymic carcinoma: is adjuvant therapy required?  

PubMed Central

Although the prognosis of advanced thymic carconoma remains poor, previous reports have shown survival rates of 70% to 100% in patients with Masaoka stage I or stage II of the disease who were treated with surgery followed by adjuvant therapy. However, the role of adjuvant therapy in these stages is controversial. We retrospectively evaluated the outcome of 4 patients with Masaoka stage II thymic carcinoma who were treated with surgery alone between 1992 and 2008. No patient had stage I of the disease. Primary tumors were preoperatively evaluated by chest X-ray and computed tomography. Needle biopsy was not performed because the tumors were clinically diagnosed as noninvasive thymomas. The largest diameter of the primary tumor was 65 mm. Mediastinal lymphadenopathy was not detected by computed tomography. All patients underwent transsternal thymectomy. Mediastinal lymph node dissection was not performed. None of the patients received adjuvant chemotherapy and/or irradiation. Histopathologic examination revealed squamous cell carcinoma in 3 patients and undifferentiated carcinoma in one. Pathologic invasion to the adjacent organs or lymph node metastasis was not detected. All patients were alive and free from relapse at a follow-up of 72 months (range, 12-167 months). Radical resection without adjuvant therapy could be a treatment option for early Masaoka stage thymic carcinoma with low-grade histology. PMID:23585943

Onuki, Takuya; Inagaki, Masaharu; Yamaoka, Masatoshi; Kitazawa, Shinsuke; Kobayashi, Keisuke; Iguchi, Kesato; Kikuchi, Shinji; Goto, Yukinobu; Onizuka, Masataka; Sato, Yukio

2013-01-01

148

Early-stage thymic carcinoma: is adjuvant therapy required?  

PubMed

Although the prognosis of advanced thymic carconoma remains poor, previous reports have shown survival rates of 70% to 100% in patients with Masaoka stage I or stage II of the disease who were treated with surgery followed by adjuvant therapy. However, the role of adjuvant therapy in these stages is controversial. We retrospectively evaluated the outcome of 4 patients with Masaoka stage II thymic carcinoma who were treated with surgery alone between 1992 and 2008. No patient had stage I of the disease. Primary tumors were preoperatively evaluated by chest X-ray and computed tomography. Needle biopsy was not performed because the tumors were clinically diagnosed as noninvasive thymomas. The largest diameter of the primary tumor was 65 mm. Mediastinal lymphadenopathy was not detected by computed tomography. All patients underwent transsternal thymectomy. Mediastinal lymph node dissection was not performed. None of the patients received adjuvant chemotherapy and/or irradiation. Histopathologic examination revealed squamous cell carcinoma in 3 patients and undifferentiated carcinoma in one. Pathologic invasion to the adjacent organs or lymph node metastasis was not detected. All patients were alive and free from relapse at a follow-up of 72 months (range, 12-167 months). Radical resection without adjuvant therapy could be a treatment option for early Masaoka stage thymic carcinoma with low-grade histology. PMID:23585943

Sakai, Mitsuaki; Onuki, Takuya; Inagaki, Masaharu; Yamaoka, Masatoshi; Kitazawa, Shinsuke; Kobayashi, Keisuke; Iguchi, Kesato; Kikuchi, Shinji; Goto, Yukinobu; Onizuka, Masataka; Sato, Yukio

2013-04-01

149

Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy  

Microsoft Academic Search

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic

Yun Sun; Zhi-long Chen; Xiao-xia Yang; Peng Huang; Xin-ping Zhou; Xiao-xia Du

2009-01-01

150

Monitoring of photobleaching in photodynamic therapy using fluorescence spectroscopy.  

PubMed

Photodynamic therapy (PDT) utilizing aminolevulinic acid (ALA) as a photosensitiser has been used to ablate premalignant/malignant skin conditions including superficial basal cell carcinoma (BCC) with acceptable cosmetic outcome. Clinicians continue however to face difficulties in determining the exact dose that is sufficient to achieve a complete healing from the condition where the experience of the clinician remains the only determinant factor. This inaccuracy sometimes leads to undertreating these lesions. Here, we have clinically evaluated the use of fluorescence imaging system as monitor of protoporphyrin IX (PpIX) photobleaching in patients with BCC and compares this to the clinical outcome. Four readings were acquired from each patient (n=14) "pre-PDT", "peri-PDT" (333secs), "peri-PDT" (660secs) and post-PDT. It was found that red fluorescence values decreased markedly during PDT, and considered to be significant when compared to pre-PDT (P = 0.0018) and post- PDT (P = 0.0025). The red fluorescence value in pre-PDT was found to be higher in BCC of cheek and scalp (where the response rate, RR = 100%) in comparison to the temple (RR = 75%) and nose (RR = 33%). By comparison, the post- PDT red fluorescence values in cheek and scalp were lower than that of the temple and nose, respectively; this may be a useful indicative of the response rate of tissue to therapy. PMID:25316396

Sharwani, A; Alharbi, F A

2014-07-01

151

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

152

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

153

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

154

Photodynamic therapy for the prevention of restenosis after angioplasty  

NASA Astrophysics Data System (ADS)

The purpose of this study was to evaluate whether photodynamic therapy (PDT) can destroy the proliferating smooth muscle cells and therefore suppress the occurrence of restenosis after angioplasty. PDT following administration of hematoporphyrin derivatives (HpD) 24 hours before irradiation was performed on 30 rabbits immediately (0D), 3 days (3D), 1 week (1W) and 2 weeks (2W) after balloon injury. HpD accumulation of each group was investigated simultaneously. Irradiation of 27 J/10 mm2 from an Hg-Xe flash lamp light transmitted through an 800 micrometers quartz fiber with a diffusing tip was used. All rabbits were sacrificed 4 weeks after balloon injury. The results were expressed in terms of intima:media thickness ratio at the site of fiber contact (I/M) and intima:media area ratio of the cross section (IA/MA). Inhibition of intimal thickening evaluated on the basis of the I/M ratio was recognized in the 3D-, 1W-, and 2W-PDT group. The most effective photoradiation was at the 1W-PDT (I/M equals 0.78 +/- 0.67), but in 2W-PDT intimal necrosis resulting in a small amount of thickness was observed with less media necrosis. ThreeD and 0D PDT effects reduced with media necrosis. We conclude that PDT after angioplasty would be an ideal preventional therapy of restenosis.

Asahara, Takayuki; Usui, Mikio; Amemiya, Takashi; Oike, Yasuhisa; Shiraishi, Hiromori; Miyagi, Manabu; Nakajima, Hitoshi; Kato, Tomitsugu; Naito, Yuichi; Ibukiyama, Chiharu

1993-06-01

155

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

156

Endoscopic laser therapy in malignant tracheobronchial obstruction using sequential Nd YAG laser and photodynamic therapy  

PubMed Central

BACKGROUND: Because the survival after treatment of advanced inoperable endo-tracheobronchial carcinoma is so poor, a pilot study was undertaken to evaluate the combined cumulative effect on survival of neodymium yttrium aluminium garnet (Nd YAG) laser followed by photodynamic treatment used endoscopically. METHODS: Seventeen patients who presented between January 1992 and March 1996 with inoperable tracheobronchial lesions causing more than 50% endoluminal obstruction were selected to enter the pilot study. Initially they had bronchoscopic Nd YAG laser treatment to debulk the tumour, and this was followed six weeks later by photodynamic therapy to treat the residual tumour. RESULTS: All patients had symptomatic relief and at least a partial response, and seven had a complete response for 3-6 months. Eight of the 17 (47%) survived for at least two years and 11 (65%) survived for a year or more. The median survival of the 10 patients who had died by the time of writing was 18.5 months (range 5-39), 95% confidence interval (CI) 9.9 to 29.5. CONCLUSIONS: Combined Nd YAG laser and endoscopic photodynamic therapy may be an effective palliative treatment for patients with inoperable endotracheobronchial cancer. ??? PMID:9093347

Moghissi, K.; Dixon, K.; Hudson, E.; Stringer, M.; Brown, S.

1997-01-01

157

[Laparoscopic surgery and adjuvant therapy for colon cancer].  

PubMed

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

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

2009-01-01

158

Methyl - aminolevulinic acid photodynamic therapy and topical tretinoin in a patient with vulvar extramammary Paget's disease.  

PubMed

Extramammary Paget's disease is a rare neoplasm of apocrine gland-bearing areas of the skin. The most common site of presentation is the vulva. Surgery is the most frequently reported therapy so far; however, it is invasive and it is complicated by a high rate of recurrence. For this reason, several less-invasive treatments have been recently proposed, including photodynamic therapy. We describe in this article the case of an 84-year-old patient with a noninvasive vulvar extramammary Paget's disease successfully treated with methyl-aminolevulinic acid photodynamic therapy associated with topical tretinoin. PMID:23551374

Magnano, Michela; Loi, Camilla; Bardazzi, Federico; Burtica, Elena Cleopatra; Patrizi, Annalisa

2013-01-01

159

Specific inhibition of the ABCG2 transporter could improve the efficacy of photodynamic therapy.  

PubMed

Photodynamic therapy is based on the selective accumulation of a photosensitizer in tumors, followed by destruction of the target tissue by a light source. Protoporphyrin IX, a well-known photosensitizer, was recently reported as an endogenous substrate for the multidrug transporter ABCG2. We investigated the role of ABCG2 protein in the porphyrin extrusion ability of keratinocytes, with regard to the impact of the specific inhibition of ABCG2 by a non-toxic fumitremorgin C analog, Ko-134, on photodynamic therapy efficacy. We studied the level of porphyrin accumulation in response to delta-aminolevulinic acid pretreatment in proliferating and highly differentiated HaCaT keratinocytes. An in vitro model of photodynamic therapy on HaCaT cells was established with a therapeutically approved narrow-bandwidth red-light source. The porphyrin extrusion ability of HaCaT cells proved to correlate with their ABCG2 expression which was higher in proliferating cells than in differentiated cells. Moreover, the specific inhibition of ABCG2 by Ko-134 enhanced the sensitivity of keratinocytes to photodynamic therapy in vitro. These results suggest that ABCG2 may serve as a target molecule via which to improve the photodynamic therapy of skin lesions: its inhibition by the non-toxic Ko-134 is a promising therapeutic modality. PMID:21911299

Bebes, Attila; Nagy, Tünde; Bata-Csörgo, Zsuzsanna; Kemény, Lajos; Dobozy, Attila; Széll, Márta

2011-11-01

160

Treatment of Canine Osseous Tumors with Photodynamic Therapy: A Pilot Study  

PubMed Central

Photodynamic therapy uses nonthermal coherent light delivered via fiber optic cable to locally activate a photosensitive chemotherapeutic agent that ablates tumor tissue. Owing to the limitations of light penetration, it is unknown whether photodynamic therapy can treat large osseous tumors. We determined whether photodynamic therapy can induce necrosis in large osseous tumors, and if so, to quantify the volume of treated tissue. In a pilot study we treated seven dogs with spontaneous osteosarcomas of the distal radius. Tumors were imaged with MRI before and 48 hours after treatment, and the volumes of hypointense regions were compared. The treated limbs were amputated immediately after imaging at 48 hours and sectioned corresponding to the MR axial images. We identified tumor necrosis histologically; the regions of necrosis corresponded anatomically to hypointense tissue on MRI. The mean volume of necrotic tissue seen on MRI after photodynamic therapy was 21,305 mm3 compared with a pretreatment volume of 6108 mm3. These pilot data suggest photodynamic therapy penetrates relatively large canine osseous tumors and may be a useful adjunct for treatment of bone tumors. PMID:19159117

London, C.; Seguin, B.; Rodriguez, C.; Wilson, B. C.; Bisland, S. K.

2009-01-01

161

Contrast-enhanced MRI-guided photodynamic cancer therapy with a pegylated bifunctional polymer conjugate  

PubMed Central

Purpose To study contrast-enhanced MRI guided photodynamic therapy with a pegylated bifunctional polymer conjugate containing an MRI contrast agent and a photosensitizer for minimally invasive image-guided cancer treatment. Methods Pegylated and non-pegylated poly-(L-glutamic acid) conjugates containing mesochlorin e6, a photosensitizer, and Gd(III)-DO3A, an MRI contrast agent, were synthesized. The effect of pegylation on the biodistribution and tumor targeting was non-invasively visualized in mice bearing MDA-MB-231 tumor xenografts with MRI. MRI-guided photodynamic therapy was carried out in the tumor bearing mice. Tumor response to photodynamic therapy was evaluated by dynamic contrast enhanced MRI and histological analysis. Results The pegylated conjugate had longer blood circulation, lower liver uptake and higher tumor accumulation than the non-pegylated conjugate as shown by MRI. Site-directed laser irradiation of tumors resulted in higher therapeutic efficacy for the pegylated conjugate than the non-pegylated conjugate. Moreover, animals treated with photodynamic therapy showed reduced vascular permeability on DCE-MRI and decreased microvessel density in histological analysis. Conclusions Pegylation of the polymer bifunctional conjugates reduced non-specific liver uptake and increased tumor uptake, resulting in significant tumor contrast enhancement and high therapeutic efficacy. The pegylated poly(L-glutamic acid) bifunctional conjugate is promising for contrast enhanced MRI guided photodynamic therapy in cancer treatment. PMID:18584312

Vaidya, Anagha; Sun, Yongen; Feng, Yi; Emerson, Lyska; Jeong, Eun-Kee; Lu, Zheng-Rong

2008-01-01

162

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

163

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

164

Photodynamic therapy induced vascular damage: an overview of experimental PDT  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed.

Wang, W.; Moriyama, L. T.; Bagnato, V. S.

2013-02-01

165

Effects of vascular targeting photodynamic therapy on lymphatic tumor metastasis  

NASA Astrophysics Data System (ADS)

Vascular targeting photodynamic therapy (vPDT) is currently in clinical trial for prostate cancer (PCa) treatment. In order to study the effect of vPDT on tumor metastasis, GFP-PC3 or PC-3 xenografts were treated with verteporfin (BPD) PDT. Vascular function was assessed by ultrasound imaging; lymph node and lung metastasis were assessed by fluorescence imaging. vPDT significantly reduced tumor blood flow within 30minutes to 2 hours of treatment. Sub-curative treatment resulted in re-perfusion within 2 weeks of treatment and increased lymph node metastasis. With curative doses, no metastasis was observed. In order to identify cellular or matrix factors and cytokines implicated, conditioned medium from BPD PDTtreated endothelial cells was incubated with PC3 cells in vitro. Tumor cell proliferation and migration was assessed. By immunoblotting, we evaluated the change in mediators of intracellular signaling or that may determine changes in tumor phenotype. Low sub-curative dose (200ng/ml BPD) of endothelial cells was associated with ~15% greater migration in PC3 cells when compared with control. This dose was also associated with sustained activation of Akt at Ser 473, an upstream effector in the Akt/ mTOR pathway that has been correlated with Gleason scores in PCa and with survival and metastasis in vitro and in vivo. In conclusion, the study implicates efficacy of PDT of endothelial cells as an important determinant of its consequences on adjacent tumor proliferation and metastasis.

Fateye, B.; He, C.; Chen, B.

2009-06-01

166

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

167

Absence of bacterial resistance following repeat exposure to photodynamic therapy  

NASA Astrophysics Data System (ADS)

The prevalence of antibiotic resistant bacteria necessitates exploration of alternative approaches to treat hospital and community acquired infections. The aim of this study was to determine whether bacterial pathogens develop resistance to antimicrobial photodynamic therapy (aPDT) during repeated sub-lethal challenge. Antibiotic sensitive and resistant strains of S. aureus and antibiotic sensitive E. coli were subjected to repeat PDT treatments using a methylene blue photosensitizer formulation and 670 nm illumination from a non-thermal diode laser. Parameters were adjusted such that kills were <100% so that surviving colonies could be passaged for subsequent exposures. With each repeat, kills were compared to those using non-exposed cultures of the same strain. Oxacillin resistance was induced in S. aureus using a disc diffusion method. For each experiment, "virgin" and "repeat" cultures were exposed to methylene blue at 0.01% w/v and illuminated with an energy dose of 20.6 J/cm2. No significant difference in killing of E. coli (repeat vs. virgin culture) was observed through 11 repeat exposures. Similar results were seen using MSSA and MRSA, wherein kill rate did not significantly differ from control over 25 repeat exposures. In contrast, complete oxacillin resistance could be generated in S. aureus over a limited number of exposures. PDT is effective in the eradication of pathogens including antibiotic resistance strains. Furthermore, repeated sub-lethal exposure does not induce resistance to subsequent PDT treatments. The absence of resistance formation represents a significant advantage of PDT over traditional antibiotics.

Pedigo, Lisa A.; Gibbs, Aaron J.; Scott, Robert J.; Street, Cale N.

2009-06-01

168

Important factors for pain during photodynamic therapy for actinic keratosis.  

PubMed

Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A common problem, however, is pain. The aim of this study was to investigate pain during PDT for actinic keratosis. The possibility of using capsaicin cream for pain relief was also assessed. Pain was investigated during aminolaevulinic acid PDT in 91 patients. Size, redness, scaling and induration of the lesions were recorded. Maximum pain during treatment was registered, using a visual analogue scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study in six patients (10 lesions). These patients were pre-treated with capsaicin cream for one week before commencing PDT. Pain was found to be normally distributed around a mean value of visual analogue scale 4.6. Larger lesions gave more pain (p=0.001). The redness of the actinic lesions was found to be related to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the cure rate (p=0.01). The redder the actinic area, the better the treatment outcome and the more pain experienced. Patients with the largest reduction in the actinic area experienced more pain (p=0.053). The most important factors for presence of pain seem to be the size and the redness of the lesion. No significant pain relief was experienced after pre-treatment with capsaicin. PMID:16955183

Sandberg, Carin; Stenquist, Bo; Rosdahl, Inger; Ros, Anne-Marie; Synnerstad, Ingrid; Karlsson, Maria; Gudmundson, Fredrik; Ericson, Marica B; Larkö, Olle; Wennberg, Ann-Marie

2006-01-01

169

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

170

Mycoplasma Removal from Cell Culture Using Antimicrobial Photodynamic Therapy  

PubMed Central

Abstract Objective: The objective of this research was to determine the effectiveness of antimicrobial photodynamic therapy (aPDT) in the removal of mycoplasmas from contaminated cells. Background data: Mycoplasmas often contaminate cell cultures. The cell-contaminating mycoplasmas are removed by antibiotics, but the use of antibiotics usually induces antibiotic-resistant bacteria. aPDT is expected to be a possible alternative to antibiotic treatments for suppressing infections. Materials and Methods: Mycoplasma salivarium (Ms)-infected human embryonic kidney (HEK) 293 cells were irradiated using a red light-emitting diode (LED) in the presence of methylene blue (MB) as a photosensitizer. The Ms viable count was determined using culture on agar plates or using a mycoplasma detection kit. Results: aPDT performed using red LED irradiation was effective in decreasing live Ms in the presence of MB without damaging the HEK293 cells. aPDT removed live Ms from the infected cells after washing the cells with sterilized phosphate-buffered saline (PBS) to decrease the initial number of live Ms before aPDT. Conclusions: This study suggests that aPDT could remove mycoplasmas from contaminated cells. PMID:23402393

Hasebe, Akira; Ishikawa, Isao; Shamsul, Haque M.; Ohtani, Makoto; Segawa, Taku; Saeki, Ayumi; Tanizume, Naoho; Oouchi, Manabu; Okagami, Yoshihide; Okano, Teruo

2013-01-01

171

Application of chemiluminescence with FCLA in photodynamic therapy  

NASA Astrophysics Data System (ADS)

In photodynamic therapy (PDT), a target tissue with pre-administered photosensitizer is exposed to laser light. The photochemical process produces reaction oxygen species (ROS), such as singlet oxygen and superoxide, and leads to ultimate cell death. A direct monitoring of ROS production during PDT, thus, may provide important information in both basic science and clinical practice. A cypridina luciferin analogue (FCLA) is a chemiluminescence (CL) probe that selectively detects singlet oxygen and superoxide. In this study, FCLA was used as an optical reporter of ROS produced by photosensitization reaction of Photofrin in Hanks solution and the CL was measured by a photomultiplier system operated at single photon counting mode. By varying the amount of PDT dosage (photosensitizer dose, light irradiation fluence rate) and the amount of FCLA, the intensity of CL were investigated. The results showed the FCLA concentration affects the ratio of the signal to background CL. The decay time of the photosensitized CL was approximately 10 sec., after the excitation source was turned off. In addition, the intensity of the CL-FCLA increased with increasing concentration of Photofrin and fluence rate. The work supported the potential application of FCLA-chemiluminescence probe as a dosimetric tool for PDT.

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

2005-01-01

172

Skin photosensitivity as a model in photodynamic therapy  

NASA Astrophysics Data System (ADS)

Skin photosensitivity is the most common side effect of photodynamic therapy (PDT) and in clinical situations needs to be avoided or at least minimized. However, because of the accessibility of skin tissue, skin photosensitivity represents a useful test system in vivo for evaluation of the pharmacokinetics of photosensitizers and light sources. Pig skin resembles in many aspects human skin and, therefore, is most suitable for these tests. Using pig skin photosensitivity as an end point, we evaluate the effect of cell loading with a photosensitizer, benzoporphyrin derivative (BPD verteporfin) following its intravenous administration either as a rapid bolus or slow infusion. Skin response to light activation indicated a very similar cell content of BPD. These results were in agrement with those obtained in an in vitro model. In addition, in the same pig skin photosensitivity model we compared the efficiency of activation of BPD with either laser (690 plus or minus 3 nm) or light-emitting diode (LED; 690 plus or minus 12 nm) light. Results indicated the equivalency of the two light sources in this test system, with LED light being slightly more efficient, due possibly to a fluence rate lower than laser light.

Richter, Anna M.; Jain, Ashok K.; Canaan, Alice J.; Meadows, Howard; Levy, Julia G.

1996-01-01

173

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

174

Safety assessment of oral photodynamic therapy in rats.  

PubMed

Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a photosensitizer) and visible light to destroy target cells (e.g., malignant, premalignant, or bacterial cells). The aim of this study was to investigate the response of normal rat tongue mucosa to PDT following the topical application of hematoporphyrin derivative (Photogem®), Photodithazine®, methylene blue (MB), and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One hundred and thirty three rats were randomly divided in various groups: the PDT groups were treated with the photosensitizers for 10 min followed by exposure to red light. Those in control groups received neither photosensitizer nor light, and they were subjected to light exposure alone or to photosensitizer alone. Fluorescent signals were obtained from tongue tissue immediately after the topical application of photosensitizers and 24 h following PDT. Histological changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT treatment. Fluorescence was detected immediately after the application of the photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in all experimental groups at all evaluation time points. The results suggest that there is a therapeutic window where PDT with Photogem®, Photodithazine®, MB, and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria without damaging normal oral tissue. PMID:22467011

Fontana, Carla R; Lerman, Mark A; Patel, Niraj; Grecco, Clovis; Costa, Carlos A de Souza; Amiji, Mansoor M; Bagnato, Vanderlei S; Soukos, Nikolaos S

2013-02-01

175

Necrosis prediction of photodynamic therapy applied to skin disorders  

NASA Astrophysics Data System (ADS)

The great selectivity and the lack of side effects of Photodynamic Therapy make it more advantageous than radiotherapy or chemotherapy. The application of PDT to skin diseases is particularly appropriate, due to the accessibility of this tissue. Common disorders like nonmelanoma skin cancer, that includes basocelullar or squamous cell carcinomas, can be treated with PDT. Conventional procedures, like surgery or radiotherapy, are not so efficient and do not, in general, obtain the same favourable results. PDT in dermatology medical praxis uses fixed protocols depending on the photosensitizer and the optical source used. These protocols are usually provided by the photosensitizer laboratory, and every lesion is treated with the same parameters. In this work we present a photo-chemical model of PDT applied to skin disorders treated with topical photosensitizers. Optical propagation inside the tissue is calculated by means of a 3D diffusion equation, solved via a finite difference numerical method. The photosensitizer degradation or photobleaching is taken into account, as the drug looses efficiency with the irradiation time. With these data the necrosis area is estimated, so this model could be used as a predictive tool to adjust the optical power and exposition time for the particular disease under treatment.

Fanjul-Vélez, F.; Romanov, O. G.; López-Escobar, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

2009-02-01

176

Photodynamic therapy for malignant tumours of the ampulla of Vater.  

PubMed Central

Ten patients with ampullary carcinoma, not suitable for surgery, were treated with endoscopic photodynamic therapy (PDT) to evaluate the feasibility and safety of treatment. Patients received 4 mg kg-1 of haematoporphyrin derivative intravenously. Two days later, a duodenoscopy was performed and red (630 nm) light delivered to the tumour at fixed energy densities of 50 J or 200 J cm-1 per application, depending on the type of optical fibre used. The tumours were treated by three or four light applications at each session. Treatment was repeated up to five times at intervals of three to six months. The sole complication of PDT was moderate skin photosensitivity, which occurred in three patients. Tumour size was assessed at four to eight weekly intervals. In the absence of macroscopic tumour, biopsy specimens were taken. In three patients with small tumours confined to the ampulla, remission was obtained for periods ranging from eight to 12 months. In a further four patients with small tumours bulk was greatly reduced. There was little response in three patients with extensive duodenal involvement. Therefore PDT for ampullary carcinoma is both feasible and safe, and with refinement may prove curative for small tumours. Images Figure 1 Figure 2 PMID:7615273

Abulafi, A M; Allardice, J T; Williams, N S; van Someren, N; Swain, C P; Ainley, C

1995-01-01

177

Photodynamic therapy in thoracic oncology: a single institution experience  

NASA Astrophysics Data System (ADS)

We have performed 800 photodynamic therapy (PDT) treatments in over 300 patients at the University of Pittsburgh since 1996. Over 150 patients have undergone PDT for palliation of dysphagia for esophageal cancer. Of the first 77 dysphagia improved in 90.8% with a mean dysphagia-free interval of 80 days. An expandable metal stent was required for extrinsic compression in 19 patients. We have treated 14 high-risk patients with early esophageal cancer or Barrett's high-grade dysplasia for curative intent. At a median follow-up of 12.8 months eight remain free of cancer. Over 100 patients have undergone PDT for lung cancer. Sixty-two patients received 77 courses for palliation. Thirty-five patients were treated for non-massive hemoptysis with resolution in 90%. Forty-four patients were treated for dyspnea with improvement in 59%. A subset of seven high-risk patients with early lung cancer were treated with curative intent. A complete response was seen in 7/10 lesions at a mean follow-up of 30 months. PDT offers good palliation for both advanced esophageal and lung cancer. The role of PDT for curative intent needs further investigation in protocol settings. In our preliminary experience we have treated a small number of non-surgical, high-risk patients with a reasonable success rate.

Luketich, James D.; Fernando, Hiran C.; Christie, Neil A.; Litle, Virginia R.; Ferson, Peter F.; Buenaventura, Percival O.

2001-04-01

178

Chemical modification of normal tissue damage induced by photodynamic therapy.  

PubMed Central

One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 nm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A light dose response as well as a drug dose response was obtained. The results indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg-1), and 630 nm light (180 J cm-2) pretreatment with either WR-2721 or WR-3689 resulted in significant protection of the vascular effects of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light on photosensitized skin. They do so in a drug dose-dependent fashion with maximum protection at the highest drug doses. PMID:8763855

Sigdestad, C. P.; Fingar, V. H.; Wieman, T. J.; Lindberg, R. D.

1996-01-01

179

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

180

Differential cell photosensitivity in photodynamic therapy of the rat endometrium  

NASA Astrophysics Data System (ADS)

The purpose of this study was to determine the optical dose needed for both lasting endometrial destruction and prevention of implantation by photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) as a photosensitizer. Three hours after topical drug administration 74 female Sprague-Dawley received varying optical doses of 630 nm light delivered by an intrauterine cylindrical light diffusing fiber. Histologic evaluation of the endometrium 1 and 21 days after PDT as well as the number of implantation sacs after mating were assessed. Irreversible endometrial destruction was determined measuring the thickness of the endometrial layer 3 weeks after treatment. An in situ dose of 64 J/cm2 was required to eradicate endometrial glands and prevent regeneration. In contrast, a 43 J/cm2 in situ dose visibly damaged the endometrial stroma and myometrium but the endometrial glands survived and the endometrium regenerated to its full thickness within 21 days. However, implantation potential was significantly reduced at these low light levels. Due to differential cell photosensitivity, the optical threshold for lasting endometrial destruction is higher than for functional damage. For lasting endometrial destruction the endometrial glands must be destroyed, whereas for reproductive impairment, damage to the endometrial stroma seems to be sufficient.

Fehr, Mathias K.; Svaasand, Lars O.; Tromberg, Bruce J.; Ngo, Phat; Berns, Michael W.; Tadir, Yona

1996-01-01

181

Photodynamic therapy and fluorescent diagnostics of breast cancer  

NASA Astrophysics Data System (ADS)

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

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

2004-06-01

182

Core - shell upconversion nanoparticle - semiconductor heterostructures for photodynamic therapy.  

PubMed

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

183

Development and optimization of a diode laser for photodynamic therapy  

PubMed Central

Background and Aims: This study demonstrated the development of a laser system for cancer treatment with photodynamic therapy (PDT) based on a 635 nm laser diode. In order to optimize efficacy in PDT, the ideal laser system should deliver a homogeneous nondivergent light energy with a variable spot size and specific wavelength at a stable output power. Materials and Methods: We developed a digital laser beam controller using the constant current method to protect the laser diode resonator from the current spikes and other fluctuations, and electrical faults. To improve the PDT effects, the laser system should deliver stable laser energy in continuous wave (CW), burst mode and super burst mode, with variable irradiation times depending on the tumor type and condition. Results and Comments: The experimental results showed the diode laser system described herein was eminently suitable for PDT. The laser beam was homogeneous without diverging and the output power increased stably and in a linear manner from 10 mW to 1500 mW according to the increasing input current. Variation between the set and delivered output was less than 7%. Conclusions: The diode laser system developed by the author for use in PDT was compact, user-friendly, and delivered a stable and easily adjustable output power at a specific wavelength and user-set emission modes. PMID:24155529

Lim, Hyun Soo

2011-01-01

184

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

185

Outcome of Photodynamic Therapy for Early Esophageal Cancer  

PubMed Central

Background/Aims Endoscopic treatment as an alternative to surgery has become increasingly popular for improving the quality of life. Although photodynamic therapy (PDT) has been used for the endoscopic treatment of digestive cancer, its curative efficacy remains unclear. We evaluated the curative efficacy of PDT in superficial esophageal cancer in inoperable patients. Methods Ten male patients with histologically proven early esophageal cancer (surgery was contraindicated for age > 80 years, surgery was contraindicated, Karnofsky performance status of at least 30%, or refusal of surgery) were intravenously injected with a hematoporphyrin derivative (2 mg/kg), and PDT was performed 48 h later. The response to treatment was assessed by gastroscopy with biopsies. Results The mean follow-up period was 27.6 months (range, 9.6-58.7 months). Endoscopic ultrasonography revealed that all ten cases were at tumor stage T1. Complete remission (CR) to initial and subsequent PDT was observed in all patients. For the CR cases, the recurrence rate was 10% (1/10) and the time from initial PDT to recurrence was 9.6 months. Conclusions For patients in whom surgery is risky or refused, PDT may represent an acceptable alternative treatment modality, especially for superficial esophageal cancer without lymph node metastasis. However, a study involving long-term follow-up in a large population is needed for confirmation. PMID:20485628

Kim, Wan Jung; Cho, Joo Young; Lee, Joon Seong; Lee, Moon Sung; Shim, Chan Sup

2007-01-01

186

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

187

Tumor Vascular Microenvironment Determines Responsiveness to Photodynamic Therapy  

PubMed Central

The efficacy of photodynamic therapy (PDT) depends upon the delivery of both photosensitizing drug and oxygen. In this study, we hypothesized that local vascular microenvironment is a determinant of tumor response to PDT. Tumor vascularization and its basement membrane (collagen) were studied as a function of supplementation with basement membrane matrix (Matrigel) at the time of tumor cell inoculation. Effects on vascular composition with consequences to tumor hypoxia, photosensitizer uptake and PDT response were measured. Matrigel-supplemented tumors developed more normalized vasculature, composed of smaller and more uniformly-spaced blood vessels than their unsupplemented counterparts, but these changes did not affect tumor oxygenation or PDT-mediated direct cytotoxicity. However, PDT-induced vascular damage increased in Matrigel-supplemented tumors, following an affinity of the photosensitizer Photofrin for collagen-containing vascular basement membrane coupled with increased collagen content in these tumors. The more highly-collagenated tumors demonstrated more vascular congestion and ischemia after PDT, along with a higher probability of curative outcome that was collagen dependent. In the presence of photosensitizer-collagen localization, PDT effects on collagen were evidenced by a decrease in its association with vessels. Together, our findings demonstrate that photosensitizer localization to collagen increases vascular damage and improves treatment efficacy in tumors with greater collagen content. The vascular basement membrane is thus identified to be a determinant of therapeutic outcome in PDT of tumors. PMID:22374982

Maas, Amanda L.; Carter, Shirron L.; Wileyto, E. Paul; Miller, Joann; Yuan, Min; Yu, Guoqiang; Durham, Amy C.; Busch, Theresa M.

2012-01-01

188

Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling  

PubMed Central

Singlet oxygen (1O2) is the major cytotoxic agent responsible for cell killing for type-II photodynamic therapy (PDT). An empirical four-parameter macroscopic model is proposed to calculate the “apparent reacted 1O2 concentration”, [1O2]rx, as a clinical PDT dosimetry quantity. This model incorporates light diffusion equation and a set of PDT kinetics equations, which can be applied in any clinical treatment geometry. We demonstrate that by introducing a fitting quantity “apparent singlet oxygen threshold concentration” [1O2]rx,sd, it is feasible to determine the model parameters by fitting the computed [1O2]rx to the Photofrin-mediated PDT-induced necrotic distance using interstitially-measured Photofrin concentration and optical properties within each mouse. After determining the model parameters and the [1O2]rx,sd, we expect to use this model as an explicit dosimetry to assess PDT treatment outcome for a specific photosensitizer in an in vivo environment. The results also provide evidence that the [1O2]rx, because it takes into account the oxygen consumption (or light fluence rate) effect, can be a better predictor of PDT outcome than the PDT dose defined as the energy absorbed by the photosensitizer, which is proportional to the product of photosensitizer concentration and light fluence. PMID:20222102

Wang, Ken Kang-Hsin; Finlay, Jarod C.; Busch, Theresa M.; Hahn, Stephen M.; Zhu, Timothy C.

2011-01-01

189

Stimulation of dendritic cells enhances immune response after photodynamic therapy  

NASA Astrophysics Data System (ADS)

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

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

2009-02-01

190

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

191

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

192

How we treat a superficial basal cell carcinoma with topical photodynamic therapy in Dundee.  

PubMed

Topical photodynamic therapy (PDT) is a highly effective treatment for superficial basal cell carcinoma (SBCC) (Morton CA, Brown SB, Collins S, et al. Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group. Br J Dermatol 2004;146:552-67). Treatment is well tolerated, performed on an outpatient basis and can be repeated, and excellent outcomes and cosmetic results can be achieved. We have experience of over 3000 topical PDT treatments for superficial non-melanoma skin cancer and dysplasia in the Photobiology Unit in Dundee and I will present our own experience of how to treat an SBCC with topical PDT in this article (Ibbotson SH, Moseley H, Brancaleon L, et al. Photodynamic therapy in dermatology: Dundee clinical and research experience. Photodiagn Photodyn Ther 2004;1:211-23). PMID:25049104

Ibbotson, Sally H

2006-06-01

193

Photodynamic Therapy with ATX-S10·Na(II) Inhibits Synovial Sarcoma Cell Growth  

Microsoft Academic Search

Photodynamic therapy (PDT) is an effective cancer treatment modality that allows selective destruction of malignant tumor\\u000a cells. We asked whether PDT could inhibit in vivo and in vitro growth of synovial sarcoma cells. We analyzed PDT using ATX-S10·Na(II)\\u000a and a diode laser for a synovial sarcoma cell line (SYO-1). Photodynamic therapy with ATX-S10·Na(II) showed an in vitro cytotoxic\\u000a effect on the cultured SYO-1

Ken Takeda; Toshiyuki Kunisada; Shinichi Miyazawa; Yoshinori Nakae; Toshifumi Ozaki

2008-01-01

194

Three-photon absorption measurements in hematoporphyrin IX: ``Ground-breaking opportunities in deep photodynamic therapy''  

NASA Astrophysics Data System (ADS)

In this Letter, we report the three-photon absorption of hematoporphyrin IX (HpD-IX) in DMSO solution pumping at 1200 nm with a 25 ps pulse laser-OPG system. The obtained three-photon absorption cross-section in HpD-IX, ?3'=1.2×10-78cm6s2ph-2, is considerably high. Because HpD-IX is one of the main constituent of Photofrin ® II, the only approved photodynamic therapy drug by the Food and Drug Association, this result is expected to have an impact in deep bioimaging and photodynamic therapy using currently available photosensitisers.

Cohanoschi, Ion; Echeverría, Lorenzo; Hernández, Florencio E.

2006-02-01

195

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

196

Biomarkers to individualise adjuvant systemic therapy in early breast cancer patients.  

E-print Network

??Background Adjuvant chemotherapy, endocrine therapy, anti-HER2 therapy and radiotherapy significantly improve recurrence free and overall survivals in early breast cancers. Indications for a particular therapy… (more)

Moe, Maung

2013-01-01

197

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

198

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

199

Assessing autophagy in the context of photodynamic therapy  

PubMed Central

Photodynamic therapy (PDT) is a procedure that has applications in the selective eradication of neoplasia where sites of malignant lesions are clearly delineated. It is a two-step process whereby cells are first sensitized to light and then photoirradiated. This results in the formation of singlet molecular oxygen and other reactive oxygen species that can cause photodamage at sites where the photosensitizing agent has localized. Photosensitizers found to be clinically useful show affinity for the endoplasmic reticulum (ER), mitochondria, lysosomes, or combinations of these sites. The induction of apoptosis and/or autophagy in photosensitized cells is a common outcome of PDT. This report explores the following issues: (1) Does the induction of autophagy in PDT protocols occur independent of, or in association with, apoptosis? (2) Does the resulting autophagy play a prosurvival or prodeath role? (3) Do photosensitizers damage/inactivate specific proteins that are components of, or that modulate the autophagic process? (4) Can an autophagic response be mounted in cells in which lysosomes are specifically photodamaged? In brief, autophagy can occur independently of apoptosis in PDT protocols, and appears to play a prosurvival role in apoptosis competent cells, and a prodeath role in apoptosis incompetent cells. Mitochondrial and ER-localized sensitizers cause selective photodamage to some (i.e., Bcl-2, Bcl-xL, mTOR) proteins involved in the apoptotic/autophagic process. Finally, an aborted autophagic response occurs in cells with photodamaged lysosomes. Whereas autophagosomes form, digestion of their cargo is compromised because of the absence of functional lysosomes. PMID:19855190

Reiners, John J.; Agostinis, Patrizia; Berg, Kristian; Oleinick, Nancy L.; Kessel, David

2010-01-01

200

Photosensitizer fluorescence emission during photodynamic therapy applied to dermatological diseases  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) is an optical treatment modality that allows malignant tissue destruction. It is based on the administration of a photosensitizer and the posterior irradiation by an optical source. Photosensitizer molecules absorb the excitation light photons triggering a series of photochemical reactions in the presence of oxygen in the target tissue. During such interactions it is produced the de-excitation of the photosensitizer molecules in the singlet excited state which return to their minimum energy state by emitting fluorescence photons. These days, there are fixed clinical PDT protocols that make use of a particular optical dose and photosensitizer amount. However treatment response varies among patients and the type of pathology. In order to adjust an optimal dosimetry, the development of accurate predictive models plays an important role. The photosensitizer fluorescence can be used to estimate the degradation of the photoactive agent and as an implicit dosimetric measurement during treatment. However it is complex to know the fluorescence dependence with the depth in the tumor from observed fluorescence in the pathology surface. We present a first approach to predict the photosensitizer fluorescence dependence with depth during the PDT treatment applied to a skin disease commonly treated in the dermatological clinical practice. The obtained results permit us to know the photosensitizer temporal fluorescence evolution in different points of the tumor sample during the photochemical reactions involved in PDT with a predictive purpose related to the treatment evolution. The model presented also takes into account the distribution of a topical photosensitizer, the propagation of light in a biological media and the subsequent photochemical interactions between light and tissue. This implies that different parameters related with the photosensitizer distribution or the optical source characteristics could be adjusted to provide a specific treatment to a particular pathology.

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

2012-02-01

201

Photosensitizer fluorescence emission during photodynamic therapy applied to dermatological diseases  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) is an optical treatment modality that allows malignant tissue destruction. It is based on the administration of a photosensitizer and the posterior irradiation by an optical source. Photosensitizer molecules absorb the excitation light photons triggering a series of photochemical reactions in the presence of oxygen in the target tissue. During such interactions it is produced the de-excitation of the photosensitizer molecules in the singlet excited state which return to their minimum energy state by emitting fluorescence photons. These days, there are fixed clinical PDT protocols that make use of a particular optical dose and photosensitizer amount. However treatment response varies among patients and the type of pathology. In order to adjust an optimal dosimetry, the development of accurate predictive models plays an important role. The photosensitizer fluorescence can be used to estimate the degradation of the photoactive agent and as an implicit dosimetric measurement during treatment. However it is complex to know the fluorescence dependence with the depth in the tumor from observed fluorescence in the pathology surface. We present a first approach to predict the photosensitizer fluorescence dependence with depth during the PDT treatment applied to a skin disease commonly treated in the dermatological clinical practice. The obtained results permit us to know the photosensitizer temporal fluorescence evolution in different points of the tumor sample during the photochemical reactions involved in PDT with a predictive purpose related to the treatment evolution. The model presented also takes into account the distribution of a topical photosensitizer, the propagation of light in a biological media and the subsequent photochemical interactions between light and tissue. This implies that different parameters related with the photosensitizer distribution or the optical source characteristics could be adjusted to provide a specific treatment to a particular pathology.

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

2011-09-01

202

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

203

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

204

Two-photon excitation photodynamic therapy with Photofrin  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) based on simultaneous two-photon (2-?) excitation has a potential advantage of highly targeted treatment by means of nonlinear localized photosensitizer excitation. One of the possible applications of 2-? PDT is a treatment of exodus age-related macular degeneration where highly targeted excitation of photosensitizer in neovasculature is vital for reducing collateral damage to healthy surrounding tissue. To investigate effect of 2-? PDT Photofrin was used as an archetypal photosensitizer. First, 2-? absorption properties of Photofrin in the 750 - 900 nm excitation wavelength range were investigated. It was shown that above 800 nm 2-? interaction was dominant mode of excitation. The 2-? cross section of Photofrin was rather small and varied between 5 and 10 GM (1 GM = 10-50 cm4s/photon) in this wavelength range. Next, endothelial cells treated with Photofrin were used to model initial effect of 2-? PDT on neovasculature. Ultrashort laser pulses provided by mode-locked Ti:sapphire laser (pulse duration at the sample 300 fs, repetition rate 90 MHz, mean laser power 10 mW, excitation wavelength 850 nm) were used for the excitation of the photosensitizer. Before 2-? excitation of the Photofrin cells formed a single continuous sheet at the bottom of the well. The tightly focused laser light was scanned repeatedly over the cell layer. After irradiation the cell layer of the control cells stayed intact while cells treated with photofrin became clearly disrupted. The light doses required were high (6300 Jcm(-2) for ~ 50% killing), but 2-? cytotoxicity was unequivocally demonstrated.

Karotki, Aliaksandr; Khurana, Mamta; Lepock, James R.; Wilson, Brian C.

2005-09-01

205

Effects of photodynamic therapy on the endocytic pathway.  

PubMed

In this report, we describe an effect of photodynamic therapy (PDT) on membrane trafficking in murine 1c1c7 hepatoma cells. A brief exposure of 1c1c7 cells to a 20 nM concentration of the phosphatidylinositol kinase class-3 antagonist wortmannin led to the rapid appearance of cytoplasmic vacuoles. Fluorescence monitoring of plasma membrane-associated 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TDPH) over time demonstrated that the wortmannin-induced vacuoles were derived from endocytosed plasma membrane. Low-dose photodamage catalyzed by the lysosomal photosensitizer NPe6, prior to the addition of wortmannin, prevented formation of these vacuoles. NPe6 was found to suppress for several hours the normal trafficking of TDPH-labeled plasma membrane to the cytosol, and the formation of punctate TDPH-labeled cytoplasmic vesicles. The ability of NPe6-induced photodamage to suppress wortmannin-induced vacuolization occurred under conditions that did not disrupt lysosomes and were at or below the threshold of cytostatic/cytotoxic effects. Furthermore, the suppressive effects of NPe6-PDT were not prevented by inclusion of an agent that stabilized lysosomal membranes, or by E64d, an inhibitor of lysosomal cathepsin proteases. Mitochondrial photodamage was less effective at preventing wortmannin-induced vacuole formation and PDT directed against the ER had no effect. The role of photodamage to the endocytic pathway may be a hitherto unexplored effect on cells that selectively accumulate photosensitizing agents. These results indicate that photodamage directed against endosomes/lysosomes has effects independent of the release of lysosomal proteases. PMID:21125114

Kessel, David; Price, Michael; Caruso, Joseph; Reiners, John

2011-04-01

206

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

207

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

208

Galactodendritic phthalocyanine targets carbohydrate-binding proteins enhancing photodynamic therapy.  

PubMed

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

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

2014-01-01

209

Adjuvant therapies for HIV-associated neurocognitive disorders  

PubMed Central

Objective HIV-associated neurocognitive disorder (HAND) is a frequent and heterogeneous complication of HIV, affecting nearly 50% of infected individuals in the combined antiretroviral therapy (cART) era. This is a particularly devastating statistic because the diagnosis of HAND confers an increased risk of HIV-associated morbidity and mortality in affected patients. While cART is helpful in the treatment of the more severe forms of HAND, there is a therapeutic gap in the milder forms of HAND, where cART is less effective. Multiple adjuvant therapies with various mechanisms of action have been studied (N-methyl D-aspartate [NMDA]-receptor antagonists, MAO-B inhibitors, tetracycline-class antibiotics, and others), but none have shown a clear positive effect in HAND. While this lack of efficacy may be because the appropriate therapeutic targets have not yet been determined, we aimed to discuss that study results may also influenced by clinical trial design. Methods This report is a systematic review of clinical trials of adjuvant therapies for HAND performed from January 1996 through June 2014. Results Possible drawbacks in study design, including lack of standardized case definitions, poorly defined target populations, inappropriate dose selection and measurable outcomes, and brief study durations may have masked true underlying mechanistic effects of previously investigated adjuvant therapies for HAND in specific patient populations. Conclusions A proposal for streamlining and maximizing the likelihood of success in future clinical studies using a ‘learning and confirming’ investigational paradigm, incorporating stronger adaptive Phase I/II study designs, computerized modeling, and population/goal of treatment-specific Phase III clinical trials is presented. PMID:25540809

McGuire, Jennifer L; Barrett, Jeffrey S; Vezina, Heather E; Spitsin, Sergei; Douglas, Steven D

2014-01-01

210

The potential for adjuvant therapy in early-stage cervical cancer  

Microsoft Academic Search

Summary Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy. Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy, but many patients are treated with radical radiotherapy. At present there is no method of accurately identifying patients

E. J. Buxton; N. Saunders; G. R. P. Blackledge; K. Kelly; C. W. E. Redman; J. Monaghan; M. E. L. Paterson; D. M. Luesley

1990-01-01

211

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

212

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.

213

Adjuvant antiarrhythmic therapy in patients with implantable cardioverter defibrillators.  

PubMed

The risk of sudden cardiac death from ventricular fibrillation or ventricular tachycardia in patients with cardiomyopathy related to structural heart disease has been favorably impacted by the wide adaptation of implantable cardioverter defibrillators (ICDs) for both primary and secondary prevention. Unfortunately, after ICD implantation both appropriate and inappropriate ICD therapies are common. ICD shocks in particular can have significant effects on quality of life and disease-related morbidity and mortality. While not indicated for primary prevention of ICD therapies, beta-blockers and antiarrhythmic drugs are a cornerstone for secondary prevention of them. This review will summarize our current understanding of adjuvant antiarrhythmic drug therapy in ICD patients. The review will also discuss the roles of nonantiarrhythmic drug approaches that are used in isolation and in combination with antiarrhythmic drugs to reduce subsequent risk of ICD shocks. PMID:24288157

Bunch, T Jared; Anderson, Jeffrey L

2014-04-01

214

Racial and Ethnic Differences in Adjuvant Hormonal Therapy Use  

PubMed Central

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

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

2012-01-01

215

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

216

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.  

PubMed Central

The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8562339

Lilge, L.; Olivo, M. C.; Schatz, S. W.; MaGuire, J. A.; Patterson, M. S.; Wilson, B. C.

1996-01-01

217

Manual and Rotary Instrumentation Ability to Reduce Enterococcus faecalis Associated with Photodynamic Therapy in Deciduous Molars.  

PubMed

This aim of this study was to assess the ability of manual or rotary instrumentation associated with photodynamic therapy (PDT) to reduce Enterococcus faecalis using three combinations of light/photosensitizers: toluidine blue O/laser, fuchsin/halogen light and fuchsin/LED. Twenty deciduous molars were selected and contaminated with Enterococcus faecalis (McFarland 0.5 scale). Working length determination was performed by visual method. The teeth were randomly divided into two groups: G1 (n=10): manual instrumentation (Kerr-type files) and G2 (n=10): rotary instrumentation (ProTaper system). The bacteria were collected three times using sterile paper cones compatible with the anatomic diameter of the root canal for 30 s before and after instrumentation and after PDT. The samples were diluted in peptone water, seeded on blood agar plates and incubated in an oven at 37 °C for colony-forming units counting. The decrease of E. faecalis counts after instrumentation and after PDT was compared using the Wilcoxon test, t-test and Kruskal Wallis test. A significant reduction of E. faecalis occurred after manual and rotary instrumentation and after PDT using the three combinations of light/photosensitizer (p<0.05). It may be concluded that both rotary and manual instrumentation reduced E. faecalis. Fuchsin with halogen light or LED irradiation and toluidine blue O with laser irradiation can be used to reduce E. faecalis in root canals of primary molars. PDT can be used as an adjuvant to conventional endodontic treatment. PMID:25590196

Pinheiro, Sérgio Luiz; Silva, Josianne Neres da; Gonçalves, Rafael Orro; Villalpando, Karina Teixeira

2014-12-01

218

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

NASA Astrophysics Data System (ADS)

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

Tajiri, Hisao

1988-06-01

219

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

E-print Network

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

Cao, Wenwu

220

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

221

Nicotinamide augments the survival and incidence of apoptosis in glioma cells following photodynamic therapy in vitro  

Microsoft Academic Search

The ability to customize photodynamic therapy (PDT) parameters with regards to timing and dosing of administered drug and light can be beneficial in determining target specificity and mode of cell death. Sustained, low level PDT or metronomic PDT (mPDT) may afford enhanced apoptotic cell death. This is of particular importance when considering PDT for the treatment of brain tumors as

Stuart K. Bisland; Nayan Modi; Brian C. Wilson

2004-01-01

222

Light-activated ruthenium complexes photobind DNA and are cytotoxic in the photodynamic therapy window.  

PubMed

Incorporation of biquinoline ligands into Ru(II) polypyridyl complexes produces light-activated systems that eject a ligand and photobind DNA after irradiation with visible and near-IR light. Structural analysis shows that distortion facilitates the photochemistry, and gel shift and cytotoxicity studies prove the compounds act as anti-cancer photodynamic therapy (PDT) agents in the tissue penetrant region. PMID:22908094

Wachter, Erin; Heidary, David K; Howerton, Brock S; Parkin, Sean; Glazer, Edith C

2012-10-01

223

Application of femtosecond ultrashort pulse laser to photodynamic therapy mediated by indocyanine green  

Microsoft Academic Search

Backgrounds\\/aims: To evaluate treatment with high peak power pulse energy by femtosecond ultrashort pulse laser (titanium sapphire laser) delivered at an 800 nm wavelength for corneal neovascularisation using photodynamic therapy (PDT) mediated by indocyanine green (ICG).Methods: Using a gelatin solid as an in vitro corneal model, the safety of laser power was studied to determine if it degenerated gelatin with

M Sawa; K Awazu; T Takahashi; H Sakaguchi; H Horiike; M Ohji; Y Tano

2004-01-01

224

Modeling of a Type II Photofrin-mediated Photodynamic Therapy Process in a Heterogeneous Tissue Phantom  

Microsoft Academic Search

We present a quantitative framework to model a Type II photodynamic therapy (PDT) process in the time domain in which a set of rate equations are solved to describe molecular reactions. Calculation of steady-state light distributions using a Monte Carlo method in a heterogeneous tissue phantom model demonstrates that the photon density differs signifi- cantly in a superficial tumor of

Xin-Hua Hu; Yuanming Feng; Jun Q. Lu; Ron R. Allison; Rosa E. Cuenca; Gordon H. Downie; Claudio H. Sibata

2005-01-01

225

A charge-switchable, four-armed polymeric photosensitizer for photodynamic cancer therapy.  

PubMed

A water-soluble, charge-switchable, four-armed polymeric photosensitizer (C4P-PS), in which charge switching is pH dependent, has been designed as a new class of photosensitizer for photodynamic cancer therapy. PMID:24643769

Lee, Chung-Sung; Park, Wooram; Jo, Young Um; Na, Kun

2014-04-28

226

Timing the multiple cell death pathways initiated by Rose Bengal acetate photodynamic therapy  

Microsoft Academic Search

Rose Bengal acetate photodynamic therapy (RBAc–PDT) induced multiple cell death pathways in HeLa cells through ROS and ER stress. Indeed, apoptosis was the first preferred mechanism of death, and it was triggered by at least four different pathways, whose independent temporal activation ensures cell killing when one or several of the pathways are inactivated. Apoptosis occurred as early as 1

E Panzarini; V Inguscio; L Dini

2011-01-01

227

Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response  

Microsoft Academic Search

BACKGROUND: Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the

Ramaswamy Bhuvaneswari; Yik Yuen Gan; Khee Chee Soo; Malini Olivo

2009-01-01

228

Phage Therapy and Photodynamic Therapy: Low Environmental Impact Approaches to Inactivate Microorganisms in Fish Farming Plants  

PubMed Central

Owing to the increasing importance of aquaculture to compensate for the progressive worldwide reduction of natural fish and to the fact that several fish farming plants often suffer from heavy financial losses due to the development of infections caused by microbial pathogens, including multidrug resistant bacteria, more environmentally-friendly strategies to control fish infections are urgently needed to make the aquaculture industry more sustainable. The aim of this review is to briefly present the typical fish farming diseases and their threats and discuss the present state of chemotherapy to inactivate microorganisms in fish farming plants as well as to examine the new environmentally friendly approaches to control fish infection namely phage therapy and photodynamic antimicrobial therapy. PMID:19841715

Almeida, Adelaide; Cunha, Ângela; Gomes, Newton C.M.; Alves, Eliana; Costa, Liliana; Faustino, Maria A.F.

2009-01-01

229

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

230

Optimization of light dosimetry for photodynamic therapy of Barrett's esophagus  

NASA Astrophysics Data System (ADS)

Background and Objective: Photodynamic therapy (PDT) may be used for ablation of high grade dysplasia and/or early cancer (HGD/T1) in Barrett's esophagus. A complication of PDT is esophageal stricture. The objective of this study was to find the lowest light dose to potentially reduce the incidence of strictures while effectively ablating HGD/T1. Materials and Methods: Patients (n=113) with HGD/T1 received an intravenous injection of porfimer sodium (2 mg/kg). Three days later, laser light (630 nm) was delivered using a cylindrical diffuser inserted in a 20 mm.diameter PDT balloon. Patients were treated at light doses of 115 J/cm, 105 J/cm, 95 J/cm and 85 J/cm. The efficacy was determined by four quadrant biopsies of the treated area three months after PDT. The formation of stricture was determined by the incidence of dysphagia and the need for esophageal dilation. Strictures were considered mild if they required less than 6 dilations, and severe if 6 or more dilations were required. Efficacy and incidence of strictures were tabulated as a function of light dose. Results: Using 115 J/cm, there were 17% of patients with residual HGD/T1 after one treatment. However, when the light doses of 105 J/cm, 95 J/cm and 85 J/cm were used, the residual HGD/T1 after one PDT session was increased to 33%, 30%, and 32% respectively. The overall incidence of strictures (mild and severe) was not correlated to the light dose. However, the incidence of severe strictures was directly proportional to the light dose. Using the light dose of 115 J/cm, 15.3% of patients developed severe strictures compared to about 5% in the groups of patients who received the lower light doses. Conclusions: Decreasing the light dose below 115 J/cm doubled the rate of residual HGD/T1 after one treatment while reducing the incidence of severe strictures to one-third of cases from 115 J/cm. The results may be used to evaluate the risks and benefits of different light doses.

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

2004-06-01

231

A rationale for treating leg length discrepancy using photodynamic therapy  

NASA Astrophysics Data System (ADS)

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

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

2005-09-01

232

Using antimicrobial adjuvant therapy in cancer treatment: a review  

PubMed Central

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

2012-01-01

233

Evaluation of Vitamin C for Adjuvant Sepsis Therapy  

PubMed Central

Abstract Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis. Antioxid. Redox Signal. 19, 2129–2140. PMID:23682970

2013-01-01

234

Reduction of thermal damage in photodynamic therapy by laser irradiation techniques  

NASA Astrophysics Data System (ADS)

General application of continuous-wave (CW) laser irradiation modes in photodynamic therapy can cause thermal damage to normal tissues in addition to tumors. A new photodynamic laser therapy system using a pulse irradiation mode was optimized to reduce nonspecific thermal damage. In in vitro tissue specimens, tissue energy deposition rates were measured in three irradiation modes, CW, pulse, and burst-pulse. In addition, methods were tested for reducing variations in laser output and specific wavelength shifts using a thermoelectric cooler and thermistor. The average temperature elevation per 10 J/cm2 was 0.27°C, 0.09°C, and 0.08°C using the three methods, respectively, in pig muscle tissue. Variations in laser output were controlled within ±0.2%, and specific wavelength shift was limited to ±3 nm. Thus, optimization of a photodynamic laser system was achieved using a new pulse irradiation mode and controlled laser output to reduce potential thermal damage during conventional CW-based photodynamic therapy.

Lim, Hyun Soo

2012-12-01

235

Ocular photodynamic therapy for serous macular detachment in the diffuse retinal pigment epitheliopathy variant of idiopathic central serous chorioretinopathy  

Microsoft Academic Search

PurposeTo describe the anatomical and functional outcome of verteporfin ocular photodynamic therapy (PDT) in serous retinal detachment caused by the diffuse retinal pigment epitheliopathy form of chronic idiopathic central serous chorioretinopathy.

Christina Canakis; Charalampos Livir-Rallatos; Zafirakis Panayiotis; Gerasimos Livir-Rallatos; Efstratios Persidis; Mandi D. Conway; Gholam A. Peyman

2003-01-01

236

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

237

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 18h followed by illumination at 12 or 36Jcm(-2), using a xenon arc lamp (600±2nm). A total photoinactivation of C. albicans biofilm cells was achieved using 300?M of FSc with 18h of incubation, followed by illumination at 36Jcm(-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

2014-09-16

238

Preclinical In Vivo Evaluation of Npe6-Mediated Photodynamic Therapy on Normal Vasculature  

PubMed Central

Background and Objective Current treatments of port-wine stain birthmarks typically involve use of a pulsed dye laser (PDL) combined with cooling of the skin. Currently, PDL therapy protocols result in varied success, as some patients experience complete blanching, while others do not. Over the past decade, we have studied the use of photodynamic therapy (PDT) as either a replacement or adjuvant treatment option to photocoagulate both small and large vasculature. The objective of the current study was to evaluate a PDT protocol that involves use of an alternate intravascular photosensitizer mono-L-aspartylchlorin-e6 (NPe6) activated by an array of low-cost light emitting diodes. Study Design/Materials and Methods To monitor the microvasculature, a dorsal window chamber model was installed on 22 adult male mice. The light source consisted of a custom-built LED array that emitted 10 W at a center wavelength of 664 nm (FWHM = 20 nm). The light source was positioned at a fixed distance from the window chamber to achieve a fixed irradiance of 127 mW/cm2. A retroorbital injection of NPe6 (5 mg/kg) was performed to deliver the drug into the bloodstream. Laser irradiation was initiated immediately after injection. To monitor blood-flow dynamics in response to PDT, we used laser speckle imaging. We employed a dose–response experimental design to evaluate the efficacy of NPe6-mediated PDT. Results We observed three general hemodynamic responses to PDT: (1) At low radiant exposures, we did not observe any persistent vascular shutdown; (2) at intermediate radiant exposures, we observed an acute decrease in blood flow followed by gradual restoration of blood flow over the 7-day monitoring period; and (3) at high radiant exposures, we observed acute vascular shutdown that persisted during the entire 7-day monitoring period. Dose–response analysis enabled identification of 85 J/cm2 as a characteristic radiant exposure required to achieve persistent vascular shutdown at Day 7 following PDT. Conclusion The experimental data suggest that NPe6-mediated PDT can achieve persistent vascular shutdown of normal microvasculature. PMID:22334298

Moy, Wesley J.; Patel, Shreyas J.; Lertsakdadet, Ben S.; Arora, Rajan P.; Nielsen, Katherine M.; Kelly, Kristen M.; Choi, Bernard

2012-01-01

239

Real-time monitoring of singlet oxygen in photodynamic therapy with chemiluminescence  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is a cancer therapy most of which using light excites sensitizer mainly to produce singlet oxygen (1O2) to kill tumor cells by oxidation reaction. Monitoring the singlet oxygen production is an important task for getting more useful dosage information in photodynamic therapy to enhance the effect. In order to monitor singlet oxygen in PDT, the Chemiluminescence (CL) probe, which could react with singlet oxygen and emit photons, was selected and employed on mice to produce CL. The CL was collected and recorded by a single photon detection system in real time. The results showed that the signal intensity was high and indicated that the chemiluminescence could measure singlet oxygen in vivo sensitively. And during photodynamic therapy the CL signal dropped gradually. Different therapy dosages had different decay life. Any of the decay had two different parts: the rapid component and the slow component. During PDT, reactive oxygen would oxidize biomolecules of tissue, and oxygen was consumed. It would cause a rapid component; by combining with chemiluminescence and fluorescence detection technique, the first-order elimination coefficient of tissue was proved to be degressive during PDT. We deduced that the damaged vascular in PDT would provide littler oxygen and tissue hypoxia was more severely. It may quicken CL decay and caused the slow component. In conclusion, the results proved that monitoring 1O2 by CL could give useful information not only to evaluate the effect of PDT but also to judge the tissue oxygen depletion.

Wei, Yan chun; Yang, Li yong; Song, Jia xing

2008-12-01

240

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody.  

PubMed Central

Fifty-two patients with epithelial ovarian cancer were treated with yttrium-90-labelled monoclonal antibody HMFG1 administered intraperitoneally following conventional surgery and chemotherapy as part of an extended phase I-II trial. The treatment was well tolerated and the only significant toxicity observed was reversible myelosuppression as previously described. Following conventional surgery and chemotherapy, 21 out of the 52 patients had no evidence of residual disease and were regarded as receiving treatment in an adjuvant setting. To date, two of these patients have died of their disease (follow-up 3-62 months, median follow-up 35 months). This extended phase I-II study suggests that patients with advanced ovarian cancer who achieve a complete remission following conventional therapy may benefit from further treatment with intraperitoneal radioactive monoclonal antibody. PMID:8347497

Hird, V.; Maraveyas, A.; Snook, D.; Dhokia, B.; Soutter, W. P.; Meares, C.; Stewart, J. S.; Mason, P.; Lambert, H. E.; Epenetos, A. A.

1993-01-01

241

Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 µM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

Sun, Yun; Chen, Zhi-long; Yang, Xiao-xia; Huang, Peng; Zhou, Xin-ping; Du, Xiao-xia

2009-04-01

242

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

243

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

244

Two-Photon Photodynamic Therapy by Water-Soluble Self-Assembled Conjugated Porphyrins  

PubMed Central

Studies on two-photon absorption (2PA) photodynamic therapy (PDT) by using three water-soluble porphyrin self-assemblies consisting of ethynylene-linked conjugated bis (imidazolylporphyrin) are reviewed. 2PA cross-section values in water were obtained by an open aperture Z-scan measurement, and values were extremely large compared with those of monomeric porphyrins such as hematoporphyrin. These compounds were found to generate singlet oxygen efficiently upon one- as well as two-photon absorption as demonstrated by the time-resolved luminescence measurement at the characteristic band of singlet oxygen at 1270 nm and by using its scavenger. Photocytotoxicities for HeLa cancer cells were examined and found to be as high as those of hematoporphyrin, demonstrating that these compounds are potential candidates for 2PA-photodynamic therapy agents. PMID:23484074

Ogawa, Kazuya; Kobuke, Yoshiaki

2013-01-01

245

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

246

Photodynamic therapy as a novel antimicrobial strategy against biofilm-based nosocomial infections: study protocols.  

PubMed

Hospital-acquired infections (HAIs), also known as nosocomial infections, are one of the most serious health-care issues currently influencing health-care costs. Among them, those sustained by microbial biofilm represent a major public health concern. Here, we describe the experimental protocols for microbial biofilm inactivation relying on antimicrobial photodynamic therapy (APDT) as a new strategy for the control of these kinds of infections. PMID:24664842

Giuliani, Francesco

2014-01-01

247

Synthesis and characterization of glycoconjugated porphyrin triphenylamine hybrids for targeted two-photon photodynamic therapy.  

PubMed

In order to avoid side effects at the time of cancer eradication to the patients, the selectivity of treatments has become of strategic importance. In the case of photodynamic therapy (PDT), two-photon absorption combined with active targeting of tumors could allow both spatial and chemical selectivity. In this context, we present the synthesis, spectroscopic, and biological properties of a series of porphyrin-triphenylamine hybrids with excellent singlet oxygen production capacities and good two-photon absorption. PMID:24433138

Hammerer, Fabien; Garcia, Guillaume; Chen, Su; Poyer, Florent; Achelle, Sylvain; Fiorini-Debuisschert, Céline; Teulade-Fichou, Marie-Paule; Maillard, Philippe

2014-02-01

248

Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours  

Microsoft Academic Search

The possibility of enhancing aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) by simultaneous application of localised hyperthermia (HT) was evaluated. Treatments of rat DS-sarcomas included: (i) control, (ii) ALA administration (375 mg kg?1, i.p.), no illumination, (iii) ‘nonthermal’ illumination, (iv) ALA-PDT: that is, ALA administration, ‘nonthermal’ illumination, (v) localised HT, 43°C, 60 min (vi) ALA-PDT+HT: ALA administration with full spectrum irradiation

D K Kelleher; J Bastian; O Thews; P Vaupel

2003-01-01

249

Two-photon excitation of porphyrin-functionalized porous silicon nanoparticles for photodynamic therapy.  

PubMed

Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2-photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose-functionalized pSiNPs can be vectorized to MCF-7 human breast cancer cells through a mannose receptor-mediated endocytosis mechanism to provide a 3-fold enhancement of the 2-photon PDT effect. PMID:25323443

Secret, Emilie; Maynadier, Marie; Gallud, Audrey; Chaix, Arnaud; Bouffard, Elise; Gary-Bobo, Magali; Marcotte, Nathalie; Mongin, Olivier; El Cheikh, Khaled; Hugues, Vincent; Auffan, Mélanie; Frochot, Céline; Morère, Alain; Maillard, Philippe; Blanchard-Desce, Mireille; Sailor, Michael J; Garcia, Marcel; Durand, Jean-Olivier; Cunin, Frédérique

2014-12-01

250

Treatment of herpes zoster related corneal neovascularisation and lipid keratopathy by photodynamic therapy.  

PubMed

Traditionally, photodynamic therapy (PDT) has been used to treat choroidal neovascularisation. More recently, its use in corneal neovascularisation has provided promising clinical results. The major advantage of PDT is that it is minimally invasive, resulting in closure of the neovascular network without damaging the surrounding healthy tissue. This report describes the positive results of PDT, clinically and microstructurally, as imaged by in vivo confocal microscopy, for treating corneal neovascularisation with lipid keratopathy, secondary to herpes zoster infection. PMID:24112362

Goh, Yi Wei; McGhee, Charles Nj; Patel, Dipika V; Barnes, Rachel; Misra, Stuti

2014-05-01

251

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

252

[Adjuvant therapy in patients with acute myocardial infarct].  

PubMed

Besides the thrombolytic therapy several adjuvant therapeutic measures were identified which significantly improve the prognosis of patients with acute myocardial infarction (AMI). These measures include the treatment by means of acetylsalicylic acid (ASA), beta-blockers and ACE inhibitors. Early administration of ASA and beta-blockers are indicated in all patients with AMI who have no contraindications for this therapy. They are especially the patients with manifest heart failure or asymptomatic left ventricular dysfunction who benefit from ACE inhibitors. The effectivity of routine administration of other medicaments such as anticoagulants, nitrates, calcium channel blockers and magnesium, have not been convincingly proved. However, some selected patients with AMI can benefit from these medicaments. Intravenous administration of heparin is unambiguously justified only in thrombolysis with t-PA. Thrombolyses with streptokinase, urokinase, and anistreplase are justified only at high risk of thromboembolic complications. Their prevention and therapy include also the necessity to restrict the administration of pelentan. The use of nitrates is indicated in patients with AMI in case of sustaining stenocardia, arterial hypertension and manifest heart left ventricular failure. Until the definitive standpoint is gained regarding the effect of magnesium in patients with AIM, its administration remains especially indicated in cases of arterial hypertension, tachycardiac disturbances of the heart rhythm and states of assumed or proved hypomagnesiemia. In AMI cases when magnesium is used in order to protect the patient from reperfusion lesion, it must be administered prior to the reperfusion therapy. An intensive research in the field of therapeutical measures in patients with AMI still continues. It is certain that it will soon bring further knowledge which will in turn improve the prognosis and quality of life of patients with AMI. (Tab. 4, Ref. 133.) PMID:8925311

Jurkovicová, O; Cagán, S

1996-07-01

253

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

254

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

255

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

PubMed

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

256

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

257

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

258

Photodynamic therapy with recombinant adenovirus AdmIL-12 enhances anti-tumour therapy efficacy in human papillomavirus 16 (E6/E7) infected tumour model  

PubMed Central

Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. Here we investigated the utility of adenoviral delivery of interleukin-12 (AdmIL-12) as an adjuvant for PDT in mouse tumour challenge model. PDT was performed by irradiating Radachlorin in C57BL/6 mice transplanted with TC-1 cells. PDT plus AdmIL-12 treatment for tumour suppression as well as specific immune responses were evaluated with the following tests: in vitro and in vivo tumour growth inhibition, interferon-? (IFN-?) and tumour necrosis factor-? (TNF-?) assay, and cytotoxic T lymphocyte (CTL) assay. Direct intratumoral injection of AdmIL-12 resulted in a significant suppression of tumour growth compared to the control group. Treatment of PDT along with AdmIL-12 further enhanced antitumour effects significantly higher than either AdmIL-12 or PDT alone. This combined treatment resulted in complete regression of 9-mm sized tumour in every animal. We also evaluated immune responses induced by these treatments. Combined treatment significantly increased the production level of IFN-? and TNF-? compared with that by AdmIL-12 or PDT alone. PDT plus AdmIL-12 enhanced antitumour immunity through increased expansion of the CTL subset mediated by CD8+ T cells. Taken together, these results indicate that the high anti-cancer activity of PDT with AdmIL-12 is a powerful tool against cancer therapy and is a promising subject for further investigation. PMID:18397271

Park, Eun Kyung; Bae, Su-Mi; Kwak, Sun-Young; Lee, Sung Jong; Kim, Yong-Wook; Han, Chan-Hee; Cho, Hyun-Jung; Kim, Kyung Tae; Kim, Young-Jae; Kim, Hyun-Jung; Ahn, Woong Shick

2008-01-01

259

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

260

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.

261

Massage as adjuvant therapy in the management of acute postoperative pain: a preliminary study in men  

Microsoft Academic Search

BackgroundOpioid analgesia alone may not fully relieve all aspects of acute postoperative pain. Complementary medicine techniques used as adjuvant therapies have the potential to improve pain management and palliate postoperative distress.

Marcia M Piotrowski; Cynthia Paterson; Allison Mitchinson; Hyungjin Myra Kim; Marvin Kirsh; Daniel B Hinshaw

2003-01-01

262

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

263

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

264

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

NASA Astrophysics Data System (ADS)

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

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

1994-10-01

265

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

266

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

267

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

PubMed Central

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

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

2011-01-01

268

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis  

Microsoft Academic Search

Background  Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical\\u000a resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review\\u000a was conducted to examine the exact role of adjuvant therapy in renal cancer setting.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Randomized controlled trials were searched comparing adjuvant therapy

Adolfo JO Scherr; Joao Paulo SN Lima; Emma C Sasse; Carmen SP Lima; André D Sasse

2011-01-01

269

Successful management of chronic multifocal Q fever Osteomyelitis with adjuvant interferon-gamma therapy.  

PubMed

We present a 3-year-old girl who had chronic recurrent multifocal osteomyelitis caused by Coxiella burnetii despite long-term dual antibiotic therapy. Excellent clinical response was achieved and sustained when immunomodulatory therapy with interferon-? was initiated. This is the case of a first child who was successfully treated with interferon-? as adjuvant therapy for chronic multifocal Q fever osteomyelitis. PMID:21372749

Neth, Olaf Werner; Falcon, Dolores; Peromingo, Estrella; Soledad Camacho, Maria; Rodríguez-Gallego, Carlos; Obando, Ignacio

2011-09-01

270

The role of reperfusion injury in photodynamic therapy with 5-aminolaevulinic acid – a study on normal rat colon  

PubMed Central

Reperfusion injury can occur when blood flow is restored after a transient period of ischaemia. The resulting cascade of reactive oxygen species damages tissue. This mechanism may contribute to the tissue damage produced by 5-aminolaevulinic acid-induced photodynamic therapy, if this treatment temporarily depletes oxygen in an area that is subsequently reoxygenated. This was investigated in the normal colon of female Wistar rats. All animals received 200?mg?kg?1 5-aminolaevulinic acid intravenously 2?h prior to 25?J (100?mW) of 628?nm light, which was delivered continuously or fractionated (5?J/150 second dark interval/20?J). Animals were recovered following surgery, killed 3 days later and the photodynamic therapy lesion measured macroscopically. The effects of reperfusion injury were removed from the experiments either through the administration of free radical scavengers (superoxide dismutase (10?mg?kg?1) and catalase (7.5?mg?kg?1) in combination) or allopurinol (an inhibitor of xanthine oxidase (50?mg?kg?1)). Prior administration of the free radical scavengers and allopurinol abolished the macroscopic damage produced by 5-aminolaevulinic acid photodynamic therapy in this model, regardless of the light regime employed. As the specific inhibitor of xanthine oxidase (allopurinol) protected against photodynamic therapy damage, it is concluded that reperfusion injury is involved in the mechanism of photodynamic therapy in the rat colon. British Journal of Cancer (2002) 86, 989–992. DOI: 10.1038/sj/bjc/6600178 www.bjcancer.com © 2002 Cancer Research UK PMID:11953834

Curnow, A; Bown, S G

2002-01-01

271

Adjuvant therapy of breast cancer: Southwest Oncology Group studies.  

PubMed

The Southwest Oncology Group has conducted a series of randomized studies of adjuvant therapy in patients with primary breast cancer and positive axillary nodes. The first study, during which combined chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) administered for 1 year was compared with single agent therapy with melphalan (L-PAM) for 2 years, was activated in 1975 and closed in 1978. Of the 366 patients who were eligible, 191 received L-PAM and 175 were given CMFVP. The 2 groups were comparable with regard to known prognostic factors. At a median follow-up of 8 years, CMFVP continues to be superior to L-PAM in disease-free (P = .005) and overall survival (P = .01). Thirty-five percent of patients on CMFVP have died compared with 46% on L-PAM. The greatest survival benefit is apparent in premenopausal women and women with 4 or more positive axillary nodes. Acute toxicity was more frequent with CMFVP than with L-PAM, but it was acceptable and reversible with both regimens. Long-term toxicity was limited to myeloproliferative disease in 2 patients on L-PAM and 1 on CMFVP. The second-generation series of studies, activated in 1979, were designed according to nodal status, estrogen receptor (ER) status, and menopausal status. We randomized ER-negative, node-negative patients to 6 months of combination chemotherapy or to no treatment. Because of slow accrual, the study was closed and patients are now being entered onto a similar intergroup study with the Eastern Cooperative Oncology Group. We randomized ER-negative, node-positive patients to either 1 or 2 years of CMFVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3534592

Osborne, C K; Rivkin, S E; McDivitt, R W; Green, S; Stephens, R L; Costanzi, J J; O'Bryan, R

1986-01-01

272

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

273

Pheophorbides as photosensitizers for the photodynamic therapy of tumors  

NASA Astrophysics Data System (ADS)

Quantum yields for formation of singlet molecular oxygen have been measured for sodium pheophorbides (Na-Phdes) a and b in aqueous and non-aqueous media. Measurements have been made for both steady-state and pulsed laser excitation with the resultant singlet molecular oxygen being detected by photo-oxygenation reactions or time-resolved luminescence spectroscopy, respectively. Singlet oxygen production sensitized by Na-Phdes a or b is insignificant in aqueous media but occurs with a good efficiency in organic solvents. Plasmid DNA is efficiently photocleaved by Na-Phdes a and b in the absence of oxygen as well as in the presence of oxygen. Fluorescence microscopic observation shows a rapid incorporation of Na-Phde a into nuclei, mitochondria, and lysosome of human oral mucosa cells. In contrast Na-Phde b is incorporated only into the plasma membrane. The photodynamic activity of these pigments in living tissues is probably determined by the monomeric pigment molecules formed in hydrophobic cellular structures.

Tanielian, Charles; Wolff, Christian; Kobayashi, Masami

1995-01-01

274

Targeting Tumor Vasculature and Cancer Cells in Orthotopic Breast Tumor by Fractionated Photosensitizer Dosing Photodynamic Therapy1  

Microsoft Academic Search

Photodynamic therapy (PDT) is a locally administered therapy cur- rently being investigated in various clinical and preclinical settings. Tu- mor-host interaction is an important determinant of tumor biology and response to treatments. Here we report for the first time the effects of PDT on an orthotopic, murine mammary tumor model. PDT utilizes two individually nontoxic components: (a) the localization in

Dennis E. J. G. J. Dolmans; Ananth Kadambi; John S. Hill; Kevin R. Flores; Joseph N. Gerber; Jeffrey P. Walker; Borel Rinkes; Rakesh K. Jain; Dai Fukumura

2002-01-01

275

Adjuvant therapy in high-risk early endometrial carcinoma: a retrospective analysis of 46 cases  

PubMed Central

Objective We assessed the prognostic factors and the efficacy of adjuvant therapy and reviewed randomized studies carried out on patients receiving adjuvant therapy with early endometrial carcinoma. Methods One hundred and five patients that received primary surgical treatment for stage IB, IC and II endometrial cancer were enrolled in this study. The clinical outcomes were compared among the patients with variable prognostic factors and adjuvant treatments. Results One hundred and five patients fulfilled the eligibility criteria and 46 patients (43.8%) underwent adjuvant therapy. Disease recurrence occurred in nine patients within a median time of 24 months. Cervical involvement was an independent prognostic factor for the disease-free survival rates. Eight of 16 patients with FIGO stage II disease received adjuvant chemotherapy consisting of cisplatin and etoposide (or cyclophosphamide) or combined chemoradiation. The 5-year disease-free survival rate for these patients was 87.5%, a value significantly higher than for patients that received radiation therapy alone (30%). Conclusion Adjuvant chemotherapy or combination chemo-radiotherapy might be superior to radiation therapy alone in high-risk early endometrial cancer patients. PMID:19471649

Kim, Jin Hwi; Lee, Sung Jong; Bae, Jeong Hoon; Lee, Sung Ha; Bae, Seog Nyeon; Namkoong, Sung Eun

2008-01-01

276

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

277

Solitary giant neurofibroma of the neck subjected to photodynamic therapy: case study  

PubMed Central

Photodynamic therapy (PDT) - the fourth modality - has been successfully used in the management of early and advanced pathologies of the head and neck. We studied the effect of this modality on a giant solitary neurofibroma of the neck. A 70-year-old Caucasian female presented with left neck pain and disfigurement associated with slight shortness of breath and dysphagia. Examination revealed a large mass in the neck with no neurovascular compromise. Magnetic resonance imaging (MRI) reported a heterogeneously enhancing mass extending from the left angle of the mandible to the base of the neck. A core biopsy was performed and histopathological examination revealed a disorganised array of peripheral nerve fascicles. The patient elected to receive photodynamic therapy as the primary intervention. The multi-disciplinary meeting approved the treatment plan. The photosensitizing agent was mTHPC (0.15?mg/kg), which was systemically administered 96-hours prior to ultrasound (US)-guided light delivery to the mass, which was undertaken under general anaesthesia. Recovery was uneventful.Post-PDT follow-up showed that the patient’s pain, dysphagia and shortness of breath issues had improved. The disfigurement of the neck caused by the mass was no longer a problem. Three months post-PDT, MRI revealed a significant reduction in the neurofibroma size. PDT was proven as a successful primary intervention for this pathology. However, higher evidence-based studies are required before this therapy can be proposed as a replacement to any of the other conventional therapies. PMID:22673101

2012-01-01

278

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

279

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

NASA Astrophysics Data System (ADS)

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

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

2014-03-01

280

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

281

Gold nanorods as dual photo-sensitizing and imaging agents for two-photon photodynamic therapy  

NASA Astrophysics Data System (ADS)

Gold nanorods with three different aspect ratios were prepared and their dual capabilities for two-photon imaging and two-photon photodynamic therapy have been demonstrated. These gold nanorods exhibit large two-photon absorption action cross-sections, about two orders of magnitude larger than small organic molecules, which makes them suitable for two-photon imaging. They can also effectively generate singlet oxygen under two-photon excitation, significantly higher than traditional photosensitizers such as Rose Bengal and Indocyanine Green. Such high singlet oxygen generation capability under two-photon excitation was ascribed to their large two-photon absorption cross-sections. Polyvinylpyrrolidone (PVP) coated gold nanorods displayed excellent biocompatibility and high cellular uptake efficiency. The two-photon photodynamic therapy effect and two-photon fluorescence imaging properties of PVP coated gold nanorods have been successfully demonstrated on HeLa cells in vitro using fluorescence microscopy and indirect XTT assay method. These gold nanorods thus hold great promise for imaging guided two-photon photodynamic therapy for the treatment of various malignant tumors.Gold nanorods with three different aspect ratios were prepared and their dual capabilities for two-photon imaging and two-photon photodynamic therapy have been demonstrated. These gold nanorods exhibit large two-photon absorption action cross-sections, about two orders of magnitude larger than small organic molecules, which makes them suitable for two-photon imaging. They can also effectively generate singlet oxygen under two-photon excitation, significantly higher than traditional photosensitizers such as Rose Bengal and Indocyanine Green. Such high singlet oxygen generation capability under two-photon excitation was ascribed to their large two-photon absorption cross-sections. Polyvinylpyrrolidone (PVP) coated gold nanorods displayed excellent biocompatibility and high cellular uptake efficiency. The two-photon photodynamic therapy effect and two-photon fluorescence imaging properties of PVP coated gold nanorods have been successfully demonstrated on HeLa cells in vitro using fluorescence microscopy and indirect XTT assay method. These gold nanorods thus hold great promise for imaging guided two-photon photodynamic therapy for the treatment of various malignant tumors. Electronic supplementary information (ESI) available: More data on singlet oxygen generation capability of Au NRs, RB and ICG under one- and two-photon excitation; extinction spectra of Au NRs/CTAB and Au NRs/PVP dispersed in DI water; stability of Au NRs/PVP dispersed in DMEM and EB fluorescence imaging of Au NRs/PVP and RB-loaded HeLa cells without laser irradiation; viability of cancer cells in the presence of Au NRs after CW laser irradiation at 808 nm; fs laser induced temperature change; effect of aggregation of Au NRs on singlet oxygen generation. See DOI: 10.1039/c2nr32196c

Zhao, Tingting; Shen, Xiaoqin; Li, Lin; Guan, Zhenping; Gao, Nengyue; Yuan, Peiyan; Yao, Shao Q.; Xu, Qing-Hua; Xu, Guo Qin

2012-11-01

282

In vivo photodynamic therapy with meso-tetra(m-hydroxyphenyl)chlorin (mTHPC): influence of light intensity and optimization of photodynamic efficiency  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) consists in administering a photosensitizer generating cytotoxic radical species when submitted to light irradiation. One of the difficulties encountered in PDT is to find a photosensitizer absorbing at a wavelength penetrating tissues deeply. Meso-tetra(m- hydroxyphenyl)chlorin(mTHPC) presents this characteristic since it is activated at 650 nm. The photodynamic efficiency of mTHPC (0.3 mg/kg) was evaluated 72 hrs after intraperitoneal injection in HT29 human tumor bearing mice. This interval has been determined by a biodistribution study using fluorescence spectroscopy and HPLC. Mice were irradiated at 650 nm, 10 J/cm2 using a dye laser. The photodynamic efficiency was evaluated by two methods: tumor growth after photodynamic treatment and macroscopic measurement of necrosis depth after tumoral resection using in vivo staining procedure with Evans blue dye. The normalization of the tumor volume (V equals 1/6 pi D3) to the initial volume showed no significant difference of control and treated mice, no regression was observed. Secondly the necrosis depth was determined 24 hrs after irradiation using Evans blue which circulates in vessels not damaged by the treatment. Only tumors from treated animals presented measurable necrosis area, mostly localized in surface around the irradiated site with a mean depth of 3.0 plus or minus 0.3 mm. No prolonged tumoral regression was observed. Unexpectedly, the photodynamic activity was higher when using a low irradiance (32 mW/cm2) than when using a higher one (160 mW/cm2). These results were not related to intratumoral mTHPC photodestruction. Tumor eradication may occur either in tumors measuring less than 3 mm, with a small light intensity, or through fractionated irradiation.

Rezzoug, Hadjira; A'Amar, Ousama M.; Barberi-Heyob, Muriel; Merlin, Jean-Louis; Guillemin, Francois H.

1996-12-01

283

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

284

In vitro evaluation of Radachlorin sensitizer for photodynamic therapy.  

PubMed

This paper reports the evaluation of a new photosensitizer, Radachlorin in comparison with one of its well known components but used solely, Chlorin e(6). The photodynamic properties and cell uptake and localisation of the two drugs were compared. In vitro studies were conducted on human adenocarcinoma cells (HT29) and lung carcinoma cell line (A549). Both dyes showed an absorption maximum between 640 and 650 nm, but those absorption peaks are enhanced by interactions with serum, with a shifted maximum at 661 and 664 nm, and much higher absorbance. As Radachlorin is constituted of different products and as photoreactivity is dependent on absorbed light energy, we chose to adapt concentrations so that both drugs had the same absorption at the irradiation wavelength (664 nm) for photoreactivity tests, and express concentrations in optical density at 664 nm. The capacity of the two drugs to generate Reactive Oxygen Species was identical, but on HT29 cells, Radachlorin reaches its optimal LD50 sooner than Chlorin e(6). Radachlorin LD50 on HT29 cells was 0.0251 OD(664 nm) after 2 h and 0.0672 OD(664 nm) for Chlorin e(6) for a 20 J cm(-2) irradiation. Radachlorin gave very similar results on A549 cells, LD50 being 0.05 for 5 J irradiation, and 0.026 for 10 and 20 J cm(-2). Pharmacokinetics using fluorescence showed that, even if Radachlorin quickly crossed HT29 (a human colonic cancer line) cell membrane, cellular distribution evolved from a diffuse cytoplasmic repartition 1 hour after Radachlorin addition to a delimited localisation into organelles all around the nucleus. Radachlorin intracellular fluorescence decreased after 4 h, whereas we did not observe a decrease of Chlorin e(6) intracellular fluorescence for times up to 24 h. In both case, a quick decline was observed as soon as the culture medium was replaced with a drug-free one. Radachlorin appears to be an excellent photosensitizer, with similar phototoxicity to Chlorin e(6) on cell cultures, but with quicker kinetics, which could be an improvement if confirmed on further in vivo studies. PMID:20064726

Douillard, Samuel; Lhommeau, Isabelle; Olivier, David; Patrice, Thierry

2010-02-12

285

Photodynamic therapy in Bowen disease of the first web space of the hand.  

PubMed

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; Kim, You Chan

2015-02-01

286

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.

Jung, Soo-Eun; Kim, Sue Kyung

2015-01-01

287

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

PubMed

Photodynamic therapy (PDT) has clinical approval for use as a minimally invasive therapeutic procedure that is able to exert selective cytotoxic activity toward pathological cells, particularly malignant cells. Following a number of recent technological improvements, PDT has been widely applied to the diagnosis and treatment of malignancies, including lung, esophageal, gastrointestinal, bladder, prostate, head and neck, oral and skin cancer. Studies have shown that osteosarcoma is a malignant tumor afflicting young adults worldwide, and recently, the incidence of bone and soft-tissue malignant tumors has been shown to be increasing, so the use of PDT has become an area of focus for the diagnosis and treatment of musculoskeletal sarcoma. PMID:25202342

Zhang, Xianghong; Liu, Tang; Li, Zhihong; Zhang, Xiangsheng

2014-10-01

288

Solar keratoses: photodynamic therapy, cryotherapy, 5-fluorouracil, imiquimod, diclofenac, or what? Facts and controversies.  

PubMed

Actinic keratosis is a common dermatologic condition that may regress, remain stable, or progress to squamous cell carcinoma. Some question whether all actinic keratoses should be routinely treated, whereas others contend that the unpredictable natural history of this disease necessitates treatment to prevent malignant transformation. Available treatments include photodynamic therapy, cryotherapy, 5-fluorouracil, imiquimod, and diclofenac. Each of these options has its advantages and disadvantages, although they all have a place in the management of actinic keratosis. An overview of these treatment modalities is presented, as are the controversies surrounding the treatment of actinic keratosis. PMID:24160275

Schmitt, Adam R; Bordeaux, Jeremy S

2013-01-01

289

Lightpipe device for delivery of uniform illumination for photodynamic therapy of the oral cavity  

PubMed Central

A compact and efficient lightpipe device to deliver light to the human oral cavity for photodynamic therapy was designed and fabricated, having dimensions 6.8 mm × 6.8 mm × 46 mm. An average irradiance of 76 mW/cm2 with an average deviation of 5% was measured on a square 25 mm2 treatment field for an input power of 100 mW. The device limits irradiation of healthy tissue and offers potential for improvement over the current treatment procedure, which requires shielding of the whole cavity to avoid damage to healthy tissue. PMID:21629308

Canavesi, Cristina; Cassarly, William J.; Foster, Thomas H.; Rolland, Jannick P.

2011-01-01

290

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

291

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

SciTech Connect

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

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

2008-11-01

292

Treatment of oral fungal infections using antimicrobial photodynamic therapy: a systematic review of currently available evidence.  

PubMed

The aim was to review the efficacy of antimicrobial photodynamic therapy (PDT) in the treatment of oral fungal infections. To address the focused question "Should PDT be considered a possible treatment regimen for oral fungal infections?" PubMed/Medline and Google-Scholar databases were searched from 1997 up to March 2014 using various combinations of the following key words: "Candida albicans"; "Candidiasis"; "Candidosis"; "denture stomatitis"; "oral" and "photodynamic therapy". Original studies, experimental studies and articles published solely in English language were sought. Letters to the editor, historic reviews and unpublished data were excluded. Pattern of the present literature review was customized to mainly summarize the pertinent information. Fifteen studies (3 clinical and 12 experimental) were included. All studies reported antimicrobial PDT to be an effective antifungal treatment strategy. One study reported PDT and azole therapy to be equally effective in the treatment of oral fungal infections. Methylene blue, toluidine blue and porphyrin derivative were the most commonly used photosensitizers. The laser wavelengths and power output ranged between ?455 nm-660 nm and 30 mW-400 mW. The energy fluence ranged between 26-245 J cm(-2) and the duration or irradiation ranged between 10 seconds and 26 minutes. Clinical effectiveness of antimicrobial PDT as a potent therapeutic strategy for oral fungal infections requires further investigations. PMID:24686309

Javed, Fawad; Samaranayake, Lakshman P; Romanos, Georgios E

2014-05-01

293

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

PubMed Central

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

Gill, Sharlene

2014-01-01

294

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

PubMed

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

2014-12-23

295

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

296

Virus Capsids as Targeted Nanoscale Delivery Vessels of Photoactive Compounds for Site-Specific Photodynamic Therapy  

NASA Astrophysics Data System (ADS)

The research presented in this work details the use of a viral capsid as an addressable delivery vessel of photoactive compounds for use in photodynamic therapy. Photodynamic therapy is a treatment that involves the interaction of light with a photosensitizing molecule to create singlet oxygen, a reactive oxygen species. Overproduction of singlet oxygen in cells can cause oxidative damage leading to cytotoxicity and eventually cell death. Challenges with the current generation of FDA-approved photosensitizers for photodynamic therapy primarily stem from their lack of tissue specificity. This work describes the packaging of photoactive cationic porphyrins inside the MS2 bacteriophage capsid, followed by external modification of the capsid with cancer cell-targeting G-quadruplex DNA aptamers to generate a tumor-specific photosensitizing agent. First, a cationic porphyrin is loaded into the capsids via nucleotide-driven packaging, a process that involves charge interaction between the porphyrin and the RNA inside the capsid. Results show that over 250 porphyrin molecules associate with the RNA within each MS2 capsid. Removal of RNA from the capsid severely inhibits the packaging of the cationic porphyrins. Porphyrin-virus constructs were then shown to photogenerate singlet oxygen, and cytotoxicity in non-targeted photodynamic treatment experiments. Next, each porphyrin-loaded capsid is externally modified with approximately 60 targeting DNA aptamers by employing a heterobifunctional crosslinking agent. The targeting aptamer is known to bind the protein nucleolin, a ubiquitous protein that is overexpressed on the cell surface by many cancer cell types. MCF-7 human breast carcinoma cells and MCF-10A human mammary epithelial cells were selected as an in vitro model for breast cancer and normal tissue, respectively. Fluorescently tagged virus-aptamer constructs are shown to selectively target MCF-7 cells versus MCF-10A cells. Finally, results are shown in which porphyrin-virus-aptamer constructs selectively target and kill cancer cells versus non-cancer cells. Specifically, the results show that MS2 is a viable candidate as an addressable nanodelivery vessel of photoactive compounds, and the implications are that the nucleotide-driven packaging approach for modifying MS2 can be used to impart new functionalities for a host of diagnostic or therapeutic applications.

Cohen, Brian A.

297

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

NASA Astrophysics Data System (ADS)

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

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

2014-09-01

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

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

1994-10-01

300

Autophagy Contributes to the Death/Survival Balance in Cancer PhotoDynamic Therapy  

PubMed Central

Autophagy is an important cellular program with a “double face” role, since it promotes either cell survival or cell death, also in cancer therapies. Its survival role occurs by recycling cell components during starvation or removing stressed organelles; when damage becomes extensive, autophagy provides another programmed cell death pathway, known as Autophagic Cell Death (ACD). The induction of autophagy is a common outcome in PhotoDynamic Therapy (PDT), a two-step process involving the irradiation of photosensitizer (PS)-loaded cancer cells. Upon tissue oxygen interaction, PS provokes immediate and direct Reactive Oxygen Species (ROS)-induced damage to Endoplasmic Reticulum (ER), mitochondria, plasma membrane, and/or lysosomes. The main biological effects carried out in cancer PDT are direct cytotoxicity to tumor cells, vasculature damage and induction of inflammatory reactions stimulating immunological responses. The question about the role of autophagy in PDT and its putative immunological impact is hotly controversial and largely studied in recent times. This review deals with the induction of autophagy in PDT protocols and its dual role, also considering its interrelationship with apoptosis, the preferential cell death program triggered in the photodynamic process. PMID:24710486

Inguscio, Valentina; Panzarini, Elisa; Dini, Luciana

2012-01-01

301

System for interstitial photodynamic therapy with online dosimetry: first clinical experiences of prostate cancer  

NASA Astrophysics Data System (ADS)

The first results from a clinical study for Temoporfin-mediated photodynamic therapy (PDT) of low-grade (T1c) primary prostate cancer using online dosimetry are presented. Dosimetric feedback in real time was applied, for the first time to our knowledge, in interstitial photodynamic therapy. The dosimetry software IDOSE provided dose plans, including optical fiber positions and light doses based on 3-D tissue models generated from ultrasound images. Tissue optical property measurements were obtained using the same fibers used for light delivery. Measurements were taken before, during, and after the treatment session. On the basis of these real-time measured optical properties, the light-dose plan was recalculated. The aim of the treatment was to ablate the entire prostate while minimizing exposure to surrounding organs. The results indicate that online dosimetry based on real-time tissue optical property measurements enabled the light dose to be adapted and optimized. However, histopathological analysis of tissue biopsies taken six months post-PDT treatment showed there were still residual viable cancer cells present in the prostate tissue sections. The authors propose that the incomplete treatment of the prostate tissue could be due to a too low light threshold dose, which was set to 5 J/cm2.

Swartling, Johannes; Axelsson, Johan; Ahlgren, Göran; Kälkner, Karl Mikael; Nilsson, Sten; Svanberg, Sune; Svanberg, Katarina; Andersson-Engels, Stefan

2010-09-01

302

Photothrombosis of Corneal Neovascularization by Photodynamic Therapy Utilizing Verteporfin and Diode Laser  

PubMed Central

Introduction: The aim of the present study was to evaluate the effect of photodynamic therapy in the treatment of experimental corneal neovascularization (NV) with benzoporphyrin derivative (BPD). Methods: One group was considered as control (n=6 eyes) then, corneal NV was induced in 30 New Zealand male rabbits (n=60 eyes) by placing 7.0 silk sutures at midstromal depth approximately1mm from the limbus. Fifteen rabbits with corneal NV were left without any treatment, and 15 rabbits were subjected to photodynamic therapy (PDT) by intravenous injection with Verteporfin at a dose of 1.5 mg /Kg. Diode laser (660 nm) was applied after 15 minutes for 5 minutes with a power of 50 mW/cm2. All rabbits were successively followed up by slit lamp examination for periods of 1 day, 1, 2, 3 and 4 weeks. Three rabbits were selected and sacrificed weekly (n=6 eyes each) and the corneas were isolated for histopathological examination. Results: The results of slit lamp examination indicated the gradual regression of the cornea neovascularization 4 weeks of PDT. Furthermore, regression of corneal neovascularization was documented clinically by decrease number and length of blood vessels and by histopathological examination. Conclusion: PDT with Verteporfin can provide efficacious treatment of corneal neovascularization.

Ahmed Hassan, Aziza; Foad Ghoneim, Dina; Abdelraheem El-dib, Amr; Abdelkawi Ahmed, Salwa; Abdel- Salam, Ahmed Medhat

2013-01-01

303

Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species  

NASA Astrophysics Data System (ADS)

Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

2013-02-01

304

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

305

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

306

Study of the efficacy of 5-ALA mediated photodynamic therapy on human rhabdomyosarcoma cell line (RD)  

NASA Astrophysics Data System (ADS)

The aim of this study was to investigate the mechanism of cell death by photodynamic therapy (PDT) in the Rhabdomyosarcoma (RD) cell line. The present study evaluates the effects of photodynamic therapy (PDT) with 5-ALA as photosensitizer using human muscle cancer cells as experimental model. We study the photosensitizer uptake, cytotoxicity, phototoxicity, and cellular viability of the RD cells which was estimated by means of neutral-red spectrophotometric assay. The given experiment was consisted of two steps. For the first one, RD cells were exposed to 5-ALA at concentrations of 0 up to 1000 ?g of ALA/ml in minimum essential medium (MEM). The optimal uptake of photosensitizer (5-ALA) in RD cells was investigated by means of spectrometric measurements. Cells viability was determined by means of neutral red assay (NRA). In the second step, 5-ALA exposed RD cells were irradiated with red light (a diode laser, ? = 635 nm) at total light dose of 80 J/cm2. The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the viability of RD cells were investigated. It was observed that sensitizer concentration or light doses have no significant effect on cells viability when studied independently. The maximal cellular uptake occurred after 47 hours in vitro incubation. The phototoxic assay showed that ALA-PDT induced killing of 76% of the cells at 250 ?g/ml drug dose and 80 J/cm2 light dose.

Atif, M.; Fakhar-e-Alam, M.; Firdous, S.; Zaidi, S. S. Z.; Suleman, R.; Ikram, M.

2010-10-01

307

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

308

Sulfonated aluminum phthalocyanines for two-photon photodynamic cancer therapy: the effect of the excitation wavelength  

NASA Astrophysics Data System (ADS)

Sulfonated aluminum phthalocyanine (AlPcS) is a well-studied photosensitizer which has been widely used in research and in clinical applications of the photodynamic therapy of cancers. Conventionally, one-photon excitation was used, but it was unknown whether two-photon excitation of AlPcS was equally effective. In this study, the two-photon absorption cross sections of AlPcS at near infrared wavelengths were deduced from femtosecond (fs) laser-induced fluorescence. We found that the two-photon absorption cross section of AlPcS was strongly dependent on the excitation wavelength. It was about 19 GM when excited at 800 nm, but grew to 855 GM when excited at 750 nm. The 750 nm fs-laser-induced fluorescence images of AlPcS in human nasopharyngeal carcinoma cells were clearly visible while the corresponding images were very dim when excited at 800 nm. Singlet oxygen production was 13 times higher when excited at 750 nm relative to 800 nm. Our subsequent in vitro experiments showed that 750 nm two-photon excitation with an unfocused fs laser beam damaged cancer cells in a light-dose-dependent manner typical of photodynamic therapy (PDT). The killing at 750 nm was about 9–10 times more efficient than at 800 nm. These results demonstrated for the first time that AlPcS has good potential for two-photon PDT of cancers.

Wang, J.; Li, W.; Yu, H. B.; Cheung, N. H.; Chen, J. Y.

2014-03-01

309

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

310

Neoadjuvant vs adjuvant therapy for resectable pancreatic cancer: the evolving role of radiation.  

PubMed

A major challenge with pancreatic cancer management is in the discrimination of clearly resectable tumors from those that would likely be accompanied by a positive resection margin if upfront surgery was attempted. The standard of care for clearly resectable pancreatic cancer remains surgery followed by adjuvant therapy, but there is considerable controversy over whether such therapeutic adjuvant strategies should include radiotherapy. Furthermore, in a malignancy with such high rates of distant metastasis, investigators are now exploring the feasibility and outcomes of delivering therapy in the neoadjuvant setting, both for clearly resectable as well as borderline resectable tumors. In this review, we explore the current standard of care of upfront surgery for clearly resectable cancers followed by adjuvant therapy, focusing on the role of radiotherapy. We highlight the difficulties in interpreting a literature fraught with inconsistencies in how resectable vs borderline resectable cancers are defined and treated. Finally, we explore the role of neoadjuvant strategies in the modern era. PMID:24635868

Hoffe, Sarah; Rao, Nikhil; Shridhar, Ravi

2014-04-01

311

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

PubMed Central

ABSTRACT BACKGROUND: The 5-year survival of pancreatic adenocarcinoma with surgery and adjuvant chemotherapy is below 25%. The original Gastrointestinal Tumor Study Group (GITSG) adjuvant study demonstrated a survival benefit attributed to weekly intravenous boluses of 5-fluorouracil (5-FU) for 2 years in addition to chemoradiation compared to surgery alone. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that remain in G0 arrest and kill them as they infrequently enter the G1/S phase. We retrospectively evaluated outcomes in patients who were treated with adjuvant chemotherapy and maintenance capecitabine compared with those who received only adjuvant chemotherapy. METHODS: Patients who had undergone surgical resection with curative intent and received adjuvant chemotherapy were analyzed. Those who subsequently received maintenance capecitabine therapy were compared to those who received adjuvant chemotherapy only. The primary end points were disease recurrence and all-cause mortality. RESULTS: The median overall survival (OS) of patients receiving maintenance capecitabine was greater than 48.4 months (the exact estimate was not available, since the survival probability curve does not cross 0.5). It was 22.0 months (95% confidence interval [CI], 16.6–29.2) in patients who received adjuvant chemotherapy only (P < .001 by log-rank test). The median recurrence-free survival (RFS) was also longer in the maintenance capecitabine group: 54.3 (95% CI, 22.2–Inf) compared to 14.1 (95% CI, 11.6–16.7) months (P < .001, by log-rank test). CONCLUSIONS: In this retrospective study, patients with resected pancreatic adenocarcinoma who received adjuvant chemotherapy had improved OS and RFS with additional maintenance therapy with capecitabine. These findings should be confirmed with a randomized, controlled trial. PMID:25276262

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

2014-01-01

312

Photodynamic therapy with Pd-bacteriopheophorbide (TOOKAD): Successfulin vivo treatment of human prostatic small cell carcinoma xenografts  

Microsoft Academic Search

Small cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was there- fore tempting to evaluate the response of this violent malig- nancy and its bone lesions to Pd-Bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive non- epithelial solid tumors.

Natalia V. Koudinova; Jehonathan H. Pinthus; Alexander Brandis; Ori Brenner; Peter Bendel; Jacob Ramon; Zelig Eshhar; Avigdor Scherz; Yoram Salomon

2003-01-01

313

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

314

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

PubMed

Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen ((1)O2) 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 (1)O2 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 (1)O2 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

315

Chondrodermatitis nodularis chronica helicis and photodynamic therapy: a new therapeutic option?  

PubMed

Chondrodermatitis nodularis chronica helicis (CNCH) is a fairly frequent disorder of unknown etiology. Although the elective therapy is surgery, local application of topical steroids, antibiotic ointments, intralesional injection of collagen, cryotherapy, curettage followed by diathermy, and CO(2) laser treatment have also been proposed. The aim of the study was to test the utility of photodynamic therapy (PDT) for CNCH. Two patients with painful CNCH underwent PDT with a 635 nm light source for 20 minutes (70 J/cm(2) ) after application of cream containing 20% 5-aminolevulinic acid (5-ALA) and occlusion for 3 hours. The lesions decreased considerably in size and pain ceased within a few weeks. The results suggest that this method can be useful for treating CNCH, especially in patients with contraindications for surgery. PMID:21276169

Pellegrino, M; Taddeucci, P; Mei, S; Peccianti, C; Fimiani, M

2011-01-01

316

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

317

Effects of zinc phthalocyanine tetrasulfonate-based photodynamic therapy on rat brain isolated mitochondria.  

PubMed

PDT has been used in the treatment of malignant brain tumors for the last 2 decades. It is based on the interaction of a photosensitizer (PS) and light of an appropriate wavelength, with generation of oxygen species, mainly singlet oxygen. Brain is particularly susceptible to oxidative stress; therefore the study of PDT effects on cerebral mitochondria might provide mechanistic insights into the action of the therapy, contributing to its optimization. In the present study, we addressed the mitochondrial toxicity of the second generation PS, zinc phthalocyanine tetrasulfonate (ZnPcS4), on rat brain isolated mitochondria, by investigating both intrinsic toxicity and photodynamic action. At higher concentrations (15 and 25 microM/mg protein) ZnPcS4 caused (a) inhibition of state-3 respiration and (b) decrease of RCR and ADP/O. Electrochemical potential, state-4 respiration and Ca2+ retention capacity were not affected. Cytochrome c release was not observed. Coupled with 600 or 1800 mJ/cm2 laser irradiation, ZnPcS4 (5 microM/mg protein) caused more intense effects on state 3, RCR and ADP/O; moreover state-4 respiration and membrane potential were affected. Besides that, Ca2+ and cytochrome c release were induced. Cyclosporine A (CsA) decreased Ca2+ release and ameliorated the electrochemical potential, suggesting that membrane permeability transition (MPT) might be involved in the photodynamic effect. The low intrinsic toxicity and the high photodynamic effect on rat brain mitochondria induced by ZnPcS4, allied to its improved photophysical properties, might indicate its potential for the treatment of malignant brain tumors. PMID:19330886

Medina, Wanessa Silva Garcia; dos Santos, Neife Aparecida Guinaim; Curti, Carlos; Tedesco, Antonio Cláudio; dos Santos, Antonio Cardozo

2009-05-15

318

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

319

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

320

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

PubMed

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

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

2010-01-01

321

Influence of the photosensitizer photobleaching in the propagation of light during photodynamic therapy  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) is an optical treatment modality used to destroy malignant tissues. Nowadays there are fixed clinical PDT protocols that make use of a particular optical dose, photosensitizer amount and drug-light interval. However the treatment response varies depending on the type of pathology and the patient. In order to adjust current dosimetry to get an optimal treatment outcome, the development of accurate predictive models has emerged as the ideal tool to achieve new personal protocols. Several attempts have been made in this way although the influence of the photosensitizer distribution on the optical parameters has not been taken into account until this moment. We present a first approach to predict the spatial-temporal variation of the absorption coefficient during the photodynamic process applied to a dermatological disease taking into account the photobleaching of a topical photosensitizer. The model presented also takes into account an inhomogeneous initial distribution of the photosensitizer, the propagation of light in the biological media and the evolution of the molecular concentrations of different components involved in the photochemical reactions. The obtained results permit us to investigate how the depletion of the photosensitizer during the photochemical reactions affects to the light absorption as it propagates within the target tissue.

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

2012-02-01

322

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

323

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

NASA Astrophysics Data System (ADS)

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

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

1994-07-01

324

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

PubMed

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

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

2014-01-01

325

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

326

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

327

Necrosis response to photodynamic therapy using light pulses in the femtosecond regime.  

PubMed

One of the clinical limitations of the photodynamic therapy (PDT) is the reduced light penetration into biological tissues. Pulsed lasers may present advantages concerning photodynamic response when compared to continuous wave (CW) lasers operating under the same average power conditions. The aim of this study was to investigate PDT-induced response when using femtosecond laser (FSL) and a first-generation photosensitizer (Photogem) to evaluate the induced depth of necrosis. The in vitro photodegradation of the sensitizer was monitored during illumination either with CW or an FSL as an indirect measurement of the PDT response. Healthy liver of Wistar rats was used to evaluate the tissue response. The photosensitizer was endovenously injected and 30 min after, an energy dose of 150 J?cm(-2) was delivered to the liver surface. We observed that the photodegradation rate evaluated via fluorescence spectroscopy was higher for the FSL illumination. The FSL-PDT produced a necrosis nearly twice as deep when compared to the CW-PDT. An increase of the tissue temperature during the application was measured and was not higher than 2.5 °C for the CW laser and not higher than 4.5 °C for the pulsed laser. FSL should be considered as an alternative in PDT applications for improving the results in the treatment of bulky tumors where higher light penetration is required. PMID:23064891

Grecco, Clóvis; Moriyama, Lilian Tan; Cosci, Alessandro; Pratavieira, Sebastião; Bagnato, Vanderlei Salvador; Kurachi, Cristina

2013-07-01

328

Photochemical predictive analysis of photodynamic therapy with non-homogeneous topical photosensitizer distribution in dermatological applications  

NASA Astrophysics Data System (ADS)

Photodynamic Therapy (PDT) is a therapeutic technique widely used in dermatology to treat several skin pathologies. It is based in topical or systemic delivery of photosensitizing drugs followed by irradiation with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell necrosis. In this work we present a PDT model that tries to predict the photodynamic effect on the skin with a topically administered photosensitizer. The time dependent inhomogeneous distribution of the photoactive compound protoporphyrin IX (PpIX) is calculated after obtaining its precursor distribution (Methyl aminolevulinate, MAL) which depends on the drug permeability, diffusion properties of the skin, incubation time and conversion efficiency of MAL to PpIX. Once the optical energy is obtained by means of the Beer Lambert law, a photochemical model is employed to estimate the concentration of the different molecular compounds taking into account the electronic transitions between molecular levels and particles concentrations. The results obtained allow us to know the evolution of the cytotoxic agent in order to estimate the necrotic area adjusting parameters such as the optical power, the photosensitizer concentration, the incubation and exposition time or the diffusivity and permeability of the tissue.

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

2010-04-01

329

Production of reactive oxygen species after photodynamic therapy by porphyrin sensitizers.  

PubMed

The objectives of this study was to investigate the production of reactive oxygen species (ROS) after photodynamic therapy (PDT) in vitro. We examined second generation sensitizers, porphyrines (TPPS4, ZnTPPS4 and PdTPPS4) and compared their effectivity on ROS generation in G361 cell line. Used porphyrines are very efficient water-soluble aromatic dyes with potential to use in photomedicine and have a high propensity to accumulate in the membranes of intracellular organelles like lysosomes and mitochondria. Interaction between the triplet excited state of the sensitizer and molecular oxygen leads to produce singlet oxygen and other ROS to induce cell death. Production of ROS was verificated by molecular probe CM-H2DCFDA and viability of cells was determined by MTT assay. Our results demonstrated that ZnTPPS4 induces the highest ROS production in cell line compared to TPPS4 and PdTPPS4 at each used concentration and light dose. These results consist with a fact that photodynamic effect depends on sensitizer type, its concentration and light dose. PMID:18645224

Kolarova, H; Nevrelova, P; Tomankova, K; Kolar, P; Bajgar, R; Mosinger, J

2008-06-01

330

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.

1994-10-01

331

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

332

Lipid coated upconverting nanoparticles as NIR remote controlled transducer for simultaneous photodynamic therapy and cell imaging.  

PubMed

The application of photodynamic therapy in deep tissue is constrained by some pending problems, such as the limited penetration depth of excitation light and lacking of targeting ability. In this paper, a new kind of lipid coated upconverting nanoparticles consisiting of upconerting nanocrystal core and targeted lipid polymer shell was first reported for NIR triggered photodynamic therapy and cell imaging simultaneously. The lipid coated upconverting nanoparticles offers advantages to overcome the problem mentioned above. The UCN core works as a transducer to convert deeply penetrating near-infrared light to visible lights for activating photosensitizer and cell fluorescence imaging simultaneously. The amphiphilic lipid polymer RGD peptide conjugated poly (maleic anhydride-alt-1-octadecene) grafted dioleoyl l-?-phosphatidylethanolamine (RGD-PMAO-DOPE) acts as a shield. It can protect the system from catching by RES and target the whole system to the lesions. The experiment results show that the lipid coated upconverting nanoparticle is individual nanosphere with an average size of 20 nm. The drug loading can reach 9%. After NIR exposed, the MC540 was activated to produce singlet oxygen (ROS) successfully by the upconverting fluorescence emitted from UCN. Importantly, compared with nanoparticle without RGD decoration, the lipid coated upconverting nanoparticle can co-deliver the MC540 and UCNs into the same cell with higher efficiency. Besides, the MC540 loaded UCN/RGD-PMAO-DOPE nanoparticles showed significant inhibitory effect on tumor cells after NIR shining. Our data suggests that MC540 loaded UCN/RGD-PMAO-DOPE nanoparticle may be a useful nanoplatform for future PDT treatment in deep-cancer therapy. PMID:24657139

Wang, Hanjie; Dong, Chunhong; Zhao, Peiqi; Wang, Sheng; Liu, Zhongyun; Chang, Jin

2014-05-15

333

Adjuvant bisphosphonates in endocrine-responsive breast cancer: what is their place in therapy?  

PubMed

Recent advances in the treatment of early breast cancer have improved clinical outcomes and prolonged survival, especially in women with endocrine-responsive disease. However, cancer therapies including cytotoxic chemotherapy, ovarian suppression, and aromatase inhibitors can drastically reduce circulating estrogen, increasing bone loss and fracture risk. Because most women with early breast cancer will live for many years, it is important to protect bone health during cancer therapy. Several recent clinical trials combining adjuvant endocrine therapy with bisphosphonates have demonstrated efficacy for preventing cancer treatment-induced bone loss in pre- and postmenopausal women with early breast cancer. The largest body of evidence supporting the use of adjuvant bisphosphonates comes from studies with zoledronic acid; however, studies with risedronate, ibandronate, and denosumab (a biologic agent) have also demonstrated efficacy for preventing bone loss. Adding zoledronic acid to endocrine therapy prevents bone loss and improves bone mineral density (BMD). In addition, preclinical studies suggest that bisphosphonates have direct and indirect antitumor activity, such as inducing tumor cell apoptosis, reducing tumor cell adhesion and invasion, reducing angiogenesis, activating immune responses, and synergy with chemotherapy agents, among others. Clinical trials have demonstrated significantly improved disease-free survival in patients receiving adjuvant endocrine therapy plus zoledronic acid compared with endocrine therapy alone. Ongoing studies will further define the role of adjuvant bisphosphonates in maintaining bone health and improving clinical outcomes. The available evidence suggests that pre- and postmenopausal patients may receive clinical benefit from including bisphosphonates as part of their adjuvant treatment regimen for endocrine-responsive early breast cancer. PMID:21789117

Gnant, Michael; Blaha, Peter; Dubsky, Peter; Exner, Ruth; Fitzal, Florian; Sporn, Emanuel; Panhofer, Peter; Borgo, Andrea Dal; Bigenzahn, Sinda; Steger, Guenther; Jakesz, Raimund

2009-11-01

334

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

335

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

336

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

337

Improved low-power semiconductor diode lasers for photodynamic therapy in veterinary medicine  

NASA Astrophysics Data System (ADS)

Cryogenically cooling semiconductor diode lasers provides higher power output, longer device lifetime, and greater monochromaticity. While these effects are well known, such improvements have not been quantified, and thus cryogenically operated semiconductor lasers have not been utilized in photodynamic therapy (PDT). We report quantification of these results from laser power meter and photospectrometer data. The emission wavelengths of these low power multiple quantum well semiconductor lasers were found to decrease and become more monochromatic with decreasing temperature. Significant power output improvements also were obtained at cryogenic temperatures. In addition, the threshold current, i.e. the current at which lasing begins, decreased with decreasing temperature. This lower threshold current combined with the increased power output produced dramatically higher device efficiencies. It is proposed that cryogenic operation of semiconductor diode lasers will reduce the number of devices needed to produce the requisite output for many veterinary and medical applications, permitting significant cost reductions.

Lee, Susanne M.; Mueller, Eduard K.; Van de Workeen, Brian C.; Mueller, Otward M.

2001-05-01

338

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

339

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

340

Targeting the 90 kDa Heat Shock Protein Improves Photodynamic Therapy  

PubMed Central

The geldanamycin derivative, 17-allylamino-17-demethoxygeldanamycin (17-AAG), binds to the amino-terminal ATP binding pocket of the 90 kDa heat shock protein (Hsp-90) and inhibits this chaperone from stabilizing client proteins involved with the malignant phenotype. We examined the effects of a combined modality protocol involving photodynamic therapy (PDT) and 17-AAG in mouse mammary carcinoma cells and tumors. PDT increased the expression of the anti-apoptotic and pro-angiogenic proteins survivin, Akt, HIF-1?, MMP-2 and VEGF in tumor tissue and this expression decreased significantly when 17-AAG was included in the treatment regimen. Tumor bearing mice treated with PDT and 17-AAG had improved long-term tumoricidal responses when compared with individual treatment protocols. We conclude that Hsp-90 plays an active role in modulating tumor responsiveness following PDT and targeting Hsp-90 with 17-AAG enhances the therapeutic effectiveness of PDT. PMID:19733005

Ferrario, Angela; Gomer, Charles J.

2009-01-01

341

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

PubMed

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

Feng, Xiaohui; Zhang, Shaokun; Lou, Xia

2013-07-01

342

Tumor delivery of Photofrin® by PLL-g-PEG for photodynamic therapy.  

PubMed

Photofrin® (porfimer sodium) is a photosensitive reagent used for photodynamic therapy (PDT) of tumors and dysplasias. Because only photo-irradiated sites are damaged, PDT is less invasive than systemic treatments. However, a photosensitive reaction is a major side effect of systemically delivered Photofrin. To enhance localization of Photofrin to tumors, we have formulated Photofrin with the tumor-localizing graft copolymer poly(ethylene glycol)-grafted poly(l-lysine), PLL-g-PEG. We demonstrate that Photofrin preferentially interacts with PLL-g-PEG through both ionic and hydrophobic interactions. The serum competitive study showed that the highly PEG-grafted PLL is better for preventing serum binding to the Photofrin/PLL-g-PEG complex. In tumor-bearing mice, formulation of Photofrin with PLL-g-PEG enhanced tumor localization of Photofrin as twice as Photofrin alone and concomitantly suppressed the photosensitivity reaction drastically. PMID:23454112

Kano, Arihiro; Taniwaki, Yuki; Nakamura, Izumi; Shimada, Naohiko; Moriyama, Kenji; Maruyama, Atsushi

2013-05-10

343

Subcellular Targets for Photodynamic Therapy: Implications for Initiation of Apoptosis and Autophagy  

PubMed Central

Direct lethal effects of photodynamic therapy (PDT) on a cell population were initially shown to occur via initiation of apoptosis, with high doses having a necrotic effect. Selective induction of cellular “self-digestion,” better known as autophagy, represents a novel therapeutic target for the prevention of tumor growth and metastasis. It should be noted that autophagy has conflicting roles in the regulation of cell death, which, when applied to oncology, may produce both positive and negative effects on tumor development. Through better understanding the complex parts played by autophagy among diverse cellular signaling pathways in preclinical models, it may be possible to selectively regulate autophagy in response to specific stimuli, thereby inhibiting its oncogenic tendencies while preserving its tumor-suppressive capabilities. PMID:23055218

Kessel, David

2015-01-01

344

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.

1994-10-01

345

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

346

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

347

G-quadruplex DNA/protoporphyrin IX-based synergistic platform for targeted photodynamic cancer therapy.  

PubMed

Photodynamic therapy (PDT) is an emerging technique to induce cancer cell death. However, the tumor specificity, cellular uptake and biodistribution of many photosensitizers urgently need to be improved. In this regard, we show here that the integrated nanoassemblies based on G-quadruplex DNAs (GQDs)/protoporphyrin IX (PPIX) can serve as a synergistic platform for targeted high-performance PDT. In the nanoassemblies, GQDs function as carriers of sensitiser PPIX and confers the system cancer cell targeting ability. After nucleolin-mediated efficient binding and cellular uptake of GQDs/PPIX assemblies, the strong red fluorescence of GQDs/PPIX complex provides a powerful tool for biological imaging. Moreover, the reactive oxygen species (ROS) generated by GQDs/PPIX under light illumination can effectively kill cancer cells. The present approach is simply composed by DNA and photosensitizers, thereby avoiding any complicated and time-consuming covalent modification or chemical labeling procedure. PMID:25618671

Zhou, Zhixue; Li, Dan; Zhang, Libing; Wang, Erkang; Dong, Shaojun

2015-03-01

348

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

349

In vitro investigation of efficient photodynamic therapy using a nonviral vector; hemagglutinating virus of Japan envelope  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) is a photochemical modality approved for cancer treatment. PDT has demonstrated efficacy in early stage lung cancer and esophageal cancer. The accumulation of photosensitizers in cancer cells is necessary to enhance the therapeutic benefits of PDT; however, photosensitizers have low uptake efficiency. To overcome this limitation, a drug delivery system, such as the hemagglutinating virus of Japan envelope (HVJ-E) vector, is required. In this study, the combination of PDT and HVJ-E was investigated for enhancing the efficacy of PDT. The photosensitizers that were evaluated included 5-aminolaevulinic acid (5-ALA), protoporphyrin IX (PPIX), and HVJ-PPIX. The uptake of the photosensitizers as increased twenty-fold with the addition of HVJ-E. The cytotoxicity of conventional 5-ALA was enhanced by the addition of HVJ-E vector. In conclusion, HVJ-E vector improved the uptake of photosensitizers and the PDT effect.

Sakai, Makoto; Fujimoto, Naohiro; Ishii, Katsunori; Nakamura, Hiroyuki; Kaneda, Yasufumi; Awazu, Kunio

2012-07-01

350

Photodynamic Therapy in Early Lung Cancer: A Report of Two Cases  

PubMed Central

Photodynamic therapy (PDT) that is based on the science of photochemistry has been recognized as a lung sparing local therapeutic modality that can achieve remarkable responses. It is an alternative treatment for early stage lung cancer patients who have poor lung function or multiple sites of cancer. Recently we treated a 70-year-old man who presented with squamous carcinoma in situ at a previous pneumonectomy site, and a 64-year-old man with a newly developed secondary superficial lung cancer, with PDT. There were no complications related to the procedure. Both patients had poor lung function due to prior lung cancer surgery. Clinical and histological complete remissions were achieved without any evidence of recurrence during 30 months of follow-up in both patients. PMID:17017667

Kim, Hee Kyoo; Oak, Chul Ho; Jung, Mann Hong

2006-01-01

351

Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer  

NASA Astrophysics Data System (ADS)

With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately ±2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D90, was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D90 less than 23 J cm-2 had complete biopsy response, while 8/13 (62%) of patients with a D90 greater than 23 J cm-2 had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

Davidson, Sean R. H.; Weersink, Robert A.; Haider, Masoom A.; Gertner, Mark R.; Bogaards, Arjen; Giewercer, David; Scherz, Avigdor; Sherar, Michael D.; Elhilali, Mostafa; Chin, Joseph L.; Trachtenberg, John; Wilson, Brian C.

2009-04-01

352

Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy  

PubMed Central

Cutaneous malignant melanoma remains a therapeutic challenge, and patients with advanced disease have limited survival. Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of melanin contribution to melanoma resistance to PDT was investigated in a set of melanoma cell lines that markedly differ in the levels of pigmentation; 3 new bacteriochlorins successfully overcame the resistance. Cell killing studies determined that bacteriochlorins are superior at (LD50?0.1 ?M) when compared with controls such as the FDA-approved Photofrin (LD50?10 ?M) and clinically tested LuTex (LD50?1 ?M). The melanin content affects PDT effectiveness, but the degree of reduction is significantly lower for bacteriochlorins than for Photofrin. Microscopy reveals that the least effective bacteriochlorin localizes predominantly in lysosomes, while the most effective one preferentially accumulates in mitochondria. Interestingly all bacteriochlorins accumulate in melanosomes, and subsequent illumination leads to melanosomal damage shown by electron microscopy. Fluorescent probes show that the most effective bacteriochlorin produces significantly higher levels of hydroxyl radicals, and this is consistent with the redox properties suggested by molecular-orbital calculations. The best in vitro performing bacteriochlorin was tested in vivo in a mouse melanoma model using spectrally resolved fluorescence imaging and provided significant survival advantage with 20% of cures (P<0.01).—Mroz, P., Huang, Y.-Y., Szokalska, A., Zhiyentayev, T., Janjua, S., Nifli, A.-P., Sherwood, M. E., Ruzié, C., Borbas, K. E., Fan, D., Krayer, M., Balasubramanian, T., Yang, E., Kee, H. L., Kirmaier, C., Diers, J. R., Bocian, D. F., Holten, D., Lindsey, J. S., Hamblin, M. R. Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy. PMID:20385618

Mroz, Pawel; Huang, Ying-Ying; Szokalska, Angelika; Zhiyentayev, Timur; Janjua, Sahar; Nifli, Artemissia-Phoebe; Sherwood, Margaret E.; Ruzié, Christian; Borbas, K. Eszter; Fan, Dazhong; Krayer, Michael; Balasubramanian, Thiagarajan; Yang, Eunkyung; Kee, Hooi Ling; Kirmaier, Christine; Diers, James R.; Bocian, David F.; Holten, Dewey; Lindsey, Jonathan S.; Hamblin, Michael R.

2010-01-01

353

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.

354

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

355

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

356

Longterm outcome of photodynamic therapy compared with biliary stenting alone in patients with advanced hilar cholangiocarcinoma  

PubMed Central

Objectives This study aimed to determine longterm outcomes and factors associated with increased survival after photodynamic therapy (PDT) compared with endoscopic biliary drainage alone in patients presenting with advanced hilar cholangiocarcinoma (CC). Methods A retrospective analysis of the institutional database identifying all patients who presented with a diagnosis of hilar CC between December 1999 and January 2011 was conducted. Results Of the 232 patients identified, 72 (31%) were treated with PDT (Group A) and 71 (31%) were treated with endoscopic biliary drainage alone (Group B). Median survival was 9.8 months [95% confidence interval (CI) 7.42–12.25] in Group A and 7.3 months (95% CI 4.79–9.88) in Group B (P= 0.029). On multivariate analysis, biliary drainage without PDT (P= 0.025) and higher T-stage (P= 0.002) were significant predictors of shorter survival in all patients. In a subgroup analysis of patients in the PDT group, lower pre-PDT bilirubin level (P= 0.005), multiple PDT treatments (P= 0.044) and shortened time to treatment after diagnosis (P= 0.013) were significant predictors of improved survival. Median metal stent patency was longer in Group A than in Group B (215 days vs. 181 days; P= 0.018). Conclusions Photodynamic therapy with stenting resulted in longer survival than stenting alone. Early PDT after diagnosis and multiple PDT treatments were shown to have survival benefits. Metal stent patency was longer in patients receiving PDT. Higher T-stage appears to be a predictor of early mortality in advanced bile duct cancer treated with PDT. PMID:22321037

Cheon, Young Koog; Lee, Tae Yoon; Lee, Seung Min; Yoon, Jung Yoon; Shim, Chan Sup

2012-01-01

357

Taxanes in adjuvant and neoadjuvant therapies for breast cancer.  

PubMed

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

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

1998-01-01

358

Photodynamic Therapy  

MedlinePLUS

... things like using ointments containing ferrous or cobalt ions and using hydrogen peroxide on the treated area ... by application of ointment containing ferrous or cobaltous ions concomitant with the use of topical protoporphyrin IX ...

359

[Evaluation of low-dose FP therapy as adjuvant therapy for gastric cancer].  

PubMed

In the present study, we demonstrate the result of low-dose FP treatment as an adjuvant therapy for 30 patients of stage II or more progressive gastric cancer. 5-FU and CDDP were injected intravenously for 10 days from day 1 through day 5, and day 8 through 12 for 2 weeks at a dose of 250 mg/body and 10 mg/body, or for 14 days at a dose of 250 mg/m2/day and 5 mg/m2/day, respectively. Patients were excluded if they received less than 80% of the respective doses in a course of treatment by the protocol. This constituted a course of chemotherapy, which was repeated every 4 weeks. Grade 3 neutropenia was observed in one case. Other toxicities were anorexia, nausea, weight loss, diarrhea, general fatigue and elevation of serum creatinine, but they were not so severe. The two-year survival rate was 100% in cur A cases, 85% in cur B, and 0% in cur C. The median survival time of the cur C patients was 10 months. These results indicate that low-dose FP therapy is safe and recommendable for cur A and cur B patients. However, other treatment methods such as sequential chemotherapy are needed for cur C gastric cancer patients. PMID:15791822

Maeda, Yoshiaki; Sato, Yuji; Yamamoto, Mitsugu; Shomura, Hiroki; Honnma, Shigenori; Kohashi, Shigechika; Shinohara, Toshiki; Takahashi, Shusaku; Kondo, Masao; Todo, Satoru

2005-03-01

360

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

361

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

PubMed

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

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

2014-08-01

362

Transcutaneous electrical nerve stimulation therapy: An adjuvant pain controlling modality in TMD patients — A clinical study  

PubMed Central

Background: The use of transcutaneous electrical nerve stimulation (TENS) in dentistry was first described in 1967, by Shane and Kessler, but it has yet to gain widespread acceptance in dentistry. A study was undertaken to evaluate the effectiveness of TENS therapy as an adjuvant modality and to compare it with the conventional medication in controlling pain in temporomandibular disorder (TMD) patients. Materials and Methods: The study was carried out in the Department of Oral Medicine and Radiology, Yenepoya Dental College and Hospital, Mangalore. A total of 40 patients with the clinical symptom of pain associated with TMDs were randomly divided into two groups. Group A (control) patients were treated with medication (analgesics and muscle relaxants) alone, while group B patients were treated with TENS therapy in combination with medication. The intensity of the pain was assessed using the Visual Analog Scale (VAS). The results were analyzed with the student's ‘t’ test. A P-value < 0.05 was considered as significant. Results: A significant improvement was observed in both the TENS and the control group in terms of pain control. On comparative analysis, adjuvant TENS therapy was found to be more effective than medication alone, in controlling pain. (P value = 0.019). Conclusion: The observed data suggest that TENS therapy can be used as an adjuvant modality in the management of pain associated with TMDs. This study justifies the use of TENS therapy in the management of TMD.

Shanavas, Muhammad; Chatra, Laxmikanth; Shenai, Prashanth; Rao, Prasanna Kumar; Jagathish, Veena; Kumar, Sreeja Prasanna; Naduvakkattu, Bilahari

2014-01-01

363

Targeted Multifunctional Nanoparticles cure and image Brain Tumors: Selective MRI Contrast Enhancement and Photodynamic Therapy  

NASA Astrophysics Data System (ADS)

Aimed at targeted therapy and imaging of brain tumors, our approach uses targeted, multi-functional nano-particles (NP). A typical nano-particle contains a biologically inert, non-toxic matrix, biodegradable and bio-eliminable over a long time period. It also contains active components, such as fluorescent chemical indicators, photo-sensitizers, MRI contrast enhancement agents and optical imaging dyes. In addition, its surface contains molecular targeting units, e.g. peptides or antibodies, as well as a cloaking agent, to prevent uptake by the immune system, i.e. enabling control of the plasma residence time. These dynamic nano-platforms (DNP) contain contrast enhancement agents for the imaging (MRI, optical, photo-acoustic) of targeted locations, i.e. tumors. Added to this are targeted therapy agents, such as photosensitizers for photodynamic therapy (PDT). A simple protocol, for rats implanted with human brain cancer, consists of tail injection with DNPs, followed by 5 min red light illumination of the tumor region. It resulted in excellent cure statistics for 9L glioblastoma.

Kopelman, Raoul

2008-03-01

364

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

365

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

366

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

367

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

368

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

Microsoft Academic Search

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

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

1995-01-01

369

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

PubMed Central

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

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

1996-01-01

370

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

371

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

372

Treatment of malignant melanoma by high-peak-power 1064 nm irradiation followed by photodynamic therapy.  

PubMed

Irradiation of B16 pigmented melanoma subcutaneously transplanted in C57 mice with a single 650 mJ pulse (10 ns) of 1064 nm light from a Q-switched Nd: YAG laser caused instantaneous bleaching of the pigmented tissue. Visual and histological examination of the resulting gray-colored tumor revealed the breakdown of melanosomes with no detectable alteration of the normal and tumor-overlying skin. Histological examination of the irradiated tumor showed some degree of vascular damage; the depth of the photodamage was not affected by the successive delivery of three consecutive light pulses. The bleached tumor grew at a modestly slower rate but the high-peak-power (HPP) laser treatment did not affect the tumor concentration of a photodynamic sensitizer Si(i.v.)-naphthalocyanine (isoBO-SiNc) intravenously injected 24 h before Nd:YAG irradiation. Treatment of the B16 pigmented melanoma by photodynamic therapy (PDT: 1 mg/kg isoBO-SiNc, 300 mW/cm2, 520 J/cm2) from a 774 nm diode laser immediately after the 1064 nm irradiation resulted in a 16 day delay of tumor regrowth, which was markedly longer than the delay (ca 6 days) obtained after PDT under identical conditions without the preirradiation. Thus, pretreatment of pigmented tumors with HPP 1064 nm light appears to enhance their susceptibility to conventional PDT. The tumor response was further enhanced by repeating the combined HPP/PDT treatment at an interval of 10 days (regrowth delay: 27 days), as well as by applying hyperthermia immediately after HPP/PDT (regrowth delay: ca 34 days). PMID:9747592

Busetti, A; Soncin, M; Jori, G; Kenney, M E; Rodgers, M A

1998-09-01

373

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

NASA Astrophysics Data System (ADS)

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

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

2014-03-01

374

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

375

Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies  

NASA Astrophysics Data System (ADS)

A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer RadachlorineTM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm2. Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

Privalov, Valeriy A.; Lappa, Alexander V.; Bigbov, Elmir N.

2011-02-01

376

In vivo study of laser irradiation of fractionated drug administration based mechanism for effective photodynamic therapy in rat liver  

NASA Astrophysics Data System (ADS)

Up-regulation of stress-activated proteins in cancer cells plays a protective role against photodynamic induced apoptosis. Post photodynamic therapy extracted normal rat liver tissue usually shows a fraction of surviving cells, the photodynamic resistant cells, residing in the necrotic region. To treat these photodynamic resistant cells a technique has been proposed based on fractionated drug administration of diluted photosensitizer, keeping the net concentration (5 mg/kg) constant, and subsequently varying drug light interval (DLI). Flourescence measurements were made for the presence of photosensitizer in a tissue. For qualitative analysis both histological and morphological studies were made. Although preliminary aim of this approach was not achieved but there were some interesting observation made i.e. for higher dilution of photosensitizer there was a sharp boundary between necrotic and normal portion of tissue. An increase in the absorption coefficient (?) from 2.7 ? 2.9 was observed as photosensitizer was diluted while the corresponding threshold dose (D th) persistently decreases from (0.10 ? 0.02) J/cm2 when irradiated with a 635 nm laser fluence of 150 J/cm2.

Khurshid, A.; Firdous, S.; Ahmat, L.; Ferraria, J.; Vollet-Filho, J. D.; Kurachi, C.; Bagneto, V. S.; Nawaz, M.; Ikram, M.; Ahmad, M.

2011-11-01

377

In vitro study of reactive oxygen species production during photodynamic therapy in ultrasound-pretreated cancer cells.  

PubMed

Several recent studies bring evidence of cell death enhancement in photodynamic compound loaded cells by ultrasonic treatment. There are a number of hypotheses suggesting the mechanism of the harmful ultrasonic effect. One of them considers a process in the activation of photosensitizers by ultrasonic energy. Because the basis of the photodynamic damaging effect on cells consists in the production of reactive oxygen species (ROS), we focused our study on whether the ultrasound can increase ROS production within cancer cells. Particularly, we studied ROS formation in ultrasound pretreated breast adenocarcinoma cells during photodynamic therapy in the presence of chloroaluminum phthalocyanine disulfonate (ClAlPcS2). Production of ROS was investigated by the molecular probe CM-H2DCFDA. Our results show that ClAlPcS2 induces higher ROS production in the ultrasound pretreated cell lines at a concentration of 100 microM and light intensity of 2 mW/cm2. We also observed a dependence of ROS production on photosensitizer concentration and light dose. These results demonstrate that the photodynamic effect on breast cancer cells can be enhanced by ultrasound pretreatment. PMID:17552898

Kolárová, H; Bajgar, R; Tománková, K; Krestýn, E; Dolezal, L; Hálek, J

2007-01-01

378

EGFR-mediated intracellular delivery of Pc 4 nanoformulation for targeted photodynamic therapy of cancer: in vitro studies  

Microsoft Academic Search

In photodynamic therapy (PDT), the light activation of a photosensitizer leads to the generation of reactive oxygen species that can trigger various mechanisms of cell death. Harnessing this process within cancer cells enables minimally invasive yet targeted cancer treatment. With this rationale, here we demonstrate tumor-targeted delivery of a highly hydrophobic photosensitizer Pc 4 loaded within biocompatible poly(ethylene glycol)–poly(?-caprolactone) block

Alyssa M. Master; Yizhi Qi; Nancy L. Oleinick; Anirban Sen Gupta

379

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

380

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

PubMed

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

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

2014-01-01

381

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

382

Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response  

PubMed Central

To improve anticancer therapeutic success of photodynamic therapy (PDT), combination treatments represent a viable strategy. Sphingolipid analogs combined with anticancer drugs can enhance tumor response. We have shown that LCL29, a C6-pyridinium ceramide, promotes therapeutic efficacy of Photofrin-PDT in mouse SCCVII squamous cell carcinoma tumors. The long-term effect of the combination PDT + LCL29 is unknown. In this study we used the same model to test the long-term curative potential of Foscan-PDT + LCL29. We show that treatment of SCCVII tumors with the combination led to enhanced long-term tumor cure compared to PDT alone. LCL29 itself did not prevent tumor growth. All treatments triggered early increases in tumor-associated C16-ceramide, C18-ceramide, dihydrosphingosine, and global levels of dihydroceramides. PDT-evoked increases in tumor-associated sphingosine-1-phosphate and dihydrosphingosine-1-phosphate remained elevated or were attenuated after the combination, respectively; in contrast, LCL29 had no effect on these two sphingolipids. Our data demonstrate that adjuvant LCL29 improves PDT long-term therapeutic efficacy, implying translational potential of the combination. Furthermore, our findings indicate that changes in the sphingolipid profile might serve as predictive biomarkers of tumor response to treatments. PMID:21152858

Separovic, D.; Bielawski, J.; Pierce, J.S.; Merchant, S.; Tarca, A.L.; Bhatti, G.; Ogretmen, B.; Korbelik, M.

2012-01-01

383

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

PubMed

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

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

2014-06-01

384

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

NASA Astrophysics Data System (ADS)

Background: Subjective measures are considered the gold standard in palliative care evaluation, but no studies have evaluated palliative photodynamic therapy (PDT) subjectively. If PDT is to be accepted as a palliative therapy for later-stage obstructing esophageal and lung cancer, evidence of its effectiveness and acceptability to patients must be made known. Study Design/Materials and Methods: This ongoing study's major aim is to evaluate subjective outcomes of PDT in patients with obstructing esophageal and lung cancer. Existing measures of health status, dysphagia and performance status were supplemented with an instrument developed to evaluate PDT symptom relief and side effect burden, the PDT Side Effects Survey (PSES). Results: PDT patients treated with porfimer sodium (Photofrin) and 630-nm light experienced reduced dysphagia grade and stable performance status for at least one month after PDT (N= 10-17), but these effects did not necessarily persist at three months. Fatigue, appetite and quality of life may be the most burdensome issues for these patients. Conclusions: Preliminary data suggest that the PSES is an acceptable and valid tool for measuring subjective outcomes of palliative PDT. This study is the first attempt to systematically evaluate subjective outcomes of palliative PDT. Multi-center outcomes research is needed to draw generalizable conclusions that will establish PDT's effectiveness in actual clinical practice and enhance the wider adoption of PDT as a cancer symptom relief modality.

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

2002-06-01

385

Combination approaches to potentiate immune response after photodynamic therapy for cancer†  

PubMed Central

Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not advanced to a mainstream cancer treatment. Although it has been shown to be an efficient way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT great potential to become more widely used. Although the stimulation of tumor-specific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. This review will cover these combination approaches using immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen-associated molecular patterns, cytokines growth factors, and approaches that target regulatory T-cells. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised. PMID:21479313

St Denis, Tyler G.; Aziz, Kanza; Waheed, Anam A.; Huang, Ying-Ying; Sharma, Sulbha K.; Mroz, Pawel; Hamblin, Michael R.

2012-01-01

386

Methyl-aminolevulinate photodynamic therapy for the treatment of erythroplasia of Queyrat in 23 patients.  

PubMed

Erythroplasia of Queyrat (EQ) is an intraepithelial squamous cell carcinoma localized on the mucosal or transitional surfaces. Standard therapy usually consists of the surgical removal of the cancer. The use of non-invasive alternative procedures, such as photodynamic therapy (PDT), has been considered for the treatment of EQ, although only a few reports regarding isolated cases or small series exist. We describe our cumulative experience with PDT, using topical methyl-aminolevulinate (MAL), for the management of 23 male patients with EQ of the glans penis and/or prepuce. Patients underwent two consecutive weekly MAL-PDT sessions, with the second session postponed in seven patients because of an excessive local reaction. Nineteen patients obtained a complete clinical remission without any sign of recurrence over an average post-treatment period of 18 months (range, 8-30 months). Cosmetic outcome was excellent in most patients, while dyschromic changes occurred in four cases. All patients experienced transient local adverse reactions and 22 of them reported severe or very severe symptoms during the session. PMID:21888568

Fai, Dario; Romano, Ivana; Cassano, Nicoletta; Vena, Gino A

2012-10-01

387

Superficial photodynamic therapy with topical 5-aminolaevulinic acid for superficial primary and secondary skin cancer.  

PubMed Central

Between January 1991 and December 1992 a phase I trial of superficial photodynamic therapy (PDT) using topical application of 5-aminolaevulinic acid (ALA) was undertaken to treat Bowen's disease, superficial basal cell carcinomas (BCCs) and metastatic skin secondaries from breast (adenocarcinoma) or pinna (squamous cell carcinoma). Promising results were obtained with 36 areas of Bowen's disease, with a complete response rate of 89% at a median follow-up of 18 months. The treatment of BCCs was less successful, with 50% complete responses in 16 lesions at a median follow-up of 17 months. Metastatic nodules responded poorly. The treatment was well tolerated and discomfort during light irradiation could be reduced by prior application of 'Emla' cream. Lesions wept for 1-2 weeks following treatment and healed over a period of approximately 2 months. For large areas of Bowen's disease, particularly in anatomically difficult areas and in elderly patients, PDT using ALA may constitute a single simple alternative outpatient treatment to existing therapies. Further work is required to improve the results with BCCs. Images Figure 1 PMID:8123497

Cairnduff, F.; Stringer, M. R.; Hudson, E. J.; Ash, D. V.; Brown, S. B.

1994-01-01

388

Photodynamic therapy stimulates anti-tumor immunity in a murine mastocytoma model  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species that eventually cause vascular shutdown and tumor cell apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, recognition of tumor-specific antigens, and induction of heat-shock proteins, while the three commonest cancer therapies (surgery, chemotherapy and radiotherapy) all tend to suppress the immune system. Like many other immunotherapies, the extent of the immune response after PDT tends to depend on the antigenicity of the particular tumor, or in other words, whether the tumor contains proteins with the correct characteristics to provide peptides that can bind to MHC class I molecules and provide a target for cytolytic T lymphocytes. We have described certain mouse tumors containing defined or naturally occurring tumor associated antigens that respond particularly well to PDT, and potent immune responses capable of destroying distant untreated tumors can be induced. In this report we address the induction of immunity after PDT of the DBA2 mastocytoma known as P815. This tumor was the first mouse tumor to be shown to possess a tumor-rejection antigen capable of being recognized by cytotoxic T-cells.

Mroz, Pawel; Hamblin, Michael R.

2008-02-01

389

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

390

Hydrophobic IR780 encapsulated in biodegradable human serum albumin nanoparticles for photothermal and photodynamic therapy.  

PubMed

It has been reported that IR780 iodide, a near-infrared dye, can be applied for cancer imaging, photodynamic therapy (PDT) and photothermal therapy (PTT). However, the hydrophobicity and toxicity of IR780 severely limit its further clinical applications. In this study, human serum albumin was used to load IR780 to form nanoparticles (HSA-IR780 NPs) by protein self-assembly. Compared to free IR-780, the solubility of HSA-IR780 NPs was greatly increased (1000-fold) while the toxicity was decreased (from 2.5mgkg(-1) to 25mgkg(-1)). Moreover, both PTT and PDT could be observed in HSA-IR780 NPs, as determined by increased temperature and enhanced generation of singlet oxygen after laser irradiation at a wavelength of 808nm. In vivo studies also showed a great tumor inhibition by the injection of HSA-IR780 NPs into tumor-bearing mice. Therefore, HSA-IR780 NPs may serve as a promising substitute for IR780 in further clinical PDT and PTT. PMID:25463484

Jiang, Chenxiao; Cheng, Hao; Yuan, Ahu; Tang, Xiaolei; Wu, Jinhui; Hu, Yiqiao

2015-03-01

391

Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies.  

PubMed

Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT), due to their specific spatiotemporal selectivity and minimal invasiveness, have been widely investigated as alternative treatments of malignant diseases. Graphene and its derivatives not only have been used as carriers to deliver photosensitizers for PDT, but also as photothermal conversion agents (PTCAs) for PTT. Herein, we strategically designed and produced a novel photo-theranostic platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated graphene oxide (GO-PEG-DVDMS) for enhanced fluorescence/photoacoustic (PA) dual-modal imaging and combined PDT and PTT. The GO-PEG carrier drastically improves the fluorescence of loaded DVDMS via intramolecular charge transfer. Concurrently, DVDMS significantly enhances the near-infrared (NIR) absorption of GO for improved PA imaging and PTT. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. This novel theranostics is well suited for fluorescence/PA dual-modal imaging and synergistic PDT/PTT. PMID:25573051

Yan, Xuefeng; Hu, Hao; Lin, Jing; Jin, Albert J; Niu, Gang; Zhang, Shaoliang; Huang, Peng; Shen, Baozhong; Chen, Xiaoyuan

2015-01-28

392

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

PubMed

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

2010-11-01

393

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

394

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.

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

2014-01-01

395

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

396